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1
Ali, Zulfiqar, Nelofar Hassan, Saqib Mehdi, Mubashir A. Shah, Akram Hussain Bijli, and Talib Khan. "A review of the blood transfusion practices in neuroanesthesia in the perioperative period in a tertiary care hospital." International Journal of Research in Medical Sciences 5, no. 5 (April 26, 2017): 1858. http://dx.doi.org/10.18203/2320-6012.ijrms20171806.
Анотація:
Background: Blood transfusion involves the administration of blood and blood components. Neurosurgical procedures are associated with significant blood loss with the need for blood transfusion in the preoperative, intraoperative and postoperative period to maintain optimal hemodynamic and cerebral oxygenation. Various neurosurgical procedures as traumatic brain injury, complex spinal surgeries, and endovascular neurosurgical procedures may need blood transfusions to maintain the optimal physiology.Methods: This study was performed prospectively at a tertiary care hospital in northern India with about a work load of 800 to 1000 elective neurosurgical surgical procedures being done per year. This data was collected prospectively over a period of one year from the patients being operated for elective neurosurgical procedures and later on shifted to the neurosurgical intensive care unit and the neurosurgical wards. The patients operated for emergency procedures for traumatic brain surgery were not included in the study.Results: A total of 455 elective neurosurgical procedures were done during the study period. Out of these 455 patients there were 95 patients who were in the paediatric age group with age less than 12 years. Out of 360 adult patients 85 patients were in need of blood transfusion which constituted 23.6 percent of the operated patients. Out of these 85 patients 45 patients needed two transfusions in the form of whole blood or packed cells, 40 patients needed a single transfusion.42 units of fresh frozen plasma were transfused to 17 patients with 15 patients receiving platelet transfusions.Conclusions: In conclusion, neurosurgical population is associated with significant blood loss and a requirement of blood transfusion. About 47 percent of paediatric population needed blood transfusion in our study with around 24 percent of adult population. The transfusion requirement was mainly seen in patients with craniostenosis, meningiomas, cerebello pontine tumours and meningiomas.
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Zhou, Li Hong, Hai Yan Wu, Quan Yuan, Xiang Dong Li, Pei Wei Xu, Rong Wang, Feng Xia та Jian Zhong Xiao. "Sensing Properties of YSZ-Based NO Sensors with Double-Perovskite (La0.8Sr0.2)2FeNiO6-δ Sensing Electrodes". Key Engineering Materials 602-603 (березень 2014): 845–50. http://dx.doi.org/10.4028/www.scientific.net/kem.602-603.845.
Анотація:
The powder of (La0.8Sr0.2)2FeNiO6-δ (LSFN) oxide with double-perovskite structure was synthesized by polymeric precursor method. Then the YSZ-based NO sensors with LSFN sintered at different temperatures (1000, 1100, 1200 and 1300 °C) as sensitive electrode (SE) were fabricated. All samples were characterized by XRD. The morphologies of the LSFN-SEs were observed with ESEM. The NO sensing properties of the sensors were investigated in the operating temperature range of 350-650 °C in 10 vol. % O2. Results demonstrated that the sensor with LSFN-SE sintered at 1300 °C exhibited highest response to 500 ppm NO at 400 °C, which was about 85 mV. A linear relationship was obtained between the emf and the logarithm of NO concentration from 500 to 800 ppm at 400 and 500 °C. Moreover, both magnitude and slope to NO response decreased as operating temperature increased. And both the response time and recovery time shortened as temperature increased. But the recovery rate was slower than the response rate, especially at and below 450 °C. The optimal sensor response was obtained at 500-550 °C.
3
Sarnelli, Anna, Maria Belli, Valentina Di Iorio, Emilio Mezzenga, Monica Celli, Stefano Severi, Elisa Tardelli, et al. "Dosimetry of 177Lu-PSMA-617 after Mannitol Infusion and Glutamate Tablet Administration: Preliminary Results of EUDRACT/RSO 2016-002732-32 IRST Protocol." Molecules 24, no. 3 (February 11, 2019): 621. http://dx.doi.org/10.3390/molecules24030621.
Анотація:
Radio-ligand therapy (RLT) with177Lu-PSMA-617 is a promising option for patients with metastatic castration-resistant prostate-cancer (mCRPC). A prospective phase-II study (EUDRACT/RSO,2016-002732-32) on mCRPC is ongoing at IRST (Meldola, Italy). A total of 9 patients (median age: 68 y, range: 53–85) were enrolled for dosimetry evaluation of parotid glands (PGs), kidneys, red marrow (RM) and whole body (WB). Folic polyglutamate tablets were orally administered as PGs protectors and 500 mL of a 10% mannitol solution was intravenously infused to reduce kidney uptake. The whole body planar image (WBI) and blood samples were acquired at different times post infusion (1 h, 16–24 h, 36–48 h and 120 h). Dose calculation was performed with MIRD formalism (OLINDA/EXM software). The median effective half-life was 33.0 h (range: 25.6–60.7) for PGs, 31.4 h (12.2–80.6) for kidneys, 8.2 h (2.5–14.7) for RM and 40.1 h (31.6–79.7) for WB. The median doses were 0.48 mGy/MBq (range: 0.33–2.63) for PGs, 0.70 mGy/MBq (0.26–1.07) for kidneys, 0.044 mGy/MBq (0.023–0.067) for RM and 0.04 mGy/MBq (0.02–0.11) for WB. A comparison with previously published dosimetric data was performed and a significant difference was found for PGs while no significant difference was observed for the kidneys. For PGs, the possibility of reducing uptake by administering glutamate tablets during RLT seems feasible while further research is warranted for a more focused evaluation of the reduction in kidney uptake.
4
Sartor, A. Oliver, Daniel Heinrich, Joe M. O'Sullivan, Sophie D. Fossa, Ales Chodacki, Pawel J. Wiechno, John P. Logue, et al. "Radium-223 chloride (Ra-223) impact on skeletal-related events (SREs) and ECOG performance status (PS) in patients with castration-resistant prostate cancer (CRPC) with bone metastases: Interim results of a phase III trial (ALSYMPCA)." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 4551. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.4551.
Анотація:
4551 Background: Ra-223, a 1st-in-class alpha-pharmaceutical, targets bone metastases (mets) with high-energy alpha-particles of short range (<100 μm). ALSYMPCA, a phase III, double-blind, randomized, multinational study, compared Ra-223 plus best standard of care (BSC) v placebo (pbo) plus BSC in patients (pts) with bone mets in CRPC. The primary endpoint was OS; secondary endpoints included SREs and ECOG PS. Methods: Eligible pts had progressive, symptomatic CRPC with ≥ 2 bone mets on scintigraphy and no known visceral mets; were receiving BSC; and either previously received docetaxel, were docetaxel ineligible, or refused docetaxel. Pts were randomized 2:1 to 6 injections of Ra‑223 (50 kBq/kg IV) q4 wks or matching pbo and stratified by prior docetaxel use, baseline ALP level, and current bisphosphonate use. Results: 921 pts were randomized from 6/2008-2/2011. In a planned interim analysis (n = 809), Ra-223 significantly improved OS v pbo (median OS 14.0 v 11.2 mo, respectively; two-sided P = .00185; HR = .695; 95% CI, .552-.875).SREs were lower in the Ra-223 v pbo group, and time to 1st SRE was significantly delayed (median time to SRE 13.6 mo v 8.4 mo, respectively; P = .00046; HR = .610; 95% CI, .461-.807). The proportion of pts with ECOG PS deterioration (≥ 2 points) was less in Ra-223 v pbo group at Wk 12 and Wk 24 (4%, 15/389 v 9%, 16/180 and 7%, 16/236 v 12%, 10/83, respectively). Time to ECOG PS deterioration (≥ 2 points) was significantly delayed by Ra-223 v pbo (P = .003; HR = .62; 95% CI, .46-.85). Conclusions: Ra-233 significantly delayed time to 1st SRE and SRE components, notably SCC. Fewer pts in the Ra-223 group had ECOG PS deterioration. Ra-223 improves OS with excellent safety and may provide a new standard of care for CRPC pts with bone mets. [Table: see text]
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Garcia-Manero, Guillermo, Mikkael A. Sekeres, Alan F. List, H. Jean Khoury, Anjali Advani, Elias Jabbour, Hagop M. Kantarjian, et al. "Phase 1 Dose-Escalation/Expansion Study Of ARRY-614 In Patients With IPSS Low/Int-1 Risk Myelodysplastic Syndromes." Blood 122, no. 21 (November 15, 2013): 387. http://dx.doi.org/10.1182/blood.v122.21.387.387.
Анотація:
Abstract Background Emerging data support a role for both p38 MAPK (p38) and Tie2 in the molecular mechanisms underlying MDS pathophysiology and suggest that inhibition of p38/Tie2 has the potential to improve hematopoiesis. ARRY-614 is an orally bioavailable, dual inhibitor of p38 and Tie2 that has demonstrated multi-lineage hematologic improvement (HI) and acceptable tolerability with a powder-in-capsule (PIC) formulation. However, due to suboptimal PK properties of the PIC, a Phase 1 study in patients (pts) with MDS was initiated to evaluate an optimized formulation of ARRY-614. Methods The aims of this study were to determine the MTD, establish a recommended Phase 2 dose and evaluate the safety, PK profile and PD effects of a formulated capsule of ARRY-614 administered once daily (QD) and twice daily (BID) in continuous 28-day cycles. Pts with IPSS low/intermediate-1 risk MDS, ≥ 1 cytopenia (per IWG 2006 criteria) and adequate ECOG performance status, hepatic and renal function were eligible. Prior therapy for MDS was permitted; CMML per FAB criteria and secondary MDS were allowed. The study used a 3+3 dose escalation design modified to allow additional pt accrual at lower dose levels already determined to be tolerable. Additional expansions were permitted at selected dose levels to determine the recommended Phase 2 dose. Response was assessed using IWG 2006 criteria. In addition, platelet transfusion dependent pts (TD, ≥ 1 platelet transfusion within 8 weeks prior to starting treatment) were assessed for transfusion independence (TI) or transfusion reduction (TR, 50% decrease). Results At the time of this analysis (01 May 2013), 62 pts with IPSS low (n = 16) or intermediate-1 (n = 46) risk MDS were enrolled (median age 72 years, range 46-85). Patients had received a median of 3 prior regimens (range 0-6); 5 pts had no prior therapy. Prior regimens included: hypomethylating agents (HMAs; 85%), erythropoiesis-stimulating agents (65%) and lenalidomide (32%). ARRY-614 was administered at doses of 200-1000 mg QD (n=50) and 100-200 mg BID (n=12), with a median treatment duration of 13 weeks (range 1 day to 65 weeks). The MTD of the QD schedule was determined to be 800 mg QD after 2/6 pts experienced dose limiting toxicities (DLTs) of atrial fibrillation at the 1000 mg QD dose. The 200 mg BID dose was deemed not tolerable after 3/8 pts developed DLTs of Grade 3 rash (2 pts) and Grade 3 ECG QT prolongation (1 pt). The most common treatment-related adverse events (> 5% of total pts) included rash, nausea, atrial fibrillation, decreased appetite, fatigue, asthenia and vomiting. The majority of these events were mild or moderate. Nineteen pts remain on study (median time on treatment of 10 weeks). To date, 12 of 54 (22%) evaluable pts and 9 of 31 (29%) pts on treatment ≥ 16 weeks experienced HI per IWG 2006 criteria and/or achieved platelet TR or TI. Responses were observed at all dose levels. HI-E, HI-P, and HI-N responses were observed in 6% (3/49), 21% (7/34) and 31% (5/16) of the pts, respectively. In addition, of the 12 pts who were platelet TD, a total of 50% (6/12) achieved at least a TR, and 33% (4/12) achieved complete TI. All pts who experienced a response had received prior treatment with an HMA. ARRY-614 and its metabolite AR00451575 demonstrated increasing exposure with increasing dose, which was approximately dose proportional based on Cmax and AUC. At doses ≥ 400 mg QD, the plasma concentrations exceeded the predicted p38 and Tie2 IC50 values (113 ng/mL and 1150 ng/mL, respectively, plasma protein binding corrected). Preliminary biomarker analyses demonstrated primary target inhibition with persistent reduction in phospho-p38 levels in the bone marrow as compared to baseline during the course of treatment. In addition to primary target inhibition, observed decreases in plasma chemokines during the course of treatment were consistent with functional inhibition of p38. Conclusions The ARRY-614 formulated capsule demonstrates good tolerability and on-target activity at doses up to 800 mg QD, as well as a more favorable PK profile than the previous formulation. In addition, HI responses were seen across dose levels and across lineages in pts previously treated with HMAs, suggesting ARRY-614 may provide a treatment option for pts with lower-risk disease failing standard therapies. Next steps will be to explore the 400 mg and 800 mg dosing schedules further.</abstract> Disclosures: Garcia-Manero: Array BioPharma: steering committee participation Other. Sekeres:Amgen: data safety monitoring board, data safety monitoring board Other; Celgene: advisory board Other. List:Array BioPharma: Member of advisory board on MDS Other. Khoury:Array BioPharma: steering committee participation Other. Kantarjian:Array BioPharma: Research Funding. Cable:Array BioPharma: Employment. Guthrie:Array BioPharma: Employment. Hogeland:Array BioPharma: Employment. Ptaszynski:Array BioPharma: Employment. Maloney:Array BioPharma: Employment. Corson:Array BioPharma: Employment. Komrokji:Array BioPharma: steering committee participation Other.
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Kamuhu, Regina, Beatrice Mugendi, and Judith Kimiywe. "Cardiovascular Disease Risk Factors in HIV-Infected Adults in Nyeri County, Kenya." International Journal of Health Sciences and Research 11, no. 5 (May 7, 2021): 117–24. http://dx.doi.org/10.52403/ijhsr.20210516.
Анотація:
Cardiovascular diseases (CVD) is currently second, after cancer, as the most frequent cause of death among HIV-positive subjects in areas of the world where Highly active anti-retroviral therapy (HAART) is widely available. The purpose of this study was to investigate cardiovascular disease markers in HIV-infected adults attending comprehensive care clinic in Nyeri Level- 5- Hospital. The results are based on a sample of 85 participants that randomly selected for an intervention study with two study arms. Descriptive statistics were used to analyze all study variables. Relationships between all and individual CVD risk factors were analyzed using Spearman’s correlation coefficient. Criterion for statistical significance was at p < 0.05 and 90% power of test. Twenty nine percent of the respondents were aged fifty years and above while 48.2% were between 40-49 years. Only 5.9% of the respondents smoked while 8.2% drunk alcohol. Twenty seven percent (27.1%) had low physical activity while 24.7% had obesity class I (30-34.9), 8.2% had obesity class II (35-39.9) while 1.5% had obesity class III (> 40). Another 31.8% were overweight (25-29.9). 28.2% had hypertension stage I (140-159) and another 11.8% had hypertension stage II (>160). Twenty two percent (22.4%) had high total cholesterol (>6.2), while 34.1% had high serum triglycerides (2.25-5.6) and another 4.7% had very high serum LDL-C (>4.91). Framingham’s risk score was used to determine the 10-year risk of developing a coronary heart disease. Majority of the participants (60%) had low (<10%) 10-year risk of coronary heart disease at the baseline. There is a high prevalence of hypertension and overweight/obesity among HIV+ patients. Key words: Cardiovascular risk factors, cardiovascular risk score, lipid profile, Framingham risk score.
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Bibel, Yu O., and L. M. Chernobai. "Dependence of the grain filling intensity and moisture-yielding ability on valuable economic features in corn." Plant Breeding and Seed Production, no. 124 (December 27, 2023): 66–75. http://dx.doi.org/10.30835/2413-7510.2023.293891.
Анотація:
Purpose. To analyze the dependence of the corn grain filling intensity and moisture-yielding ability of corn grain on morphological and economic characteristics in each ripeness group of corn lines.
Material and Methods. The study was carried out in the Laboratory of Introduction and Preservation of Plant Genetic Resources and the Laboratory of Corn Breeding and Seed Production of the Yuriev Plant Production Institute of NAAS in 2017-2019. The accessions were sown by the standard method in two-row plots of 9.8 m2 in three replications. The reference accessions were placed after every 20 plots: early ripening - F2 line; medium-early – UKh 52; medium-ripening - DS 103, UKhS 126, and SO 125; medium-late - А 619, Kharkivska 215, and KhА 408. During the growing period, the accessions were evaluated in the field 24 times for typicality. In the laboratory, the grain moisture was determined thermogravimetrically four times for each line during its ripening period, every ten days, starting on day 30 after pollination. For comparison, the moisture content in grain was also determined in the field using an AVD 6100 needle moisture meter for wood.
Results and Discussion. Lines with the maximum yield of moisture per day were selected: six medium-early lines (LPL 79 A, UKhK 5, UChS 85, UKhK 590, UChS 85, SL 73-85-2 (Ukraine), СО 190 (Canada), and B 267 (Russia)), 24 medium-ripening lines (of them, 20 lines were bred in Ukraine; one line is from Russia (B 321), and three lines are from the USA (W 83, A 619, and B 143)), and 25 medium-late lines (20 Ukrainian lines (UKhK 472, KhLH 78, LNAU 18, ОV 1248, UKh 804, and others), two Russian lines, 1 Kazakhstanian line, and 1 line from the USA). We noted the dependences of the grain filling intensity, moisture release during ripening, and grain drying rate on morphobiological and so-called "specific" characteristics (peduncle length, sheath number, density of sheath adhesion to the ear, grain consistency). Corn lines with intensive grain filling and a set of valuable economic features were distinguished.
Having studied inbred corn lines, we found a strong positive correlation between dry matter accumulation and performance (r = 0.90) and moderate positive correlations between dry matter accumulation and kernel number per ear (r = 0.45), between dry matter accumulation and plant height (r = 0.40), and between dry matter accumulation and ear attachment height (r = 0.39).
Conclusions. The best lines were selected in each group of ripeness according to the intensity of moisture egress from grain and valuable economic characteristics. In the medium-early group, eight best lines were selected. However, only 6 lines had good economic characteristics. Most of the medium-early lines were superior to the reference accession, UKh 52, in terms of performance and thousand kernel weight. In the medium-ripening group, 24 best lines were selected in comparison with UChS 126 (reference accession).
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Srirungruang, Siriporn, Buraya Mahajindawong, Panachai Nimitpanya, Uthaitip Bunkasem, Pattama Ayuyoe, Surang Nuchprayoon, and Vivornpun Sanprasert. "Comparative Study of DNA Extraction Methods for the PCR Detection of Intestinal Parasites in Human Stool Samples." Diagnostics 12, no. 11 (October 25, 2022): 2588. http://dx.doi.org/10.3390/diagnostics12112588.
Анотація:
Stool samples typically contain PCR inhibitors; however, helminths are difficult to lyse and can cause false-negative PCR results. We assessed the effective methods for extracting DNA from different kinds of intestinal parasites. We compared the most common DNA extraction methods from stool samples, including the phenol-chloroform technique with or without a bead-beating step (P and PB), a QIAamp Fast DNA Stool Mini Kit (Q), and a QIAamp PowerFecal Pro DNA Kit (QB). Genomic DNA was extracted from 85 stool samples collected from patients infected with Blastocystis sp., Ascaris lumbricoides, Trichuris trichiura, hookworm, and Strongyloides stercoralis. DNA quantity and DNA quality were evaluated via spectrophotometry, and DNA integrity was assessed by PCR. We found that P and PB provided higher DNA yields (~4 times) than when using Q and QB. However, P showed the lowest detection rate of PCR (8.2%), wherein only S. stercoralis (7 out of 20 samples) was detected. QB showed the highest detection rate of PCR (61.2%). After plasmid spikes, only 5 samples by QB were negative while 60 samples by P were still negative. Remarkably, QB could extract DNA from all the groups of parasites that we tested. These results indicate that QB is the most effective DNA extraction method for the diagnosis and monitoring of intestinal parasites via PCR.
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Margan, DE, NM Graham, and TW Searle. "The energy value of whole oats grain in adult wether sheep." Australian Journal of Experimental Agriculture 27, no. 2 (1987): 223. http://dx.doi.org/10.1071/ea9870223.
Анотація:
Samples of Cooba and Coolabah oats were chosen on chemical analysis to represent relatively high and low quality grain. Each was evaluated by measuring energy, nitrogen and carbon balances in 4 adult sheep at several levels of feeding and during starvation. The Cooba contained, on a dry matter (DM) basis, 14% crude protein (CP), 23% cell wall constituents (CWC) and 19.1 MJ/kg gross energy (GE); the Coolabah had 10% CP, 31% CWC and 19.6 MJ/kg. With ad libitum feeding, respective DM intakes were 1.4 and 1.8 kg/day (3.3 and 4.4 times maintenance) giving daily retentions of 6.6 and 8.2 MJ and 6.2 and 8.0 g nitrogen. The availabilities of the gross energy of the Cooba at maintenance were 85% digestible energy (DE), 71% metabolisable energy (ME) (13.6 MJ/kg DM), 59% net energy (NE); when assessed as a production supplement, the values were 79,74 and 38% respectively. The results for Coolabah were 76% DE, 68% ME (1 3.3 MJ/ kg), 53% NE (maintenance); 64% DE, 6 1% ME, 36% NE (production supplement). It is apparent from the present and previously published results that the GE and ME/DE values of oats are higher than commonly supposed. Furthermore, although protein and fibre content indicate the relative digestibilities of feeds, they are not a good guide to relative NE values nor to attainable production in terms of either energy or protein.
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Shaikh, Yasar Arafath. "Study of pleural effusion in chronic kidney disease patient undergoing hemodialysis in Andhra Pradesh population." International Journal of Advances in Medicine 6, no. 4 (July 24, 2019): 1262. http://dx.doi.org/10.18203/2349-3933.ijam20193282.
Анотація:
Background: About 85 patients aged between 30 to 65 years suffering with chronic kidney disease with pleural effusion undergoing hemodialysis were studied.Methods: X-ray, USG and Biochemical study was performed to confirm the Diagnosis.Results: The clinical manifestation was 17 (20%) had hypertension (HTN), 16 (18.8%) had DM (Diabetes mellitus), 12 (14.1%) had cardiac disease 9 (10.5%), had cardiovascular disease, 5 (5.8%) had malignancy. 10 (11.7%), had COPD, 13 (15.2%) had hepatitis 3 (3.5%) had thyroid disease, Hb%, profile was 40 (47%), had 9 to 9.5%, 45 (52.9%) had 10 to 10.5, protein (total) 39 (45.8%) had 6.2 to 6.5 g/dl and 46 (54.1%) had 66 to 6.9 g/dl Albumin 43 (50.5%) was 3.1 to 3.5 g/dl, 42 (49.4%) had 3.6 to 3.8 g/dl. Uric acid in 38 (44.7%) was 7.1 to 7.5 mg/dl, 47 (55.2%) had 7.6 to 8.2 mg/dl, Urea nitrogen in 44 (48.2%) was 88 to 89.2 mg/dl 44(51.7%) had 90 to 96.2 mg/dl GFR in 37 (43.5%) was 5.25 to 5.32 and 48 (56.4%) 5.33 to 6.24 ml/min/1.73 Acess to hemodialysis 50 (58.8%) had arterio- venous fistula or graft and 35 (41.1%) had catheter. The degree of pleural effusion in 58 (68.2%) had mild 22 (25.8%) had moderate 5 (5.8%) had severe degree of effusion.Conclusions: This pragmatic study will be quite useful to physician, urologist, nephrologist to treat such patients efficiently so that the life span of such patients will be increased and avoid the morbidity and long stay in hospitals.
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Ke, Ya-Ting, An-Chi Peng, Yi-Min Shu, Min-Hsien Chung, Kang-Ting Tsai, Ping-Jen Chen, Tzu-Chieh Weng, Chien-Chin Hsu, Hung-Jung Lin, and Chien-Cheng Huang. "Prevalence of Geriatric Syndromes and the Need for Hospice Care in Older Patients of the Emergency Department: A Study in an Asian Medical Center." Emergency Medicine International 2020 (July 17, 2020): 1–9. http://dx.doi.org/10.1155/2020/7174695.
Анотація:
Background. The prevalence of geriatric syndromes and the need for hospice care in the emergency department (ED) in Asian populations remain unclear. This study was conducted to fill the data gap. Methods. Using a newly developed emergency geriatric assessment (EGA), we investigated the prevalence of geriatric syndromes and the need for hospice care in older ED patients of a tertiary medical center between September 1, 2016, and January 31, 2017. Results. We recruited a total of 693 patients with a mean age of 78.0 years (standard deviation 8.2 years), comprising 46.6% of females. According to age subgroups, 37.4% of patients were aged 65–74 years, 37.4% were aged 75–84 years, and 25.2% were aged ≥85 years. The prevalence rates of geriatric syndromes were as follows: delirium (11.4%), depression (23.4%), dementia (43.1%), deterioration of activities of daily living (ADL) for <1 year (29.4%), vision impairment (22.2%), hearing impairment (23.8%), sleep disturbance (13.1%), any fall in <1 year (21.8%), polypharmacy (28.7%), pain (35.1%), pressure ulcer (5.6%), incontinence or retention (29.6%), indwelling device or physical restrain (21.6%), nutrition problem (35.7%), frequent use of medical resources (50.1%), lack of advance care planning (84.0%), caregiver problem (4.6%), socioeconomic problem (5.5%), and need for family meeting (6.2%). The need for hospice care was 11.9%. Most geriatric syndromes increased with advancing age except depression, sleep disturbance, polypharmacy, pain, nutrition problem, lack of advance care planning, caregiver problem, and socioeconomic problem. Conclusion. Geriatric syndromes and the need for hospice care were common in the older ED patients. Further studies about subsequent intervention for improving geriatric care are needed.
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Chang, Jer-Ming, Hung-Chun Chen, Shang-Jyh Hwang, Jer-Chia Tsai, and Yung-Hsiung Lai. "Does Amino Acid–Based Peritoneal Dialysate Change Homocysteine Metabolism in Continuous Ambulatory Peritoneal Dialysis Patients?" Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 23, no. 2_suppl (December 2003): 48–51. http://dx.doi.org/10.1177/089686080302302s10.
Анотація:
Objective We examined whether amino acid–based peritoneal dialysate that contains 85 mg/dL L-methionine affects homocysteine (Hcy) metabolism. Design The study enrolled 17 adult CAPD patients (11 men, 6 women) who had been receiving CAPD for at least 6 months and who had low serum albumin levels (<3.7 g/dL). Diet was not specifically changed. All of the study patients received daily 4-exchange CAPD treatment, and they used Nutrineal (Baxter Healthcare, Deerfield, IL, U.S.A.) as one of their daily exchanges (first or second exchange). Blood samples were collected every 2 weeks, and Hcy was measured. Results After use of Nutrineal, serum albumin was unchanged, but blood urea nitrogen (BUN) and total protein were increased. Before the study began, 1 patient had a very high Hcy level (256 μmol/L); his data were excluded from the analysis. In the remaining 16 patients, baseline Hcy was 24.4 ± 7.0 μmol/L. Levels of Hcy progressively increased with the use of Nutrineal: 28.1 ± 6.2 μmol/L in week 2, 28.4 ± 7.1 μmol/L in week 4, 29.1 ± 7.6 μmol/L in week 6, 29.3 ± 9.0 μmol/L in week 8, 27.5±9.7 μmol/L in week 10, and 30.3 ± 8.2 μmol/L in week 12. Conclusions Nutrineal might help to replenish daily protein loss, but it also increased formation of Hcy and, therefore, the potential risk of cardiovascular illness. Further studies will be needed to examine the effect of folic acid and vitamin B12 supplementation in the rescue of that Hcy increase, and also a possible correlation with methylenetetrahydrofolate reductase gene polymorphism.
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Merle, Philippe, Mohamed Bouattour, Jean-Frédéric Blanc, Jean-Marie Peron, Marilyne Debette-Gratien, Pierre Nahon, Eric Nguyen-Khac, et al. "Cabozantinib (CABO) tolerance and efficacy for patients with advanced hepatocellular carcinoma (HCC) after failure of sorafenib (SOR) in a French population: CLERANCE, a phase 4 trial." Journal of Clinical Oncology 41, no. 4_suppl (February 1, 2023): 573. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.573.
Анотація:
573 Background: CABO is approved in second (2L) or third line (3L) systemic therapy for pts with advanced HCC after SOR failure, based on results of the CELESTIAL phase 3. CLERANCE was designed to evaluate safety and efficacy of CABO in pts with HCC in real-world practice in a French population. Methods: This prospective, French multicentre (n=17), interventional study aims to recruit 110 pts with unresectable HCC when a decision of CABO treatment was made in 2L or 3L after prior sorafenib (SOR) failure, according to the French health authority approved label. The primary endpoint is the incidence of treatment-related adverse events (TRAE) of grade > 2 (NCI-CTCAE v5) by a central review committee. Secondary endpoints include overall survival (OS), objective response rate (ORR) (RECIST v1.1 per investigator assessed), progression-free survival (PFS), time to progression (TTP) and profiles of CABO administration. Results: Of 110 pts enrolled, the final analysis focused on the 99 pts who starting CABO (11 pts withdrawn due to screen failure) and followed up to 12 mo (data cut-off: November 8, 2021). Pts were mainly males (89%), 69 years median age (range 24-85), Child-Pugh A (94.9%) / B7 (5.1%), and ALBI score-1 (33%), 2 (60%), 3 (5%), not evaluated (NE) (2%). About 59% pts received CABO in 2L after SOR, whereas 41% were in 3L after SOR and another line (TKI or IO). SOR was discontinued due to tumor progression (68%) or intolerance (32%) with a median duration of 4.2 mo (95% CI 3.5-4.8) and a median dose of 800 mg (95% CI 631-800). In the 99 pts starting CABO, 128 treatment-emergent adverse events (TEAE) of grade > 2 were reported, 40 of them classified as TRAE: hand foot skin reaction (14%), diarrhea (11%), asthenia and/or anorexia and/or weight loss (12%), arterial hypertension (4%). The ORR was 7% with 58% of disease control rate (DCR). Median PFS was 6.2 mo (95% CI, 5.3-8.7), TTP 8.2 mo (95% CI 6.1-12.8), without any difference when CABO used in 2L or 3L line (with prior IO [11%] or not). OS was 11.5 mo (95% CI 9.2-14.6) since start of CABO and 23 mo (95% CI 17.3-29.4) since the first systemic line. ALBI score at 1 was an independent marker of better OS in multivariate analysis (Exp[b] 3.26, 95% CI 1.86-5.69, p<0.0001). The median duration of CABO was 5.2 mo (95% CI 3.5-6.0), the median daily dose 40 mg (95% CI 32.3-43.6), 66% of pts needed dose reduction, and permanent CABO discontinuation in 75.8% pts, due to: i) death (7%), tumor progression (54%) (median time to progression 5.3 mo; 95% CI 3.7-12.8), or AE (15.2%) (median time to AE 2.6 mo; 95% CI 1.5-7.7). Conclusions: In this final analysis of CLERANCE, most pts could start CABO (90%) 2L or 3L among the 110 enrolled pts. In real-life setting in CLERANCE, tolerability and efficacy were similar to those observed in CELESTIAL. The baseline ALBI score at 1 was strongly and independently associated with a better outcome. Clinical trial information: NCT03963206 .
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Kulkarni, Radhika, Oscar Hinojosa, and Vijayalakshmi Donthireddy. "Real World Analysis of G6PD Testing Prior to the Use of Rasburicase in Hematologic Malignancies; A Single Center Experience." Blood 142, Supplement 1 (November 28, 2023): 7332. http://dx.doi.org/10.1182/blood-2023-173264.
Анотація:
Introduction: The use of Rasburicase is contraindicated in patients with (Glucose -6-Phosphate Dehydrogenase) G6PD deficiency. The FDA recommends screening for G6PD deficiency prior to the use of Rasburicase, especially in those of African or Mediterranean ancestry. This recommendation, however, is not implemented uniformly. Methods: This was an IRB approved study. A retrospective chart analysis of adult patients with hematological malignancies treated in both the inpatient and outpatient setting between 2019 and 2022 was conducted. Data was reviewed and collected by investigators and compiled in a confidential platform. Results: A total of 437 patients were reviewed. The median age was 67 years. 54.9% were male and 45.1% were female. 65.6% of the patients were White, 23.5% were Black. Other ethnicities included Hispanics 3.8%, Asians 3.7%, Native American or Alaskan Natives 0.4% and unknown ethnicity in 4.3%. 37.3% of the patients had a diagnosis of Diffuse Large B Cell Lymphoma/High Grade B Cell Lymphoma, 34.1% had AML, 29.1% had CLL, 6.2 % had B or T-ALL, 2% had Burkitt lymphoma, and 1.6% had anaplastic T cell lymphoma. Rasburicase was utilized in 85/437 (19.5%) patients for the treatment of hyperuricemia of malignancy 50/85 (59%) and in 35/85 (41%) patients for the treatment of tumor lysis syndrome. G6PD was tested in 197 patients (45%) of which 39.5% were White, 21.8% were Black, 3.5% were Hispanic, 1% were Asian and 2.5% of unknown ethnicity. G6PD status was unknown in 55% patients. 7 cases of G6PD deficiency were identified, and 2 cases were highly suspicious for it due to the development of hemolysis after Rasburicase administration. 8/9 of these patients were African-American. In those patients who received Rasburicase, 70/85 (82.3%) received the medication prior to the G6PD results being available; 6 patients developed hemolysis and 1 patient developed methemoglobinemia. Of these 7 patients, 4 had unknown G6PD status, 2 had G6PD levels which were elevated but sent after signs of hemolysis were present and 1 was G6PD deficient. Of these patients, 3 were Black, 3 were Hispanic and 1 was White. Conclusions: G6PD testing was requested in 45% of patients being evaluated for hematologic malignancies. Of these, only 17.7% had results available before the administration of Rasburicase. 2% of this sample were found to either be G6PD deficient or had clinical suspicion for the same. 89% of them were Black. 8.2% of patients receiving Rasburicase developed complications related to oxidant injury caused by G6PD of which 43% were Black and 43% were Hispanic, though they constituted only 27.3% of the population. This study goes on to highlight the ethnic prevalence of G6PD deficiency, especially in the Black population. Strategies to increase testing for G6PD for all new diagnoses of hematological malignancies known to have a risk of TLS and reducing the time to resulting of G6PD levels can mitigate known adverse events from Rasburicase. The incorporation of G6PD testing as part of chemotherapy order set labs or use of hard stops prior to signing the treatment plan can be potential options to increase testing and screening.
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Yoon, Beomhee, Chul-Soon Park, Hyung-Jun Song, Jeonghun Kwak, Sang-Shin Lee, and Hyunho Lee. "Perovskite solar cells integrated with blue cut-off filters for mitigating light-induced degradation." Optics Express 30, no. 17 (August 12, 2022): 31367. http://dx.doi.org/10.1364/oe.465848.
Анотація:
The stability of methylammonium (MA)-based perovskite solar cells (PSCs) remains one of the most urgent issues that need to be addressed. Inherent weak binding forces between MAs and halides cause the perovskite structure to become unstable under exposure to various external environmental factors such as moisture, oxygen, ultraviolet radiation, and heat. In particular, the degradation of perovskite films under light exposure accelerates the deterioration of the device, mainly due to the migration of halide ions. In this study, we investigated the effect of light energy on the degradation of inverted PSCs by introducing red ( = 610–800 nm), green (500–590 nm), and blue (300–500 nm) light-pass filters. After 30 h, the inverted PSCs of blue-light-induced devices retained a power conversion efficiency (PCE) of 70%, while those of the green and red light-induced devices retained PCEs of 85% and 90%, respectively. Direct evidence of light-induced degradation was obtained by investigating morphological changes in the perovskite films and the amount of ion accumulation on the Ag electrode. This evidence highlights the varying effect of light with different energies on device degradation. Furthermore, to minimize light-induced device degradation, we designed two types of blue cut-off filters that can selectively block light ranging from = 400 to 500 nm, comprising a multilayered inorganic metasurface. An optical simulation was used to optimize the performance of the designed filters. By investigating the changes in the photovoltaic parameters and the amount of ion accumulation on the Ag electrode, we confirmed that integrating blue cut-off filters into PSCs greatly improved the operational lifetime of the devices.
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Kindler, Hedy L., Theodore G. Karrison, Buerkley Rose, Y.-H. Carol Tan, Arun Khattri, Rajesh Acharya, Christopher M. Straus, and Tanguy Y. Seiwert. "Biomarkers of pembrolizumab (P) activity in mesothelioma (MM): Results from a phase II trial." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 8557. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.8557.
Анотація:
8557 Background: PD-L1 expression and the Interferon-Gamma gene expression profile (IFN-G GEP) are predictive of response to checkpoint blockade in several solid tumors. Relevant biomarkers in mm pts treated with these agents have not been determined; these were evaluated in a phase 2 trial of P in mm (NCT02399371). Methods: Eligible pts had histologically confirmed MM, PS 0-1, disease progression on 1-2 prior regimens. P 200 mg was given Q21 days. Part A (N = 35) determined the response rate (RR) of P in PD-L1 unselected mm pts and assessed an optimal PD-L1 threshold (22C3 IHC assay). If ≥3 responses, the study proceeded to Part B (N = 30), using a biomarker enrichment strategy if a threshold was found. Nanostring nCounter was used to assess IFN-G GEP (6 gene). Results: 35 pts enrolled in Part A 5/15-2/16; 1 withdrew. Median age 66 (range 26-85); PS 0: 62%; male: 82%; epithelial/sarcomatoid/biphasic/NOS: 74%/21%/3%/3%; pleural/peritoneal: 85%/15%; 2nd-line: 59%. Partial response (PR): 7 (21%), stable disease (SD): 20 (59%). Median response duration: not reached. Median progression-free survival (PFS): 6.2 months (95% CI: 3.2, 8.2). Median overall survival: 11.9 months (95% CI: 6.4, --). Toxicity ≥ grade 3: adrenal insufficiency, fatigue, pneumonitis 6%; colitis, confusion, hepatitis, hyponatremia, neutropenia, rash 3%. PD-L1 expression by tumor proportion score (N = 32): none (53%); 1-49%: (22%); ≥50%: (25%). PD-L1 IHC (ROC area 0.63; 95% CI: 0.37, 0.89), CD274 mRNA expression, and IFN-G GEP did not correlate statistically with response. Responses occurred in GEP low, non-inflamed tumors, and in PD-L1- tumors. RR was numerically higher in PD-L1+ (27%) than in PD-L1- pts (12%); there was a trend towards longer PFS and OS in PD-L1+ pts. Conclusions: P has clinically meaningful single-agent activity in PD-L1 unselected, previously treated mm pts, achieving a 21% RR and a disease control rate of 80%. Biomarkers established in other cancers, such as PD-L1 IHC and IFN-G GEP, may not be as useful in MM. Novel biomarkers including MM-specific gene signatures may be necessary and are being evaluated. Part B of the study is ongoing with no PD-L1 pre-selection (19/30 pts enrolled), and will be used as a biomarker validation cohort. Funded by a MARF grant. Clinical trial information: NCT02399371.
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Bublienko, Natalia, Ruslana Zakharova, and Natalia Stetsenko. "BIOTRANSFORMATION OF WASTEWATER PRODUCTION OF BAKERY YEAST WITH BIOGAS GENERATION." WATER AND WATER PURIFICATION TECHNOLOGIES. SCIENTIFIC AND TECHNICAL NEWS 32, no. 1 (June 27, 2022): 16–22. http://dx.doi.org/10.20535/2218-930012022251698.
Анотація:
Baking yeast enterprises are a source of environmental pollution by concentrated wastewater. They are usually diluted with water and discharged into sewerage. It is rational to use methane fermentation, which will ensure the removal of pollutants and make the process cost-effective through the use of biogas and digestion. Therefore, it is relevant to study the question of the influence of fermentation parameters on the cleaning efficiency. The aim of the work is to study the methane fermentation of yeast production effluents in a continuous mode. Objectives: analysis of solving the problem of wastewater treatment of yeast plants, study of the influence of process parameters (dilution rate, addition of cobalt salts) on the efficiency of treatment; gas generation; vitamin production. Initial COD of effluents 4500 mg O2/dm3, pH 6. Cultivation regime – continuous, dilution rate 4,1·10–3, 6,2·10–3, 8,2·10–3, 12,4·10–3 hours–1. Cleaning efficiency 78,9 %. High values of dilution rate cause overload of activated sludge, which leads to reduced cleaning efficiency. The presence of cobalt also has a depressant effect. A significant amount of biogas (up to 5,2 dm3/dm3) is produced with a high content of methane (up to 85 %), which is an alternative fuel. As the dilution rate increases, the biogas and methane content decrease. With increasing dilution rate from 4,1·10–3 to 12,4·10–3 hours–1, biogas decreased from 1,11 to 0,94 dm3/g CODloading, and from 1,43 to 1,39 dm3/g CODfermentation. Similarly to the effect on the depth of purification, the inhibitory effect of cobalt on methanogeneration is observed. Digestion is a valuable fertilizer with a significant content of cobalamin vitamins (up to 95 μсg/g). The addition of cobalt salts stimulates the synthesis of vitamins, providing an increase of 26,7 to 51,6 %, improving the ratio between active and inactive forms.
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Wilde, Craig, Ali Poostchi, Georgios D. Panos, Jonathan G. Hillman, Hamish K. MacNab, Harminder Dua, Winfried M. Amoaku, and Stephen A. Vernon. "Prevalence of Reduced Vision among UK Elderly Drivers: The Bridlington Eye Assessment Project (BEAP)—A Cross-Sectional Study." Journal of Ophthalmology 2022 (September 15, 2022): 1–8. http://dx.doi.org/10.1155/2022/8321948.
Анотація:
Self-assessment of driving fitness is mandatory in the United Kingdom. A paucity of data on visual function among drivers exists. We report prevalence of elderly drivers below legal visual acuity (VA) standard from a population study (The Bridlington Eye Assessment Project (BEAP)) conducted from 2002 to 2006. All residents aged ≥65 years were invited, 3459 undergoing structured interviews/ophthalmic examinations. Driving status was recorded, VA measured, and visual field (VF) testing performed. Outcomes were prevalence and characteristics of drivers below VA legal standard and prevalence of bilateral VF defects. Conditions causing reduced VA were explored and those with treatable conditions allowing visual improvement identified. Duration since last optometry review was recorded. Associations were explored using unpaired t-tests for continuous and chi-squared for discrete variables. Logistic regression was used for multivariate analysis and to determine odd ratios in the final adjusted model. Statistical analysis was performed using Stata 14.0 (Stata Corp, Tx). Within this sample, 7.1% (95% CI 6.0–8.3) of drivers fell below the VA legal driving standard (6/12) in their better eye, with 20% not having seen an optometrist for 2 years, including 8.2% who had not attended for over 5 years. The percentage of drivers falling below the VA minimum increases with age reaching 22.8% (95% CI 13.7–35.3) among those aged 85–89 years. 7.2% (95% CI 6.2–8.6) of drivers had bilateral visual field defects. 93% of drivers with reduced VA below legal standard had a cataract, refractive error or both in at least one eye. Significant numbers of elderly drive with VA below legal standard, most having easily correctable causes. Poor attendance with optometrists appears commonplace. Public education raised awareness of legal driving standards and encouraged compliance are required. Regular eye tests, appropriate refractive correction, and cataract surgery when needed should be encouraged.
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Van Sambeek, J. W., Nadia E. Navarrete, and John E. Preece. "Rooting Softwood Cuttings from Forced Stem Segments of Adult White Ash." HortScience 33, no. 3 (June 1998): 503e—504. http://dx.doi.org/10.21273/hortsci.33.3.503e.
Анотація:
On 10 Apr. 1997, the smaller branch on forked Fraxinus americana L. (white ash) trees in an 8-year-old clonal plantation were removed, cut into 25-cm-long stem sections, and placed horizontally in perlite under seven different forcing regimes. Sprouts from latent buds were excised 67 and 99 days later and trimmed to retain the apical pair of leaves and terminal bud. The basal 2 cm of each cuttings was set for 30 to 60 min in one of six aqueous dilutions made from a stock solution of 1% IBA and 0.5% NAA (Dip `n Grow) before placing in a 1 perlite: 1 vermiculite medium. Eight weeks after treating, cuttings data were collected. Most cuttings treated with 3200 mg/L IBA plus 1600 mg/L NAA quickly died. Survival (85%) and rooting percentage (86%) were similar for the remaining auxin-treated cuttings and controls with water only. Cuttings treated with 1600 mg/L IBA plus 800 mg/L NAA produced the most adventitious roots (6.2 roots), the longest adventitious root (22 cm), and longest combined sum of all adventitious roots (51 cm); however, these rooted cuttings died when transplanted to soil. Cuttings treated with 100 mg/L IBA plus 50 mg/L NAA or 400 mg/L IBA plus 200 mg/L NAA had more adventitious roots (3.2 roots) and total length of adventitious roots (370 mm/cutting) than cuttings treated with 40 mg/L IBA plus 20 mg/L NAA or controls with water only (2.2 roots, 220 mm long). Results indicate softwood cuttings forced on stem segments of adult white ash readily root under mist following a brief soak in a 400 mg/L IBA plus 200 mg/L NAA solution.
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Loyd, J. E., J. M. Bolds, J. R. Sheller, S. S. Duke, A. W. Gillette, A. W. Malcolm, B. O. Meyrick, and K. L. Brigham. "Acute effects of thoracic irradiation on lung function and structure in awake sheep." Journal of Applied Physiology 62, no. 1 (January 1, 1987): 208–18. http://dx.doi.org/10.1152/jappl.1987.62.1.208.
Анотація:
To investigate the acute physiological and structural changes after lung irradiation, the effects of whole-lung irradiation were investigated in fourteen sheep. Ten sheep were prepared with vascular and chronic lung lymph catheters, then a week later were given 1,500 rad whole-lung radiation and monitored for 2 days. Four sheep were given the same dose of radiation and were killed 4 h later for structural studies. Lung lymph flow increased at 3 h after radiation (14.6 +/- 2.1 ml/h) to twice the base-line flow rate (7.5 +/- 1.3), with a high lymph-to-plasma protein concentration. Pulmonary arterial pressure increased twofold from base line (18 +/- 1.6 cmH2O) at 2 h after radiation (33 +/- 3.8). Cardiac output and systemic pressure in the aorta did not change after lung radiation. Arterial O2 tension decreased from 85 +/- 3 to 59 +/- 4 Torr at 1 day after radiation. Lymphocyte counts in both blood and lung lymph decreased to a nadir by 4 h and remained low. Thromboxane B2 concentration in lung lymph increased from base line (0.07 +/- 0.03 ng/ml) to peak at 3 h after radiation (8.2 +/- 3.7 ng/ml). The structural studies showed numerous damaged lymphocytes in the peripheral lung and bronchial associated lymphoid tissue. Quantitative analysis of the number of granulocytes in peripheral lung showed no significant change (base line 6.2 +/- 0.8 granulocytes/100 alveoli, 4 h = 10.3 +/- 2.3). The most striking change involved lung airways. The epithelial lining of the majority of airways from intrapulmonary bronchus to respiratory bronchiolus revealed damage with the appearance of intracellular and intercellular cell fragments and granules. This new large animal model of acute radiation lung injury can be used to monitor physiological, biochemical, and morphological changes after lung radiation. It is relevant to the investigation of diffuse oxidant lung injury as well as to radiobiology per se.
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Ivan Dieb, Miziara, and Carmen Miziara Silvia Molleis Galego. "Victim of violent death: what is the role of alcoholemia?" Journal of Forensic Science and Research 5, no. 1 (August 25, 2021): 048–52. http://dx.doi.org/10.29328/journal.jfsr.1001027.
Анотація:
Introduction: The tendency to impulsive behaviors and/or violence is exacerbated after alcohol consumption. Still, the relation between alcohol/violent deaths reported in the literature is not accurate, and in general, alcohol is only seen as a trigger to aggressive actions. The relationship of the victims with their blood alcohol is less studied. They were especially concerned about the role of alcohol as a risk factor for victims of unnatural death. Thus, our goal is to check the influence of alcohol in victims of violent deaths as homicides, suicides, and accidents. Materials and methods: Retrospectively the medical records of 805 autopsies performed at the Institute of Forensic Medicine (IML) of Franco da Rocha, in the period 2001 to 2017 were reviewed. The variables studied were sex, age, types of violent death rates, and alcohol - these were considered positive when above 0.3 mg/ml. The dosage of blood alcohol concentration (BAC) was performed using samples of 10 ml of blood collected at necropsy, is preferably taken from the cardiac chambers or of the right femoral vein. Dosages of alcohol in blood samples were done in the Forensic Toxicology Center of the IML by gas chromatography, using the technique of separation “headspace” and double column. Results: Drug testing for alcohol was available for 488 (79.1%) of 617 necropsies. Of the 617 subjects studied, 532 (85.7%) were male, and 85 (13.8%) were females (with high rates of adolescents). The vast majority (n = 230) were killed, and 40.5% of victims had BAC above 0.3 mg/ml of blood. Traffic accidents came next, accounting for 181 deaths, with 41% of victims presenting positive BAC. Discussion: High blood alcohol levels of the victims were associated mainly with the genesis of accidents (drowning, falls, traffic, aspiration/ smothering) and murder (with impaired ability to resist or by causing the release of impulses to engage in violent situations), about 40% of cases. Conclusion: Our results indicate that alcohol abuse is a risk factor for victims of violent death. In these cases, alcohol has two types of action. Direct: contributes to accidents of various kinds - from traffic by decreasing powers of concentration, attention, and loss of reflexes, to other types of accidents such as drowning, falls, swallowing disorders causing airway obstruction, and mechanical asphyxia. And they were indirect, making it easier for individuals to engage in conflict (and thus become victims of crimes).
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Felten, R., L. Widawski, L. Spielmann, C. Gaillez, W. Bao, J. E. Gottenberg, P. M. Duret, and L. Messer. "POS1065 IMPACT OF HYPERURICEMIA ON CLINICAL PHENOTYPE, COMORBIDITIES, AND RESPONSE TO SECUKINUMAB IN PSORIATIC ARTHRITIS: POST HOC ANALYSIS OF FUTURE AND MAXIMISE STUDIES." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 855.1–855. http://dx.doi.org/10.1136/annrheumdis-2022-eular.807.
Анотація:
BackgroundHyperuricemia (HU) is a metabolic abnormality associated with psoriasis (PsO) and psoriatic arthritis (PsA)1. The prevalence of HU is 2–13% in general population, 19–20% in PsO patients (pts), and 27–32% in PsA pts1,2. Pts with PsO/PsA are at significantly increased risk of HU and development of gout1. The pathogenic role of chronic HU in the development and maintenance of PsA is based on epidemiological, clinical, and fundamental arguments and hence does not appear fortuitous. These processes can influence each other3. Moreover, PsA with HU has been shown to be more peripheral, destructive, and challenging to treat4.ObjectivesTo evaluate the impact of HU on PsA in terms of clinical presentation, severity, comorbidities, and response to secukinumab (SEC) over 1-year.MethodsThis post hoc analysis included pooled data from PsA pts enrolled in the FUTURE 2–5 and MAXIMISE phase 3 trials. Pts were stratified into 2 groups based on baseline (BL) serum uric acid (SUA) level (HU: ≥360 µmol/L; without HU: <360 µmol/L and no history of gout and/or uric acid lowering therapies [ULT]). Demographic and disease characteristics, PsA and therapeutic history, and comorbidities data, were collected at BL. Evaluations included ACR20/50/70 responses, Psoriasis Area and Severity Index (PASI) 90 response, resolution of enthesitis and dactylitis, Health Assessment Questionnaire Disability Index (HAQ-DI), and mean change in SUA level, up to Week 52. All analyses were performed at a descriptive level and data presented as observed.ResultsOverall, 2504 PsA pts were included in the analysis, of which 822 (32.8%) had HU (62 [2.5%] with gout; 49 [2.0%] treated with ULT). At BL, pts with HU were mostly male (76.0% vs 34.2%) and had a higher body mass index (30.9 vs 28.3 kg/m2) with more comorbidities, such as hypertension (43.8% vs 31.3%), compared to pts without HU. A higher proportion of pts with HU had dactylitis (34.5% vs 25.9%), and PsO (48.3% vs 36.3%) with a greater mean PASI score (13.6 vs 10.2), compared to pts without HU (Table 1). The proportion of pts achieving ACR50, resolution of enthesitis/dactylitis, and mean change in HAQ-DI score were comparable up to Week 52 irrespective of BL HU status. The PASI90 response rate was higher in pts without HU with SEC 150 mg (with and without load) and similar in SEC 300 mg group irrespective of BL HU status (Figure 1).Table 1.Demographics and baseline characteristicsParameters, mean ± SD unless specifiedWith hyperuricemia (N=822)Without hyperuricemia (N=1682)Age (Years)48.5 ± 12.4148.3 ± 12.19Gender (Male), n (%)625 (76.0)576 (34.2)Weight (kg)92.71 ± 18.6279.59 ± 17.55BMI (kg/m2)30.90 ± 5.8628.33 ± 5.91History of hypertension, n (%)360 (43.8)526 (31.3)History of diabetes mellitus, n (%)85 (10.3)144 (8.6)TJC20.6 ± 15.5221.3 ± 16.25SJC10.9 ± 9.3110.8 ± 9.13Enthesitis, n (%)412 (50.1)852 (50.7)Dactylitis, n (%)284 (34.5)436 (25.9)Evidence of current psoriasis; n (%)397 (48.3)611 (36.3)Mean PASI score*13.61 ± 11.0310.16 ± 9.13TNFi naїve, n (%)477 (58.0)938 (55.8)MTX use at randomization, n (%)321 (39.1)685 (40.7)Serum uric acid (µmol/L)420.7 ± 57.11274.9 ± 51.98CRP (mg/L)11.6 ± 18.6610.7 ± 23.36*not collected in MAXMISEBMI, body mass index; CRP, C-reactive protein; MTX, methotrexate; SJC, swollen joint count; TJC, tender joint count; TNFi, tumor necrosis factor inhibitorConclusionIn this pooled analysis of SEC PsA studies, pts with HU reported a higher prevalence of hypertension, with more clinical dactylitis, and more PsO, with higher PASI score compared to pts without HU. Efficacy across all musculoskeletal manifestations was similar with SEC 150 and 300 mg; while PASI90 response rate was slightly better in patients without HU with SEC 150 mg, and similar with SEC 300 mg irrespective of HU status, at 1-year.References[1]Tripolino C, et al. Front Med. 2021;8:737573[2]AlJohani R, et al. J Rheumatol. 2018;45(2):213–7[3]Felten R, et al. Clin Rheumatol. 2020;39:1405–13[4]Widawski L, et al. Clin Rheumatol. 2022. https://doi.org/10.1007/s10067-022-06061-xDisclosure of InterestsRenaud FELTEN Consultant of: Novartis (Advisory board), Laura Widawski: None declared, Lionel Spielmann: None declared, Corine Gaillez Shareholder of: Novartis, Employee of: Novartis, Weibin Bao Shareholder of: Novartis, Employee of: Novartis, Jacques-Eric Gottenberg Consultant of: Novartis (Advisory board), Pierre-Marie Duret: None declared, Laurent Messer: None declared
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Freitas-Astúa, Juliana, Lisela Moreira, Carmen Rivera, Carlos M. Rodríguez, and Elliot W. Kitajima. "First Report of Orchid fleck virus in Costa Rica." Plant Disease 86, no. 12 (December 2002): 1402. http://dx.doi.org/10.1094/pdis.2002.86.12.1402d.
Анотація:
Orchid fleck virus (OFV), a tentative member of the family Rhabdoviridae, infects orchids in several countries. The virus is vectored worldwide by the mite Brevipalpus californicus (Banks) (Acari: Tenuipalpidae). Eleven plants of Oncidium spp. and one plant each of the genera Cymbidium and Maxillaria exhibiting numerous yellow flecks and necrotic ringspot lesions on leaves were collected in two private orchid collections in Costa Rica. Presence of OFV was assessed by plate-trapped antigen enzyme-linked immunosorbent assay (PTA-ELISA) using an antiserum developed against an OFV isolate in Japan (2), analyses of ultrathin sections of the host cell with transmission electron microscopy (TEM), and reverse transcription-polymerase chain reaction (RT-PCR) amplification using specific primers for the viral nucleocapsid gene (1). Eight of eleven Oncidium samples, and both Cymbidium and Maxillaria samples tested positive for OFV with PTA-ELISA having A405 values ranging from 3.9 to 14.6 times higher than negative controls. Thin sections from individual samples of Cymbidium, Oncidium, and Maxillaria revealed electron-lucent intranuclear viroplasm and short, rodlike particles (40 to 50 × 100 nm) in the nucleus or cytoplasm typical of OFV-infected cells. RT-PCR amplifications from one sample of each genera resulted in PCR-product bands of approximately 800 bp. The Cymbidium RT-PCR product was cloned into a pGEM-T-Easy expression vector and sequenced using an ABI 3700 sequencer. The 619-bp nucleocapsid gene consensus sequence had 98% homology with the OFV isolate 0023 identified in Germany (GenBank Accession No. AF343870) (1). However, it had only approximately 85% nucleocapsid gene homology with other OFV isolates available through GenBank, including those from countries geographically closer to Costa Rica, such as Brazil (1). To our knowledge, this is the first report of OFV infecting orchids in Costa Rica. References: (1) A. L. Blanchfield et al. J. Phytopathol. 149:713, 2001. (2) H. Kondo et al. Bull. Res. Inst. Bioresour. Okayama Univ. 4:149, 1996.
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Fessas, Petros, Ahmed Omar Kaseb, Yinghong Wang, Anwaar Saeed, David Szafron, Tomi Jun, Sirish Dharmapuri, et al. "Post-registration experience of nivolumab (nivo) therapy in patients with advanced hepatocellular carcinoma (HCC): An international study." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e16677-e16677. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e16677.
Анотація:
e16677 Background: Nivo is FDA-approved in sorafenib-experienced, advanced HCC. Post-registration data to portray treatment in a real-world setting is lacking. Methods: We describe safety and efficacy of nivo in patients (pts) from 8 centres (USA n = 181, Asia n = 47, Europe n = 5), documenting overall (OS), progression-free survival (PFS), overall response (ORR) and disease control rates (DCR) (RECIST). Results: We analysed 233 pts, mostly cirrhotic (n = 176, 75%) due to hepatitis C (n = 95, 54.0%) with Barcelona Clinic Stage (BCLC) C HCC (n = 178, 76.4%), Child-Pugh class (CP) A (n = 158, 67.8%) or B (n = 75, 32.2%), and AFP > 400 IU/mL (n = 132, 56.7%). Nivo was given as first (1L, n = 85, 36.5%), second line (2L, n = 130, 55.8%) or > 2L (n = 18, 7.7%), after local (n = 191, 82%) and systemic therapy (n = 148, 63.5%), mostly sorafenib (n = 142, 60.9%). Median duration of nivo was 6.0 months (mo, interquartile range [IQR] 2.6-11.9) and stopped due to progression (n = 109, 46.8%) or toxicity (n = 8, 3.4%). After median follow up of 7 mo (IQR 3.0-12.3), ORR was 22.4% and DCR was 52.1%. Best responses (n = 219, 94%) included complete and partial responses in 18 (7.7%) and 31 (13.3%) pts respectively, stable disease in 65 (27.9%) and progressive disease in 105 (45.1%), not dissimilar by CP (p = 0.26). Median OS was 12.2 mo (95%CI 8.4-16.0) and predicted by CP (CPA 16.3 mo 95%CI 11.7-20.8; CPB 7.3 mo 95%CI 4.2-10.4; hazard ratio [HR] 1.9, p = 0.01), nivo line (1L 16.3 mo 95%CI 8.0-24.5; > 1L 10.4 mo 95%CI 7.4-13.5; HR 0.68, p = 0.05), and PVT (PVT- 13.8 mo 95%CI 11.7-16.0; PVT+ 10.4 mo 95%CI 7.8-13.0; HR 1.8, p = 0.015) but not cirrhosis, AFP, BCLC or steroid use (p > 0.05). Median PFS was 10.1 mo (95%CI 6.1-14.2), predicted by BCLC (A-B 19.0 mo 95%CI 7.1-30.8; C 8.2 mo 95%CI 4.9-11.4; HR 2.8, p = 0.002) and line (1L 18.2 mo 95%CI 10.4-25.9; > 1L 8.2 mo 95% CI 6.2-10.2; HR 0.60, p = 0.021), but not cirrhosis, AFP, or steroid use (p > 0.05). 26 pts (11.2%) suffered > = Grade 2 toxicities, most commonly fatigue (n = 29, 24.7%). Conclusions: Real-world use of nivo in advanced HCC across line of therapy suggests reproducible clinical efficacy and safety compared to prospective trials.
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Mortada, M. A., R. Hassan, and Y. A. Amer. "POS1276 LONG TERM OUTCOME OF MULTIPLE ULTRASOUND GUIDED SUPRASCAPULAR NERVE BLOCK IN TREATMENT OF FROZEN SHOULDER IN DIABETIC PATIENTS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 922.2–922. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2951.
Анотація:
Background:Frozen shoulder is prevalent among diabetic patients, and usually has aggressive course, with more tendency to be bilateral and resistant to treatment. Suprascapular nerve block (SSNB) is used with increasing frequency by anesthetists and rheumatologists in the management of frozen shoulder. We previously introduced a protocol of nine injections for SSNB with better short term outcome than single SSNB injection (1). Long term outcome of SSNB in management of frozen shoulder is still not detected.Objectives:To evaluate the long term effect of multiple (nine) ultrasound guided supra-scapular nerve block in treatment of diabetic frozen shoulder.Methods:A retrospective cohort study followed up 40 diabetic patients who received a course of ultrasound guided multiple supra-scapular nerve block (9 injections) on 2014. In this study we retrospectively assessed the patients from previously recorded data at a mean duration of 6 years after completing the 9 injection course SSNB clinically by measuring the shoulder active range of motion (using a goniometer in three planes: abduction, internal, and external rotation). Visual analogue scale and Functional assessment by shoulder pain and disability index (SPADI).Results:Thirty four patients (85% of original cohort) completed the long term follow up.The patients were 19 (55.9%) females, 60.6 y mean age, and the mean of disease duration was 85.6 months. The majority of patients (33 patients 97.05%) continues improvement and gained within normal complete range of motions in all directions and excellent grades of shoulder function (Table 1).Table 1.Clinical ParametersAt base lineAt 4 monthsLast follow up at (72months±4)**P valueSPADI pain score (100)(68.8 ± 0.5)a(10.3 ± 7.4)b(0.9±1.9)c0.00*SPADI disability score (100)(69.2 ± 7.7)a(6.25 ± 2.25)b(0.4±0.8)c0.00*SPADI total (100)(69.1 ± 8.5)a(8.15 ± 5.4)b(1.1±0.9)c0.00*Patient global assessment (100)(90.2 ± 8.2)a(8.2 ± 4.2)b(0.4±2.1)c0.00*Night pain (100)(55.4±10.2)a(10.3 ± 4.9)b(2.3±1.1)c0.00*Abduction (180°)(77.5 ± 4.7)a(170.3 ± 10.3)b(174.2±6.2)b0.00*External rotation (100 °)(46 ± 12.6)a(80.1 ± 10.2)b(86.4±10.3)b0.00*Internal rotation (70 °)(34.5 ± 2.4)a(55.4 ± 10.1)b(60.2±9.5)b0.00** P <0.05 there was a statistical significant difference•A,b,c--- the alphabet of different symbols ---means a significant statistical difference between groupsSPADI: shoulder pain and disability indexConclusion:The multiple injection courses for supra-scapular nerve block has an excellent long term efficacy as treatment of diabetic frozen shoulder. This method should be the treatment of choice in patients of diabetic frozen shoulder who do not respond to physiotherapy.References:[1]Mortada, M. A., Ezzeldin, N., Abbas, S. F., Ammar, H. A. & Salama, N. A. Multiple versus single ultrasound guided suprascapular nerve block in treatment of frozen shoulder in diabetic patients. J. Back Musculoskelet. Rehabil. 30, 537–542 (2017).Disclosure of Interests:None declared
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Neu, Alicia M., Anja Sander, Dagmara Borzych–Dużałka, Alan R. Watson, Patricia G. Vallés, Il Soo Ha, Hiren Patel, et al. "Comorbidities in Chronic Pediatric Peritoneal Dialysis Patients: A Report of the International Pediatric Peritoneal Dialysis Network." Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 32, no. 4 (July 2012): 410–18. http://dx.doi.org/10.3747/pdi.2012.00124.
Анотація:
Background, Objectives, and Methods Hospitalization and mortality rates in pediatric dialysis patients remain unacceptably high. Although studies have associated the presence of comorbidities with an increased risk for death in a relatively small number of pediatric dialysis patients, no large-scale study had set out to describe the comorbidities seen in pediatric dialysis patients or to evaluate the impact of those comorbidities on outcomes beyond the newborn period. In the present study, we evaluated the prevalence of comorbidities in a large international cohort of pediatric chronic peritoneal dialysis (CPD) patients from the International Pediatric Peritoneal Dialysis Network registry and began to assess potential associations between those comorbidities and hospitalization rates and mortality. Results Information on comorbidities was available for 1830 patients 0 – 19 years of age at dialysis initiation. Median age at dialysis initiation was 9.1 years [interquartile range (IQR): 10.9], median follow-up for calculation of hospitalization rates was 15.2 months (range: 0.2 – 80.9 months), and total follow-up time in the registry was 2095 patient–years. At least 1 comorbidity had been reported for 602 of the patients (32.9%), with 283 (15.5%) having cognitive impairment; 230 (12.6%), motor impairment; 167 (9.1%), cardiac abnormality; 76 (4.2%), pulmonary abnormality; 212 (11.6%), ocular abnormality; and 101 (5.5%), hearing impairment. Of the 150 patients (8.2%) that had a defined syndrome, 85% had at least 1 nonrenal comorbidity, and 64% had multiple comorbidities. The presence of at least 1 comorbidity was associated with a higher hospitalization rate [hospital days per 100 observation days: 1.7 (IQR: 5.8) vs 1.2 (IQR: 3.9), p = 0.001] and decreased patient survival (4-year survival rate: 73% vs 90%, p < 0.0001). Conclusions Nearly one third of pediatric CPD patients in a large international cohort had at least 1 comorbidity, and multiple comorbidities were frequently reported among patients with a defined syndrome. Preliminary analysis suggests an association between comorbidity and poor outcome in those patients. As this powerful international registry matures, further multivariate analyses will be important to more clearly define the impact of comorbidities on hospital-ization rates and mortality in pediatric CPD patients.
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Brunet, Stefan, Vladimir Canadanovic, Nikola Babic, Aleksandar Miljkovic, Sandra Jovanovic, and Sava Barisic. "Dry eye syndrome and cataract surgery." Medical review 72, no. 3-4 (2019): 105–9. http://dx.doi.org/10.2298/mpns1904105b.
Анотація:
Introduction. Dry eye syndrome has become a common problem after ocular surgeries with a significant impact on the quality of life. Many patients, who have undergone cataract surgery, postop?eratively developed dry eye symptoms. Dry eye syndrome is one of the risk factors associated with cataract surgery. Material and Methods. The prospective study included 80 patients. We recorded the self-reported dry eye symptoms, the values of Schirmer test, tear breakup time, and best corrected visual acuity preoperatively, as well as 7 days and 1 month after the surgery. Results. A total of 80 patients were included in the study, 45 (56.2%) females and 35 (43.8%) males. The mean age of patients was 61.5 years (SD ? 6.2, range 57 - 70 years). The best corrected visual acuity at the time of surgery was 0.4 or less in 70 patients (87.5%). Most patients reported a significant improvement in visual acuity after surgery; 68 (85%) eyes achieved a best corrected visual acuity of 0.5 or higher (median 0.7; range 0.5 - 1.0). The mean tear breaking time in cata?ract patients before surgery was 12.4 sec, 7 days after the surgery it was 8.2 sec (p < 0.05) and 1 moth after the surgery 11.1 sec. The majority of patients had mild (47.5%) and moderate (33.75%) Schirmer test values. Dry eye with wetting < 5 mm after 5 minutes was found in 16.2% of patients before cataract surgery; 7 days after the surgery (p < 0.05) it was found in 23.75% of patients and one month after surgery 11.1 sec. A foreign body sensation and watery eye were the most reported symptoms before cataract surgery. Seven days after the surgery foreign body sensation was present in 48.75% and watery eyes in 40% of patients. Conclusion. Significant increase in dry eye symptoms after cataract surgery was found with increasing age. Self reported dry eye problems are more common in patients with lower Schirmer test and best corrected visual acu?ity values before cataract surgery. Patients with concomitant dry eye disease require preoperative and postoperative treatment of dry eye to prevent aggravation of the existing symptoms that may affect the visual outcome after cataract surgery.
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van Donkelaar, A., R. V. Martin, W. R. Leaitch, A. M. Macdonald, T. W. Walker, D. G. Streets, Q. Zhang, et al. "Analysis of aircraft and satellite measurements from the Intercontinental Chemical Transport Experiment (INTEX-B) to quantify long-range transport of East Asian sulfur to Canada." Atmospheric Chemistry and Physics 8, no. 11 (June 17, 2008): 2999–3014. http://dx.doi.org/10.5194/acp-8-2999-2008.
Анотація:
Abstract. We interpret a suite of satellite, aircraft, and ground-based measurements over the North Pacific Ocean and western North America during April–May 2006 as part of the Intercontinental Chemical Transport Experiment Phase B (INTEX-B) campaign to understand the implications of long-range transport of East Asian emissions to North America. The Canadian component of INTEX-B included 33 vertical profiles from a Cessna 207 aircraft equipped with an aerosol mass spectrometer. Long-range transport of organic aerosols was insignificant, contrary to expectations. Measured sulfate plumes in the free troposphere over British Columbia exceeded 2 μg/m3. We update the global anthropogenic emission inventory in a chemical transport model (GEOS-Chem) and use it to interpret the observations. Aerosol Optical Depth (AOD) retrieved from two satellite instruments (MISR and MODIS) for 2000–2006 are analyzed with GEOS-Chem to estimate an annual growth in Chinese sulfur emissions of 6.2% and 9.6%, respectively. Analysis of aircraft sulfate measurements from the NASA DC-8 over the central Pacific, the NSF C-130 over the east Pacific and the Cessna over British Columbia indicates most Asian sulfate over the ocean is in the lower free troposphere (800–600 hPa), with a decrease in pressure toward land due to orographic effects. We calculate that 56% of the measured sulfate between 500–900 hPa over British Columbia is due to East Asian sources. We find evidence of a 72–85% increase in the relative contribution of East Asian sulfate to the total burden in spring off the northwest coast of the United States since 1985. Campaign-average simulations indicate anthropogenic East Asian sulfur emissions increase mean springtime sulfate in Western Canada at the surface by 0.31 μg/m3 (~30%) and account for 50% of the overall regional sulfate burden between 1 and 5 km. Mean measured daily surface sulfate concentrations taken in the Vancouver area increase by 0.32 μg/m3 per 10% increase in the simulated fraction of Asian sulfate, and suggest current East Asian emissions episodically degrade local air quality by more than 1.5 μg/m3.
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Earl, H., L. Hiller, J. A. Dunn, S. Bathers, R. J. Grieve, D. Spooner, R. K. Agrawal, L. Foster, C. Twelves, and C. J. Poole. "The National Epirubicin Adjuvant Trial (NEAT) and Scottish Cancer Trials Breast Group (SCTBG) br9601 randomized phase III adjuvant early breast cancer trials: The updated definitive joint analysis." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 534. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.534.
Анотація:
534 Background: NEAT and the SCTBG BR9601 trial address the role of Epirubicin (E) as an adjunct to CMF in adjuvant chemotherapy for women with early breast cancer (EBC). Methods: NEAT compared E (100mg/m2 x4cycles) followed by classical (c)CMF (x4cycles) with cCMF (x6cycles); BR9601 compared E (100mg/m2 × 4cycles) followed by iv dose modified CMF q3w (750:50:600 ×4cycles) with iv CMF (x8cycles). Eligibility was completely excised EBC, requiring adjuvant chemotherapy, and start of treatment <10 wks from surgery. Primary outcome measures were relapse-free-survival (RFS) and overall survival (OS). A joint efficacy analysis of NEAT (n=2,021) and BR9601 (n=370) triggered by planned 5-year median follow-up (FU) and estimated 800 RFS events and 600 deaths has 85% power to detect 5% two-sided differences. Results: In 2,391 eligible patients, characteristics were balanced across treatments: 72% node +ve; 59% <50 years old; 47% pre-menopausal; 58% tumours grade 3; 55% >2cms; 32% ER-ve, 50% ER+ve (18% NA). At a median FU of 6.2 yrs, 710 relapses or deaths without relapse and 570 deaths are observed. Despite lower than anticipated event rates in the control arm, these updated results confirm a highly significant benefit in favour of ECMF for both RFS (HR 0.75 (95%CI 0.64–0.87) p=0.0002) and OS (HR 0.74 (0.62–0.87) p=0.0004), independent of trial and prognostic factors. In 1458 NEAT patients (in whom data are available), 68% were to receive tamoxifen; chemotherapy scheduling data is available for 843, of whom 46% were declared concurrent and 54% sequential. In a non-pre-planned retrospective analysis, sequential tamoxifen shows a trend for advantage on RFS (HR 0.78 (0.59–1.02) p=0.06). We have amenorrhoea data on 598 NEAT and BR9601 pre-menopausal women, of whom 72% became amenorrhoeic by the end of chemotherapy. In this instance, developing amenorrhoea showed no advantage for RFS (HR 0.90 (0.65–1.24) or OS (HR 0.99 (0.68–1.44)). Conclusions: This updated definitive analysis adds to the Overview in respect of an anthracycline advantage and confirms ECMF as an established and effective standard adjuvant therapy for EBC. [Table: see text]
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Qin, Shukui, Jiafu Ji, Rui-hua Xu, Wei Wang, Yong Tang, Feng Bi, Jin Li, et al. "Treatment patterns and outcomes in Chinese gastric cancer by HER2 status: A non-interventional registry study (EVIDENCE)." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 4025. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.4025.
Анотація:
4025 Background: Gastric cancer (GC) is the second leading cause of cancer-related deaths in China. Trastuzumab (TRA) has been used to treat HER2+ metastatic gastric cancer (mGC) in China since 2012. However, real-world data on effectiveness and safety in Chinese patients are limited. Methods: This prospective, multicenter (85 hospitals), real-world noninterventional registry study evaluated the effectiveness and safety of TRA in five cohorts of Chinese GC patients with different HER2 statuses from April 2013 to June 2018. Effectiveness analysis was conducted in three cohorts: Cohort I (HER2+ mGC with TRA), Cohort II (HER2+ mGC untreated with TRA) and Cohort IV (HER2− mGC untreated with TRA). Safety outcomes of TRA-related adverse events (AEs) were analyzed in Cohort I. Results: Cohorts I, II and IV included 709 patients (174, 113 and 422, respectively; mean age 57.8 years; 72% male); 64.9% of patients were ECOG 0–1, 93.7% had a primary GC tumor and 42.3% were at stage T4. Progressive disease was the cause of death in 32.8%, 27.4% and 29.9% in Cohorts I, II and IV, respectively. Respective mean duration of follow-up was 422.5, 287.5 and 277.5 days. Median overall survival (OS) was 22.3, 17.2 and 17.4 months, respectively. After excluding patients who had surgery, the respective median OS was 19.9, 15.3, and 12.6 months. For the first-line treatment, the median OS in Cohort I was 22.1 months, and the median progression free survival (PFS) was 8.2, 6.9 and 6.2 months in Cohorts I, II and IV, respectively. Response rates (RR) for first-line treatment in Cohorts I, II and IV were 51.7%, 18.4% and 32.8%, respectively. After propensity score matching, OS, PFS and RR were all significantly better in Cohort I versus II (all P<0.05). The most common regimen, TRA+XELOX (capecitabine+oxaliplatin), was estimated to have the longest median OS at 34.6 months. Grade ≥3 AEs were reported in 33.9% (59/174) of patients in Cohort I; anemia was the most common AE (12.1%). Conclusions: TRA improved OS and PFS in Chinese HER2+ mGC patients compared with chemotherapy alone and was well tolerated and effective when combined with a range of other therapies in a real-world setting. Clinical trial information: NCT01839500.
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Regierer, A., A. Weiß, M. Bohl-Buehler, X. Baraliakos, F. Behrens, G. Schett, and A. Strangfeld. "OP0225 DEPRESSIVE SYMPTOMS IN PSA: A CROSS-SECTIONAL ANALYSIS FROM THE NATIONAL GERMAN RABBIT-SPA REGISTRY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 135.2–136. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2130.
Анотація:
Background:Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting the musculoskeletal system as well as skin and nails. The prevalence of depression in psoriasis and PsA is high and ranges from 7-40% [1]. Persistent depressive mood may influence disease activity outcome in PsA, especially patient-reported outcomes.Objectives:To assess the correlation of depressive symptoms with PsA-specific outcome parameters.Methods:RABBIT-SpA is a prospective longitudinal cohort study including PsA patients enrolled at start of a new conventional treatment or b/tsDMARD treatment. In regularly provided follow-up questionnaires, physician- and patient-reported information on the disease course including the depression screening tool WHO-5 to assess mental health is collected. For the current analysis, the WHO-5 score was categorised into 4 groups using validated cut-offs: severe depressive symptoms <13, moderate depressive symptoms 13-28, mild depressive symptoms 29-50, well-being >50. Spearman correlation coefficient was calculated to analyse the relationship between the WHO-5 score and various PsA related outcome parameters.Results:936 PsA patients were included. Baseline characteristics are shown in Table 1. In 411 patients (43.9%) the WHO-5 score indicated well-being, 249 (26.6%) had mild depressive, 203 (21.7%) moderate depressive and 73 patients (7.8%) severe depressive symptoms. WHO-5 results correlated with patient reported skin involvement (DLQI: -0.25, patient assessment skin: -0.17), and the composite scores DAPSA (-0.33) and DAS28 (-0.28) as well as with patient reported pain (-0.43) and patient global disease assessment (-0.42). The highest correlation was found for physician assessed global health status (-0.51) and PSAID (-0.62). No significant correlation was found with CRP, swollen joint count and physician assessed skin involvement including body surface area (BSA).Table 1.Baseline characteristics of patients included in the analysis stratified by WHO-5 categories.ParameterWHO-5 (<13) severeN=73WHO-5 (13-28) moderateN=203WHO-5 (29-50) mildN=249WHO-5 (>50) well-beingN=411TotalN=936Age, mean (SD)52.6 (11.4)51 (11.3)51.4 (12.5)52.8 (12.7)52 (12.2)Female, n (%)52 (71.2)127 (62.6)157 (63.1)227 (55.2)563 (60.1)Disease duration, years, mean (SD)8.3 (8.7)6 (7.9)6.2 (6.7)6.4 (7.5)6.4 (7.5)Dactylitis, n (%)14 (19.7)31 (15.5)46 (18.5)77 (18.8)168 (18.1)Axial involvement, n (%)14 (19.7)54 (26.9)49 (19.7)71 (17.3)188 (20.2)Nail involvement, n (%)34 (47.2)85 (42.3)106 (42.6)158 (38.6)383 (41.1)BMI>=30, n (%)37 (51.4)75 (37.1)98 (39.5)125 (30.9)335 (36.2)CRP of >=5 mg/L, n (%)33 (51.6)84 (45.4)99 (46.5)138 (39.1)354 (43.4)BSA (0-100), mean (SD)10.1 (18.3)9.5 (16.8)8.5 (14.9)8.1 (14.6)8.7 (15.5)Physician assessed global health (NRS 0-10), mean (SD)6.3 (1.5)5.6 (1.8)5.2 (1.7)4.9 (1.9)5.2 (1.9)TJC68, mean (SD)9.9 (7.1)8.6 (7.6)8.2 (7.6)7.3 (8.2)8 (7.8)SJC66, mean (SD)6 (5.2)4.8 (4.9)4.7 (4.4)4.3 (3.8)4.6 (4.4)DAPSA, mean (SD)29.3 (11.1)25.1 (12.9)23.4 (12.1)18.9 (12.4)22.3 (12.8)DAS28-CRP, mean (SD)4.1 (1)3.8 (1.2)3.7 (1.1)3.2 (1.1)3.6 (1.2)Patient assessed global health (NRS 0-10), mean (SD)7.9 (2.1)6.6 (2.1)5.9 (2)4.8 (2.3)5.7 (2.4)Patient assessed pain (NRS 0-10), mean (SD)7.8 (1.8)6.4 (2.1)5.8 (2)4.6 (2.4)5.5 (2.4)DLQI (0-30), mean (SD)8.5 (8.2)7.8 (7.2)5.4 (5.7)4.1 (4.9)5.6 (6.2)PSAID (0-10), mean (SD)6.9 (1.8)5.5 (1.8)4.4 (1.7)3 (1.7)4.2 (2.2)Conclusion:The impact of depressive symptoms on outcome parameters used in rheumatology is increasingly being recognised. Interestingly, direct measures of inflammatory disease activity of joint and skin disease such as BSA, CRP, and swollen joint count were not correlated with depressive symptoms. The highest correlation was found for broader assessments like global health status and PSAID.References:[1]Haugeberg et al. Arthritis research & Therapy, 2020, 22:198Acknowledgements:RABBIT-SpA is supported by a joint, unconditional grant from AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris.We thank all participating rheumatologists and patients.Disclosure of Interests:Anne Regierer Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris., Anja Weiß Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris., Martin Bohl-Buehler: None declared, Xenofon Baraliakos: None declared, Frank Behrens: None declared, Georg Schett: None declared, Anja Strangfeld Grant/research support from: AbbVie, Amgen, Biogen, Hexal, Janssen-Cilag, Lilly, MSD, Novartis, Pfizer, UCB and Viatris.
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Baldacci, Simon, Virginie Avrillon, Benjamin Besse, Bertrand Mennecier, Michael Duruisseaux, Julien Mazieres, Renaud Descourt, et al. "Lorlatinib for advanced ALK and ROS1+ non-small cell lung cancer (NSCLC): Efficacy and treatment sequences in the IFCT-1803 LORLATU expanded access program (EAP) cohort." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 9615. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.9615.
Анотація:
9615 Background: Lorlatinib, a third-generation tyrosine kinase inhibitor targeting ALK and ROS1, has been made available in France starting October 2015 through an EAP for advanced, refractory, ALK+ NSCLC after the failure of chemotherapy and TKIs. Besides the landmark, multi-cohort phase II trial that assessed lorlatinib in ALK+ NSCLC, real-life evidence regarding the efficacy and safety, as well as treatment sequences including lorlatinib, is lacking. Methods: We report the cohort of consecutive patients with advanced, refractory, ALK or ROS1+ NSCLC enrolled in the French EAP of lorlatinib from October 2015 to October 2019. Data were collected from medical records by French Cooperative Thoracic Intergroup (IFCT) research study assistants on site. Primary endpoint was progression-free survival. Results: 200 patients were included: 143 (71.5%) ALK+, 57 (28.5%) ROS1+, 87 (44%) men, 127 (66%) never-smokers, and 167 (85%) stage IV disease. Mean age was 59 years. At the time of initiation of lorlatinib, 146 (74%) patients had Central Nervous System (CNS) disease (78 % for ALK+, 63% for ROS1+), 131 (76%) were PS 0/1. Lorlatinib was delivered as 2nd/3rd/4th/5th+ line in 3%/17%/27%/53%of ALK+ patients and in 30%/30%/16%/24%of ROS1+ patients, respectively. 150 (75%), 185 (93%), 138 (69%), and 80 (40%) patients had received prior chemotherapy, crizotinib, 2nd generation TKIs, and brain radiotherapy, respectively. Median PFS and OS from the initiation of lorlatinib were 11.8 (95% CI 7.3-14.6) months and NR (95% CI 18.6-NR) months, respectively for ALK+ patients and 7.6 (95% CI 6.2-10.2) months and 20.9 (95% CI 10.0-NR) months, respectively for ROS1+ patients. ORR and DCR were 46.2% (95% CI 37.6-54.7) and 86.2% (95% CI 80.2-92.1), respectively for ALK+ patients and 47.1% (95% CI 33.4-60.8) and 88.2% (95% CI 79.4-97.1), respectively for ROS1+ patients. CNS ORR was 41.7% (95% CI 33.3-50.1) and 37.7% (95% CI 24.7-50.8), respectively. With a median follow-up of 15.6 (95% CI 14.0-17.6) months, progression under lorlatinib treatment was observed in 71 (50%) ALK+ patients and 35 (61%) ROS1+ patients, and CNS progression in 24 (34%) and 8 (23%) patients, respectively. The safety profile of lorlatinib was consistent with published data. Conclusions: These real-life results confirmed lorlatinib as a major treatment option for patients with advanced refractory ALK or ROS1+ NSCLC.
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Brubacher, J. R., G. Sutton, C. Lam, A. Trajkovski, R. Yip, T. Liu, and H. Chan. "P023: Emergency department data provides a realistic count of pedestrian injuries." CJEM 19, S1 (May 2017): S85. http://dx.doi.org/10.1017/cem.2017.225.
Анотація:
Introduction: Walking as a form of active transportation is promoted by health professions and environmentalists alike. While the health benefits are indisputable, active transportation is not without risk. Pedestrians are vulnerable road users who often suffer serious injuries especially when involved with collisions with motor-vehicles. While pedestrian injuries involving motor-vehicles are captured in road trauma surveillance systems based on police crash reports, non-collision injuries in this population may be caused by poorly designed infrastructure but are seldom counted as road trauma. This gap hinders road improvement efforts aiming to increase safety for all road users. This study aims to address this knowledge gap. Our objective is to study the profile and circumstances of injuries in pedestrians presenting to ED. Methods: This was a cross-sectional historical chart review study. All injured patients attending our ED are electronically flagged according to mechanism of injury. We reviewed the medical charts of all ED visits flagged as “Pedestrian” or “Fall” to identify all injured pedestrians (defined in this study as anyone walking on a public roadway or getting on/off public transportation). All pedestrian injuries occurred in 2015 were included for chart review. Results: In 2015, a total of 6192 ED presentations were flagged as pedestrian (n=436) or fall (n=5756), and 1108 of these met our inclusion criteria. Of these, 181 (16%) were admitted to hospital. Older pedestrians (≥70 yrs) had a higher hospital admission rate (78/303; 27%) compared to younger ones (<70 yrs: 103/805; 13%). Collision with motor vehicles (MVCs) resulted in only 25% of pedestrian injuries while fall (or tripping) accounted for about 72%. MVC related injuries were more common in younger pedestrians (29% vs 13%) whereas fall related injuries occurred more in older pedestrians (85% vs 67%). The most commonly sustained injuries among the fallers were abrasions followed by fractures. Conclusion: Police crash reports (which capture only MVC related pedestrian injuries) or hospital admission data (which miss those who are treated and released from ED) do not capture all cases of pedestrian injury. ED visit data provides a more realistic count of pedestrian injuries. More pedestrian injuries are caused by falls than by MVCs and policymakers should pay more attention to fall prevention strategies for older pedestrians outside their home environment.
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Kapoor, Vidit, Sylvia Keiser, Qianqian Liu, Joel Michalek, and Sukeshi Patel Arora. "Comprehensive molecular profiling in patients with advanced biliary tract cancers (BTC) in a Latinx-rich cohort." Journal of Clinical Oncology 41, no. 4_suppl (February 1, 2023): 605. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.605.
Анотація:
605 Background: BTC are genetically diverse and heterogeneous. Despite knowledge of molecular subtypes of BTC, the distribution of molecular aberrations in the Latinx population has been understudied. These may have prognostic and/or predictive implications. Therefore, we analyzed our cohort of Latinx-rich patients with advanced BTC. Methods: We analyzed patients with advanced BTC, who were seen at the Mays Cancer Center from Jan 2018-Dec 2021. Tumor samples profiled by Next Generation Sequencing (NGS) were identified retrospectively. Associations between demographics, clinical characteristics, and genetic alterations were identified. Results: 88 patients with locally advanced/metastatic BTC were identified. 50 (56.2%) were Latinx. 42 (47.7%) had intrahepatic CA (IHCA), 14 (15.9%) had extrahepatic CA (EHCA), 16 (18.2%) had Gall Bladder Carcinoma (GBC) and 16 (18.2%) had Ampullary/Periampullary Carcinoma (APC). 49 (56%) had NGS on their tumors out of which 30 (61.2%) were Latinx and 19 (38.8%) were non-Latinx. The most commonly altered genes were TP53 (34.7%), KRAS (24.5%), ARID1A (16.3%), BRCA-2 (12.2%), PDL-1 (12.2%), FGFR (12.2%), MET (10.2%), PTEN (10.2%) and HER-2 (8.2%). 14.3% patients had no identifiable mutations. There was no significant difference observed in the rates of different molecular mutations between Latinx and non-Latinx (p=1) and among different histologies of IHCA, EHCA, GBC and APC (p=1). The Median Overall Survival (OS) for Latinx population was 16.1 months (95% CI 12.3-28.2) which was similar to the median OS for non-Latinx population of 15.5 months (95% CI 11.6-28.6) (p=0.69). The median OS was not different due to the presence or absence of any one mutation (p values ranged from 0.04 to 0.9). Conclusions: BTCs are genetically diverse. Somatic alterations were identified in 85% patients who were tested. Only 56 % had molecular testing, when it should be 100% in advanced BTC, per NCCN guidelines. This may be due to inadequate tissue, lack of funding, use of alternate ctDNA, or the patient may have died before getting to testing/repeat biopsy. The likelihood of having a genetic alteration was similar between Latinx and non-Latinx patients and among different sites of disease. Latinx and Non Latinx with advanced BTC had similar survival rates. Survival rate was not different due to the presence or absence of any one mutation. Future studies should prospectively investigate implementation programs for NGS in tumor and blood in all patients with BTCs.
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Kuo, Ching-Yuan, Po-Nan Wang, Wen Li Hwang, Cheng-Hwai Tzeng, Li-Yuan Bai, Jih-Luh Tang, Ming-Chih Chang, et al. "Safety and Efficacy of Nilotinib (NIL) in Patients (Pts) with Chronic Phase (CP) or Accelerated Phase (AP) Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia (CML) with Resistance or Intolerance to Imatinib Mesylate (IM): Results from the Multicenter, Observational NOVEL Study in Taiwan." Blood 126, no. 23 (December 3, 2015): 1593. http://dx.doi.org/10.1182/blood.v126.23.1593.1593.
Анотація:
Abstract Background: The selective tyrosine kinase inhibitor (TKI) NIL is approved for the treatment of IM resistant CML-CP or CML-AP pts globally, including Taiwan. A non-interventional, multi-center observational study of N ilotinib in pts with CP or AP Philadelphia chrOmosome positiVe (Ph+) chronic myElogenous Leukemia (NOVEL) was conducted to assess the safety and efficacy of NIL in Taiwanese patients with IM intolerance or resistance. Methods: NOVEL was an open-label, single arm, study conducted across 12 centers in Taiwan for a period of up to 2 years (y). Adult CML-CP or CML-AP pts with confirmed Ph+ chromosome (or BCR-ABL) and resistant or intolerant to ≥1 prior CML therapy were enrolled. Also, IM resistant or intolerant pts with prior second-generation TKI therapy could be included. The primary objective was to collect long-term safety data in pts treated with NIL 400 mg twice daily. Efficacy data were collected as secondary objectives. Results: A total of 85 pts including CML-CP (n = 76) pts and CML-AP (n = 9) were enrolled. Median age was 47 y (range, 21-85); 56.5% were males. At baseline, median duration of CML diagnosis was 20.3 (range: 1.4-287.7) months (mo). In 7 pts, confirmed BCR-ABL mutations (E450G, E543A, F317L, F486S, G250E, M244V, M351T) were found, 26 (30.6%) did not have mutations, and 52 (61.2%) did not perform BCR-ABL mutation analysis. All pts (100%) had been treated with prior IM, while 19 pts (22.4%) pts had also received dasatinib; 61 (71.8%) pts had complete hematologic response (CHR) prior to NIL initiation. Of the 85 pts, 54 (63.5%) completed the study while 31 (36.5%) discontinued due to unsatisfactory therapeutic effect (n = 14), consent withdrawal (n = 5), adverse events (n = 4), deaths (n = 3), pregnancy (n = 1), administrative problems (n = 1), unknown (n = 1), and other reasons (n = 2). A total of 1166 AEs were reported by 80 (94.1%) pts, of which 70 (6%) AEs in 28 (32.9%) pts were serious. Of the total AEs, 336 (28.8%) drug-related AEs were reported in 60 (70.6%) pts with the majority (87.5%) being Grade 1 or 2. Of the total drug-related AEs, 85 (25.3%) were hematological and 251 (74.7%) were non-hematological. Common hematological AEs (≥5 % of pts) were thrombocytopenia (n=18; 21.18%) and anemia (n=12; 14.1%). Frequent non-hematological AEs (≥5 % of pts) were increased alanine amino-transferase ([ALT], n = 18; 21.2%), pruritus (n = 15; 17.7%), increased bilirubin (n=12; 14.1%), rash (n = 10; 11.8%), increased aspartate transaminase ([AST], n = 7; 8.2%, and increased lipase (n = 5; 5.9%). Seven deaths were reported during the study and follow-up period, respectively due to cardiopulmonary failure (suspected to be related to study-drug), acute myelogenous leukemia, accident, exacerbation of chronic obstructive pulmonary disease, subarachnoid hemorrhage, pneumonia, and sepsis. Of the 19 pts, who switched to NIL due to known AEs with IM, AEs resolved in 16 (84.2%) pts (Table). Cumulative CHR, major cytogenetic response (MCyR), complete cytogenetic response (CCyR), major molecular response (MMR), MR4.0 (BCR-ABLIS <0.01%) and MR4.5 (BCR-ABLIS <0.0032%) rates are presented in figure. Almost 50% of pts achieved MMR by 18 mo. In pts with confirmed BCR-ABL mutations, the median time to CHR and MMR were 11.9 mo and 37.0 mo compared to 2.3 mo and 16.9 mo in other pts, respectively. In pts without CHR at baseline, median time to CHR and MMR was 3.1 mo and 15.4 mo, respectively. Statistically significant benefit on overall survival (OS) and progression-free survival (PFS) was seen in pts with CML-CP versus pts with CML-AP at screening. Median OS and PFS were not reached for CML-CP pts. In CML-AP pts, median OS was 42.3 mo (95% Confidence interval [CI], 4.4-42.3), and median PFS was 42.3 mo (95% CI, 3.3-42.3). Conclusions: The NOVEL study demonstrates that treatment with NIL was effective in achieving cytogenetic and molecular responses in pts resistant or intolerant to IM in the real world setting. The response outcomes appeared to be influenced by BCR-ABL mutation status and CHR status at baseline, while OS and PFS were influenced by disease status (CML-CP or CML-AP) at screening. Safety profile of NIL was consistent with earlier reports. A number of AEs had lower incidences, with no incidence of peripheral arterial occlusive disorder (PAOD) reported, reflecting appropriate disease management among clinicians in Taiwan. More than 80% of AEs due to IM were resolved after switching to NIL. Disclosures Tang: Novartis: Consultancy, Honoraria. Chang:Novartis: Honoraria. Hseih:Novartis: Employment. Lin:Novartis: Employment. Darko:Novartis: Employment. Cheng-Shyong:Novartis: Honoraria, Speakers Bureau.
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Mahmud, Reaz, Mansur Habib, Sharif Uddin Khan, and Asma Khan. "Risk Factors and Morphological Differences of Ruptured Saccular Aneurysm in Different Sites of Anterior Circulation in Patients Presenting with Subarachnoid Haemorrhage." Journal of National Institute of Neurosciences Bangladesh 3, no. 1 (April 6, 2018): 21–28. http://dx.doi.org/10.3329/jninb.v3i1.36268.
Анотація:
Background: All sites of intracranial aneurysms have always been considered together in most of the studies of risk factors of aneurysm rupture. Therefore, it is not known whether some risk factors predispose to aneurysm rupture at a particular location. Morphologies also vary in accordance to different sites of the aneurysm.Objective: The purpose of the present study was to observe the differences in the risk factors, the size, aspect ratio and size ratio among the anterior circulation aneurysms.Methodology: This hospital based cross-sectional study carried out in the Department of Neurology at Dhaka Medical College Hospital (DMCH), Dhaka during July 2013 to June 2015 for a period of two (02) years. Patients with subarachnoid haemorrhage caused by ruptured anterior circulation saccular aneurysms admitted in the Departments of Neurology, Internal Medicine and Neurosurgery Departments at Dhaka Medical College Hospital (DMCH), Dhaka and the Department of Neurointervention at National Institute of Neurosciences and Hospital, Dhaka were enrolled in this study. Patients’ ≥18 years of age with subarachnoid haemorrhage caused by anterior circulation aneurysm which was confirmed by computed tomogram (CT-scan) and/or CSF study and digital subtraction angiography were included in this study. The risk factors were identified by interviewing the patients and the morphology were measured from the digital subtraction angiogram.Results: A total number of 85 patients with ruptured saccular anterior circulation aneurysm were enrolled in this study. In this study anterior communicating artery aneurysm (ACom) was the most frequent site of aneurysm (42%). The mean age of the patients with ACom aneurysm (51.72 ± 9.26 years) was significantly higher than posterior communicating artery (47.5 ± 8.2 years) aneurysm and middle cerebral artery (MCA) (43.41 ± 8.0 years) aneurysm. Above the age of 50 ACom aneurysm was the most frequent aneurysm (OR 5.5, p<0.05). Among the female Posterior communicating artery (PCom) aneurysm (46.7%) was the most frequent aneurysm and among the male ACom aneurysm (37.5%) was the most frequent aneurysm. Family history was exclusive in MCA aneurysm (3.5%). The mean size of MCA (7.79 ± 0.71 cm) was higher than ACom (6.12 ± 2.7cm) aneurysm and PCom (6.5 ± 2.4 cm) aneurysm and proportion of aneurysm >10 mm was also higher among the middle cerebral artery (35.6%) aneurysms. The size ratio was significantly higher in ACom (3.08±1.23) and MCA (3.04±0.97) aneurysm. ACom (76.4%) and MCA (83.3%) had also more frequent high risk size ratio.Conclusion: In conclusion anterior circulation aneurysms differ in respects of risk factors and morphology.Journal of National Institute of Neurosciences Bangladesh, 2017;3(1): 21-28
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Angevin, Eric, Stefanie L. Groenland, Annette May Ling Lim, Juan Martin-Liberal, Victor Moreno, Jose Manuel Trigo, Christophe Le Tourneau, et al. "Updated analysis of the inducible T-cell co-stimulatory receptor (ICOS) agonist, GSK3359609 (GSK609), combination with pembrolizumab (PE) in patients (pts) with anti-PD-1/L1 treatment-naïve head and neck squamous cell carcinoma (HNSCC)." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 6517. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.6517.
Анотація:
6517 Background: INDUCE-1 (NCT02723955) is a first-in-human study investigating GSK609, an IgG4 ICOS agonist non-T-cell depleting antibody, as monotherapy and combination therapy with anti-cancer agents that includes PE. A range of GSK609 dose levels (≥0.1–1 mg/kg) having biological and clinical activity were identified and evaluated in the expansion phase with GSK609 0.3 mg/kg selected as the dose for further investigation. Results from the HNSCC expansion cohorts (ECs) showed GSK609 has single agent activity in pts with relapsed/refractory disease, and early clinical activity in combination with PE in pts with anti-PD-1/L1 treatment-naïve disease (Rischin, et al. Annals of Oncol 2019;30[Supplement_5]:v454–5). Updated results from the GSK609/PE HNSCC EC are presented. Methods: Eligible pts for the HNSCC EC had anti-PD-1/L1 treatment-naïve disease, ≤5 prior lines of therapy, measurable disease, and no active autoimmune disease. Pts received GSK609 0.3 mg/kg + PE 200 mg every 3 weeks (wks) until disease progression or unacceptable toxicity, up to 2 years (yrs)/35 cycles. Disease assessments were performed every 9 wks through wk 54 then every 12 wks thereafter. Pts were followed for survival and subsequent anti-cancer therapy. Results: As of 11 October 2019, 34 pts were enrolled and evaluable for efficacy analyses. The median age of this population was 61.5 yrs (range: 37–77); 85% were male; 53% received ≥1 prior line of therapy in the metastatic setting. ORR was 26% (95% CI: 12.9, 44.4; n = 9 with 4 complete and 5 partial responses); disease control rate was 68% (95% CI: 49.5, 82.6; n = 23). Among pts with PD-L1 IHC status by 22C3 pharmDx assay (n = 24; 71%), the majority of pts with a response or stable disease (SD) had PD-L1 CPS status < 20 (11 of 15 pts including 1 SD pt with CPS < 1). Median PFS was 5.6 months (95% CI: 3.9, 6,2). Median OS was not reached at time of analysis (95% CI: 8.2, NR); 6-month OS rate was 84% (95% CI: 66, 93). Treatment-related adverse events were reported in 66% of pts; the majority of events were Grades 1 or 2 with < 10% of pts experiencing ≥ Grade 3 events. Conclusions: This updated analysis with a more mature dataset shows promising clinical activity that supports further randomized investigation of GSK609 in combination with PE with an OS endpoint in HNSCC. Clinical trial information: NCT02723955 .
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Kutluk, M. T., and M. A. Yeşilipek. "Pediatric Cancer Registry in Turkey (Turkish Pediatric Oncology Group & Turkish Pediatric Hematology Association)." Journal of Global Oncology 4, Supplement 2 (October 1, 2018): 67s. http://dx.doi.org/10.1200/jgo.18.25100.
Анотація:
Background: Each year more than 200,000 new cancer cases are expected in children & adolescents aged 0-14 years at global level. Although the long term survival rates have been improved to 85% in high income countries, it is still lower than this LMICs with a wide range around the world. Pediatric registries are critical for planning for pediatric cancer care. This study summarizes the update of pediatric cancer registry in Turkey. Aim: To analyze the pediatric cancer distribution through Turkish Pediatric Cancer Registry for the years of 2009-2017. Method: Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association established a Web based cancer registry in Turkey in 2002. The registry information for 2002-2008 was presented earlier. This study, now, is presents the distribution of pediatric cancers for the years of 2009-2017. International Childhood Classification System was used in classification. Basic demographic findings, ICD-O-3 morphology & topography codes were recorded for each cases. This is an update of the Turkish Pediatric Cancer Registry. Results: During the 9 years from 2009 to 2017, 14,769 pediatric cancer cases were recorded. For all cases, median age was 6.7 years (0-17 M/F 8318/6443, 3 hermaphrodite 5 unknown). Age distribution was 0-4 yrs, 40.8%; 5-9 yrs, 24.5%; 10-14 yrs, 23.3%; 15-19 yrs, 11.4%. The distribution of tumor types were [number of cases, percentage of total, median age years, M/F]: leukemia (4114, 27.9%, 5.5, 2366/1748); lymphoma and other RES tumors (2823, 19.1%, 9.6, 1904/914, 1 hermaphrodite 4 unknown); CNS [brain & spinal] (1950, 13.2%, 7.1, 1072/828); sympathetic system (1166, 7.9%, 2.4, 609/557); retinoblastoma (351, 2.4%, 1.4, 197/154); renal (736, 5.0%, 3.3, 345/391); liver (242, 1.6%, 1.8, 132/110); malignant bone (965, 6.5%, 12.6, 527/438); soft tissue sarcomas (991, 6.7%, 7.4, 580/411); germ cell (911, 6.2%, 8.2, 331/577, 2 hermaphrodite, 1 unknown); carcinoma and other malignant epithelial (436, 3.0%, 13.6, 212/224); other/nonspecific malignant (84, 0.6%, 7.1, 43/41) tumors. Five year survival rate was found as 67.8%. Conclusion: Registry provides the essential information for planning the pediatric cancer care. This registry became a critical source for health care professionals in Turkey since beginning. Survival rates for children increased to 67.8% based on this study. This is compatible with the survival rates from other upper middle income countries. This data also allows the comparison of the national data with the national and international studies. Investment on the pediatric cancer registry is one of the first steps of investments on pediatric cancer care.
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Soleto, C. Y., B. Serrano Benavente, L. A. Torrens Cid, J. Martínez-Barrio, J. Molina Collada, J. Rivera, T. González, et al. "AB0357 USE OF TOFACITINIB AND REASONS FOR DISCONTINUATION IN CLINICAL PRACTICE." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1478.2–1479. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5789.
Анотація:
Background:Tofacitinib is an oral JAK 1 and 3 inhibitor for the treatment of moderate to severe active rheumatoid arthritis (RA) or psoriatic arthritis (PsA) in adults with inadequate response or intolerant to one or more conventional disease-modifying antirheumatic drugs (cDMARDs). Since its approval by the European Medicines Agency (EMA), there is limited data about its use in daily practice in Europe.Objectives:To describe rates and reasons for discontinuation of Tofacitinib in patients with RA and other inflammatory conditionsMethods:We identified patients with a prescription for tofacitinib at our academic center from January 2017 to January 2020. Patients were treated according to their rheumatologist evaluation following standards of care. The following variables were retrospectively collected from the electronic medical chart: age, gender, diagnosis, date of treatment initiation, date and reasons for treatment discontinuation, the use of concomitant or previous cDMARDs and of biologics. A comparison between patients continuing and stopping tofacitinib was performed through chi2or t-test for qualitative and quantitative variables, respectively. Survival analysis was done by Kaplan-Meier methodResults:Ninety patients receiving tofacitinib were identified, 81 with RA, 6 with PsA, 1 with Dermatomyositis, 1 with Sjögren´s and 1 with juvenile idiopathic arthritis. Table 1 shows the baseline characteristics. 84% percent patients were women and the mean (SD) age was 58.5 (14.2) years. 51% patients started tofacitinib in monotherapy. When used, methotrexate was the most frequent cDMARD (61.3%); 10% patients used tofacitinib as first line after cDMARD and the majority used it after 1 or 2 previous biologics (46.7%).Table 2.Clinical coutcome of patients who developed HZ at initiation of baricitinibAll patients(n=90, 100%)Continue Tofacitinib(n=58; 64%)Not continue Tofacitinib(n=32; 35.5%)p-valueFemale (%)76 (84.4)48 (82.7)28 (87.5)0.55Age (year) – mean (SD)58.5 (14.2)58 (12.9)59.5 (16.5)0.63Diagnosis0.66Rheumatoid arthritis81 (90)52 (89.6)29 (90.6)Psoriatic arthritis6 (6.7)4 (6.8)2 (6.2)Other3 (3.3)2 (3.4)1 (3.1)Treatment duration (months) – mean (SD)10.6 (6.9)11.9 (7.3)8.2 (5.5)0.02Prednisone (mg) – mean (SD)1.75 (3.2)1.20 (2.5)2.73 (4.1)0.03Monotherapy (%)46 (51.1)28 (48.2)18 (56.2)0.244Concomitant csDMARDs (%)44 (48.8)30 (51.7)14 (43.7)0.62Methotrexate (%)27 (30)17 (29.3)10 (31.2)Leflunomide (%)10 (11.1)8 (13.7)2 (6.2)Other (%)7 (7.7)5 (8.6)2 (6.2)Prior biologic treatment0.13None (%)9 (10)6 (10.3)3 (9.3)1-2 (%)42 (46.6)28 (48.2)14 (43.7)≥3 (%)39 (43.3)24 (41.3)15 (46.8)Survival rates when used as first or second line were 85% at 6 months and 70% at 12 months; when used as third line or further, 76% and 70%, respectively (graphic 1).Factors associated to tofacitinib discontinuation were treatment duration and baseline prednisone dose. In contrast concomitant csDMARD and number of previous biologics were not. Reasons for tofacitinib discontinuation were: lack/loss of efficacy 46.9%, adverse events 50% (including intolerance -22%- herpes zoster -16%-, other infections 12%) and others.Conclusion:Tofacitinib in our experience is mostly used in RA patients after biologic failure. Overall survival rate at 12 months was good regardless line of therapy. Adverse event rates were similar to other biologic treatments. Herpes zoster was the most common infectious AE.Graphic 1:References:[1]Wollenhaupt J, Lee EB, Curtis JR, et al. Safety and efficacy of tofacitinib for up to 9.5 years in the treatment of rheumatoid arthritis: final results of a global, open-label, long-term extension study. Arthritis Res Ther. 2019;21(1):89.Disclosure of Interests:Christian Y Soleto: None declared, Belén Serrano Benavente: None declared, Luis A Torrens Cid: None declared, Julia Martínez-Barrio Consultant of: UCB Pharma, Juan Molina Collada: None declared, Javier Rivera: None declared, Teresa González: None declared, Indalecio Monteagudo: None declared, Carlos Gonzalez Consultant of: Gilead, Janssen, Novartis,, Speakers bureau: Abbvie, Celgene, Gilead, Janssen, Novartis, Pfizer, Roche, Isabel Castrejon: None declared, Jose-Maria Alvaro-Gracia Grant/research support from: Abbvie, Elli-Lilly, MSD, Novartis, Pfizer, Consultant of: Abbvie, BMS, Janssen-Cilag, Elli-Lilly, MSD, Novartis, Pfizer, Sanofi, Tigenix, Roche, UCB, Paid instructor for: Elli-Lilly, Pfizer, Roche, Speakers bureau: Abbvie, BMS, Janssen-Cilag, Elli-Lilly, Gedeon Richter, MSD, Novartis, Pfizer, Sanofi, Tigenix, Roche, UCB
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Ageno, Walter, Nicoletta Riva, Soo-Mee Bang, Maria Teresa Sartori, Elvira Grandone, Jan Beyer-Westendorf, Giovanni Barillari, et al. "Antithrombotic Treatment of Splanchnic Vein Thrombosis: Results of an International Registry." Blood 120, no. 21 (November 16, 2012): 499. http://dx.doi.org/10.1182/blood.v120.21.499.499.
Анотація:
Abstract Abstract 499 Background: Treatment of splanchnic vein thrombosis (SVT) is a clinical challenge due to heterogeneity of clinical presentations, increased bleeding risk and lack of evidences from clinical trials. We carried out an international registry aimed to describe current treatment strategies and factors associated with therapeutic decisions in a large prospective cohort of SVT patients. Methods: Between May 2008 and January 2012, consecutive SVT patients were enrolled in the registry and information on clinical presentation, risk factors, and therapeutic strategies was collected in an electronic database. Clinical outcomes during the first month of treatment were documented. A two-year follow up is ongoing. Results: 613 patients from 12 countries were enrolled in the registry. Mean age was 53.1 (SD ± 14.8) years (range 16–85); 62.6% were males, 74.4% Caucasians. SVT occurred in the portal vein in 470 patients, in the mesenteric vein in 266, in the splenic vein in 139, and in the supra-hepatic veins in 56; 38.8% of patients had multiple vein segments involved. In 29.8% of patients SVT diagnosis was incidental. Most common risk factors included cirrhosis (27.8%), solid cancer (22.3%), intra-abdominal inflammation/infection (11.5%), surgery (8.9%), and myeloproliferative neoplasm (MPN)(8.2%); in 27.6% of patients SVT was idiopathic. During the acute phase, 471 (76.8%) patients were treated with anticoagulant drugs: unfractionated heparin (10.4%), low molecular weight heparin or fondaparinux (66.4%), vitamin K antagonists (VKA) (48.5%). Four patients received aspirin, 9 received thrombolysis. A total of 135 patients (22.0%) remained untreated. Of patients with incidentally diagnosed SVT, 61.1% received anticoagulant treatment. Incidental diagnosis (p<0.0001), single vein thrombosis (p<0.0001), gastrointestinal bleeding (p0.008), thrombocytopenia (p0.0003), cancer (p0.009) and cirrhosis (p<0.0001) were significantly associated with no anticoagulant treatment. History of venous thrombosis (p0.003), myeloproliferative neoplasm (p0.003), surgery (p0.001), and hormonal treatment (p0.013) were significantly associated with the use of anticoagulant treatment. Decision to start patients on VKA was significantly associated with younger age (p<0.0001), symptomatic onset (p<0.0001), multiple veins involvement (p0.012) and unprovoked thrombosis (p<0.0001). Continued treatment with parenteral anticoagulants was significantly associated with anaemia (p0.013), thrombocytopenia (p<0.0001), cancer (p<0.0001), and cirrhosis (p<0.0001). During the first month after diagnosis, 2 patients on anticoagulant treatment (0.4%) and 3 untreated patients (2.2%) had thrombosis extension, 2 (0.4%) treated and 2 (1.5%) untreated patients had major bleeding, 11 patients died (7 and 4, respectively). Conclusions: Despite the increased bleeding risk and recent guidelines suggesting not to treat incidentally detected SVT, 76.8% of newly diagnosed SVT receive anticoagulant therapy in clinical practice. Treatment strategies vary according to patients characteristics, with this patient selection resulting safe and effective during the acute phase of therapy. The ongoing two-year follow up will provide additional information. Disclosures: No relevant conflicts of interest to declare.
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Diallo, Kalilou, Dame Mbengue, Habibou Sarr, Abdou Badiane, Khadidiatou Diallo, Mame Ngoné Coly, Ludmillie Annie Badji, et al. "Impact of Dolutegravir-based Regimen on Tolerance and Virologic Suppression, Compared to Non-dolutegravir Regimen among PLHIV in Southern Senegal." Asian Journal of Research in Infectious Diseases 15, no. 3 (April 4, 2024): 33–43. http://dx.doi.org/10.9734/ajrid/2024/v15i3336.
Анотація:
Background: In 2020, Senegal began a transition to a Dolutgravir-based treatment as a first-line regimen in all new ART initiators in accordance with WHO recommendations. Aims: To determine the virological suppression and the tolerance on patients under a dolutegravir-based regimen by comparison with patients on a regimen without dolutegravir after at least 6 months of treatment. Materials and Methods: A cross-sectional study based on retrospective data (from January 2nd, 2017 to June 30th; 2022) involving 469 patients, 219 people were initiated with Dolutegravir regimen ART between Jan 2nd, 2020, and June 30th, 2022, and 250 patients treated using the old protocol (non-dolutegravir regimen). Patients who had received both the old protocol then switched to a DTG based regimen were excluded from the study. A single questionnaire was used to collect data. Sociodemographic, clinical and virological parameters and the last control of the virological load were analyzed with Stata 16 software. Descriptive statistics and univaried analysis were also carried-out. Results: In the dolutegravir regimen ART group, 161 (73, 52%) of 219 were women and 58 (26.48) were men. The median participant age was 43·0 years (IQR 33·0–53·0) and the median time on ART was 28·0 months (23·0–36·0). The dolutegravir-based regimen combined tenofovir, lamivudine and dolutegravir. 15 (6, 85 %) were receiving tuberculosis treatment at the time of ART initiation. The proportion of patients screened at an advanced clinical stage of AIDS (WHO stage 3 or 4) were 63, 47%. People initiated on dolutegravir were more likely to be retained in care at 12 months (100% vs. 95.20%; p=0.075) and having viral suppression (96.80%vs. 96.40% ; p=0,810) compared with those initiated on non-dolutegravir-based regimens but the difference was not statistically significant. Fewer patients presented side effects due to triple therapy in the dolutegravir-based regimen group compared to the non-dolutegravir group (2.74% vs. 3.20%; p=0.77). In the dolutegravir based regimen the side effects were mainly vomiting, insomnia, and dizziness. The mean gain weight was 6,7± 8,2 kilograms. For the non-dolutegravir regimen group, 195 (78.00%) were women. The median participants age was 43·0 years (IQR 34·0–53·0) and the median time on ART was 55·0 years (48·0–65·0) months. 18 (7, 20%) were receiving tuberculosis treatment at time of ART initiation. The therapeutic protocol combined TDF, lamivudine, Efavirenz in 225 cases (90%). A percentage of 59.20% patients were screened at an advanced clinical stage of AIDS (WHO Stage 3 and 4). In this group the side effects were mainly nausea and insomnia and the mean gain weight was 7,2 ± 6,2 kilograms. Conclusion: The results of our study show a high rate of viral suppression, and good tolerance of the dolutegravir-based regimen in a decentralized setting.
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Kalouche-Khalil, L., R. Gandhi, L. Hao, E. Smolkina, and F. Schumacher. "POS0319 DISEASE BURDEN OF PRIMARY SJOGREN SYNDROME: A RETROSPECTIVE UNITED STATES CLAIMS DATABASE STUDY." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 410.1–411. http://dx.doi.org/10.1136/annrheumdis-2022-eular.2548.
Анотація:
BackgroundPrimary Sjögren’s syndrome (pSjS) is a chronic and complex systemic autoimmune disease, primarily characterised by inflammation and progressive destruction of the exocrine glands (ie, autoimmune epithelitis) [1].ObjectivesWe evaluated disease progression, treatment patterns, mortality, and healthcare resource utilization (HCRU) of pSjS patients in the United States (US) to understand the real-world experiences of patients with pSjS.MethodsThis retrospective cohort study utilised data from US Optum Clinformatics claims between 01 May 2000 and 31 December 2020. The study included pSjS patient cohort and general population cohort, matched (1:1) on age, sex, and index date. Baseline period of 365 days prior to the index date was used for assessment of baseline comorbidities. Descriptive statistics were used to describe baseline characteristics, HCRU, and treatment pattern while multivariable models were used to assess hazard ratios (HRs) and risk factors.ResultsOverall, 23,168 patients with pSjS (ICD-9 710.2 Sicca syndrome and ICD-10 M 35.0 Sjogren Syndrome and excluding patients with Rheumatoid arthritis [RA], Systemic sclerosis [SS] and Systemic lupus erythematosus [SLE] diagnoses codes) were included in the cohort (mean [SD] age: 61.5 [15.3] years; females: 85%). At baseline, 79.4% and 8.2% of pSjS patients had systemic complications and organ-specific autoimmune comorbidities, respectively. In a sub-set of the cohort including patients with at least 5 years of follow-up, by the end of 5 years 96.8% and 16.5% of patients developed systemic complications and organ-specific autoimmune comorbidities, respectively (Table 1). The most frequently occurring organ-specific autoimmune comorbidities over the 5-year follow-up included Graves disease (5.4%), Hashimoto disease (3.7%), and discoid/subacute cutaneous lupus erythematosus (3.5%). Mortality was reported in 7.4% of the patients during 5-year follow-up. Risk factors associated with higher mortality included systemic complications in renal (HR [95% CI]: 2.29 [2.09–2.52]), cardiovascular (HR [95% CI]: 2.42 [2.19–2.67]), lungs (HR [95% CI]: 3.73 [3.41–4.09]) and haematological domains (HR [95% CI]: 2.83 [2.56–3.13]), non-Hodgkin’s lymphoma (HR [95% CI]: 2.58 [2.12–3.14]), and primary biliary cirrhosis (HR [95% CI]: 2.17 [1.60–2.96]). Corticosteroids (28.2%), hydroxychloroquine (15.7%), and cyclosporine (10.9%) were most frequently used medications. During the year following the first pSjS diagnosis, defined as the first claim with the Sjogren Syndrome ICD code (index date), the mean all-cause healthcare costs have increased by 27% from $21,634 to $27,526 per patient per year.Table 1.Occurrence of systemic complications and organ-specific autoimmune comorbidities over follow-up of 5 yearsVariable, n (%)Baseline (N=6000)Within 5 years (N=6000)Any systemic complication4,555 (75.9%)5,806 (96.8%)Articular involvement3,176 (52.9%)5,026 (83.8%)Renal involvement352 (5.9%)1,185 (19.8%)Cardiovascular complications342 (5.7%)826 (13.8%)Muscles1,390 (23.2%)2,732 (45.5%)Pancreatic31 (0.5%)88 (1.5%)Lungs373 (6.2%)1,383 (23.1%)Peripheral nervous system766 (12.8%)2,109 (35.2%)Haematological1,016 (16.9%)2,507 (41.8%)Glandular542 (9.0%)2,274 (37.9%)Central nervous system212 (3.5%)556 (9.3%)Biological153 (2.6%)408 (6.8%)Skin517 (8.6%)1,327 (22.1%)Lymphadenopathy374 (6.2%959 (16.0%) Non-Hodgkin’s lymphoma59 (1.0%)131 (2.2%)Any organ-specific autoimmune disease464 (7.7%)992 (16.5%)ConclusionThese results provide additional evidence that pSjS is associated with substantial morbidity and clinical burden supporting the need for safe and efficacious disease modifying treatment options in this patient population.References[1]Mariette X, Criswell LA. N Engl J Med. 2018;378(10): 931-939.AcknowledgementsMedical writing and editorial assistance were provided by Sanjeev Kallapari and Chiranjit Ghosh, PhD of Sanofi. This study was funded by Sanofi.Disclosure of InterestsLAMA KALOUCHE-KHALIL Shareholder of: May hold stock/stock options in Sanofi., Employee of: Employee of Sanofi., Roopali Gandhi Shareholder of: May hold stock/stock options in Sanofi., Employee of: Employee of Sanofi., Lichen Hao Shareholder of: May hold stock/stock options in Sanofi., Employee of: Employee of Sanofi., Ekaterina Smolkina Shareholder of: May hold stock/stock options in Sanofi., Employee of: Employee of Sanofi., Fabienne Schumacher Shareholder of: May hold stock/stock options in Sanofi., Employee of: Employee of Sanofi.
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D'Souza, Anita, Baldeep Wirk, Mei-Jie Zhang, Jiaxing Huang, Amrita Krishnan, Tomer M. Mark, Cristina J. Gasparetto, and Parameswaran N. Hari. "Improved Outcomes of Autologous Hematopoietic Cell Transplantation (AHCT) for Light Chain (AL) Amyloidosis: A Center for International Blood and Marrow Transplant Registry (CIBMTR) Study." Blood 124, no. 21 (December 6, 2014): 193. http://dx.doi.org/10.1182/blood.v124.21.193.193.
Анотація:
Abstract Background: Light chain (AL) amyloidosis is a rare plasma cell neoplasm associated with systemic amyloid deposition leading to organ dysfunction and death without treatment. The use of AHCT in AL amyloidosis remains controversial as a prospective randomized control trial suggested inferior outcomes when compared with standard chemotherapy, driven primarily by high peri-transplant mortality (TRM) up to 24%. Improved patient selection criteria, supportive care and risk-adapted therapy have reduced TRM in recent single center studies. We analyzed trends and prognostic factors associated with AHCT outcomes in AL amyloidosis patients. Methods: We identified 1532 AL amyloidosis patients who underwent AHCT following high dose melphalan (MEL) within 24 months of diagnosis between 1995 and 2012 from the CIBMTR database. A subset of patients with more complete level of research data reported between 2001 and 2012 was analyzed for multivariate analysis (n=354). The primary endpoints were day30 and day100 mortality, hematologic progression free survival (PFS), hematologic relapse/progression and overall survival (OS). Data regarding cardiac, renal, hepatic and neurologic amyloid involvement was collected. Hematologic and organ response and progression were defined based on the 2004 uniform consensus criteria. Results: The median age at transplant was 57 years, with 61% males. AHCT was performed within 6 months of diagnosis in 66% patients. Karnofsky performance score (KPS) was <80 in 14%, HCT-CI was ≥ 3 in 20% and 69% had a lambda isotype. Organ involvement included renal, cardiac, hepatic and autonomic nervous system involvement in 74%, 38%, 16% and 11% respectively. Coexistent myeloma (>10% bone marrow plasma cells) was seen in 14%. Progressively higher numbers of patients received AHCT from 1995-2000 (n=140) to 2001-2006 (n=595) and 2007-2012 (n=800). The majority were untreated pre-transplant (77%) while 8% received melphalan, 6% thalidomide and 4% each received lenalidomide and bortezomib based pre-AHCT therapy. The median CD34 cell dose infused was 4.4 X 106/kg cells (IQR 3.3-6.2). MEL dose reduction was common (60% received < MEL 180 mg/m2 and 38% < MEL 140 mg/m2). The median length of hospital stay was 17 days (IQR 13-23). The median follow-up of patients from the time of transplant was 61 months (range 3-145). Day100 response included hematologic complete response, CR (12%), partial response, PR (26%), stable disease, SD (23%), and renal response (12%) with an ultimate best response of hematologic CR (33%), PR (28%), SD (19%) and renal response in 31%. Table 1 shows day30 and day100 mortality and OS at 1, 3 and 5 years showing steady declines in mortality rates and improvements in survival in successive time cohorts. Figure 1 shows the 5 year OS in each of the time cohorts. On multivariate analysis, albumin ≥ 3 g/dl at diagnosis, KPS ≥80, pre-transplant anti-plasma cell therapy and MEL ≥180 mg/m2 were associated with lower hematologic relapse/progression. KPS ≥80 and predominant renal involvement were associated with superior hematologic PFS while KPS ≥80 and < 2 organ involvement correlated with OS. Table 1 Outcomes of AHCT in AL amyloidosis. Values are expressed as probabilities with 95% confidence intervals. 1995-2000 N=140 2001-2006 N=595 2007-2012 N=800 Day 30 mortality 11 (7-17) 5 (4-7) 3 (2-4) Day 100 mortality 20 (14-27) 11 (8-13) 5 (4-7) 1 year survival 75 (67-82) 85 (81-87) 90 (88-92) 3 year survival 64 (56-72) 72 (68-75) 83 (80-86) 5 year survival 55 (46-63) 61 (57-65) 77 (72-82) Conclusions: There has been a significant improvement in survival of AL patients after AHCT driven primarily by a reduction in early peri-transplant mortality. Limited organ involvement, higher KPS, use of pre-transplant therapy and higher dose melphalan conditioning contributed to superior outcomes. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.
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Cohen, Alexander T., Gabriel J. Weston, Andrew J. Tasker, Greg A. Fellows, and Rosalind Wilmott. "Fatal Pulmonary Embolism and Cancer - a Post Mortem Study." Blood 104, no. 11 (November 16, 2004): 2593. http://dx.doi.org/10.1182/blood.v104.11.2593.2593.
Анотація:
Abstract Introduction: During the period of 1965–1990 and 1991–2000, two separate analyses were carried out at King’s College Hospital, London, taking a retrospective review of all autopsy reports during this time. The initial aims of these reviews were to determine the number of deaths from autopsy-confirmed fatal pulmonary embolism (FPE) in hospitalised patients, and the clinical characteristics of these patients. Methodology: Cases for inclusion were identified and data derived from manually examining copies of post-mortem reports. The data form recorded the patient gender, age, race, height, weight and surgical status. In addition, evidence of DVT, myocardial infarction (MI), stroke, chronic obstructive pulmonary disease (COPD), cardiac failure, infection or cancer was recorded from the autopsy report. Cases of fatal PE were classified as occurring in either surgical (if death occurred within 8 weeks of surgery), or non-surgical patients. The outcome of fatal pulmonary embolism was recorded as the cause of death only when the post-mortem stated that embolism was the main or contributing cause of death and identified emboli present either in the main pulmonary trunk or in the proximal right or left pulmonary arteries formed from the bifurcation of the main trunk. Emboli found in the distal pulmonary arteries after further division of the right and left pulmonary arteries were not included. Emboli derived from bone marrow, fat, tumour, or amniotic fluid were also excluded from the analysis. Ethical approval for the study was obtained from the local research ethics committee. The identity of deceased patients was protected by the use of code numbers on the data forms. Results: Over the 35 year period there were 45,575 hospital deaths and 16,862 (37%) post-mortems. FPE was recorded as cause of death in 1,040 (6.2%) adult patients. Of these 85% (n=885) were in non-surgical patients, and 15% (n=155) in post-operative patients. Of the fatal pulmonary emboli, 347 of 1040 (33%) had either cancer (active malignancy) or a past history of cancer. Of this cancer group, 93% (n= 323) had an active malignancy, with 7% (n= 24) giving a past history of cancer. Cancer sites were gastro-intestinal in 34% (n= 119), lung 24% (n= 82), urological 10% (n= 33), gynaecological 8% (n= 29) and breast 8% (n= 28), 5% haematological (n= 17) endocrine 5% (n= 16), and dermatological 1% (n= 3). The majority of active cancers were found within the peritoneal cavity (60%, n= 194). Infection was the additional risk factor that was most prevalent in all those with FPE occurring in 32% (n=334), 76.3% (n=808) had one or more additional risk factors. Conclusions: Most fatal pulmonary emboli occur in non-surgical patients, cancer is a very common association (33%). Active cancer is seen in 93% of all FPE deaths associated with cancer. Intra-peritoneal cavity tumours are the commonest type to be associated with FPE. Infection is a common associated risk factor.
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Epstein, Larissa, Carina Franco, Alexandra Coward, Jason Heard, Soman Sen, Tina L. Palmieri, and Kathleen S. Romanowski. "560 Is the Need for Follow up Lost in Translation?" Journal of Burn Care & Research 45, Supplement_1 (April 17, 2024): 153. http://dx.doi.org/10.1093/jbcr/irae036.194.
Анотація:
Abstract Introduction There is limited research evaluating patients of limited English proficiency (LEP) on outcomes after burn injury. Studies have shown that patients with LEP have reduced access to care, longer admissions, are more likely to be discharged to a nursing facility and are more likely to return to the emergency department (ED). Burns require significant inpatient and outpatient coordinated care for successful discharge planning and patient education regardless of language preference. This study examines the effect of LEP on outcomes following burn injury. We hypothesize that burn patients with LEP will have longer hospital stays, fewer follow up (F/U) visits, and more ED visits after discharge. Methods Following IRB approval, a retrospective chart review was conducted using electronic medical records for burn patients admitted from January 2018 to December 2019. Data collected includes patient demographics, burn injury, burn outcomes, preferred language, and F/U care. Analysis was conducted with SAS statistical software, version 9.4 (SAS Institute, Cary, NC, USA) using Chi-square, Fisher Exact, Spearman Correlation, Wilcoxon 2-sample and Kruskal-Wallis tests. Results A total of 760 patients with a median age of 46 years (Interquartile range (IQR) = 26) were analyzed. Median total body surface area (TBSA) burn was 6.5 (IQR = 12) and 15% had inhalation injury. The median length of stay (LOS) was 9 days (IQR = 18) and 38 patients (5%) died. Reviewing post-burn care, 613 patients (81%) scheduled F/U, 397 patients (52.7%) attended a F/U appointment within 30 days of discharge, 85 patients (11.2%) presented to the ED, and 46 patients (6.1%) were readmitted. Only 61 patients (8%) preferred a language other than English. Among patients with LEP, Spanish was the most spoken language (5.6%), followed by Hmong (0.92%). When patients with LEP were compared with English speakers there was no difference in age (42 (22) vs. 46 (26), p=0.67), TBSA (5.5 (10.5) vs. 6.6 (11.8), p=0.32), mortality (3.3% vs. 4.7%, p=1), LOS (8 (16) vs. 9 (18), p=0.43), ICU days (2 (16) vs. 3 (15), p=0.43), inhalation injury (13.1% vs. 14.9%, p=0.87), and discharge to home (86.9% vs. 75.9%, p=0.44). Patients with LEP were more likely to have follow up scheduled at discharge (93.4% vs. 80.2%, p=0.04), attend F/U (78.7% vs. 50.7%, p=0.0005), and present to the ED after discharge (19.7% vs. 10.5%, p=0.03). There was a trend towards them being readmitted more than native English speakers (11.5% vs. 5.6%, p=0.08). Conclusions Patients with LEP were no different from their English-speaking counterpart with respect to traditional outcome measures (LOS or mortality) but had increased healthcare utilization (F/U or return to the ED). Applicability of Research to Practice As the number of patients with LEP increases, health care providers must be aware of the influence this has on outcomes following burn.
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Yoon, Shinkyo, Dok Hyun Yoon, Shin Kim, Kyoungmin Lee, Eun Hee Kang, Sang-wook Lee, Chan-Jeoung Park, Chan-Sik Park, Jooryung Huh, and Cheolwon Suh. "Proposal of New Prognostic Index for Patients with Diffuse Large B-Cell Lymphoma in the Rituximab Era." Blood 124, no. 21 (December 6, 2014): 1668. http://dx.doi.org/10.1182/blood.v124.21.1668.1668.
Анотація:
Abstract Background The International Prognostic Index (IPI) has been useful prognostic tool to predict prognosis of aggressive non-Hodgkin lymphoma in the last 20 years. Since the advent of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy for diffuse large B-cell lymphoma (DLBCL), its utility has been challenged and other prognostic index including revised IPI and National Comprehensive Cancer Network (NCCN)-IPI were proposed, which are not popularly used yet. We aimed to develop new prognostic model for DLBCL in rituximab era. Method Between March 2004 and June 2012, patients with DLBCL treated with R-CHOP were identified in the database of the Asan Medical Center (AMC) Lymphoma Registry. Primary end point was to devise a new prognostic index for DLBCL. Secondary end point was to validate the NCCN-IPI in our cohort. We tested new prognostic index model in the training set of AMC cohort consisted of randomly selected 80% of the sample (503 patients). The remaining 20% (118 patients) was used as an internal validations set. Results The AMC cohort consisted of 621 patients. Median follow-up duration was 43.3 months (6.2-122.5 months). Baseline characteristics of AMC cohort are presented in table 1. Median age was 57 years (range, 16-85 years). Median ϐ-2 microglobulin (ϐ-2 MG) was 2.10 mg/L (range, 1.0-66.0 mg/L). The univariate analysis of baseline characteristics revealed that age (≦60 vs. >60 years), LDH (within normal vs. increased), ECOG performance (0 or 1 vs. ≧2), advanced stage (Ann Arbor stage I/II vs. III/IV), extra-nodal involvement (≦1 vs. >1), B symptoms (no vs. yes), and ϐ-2 MG (≦2.5 vs. >2.5) could predict overall survival (OS), whereas bulky disease and gender did not (p value 0.140, 0.621, respectively). In the multivariate analysis, age, LDH, ECOG performance status, and ϐ-2 MG were significantly associated with OS (p value 0.001, <0.001, 0.004, and 0.019, respectively), while stage, extra-nodal involvement, and B symptom did not (p value 0.057, 0.233, and 0.577, respectively). We developed a new prognostic model with these 4 significant factors in the multivariate analysis. One point is assigned for each of the risk factors without refined categorization. Four risk groups were composed as followings: low (0 point), low-intermediate (1 point), high-intermediate (2-3 points), and high (4 points). The new prognostic model showed better discriminative power compared with classic IPI (Figure 1A). Five-year OS of low- and high-risk subgroup in new scoring model and classic IPI model in AMC cohort were 95% and 32% versus 89% and 45%, respectively. Our model was validated in an internal validation set (Figure 1B). NCCN-IPI also could stratify four risk groups (Figure 1 A and B). Conclusion We propose a new prognostic index model for DLBCL in rituximab era with age, LDH, ECOG performance and ϐ-2 MG, which has good discriminative power and convenient to apply. It warrants further validation using an independent cohort. Table 1. Baseline Characteristics Characteristics Total N=621 % Training set N=503 % Validation set N=118 % Age, years Median, range ≦ 60 years > 60 years 57.0 377 244 16-85 60.7 39.3 57.0 300 203 16-84 59.6 40.4 57.0 77 41 17-85 65.3 34.7 Sex Male Female 343 278 55.2 44.8 273 230 54.3 45.7 70 48 59.3 40.7 ECOG PS 0 or 1 ≧ 2 569 52 91.6 8.4 462 41 91.8 8.2 107 11 90.7 9.3 Serum lactate dehydrogenase levels Normal Elevated 334 287 53.8 46.2 279 224 55.5 44.4 55 63 46.6 53.4 Ann Arbor stage I and II III and IV 293 328 47.2 52.8 236 267 46.9 53.1 57 61 48.3 51.7 Number of extranodal sites <2 ≧ 2 403 218 64.9 35.1 329 174 65.4 34.6 74 44 62.7 37.3 B symptoms No Yes 549 72 88.4 11.6 447 56 88.9 11.1 102 16 86.4 13.6 International prognostic index Low/ low-intermediate High-intermediate/high 404 217 65.1 34.9 327 176 65.0 35.0 77 41 65.3 34.7 ¥Â -2 microglobulin, mg/L Median, range ≦ 2.5 mg/L > 2.5 mg/L 2.1 422 199 1.0-66.0 68.0 32.0 2.1 339 164 1.0-29.6 67.4 32.6 2.1 83 35 1.0-66.0 70.3 28.7 Table 2. Multivariate Analysis for Factors Associated with Overall Survival Factors HR 95% CI P value Score Age, years ≦ 60 years > 60 years 1.000 2.051 1.362-3.090 0.001 1 Serum lactate dehydrogenase levels Normal Elevated 1.000 3.165 1.951-5.135 <0.001 1 ECOG PS 0 or 1 ≧ 2 1.000 2.073 1.261-3.407 0.004 1 ϐ -2 microglobulin, mg/L ≦ 2.5 mg/L > 2.5 mg/L 1.000 1.691 1.0391-2.622 0.019 1 Figure 1. IPI versus NCCN IPI versus new prognostic index model in Asan Medical Center training set (A) and internal validation set (B) Figure 1. IPI versus NCCN IPI versus new prognostic index model in Asan Medical Center training set (A) and internal validation set (B) Disclosures No relevant conflicts of interest to declare.
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Jabbour, Elias, Hagop M. Kantarjian, Jenny Shan, Susan O'Brien, MD, Tapan Kadia, Gautam Borthakur, Alfonso Quintas-Cardama, Guillermo Garcia-Manero, Farhad Ravandi, and Jorge Cortes. "The Achievement of An Early Complete Cytogenetic Response (CCyR) Is A Major Determinant for Outcome In Patients (pts) with Early Chronic Phase (CP) Chronic Myeloid Leukemia (CML) Treated with Tyrosine Kinase Inhibitors (TKIs)." Blood 116, no. 21 (November 19, 2010): 3429. http://dx.doi.org/10.1182/blood.v116.21.3429.3429.
Анотація:
Abstract Abstract 3429 The achievement of a CCyR is a known major surrogate endpoint in the treatment of pts with CML that has shown correlation with survival improvement. Second generation TKIs (2nd TKI) have shown significant activity in pts with CML post imatinib (IM) failure and have recently shown superiority when compared to IM 400 mg standard of care in pts with newly diagnosed CML –CP. We assessed the correlation between the achievement of an early CCyR and event-free survival (EFS as defined by the IRIS trial) and overall survival (OS) in sequential phase II trials run at our institution in pts with newly diagnosed CML in CP treated with IM 400 mg daily (n=73), IM 400 mg BID (n=208), and 2nd TKI (n=154). Patient and disease characteristics at start of treatment were listed in Table 1. The overall rates of CCyR were 87 %, 91%, and 96% for pts receiving IM 400 mg/d, 400 mg BID, and 2nd TKI (p = 0.06). The rates of major molecular response (MMR) were 77%, 87%, and 89%, respectively (p = 0.05). Their 3-year EFS and OS rates were 85%, 92%, and 97% (p=0.01), and 93%, 97%, and 100% (p = 0.18), for pts receiving IM 400 mg daily, IM 400 mg BID, and 2nd TKI, respectively. The rates of 3-, 6-, and 12-month (mo) CCyR of the total group were 65%, 83%, and 89%, respectively. Pts with 3-, 6-, and 12-mo CCyR had statistically a significantly better outcome with 3-year EFS and OS rates of 98%, 97%, and 98% and 99%, 99%, and 99%, respectively compared to 83%, 72%, and 67% and 95%, 90%, and 94%, in pts who did not achieve a CCyR. There was no difference in EFS and OS in pts who achieved a CCyR whether they received IM 400 mg daily, IM 400 mg BID, or 2nd TKI (Table 2.). In conclusion, 2nd TKI induced higher rates of CCyR and MMR than IM. The achievement of an early CCyR remains a major determinant for outcome of pts with early CP-CML regardless of the TKI. Table 1. Patients characteristics Parameter 400mg 800mg 2nd TKI No. patient treated 73 208 154 Age (years) Median (range) 48 (15–78) 48 (17–84) 47 (18–85) Splenomegaly Yes (%) 16 (22) 59 (28) 41 (27) Hemoglobin (g/dl) Median (range) 12.7 (7.9–15.7) 12.4 (6.2–16.7) 12.2 (6.7–15.8) WBC (× 109/L) Median (range) 20.5 (1.6–277) 27.9 (2.2–283) 31.8 (0.8–342.5) Platelets (× 109/L) Median (range) 367 (103–1043) 353 (58–1476) 299 (73–2000) Peripheral blast % Median (range) 0 (0–2) 0 (0–12) 0 (0–7) baso % Median (range) 3 (0–16) 3 (0–19) 3 (0–19) Marrow blast % Median (range) 1 (0–6) 2 (0–14) 2 (0–8) baso % Median (range) 2 (0–9) 3 (0–15) 2 (0–12) Sokal risk, no (%) Low 50 (68) 132 (63) 118 (77) Intermediate 22 (30) 57 (27) 27 (18) High 1 (2) 19 (9) 9 (6) Ph + > 90 % yes (%) 67/72 (93) 195 (94) 133 (86) Clonal evolution (%) Yes (%) 2 (3) 7 (3) 11/151 (7) Table 2. Outcome Total group 3mo-CCyR 6mo-CCyR 12mo-CCyR y n p y n P Y n P 3-yr EFS 98 83 <0.001 97 72 <0.001 98 67 <0.001 3-yr OS 99 95 0.07 99 90 <0.001 99 94 0.001 IM 400mg 3-yr EFS 92 81 0.12 97 74 0.001 98 72 <0.001 3-yr OS 100 88 0.046 100 87 0.09 100 88 0.046 IM 800 mg 3-yr EFS 97 84 0.005 97 68 <0.001 98 58 <0.001 3-yr OS 98 97 0.93 99 92 0.001 99 100 0.03 2nd TKI 3-yr EFS 100 80 <0.001 99 67 <0.001 99 NA (no patient) NA 3-yr OS 100 100 NA (no death) 100 100 na 100 NA (no patient) NA p-value (PFS/OS) 0.13/0.24 0.41/0.92 0.9/0.6 Disclosures: Jabbour: Novartis: Honoraria; BMS: Honoraria. Kantarjian:Novartis: Research Funding. Cortes:Novartis: Research Funding; BMS: Research Funding; Pfizer: Consultancy, Research Funding.
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Bazhenov, Aleksei, Gennadii M. Galstian, Vera V. Troitskaya, Elena N. Parovichnikova, Sergei Makhinya, Mikhail Yu Drokov, Oleg Latishkevich, Alexandra Zvereva, and Valery G. Savchenko. "Outcomes of Pregnant Women with Acute Leukemia Treated for Life-Threatening Complications." Blood 128, no. 22 (December 2, 2016): 5976. http://dx.doi.org/10.1182/blood.v128.22.5976.5976.
Анотація:
Abstract Background: Acute leukemia (AL) during pregnancy is a rare event. The incidence of AL in pregnancy has been reported as one in 100 000 [1]. The serious complications may be caused in these women as by pregnancy as by AL and chemotherapy. Aim: To evaluate the outcomes of pregnant women with AL admitted in ICU due to life-threatening complications before delivery. Patients (Pts) and Methods: 20 pregnant women with AL admitted in the intensive care unit (ICU) due to the life-threatening complications were included in retrospective study (1996-2016). The reasons for ICU admission, chemotherapy, delivery features and outcomes of mothers and children were assessed. Results: 14 pts had acute myeloid leukemia (AML), 2 two of them with acute promyelocytic leukemia, 6 pts had acute lymphoblastic leukemia (ALL), age 18-40 yrs., median 30 yrs. Gestation age on ICU admission was 14-36 week, median 32 week. In 19 women AL was manifested during pregnancy, one woman had relapse of AL. 15 pts received induction chemotherapy before ICU admission (7+3, AIDA ALL-2009). 12 pts were severe neutropenic (WBC <0.5*109/l). The reasons for ICU admission were hypoxemic acute respiratory failure (ARF) (13 pts), acute renal failure (4 pts), sepsis (6 pts). ARF developed as result of pneumonia (10), pulmonary edema (2), ATRA syndrome (1). Lung ultrasound was used in pts with ARF to avoid radiation exposure. Bronchoalveolar lavage was done in 6 pts. The most common pathogen causing pneumonia was Pneumocystis jirovecii (4 pts), all of them were treated with trimethoprim/sulfamethoxazole. One woman had cytomegalovirus infection. 2 pts were noninvasive ventilated and 2 patients were mechanically ventilated. 4 pts received noradrenaline. Hemodialysis was required in 1 pregnant woman. All women had anemia (Hb levels from 65 to 114 g/l, median 85 g/l) and thrombocytopenia (from 10*109/l to 140*109/l, median 65*109/l). 1 woman with pneumocystic pneumonia had miscarriage and died 3 days after due to ARF. One woman died due to ARF on the 18-20 weeks of gestation age. Fast improvement was achieved in 3 women and they were discharged from ICU before delivery. Remained 15 women required urgent cesarean section and they delivered in ICU. In total, only 1 woman had vaginal birth, 17 pts required cesarean section. Cesarean sections were performed under general anesthesia in 13 pts and spinal anesthesia in 3 pts. Blood loss was from 200 to 1500 ml, median 803 ml. 16 children were born alive (APGAR scores 6-8), 1 child died 11 days after delivery due to ARF, 1 child was born with Down's syndrome and heart malformation. After delivery all women were discharged from ICU. In all pts the chemotherapy of AL was continued after delivery. The median overall survival of pts with acute leukemia who required ICU admission during pregnancy was 13.9 months. Conclusion: In the most pregnant pts life-threatening complication were associated with neutropenia. The frequent complication was ARF due to pneumonia, especially caused Pneumocystis jirovecii. Despite life-threatening complications, potentially adverse effect on the fetus of antibiotic therapy and chemotherapy the majority of pregnant women delivered the healthy children. Reference. 1.Hurley TJ, McKinnell JV, Irani MS. Hematologic malignancies in pregnancy. Obstet Gynecol Clin North Am. 2005; 32: 595-614. Disclosures No relevant conflicts of interest to declare.
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Cantinieaux, Brigitte F., Véronique Kerrels, Zaïna Kassengera, Marie Guivarch, Christophe Kails, Claudine Kanengele-Mukalay та Francine Ntakibirora. "Dissociation of Phospholipids “Flip-Flop” and CD16 Downregulation in Stimulated Neutrophils with FMLP and TNFα in Relationship with ROS Production." Blood 104, № 11 (16 листопада 2004): 2382. http://dx.doi.org/10.1182/blood.v104.11.2382.2382.
Анотація:
Abstract There are 3 kinds of PMN apoptosis: spontaneous, Fas or TNFα mediated system and ROS induced. The purpose of this work is to investigate the mechanisms of modulation of the CD16 decrease and the phospholipids “flip-flop” which are classically described as simultaneous events in apoptosis in relationship with the intracellular production of H2O2. Incubations during different times of PMN suspensions from healthy controls were performed in presence of Phorbol Myristate Acetate (PMA) at priming (10−9 M) and stimulating (2 10−6 M) concentrations, of fMLP 5 10−6M, of TNFα at 200ng/ml and finally of agonistic anti-Fas antibodies at 1 μg/ml. Inhibitors of PKC (staurosporin 10−5 M) and of the oxidase (DPI 400 μM) were tested with stimulating PMA. Standard two-colour flow-cytometry was performed for detection on one side of FITC-Annexin-V fixation and membrane impermeability to Propidium Iodide and on the other side of DCFH-DA for the intracellular H2O2 detection and CD16-PECy5. Results after 3 hours incubation are given in Table 1. Table 1. MEAN +/− SD CD16 % ANNEXIN V % DCFH-DA % n Wilcoxon test*: between spontaneous and the stimulant;°: between PMA and the inhibitor SPONTANEOUS 85 +/−7.1 7 +/− 4.7 1 +/−0.9 33 PMA 10-9 M 75 +/−9.0 9 +/− 5.2 1 +/− 0.9 10 PMA 2 10-6 M 21 +/−27.1 *** 51 +/− 21.4 *** 83 +/− 11.8 *** 33 PMA & STAURO 51 +/−23.3 °°° 23 +/− 16.0 °° 1 +/− 2.0 15 PMA & DPI 20 +/− 33.4 20 +/− 17.1 °° 3 +/− 6.2 20 fMLP 5 10-6M 41 +/− 19.3 *** 11 +/− 6.9 8 +/− 9.7 * 23 α TNF 200 ng/ml 42 +/− 19.2 * 5 +/− 3.5 * 8 +/− 9.5 * 7 Anti-Fas μg/ml 1 40 +/− 25.2 * 17 +/− 8.2 ** 1 +/− 0.9 7 Stimulating PMA induced both intracellular H2O2 production and apoptosis with increase of Annexin V fixation and CD16 down-regulation. Partial prevention of both features was observed when the ROS production was completely inhibited in presence of staurosporin. DPI had an effect on Annexin V fixation but no effect on CD16 decrease dissociating the 2 apoptotic features. Neutrophils activated with fMLP generated mainly extra-cellular H2O2 and did not undergo apoptosis measured thanks to Annexin V fixation, but CD16 down-regulation was observed. In presence of TNFα, a very slight stimulation of intracellular H2O2 production was observed with an inhibition of the Annexin V fixation and a CD16 down-regulation. The Fas mediated signalling system induced moderately both Annexin fixation and CD16 down-regulation without ROS production. Discussion: CD16 down-regulation seems to be present with fMLP and TNFα without other apoptotic features. Moreover, TNFα at 200ng/ml offers a protection for the phospholipids “flip-flop”. Dissociation of the classical PMN apoptotic features CD16 down-regulation and Annexin-V fixation with TNFα and fMLP demonstrates the complexity of the transduction signals used by these stimulants, and for the first time the independence of CD16 down-regulation from the phospholipids “flip-flop” which appears to be strongly dependent of intracellular ROS or more moderately of Fas stimulation and is never present without CD16 decrease. Only the presence of both events demonstrates apoptosis with certitude. On the opposite, it appears that the CD16 decrease alone cannot reflect the presence of the cell apoptosis. This decrease in absence of phospholipids “flip-flop”could be induced by extra-cellular ROS.
50
Oliveira, M., R. Santos, R. Chebel, and D. Demetrio. "10 Pregnancy rates following artificial insemination or embryo transfer in lactating Holstein cows." Reproduction, Fertility and Development 32, no. 2 (2020): 130. http://dx.doi.org/10.1071/rdv32n2ab10.
Анотація:
Excessive heat affects the fertility of high production lactating cows, and reduced pregnancy rates (PR) are observed during summer and early fall. Embryo production programs are used to produce more calves from high genetic merit animals, but could it also increase fertility by bypassing all the negative variables affecting the embryo development before Day 7 (oocyte development, ovulation, fertilization, early embryo development)? The data from AIs and embryo transfers (ET) between June 2017 and May 2019 were analysed. June, July, August, September, and October were called critical months (first-service AI conception rate dropped below 44%). The cows were located at Maddox Dairy in Riverdale, CA, USA, a Holstein herd that milks 3500 cows with a 305-day mature-equivalent milk production of 12 800 kg. First- and second-lactation cows were enrolled in a Presynch-Ovsynch oestrus-synchronization program and scheduled for the first AI at 86 days after calving or to receive an embryo 7 or 8 days after the expected heat. The embryos were produced invivo or invitro from Holstein donors and were transferred fresh or frozen. Blood was sampled on Day 30 after expected heat day (23 days after embryo transfer), and pregnancy was detected by the IDEXX PAG Bovine Pregnancy Test. Table 1 summarises the results, where ET PR% is the number of pregnant cows divided by the number of cows that received and embryo. All the cows synchronized for AI were bred, but only cows with the presence of a corpus luteum (CL) on ET day received an embryo. The presence of a CL was not detected in 28.7% (471/1642) of the cows (32.2% in the critical months and 25.7% in the others). Unfortunately, we could not detect the presence of a CL by ultrasonography every time we transferred embryos, so the nonovulation rate might be overestimated. The cows without a CL were considered open and used to calculate the adjusted PR (AdjPR%). Embryo transfer PR is superior to that of AI, especially during the critical months. Fresh invivo embryos have the most impact. When the cows without CLs are considered open, the difference between AI and ET is still evident for fresh invivo embryos. Besides producing animals with higher genetic merit, depending on the type of embryo used, ET can increase fertility in lactating Holstein cows, especially during the critical months. The other benefit of using ET is that cows that do not ovulate are synchronized right away, which is not the case for AI cows. Table 1.AI×embryo transfer in lactating Holstein cows1 from June 2017 to May 20192 Item Critical months (June to October) Other months (November to May) All year %PR n Adj PR% n %PR n Adj PR% n %PR n Adj PR% n Artificial insemination 41.2% 896 41.2% 896 47.7% 1767 47.7% 1767 45.5% 2663 2663 Fresh invivo embryo 62.7% 373 47.5% 493 69.5% 262 55.3% 329 65.5% 635 50.6% 822 Frozen invivo embryo 59.3% 221 44.8% 292 59.4% 256 47.3% 322 59.3% 477 46.1% 614 IVF fresh embryo 47.9% 167 36.2% 221 54.0% 363 43.0% 456 52.1% 530 40.8% 677 Total embryos 58.5% 761 44.2% 1006 60.2% 881 47.9% 1107 59.4% 1642 46.1% 2113 1Lactating Holstein cows, first and second lactation, first service, Presynch-Ovsynch, 85 DIM. 2PR%=the number of pregnant cows divided by the number of cows that received and embryo; AdjPR%=adjusted pregnancy rate.