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1
Reynolds, A. M., and K. M. Mullins. "0407 Sleep, Stress, Cardiovascular, and Psychological Health in College Students." Sleep 43, Supplement_1 (April 2020): A156. http://dx.doi.org/10.1093/sleep/zsaa056.404.
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Abstract Introduction Epidemiological studies have long established that sleep factors, stress, and cardiovascular health are related. College students often struggle with the demands of college life, which leads to increased stress, symptoms of depression and anxiety, and poor sleep. The focus of the current study was to examine habitual sleep habits in college students, in association with psychological factors and physiological factors. Methods Participants included 51 undergraduate students (18 men, average age M=20.25 years, SD=1.78) who wore wrist actigraphs to measure their typical sleep habits. After one week, participants completed questionnaires about psychological symptoms (i.e., depression, anxiety, and stress; Depression Anxiety Stress Scale, DASS-21) and subjective physiological symptoms (i.e., fatigue; Multidimensional Assessment of Fatigue Scale, MAF). Blood pressure and heart rate were measured using a wrist cuff. Results Overall total sleep time was 6.59 hours and sleep efficiency was 82.55%. Pearson correlational analyses revealed a negative moderate association between sleep efficiency and diastolic blood pressure (r(49) = -.318, p = .024). Global PSQI scores were moderately associated with stress (r(49) = .419, p = .002). MAF Global Fatigue Index scores revealed positive associations with depression (r(49) = .344, p =.014), anxiety (r(49) = .474, p<.001), and stress (r(49) = .620 p<.001). Heart rate was positively associated with depressive symptoms r(49) = .296, p= .035), stress symptoms r(49) = .447, p= .001), and fatigue r(49) = .456, p= .001). Conclusion As expected, college students’ sleep was short in duration and poor in efficiency. Sleep factors, cardiovascular factors, psychological factors, and stress were all related, demonstrating the importance of sleep on physiological and psychological health. More research should be conducted to further examine the relationships and directionality between sleep, psychological factors, and stress as there may be underlying mechanisms important for cardiovascular health. Support None.
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Micol, Jean-Baptiste, Nicolas Boissel, Aline Renneville, Sylvie Castaigne, Claude Gardin, Claude Preudhomme, and Herve Dombret. "The Role of Cytogenetic Abnormalities in Acute Myeloid Leukemia with NPM1 mutations and No FLT3 Internal Tandem Duplication." Blood 114, no. 22 (November 20, 2009): 1594. http://dx.doi.org/10.1182/blood.v114.22.1594.1594.
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Abstract Abstract 1594 Poster Board I-620 Background Nucleophosmin (NPM1) gene mutations are observed in almost one-third of adult acute myeloid leukemia (AML). If the favorable genotype defined by the presence of NPM1 mutations without fms-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is known to be associated with favorable outcome in patients with cytogenetically normal (CN) acute myeloid leukemia (AML), impact of these molecular abnormalities are still debated in those with cytogenetically abnormal (CA) AML. Patients and Methods We analyzed the role of these factors in newly diagnosed AML patients homogeneously treated in the Acute Leukemia French Association (ALFA) trials between 1990 and 2006 (ALFA 9000, 9801, 9802). Among 1529 patients (15-70 years of age), 554 patients were screened for NPM1 mutation, FLT3-ITD and have informative karyotype. Mutations screening were centrally performed according to previously described procedures. Karyotype was considered as normal if at least 20 normal marrow metaphases were present without any abnormal marrow metaphases. Favorable core binding factor (CBF) AML (74 patients) were excluded from this analysis. Results Among the 480 remaining patients, 137 (29%; median age 48 years, range 17-68) were NPM1 mutated, 22 of them (16%) having CA-AML. We found no difference between NPM1 mutated CN-AML patients (n=115) and NPM1 mutated non-CBF CA-AML patients (n=22) in term of complete remission rate (88% vs 83%; P= .49), overall survival (OS) (39% vs 38 % at 5 years, P= .85), event-free survival (EFS) (33% vs 25% at 5 years, P= .39). However, in the context of the favorable genotype, EFS was significantly longer in the 79 CN- than in the 16 CA-AML patients (41% vs 19% at 5 years ; P= .04) with a trend to better OS (51% vs 31% at 5 years ; P= .12). No significant differences were observed in patients with NPM1 mutated AML but FLT3-ITD (5-year EFS, 12% vs 40%; 5-year OS, 20% vs 60%; P= .47 and .27, respectively), even if the numbers of patients were here very low (35 CN- vs 5 CA-AML). More importantly, the favorable genotype was predictive of a longer EFS and OS in the 267 patients with CN-AML (5-year EFS, 41% vs 19%; 5-year OS, 51% vs 30%; P= .0001 and .001, respectively), while no differences were observed in the 213 patients with non-CBF CA-AML (5-year EFS, 19% vs 16%; 5-year OS, 31% vs 27%; P= .38 and .36, respectively). Conclusion As shown, patients with the favorable genotype but CA-AML had an outcome relatively similar to those with a non favorable genotype and either CA- or CN-AML. The favorable outcome associated with NPM1 mutation in the absence of FLT3-ITD might thus depend on the presence of a normal karyotype. We thus think that larger studies or overviews are needed to definitely answer this question. Disclosures Dombret: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
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Keating, Michael J., Susan O’Brien, Maher Albitar, Susan Lerner, William Wierda, and Hagop Kantarjian. "Extended Follow-Up of a Chemo-Immunotherapy Regimen FCR (Fludarabine, F; Cyclophosphamide, C; and Rituximab, R) as Initial Therapy for Chronic Lymphocytic Leukemia (CLL)." Blood 106, no. 11 (November 16, 2005): 2118. http://dx.doi.org/10.1182/blood.v106.11.2118.2118.
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Abstract Combination regimens are increasingly being used in CLL. The addition of R to F±C has increased the complete response (CR) rate in previously untreated patients (pts) with CLL. FCR was given to 300 previously untreated pts with CLL; 70.3% male, 33% Rai stage III-IV, with median value and ranges for age − 57 years (17–86), hemoglobin − 12.5G% (6.1–18.7), white cell count − 76 x 103/μl (2.1–620), platelets − 154 x 103/μl (8–406). 51% had splenomegaly. All pts fulfilled the NCIWG indications for therapy. 72% achieved CR, 10% nodular partial remission (NPR), and 12% PR. The pretreatment characteristic most strongly associated with CR was the beta-2-microglobulin level (P<.001) with significant differences between those with a value less than twice normal versus higher values. Advanced age (≥ 70 yrs), advanced stage, low hemoglobin (<11G%), low albumin (<3.6G%), and elevated BUN (>23mg%) were all significantly associated with a lower CR rate (P<.01). CD38 was not associated with CR. Mutation status, ZAP70, and FISH cytogenetics were not routinely measured. Median follow-up was 43 months (18–73). Several characteristics were associated with remission duration (R Dur). Multivariate analysis showed that (1) PCR for IgVH, (2) NCIWG response, and (3) flow responses were all independently associated with R Dur. PCR negativity for IgVH was most strongly correlated with R Dur. Seven of 79 PCR negative pts have relapsed at 31, 39, 43, 44, 62, 64, and 67 months. Response Patients 4-Yr. R Dur Θ 4-Year Surv. Flow CR† PCR Neg.$ *P<.01;𝛉Projected;†Marrow CD5+CD19<1%;$PCR IgVH CR 217 83%* 84%* 165/208 (79%) 69/160 (43%) NPR 31 64% 84% 10/27 (37%) 7/19 (37%) PR 37 38% 50% 10/26 (38%) 3/13 (23%) Overall 300 77% (CR+PR) 83% 185/261 (71%) NA There was no significant difference in survival between CR and NPR pts despite a significantly shorter R Dur (P<.01) for NPR pts. Survival was similar for progressive Rai 0-II and III-IV pts with projected four-year survival of >80%. The median survival for the 300 patients and various prognostic subgroups has not been reached. Second cancers occurred in 53 cases (20 with non-melanomatous skin cancers). Three cases of AML and 3 additional cases of myelodysplastic syndrome occurred. Autoimmune hemolytic anemia (AIHA) or red cell aplasia (RCA) occurred in 25 and 6 cases respectively. These complications remain a significant clinical problem in CLL. There was no significant difference in the IgA or IgM levels over time but a lower mean initial IgG (837±567mg%) versus 690±338mg% six months after FCR was completed (P<.005) was noted. 56/72 (78%) who failed or relapsed have been started on salvage therapy. The salvage response rate on retreatment with FCR+alemtuzumab was 9/17 (53%). More pts failing after initial CR or NPR claimed a second response (17/29, 59%) compared with the PR or refractory pts (3/20, 16%; P=.002). Multivariate analysis of characteristics associated with CR rate and survival for FCR and preceding non-R protocols demonstrated a significant advantage for FCR (P<.001). Conclusion When compared with other completed chemotherapy protocols without R, FCR significantly improved CR rate, time-to-progression and treatment failure, and overall survival establishing FCR as the most successful protocol which we have conducted to date.
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Coustan-Smith, Elaine, Jose Sancho, Frederick G. Behm, Michael L. Hancock, Bassem I. Razzouk, Raul C. Ribeiro, Gaston K. Rivera, et al. "Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in childhood acute lymphoblastic leukemia." Blood 100, no. 1 (July 1, 2002): 52–58. http://dx.doi.org/10.1182/blood-2002-01-0006.
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Abstract Early clearance of leukemic cells is a favorable prognostic indicator in childhood acute lymphoblastic leukemia (ALL). However, identification of residual leukemic cells by their morphologic features is subjective and lacks sensitivity. To improve estimates of leukemia clearance, we applied flow cytometric techniques capable of detecting 1 leukemic cell in 10 000 or more normal cells and prospectively measured residual leukemia in bone marrow samples collected on day 19 of remission-induction chemotherapy from 248 children with newly diagnosed ALL. In 134 samples (54.0%), we identified at least 0.01% leukemic cells (0.01%-< 0.1% in 51 samples [20.6%], 0.1%-< 1% in 36 [14.5%], and ≥ 1% in 47 [19.0%]). Among 110 children treated within a single chemotherapy program, the 5-year mean ± SE cumulative incidence of relapse or failure to achieve remission was 32.2% ± 6.5% for the 59 patients with 0.01% residual leukemic cells or greater on day 19 and 6.0% ± 3.4% for the 51 patients with less than 0.01% leukemic cells (P < .001). The prognostic value of day-19 bone marrow status defined by flow cytometry was superior to that defined by morphologic studies and remained significant after adjustment for other clinical and biologic variables. Lack of detectable leukemic cells on day 19 was more closely associated with relapse-free survival than was lack of detectable residual disease at the end of remission induction (day 46). Thus, approximately half of the children with ALL achieve profound clearance of leukemic cells after 2 to 3 weeks of remission-induction chemotherapy, and these patients have an excellent treatment outcome.
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Fu, Guodong, Ronald S. Chazen, Christina MacMillan, and Ian J. Witterick. "Discriminating Interpatient Variabilities of RAS Gene Variants for Precision Detection of Thyroid Cancer." JAMA Network Open 7, no. 5 (May 17, 2024): e2411919. http://dx.doi.org/10.1001/jamanetworkopen.2024.11919.
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ImportanceInterpatient variabilities in genomic variants may reflect differences in tumor statuses among individuals.ObjectivesTo delineate interpatient variabilities in RAS variants in thyroid tumors based on the fifth World Health Organization classification of thyroid neoplasms and assess their diagnostic significance in cancer detection among patients with thyroid nodules.Design, Setting, and ParticipantsThis prospective diagnostic study analyzed surgically resected thyroid tumors obtained from February 2016 to April 2022 and residual thyroid fine-needle aspiration (FNA) biopsies obtained from January 2020 to March 2021, at Mount Sinai Hospital, Toronto, Ontario, Canada. Data were analyzed from June 20, 2022, to October 15, 2023.ExposuresQuantitative detection of interpatient disparities of RAS variants (ie, NRAS, HRAS, and KRAS) was performed along with assessment of BRAF V600E and TERT promoter variants (C228T and C250T) by detecting their variant allele fractions (VAFs) using digital polymerase chain reaction assays.Main Outcomes and MeasuresInterpatient differences in RAS, BRAF V600E, and TERT promoter variants were analyzed and compared with surgical histopathologic diagnoses. Malignancy rates, sensitivity, specificity, positive predictive values, and negative predictive values were calculated.ResultsA total of 438 surgically resected thyroid tumor tissues and 249 thyroid nodule FNA biopsies were obtained from 620 patients (470 [75.8%] female; mean [SD] age, 50.7 [15.9] years). Median (IQR) follow-up for patients who underwent FNA biopsy analysis and subsequent resection was 88 (50-156) days. Of 438 tumors, 89 (20.3%) were identified with the presence of RAS variants, including 51 (11.6%) with NRAS, 29 (6.6%) with HRAS, and 9 (2.1%) with KRAS. The interpatient differences in these variants were discriminated at VAF levels ranging from 0.15% to 51.53%. The mean (SD) VAF of RAS variants exhibited no significant differences among benign nodules (39.2% [11.2%]), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) (25.4% [14.3%]), and malignant neoplasms (33.4% [13.8%]) (P = .28), although their distribution was found in 41.7% of NIFTPs and 50.7% of invasive encapsulated follicular variant papillary thyroid carcinomas (P &lt; .001). RAS variants alone, regardless of a low or high VAF, were significantly associated with neoplasms at low risk of tumor recurrence (60.7% of RAS variants vs 26.9% of samples negative for RAS variants; P &lt; .001). Compared with the sensitivity of 54.2% (95% CI, 48.8%-59.4%) and specificity of 100% (95% CI, 94.8%-100%) for BRAF V600E and TERT promoter variant assays, the inclusion of RAS variants into BRAF and TERT promoter variant assays improved sensitivity to 70.5% (95% CI, 65.4%-75.2%), albeit with a reduction in specificity to 88.8% (95% CI, 79.8%-94.1%) in distinguishing malignant neoplasms from benign and NIFTP tumors. Furthermore, interpatient differences in 5 gene variants (NRAS, HRAS, KRAS, BRAF, and TERT) were discriminated in 54 of 126 indeterminate FNAs (42.9%) and 18 of 76 nondiagnostic FNAs (23.7%), and all tumors with follow-up surgical pathology confirmed malignancy.Conclusions and RelevanceThis diagnostic study delineated interpatient differences in RAS variants present in thyroid tumors with a variety of histopathological diagnoses. Discrimination of interpatient variabilities in RAS in combination with BRAF V600E and TERT promoter variants could facilitate cytology examinations in preoperative precision malignancy diagnosis among patients with thyroid nodules.
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Chow, Ryan Dz-Wei, Jessica B. Long, Sirad Hassan, Stephanie B. Wheeler, Lisa Spees, Michael Leapman, Michael E. Hurwitz, Hannah Dzimitrowicz McManus, Cary Philip Gross, and Michaela Ann Dinan. "Evolution of systemic therapy from 2015 to 2019 for older patients in the United States with metastatic renal cell carcinoma." Journal of Clinical Oncology 41, no. 6_suppl (February 20, 2023): 610. http://dx.doi.org/10.1200/jco.2023.41.6_suppl.610.
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610 Background: Immune checkpoint inhibitors (IOs) and oral anti-cancer agents (OAAs) have demonstrated survival improvements in randomized trials of patients with metastatic renal cell carcinoma (mRCC). IOs were approved as second-line mRCC therapy in 2015 (nivolumab), followed by first-line approval in 2018 (ipilimumab/nivolumab). Real-world changes in overall treatment rates and IO usage have not been examined in patients over 65, who are often underrepresented in trials. Disparities in mRCC outcomes have persisted in the era of these novel therapies, raising the question of whether receipt of IOs and OAAs varies by race and ethnicity. Methods: We conducted a retrospective cohort study of Medicare beneficiaries over age 65 diagnosed with mRCC from 2015 through 2019 who were enrolled in fee-for-service Medicare Parts A, B, and D from 1 year prior to diagnosis through 1 year after presumed diagnosis or until death. We identified our cohort using diagnosis codes for primary or secondary kidney malignancy. We queried claims from 2014-2020, identifying receipt of IO, OAA, or other systemic therapies in the 2 months before through 1 year after diagnosis. Patients that received both IOs and OAAs were categorized as IO if both therapies were started within 60 days; otherwise, patients were categorized by the first therapy received. We assessed trends in treatment from 2015-2019, stratifying by race and ethnicity to compare non-Hispanic White (NHW) patients with Hispanic, Black, Asian, Pacific Islander, American Indian, Native Alaskan, or Other patients (grouped as non-NHW due to limited sample sizes). Results: We identified 15,407 patients who were diagnosed with mRCC between 2015-2019 and met study criteria. Non-Hispanic White patients comprised 84% of our sample. Receipt of IOs increased from 4% of patients in 2015 to 37% in 2019 ( P < .001). Among NHW patients, IO treatment receipt increased from 4% in 2015 to 38% in 2019 ( P < .001); for non-NHW patients, IO receipt grew from 3% in 2015 to 31% in 2019 ( P < .001). OAA usage decreased over time, from 31% of all patients in 2015 to 11% in 2019 ( P < .001). The percent of NHW patients treated with any systemic therapy increased from 51% in 2015 to 60% in 2019 ( P < .001), while there was no significant change for non-NHW patients (51% in 2015 to 54% in 2019; P = 0.27). Conclusions: Among Medicare beneficiaries, receipt of IO therapy for mRCC increased from 2015-2019. Receipt of any systemic therapy significantly increased over time for NHW patients, but not for non-NHW patients. [Table: see text]
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Fonseca, A. J. M., A. A. Dias-da-Silva, and A. L. G. Lourenço. "Effects of maize and citrus-pulp supplementation of urea-treated wheat straw on intake and productivity in female lambs." Animal Science 73, no. 1 (April 2001): 123–36. http://dx.doi.org/10.1017/s1357729800058124.
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AbstractTwo experiments with lambs given food indoors and individually penned were designed to study the effects of different levels of ground maize and citrus pulp as supplements of a diet based on urea-treated straw (5 kg urea per 100 kg straw) offered ad libitum over a period of 16 weeks (experiment 1) or 10 weeks (experiment 2). The voluntary intake, live-weight gain (LWG), organic matter digestibility (OMD), urinary allantoin-nitrogen (UAN) excretion and acetate clearance rate were measured. The lambs were blocked on weight and randomly assigned to the treatments described below. Ruminal outflow rate of the solid and liquid phases from the rumen were also measured in experiment 2.In experiment 1, 20 female lambs from the Ile-de-France breed, with an initial live weight (LW) of 43 (s.e. 3·3) kg were used. Wheat straw (WS) was supplemented with 50 g/kg of fish meal (FM) and with 0, 100, 200 or 300 g/kg of ground maize on a dry-matter (DM) basis (M0, M1, M2 and M3, respectively). In experiment 2, 25 female lambs from the Portuguese breed Churra-da-Terra-Quente, with an initial LW of 24·2 (s.e. 4·3) kg were used. The straw was offered ad libitum during 10 weeks and supplemented with 50 g/kg of FM and 0, 100, 200, 300, or 400 g/kg of dried citrus pulp on a DM basis (CP0, CP1, CP2, CP3 and CP4, respectively).During the experiments, all animals were moved to metabolism cages to measure OMD and UAN excretion. Two additional incubation studies were carried out with rumen fistulated rams (experiment 1) or cows (experiment 2) given the diets described above close to the maintenance feeding level.In experiment 1 daily straw DM intake linearly decreased (P < 0·05) from 21·6 to 17·7 g/kg LW and LWG linearly increased (P < 0·05) from 51 to 154 g/day for treatments M0, M1, M2 and M3, respectively. The rate of straw DM degradation was significantly decreased (P < 0·01) by maize supplementation. Straw OMD (kg/kg) was 0·562, 0·583, 0·547 and 0·520 and UAN (mg/day) was 620, 790, 854 and 859 for treatments M0, M1, M2 and M3, respectively. Acetate clearance rate, increased (P < 0·05) as the level of maize inclusion increased.In experiment 2 daily straw DM intake was 23·3, 25·8, 24·7, 23·5 and 18·6 g/kg LW per day and LWG was –9, 28, 44, 64 and 67 g/day for treatments CP0, CP1, CP2, CP3 and CP4, respectively. Supplementation significantly increased LWG (P < 0·001) but at the 400 g/kg level depressed straw DM intake. Straw OMD linearly decreased (P < 0·05) from 0·484 (CP0) to 0·428 (CP4) g/kg and UAN (mg/day) was 181, 303, 363, 384 and 392 for treatments CP0, CP1, CP2, CP3 and CP4, respectively. Rumen outflow rate of fibre particles was unaffected by supplementation while the outflow of liquid phase tended to be increased (P < 0·10). The rate of DM degradation was significantly reduced (P < 0·01) by citrus-pulp inclusion. Acetate clearance rate was unaffected (P > 0·05) by citrus-pulp supplementation.The results of these experiments demonstrate that supplementation of urea-treated straw with ground maize up to 200 g/kg or with citrus pulp up to 300 g/kg of the diet DM increased or did not depress straw intake, increased the supply of microbial protein and have no significant effect on straw digestibility. The efficiency of utilization of absorbed energy was apparently improved by maize but not by citrus-pulp supplementation.
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Abu Zaid, Mohammad, Paul C. Dinh, Patrick O. Monahan, Chunkit Fung, Omar El-Charif, Darren R. Feldman, Robert J. Hamilton, et al. "Adverse Health Outcomes in Relationship to Hypogonadism After Chemotherapy: A Multicenter Study of Testicular Cancer Survivors." Journal of the National Comprehensive Cancer Network 17, no. 5 (May 2019): 459–68. http://dx.doi.org/10.6004/jnccn.2018.7109.
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Background: This study examined the prevalence of hypogonadism, its clinical and genetic risk factors, and its relationship to adverse health outcomes (AHOs) in North American testicular cancer survivors (TCS) after modern platinum-based chemotherapy. Patients and Methods: Eligible TCS were <55 years of age at diagnosis and treated with first-line platinum-based chemotherapy. Participants underwent physical examinations and completed questionnaires regarding 15 AHOs and health behaviors. Hypogonadism was defined as serum testosterone levels ≤3.0 ng/mL or use of testosterone replacement therapy. We investigated the role of 2 single nucleotide polymorphisms (rs6258 and rs12150660) in the sex hormone–binding globulin (SHBG) locus implicated in increased hypogonadism risk in the general population. Results: Of 491 TCS (median age at assessment, 38.2 years; range, 18.7–68.4 years), 38.5% had hypogonadism. Multivariable binary logistic regression analysis identified hypogonadism risk factors, including age at clinical evaluation (odds ratio [OR], 1.42 per 10-year increase; P= .006) and body mass index of 25 to <30 kg/m2 (OR, 2.08; P= .011) or ≥30 kg/m2 (OR, 2.36; P= .005) compared with <25 kg/m2. TCS with ≥2 risk alleles for the SHBG SNPs had a marginally significant increased hypogonadism risk (OR, 1.45; P= .09). Vigorous-intensity physical activity appeared protective (OR, 0.66; P= .07). Type of cisplatin-based chemotherapy regimen and socioeconomic factors did not correlate with hypogonadism. Compared with TCS without hypogonadism, those with hypogonadism were more likely to report ≥2 AHOs (65% vs 51%; P= .003), to take medications for hypercholesterolemia (20.1% vs 6.0%; P<.001) or hypertension (18.5% vs 10.6%; P= .013), and to report erectile dysfunction (19.6% vs 11.9%; P= .018) or peripheral neuropathy (30.7% vs 22.5%; P= .041). A marginally significant trend for increased use of prescription medications for either diabetes (5.8% vs 2.6%; P= .07) or anxiety/depression (14.8% vs 9.3%; P= .06) was observed. Conclusions: At a relatively young median age, more than one-third of TCS have hypogonadism, which is significantly associated with increased cardiovascular disease risk factors, and erectile dysfunction. Providers should screen TCS for hypogonadism and treat symptomatic patients.
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Elliott, Cara G., Ally Murji, John Matelski, Adebanke Bianca Adekola, Jessica Chrzanowski, and Lindsay Shirreff. "Unexpected malignancy at the time of hysterectomy performed for a benign indication: A retrospective review." PLOS ONE 17, no. 4 (April 1, 2022): e0266338. http://dx.doi.org/10.1371/journal.pone.0266338.
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Objective To determine the proportion of patients undergoing hysterectomy for a benign indication who have unexpected malignancy (UM) on postoperative pathology and characterize the nature of UMs. Methods This was a multi-center, retrospective study of patients undergoing hysterectomy for a benign indication from July 2016 to December 2019 at 7 Ontario, Canada hospitals (4 academic, 3 community). Hysterectomies for invasive placentation, malignant, and premalignant indications were excluded. Primary outcome was rate of unexpected malignancy as defined by the number of patients with malignancy on final pathology divided by the total number of hysterectomy cases. Data was extracted from health records and electronic charts. Patient, surgical, and surgeon characteristics were compared between benign and UM groups using bivariate methods. Associations between UM status and perioperative variables were assessed using bivariate logistic regression. Results In the study period, 2779 hysterectomies were performed. UM incidence was 1.8% (51 malignancies/2779 cases), with one patient having two malignancies (total UMs = 52). The most common UM types were endometrial (27/52, 51.9%) and sarcoma (13/52, 25%). Patients with UM were older (57.2 ± 11.4 years vs. 52.8 ± 12.5 years, p = .015), had more previous laparotomies (2 (1.25, 2.0) vs. 1 (1.0, 1.0), p < .001), and higher BMI (29.7 ± 7.2 kg/m2 vs. 28.0 ± 5.9 kg/m2, p = .049) and ASA class (p < .028). Regarding surgical factors, patients with UM had more adhesions (p = .001), transfusions (p = .020), and blood loss (p = .006) compared to those with benign pathology. Patient characteristics most strongly associated with UM were age (OR 2.57, 95% CI 1.78–3.72, p < .001) and preoperative diagnosis of pelvic mass (OR 2.76, 95% CI 1.11–6.20, p = .019). Conclusion Incidence of UM at hysterectomy for benign indication was 1.8%. Several perioperative variables are associated with an increased chance of UM.
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Luna, Marcos. "Effect of reproductive indices and bovine somatotropin on milk yield in Holstein cows experiencing climatic sub-fertility." Mljekarstvo 73, no. 3 (June 19, 2023): 155–63. http://dx.doi.org/10.15567/mljekarstvo.2023.0302.
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This study aimed at determining the association between reproductive indexes and the total milk yield in non-planed lactations ≥600 days in sub-fertile Holstein cows treated or not with recombinant bovine somatotropin (rbST) and experienced prolonged hyperthermia. A total of 1141 cows with a single lactation were enrolled in the study: 622 were not treated with rbST (control) and 519 were treated with rbST (500 mg every 14 days throughout lactation). Across parities, control cows with >480 days open, produced 5642 kg more milk (p<0.01) than cows with <380 days open. rbST-treated cows produced 5994 more (p<0.01) kg of milk during the entire lactation than cows with <380 days open. In control cows receiving ≥10 services, the average total milk yield was 1811 kg higher (p<0.01) than in cows receiving ≤10 services. In rbST-treated cows, the average total milk yield was 1680 kg higher (p<0.01) in cows receiving ≥10 services, compared to cows receiving ≤10 services. The overall conception rate for all services was 51% and 73% (p<0.01) for control and rbST-treated cows, respectively. In conclusion, the greater the delay to get pregnant and the greater the number of services per lactation the higher the total milk yield per lactation were observed. Thus, in this unusual situation where sub-fertile cows are retained with >380 days open and they continue to be inseminated after 10 unsuccessful services, the impact of delayed conception is not entirely negative as this disadvantage is more than outweighed by the extra milk that is produced when lactation is extended.
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Tiu, Ramon V., Lukasz P. Gondek, Christine L. O'Keefe, Jungwon Huh, Mikkael A. Sekeres, Paul Elson, Michael A. McDevitt, et al. "New Lesions Detected by Single Nucleotide Polymorphism Array–Based Chromosomal Analysis Have Important Clinical Impact in Acute Myeloid Leukemia." Journal of Clinical Oncology 27, no. 31 (November 1, 2009): 5219–26. http://dx.doi.org/10.1200/jco.2009.21.9840.
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PurposeCytogenetics is the primary outcome predictor in acute myeloid leukemia (AML). Metaphase cytogenetics (MC) detects an abnormal karyotype in only half of patients with AML, however. Single nucleotide polymorphism arrays (SNP-A) can detect acquired somatic uniparental disomy (UPD) and other cryptic defects, even in samples deemed normal by MC. We hypothesized that SNP-A will improve detection of chromosomal defects in AML and that this would enhance the prognostic value of MC.Patients and MethodsWe performed 250K and 6.0 SNP-A analyses on 140 patients with primary (p) and secondary (s) AML and correlated the results with clinical outcomes and Flt-3/nucleophosmin (NPM-1) status.ResultsSNP-A is more sensitive than MC in detecting unbalanced lesions (pAML, 65% v 39%, P = .002; and sAML, 78% v 51%, P = .003). Acquired somatic UPD, not detectable by MC, was common in our AML cohort (29% in pAML and 35% in sAML). Patients with SNP-A lesions including acquired somatic UPD exhibited worse overall survival (OS) and event-free survival (EFS) in pAML with normal MC and in pAML/sAML with abnormal MC. SNP-A improved the predictive value of Flt-3 internal tandem duplication/NPM-1 status, with inferior survival seen in patients with additional SNP-A defects. Multivariate analyses confirmed the independent predictive value of SNP-A defects for OS (hazard ratio [HR] = 2.52; 95% CI, 1.29 to 5.22; P = .006) and EFS (HR = 1.72; 95% CI, 1.12 to 3.48; P = .04).ConclusionSNP-A analysis allows enhanced detection of chromosomal abnormalities and provides important prognostic impact in AML.
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Soverini, Simona, Sabrina Colarossi, Alessandra Gnani, Gianantonio Rosti, Fausto Castagnetti, Angela Poerio, Ilaria Iacobucci, et al. "Frequency, Distribution and Prognostic Value of ABL Kinase Domain (KD) Mutations in Different Subsets of Philadelphia-Positive (Ph+) Patients (Pts) Resistant to Imatinib (IM) by the Gimema Working Party on CML." Blood 106, no. 11 (November 16, 2005): 435. http://dx.doi.org/10.1182/blood.v106.11.435.435.
Abstract:
Abstract Using denaturing-high performance liquid chromatography and sequencing, we screened for ABL KD mutations 319 IM-resistant Ph+ pts. Median time between diagnosis and IM start at 400–600 mg/d was 40 (0–160) months. Median duration of IM was 27 (9–62) months. Evaluable pts were 256/319 (80%). At the time of analysis, 178/256 (70%) pts were in chronic phase (CP)(36 previously untreated, 142 post-IFN failure), 16 (6%) pts were in accelerated phase (AP), 26 (10%) pts were in myeloid blast crisis (myBC), 36 (14%) were in lymphoid blast crisis (lyBC) or had Ph+ acute lymphoblastic leukemia (ALL). One hundred and forty-two pts had primary resistance to IM, 114 had acquired resistance. Ninety-eight mutations were found in 91/256 (36%) pts. In 6 pts (2 Ph+ ALL, 2myBC, 1 lyBC, 1 CP post-IFN failure) multiple mutations simultaneously occurred. Mutations mapped to 15 codons, the most frequent ones being E255K/V (15 pts), Y253F/H (12 pts), T315I (10 pts), M351T (10 pts), F359V/I (10 pts), M244V (9 pts), G250E (8 pts). Three novel amino acid substitutions (F311I; E355D; F359I) and a novel mutated codon (P296H) were detected; biochemical/structural characterization will be presented. Mutations were found in 36/178 (26%) CP pts (4/36 (11%) previously untreated, 32/142 (22%) post-IFN failure), 7/16 (44%) AP pts, 19/26 (73%) myBC pts and 29/36 (81%) lyBC/Ph+ ALL pts (CP vs. AP, p=.04; AP vs. BC, p=.01; CP vs. BC, p<.001). Mutations were associated in 41/142 (29%) pts with primary resistance (4/8 hematologic and 37/134 cytogenetic) and in 50/114 (44%) pts with acquired resistance (10/50 pts who lost CCgR, 16/32 pts who lost HR, 24/32 pts who progressed to AP/BC)(primary vs. acquired, p=.009). Thirty-nine out of 49 pts with P-loop or T315I mutations had already progressed to AP/BC at the time of mutation detection; 4 additional pts subsequently progressed. In contrast, only 17 of the 42 remaining pts with mutations had progressed or subsequently progressed (p<.001). In a subset of 93 IM-resistant CP pts who were homogeneously treated in the CML/002/STI571 trial, with a follow-up ranging between 10 and 51 months, presence of a mutation was significantly associated with greater likelihood of progression (Log-Rank p<.001) and shorter survival (Log-Rank p=.005). Pts carrying P-loop or T315I mutations showed a particularly poor outcome both in terms of time to progression (Log-Rank p=.003) and in terms of survival (Log-Rank p=.02). We conclude that: a) there is a significantly higher probability of mutations according to disease phase (Ph+ ALL and BC>AP>CP); b) there is a significantly higher probability of mutations in pts with acquired resistance vs. pts with primary resistance; c) mutations, and in particular those affecting P-loop or codon 315, are associated with a worse outcome. Supported by AIL, AIRC, Fondazione del Monte di Bologna e Ravenna.
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Ginn, Brian K., Brian F. Cumming, and John P. Smol. "Assessing pH changes since pre-industrial times in 51 low-alkalinity lakes in Nova Scotia, Canada." Canadian Journal of Fisheries and Aquatic Sciences 64, no. 8 (August 1, 2007): 1043–54. http://dx.doi.org/10.1139/f07-078.
Abstract:
Diatom-based paleolimnological techniques were used to reconstruct lake acidification trends in 51 low-alkalinity Nova Scotia lakes that spanned gradients of dissolved organic carbon (DOC) concentrations and sulphate deposition. Pre-industrial, diatom-inferred pH values of these lakes were <6.8, with 31 lakes having pre-industrial pH < 6.0 and two lakes having pH < 5.5. Lakes in Kejimkujik National Park documented the greatest pH decline (–0.4 pH unit (±0.2)) since the 19th century, whereas those in northern parts of the province (e.g., Cape Breton Highlands National Park) experienced little or no acidification, with a net mean pH decline = –0.1 pH unit (±0.2). While the sulphate deposition and diatom-inferred pH changes have not been as great as those observed in other acidified areas of northeastern North America (e.g., Adirondack region of New York or New England), Nova Scotia lakes have experienced biological changes toward more acidophilous diatom assemblages, especially in lakes with low pre-industrial pH values (currently with high DOC concentrations) located in Kejimkujik National Park, which receives the highest loading of sulphate deposition in Nova Scotia. However, the generally low pre-industrial pH values inferred for most of the study lakes suggest that many of these lakes were somewhat naturally acidic, but acidified further as a result of atmospheric deposition.
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Abram, Simon G. F., Andrew Judge, David J. Beard, Hannah A. Wilson, and Andrew J. Price. "Temporal trends and regional variation in the rate of arthroscopic knee surgery in England: analysis of over 1.7 million procedures between 1997 and 2017. Has practice changed in response to new evidence?" British Journal of Sports Medicine 53, no. 24 (October 2, 2018): 1533–38. http://dx.doi.org/10.1136/bjsports-2018-099414.
Abstract:
ObjectivesWe investigated trends and regional variation in the rate of arthroscopic knee surgery performed in England from 1997–1998 to 2016–2017.DesignCross-sectional study of the national hospital episode statistics (HES) for England.MethodsAll hospital episodes for patients undergoing a knee arthroscopy between 1 April 1997 and 31 March 2017 were extracted from HES by procedure code. Age and sex-standardised rates of surgery were calculated using Office for National Statistic population data as the denominator. Trends in the rate of surgery were analysed by procedure both nationally and by Clinical Commissioning Group (CCG).ResultsA total of 1 088 872 arthroscopic partial meniscectomies (APMs), 326 600 diagnostic arthroscopies, 308 618 knee washouts and 252 885 chondroplasties were identified (1 759 467 hospital admissions; 1 447 142 patients). The rate of APM increased from a low of 51/100 000 population (95% CI 51 to 52) in 1997–1998 to a peak at 149/100 000 (95% CI 148 to 150) in 2013–2014; then, after 2014–2015, rates declined to 120/100 000 (95% CI 119 to 121) in 2016–2017. Rates of arthroscopic knee washout and diagnostic arthroscopy declined steadily from 50/100 000 (95% CI 49 to 50) and 47/100 000 (95% CI 46 to 47) respectively in 1997–1998, to 4.8/100 000 (95% CI 4.6 to 5.0) and 8.1/100 000 (95% CI 7.9 to 8.3) in 2016–2017. Rates of chondroplasty have increased from a low of 3.2/100 000 (95% CI 3.0 to 3.3) in 1997–1998 to 51/100 000 (95% CI 50.6 to 51.7) in 2016–2017. Substantial regional and age–group variation in practice was detected. In 2016–2017, between 11% (22/207) and 16% (34/207) of CCGs performed at least double the national average rate of each procedure.ConclusionsOver the last 20 years, and likely in response to new evidence, rates of arthroscopic knee washout and diagnostic arthroscopy have declined by up to 90%. APM rates increased about 130% overall but have declined recently. Rates of chondroplasty increased about 15-fold. There is significant variation in practice, but the appropriate population intervention rate for these procedures remains unknown.
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Cheng, Phoebe Tsz Man, Diego Villa, Alina S. Gerrie, Ciara L. Freeman, Graham W. Slack, David W. Scott, Joseph M. Connors, Laurie Helen Sehn, and Kerry J. Savage. "Outcome of elderly patients with classical Hodgkin lymphoma (HL) in British Columbia." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 8031. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.8031.
Abstract:
8031 Background: Outcomes in elderly patients (pts) with Hodgkin lymphoma (HL) have traditionally been poor. We evaluated the survival of elderly pts (>60 years [y]) with classical HL in British Columbia (BC). Methods: All pts aged >60 y newly diagnosed with classical HL from 1961 to 2019 were identified in the BC Cancer Lymphoid Cancer Database. Limited stage was defined as non-bulky (<10 cm) stage 1A/IB or 2A (before 2000 1B = advanced stage), with the remainder considered advanced stage. Results: Following exclusions (HIV positive n=4, incomplete data n=21, prior or concurrent other lymphoproliferative disease n=67), 713 pts were identified. With a median follow up of 6.0 y (0.1 - 24.0 y) in living pts, there has been an improvement in 5 y DSS/OS (both p<.001) by decade comparison: 1960s (n=52) 25%/17%; 1970s (n=75) 38%/31%; 1980s (n=90) 51%/43%; 1990s (n=115) 53%/42%; 2000s (n=180) 66%/57%; 2010s (n=201) 63%/53%. To account for advances in diagnosis, staging, supportive care, and therapy in the modern era, we evaluated the outcome of pts diagnosed since 01/1995. A total of 368 pts were treated with curative intent (Table). Most pts received multi-agent chemotherapy (n=359, 98%: ABVD[like] n=351, alkylator-based n=7, CHOP n=1), 8 pts had radiotherapy (RT) alone, and 1 pt had surgery (primary CNS HL). The 5 y DSS, PFS, and OS were 74%, 57%, and 62%, respectively. Increasing age was associated with inferior outcomes (5 y DSS/PFS/OS): 61-70 y (81%/70%/74%), 71-80 y (69%/47%/52%), and >80 y (59%/27%/31%) (DSS p=.011; PFS p<.0001; OS p<.0001). Of 318 pts that received bleomycin, 60 (19%) developed pulmonary toxicity, including 22 cases that occurred after cycles 1 and 2. Overall, 24/368 pts (7%) died of acute treatment toxicity (pulmonary [bleomycin n=10, radiation n=1], infection n=10, cardiac n=3). There was no association between age and developing bleomycin (p=.80) or lethal treatment toxicities (p=.74). Conclusions: The outcome of elderly pts with HL has improved in recent decades. However, treatment related toxicity remains a concern and use of multi-agent chemotherapy, particularly bleomycin-containing regimens, should be undertaken with caution. [Table: see text]
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Spiegl, Ulrich J. A., Philipp Schenk, Klaus John Schnake, Bernhard W. Ullrich, Georg Osterhoff, Max J. Scheyerer, Gregor Schmeiser, et al. "Treatment and Outcome of Osteoporotic Thoracolumbar Vertebral Body Fractures With Deformation of Both Endplates With or Without Posterior Wall Involvement (OF 4): Short-Term Results from the Prospective EOFTT Multicenter Study." Global Spine Journal 13, no. 1_suppl (April 2023): 36S—43S. http://dx.doi.org/10.1177/21925682221140831.
Abstract:
Study Design Multicenter prospective cohort study Objective To analyse therapeutical strategies applied to osteoporotic thoracolumbar OF 4 injuries, to assess related complications and clinical outcome. Methods A multicenter prospective cohort study (EOFTT) including 518 consecutive patients who were treated for an Osteoporotic vertebral compression fracture (OVCF). For the present study, only patients with OF 4 fractures were analysed. Outcome parameters were complications, Visual Analogue Scale, Oswestry Disability Questionnaire, Timed Up & Go test, EQ-5D 5L, and Barthel Index after a minimum follow-up of 6 weeks. Results A total of 152 (29%) patients presented with OF 4 fractures with a mean age of 76 years (range 41-97). The most common treatment was short-segment posterior stabilization (51%; hybrid stabilization in 36%). Mean follow up was 208 days (±131 days), mean ODI was 30 ± 21. Dorsoventral stabilized patients were younger compared to the other groups ( P < .001) and had significant better TuG compared to hybrid stabilization ( P = .049). The other clinical outcomes did not differ in the therapy strategies (VAS pain: P = 1.000, ODI: P > .602, Barthel: P > .252, EQ-5D 5L index value: P > .610, VAS-EQ-5D 5L: P = 1.000). The inpatient complication rate was 8% after conservative and 16% after surgical treatment. During follow-up period 14% of conservatively treated patients and 3% of surgical treated patients experienced neurological deficits. Conclusions Conservative therapy of OF 4 injuries seems to be viable option in patients with only moderate symptoms. Hybrid stabilization was the dominant treatment strategy leading to promising clinical short-term results. Stand-alone cement augmentation seems to be a valid alternative in selected cases.
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Kuguyo, Oppah, Racheal S. Dube Mandishora, Nicholas Ekow Thomford, Rudo Makunike-Mutasa, Charles F. B. Nhachi, Alice Matimba, and Collet Dandara. "High-risk HPV genotypes in Zimbabwean women with cervical cancer: Comparative analyses between HIV-negative and HIV-positive women." PLOS ONE 16, no. 9 (September 28, 2021): e0257324. http://dx.doi.org/10.1371/journal.pone.0257324.
Abstract:
Background High-risk human papillomavirus HPV (HR-HPV) modifies cervical cancer risk in people living with HIV, yet African populations are under-represented. We aimed to compare the frequency, multiplicity and consanguinity of HR-HPVs in HIV-negative and HIV-positive Zimbabwean women. Methods This was a cross-sectional study consisting of women with histologically confirmed cervical cancer attending Parirenyatwa Group of Hospitals in Harare, Zimbabwe. Information on HIV status was also collected for comparative analysis. Genomic DNA was extracted from 258 formalin fixed paraffin embedded tumour tissue samples, and analysed for 14 HR-HPV genotypes. Data was analysed using Graphpad Prism and STATA. Results Forty-five percent of the cohort was HIV-positive, with a median age of 51 (IQR = 42–62) years. HR-HPV positivity was detected in 96% of biospecimens analysed. HPV16 (48%), was the most prevalent genotype, followed by HPV35 (26%), HPV18 (25%), HPV58 (11%) and HPV33 (10%), irrespective of HIV status. One third of the cohort harboured a single HPV infection, and HPV16 (41%), HPV18 (21%) and HPV35 (21%) were the most prevalent. HIV status did not influence the prevalence and rate of multiple HPV infections (p>0.05). We reported significant (p<0.05) consanguinity of HPV16/18 (OR = 0.3; 95% CI = 0.1–0.9), HPV16/33 (OR = 0.3; 95% CI = 0.1–1.0), HPV16/35 (OR = 3.3; 95% CI = 2.0–6.0), HPV35/51 (OR = 6.0; 95%CI = 1.8–15.0); HPV39/51 (OR = 6.4; 95% CI = 1.8–15), HPV31/52 (OR = 6.2; 95% CI = 1.8–15), HPV39/56 (OR = 11 95% CI = 8–12), HPV59/68 (OR = 8.2; 95% CI = 5.3–12.4), HPV66/68 (OR = 7; 95% CI = 2.4–13.5), independent of age and HIV status. Conclusion We found that HIV does not influence the frequency, multiplicity and consanguinity of HR-HPV in cervical cancer. For the first time, we report high prevalence of HPV35 among women with confirmed cervical cancer in Zimbabwe, providing additional evidence of HPV diversity in sub-Saharan Africa. The data obtained here probes the need for larger prospective studies to further elucidate HPV diversity and possibility of selective pressure on genotypes.
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Manian, Farrin A., and John J. Ponzillo. "Compliance With Routine Use of Gowns by Healthcare Workers (HCWs) and Non-HCW Visitors on Entry Into the Rooms of Patients Under Contact Precautions." Infection Control & Hospital Epidemiology 28, no. 3 (March 2007): 337–40. http://dx.doi.org/10.1086/510811.
Abstract:
Background.Modified contact precautions (MCP), defined as routine donning of isolation gowns (along with routine gloving) on entry into the rooms of patients under contact precautions, regardless of the likelihood of direct exposure to the patient or their immediate environment, were instituted at our medical center to reduce nosocomial transmission of common hospital pathogens.Objectives.To study compliance with MCP policy regarding routine gowning in intensive care units (ICUs) and general wards and to determine the relationship between gown and glove use in the care of patients under MCP in ICUs.Design.Prospective observational study from February 20, 2004, through January 8, 2005, involving 2,110 persons (1,504 healthcare workers [HCWs] and 606 non-HCW visitors).Setting.A 900-bed tertiary care teaching community hospital.Results.Overall compliance with routine gown use was observed for 1,542 persons (73%), including 1,150 HCWs (76%) and 392 visitors (65%) (odds ratio [OR], 1.8 [95% confidence interval {CI}, 1.4-2.2]; P < .001). Visitors in the ICUs (186 [91%] of 204) were more likely than visitors in the general wards (202 [51%] of 398) to comply with gown use (OR, 10 [95% CI, 6.0-17.0]; P < .001). In logistic regression analysis, independent predictors of gown compliance among HCWs were female sex (OR, 2.3 [95% CI, 1.8-3.0]; P < .001) and ICU setting (OR, 2.2 [95% CI, 1.7-2.9]; P < .001). In the ICUs, gown use was highly predictive of glove use among HCWs (positive predictive value, 95%).Conclusion.Improvement in compliance with gown use at our medical center will require more-intensive educational efforts targeted at male HCWs and at HCWs and visitors on general wards. In the care of ICU patients under MCP, HCW compliance with gown use may be used as a proxy for their compliance with glove use.
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Guglielmelli, Paola, Giada Rotunno, Annalisa Pacilli, Elisa Rumi, Vittorio Rosti, Federica Delaini, Margherita Maffioli, et al. "Prognostic Impact of Bone Marrow Fibrosis in Primary Myelofibrosis: A Study of Agimm Group on 540 Patients." Blood 126, no. 23 (December 3, 2015): 351. http://dx.doi.org/10.1182/blood.v126.23.351.351.
Abstract:
Abstract Background. The prognostic significance of bone marrow (BM) fibrosis grade in pts with primary myelofibrosis (PMF) is debated. A fibrosis grade greater than 1 was associated with a 2-fold higher risk of death compared with pts with early/prefibrotic MF (grade 0) [Thiele J, Ann Hematol 2006]. Recent data suggest that more accurate prediction of survival is achieved when fibrosis grade is added to IPSS [Verner C, Blood 2008; Giannelli U, Mod Pathol 2012]. Aim. To analyze the prognostic impact of fibrosis in diagnostic BM samples of 540 WHO-2008 diagnosed PMF pts with extensive clinical and molecular information collected in 6 Italian centers belonging to AGIMM (AIRC-Gruppo Italiano Malattie Mieloproliferative). Methods. The clinical variables assessed were those previously identified as prognostically relevant in the IPSS score. Published methods were used to screen mutations of JAK2, MPL, CALR, EZH2, ASXL1, IDH1/2 and SRSF2. European consensus scoring system was used to grade fibrosis (on a scale of MF-0 to MF-3). The prognostic value of fibrosis with regard to overall survival (OS) was estimated by Kaplan-Meier method and Cox regression. Results. Pts' median age was 61y; median follow-up 3.7y; median OS 10.5y; 184 pts (34.1%) died. IPSS risk category: low 33.7%, Int-1 27.7%, Int-2 19.1%, High-risk 19.5%. Mutational rate: JAK2 V617F 62.6%, CALR 20.7% (type-1/1-like 77.7%, type2/2-like-2 21.4%), MPL W515 5.9%; 62 (11.5%) were triple negative (TN). 171 pts (31.7%) were High-Molecular Risk (HMR) category (Vannucchi AM, Leukemia 2013); mutation rate: EZH2 7.2%, ASXL1 22.2%, IDH1-2 2.4%, SRSF2 8.3%. According to fibrosis grading, 50 pts were MF-0 (9.3%), 180 MF-1 (33.3%), 196 MF-2 (36.3%), 114 MF-3 (21.1%). Compared with both MF-0 and MF-1, MF-2 and MF-3 pts presented more frequently constitutional symptoms (P<.0001), larger splenomegaly (P<.0001), greater risk of developing anemia (P<.0001) or thrombocytopenia (P=.003). We found a significant association (P<.0001) between IPSS higher/Int-2 risk categories and MF-2 and -3 (20.5% and 37.8%, respectively, vs 14.8% and 6.0% for MF-0 and -1). There was no correlation between fibrosis grade and phenotypic driver mutations; in particular, TN pts were equally distributed among MF fibrosis grades (10%, 10.6%, 14.3% and 8.8% from MF-0 to -3, respectively). Conversely, the frequency of HMR pts increased progressively according to fibrosis grade: 8 pts MF-0 (16%), 46 MF-1 (25.6%), 66 MF-2 (33.7%) and 51 MF-3 (44.7%) (P<.0001). In particular, we found a significant association between fibrosis grade and ASXL1 (12%, 15%, 23.5% and 36% from MF-0 to -3; P<.0001) and EZH2 (2%, 3.9%, 8.2%, 13.2%; P=.01) mutations. Also, pts with 2 or more HMR mutated genes were preferentially MF-2 or -3 ( 0%, 4.4% 10.2% and 10.5% from MF-0 to -3; P=.001). Median OS was significantly shorter in pts with MF-2 (OS 6.7y, HR 7.3, IC95% 2.7-20.0; P<.0001) and MF-3 (OS 7.2y, HR 8.7, IC95% 3.1-24.2; P<.0001) compared with MF-1 (14.7y; HR 3.9, IC95% 1.4-10.9, P=.008) and MF-0 (P<.0001) used as reference group (OS not reached) (Figure). Excluding MF-0, MF-2 and -3 maintained negative prognostic impact with HR 1.9 (1.3-2.6; P=.001) and 2.2 (1.5-3.3; P<.0001) respectively vs MF-1. The impact of fibrosis on OS was maintained when analysis was restricted to younger (≤65y) pts. In multivariate analysis using the individual IPSS variables, grade MF-2 and -3 were independently predictive of survival (HR 3.9 (1.4-10.8), and HR 4.2 (1.5-12.0), respectively, P=.008 for both). The negative impact on survival of MF-2/-3 was maintained regardless of IPSS category, HMR status, number of HMR mutated genes and driver mutations, included as covariates (Table). In low, Int-1 and Int-2, but not high-risk IPSS categories, MF-2/-3 associated with reduced survival (P<.03). Conclusions. Overall, these results indicate that higher grades (MF-2 and MF-3) of fibrosis correlate with defined clinical and molecular variables and independently negatively impact on OS in PMF, suggesting the opportunity to explore its value in the setting of clinical and molecular prognostic scores for PMF. Table. Multivariate Analysis Variables HR 95% CI P value HMR status 2.4 1.5-3.7 <.0001 HMR≥2mutations 4.3 2.8-6.4 .009 IPSS scoring Int1 2.9 1.6-5.1 <.0001 Int2 10.0 5.6-17.7 <.0001 High 9.7 5.5-17.2 <.0001 Driver mutations CALR type2 3.4 1.3-8.6 .010 JAK2/MPL 2.4 1.4-4.3 .003 TN 4.5 2.3-8.8 <.0001 Fibrosis MF-2/MF-3 3.8 1.4-10.6 .010 Figure 1. Figure 1. Disclosures Passamonti: Novartis: Consultancy, Honoraria, Speakers Bureau. Barbui:Novartis: Speakers Bureau. Vannucchi:Shire: Speakers Bureau; Novartis: Other: Research Funding paid to institution (University of Florence), Research Funding; Baxalta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.
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Hosseinzadeh, Shayan, Ata M. Kiapour, Daniel A. Maranho, Seyed Alireza Emami, Gabriela Portilla, Young-Jo Kim, and Eduardo N. Novais. "The metaphyseal fossa surrounding the epiphyseal tubercle is larger in hips with moderate and severe slipped capital femoral epiphysis than normal hips." Journal of Children's Orthopaedics 14, no. 3 (June 1, 2020): 184–89. http://dx.doi.org/10.1302/1863-2548.14.200010.
Abstract:
Purpose To compare the 3D morphology of the metaphyseal fossa among mild, moderate and severe stable slipped capital femoral epiphysis (SCFE) and normal hips. Methods We identified pelvic CT of 51 patients (55% male; mean 12.7 years (sd 1.9; 8-15)) with stable SCFE. In all, 16 of 51 hips (31%) had mild, 14 (27%) moderate and 21 (41%) severe SCFE. A total of 80 patients (50% male; mean age 11.5 years (sd 2.3; 8 to 15)) with normal hips who underwent pelvic CT due to abdominal pain made up the control cohort. CT scans were segmented, and the femur was reformatted using 3D software. We measured the metaphyseal fossa depth, width, length and surface area after the epiphysis was subtracted from the metaphysis in the 3D model. Results The metaphyseal fossa width was significantly larger in severe (adjusted difference: 6.9%; 95% confidence interval (CI) 2.1 to 11.8; p = 0.001), moderate (6.5%; 95% CI 0.8 to 12.2; p = 0.02) and mild SCFE (6.2%; 95% CI 0.8 to 11.6; p = 0.01), in comparison with normal hips. Severe SCFE showed larger fossa length compared with mild SCFE (6.8%; 95% CI 0.6 to 13.0; p = 0.02) and normal hips (6.0%; 95% CI 1.4 to 10.6; p = 0.004). The fossa surface area was larger in severe (3.5%; 95% CI 1.3 to 5.7; p < 0.001) and moderate SCFE (2.7%; 95% CI 0.1 to 5.2; p = 0.03) when compared with normal hips. There were no differences in fossa depth between SCFE and normal hips. Conclusion The metaphyseal fossa is wider and more extensive but not deeper in hips with moderate and severe SCFE in comparison with normal hips. Although hips with severe SCFE had larger length and surface area than mild SCFE hips, further research is needed to clarify whether enlargement of the metaphyseal fossa is a consequence of slip progression. Level of Evidence III
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Sekeres, Mikkael A., Jaroslaw P. Maciejewski, David W. Donley, David L. Grinblatt, Mohit Narang, James M. Malone, Rami S. Komrokji, et al. "A Study Comparing Dosing Regimens and Efficacy of Subcutaneous to Intravenous Azacitidine (AZA) for the Treatment of Myelodysplastic Syndromes (MDS)." Blood 114, no. 22 (November 20, 2009): 3797. http://dx.doi.org/10.1182/blood.v114.22.3797.3797.
Abstract:
Abstract Abstract 3797 Poster Board III-733 Background AZA, the most commonly used disease-modifying therapy for MDS in the US, demonstrates a survival advantage in higher-risk (International Prognostic Scoring System [IPSS] Int-2, High, or excess blasts) MDS subtypes. It was approved by the US FDA in 2004 as a 7-day per 28-day, subcutaneous (SC) regimen, based on response rates, with the 7-day intravenous (IV) route approved in 2007 based on efficacy data from the CALGB 8421 study and pharmacokinetic data. This registry allows for the evaluation of community based practices for dosing and effectiveness of IV compared with SC administration in MDS. Methods AVIDA, a prospective, longitudinal, multicenter US patient (pt), registry collects data from community-based hematology clinics on the history and management of pts with MDS treated with AZA. Interim analyses were conducted on data collected from October 2006 – May 2009 with investigator chosen regimens according to the most commonly used per pt. Responses used 2006 International Working Group criteria, quantified as hematologic improvement (HI) or better and were assessed centrally. ANCOVA models were used for dose per cycle analyses and generalized estimating equations were used for analyses of cycle delay. Cox models incorporating survival were used for multivariate analyses. Results Of 380 registry pts (median age, 75 years [range, 29-91], 104 (31%), female), 331 had MDS or oligoblastic leukemia, of whom 190 (57%) most commonly received AZA via IV and 141 (43%) by SC (both for a median of 4 cycles). Median time since MDS diagnosis was 2 months (range, 0-207), and 10% of pts had secondary MDS. Baseline bone marrow blast % was: <5% (46%); 5-10% (26%); 11-20% (14%); 21-30% (3%); and unknown (11%); IPSS cytogenetic groups were: good (61%); intermediate (10%); poor (17%); unknown (11%), with 6% and 9% of pts having a chromosome 7 and 7q abnormalities, respectively. IPSS risk groups were: Low (11%); Int-1 (36%); Int-2 (15%); High (6%); unknown (33%). ECOG performance status was: 0 (25%); 1 (53%); 2 (16%); 3 (6%). Only 17% of pts received the FDA-approved continuous 7-day dosing schedule; 51% received <7 days; 30% 7 days with breaks; and 2% >7 days. There were no significant differences between SC and IV AZA recipients for any of the above baseline parameters. At the interim analysis time point of 600 days, there were 21 deaths (15%) in the SC group and 32 deaths (17%) in the IV group. In univariate analyses, the following predicted for worse survival: black race (versus white, P = .02); higher-risk MDS (P = .02); cytogenetic abnormalities (P = .004); IPSS poor risk cytogenetic group (P = .04); low body mass index (BMI, P = .03), high blast % (P = .01)and baseline low hemoglobin (hgb, P = .007), or low platelets (plt, P = .05), all analyzed continuously. SC vs. IV dosing had no differing effect on HI rate (24% overall). In multivariate analyses, significant variables included low hgb (P = .006), low plt (P = .05), high blast % (P = .04), cytogenetic abnormalities (P = .05), and low BMI (P = .002). Delays in cycle start times (>28 days from previous cycle start) were related in multivariate analyses to higher blast % (P = .004), male gender (P = .03), dosing schedule (P = .02), a trend with IV dosing (P = .1), cytogenetic risk score (P = .1) and del (5q) (P = .09). Lower AZA doses per cycle were related in multivariate analyses to IV dosing (P = .001, on average 12 mg lower); older age (P = .01, on average .6mg less per year); BMI (P < .001), female gender (P < .001), and, as expected, dosing schedule (P = .04). Conclusions In this interim analysis of the ongoing AVIDA Registry, IV AZA appears equi-efficacious to SC, although dose, schedule, and treatment differed between groups. Though the FDA-approved continuous dosing schedule of AZA was infrequently used, this has not negatively impacted efficacy to date. In multivariate analyses, traditional IPSS predictors of survival are still relevant in pts treated with AZA. These analyses also reveal other potentially significant factors, such as low BMI, the effect of gender, and age on treatment intensity and clinical outcomes in patients receiving AZA. Disclosures: Baker: Celgene: Employment, Equity Ownership. Sullivan:Celgene: Employment, Equity Ownership.
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Brodsky, Robert A., Neal S. Young, Elisabetta Antonioli, Antonio M. Risitano, Hubert Schrezenmeier, Jörg Schubert, Anna Gaya, et al. "Multicenter phase 3 study of the complement inhibitor eculizumab for the treatment of patients with paroxysmal nocturnal hemoglobinuria." Blood 111, no. 4 (February 15, 2008): 1840–47. http://dx.doi.org/10.1182/blood-2007-06-094136.
Abstract:
The terminal complement inhibitor eculizumab was recently shown to be effective and well tolerated in patients with paroxysmal nocturnal hemoglobinuria (PNH). Here, we extended these observations with results from an open-label, non–placebo-controlled, 52-week, phase 3 clinical safety and efficacy study evaluating eculizumab in a broader PNH patient population. Eculizumab was administered by intravenous infusion at 600 mg every 7 ± 2 days for 4 weeks; 900 mg 7 ± 2 days later; followed by 900 mg every 14 ± 2 days for a total treatment period of 52 weeks. Ninety-seven patients at 33 international sites were enrolled. Patients treated with eculizumab responded with an 87% reduction in hemolysis, as measured by lactate dehydrogenase levels (P < .001). Baseline fatigue scores in the FACIT-Fatigue instrument improved by 12.2 ± 1.1 points (P < .001). Eculizumab treatment led to an improvement in anemia. The increase in hemoglobin level occurred despite a reduction in transfusion requirements from a median of 8.0 units of packed red cells per patient before treatment to 0.0 units per patient during the study (P < .001). Overall, transfusions were reduced 52% from a mean of 12.3 to 5.9 units of packed red cells per patient. Forty-nine patients (51%) achieved transfusion independence for the entire 52-week period. Improvements in hemolysis, fatigue, and transfusion requirements with eculizumab were independent of baseline levels of hemolysis and degree of thrombocytopenia. Quality of life measures were also broadly improved with eculizumab treatment. This study demonstrates that the beneficial effects of eculizumab treatment in patients with PNH are applicable to a broader population of PNH patients than previously studied. This trial is registered at http://clinicaltrials.gov as NCT00130000.
23
Schneider, François, Gérard Lefebvre, Michèle Ribolzi-Chery, Jean-Michel Bertin, and Robert Gay. "Purification et quelques propriétés de l'AMPc phosphodiestérase d'Arthrobacter crystallopoietes." Biochemistry and Cell Biology 66, no. 5 (May 1, 1988): 454–59. http://dx.doi.org/10.1139/o88-055.
Abstract:
cAMP phosphodiesterase was purified 8250-fold from extracts of Arthrobacter crystallopoietes, primarily by hydrophobic chromatography. The molecular weight of this enzyme was estimated as 51 000 by gel filtration and density-gradient centrifugation. The results suggest that the enzyme consists of two subunits with a molecular weight of 25 600. Properties of this enzyme are reported, including its negative cooperativity. This phosphodiesterase specifically catalyzes the hydrolysis of 3′,5′-cyclic nucleotides. Divalent ions either have no effect on activity or are weak inhibitors. Photooxidation of the enzyme with methylene blue and treatment with mercuribenzoates suggest that this enzyme may possess an imidazole group within its active site. The effects of thiols and Fe2+ on activity suggests that this enzyme may be a metalloenzyme.
24
Stem, Maxwell S., Danny A. Mammo, Yoshihiro Yonekawa, Bozho Todorich, Benjamin J. Thomas, and George A. Williams. "Centenarians With Age-Related Macular Degeneration." Journal of VitreoRetinal Diseases 1, no. 5 (August 21, 2017): 310–13. http://dx.doi.org/10.1177/2474126417726858.
Abstract:
Purpose: To report the clinical findings in patients ≥100 years old who have age-related macular degeneration (AMD). Methods: We identified patients ≥100 years old who had non-neovascular AMD, neovascular AMD or both. Results: Sixty-two patients were included. The mean (SD) age was 102 (1.4) years (range, 100-106 years). Most patients were white (n = 51, 82%), women (n = 51, 82%), and had at least 1 eye affected by neovascular AMD (n = 55, 89%). The mean Snellen visual acuity (VA) among eyes with neovascular AMD was worse than that for eyes with non-neovascular AMD (20/600 [range, 20/40-hand motions] vs 20/250 [range, 20/20-hand motions], respectively, P = .03). Eyes with an intact subfoveal ellipsoid zone (EZ) had much better mean VA than eyes with an absent or disrupted EZ (20/50 vs 20/500, P = .002). Conclusion: Most centenarians with AMD in our cohort had the neovascular form, and these individuals tended to have poorer vision than those with non-neovascular AMD. The presence of an intact subfoveal EZ is associated with better VA in eyes with neovascular or non-neovascular AMD compared to eyes with an absent or disrupted EZ.
25
Sullivan, Thomas P., John A. Krebs, and Paul K. Diggle. "Prediction of stand susceptibility to feeding damage by red squirrels in young lodgepole pine." Canadian Journal of Forest Research 24, no. 1 (January 1, 1994): 14–20. http://dx.doi.org/10.1139/x94-003.
Abstract:
This paper provides a forecast model to predict when and where significant feeding damage by red squirrels (Tamiasciurushudsonicus Erxleben) will occur in managed stands of lodgepole pine (Pinuscontorta Dougl. var. latifolia Engelm.). Information from 51 managed stands (average DBH > 6.0 cm) in the interior of British Columbia and from past squirrel population studies was used to formulate the model. Incidence of damage was significantly greater in stands originating from wildfire than from harvesting. Stands within the Montane Spruce biogeoclimatic zone had the highest levels of damage of the five zones sampled. There was no relationship between damage incidence and average stand diameter, area of managed stand, or site class. In a subset of stands where understory shrub data were available, shrub cover was positively related to incidence of damage. Major factors in the forecast model that influence stand susceptibility include (i) stand origin and proximity to mature timber; (ii) frequency of cone crops leading to squirrel population increases in juvenile pine; and (iii) shrub cover, which may provide security from predators. Additional potential factors include (iv) switching of predators from squirrels to snow-shoe hares (Lepusamericanus Erxleben) during peak years of the hare cycle and (v) fertilization. A decisionmaking profile is outlined for prespacing surveys to identify susceptible stands.
26
Dolbachev, A. P., N. A. Belov, and T. K. Akopyan. "Experimental study of single tracks obtained from a mixture of Ti and Al powders with varying selective laser melting parameters." Izvestiya Vuzov. Tsvetnaya Metallurgiya (Universities' Proceedings Non-Ferrous Metallurgy), no. 4 (August 13, 2021): 51–58. http://dx.doi.org/10.17073/0021-3438-2021-4-51-58.
Abstract:
The paper studies the effect of the laser scanning speed (vs) on the morphology of single tracks obtained from a mixture of Ti and Al powders in a stoichiometric ratio of 1 : 1 in longitudinal and cross sections. Droplets of splashed liquid were found on the outer surface of the track obtained at vs = 300 mm/s. Their appearance is resulted most likely from the release of gas bubbles formed due to the evaporation of aluminum having a lower melting point. A distortion of a single track along its length was observed with an increase in vs values up to 600 mm/s. It was found that tracks loose stability as the laser beam speed increases with «balls» formed on the track surface due to the significant Marangoni convection and the capillary liquid instability in the molten bath. An increase in the laser speed led to the appearance of pores mainly concentrated in the formed balls, and also influenced the track morphology in the cross section, namely, the width and height of the track, as well as the depth of substrate fusion. An increase in the scanning speed from 300 to 900 mm/s led virtually no substrate fusion, and the track width decreased from 194 to 136 μm, while its height increased almost 4 times – from 21 to 88 μm. X-ray microanalysis was conducted and element distribution maps were obtained to assess the structure of the tracks under study. It was found that the degree of liquid mixing in the molten bath is insufficient at scanning speeds of 300 and 600 mm/s, which leads to the segregation of elements over the track cross section. The central zone turns out to be enriched in aluminum, while titanium predominates at the base and is practically absent in the extreme zone (4.57 at.% Ti). X-ray microanalysis revealed the presence of unmelted titanium powder particles at vs = 900 mm/s. Presumably, it may be caused by insufficient laser power at such a high scanning speed.
27
Kara, K. "Milk urea nitrogen and milk fatty acid compositions in dairy cows with subacute ruminal acidosis." Veterinární Medicína 65, No. 8 (August 16, 2020): 336–45. http://dx.doi.org/10.17221/51/2020-vetmed.
Abstract:
The present study was aimed at comparing the milk urea nitrogen (MUN) and milk fatty acid (MFA) compositions in Holstein cows with subacute ruminal acidosis (SARA) to those values of Holstein cows that did not have SARA. Also, the correlations among rumen pH value and the compositions of MUN and MFA in milk were determined. Dairy cows (n = 16) with subacute ruminal acidosis (SARA) (pH value 5.60 ± 0.02) and control dairy cows (n = 16) (control) (pH value 6.20 ± 0.04) were studied. The MUN concentrations (578 µg/l) of the dairy cows with SARA was lower than those (1 315 µg/l) of the control dairy cows (P < 0.001). In the milk of the dairy cows with SARA, the unsaturated fatty acids (UFA), thrombogenic index (TI), and hypocholesterolemic fatty acid index (hcFA) decreased; but the saturated fatty acids (SFA), atherogenic (AI) and hypercholesterolemic fatty acid (HcFA) indexes (P < 0.01) increased. The rumen pH value and the concentration of the MUN were positively correlated with the proportions of the monounsaturated fatty acids (MUFA), polyunsaturated fatty acids (PUFA), omega-3 fatty acids (n-3), omega-6 fatty acids (n-6), omega-9 fatty acids (n-9), long-chain fatty acids (LCFA) and very-long-chain fatty acids (VLCFA) and the n-3/n-6 ratio of the milk samples (P < 0.05). Consequently, the dairy cow with SARA that are in early-lactation can affect the carbohydrate fermentation, fatty acid hydrogenation and protein degradation. The MUN concentration in the dairy cows with SARA seriously decreased. The SARA changes the milk fatty acid composition and decreases the MUFA, PUFA, n-3, oleic acid and hypocholesterolemic fatty acids and the hypocholesterolemic/hypercholesterolemic ratio (h/H) values of milk. Therefore, the nutritional and functional quality for human nutrition decreases in the milk of dairy cows with SARA.
28
Markussen, Marianne S., Marit B. Veierød, Giske Ursin, and Lene F. Andersen. "The effect of under-reporting of energy intake on dietary patterns and on the associations between dietary patterns and self-reported chronic disease in women aged 50–69 years." British Journal of Nutrition 116, no. 3 (June 6, 2016): 547–58. http://dx.doi.org/10.1017/s000711451600218x.
Abstract:
AbstractThe aim of this cross-sectional study was to investigate whether under-reporting of energy intake affects derived dietary patterns and the association between dietary patterns and self-reported chronic disease. Diets of 6204 women aged 50–69 years participating in the Norwegian Breast Cancer Screening Program were assessed using a 253-item FFQ. We identified dietary patterns using principal component analysis. According to the revised Goldberg cut-off method, women with a ratio of reported energy intake:estimated BMR<1·10 were classified as low energy reporters (n 1133, 18 %). We examined the associations between dietary patterns and self-reported chronic diseases by log-binomial regression, and the results are presented as prevalence ratios (PR) and CI. ‘Prudent’, ‘Western’ and ‘Continental’ dietary patterns were identified among all reporters and plausible reporters. The PR expressing the associations between the ‘Western’ and ‘Prudent’ dietary pattern scores and self-reported chronic diseases were consistently highest among plausible reporters except for joint/muscle/skeletal disorders. The largest difference in PR among plausible v. all reporters was found for the association between the ‘Prudent’ pattern and diabetes (PR for highest v. lowest tertile: PRall reporters 2·16; 95 % CI 1·50, 3·13; Ptrend<0·001; PRplausible reporters 2·86; 95 % CI 1·81, 4·51; Ptrend<0·001). In conclusion, our results suggest that under-reporting can result in systematic error that can affect the association between dietary pattern and disease. In studies of dietary patterns, investigators ought to consider reporting effect estimates both for all individuals and for plausible reporters.
29
Fungomeli, Maria, Anthony Githitho, Fabrizio Frascaroli, Saidi Chidzinga, Marcus Cianciaruso, and Alessandro Chiarucci. "A new Vegetation-Plot Database for the Coastal Forests of Kenya." Vegetation Classification and Survey 1 (June 16, 2020): 103–9. http://dx.doi.org/10.3897/vcs/2020/47180.
Abstract:
Biodiversity data based on standardised sampling designs are key to ecosystem conservation. Data of this sort have been lacking for the Kenyan coastal forests despite being biodiversity hotspots. Here, we introduce the Kenyan Coastal Forests Vegetation-Plot Database (GIVD ID: AF-KE-001), consisting of data from 158 plots, subdivided into 3,160 subplots, across 25 forests. All plots include data on tree identity, diameter and height. Abundance of shrubs is presented for 316 subplots. We recorded 600 taxa belonging to 80 families, 549 of which identified to species and 51 to genus level. Species richness per forest site varied between 43 and 195 species; mean diameter between 13.0 ± 9.8 and 30.7 ± 20.7 cm; and mean tree height between 5.49 ± 3.99 and 12.29 ± 10.61 m. This is the first plot-level database of plant communities across Kenyan coastal forests. It will be highly valuable for analysing biodiversity patterns and assessing future changes in this ecosystem. Taxonomic reference: African Plant Database (African Plant Database version 3.4.0). Abbreviations: DBH = diameter at breast height; GIVD = Global Index of Vegetation-Plot Databases; KECF-VPD = Kenyan Coastal Forests Vegetation Plot Database.
30
Portuguese, Andrew J., Aya Albittar, Emily C. Liang, Jennifer J. Huang, Alexandre V. Hirayama, Erik L. Kimble, Lorenzo Iovino, et al. "Lisocabtagene Maraleucel Versus Axicabtagene Ciloleucel: Efficacy and Toxicity in a Real-World Setting." Blood 142, Supplement 1 (November 28, 2023): 2131. http://dx.doi.org/10.1182/blood-2023-172978.
Abstract:
CD19 CAR-T therapy has revolutionized the management of high-risk and relapsed/refractory (R/R) large B-cell lymphoma (LBCL) but remains limited by significant toxicities leading to morbidity/mortality and high resource utilization. Single-arm studies have suggested differences in efficacy and toxicity across FDA-approved CD19 CAR-T products. A matching-adjusted indirect treatment comparison showed comparable efficacy and more favorable safety with lisocabtagene maraleucel (liso-cel) compared to axicabtagene ciloleucel (axi-cel), but was limited to clinical trial patients (pts) and suffered from an absence of patient-level data (Maloney, J Hematol Oncol, 2021). In the absence of randomized clinical trial data, adjusted comparative analyses using pt-level data are critically needed to guide product choice. Therefore, we retrospectively evaluated the impact of CAR-T product type on the outcomes of 129 LBCL pts receiving liso-cel or axi-cel per standard of care. All LBCL pts treated at our center with liso-cel or axi-cel outside of a clinical trial between 1/2018 and 5/2023 were included. Best response was determined within 3 months of CAR-T infusion by PET-CT imaging per Lugano 2014 criteria. Cytokine release syndrome (CRS) and immune-effector cell-associated neurotoxicity syndrome (ICANS) were graded using ASTCT criteria. Of 129 total pts, 37% (n=48) and 63% (n=81) received liso-cel and axi-cel, respectively. Seven pts received out-of-specification liso-cel on an expanded access protocol. Pts who received liso-cel were older (median 67 vs 62 years, p=.003). Other baseline characteristics, including male sex (liso-cel vs axi-cel: 63% vs 69%, p=.4), HCT-CI score (1.0 vs 1.0, p=.6), pre-lymphodepletion (LD) LDH (178 vs 214 U/L, p=.14) and ALC (0.65 vs 0.60 x 10³/µL, p=.3), largest lesion diameter (3.1 vs 3.0 cm, p=.4), and extranodal disease (56% vs 56%, p>.9) were similar. The vein-to-vein time (time from leukapheresis to CAR-T infusion) was longer for liso-cel: median, 35 vs 27 days (p<.001). After liso-cel, the total inpt duration was shorter (median, 5 vs 14 days, p<.001) and fewer pts had ≥2 admissions (8.3% vs 22%, p=0.043). In pts with measurable disease prior to LD (n=113), we observed comparable efficacy with liso-cel vs axi-cel: ORR, 82% vs 77% (p=.5); CR, 56% vs 51% (p=.8). After a median follow-up of 17.7 months, we observed comparable 1-year outcomes with liso-cel vs axi-cel: duration of response (DOR), 56% vs 61% (p=.7); progression-free survival (PFS), 47% vs 47% (p=.99; Figure); and overall survival (OS), 69% vs 60% (p=.39). In pts evaluable for toxicity assessment (n=129), liso-cel was associated with lower rates of CRS and ICANS compared to axi-cel: any grade CRS, 62% vs 88% (p=.001); ICANS any grade, 32% vs 56% (p=.010); days with fever, median 2 vs 5 days (p<.001). Grade 3-4 CRS, 2.1% vs 9.9% (p=.2) or grade 3-4 ICANS, 23% vs 19% (p=0.5) were similar. We measured lower peak serum inflammatory markers after liso-cel: CRP, 58 vs 114 mg/L (p<.001); ferritin, 622 vs 1,315 ng/mL (p=0.007); IL-6, 55 vs 204 pg/mL (p=.010); and D-dimer, 1.4 vs 2.4 mg/L (p=.017). The incidence of infectious complications after liso-cel vs axi-cel was as follows: bacteremia: 6% vs 9% (p=.7); CMV viremia: 13% vs 6.2% (p=.3). Post-infusion median nadir cytopenias were less severe after liso-cel: ANC, 0.32 vs 0.04 x 10³/µL (p<.001); Plt, 69 vs 35 x 10³/µL (p=.003); and Hgb, 8.9 vs 8.2 g/dL (p<.001). Fewer pts developed severe neutropenia after liso-cel: 72% vs 93% (p=0.002). In multivariable analysis including pre-LD LDH and ALC, largest lesion diameter, age and HCT-CI score, we could not confirm an independent impact of the product type on CR, PFS, or OS ( Table). However, axi-cel remained independently associated with a higher odds of any grade CRS (adjusted OR [aOR] 4.56, 95% CI 1.65-13.5, p=.004) and any grade ICANS (aOR 3.44, 95% CI 1.42-8.85, p=.008). Our analysis of CD19 CAR-T therapy for R/R LBCL in the non-trial setting showed similar rates of durable responses following liso-cel and axi-cel. Pts who received liso-cel were older, with otherwise comparable baseline characteristics. Although liso-cel was associated with less toxicity, its vein-to-vein time was longer. In multivariable analyses, pre-LD LDH and largest lesion diameter were the only factors independently associated with response outcomes. We conclude that liso-cel is a robust alternative to other CD19 CAR-T products in older and frailer LBCL pts.
31
De Simoni, Ottavia, Marco Scarpa, Caterina Soldà, Francesca Bergamo, Sara Lonardi, Alberto Fantin, Pierluigi Pilati, and Mario Gruppo. "Could Total Neoadjuvant Therapy Followed by Surgical Resection Be the New Standard of Care in Pancreatic Cancer? A Systematic Review and Meta-Analysis." Journal of Clinical Medicine 11, no. 3 (February 3, 2022): 812. http://dx.doi.org/10.3390/jcm11030812.
Abstract:
Background. Total neoadjuvant therapy (TNT), intended as induction chemotherapy (IC) followed by radio-chemotherapy (RCT), has been taking hold in the treatment of pancreatic ductal adenocarcinoma (PDAC). The aim of this review is to summarize the available evidence on the role of TNT followed by curative surgery. Methods. Eligible studies were those reporting on patients with PDAC undergoing curative surgery after TNT. The primary endpoint was overall survival (OS). Results. A total of 1080 patients with PDAC who had undergone TNT were analyzed. The most common IC regimen was Gemcitabine (N 620, 57%). Toxicity during IC varied from 14% to 51%. Disease progression during IC varied from 3% to 25%. 607 (62%) patients underwent curative surgery after IC + CRT. In meta-analysis, the available data on lymph node metastases radicality and 2 years OS had better results in favor of TNT groups (OR 1.77, 95% CI 1.20–2.60, p = 0.004 and OR 2.03, 95% CI 1.19–3.47, p = 0.01 and OR 1.64, CI 1.09–2.47, p = 0.02, respectively). Conclusions. Despite the heterogeneity of the studies, different selection criteria, and non-negligible drop-out rate, TNT demonstrated a potential superiority to NAT without CRT in oncological and pathological outcomes, even if the main differences seem to depend on the IC regimen.
32
Chernova, L. N. "ESSENTIAL TRACE ELEMENTS: POSSIBLE ROLE IN THE ETIOPATHOGENESIS OF AUTISM SPECTRUM DISORDER AND SPEECH DEVELOPMENT DELAY IN CHILDREN OF DIFFERENT AGES." Trace Elements in Medicine (Moscow) 22, no. 1 (March 2021): 44–51. http://dx.doi.org/10.19112/2413-6174-2021-22-1-44-51.
Abstract:
An imbalance of trace elements plays a significant role in the etiopathogenesis of Autism Spec-trum Disorder (ASD) and Speech Development Delay (SDD). The aim of the study was to analyze an essential trace elements content in the hair samples of children with ASD and SDD for better understanding age and gender related diversity. The study included 258 children with ASD and 239 children with SDD. Control group consisted of 620 healthy children of similar age. All children were divided into two age categories (1.5 to 3 years old and 4 to 13 years old). It was shown that girls with ASD had more deviations in hair essential trace elements levels than boys. Children with ASD and SDD (1.5 to 3 years old) had significantly decreased hair iodine level (by 48-58%, p < 0.0001). Low iodine level can be a significant indicator of mental and speech development delay. Normalization of hair iodine level in older boys with ASD accompanied by significant decrease in hair cobalt level (by 24%, p = 0.0001) may reflect age-related characteristics of iodine and cobalt metabolism. Low hair manganese level (by 12-44%, p < 0.05) was observed in all groups of children. It’s possibly associated with decreased manganese excretion from the body and can provoke manganese-induced neurotoxicity. The decrease in copper levels in girls of different ages (by 9-17%, p < 0.01) is probably influenced by hormonal status and earlier onset of puberty.
33
Sampson, M., M. Ruddel, and R. J. Elin. "Effects of specimen turbidity and glycerol concentration on nine enzymatic methods for triglyceride determination." Clinical Chemistry 40, no. 2 (February 1, 1994): 221–26. http://dx.doi.org/10.1093/clinchem/40.2.221.
Abstract:
Abstract We compared the effects of specimen turbidity and glycerol concentration on nine enzymatic methods for triglyceride measurement. We assayed 51 specimens with triglyceride concentrations of 0.85-8.21 mmol/L (75-727 mg/dL) and turbidity at 420 nm equivalent to > or = 0.1 mmol/L (8.8 mg/dL) triglyceride (measured as part of our comparison method). The data were analyzed by multiple regression, which gave coefficients for the effects of glycerol concentration and the change in turbidity during the reaction. The effects of specimen turbidity and glycerol concentration were method-dependent and ranged from 6.20% to -15.67% of the measured result. The magnitude of the turbidity effect (in assays with a significant turbidity interference) was similar to that for glycerol (in assays with a significant glycerol interference). A triglyceride assay with a bichromatic measurement was less subject to interference from turbidity.
34
Todd, MB, JA Waldron, TA Jennings, LS Rome, SD Markowitz, TR Holford, JP Gardner, JP Wolak, and HL Malech. "Loss of myeloid differentiation antigens precedes blastic transformation in chronic myelogenous leukemia." Blood 70, no. 1 (July 1, 1987): 122–31. http://dx.doi.org/10.1182/blood.v70.1.122.122.
Abstract:
Abstract In order to determine whether antigenic patterns alter with disease progression and are thereby suggestive of impending blast crisis in chronic myelogenous leukemia, 50 bone marrow biopsy specimens from 32 patients were examined retrospectively using indirect immunoperoxidase labeling with three monoclonal antibodies that detect myeloid antigens. Monoclonal antibodies PMN13F6, PMN7C3, and PMN8C7 detect human neutrophil antigens that first appear at the myeloblast, promyelocyte, and metamyelocyte stages of differentiation, respectively, and persist throughout later differentiation. Percentages of antigen-positive bone marrow cells during the chronic phase were compared with percentages of antigen-positive cells at blast transformation, and time from bone marrow biopsy until blast crisis was correlated with the percentage of bone marrow cells expressing these antigens. Bone marrow biopsy samples from patients in the chronic phase who continue to remain clinically stable 4 to 106 months after biopsy expressed PMN13F6 antigen on 82% +/- 9% (mean +/- SD) of cells, PMN7C3 antigen on 62% +/- 14% of cells, and PMN8C7 on 68% +/- 14% of cells. Bone marrow biopsy specimens obtained from patients 1 or more years prior to blast transformation expressed PMN13F6 antigen on 81% +/- 12%, PMN7C3 antigen on 71% +/- 16%, and PMN8C7 on 64% +/- 16% of cells. Bone marrow biopsy samples obtained between 2 months and 1 year prior to blast crisis expressed PMN13F6 antigen on 68% +/- 15%, PMN7C3 on 51% +/- 17%, and PMN8C7 antigen on 46% +/- 18% of cells. Bone marrow biopsy specimens taken at the time of blast transformation expressed PMN13F6 antigen on 20% +/- 25%, PMN7C3 antigen on 19% +/- 25%, and PMN8C7 antigen on 13% +/- 25% of cells. The difference between the mean of antigen-positive cells from bone marrow biopsy samples obtained at the time of blast crisis was significant compared with the mean of positive cells from biopsy specimens obtained at all other phases of the disease (P less than .001 for all three antibodies). There was a positive correlation between loss of myeloid antigens and disease progression as determined by simple regression of log time and correlation analysis (PMN13F6, r = .6533, P less than .005; PMN7C8, r = .6304, P less than .005; PMN8C7, r = .5215, P less than .05). There was a negative correlation between percentage of immature cells and time to blastic crisis (r = -.6206, P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)
35
Todd, MB, JA Waldron, TA Jennings, LS Rome, SD Markowitz, TR Holford, JP Gardner, JP Wolak, and HL Malech. "Loss of myeloid differentiation antigens precedes blastic transformation in chronic myelogenous leukemia." Blood 70, no. 1 (July 1, 1987): 122–31. http://dx.doi.org/10.1182/blood.v70.1.122.bloodjournal701122.
Abstract:
In order to determine whether antigenic patterns alter with disease progression and are thereby suggestive of impending blast crisis in chronic myelogenous leukemia, 50 bone marrow biopsy specimens from 32 patients were examined retrospectively using indirect immunoperoxidase labeling with three monoclonal antibodies that detect myeloid antigens. Monoclonal antibodies PMN13F6, PMN7C3, and PMN8C7 detect human neutrophil antigens that first appear at the myeloblast, promyelocyte, and metamyelocyte stages of differentiation, respectively, and persist throughout later differentiation. Percentages of antigen-positive bone marrow cells during the chronic phase were compared with percentages of antigen-positive cells at blast transformation, and time from bone marrow biopsy until blast crisis was correlated with the percentage of bone marrow cells expressing these antigens. Bone marrow biopsy samples from patients in the chronic phase who continue to remain clinically stable 4 to 106 months after biopsy expressed PMN13F6 antigen on 82% +/- 9% (mean +/- SD) of cells, PMN7C3 antigen on 62% +/- 14% of cells, and PMN8C7 on 68% +/- 14% of cells. Bone marrow biopsy specimens obtained from patients 1 or more years prior to blast transformation expressed PMN13F6 antigen on 81% +/- 12%, PMN7C3 antigen on 71% +/- 16%, and PMN8C7 on 64% +/- 16% of cells. Bone marrow biopsy samples obtained between 2 months and 1 year prior to blast crisis expressed PMN13F6 antigen on 68% +/- 15%, PMN7C3 on 51% +/- 17%, and PMN8C7 antigen on 46% +/- 18% of cells. Bone marrow biopsy specimens taken at the time of blast transformation expressed PMN13F6 antigen on 20% +/- 25%, PMN7C3 antigen on 19% +/- 25%, and PMN8C7 antigen on 13% +/- 25% of cells. The difference between the mean of antigen-positive cells from bone marrow biopsy samples obtained at the time of blast crisis was significant compared with the mean of positive cells from biopsy specimens obtained at all other phases of the disease (P less than .001 for all three antibodies). There was a positive correlation between loss of myeloid antigens and disease progression as determined by simple regression of log time and correlation analysis (PMN13F6, r = .6533, P less than .005; PMN7C8, r = .6304, P less than .005; PMN8C7, r = .5215, P less than .05). There was a negative correlation between percentage of immature cells and time to blastic crisis (r = -.6206, P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)
36
Fryburg, D. A. "Insulin-like growth factor I exerts growth hormone- and insulin-like actions on human muscle protein metabolism." American Journal of Physiology-Endocrinology and Metabolism 267, no. 2 (August 1, 1994): E331—E336. http://dx.doi.org/10.1152/ajpendo.1994.267.2.e331.
Abstract:
The effect of a 6-h intra-arterial infusion of recombinant human (rh) insulin-like growth factor I (IGF-I) on forearm muscle metabolism was studied in 19 postabsorptive subjects. Forearm glucose, lactate, and phenylalanine (Phe) balances, as well as estimates of protein degradation (Phe Ra) and synthesis (Phe Rd) were measured before and at 3 and 6 h into an infusion of rhIGF-I at a dose of 1.8 (n = 6), 6.0 (n = 8), or 10.0 (n = 5) micrograms.kg-1.h-1. In response to intra-arterial IGF-I, deep venous IGF-I rose by 55, 141, and 315%, respectively (all P < 0.01), and forearm blood flow accelerated by 75 (1.8 microgram), 213 (6.0 micrograms), and 159% (10.0 micrograms; all P < 0.02). No change in forearm glucose uptake was observed at the lowest dose, whereas four- to sixfold increases were observed at both the 6 and 10 micrograms.kg-1.h-1 doses (both P < 0.02). Forearm Phe balance shifted positively at all three doses by 27 +/- 6, 48 +/- 7, and 51 +/- 9 nmol.min-1 x 100 ml-1, respectively (all P < 0.01). At all three doses, Phe Rd increased comparably by 49-74% (all P < 0.05). At the 6.0 and 10.0 but not the 1.8 microgram.kg-1.h-1 dose, Phe Ra decreased by approximately 45% (P < 0.02). Forearm muscle metabolism was also studied in the contralateral non-IGF-infused arm at these three doses. Despite increases in deep venous IGF-I up to 517 ng/ml due to recirculating IGF-I (10.0 micrograms.kg-1.h-1 dose), contralateral forearm muscle glucose, lactate, or Phe handling did not change. In conclusion, intra-arterial IGF-I exhibits growth hormone-like effects at all doses tested, whereas the insulin-like effects are observed at higher doses; these effects appear dependent on the route of administration.
37
Plavec, Tanja, Žiga Žagar, and Martin Kessler. "Klinisch-pathologische Befunde, postoperative Überlebenszeiten und prognostische Faktoren bei Hunden mit primären Lungenkarzinomen." Tierärztliche Praxis Ausgabe K: Kleintiere / Heimtiere 50, no. 05 (October 2022): 317–28. http://dx.doi.org/10.1055/a-1949-0125.
Abstract:
Zusammenfassung Einleitung Primäre Karzinome der Lunge (PLK) beim Hund sind selten, ihre Behandlung erfolgt chirurgisch. Ziel dieser Studie war die Untersuchung klinisch-pathologischer Befunde, postoperativer medianer Überlebenszeiten (mÜZ) und prognostischer Faktoren. Material und Methoden Retrospektive Auswertung von 61 Hunden mit 62 PLK, die zwischen 2007 und 2017 chirurgisch behandelt wurden. Die statistische Auswertung erfolgte mittels Kaplan-Meier und Logrank Methoden. Ergebnisse Von 62 PLKs lagen 35 (56 %) peripher im Lungenlappen, 21 (34 %) hilusnah und 6 (10 %) betrafen den gesamten Lungenlappen. In 49 Fällen lagen differenzierte Adenokarzinome vor; niedrig differenzierte bzw. anaplastische Karzinome (n = 10) und Plattenepithelkarzinome (n = 2) waren deutlich seltener. Eine Prädisposition für bestimmte Lungenlappen war nicht nachzuweisen. Dreizehn (21 %) Patienten zeigten keine und 10 (16 %) nur unspezifische, nicht auf den Respirationstrakt hinweisende Symptome. Insgesamt zeigten 48 (79 %) Hunde klinische Symptome wie Husten, Dyspnoe, Lethargie, Gewichtsverlust, Leistungsschwäche, Erbrechen und/oder Fieber. Die tracheobronchialen Lymphknoten (TBLN) waren in 9 von 51 untersuchten Fällen histologisch positiv für Metastasierung (N1) und negativ (N0) in 42 Fällen (nicht untersucht n = 10). Daten zum Langzeitverlauf waren für 50 Patienten verfügbar. Prognostisch relevante Variablen waren Lymphknotenmetastasierung in die TBLN (mÜZ: N1 41 Tage, N0 570 Tage; p < 0,01), Lungenmetastasen (mÜZ: M1 125 Tage, M0 630 Tage; p < 0,01), histologischer Subtyp (mÜZ: differenzierte Karzinome 620 Tage; andere Karzinome 135 Tage; p < 0,01), Tumordurchmesser größer als 3 cm (mÜZ < 3 cm 1155 Tage, ≥ 3 cm 330 Tage; p = 0,02) und Tumorlokalisation (mÜZ: hilusnah 330 Tage, peripher 650 Tage; p = 0,04). Schlussfolgerung Beim PLK sind TBLN Status, Organmetastasen, Tumorlokalisation, histologischer Subtyp und Tumorgröße prognostisch relevante Kriterien. Hunde ohne prognostisch negative Faktoren können lange Überlebenszeiten aufweisen. In mehr als einem Drittel der Fälle bleiben die Tumoren asymptomatisch (21 %) bzw. ohne respirationstraktspezifische (16 %) Symptome.
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Quintela-Fandino, Miguel, Ricardo Hitt, Pedro P. Medina, Soledad Gamarra, Luis Manso, Hernan Cortes-Funes, and Montserrat Sanchez-Cespedes. "DNA-Repair Gene Polymorphisms Predict Favorable Clinical Outcome Among Patients With Advanced Squamous Cell Carcinoma of the Head and Neck Treated With Cisplatin-Based Induction Chemotherapy." Journal of Clinical Oncology 24, no. 26 (September 10, 2006): 4333–39. http://dx.doi.org/10.1200/jco.2006.05.8768.
Abstract:
Purpose Cisplatin kills tumor cells through DNA cross linking. Alterations in the function of DNA repair genes may affect DNA repair proficiency and influence cancer patients' response to cisplatin. We studied whether single nucleotide polymorphisms (SNPs) of DNA repair genes predict the response to cisplatin or prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN). Methods A polymerase chain reaction–restriction fragment length polymorphism (RFLP) approach was used to determine the frequency of the SNPs: XPD-Asp312Asn, XPD-Lys751Gln, ERCC1-C8092A, and XRCC1-Arg399Gln in DNA from peripheral lymphocytes of 103 stage IV SCCHN patients. Results The frequencies of the distinct genotypes were, respectively, for the homozygous common allele, heterozygous and homozygous polymorphic variant: 53%, 40%, and 7% for ERCC1; 50%, 42%, and 8% for XPD-312; 35%, 57%, and 8% for XPD751; and 35%, 51%, and 13% for XRCC1. Patients with only common alleles at all the SNPs tested had a median overall survival of 5.1 months (range, 4.3 to 6.0 months) as compared with not reached for patients with at least one polymorphic variant (P < .001). Estimates from Cox's multivariate analysis suggest that the accumulation of each polymorphic variant decreases the probability of dying by a factor of 2.1 (P < .001; the presence of seven polymorphic variants confers a 175-fold protection). The accumulation of polymorphic variants increases by 2.94-fold the probability of achieving a complete response to treatment (P = .041). Conclusion Using a multivariate model, the presence of polymorphic variants in DNA-repair genes are powerful prognosis factors and response to cisplatin predictors among SCCHN patients.
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Codl, Radim, Jaromír Ducháček, Mojmír Vacek, Jan Pytlík, Luděk Stádník, and Marek Vrhel. "Relationship between daily activities duration and oestrus in dairy cows over the year." Acta Veterinaria Brno 91, no. 1 (2022): 11–16. http://dx.doi.org/10.2754/avb202291010011.
Abstract:
The aim of this study was to evaluate the amounts of time that selected crossbreeds of Holstein (H), Red-Holstein (R), and Czech Fleckvieh (C) cattle spent chewing, eating, being physically active using a Vitalimetr 5P neck responder during the period around oestrus in all seasons of the year. Oestrus and the days preceding it greatly affected the times of events of increased activity, eating, and rumination. Eating and chewing times were longest for H cows, at 51–74%, and shortest for C cows, at > 88%. The number of events of increased activity was highest (533.4 ± 8.94 events, P < 0.01) for cows R 51–74%. Oestrus in dairy cows was manifested by decreases in the times of chewing and eating and the frequency of events of increased activity. Feeding time decreased by 8.01 min from the second day before oestrus to the day of oestrus. Rumination time also decreased from the second day before oestrus to the day of oestrus. Rumination time on the day of oestrus decreased by an average of 61.80 min but increased the next day by 33.39 min. In contrast, events of increased activity were highest on the day of oestrus (623 ± 7.68 events). Our findings on differences between breeds, lactation order, and months may contribute to the improvement of algorithms for detecting oestrus, thereby improving the economic status of farms.
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Sonnenberg, H., U. Honrath, and D. R. Wilson. "Effects of increased perfusion pressure on medullary collecting duct function." Canadian Journal of Physiology and Pharmacology 68, no. 3 (March 1, 1990): 402–7. http://dx.doi.org/10.1139/y90-056.
Abstract:
The role of the medullary collecting duct in pressure natriuresis has not been established. In vivo microcatheterization was used to study the effect of an acute increase in blood pressure induced by bilateral carotid artery and vagal nerve ligation on medullary collecting duct function in anaesthetized rats. Increased fluid and electrolyte excretion during pressure natriuresis were accompanied by increased delivery of water, sodium, chloride, and potassium to the beginning of the medullary collecting duct, a change that was significantly greater than in a second series of time-control animals. These increases in delivery were within the range for which constant fractional NaCl reabsorption had been found previously. However, during increased perfusion pressure, reabsorption of both sodium and chloride in the medullary collecting duct as a fraction of delivered load were reduced from 81 ± 4.1 to 51 ± 9.3% (p < 0.01) and from 65.7 ± 6.0 to 42.7 ± 9.1% (p < 0.01), respectively. No significant changes in medullary collecting reabsorption were seen in the time controls. We conclude that increased perfusion pressure, in addition to increasing delivery to the medullary collecting duct, also inhibits sodium chloride reabsorption in this nephron segment.Key words: hypertension, vagotomy, collecting duct, sodium excretion, atrial natriuretic factor.
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KAIPOV, ARTUR E., ROIN K. GEORGIKIA, ILDAR V. ABDULYANOV, MURAT N. MUKHARYAMOV, ILDAR I. VAGIZOV, RUSLAN R. BIKCHURIN, and ANNA S. SHORNINA. "PULMONARY HYPERTENSION INFLUENCE ON OUTCOMES OF SECONDARY TRICUSPID INSUFFICIENCY CORRECTION IN PATIENTS FOR VALVULAR HEART DISEASE." Bulletin of Contemporary Clinical Medicine 15, no. 1 (February 2022): 43–51. http://dx.doi.org/10.20969/vskm.2022.15(1).43-51.
Abstract:
Aim. The aim of the study is to compare the effect of pulmonary hypertension on the outcome of tricuspid valve plasty in the groups with moderate and significant pulmonary hypertension. Material and methods. The results of surgical treatment of 620 patients with cardiac valve diseases were analyzed. Pulmonary artery systolic pressure (PASP) measured by echocardiography. Two groups were distinguished: Group 1 – pulmonary artery systolic pressure ˂ 50 mmHg. – 250 patients, Group 2-systolic pulmonary artery pressure ≥50 mm Hg. – 370 patients. Depending on the method of tricuspid insufficiency correction, subgroups were identified in each group: subgroup A – suture plasty was used, subgroup B – annuloplasty ring. Mann-Whitney U test was used to compare two independent samples. Chi-square test was used to compare the percentages in the groups. Results and discussion. In group I (PASP up to 50 mmHg) pressure in the PA decreased in the postoperative period, however in the long-term period in the suture plasty subgroup (subgroup A) PASP increased (p=0.01), in the annuloplasty ring subgroup (subgroup B) PASP after surgery and in the long-term period has not changed significantly. The mean value of tricuspid regurgitation (TR) was 1.27±0.4 in subgroup B and 2.1±0.6 in subgroup A (p=0.0227). In group II (significant pulmonary hypertension), postoperative PASP decreased to 50.5±13.2 (subgroup A) and 53.4±8.0 (subgroup B) mm Hg, however in the long-term follow-up there was an increase of pressure in PA to 58.3±10.7 and 56.4±11.8 mm Hg, respectively. In subgroup B, the long-term results were better in terms of TR degree, 1.6±0.5, in contrast to subgroup A, where the average degree was 2.6±0.7 (p=0.001). Tricuspid valve (TV) plasty with a annuloplasty ring preserved coaptation of the TV cusps and prevented residual tricuspid insufficiency despite the intensity of pulmonary hypertension. Conclusion. Surgical treatment of mitral and aortic heart diseases leads to decrease or normalization of pulmonary artery pressure. Pulmonary hypertension in the postoperative period is a factor that influences the intensity of TR. All patients with significant functional TR as an outcome of left heart valve pathology should undergo TV annuloplasty. Correction with annuloplasty ring only is recommended for patients with significant pulmonary hypertension and significant TR.
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Breiter, Karel, Michaela Vaňková, Michaela Vašinová Galiová, Zuzana Korbelová, and Viktor Kanický. "Lithium and trace-element concentrations in trioctahedral micas from granites of different geochemical types measured via laser ablation ICP-MS." Mineralogical Magazine 81, no. 1 (February 2017): 15–33. http://dx.doi.org/10.1180/minmag.2016.080.137.
Abstract:
AbstractThe compositions of trioctahedral micas from 51 samples of granitoids with different geochemical affiliations and grades of differentiation from the Bohemian Massif, Central Europe, were analysed using electron microprobe (major elements) and laser ablation inductively coupled plasma mass spectrometry (Li, Sc, Ga, Ge, Nb, In, Sn, Cs, Ta, W, Tl). The micas form a continuous evolutionary series from phlogopite to zinnwaldite. The phlogopites and biotites from the I-type rocks are characterized by 5.5–5.7 Si, 2.4–2.6 Al, <0.1 Li atoms per formula unit [apfu] and Mg/(Mg + Fe) = 0.4–0.8. The biotites from the S-type granites usually contain 5.3–5.7 Si, 3.2–3.6 Al, 0.1–0.3 Li apfu and Mg/(Mg + Fe) = 0.15–0.4. The annites and zinnwaldites from the rare-metal granites contain 5.7–6.8 Si, 3.2–3.8 Al, 0.6–2.6 Li apfu and Mg/(Mg + Fe) < 0.1. The concentrations of F, Rb, Cs and Tl increase from the phlogopites and biotites to zinnwaldites: F 0.1 → 8 wt.%, Rb2O 0.05 → 1.7 wt.%, Tl 2 → 50 ppm and Cs 40 → 2000 ppm. The concentrations of Sn, Nb, Ta and W in phlogopites and biotites from the I- and S-type granitoids generally correlate with those of the parent rocks and reach values of (in ppm) 20–100 Sn, 20–250 Nb, 1–20 Ta and <5 W. The highest concentrations were found in the Li-annites in the relatively early facies of rare-metal granites (in ppm): 250–600 Sn, 400–600 Nb, 60–120 Ta and 50– 120 W. The zinnwaldites in the late rare-metal granites facies are impoverished in these elements, which is explained by contemporaneous crystallization of cassiterite and columbite. Lithium enters the crystal lattice of trioctahedral micas via the exchange vector Li3□Si3Fe–6Al–1up to concentrations of ∼2.5 wt.% Li2O (1.5 apfu Li). At higher Li concentrations, Li is incorporated through the exchange vector Li3Si1□–1Fe–2Al–1.
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Li, Xin, Noel A. Brownlee, Thomas A. Sporn, Annabelle Mahar, and Victor L. Roggli. "Malignant (Diffuse) Mesothelioma in Patients With Hematologic Malignancies: A Clinicopathologic Study of 45 Cases." Archives of Pathology & Laboratory Medicine 139, no. 9 (April 6, 2015): 1129–36. http://dx.doi.org/10.5858/arpa.2014-0569-oa.
Abstract:
Context Ionizing radiation has a role in the development of malignant mesothelioma, in several epidemiologic studies, including patients with hematologic malignancies. Objective To study the clinicopathologic characteristics of patients with malignant mesothelioma and hematologic malignancies with and without a history of radiotherapy. Design From a database of approximately 3600 patients with malignant mesothelioma, we identified 45 patients (1%) who also had hematologic malignancies. We examined clinicopathologic features and noted whether the patient had received radiotherapy for malignancy, comparing those with and those without such exposure. Results Among the 45 cases, 18 (40%) had Hodgkin lymphoma, 15 (33%) had non-Hodgkin lymphoma, 10 (4%) had chronic lymphocytic leukemia, and 2 (22%) had chronic myelogenous leukemia; 20 patients (44%) had a history of radiotherapy, and 23 (51%) did not. Most patients with Hodgkin lymphoma (16 of 18; 90.0%) received radiation, whereas none of the patients with leukemia (0 of 12) and only 20% (3 of 15) of the patients with non-Hodgkin lymphoma did so. Patients without radiation were older than patients who received radiotherapy (median, 73 versus 54 years, respectively; P < .001), had a shorter interval from diagnosis of hematologic malignancy to that of mesothelioma (median, 2 versus 24 years, respectively; P < .001), and had a shorter survival period (median, 6.0 versus 14.0 months, respectively; P = .02). Epithelial mesotheliomas were proportionately more common in patients with a history of radiotherapy. Conclusions Patients with mesothelioma and hematologic malignancies with a history of radiation tended to be younger, had a longer interval from diagnosis of hematologic malignancy to that of mesothelioma, had a longer survival period, and were more likely to have the epithelial variant compared with patients without radiotherapy.
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Struyf, E., W. Opdekamp, H. Backx, S. Jacobs, D. J. Conley, and P. Meire. "Vegetation and proximity to the river control amorphous silica storage in a riparian wetland (Biebrza National Park, Poland)." Biogeosciences 6, no. 4 (April 23, 2009): 623–31. http://dx.doi.org/10.5194/bg-6-623-2009.
Abstract:
Abstract. Wetlands can modify and control nutrient fluxes between terrestrial and aquatic ecosystems, yet little is known of their potential as biological buffers and sinks in the biogeochemical silica cycle. We investigated the storage of amorphous silica (ASi) in a central-European riparian wetland. The variation in storage of ASi in the soil of an undisturbed wetland was significantly controlled by two factors: dominance of sedges and grasses and distance to the river (combined (R2=78%). Highest ASi storage was found near the river and in sites with a dominance of grasses and sedges, plants which are well known to accumulate ASi. The management practice of mowing reduced the amount of variation attributed to both factors (R2=51%). Although ASi concentrations in soils were low (between 0.1 and 1% of soil dry weight), ASi controlled the availability of dissolved silica (DSi) in the porewater, and thus potentially the exchange of DSi with the nearby river system through both diffusive and advective fluxes. A depth gradient in ASi concentrations, with lower ASi in the deeper layers, indicates dissolution. Our results show that storage and recycling of ASi in wetland ecosystems can differ significantly on small spatial scales. Human management interferes with the natural control mechanisms. Our study demonstrates that wetlands have the potential to modify the fluxes of both DSi and ASi along the land-ocean continuum and supports the hypothesis that wetlands are important ecosystems in the biogeochemical cycling of silica.
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Araujo, Aline Neves, Cléber Pinto Camacho, Thais Biude Mendes, Susan Chow Lindsey, Lais Moraes, Marta Miyazawa, Rosana Delcelo, et al. "Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent AIFM3 and DLK1 Copy Gain in Medullary Thyroid Carcinoma." Cancers 13, no. 2 (January 9, 2021): 218. http://dx.doi.org/10.3390/cancers13020218.
Abstract:
Medullary thyroid carcinoma (MTC) is a malignant tumor originating from thyroid C-cells that can occur either in sporadic (70–80%) or hereditary (20–30%) form. In this study we aimed to identify recurrent copy number alterations (CNA) that might be related to the pathogenesis or progression of MTC. We used Affymetrix SNP array 6.0 on MTC and paired-blood samples to identify CNA using PennCNV and Genotyping Console software. The algorithms identified recurrent copy number gains in chromosomes 15q, 10q, 14q and 22q in MTC, whereas 4q cumulated losses. Coding genes were identified within CNA regions. The quantitative PCR analysis performed in an independent series of MTCs (n = 51) confirmed focal recurrent copy number gains encompassing the DLK1 (14q32.2) and AIFM3 (22q11.21) genes. Immunohistochemistry confirmed AIFM3 and DLK1 expression in MTC cases, while no expression was found in normal thyroid tissues and few MTC samples were found with normal copy numbers. The functional relevance of CNA was also assessed by in silico analysis. CNA status correlated with protein expression (DLK1, p = 0.01), tumor size (DLK1, p = 0.04) and AJCC staging (AIFM3p = 0.01 and DLK1p = 0.05). These data provide a novel insight into MTC biology, and suggest a common CNA landscape, regardless of if it is sporadic or hereditary MTC.
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Araujo, Aline Neves, Cléber Pinto Camacho, Thais Biude Mendes, Susan Chow Lindsey, Lais Moraes, Marta Miyazawa, Rosana Delcelo, et al. "Comprehensive Assessment of Copy Number Alterations Uncovers Recurrent AIFM3 and DLK1 Copy Gain in Medullary Thyroid Carcinoma." Cancers 13, no. 2 (January 9, 2021): 218. http://dx.doi.org/10.3390/cancers13020218.
Abstract:
Medullary thyroid carcinoma (MTC) is a malignant tumor originating from thyroid C-cells that can occur either in sporadic (70–80%) or hereditary (20–30%) form. In this study we aimed to identify recurrent copy number alterations (CNA) that might be related to the pathogenesis or progression of MTC. We used Affymetrix SNP array 6.0 on MTC and paired-blood samples to identify CNA using PennCNV and Genotyping Console software. The algorithms identified recurrent copy number gains in chromosomes 15q, 10q, 14q and 22q in MTC, whereas 4q cumulated losses. Coding genes were identified within CNA regions. The quantitative PCR analysis performed in an independent series of MTCs (n = 51) confirmed focal recurrent copy number gains encompassing the DLK1 (14q32.2) and AIFM3 (22q11.21) genes. Immunohistochemistry confirmed AIFM3 and DLK1 expression in MTC cases, while no expression was found in normal thyroid tissues and few MTC samples were found with normal copy numbers. The functional relevance of CNA was also assessed by in silico analysis. CNA status correlated with protein expression (DLK1, p = 0.01), tumor size (DLK1, p = 0.04) and AJCC staging (AIFM3p = 0.01 and DLK1p = 0.05). These data provide a novel insight into MTC biology, and suggest a common CNA landscape, regardless of if it is sporadic or hereditary MTC.
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Sanders, F. R. K., M. Backes, S. A. Dingemans, J. M. Hoogendoorn, N. W. L. Schep, J. Vermeulen, J. C. Goslings, and T. Schepers. "Functional outcome of implant removal following fracture fixation below the level of the knee." Bone & Joint Journal 101-B, no. 4 (April 2019): 447–53. http://dx.doi.org/10.1302/0301-620x.101b4.bjj-2018-0745.r1.
Abstract:
AimsThe aim of this study was to evaluate the functional outcome in patients undergoing implant removal (IR) after fracture fixation below the level of the knee.Patients and MethodsAll adult patients (18 to 75 years) undergoing IR after fracture fixation below the level of the knee between November 2014 and September 2016 were included as part of the WIFI (Wound Infections Following Implant Removal Below the Knee) trial, performed in 17 teaching hospitals and two university hospitals in The Netherlands. In this multicentre prospective cohort, the primary outcome was the difference in functional status before and after IR, measured by the Lower Extremity Functional Scale (LEFS), with a minimal clinically important difference of nine points.ResultsA total of 179 patients were included with a median age of 50 years (interquartile range (IQR) 37 to 60), of whom 71 patients (39.7%) were male. With a median score of 60 before IR (IQR 45 to 72) and 66 after IR (IQR 51 to 76) on the LEFS, there was a statistically significant improvement in functional outcome (p < 0 .001). A total of 31 surgical site infections (17.3%) occurred.ConclusionAlthough IR led to a statistically significant improvement of functional outcome, the minimal clinically important difference was not reached. In conclusion, this study shows that IR does not result in a clinically relevant improvement in functional outcome. These results, in combination with the high complication rate, highlight the importance of carefully reviewing the indication for IR. Cite this article: Bone Joint J 2019;101-B:447–453.
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Schüler, Frank, Malte Leithäuser, Thomas Kiefer, Saskia Richter, and Gottfried Dolken. "Favorable Molecular Responses to Imatinib in CML Patients in Early Chronic Phase in Comparison to Late Chronic Phase Patients after Treatment with Hydroxyurea and Interferon." Blood 108, no. 11 (November 16, 2006): 4794. http://dx.doi.org/10.1182/blood.v108.11.4794.4794.
Abstract:
Abstract Peripheral blood samples from 70 patients treated with imatinib were regularly sent to us for the determination of bcr-abl transcript levels by a standardized quantitative real-time PCR (TaqMan®). 45 patients with early chronic phase CML were treated with imatinib as a first line therapy and 25 patients in late chronic phase received imatinib as a second line therapy after hydroxyurea plus interferon. The median pre-treatment time with hydroxyurea plus interferon in these late chronic patients was 43 months (6 – 130). The median follow-up was 18.4 months (1–51) for first line patients and 18.0 months (1–48) for second line patients. Patients received a median dosage between 400–600 mg imatinib in both groups. At the time of diagnosis the median bcr-abl/abl ratio was 248 % (26–460%, SD: 148%) in patient receiving imatinib as a first line treatment. Patients receiving imatinib as second line treatment had a median bcr-abl/abl ratio of 24,84% (1–256%, SD: 78%) just before the imatinib treatment was initiated. Early chronic phase CML patients treated with imatinib as a first line therapy showed a strong biphasic decay of their bcr-abl transcript with a fast reduction between 1-2-log during the first 6–9 months followed by a slower rate of reduction afterwards. A bcr-abl/abl ratio <0.1% could be observed in 19/51 (37%) patients and in 12/51 (23%) patients a bcr-abl/abl ratio < 0.01% was found. After 18 months of therapy the median reduction of bcr-abl was about 2.5-log, after 36 months about 3-log. 12/51 (23%) patients showed a suboptimal response or had a subsequent increase of their bcr-abl transcript levels. Best responding patients could be identified by a >2-log reduction after 6 months and > 3-log reduction after 18 months of therapy. In late chronic phase CML patients pre-treated with hydroxyurea and interferon the overall median decrease of bcr-abl transcript levels was about 1-log after a median follow-up of 18 as well as after 36–48 months. Obviously, there are at least three subgroups of patients with a different molecular response. We identified 7/25 (28%) patients with no significant reduction of bcr-abl transcripts after 18 months as well as after 36 months of imatinib therapy. In contrast, another group of 4/25 (16%) patients showed a 2-log reduction of bcr-abl/abl ratio after 18 months with a subsequent reduction of 3-log after 36 months. Within the largest group of 14/25 (56%) patients a 1-log reduction after 18 months and a 1-2-log reduction after 36 months was observed. No patient had > 3-log reduction within the whole group of 25 late chronic phase patients. The reduction of bcr-abl transcript levels as a result of imatinib therapy is significantly superior in CML patients receiving imatinib as first line treatment for CML in early chronic phase compared to patients treated with imatinib after a long term pre-treatment with hydroxyurea and interferon.
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Shull, J. Michael, and Georgia V. Panopoulou. "Variations of Interstellar Gas-to-dust Ratios at High Galactic Latitudes." Astrophysical Journal 961, no. 2 (January 26, 2024): 204. http://dx.doi.org/10.3847/1538-4357/ad0f20.
Abstract:
Abstract Interstellar dust at high Galactic latitudes can influence astronomical foreground subtraction, produce diffuse scattered light, and soften the UV spectra of quasars. In a sample of 94 sight lines toward quasars at high latitude and low extinction, we evaluate the interstellar “gas-to-dust ratio” N H/E(B − V), using hydrogen column densities (H i and H2) and far-IR (FIR) estimates of dust reddening. In the Galactic plane, this ratio is 6.0 ± 0.2 (in units of 1021 cm−2 mag−1). On average, recent Planck estimates of E(B − V) in low-reddening sight lines are 12% higher than those from Schlafly & Finkbeiner, and N H I exhibits significant variations when measured at different radio telescopes. In a sample of 51 quasars with measurements of both H i and H2 and 0.01 ≤ E(B − V) ≲ 0.1, we find mean ratios 10.3 ± 0.4 (gas at all velocities) and 9.2 ± 0.3 (low-velocity only) using Planck E(B − V) data. High-latitude H2 fractions are generally small (2%–3% on average), although nine of 39 sight lines at ∣b∣ ≥ 40° have f H2 of 1%–17%. Because FIR-inferred E(B − V) is sensitive to modeled dust temperature T d and emissivity index β, gas-to-dust ratios have large, asymmetric errors at low E(B − V). The ratios are elevated in sight lines with high-velocity clouds, which contribute N H but little reddening. In Complex C, the ratio decreases by 40% when high-velocity gas is excluded. Decreases in dust content are expected in low-metallicity gas above the Galactic plane, resulting from grain destruction in shocks, settling to the disk, and thermal sputtering in hot halo gas.
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Denisow, Bożena, Monika Strzałkowska-Abramek, Małgorzata Bożek, and Anna Jeżak. "Ornamental Representatives of the Genus Centaurea L. as a Pollen Source for Bee Friendly Gardens." Journal of Apicultural Science 58, no. 2 (December 1, 2014): 49–58. http://dx.doi.org/10.2478/jas-2014-0016.
Abstract:
Abstract The flowering phenology and pollen production of three ornamental Centaurea species were investigated in the years 2009 and 2012-2013. The study objects, Centaurea montana L. = Cyanus montanus (L.) Hill, Centaurea mollis Waldst & Kit, and Centaurea dealbata Willd. were cultivated within an area of the UMCS Botanical Garden in Lublin, Poland (51° 14’ N, 22° 34’ E). Under the environmental conditions of SE Poland, the Centaurea species flowered continuously from mid-May to the first week of June. The mass of pollen in anthers was found to be species-related: 3.70 mg (C. montana), 4.02 mg (C. mollis), and 6.01 mg (C. dealbata) per 100 anthers. The total pollen yield was related to the mass of pollen produced in flowers and the abundance of blooming. Pollen grains were medium-sized, spheroid (C. dealbata) or prolato-spheroid (C. mollis and C. montana) in shape, and characterized by high viability (over 80% on average). The pollen provided by the plants of ornamental Centaurea species amounted to 6.0 - 7.9 g per m2 on average. The honeybee was the most frequent visitor of C. dealbata, accounting for 55.2% of the total pollinators, and bumblebee species predominated on the flowers of both C. montana (77.7%) and C. mollis (85.6%). Solitary bees and dipterans were also observed on the flowers of all species studied, but C. mollis was avoided by lepidopterans. Ornamental Centaurea species provide pollen reserves that could support communities of invertebrate pollinators, although the period of effective supply fluctuates annually due to changeable periods of blooming.