Littérature scientifique sur le sujet « 338.1/9 »

To examine the fetal cardiovascular responses to a sustained reduction in O2 delivery (DO2), studies were conducted on 13 chronically instrumented fetal lambs (128-138 days gestation) made hypoxemic for 7.9 +/- 0.5 h by lowering maternal inspired O2 concentration to 9-10%. Fetal descending aortic PO2 fell initially from 18.0 +/- 1.0 to 10.7 +/- 0.6 mmHg, whereas pH decreased progressively from 7.326 +/- 0.006 to 6.843 +/- 0.023. Blood flow to the cerebral hemispheres, myocardium, and adrenal glands rose maximally by 110.2 +/- 22.5, 253.7 +/- 41.1, and 338.7 +/- 55.0%. Cerebral hemispheric DO2 fell progressively, whereas DO2 to the myocardium and adrenal was maintained until 7.9 h, when it fell significantly. There was also a rise in blood flow to brown adipose tissue. Blood flow to the gut and skeletal muscle was maintained, whereas flow to the spleen and kidney fell. DO2 to all these tissues fell markedly because of the progressive decline in blood O2 content. It is concluded that fetal cardiovascular function was well maintained in the face of severe hypoxemia and marked acidemia.

Aim. To carry out a 12-month study on the prognostic role of humoral markers responsible for the main mechanisms of initiation of cardiotoxic myocardial damage (endothelin-1, soluble Fas-L, N-terminal pro-brain natriuretic peptide (NT-proBNP), tumor necrosis factor-α, interleukin (IL)-1β, matrix metalloproteinase (MMP)-2 and MMP9, soluble form of the ST2 protein (sST2), a tissue inhibitor of metalloproteinase-1, and tetranectin) in assessing the risk of progression of anthracycline-related left ventricular dysfunction.Materials and methods. The study included a total of 114 women aged 48.0 (46.0; 52.0) years without concomitant cardiovascular diseases and risk factors who received chemotherapy with anthracyclines in the past. The levels of serum biomarkers were determined using the enzyme immunoassay. Transthoracic echocardiography was performed at baseline and at 12 months of follow-up.Results. After 12 months of follow-up, all patients were retrospectively divided into 2 groups: group 1 (n = 54) included patients with an unfavorable course of anthracycline-related cardiac dysfunction (ARCD), group 2 (n = 60) encompassed patients with a favorable course of the disease. According to the ROC analysis, MMP-2 ≥ ≥ 338.8 pg / ml (sensitivity 57%, specificity 78%; AUC = 0.629; p = 0.025), MMP-9 ≥ 22.18 pg / ml (sensitivity 89%, specificity 87%; AUC = 0.886; p < 0.001), sST2 ≥ 32.4 ng / ml (sensitivity 64%, specificity 70.5%; AUC = 0.691; p = 0.002), and tetranectin ≤ 15.4 pg / ml (sensitivity 69%, specificity 72%; AUC = 0.764; p < 0.001) were identified as predictors of an adverse course of ARCD. When comparing ROC curves, it was found that the concentration of MMP-9 (p = 0.002) was the most significant predictor of the progression of ARCD.Conclusion. MMP-2 and -9, soluble ST2, and tetranectin can be considered as non-invasive markers for assessing the risk of ARCD progression. At the same time, an increased level of MMP-9 is the most significant predictor of ARCD progression.

156 Background: AVPC are morphologically heterogeneous tumors that share clinical features with the rare, virulent, androgen-indifferent and platinum-sensitive, small cell histologic variant. The AVPC-ms is composed of ≥2 defects in TP53, RB1 and PTEN, is detectable in »30% of advanced prostate cancers and predicts for benefit from platinum combinations (Corn et al. Lancet Oncol, 2019). Preclinical studies link the AVPC-ms with androgen indifference, but a prospective clinical association with decreased sensitivity to androgen signaling inhibitors is lacking. Methods: In a phase II trial (NCT02703623), men with metastatic castration resistant prostate cancer (mCRPC) treated with abiraterone and apalutamide were classified at week 8 as having a ‘satisfactory’ decline in PSA (≥ 50% from baseline) and CTC (≤5/7.5mL) or ‘unsatisfactory’. Pretreatment biopsies were obtained for immunohistochemistry (IHC) for TP53, RB1 and PTEN and RNA sequencing. Results: 198 men were registered. 59 (31.5%) of 187 evaluable had ‘unsatisfactory’ marker declines. Age, race/ethnicity, and baseline ECOG, PSA and LDH were similar between the groups. Men in the ‘unsatisfactory’ group had higher median total alkaline phosphatase (120 vs. 86; p=0.002), bone-specific alkaline phosphatase (21 vs. 16; p=0.01), CTC (9 vs. 1; p<0.001), and urine n-telopeptides (338.5 vs 182.5; p=0.003) levels. Unsupervised clustering of RNA profiles from 45 tumor biopsies revealed two distinct clusters. The top enriched gene set (FDR q-val<0.000) included ‘epithelial mesenchymal transition’, ‘E2F targets’ and ‘G2M checkpoint’ genes in one (n=18) and ‘androgen response’ in another (n=27) cluster. Six (33.3%) and 9 (33.3%) of the samples respectively belonged to patients in the ‘unsatisfactory’ decline group. IHC and RNA sequencing of the remaining samples are ongoing. Conclusions: Signaling pathways associated with androgen indifference can be identified in the tumor biopsies of men with early mCRPC, prior to exposure to secondary androgen signaling inhibitors. Their association with the AVPC-ms and patient outcomes will be presented. If confirmed, these markers could be used to inform therapy selection. Clinical trial information: NCT02703623.

This research was carried out to determinate the effect of the atmosphere processing conditions (air and argon) and two specific thermal treatments, on the properties of specimens made from the nickel-based alloy Hastelloy C-22 by plasma transferred arc (PTA). Firstly, the additive manufacturing parameters were optimized. Following, two walls were manufactured in air and argon respectively. Afterwards, a determinate number of specimens were cut out and evaluated. Regarding the comparison performed with the extracted specimens from both walls, three specimens of each wall were studied as-built samples. Furthermore, a commonly used heat treatment in Hastelloy, with two different cooling methods, was selected to carry out additional comparisons. In this respect, six additional specimens of each wall were selected to be heat treated to a temperature of 1120 °C for 20 min. After the heat treatment, three of them were cooled down by rapid air cooling (RAC), while the other three were cooled down by water quenching (WQ). In order to study the influence degree of the processing conditions, and how the thermal treatments could modify the final properties of the produced specimens, a detailed characterization was performed. X-ray diffraction and microstructural analyses revealed the phases-presence and the apparition of precipitates, varying the thermal treatment. Moreover, the results obtained after measuring mechanical and tribological properties showed slight changes caused by the variation of the processing atmosphere. The yield strength of the extracted specimens from the two walls achieved values closer to the standards ones in air 332.32 MPa (±21.36 MPa) and in argon 338.14 MPa (±9 MPa), both without thermal treatment. However, the effect of the cooling rate resulted as less beneficial, as expected, reducing the deformation properties of the specimens below 11%, independently of the air or argon manufacturing atmosphere and the cooling rate procedure.

Vaso-occlusive episodes (VOEs) are a hallmark of sickle cell disease (SCD), and account for >90% of health care encounters for this patient population. The Cooperative Study of Sickle Cell Disease, a large study enrolling >3000 patients, showed that the majority of SCD patients (80%) experienced 0–3 major pain crises/year. Only a small minority (~5%) experienced ≥6 VOEs/year. Our study sought to further understand this difference in VOE frequency between SCD patients. We analyzed 25 patients (13M/12F, mean age of 28.8) with ≥6 ED visits or hospitalizations/year (high utilizers), and compared these with 9 patients (6M/3F, mean age of 37.6) who had ≤2 ED visits or hospitalizations/year (low utilizers). All subjects were given a demographic survey along with questionnaires for depression, anxiety, and Health Locus of Control. Each subject then underwent quantitative sensory testing (QST) with three different modalities: pressure pain sensitivity, heat and cold sensitivity, and Von Frey monofilament testing. Laboratory and clinical data were collected through subjects’ medical records. CBC and chemistry analysis showed high utilizers had higher WBC (p<0.01), ANC (p<0.01), total bilirubin (p = 0.02), and lower MCV (p = 0.03). Opioid use (morphine equivalents) over the past 6 months was significantly higher in the high utilizer group (12125.7 mg vs 2423.1 mg, p = 0.005). QST results showed lower pressure pain threshold at the ulna (224.4 KPa vs 338.9 KPa, p = 0.04) in the high utilizer group. High utilizers also had higher anxiety (9.0 vs 4.6, p = 0.04) and depression scores (10.0 vs 6.0, p = 0.051). While the low utilizer group had higher education levels with more associate and bachelor degrees (p = 0.009), there was no difference in income or employment. These data show that many biological and psychosocial factors contribute to high health care utilization in SCD. A multi-disciplinary and multi-faceted approach will be required to address this complex problem.

SUMMARY Using radionuclide-labeled 15-μm-diameter microspheres injected into the left ventricle, we examined blood flow to the thyroid gland, adrenal glands, kidneys, and various gastrointestinal tract tissues in 9 healthy horses while they were standing quietly (rest) and during exercise at 2 work intensities (8 and 13 m/s). Hemodynamic measurements were made during steady-state conditions, as judged by the stability of heart rate as well as aortic, pulmonary, and right atrial pressures. The similarity of blood flow values for the left and the right kidneys during each of the 3 conditions indicated adequate mixing of microspheres with blood. In standing horses, of all tissues examined, the thyroid gland had the highest blood flow (1,655.2 ± 338.5 ml/min/100 g)—being about threefold that in the kidneys. Adrenal blood flow, by contrast, was only 25% of that in the kidneys (589.5 ± 50.4 ml/min/100 g). Among the gastrointestinal tract tissues, glandular stomach and pancreas had the highest blood flows (214.3 ± 21.6 and 197.6 ± 23.4 ml/min/100 g, respectively). Small intestinal perfusion was not different from that in the ventral colon and cecum, but their values exceeded those for the dorsal and small colons. Exercise at 8 and 13 m/s caused significant increase in adrenal blood flow as vascular resistance decreased significantly. In the kidneys, blood flow was only insignificantly affected during exercise at 8 m/s, but at 13 m/s there was a profound reduction in renal blood flow as intense renal vasoconstriction occurred. Vasoconstriction also caused thyroid and pancreatic blood flow to decrease significantly at both levels of exertion. Significant vasoconstriction occurring in all gastrointestional tract tissues at 8 and 13 m/s caused blood flow to be diverted away from these vascular beds. Thus, our data indicated that renal, adrenal, and splanchnic organ/tissue blood flow responses of strenuously exercising horses closely resemble those described for exercising ponies.

e16134 Background: Rational and effective treatment strategies for patients with unresectable hepatocellular carcinoma (uHCC) presenting portal vein tumor thrombus (PVTT) are lacking, and hepatic artery infusion chemotherapy (HAIC) combined with tyrosine kinase inhibitors and immune checkpoint inhibitors could be an effective therapy. Herein, we evaluated the efficacy and safety of HAIC combined with donafenib and camrelizumab in patients with uHCC presenting PVTT. Methods: This prospective, single-arm, single-center study enrolled patients with uHCC presenting PVTT (distant metastases were allowed), BCLC stage C, Child-Pugh scores ≤ 7, ECOG PS ≤1, and no previous local or systemic treatment. Patients received mFOLFOX6-HAIC (every 3 weeks, no more than 6 cycles), followed by peroral donafenib (200 mg BID every day) and intravenous camrelizumab (200 mg every 3 weeks). The primary endpoint was the objective response rate (ORR; per RECIST1.1 and mRECIST). Secondary endpoints included surgical conversion rate, disease control rate, progression-free survival (PFS), overall survival (OS), duration of response, and safety. Results: Between November 2021 and September 2022, we enrolled 15 eligible patients with a median age of 53 years (range, 36-76), including 12 (80%) males. Considering enrolled patients, 14 (93.3%) were HBV+, 13(86.7%) presented with PVTT invasion into the main portal vein, Child-Pugh scores 5/6/7: 9/5/1, ECOG PS 0/1: 10/5, median tumor size was 8.4 cm (range, 5.2-13.6), and 5 (33.3%) had extrahepatic metastases. The median number of HAIC procedures was 5 (range, 1-6). The median follow-up time was 338.0 days (95% CI, 298.7-377.4). Considering the 15 evaluable patients (completed at least one cycle of treatment), the ORR was 66.7% (10/15) according to RECIST 1.1, with 0 complete response (CR) and 10 partial responses (PR). According to mRECIST, the ORR was 73.3% (11/15), with 2 CR and 9 PR. Three patients (20%) became eligible for surgical resection, with one undergoing surgical resection (two refused surgery for financial reasons). Median PFS and OS were insufficient. All 15 (100%) patients experienced treatment-related adverse events (TRAEs). Common TRAEs included hand-and-foot skin reaction (HFSR; 93.3%), abdominal pain (73.3%), hypoalbuminemia (60.0%), platelet count decreased (60.0%), nausea (60%), aspartate aminotransferase increased (53.3%), and vomiting (53.3%). Grade 3/4 TRAEs included platelet count decreased (13.3%), HFSR (13.3%), hepatic function abnormal (6.7%), and ascites (6.7%). No grade 5 TRAEs were observed. TRAEs led to drug reduction in 8 patients (53.3%). Conclusions: HAIC combined with donafenib and camrelizumab afforded promising efficacy and safety in patients with uHCC presenting PVTT. Longer follow-up is required for further evaluation. Clinical trial information: ChiCTR2100051714 .

The purpose of this research was to quantify and compare carbon stocks in two selected dry evergreen montane forests of the Choke Mountain ecosystem that are under different management regimes. The study also attempted to assess the carbon stock along environmental gradients. The average carbon stock throughout the whole plots investigated in Anshirava forest (protected) was 180.18 t·ha−1 (53%) in AGB, 111.43 t·ha−1 (33%) in soil, 36.43 t·ha−1 (11%) in BGB, 6.09 t·ha−1 (2%) in USB, 2.69 t·ha−1 (1%) in litter, and 1.36 t·ha−1 (less than 1%) in DW. In Ziba forest (high human intervention), the average carbon stock was 106.71 t·ha−1 (44%) in AGB, 100.07 t·ha−1 (42%) in soil, 21.34 t·ha−1 (9%) in BGB, 5.41 t·ha−1 (2%) in USB, 4.82 t·ha−1 (2%) in litter, and 2.00 t·ha−1 (1%) in DW. The AGB had the greatest carbon share in both forests, followed by soil. In Anshirava and Ziba forests, the mean total carbon stocks (TCS) were 338.18 t·ha−1 and 240.36 t·ha−1, with CO2 equivalents of 1241.14 t·ha−1 and 882.12 t·ha−1, respectively. The study indicated a significant variation between the two forests. Anshirava forest has larger total carbon stocks than Ziba forest. For lower, medium, and higher altitudes, the total carbon stock variation along an altitudinal gradient was 289.67 t·ha−1, 347.93 t·ha−1, and 414.89 t·ha−1 in Anshirava forest and 270.99 t·ha−1, 204.24 t·ha−1, and 224.82 t·ha−1 in Ziba forest, respectively. As a result, a greater amount of carbon was stored at higher altitudes in Anshirava and at lower altitudes in Ziba, with no significant difference in both forests. The total carbon stock variation along slope gradient was 392.60 t·ha−1, 344.59 t·ha−1, and 295.49 t·ha−1 in Anshirava forest and 258.74 t·ha−1, 222.46 t·ha−1, and 171.46 t·ha−1 in Ziba forest for flat, intermediate, and steep slopes, respectively. This resulted in higher carbon being stored in flat slopes in both forests. Also, only at the Ziba site, a significant difference was found along the slope gradient. In each forest, eight distinct aspect facings were observed, with the western (W) aspect containing the highest value of total carbon stock in both forests. Lower values, on the other hand, were recorded in the south (S) and flat (F) aspects of Anshirava and Ziba forests, respectively. The slope aspects of both forests varied significantly. As a result, the research reveals that environmental factors have a significant impact on carbon stock value of Choke Mountain forest ecosystem, but the impact is not consistent among carbon pools.

Background:Previous systemic lupus erythematosus (SLE) studies have identified potential clusters of SLE clinical manifestations post diagnosis.Objectives:To describe the presentation of SLE at diagnosis across different cohorts of patients and describe management and outcomes after diagnosis within clusters.Methods:Cross-sectional study of 263 rheumatologists in the US and EU5. Data were collected from the Adelphi Real World 2015 Lupus Disease Specific Programme. Rheumatologists completed patient record forms (PRFs) for the next 5 prospectively consulting SLE patients; these patients completed patient self-completion (PSC) forms describing how SLE affected them. PRF data includes patient’s characteristics and management history. PSCs focused on similar data collection, including patient reported outcome measures on the humanistic burden. Age at diagnosis, symptoms at diagnosis, organ involvement at diagnosis, and severity at diagnosis were used as covariates in a latent cluster analysis.Results:Data were extracted from 1376 PRFs. Cluster analysis resulted in up to 6 clusters, and disease understanding led to the selection of a 4-cluster solution.Cluster 1 displayed the mildest disease, characterised by joint involvement, while cluster 2 displayed more skin involvement in conjunction with joint. Cluster 3 were characterised by renal involvement and cluster 4 had skin and joint involvement, but also high constitutional and haematological involvement at diagnosis (Table 1).Table 1Cluster analysisClustersOrgan involvement at diagnosis, n (%)Overall(n=1304)1(n=210)2(n=493)3(n=162)4(n=439)p-valueMusculoskeletal1145 (87.8)174 (82.9)444 (90.1)134 (82.7)393 (89.5)0.0065Mucocutaneous898 (68.9)5 (2.4)397 (80.5)95 (58.6)401 (91.3)<0.0001Neuropsychiatric87 (6.7)19 (9.0)9 (1.8)16 (9.9)43 (9.8)<0.0001Cardiorespiratory176 (13.5)36 (17.1)14 (2.8)22 (13.6)104 (23.7)<0.0001Gastrointestinal44 (3.4)8 (3.0)14 (2.8)8 (4.9)14 (3.2)0.6115Opthalmic47 (3.6)020 (4.1)10 (6.2)17 (3.9)0.0102Renal213 (16.6)15 (7.1)9 (1.8)162 (100)27 (6.2)<0.0001Constitutional425 (32.6)45 (21.4)89 (18.1)55 (34.0)236 (53.8)<0.0001Haematological452 (34.7)64 (30.5)22 (4.5)80 (49.4(286 (65.1)<0.0001Severity at diagnosis, n (%)Mild209 (16.0)55 (26.2)99 (20.1)1 (0.6)54 (12.3)<0.0001Moderate806 (61.8)122 (58.1)324 (65.7)75 (46.3)285 (64.9)Severe289 (22.2)33 (15.7)70 (14.2)86 (53.1)100 (22.8)Significant between-cluster differences were observed when comparing outcomes; cluster 4 have been diagnosed longest (mean weeks diagnosed 354.6 v. 1: 232.6, 2: 228.7, 3: 338.2, p<0.0001). Cluster 3 consulted more in the last 12 months (mean number of visits 7.9 vs. 1: 5.7, 2: 6.3, 4: 7.6).Significant differences were also observed between clusters in relation to current treatment proportions: corticosteroid (highest cluster 3: 78.4%), immunosuppressant (highest cluster 3: 75.3%), biologic DMARD (highest cluster 4: 17.8%) and antidepressant (highest cluster 4: 4.1%).Conclusion:This study demonstrates the heterogeneity of SLE at diagnosis and highlights four distinct presentations of the disease at diagnosis. Significant proportions of patients present with advanced disease, these clusters go on to present the greatest burden demonstrating the need for better diagnostic tools and novel earlier intervention.Study funded by Johnson and Johnson.Disclosure of Interests:Zahi Touma Consultant of: Consultant for Janssen, Ben Hoskin Consultant of: Consultant for Janssen, Christian Atkinson Consultant of: Consultant for Janssen, David Bell Consultant of: Janssen, Olivia Massey Consultant of: Janssen, Jennifer H. Lofland Employee of: Janssen, Pamela Berry Employee of: Janssen, Chetan Karyekar Shareholder of: Johnson & Johnson, Consultant of: Janssen, Employee of: Janssen Global Services, LLC. Previously, Novartis, Bristol-Myers Squibb, and Abbott Labs., Karen Costenbader Grant/research support from: Merck, Consultant of: Astra-Zeneca

Introduction: Robotic-assisted minimally invasive esophagectomy (RAMIE) is a recently developed technique for the treatment of resectable esophageal cancer. The present study compares the outcomes of RAMIE and video-assisted thoracoscopic esophagectomy (VATE). Method: Patients undergoing minimally invasive esophageal surgery between December 2020 and September 2022 were included in the study, while those undergoing conventional surgery were excluded. The patients were divided into two groups, as those undergoing RAMIE (Group 1) and those undergoing VATE (Group 2). The demographic and clinical characteristics, intraoperative parameters, pathological data, and postoperative parameters of the groups were compared. Results: A total of 28 patients were included in the study, with 13 patients in Group 1 and 15 patients in Group 2. The gender distribution was similar (P = 0.488), and the mean age was 64.7 and 59.0 years in Groups 1 and 2, respectively (P = 0.068). The majority of the sample was in the ASA2 category (46.2% vs. 66.7%, P = 0.341); Ca19.9 levels were higher in Group 1 than in Group 2 (25.7 vs. 13.7, P = 0.027); preoperative Hb was lower in Group 1 than in Group 2 (10.9 g/dL vs. 12.2 g/dL, P = 0.043); the most commonly performed surgery was the McKeown procedure (69.2% vs. 66.7%, P = 0.492); an intraoperative feeding jejunostomy was placed only in Group 2; the operation time was similar between the groups (338.5 min vs. 340 min, P = 0.916); and the distribution of tumor localizations was similar between the groups (P = 0.407). In terms of tumor histology, squamous cell carcinoma (SCC) was the most common tumor type in the two groups (84.6% vs. 80%, P = 0.636); the tumor diameter was similar between the groups (14.9 vs. 18.1, P = 0.652); the number of removed lymph nodes was similar between the groups (24.9 vs. 22.5, P = 0.419); and the number of metastatic lymph nodes was higher in Group 2 (0.08 vs. 1.07, P = 0.27). One patient in Group 2 underwent repeat surgery due to suspected ischemic anastomosis; the distribution of postoperative complications according to the Clavien–Dindo classification system was similar in the two groups (P = 0.650); there was no early mortality within the first 30 days in either group; one patient in Group 2 was re-admitted within 90 days of discharge with decreased oral intake; the length of hospital stay was shorter in Group 1 (9 days vs. 16.5 days, P = 0.006); and the patients in Group 2 more often received neoadjuvant therapy in proportion to the disease stage (15.4% vs. 60%, P = 0.016). Conclusion: Robotic procedures can be safely performed in esophageal cancers with complication rates and oncological radicality similar to those of other minimally invasive techniques.