Prevalence of HIV, hepatitis B and hepatitis C infections among patients with thalassemia attending a tertiary care (rural) hospital.

Introduction: The Sunderban area of West Bengal is home to tribal and religious minorities inhabiting various islands. There is a high prevalence of thalassemia among poverty-stricken residents of this region living with meagre health care facilities. This work was planned to determine the proportion of four viral transfusion-transmitted infections (TTIs): HIV-1, HIV-2, hepatitis B virus (HBV) and hepatitis C virus (HCV) among thalassemia patients attending the sole rural medical college in the region. Materials and Methods: Thalassemia patients (n = 359, age ranging from 1 year to 60 years) attending the thalassemia clinic or being admitted to the indoor facilities for better management were included in the study. Only patients diagnosed with high-performance liquid chromatography (HPLC) and with classical clinical features were included in the study. Blood samples of these patients were tested for HIV as per NACO protocol. For HBV and HCV, samples were first tested serologically; reactive samples were collected and sent in the cold chain to a higher centre for nucleic acid amplification testing (NAAT) for qualitative and quantitative estimation. Clinical and laboratory data was collected, patients were followed up for complications and hospitalisation during the study period, and statistical analysis was performed. Results: Majority of our patients had E-beta-thalassemia (245, 59.81%), followed by beta-thalassemia major (102, 28.30%). NAAT-confirmed HCV infection (14.21%) infection was the most common, followed by HBV (2.51%), and lastly by HIV-1 (0.58%) infection. Among infected thalassemia patients, the mean HCV RNA was 741063 ± 438514.67 IU/ml while the mean HBV DNA level was 4082863 ± 7298514 IU/ml. Co-infections of HIV-1 and HCV and that of HBV and HCV were noted in one patient each (0.28%). HCV-related liver disease (14.21%) and growth retardation (10.31%) were the most typical complication noted, and death occurred in five patients (1.39%) during the study period. Conclusion: Primary care physicians should know HCV infection is the most common TTI among thalassemia patients in rural eastern India.

An Insight Into Various Manifestations of Leptospirosis: A Unique Case Series From a State in Eastern India.

BACKGROUND: Leptospirosis presents with highly variable clinical manifestations affecting different organ systems in different individuals. The presentation ranges from an asymptomatic or mild disease to a severe disease associated with multiorgan failure and higher mortality. Leptospirosis is highly underreported due to a lack of diagnostic modalities and less suspicion among clinicians. METHODOLOGY: We present this single-center retrospective case series of 12 cases, which include various common and uncommon scenarios by which the disease can present and can be missed due to lack of suspicion. The study contains individual patient characteristics including demographic, laboratory, clinical, and treatment data. The association between these variables and mortality was analyzed using p-values and results were described. A p-value of<0.05 was considered statistically significant. RESULTS: A total of 12 cases were included in the study. The male-to-female ratio was 3:1. The mean age was higher (37.75±9.81 years) in cases who died than those who recovered (34.25±14.09). Factors like history of alcoholism, presence of chronic liver disease (CLD), jaundice, acute renal failure, requirement of dialysis, and requirement of intensive care were significantly associated with increased risk of death (odds ratio >1, p-value <0.05). The most common symptom of presentation was fever in 11 (91.66%) cases. Jaundice and renal failure were significantly associated with death (odds ratio 1.2, p-value 0.04). The requirement of intensive care treatment (odds ratio 2.1, p-value 0.05) and dialysis (odds ratio 39.66, p-value 0.03) were also significantly associated with death. The percentage of death was lower in the group of patients who received combination antibiotic therapy. CONCLUSION: Leptospirosis has varied presentations in different individuals and the diagnosis can be missed due to lack of specific signs and symptoms. Severe diseases involving multiple organs and preexisting comorbidities are associated with higher mortality rates. Timely diagnosis and treatment are necessary to reduce mortality and increase survival.

Advancing glioma diagnosis: Integrating custom U-Net and VGG-16 for improved grading in MR imaging.

In the realm of medical imaging, the precise segmentation and classification of gliomas represent fundamental challenges with profound clinical implications. Leveraging the BraTS 2018 dataset as a standard benchmark, this study delves into the potential of advanced deep learning models for addressing these challenges. We propose a novel approach that integrates a customized U-Net for segmentation and VGG-16 for classification. The U-Net, with its tailored encoder-decoder pathways, accurately identifies glioma regions, thus improving tumor localization. The fine-tuned VGG-16, featuring a customized output layer, precisely differentiates between low-grade and high-grade gliomas. To ensure consistency in data pre-processing, a standardized methodology involving gamma correction, data augmentation, and normalization is introduced. This novel integration surpasses existing methods, offering significantly improved glioma diagnosis, validated by high segmentation dice scores (WT: 0.96, TC: 0.92, ET: 0.89), and a remarkable overall classification accuracy of 97.89%. The experimental findings underscore the potential of integrating deep learning-based methodologies for tumor segmentation and classification in enhancing glioma diagnosis and formulating subsequent treatment strategies.

Metabolism of the 4-Hydroxyphenylpyruvate Dioxygenase Inhibitor, Mesotrione, in Multiple-Herbicide-Resistant Palmer amaranth (Amaranthus palmeri).

Metabolic resistance to the maize-selective, HPPD-inhibiting herbicide, mesotrione, occurs via Phase I ring hydroxylation in resistant waterhemp and Palmer amaranth; however, mesotrione detoxification pathways post-Phase I are unknown. This research aims to (1) evaluate Palmer amaranth populations for mesotrione resistance via survivorship, foliar injury, and aboveground biomass, (2) determine mesotrione metabolism rates in Palmer amaranth populations during a time course, and (3) identify mesotrione metabolites including and beyond Phase I oxidation. The Palmer amaranth populations, SYNR1 and SYNR2, exhibited higher survival rates (100%), aboveground biomass (c.a. 50%), and lower injury (25-30%) following mesotrione treatment than other populations studied. These two populations also metabolized mesotrione 2-fold faster than sensitive populations, PPI1 and PPI2, and rapidly formed 4-OH-mesotrione. Additionally, SYNR1 and SYNR2 formed 5-OH-mesotrione, which is not produced in high abundance in waterhemp or naturally tolerant maize. Metabolite features derived from 4/5-OH-mesotrione and potential Phase II mesotrione-conjugates were detected and characterized by liquid chromatography-mass spectrometry (LCMS).

Platelet function testing and clinical outcomes in peripheral arterial disease: Systematic review and narrative synthesis.

OBJECTIVE: This systematic review aims to comprehensively assess the contemporary literature on platelet function testing (PFT) in individuals undergoing revascularization therapy for peripheral arterial disease (PAD). The goal is to identify whether PFT can aid in detecting antiplatelet resistance, predicting post-procedural thrombotic complications, and informing tailored treatment strategies. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature review was conducted using PubMed databases. Search terms included relevant medical subject headings (MeSH) terms. Eligible articles published in English between 1990 and 2023 were analyzed. Studies that examined PFT outcomes in patients with PAD after lower extremity revascularization were included. RESULTS: Ten studies met the inclusion criteria. Various PFT methods were used, including thromboelastography with platelet mapping, multiplate analyzer, Cytochrome P450 2C19 testing, VerifyNow, corrected whole blood aggregometry, platelet function analyzer-100, and light transmission aggregometry. PFT identified individuals who were resistant or non-sensitive to antiplatelet therapy, with such patients facing increased risks of graft/stent thrombosis, amputation, and reintervention. However, substantial heterogeneity in surgical procedures, drug regimens, and testing methods was observed among the studies. CONCLUSIONS: PFTs can play a crucial role in detecting resistance and non-sensitivity to antiplatelet drugs in patients with PAD post-revascularization. However, heterogeneity of data and methods underlines the need for standardized protocols and consensus-building among PFTs. Enhancing clinical utility and reliability could help optimize antiplatelet thromboprophylaxis, minimize thrombotic complications, and improve treatment strategies in vascular surgery. Further research is necessary to solidify the role of PFTs in guiding antiplatelet therapy post-revascularization in patients with PAD.

Advancing Precision in Post-mastectomy Chest Wall Radiotherapy: A Comparative Dosimetric Analysis of Volumetric-Modulated Arc Therapy (VMAT) and Intensity-Modulated Radiotherapy (IMRT) Based on Institutional Experience.

BACKGROUND: Post-mastectomy radiation therapy (PMRT) is an important component in the management of breast cancer patients who have undergone mastectomy. Intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) are two popular methods of delivering PMRT. With IMRT, high radiation doses are directed at the tumor, while exposure to healthy tissue is kept to a minimum. VMAT, on the other hand, is a more advanced version of IMRT that allows for faster radiation dose delivery while maintaining precision. The complexity of the VMAT treatment planning and delivery process, on the other hand, may increase the risk of technical errors, which can reduce treatment effectiveness.  Studies have compared VMAT and IMRT in PMRT for breast cancer patients, but most have found no significant differences in treatment outcomes between the two methods. Individual patient factors such as treatment goals, available resources, and other characteristics may influence the choice between the two techniques. PURPOSE:  This prospective observational study aimed to compare the dosimetry of two cutting-edge modern radiotherapy techniques for post-mastectomy breast cancer patients receiving hypofractionated doses. METHODS:  For 58 patients with breast cancer, 116 plans for radiotherapy treatment were generated by both VMAT and IMRT. To maintain the uniformity of contouring, every CT image was contoured by the same physician, and Radiotherapy Oncology Group (RTOG) contouring guidelines were strictly followed during contouring. RESULTS: Both techniques had comparable target volume coverage, but VMAT produced a significantly better conformity index than IMRT for both the left (0.71 vs. 0.65) and right (0.72 vs. 0.66) breasts (p-value < 0.05). VMAT plans had significantly higher low-dose spillage to the ipsilateral lung (V5Gy and V10Gy) but significantly lower high-dose spillage (V20Gy, V30Gy, and V40Gy) than IMRT plans (p-value < 0.05). Dmax and Dmean for the ipsilateral lung were comparable for both techniques. When compared to alternative treatment approaches, IMRT treatment plans were found to be more effective in minimizing radiation exposure to the heart for all patients with right-sided breast cancer, resulting in considerably lower levels of Dmean, V5Gy, V10Gy, V20Gy, and V35Gy. Plans for VMAT treatment were found to be significantly superior to left-side chest wall radiotherapy in terms of lower exposure to the heart for higher doses. IMRT plans, on the other hand, were successful in dramatically lowering the levels of Dmax that reached the spinal cord for both right- and left-sided breast cancers. CONCLUSION: Apart from similar planning target volume (PTV) coverage to IMRT plans, VMAT produced significantly better conformity. VMAT plans have more low-dose spillage to normal tissues, while IMRT plans spare various organs at risk significantly better at lower doses in both right and left-sided breast cancer. VMAT was found to be better at sparing the heart (in left-sided breast cancer only) and ipsilateral lung at a high dose range. The best radiotherapy approach for breast cancer should be established on an individual basis, taking into account tumor laterality and the risk-benefit ratio.

Preoperative Anemia is Associated with Poorer Postoperative Outcomes in Patients Undergoing Infrainguinal Bypass Surgery.

BACKGROUND: Preoperative anemia is an important, modifiable risk factor among surgical patients. However, data are scarce on the impact of preoperative anemia on postoperative outcomes after infrainguinal bypass. METHODS: In this multi-institutional analysis, data were retrospectively collected on all infrainguinal bypass procedures performed between 2010 and 2020. Patients were grouped by preoperative hemoglobin as per the National Cancer Institute anemia scale (mild, 10 g/dL-lower limit of normal; moderate, 8.0-9.9 g/dL; severe, 6.5-7.9 g/dL). Multivariable comparisons were performed using logistic regression analysis. RESULTS: A total of 492 patients underwent bypass for peripheral artery disease over the 10-year study period. Median preoperative hemoglobin was 11.0 g/dL (interquartile range 9.5-12.7) and median follow-up was 1.7 years. Preoperative anemia was prevalent among bypass patients (mild 52.4% [n = 258], moderate 26.4% [n = 130], and severe 5.1% [n = 25]). Women were more likely to have moderate (49.2% [women] vs. 50.8% [men]) or severe anemia (52.0% [women] vs. 48.0% [men]) compared with normal hemoglobin (17.7% [women] vs. 82.3% [men]) (P < 0.001). Patients with preoperative anemia were more likely to present with tissue loss (22.8% [normal] vs. 47.7% [moderate] vs. 52.0% [severe], P = 0.01). Bypass target and conduit types were similar between groups. Anemic patients had longer median hospital length of stay compared with nonanemic patients (4 days [normal] vs. 5 days [mild] vs. 6 days [moderate] vs. 7 days [severe], P < 0.001). Postoperative mortality at 30 days was similar across anemia groups (2.5% [normal] vs. 4.6% [moderate] vs. 8.0% [severe], P = 0.23). On multivariable analysis, however, postoperative mortality was independently associated with severe anemia (odds ratio 7.5 [1.2-48.8], P = 0.04) and male gender (odds ratio 7.5 [1.2-26.4], P = 0.03). CONCLUSIONS: Preoperative anemia is common among patients undergoing infrainguinal bypass surgery and is an independent risk factor for postoperative mortality. Future investigation is needed to determine whether correction of anemia improves postoperative outcomes in these high-risk patients.

Outcomes of Femoropopliteal Bypass for Lifestyle-Limiting Claudication in the Endovascular Era.

INTRODUCTION: Outcomes after femoropopliteal bypass for intermittent claudication (IC) remain unclear in the endovascular era. METHODS: A multi-institutional database was retrospectively queried for all femoropopliteal bypass procedures performed between 1995 and 2020. Demographics, operative details, and outcomes were documented. A statistical analysis included Kaplan-Meier curves and Cox proportional hazards ratios (HR). RESULTS: A total of 282 patients underwent femoropopliteal bypass surgery for IC. Median age was 68 y (interquartile range, 61-73 y). Bypass conduits included great saphenous vein (GSV) (48.2%), prosthetic grafts (48.9%), and non-GSV autogenous grafts (2.8%). Distal bypass target was above-knee in 62.1% and below-knee in 37.9% of patients. The most common postoperative complications were wound infections (14.2%) followed by unplanned 30-d hospital readmissions (12.4%). Mortality rates were low at 0.4% (30 d) and 3.2% (1 y). Five-year primary patency rates trended highest for claudicants undergoing above-knee bypass with GSV conduit (log-rank P = 0.065). Five-year amputation-free survival rates were highest using GSV conduit regardless of distal bypass target (log-rank P = 0.017). On a multivariable analysis, age (HR 1.02 [1.00-1.04], P = 0.023) and active smoking (HR 1.48 [1.06-2.06], P = 0.021) were identified as risk factors for diminished primary graft patency. Risk factors for amputation-free survival included age (HR 1.03 [1.01-1.05], P < 0.001) and GSV conduit type (HR 0.65 [0.46-0.90], P = 0.011). CONCLUSIONS: Femoropopliteal bypass among claudicants is associated with high rates of wound infection and hospital readmission. Active smoking portends worse outcomes in this population. These data may inform clinical decision-making regarding surgical intervention for claudication in the endovascular era.

Impact of anticoagulation/antiplatelet therapy on femoropopliteal bypass graft outcomes.

BACKGROUND: Anticoagulant and antiplatelet (AC/AP) medications have been reported to improve bypass graft patency, however, the optimal AC/AP strategy remains unclear in the heterogenous peripheral artery disease population. METHODS: A multi-institutional retrospective review utilizing the Research Patient Data Registry database from 1995 to 2020 was performed for all patients who underwent femoropopliteal bypass procedures. Electronic medical records were used to obtain demographic information, comorbidities, smoking status, operative details (bypass target), postoperative AC/AP medications, postoperative complications, and long-term outcomes and were reviewed for the cohort. Cox proportional hazards model was used to determine independent risk factors for major adverse limb events (MALE) after bypass. MALE was defined as reintervention for patency or major amputation of index limb (above- or below-knee amputation). RESULTS: A total of 1421 patients underwent femoropopliteal bypass between 1995 and 2020 throughout five institutions included in this study. Complete data were available for 1292 of the 1421 patients (90.9%). The indications for bypass included intermittent claudication (21.4%), rest pain (30.3%), tissue loss (33.5%), and nonatherosclerotic disease (14.8%). Distal bypass targets comprised above-knee (38.6%) and below-knee (61.4%) popliteal arteries. Patients were divided into six groups based on postoperative AC/AP use including none (n = 57 [4.4%]), monoantiplatelet therapy (n = 587 [45.4%]), dual AP therapy (n = 214 [16.6%]), AC alone (n = 73 [5.7%]), AC + monoantiplatelet therapy (n = 319 [24.7%]), and AC + dual AP therapy (n = 42 [3.3%]). Postoperative bleeding complications were low for both hematoma (3.7%) and pseudoaneurysm (0.7%). There was no difference in bleeding complications across AC/AP groups (hematoma, P = .61; pseudoaneurysm, P = .31). After adjusting for patient factors, below-knee bypass target (hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.04-1.52; P = .019) and bypass for tissue loss (HR, 1.40; 95% CI, 1.04-1.88; P = .028) were independent predictors for MALE. Great saphenous vein conduit trended toward protection for MALE, compared with prosthetic grafts (HR, 0.84; 95% CI, 0.70-1.01; P = .06). No AC/AP regimen was associated with of MALE, even stratifying by above-knee and below-knee bypass cohorts. The median follow-up period was 2 years. CONCLUSIONS: Among patients undergoing femoropopliteal bypass grafting, no combination of AC or AP medications was associated with improved graft patency; however, a below-knee target and tissue loss were associated with adverse limb events. AC and AP regimen may be individualized after bypass with regard to other concomitant medical comorbidities.

Risk factors and consequences of graft infection after femoropopliteal bypass: A 25-year experience.

OBJECTIVE: In this multi-institutional series, we aimed to determine the incidence, risk factors, and long-term outcomes of graft infection in patients post-femoropopliteal bypass. METHODS: A multi-institutional database was retrospectively queried for all femoropopliteal bypass procedures from 1995 through 2020. Cumulative incidence function estimated the long-term rate of bypass graft infection (BGI), and the Fine-Gray model was used to determine independent risk factors for BGI to account for death as a competing risk. RESULTS: Over the 25-year period, 1315 femoral popliteal bypasses were identified with a median follow-up of 2.89 years (interquartile range, 0.75-6.55 years). BGI was diagnosed in 34 patients (2.6%). BGI occurred between 9 days and 11.2 years postoperatively, with a median of 109 days. Estimated 1- and 5-year incidence of BGI was 2.1% (95% confidence interval [CI], 1.4%-3.1%) and 2.8% (95% CI, 1.9%-3.9%), respectively. Medical comorbidities, indications for bypass, and popliteal bypass targets (above- vs below-knee) were similar between patients with BGI and all patients (P = not significant for each). Patients with BGI were more frequently complicated by postoperative hematoma (14.7% vs 3.7%), superficial wound infection (38.2% vs 19.2%), lymphocele/lymphorrhea (8.8% vs 2.1%), and 30-day readmission rates (47.1% vs 21.3%) (P < .05 for each). Most commonly isolated pathogens were Staphylococcus aureus (n = 19; 55.9%) and polymicrobial cultures (n = 5; 14.7%). Reoperation for BGI involved incision and drainage (n = 7; 20.6%), graft excision without reconstruction (n = 12; 35.3%), graft excision with in-line reconstruction (n = 11; 32.4%), and graft excision with extra-anatomic reconstruction (n = 2; 5.9%). Nine patients with BGI (26.5%) ultimately required major amputation. Prosthetic bypass (subdistribution hazard ratio [SHR], 3.73; 95% CI, 1.64-8.51; P = .002), postoperative hematoma (SHR, 3.44; 95% CI, 1.23-9.61; P = .018), and 30-day readmission (SHR, 2.75; 95% CI, 1.27-5.44; P = .010) were independently associated with BGI. One-year amputation-free survival was 50% (95% CI, 31.9%-65.7%) after BGI. CONCLUSIONS: BGI is a rare complication of femoral-popliteal bypass with significant morbidity. Graft infection is associated with the use of prosthetic grafts, postoperative hematoma, and unplanned hospital readmission. Mitigation of these risk factors may decrease the risk of this dreaded complication.

The Weekend Effect in Carotid Endarterectomy for Symptomatic Carotid Stenosis.

BackgroundRecent studies report a limited window in which carotid endarterectomy (CEA) provides the greatest benefit for symptomatic carotid stenosis. Given the time-sensitive nature of CEA for symptomatic stenosis, it is important to understand whether patient outcomes are adversely affected by undergoing CEA over the weekend. Currently, it is unclear whether CEA is impacted by the "weekend effect" phenomenon. Methods A multi-institutional database was queried for all patients undergoing CEA for symptomatic carotid artery stenosis from 2015 to 2020 via ICD-9 codes. A total of 288 patients were identified during the study period. Univariate and multivariate analysis were used to compare outcomes based on weekend vs weekday surgery. Results A total of 261 patients (90.6%) underwent weekday CEA, as compared to 27 (9.4%) on the weekend. There were no differences in age, race, gender, or medical comorbidities between groups. Primary surgeon specialty was predominantly vascular surgery (77.0% weekday and 74.1% weekend) followed by neurosurgery (19.9% weekday and 25.9% weekend). Operative time was similar between groups (3.1 (weekday) vs 2.9 hr (weekend), P = .33) as well as estimated blood loss (100 vs 100 mL, P = .54). Hospital length of stay did not differ between groups (P = .69). Combined stroke and 30-day mortality rate was 2.0% on weekdays, compared to 3.7% on weekends (P = .75). On multivariate analysis, weekend surgery was not predictive of postoperative stroke or 30-day mortality (odds ratio .11 [95% CI: -1.57 to 1.85], P = .90). Conclusion In our multi-institutional experience, we did not identify a "weekend effect" in patients undergoing CEA for symptomatic carotid artery stenosis. Surgical revascularization should not be withheld on account of a weekend procedure in similar academic medical centers.

Neutralizing anti-IL-1 receptor antagonist autoantibodies induce inflammatory and fibrotic mediators in IgG4-related disease.

BACKGROUND: IgG4-related disease (IgG4-RD) is a fibroinflammatory condition involving loss of B-cell tolerance and production of autoantibodies. However, the relevant targets and role of these aberrant humoral immune responses are not defined. OBJECTIVE: Our aim was to identify novel autoantibodies and autoantigen targets that promote pathogenic responses in IgG4-RD. METHODS: We sequenced plasmablast antibody repertoires in patients with IgG4-RD. Representative mAbs were expressed and their specificities characterized by using cytokine microarrays. The role of anti-IL-1 receptor antagonist (IL-1RA) autoantibodies was investigated by using in vitro assays. RESULTS: We identified strong reactivity against human IL-1RA by using a clonally expanded plasmablast-derived mAb from a patient with IgG4-RD. Plasma from patients with IgG4-RD exhibited elevated levels of reactivity against IL-1RA compared with plasma from the controls and neutralized IL-1RA activity, resulting in inflammatory and fibrotic mediator production in vitro. IL-1RA was detected in lesional tissues from patients with IgG4-RD. Patients with anti-IL-1RA autoantibodies of the IgG4 subclass had greater numbers of organs affected than did those without anti-IL-1RA autoantibodies. Peptide analyses identified IL-1RA epitopes targeted by anti-IL-1RA antibodies at sites near the IL-1RA/IL-1R interface. Serum from patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) also had elevated levels of anti-IL-1RA autoantibodies compared with those of the controls. CONCLUSION: A subset of patients with IgG4-RD have anti-IL-1RA autoantibodies, which promote proinflammatory and profibrotic meditator production via IL-1RA neutralization. These findings support a novel immunologic mechanism underlying the pathogenesis of IgG4-RD. Anti-IL-1RA autoantibodies are also present in a subset of patients with SLE and RA, suggesting a potential common pathway in multiple autoimmune diseases.

A systematic review of thromboelastography utilization in vascular and endovascular surgery.

OBJECTIVE: Thromboelastography (TEG) is diagnostic modality that analyzes real-time blood coagulation parameters. Clinically, TEG primarily allows for directed blood component resuscitation among patients with acute blood loss and coagulopathy. The utilization of TEG has been widely adopted in among other surgical specialties; however, its use in vascular surgery is less prominent. We aimed to provide an up-to-date review of TEG utilization in vascular and endovascular surgery. METHODS: Using Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, a literature review with the Medical Subject Headings (MeSH) terms "TEG and arterial events", "TEG and vascular surgery", "TEG and vascular", "TEG and endovascular surgery", "TEG and endovascular", "TEG and peripheral artery disease", "TEG and prediction of arterial events", "TEG and prediction of complications ", "TEG and prediction of thrombosis", "TEG and prediction of amputation", and "TEG and amputation" was performed in Cochrane and PubMed databases to identify all peer-reviewed studies of TEG utilization in vascular surgery, written between 2000 and 2021 in the English language. The free-text and MeSH subheadings search terms included diagnosis, complications, physiopathology, surgery, mortality, and therapy to further restrict the articles. Studies were excluded if they were not in humans or pertaining to vascular or endovascular surgery. Additionally, case reports and studies with limited information regarding TEG utilization were excluded. Each study was independently reviewed by two researchers to assess for eligibility. RESULTS: Of the 262 studies identified through the MeSH strategy, 15 studies met inclusion criteria and were reviewed and summarized. Literature on TEG utilization in vascular surgery spanned cerebrovascular disease (n = 3), peripheral arterial disease (n = 3), arteriovenous malformations (n = 1), venous thromboembolic events (n = 7), and perioperative bleeding and transfusion (n = 1). In cerebrovascular disease, TEG may predict the presence and stability of carotid plaques, analyze platelet function before carotid stenting, and compare efficacy of antiplatelet therapy after stent deployment. In peripheral arterial disease, TEG has been used to predict disease severity and analyze the impact of contrast on coagulation parameters. In venous disease, TEG may predict hypercoagulability and thromboembolic events among various patient populations. Finally, TEG can be utilized in the postoperative setting to predict hemorrhage and transfusion requirements. CONCLUSIONS: This systematic review provides an up-to-date summarization of TEG utilization in multiple facets of vascular and endovascular surgery.

The current status of the diversity pipeline in surgical training.

OBJECTIVE: Recent initiatives have emphasized the importance of diversity, equity, and inclusion in academic surgery. Racial/ethnic disparities remain prevalent throughout surgical training, and the "diversity pipeline" in resident recruitment and retention remains poorly defined. METHODS: Data was retrospectively collected using two separate datasets. The Association of American Medical Colleges database was used to obtain demographic data on US medical school graduates. The US Graduate Medical Education annual report was used to obtain demographic data on surgical residents. Wilcoxon signed-rank test was used to compare racial/ethnic distribution within surgical residency programs with graduating medical students. Linear regression analysis was performed to analyze population trends over time. RESULTS: The study population included 184,690 surgical residents from 2011 to 2020. Nine resident cohorts were created according to surgical specialty - general surgery, neurosurgery, ophthalmology, orthopedic surgery, otolaryngology, plastic surgery, cardiothoracic surgery, urology, and vascular surgery. Among surgical programs, White residents were overrepresented in 8 of 9 specialties compared to the concurrent graduating medical student class for all years (p < 0.01 each, no difference in ophthalmology). Black residents were underrepresented in 8 of 9 specialties (p < 0.01 each, no difference in general surgery). Asian representation was mixed among specialties (4 overrepresented, 1 equal, 4 underrepresented), as was Hispanic representation (5 overrepresented, 4 equal) (p < 0.01 each). CONCLUSIONS: These data suggest that racial/ethnic disparities are inherent to the process of recruitment and retention of surgical residents. Efforts to improve the "diversity pipeline" should focus on mentorship and development of minority medical students and creating an equitable learning environment.

Role of solute carrier transporters SLC25A17 and SLC27A6 in acquired resistance to enzalutamide in castration-resistant prostate cancer.

Enzalutamide (XTANDI®), an antiandrogen, is used for the treatment of advanced-stage prostate cancer. Approximately, 60% of patients receiving enzalutamide show initial remission followed by disease relapse with the emergence of highly aggressive castration-resistant prostate cancer. Solute carrier (SLC) proteins play a critical role in the development of drug resistance by altering cellular metabolism. Transcriptome analysis revealed the predominance of SLC25A17 and SLC27A6 in enzalutamide-resistant prostate cancer cells; however, their role in antiandrogen resistance has not been elucidated. sgRNA-mediated knockdown of SLC25A17 and SLC27A6 suppressed cell proliferation and migration in enzalutamide-resistant cells. An induction of G1/S cell cycle arrest and abundance of hypo-diploid cells along with the reduction in the protein expression CyclinD1 and CDK6, the checkpoint factors, was observed including increased cell death as evident by BAX upregulation in knockdown cells. Inhibition of SLC25A17 and SLC27A6 resulted in downregulation of fatty acid synthase and acetyl-CoA carboxylase with parallel decrease in the levels of lactic acid in enzalutamide resistant cells. However, downregulation of triglyceride and citric acid was only observed in SLC25A17 silenced cells. The protein-protein interaction of SLC25A17 and SLC27A6 revealed alteration in some common drug-resistant and metabolism-related genes. Analysis of The Cancer Genome Atlas database exhibiting high SLC25A17 and SLC27A6 gene expression in prostate cancer patients were associated with poor survival than those with low expression of these proteins. In conclusion, SLC25A17 and SLC27A6 and its interactive network play an essential role in the development of enzalutamide resistance through metabolic reprogramming and may be identified as therapeutic target(s) to circumvent drug resistance.

Resistance to a nonselective 4-hydroxyphenylpyruvate dioxygenase-inhibiting herbicide via novel reduction-dehydration-glutathione conjugation in Amaranthus tuberculatus.

Metabolic resistance to 4-hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting herbicides is a threat in controlling waterhemp (Amaranthus tuberculatus) in the USA. We investigated resistance mechanisms to syncarpic acid-3 (SA3), a nonselective, noncommercial HPPD-inhibiting herbicide metabolically robust to Phase I oxidation, in multiple-herbicide-resistant (MHR) waterhemp populations (SIR and NEB) and HPPD inhibitor-sensitive populations (ACR and SEN). Dose-response experiments with SA3 provided ED50 -based resistant : sensitive ratios of at least 18-fold. Metabolism experiments quantifying parent SA3 remaining in excised leaves during a time course indicated MHR populations displayed faster rates of SA3 metabolism compared to HPPD inhibitor-sensitive populations. SA3 metabolites were identified via LC-MS-based untargeted metabolomics in whole plants. A Phase I metabolite, likely generated by cytochrome P450-mediated alkyl hydroxylation, was detected but was not associated with resistance. A Phase I metabolite consistent with ketone reduction followed by water elimination was detected, creating a putative α,ß-unsaturated carbonyl resembling a Michael acceptor site. A Phase II glutathione-SA3 conjugate was associated with resistance. Our results revealed a novel reduction-dehydration-GSH conjugation detoxification mechanism. SA3 metabolism in MHR waterhemp is thus atypical compared to commercial HPPD-inhibiting herbicides. This previously uncharacterized detoxification mechanism presents a unique opportunity for future biorational design by blocking known sites of herbicide metabolism in weeds.

Metabolic Pathways for S-Metolachlor Detoxification Differ Between Tolerant Corn and Multiple-Resistant Waterhemp.

Herbicide resistance in weeds can be conferred by target-site and/or non-target-site mechanisms, such as rapid metabolic detoxification. Resistance to the very-long-chain fatty acid-inhibiting herbicide, S-metolachlor, in multiple herbicide-resistant populations (CHR and SIR) of waterhemp (Amaranthus tuberculatus) is conferred by rapid metabolism compared with sensitive populations. However, enzymatic pathways for S-metolachlor metabolism in waterhemp are unknown. Enzyme assays using S-metolachlor were developed to determine the specific activities of glutathione S-transferases (GSTs) and cytochrome P450 monooxygenases (P450s) from CHR and SIR seedlings to compare with tolerant corn and sensitive waterhemp (WUS). GST activities were greater (∼2-fold) in CHR and SIR compared to WUS but much less than corn. In contrast, P450s in microsomal extracts from CHR and SIR formed O-demethylated S-metolachlor, and their NADPH-dependent specific activities were greater (>20-fold) than corn or WUS. Metabolite profiles of S-metolachlor generated via untargeted and targeted liquid chromatography-mass spectrometry from CHR and SIR differed from WUS, with greater relative abundances of O-demethylated S-metolachlor and O-demethylated S-metolachlor-glutathione conjugates formed by CHR and SIR. In summary, our results demonstrate that S-metolachlor metabolism in resistant waterhemp involves Phase I and Phase II metabolic activities acting in concert, but the initial O-demethylation reaction confers resistance.

Molecular insights into enhanced resistance of Papaver somniferum against downy mildew by application of endophyte bacteria Microbacterium sp. SMR1.

Downy mildew is one of the most serious diseases of Papaver somniferum. Endophytes isolated from different parts of P. somniferum were screened for their ability to enhance resistance against downy mildew caused by the obligate biotrophic oomycete Peronospora meconopsidis. Two endophytes (SMR1 and SMR2) reduced the downy mildew on three P. somniferum genotypes (Sampada, J-16, and I-14). SMR1 (Microbacterium sp.) also enhanced the resistance of P. somniferum against downy mildew under field conditions. The biochemical markers of plant susceptibility under biotic stresses (proline and malondialdehyde) were found to be reduced in P. somniferum upon SMR1 treatment. To understand the mechanisms underlying the enhanced resistance to downy mildew in SMR1 endophyte-treated P. somniferum genotype J-16, we compared the expression profiles using the next-generation RNA sequencing approach between P. somniferum pretreated with SMR1 and untreated endophyte-free control plants following exposure to downy mildew pathogen. Comparative transcriptome analysis revealed differential expression of transcripts belonging to broad classes of signal transduction, protein modification, disease/defense proteins, transcription factors, and phytohormones in SMR1-primed P. somniferum after infection with downy mildew pathogen. Furthermore, enhanced salicylic acid content was observed in SMR1-primed P. somniferum after exposure to downy mildew pathogen. This study sheds light on molecular mechanisms underlying enhanced resistance to downy mildew in SMR1-primed P. somniferum. Finally, we propose that the SA-dependent defense pathway, the hallmark of systemic acquired resistance, is activated in SMR1-primed P. somniferum, triggering the endophyte-induced resistance.