Cardiotoxicity in Acute Myeloid Leukemia in Adults: A Scoping Study.

Introduction: According to the National Cancer Institute of the NIH, acute myeloid leukemia (AML) is a rapidly growing cancer with a large quantity of myeloblasts. AML is most often observed in adults over the age of 35, accounting for 1% of all cancer types. In 2023, the number of new cases being reported was estimated to reach around 20,380 in total and the rate of mortality in the same year was 1.9%, or 11,310 cases, in the US. Purpose: This scoping study aims to extensively assess and explore the degree of cardiotoxicity in patients with AML that can be caused due to pharmaceutical treatments prescribed by hematologists. This is achieved by performing extensive searches of different scientific databases including PubMed, Scopus, and ScienceDirect. Results: A variety of options are available that are summarized in tables included herein, with each having their advantages and risks of adverse effects, among these being cardiotoxicity. Important medications found to play a significant role include gemtuzumab ozogamicin, venetoclax, and vyxeos. Conclusions: It is understandable that being familiar with all the treatment options available and every potential adverse effect is impossible. However, hematologists and, in general, physicians must try to be updated with the most recent information released to improve the quality of life of their patients and minimize the risk of additional complications.

Coping with Examination Stress: An Emotion Analysis.

Stress is an important factor affecting human behavior, with recent works in the literature distinguishing it as either productive or destructive. The present study investigated how the primary emotion of stress is correlated with engagement, focus, interest, excitement, and relaxation during university students' examination processes. Given that examinations are highly stressful processes, twenty-six postgraduate students participated in a four-phase experiment (rest, written examination, oral examination, and rest) conducted at the International Hellenic University (IHU) using a modified Trier protocol. Network analysis with a focus on centralities was employed for data processing. The results highlight the important role of stress in the examination process; correlate stress with other emotions, such as interest, engagement, enthusiasm, relaxation, and concentration; and, finally, suggest ways to control and creatively utilize stress.

Gestational Diabetes Mellitus and Its Correlation in the Development of Pancreatic Cancer: A 10-Year Systematic Review.

PURPOSE: Pancreatic cancer (PC) is a fatal malignancy with an aggressive course derived from the cells of pancreatic tissue. Gestational diabetes mellitus (GDM) is a state of spontaneous hyperglycemia occurring during gestation and has been suggested as a risk factor PC. Women with a history of GDM revealed a risk rate of 7.1% for the development of PC. The current systematic review aims to investigate the correlation between GDM and the degree to the prevalence of PC. METHODOLOGY: For this systematic review, the PICO model was prepared to construct and outline the exact questions of the study, a PRISMA flow diagram was prepared and quality assessment was conducted using the Newcastle Ottawa Scale (NOS) for Cohort Studies, the NIH Quality Assessment Tool-Criteria for Case Reports and the Cochrane quality assessment tool for Systematic Reviews and Meta-analysis studies. RESULT: A total of eight articles were retrieved from the main databases, and a table was created to summarize the information found. Even though the data found were limited, the quality assessment performed revealed that the articles were of high validity. CONCLUSIONS: It can be concluded that GDM has an association with the development of PC and can be considered as a risk factor.

DNA hydroxymethylation differences underlie phenotypic divergence of somatic growth in Nile tilapia reared in common garden.

Phenotypic plasticity of metabolism and growth are essential for adaptation to new environmental conditions, such as those experienced during domestication. Epigenetic regulation plays a key role in this process but the underlying mechanisms are poorly understood, especially in the case of hydroxymethylation. Using reduced representation 5-hydroxymethylcytosine profiling, we compared the liver hydroxymethylomes in full-sib Nile tilapia with distinct growth rates (3.8-fold difference) and demonstrated that DNA hydroxymethylation is strongly associated with phenotypic divergence of somatic growth during the early stages of domestication. The 2677 differentially hydroxymethylated cytosines between fast- and slow-growing fish were enriched within gene bodies (79%), indicating a pertinent role in transcriptional regulation. Moreover, they were found in genes involved in biological processes related to skeletal system and muscle structure development, and there was a positive association between somatic growth and 5hmC levels in genes coding for growth factors, kinases and receptors linked to myogenesis. Single nucleotide polymorphism analysis revealed no genetic differentiation between fast- and slow-growing fish. In addition to unveiling a new link between DNA hydroxymethylation and epigenetic regulation of growth in fish during the initial stages of domestication, this study suggests that epimarkers may be applied in selective breeding programmes for superior phenotypes.

Robotic versus laparoscopic gastrectomy for adenocarcinoma in the US: a propensity score-matching analysis of 11,173 patients on oncological adequacy.

INTRODUCTION: Surgery remains the cornerstone treatment for gastric cancer. Previous studies have reported better lymphadenectomy with minimally invasive approaches. There is a paucity of data comparing robotic and laparoscopic gastrectomy in the US. Herein, we examined whether oncological adequacy differs between laparoscopic and robotic approaches. METHODS: The National Cancer Database was utilized to identify patients who underwent gastrectomy for adenocarcinoma between 2010 and 2019. A propensity score-matching analysis between robotic gastrectomy (RG) versus laparoscopic gastrectomy (LG) was performed. The primary outcomes were lymphadenectomy ≥ 16 nodes and surgical margins. RESULTS: A total of 11,173 patients underwent minimally invasive surgery for gastric adenocarcinoma between 2010 and 2019. Of those 8320 underwent LG and 2853 RG. Comparing the unmatched cohorts, RG was associated with a higher rate of adequate lymphadenectomy (63.5% vs 57.1%, p < .0.0001), higher rate of negative margins (93.8% vs 91.9%, p < 0.001), lower rate of prolonged length of stay (26.0% vs 29.6%, p < .0.001), lower 90-day mortality (3.7% vs 5.0%, p < 0.0001), and a better 5-year overall survival (OS) (56% vs 54%, p = 0.03). A propensity score-matching cohort with a 1:1 ratio was created utilizing the variables associated with lymphadenectomy ≥ 16 nodes. The matched analysis revealed that the rate of adequate lymphadenectomy was significantly higher for RG compared to LG, 63.5% vs 60.4% (p = 0.01), respectively. There was no longer a significant difference between RG and LG regarding the rate of negative margins, prolonged length of stay, 90-day mortality, rate of receipt of postoperative chemotherapy, and OS. CONCLUSIONS: This propensity score-matching analysis with a large US cohort shows that RG was associated with a higher rate of adequate lymphadenectomy compared to LR. RG and LG had a similar rate of negative margins, prolonged length of stay, receipt of postoperative chemotherapy, 90-day mortality, and OS, suggesting that RG is a comparable surgical approach, if not superior to LG.

HIV-associated lung disease.

Lung disease encompasses acute, infectious processes and chronic, non-infectious processes such as chronic obstructive pulmonary disease, asthma and lung cancer. People living with HIV are at increased risk of both acute and chronic lung diseases. Although the use of effective antiretroviral therapy has diminished the burden of infectious lung disease, people living with HIV experience growing morbidity and mortality from chronic lung diseases. A key risk factor for HIV-associated lung disease is cigarette smoking, which is more prevalent in people living with HIV than in uninfected people. Other risk factors include older age, history of bacterial pneumonia, Pneumocystis pneumonia, pulmonary tuberculosis and immunosuppression. Mechanistic investigations support roles for aberrant innate and adaptive immunity, local and systemic inflammation, oxidative stress, altered lung and gut microbiota, and environmental exposures such as biomass fuel burning in the development of HIV-associated lung disease. Assessment, prevention and treatment strategies are largely extrapolated from data from HIV-uninfected people. Smoking cessation is essential. Data on the long-term consequences of HIV-associated lung disease are limited. Efforts to continue quantifying the effects of HIV infection on the lung, especially in low-income and middle-income countries, are essential to advance our knowledge and optimize respiratory care in people living with HIV.

Gastric Cancer Surgery in the US: a Contemporary Trend Analysis of Lymphadenectomy and the Impact of Minimally Invasive Approaches.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend harvesting 16 or more lymph nodes for the adequate staging of gastric adenocarcinoma. This study examines the rate of adequate lymphadenectomy over recent years, its predictors, and its impact on overall survival(OS). STUDY DESIGN: The National Cancer Database was utilized to identify patients who underwent surgical treatment for gastric adenocarcinoma between 2006-2019. Trend analysis was performed for lymphadenectomy rates during the study period. Logistic regression, Kaplan-Meier survival plots, and Cox proportional hazard regression were utilized. RESULTS: A total of 57,039 patients who underwent surgical treatment for gastric adenocarcinoma were identified. Only 50.5% of the patients underwent a lymphadenectomy of ≥ 16 nodes. Trend analysis showed that this rate significantly improved over the years, from 35.1% in 2006 to 63.3% in 2019 (p < .0001). The main independent predictors of adequate lymphadenectomy included high-volume facility with ≥ 31 gastrectomies/year (OR: 2.71; 95%CI:2.46-2.99), surgery between 2015-2019 (OR: 1.68; 95%CI: 1.60-1.75), and preoperative chemotherapy (OR:1.49; 95%CI:1.41-1.58). Patients with adequate lymphadenectomy had better OS than patients who did not: median survival: 59 versus 43 months (Log-Rank: p < .0001). Adequate lymphadenectomy was independently associated with improved OS (HR:0.79; 95%CI:0.77-0.81). Laparoscopic and robotic gastrectomies were independently associated with adequate lymphadenectomy compared to open, OR: 1.11, 95%CI:1.05-1.18 and OR: 1.24, 95%CI:1.13-1.35, respectively. CONCLUSION: Although the rate of adequate lymphadenectomy improved over the study period, a large number of patients still lacked adequate lymph node dissection, negatively impacting their OS despite multimodality therapy. Laparoscopic and robotic surgeries were associated with a significantly higher rate of lymphadenectomy ≥ 16 nodes.

Genome-wide hydroxymethylation profiles in liver of female Nile tilapia with distinct growth performance.

The mechanisms underlying the fast genome evolution that occurs during animal domestication are poorly understood. Here, we present a genome-wide epigenetic dataset that quantifies DNA hydroxymethylation at single nucleotide resolution among full-sib Nile tilapia (Oreochromis niloticus) with distinct growth performance. In total, we obtained 355 million, 75 bp reads from 5 large- and 5 small-sized fish on an Illumina NextSeq500 platform. We identified several growth-related genes to be differentially hydroxymethylated, especially within gene bodies and promoters. Previously, we proposed that DNA hydroxymethylation greatly affects the earliest responses to adaptation and potentially drives genome evolution through its targeted enrichment and elevated nucleotide transversion rates. This dataset can be analysed in various contexts (e.g., epigenetics, evolution and growth) and compared to other epigenomic datasets in the future, namely DNA methylation and histone modifications. With forthcoming advancements in genome research, this hydroxymethylation dataset will also contribute to better understand the epigenetic regulation of key genomic features, such as cis-regulatory and transposable elements.

The robotic future of minimally invasive cytoreduction and hyperthermic intraperitoneal chemotherapy for peritoneal surface malignancies.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has been increasingly utilized for peritoneal surface malignancies. This has been commonly utilized for a variety of neoplasms, but, especially mucinous neoplasms of the appendix, ovarian cancer, gastric cancer, colorectal cancer and mesothelioma. Traditionally, CRS/HIPEC has been performed as an open, extensive operation associated with prolonged hospitalization. However, when the peritoneal carcinomatosis index (PCI) is small (<10), minimally invasive approaches can be considered. Such less invasive approaches may be associated with improved postoperative recovery, less complications while preserving oncologic outcomes. The robotic platform offers distinct advantages over laparoscopy with superior visualization and ergonomics which account for its increased utilization in oncologic surgery. Herein, we review available data on minimally invasive approaches to CRS/HIPEC procedures, focusing on patient selection and comparative studies to open CRS/HIPEC. We summarize the existing initial studies on robotically assisted CRS/HIPEC and provide technical insights about our approach to robotically assisted CRS/HIPEC. Current data suggests that treatment of peritoneal surface malignancies with minimally invasive CRS/HIPEC is feasible in selected cases and is associated with improved postoperative recovery. The robotically assisted platform for CRS/HIPEC deserves further investigation and may improve outcomes after this procedure in the future for carefully selected patients with low PCI.

Tumor extent impacts survival benefit in minimally invasive colectomy for T4 colon cancer: A propensity matched national cohort analysis.

BACKGROUND: T4 colon cancers have been underrepresented in randomized trials comparing minimally invasive colectomy (MC) versus open colectomy (OC). Retrospective studies suggest improved survival with MC versus OC, but have not addressed the impact of tumor extent. METHODS: Using the National Cancer Database (NCDB), we analyzed patients undergoing colectomy for T4 colon adenocarcinoma from 2010 to 2014. Propensity score matching was performed between MC and OC patients. Tumor extent was defined by zones based on adjacent organ involvement. RESULTS: Of the 19 178 eligible patients, 6564 (34%) underwent MC. After matching, MC was associated with improved overall survival (hazard ratios: 0.71, 95% confidence interval: 0.67-0.76; median OS 59 vs. 42 months, p < 0.001). Compared to MC patients, those undergoing OC had: a higher margin positive rate (p = 0.009); lower median nodes examined (p < 0.001); a lower rate of adjuvant chemotherapy (p < 0.001); and a longer median time to chemotherapy (p < 0.001). Stratified survival analyses demonstrated that MC was associated with improved overall survival compared to OC in all zones except zone 3 and 4. CONCLUSIONS: Compared to OC, MC for T4 colon cancer is associated with improved oncologic outcomes when performed for zone 0-2 tumors. For, zone 3 and 4 tumors MC and OC have similar oncologic outcomes and patients should be cautiously selected.

The Influence of Smoking on Healing of Scaphoid Non-union after a Vascularized Pedicle Bone Flap Operation: A Review and Meta-analysis.

Background: The purpose of this study is to compare the vascularized bone flaps (VBF) that are used in operations for scaphoid non-union in smokers and non-smokers and to scrutinize if the better biological potential of the VBFs can counteract the negative influence of smoking on healing. Materials and Methods: Our study included articles published until 2016, with scaphoid non-union patients who were operated on with a VBF or a VBG. Results: Eighteen articles met eligibility criteria with 335 non-smokers and 136 smokers totally. Healing of the scaphoid non-union was significantly more probable in the non-smoking group (OR=5.54, p<0.001). Patients with avascular necrosis in the proximal pole of the scaphoid (AVNPP) and non-AVNPP showed that non-smoking favors a better healing rate in both of these subgroups (p<0.001 and p<0.001, respectively). Non-smokers have 11 times and the non-AVNPP patient's 7.7 times greater probability of healing of the non-union. Meta-analysis of the data for time for healing showed a longer time in the smokers' group by 2.46 weeks, though non-statistically significant. The analysis could not prove that smoking is a predisposing factor for the development of AVNPP (spearman=0.094, p<0.05). Despite that, preoperative smoking cessation proved to be an inadequate healing moderator (OR=3.5, p=0.268). Finally, VBFs showed a significantly better healing rate compared with nVBGs in smokers (p=0.001). Conclusions: A hand surgeon should always take into consideration that smoking negatively influences the healing potential of a scaphoid non-union despite the theoretically superior biological background that VBFs offer. In patients who refuse to quit smoking, a VBF may be considered a better choice than a conventional graft.

Pulmonary Function Trajectories in People with HIV: Analysis of the Pittsburgh HIV Lung Cohort.

Rationale: Human immunodeficiency virus (HIV) infection is associated with chronic lung disease and impaired pulmonary function; however, longitudinal pulmonary function phenotypes in HIV are undefined. Objectives: To identify pulmonary function trajectories, their determinants, and outcomes. Methods: We used data from participants with HIV in the Pittsburgh HIV Lung Cohort with three or more pulmonary function tests between 2007 and 2020. We analyzed post-bronchodilator forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/FVC, and diffusing capacity of the lung for carbon monoxide (DlCO) using group-based trajectory modeling to identify subgroups of individuals whose measurements followed a similar pattern over time. We examined the association between participant characteristics and trajectories using multivariable logistic regression. In exploratory adjusted analyses restricted to individuals with available plasma cytokine data, we investigated the association between 18 individual standardized cytokine concentrations and trajectories. We compared mortality, dyspnea prevalence, respiratory health status, and 6-minute-walk distance between phenotypes. Results: A total of 265 participants contributed 1,606 pulmonary function measurements over a median follow-up of 8.1 years. We identified two trajectories each for FEV1 and FVC: "low baseline, slow decline" and "high baseline, rapid decline." There were three trajectory groups for FEV1/FVC: "rapid decline," "moderate decline," and "slow decline." Finally, we identified two trajectories for DlCO: "baseline low" and "baseline high." The low baseline, slow decline FEV1 and FVC, rapid decline, and moderate decline FEV1/FVC, and baseline low DlCO phenotypes were associated with increased dyspnea prevalence, worse respiratory health status, and decreased 6-minute-walk distance. The baseline low DlCO phenotype was also associated with worse mortality. Current smoking and pack-years of smoking were associated with the adverse FEV1, FEV1/FVC, and DlCO phenotypes. Detectable viremia was the only HIV marker associated with the adverse DlCO phenotype. C-reactive protein and endothelin-1 were associated with the adverse FEV1 and FVC phenotypes, and endothelin-1 trended toward an association with the adverse DlCO phenotype. Conclusions: We identified novel, distinct longitudinal pulmonary function phenotypes with significant differences in characteristics and outcomes. These findings highlight the importance of lung dysfunction over time in people with HIV and should be validated in additional cohorts.

Biogeography pattern of the marine angiosperm Cymodocea nodosa in the eastern Mediterranean Sea related to the quaternary climatic changes.

We investigated the population dynamics of a highly clonal marine angiosperm, Cymodocea nodosa, in the eastern Mediterranean Sea, to identify the historical dynamics, demography, and connectivity of the species in the area. Eighteen microsatellite loci were used in conjunction with coalescent methods to investigate the genetic structure and demographic history of C. nodosa meadows. Approximate Bayesian computation (ABC) modeling was used to examine the pattern of divergence over time in the context of environmental change over the course of the Quaternary period. ABC analysis revealed an initial split of the C. nodosa populations between the north-western, northern, and north-eastern Aegean Sea during the Pleistocene epoch, followed by a more recent divergence of the north-western population and the central-western part of the Aegean Sea. According to the results, the most parsimonious historical scenario is that of a pervasive genetic signature of the effects of the drop in sea level during the Pleistocene epoch. This scenario supports the isolation of the north-western, north, and north-eastern area, and the subsequent recolonization after post-glaciation sea level rise that may explain the north-western differentiation as well present-day detected dispersion of C. nodosa.

The Influence of Smoking on Healing of Scaphoid Non-union after a Vascularized Pedicle Bone Flap Operation: A Review and Meta-analysis.

Background: The purpose of this study is to compare the vascularized bone flaps (VBF) that are used in operations for scaphoid non-union in smokers and non-smokers and to scrutinize if the better biological potential of the VBFs can counteract the negative influence of smoking on healing. Materials and Methods: Our study included articles published until 2016, with scaphoid non-union patients who were operated on with a VBF or a VBG. Results: Eighteen articles met eligibility criteria with 335 non-smokers and 136 smokers totally. Healing of the scaphoid non-union was significantly more probable in the non-smoking group (OR=5.54, p<0.001). Patients with avascular necrosis in the proximal pole of the scaphoid (AVNPP) and non-AVNPP showed that non-smoking favors a better healing rate in both of these subgroups (p<0.001 and p<0.001, respectively). Non-smokers have 11 times and the non-AVNPP patient's 7.7 times greater probability of healing of the non-union. Meta-analysis of the data for time for healing showed a longer time in the smokers' group by 2.46 weeks, though non-statistically significant. The analysis could not prove that smoking is a predisposing factor for the development of AVNPP (spearman=0.094, p<0.05). Despite that, preoperative smoking cessation proved to be an inadequate healing moderator (OR=3.5, p=0.268). Finally, VBFs showed a significantly better healing rate compared with nVBGs in smokers (p=0.001). Conclusions: A hand surgeon should always take into consideration that smoking negatively influences the healing potential of a scaphoid non-union despite the theoretically superior biological background that VBFs offer. In patients who refuse to quit smoking, a VBF may be considered a better choice than a conventional graft.

Pancreatic Neuroendocrine Tumors: The Effect of Facility Type on Patient Survival.

OBJECTIVES: During the last decades, significant progress has been made in the management of patients with pancreatic neuroendocrine tumors (pNETs). It is unclear how the type of the treating health care facility alters patient outcomes. METHODS: Data from pNETs reported to the National Cancer Database between 2004 and 2016 were examined. Types of institutions were as follows: academic/research cancer program (ARP), comprehensive community cancer program (CCCP), integrated network cancer program (INCP), and community cancer program (CCP). RESULTS: A total of 17,887 patients with pNETs were analyzed. Treatment at ARPs was significantly associated with receipt of surgery (ARP, 61.9%; CCCP, 45.6%; CCP, 29.9%; INCP, 55.5%; P < 0.001), both for patients with very early tumors ≤2 cm (ARP, 74.7%; CCCP, 66.5%; CCP, 52.4%; INCP, 71.6%; P < 0.001) and for patients with liver metastases (ARP, 21.3%; CCCP, 10.6%; CCP, 5%; INCP, 16.8%; P < 0.001). Treatment at ARPs was associated with improved survival (median overall survival: ARP, 91 mo; CCCP, 47 mo; CCP, 24.5 mo; INCP, 72 mo; P < 0.001). CONCLUSIONS: Treatment of pNETs at academic/research programs is associated with more frequent resections and best survival outcomes. This survival benefit exists for early and late stages and after adjusting for known cofactors.

The impact of minimally invasive surgery and frailty on post-hepatectomy outcomes.

BACKGROUND: The impact of patient frailty on post-hepatectomy outcomes is not well studied. We hypothesized that patient frailty is a strong predictor of 30-day post-hepatectomy complications. METHODS: The liver-targeted National Surgical Quality Improvement Program (NSQIP) database for 2014-2019 was reviewed. A validated modified frailty index (mFI) was used. RESULTS: A total of 24,150 hepatectomies were reviewed. Worsening frailty was associated with increased incidence of Clavien-Dindo grade IV complications (mFI 0, 1, 2, 3, 4 was 3.9%, 6.3%, 10%, 8.1%, 50% respectively; p < 0.001). Minimally invasive hepatectomies had a lower rate of Clavien-Dindo grade IV complications for non-frail (Laparoscopic: 1%, Robotic: 2.6%, Open: 4.6%; p < 0.001) and frail patients (Laparoscopic: 3%, Robotic: 2.3%, Open: 7.7%; p < 0.001). Frail patients experienced higher incidence of post-hepatectomy liver failure (5.4% vs 4.1% for non-frail; p < 0.001) and grade C liver failure (28% vs 21.1% for non-frail; p = 0.03). Incorporating mFI to Albumin-Bilirubin score (ALBI) improved its ability to predict Clavien-Dindo grade IV complications (AUC improved from 0.609 to 0.647; p < 0.001) and 30-day mortality (AUC improved from 0.663 to 0.72; p < 0.001). CONCLUSION: Worsening frailty correlates with increased incidence of Clavien-Dindo grade IV complications post-hepatectomy, whereas minimally invasive approaches decrease this risk. Incorporating frailty assessment to ALBI improves its ability to predict major postoperative complications and 30-day mortality.

CD4+ T-Cell Dysfunction in Severe COVID-19 Disease Is Tumor Necrosis Factor-α/Tumor Necrosis Factor Receptor 1-Dependent.

Rationale: Lymphopenia is common in severe coronavirus disease (COVID-19), yet the immune mechanisms are poorly understood. As inflammatory cytokines are increased in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we hypothesized a role in contributing to reduced T-cell numbers. Objectives: We sought to characterize the functional SARS-CoV-2 T-cell responses in patients with severe versus recovered, mild COVID-19 to determine whether differences were detectable. Methods: Using flow cytometry and single-cell RNA sequence analyses, we assessed SARS-CoV-2-specific responses in our cohort. Measurements and Main Results: In 148 patients with severe COVID-19, we found lymphopenia was associated with worse survival. CD4+ lymphopenia predominated, with lower CD4+/CD8+ ratios in severe COVID-19 compared with patients with mild disease (P < 0.0001). In severe disease, immunodominant CD4+ T-cell responses to Spike-1 (S1) produced increased in vitro TNF-α (tumor necrosis factor-α) but demonstrated impaired S1-specific proliferation and increased susceptibility to activation-induced cell death after antigen exposure. CD4+TNF-α+ T-cell responses inversely correlated with absolute CD4+ counts from patients with severe COVID-19 (n = 76; R = -0.797; P < 0.0001). In vitro TNF-α blockade, including infliximab or anti-TNF receptor 1 antibodies, strikingly rescued S1-specific CD4+ T-cell proliferation and abrogated S1-specific activation-induced cell death in peripheral blood mononuclear cells from patients with severe COVID-19 (P < 0.001). Single-cell RNA sequencing demonstrated marked downregulation of type-1 cytokines and NFκB signaling in S1-stimulated CD4+ cells with infliximab treatment. We also evaluated BAL and lung explant CD4+ T cells recovered from patients with severe COVID-19 and observed that lung T cells produced higher TNF-α compared with peripheral blood mononuclear cells. Conclusions: Together, our findings show CD4+ dysfunction in severe COVID-19 is TNF-α/TNF receptor 1-dependent through immune mechanisms that may contribute to lymphopenia. TNF-α blockade may be beneficial in severe COVID-19.

Minimally invasive vs open pancreatoduodenectomy on oncological adequacy: a propensity score-matched analysis.

BACKGROUND: The adoption of minimally invasive pancreatoduodenectomy (MIPD) has increased over the last decade. Most of the data on perioperative and oncological outcomes derives from single-center high-volume hospitals. The impact of MIPD on oncological outcomes in a multicenter setting is poorly understood. METHODS: The National Cancer Database was utilized to perform a propensity score matching analysis between MIPD vs open pancreatoduodenectomy (OPD). The primary outcomes were lymphadenectomy ≥ 15 nodes and surgical margins. Secondary outcomes were 90-day mortality, length of stay, and overall survival. RESULTS: A total of 10,246 patients underwent pancreatoduodenectomy for ductal adenocarcinoma between 2010 and 2016. Among these patients, 1739 underwent MIPD. A propensity score matching analysis with a 1:2 ratio showed that the rate of lymphadenectomy ≥ 15 nodes was significantly higher for MIPD compared to OPD, 68.4% vs 62.5% (P < .0001), respectively. There was no statistically significant difference in the rate of positive margins, 90-day mortality, and overall survival. OPD was associated with an increased rate of length of stay > 10 days, 36.6% vs 33% for MIPD (P < .01). Trend analysis for the patients who underwent MIPD revealed that the rate of adequate lymphadenectomy increased during the study period, 73.1% between 2015 and 2016 vs 63.2% between 2010 and 2012 (P < .001). In addition, the rate of conversion to OPD decreased over time, 29.3% between 2010 and 2012 vs 20.2% between 2015 and 2016 (P < .001). CONCLUSION: In this propensity score matching analysis, the MIPD approach was associated with a higher rate of adequate lymphadenectomy and a shorter length of stay compared to OPD. The surgical margins status, 90-day mortality, and overall survival were similar between the groups.

Trends and outcomes of minimally invasive surgery for gastrointestinal stromal tumors (GIST).

OBJECTIVE: Minimally invasive surgery (MIS) is increasingly being utilized for the resection of gastrointestinal cancers. National trends for perioperative and oncologic outcomes of MIS for gastrointestinal stromal tumors (GIST) are unknown. We hypothesized that with increased use of MIS, the perioperative outcomes and survival for GIST are preserved. METHODS: The National Cancer Database (2010-2016) was utilized to assess perioperative and oncologic outcomes for GIST of the stomach and small bowel. Kaplan-Meier method and log rank test were used to compare survival outcomes. RESULTS: Data from 8923 gastric and 3683 small bowel resections were analyzed. Over the study period, MIS became the prevalent modality for gastrectomies (2010: robotic: 2.4%, laparoscopic: 26.1%, open: 71.5% vs. 2016: robotic: 9.6%, laparoscopic: 48.8%, open: 41.6%; p < 0.001), with a smaller increase in enterectomies (2010: robotic: 1%, laparoscopic: 17.3%, open: 81.6% vs. 2016: robotic: 3.9%, laparoscopic: 27.2%, open: 68.9%; p < 0.001). Age and Charlson comorbidity index were similar among groups. MIS approaches were associated with fewer readmissions and lower 90 day mortality for gastrectomies and similar rates for enterectomies. MIS did not compromise patient survival even in patients who underwent neoadjuvant treatment or harbored tumors ≥ 10 cm. CONCLUSION: Minimally invasive surgery is increasingly being utilized for resection of gastric and small bowel GIST, with improved postoperative outcomes. In this retrospective review, overall survival after minimally invasive or open surgery was comparable, even in challenging scenarios of neoadjuvant treatment or large tumors (≥ 10 cm).