Ashwagandha Diminishes Hippocampal Apoptosis Induced by Microwave Radiation by Acetylcholinesterase Dependent Neuro-Inflammatory Pathway in Male Coturnix coturnix Japonica.

Microwave radiation (MWR) has been linked to neurodegeneration by inducing oxidative stress in the hippocampus of brain responsible for learning and memory. Ashwagandha (ASW), a medicinal plant is known to prevent neurodegeneration and promote neuronal health. This study investigated the effects of MWR and ASW on oxidative stress and cholinergic imbalance in the hippocampus of adult male Japanese quail. One control group received no treatment, the second group quails were exposed to MWR at 2 h/day for 30 days, third was administered with ASW root extract orally 100 mg/day/kg body weight and the fourth was exposed to MWR and also treated with ASW. The results showed that MWR increased serum corticosterone levels, disrupted cholinergic balance and induced neuro-inflammation. This neuro-inflammation further led to oxidative stress, as evidenced by decreased activity of antioxidant enzymes SOD, CAT and GSH. MWR also caused a significant decline in the nissil substances in the hippocampus region of brain indicating neurodegeneration through oxidative stress mediated hippocampal apoptosis. ASW, on the other hand, was able to effectively enhance the cholinergic balance and subsequently lower inflammation in hippocampus neurons. This suggests that ASW can protect against the neurodegenerative effects of MWR. ASW also reduced excessive ROS production by increasing the activity of ROS-scavenging enzymes. Additionally, ASW prevented neurodegeneration through decreased expression of caspase-3 and caspase-7 in hippocampus, thus promoting neuronal health. In conclusion, this study showed that MWR induces apoptosis and oxidative stress in the brain, while ASW reduces excessive ROS production, prevents neurodegeneration and promotes neuronal health.

Bioimpedance: A Tool for Screening Oral Cancer - A Systematic Review.

Objective: The successful management of cancer depends on proper screening and treatment methods. Bioimpedance spectroscopy (BIS) is an established technique in detecting breast cancer, cervical cancer, and prostate cancer. This systematic review sought to investigate the current evidence regarding the clinical application of bioimpedance in the detection of oral squamous cell carcinoma and oral potentially malignant disorders. Study Design: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to perform this review. Electronic databases such as PubMed, MEDLINE, Embase, EBSCOhost, and Google Scholar were searched till March 2022. Articles published in the English medical literature on human participants report on the application of BIS in the screening of precancerous and cancerous lesions. The primary endpoint was defined as the ability to differentiate between normal and cancerous tissue. Results: A total of 6754 articles were identified; of which 481 were eligible for inclusion. Only five articles met the eligibility criteria and were included in the study. Qualitative analysis for each study was done to assess the data provided. All the studies demonstrated a significant divergence in BIS metrics between cancerous and normal tissue at 20 Hz and 50 KHz. Conclusion: Bioimpedance appears to be a promising novel tool for the detection of various malignancies which can be used in community screening due to its noninvasiveness and portability.

The impact of RNA stability and degradation in different tissues to the determination of post-mortem interval: A systematic review.

Postmortem interval (PMI) in legal medicine is extremely important for both criminal and civil cases, and several sorts of techniques have been recommended. This systematic review solely focuses on approaches linked to RNA analysis, instead of including all proposed methods for determining the PMI. The term PMI will be used in this review to indicate the time between a person's death and the postmortem examination of the body. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines when conducting this systematic review. The majority of studies on various tissues at various time intervals at various temperatures are non-human, and just a small number are on humans. The results are then provided using various statistical approaches. To calculate the PMI, post-mortem RNA degradation was examined using several tissues. The result so obtained had an opposite polarity. While some studies show that RNA stability in various tissues remained constant for several days after death, the other group of studies showed evident RNA degradation over time post-mortem, which was significantly influenced by temperature and other agonal factors. These factors have an impact on the multi-parametric mathematical model of ante and post-mortem factors on RNA degradation, as well as its applicability and feasibility. The estimation of PMI using RNA degradation can prove to be highly objective and efficient after controlling for the various factors and challenges that pose the estimation of RNA in forensic samples difficult.

Coumarin as a Privileged and Medicinally Important Scaffold in the Treatment of Tuberculosis.

Coumarin and its derivatives, which are abundant in nature, have a significant role in medicinal chemistry due to their ability to bind with different targets or receptors. In addition, these possess a wide range of biological activity. Thus coumarin-based scaffold has inspired even further research into coumarin and its substituted derivatives, allowing for the creation of a huge variety of structurally different substituted products. In recent, these were reported to have potent antitubercular activity. Tuberculosis (TB) is a serious deadly infectious bacterial disease caused by grampositive Mycobacterium tuberculosis. This review discusses various developments going on in the field of medicinal chemistry towards designing, synthesizing, and discovering coumarin-based antitubercular agents all across the globe.

Potential of Lipid-Based Nanocarriers against Two Major Barriers to Drug Delivery-Skin and Blood-Brain Barrier.

Over the past few years, pharmaceutical and biomedical areas have made the most astounding accomplishments in the field of medicine, diagnostics and drug delivery. Nanotechnology-based tools have played a major role in this. The implementation of this multifaceted nanotechnology concept encourages the advancement of innovative strategies and materials for improving patient compliance. The plausible usage of nanotechnology in drug delivery prompts an extension of lipid-based nanocarriers with a special reference to barriers such as the skin and blood-brain barrier (BBB) that have been discussed in the given manuscript. The limited permeability of these two intriguing biological barriers restricts the penetration of active moieties through the skin and brain, resulting in futile outcomes in several related ailments. Lipid-based nanocarriers provide a possible solution to this problem by facilitating the penetration of drugs across these obstacles, which leads to improvements in their effectiveness. A special emphasis in this review is placed on the composition, mechanism of penetration and recent applications of these carriers. It also includes recent research and the latest findings in the form of patents and clinical trials in this field. The presented data demonstrate the capability of these carriers as potential drug delivery systems across the skin (referred to as topical, dermal and transdermal delivery) as well as to the brain, which can be exploited further for the development of safe and efficacious products.

Focal Cortical Dysplasia with hippocampal sclerosis.

Focal Cortical Dysplasia (FCD) is a group of focal developmental malformations of the cerebral cortex cytoarchitecture. FCD usually manifests as medically intractable epilepsy, especially in young children. Live patients are diagnosed by radiological examination such as magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG PET), magnetoencephalography (MEG), diffusion-tensor imaging (DTI), and intracranial electroencephalogram (EEG). While some cases can be missed by radiological examination, they are usually diagnosed on the histopathological examination of the surgically removed specimens of medically intractable epilepsy patients. We report a case of a young girl with cerebral palsy, mental retardation, and seizure disorder who died in her sleep. The deceased was diagnosed with FCD type III with hippocampal sclerosis on histopathological examination at autopsy. H & E stain and NeuN immunohistochemistry neuronal cell marker were used to demonstrate the findings of FCD.

Long-term Functional Outcomes Among Older Adults Undergoing Video-assisted Versus Open Surgery for Lung Cancer: A Population-based Cohort Study.

OBJECTIVE: To examine the long-term healthcare dependency outcomes of older adults undergoing VATS compared to open lung cancer resection. SUMMARY OF BACKGROUND DATA: Although the benefits of VATS for lung cancer resection have been reported, there is a knowledge gap related to long-term functional outcomes central to decision-making for older adults. METHODS: We conducted a population-based retrospective comparative cohort study of patients ≥70 years old undergoing lung cancer resection between 2010 and 2017 using linked administrative health databases. VATS was compared to open surgery for lung cancer resection. Outcomes were receipt of homecare and high time-at-home, defined as <14 institution-days within 1 year, in 5 years after surgery. We used time-to-event analyses. Homecare was analyzed as recurrent dichotomous outcome with Andersen-Gill multivariable models, and high time-at-home with Cox multivariable models. RESULTS: Of 4974 patients, 2951 had VATS (59.3%). In the first three months postoperatively, homecare use ranged from 17.5% to 34.4% for VATS and 23.0% to 36.6% for open surgery. VATS was independently associated with lower need for postoperative homecare over 5 years (hazard ratio 0.82, 95% confidence interval 0.74-0.92). 1- and 5-year probability of high "time-at-home" were superior for VATS (74.4% vs 66.7% and 55.6% vs 45.4%, p < 0.001). VATS was independently associated with higher probability of high "time-at-home" (hazard ratio 0.81, 95% confidence interval 0.74-0.89) compared to open surgery. CONCLUSIONS: Compared to open surgery, VATS was associated with lower homecare needs and higher probability of high "time-at-home," indicating reduced long-term functional dependence. Those important patient-centered endpoints reflect the overall long-term treatment burden on mortality and morbidity that can inform surgical decision-making.

Symptom Assessment Following Surgery for Lung Cancer: A Canadian Population-based Retrospective Cohort Study.

OBJECTIVE: To conduct a population-level analysis of temporal trends and risk factors for high symptom burden in patients receiving surgery for non-small cell lung cancer (NSCLC). BACKGROUND: A population-level overview of symptoms after curative intent surgery is necessary to inform decision making and supportive care for patients with lung cancer. METHODS: Retrospective cohort study of patients receiving surgery for stages I to III NSCLC between January 2007 and September 2018. Prospectively collection Edmonton Symptom Assessment System (ESAS) scores, linked to provincial administrative data, were used to describe the prevalence, trajectory, and predictors of moderate-to-severe symptoms in the year following surgery. RESULTS: A total of 5350 patients, with 28,490 unique ESAS assessments, were included in the analysis. Moderate-to-severe tiredness (68%), poor wellbeing (63%), and shortness of breath (60%) were the most common symptoms reported. The rise and fall in the proportion of patients experiencing moderate-to-severe symptoms after surgery coincided with the median time to first (58 days, interquartile range: 47-72) and last cycle of chemotherapy (140 days, interquartile range: 118-168), respectively. There was eventual stabilization, albeit above the preoperative baseline, within 6 to 7 months after surgery. Female sex (relative risk [RR] 1.09- 1.26), lower income (RR 1.08-1.23), stage III disease (RR 1.15-1.43), adjuvant therapy (RR 1.09-1.42), chemotherapy within 2 weeks of an ESAS assessment (RR 1.14-1.73), and pneumonectomy (RR 1.05-1.15) were associated with moderate-to-severe symptoms following surgery. CONCLUSIONS: Knowledge of population-level prevalence, trajectory, and predictors of moderate-to-severe symptoms after surgery for NSCLC can be used to facilitate shared decision making and improve symptom management throughout the course of illness.

Focal Cortical Dysplasia with hippocampal sclerosis

ABSTRACT Focal Cortical Dysplasia (FCD) is a group of focal developmental malformations of the cerebral cortex cytoarchitecture. FCD usually manifests as medically intractable epilepsy, especially in young children. Live patients are diagnosed by radiological examination such as magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG PET), magnetoencephalography (MEG), diffusion-tensor imaging (DTI), and intracranial electroencephalogram (EEG). While some cases can be missed by radiological examination, they are usually diagnosed on the histopathological examination of the surgically removed specimens of medically intractable epilepsy patients. We report a case of a young girl with cerebral palsy, mental retardation, and seizure disorder who died in her sleep. The deceased was diagnosed with FCD type III with hippocampal sclerosis on histopathological examination at autopsy. H & E stain and NeuN immunohistochemistry neuronal cell marker were used to demonstrate the findings of FCD.

Spray-Deposited Anisotropic Assemblies of Plasmonic Nanowires for Direction-Sensitive Strain Measurement.

The development of nanoscale composites with hierarchical architecture and complex anisotropies enables the fabrication of new classes of devices. Stretchable strain sensors have been developed in the past for applications in various fields such as wearable electronics and soft robotics, yet the sensing capacities of most of these sensors are independent of the direction of deformation. In the present work, we report on the preparation of a direction-sensitive strain sensor using the anisotropic optical properties of a monolayer of oriented plasmonic 1D nano-objects. Grazing incidence spraying (GIS) is used for depositing a monolayer of in-plane aligned silver nanowires with a controlled density on a deformable and transparent substrate. Using the selective excitation of transverse and longitudinal localized plasmon resonance modes of silver nanowires by polarized UV-visible-NIR spectroscopy, we show that the macroscopic anisotropic properties of the monolayer upon stretching are highly dependent on the stretching direction and light polarization. Measuring the polarized optical properties of the anisotropic thin films upon stretching thus allow for retrieving both the local strain and the direction of the deformation using a simple model.

Safety, immunogenicity & effectiveness of the COVID-19 vaccine among healthcare workers in a tertiary care hospital.

BACKGROUND & OBJECTIVES: The COVID-19 pandemic has caused significant global morbidity and mortality. As the vaccination was rolled out with prioritization on healthcare workers (HCWs), it was desirable to generate evidence on effectiveness of vaccine in prevailing real-life situation for policy planning. The objective of the study was to evaluate the safety, effectiveness and immunogenicity of COVID-19 vaccination among HCWs in a tertiary care hospital. METHODS: This prospective observational study was undertaken on the safety, immunogenicity and effectiveness of the ChAdOx1 nCoV- 19 coronavirus vaccine (Recombinant) during the national vaccine roll out in January-March 2021, in a tertiary care hospital, New Delhi, India. RESULTS: The vaccine was found to be safe, with local pain, fever and headache as the most common adverse events of milder nature which generally lasted for two days. The adverse events following vaccination were lower in the second dose as compared to the first dose. The vaccine was immunogenic, with seropositivity, which was 51 per cent before vaccination, increasing to 77 per cent after single dose and 98 per cent after two doses. Subgroup analysis indicated that those with the past history of COVID-19 attained seropositivity of 98 per cent even with single dose. The incidence of reverse transcription (RT)-PCR positive COVID-19 was significantly lower among vaccinated (11.7%) as compared to unvaccinated (22.2%). Seven cases of moderate COVID-19 needing hospitalization were seen in the unvaccinated and only one such in the vaccinated group. The difference was significant between the fully vaccinated (10.8%) and the partially vaccinated (12.7%). The hazard of COVID-19 infection was higher among male, age >50 yr and clinical role in the hospital. After adjustment for these factors, the hazard of COVID-19 infection among unvaccinated was 2.09 as compared to fully vaccinated. Vaccine effectiveness was 52.2 per cent in HCWs. INTERPRETATION & CONCLUSIONS: ChAdOx1 nCoV-19 coronavirus vaccine (Recombinant) was safe, immunogenic as well as showed effectiveness against the COVID-19 disease (CTRI/2021/01/030582).

Expression of aldehyde dehydrogenase 1A1 in oral squamous cell carcinoma and its correlation with clinicopathological parameters.

Background: Aldehyde dehydrogenase 1A1 (ALDH1A1) is a key aldehyde dehydrogenase (ALDH) isozyme, related to the cancer stem cells which are responsible for initiating tumor growth, progression, and recurrence. High expression of ALDH1A1 has been reported in several tumor types in humans and its expression is associated with poor prognosis. The aim of this study was to assess the expression of the ALDH1A1 in oral squamous cell carcinoma (SCC) and its correlation with various clinicopathological parameters. Materials and Methods: ALDH1A1 expression was analyzed by using immunohistochemistry on paraffin blocks of 112 cases of primary oral SCC and their corresponding 68 lymph nodes with metastatic deposits. ALDH1A1 expression was also correlated with various clinicopathological parameters. Statistical analysis was done with statistical analysis software, the Statistical Package for the Social Sciences version 21.0. Results: High ALDH1A1 expression was observed in 31.2% of cases of primary oral SCC as compared to 73.5% in lymph node metastasis. A statistically significant difference (P = 0.04) was observed in high TNM stages (68.6%) of the tumor as compared to low TNM stages (31.4%). However, histopathological grades of tumor showed nonsignificant correlation with ALDH1A1 expression (P = 0.093). 40.2% of patients were expired at the end of the study, and the rate of mortality was significantly higher (P = 0.01) in patients with high ALDH1A1 expression as compared to low expression (60.0% vs. 31.2%). Conclusion: High ALDH1A1 expression was associated with higher TNM tumor stage and high nodal stage. It was also associated with high mortality rate which validates it as a marker of invasiveness and poor prognosis in oral SCC.

2.45 GHz microwave radiation induced oxidative stress: Role of inflammatory cytokines in regulating male fertility through estrogen receptor alpha in Gallus gallus domesticus.

Due to the growing number of gadgets emitting electromagnetic radiation (EMR), particularly microwave (MW) radiation, in our daily lives, it is believed that EMR have both long-term and short-term biological impacts that are quite concerning for avian as well as human health. Due to the negative impact of MW emitting equipment on the biological system this study looks into the mechanistic approach by which low-level of 2.45 GHz MW radiation causes an oxidative stress and inflammatory response in the testes micro-environment which further gets regulated by estrogen receptor alpha (ERα) expression in immature Gallus gallus domesticus leading to male infertility. Two weeks old immature male chickens were exposed to non-thermal low-level 2.45-GHz MW radiation for 2 h/day for 30 days (power density = 0.1264 mw/cm2 and SAR = 0.9978 W/kg). In the exposed group, morphometric examination of the testes revealed decreased testicular weight, volume and gonado-somatic index. Further, histological staining demonstrated a substantial reduction in the diameter of seminiferous tubules in the exposed group as compared to the control. The degree of oxidative stress was also determined showing an increase in oxidative stress parameters after exposure. The radiation exposed testes showed a significant increase in IL-1ß immunoreactivity and decline in IL-10 immunoreactivity, indicating a sense of MW radiation-induced oxidative stress-regulated inflammatory response. A substantial reduction in ERα expression was also observed in exposed testes by Western blotting. Our investigations conclude that testes being vulnerable to free radical damage become an easy target organ for MW exposure induced oxidative and inflammatory stress. Therefore it becomes evident that it may cause male infertility in chicks via downregulation of ER-α in testis.

COVID-19 in Hemodialysis Patients: Experience from a Western Indian Center.

Introduction: Chronic kidney disease patients on hemodialysis (CKD-5D) are among the worst hit by the coronavirus disease 2019 (COVID-19) pandemic. Need to travel for dialysis, comorbidities, and immunosuppressive state put them at risk of severe disease and poor outcomes. We report our experience of COVID-19 in a cohort of CKD-5D from a public sector tertiary-care center from western India. Material and Methods: We retrospectively analyzed the records of 58 CKD-5D patients with confirmed COVID-19 admitted to our COVID-19 hospital. Suspected COVID-19, acute kidney injury (AKI), or AKI on CKD were excluded. We studied the clinical, demographic, radiological, and laboratory profiles; treatment; and outcomes of the patients. We assessed the potential clinical and laboratory parameters to predict mortality. Results: The mean age of the patients was 48.7 ± 16.9 years, with 55% males. Comorbidities included hypertension (65%), diabetes (19%), and cardiovascular disease (15.5%). The presenting features included fever (69%), respiratory distress (50%), upper respiratory symptoms (36%), and diarrhea (13%). Five (8.6%) were asymptomatic. Bilateral infiltrates on chest imaging were the commonest radiological pattern. The patients were managed with oxygenation, hydroxychloroquine, steroids, anticoagulation, remdesivir, and favipiravir. Twenty-two (37.9%) patients died, predominantly due to respiratory failure. Disease severity and C-reactive protein (CRP) above 175 mg/L at admission were the only parameters predictive of mortality. Conclusion: CKD-5D patients with COVID-19 were less likely to present with the classical syndrome of fever and respiratory distress compared with reports from the general population and had higher mortality. Only disease severity and high CRP (>175 mg/L) were predictive of mortality in our cohort.

Nanotechnology in Cosmetics and Cosmeceuticals-A Review of Latest Advancements.

Nanotechnology has the potential to generate advancements and innovations in formulations and delivery systems. This fast-developing technology has been widely exploited for diagnostic and therapeutic purposes. Today, cosmetic formulations incorporating nanotechnology are a relatively new yet very promising and highly researched area. The application of nanotechnology in cosmetics has been shown to overcome the drawbacks associated with traditional cosmetics and also to add more useful features to a formulation. Nanocosmetics and nanocosmeceuticals have been extensively explored for skin, hair, nails, lips, and teeth, and the inclusion of nanomaterials has been found to improve product efficacy and consumer satisfaction. This is leading to the replacement of many traditional cosmeceuticals with nanocosmeceuticals. However, nanotoxicological studies on nanocosmeceuticals have raised concerns in terms of health hazards due to their potential skin penetration, resulting in toxic effects. This review summarizes various nanotechnology-based approaches being utilized in the delivery of cosmetics as well as cosmeceutical products, along with relevant patents. It outlines their benefits, as well as potential health and environmental risks. Further, it highlights the regulatory status of cosmeceuticals and analyzes the different regulatory guidelines in India, Europe, and the USA and discusses the different guidelines and recommendations issued by various regulatory authorities. Finally, this article seeks to provide an overview of nanocosmetics and nanocosmeceuticals and their applications in cosmetic industries, which may help consumers and regulators to gain awareness about the benefits as well as the toxicity related to the continuous and long-term uses of these products, thus encouraging their judicious use.

Osteoclastic variant of anaplastic thyroid carcinoma: An insight into a rarest of rare entity.

Anaplastic thyroid carcinoma is a rare and a very aggressive thyroid malignancy with a dismal prognosis. It has a short history and presents with a rapidly increasing neck mass associated with compressive symptoms like pain, hoarseness of voice, dysphagia and shortness of breath. Osteoclastic variant is an extremely rare variant, which is, characterize by presence of a large number of multinucleated giant cells, which resemble osteoclasts. Here we report two cases of this unusual variant in a 68 years old and 49 years old male with a short history of thyroid swelling.

Textbook Outcome and Survival in Patients With Gastric Cancer: An Analysis of the Population Registry of Esophageal and Stomach Tumours in Ontario (PRESTO).

OBJECTIVE: To examine the association between Textbook Outcome (TO)-a new composite quality measurement-and long-term survival in gastric cancer surgery. BACKGROUND: Single-quality indicators do not sufficiently reflect the complex and multifaceted nature of perioperative care in patients with gastric adenocarcinoma. METHODS: All patients undergoing gastrectomy for nonmetastatic gastric adenocarcinoma registered in the Population Registry of Esophageal and Stomach Tumours of Ontario (PRESTO) between 2004 and 2015 were included. TO was defined according to negative margins; >15 lymph nodes sampled; no severe complications; no re-interventions; no unplanned ICU admission; length of stay ≤21 days; no 30-day readmission; and no 30-day mortality. Three-year survival was estimated using the Kaplan-Meier method. A marginal multivariable Cox proportional-hazards model was used to estimate the association between achieving TO metrics and long-term survival. E-value methodology was used to assess for risk of residual confounding. RESULTS: Of the 1836 patients included in this study, 402 (22%) achieved all TO metrics. TO patients had a higher 3-year survival rate compared to non-TO patients (75% vs 55%, log-rank P < 0.001). After adjustments for covariates and clustering within hospitals, TO was associated with a 41% reduction in mortality (adjusted hazards ratio 0.59, 95% confidence interval 0.48, 0.72, P < 0.001). These results were robust to potential residual confounding. CONCLUSIONS: Achieving TO is strongly associated with improved long-term survival in gastric cancer patients and merits further focus in surgical quality improvement efforts.

Upfront Small Bowel Resection for Small Bowel Neuroendocrine Tumors With Synchronous Metastases: A Propensity-score Matched Comparative Population-based Analysis.

OBJECTIVE: We examined the impact of upfront small bowel resection (USBR) for metastatic small bowel neuroendocrine (SB-NET) compared to nonoperative management (NOM) on long-term healthcare utilization and survival outcomes. SUMMARY OF BACKGROUND DATA: The role of early resection of the primary tumor in metastatic SB-NET remains controversial. Conflicting data exist regarding its clinical and survival benefits. METHODS: This is a population-based retrospective matched comparative cohort study of adults diagnosed with synchronous metastatic SB-NET between 2001 and 2017 in Ontario. USBR was defined as resection within 6 months of diagnosis. Primary outcomes were subsequent unplanned acute care admissions and small bowel-related surgery. Secondary outcome was overall survival. USBR and NOM patients were matched 2:1 using a propensity-score. We used time-to-event analyses with cumulative incidencefunctions and univariate Andersen-Gill regression for primary outcomes. E value methods assessed the potential for residual confounding. RESULTS: Of 1000 patients identified, 785 had USBR. The matched cohort included 348 patients with USBR and 174 with NOM. Patients with USBR had lower 3-year risk of subsequent admissions (72.6% vs 86.4%, P < 0.001) than those with NOM, with hazard ratio 0.72 (95% confidence interval 0.570.91). USBR was associated with lower risk of subsequent small bowel-related surgery (15.4% vs 40.3%, P < 0.001), with hazard ratio 0.44 (95% confidence interval 0.29-0.67). E -values indicated it was unlikely that the observed risk estimates could be explained by an unmeasured confounder. Sensitivity analysis excluding emergent resections to define USBR did not alter the results. CONCLUSIONS: USBR for SB-NETs in the presence of metastatic disease was associated with better patient-oriented outcomes of decreased subsequent admissions and interventions, compared to NOM. USBR should be considered for metastatic SB-NETs.