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Introduction: Patients with localized pancreatic adenocarcinoma (PDAC) benefit from multi-modality therapy. Whether care patterns and oncologic outcomes vary if a patient was seen through a pancreatic multi-disciplinary clinic (PMDC) versus only individual specialty clinics is unclear. Methods: Using institutional Pancreatic Cancer Registry, we identified patients with localized PDAC from 2019- 2022 who eventually underwent resection. It was our standard practice for borderline resectable (BRPC) patients to undergo ≤4 months of neoadjuvant chemotherapy, ± radiation, followed by exploration, while locally advanced (LAPC) patients were treated with 4-6 months of chemotherapy, followed by radiation and potential exploration. Descriptive and multivariable analyses (MVA) were performed to examine the association between clinic type (PMDC vs individual specialty clinics i.e. surgical oncology, medical oncology, or radiation oncology) and study outcomes. Results: A total of 416 patients met inclusion criteria. Of these, 267 (64.2%) had PMDC visits. PMDC group received radiation therapy more commonly (53.9% versus 27.5%, p=0.001), as compared to individual specialty clinic group. Completion of neoadjuvant treatment (NAT) was far more frequent in patients seen through PMDC compared to patients seen through individual specialty clinics (69.3% vs 48.9%). On MVA, PMDC group was significantly associated with receipt of NAT per institutional standards (adjusted OR 2.23, 95% CI 1.46-7.07, p=0.006). Moreover, the average treatment effect of PMDC on progression-free survival (PFS) was 4.45 (95CI: 0.87-8.03) months. No significant association between overall survival (OS) and clinic type was observed. Discussion: Provision of care through PMDC was associated with significantly higher odds of completing NAT per institutional standards as compared to individual specialty clinics, which possibly translated into improved PFS. The development of multidisciplinary clinics for management of pancreatic cancer should be incentivized, and any barriers to such development should be addressed.
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Cardiovascular diseases (CVDs), which stand as the primary contributors to illness and death on a global scale, include vital risk factors like hyperlipidemia, hypertension, diabetes, and smoking, to name a few. However, conventional cardiovascular risk factors offer only partial insight into the complexity of CVDs. Lately, a growing body of research has illuminated that the gut microbiome and its by-products are also of paramount importance in the initiation and progression of CVDs. The gastrointestinal tract houses trillions of microorganisms, commonly known as gut microbiota, that metabolize nutrients, yielding substances like trimethylamine- N-oxide (TMAO), bile acids (BAs), short-chain fatty acids (SCFAs), indoxyl sulfate (IS), and so on. Strategies aimed at addressing these microbes and their correlated biological pathways have shown promise in the management and diagnosis of CVDs. This review offers a comprehensive examination of how the gut microbiota contributes to the pathogenesis of CVDs, particularly atherosclerosis, hypertension, heart failure (HF), and atrial fibrillation (AF), explores potential underlying mechanisms, and highlights emerging therapeutic prospects in this dynamic domain.
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Whole-organ pancreas, pancreatic-kidney and islet transplantation are surgical therapeutic options for the treatment of type 1 diabetes. They can enable effective glycemic control, improve quality of life and delay/reduce the secondary complications of type 1 diabetes mellitus. Radiologists are integral members of the multidisciplinary transplantation team involved in these procedures, with multimodality imaging serving as the mainstay for early recognition and management of transplant related complications. This review highlights the transplantation procedures available for patients with type 1 Diabetes Mellitus with a focus on the imaging appearance of transplantation-related complications.
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INTRODUCTION: Retroperitoneum can be the origin of a wide variety of pathologic conditions and potential space for disease spread to other compartments of the abdomen and pelvis. Computed tomography (CT) and magnetic resonance imaging (MRI) are often the initial imaging modalities to evaluate the retroperitoneal pathologies, however given the intrinsic limitations, F18-FDG PET/CT provides additional valuable metabolic information which can change the patient management and clinical outcomes. We highlight the features of retroperitoneal pathologies on F18-FDG PET/CT and the commonly encountered imaging artifacts and pitfalls. The aim of this review is to characterize primary and secondary retroperitoneal pathologies based on their metabolic features, and correlate PET findings with anatomic imaging. CONCLUSION: Retroperitoneal pathologies can be complex, ranging from oncologic to a spectrum of non-oncologic disorders. While crosse-sectional imaging (CT and MRI) are often the initial imaging modalities to localize and characterize pathologies, metabolic information provided by F18-FDG PET/CT can change the management and clinical outcome in many cases.
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Artifacts , Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography , Radiopharmaceuticals , Humans , Fluorodeoxyglucose F18/pharmacokinetics , Positron Emission Tomography Computed Tomography/methods , Radiopharmaceuticals/pharmacokinetics , Retroperitoneal Space/diagnostic imagingABSTRACT
Skin malignancies are commonly encountered as primary or incidental findings. Neoplasms that affect the skin include primary (basal cell carcinoma, squamous cell carcinoma, melanoma, and Merkel cell carcinoma) and secondary (mesenchymal neoplasms, lymphoma, and metastases) tumors. Imaging provides valuable anatomic information (tumor size, depth of involvement, presence of distant metastasis, and data for guiding biopsy) and functional information (metabolic activity and sentinel node mapping data). This information, in addition to biopsy results, improves the histopathologic characterization of tumors and treatment planning. Various histopathologic types of the same entity exhibit different biologic behavior and have different imaging features. Familiarity with the multimodality imaging features, histopathologic characteristics, and various modes of dissemination (direct invasion; perineural, lymphatic, and hematogenous spread) of the most common skin malignancies helps radiologists narrow the differential diagnosis in clinical practice. ©RSNA, 2023 Supplemental material is available for this article. Quiz questions for this article are available through the Online Learning Center.
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Carcinoma, Squamous Cell , Melanoma , Skin Neoplasms , Humans , Sentinel Lymph Node Biopsy , Lymphatic Metastasis , Skin Neoplasms/diagnostic imaging , Melanoma/diagnostic imaging , Melanoma/pathology , Melanoma/secondaryABSTRACT
Acute appendicitis secondary to amoebic infestation is a rare possibility, especially in endemic areas. If left untreated, significant postoperative morbidity and mortality can result from the spread of amoebic trophozoites and subsequent tissue reaction. Histopathological examination of the resected appendix with demonstration of invasion by the parasite is mandatory for establishing a diagnosis. Careful examination of the specimen is thus of paramount importance.
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Background: The worldwide control rate for hypertension is dismal. An inadequate number of physicians to treat patients with hypertension is one key obstacle. Innovative health system approaches such as delegation of basic tasks to non-physician health workers (task-sharing) might alleviate this problem. Massive scale up of population-wide hypertension management is especially important for low- and middle-income countries such as India. Methods: Using constrained optimization models, we estimated the hypertension treatment capacity and salary costs of staff involved in hypertension care within the public health system of India and simulated the potential effects of (1) an increased workforce, (2) greater task-sharing among health workers, and (3) extended average prescription periods that reduce treatment visit frequency (e.g., quarterly instead of monthly). Findings: Currently, only an estimated 8% (95% uncertainty interval 7%-10%) of â¼245 million adults with hypertension can be treated by physician-led services in the Indian public health system (assuming the current number of health workers, no greater task-sharing, and monthly visits for prescriptions). Without task-sharing and with continued monthly visits for prescriptions, the least costly workforce expansion to treat 70% of adults with hypertension would require â¼1.6 (1.0-2.5) million additional staff (all non-physicians), with â¼INR 200 billion (≈USD 2.7 billion) in additional annual salary costs. Implementing task-sharing among health workers (without increasing the overall time on hypertension care) or allowing a 3-month prescription period was estimated to allow the current workforce to treat â¼25% of patients. Joint implementation of task-sharing and a longer prescription period could treat â¼70% of patients with hypertension in India. Interpretation: The combination of greater task-sharing and extended prescription periods could substantially increase the hypertension treatment capacity in India without any expansion of the current workforce in the public health system. By contrast, workforce expansion alone would require considerable, additional human and financial resources. Funding: Resolve to Save Lives, an initiative of Vital Strategies, was funded by grants from Bloomberg Philanthropies; the Bill and Melinda Gates Foundation; and Gates Philanthropy Partners (funded with support from the Chan Zuckerberg Foundation).
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PURPOSE: Proactive nutrition screening and intervention is associated with improved outcomes for patients with pancreatic adenocarcinoma (PDAC). To better optimize nutrition amongst our PDAC population, we implemented systematic malnutrition screening in the Johns Hopkins pancreas multidisciplinary clinic (PMDC) and assessed the effectiveness of our nutrition referral system. METHODS: This was a single institution prospective study of patients seen in the PMDC, screened for malnutrition using the Malnutrition Screening Tool (MST) (score range=0 to 5, score > 2 indicates risk of malnutrition), and offered referrals to the oncology dietitian. Patients that requested a referral but did not attend a nutrition appointment were contacted by phone to assess barriers to seeing the dietitian. Univariate (UVA) and multivariable (MVA) analyses were carried out to identify predictors of referral status and appointment completion status. RESULTS: A total of 97 patients were included in the study, of which 72 (74.2%) requested a referral and 25 (25.8%) declined. Of the 72 patients who requested a referral, 31 (43.1%) attended an appointment with the oncology dietitian. Data on information session attendance was available for 35 patients, of which 8 (22.9%) attended a pre-clinic information session in which the importance of optimal nutrition was highlighted. On MVA, information session attendance was significantly associated with requesting a referral (OR: 11.1, 95% CI 1.12-1.0E3, p=0.037) and successfully meeting with the oncology dietitian (OR: 5.88, 95% CI 1.00-33.3, p=0.049). CONCLUSION: PMDC teams should institute educational initiatives on the importance of optimal nutrition in order to increase patient engagement with nutrition services.
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Adenocarcinoma , Malnutrition , Pancreatic Neoplasms , Humans , Nutrition Assessment , Prospective Studies , Pancreatic Neoplasms/therapy , Nutritional Status , Malnutrition/diagnosis , Malnutrition/etiology , Malnutrition/therapy , Referral and Consultation , Pancreatic NeoplasmsABSTRACT
PROBLEM: Similarity measures are widely used as an approved method for spectral discrimination or identification with their applications in different areas of scientific research. Even though a range of works have been presented, only a few showed slightly promising results for human tissue, and these were mostly focused on pathological and non-pathological tissue classification. METHODS: In this work, several spectral similarity measures on hyperspectral (HS) images of in vivo human tissue were evaluated for tissue discrimination purposes. Moreover, we introduced two new hybrid spectral measures, called SID-JM-TAN(SAM) and SID-JM-TAN(SCA). We analyzed spectral signatures obtained from 13 different human tissue types and two different materials (gauze, instruments), collected from HS images of 100 patients during surgeries. RESULTS: The quantitative results showed the reliable performance of the different similarity measures and the proposed hybrid measures for tissue discrimination purposes. The latter produced higher discrimination values, up to 6.7 times more than the classical spectral similarity measures. Moreover, an application of the similarity measures was presented to support the annotations of the HS images. We showed that the automatic checking of tissue-annotated thyroid and colon tissues was successful in 73% and 60% of the total spectra, respectively. The hybrid measures showed the highest performance. Furthermore, the automatic labeling of wrongly annotated tissues was similar for all measures, with an accuracy of up to 90%. CONCLUSION: In future work, the proposed spectral similarity measures will be integrated with tools to support physicians in annotations and tissue labeling of HS images.
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Involvement of NOX-dependent oxidative stress in the pathophysiology of metabolic disorders as well as in the maintenance of metabolic homeostasis has been demonstrated previously. In the present study, the metabolic profile in p47phox-/- and WT mice fed on a chow diet was evaluated to assess the role of metabolites in glucose intolerance and dyslipidemia under altered oxidative stress conditions. p47phox-/- mice displayed glucose intolerance, dyslipidemia, hyperglycemia, insulin resistance (IR), hyperinsulinemia, and altered energy homeostasis without any significant change in gluconeogenesis. The expression of genes involved in lipid synthesis and uptake was enhanced in the liver, adipose tissue, and intestine tissues. Similarly, the expression of genes associated with lipid efflux in the liver and intestine was also enhanced. Enhanced gut permeability, inflammation, and shortening of the gut was evident in p47phox-/- mice. Circulating levels of pyrimidines, phosphatidylglycerol lipids, and 3-methyl-2-oxindole were augmented, while level of purine was reduced in the serum. Moreover, the cecal metabolome was also altered, as was evident with the increase in indole-3-acetamide, N-acetyl galactosamine, glycocholate, and a decrease in hippurate, indoxyl sulfate, and indigestible sugars (raffinose and melezitose). Treatment of p47phox-/- mice with pioglitazone, marginally improved glucose intolerance, and dyslipidemia, with an increase in PUFAs (linoleate, docosahexaenoic acid, and arachidonic acid). Overall, the results obtained in p47phox-/- mice indicate an association of IR and dyslipidemia with altered serum and cecal metabolites (both host and bacterial-derived), implying a critical role of NOX-derived ROS in metabolic homeostasis.
Subject(s)
Dyslipidemias , Glucose Intolerance , Insulin Resistance , Mice , Animals , Insulin/metabolism , Reactive Oxygen Species/metabolism , Mice, Knockout , NADPH Oxidases/metabolism , Insulin Resistance/genetics , Metabolome , Dyslipidemias/genetics , Lipids , Mice, Inbred C57BLABSTRACT
BACKGROUND: Despite the known association between frailty and postoperative morbidity, the use of preoperative frailty in surgical practice remains limited. We sought to develop a risk tool to predict postoperative increase in functional dependence. METHODS: Patients of ≥65 years in the National Surgical Quality Improvement Project database who had a primary hepatopancreatic surgery between 2015 and 2019 were used to identify predictors of increased dependence and development of a simplified tool to calculate the risk stratification score for increased discharge care level (https://ktsahara.shinyapps.io/care_discharge/). RESULTS: Among 31,338 patients who underwent primary hepatopancreatic surgery, 4,259 (13.6%) had an increased level of care at discharge compared to their preadmission care. Patients with increased discharge care had a higher proportion of patients with a modified frailty index of at least 2 (n = 1496; 35.1%) compared with individuals with unchanged care (n = 6,760; 25.0%). In addition, 12.3% (n = 3,858) were discharged to a skilled nursing or rehabilitation facility. Of note, the odds of increased care at discharge were increased by 1.41 (95% confidence interval: 1.32-1.50), 1.11 (95% confidence interval :1.11-1.12), and 1.95 (95% confidence interval:1.86-2.04) times with every unit increase in modified frailty index, age beyond 65 years, and the number of in-hospital complications, respectively. Area under receiver operative curve for the parsimonious model used to develop the risk calculator was 0.7486 (95% confidence interval: 0.7405-0.7566) (all P < .001). CONCLUSION: Approximately, 1 in 7 patients required an increased level of care at the time of discharge compared with their preadmission status. A simplified web-based risk tool can be used in clinical practice as a surgical decision aid in post-discharge planning after complex elective surgery.
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Frailty , Aftercare , Aged , Elective Surgical Procedures/adverse effects , Frailty/complications , Frailty/diagnosis , Humans , Patient Discharge , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Risk Assessment , Risk FactorsABSTRACT
This letter describes the cytological features in a case of primary neuroendocrine tumour of breast.
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Breast Neoplasms , Carcinoma, Neuroendocrine , Neuroendocrine Tumors , Breast/pathology , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Carcinoma, Neuroendocrine/diagnosis , Carcinoma, Neuroendocrine/pathology , Cytodiagnosis , Female , Humans , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/pathologyABSTRACT
Diabetes mellitus, whether preexisting or gestational, poses significant risk to both the mother and the developing fetus. A myriad of potential fetal complications in the setting of diabetic pregnancies include, among others, congenital anomalies, delayed fetal lung maturity, macrosomia, and increased perinatal morbidity and mortality. Congenital anomalies most commonly involve the nervous, cardiovascular, genitourinary, and musculoskeletal systems. Delayed fetal lung maturity, probably secondary to hyperglycemia suppressing surfactant secretion, is a major determinant of perinatal morbidity and mortality. Besides the potential complications encountered during cesarean delivery in macrosomic fetuses, vaginal delivery is also associated with increased risks of shoulder dystocia, clavicular and humeral fractures, and brachial plexus palsy. Maternal complications are related to the increased risk of hypertensive diseases of pregnancy and associated preeclampsia and hemolysis, elevated liver function, and low platelets (HELLP) syndrome, as well as complications encountered at the time of delivery secondary to fetal macrosomia and cesarean delivery. Additional conditions encountered in the setting of maternal diabetes include polyhydramnios, placental thickening, and two-vessel umbilical cord, each of which is associated with adverse fetal and maternal outcomes including fetal growth restriction, preterm labor, placental abruption, and premature rupture of membranes. Imaging plays a vital role in the evaluation of the mother and the fetus and can provide invaluable information that can be used by maternal fetal medicine to manage this patient population effectively. The authors review the pathophysiologic alterations induced by diabetes in pregnancy, discuss the imaging spectrum of diabetic embryopathy, and provide a detailed review of potential associated maternal complications. Online supplemental material is available for this article. ©RSNA, 2021.
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Brachial Plexus Neuropathies , Diabetes Mellitus , Fetal Diseases , Cesarean Section , Female , Fetal Macrosomia , Humans , Infant, Newborn , Placenta , PregnancyABSTRACT
BACKGROUND: The effect of varying severity and timing of complications after hepatic resection on 30-day mortality has not been thoroughly examined. METHODS: National Surgical Quality Improvement Program Patient User Files (NSQIP-PUF) were used to identify patients who underwent elective hepatic resection between 2014 and 2019. The impact of number, timing, and severity of complications on 30-day mortality was examined. RESULTS: Among 25,084 patients who underwent hepatic resection, 7436 (29.9%) patients developed at least one NSQIP complication, while 2688 (10.7%) had multiple (≥2) complications. Overall, 30-day mortality was 1.7% (n=424), among whom 81.4% (n=345) patients had ≥2 complications. The 30-day mortality was highest among patients with three consecutive severe complications (47.8%), as well as patients with one non-severe and two subsequent severe complications (47.6%). The adjusted probability of 30-day mortality was 35.5% (95%CI: 29.5-41.4%) when multiple severe complications occurred within the first postoperative week and 16.2% (95%CI: 7.2-25.1%) when the second severe complication occurred at least one week apart. The adjusted risk of 30-day mortality after even two non-severe complications was as high as 5.3% (95%CI: 3.7-6.9%) when the second complication occurred within a week postoperatively. CONCLUSION: Approximately 1 in 10 patients developed multiple complications following hepatectomy. Timing and severity of complications were independently associated with 30-day mortality.
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Postoperative Complications , Quality Improvement , Hepatectomy/adverse effects , Humans , Postoperative Complications/etiology , Retrospective Studies , Risk FactorsABSTRACT
A rare presentation of primary plasmablastic lymphoma (PBL) of the adrenal gland, as lymphomatous meningitis in a patient living with HIV.
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Lymphoma, Non-Hodgkin , Meningeal Neoplasms , Meningitis , Plasmablastic Lymphoma , Humans , Lymphoma, Non-Hodgkin/pathology , Meningeal Neoplasms/diagnosis , Meningitis/diagnosis , Plasmablastic Lymphoma/diagnosis , Plasmablastic Lymphoma/pathologyABSTRACT
OBJECTIVE: To describe challenges in inpatient pediatric quality and safety during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In a previous qualitative study, our team sought to broadly describe changes in pediatric inpatient care during the pandemic. For both that study and this ancillary analysis, we purposefully sampled participants from community and children's hospitals in the 6 US states with the highest COVID-19 hospitalization rates from March to May 2020. We recruited 2 to 3 participants from each hospital (administrators, front-line physicians, nurses, caregivers) for semistructured interviews. We used constant comparative methods to identify themes regarding quality and safety challenges during the pandemic. RESULTS: We interviewed 30 participants from 12 hospitals. Participants described several impacts to clinical workflows, including decreased direct clinician-patient interactions and challenges to communication, partly addressed through innovative use of telehealth technology. Participants reported changes in the discharge and transfer process (eg, discharges, difficulties accessing specialized facilities). Participants also described impacts to hospital operations, including changes in quality monitoring and operations (eg, decreased staff, data collection), increased health risks for clinicians and staff (eg, COVID-19 exposure, testing delays), and staff and supply shortages. Participants voiced concerns that negative quality and safety impacts could include increased risk of preventable safety events and hospital readmissions, and decreased patient engagement, education, and satisfaction. CONCLUSIONS: We identified several impacts to clinical workflows and hospital operations during the pandemic that may have affected inpatient pediatric care quality and safety. Our findings highlight potentially important areas of focus for planning pandemic recovery, preparing for future pandemics, and conducting future research on inpatient pediatric quality and safety.
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BACKGROUND: The COVID-19 pandemic has necessitated rapid changes in healthcare delivery in the United States, including changes in the care of hospitalized children. The objectives of this study were to identify major changes in healthcare delivery for hospitalized children during the COVID-19 pandemic, identify lessons learned from these changes, and compare and contrast the experiences of children's and community hospitals. METHODS: We purposefully sampled participants from both community and children's hospitals serving pediatric patients in the six U.S. states with the highest COVID-19 hospitalization rates at the onset of the pandemic. We recruited 2-3 participants from each hospital (mix of administrators, front-line physicians, nurses, and parents/caregivers) for semi-structured interviews. We analyzed interview data using constant comparative methods to identify major themes. RESULTS: We interviewed 30 participants from 12 hospitals. Participants described how leaders rapidly developed new hospital policies (e.g., directing use of personal protective equipment) and how this was facilitated by reviewing internal and external data frequently and engaging all relevant stakeholders. Hospital leaders optimized communication through regular, transparent, multi-modal, and bi-directional communication. Clinicians increased use of videoconference and telehealth to facilitate physical distancing, but these technologies may have disadvantaged non-English speakers. Due to declining volumes of hospitalized children and surges of adult patients, clinicians newly provided care for hospitalized adults. This was facilitated by developing care teams supported by adult hospitalists, multidisciplinary support via videoconference, and educational resources. Participants described how the pandemic negatively impacted clinicians' mental health, and they stressed the importance of mental health resources and wellness activities/spaces. CONCLUSIONS: We identified several major changes in inpatient pediatric care delivery during the COVID-19 pandemic, including the adoption of new hospital policies, video communication, staffing models, education strategies, and staff mental health supports. We outline important lessons learned, including strategies for successfully developing new policies, effectively communicating with staff, and supporting clinicians' expanding scope of practice. Potentially important focus areas in pandemic recovery include assessing and supporting clinicians' mental health and well-being, re-evaluating trainees' skills/competencies, and adapting educational strategies as needed. These findings can help guide hospital leaders in supporting pandemic recovery and addressing future crises.
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COVID-19 , Pandemics , Adult , Child , Hospitals, Pediatric , Humans , Qualitative Research , SARS-CoV-2 , United States/epidemiologyABSTRACT
ETHNO-PHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal, commonly known as Ashwagandha, belongs to the family Solanaceae. In Ayurveda, Ashwagandha has been defined as one of the most important herb and is considered to be the best adaptogen. It is also an excellent rejuvenator, a general health tonic and cure for various disorders such as cerebrovascular, insomnia, asthma, ulcers, etc. Steroidal lactones (Withanolides: Withanolide A, Withaferin A, Withanolide D, Withanone, etc) isolated from this plant, possess promising medicinal properties such as anti-inflammatory, immune-stimulatory etc. Standardized root extract of the plant NMITLI-118R (NM) was prepared at CSIR-CIMAP, and was investigated for various biological activities at CSIR-CDRI. Among the notable medicinal properties, NM exhibited excellent neuroprotective activity in the middle cerebral artery occlusion (MCAO) rat model. AIM OF THE STUDY: Endothelial dysfunction is the primary event in the cerebrovascular or cardiovascular disorders, present study was thus undertaken to evaluate vasoprotective potential of NM and its biomarker compound Withanolide A (WA) using rat aortic rings and EA.hy926 endothelial cells. MATERIAL AND METHODS: Transverse aortic rings of 10 weeks old Wistar rats were used to evaluate effect of NM and WA on the vasoreactivity. While, mechanism of NM and WA mediated vasorelaxant was investigated in Ea.hy926 cell line by measuring NO generation, nitrite content, Serine 1177 phosphorylation of eNOS, reduced/oxidized biopterin levels and expression of endothelial nitric oxide synthase (eNOS) mRNA and protein. RESULTS: Fingerprinting of NM using HPLC identified presence of WA in the extract. NM as well as WA exerted moderate vasorelaxant effect in the endothelium intact rat aortic rings which was lesser than acetylcholine (ACh). NM and WA augmented ACh induced relaxation in the rat aortic rings. NM and WA dependent vasorelaxation was blocked by N-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4] oxadiazolo [4,3,-a]quinoxalin-1-one (ODQ), indicating role of NO/cGMP. Further Ea.hy926 cells treated with NM and WA showed accumulation of nitrite content, enhanced NO levels, eNOS expression and eNOS phosphorylation (Serine 1177). CONCLUSION: Altogether NM and WA dependent improvement in the NO availability seems to be mediated by the enhanced eNOS phosphorylation. WA, seems to be one of the active constituent of NM, and presence of other vasoactive substances cannot be ruled out. The data obtained imply that the vasorelaxant property of NM is beneficial for its neuroprotective potential.
Subject(s)
Aorta/drug effects , Nitric Oxide/metabolism , Plant Extracts/pharmacology , Vasodilator Agents/pharmacology , Withania/chemistry , Withanolides/pharmacology , Animals , Biomarkers , Cell Line , Cell Proliferation , Endothelial Cells/drug effects , Male , Plant Extracts/chemistry , Plant Roots/chemistry , Rats , Rats, Wistar , Vasoconstriction/drug effects , Vasodilator Agents/chemistry , Withanolides/chemistryABSTRACT
BACKGROUND: Inter-hospital transfer (IHT) may help reduce failure-to-rescue (FTR) by transferring patients to centers with a higher level of expertise than the index hospital. We sought to identify factors associated with an IHT and examine if IHT was associated with improved outcomes after complex gastrointestinal cancer surgery. METHODS: Medicare Inpatient Standard Analytic Files were utilized to identify patients with >1 postoperative complication following resection for esophageal, pancreatic, liver, or colorectal cancer between 2013 and 2017. Multivariable logistic regression was used to examine the association of different factors with the chance of IHT, as well as the impact of IHT on failure-to-rescue (FTR) and expenditures. RESULTS: Among 39,973 patients with >1 postoperative complications, 3090 (7.7%) patients were transferred to a secondary hospital. The median LOS at the index hospital prior to IHT was 10 days (IQR, 6-17 days). Patients who underwent IHT more often had experienced multiple complications at the index hospital compared with non-IHT patients (57.7% vs. 38.9%) (p<0.001). Transferred patients more commonly had undergone surgery at a low-volume index hospital (n=218, 60.2%) compared with non-IHT (n=10,351, 25.9%) patients (p<0.001). On multivariate analysis, hospital volume remained strongly associated with transfer to an acute care hospital (ACH) (OR 5.53; 95% CI 3.91-7.84; p<0.001), as did multiple complications (OR 2.01, 95% CI 1.56-2.57). The incidence of FTR was much higher among IHT-ACH patients (20.2%) versus non-IHT patients (11.5%) (OR 1.51, 95% CI 1.11-2.05) (p<0.001). Medicare expenditures were higher among patients who had IHT-ACH ($72.1k USD; IQR, $48.1k-$116.7k) versus non-IHT ($38.5k USD; IQR, $28.1k-$59.2k USD) (p<0.001). CONCLUSION: Approximately 1 in 13 patients had an IHT after complex gastrointestinal cancer surgery. IHT was associated with high rates of FTR, which was more pronounced among patients who underwent surgery at an index low-volume hospital. IHT was associated with higher overall CMS expenditures.