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Patients undergoing cardiac surgery often receive vasopressor and inotropic medications during the surgical procedure and during intensive care unit (ICU) management following surgery. Patients with cardiogenic shock, septic shock, and other clinical disorders associated with shock also receive vasopressor medications during their ICU care. The level of support and the duration of support are likely associated with outcomes, including mortality and new organ dysfunction, such as acute kidney injury. The vasopressor-inotropic score provides a simple method to determine the level of support during the care of these patients; this score includes the infusion rates of norepinephrine, epinephrine, dopamine, dobutamine, and other inotropic medications. It has been studied in patients undergoing cardiac surgery, coronary artery bypass grafting, cardiac transplantation, left ventricular assist device implantation, septic shock, and traumatic brain injury. Higher scores are associated with poor outcomes and complications during ICU care. The studies analyzed in this review demonstrate the utility of the vasopressor-inotropic score in a variety of clinical disorders associated with shock. Electronic medical record systems should develop algorithms to calculate this score and provide continuous up-to-date measurements. This could help clinicians identify patients at risk for mortality and important complications, such as acute kidney injury., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Dyspnea is an important non-motor symptom in Parkinson's disease (PD) that impacts quality of life. The mechanisms underlying dyspnea have been difficult to determine due to challenges separating central respiratory control abnormalities from peripheral respiratory muscle dysfunction and chest wall rigidity., Methods: A comprehensive literature review was conducted, searching the PubMed database for observational studies on respiratory dysfunction and dyspnea in PD. Inclusion criteria were studies with PD patients without other neurological disorders. Case studies were excluded. Data on study size, disease duration, control groups, and respiratory defects were extracted., Results: The search yielded 23 unique publications on pulmonary function in PD. Key findings were: 1) restrictive defects are common, with prevalence up to 85 % in some studies; 2) effects of levodopa on pulmonary function are variable across studies; 3) there is limited research on the role of central respiratory centers in dyspnea pathophysiology in PD. Proposed mechanisms include direct involvement of brainstem respiratory structures, loss of dopamine input to these regions, and astrocyte dysfunction affecting respiratory rhythm generation., Conclusion: This review outlines potential mechanisms underlying dyspnea in PD, including central respiratory dysfunction, peripheral muscle/chest wall abnormalities, impaired respiratory sensation, and medication effects. More research is needed investigating specific brainstem regions involved, chemoreceptor pathology, correlations between respiratory load and perceived dyspnea, and medication effects on pulmonary function., Competing Interests: Declaration of competing interest Suyash Jain, Shruti Patel, and Kenneth Nugent have nothing to declare related to this particular project., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Resveratrol as well as natural products biosynthetically derived from it, have been shown to have protective effects against oxidative stress. However, these compounds possess poor druglike properties. At sub-nanomolar concentrations, a novel compound (RVM-6) inspired by a resveratrol natural product prolongs synaptic viability in neuromuscular junctions in D. melanogaster exposed to acute oxidative stress., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Purpose: To evaluate the relative diagnostic yield of clinical germline genomic tests in a diverse pediatric cancer population., Patients and Methods: The KidsCanSeq study enrolled pediatric cancer patients across six sites in Texas. Germline analysis included both exome sequencing and a therapy-focused pediatric cancer gene panel. The results were categorized by participants demographics, the presence of pathogenic or likely pathogenic (P/LP) variants, and variants of uncertain significance (VUS) in cancer predisposition genes (CPGs). Pediatric actionable CPGs were defined as those with cancer surveillance recommendations during childhood., Results: Cancer P/LP variants were reported by at least one platform in 103 of 578 (17.8%) participants of which 76 were dominant cancer genes (13.1%) with no significant differences by self-described race or Hispanic ethnicity. However, the proportion of participants with VUS was greater in Asian and African American participants ( P = .0029). Diagnostic yield was 16.6% for exome versus 8.5% for panel ( P < .0001) with 42 participants with concordant germline results. Exome-only results included P/LP variants in 30 different CPGs in 54 participants, whereas panel-only results included seven participants with a copy number or structural P/LP variants in CPGs. There was no significant difference in diagnostic yield limited to pediatric actionable CPGs ( P = .6171)., Conclusion: Approximately 18% of a diverse pediatric cancer population had germline diagnostic findings with 50% of P/LP variants reported by only one platform because of CPGs not on the targeted panel and copy number variants (CNVs)/rearrangements not reported by exome. Although diagnostic yields were similar in this diverse population, increases in VUS results were observed in Asian and African American populations. Given the clinical significance of CNVs/rearrangements in this cohort, detection is critical to optimize germline analysis of pediatric cancer populations.

Aims: Prognosis of locally advanced pancreatic cancer (LAPC) remains poor with limited therapeutic options. Radiation therapy in pancreatic cancer has been restricted by the disease's proximity to radiosensitive organs at risk (OAR). However, stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) has demonstrated promise in delivering ablative doses safely. We sought to report clinical outcomes from a UK-based Compassionate Access Programme that provided access to SMART to patients with LAPC., Materials and Methods: This was a registry retrospective study conducted at a single centre with access to SMART. Patients with LAPC were treated with prescription dose of 40 Gy in 5 fractions. The planning objective was that 98% of PTV received ≥95% of the prescribed dose, prioritising duodenal, stomach and bowel UK SABR consortium constraints. Daily online adaptation was performed using magnetic resonance guidance and on-table re-optimisation. 0-3 months and > 3-month post-treatment-related toxicities, local progression-free survival, metastatic-free survival and overall survival were evaluated., Results: 55 patients were treated with SMART at our institution from 2020 to 2022. Median follow-up from date of diagnosis was 17 months (range 5-37 months). Median age was 69.87% of patients underwent induction chemotherapy. 71% of patients reported 0-1 grade acute toxicity only. No grade >3 acute toxicity was reported. 5 patients (9%) reported a grade 3 toxicity (fatigue, nausea, abdominal pain, duodenal stricture). No grade >3 toxicity after 3 months was reported. 6 (10%) of patients had grade 3 toxicity (fatigue, nausea, abdominal pain, duodenal haemorrhage). Median local PFS post diagnosis was 17 months (95% CI 15.3-18.7). Median OS post diagnosis was 19 months (95% CI 15.9-22.1). One-year local control post SMART was 65%., Conclusion: This is the first UK-reported experience of MR-guided daily adaptive pancreatic SABR. SMART shows promise in delivering ablative doses with acceptable toxicity rates and good clinical outcomes., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The combination of vancomycin and piperacillin-tazobactam (VPT) has been associated with acute kidney injury (AKI) in hospitalized patients when compared to similar combinations. Additional studies examining this nephrotoxic risk in critically ill patients have not consistently demonstrated the aforementioned association. Furthermore, patients with baseline renal dysfunction have been excluded from almost all of these studies, creating a need to examine the risk in this patient population. Methods: This was a retrospective cohort analysis of critically ill adults with baseline chronic kidney disease (CKD) who received vancomycin plus an anti-pseudomonal beta-lactam at Emory University Hospital. The primary outcome was incidence of AKI. Secondary outcomes included stage of AKI, time to development of AKI, time to return to baseline renal function, new requirement for renal replacement therapy, intensive care unit and hospital length of stay, and in-hospital mortality. Results: A total of 109 patients were included. There was no difference observed in the primary outcome between the VPT (50%) and comparator (58%) group ( P  = .4), stage 2 or 3 AKI (15.9% vs 6%; P  = .98), time to AKI development (1.7 vs 2 days; P  = .5), time to return to baseline renal function (4 vs 3 days; P  = .2), new requirement for RRT (4.5% vs 1.5%; P  = .3), ICU length of stay (7.3 vs 7.4 days; P  = .9), hospital length of stay (19.3 vs 20.1 days; P  = .87), or in-hospital mortality (15.9% vs 10.8%; P  = .4). A significant difference was observed in the duration of antibiotic exposure (3.32 vs 2.62 days; P  = .045 days). Conclusion: VPT was not associated with an increased risk of AKI or adverse renal outcomes. Our findings suggest that the use of this antibiotic combination should not be avoided in this patient population. More robust prospective studies are warranted to confirm these findings., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Hepatitis C virus is an important global cause of hepatitis and subsequently cirrhosis and hepatocellular carcinoma. These infections may also cause extrahepatic manifestations, including insulin resistance and type 2 diabetes mellitus. These two complications can potentially reduce sustained virologic responses (SVR) in some drug regimens for this infection. Metformin has important biochemical effects that can limit viral replication in cellular cultures and can improve the response to antiviral drug therapy based on ribavirin and interferon. Clinical studies comparing treatment regimens with interferon, ribavirin, metformin with these regimens without metformin have demonstrated that metformin increases viral clearance, establishes higher rates of SVRs, and increases insulin sensitivity. Metformin also reduces the frequency of hepatocellular carcinoma in patients who have had SVRs. Larger treatment trials are needed to determine metformin's short-term and long-term treatment effects in patients with diabetes using newer antiviral drugs. In particular, if metformin reduces the frequency of cirrhosis and hepatocellular carcinoma, this would significantly reduce the morbidity and mortality associated with this infection., Competing Interests: Conflict of Interest The author has no financial or other conflicts of interest to disclose., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Purpose: To report acute and late bowel, urinary, and sexual dysfunction patient-reported outcome measures, among patients with localized prostate cancer who underwent stereotactic magnetic resonance-guided daily adaptive radiation therapy (SMART)., Methods and Materials: All patients who completed a baseline 12-item Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events questionnaire, before undergoing SMART with 36.25 Gy in 5 fractions, were subsequently followed up with the same graded questionnaire at set time points. Latest prostate-specific antigen levels were recorded. The percentage of patients who reported no change from their baseline adverse event (AE) or reported a new ≥ "frequent or almost constant" or "severe grade or higher" AE grade during follow-up was calculated. The maximum 12-item Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events grade for each item was recorded for each patient. The percentage of toxicity levels for each separate AE item at set time points was calculated., Results: The total number of patients was 69 with a median follow-up of 27 months. Median age of the cohort was 73 years (range, 54-85 years). The median pretreatment prostate-specific antigen level, T stage, and Gleason score were 7.5 mmol/L (range, 4.5-32 mmol/L), T2b (range, T2-T3b), and 7 (3 + 4; range, 6-9), respectively. No patient had biochemical failure during follow-up. Regarding bowel symptoms, >80% of men reported no change from baseline toxicity during follow-up. New ≥ frequent or almost constant diarrhea was reported in 9% of patients. "Almost constant" diarrhea peaked at 1 month but was absent at >33 months. Regarding urinary symptoms, increased urinary urgency was the most common complaint (39%). Twenty percent of men reported new ≥ frequent or almost constant urinary urgency incidence peaking at 1 month but absent at >33 months. New "severe" sexual dysfunction was seen in 26% of patients and was persistent at >33 months., Conclusions: Our study is one the largest patient-reported outcomes study after prostate SMART. It shows acceptable levels of toxicity even up to 2 years after treatment., Competing Interests: We declare that none of the authors have competing interests., (© 2024 The Authors.)

Objectives: Periodically, medical publications are retracted. The reasons vary from minor situations, such as author attributions, which do not undermine the validity of the data or the analysis in the article, to serious reasons, such as fraud. Understanding the reasons for retraction can provide important information for clinicians, educators, researchers, journals, and editorial boards., Methods: The PubMed database was searched using the term "COVID-19" (coronavirus disease 2019) and the term limitation "retracted publication." The characteristics of the journals with retracted articles, the types of article, and the reasons for retraction were analyzed., Results: This search recovered 196 articles that had been retracted. These retractions were published in 179 different journals; 14 journals had >1 retracted article. The mean impact factor of these journals was 8.4, with a range of 0.32-168.9. The most frequent reasons for retractions were duplicate publication, concerns about data validity and analysis, concerns about peer review, author request, and the lack of permission or ethical violation. There were significant differences between the types of article and the reasons for retraction but no consistent pattern. A more detailed analysis of two particular retractions demonstrates the complexity and the effort required to make decisions about article retractions., Conclusions: The retraction of published articles presents a significant challenge to journals, editorial boards, peer reviewers, and authors. This process has the potential to provide important benefits; it also has the potential to undermine confidence in both research and the editorial process.

Patients with prior COVID-19 infections often develop chronic post-COVID symptoms, such as fatigue and dyspnea. Some patients have residual pulmonary disorders with abnormal pulmonary function tests and/or chest radiographs to explain their dyspnea. However, other patients appear to have dyspnea that is out of proportion to any measurable change in lung function. Some of these patients have abnormal cardiopulmonary exercise testing with definite cardiac or respiratory limits. However, others have normal cardiopulmonary exercise testing based on VO 2 measurement but pronounced dyspnea during this testing. These patients often have abnormal respiratory patterns, referred to as dysfunctional breathing, with irregular and variable respiratory rates and/or tidal volumes. Consequently, their control of breathing is impaired, and this may represent residual effects from prior COVID-19 infection involving the central nervous system. Alternatively, patients may have acquired "a memory" of respiratory symptoms during their infection which persists post-infection. These patients should participate in pulmonary rehabilitation and breathing retraining., Competing Interests: Declaration of competing interest The authors have no conflict of interest related to this manuscript., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

This case report and review describes a 31-year-old man with a history of chronic pancreatitis who presented to the hospital with shortness of breath and left-sided chest pain. Three days prior, he underwent mid-splenic artery embolization due to hematemesis attributed to a splenic artery pseudoaneurysm associated with a peripancreatic pseudocyst. Upon this presentation, the patient reported increasing shortness of breath, left-sided pleuritic chest pain, and epigastric and left upper quadrant abdominal pain. Imaging revealed left pleural effusion, splenic infarcts, and adjacent fluid collections. Thoracentesis confirmed an exudative effusion. The pleural effusion was attributed to recent splenic artery embolization, and the patient was discharged on appropriate medications in stable condition on the sixth day of hospitalization. This case underscores the importance of considering embolization-related complications in the differential diagnosis of pleural effusions following such procedures. The etiology, diagnosis, and management of splenic artery aneurysms are discussed in this review., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Hepatitis B virus (HBV) infections affect approximately 296 million people around the world, and the prevalence of any past or present HBV infection during the years 2015-2018 was as high as 4.3%. Acute HBV infection often presents with nonspecific symptoms and is usually self-limited, but 5% of patients can have persistent infections leading to chronic HBV infection and the risk of turning into chronic HBV infection is significantly higher in babies with vertical transmission (95%). Patients with chronic HBV infection are usually asymptomatic, but 15 to 40% of chronic HBV carriers develop cirrhosis and/or hepatocellular carcinoma. In addition to liver-related disorders, HBV is also associated with several extrahepatic complications, including glomerulonephritis, cryoglobulinemia, neurologic disorders, psychological manifestations, polyarthritis, and dermatologic disorders. Making the diagnosis of HBV can be challenging since patients with chronic infections can remain symptom-free for decades before developing cirrhosis or hepatocellular carcinoma, and patients with acute HBV infection may have only mild, nonspecific symptoms. Therefore, understanding how this virus causes extrahepatic complications can help clinicians consider this possibility in patients with diverse symptom presentations. The pathophysiology of these extrahepatic disorders likely involves immune-related tissue injury following immune complex formation and inflammatory cascades. In some cases, direct viral infection of extrahepatic tissue may cause a clinical syndrome. Currently, the American Association for the Study of Liver Diseases recommends treatment of chronic HBV infections with interferon therapy and/or nucleos(t)ide analogs, and this treatment has been reported to improve some extrahepatic disorders in some patients with chronic HBV infection. These extrahepatic complications have a significant role in disease outcomes and increase medical costs, morbidity, and mortality. Therefore, understanding the frequency and pathogenesis of these extrahepatic complications provides important information for both specialists and nonspecialists and may help clinicians identify patients at an earlier stage of their infection.

Introduction Falls from trees (FFTs), although rare, represent a significant public health concern due to the severe consequences they can impose. Such incidents, while statistically uncommon across the wider population, have the potential to cause drastic, lasting alterations in patients' lives. The severity of these events is often substantial, highlighted by high Injury Severity Scores (ISSs) and prolonged hospital length of stay (LOS), which brings to light the urgent need for preventive strategies and heightened awareness. Our study aims to present a current epidemiological understanding of the patterns, nature, and severity of injuries caused by FFTs. Additionally, it provides an analysis and comparison of data obtained from a de-identified trauma database of patients presenting after FFTs. Methods This review presents data from a trauma registry system detailing trauma admissions from March 31, 2016, to December 27, 2021, at the Desert Regional Medical Center in Palm Springs, California, United States, a designated Level 1 trauma center. Throughout this period of nearly five years and eight months, a total of 3,148 patients were recorded to have visited the emergency department due to falls. Specifically, the study zeroes in on the subset of patients who were admitted after experiencing FFTs. From the comprehensive retrospective examination, it was noted that among the 3,148 fall incidents, there were 50 cases that involved FFTs. Results This retrospective analysis focused on 50 patients treated at the emergency department after FFTs, with a predominantly male demographic profile of 49 (98%) and an average age of 44 years. Hospitalization was required for the vast majority (44%), with approximately one-third necessitating ICU care. Surgical procedures were necessary for 35 (70%) of these cases. Upon discharge, 36 (72% of patients) were able to return home. Vertebral fractures were the most frequent injury, present in 24 (22% of admissions), followed closely by soft tissue injuries at 23 (21%). The mean ISS was 11, although those with extended hospital stays of over 10 days had higher ISS scores of 16, in contrast to an ISS of 10 for those with shorter stays. Conclusions FFTs constitute a lesser-known category of trauma-related injuries in the broader spectrum of fall-related incidents. Although relatively infrequent, these incidents result in significant injury burdens. The objective of this review is to compile and summarize the existing body of literature on FFTs. It involves an in-depth analysis of admission, discharge, and demographic data related to FFTs, highlighting the significant consequences associated with such accidents. Additionally, this review incorporates an analysis of a specialized dataset dedicated to injuries resulting from FFTs, facilitating a comparative assessment against current research in this field., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Nugent et al.)

Competing Interests: Competing interests: None declared.

Purpose: Lower limb loss can result in an altered body image, leading to changes in self-esteem, mental health and quality of life. This scoping review explored how body image has been evaluated among people with lower limb loss., Materials and Methods: Five databases (Embase, Medline, PsychINFO, CINHAL, and Nursing and Allied Health Database) were searched from inception until March 19, 2023. Inclusion criteria: 1) people with lower limb loss; 2) evaluated a body image outcome or theme; and 3) a qualitative, quantitative or mixed methods design., Results: Twenty-four quantitative ( n  = 19 cross-sectional, n  = 3 intervention cohort and n  = 2 prospective cohort), 2 qualitative and 1 mixed methods design studies were included. The definition of body image varied across studies, with 59% of studies not reporting a conceptual or theoretical definition. People with lower limb loss perceived a more negative body image compared to control groups. In prospective cohort studies, changes in body image over time were inconclusive., Conclusion: People with lower limb loss report a negative body image when compared to other populations. Definitions and understanding of body image changed overtime and varied among studies which may impact introducing interventions to promote positive body image during rehabilitation and beyond in this population.

Introduction Falls from beds (FFBs) among outpatient elderly individuals are a prevalent issue, particularly for those aged 65 and above. This presents a notable health challenge with consequences that extend beyond personal well-being, placing a considerable strain on healthcare systems. Fall-related injuries often result in reduced independence, increased morbidity, and, in severe instances, fatalities. It is crucial to address these outpatient falls to safeguard the health and independence of the elderly population. Methods This review presents data sourced from a trauma registry covering admissions from March 31, 2016, to December 27, 2021, at Desert Regional Medical Center, a Level 1 Trauma Center in Palm Springs, USA. Over this period, 3,148 patients sought emergency care following falls. The study specifically investigates cases following FFBs, revealing 164 admissions out of the total. Furthermore, it contrasts patient demographics, injury types, and outcomes with existing literature. Results This retrospective analysis found that, among the 164 patients admitted to the emergency department over a five-year and eight-month period due to FFBs, 143 were classified as elderly, aged 65 and above. The mean age of those admitted was 76, whereas those not admitted had a mean age of 71. A significant majority, 87%, were hospitalized; within this group, 16% required intensive care. Surgical intervention was necessary for 27 individuals, and there were three fatalities. Soft tissue hematomas were the most common injuries, representing 24% of injuries at admission, closely followed by upper extremity fractures at 21%. Over half of these patients could not return home post-hospitalization, with 41% being transferred to skilled nursing facilities (SNF). Conclusions As the aging population in the United States continues to grow, the incidence of falls is on the rise, resulting in injuries like fractures and head trauma. The objectives of this review are to provide an overview of the current literature on FFBs, as well as to emphasize the significant impact of such injuries on the elderly population. Additionally, it includes an analysis of a dataset detailing injuries resulting from bed-related falls, offering a comparison to existing research., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Nugent et al.)

Background: The retraction of medical articles periodically occurs in most medical journals and can involve multiple article types. These retractions are beneficial if they remove flawed or fraudulent information from the medical literature. However, retractions may also decrease confidence in the medical literature and require significant amounts of time by editors., Methods: One publisher (Hindawi) announced that it will retract over 1200 articles. Given this, the PubMed database was searched to identify retracted publications on or related to COVID-19, and articles retracted by journals sponsored by the publisher Hindawi were then identified., Results: These journals retracted 25 articles and, in most cases, did not provide an exact explanation about the particular problem(s) resulting in the retraction. The time to retraction was 468.7 ± 109.8 days (median =  446 days). These articles had 9.3 ± 9.9 citations., Conclusion: Analysis of the titles and abstracts of the articles suggests that their removal from the medical literature would have limited effects on the near-term management decisions during the COVID-19 pandemic. Nevertheless, retraction of medical articles creates uncertainty in medical care and science and in the public regarding the validity of medical research and related publications and the level of professionalism of the individuals submitting these articles., Competing Interests: The authors report no funding or conflicts of interest., (Copyright © 2024 Baylor University Medical Center.)

Patients with cardiac disease frequently develop pleural effusions; the incidence is approximately 500,000 cases per year in the United States. These effusions often represent important clinical events for patients, indicating that either there has been an acute change in the patient's clinical status or the patient's chronic management program needs review. These effusions usually develop in both the right and left hemithorax but can be unilateral. The pathogenesis involves increased fluid transfer from parietal pleural capillaries into the pleural space and possibly decreased pleural fluid uptake into parietal pleural lymphatic structures. The increased fluid transfer develops due to increased capillary pressure secondary to elevated venous outflow pressure and secondary to decreased lymphatic flow into central vessels secondary to heart failure. Most pleural effusions associated with heart failure are transudates, but 20% to 25% have increased protein and lactate dehydrogenase levels suggesting an exudative process. Additional testing can clarify the situation and requires calculation of the serum albumin to pleural fluid albumin gradient or measurement of N-terminal pro-brain natriuretic peptide in the pleural fluid. An albumin gradient of greater than 1.2 g/dL suggests that the fluid is a transudate. The presence of a pleural effusion in a hospitalized patient at discharge is associated with an increased likelihood of rehospitalization and mortality within the next year. Patients with large symptomatic pleural effusions may require therapeutic thoracentesis. Recurrence of symptomatic effusions presents a management dilemma that might require repeated thoracenteses, indwelling intrapleural catheter placement, or other management steps used in advanced chronic heart failure., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The management of patients with complex comorbidity involving several organ systems can use an approach focused on each organ system independently or can use an approach trying to integrate various injuries and dysfunction into a single syndrome. Cardiorenal syndromes can develop with an initial injury to either the heart or kidney and then sequential involvement of the second organ. This can occur acutely or chronically. Cardiorenal syndrome type 3 is defined by acute renal injury with subsequent cardiac injury and/or dysfunction. Studies on these patients must use strict inclusion criteria. Pavan reported information on 100 patients with acute kidney injury in India to determine the frequency of cardiorenal syndrome type 3. He excluded patients with significant prior comorbidity. The most frequent causes of acute kidney injury in these patients were drug toxicity, gastroenteritis with volume contraction, and obstetrical complications. This study included 100 patients with acute kidney injury, and 29 developed cardiorenal syndrome type 3. Important outcomes included frequent mortality and chronic renal failure. Other studies have reported that cardiorenal syndrome type 3 occurs relatively infrequently. The analysis of large data bases has demonstrated that the development of acute kidney injury in hospitalized patients has important consequences, including the development of heart failure and increased mortality, but the complexity of these cohorts makes it difficult to determine the time course for the development of multisystem disorders. The pathogenesis of cardiorenal syndrome type 3 involves mitochondrial dysfunction, immune dysregulation, and ischemia-reperfusion. Cardiac events occur secondary to fluid overload, electrolyte disorders, and uremic toxins. These patients need increased attention during hospitalization and outpatient management in an effort to slow the progression of the primary disorder and treat complications., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Cardiopulmonary exercise testing (CPET) provides important information for the assessment and management of patients with heart failure. This testing measures the respiratory and cardiac responses to exercise and allows measurement of the oxygen uptake (V˙O 2 ) max and the relationship between minute ventilation (V˙E) and carbon dioxide excretion (V˙CO 2 ). These two parameters help classify patients into categories that help predict prognosis, and patients with a V˙O 2 < 14 mL/kg/min and V˙E/V˙CO 2 slope >35 have a poor prognosis. This testing has been used in drug trials to determine complex physiologic responses to medications, such as angiotensin-converting enzyme inhibitors. For example, a study with enalapril demonstrated that the peak V˙O 2 was 14.6 ± 1.6 mL/kg/min on placebo and 15.8 ± 2.0 mL/kg/min on enalapril after 15 days of treatment. The V˙E/V˙CO 2 slopes were 43 ± 8 on placebo and 39 ± 7 on enalapril. Chronic heart failure and reduced physical activity measured by cardiopulmonary exercise testing are associated with increases in BNP, and several studies have demonstrated that cardiac rehabilitation is associated with reductions in BNP and increases in V˙O 2 . Therefore, BNP measurements can help determine the benefits of cardiac rehabilitation and provide indirect estimates of changes in V˙O 2 . In addition, measurement of microRNAs can determine the status of skeletal muscle used during physical activity and the changes associated with rehabilitation. However, CPET requires complicated technology, and simpler methods to measure physical activity could help clinicians to manage their patients. Recent advances in technology have led to the development of portable cardiopulmonary exercise testing equipment, which can be used in various routine physical activities, such as walking upstairs, sweeping the floor, and making the bed, to provide patients and clinicians a better understanding of the patient's current symptoms. Finally, current smart watches can provide important information about the cardiorespiratory system, identify unexpected clinical problems, and help monitor the response to treatment. The organized use of these devices could contribute to the management of certain aspects of these patients' care, such as monitoring the treatment of atrial fibrillation. This review article provides a comprehensive overview of the current use of CPET in heart failure patients and discusses exercise principles, methods, clinical applications, and prognostic implications.

Contrast-induced nephropathy (CIN) is a significant complication in patients undergoing coronary angiography, and its development is associated with increased morbidity and mortality. Left ventricular end-diastolic pressure (LVEDP) provides one index of left heart filling status. An elevated LVEDP can reflect volume overload or abnormal diastolic function and indicates a cardiac disorder. Data on the association between an elevated LVEDP and CIN are limited and have had conflicting results. We systematically searched the databases PubMed, Embase, and Scopus for full-text articles from database inception to May 2022. Studies were included if they evaluated the association between a high LVEDP and the incidence of CIN in patients undergoing coronary angiography. The study was registered in the PROSPERO CRD42022334070. A second search in PubMed identified randomized controlled trials using LVEDP to guide fluid administration during coronary procedures. Four studies were identified that used LVEDP to classify patients into groups to determine the association between the level and the development of CIN. In these studies, 240 patients of 2441 patients (9.8%) developed CIN. One study found no association between LVEDP levels and the development of CIN. Two studies found an increased frequency of CIN in patients with elevated levels using 2 cutoff points for LVEDP, ≥20 mm Hg and >30 mm Hg. One study found that lower LVEDP levels (5-14 mm Hg) were associated with the development of CIN. Three randomized control trials used LVDEP levels to manage fluid administration in patients undergoing coronary procedures; only one study found that the use of these levels to guide fluid administration resulted in better outcomes. In patients undergoing coronary angiography, an elevated LVEDP was not consistently associated with increased risk of CIN, and using LVEDP levels to guide fluid administration during these procedures did not always improve outcomes in comparison to other protocols. The use of LVEDP levels can help classify patients with cardiac disorders but does not necessarily provide an adequate description of the hemodynamic patterns in these patients to predict or prevent CIN in patients undergoing angiography., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background Falls from roofs (FFRs), while constituting just a segment of all falls, pose a significant public health issue. They not only impact individuals in their daily lives but also pose an increased risk in the construction field. The consequences of these falls range broadly, from minor bruises to serious harm, potentially leading to chronic disability or fatality. For the general populace, such falls might happen during simple activities like maintenance, with outcomes varying from fractures to critical head or spinal injuries. In construction, where elevated work is the norm, the likelihood and potential severity of falls are significantly greater. Construction workers face the threat of falls regularly, with these mishaps often resulting in enduring disabilities that affect both life quality and work capability. Methodology This study presents data from a trauma registry system, covering trauma admissions from March 31, 2016, to December 27, 2021, at a level 1 trauma center (Desert Regional Medical Center, Palm Springs, CA). During this five-year and eight-month period, a total of 3,148 patients presented to the emergency department after a fall. This study focuses on patients admitted after an FFR. A retrospective analysis of this data showed that out of these 3,148 patients, 75 presented after an FFR. Results In this retrospective analysis of 75 patients presenting to the emergency department after an FFR, the patient profile was predominantly male (70, 93%), with an average age of 51 years. Hospitalization was required for the majority of the patients (70, 93%), with a third necessitating intensive care unit (ICU) care. The necessity for surgical procedures was high at 57 (76%). Upon discharge, 8 (11%) patients were moved to acute rehabilitation. Injuries to the extremities were most common, accounting for 21% (36) of cases, in contrast to facial injuries at 8% (15). Upper extremity fractures were the most prevalent presenting injury at 31% (50), while lower extremity fractures were the least at 6% (9). The overall Injury Severity Score (ISS) averaged 12, with patients having hospital length of stays (LOSs) over 10 days presenting higher ISS scores (18) compared to those with shorter stays (ISS of 11). There was no significant difference in ISS between patients aged 60 and above compared to younger patients. Conclusions FFRs represent a substantial cause of injury in both the construction industry and residential settings. This study aims to provide an overview and summary of the existing literature on FFRs, present effective fall prevention methods, and underscore the considerable consequences of such injuries on both construction workers and homeowners. Additionally, it includes an analysis of a dataset detailing injuries resulting from roof-related falls, offering a comparison to existing research., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Nugent et al.)

Purpose: We sought to delineate a multisystem disorder caused by recessive cysteine-rich with epidermal growth factor-like domains 1 (CRELD1) gene variants., Methods: The impact of CRELD1 variants was characterized through an international collaboration utilizing next-generation DNA sequencing, gene knockdown, and protein overexpression in Xenopus tropicalis, and in vitro analysis of patient immune cells., Results: Biallelic variants in CRELD1 were found in 18 participants from 14 families. Affected individuals displayed an array of phenotypes involving developmental delay, early-onset epilepsy, and hypotonia, with about half demonstrating cardiac arrhythmias and some experiencing recurrent infections. Most harbored a frameshift in trans with a missense allele, with 1 recurrent variant, p.(Cys192Tyr), identified in 10 families. X tropicalis tadpoles with creld1 knockdown displayed developmental defects along with increased susceptibility to induced seizures compared with controls. Additionally, human CRELD1 harboring missense variants from affected individuals had reduced protein function, indicated by a diminished ability to induce craniofacial defects when overexpressed in X tropicalis. Finally, baseline analyses of peripheral blood mononuclear cells showed similar proportions of immune cell subtypes in patients compared with healthy donors., Conclusion: This patient cohort, combined with experimental data, provide evidence of a multisystem clinical syndrome mediated by recessive variants in CRELD1., Competing Interests: Conflict of Interest Two authors report part ownership of startup companies unrelated to this work: Qiyas Higher Health (Saquib A. Lakhani) and Victory Genomics (Saquib A. Lakhani and Mustafa K. Khokha). Kirsty McWalter is an employee of GeneDx. Kimberly Nugent is currently an employee of Cooper Surgical. Bryan Mak is currently an employee of Genome Medical. All other authors declare no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Acute esophageal variceal bleeding accounts for up to 70% of upper-gastrointestinal bleeding in cirrhotic patients. About 10-20% of patients with acute variceal bleeding have refractory bleeding that is not controlled by medical or endoscopic therapy, and this condition can be life-threatening. Balloon tamponade is a long-standing therapy which is only effective temporarily and has several complications, while transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation may not be readily available at some centers. The use of self-expandable metal stents (SEMSs) in refractory esophageal variceal bleeding has been studied for effectiveness and adverse events and has been recommended for use as a bridge to a more definitive treatment. Aim: To investigate the effectiveness and safety of SEMSs in managing refractory variceal bleeding. Methods: A systematic search of the MEDLINE, EMBASE, and Cochrane library databases was performed from inception to October 2022 using the following terms: "esophageal stent", "self-expandable metal stents", "endoscopic hemostasis", "refractory esophageal varices", and "esophageal variceal bleeding". Studies were included in the meta-analysis if they met the following criteria: (1) patients' age older than 18 and (2) a study (or case series) that has at least 10 patients in the study. Exclusion criteria included (1) non-English publications, (2) in case of overlapping cohorts, data from the most recent and/or most appropriate comprehensive report were collected. DerSimonian-Laird random-effects meta-analysis was performed using the meta package in R statistical software(version 4.2.2). Results: Twelve studies involving 225 patients with 228 stents were included in the analyses. The mean age and/or median age ranged from 49.4 to 69 years, with a male-to-female ratio of 4.4 to 1. The median follow-up period was 42 days. The mean SEMS dwell time was 9.4 days. The most common cause of acute refractory variceal bleeding in chronic liver disease patients included alcohol use followed by viral hepatitis. The pooled rate of immediate bleeding control was 91% (95% CI 82-95%, I 2 = 0). The pooled rate of rebleeding was 17% (95% CI 8-32%, I 2 = 69). The pooled rate of stent ulceration was 7% (95% CI 3-13%, I 2 = 0), and the pooled rate of stent migration was 18% (95% CI 9-32%, I 2 = 38). The pooled rate of all-cause mortality was 38% (95% CI 30-47%, I 2 = 34). Conclusions: SEMSs should be primarily considered as salvage therapy when endoscopic band ligation and sclerotherapy fail and can be used as a bridge to emergent TIPS or definitive therapy, such as liver transplantation.

Objectives: This study aimed to analyze tobacco and marijuana use by middle and high school students identifying as bisexual, gay, lesbian, or heterosexual using data from the National Youth Tobacco Survey (NYTS) spanning from 2020 to 2022. By comparing substance use patterns among different sexual orientation groups, the study sought to identify disparities and potential socioeconomic factors influencing these behaviors., Methods: Data from the 2020 to 2022 NYTS were analyzed, focusing on responses regarding ever use of cigarettes, e-cigarettes, and marijuana by students of varying sexual orientations. Descriptive statistics and chi-square tests were employed to analyze differences in substance use and socioeconomic indicators between sexual orientation groups., Results: Of the 37 541 students included in the analysis, significant differences in substance use were observed among bisexual, gay, lesbian, and heterosexual students. Bisexual and gay/lesbian students exhibited higher rates of ever use of cigarettes, e-cigarettes, and marijuana compared to heterosexual students. In addition, socioeconomic differences, such as lower rates of family vehicle ownership and reduced access to vacations, were noted among bisexual and gay/lesbian students., Conclusions: The findings underscore significant differences in tobacco and marijuana use by adolescents based on sexual orientation, mirroring differences observed in LGBTQ adults. These results highlight the importance of targeted interventions, educational initiatives, and support systems tailored to the unique needs of LGBTQ youth. Addressing socioeconomic disparities and fostering inclusive environments are crucial steps in promoting the health and well-being of LGBTQ adolescents. Continued research and collaborative efforts are essential in mitigating health disparities and creating equitable environments for all adolescents., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The unprecedented impact and sequelae of COVID-19 infection are not yet fully understood, and better understanding of the pathophysiology of these infections is needed. Endothelial dysfunction might be common sequelae associated with COVID-19, and increased inflammatory responses, oxidative stress, proinflammatory cytokines, and impaired mitochondrial function also contribute to the pathophysiology of post COVID-19 medical disorders. Systemic capillary leak syndrome following COVID-19 infection, both new onset and exacerbation of a prior disorder, has been reported. The pathophysiology of SCLS is uncertain; it likely develops during transient vascular endothelial dysfunction or endotheliopathy and inflammation resulting from circulating humoral factors. Here, we report a case of adult patient with 2 episodes of systemic capillary leak syndrome following prior COVID-19 infection. This patient had a transient response to intravenous IgG., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Journal editors depend on peer reviewers to make decisions about submitted manuscripts. These reviewers help evaluate the methods, the results, the discussion of the results, and the overall organization and presentation of the manuscript. In addition, reviewers can help identify important mistakes and possible misconduct. Editors frequently have difficulty obtaining enough peer reviews which are submitted in a timely manner. This increases the workload of editors and journal managers and potentially delays the publication of clinical and research studies. This commentary discusses of the importance of peer reviews and make suggestions which potentially can increase the participation of academic faculty and researchers in this important activity., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Metformin is the preferred oral medication for patients with type 2 diabetes mellitus, and this blood glucose-lowering and insulin-sensitizing drug has immunomodulatory effects that could contribute to the management of patients with various other autoimmune and infectious diseases. Tuberculosis is one such infection, and it remains prevalent worldwide, largely due to the successful evasion of the host's immune responses by the infecting pathogen, Mycobacterium tuberculosis. This review focuses on the possible mechanisms relevant to metformin's modulation of innate and adaptive immune responses to Mycobacterium tuberculosis and its potential use as an adjunctive drug in the treatment of tuberculosis. Current data suggest that metformin increases autophagy, phagocytosis, and mitochondrial reactive oxygen species production, while limiting excess inflammation and tissue destruction. This multifaceted drug also augments cell-mediated immune responses by maintaining CD8 + T cell metabolic homeostasis and improving immunological memory. Several murine models have demonstrated that metformin can reduce tuberculosis severity and tissue pathology, and two in vitro human studies confirmed enhanced immune responses in metformin-treated cells. These studies provide convincing evidence supporting the use of metformin to augment immune responses in patients with tuberculosis., (Copyright © 2023 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Competing interests: None declared.

Background and Objective: Cystic fibrosis (CF) is a disorder that affects the cystic fibrosis transmembrane conductance regulator (CFTR). Without properly functioning CFTR channels, chloride does not exit respiratory epithelial cells, and consequently the mucus lining the surface of the cells becomes thick. This viscous mucus accumulates and causes abnormal function of the mucociliary apparatus, which can lead to bacterial colonization, infections with Staphylococcus aureus ( S. aureus ) and Pseudomonas aeruginosa ( P. aeruginosa ), and eventually lung damage. Recent studies have shown that the increased susceptibility to respiratory infections in CF patients may also be due to defects in neutrophil function, but the exact mechanism is uncertain., Methods: The PubMed database was searched on February 10, 2023 and again on July 23, 2023 to compile a comprehensive list of clinical and experimental studies to evaluate neutrophil function in CF. The first search included a combination of MeSH terms: "cystic fibrosis" and "neutrophils/physiology". A separate second search included a combination of the MeSH terms: "neutrophils" and "cystic fibrosis transmembrane conductance regulator"., Key Content and Findings: Neutrophils from patients with CF have decreased transfer of chloride into phagolysosomes after bacterial ingestion and have dysregulated degranulation. This reduces the production of toxic oxidative radicals, especially hypochlorous acid (HOCl), and reduces bactericidal activity. CFTR potentiators correct the dysregulated degranulation in patients with CF and increased neutrophil killing activity. A reduced concentration of chloride in in vitro assays also reduces neutrophil killing activity; these observations are relevant to the reduced chloride concentrations in respiratory secretions in patients with CF., Conclusions: This literature review summarizes studies that demonstrate that an important defect in CF neutrophils lies in the oxygen-dependent pathway in phagolysosomes and studies with ivacaftor demonstrate that this drug corrects CF neutrophil function. These studies demonstrate the potential utility of using easily available neutrophils to study drug effects in CF patients., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-846/coif). KN serves as an unpaid editorial board member of Journal of Thoracic Disease from August 2021 to July 2023. The other author has no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Recurrent pulmonary exacerbation due to infection and inflammation remain the major cause of mortality and morbidity in patients with cystic fibrosis (CF). Increased levels of BPI-ANCA have been linked to Pseudomonas colonization and pulmonary exacerbations in patients with CF. The majority of these studies were done in Europe, and it is unclear whether similar findings are true in CF patients who lives in United States. In our single center study of 47 patients with CF, the prevalence of BPI-ANCA was 19% at baseline and 15% at annual follow-up visit. Overall, there were no statistical differences noted in FEV1 and frequency of pulmonary exacerbations in CF patients who were positive for BPI-ANCA compared to those who were negative for BPI-ANCA. The role of BPI-ANCA in patients with CF still remains unclear., (© 2023. Springer Nature Limited.)

Background: Academic article retractions occur across all disciplines, though few studies have examined the association between research topics and retraction rates., Objectives: We assessed and compared the rate of retraction across several important clinical research topics., Methods: Information about the number of publications, the number of retractions, the retraction rate, and the time to retraction was collected for articles identified by 15 Medical Subject Headings (MeSH) terms. These articles were published between 1 January 2010 and 31 December 2020. The searches took place between 18 September 2021 and 24 October 2021. The MeSH terms were selected based on our clinical experience with the expectation that there will be multiple publications during the timeframe to use for the searches. Additional topics were selected based on the frequency of controversy in the public media and were identified by the Altmetric Top 100 report., Results: The mean number of publications for all categories was 181,975 ± 332,245; the median number of publications was 67,991 [Q1, Q3; 31951.5, 138,981.5]. The mean number of retractions was 100.3 ± 251.3, and the median number of retractions was 22 [Q1, Q3; 6.5, 53]. The mean time to retraction ranged from 114 days to 1,409.5 days; the median was 857.3 days [Q1, Q3; 684.7, 1098.6], depending on the topic. The various MeSH term categories used in this study had significant differences in retraction rate and time to retraction. The "Neoplasms" category had the highest total number of retractions (993) and one of the highest retraction rates (75.4 per 100,000 publications)., Discussion: All PubMed categories analyzed in this study had retracted articles. The median time to retraction was 857 days. The long delays in some categories could contribute to potentially misleading information which might have adverse effects on clinical decisions in patient care and on research design., Conclusion: Rate of retraction varies across research topics and further studies are needed to explore this relationship.

Background: Myocardial injury has been described in coronavirus-2019 (COVID-19). Few studies have reported cardiovascular imaging data with transthoracic echocardiography (TTE) and electrocardiography (ECG) findings in COVID-19 patients, and their correlation with mortality., Methods: We conducted a retrospective cohort study that included COVID-19 patients from March 2020 through February 2021 who had TTE and ECG during hospital admission. Myocardial injury was defined by an elevated high-sensitivity troponin T level > 20 ng/L. Bivariate analysis was used to compare patients with myocardial injury and those without. Multivariate logistic regression analysis was performed to identify the variables associated with mortality., Results: A total of 438 patients were included. The mean age was 62.1 ± 14.9 years, and 58.9% were male. A total of 149 patients died, with a mortality rate of 34%. A total of 260 patients (59.4%) had myocardial injury. The average left ventricular ejection fraction was 59.8% ± 11.2%, with 30 patients (6.8%) having an ejection fraction of < 40%. Patients with myocardial injury had higher mortality than those without ( P < 0.05, χ 2 test). A multiple regression analysis model indicated that age, race and/or ethnicity, the development of acute respiratory distress syndrome, shock, the need for vasopressors, mechanical ventilation, and hemodialysis were the variables significantly associated with mortality., Conclusion: COVID-19 patients with myocardial injury had higher mortality than those without. Age, race and/or ethnicity, acute respiratory distress syndrome, shock, the need for vasopressors, mechanical ventilation, and hemodialysis were the clinical variables associated with mortality. The TEE and ECG variables studied were not significantly associated with mortality., (© 2023 The Authors.)

Background: Promising results with the CHA 2 DS 2 -VASc risk score (CVRS) have been reported for the prediction of contrast-induced nephropathy (CIN). The aim of this study is to consolidate all the data available and examine the association between elevated CVRS and the incidence of CIN in patients undergoing percutaneous coronary intervention (PCI)., Methods: We systematically searched PubMed, Embase, and Scopus for abstracts and full-text articles from inception to May 2022. Studies were included if they evaluated the association between a high CVRS and the incidence of CIN in patients undergoing PCI. Data were integrated using the random-effects, generic inverse variance method of DerSimonian and Laird. Prospero registration: CRD42022334065., Results: Seven studies from 2016 to 2021 with a total of 7,401 patients were included. In patients undergoing PCI, a high CVRS (≥2: Odds ratio [OR]:2.98, 95% confidence interval [95% CI] 2.25-3.94, p  < .01, I 2 = 1%, ≥3: OR 4.46, 95% CI 2.27-8.78, p  < .01, I 2 =56% and ≥4: OR:2.75, 95% CI 1.76-4.30, p  < .01, I 2 = 11%) was significantly associated with an increase incidence for CIN. Subgroup analyses were done in patients with acute coronary syndrome, and association with CIN remained statistically significant (≥2: OR 2.93, 95% CI 2.11-4.07, p  < .01, I 2 =22%and ≥4: OR:2.24, 95% CI 1.36-3.69, p  < .01, I 2 = 0%,)., Conclusion: In patients undergoing PCI, an elevated CVRS is associated with an increased risk for CIN. More rigorous studies are needed to clarify this association and to identify strategies to reduce CIN.

Introduction: Online adaptive MR-guided radiotherapy allows for dose escalation to pancreatic cancer while sparing surrounding critical organs. We seek to evaluate the safety of delivering hypofractionated five-fraction, three-fraction and single-fraction MR-guided stereotactic ablative radiotherapy (SABR) to the pancreas., Methods and Analysis: This is a single-centre three-arm phase 1 non-randomised safety study. Patients with localised pancreatic cancer will receive either 50 Gy in five (biological equivalent dose (BED 10 )=100 Gy), 39 Gy in three (BED 10 =90 Gy) or 25 Gy in a single fraction (BED 10 =87.5 Gy) MR-guided daily online adaptive radiotherapy. Each fractionation regimen will be assessed as independent cohorts to determine tolerability, assessed continuously using Bayesian conjugate posterior beta distributions. The primary endpoint of the study is to establish the safety of five-fraction, three-fraction and single-fraction MR-guided hypofractionation SABR in localised pancreatic cancer by assessing dose-limiting toxicities. Secondary endpoints include overall survival, progression-free survival, local control rates, overall control rate, resection rates, long-term toxicities and freedom from second-line chemotherapy. This study plans to also explore imaging and immune biomarkers that may be useful to predict outcome and personalise treatment. The trial will recruit up to 60 patients with a safety run-in., Ethics and Dissemination: The trial is approved by the West Midlands-Black Country Research Ethics Committee 22/WM/0122. The results will be disseminated via conference presentations, peer-reviewed scientific journals and submission to regulatory authorities. The data collected for the study, including individual participant data, will be made available to researchers on request to the study team and with appropriate reason, via octo-enquiries@oncology.ox.ac.uk. The shared data will be deidentified participant data and will be available for 3 years following publication of the study. Data will be shared with investigator support, after approval of a proposal and with a signed data access agreement., Trial Registration Number: ISRCTN10557832., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Gaisbock syndrome is the term ascribed to several conditions initially observed by Felix Gaisbock, MD, (from Innsbruck, Tyrol, Austria) in 1905 when he described a group of hypertensive male patients who had high hematocrit levels, normal leukocyte counts, and no splenomegaly. These patients had an overweight, stocky habitus, a plethoric appearance with suffusion of the eyes, tense and anxious personalities, a cigarette smoking habit, vascular disease, headaches, and facial rubor. Later studies identified alcoholism, diuretic therapy, and physical or emotional stress as additional risk factors that might contribute to the onset of this syndrome. This review revisits Gaisbock syndrome based on recent literature, and will highlight contemporary studies that have established an association between erythrocytosis and hypertension and associated risk factors. Several mechanisms help explain the pathophysiology underlying Gaisbock's observations, and these include psychiatric disorders resulting in chronic stress, volume contraction secondary to diuretics and hypertension, and obstructive sleep apnea with nocturnal hypoxemia and erythropoietin production. Complications associated with this syndrome include the formation of microthrombi with cerebral infarction; treatment should focus on the management of hypertension and a reduction in risk factors, such as obesity, cigarette smoking, and alcohol use. Gaisbock syndrome involves several clinical disorders, has a complex pathogenesis, and leads to a better understanding of the causes of erythrocytosis during patient evaluation., Competing Interests: Disclosure: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Military service inherently includes frequent periods of high-stress training, operational tempo, and sustained deployments to austere far-forward environments. These occupational requirements can contribute to acute and chronic sleep disruption, fatigue, and behavioral health challenges related to acute and chronic stress and disruption of team dynamics. To date, there is no centralized mobile health platform that supports self- and supervised detection, monitoring, and management of sleep and behavioral health issues in garrison and during and after deployments., Objective: The objective of this study was to adapt a clinical decision support platform for use outside clinical settings, in garrison, and during field exercises by medics and soldiers to monitor and manage sleep and behavioral health in operational settings., Methods: To adapt an existing clinical decision support digital health platform, we first gathered system, content, and context-related requirements for a sleep and behavioral health management system from experts. Sleep and behavioral health assessments were then adapted for prospective digital data capture. Evidence-based and operationally relevant educational and interventional modules were formatted for digital delivery. These modules addressed the management and mitigation of sleep, circadian challenges, fatigue, stress responses, and team communication. Connectivity protocols were adapted to accommodate the absence of cellular or Wi-Fi access in deployed settings. The resulting apps were then tested in garrison and during 2 separate field exercises., Results: Based on identified requirements, 2 Android smartphone apps were adapted for self-monitoring and management for soldiers (Soldier app) and team supervision and intervention by medics (Medic app). A total of 246 soldiers, including 28 medics, received training on how to use the apps. Both apps function as expected under conditions of limited connectivity during field exercises. Areas for future technology enhancement were also identified., Conclusions: We demonstrated the feasibility of adapting a clinical decision support platform into Android smartphone-based apps to collect, save, and synthesize sleep and behavioral health data, as well as share data using adaptive data transfer protocols when Wi-Fi or cellular data are unavailable. The AIRE (Autonomous Connectivity Independent System for Remote Environments) prototype offers a novel self-management and supervised tool to augment capabilities for prospective monitoring, detection, and intervention for emerging sleep, fatigue, and behavioral health issues that are common in military and nonmilitary high-tempo occupations (eg, submarines, long-haul flights, space stations, and oil rigs) where medical expertise is limited., (©Anne Germain, Megan Wolfson, I Wayan Pulantara, Meredith L Wallace, Katie Nugent, George Mesias, Kristina Clarke-Walper, Phillip J Quartana, Joshua Wilk. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 28.08.2023.)

Objective: To compare the incidence of grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity for patients undergoing 3DRT versus IMRT in the postoperative setting for endometrial cancer., Methods: Eligible patients were post-operatively randomly assigned to one of two parallel groups in a 1:1 ratio, to have their RT delivered using either a 3DRT technique or using IMRT. The prescription dose was 45 Gy in 25 fractions over 5 weeks followed by vaginal vault brachytherapy. Toxicity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 3.0. Fisher's exact tests were used to test for associations between toxicity and arm. Differences in dosimetric parameters for patients with or without toxicity were tested using Mann-Whitney U -tests., Results: 84 patients with a median age of 62 were evaluable for primary outcome. The median follow-up was 52 months. 14 (35%) participants from the 3DRT arm and 15 (34%) from the IMRT arm experienced acute grade ≥2 GI toxicity with older patients having a statistically higher risk of grade ≥2 acute GI toxicity. 20 (50%) participants from the 3DRT arm and 25 (57%) from the IMRT arm experienced acute grade ≥2 GI or GU toxicity ( p = .662). 12 (30%) patients from the 3DRT arm and 17 (39%) from the IMRT arm experienced acute grade ≥2 GU toxicity ( p = .493)., Conclusion: Although IMRT can reduce dose to normal tissue, in this study no benefit in acute GI or GU toxicity outcome was seen.

Rationale: Burnout is a personal and occupational phenomenon that has been associated with negative physical and psychological outcomes in medical staff. Additionally, there are implications for healthcare organizations, as those staff who are burned out are more likely to have lower productivity or leave the organization. As with the Covid-19 pandemic, future national emergencies and potentially large-scale conflicts will require similar and likely even larger scale responses from the U.S. Military Health System, thus it is important to understand burnout in this population so that the readiness of the staff and the military can remain at a high level., Objective: This assessment was designed to examine levels of burnout among United States Military Health System (MHS) staff working at Army installations and the factors that influence the development of burnout., Methods: Anonymous data was collected from 13,558 active-duty U.S. Soldiers and civilian MHS employees. Burnout was measured using the Copenhagen Burnout Inventory and the Mini-Z., Results: Results showed nearly half of staff who responded (48%) reported being burned out, an increase since last measured in 2019 (31%). Factors related to increased burnout included concerns about work/life balance and workload, low job satisfaction and feeling disconnected from others. Burnout was associated with increases in adverse physical and behavioral health (BH) outcomes., Conclusions: Results indicate that burnout is a common problem across MHS Army staff and is related to significant adverse health consequences for the individual and reduced retention of staff for the organization. These findings highlight the need to address burnout through policies that standardize health care delivery policies and practices, providing support to leadership to promote a healthy workplace, and individual support to those who experience burnout., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

At present, the management of patients with acute respiratory distress syndrome (ARDS) largely focuses on ventilator settings to limit intrathoracic pressures by using low tidal volumes and on FiO 2 /PEEP relationships to maintain optimal gas exchange. Acute respiratory distress syndrome is a complex medical disorder that can develop in several primary acute disorders, has a rapid time course, and has several classifications that can reflect either the degree of hypoxemia, the extent of radiographic involvement, or the underlying pathogenesis. The identification of subtypes of patients with ARDS would potentially make precision medicine possible in these patients. This is a very difficult challenge given the heterogeneity in the clinical presentation, pathogenesis, and treatment responses in these patients. The analysis of large databases of patients with acute respiratory failure using statistical methods such as cluster analysis could identify phenotypes that have different outcomes or treatment strategies. However, clinical information available on presentation is unlikely to separate patients into groups that allow for secure treatment decisions or outcome predictions. In some patients, non-invasive positive pressure ventilation provides adequate support through episodes of acute respiratory failure, and the development of specialized units to manage patients with this support might lead to the better use of hospital resources. Patients with ARDS have capillary leak, which results in interstitial and alveolar edema. Early attention to fluid balance in these patients might improve gas exchange and alter the pathophysiology underlying the development of severe ARDS. Finally, more attention to the interaction of patients with ventilators through complex monitoring systems has the potential to identify ventilator dyssynchrony, leading to ventilator adjustments and potentially better outcomes. Recent studies with COVID-19 patients provide tentative answers to some of these questions. In addition, expert clinical investigators have analyzed the promise and difficulties associated with the development of precision medicine in patients with ARDS.

Microscopic colitis is a type of inflammatory bowel disease and is classified as either collagenous colitis or lymphocytic colitis. The typical presentation is chronic watery diarrhea. The disease occurs more frequently in women aged 60-65 years and is increasing in incidence. The pathophysiology of microscopic colitis remains poorly understood and has not been well-described with possible several pathogeneses. To date, the diagnosis of microscopic colitis depends on histological tissue obtained during colonoscopy. Other non-invasive biomarkers, such as inflammatory markers and fecal biomarkers, have been studied in microscopic colitis, but the results remains inconclusive. The approach to chronic diarrhea is important and being able to differentiate chronic diarrhea in patients with microscopic colitis from other diseases, such as inflammatory bowel disease, functional diarrhea, and malignancy, by using non-invasive biomarkers would facilitate patient management. The management of microscopic colitis should be based on each individual's underlying pathogenesis and involves budesonide, bile acid sequestrants, or immunosuppressive drugs in refractory cases. Cigarette smoking and certain medications, especially proton pump inhibitors, should be eliminated, when possible, after the diagnosis is made.

Background: The incidence of microscopic colitis has increased over time. To date, there is no specific biomarker for microscopic colitis, and the diagnosis relies on histopathological tissue obtained during colonoscopy which is an invasive and costly procedure. Unlike Crohn's disease and ulcerative colitis, the utility of fecal calprotectin in diagnosing or monitoring microscopic colitis has not been established, and studies on the role of fecal calprotectin in microscopic colitis are limited. In this retrospective study, we analyzed the utility of this biomarker in the diagnosis of microscopic colitis., Methods: The medical records of patients who have been diagnosed with collagenous colitis and lymphocytic colitis aged 18-89 years old were retrospectively reviewed. Patient characteristics were recorded in those who had fecal calprotectin measured., Results: There were 198 patients who were diagnosed with collagenous colitis and lymphocytic between October 1, 2015, and July 31, 2022. Twenty-three patients had fecal calprotectin levels measured and were included in this study. The mean age was 51.7 ± 7.8 years in all groups. Thirteen patients were female. Six patients (26.1%) were diagnosed with collagenous colitis, and 17 patients (73.9%) were diagnosed with lymphocytic colitis. The fecal calprotectin cut-off in this lab is 50 μg/g stool. Median fecal calprotectin levels were 30.1 μg/g (15.6, 122.5), 19.5 μg/g (16.5, 64.6), and 33.2 μg/g (15.6, 134.9) in all groups, collagenous colitis, and lymphocytic colitis, respectively., Conclusion: The utility of fecal calprotectin in diagnosing microscopic colitis is limited. Our study suggests the diagnosis should be based on histopathology tissue obtained during colonoscopy., Competing Interests: Conflict of interest None., (© 2023 Greater Baltimore Medical Center.)