Publications

Multiple clinical practice guidelines (CPGs) for heart failure management have been published to provide the best practices regarding the use of foundational therapies to reduce morbidity and mortality in this patient population. However, a critical appraisal of these heart failure guidelines has not been performed. This systematic review aimed to assess the methodological quality of current CPGs in the management of patients with heart failure. A comprehensive search of EMBASE and PubMed was conducted to identify CPGs published between January 1, 2021 and September 8, 2022. Any CPGs published in the last 2 years addressing the management of heart failure were eligible for inclusion. The methodological quality of the CPGs was assessed using the AGREE II (Appraisal of Guidelines for Research & Evaluate II) instrument. The initial search yielded 3,269 citations, of which, 6 CPGs were included. A total of 2 CPGs were each published by the cardiology associations in North America and Asia and 1 each in Europe and South America. The overall median score for the AGREE II domains were 100% for scope and purpose, 71% for stakeholder involvement, 71% for the rigor of development, 100% for clarity of presentation, 43% for applicability, 100% for editorial independence, and 64% for overall assessment. CPG developers would benefit from the use of a standardized approach to the development of CPGs and use the contents of the AGREE II tool to improve the methodological rigor, reporting, and applicability of CPGs.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is characterized by a diffuse cerebral dysfunction that accompanies sepsis in the absence of direct central nervous system infection. The endothelial glycocalyx is a dynamic mesh containing heparan sulfate linked to proteoglycans and glycoproteins, including selectins and vascular/intercellular adhesion molecules (V/I-CAMs), which protects the endothelium while mediating mechano-signal transduction between the blood and vascular wall. During severe inflammatory states, components of the glycocalyx are shed into the circulation and can be detected in soluble forms. Currently, SAE remains a diagnosis of exclusion and limited information is available on the utility of glycocalyx-associated molecules as biomarkers for SAE. We set out to synthesize all available evidence on the association between circulating molecules released from the endothelial glycocalyx surface during sepsis and sepsis-associated encephalopathy.

METHODS: MEDLINE (PubMed) and EMBASE were searched since inception until May 2, 2022 to identify eligible studies. Any comparative observational study: i) evaluating the association between sepsis and cognitive decline and ii) providing information on level of circulating glycocalyx-associated molecules was eligible for inclusion.

RESULTS: Four case-control studies with 160 patients met the inclusion criteria. Meta-analysis of biomarkers ICAM-1 (SMD 0.41; 95% CI 0.05-0.76; p = 0.03; I2 = 50%) and VCAM-1 (SMD 0.55; 95% CI 0.12-0.98; p = 0.01; I2 = 82%) revealed higher pooled mean concentration in patients with SAE compared to the patients with sepsis alone. Single studies reported elevated levels of P-selectin (MD 0.80; 95% CI -17.77-19.37), E-selectin (MD 96.40; 95% Cl 37.90-154.90), heparan sulfate NS2S (MD 19.41; 95% CI 13.37-25.46), and heparan sulfate NS+NS2S+NS6S (MD 67.00; 95% CI 31.00-103.00) in patients with SAE compared to the patients with sepsis alone.

CONCLUSION: Plasma glycocalyx-associated molecules are elevated in SAE and may be useful for early identification of cognitive decline in sepsis patients.

The prevalence of age-related cognitive disorders/dementia is increasing, and effective prevention and treatment interventions are lacking due to an incomplete understanding of aging neuropathophysiology. Emerging evidence suggests that abnormalities in gut microbiome are linked with age-related cognitive decline and getting acceptance as one of the pillars of the Geroscience hypothesis. However, the potential clinical importance of gut microbiome abnormalities in predicting the risk of cognitive decline in older adults is unclear. Till now the majority of clinical studies were done using 16S rRNA sequencing which only accounts for analyzing bacterial abundance, while lacking an understanding of other crucial microbial kingdoms, such as viruses, fungi, archaea, and the functional profiling of the microbiome community. Utilizing data and samples of older adults with mild cognitive impairment (MCI; n = 23) and cognitively healthy controls (n = 25). Our whole-genome metagenomic sequencing revealed that the gut of older adults with MCI harbors a less diverse microbiome with a specific increase in total viruses and a decrease in bacterial abundance compared with controls. The virome, bacteriome, and microbial metabolic signatures were significantly distinct in subjects with MCI versus controls. Selected bacteriome signatures show high predictive potential of cognitive dysfunction than virome signatures while combining virome and metabolic signatures with bacteriome boosts the prediction power. Altogether, the results from our pilot study indicate that trans-kingdom microbiome signatures are significantly distinct in MCI gut compared with controls and may have utility for predicting the risk of developing cognitive decline and dementia- debilitating public health problems in older adults.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of non-Hodgkin lymphoma with poor response to R-CHOP therapy due to remarkable heterogeneity. Based on gene expression, DLBCL cases were divided into two subtypes, i.e. ABC and GCB, where ABC subtype is associated with poor outcomes. Due to its association with clinical outcome, this classification, also known as cell-of-origin (COO), is an efficient way to predict the response to R-CHOP therapy. Previous COO classification methods have some shortcomings, e.g. limited number of samples in the training dataset. These shortcomings challenge the robustness of methods and make it difficult to implicate these methods at clinical level. To overcome the shortcomings of previous methods, we developed a deep learning-based classifier model on a cohort of 381 DLBCL patients using expression data of 20 genes. We implemented multilayer perceptron (MLP) to train deep learning-based classifier, named MLP-COO. MLP-COO achieved accuracy of 99.70% and 94.70% on training and testing datasets, respectively, with 10-fold cross-validation. We also assessed its performance on an independent dataset of 294 DLBCL patients. On independent dataset, we achieved an accuracy of 95.90% with MCC of 0.917. To show its broader applicability, we used this classifier to predict the clinical outcome using survival data from two large cohorts of DLBCL patients. In survival analysis, MLP-COO recapitulates the survival probabilities of DLBCL patients based on their COO in both cohorts. We anticipate that MLP-COO model developed in this study will benefit in the accurate COO prediction of DLBCL patients and their clinical outcomes.

IMPORTANCE: Cutaneous T-cell lymphoma (CTCL) is a group of rare, complex cutaneous malignant neoplasms associated with significant disease burden on patients and the health care system. Currently, the population of patients with CTCL admitted to the hospital remains largely uncharacterized and poorly understood.

OBJECTIVE: To characterize the clinical characteristics, course of hospitalization, and mortality outcomes of an inpatient CTCL cohort.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective cohort study reviewed medical records for adult patients (age ≥18 years) with a CTCL diagnosis per National Comprehensive Cancer Network guidelines admitted for inpatient hospitalization at 5 US academic medical centers with inpatient dermatology consult services and CTCL clinics between August 2016 and August 2020.

MAIN OUTCOMES AND MEASURES: Patient demographics, clinical history and findings, hospitalization courses, and mortality outcomes.

RESULTS: A total of 79 hospitalized patients with CTCL were identified, including 52 (70.3%) men and 22 (29.7%) women, with a median (IQR) age at hospitalization of 62.9 (27-92) years. The majority of admitted patients with CTCL were White (65 patients [82.3%]), had disease classified as mycosis fungoides (48 patients [61.5%]), and had advanced-stage disease (≥IIB, 70 patients [89.7%]). Most hospitalizations were complicated by infection (45 patients [57.0%]) and required intravenous antibiotic therapy (45 patients [57.0%]). In-hospital mortality occurred in 6 patients (7.6%) and was associated with higher body mass index (36.5 vs 25.3), history of thromboembolic disease (50.0% vs 12.3%), and diagnosis of sepsis on admission (66.7% vs 20.5%). At 1-year postdischarge, 36 patients (49.3%) patients had died, and mortality was associated with history of solid organ cancers (27.8% vs 10.8%), wound care as the reason for dermatology consultation (58.3% vs 24.3%), and presence of large cell transformation (58.3% vs 22.9%).

CONCLUSIONS AND RELEVANCE: The findings of this cohort study improve the understanding of hospitalized patients with CTCL and lend valuable insight into identifying factors associated with both in-hospital and long-term mortality outcomes. This refined understanding of the inpatient CTCL population provides a foundation for larger, more robust studies to identify causal risk factors associated with mortality, development of prognostic scoring systems to estimate the probability of hospital mortality. Overall, the findings may prompt physicians caring for patients with CTCL to implement preventive strategies to diminish hospitalization and improve clinical management across this unique disease spectrum.

Introduction Distal upper extremity (DUE) fractures are common and include bony fractures of the wrist, hand, and finger. DUE fractures can require hospital admission for clinical observation or surgical fixation. The trend of hospitalization rate for these injuries may more accurately predict future staffing needs, required resources, and expected revenue for orthopedic surgery hand services. The purpose of this study is to determine the trend of hospitalization percentage from 2009 to 2018 for patients presenting to the United States (US) emergency departments (EDs) with DUE fractures. Methods The National Electronic Injury Surveillance System (NEISS) was utilized to collect data from 138,700 patients with wrist, hand, or finger fractures presenting to the US EDs between 2009 and 2018. A total of 752 patients were excluded for ages less than two years old or no sex entry. The unadjusted and adjusted (age, sex, race, and fracture location) hospitalization rates across years were evaluated using binary logistic regression. Results From 2009 to 2018, 137,948 DUE fractures were reported, of which 4749 (3.4%) were hospitalized. Wrist fractures accounted for the highest amount (2953) and the highest proportion of hospitalized patients (62.2%). Higher hospitalization rates were seen among patients 40 years and older (p < 0.05). Together, the DUE fracture hospitalization rate increased significantly (p < 0.05) in 2016 (OR = 1.215, 95% CI = 1.070-1.380), 2017 (OR = 1.154, 95% CI = 1.016-1.311), and 2018 (OR = 1.154, 95% CI = 1.279-1.638) from 2009. The adjusted results showed hospitalization rate statistically increased (p < 0.05) in 2016 (OR = 1.184, 95% CI = 1.040-1.346) and 2018 (OR = 1.389, 95% CI = 1.225-1.575) compared to 2009. An inconsistent increase in hospitalization rate was seen across locations of fracture: wrist (2012, 2013, 2018), hand (2018), and finger (2016, 2018). Conclusions The hospitalization rate of patients with DUE fractures increased in 2016 and 2018 from 2009. These data may predict a need to increase future staffing and resources for orthopedic surgery hand services as hospitals resume pre-pandemic practices.

OBJECTIVES: The policies regarding resident physician work hours are constantly being evaluated and changed. However, the results of randomised control trials (RCTs) are mixed. This systematic review of RCTs aims to synthesise the evidence associated with resident duty hour restrictions and its impact on resident- and patient-based outcomes.

METHODS: A comprehensive search of the Cochrane Library, EMBASE and PubMed was conducted from inception until 31 July 2020. Any RCT evaluating the impact of longer resident physician work hours compared to shorter resident physician work hours on resident- and patient-based outcomes was eligible for inclusion. Two reviewers extracted data independently. The primary outcome was the impact of resident duty hour restrictions on emotional exhaustion, depersonalisation and personal accomplishment, as defined by the Maslach Burnout Inventory. The secondary patient-related outcomes were patient hospital length of stay, serious medical errors and preventable adverse events. Data were pooled using a random-effects model.

RESULTS: Of the 873 references, nine RCTs met the inclusion criteria. A shorter shift length compared with longer shift length was associated with significantly less emotional exhaustion (standardised mean difference [SMD] = -0.11, 95% CI = -0.21, -0.00) and less dissatisfaction with overall well-being (OR = 0.61, 95% CI 0.38, 0.99) but not with hospital length of stay (SMD = -0.01, 95% CI = -0.05, 0.02, p = 0.45) and serious medical errors per 1000 patient hours (OR = 1.07, 95% CI = 0.52, 2.21; p = 0.86).

CONCLUSIONS: Shorter resident duty hours is possibly associated with improvement in resident-based outcomes, specifically, emotional exhaustion, dissatisfaction with overall well-being, sleep duration and sleepiness. These findings may inform the policy change in support of reduced shift hours resulting in overall well-being for the residents with possible reduction in burnout without adverse impact on patient-based outcomes.

BACKGROUND: There are various published clinical practice guidelines (CPGs) for the management of pancreatic cystic lesions. However, the quality of these guidelines has not been systematically appraised. This study aimed to evaluate the quality of CPGs published in the last 5 years for the management of pancreatic cysts.

METHODS: A systematic search of the PubMed database for eligible CPGs published between January 1, 2016 and November 17, 2021, using a sensitive filter. The quality of the CPGs was independently evaluated using the Appraisal of Guidelines for Research & Evaluation II instrument, with domain scores considered sufficient quality if >60% and good quality if >80%.

RESULTS: The search yielded 4 eligible CPGs out of 426 citations. The scores varied for different domains for each CPG, with the overall median score being 79% for scope and purpose, 26% for stakeholder involvement, 51% for rigor of development, 69% for clarity of presentation, 14% for applicability, and 75% for editorial independence.

CONCLUSIONS: The study revealed that the quality of the CPGs for pancreatic cyst management in adults remains moderate at best. Patient representatives were not involved in any of the CPG development process. There is a significant scope for improvement in methodological rigor and clarity of presentation.

To examine the perspective of individuals with Hypermobile Ehlers-Danlos Syndrome (hEDS) and Generalized Hypermobility Spectrum Disorder (G-HSD), needed to help identify priorities and improve the lives of people living with these conditions. We conducted an online survey between November 2021 and January 2023. Participants were recruited through the Ehlers-Danlos Society's Research Surveys website. We obtained 483 responses and 396 were analyzed. 80% of the survey's respondents were individuals with hEDS, 90% were females, 30% were between 21 and 30, and 76% lived in North America, with 85% of the participants living in North America indicated being White or European American. Participants reported exercising from none to less than three times per week, with no physical therapy treatment. Ninety-eight percent of participants reported pain mainly at the neck (76%), lower (76%) and upper back (66%), knees (64%), shoulders (60%), and hips (60%). Approximately 80% of participants reported fatigue, joint hypermobility, joint instability, interference with daily activities, gastrointestinal problems, orthostatic hypotension, muscle weakness, and emotional distress. About 60% of respondents indicated walking issues, balance issues, and reduced joint proprioception. Nearly 40% of participants reported pelvic floor dysfunction and cardiovascular problems. Participants with hEDS and G-HSD reported pain on an average (SD) of 6.4 (± 1.3) and 5.9 (± 1.5) days in a typical week, respectively. People with hEDS and G-HSD desperately need more effective treatment options, a better diagnostic process, and education among health care providers.