Molecular remodeling in comorbidities associated with heart failure: a current update.

Recent advances in genomics and proteomics have helped in understanding the molecular mechanisms and pathways of comorbidities and heart failure. In this narrative review, we reviewed molecular alterations in common comorbidities associated with heart failure such as obesity, diabetes mellitus, systemic hypertension, pulmonary hypertension, coronary artery disease, hypercholesteremia and lipoprotein abnormalities, chronic kidney disease, and atrial fibrillation. We searched the electronic databases, PubMed, Ovid, EMBASE, Google Scholar, CINAHL, and PhysioNet for articles without time restriction. Although the association between comorbidities and heart failure is already well established, recent studies have explored the molecular pathways in much detail. These molecular pathways demonstrate how novels drugs for heart failure works with respect to the pathways associated with comorbidities. Understanding the altered molecular milieu in heart failure and associated comorbidities could help to develop newer medications and targeted therapies that incorporate these molecular alterations as well as key molecular variations across individuals to improve therapeutic outcomes. The molecular alterations described in this study could be targeted for novel and personalized therapeutic approaches in the future. This knowledge is also critical for developing precision medicine strategies to improve the outcomes for patients living with these conditions.

Pathological response and survival outcomes after neoadjuvant chemotherapy with radical cystectomy in octogenarians for muscle-invasive bladder cancer: an observational database study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) with radical cystectomy (RC) is the preferred first-line treatment for localized muscle-invasive bladder cancer (MIBC). In recent years, octogenarians have been undergoing RC uneventfully, but studies showed older adults receive NAC less often. We studied the utilization and effect of RC with or without NAC in octogenarians and compared survival outcomes between responders and non-responders. METHODS: In our retrospective study using the National Cancer Database (NCDB), we identified octogenarians with MIBC and urothelial histology who underwent RC with or without NAC between 2004 and 2018. The NAC cohort included patients who underwent RC with NAC, and the non-NAC cohort included those with or without adjuvant chemotherapy. The NAC cohort was subcategorized into responders and non-responders based on surgical pathology. Patients with comorbidity index > 1 were not included, thereby excluding patients with possible renal impairment. After propensity-matching, we compared the overall survival (OS) between NAC and non-NAC cohorts and responders and non-responders. RESULTS: 33924 patients underwent RC, and 3056 octogenarians met our selection. Among them, 396 received NAC, and 2660 did not receive NAC. Among those who received NAC, 112(28.3%) experienced downstaging, and 223(56.4%) exhibited upstaging or no change (p < 0.001). After propensity-matching, the median OS of the NAC and non-NAC cohorts were 51.6 months and 31.3 months, respectively (p<0.001). Similarly, the median OS of responders and non-responders were 89.4 months and 26.5 months, respectively(p < 0.0001). CONCLUSION: In our study, we observed that NAC with RC for MIBC may help to improve OS among healthy octogenarians. Similarly, responders had better OS than non-responders.

Gender Differences in Hospital Outcomes among COVID-19 Hospitalizations.

OBJECTIVES: Many epidemiological studies have shown that coronavirus disease 2019 (COVID-19) disproportionately affects males, compared with females, although other studies show that there were no such differences. The aim of the present study was to assess differences in the prevalence of hospitalizations and in-hospital outcomes between the sexes, using a larger administrative database. METHODS: We used the 2020 California State Inpatient Database for this retrospective analysis. International Classification of Diseases, Tenth Revision, Clinical Modification diagnosis code U07.1 was used to identify COVID-19 hospitalizations. These hospitalizations were subsequently stratified by male and female sex. Diagnosis and procedures were identified using the International Classification of Diseases, Tenth Revision, Clinical Modification codes. The primary outcome of the study was hospitalization rate, and secondary outcomes were in-hospital mortality, prolonged length of stay, vasopressor use, mechanical ventilation, and intensive care unit (ICU) admission. RESULTS: There were 95,180 COVID-19 hospitalizations among patients 18 years and older, 52,465 (55.1%) of which were among men and 42,715 (44.9%) were among women. In-hospital mortality (12.4% vs 10.1%), prolonged length of hospital stays (30.6% vs 25.8%), vasopressor use (2.6% vs 1.6%), mechanical ventilation (11.8% vs 8.0%), and ICU admission rates (11.4% versus 7.8%) were significantly higher among male compared with female hospitalizations. Conditional logistic regression analysis showed that the odds of mortality (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.38-1.44), hospital lengths of stay (OR 1.35, 95% CI 1.31-1.39), vasopressor use (OR 1.59, 95% CI 1.51-1.66), mechanical ventilation (OR 1.62, 95% CI 1.47-1.78), and ICU admission rates (OR 1.58, 95% CI 1.51-1.66) were significantly higher among male hospitalizations. CONCLUSION: Our findings show that male sex is an independent and strong risk factor associated with COVID-19 severity.

Frailty among stroke patients and its effects on hospital outcomes.

BACKGROUND: Although assessment of frailty is increasingly being included in routine practice, its effects on hospital outcomes is not well studied. In this study, we used a national database to estimate the effects of frailty on hospital outcomes among stroke patients. METHODS: This study was a retrospective analysis of data from Nationwide Inpatient Sample (NIS) database collected during the years 2016 to 2019. Adult patients 45 years and older with a primary diagnosis of stroke were included for the analysis. Primary outcome was frequency of frailty among stroke patients. Secondary outcomes were in-hospital mortality, prolonged length of stay, mechanical ventilation, and acute renal failure. Frailty levels were assessed by using the Hospital Frailty Risk Score (HFRS). RESULTS: Among 2,031,085 stroke hospitalizations, 362,140 (17.8 %) were non-frail, 1,333,000 (65.6 %) were pre-frail, and 335,945 (16.6 %) were frail. Regression analysis showed that the odds of mortality were significantly higher among frail (aOR, 2.82, 95 % CI: 2.63-3.04) and pre-frail (aOR, 1.62, 95 % CI: 1.53-1.73) patients, compared to non-frail patients. Similarly, the odds of mechanical ventilation were significantly higher among frail (aOR, 9.72, 95 % CI: 8.84-10.69) and pre-frail (aOR, 3.41, 95 % CI: 3.12-3.73) patients. The odds of acute renal failure were significantly higher among frail (aOR, 6.96, 95 % CI: 6.62-7.33) and pre-frail (aOR, 2.94, 95 % CI: 2.80-3.08) patients. CONCLUSION: Collaborative efforts by neurologists, neurosurgeons, and physiatrists towards identifying frailty and incorporating it in risk estimation measures could help improve management strategies, resource utilization, and optimization of patient outcomes among frail stroke patients.

Integrative Bioinformatics-Gene Network Approach Reveals Linkage between Estrogenic Endocrine Disruptors and Vascular Remodeling in Peripheral Arterial Disease.

Vascular diseases, including peripheral arterial disease (PAD), pulmonary arterial hypertension, and atherosclerosis, significantly impact global health due to their intricate relationship with vascular remodeling. This process, characterized by structural alterations in resistance vessels, is a hallmark of heightened vascular resistance seen in these disorders. The influence of environmental estrogenic endocrine disruptors (EEDs) on the vasculature suggests a potential exacerbation of these alterations. Our study employs an integrative approach, combining data mining with bioinformatics, to unravel the interactions between EEDs and vascular remodeling genes in the context of PAD. We explore the molecular dynamics by which EED exposure may alter vascular function in PAD patients. The investigation highlights the profound effect of EEDs on pivotal genes such as ID3, LY6E, FOS, PTP4A1, NAMPT, GADD45A, PDGF-BB, and NFKB, all of which play significant roles in PAD pathophysiology. The insights gained from our study enhance the understanding of genomic alterations induced by EEDs in vascular remodeling processes. Such knowledge is invaluable for developing strategies to prevent and manage vascular diseases, potentially mitigating the impact of harmful environmental pollutants like EEDs on conditions such as PAD.

The Impact of Patients' Primary Language on Inpatient Gastrointestinal Bleeding Outcomes.

BACKGROUND: The impact of English proficiency on gastrointestinal bleeding (GIB) outcomes remains unclear. In this analysis, we compare inpatient GIB outcomes between patients with English as their primary language (EPL) and those with a primary language other than English (PLOE). METHODS: Using the 2019 State Inpatient Databases for New Jersey, Maryland, and Michigan, we created an analysis cohort of GIB hospitalizations using International Classification of Diseases, 10th Revision codes. Patients were stratified by primary language (EPL vs PLOE) and type of bleeding (variceal upper GI bleeding [VUGIB], nonvariceal upper GI bleeding [NVUGIB], and lower GI bleeding (LGIB)]. Regression analyses were used to compare mortality, 30-day readmissions, and length of stay. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were reported. P < 0.05 was considered statistically significant. RESULTS: In the cohort, 5.5%-10% of the patients spoke a primary language other than English. Endoscopy utilization was lower among patients with PLOE vs EPL for NVUGIB (17.2% vs 21.2%, P < 0.001) and LGIB (26.3% vs 29.2%, P = 0.027). Patients with PLOE had higher odds of dying of VUGIB (aOR 1.45, 95% CI 1.16-2.48) and LGIB (aOR 1.71, 95% CI 1.22-2.12). Patients with PLOE were also more likely to be readmitted after NVUGIB (aOR 1.75, 95% CI 1.64-1.81). However, after controlling for the percentage of patients with PLOE discharged from each hospital, the disparities in mortality and readmissions were no longer detected. DISCUSSION: Disparities exist in GIB outcomes among patients with PLOE, but these gaps narrow at hospitals with higher percentages of patients with PLOE. Cultural and linguistic competence may improve outcomes in this vulnerable group.

Multi-Institutional Outcomes of Patients Aged 75 years and Older With Pancreatic Ductal Adenocarcinoma Treated With 5-Fraction Ablative Stereotactic Magnetic Resonance Image-Guided Adaptive Radiation Therapy (A-SMART).

PURPOSE: Treatment options for pancreatic ductal adenocarcinoma (PDAC) are commonly limited for patients with advanced age due to medical comorbidities and/or poor performance status. These patients may not be candidates for more aggressive chemotherapy regimens and/or surgical resection leaving few, if any, other effective treatments. Ablative stereotactic MRI-guided adaptive radiation therapy (A-SMART) is both efficacious and safe for PDAC and can achieve excellent long-term local control, however, the appropriateness of A-SMART for elderly patients with inoperable PDAC is not well understood. METHODS: A retrospective analysis was performed of inoperable non-metastatic PDAC patients aged 75 years or older treated on the MRIdian Linac at 2 institutions. Clinical outcomes of interest included overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional (LRC). Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE, v5). RESULTS: A total of 49 patients were evaluated with a median age of 81 years (range, 75-91) and a median follow-up of 14 months from diagnosis. PDAC was classified as locally advanced (46.9%), borderline resectable (36.7%), or medically inoperable (16.3%). Neoadjuvant chemotherapy was delivered to 84% of patients and all received A-SMART to a median 50 Gy (range, 40-50 Gy) in 5 fractions. 1 Year LRC, PFS, and OS were 88.9%, 53.8%, and 78.9%, respectively. Nine patients (18%) had resection after A-SMART and benefited from PFS improvement (26 vs 6 months, P = .01). ECOG PS <2 was the only predictor of improved OS on multivariate analysis. Acute and late grade 3 + toxicity rates were 8.2% and 4.1%, respectively. CONCLUSIONS: A-SMART is associated with encouraging LRC and OS in elderly patients with initially inoperable PDAC. This novel non-invasive treatment strategy appears to be well-tolerated in patients with advanced age and should be considered in this population that has limited treatment options.

A nationwide study of liver disease hospitalizations during the coronavirus pandemic in the United States.

BACKGROUND AND AIM: The impact of the Coronavirus disease-2019 (COVID-19) pandemic on patients with liver disease is not well described at the population level in the United States. We used the largest, nationwide inpatient dataset to describe inpatient liver disease outcomes in the United States during the first year of the pandemic (2020) using 2018 and 2019 as comparator years. METHODS: Using the National Inpatient Sample (2018-2020), we explored year-to-year and 2020 month-to-month trends in hospitalizations, length of stay, and inpatient mortality for liver-related complications including cirrhosis, alcohol-associated liver disease (ALD) and alcoholic hepatitis using regression modeling. We reported relative change (RC) in the study period. RESULTS: Decompensated cirrhosis hospitalizations decreased in 2020 compared with 2019 (RC: -2.7%, P < 0.001) while all-cause mortality increased by 15.5% (P < 0.001). Hospitalizations for ALD increased compared with pre-pandemic years (RC: 9.2%, P < 0.001) with a corresponding increase in mortality in 2020 (RC 25.2%, P = 0.002). We observed an increase in liver transplant surgery mortality during the peak months of the pandemic. Importantly, mortality from COVID-19 was higher among patients with decompensated cirrhosis (adjusted odds ratio [OR] 1.72, 95% confidence interval [CI] [1.53-1.94]), Native Americans (OR 1.76, 95% CI [1.53-2.02]), and patients from lower socioeconomic groups. CONCLUSIONS: Cirrhosis hospitalizations decreased in 2020 compared with pre-pandemic years but were associated with higher all-cause mortality rates particularly in the peak months of the COVID-19 pandemic. In-hospital COVID-19 mortality was higher among Native Americans, patients with decompensated cirrhosis, chronic illnesses, and those from lower socioeconomic groups.

Healthcare expenditure trends among adult stroke patients in the United States, 2011-2020.

BACKGROUND: In the US, between 2018 and 2019, approximately $57 billion were expended on stroke and related conditions. The aim of this study was to understand trends in direct healthcare expenditures among stroke patients using novel cost estimation methods and a nationally representative database. METHODS: This study was a retrospective analysis of 193,003 adults, ≥18 years of age, using the Medical Expenditure Panel Survey during 2009-2016. Manning and Mullahy's two-part model were used to calculate adjusted mean and incremental medical expenditures after adjusting for covariates. RESULTS: The mean (Standard Deviation) direct annual healthcare expenditure among stroke patients was $16,979.0 ($16,222.0- $17,736.0) and was nearly 3 times greater than non-stroke participants which were $5,039.7 ($4,951.0-$5,128.5) and were mainly spent on inpatient services, prescription medications, and office-based visits. Stroke patients had an additional healthcare expenditure of $4096.0 (3543.9, 4648.1) per person per year, compared to participants without stroke after adjusting for covariates (P<0.001). The total mean annual direct healthcare expenditure for stroke survivors increased from $16,142.0 (15,017.0-17,267.0) in 2007-2008 to $16,979.0 (16,222.0-17,736.0) in 2015-2016. CONCLUSION: Our study showed that stroke survivors had significantly greater healthcare expenses, compared to non-stroke individuals, mainly due to higher expenditures on inpatient services, prescription drugs, and office visits. These findings are concerning because the prevalence of stroke is projected to increase due to aging population and increased survival rates.

Relationship between insurance status and interhospital transfers among cancer patients in the United States.

BACKGROUND: The relationship between insurance status and interhospital transfers has not been adequately researched among cancer patients. Hence this study aimed for understanding this relationship using a nationally representative database. METHODS: A retrospective analysis was conducted using National Inpatient Sample (NIS) data collected during 2010-2016 and included all cancer hospitalization between 18 and 64 years of age. Interhospital transfers were compared based on insurance status (Medicare, Medicaid, private, and uninsured). Weighted multivariable logistic regressions were used to calculate the odds of interhospital transfers based on insurance status, after adjusting for many covariates. RESULTS: There were 3,580,908 weighted cancer hospitalizations, of which 72,353 (2.02%) had interhospital transfers. Uninsured patients had significantly higher rates of interhospital transfers, compared to those with Medicare (P = 0.005) and private insurance (P < 0.001). Privately insured patients had significantly lower rates of interhospital transfers, compared to those with Medicare (P < 0.001) and Medicaid (P < 0.001). Logistic regression analyses showed that the odds of having interhospital transfers were significantly higher among uninsured (adjusted odds ratio [aOR], 1.57, 95% CI: 1.45-1.69), Medicare (aOR, 1.38, 95% CI: 1.32-1.45) and Medicaid (aOR, 1.23, 95% CI: 1.16-1.30) patients when compared to those with private insurance coverages. CONCLUSION: Among cancer patients, uninsured and Medicare and Medicaid beneficiaries were more likely to experience interhospital transfers. In addition to medical reasons, factors such as affordability and socioeconomic status are influencing interhospital transfer decisions, indicating existing healthcare disparities. Further studies should focus on identifying the causal associations between factors explored in this study as well as additional unexplored factors.

In-hospital outcomes of transesophageal versus intracardiac echocardiography guided left atrial appendage closure.

BACKGROUND: Transesophageal echocardiogram (TEE) is the preferred imaging modality to guide transcatheter left atrial appendage closure (LAAC). Intracardiac echocardiography (ICE) has evolved as a less invasive alternative to TEE. Several observational studies have shown similar success rates and perioperative complications between TEE and ICE for LAAC. OBJECTIVES: We sought to examine the temporal trends and patient characteristics of TEE versus ICE use in LAAC using a national database. We also evaluated hospital outcomes including periprocedural complications, mortality, and length of hospital stay. METHODS: This is a retrospective analysis of data from the National Readmission Database, collected from 2016 to 2018. The primary outcome was major adverse events (MAE) defined as in-hospital mortality, cardiac arrest, pericardial effusion with or without tamponade, pericardiocentesis or window pericardiocentesis and pericardial window, pericardial effusion and tamponade, and hemorrhage requiring transfusion. RESULTS: Trend analysis showed that TEE-guided LAAC increased from 96.6% in 2016 to 98.4% in 2018 (relative increase, 1.9%), while ICE-guided LAAC decreased from 3.4% to 1.6% during the same period (relative decrease, 53%, p for trend = 0.08). In the unmatched cohorts, the MAE was significantly lower in TEE-guided LAAC compared to ICE-guided LAAC (6.5% vs. 9.3%, p = 0.022). In the propensity score matching analysis, MAE remained significant (5.6% vs. 9.4%, p < 0.001). The incidence of pericardial effusion with or without tamponade remained significantly lower in the TEE group (2.3% vs. 5.8%, p < 0.001). Length of stay (3.4 vs. 1.9 days, p < 0.001) and hospitalization cost ($34,826 vs. $20,563, p < 0.001) remained significantly lower for TEE-guided LAAC. CONCLUSIONS: Compared to ICE, the incidence of MAE was significantly lower for TEE-guided LAAC, driven mainly by less pericardial effusion events. Large-scale randomized trials are needed to confirm the findings of the current and previous studies.

Biglycan: an emerging small leucine-rich proteoglycan (SLRP) marker and its clinicopathological significance.

Extracellular matrix (ECM) plays an important role in the structural organization of tissue and delivery of external cues to the cell. Biglycan, a class I small leucine-rich proteoglycans (SLRP), is a key component of the ECM that participates in scaffolding the collagen fibrils and mediates cell signaling. Dysregulation of biglycan expression can result in wide range of clinical conditions such as metabolic disorder, inflammatory disorder, musculoskeletal defects and malignancies. In this review, we aim to update our current understanding regarding the link between altered expression of biglycan and different clinicopathological states. Biglycan interacts with toll like receptors (TLR)-2 and TLR-4 on the immune cells which initiates inflammation and aggravates inflammatory disorders. ECM unbound soluble biglycan acts as a DAMP (danger associated molecular pattern) resulting in sterile inflammation. Dysregulation of biglycan expression is also observed in inflammatory metabolic conditions such as atherosclerosis and obesity. In cancer, high-biglycan expression facilitates tumor growth, invasion and metastasis which is associated with poor clinical outcome. As a pivotal structural component of the ECM, biglycan strengthens the musculoskeletal system and its absence is associated with musculoskeletal defects. Thus, SLRP biglycan is a potential marker which is significantly altered in different clinicopathological states.

Association between vitamin D deficiency and hypothyroidism: results from the National Health and Nutrition Examination Survey (NHANES) 2007-2012.

PURPOSE: Many smaller studies have previously shown a significant association between thyroid autoantibody induced hypothyroidism and lower serum vitamin D levels. However, these finding have not been confirmed by large-scale studies. In this study, we evaluated the relationship between hypothyroidism and vitamin D levels using a large population-based data. METHODS: For this study, we used National Health and Nutrition Examination Survey (NHANES) during the years 2007-2012. We categorized participants into three clinically relevant categories based on vitamin D levels: optimal, intermediate and deficient. Participants were also split into hypothyroid and hyperthyroid. Weighted multivariable logistic regression analyses were used to calculate the odds of being hypothyroid based on vitamin D status. RESULTS: A total of 7943 participants were included in this study, of which 614 (7.7%) were having hypothyroidism. Nearly 25.6% of hypothyroid patients had vitamin D deficiency, compared to 20.6% among normal controls. Adjusted logistic regression analyses showed that the odds of developing hypothyroidism were significantly higher among patients with intermediate (adjusted odds ratio [aOR], 1.7, 95% CI: 1.5-1.8) and deficient levels of vitamin D (aOR, 1.6, 95% CI: 1.4-1.9). CONCLUSION: Low vitamin D levels are associated with autoimmune hypothyroidism. Healthcare initiatives such as mass vitamin D deficiency screening among at-risk population could significantly decrease the risk for hypothyroidism in the long-term.

Lack of Efficacy of the Neutropenic Diet in Decreasing Infections among Cancer Patients: A Systematic Review.

The objective of this systematic review is to evaluate the existing evidence supporting the effectiveness of the neutropenic diet in decreasing infection and mortality among cancer patients. We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Scopus for relevant articles published from database inception until March 2019. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed for this review. Individual studies were evaluated using the Oxford Center for Evidence-Based Medicine guidelines. A total of 473 articles were identified and 11 articles were selected after assessing eligibility. Our review showed that the neutropenic diet does not decrease infection rates or mortality among cancer patients. Currently, there is no uniform definition for the neutropenic diet across different institutions. For example, some institutions follow general food safety practices while others avoid foods that increase exposure to microbes and bacteria, and some follow both. Given these differences in practice regarding what constitutes a neutropenic diet, it is advisable that safe food handling and preparation practices recommended by the Food and Drug Administration be uniformly followed for neutropenic patients.

Predictive value of metabolomic biomarkers for cardiovascular disease risk: a systematic review and meta-analysis.

Background: Metabolomic analysis aids in the identification of novel biomarkers by revealing the metabolic dysregulations underlying cardiovascular disease (CVD) aetiology. The aim of this study was to evaluate which metabolic biomarkers could add value for the prognosis of CVD events using meta-analysis.Methods: The PRISMA guideline was followed for the systematic review. For the meta-analysis, biomarkers were included if they were tested in multivariate prediction models for fatal CVD outcomes. We grouped the metabolites in biological classes for subgroup analysis. We evaluated the prediction performance of models which reported discrimination and/or reclassification statistics.Results: For the systematic review, there were 22 studies which met the inclusion/exclusion criteria. For the meta-analysis, there were 41 metabolites grouped into 8 classes from 19 studies (45,420 subjects, 5954 events). A total of 39 of the 41 metabolites were significant with a combined effect size of 1.14 (1.07-1.20). For the predictive performance assessment, there were 21 studies, 54,337 subjects, 6415 events. The average change in c-statistic after adding the biomarkers to a clinical model was 0.0417 (SE 0.008).Conclusions: This study provides evidence that metabolomic biomarkers, mainly lipid species, have the potential to provide additional prognostic value. Current data are promising, although approaches and results are heterogeneous.

A risk model for prediction of 30-day readmission rates after surgical treatment for colon cancer.

PURPOSE: The purpose of this study was to develop a risk model for the prediction of 30-day unplanned readmission rate after surgery for colon cancer. METHOD: This study was a cross-sectional analysis of data from Nationwide Readmissions Database, collected during 2010-2014. Patients ≥ 18 years of age who underwent surgery for colon cancer were included in the study. The primary outcome of the study was 30-day unplanned readmission rate. RESULTS: There were 141,231 index hospitalizations for surgical treatment of colon cancers and 16,551 had unplanned readmissions. Age, sex, primary payer, Elixhauser comorbidity index, node positive or metastatic disease, length of stay, hospital bedsize, teaching status, hospital ownership, presence of stoma, surgery types, surgery procedures, infectious complications, surgical complications, mechanical wounds, pulmonary complications, and gastrointestinal complications were selected for the risk analysis during backward regression model. Based on the estimated coefficients of selected variables, risk scores were developed and stratified as low risk (≤ 1.08), moderate risk (> 1.08 to ≤ 1.5), and high risk (> 1.5) for unplanned readmission. Validation analysis (n = 42,269) showed that 7.1% of low-risk individuals, 11.1% of moderate-risk individuals, and 17.1% of high-risk individuals experienced unplanned readmissions (P < 0.001). Pairwise comparisons also showed statistically significant differences between low-risk and moderate-risk participants (P < 0.001), between moderate-risk and high-risk participants (P < 0.001), and between low-risk and high-risk participants (P < 0.001). The area under the ROC curve was 0.622. CONCLUSIONS: Our risk model could be helpful for risk-stratifying patients for readmission after surgical treatment for colon cancer. This model needs further validation by incorporating all possible clinical variables.

Increasing Sepsis Rates in the United States: Results From National Inpatient Sample, 2005 to 2014.

OBJECTIVES: To examine the trends in hospitalization rates, mortality, and costs for sepsis during the years 2005 to 2014. METHODS: This was a retrospective serial cross-sectional analysis of patients ≥18 years admitted for sepsis in National Inpatient Sample. Trends in sepsis hospitalizations were estimated, and age- and sex-adjusted rates were calculated for the years 2005 to 2014. RESULTS: There were 541 694 sepsis admissions in 2005 and increased to 1 338 905 in 2014. Sepsis rates increased significantly from 1.2% to 2.7% during the years 2005 to 2014 (relative increase: 123.8%; P trend < .001). However, the relative increase changed by 105.8% (P trend < .001) after adjusting for age and sex and maintained significance. Although total cost of hospitalization due to sepsis increased significantly from US$22.2 to US$38.1 billion (P trend < .001), the mean hospitalization cost decreased significantly from US$46,470 to US$29,290 (P trend < .001). CONCLUSIONS: Hospitalizations for sepsis increased during the years 2005 to 2014. Our study paradoxically found declining rates of in-hospital mortality, length of stay, and mean hospitalization cost for sepsis. These findings could be due to biases introduced by International Classification of Diseases, Ninth Revision, Clinical Modification coding rules and increased readmission rates or alternatively due to increased awareness and surveillance and changing disposition status. Standardized epidemiologic registries should be developed to overcome these biases.

Differentially Expressed Genes and Their Clinical Significance in Ischaemic Stroke: An In-Silico Study.

BACKGROUND: Ischaemic stroke (IS), a multifactorial neurological disorder, is mediated by interplay between genes and the environment and, thus, blood-based IS biomarkers are of significant clinical value. Therefore, this study aimed to find global differentially expressed genes (DEGs) in-silico, to identify key enriched genes via gene set enrichment analysis (GSEA) and to determine the clinical significance of these genes in IS. METHODS: Microarray expression dataset GSE22255 was retrieved from the Gene Expression Omnibus (GEO) database. It includes messenger ribonucleic acid (mRNA) expression data for the peripheral blood mononuclear cells of 20 controls and 20 IS patients. The bioconductor-package 'affy' was used to calculate expression and a pairwise t-test was applied to screen DEGs (P < 0.01). Further, GSEA was used to determine the enrichment of DEGs specific to gene ontology (GO) annotations. RESULTS: GSEA analysis revealed 21 genes to be significantly plausible gene markers, enriched in multiple pathways among all the DEGs (n = 881). Ten gene sets were found to be core enriched in specific GO annotations. JunD, NCX3 and fibroblast growth factor receptor 4 (FGFR4) were under-represented and glycoprotein M6-B (GPM6B) was persistently over-represented. CONCLUSION: The identified genes are either associated with the pathophysiology of IS or they affect post-IS neuronal regeneration, thereby influencing clinical outcome. These genes should, therefore, be evaluated for their utility as suitable markers for predicting IS in clinical scenarios.

Impact of Telemedicine on Mortality, Length of Stay, and Cost Among Patients in Progressive Care Units: Experience From a Large Healthcare System.

OBJECTIVES: To determine whether Telemedicine intervention can affect hospital mortality, length of stay, and direct costs for progressive care unit patients. DESIGN: Retrospective observational. SETTING: Large healthcare system in Florida. PATIENTS: Adult patients admitted to progressive care unit (PCU) as their primary admission between December 2011 and August 2016 (n = 16,091). INTERVENTIONS: Progressive care unit patients with telemedicine intervention (telemedicine PCU [TPCU]; n = 8091) and without telemedicine control (nontelemedicine PCU [NTPCU]; n = 8000) were compared concurrently during study period. MEASUREMENTS AND MAIN RESULTS: Primary outcome was progressive care unit and hospital mortality. Secondary outcomes were hospital length of stay, progressive care unit length of stay, and mean direct costs. The mean age NTPCU and TPCU patients were 63.4 years (95% CI, 62.9-63.8 yr) and 71.1 years (95% CI, 70.7-71.4 yr), respectively. All Patient Refined-Diagnosis Related Group Disease Severity (p < 0.0001) and All Patient Refined-Diagnosis Related Group patient Risk of Mortality (p < 0.0001) scores were significantly higher among TPCU versus NTPCU. After adjusting for age, sex, race, disease severity, risk of mortality, hospital entity, and organ systems, TPCU survival benefit was 20%. Mean progressive care unit length of stay was lower among TPCU compared with NTPCU (2.6 vs 3.2 d; p < 0.0001). Postprogressive care unit hospital length of stay was longer for TPCU patients, compared with NTPCU (7.3 vs 6.8 d; p < 0.0001). The overall mean direct cost was higher for TPCU ($13,180), compared with NTPCU ($12,301; p < 0.0001). CONCLUSIONS: Although there are many studies about the effects of telemedicine in ICU, currently there are no studies on the effects of telemedicine in progressive care unit settings. Our study showed that TPCU intervention significantly decreased mortality in progressive care unit and hospital and progressive care unit length of stay despite the fact patients in TPCU were older and had higher disease severity, and risk of mortality. Increased postprogressive care unit hospital length of stay and total mean direct costs inclusive of telemedicine costs coincided with improved survival rates. Telemedicine intervention decreased overall mortality and length of stay within progressive care units without substantial cost incurrences.