Endoluminal Wound Vacuum Therapy: A Paradigm Shift in Managing Esophageal Bronchial Fistula.

Esophageal bronchial fistula after Ivor Lewis esophagectomy is a challenging complication. Surgical treatment is definitive, but it carries high morbidity and mortality, whereas esophageal stents have been shown to be temporary measures. We highlight the case of a patient who was treated with endoluminal wound vacuum therapy.

A noncoding regulatory variant in IKZF1 increases acute lymphoblastic leukemia risk in Hispanic/Latino children.

Hispanic/Latino children have the highest risk of acute lymphoblastic leukemia (ALL) in the US compared to other racial/ethnic groups, yet the basis of this remains incompletely understood. Through genetic fine-mapping analyses, we identified a new independent childhood ALL risk signal near IKZF1 in self-reported Hispanic/Latino individuals, but not in non-Hispanic White individuals, with an effect size of ∼1.44 (95% confidence interval = 1.

Unique Capabilities of Genome Sequencing for Rare Disease Diagnosis.

Background: Causal variants underlying rare disorders may remain elusive even after expansive gene panels or exome sequencing (ES). Clinicians and researchers may then turn to genome sequencing (GS), though the added value of this technique and its optimal use remain poorly defined. We therefore investigated the advantages of GS within a phenotypically diverse cohort.

Inherited blood cancer predisposition through altered transcription elongation.

Despite advances in defining diverse somatic mutations that cause myeloid malignancies, a significant heritable component for these cancers remains largely unexplained. Here, we perform rare variant association studies in a large population cohort to identify inherited predisposition genes for these blood cancers. CTR9, which encodes a key component of the PAF1 transcription elongation complex, is among the significant genes identified.

Shared and distinct genetic etiologies for different types of clonal hematopoiesis.

Clonal hematopoiesis (CH)-age-related expansion of mutated hematopoietic clones-can differ in frequency and cellular fitness by CH type (e.g., mutations in driver genes (CHIP), gains/losses and copy-neutral loss of chromosomal segments (mCAs), and loss of sex chromosomes).

A genetic disorder reveals a hematopoietic stem cell regulatory network co-opted in leukemia.

The molecular regulation of human hematopoietic stem cell (HSC) maintenance is therapeutically important, but limitations in experimental systems and interspecies variation have constrained our knowledge of this process. Here, we have studied a rare genetic disorder due to MECOM haploinsufficiency, characterized by an early-onset absence of HSCs in vivo. By generating a faithful model of this disorder in primary human HSCs and coupling functional studies with integrative single-cell genomic analyses, we uncover a key transcriptional network involving hundreds of genes that is required for HSC maintenance.

Variant to function mapping at single-cell resolution through network propagation.

Genome-wide association studies in combination with single-cell genomic atlases can provide insights into the mechanisms of disease-causal genetic variation. However, identification of disease-relevant or trait-relevant cell types, states and trajectories is often hampered by sparsity and noise, particularly in the analysis of single-cell epigenomic data. To overcome these challenges, we present SCAVENGE, a computational algorithm that uses network propagation to map causal variants to their relevant cellular context at single-cell resolution.

Variant to function mapping at single-cell resolution through network propagation.

With burgeoning human disease genetic associations and single-cell genomic atlases covering a range of tissues, there are unprecedented opportunities to systematically gain insights into the mechanisms of disease-causal variation. However, sparsity and noise, particularly in the context of single-cell epigenomic data, hamper the identification of disease- or trait-relevant cell types, states, and trajectories. To overcome these challenges, we have developed the SCAVENGE method, which maps causal variants to their relevant cellular context at single-cell resolution by employing the strategy of network propagation.

Clonal hematopoiesis in sickle cell disease.

BACKGROUNDCurative gene therapies for sickle cell disease (SCD) are currently undergoing clinical evaluation. The occurrence of myeloid malignancies in these trials has prompted safety concerns. Individuals with SCD are predisposed to myeloid malignancies, but the underlying causes remain undefined.

Heparin resistance in severe thermal injury: A prospective cohort study.

Background: Low molecular-weight heparin (LMWH) is routinely administered to burn patients for thromboprophylaxis. Some studies have reported heparin resistance, yet the mechanism(s) and prevalence have not been systematically studied. We hypothesized that nucleosomes, composed of histone structures with associated DNA released from injured tissue and activated immune cells in the form of neutrophil extracellular traps (NETs or NETosis), neutralize LMWH resulting in suboptimal anticoagulation, assessed by reduction in anti-factor Xa activity.

Changes in Burn Wound Microbiology Profile Over 14 Years of an Adult Tertiary Burn Center.

Burn wound colonization can progress to invasive infection. During 14 years of this study, the burn center was relocated to a center with improved infrastructure. This study investigates the association that infrastructure, geography, and time may have on colonization.

Inpatient burden and mortality of heatstroke in the United States.

Background: This study aimed to assess inpatient prevalence, characteristics, outcomes, and resource utilisation of hospitalisation for heatstroke in the United States. Additionally, this study aimed to explore factors associated with in-hospital mortalities of heatstroke.

Methods: The 2003-2014 National Inpatient Sample database was used to identify hospitalised patients with a principal diagnosis of heatstroke.

Impact of Acute Kidney Injury on Outcomes of Hospitalizations for Heat Stroke in the United States.

This study aims to evaluate the risk factors and the association of acute kidney injury with treatments, complications, outcomes, and resource utilization in patients hospitalized for heat stroke in the United States. Hospitalized patients from years 2003 to 2014 with a primary diagnosis of heat stroke were identified in the National Inpatient Sample dataset. End stage kidney disease patients were excluded.

Epidemiology of cannabis use and associated outcomes among kidney transplant recipients: A meta-analysis.

Objective: Cannabis is the most commonly used recreational drug in the United States, and transplant acceptability for cannabis using candidates varies among transplant centers. However, the prevalence and impact of cannabis use on outcomes of kidney transplant recipients remain unclear. This study aimed to summarize the prevalence and impact of cannabis use on outcomes after kidney transplantation.

Impact of Circadian Blood Pressure Pattern on Silent Cerebral Small Vessel Disease: A Systematic Review and Meta-Analysis.

Background Abnormal circadian blood pressure (BP) variations during sleep, specifically the non-dipping (<10% fall in nocturnal BP) and reverse-dipping patterns (rise in nocturnal BP), have been associated with an increased risk of cardiovascular events and target organ damage. However, the relationship between abnormal sleep BP variations and cerebral small vessel disease markers is poorly established. This study aims to assess the association between non-dipping and reverse-dipping BP patterns with markers of silent cerebral small vessel disease.

The association between simple renal cyst and aortic diseases: A systematic review and meta-analysis of observational studies.

Objective: The objective of this meta-analysis of observational studies was to evaluate the association between simple renal cysts (SRC) and presence of aortic pathology such as aortic aneurysms and dissection.

Methods: We conducted searches in Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 1960 to August 2019 to identify observational studies that examined the association between SRCs and any aortic diseases, including aortic aneurysms and dissection. Two reviewers independently extracted the data and assessed the risk of bias.

Vitamin D deficiency is not associated with graft versus host disease after hematopoietic stem cell transplantation: A meta-analysis.

Objective: Vitamin D status plays an important role in immunoregulation, and a deficiency is believed to be related to Graft Versus Host Disease (GVHD) in patients after hematopoietic stem cell transplantation (HSCT). We aim to study the association between vitamin D deficiency and GVHD after HSCT.

Methods: A literature search was conducted utilizing MEDLINE, EMBASE, and The Cochrane Library Database from inception to July 2019.

Rate of kidney function decline and factors predicting progression of kidney disease in type 2 diabetes mellitus patients with reduced kidney function: A nationwide retrospective cohort study.

Currently, the data on independent risk factors for the progression of kidney disease in type 2 diabetes mellitus (T2DM) patients with CKD are limited. This study aimed to investigate CKD progression in T2DM patients who have reduced kidney function with baseline estimated glomerular filtration rate (eGFRs) between 15 and 59 mL/min/1.73 m .

Platelet count: A predictor of sepsis and mortality in severe burns.

Background: Platelet cells, or thrombocytes, have additional roles to haemostasis. After burn injury, platelet counts drop to a nadir at days 2-5 then rise to a peak between days 10-18. The nadir has previously been associated with mortality but there is currently no thorough investigation of its potential to predict sepsis in adults.

Idiopathic intracranial hypertension, hormones, and 11β-hydroxysteroid dehydrogenases.

Idiopathic intracranial hypertension (IIH) results in raised intracranial pressure (ICP) leading to papilledema, visual dysfunction, and headaches. Obese females of reproductive age are predominantly affected, but the underlying pathological mechanisms behind IIH remain unknown. This review provides an overview of pathogenic factors that could result in IIH with particular focus on hormones and the impact of obesity, including its role in neuroendocrine signaling and driving inflammation.