Intestinal Epithelia and Myeloid Immune Cells Shape Colitis Severity and Colorectal Carcinogenesis via High-mobility Group Box Protein 1.

Background: High-mobility group box protein 1 [HMGB1] is a ubiquitous nucleoprotein with immune-regulatory properties following cellular secretion or release in sterile and in infectious inflammation. Stool and serum HMGB1 levels correlate with colitis severity and colorectal cancer [CRC] progression, yet recent reports indicate that HMGB1 mainly operates as an intracellular determinant of enterocyte fate during colitis, and investigations into the roles of HMGB1 in CRC are lacking.

Methods: Using mice with conditional HMGB1-knockout in enterocytes [Hmgb1ΔIEC] and myeloid cells [Hmgb1ΔLysM], respectively, we explored functions of HMGB1 in pathogenetically diverse contexts of colitis and colitis-associated CRC.

Patient Outcomes and Characteristics in a Contemporary Quaternary Canadian Cardiac Intensive Care Unit.

Background: The modern-day cardiac intensive care unit (CICU) has evolved to care for patients with acute critical cardiac illness. We describe the current population of cardiac patients in a quaternary CICU.

Methods: Consecutive CICU patients admitted to the CICU at the Toronto General Hospital from 2014 to 2020 were studied.

High risk of complications and acute-on-chronic liver failure in cirrhosis patients with acute pancreatitis.

Background & Aims: Acute pancreatitis (AP) is a frequent indication for hospitalization and may present with varying degrees of severity. AP often coincides with hepatic disease, yet the impact of liver cirrhosis (LC) on the course of AP is uncertain, and early identification of patients at risk for complications remains challenging. We aimed to assess the impact of LC on the development of pancreatic and extra-pancreatic complications of AP, and to identify predictors of adverse outcomes in cirrhotic patients.

Leukocyte-Derived High-Mobility Group Box 1 Governs Hepatic Immune Responses to Listeria monocytogenes.

High-mobility group box 1 (HMGB1) is a nucleoprotein with proinflammatory functions following cellular release during tissue damage. Moreover, antibody-mediated HMGB1 neutralization alleviates lipopolysaccharide (LPS)-induced shock, suggesting a role for HMGB1 as a superordinate therapeutic target for inflammatory and infectious diseases. Recent genetic studies have indicated cell-intrinsic functions of HMGB1 in phagocytes as critical elements of immune responses to infections, yet the role of extracellular HMGB1 signaling in this context remains elusive.

Liver transplantation for acute-on-chronic liver failure predicts post-transplant mortality and impaired long-term quality of life.

Background: Among patients with cirrhosis, candidate selection and timing of liver transplantation (LT) remain problematic. Acute-on-chronic liver failure (ACLF) is a severe complication of cirrhosis with excessive short-term mortality rates under conservative therapeutic measures. The role of LT in the management of ACLF is uncertain.

Presurgical Orthopedic Intervention Prior to Cleft Lip and Palate Repair: Nasoalveolar Molding Versus Passive Molding Appliance Therapy.

Background: Nasoalveolar molding (NAM) is a widely used presurgical orthopedic device, despite disputes over its effectiveness. This study compares the outcomes after cleft lip and nose repair in patients who received NAM versus those who underwent passive alveolar molding with lip taping.

Methods: A retrospective review of patients with complete unilateral cleft lip and palate who received either NAM (n = 16) or passive molding (n = 10) treatments was conducted.

Parental well-being in times of Covid-19 in Germany.

We examine the effects of Covid-19 and related restrictions on individuals with dependent children in Germany. We specifically focus on the role of day care center and school closures, which may be regarded as a "disruptive exogenous shock" to family life. We make use of a novel representative survey of parental well-being collected in May and June 2020 in Germany, when schools and day care centers were closed but while other measures had been relaxed and new infections were low.

Management of Acute Decompensated Heart Failure in the Cardiac Intensive Care Unit: The Importance of Co-management With a Heart Failure Specialist.

Background: Heart failure (HF) is a common reason for admission to the cardiac intensive care unit. We sought to identify the role of an HF consultation service in improving the management of this patient population.

Methods: We identified all adult patients admitted to the cardiac intensive care unit (2014-2015) at the University Health Network with a diagnosis of acute decompensated HF ± cardiogenic shock (CS).

Epithelial HMGB1 Delays Skin Wound Healing and Drives Tumor Initiation by Priming Neutrophils for NET Formation.

Regenerative responses predispose tissues to tumor formation by largely unknown mechanisms. High-mobility group box 1 (HMGB1) is a danger-associated molecular pattern contributing to inflammatory pathologies. We show that HMGB1 derived from keratinocytes, but not myeloid cells, delays cutaneous wound healing and drives tumor formation.

Life expectancy and parental education.

This study analyses the relationship between life expectancy and parental education. Based on data from the German Socio-Economic Panel Study and survival analysis models, we show that maternal education is related to children's life expectancy - even after controlling for children's own level of education. This applies equally to daughters and sons as well as to children's further life expectancies examined at age 35 to age 65.

Stabilisation of acute-on-chronic liver failure patients before liver transplantation predicts post-transplant survival.

Background: Acute-on-chronic liver failure (ACLF) is a severe complication of liver cirrhosis associated with excess short-term mortality rates. Orthotopic liver transplantation (OLT) is a potentially life-saving therapeutic modality for acute-on-chronic liver failure patients, but selection of transplant candidates with an acceptable post-transplant outcome is difficult.

Aim: To assess the risk of liver transplantation in patients with ACLF, and to determine parameters that predict post-transplant survival in this patient cohort.

HMGB1 links chronic liver injury to progenitor responses and hepatocarcinogenesis.

Cell death is a key driver of disease progression and carcinogenesis in chronic liver disease (CLD), highlighted by the well-established clinical correlation between hepatocellular death and risk for the development of cirrhosis and hepatocellular carcinoma (HCC). Moreover, hepatocellular death is sufficient to trigger fibrosis and HCC in mice. However, the pathways through which cell death drives CLD progression remain elusive.

Long-Term Incisal Relationships After Palatoplasty in Patients With Isolated Cleft Palate.

Purpose: Various palatoplasty techniques have limited incisions in the hard palate due to concerns that these incisions may limit maxillary growth. There is little convincing long-term evidence to support this. Our purpose is to determine incisal relationships, an indicator for future orthognathic procedure, in patients after repair of an isolated cleft of the secondary palate.

Damage-associated molecular patterns in cancer: a double-edged sword.

Damage-associated molecular patterns (DAMPs) are released in response to cell death and stress, and are potent triggers of sterile inflammation. Recent evidence suggests that DAMPs may also have a key role in the development of cancer, as well as in the host response to cytotoxic anti-tumor therapy. As such, DAMPs may exert protective functions by alerting the immune system to the presence of dying tumor cells, thereby triggering immunogenic tumor cell death.

Criteria Used in Clinical Practice to Guide Immunosuppressive Treatment in Patients with Primary Sclerosing Cholangitis.

Background & Aims: Current guidelines recommend immunosuppressive treatment (IT) in patients with primary sclerosing cholangitis (PSC) and elevated aminotransferase levels more than five times the upper limit of normal and elevated serum IgG-levels above twice the upper limit of normal. Since there is no evidence to support this recommendation, we aimed to assess the criteria that guided clinicians in clinical practice to initiate IT in patients with previously diagnosed PSC.

Methods: This is a retrospective analysis of 196 PSC patients from seven German hepatology centers, of whom 36 patients had received IT solely for their liver disease during the course of PSC.

Intestinal microbiota modulates gluten-induced immunopathology in humanized mice.

Celiac disease (CD) is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. The recent increase in CD incidence suggests that additional environmental factors, such as intestinal microbiota alterations, are involved in its pathogenesis. However, there is no direct evidence of modulation of gluten-induced immunopathology by the microbiota.

[Establishment of a Neonatal ECMO Programme on the Basis of a Special Training Programme--A 6-year Analysis].

Background: Internationally the need for neonatal ECMO is decreasing and the Extracorporeal Life Support Organization (ELSO) recommends that centres providing neonatal ECMO should treat at least 6 children per year.

Method: After a one-year training programme and preparation of the clinical application, neonatal ECMO was established and subsequently 41 infants [median age 1 day (1-172 days), median weight 3.25 kg (1.