Integrin αVß6 - autoantigen and driver of epithelial remodeling in colon and bile ducts in primary sclerosing cholangitis and inflammatory bowel disease.

Objective: Recently, autoantibodies directed against the epithelial adhesion protein integrin αVβ6 have been identified which strongly associate with ulcerative colitis (UC). We aimed to elucidate whether anti-integrin αVβ6 (anti- αVβ6) is present in primary sclerosing cholangitis (PSC), its associated inflammatory bowel disease or other cholestatic liver diseases and their persistence after proctocolectomy.

Design: We detected anti- αVβ6 by an enzyme-linked immunosorbent assay in sera collected at two German tertiary centers, including healthy controls (N=62), UC (N=36), Crohn's disease (CD, N=65), PSC-IBD (78 samples from N=41 patients), PSC without IBD (PSC, 41 samples from N=18 patients), primary biliary cholangitis (PBC, N=24), autoimmune hepatitis (AIH, N=32), secondary sclerosing cholangitis (SSC, N=12) and metabolic dysfunction-associated steatotic liver disease (MASLD, N=24).

Gut Pathobiont-Derived Outer Membrane Vesicles Drive Liver Inflammation and Fibrosis in Primary Sclerosing Cholangitis-Associated Inflammatory Bowel Disease.

Background & Aims: Primary sclerosing cholangitis (PSC), often associated with inflammatory bowel disease (IBD), presents a multifactorial etiology involving genetic, immunologic, and environmental factors. Gut dysbiosis and bacterial translocation have been implicated in PSC-IBD, yet the precise mechanisms underlying their pathogenesis remain elusive. Here, we describe the role of gut pathobionts in promoting liver inflammation and fibrosis due to the release of bacterial outer membrane vesicles (OMVs).

[Recommended diagnostics for pruritus affecting primary non-lesional skin].

Background: Chronic pruritus affecting primary non-lesional skin (CPNL) manifests as a common symptom across a spectrum of diseases spanning various medical specialties. Given the diverse etiological factors involved, diagnosing the underlying condition poses a significant challenge.

Objectives: To provide a comprehensive overview of clinical, laboratory, and imaging diagnostics for CPNL.

Peripheral signaling pathways contributing to non-histaminergic itch in humans.

Background: Chronic itch (chronic pruritus) is a major therapeutic challenge that remains poorly understood despite the extensive recent analysis of human pruriceptors. It is unclear how the peripheral nervous system differentiates the signaling of non-histaminergic itch and pain.

Methods: Here we used psychophysical analysis and microneurography (single nerve fiber recordings) in healthy human volunteers to explore the distinct signaling mechanisms of itch, using the pruritogens β-alanine, BAM 8-22 and cowhage extract.

Spontaneous activity of specific C-nociceptor subtypes from diabetic patients and mice: Involvement of reactive dicarbonyl compounds and (sensitized) transient receptor potential channel A1.

Background: Diabetic metabolism causes changes of the chemical milieu including accumulation of reactive carbonyl species, for example, methylglyoxal (MGO). MGO activates chemosensitive TRPA1 on nociceptors, but the contribution to neuronal pathophysiology causing pain and hyperalgesia in diabetic neuropathy is not fully understood.

Methods: We employed single-nerve-fiber recordings in type 2 diabetes patients with (spDN) and without cutaneous pain (DN) and in streptozotocin-diabetic and healthy mice.

Evaluation and Management of Pruritus in Primary Biliary Cholangitis.

Chronic pruritus is a classic symptom in patients with primary biliary cholangitis. It affects up to two-thirds of patients in the course of the disease. Efficient therapy consists of topical treatment combined with systemic options such as anion exchangers, rifampicin, bezafibrate, μ-opioid receptor antagonists, selective-serotonin receptor uptake inhibitors, and gabapentinoids.

Blunt chest wall trauma: Rib fractures and associated injuries.

Blunt injuries to the chest wall, specifically those related to rib fractures, need to be promptly identified and effectively managed to reduce patient morbidity and mortality. Furthermore, judicious use of multimodal pain management and early identification of patients who will benefit from the surgical stabilization of rib fractures are paramount to optimal outcomes.

To Tranexamic Acid or Not to Tranexamic Acid? Accuracy of Antifibrinolytic Administration at Altitude.

Objective: Tranexamic acid (TXA) has demonstrated a reduction in all-cause mortality in trauma patients with hemorrhage. Administering TXA in the prehospital setting presents unique challenges because the identification of bleeding is based on clinical suspicion without advanced imaging or diagnostic tools. The objective of this study was to examine whether prehospital suspicion of bleeding is validated by in-hospital computed tomographic imaging and examination and to determine if patients received TXA in the absence of hemorrhage.

Surgical Site Infection after Surgical Stabilization of Rib Fractures: Rare but Morbid.

Although surgical stabilization for rib fractures (SSRF) has been adopted widely over the past decade, little information is available regarding the prevalence and outcomes of post-operative surgical site infection (SSI). We hypothesized that SSI after SSRF is uncommon but morbid. Patients undergoing SSRF at a level 1 trauma center from 2010-2020 were reviewed.

Left ventricular dyssynchrony in long-term childhood cancer survivors treated with anthracyclines: a retrospective cross-sectional study.

The purpose of this study was to investigate left ventricular contraction patterns in asymptomatic Childhood cancer survivors (CCS) using two-dimensional speckle tracking echocardiography (2DSTE). Left ventricular longitudinal and circumferential myocardial parameters were assessed using 2DSTE, in asymptomatic CCS and age matched healthy controls. Time to peak (T2P) systolic strain was quantified.

Lysophosphatidic acid activates nociceptors and causes pain or itch depending on the application mode in human skin.

Lysophosphatidic acid (LPA) is involved in the pathophysiology of cholestatic pruritus and neuropathic pain. Slowly conducting peripheral afferent C-nerve fibers are crucial in the sensations of itch and pain. In animal studies, specialized neurons ("pruriceptors") have been described, expressing specific receptors, eg, from the Mas-related G-protein-coupled receptor family.

Endogenous Opioid Levels Do Not Correlate With Itch Intensity and Therapeutic Interventions in Hepatic Pruritus.

Chronic pruritus affects up to 70% of patients with immune-mediated hepatobiliary disorders. Antagonists of the μ-opioid receptor (MOR) and agonists of the κ-opioid receptor (KOR) are used to treat hepatic itch, albeit with limited success. An imbalance between ligands of MOR and KOR receptors has recently been suggested as a potential mechanism of hepatic pruritus.

The Effect of Chronic Preoperative Opioid Use on Surgical Site Infections, Length of Stay, and Readmissions.

Background: Chronic opioid use in the United States is a well-recognized public health concern with many negative downstream consequences. Few data exist regarding the use of preoperative opioids in relation to outcomes after elective colorectal surgery.

Objective: The purpose of this study was to determine if chronic opioid use before colorectal surgery is associated with a detriment in postoperative outcomes.

Mas-related G protein-coupled receptor X2 and its activators in dermatologic allergies.

The Mas-related G protein-coupled receptor X2 (MRGPRX2) is a multiligand receptor responding to various exogenous and endogenous stimuli. Being highly expressed on skin mast cells, MRGPRX2 triggers their degranulation and release of proinflammatory mediators, and it promotes multicellular signaling cascades, such as itch induction and transmission in sensory neurons. The expression of MRGPRX2 by skin mast cells and the levels of the MRGPRX2 agonists (eg, substance P, major basic protein, eosinophil peroxidase) are upregulated in the serum and/or skin of patients with inflammatory and pruritic skin diseases, such as chronic spontaneous urticaria or atopic dermatitis.

Myocardial 2D Strain During Long-Term (>5 Years) Follow-Up of Childhood Survivors of Acute Lymphoblastic Leukemia Treated With Anthracyclines.

Anthracycline-induced cardiotoxicity can lead to clinical and subclinical heart failure. Decrease of global longitudinal strain is a predictor for heart failure. Early detection of subclinical cardiotoxicity is crucial for timely intervention and prevention of further progression.

Resuscitative Endovascular Balloon Occlusion of the Aorta Process Improvement: Examining a Novel Case Evaluation Tool and Standardized Simulations.

A quality improvement project was undertaken. The objectives of this study were to describe an original case evaluation tool, discuss barriers encountered, present a standardized simulation course, and evaluate the efficacy of this course. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an emerging adjunct in the trauma bay for patients with noncompressible subdiaphragmatic hemorrhage.

Treatment of Pruritus Secondary to Liver Disease.

Purpose Of Review: Pruritus is a common extrahepatic symptom in various liver disorders, in particularly those with cholestatic features. This review summarizes epidemiology, pathophysiology, evidence-based therapeutic recommendations and currently investigated drugs for pruritus in hepatobiliary disorders.

Recent Findings: Recent epidemiological data suggest pruritus as a common and relevant symptom in immune-mediated liver diseases, i.

Methylglyoxal causes pain and hyperalgesia in human through C-fiber activation.

The endogenous metabolite methylglyoxal (MG) accumulates in diabetic patients with neuropathic pain. Methylglyoxal could be a mediator of diabetes-induced neuropathic pain through TRPA1 activation and sensitization of the voltage-gated sodium channel subtype 1.8.

Association of Angiotensin-Converting Enzyme Inhibitors with Increased Mortality Among Patients with Isolated Severe Traumatic Brain Injury.

Background: Traumatic brain injury (TBI) is associated with one-third of all deaths from trauma. Preinjury exposure to cardiovascular drugs may affect TBI outcomes. Angiotensin-converting enzyme inhibitors (ACEIs) exacerbate brain cell damage and worsen functional outcomes in the laboratory setting.

The danger zone: Injuries and conditions associated with immediately fatal motorcycle crashes in the state of Michigan.

Background: Immediately fatal motorcycle crashes have not been well characterized. This study catalogues injuries sustained in fatal motorcycle crashes and assesses the impact of crash conditions on injury patterns.

Methods: Autopsy records from the office of the medical examiner of Kent County, MI and publicly available traffic reports were queried for information pertaining to motorcyclists declared dead on-scene between January 1, 2007, and December 31, 2016.

Management of Chronic Hepatic Itch.

Hepatic itch remains among the most agonizing symptoms for affected patients and a major clinical challenge for physicians. Pruritus may occur in almost all liver diseases, particularly those with cholestatic features. Hepatic itch arises irrespective of the severity of the underlying liver disease or extent of cholestasis.