Proteolytic shedding of CD46 from human hepatocytes indicates liver stress.

Background: Routine liver function tests capture information about the metabolic and inflammatory condition of the liver, but we lack sensitive biomarkers of early hepatocyte stress. In humans, soluble CD46 (sCD46) levels in blood were recently identified as an accurate biomarker of hepatic steatosis. Here, we explore the diagnostic utility of sCD46 in other liver diseases.

Restricting datasets to classifiable samples augments discovery of immune disease biomarkers.

Immunological diseases are typically heterogeneous in clinical presentation, severity and response to therapy. Biomarkers of immune diseases often reflect this variability, especially compared to their regulated behaviour in health. This leads to a common difficulty that frustrates biomarker discovery and interpretation - namely, unequal dispersion of immune disease biomarker expression between patient classes necessarily limits a biomarker's informative range.

Dynamics of multisystem inflammatory syndrome in children associated to COVID-19 in Chile: Epidemiologic trends during pandemic, before and after children vaccination.

Background: Multisystem inflammatory syndrome associated to Covid-19 (MIS-C) is one of the most severe outcomes of SARS-CoV-2 in children. Covid-19 vaccines were successfully implemented in Chile for the pediatric population since 2021, using both mRNA and inactivated platforms. Effectiveness against MIS-C has been reported for mRNA vaccines.

Soluble CD46 as a diagnostic marker of hepatic steatosis.

Background: The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) incurs substantial morbidity, mortality and healthcare costs. Detection and clinical intervention at early stages of disease improves prognosis; however, we are currently limited by a lack of reliable diagnostic tests for population screening and monitoring responses to therapy. To address this unmet need, we investigated human invariant Natural Killer T cell (iNKT) activation by fat-loaded hepatocytes, leading to the discovery that circulating soluble CD46 (sCD46) levels accurately predict hepatic steatosis.

The Akin osteotomy without fixation in open hallux abducto-valgo correction surgery - A single center retrospective analysis of 286 cases.

Background: Description of a large cohort of Akin osteotomies without fixation (286 feet), to depict the mean angular correction, to analyze complication rates and to pull over with rates described in the literature with other techniques.

Methods: Retrospective single-center cohort study. Five radiologic measurements analyzed preoperatively and postoperatively until fusion was completed.

Preparing fourth year medical students to care for patients with opioid use disorder: how this training affects their intention to seek addiction care opportunities during residency.

Background & Objectives: In 2021, the USA recorded 100,000 annual deaths from drug overdose, representing the most frequent cause of death in adults under age 55. The integration of care for substance use disorders (SUDs) into undergraduate medical education is not well established. It is unclear whether a short course on management of opioid use disorder (OUD) offered to fourth year medical students could increase graduating students' knowledge and preparedness to treat these disorders.

External validation of biomarkers for immune-related adverse events after immune checkpoint inhibition.

Immune checkpoint inhibitors have revolutionized treatment of advanced melanoma, but commonly cause serious immune-mediated complications. The clinical ambition of reserving more aggressive therapies for patients least likely to experience immune-related adverse events (irAE) has driven an extensive search for predictive biomarkers. Here, we externally validate the performance of 59 previously reported markers of irAE risk in a new cohort of 110 patients receiving Nivolumab (anti-PD1) and Ipilimumab (anti-CTLA-4) therapy.

Genome Sequences of 408 SARS-CoV-2 Strains Obtained from Nasopharyngeal Swabs in La Araucanía Region, Southern Chile.

Here, we announce the genome sequences of 408 strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) obtained from nasopharyngeal swabs in the Araucanía Region, Southern Chile. The genomes obtained are valuable to expand the availability of useful genomic data for future epidemiological studies of SARS-CoV-2 in Chile and worldwide.

Non-ST-elevation myocardial infarction hiding behind myopericarditis in a patient with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic inflammatory condition with various cardiovascular sequelae. Pericarditis is the most common cardiac manifestation, yet patients also have a markedly elevated risk of premature atherosclerosis and acute coronary syndrome (ACS). This makes the diagnosis of ischaemic chest pain both challenging and crucial in these patients.

Expanding the Team: Optimizing the Multidisciplinary Management of Drug Use-Associated Infective Endocarditis.

Amidst a substance use epidemic, hospitalizations and valve surgeries related to drug use-associated infective endocarditis (DU-IE) rose substantially in the last decade. Rates of reoperation and mortality remain high, yet in many hospitals patients are not offered valve surgery or evidence-based addiction treatment. A multidisciplinary team approach can improve outcomes in patients with infective endocarditis; however, the breadth of expertise that should be incorporated into this team is inadequately conceptualized.

Development of a Flow Cytometry Assay to Predict Immune Checkpoint Blockade-Related Complications.

Treatment of advanced melanoma with combined immune checkpoint inhibitor (ICI) therapy is complicated in up to 50% of cases by immune-related adverse events (irAE) that commonly include hepatitis, colitis and skin reactions. We previously reported that pre-therapy expansion of cytomegalovirus (CMV)-reactive CD4 effector memory T cells (T) predicts ICI-related hepatitis in a subset of patients with Stage IV melanoma given αPD-1 and αCTLA-4. Here, we develop and validate a 10-color flow cytometry panel for reliably quantifying CD4 T cells and other biomarkers of irAE risk in peripheral blood samples.

Virus-specific memory T cell responses unmasked by immune checkpoint blockade cause hepatitis.

Treatment of advanced melanoma with combined PD-1/CTLA-4 blockade commonly causes serious immune-mediated complications. Here, we identify a subset of patients predisposed to immune checkpoint blockade-related hepatitis who are distinguished by chronic expansion of effector memory CD4 T cells (T cells). Pre-therapy CD4 T cell expansion occurs primarily during autumn or winter in patients with metastatic disease and high cytomegalovirus (CMV)-specific serum antibody titres.

Aseptic abscess syndrome.

A 43-year-old woman with Crohn's disease was admitted to the hospital with weight loss and 1 week of fever, abdominal pain and diarrhoea. At presentation, the patient was not on steroids or other immunosuppressive agents. Cross-sectional imaging of the abdomen revealed active colitis and multiple splenic and hepatic abscesses.

Myeloid-Derived Suppressor Cells in Kidney Transplant Recipients and the Effect of Maintenance Immunotherapy.

Myeloid-derived suppressor cells (MDSC) represent a heterogeneous group of myeloid regulatory cells that were originally described in cancer. Several studies in animal models point to MDSC as important players in the induction of allograft tolerance due to their immune modulatory function. Most of the published studies have been performed in animal models, and the data addressing MDSCs in human organ transplantation are scarce.

[Screening of hepatitis B in high risk Chilean and immigrant pregnant women: Management of mother to child transmission].

Background: Chile is a low-endemic HBV country, but countries with the highest migratory flow to Chile have an intermediate-high endemicity. In order to avoid vertical transmission of HBV, immunoprophylaxis (IP) in the newborn (NB) is a key factor.

Aim: To identify HBsAg prevalence in pregnant immigrants and Chilean pregnant women with risk behaviors (RB) and to asses IP use in the NB.

Novel molecules mediate specialized functions of human regulatory macrophages.

Purpose Of Review: Now that adoptive transfer of regulatory macrophages (Mregs) is clinically practicable, we ask whether this approach could be used to achieve self-sustaining peripheral regulation and what mechanisms may be involved.

Recent Findings: Dehydrogenase/reductase 9 (DHRS9)-expressing Mregs are a specialized subset of monocyte-derived macrophages that are currently being investigated as a tolerogenic cell-based therapy. Human Mregs are defined by their capacity to convert naïve CD4 T cells to IL-10-secreting FoxP3 regulatory T cells (Tregs) through an activation-dependent process involving signals mediated by TGF-β, retinoic acid, indoleamine 2,3-dioxygenase activity, notch and progestagen associated endometrial protein (PAEP).

TIGIT iTregs elicited by human regulatory macrophages control T cell immunity.

Human regulatory macrophages (Mreg) have shown early clinical promise as a cell-based adjunct immunosuppressive therapy in solid organ transplantation. It is hypothesised that recipient CD4 T cell responses are actively regulated through direct allorecognition of donor-derived Mregs. Here we show that human Mregs convert allogeneic CD4 T cells to IL-10-producing, TIGIT FoxP3-induced regulatory T cells that non-specifically suppress bystander T cells and inhibit dendritic cell maturation.

Postoperative cellular stress in the kidney is associated with an early systemic γδ T-cell immune cell response.

Background: Basic science data suggest that acute kidney injury (AKI) induced by ischemia-reperfusion injury (IRI) is an inflammatory process involving the adaptive immune response. Little is known about the T-cell contribution in the very early phase, so we investigated if tubular cellular stress expressed by elevated cell cycle biomarkers is associated with early changes in circulating T-cell subsets, applying a bedside-to-bench approach.

Methods: Our observational pilot study included 20 consecutive patients undergoing endovascular aortic repair for aortic aneurysms affecting the renal arteries, thereby requiring brief kidney hypoperfusion and reperfusion.

Tunable entanglement distillation of spatially correlated down-converted photons.

We report on a new technique for entanglement distillation of the bipartite continuous variable state of spatially correlated photons generated in the spontaneous parametric down-conversion process (SPDC), where tunable non-Gaussian operations are implemented and the post-processed entanglement is certified in real-time using a single-photon sensitive electron multiplying CCD (EMCCD) camera. The local operations are performed using non-Gaussian filters modulated into a programmable spatial light modulator and, by using the EMCCD camera for actively recording the probability distributions of the twin-photons, one has fine control of the Schmidt number of the distilled state. We show that even simple non-Gaussian filters can be finely tuned to a ∼67% net gain of the initial entanglement generated in the SPDC process.