Hormonal profiles and biomarkers leading to parturition in cattle†.

This study aimed to understand the physiological mechanisms regulating parturition and to identify potential biomarkers to predict onset of birth. Additionally, we compared hormone profiles between cows with shorter and longer gestation lengths. Twenty-eight days before due date until 3d postpartum, cows (n = 18) were blood-sampled daily.

Autoimmune Disorders Associated With Surgical Remission of Cushing's Disease : A Cohort Study.

Background: Glucocorticoids suppress inflammation. Autoimmune disease may occur after remission of Cushing's disease (CD). However, the development of autoimmune disease in this context is not well described.

Clinically Recognized Depression and Mental Health Treatment in a Single Center Cohort of Patients with Systemic Sclerosis.

Introduction: In this study, we investigated the prevalence of depression, depression treatment, and symptom burden in patients with systemic sclerosis (SSc) and examined their associations with the center for epidemiologic studies depression scale revised (CESD-R) scores.

Methods: The Prospective Registry in Scleroderma at Massachusetts General Hospital (PRISM) is a longitudinal registry of patients with SSc. Among participants with CESD-R score ≥ 16, indicating possible depression, a chart review was performed for mental health diagnoses and treatments.

Treatment of plaque psoriasis with deucravacitinib (POETYK PSO-1 study): a plain language summary.

What Is This Summary About?: This is a summary of a paper published in a medical journal that describes the results of a study called POETYK PSO-1, which looked at a new treatment called deucravacitinib for plaque psoriasis. Plaque psoriasis appears on the body as round or oval raised patches (called plaques) typically covered by scales. This can cause the skin to itch, crack or bleed, and the associated itching and pain can make it difficult to perform basic everyday tasks.

Pre-Existing Autoimmune Disease Increases the Risk of Cardiovascular and Noncardiovascular Events After Immunotherapy.

Background: The use of immune checkpoint inhibitors (ICI) is associated with cardiovascular (CV) events, and patients with pre-existing autoimmune disease are at increased CV risk.

Objectives: The aim of this study was to characterize the risk for CV events in patients with pre-existing autoimmune disease post-ICI.

Methods: This was a retrospective study of 6,683 patients treated with ICIs within an academic network.

Effect of a multidisciplinary Severe Immunotherapy Complications Service on outcomes for patients receiving immune checkpoint inhibitor therapy for cancer.

Background: In 2017, Massachusetts General Hospital implemented the Severe Immunotherapy Complications (SIC) Service, a multidisciplinary care team for patients hospitalized with immune-related adverse events (irAEs), a unique spectrum of toxicities associated with immune checkpoint inhibitors (ICIs). This study's objectives were to evaluate the intervention's (1) effect on patient outcomes and healthcare utilization, and (2) ability to collect biological samples via a central infrastructure, in order to study the mechanisms responsible for irAEs.

Methods: A hospital database was used to identify patients who received ICIs for a malignancy and were hospitalized with severe irAEs, before (April 2, 2016-October 3, 2017) and after (October 3, 2017-October 24, 2018) SIC Service initiation.

Temporal Trends and Outcomes Among Patients Admitted for Immune-Related Adverse Events: A Single-Center Retrospective Cohort Study from 2011 to 2018.

Background: The aim of this study was to characterize severe immune-related adverse events (irAEs) seen among hospitalized patients and to examine risk factors for irAE admissions and clinically relevant outcomes, including length of stay, immune checkpoint inhibitor (ICI) discontinuation, readmission, and death.

Methods: Patients who received ICI therapy (ipilimumab, pembrolizumab, nivolumab, atezolizumab, durvalumab, avelumab, or any ICI combination) at Massachusetts General Hospital (MGH) and were hospitalized at MGH following ICI initiation between January 1, 2011, and October 24, 2018, were identified using pharmacy and hospital admission databases. Medical records of all irAE admissions were reviewed, and specialist review with defined criteria was performed.

Immunomodulation as Treatment for Severe Coronavirus Disease 2019: A Systematic Review of Current Modalities and Future Directions.

In severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, viral load peaks early and declines quickly after symptom onset. Severe coronavirus disease 2019 (COVID-19) is marked by aberrant innate and adaptive immune responses with an abnormal cytokine profile and multiorgan system dysfunction that persists well after viral clearance. A purely antiviral treatment strategy may therefore be insufficient, and antiviral agents have not shown a benefit later in the illness course.

Efficacy of Tocilizumab in Patients Hospitalized with Covid-19.

Background: The efficacy of interleukin-6 receptor blockade in hospitalized patients with coronavirus disease 2019 (Covid-19) who are not receiving mechanical ventilation is unclear.

Methods: We performed a randomized, double-blind, placebo-controlled trial involving patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hyperinflammatory states, and at least two of the following signs: fever (body temperature >38°C), pulmonary infiltrates, or the need for supplemental oxygen in order to maintain an oxygen saturation greater than 92%. Patients were randomly assigned in a 2:1 ratio to receive standard care plus a single dose of either tocilizumab (8 mg per kilogram of body weight) or placebo.

Calcinosis is associated with ischemic manifestations and increased disability in patients with systemic sclerosis.

Objective: Calcinosis is a debilitating complication of systemic sclerosis (SSc) with no effective treatments. We sought to identify clinical correlations and to characterize complications and disability associated with calcinosis in a multi-center, international cohort of SSc patients.

Methods: We established a cohort of 568 consecutive SSc patients who fulfill 2013 revised ACR/EULAR criteria at 10 centers within North America, Australia, and Mexico.

A case of Wong-type dermatomyositis treated with rituximab and IVIG.

A 37-year-old woman presented to our rheumatology-dermatology clinic with a rash, muscle weakness and fatigue. She has had prior diagnoses of cutaneous lupus and lichen planus based on skin biopsies. She did not respond to topical steroids, hydroxychloroquine and dapsone.

Rethinking the role of hydroxychloroquine in the treatment of COVID-19.

There are currently no proven or approved treatments for coronavirus disease 2019 (COVID-19). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID-19 are treated with these agents and more evidence accumulates, there continues to be no high-quality clinical data showing a clear benefit of these agents for this disease.

Immune-Related Adverse Events in the Setting of PD-1/L1 Inhibitor Combination Therapy.

In 2018, a multi‐disciplinary workshop was held at the Massachusetts General Hospital to discuss challenges in defining, diagnosing, and treating immune‐related adverse events (irAE), including those that occur in patients administered PD‐1/L1 inhibitor combination therapy. In this commentary, the workshop participants present a clinical case that illustrates the complexity of irAE diagnosis and management in a patient receiving PD‐1/L1 combination therapy, summarize the current state of PD‐1/L1 combination therapy, and discuss challenges and opportunities for the evaluation of irAEs as these combinations become more widely used to treat patients with cancer.

Diagnosis and Management of Rare Immune-Related Adverse Events.

Oncologic treatment is being revolutionized by a burgeoning number of immune checkpoint inhibitors (ICPis). To date, seven ICPis have received Food and Drug Administration approval, targeting cytotoxic T-lymphocyte antigen, programmed cell death, or programmed cell death ligand. Adverse events associated with checkpoint inhibition have been described in the literature.

Musculoskeletal rheumatic complications of immune checkpoint inhibitor therapy: A single center experience.

Background: The use of immune checkpoint inhibition (ICI) has revolutionized cancer treatment. However, these medications are associated with significant and potentially debilitating immune-related adverse events (irAEs). While certain toxicities have been well studied, rheumatic complications have been less widely recognized and characterized.

Survival benefit of statin use in ankylosing spondylitis: a general population-based cohort study.

Objectives: Recent studies have shown an increase in both cardiovascular and all-cause mortality in ankylosing spondylitis (AS). We examined the potential survival benefit of statin use in AS within a general population context.

Methods: We performed an incident user cohort study with time-stratified propensity score matching using a UK general population database between 1 January 2000 and 31 December 2014.

Evaluation and management approaches for scleroderma lung disease.

Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are leading causes of morbidity and mortality in systemic sclerosis (SSc). As symptoms are often under-reported in SSc, early screening of ILD and PAH is of paramount importance, and early treatment may be associated with better clinical outcomes. Serologies are particularly helpful in identifying patients at risk for pulmonary involvement.

PTEN Regulates Glutamine Flux to Pyrimidine Synthesis and Sensitivity to Dihydroorotate Dehydrogenase Inhibition.

Metabolic changes induced by oncogenic drivers of cancer contribute to tumor growth and are attractive targets for cancer treatment. Here, we found that increased growth of -mutant cells was dependent on glutamine flux through the pyrimidine synthesis pathway, which created sensitivity to the inhibition of dihydroorotate dehydrogenase, a rate-limiting enzyme for pyrimidine ring synthesis. S-phase -mutant cells showed increased numbers of replication forks, and inhibitors of dihydroorotate dehydrogenase led to chromosome breaks and cell death due to inadequate ATR activation and DNA damage at replication forks.

Pertussis Vaccine Effectiveness in the Setting of Pertactin-Deficient Pertussis.

Background: In the United States, the proportion of Bordetella pertussis isolates lacking pertactin, a component of acellular pertussis vaccines, increased from 14% in 2010 to 85% in 2012. The impact on vaccine effectiveness (VE) is unknown.

Methods: We conducted 2 matched case-control evaluations in Vermont to assess VE of the 5-dose diphtheria, tetanus, and acellular pertussis vaccine (DTaP) series among 4- to 10-year-olds, and tetanus, diphtheria, and acellular pertussis vaccine (Tdap) among 11- to 19-year-olds.