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Pericardial effusion (PEF) in PAH may be a marker of worsening disease or associated with autoimmune conditions. Sotatercept was not initially reported as associated with the development or progression of PEF. We describe PAH patients taking sotatercept who were found to have new or worsening PEF and examine associated comorbidities.

Purpose of Review Prostacyclin pathway medications have been shown to be highly efficacious in the treatment of pulmonary arterial hypertension (PAH) through multiple prospective clinical trials and more than two decades of clinical experience. The strongest support for prostacyclin use in PAH management is with parenteral administration. Numerous risks and limitations of parenteral delivery systems as well as significant patient burdens restrict widespread parenteral use. Highly effective and tolerable oral prostacyclin preparations to manage PAH have long been sought. We review the development of the oral prostacyclin agents beraprost, treprostinil, and selexipag and including current indications and limitations. Research into new approaches to the management of PAH, expanding indications for existing agents, and development of novel agents are also discussed. Recent Findings Two oral prostacyclin pathway medications, oral treprostinil and selexipag, were FDA approved in December 2013 and 2015, respectively. Current guidelines recommend use of selexipag in WHO-FC II and III (class 1, level B recommendation) and oral treprostinil in WHO-FC III (class 2b, level B recommendation). The use of these medications is challenging due to complexity in dosing and their side effect profiles which limit patient tolerability and acceptance. Summary There is a promising role for oral prostacyclin pathway medications in patients with PAH. Future investigations are underway of alternative dose regimens and transitioning from parenteral therapies in order to improve efficacy and tolerability.

Background Pneumonia is the most common infection after out-of-hospital cardiac arrest (OHCA) occurring in up to 65% of patients who remain comatose after return of spontaneous circulation. Preventing infection after OHCA may (1) reduce exposure to broad-spectrum antibiotics, (2) prevent hemodynamic derangements due to local and systemic inflammation, and (3) prevent infection-associated morbidity and mortality. Methods The ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arrest (PROTECT) trial is a randomized, placebo-controlled, single-center, quadruple-blind (patient, treatment team, research team, outcome assessors), non-commercial, superiority trial to be conducted at Maine Medical Center in Portland, Maine, USA. Ceftriaxone 2 g intravenously every 12 h for 3 days will be compared with matching placebo. The primary efficacy outcome is incidence of early-onset pneumonia occurring < 4 days after mechanical ventilation initiation. Concurrently, T cell-mediated inflammation bacterial resistomes will be examined. Safety outcomes include incidence of type-one immediate-type hypersensitivity reactions, gallbladder injury, and C lostridioides difficile -associated diarrhea. The trial will enroll 120 subjects over approximately 3 to 4 years. Discussion The PROTECT trial is novel in its (1) inclusion of OHCA survivors regardless of initial heart rhythm, (2) use of a low-risk antibiotic available in the USA that has not previously been tested after OHCA, (3) inclusion of anti-inflammatory effects of ceftriaxone as a novel mechanism for improved clinical outcomes, and (4) complete metagenomic assessment of bacterial resistomes pre- and post-ceftriaxone prophylaxis. The long-term goal is to develop a definitive phase III trial powered for mortality or functional outcome. Trial registration ClinicalTrials.gov NCT04999592 . Registered on August 10, 2021.

Pulmonary hypertension is a condition with high morbidity and mortality. Resting transthoracic echocardiography is a pivotal diagnostic and screening test for pulmonary hypertension. The role of exercise stress echocardiography in the diagnosis of pulmonary hypertension is not well-established. We studied right ventricular size changes during exercise using exercise stress echocardiography to assess differences between normal and pulmonary hypertension patients and evaluate test safety, feasibility, and reproducibility. Healthy control and pulmonary hypertension patients performed recumbent exercise using a bicycle ergometer. Experienced echocardiography sonographers recorded the following resting and peak exercise right ventricular parameters using the apical four chamber view: end-diastolic area; end-systolic area; mid-diameter; basal diameter; and longitudinal diameter. Two cardiologists masked to clinical information subsequently analyzed the recordings. Parameters with acceptable inter-rater reliability were analyzed for statistical differences between the normal and pulmonary hypertension patient groups and their association with pulmonary hypertension. We enrolled 38 healthy controls and 40 pulmonary hypertension patients. Exercise stress echocardiography testing was found to be safe and feasible. Right ventricular size parameters were all readily obtainable and all had acceptable inter-observer reliability except for right ventricular longitudinal diameter. During exercise, healthy controls demonstrated a decrease in right ventricular end-systolic area, end-diastolic area, mid-diameter, and basal diameter (P < 0.05). Conversely, pulmonary hypertension patients demonstrated an increase in right ventricular end-systolic area, end-diastolic area, and mid-diameter (P < 0.05). These changes were unaffected by multivariate corrections. The sensitivity for pulmonary hypertension of an increase in right ventricular size was 97.2% with a negative predictive value of 95.2%. The ROC C-statistic for increase in right ventricular size was 0.93. This transient exertional dilation (TED) of the right ventricle is observed in pulmonary hypertension patients but not in healthy controls. Recumbent right ventricular exercise stress echocardiography is a feasible and safe diagnostic test for pulmonary hypertension which warrants additional study.

Pulmonary arterial hypertension (PAH) is a progressive potentially fatal disease. Multiple pharmacologic options are now available, which facilitated transitions between different therapeutic options, although the evidence for such transitions has not been well described. We sought to review the evidence supporting the safety and/or efficacy of transitioning between PAH-specific medications. We performed a systematic review of all published studies in the Medline database between 1 January 2000 and 30 June 2016 reporting on any transition between the currently Food and Drug Administration (FDA)-approved PAH-specific medications. Studies reporting on three or more adult patients published in the English language reporting on transitions between FDA-approved PAH medications were extracted and tabulated. Forty-one studies met the selection criteria, nine of which included less than eight patients (and thus were reported separately in the supplement), for a total of 32 studies. Transitioning from parenteral epoprostenol to parenteral treprostinil appears to be safe and efficacious in patients who have less severe disease and more favorable hemodynamics. Transitioning from a prostacyclin analogue to an oral medication may be successful in patients who have favorable hemodynamics and stable disease. There is conflicting evidence supporting the transition from a parenteral to an inhaled prostacyclin analogue, even in patients who are on background oral therapy. Currently, the only evidence in support of transitioning between oral PDE5 inhibitors is from sildenafil to tadalafil. Patients on higher doses of sildenafil are more likely to fail. In patients with liver abnormalities due to bosentan or sitaxentan, the transition to ambrisentan appears to be safe and can result in clinical improvement. Studies regarding PAH medication transitions are limited. Patients who have less severe disease, better functional status, and are on lower medications doses may be more successful at transitioning.

To study the clinical characteristics and prognosis of patients with diffuse pulmonary arteriovenous malformations (AVMs). Retrospective chart review of all patients (n = 16) with diffuse pulmonary AVMs seen at Yale New Haven Hospital, Johns Hopkins Hospital, and St. Michael's Hospital. Up-to-date follow-up information was obtained in all living patients. All patients were severely hypoxic. Neurologic complications (stroke or brain abscess) had occurred in 70% of patients by the time of diagnosis. During the follow-up period (mean, 6 years), three patients died and two others developed new neurologic complications. One of the deaths occurred perioperatively during lung transplantation. All patients underwent transcatheter embolotherapy of any large pulmonary AVMs. A selected group underwent pulmonary flow redistribution, a novel technique. Oxygenation did not improve significantly with embolotherapy of the larger AVMs, but there was a small significant improvement in those patients who underwent pulmonary flow redistribution. The majority (85%) of the living patients are currently working or studying full-time. Patients with diffuse pulmonary AVMs are at increased risk of neurologic complications. Transcatheter embolotherapy does not significantly improve the profound hypoxia, but it may reduce the risk of neurologic complications. Antibiotic prophylaxis is recommended for bacteremic procedures to prevent brain abscess. These patients can live for many years and lead productive lives. We do not recommend lung transplantation because survival with disease is difficult to predict and we have observed a perioperative transplant death.

Myosin diversity in the human epithelial cell line Caco-2BBe, the porcine epithelial cell line LLC-PK1(CL-4), human peripheral blood leukocytes, and human liver was analyzed. PCR amplification yielded 8-11 putative myosins (depending on the cDNA source) representing six distinct myosin classes. Analysis of clones obtained by hybridization screening demonstrated that the original PCR products correspond to bona fide myosins, based on the presence of sequences highly conserved in other myosins. RNase protection analysis confirmed mRNA expression of 11 myosins in Caco-2BBecells. Immunoblot analysis showed that at least 6 myosin immunogens are expressed in Caco-2BBecells. The results reveal the existence of at least 11 unconventional human myosin genes, most of which are expressed in an overlapping fashion in different cell types. The abundance of myosins suggests that the myosin I vs. myosin II paradigm is inadequate to explain actin-based cellular motility.

To compare the relative numbers andhospital course of men vs women admitted at least twice with asthma orstatus asthmaticus to Yale-New Haven Hospital (YNHH) during the periodfrom 1985 to 1994. A retrospective chartreview. YNHH. High-risk men and women (age range, 18 to 50 years) admitted at leasttwice during the study period with the discharge diagnosis of asthma orstatus asthmaticus. Of 561 adult asthmapatients admitted during the study period, 188 were admitted at leasttwice and accounted for 68% of the total asthma admissions. Onehundred three of the 188 patients were randomly selected, and all oftheir asthma admissions were retrospectively reviewed. The 103 patientsaccounted for 382 admissions. Seventy-two percent of these patients and68.6% of the admissions were women. The proportions of each genderrequiring admission to the medical ICU (15.65% women vs 11.67% men)or intubation (8.00% women vs 5.80% men) were not significantlydifferent. Women did exhibit a definite trend toward longer admissions(4.92 days vs 4.04 days; p < 0.554). A significantly higherproportion of female patient admissions underwent initial arterialblood gas analysis than men (56.9% vs 44.2%; p < 0.05). Factorialanalysis demonstrated a highly significant main effect of gender on, Pco2 levels (p < 0.0001). Men, overall, hadhigher Pco2 levels than women (48.73 mm Hg vs41.04 mm Hg; p < 0.036). Male patients admitted to the medical ICUor requiring intubation had significantly higher, Pco2 levels than their respective femalecounterparts (p < 0.05). At YNHH, 68% of all admissions for asthma in this age group are attributable tohigh-risk patients. High-risk female patients are admitted twice asoften as high-risk male patients and tend to have longer admissions. Once admitted, however, the proportion of men and women requiring themedical MICU or intubation were similar. High-risk male patients onpresentation are consistently more hypercapneic than high-risk femalepatients. Therefore, the mechanisms contributing to the genderdifferences in asthma admissions may include differences in theventilatory response to hypercapnea or in the tolerance to airwayobstruction.

We describe a case of pulmonary hypertension, initially thought to be idiopathic, which resolved after treatment of Graves' hyperthyroidism. Results of pulmonary artery catheterization before and after treatment are reported, and the effects of thyrotoxicosis on hemodynamics and pulmonary function are briefly reviewed. Possible mechanisms for development of pulmonary hypertension caused by hyperthyroidism include pulmonary vascular endothelial dysfunction or damage because of autoimmunity or the high cardiac output state, or increased metabolism of intrinsic pulmonary vasodilators.