Immune-related adverse events in patients with pre-existing autoimmune rheumatologic disease on immune checkpoint inhibitor therapy.

Introduction: Immune checkpoint inhibitors (ICIs) enhance the immune system's ability to target and destroy cancer cells, but this non-specific immune overactivation can result in immune-related adverse events (irAEs). Patients with underlying autoimmune diseases were excluded from the original ICI clinical trials because of the theoretical risk of irAEs. This study aimed to evaluate the risk of irAEs in patients with pre-existing rheumatologic diseases on ICIs, impact of anti-rheumatic therapy on irAEs, and malignancy outcomes.

Novel non-classic CYP21A2 variants, including combined alleles, identified in patients with congenital adrenal hyperplasia.

Objective: Congenital adrenal hyperplasia (CAH) is an inborn error of metabolism and a common disorder of sex development where >90% of all cases are due to 21-hydroxylase deficiency. Novel and rare pathogenic variants account for 5% of all clinical cases. Here, we sought to investigate the functional and structural effects of four novel (p.

Safety and efficacy of thrombopoeitin mimetics for refractory immune thrombocytopenia purpura in patients with systemic lupus erythematosus or antiphospholipid syndrome: a case series.

Background While thrombopoeitin (TPO) agonists that act to simulate platelet production have been approved for use in steroid-refractory chronic immune thrombocytopenia purpura (ITP), there are few data on the safety and efficacy of these medications in patients with concurrent systemic lupus erythematosus (SLE) or antiphospholipid syndrome (APS). Given that these agents can increase all hematopoietic cell lineages, it is unclear if there is an increased risk for exacerbation of the underlying lymphocyte-driven autoimmune disease in this population. Case summaries This case series includes four patients with SLE, one with concurrent APS, who were treated for steroid-refractory ITP with TPO mimetics at the University of Virginia between 2005 and 2015.

Functional and Structural Consequences of Nine Mutations Ranging from Very Mild to Severe Effects.

We present the functional and structural effects of seven novel (p.Leu12Met, p.Arg16Cys, p.

Indicators of walking speed in rheumatoid arthritis: relative influence of articular, psychosocial, and body composition characteristics.

Objective: To explore the contributions from and interactions between articular swelling and damage, psychosocial factors, and body composition characteristics on walking speed in rheumatoid arthritis (RA).

Methods: RA patients underwent the timed 400-meter long-corridor walk. Demographics, self-reported levels of depressive symptoms and fatigue, RA characteristics, and body composition (using whole-body dual X-ray absorptiometry, and abdominal and thigh computed tomography) were assessed and their associations with walking speed explored.

Molecular diagnosis of 5α-reductase type II deficiency in Brazilian siblings with 46,XY disorder of sex development.

The steroid 5α-reductase type II enzyme catalyzes the conversion of testosterone (T) to dihydrotestosterone (DHT), and its deficiency leads to undervirilization in 46,XY individuals, due to an impairment of this conversion in genital tissues. Molecular analysis in the steroid 5α-reductase type II gene (SRD5A2) was performed in two 46,XY female siblings. SRD5A2 gene sequencing revealed that the patients were homozygous for p.

Folate intake, MTHFR genotype, and sex modulate choline metabolism in mice.

Choline and folate are interrelated in 1-carbon metabolism, mostly because of their shared function as methyl donors for homocysteine remethylation. Folate deficiency and mutations of methylenetetrahydrofolate reductase (MTHFR) reduce the availability of a major methyl donor, 5-methyltetrahydrofolate, which in turn may lead to compensatory changes in choline metabolism. This study investigated the hypothesis that reductions in methyl group supply, either due to dietary folate deficiency or Mthfr gene deletion, would modify tissue choline metabolism in a sex-specific manner.

Predictors of postoperative complications in high-risk octogenarians undergoing cardiac operations.

Background: Cardiac operations in octogenarians are currently reserved for selected patients with severe symptoms and low extracardiac comorbidity; early and midterm results are satisfactory. We evaluated the outcome of high-risk octogenarians undergoing cardiac operations and investigated the predictors of postoperative complications.

Methods: Between June 1998 and March 2001, 73 consecutive octogenarians (mean age = 83.

Tricuspid valve repair with the Cosgrove-Edwards annuloplasty system: early clinical and echocardiographic results.

Background: The use of flexible rings for tricuspid valve repair is becoming popular. The purpose of this study was to evaluate the Cosgrove-Edwards annuloplasty system for tricuspid regurgitation.

Methods: From June 1998 to December 2000, 22 patients with significant secondary tricuspid regurgitation underwent tricuspid valve repair with the Cosgrove-Edwards annuloplasty system.

[Reconstructive surgery of the mitral and tricuspid valves with a Cosgrove-Edwards flexible ring].

Background: Mitral and tricuspid valve asymmetric annular dilation represents the most important mechanism which produces insufficiency. Recent computerized in vitro and in vivo three-dimensional models have been developed in order to better understand the competing factors (annular dilation, displacement of papillary muscles, left and right ventricular geometry). The leading cause of mitral and tricuspid competence is a sphincteric action of both annuli, during systole and diastole, the loss of which produces asymmetric dilation and therefore the absence of cusp coaptation.

Perioperative prognostic value of dipyridamole echocardiography in vascular surgery: A large-scale multicenter study in 509 patients. EPIC (Echo Persantine International Cooperative) Study Group.

Background: Patients undergoing major vascular surgery are at a relatively high risk of cardiac events, and pharmacological stress echocardiography is increasingly used for perioperative risk stratification. The aim of the current study was to evaluate the value of dipyridamole echocardiography test (up to 0.84 mg/kg over 10 minutes) in predicting cardiac events in a large-scale, multicenter, prospective, observational study design.

Cardiologic complications of subarachnoid hemorrhage.

Cardiac complications are frequent in patients with subarachnoid hemorrhage (SAH). They include ECG abnormalities, cardiac arrhythmias, myocardial damage, and neurogenic pulmonary edema. The pathophysiology of these abnormalities is related to an imbalance of the autonomic cardiovascular control and to increased circulating and local myocardial tissue catecholamines.

Type and extent of myocardial injury related to brain damage and its significance in heart transplantation: a morphometric study.

Background: Focal myocardial necrosis reported in patients who died of brain lesions and in donor hearts soon after insertion has been attributed to catecholamine-related injury induced before operation, or in the perioperative period. Interpretation of the morphofunctional type of myocardial injury observed and its quantification may help understand both its pathophysiology and clinical relevance.

Methods: In 27 patients without heart disease who died of intracranial brain hemorrhage after berry aneurysm rupture, terminal clinical signs were correlated with the presence of absence of myocardial injury.

The value of dipyridamole echocardiography in risk stratification before vascular surgery. A multicenter study. The EPIC (Echo Persantine International Study) Group--Subproject: Risk Stratification Before Major Vascular Surgery.

Purpose: Patients undergoing major vascular surgery are at relatively high risk of cardiac events, and pharmacological stress echocardiography is increasingly used for peri-operative risk stratification.

Patients And Methods: One hundred and twenty-one patients undergoing vascular surgery (age 65 +/- 7 years) were studied by dipyridamole echocardiography testing in six different centres. Of the total 136 patients, 15 were subsequently excluded because surgery was either cancelled (n = 8) or postponed pending cardiac revascularization (n = 7) because of the presence of a 'high-risk' stress echo response (identified 'a priori' as a positive dipyridamole echocardiography testing with a dipyridamole-time < 5 min and/or a peak wall motion score index > 2, upon scoring each segment from 1 = normal to 4 = dyskinetic in an 11-segment model).

Preoperative noninvasive coronary risk stratification in candidates for carotid endarterectomy.

Background And Purpose: Patients with symptomatic carotid stenosis who are candidates for carotid endarterectomy are at high short- and long-term risk of coronary events. To stratify patients at different risk of coronary events we investigated the usefulness of a noninvasive preoperative cardiological workup.

Methods: We studied 172 consecutive patients admitted to the Neurosurgical Department for symptomatic high-grade (70% to 99%) carotid stenosis (age, 42 to 74 years; mean, 57.

Frequency and prognostic significance of silent coronary artery disease in patients with cerebral ischemia undergoing carotid endarterectomy.

To evaluate the prevalence and prognostic role of silent coronary artery disease (CAD) in patients with symptomatic high-grade carotid stenosis (70 to 99%) undergoing carotid endarterectomy, and with neither history nor symptoms of CAD, 106 patients (76 men, 30 women, mean age 58.7 years [range 42 to 71]) with recent cerebral ischemia were prospectively studied. Patients were stratified as to the presence (n = 27, 25%) or absence (n = 79, 75%) of silent CAD defined by concordant abnormal exercise electrocardiographic testing and thallium-201 myocardial scintigraphy.

Heart-brain interactions in cerebral ischaemia: a non-invasive cardiologic study protocol.

The cardiologic evaluation of patients with cerebral ischaemia should be aimed at: (1) identifying potential cardiac sources for cerebral emboli, (2) detecting a coexisting ischaemic heart disease, even asymptomatic. The present data concerns a ten-year experience of a systematic cardiologic evaluation of patients admitted to the 1st Division of Neurosurgery, Bellaria Hospital, Bologna, Italy, for cerebral ischaemia. A two-dimensional echocardiography was carried out in 344 consecutive patients (mean age 53 years), cardiac abnormalities were observed in 92 (28%) out of the 328 cases with technically adequate examination, embologenic lesions in 57 (17%).

Etiopathogenesis and prognosis of cerebral ischemia in young adults. A survey of 155 treated patients.

Etiology and long-term prognosis were prospectively investigated in 155 consecutive patients (96 men and 59 women), aged 16 to 45 years, referred to our Neurosurgical Unit with cerebral transient ischemic attacks or infarction during the period 1978-1988. All patients underwent neurological and medical-cardiological evaluation, cerebral computerized tomography scanning, electrocardiogram, and laboratory tests. Two-dimensional echocardiography was performed in 123 cases (79%), cerebral angiography in 147 (95%).

[Cardiopathy and acute cerebrovascular insufficiency. Prospective study with two-dimensional echocardiography].

Many cardiac disorders can cause acute cerebrovascular insufficiency. The spectrum of potentially embolic cardiac conditions is wide; early recognition may determine a definite change in the management and prognosis of patients. In recent years the relevance of echocardiography in the screening of patients with cerebral ischemia has been emphasized.

Comparative efficacy of nicardipine, a new calcium antagonist, versus nifedipine in stable effort angina.

The relative efficacy of nicardipine and nifedipine was examined in a double-blind placebo-controlled randomized crossover trial. We studied 12 patients with chronic effort angina involving reproducible angina and greater than or equal to 1.5 mm of ST-segment depression on exercise treadmill test performed before and after a 1-week control period of single-blind placebo administration.