Calcium-sensing receptor autoantibodies are relevant markers of acquired hypoparathyroidism

We investigated the presence of autoantibodies (aAbs) directed against the parathyroid gland in 17 patients with spontaneous isolated acquired hypoparathyroidism. Fourteen patients with acquired hypoparathyroidism (AH) associated with type I or II autoimmune polyendocrinopathy syndrome were also tested in comparison with a control group of 68 subjects without AH, including patients with other autoimmune diseases and healthy blood donors. aAbs against parathyroid tissue were screened using an indirect immunofluorescence technique on primate parathyroid tissue and human parathyroid adenoma. aAbs against the calcium-sensing receptor (CaSR) were analyzed using an immunoblotting assay with the recombinant extracellular domain of the human CaSR as antigen. Seven of the 31 patients with AH were positive for CaSR aAbs. Five of the positive sera were obtained from the group with isolated AH. The two other positive sera were from patients with autoimmune polyendocrinopathy syndrome. The sensitivity of the immunoblotting technique was higher than that of both the radioimmunological test using the extracellular domain of the CaSR and the indirect immunofluorescence technique. There were no positive sera in the control group. In conclusion, using an immunoblotting assay, we demonstrate the presence of CaSR aAbs in about one third of the patients with isolated AH, pointing out the value of detecting such aAbs to assess the autoimmune origin of the disease.     

Prognostic value of aerobic capacity and exercise oxygen pulse in postaortic dissection patients

BackgroundAlthough recommendations encourage daily moderate activities in post aortic dissection, very little data exists regarding cardiopulmonary exercise testing (CPET) to personalize those patient''s physical rehabilitation and assess their cardiovascular prognosis.DesignWe aimed at testing the prognostic insight of CPET regarding aortic and cardiovascular events by exploring a prospective cohort of patients followed‐up after acute aortic dissection.MethodsPatients referred to our department after an acute (type A or B) aortic dissection were prospectively included in a cohort between September 2012 and October 2017. CPET was performed once optimal blood pressure control was obtained. Clinical follow‐up was done after CPET for new aortic event and major cardio‐vascular events (MCE) not directly related to the aorta.ResultsAmong the 165 patients who underwent CPET, no adverse event was observed during exercise testing. Peak oxygen pulse was 1.46(1.22‐1.84) mlO2/beat, that is, 97 (83–113) % of its predicted value, suggesting cardiac exercise limitation in a population under beta blockers (92% of the population). During a follow‐up of 39(20‐51) months from CPET, 42 aortic event recurrences and 22 MCE not related to aorta occurred. Low peak oxygen pulse (<85% of predicted value) was independently predictive of aortic event recurrence, while low peak oxygen uptake (<70% of predicted value) was an independent predictor of MCE occurrence.ConclusionCPET is safe in postaortic dissection patients should be used to not only to personalize exercise rehabilitation, but also to identify those patients with the highest risk for new aortic events and MCE not directly related to aorta.     

Trastuzumab-induced cardiotoxicity in elderly women with HER-2-positive breast cancer: a meta-analysis of real-world data

Background: We conducted a meta-analysis to assess the overall risk of cardiac toxicity associated with trastuzumab treatment in elderly breast cancer patients.

Methods: We searched databases from PubMed, EMBASE and Cochrane Central Registry of Controlled Trials to identify relevant studies. Statistical analyses were conducted to calculate the incidence rate, overall hazard ratio (HR) and 95% CIs using a fixed effects model.

Results: A total of 116,342 and 360 elderly patients from five cohort studies and two randomized clinical trials (RCTs) were included for analysis. The pooled incidences of symptomatic congestive heart failure (CHF) and CHF/HF/CM were 6.4% (95% CI 4.1% – 9.4) and 16.4% (95% CI 16.19% – 16.61) in patients with median age of 67.5 years from two RCTs and in patients with median age of 67.5 (60 – 75), 71 (66 – 80+), 74.5 (65 – 89), 75 (66 – 81+) and 79.5 (60 – 99) from five cohort studies, respectively. Trastuzumab was significantly correlated with an increased risk of defined cardiac toxicities in five cohort studies (HR = 1.89, 95% CI 1.72 – 2.07, p < 0.00001) and two RCTs (HR = 3.00, 95% CI 1.71, 5.26, p < 0.00001). Sub-group analysis showed that the anthracycline-based chemotherapy increased the risk of CHF/HF and CM in patients among five cohort studies (HR = 2.16, 95% CI: 1.8 – 1.87, p < 0.00001).

Conclusion: Trastuzumab is likely associated with an increased risk of cardiac toxicity in elderly patients with HER-2-positive breast cancer. Carefully monitoring cardiac function in elderly patients receiving trastuzumab, particularly with concurrent use of anthracycline, is warranted.     

Host defense and inflammatory gene polymorphisms are associated with outcomes after HLA-identical sibling bone marrow transplantation

We made the hypothesis that donor and recipient gene polymorphisms that drive the host response to microorganisms could be associated with infections after bone marrow transplantation (BMT). HLA-identical BMT was performed for patients with acute (n = 39) or chronic leukemia (n = 68). Genotyping was performed in 107 D/R DNA pairs for gene polymorphisms of cytokines (tumor necrosis factor-alpha [TNF-alpha] and TNF-beta, interleukin-1 receptor antagonist [IL-1Ra], IL-6, and IL-10), adhesion molecules (CD31 and CD54), Fcgammareceptors (FcgammaRIIa, IIIa, IIIb), mannose-binding lectin (MBL), and myeloperoxidase (MPO). First infection (overall) and first episodes of bacterial, viral, or invasive fungal infection were studied retrospectively for 180 days after BMT. Univariate and multivariate analyses, using death as a competing event, were performed to study risk factors. In multivariate analysis, first overall infections were increased in patients with the FcgammaRIIa R-131 genotype (hazard ratio [HR] = 1.92; P =.04), and severe bacterial infections were increased when the MPO donor genotype was AG or AA (HR = 2.16; P =.03). Viral and invasive fungal infections were not influenced by any genetic factor studied. Interestingly, we also found that (1) time to neutrophil recovery was shorter when donors were FcgammaRIIIb HNA-1a/HNA-1b (HR = 1.77; P =.002); (2) donor IL-1Ra (absence of IL-1RN*2) increased the risk for acute graft-versus-host disease (GVHD) (II-IV) (HR = 2.17; P =.017); and (3) recipient IL-10 (GG) and IL-1Ra genotypes increased the risk for chronic GVHD (P =.03 and P =.03, respectively). Finally, 180-day transplantation-related mortality rates were increased when donors were FcgammaRIIIb HNA-1a/HNA-1a or HNA-1b/HNA-1b (HR = 2.57; P =.05) and donor MPO genotype was AA (HR = 5.14; P =.004). In conclusion, donor and recipient gene polymorphisms are informative genetic risk factors for selecting donor/recipient pairs and could help in the understanding of mechanisms involved in host defenses of BM transplant recipients.     

Characteristics of atherosclerotic plaque distribution in coronary artery bifurcations: an intravascular ultrasound analysis

OBJECTIVE: Vessel bifurcations are prone to atherosclerotic plaque accumulation. Using volumetric intravascular ultrasound analysis, we investigated atheroma distribution at human coronary bifurcations in vivo. METHODS: We analyzed plaque distribution in 49 left anterior descending coronary artery-diagonal and 20 left circumflex coronary artery-obtuse marginal bifurcations with <50% angiographic stenosis. Cross-sections were analyzed at 1 mm intervals in segments 5 mm proximal and distal from the bifurcation. Planimetry of the lumen and external elastic membrane (EEM) was performed and plaque thickness measured at four different points relative to the branch: 0 degrees, 90 degrees, 180 degrees and 270 degrees. EEM, lumen and plaque volume and percentage plaque burden (plaque volume/EEM volume) were calculated in the proximal and distal segments. The side-branch take-off angle was analyzed in the cross-sectional images. RESULTS: Volumetric analysis showed that EEM, lumen and plaque were larger (P<0.001) in proximal segments than distal segments, whereas percent plaque burden was similar in these segments. Plaque accumulated on the opposite wall to the flow divider. Plaque distribution tended to be more eccentric in distal segments (P=0.05) compared to proximal segments. In 26 of 69 lesions, an asymmetric side-branch take-off was found and was associated with asymmetric plaque distribution compared to those lesions that had a symmetric side-branch take-off (P<0.01). CONCLUSION: We found characteristic patterns of plaque distribution at coronary bifurcations. Proximal segments demonstrated larger plaque volume than distal segments, despite similar percentages of plaque burden. Plaque volume accumulated opposite to the flow divider, especially in distal segments. The side-branch take-off angle in the cross-sectional plane influenced the plaque distribution in bifurcation lesions.     

Rapid tranquilization: An audit of Irish mental health nursing practice

Rapid tranquillization is a pharmacological intervention sometimes employed in mental health care for the management of acute behavioural disturbance. It is a form of restrictive practice, which, along with seclusion and restraint, is a conventional and controversial intervention in the therapeutic management of risk in mental health settings. This study surveyed mental health nurses practice in rapid tranquillization. A self‐report questionnaire was utilized which addressed aspects such as definitions of rapid tranquillization, presence of rapid tranquillization policy, types of incidents where it is used and postintervention monitoring. The results demonstrate that rapid tranquillization is an intervention used in the management of acute behavioural disturbance in various mental health settings in Ireland. Respondents showed a basic understanding of rapid tranquillization as an intervention; however, some areas reported not having a specific rapid tranquillization policy. There was some evidence of a variation in postrapid tranquillization monitoring of psychiatric/mental health and physical health. Service user debriefing following rapid tranquillization was reported to be common; however, the content of this was not elaborated on. In the light of variations in practice, specific training and the development of rapid tranquillization policies are recommended.     

Optimized Cholesterol-siRNA Chemistry Improves Productive Loading onto Extracellular Vesicles

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