Chronic Pain,Functional Status,and Life Satisfaction Are Associated With Patients Living With HIV Discussing Advance Care Planning With Their Family or Friends

Context

In the era of effective antiretroviral therapy, persons living with HIV/AIDS (PLWHA) are living longer, transforming HIV from a universally fatal disease to a serious chronic illness, warranting discussions between patients and their loved ones about advance care planning (ACP). Evidence is needed on factors associated with patients' likelihood to discuss ACP with loved ones.

Impacto del primer año de tratamiento sustitutivo renal en la hospitalización de una comunidad autónoma

Introduction and objectivesChronic kidney disease has a high prevalence and economic impact, and an increased risk of hospitalization. Although there are public regional and country registries, we have not found references to estimate the impact of renal replacement therapy (RRT) on hospital admissions.MethodsWe obtained authorization from the ethics committee and health authorities to integrate the REMER [Madrid Kidney Disease Registry] (2013-2014) and Minimum Basic Data Set (2013-2015) databases and to analyze the admissions during the first year of RRT.Results767 patients started RRT in all the hospitals of our region across all RRT modalities. More than a third of the patients start dialysis during a hospital admission. This unplanned start, more common in HD than PD, shows relevant differences in patient profile or admission characteristics.Without considering this initial episode, almost 60% of patients were admitted during their first year. The hospitalization rate was 1.2 admissions/patient, higher in HD than in TX or PD; the mean length of stay was 8.6 days.The estimated cost of admissions during the first year is €12,006/patient. Our analysis ensures the exhaustive inclusion of all episodes and accurate estimation based on the discharge form.ConclusionThe impact of RRT on hospitals has been underestimated and is very relevant when calculating the total cost of RRT. Results from other countries cannot be extrapolated due to differences in the health system and patient profile. The integration of clinical databases could open up an opportunity that needs only institutional support for its development.     

Importance of monitoring zones in the detection of arrhythmias in patients with implantable cardioverter-defibrillators under remote monitoring

Introduction

Implantable cardioverter-defibrillator (ICD) monitoring zones (MZ) provide passive features that do not interfere with the functioning of active treatment zones. However, it is not known for certain whether programming an MZ affects arrhythmia detection by the ICD. The aim of the present study is to assess the clinical relevance of MZ in a population of patients with ICDs.

Oncogenic properties and signaling basis of the PAX8-GLIS3 fusion gene

Hyalinizing trabecular tumors of the thyroid are rare and mostly benign epithelial neoplasms of follicular cell origin, which have recently been shown to be underpinned by the PAX8-GLIS3 fusion gene. In our study, we sought to investigate the potential oncogenic mechanisms of the PAX8-GLIS3 fusion gene. Forced expression of PAX8-GLIS3 was found to increase proliferation, clonogenic potential and migration of human nonmalignant thyroid (Nthy-ori 3-1) and embryonic kidney (HEK-293) cells. Moreover, in xenografts, Nthy-ori 3-1 PAX8-GLIS3 expressing cells generated significantly larger and more proliferative tumors compared to controls. These oncogenic effects were found to be mediated through activation of the Sonic Hedgehog (SHH) pathway. Targeting of smoothened (SMO), a key protein in the SHH pathway, using the small molecule inhibitor Cyclopamine partially reversed the increased proliferation, colony formation and migration in PAX8-GLIS3 expressing cells. Our data demonstrate that the oncogenic effects of the PAX8-GLIS3 fusion gene are, at least in part, due to an increased activation of the SHH pathway.     

Severe epidermolysis bullosa simplex phenotype caused by codominant mutations p.Ile377Thr in keratin 14 and p.Gly138Glu in keratin 5

Epidermolysis bullosa simplex (EBS) is a rare skin disease usually inherited in an autosomal dominant pattern. EBS is resulting from mutations in keratin 5 (KRT5) and keratin 14 (KRT14) genes encoding the keratins 5 and 14 proteins expressed in the keratinocytes of the basal layer of the epidermis. To date, seven pathogenic mutations have been reported to be responsible for EBS in the Canadian population from the province of Quebec: p.Pro25Leu, p.Leu150Pro, p.Met327Thr and p.Arg559X in KRT5; p.Arg125Ser, p.Ile377Thr and p.Ile412Phe in KRT14. Here, we present a novel French-Canadian patient diagnosed with EBS confined to the soles but presenting a severe complication form including blisters, hyperkeratosis, skin erosions and toenail abnormalities. Mutation screening was performed by direct sequencing of the entire coding regions of KRT5 and KRT14 genes and revealed the previously reported missense heterozygous mutation c. 1130T > C in KRT14 (p.Ile377Thr). Furthermore, this patient is carrying a second mutation in KRT5, c.413G > A (p.Gly138Glu), which has been linked to an increased risk of basal cell carcinoma in the literature. We suspect an impact of the p.Gly138Glu variant on the EBS phenotype severity of the studied patient. The pathogenicity and consequences of both genetic variations were simulated by in silico tools.