Review of the renal endpoints used in cardiovascular safety clinical trials in type 2 diabetes mellitus patients and their importance in primary care

Chronic kidney disease (CKD) is one of the most common complications of type 2 diabetes mellitus (T2DM). Furthermore, CKD confers a considerable increase in the risk of cardiovascular (CV) morbidity and mortality. In line with the need to improve knowledge in this field, this article aims to describe the renal endpoints used in the different cardiovascular outcome trials (CVOTs). The objective is to better know the renal variables used in the different CVOTs in order to optimize the implementation of advances in the prevention of progressive diabetic kidney disease in patients with T2DM in clinical practice.     

Does choice of antiretroviral drugs matter for inflammation?

Introduction: The massive implementation of combination antiretroviral therapy (cART) has forever changed the landscape of HIV infection. This unprecedented success has turned HIV infection into a manageable chronic disease. The increased survival of people living with HIV is, however, shadowed by a high burden of aging-related comorbidities. The pathogenic basis underlying this excess of co-morbid conditions is most likely a persistent inflammatory and immune activation state, despite an optimal control of HIV replication, which in turn has largely been attributed to bacterial or bacterial products translocation from the gut.

Area covered: This review is focused on the relationship between cART and the chronic inflammatory and immune activation status in otherwise virologically well-controlled people living with HIV (PLWH). Particular focus will be placed on the differences, if any, between distinct cART modalities, with emphasis on less-drug cART regimens, and especially on dual therapies.

Expert opinion: Research to address the increased inflammatory and immune activation status of cART-treated, HIV-infected patients, should focus on adjuvant means of therapy, rather than on the cART regime itself. With current antiretrovirals, no difference between dual and triple regimens has been demonstrated, provided that virological and immunological outcomes be non-inferior.     

Diagnostic Criteria for Primary Autoimmune Cerebellar Ataxia—Guidelines from an International Task Force on Immune-Mediated Cerebellar Ataxias

Aside from well-characterized immune-mediated ataxias with a clear trigger and/or association with specific neuronal antibodies, a large number of idiopathic ataxias are suspected to be immune mediated but remain undiagnosed due to lack of diagnostic biomarkers. Primary autoimmune cerebellar ataxia (PACA) is the term used to describe this later group. An International Task Force comprising experts in the field of immune ataxias was commissioned by the Society for Research on the Cerebellum and Ataxias (SRCA) in order to devise diagnostic criteria aiming to improve the diagnosis of PACA. The proposed diagnostic criteria for PACA are based on clinical (mode of onset, pattern of cerebellar involvement, presence of other autoimmune diseases), imaging findings (MRI and if available MR spectroscopy showing preferential, but not exclusive involvement of vermis) and laboratory investigations (CSF pleocytosis and/or CSF-restricted IgG oligoclonal bands) parameters. The aim is to enable clinicians to consider PACA when encountering a patient with progressive ataxia and no other diagnosis given that such consideration might have important therapeutic implications.

     

La fragilidad en candidatos a trasplante renal

Frailty is a concept that has been mainly developed in geriatrics and it came from the need of identifying subjects at risk to develop complications when they faced a stressful event. Frail patients have higher risk of mortality, poor outcomes and disability, and this is independent from their age or comorbidities. Chronic kidney disease patients present with high prevalence of frailty, especially those who are in renal replacement therapy. Frail or pre-frail patients on the kidney transplant waiting list represent 20-30%, and these patients are proven to have poorer results after the transplant, which is a stressful event itself. Tools for frailty assessment, both scales or indexes, may be useful to identify which subjects might be at risk for complications after transplant, and this is necessary to adapt our clinical practice and minimize morbidity. The most used frailty scale in kidney patients is Fried scale, which is based in five phenotypic items. Besides that, knowing frail population allows potential interventions such as prehabilitation while the patient is waiting for the kidney transplant, which the aim of improving their vulnerability prior to transplant and, therefore, optimizing results after transplant. More studies are needed amongst kidney patients to improve and prevent frailty.     

Comprehensive analysis of isolated der(1;7)(q10;p10) in a large international homogenous cohort of patients with myelodysplastic syndromes

The karyotype is a strong independent prognostic factor in myelodysplastic syndromes (MDS). Since the implementation of the new comprehensive cytogenetic scoring system for MDS, chromosome 7 anomalies are no longer generally assigned to poor risk features but are thoroughly separated. However, der(1;7)(q10;p10), hereinafter der(1;7), is merged into the group labeled “any other single” and belongs to the intermediate risk group, just by definition due to lack of adequate clinical data. The aim of our international collaborative was to clarify the “real” prognostic impact of der(1;7) on a homogenous and well‐documented data base. We performed detailed analysis of 63 MDS patients with isolated der(1;7) constituting the largest cohort hitherto reported. Furthermore, clinical data are compared with those of patients with isolated del(7q) and isolated monosomy 7. Median overall survival (OS) of patients with der(1;7) is 26 months (hazard ratio (HR) 0.91 for del(7q) vs der(1;7) and 2.53 for monosomy 7 vs der(1;7)). The der(1;7) is associated with profound thrombocytopenia most probably causing the reduced OS which is in striking contrast to the low risk for AML transformation (HR 3.89 for del(7q) vs der(1;7) and 5.88 for monosomy 7 vs der(1;7)). Molecular karyotyping indicates that der(1;7) is generated in a single step during mitosis and that a chromosomal imbalance rather than a single disrupted gene accounts for malignancy. Thus, the current cytogenetic scoring system assigning isolated der(1;7) to the intermediate risk group is now confirmed by a sufficient data set.     

Molecular profiling refines minimal residual disease‐based prognostic assessment in adults with Philadelphia chromosome‐negative B‐cell precursor acute lymphoblastic leukemia

Minimal residual disease (MRD) assessment is an essential tool in contemporary acute lymphoblastic leukemia (ALL) protocols, being used for therapeutic decisions such as hematopoietic stem cell transplantation in high‐risk patients. However, a significant proportion of adult ALL patients with negative MRD still relapse suggesting that other factors (ie, molecular alterations) must be considered in order to identify those patients with high risk of disease progression. We have identified partial IKZF1 gene deletions and CDKN2A/B deletions as markers of disease recurrence and poor survival in a series of uniformly treated adolescent and adult Philadelphia chromosome‐negative B‐cell progenitor ALL patients treated according to the Programa Español de Tratamientos en Hematología protocols. Importantly, CDKN2A/B deletions showed independent significance of MRD at the end of induction, which points out the need for treatment intensification in these patients despite being MRD‐negative after induction therapy.     

Mutations in TIMM50 cause severe mitochondrial dysfunction by targeting key aspects of mitochondrial physiology

3‐Methylglutaconic aciduria (3‐MGA‐uria) syndromes comprise a heterogeneous group of diseases associated with mitochondrial membrane defects. Whole‐exome sequencing identified compound heterozygous mutations in TIMM50 (c.[341 G>A];[805 G>A]) in a boy with West syndrome, optic atrophy, neutropenia, cardiomyopathy, Leigh syndrome, and persistent 3‐MGA‐uria. A comprehensive analysis of the mitochondrial function was performed in fibroblasts of the patient to elucidate the molecular basis of the disease. TIMM50 protein was severely reduced in the patient fibroblasts, regardless of the normal mRNA levels, suggesting that the mutated residues might be important for TIMM50 protein stability. Severe morphological defects and ultrastructural abnormalities with aberrant mitochondrial cristae organization in muscle and fibroblasts were found. The levels of fully assembled OXPHOS complexes and supercomplexes were strongly reduced in fibroblasts from this patient. High‐resolution respirometry demonstrated a significant reduction of the maximum respiratory capacity. A TIMM50‐deficient HEK293T cell line that we generated using CRISPR/Cas9 mimicked the respiratory defect observed in the patient fibroblasts; notably, this defect was rescued by transfection with a plasmid encoding the TIMM50 wild‐type protein. In summary, we demonstrated that TIMM50 deficiency causes a severe mitochondrial dysfunction by targeting key aspects of mitochondrial physiology, such as the maintenance of proper mitochondrial morphology, OXPHOS assembly, and mitochondrial respiratory capacity.     

Roughness and bonding strength of bioactive apatite layer on dental implants

This study examined the roughness and bonding strength of the chemical-made apatite layer in comparison with the titanium surface and the plasma-sprayed apatite. Commercially pure titanium plates were heated and chemically treated to deposit crystalline apatite on their surface. The roughness of the titanium surface of the original samples and the apatite surface was analyzed by a roughness surface tester. A scratch test was used to compare the adhesion of the chemical apatite layer to the titanium with the adhesion of a plasma-sprayed layer. A dense bone-like apatite layer was formed on the surface of the titanium by a simple chemical method. The surface roughness test showed that the chemical apatite coating increased the roughness of the samples. The scratch test showed that the bonding strength of the chemical-made apatite coatings to the titanium substrate was higher than the plasma-sprayed apatite coatings. The apatite layer produced by chemical treatment did not show a lower roughness than the titanium substrate. This chemical apatite layer also bonded tighter to the titanium than the plasma-sprayed apatite. This chemically made apatite coating is expected to provide a long-term implant-bone fixation.     

Evolución del cierre de ileostomía en una unidad de cirugía colorrectal. Análisis comparativo según la técnica

Introduction

The objective of this study is to assess whether the results of loop ileostomy closure in terms of morbidity and hospital stay are influenced by the type of anastomosis and suture used.

Method

All patients who underwent loop ileostomy closure were reviewed. A retrospective cohort study comparing morbidity and hospital stay according to the type of anastomosis (TT/LL) and the type of suture (hand sewn/mechanical) was performed.

Results

From January 2003 to November 2011 a total of 167 loop ileostomy closures were analized. The groups were: type of anastomosis (TT 95/LL 72) and type of suture (manual 105/stapled 62). In 76% of the observed population the underlying disease was cancer. Mortality occurred in one case. The stratified morbidity analysis by type of complications showed no significant differences between the groups in terms of local (7.4% TT, LL 8.3%, 6.7% hand sewn, stapled 9.7%), general (TT 9.5%, 16.7% LL, hand sewn 6.7%, 6.5% stapled) and surgical (TT 15.8%, 19.4% LL, hand sewn 17.1%, 17.7% stapled) complications, nor in the rate of reoperations (TT 6.3%, 6.9% LL, hand sewn 6.7%, 6.5% stapled) and hospital stay in days (TT 7.8, 8 LL, hand sewn 8.6, stapled 6.7)

Conclusions

Closure of loop ileostomy can be performed regardless of the type of suture or anastomosis used, with the same rate of morbidity and hospital stay.