A Novel Nomogram to Identify Candidates for Extended Pelvic Lymph Node Dissection Among Patients with Clinically Localized Prostate Cancer Diagnosed with Magnetic Resonance Imaging-targeted and Systematic Biopsies

Background

Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.

Genotypes and haplotypes in the IL-1 gene cluster: analysis of two genetically and diagnostically distinct groups of Alzheimer patients

Increased risk of Alzheimer's disease (AD) has been associated with polymorphisms in the IL-1 gene cluster, and in particular with the IL-1alpha-889 T/T genotype. However, this association is still unclear, and needs further investigation. In order to clarify the role of these polymorphisms in the complex pathogenesis of AD we examined genotype and haplotype frequencies of the two C-to-T SNPs at position -889 and -551 in the IL-1alpha and IL-1beta genes, respectively, and of the 86 bp VNTR intron-2 polymorphisms in the IL-1Ra gene. The analysis was performed in two genetically and diagnostically distinct groups of sporadic AD from Italy and the USA. In the Italian group a significant association between the IL-1alpha-889 T/T genotype and AD (OR=3.022, 95% CI: 1.001-9.119) was found, whereas no difference was found in the group from the USA. Results were also compared with previously published studies that analyzed the same IL-1 polymorphisms in AD. In both groups, the analysis of the estimated haplotypes shows that AD patients and controls who carry the IL-1beta-511 C allele, were also more frequently carriers of the IL-1Ra 1 allele (haplotypes -C-1). The total frequency of the two -C-1 haplotypes (C-C-1 plus T-C-1) was about one half of the total frequency of the eight estimated haplotypes. This was confirmed by significant linkage disequilibrium between these two loci in both the Italian and USA groups. In the Italian group a weak association of the T-C-2 haplotype with the disease (OR=1.648, 95% CI: 1.519-1.788) was also found, whereas in the USA group no difference was found. Although ours and other published data on different samples of Caucasian and non-Caucasian AD show a great heterogeneity in the frequencies of the IL-1alpha-889, the IL-1beta-511 and the IL-1Ra VNTR gene polymorphisms, we confirm the role of the IL-1alpha-889 T/T genotype as a risk factor for sporadic AD, and show the presence of an allelic association between IL-1beta C and IL-1Ra 1 alleles in both the Italian and the USA groups, confirmed by the presence of significant levels of linkage disequilibrium between these two loci.     

Searching for archaic contribution in Africa

Abstract

Context: Africa’s role in the narrative of human evolution is indisputably emphasised in the emergence of Homo sapiens. However, once humans dispersed beyond Africa, the history of those who stayed remains vastly under-studied, lacking the proper attention the birthplace of both modern and archaic humans deserves. The sequencing of Neanderthal and Denisovan genomes has elucidated evidence of admixture between archaic and modern humans outside of Africa, but has not aided efforts in answering whether archaic admixture happened within Africa.

Objectives: This article reviews the state of research for archaic introgression in African populations and discusses recent insights into this topic.

Methods: Gathering published sources and recently released preprints, this review reports on the different methods developed for detecting archaic introgression. Particularly it discusses how relevant these are when implemented on African populations and what findings these studies have shown so far.

Results: Methods for detecting archaic introgression have been predominantly developed and implemented on non-African populations. Recent preprints present new methods considering African populations. While a number of studies using these methods suggest archaic introgression in Africa, without an African archaic genome to validate these results, such findings remain as putative archaic introgression.

Conclusion: In light of the caveats with implementing current archaic introgression detection methods in Africa, we recommend future studies to concentrate on unravelling the complicated demographic history of Africa through means of ancient DNA where possible and through more focused efforts to sequence modern DNA from more representative populations across the African continent.     

Producción científica en educación médica en Latinoamérica en Scopus, 2011-2015

Objective

To describe the scientific production in medical education in Latin America in Scopus, in the period 2011-2015.

The role of multiparametric MRI in active surveillance for low-risk prostate cancer: The ROMAS randomized controlled trial

BackgroundWe aim to evaluate the impact of multiparametric magnetic resonance imaging and fusion-target biopsy for early reclassification of patients with low-risk Prostate Cancer in a randomized trial.Materials and methodsBetween 2015 and 2018, patients diagnosed with Prostate Cancer after random biopsy fulfilling PRIAS criteria were enrolled and centrally randomized (1:1 ratio) to study group or control group. Patients randomized to study group underwent multiparametric magnetic resonance imaging at 3 months from enrollment: patients with positive findings (PIRADS-v2>2) underwent fusion-target biopsy; patients with negative multiparametric magnetic resonance imaging or confirmed ISUP - Grade Group 1 at fusion-target biopsy were managed according to PRIAS schedule and 12-core random biopsy was performed at 12 months. Patients in control group underwent PRIAS protocol, including a confirmatory 12-core random biopsy at 12 months. Primary endpoint was a reduction of reclassification rate at 12-month random biopsy in study group at least 20% less than controls. Reclassification was defined as biopsy ISUP Grade Group 1 in >2 biopsy cores or disease upgrading.ResultsA total of 124 patients were randomized to study group (n = 62) or control group (n = 62). Around 21 of 62 patients (34%) in study group had a positive multiparametric magnetic resonance imaging, and underwent fusion-target biopsy, with 11 (17.7%) reclassifications. Considering the intention-to-treat population, reclassification rate at 12-month random biopsy was 6.5% for study group and 29% for control group, respectively (P < 0.001).ConclusionsThe early employment of multiparametric magnetic resonance imaging for active surveillance patients enrolled after random biopsy consents to significantly reduce reclassifications at 12-month random biopsy.     

Comparison between small renal masses 0-2 cm vs. 2.1-4 cm in size: A population-based study

BackgroundThe NCCN guidelines recommend active surveillance (AS) as an option for the initial management of cT1a 0-2 cm renal lesions. However, data about comparison between renal cell carcinoma (RCC) 0-2 cm vs. 2.1-4 cm are scarce.MethodsWithin the Surveillance, Epidemiology, and End Results database (2002–2016), 46,630 T1a N_anyM_any stage patients treated with nephrectomy were identified. Data were tabulated according to histological subtype, tumor grade (low [LG] vs. high [HG]), as well as age category and gender. Additionally, rates of synchronous metastases were quantified.ResultsOverall, 69.3 vs. 74.1% clear cell, 21.4 vs. 17.6% papillary, 6.9 vs. 6.8% chromophobe, 2.0 vs. 1.1% sarcomatoid dedifferentiation, 0.2 vs. 0.2% collecting duct histological subtype were identified for respectively 0-2 cm and 2.1-4 cm RCCs. In both groups, advanced age was associated with higher rate of HG clear cell and HG papillary histological subtype. In 0-2 cm vs. 2.1-4 cm RCCs, 13.8% vs. 20.2% individuals operated on harbored HG tumors and were more prevalent in males. Lower synchronous metastases rates were recorded in 0-2 cm RCC and ranged from 0 in respectively multilocular cystic to 0.9% in HG papillary histological subtype. The highest synchronous metastases rates were recorded in sarcomatoid dedifferentiation histological subtype (13.8% and 9.7%) in both groups.ConclusionsRelative to 2.1-4 cm RCCs, 0-2 cm RCCs harbored lower rates of HG tumors, lower rates of aggressive variant histology and lower rates of synchronous metastases. The indications and demographics of patients selected for AS may be expanded in the future to include younger and healthier patients.     

Range of motion of foot joints following total ankle replacement and subtalar fusion

BackgroundIn severe cases of ankle and subtalar arthritis, arthrodesis of the subtalar joint is performed in combination with ankle arthroplasty. In these special cases gait analysis reveals real motion at the replaced tibiotalar joint.MethodsTwenty-three patients affected by ankle and subtalar arthritis, treated either with a 3-component or a 2-component prosthesis in combination with subtalar arthrodesis, were clinically evaluated preoperatively and at a minimum of 1-year follow-up. Gait analysis was performed postoperatively using a multi-segment foot protocol. Foot kinematics were compared to corresponding data from a healthy control group.ResultsClinical scores significantly improved from preoperative to follow-up. The clinically measured passive ankle dorsiflexion/plantarflexion significantly improved at the follow-up. Patients’ normalized walking speed and stride length were significantly lower than those in control. With exception of the ankle frontal-plane motion, sagittal-plane mobility of foot joints was about 50% than that in healthy joints.ConclusionsImprovement in clinical scores was found for both prostheses. Normal spatio-temporal parameters were not restored. In these patients, fusion of the subtalar joint appeared to be compensated by larger frontal-plane motion at the tibiotalar joint.Level of evidenceLevel III- retrospective comparative study.The study was approved by the local Ethics Committee as protocol MAT (protocol registration at clinicaltrials.gov NCT03356951).     

Feasibility of health-related quality of life (HRQoL) assessment for cancer patients using electronic patient-reported outcome (ePRO) in daily clinical practice

Quality of Life Research - Routine Electronic Monitoring of Health-Related Quality of Life (HRQoL) (REMOQOL) in clinical care with real-time feedback to physicians could help to enhance...     

SMC1 involvement in fragile site expression

Common fragile sites have been involved in neoplastic transformation, although their molecular basis is still poorly understood. Here, we demonstrate that inhibition of the SMC1 by RNAi is sufficient to induce fragile site expression. By investigating normal, ATM- and ATR-deficient cell lines, we provide evidence that the contribution of SMC1 in preventing the collapse of stalled replication fork is an Atr-dependent pathway. Using a fluorescent antibody specific for gamma-H2AX, we show that very rare discrete nuclear foci appear 1 and 2 h after exposure to aphidicolin and/or RNAi-SMC1, but became more numerous and distinct after longer treatment times. In this context, fragile sites might be viewed as an in vitro phenomenon originating from double-strand breaks formed because of a stalled DNA replication that lasted too long to be managed by physiological rescue acting through the Atr/Smc1 axis. We propose that in vivo, following an extreme replication block, rare cells could escape checkpoint mechanisms and enter mitosis with a defect in genome assembly, eventually leading to neoplastic transformation.