Emergence and Spread of a B.1.1.28-Derived P.6 Lineage with Q675H and Q677H Spike Mutations in Uruguay.

Uruguay controlled the viral dissemination during the first nine months of the SARS-CoV-2 pandemic. Unfortunately, towards the end of 2020, the number of daily new cases exponentially increased. Herein, we analyzed the country-wide genetic diversity of SARS-CoV-2 between November 2020 and April 2021. We identified that the most prevalent viral variant during the first epidemic wave in Uruguay (December 2020-February 2021) was a B.1.1.28 sublineage carrying Spike mutations Q675H + Q677H, now designated as P.6, followed by lineages P.2 and P.7. P.6 probably arose around November 2020, in Montevideo, Uruguay's capital department, and rapidly spread to other departments, with evidence of further local transmission clusters; it also spread sporadically to the USA and Spain. The more efficient dissemination of lineage P.6 with respect to P.2 and P.7 and the presence of mutations (Q675H and Q677H) in the proximity of the key cleavage site at the S1/S2 boundary suggest that P.6 may be more transmissible than other lineages co-circulating in Uruguay. Although P.6 was replaced by the variant of concern (VOC) P.1 as the predominant lineage in Uruguay since April 2021, the monitoring of the concurrent emergence of Q675H + Q677H in VOCs should be of worldwide interest.

Percutaneous pulmonary valve implantation (PPVI) in non-obstructive right ventricular outflow tract: limitations and mid-term outcomes.

BACKGROUND: Percutaneous pulmonary valve implantation (PPVI) has been established as a safe and effective alternative to surgery treating patients with a failing pulmonary valve conduit. Nevertheless, the majority of patients in need of a valve have a native, non-obstructive right ventricular outflow tract (RVOT). The current approved stent-valves have a balloon-expandable design. Pre-stenting of the RVOT to create a landing zone and also protect the valve stability is usually mandatory; large, non-obstructive RVOTs need pre-stenting to reduce the RVOT-diameter for a balloon-expandable valve implantation. METHODS: A retrospective study design was used to analyze the medium-term outcome after PPVI in a series of 26 patients with native or reconstructed RVOT. RESULTS: PPVI was successfully performed in all, but 1 (96%). Within the follow-up of a minimum of 2 years, the percutaneous implanted valves remained competent; a significant pressure gradient was not detected. Furthermore, no PPVI-related complications such as endocarditis, migration or stent fractures were observed. The electrocardiogram at rest, in particular the QRS duration remained unchanged immediate post-PPVI as well as at medium-term follow-up of 24 months. However, ventricular arrhythmias were documented in 3 patients (11.5%); all patients were successfully treated with antiarrhythmic drugs, utilizing metoprolol. A trial of an invasive catheter based RVOT-ablation in one remained unsuccessful; pre-stented RVOT did not allow a successful intervention. CONCLUSIONS: Medium-term follow-up showed excellent results of the mechanical valve function. PPVI utilizing balloon-expandable stent-valves in a native RVOT remains an off-label use. Despite our encouraging results, advanced manipulations of the patched or native RVOT might be associated with significant ventricular arrhythmias. There is a need for less invasive RVOT reduction devices.

Safety and effectiveness of vinflunine in patients with metastatic transitional cell carcinoma of the urothelial tract after failure of one platinum-based systemic therapy in clinical practice.

BACKGROUND: Patients with transitional cell carcinoma of the urothelial tract (TCCU) who fail initial platinum-based chemotherapy for advanced disease represent a challenge in daily clinical practice. Vinflunine is approved by the European Medicine Agency (EMA) but, up to now, limited experience has been reported outside clinical trials. METHODS: We assessed the efficacy and safety of vinflunine in an unselected group of 102 consecutive patients with metastatic TCCU. RESULTS: The median age was 67 years (range 45-83). Among the most common comorbidities that patients presented at baseline were hypertension (50.5%) and diabetes (20.7%).Distant metastases were present in retroperitoneal nodes (58%), lung (29.3%), and bone (20.2%). The ECOG 0, 1 and 2 performance status at the start of vinflunine were 31.3%, 60.6% and 8.1%, respectively. The most commonly reported adverse events of any grade were constipation 70.6% (5.9% grade 3-4), vomiting 49.1% (2% grade 3-4), neutropenia 48.1% (12.8% grade 3-4) and abdominal pain 34.3% (4.9% grade 3-4). A median of 4 cycles of vinflunine was administered per patient (range 1-18). Median progression free and overall survival for all patients (N = 102) were 3.9 months (2.3-5.5) and 10 months (7.3-12.8), respectively. Time to tumor progression was 4.3 months (2.6-5.9). Two patients (2%) achieved CR, 23 (22.5%) patients had PR, and 42 (41.2%) presented SD as best response. The clinical benefit rate with vinflunine was 65.7%. CONCLUSIONS: Our results show that the behavior of vinflunine in routine clinical practice resembles that of the pivotal phase III randomized study.

Cardiovascular risk in women attending primary care centres: baseline data of the EVA study.

BACKGROUND: The purpose of this study was to determine the prevalence of hypertension, cardiovascular risk factors and target organ damage using baseline data from the EVA study. METHODS: EVA is a 5-year multicentre prospective study of women aged between 40 and 70 years attending primary care centres in a rural-urban area in the north of Spain. The recruitment period was between October 2009 and January 2010. The following variables were analysed: associated cardiovascular risk factors, target organ damage and cardiovascular or renal disease defined according to the 2007 European Society of Hypertension and the European Society of Cardiology Guidelines (2007 ESH/ESC 2007). Blood pressure <140/90 mmHg and <130/80 in diabetics were considered target blood pressure values. Cardiovascular risk was stratified according to the 2007 ESC-ESH guidelines. RESULTS: The study sample comprised of 903 women with a mean age of 59.6 ± 8 years. The prevalence of hypertension, Type 2 diabetes and dyslipidaemia was 45.6, 13.3 and 41.7%, respectively. Target organ damage affected 17.6% of women and manifested as microalbuminuria (1.8%), slight increase in plasma creatinine (1.6%) and left ventricular hypertrophy (2.9%). Overall, 9.3% had cardiovascular disease, 3.4% coronary heart disease, 1.8% heart failure, 1.8% peripheral artery disease and 1.4% renal disease; 2.2% of patients had experienced a stroke. The prevalence of cardiovascular risk factors in hypertensive women (HT) with respect to non-hypertensive women (NHT) was as follows: obesity 44.7 versus 18.9%, dyslipidaemia 48.8 versus 35.8% and Type 2 diabetes 21.8 versus 6.1%. The target organ damage was more prevalent in hypertensive women: 27.3 versus 9.4%. Cardiovascular disease was present in 14.8% of HT and 4.7% of NHT. High or very high cardiovascular risk affected 65.3% of HT and 26.9% of NHT. CONCLUSIONS: Four in 10 women attending primary care centres had a high or very high cardiovascular risk. Percentages of classic cardiovascular risk factors were higher in HT than in NHT and increased significantly with age. The most commonly used drugs were renin-angiotensin system blockers and diuretics.

Chromosomal imbalances identified by comparative genomic hybridization in sporadic parathyroid adenomas.

OBJECTIVE: To identify chromosomal gains and losses in sporadic parathyroid adenomas (PAs). METHODS: Fourteen sporadic PAs were studied by comparative genomic hybridization (CGH). RESULTS: The fourteen studied PAs showed chromosomal imbalances. All cases except one exhibited two or more abnormalities. Chromosomal gains were found in all cases, and three cases (21%) also presented chromosomal losses. Genomic amplification was not observed. Chromosome 9 was involved in ten cases. Recurrent genetic gain was found on 9p22-24 and on 9q34, each in 6 of 14 cases (43%). Other recurrent gains included Xq26 in 6 PAs (43%) and 4q21-28 and 8p22-23, each in 4 of 14 cases (29%). Regions of recurrent genetic loss involved whole chromosome 11 and 20q12-13, each in 2 of 14 cases (14%). CONCLUSIONS: Our findings show chromosomal imbalances in all sporadic PAs studied by CGH, partly confirming previous reports, with the exception that we observed more chromosomal gains than losses. Several regions (9p22-24, 9q34, Xq26, 4q21-28, and 8p22-23) probably deserve further investigation in order to discard the presence of genes involved in parathyroid tumorigenesis.