Littletimm3087

To assess real-life effectiveness of a perindopril/indapamide (Per/Ind) single-pill combination (SPC) in patients with hypertension (HT) and type2 diabetes mellitus (T2DM), obesity and/or metabolic syndrome (MetS).

This post hoc analysis pooled raw data from four large observational studies (FORTISSIMO, FORSAGE, ACES, PICASSO). Patients, most with uncontrolled blood pressure (BP) on previous treatments were switched to Per/Ind (10mg/2.5mg) SPC at study entry. Office systolic and diastolic blood pressures (SBP and DBP) were measured at baseline, 1month and 3months.

In the overall pooled population (N = 16,763), mean age was 61 ± 12years, HT duration 11 ± 8years, and baseline SBP/DBP 162/94mmHg. T2DM, obesity and MetS were present in 21%, 49% and 27% of patients, respectively. Subgroups had similar mean age and HT duration to the overall population; patients with T2DM were slightly older (64 ± 10years) with a longer HT duration (13 ± 8years). Mean BP was approximately 160/95mmHg in each subgroup. At 1montMetS. BP control was achieved in 6-7 out of 10 previously treated but uncontrolled patients. Treatment was well tolerated. The results confirm the beneficial effects of a Per/Ind SPC for difficult-to-control patient populations.Recently, a discussion has begun on the global management strategy against COVID-19 based on the hypothesis that individuals' macro- and micronutrient status combined with antiviral drugs and herbs can be an ally against the infection. The hypothesis is that people's nutritional and oxidative scavenging capacity may provide fundamental data to predict severe and acute pulmonary distress following SARS-Cov2 infection. Consequently, the scientific community has addressed the role of balanced diets, nutritional supplements, and micronutrients, including folk herbal formulations, in reducing hospitalization and the severity of pulmonary impact in COVID-19 by preventing the most serious forms of the infection. This led to an animated debate on the potential effectiveness of some vitamins, micronutrients, and traditional Chinese medicine in preventing COVID-19, with some authors convinced that plant extracts could act oppositely, exacerbating the effect of the infection. While current research is still far to assess the suggestions and issues raised in this short communication, it is undoubtedly true that determining an individual's current metabolic status, including macro- and micronutrients, is an essential factor in defining any individuals' deficiencies, which will need to be addressed urgently through a proper diet, specific personalized nutritional supplementation, and lifestyle changes.

Daratumumab is a human IgGκ monoclonal antibody targeting CD38. Despite the demonstrated benefit of daratumumab in multiple myeloma, not all patients have access to commercially available daratumumab. Here we report a pooled analysis of patients from the UK, Spain, Italy, and Russia enrolled in an open-label, early access treatment protocol (EAP) that provided daratumumab (16mg/kg) monotherapy to patients with heavily pre-treated relapsed or refractory multiple myeloma (RRMM).

Intravenous daratumumab 16mg/kg was administered to patients who had received ≥ 3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or who were double refractory to both a PI and an IMiD. Safety and patient-reported outcomes data were collected.

A total of 293 patients received  ≥ 1 dose of daratumumab. The median duration of daratumumab exposure was 4.2 (range 0.03-24.1) months, with a median number of 13 (range 1-37) infusions. The overall response rate was 33.1%, and the median progression-free survival was 4.63months. Grade 3/4 treatment-emergent adverse events occurred in 60.1% of patients, of which the most common were thrombocytopenia (18.8%), anemia (11.9%), and neutropenia (11.6%). The most common serious adverse events were pneumonia (4.4%) and pyrexia (4.1%). Infusion-related reactions occurred in 45.1% of patients. The median change from baseline in all domains of patient-reported outcome instruments (European Quality of Life Five Dimensions Questionnaire [EQ-5D-5L], European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire [QLQ-C30], and EORTC Multiple Myeloma Module [QLQ-MY20]) was generally 0 or close to 0.

These EAP results are consistent with those from previous trials of daratumumab monotherapy and confirm its safety in patients from Europe and Russia with heavily pre-treated RRMM.

ClinicalTrials.gov identifier, NCT02477891.

ClinicalTrials.gov identifier, NCT02477891.

Coronavirus disease 2019 (COVID-19) lockdown restrictions may impact lifestyle and therefore also physical (in)activity patterns in patients with cardiovascular disease (CVD). This study aimed to evaluate the effect of lockdown on physical activity and sedentary behaviour.

Atotal of 1565 Dutch CVD patients participated in this prospective cohort study, in which we compared physical activity and sedentary behaviour before and during the COVID-19 lockdown period. Baseline measures were assessed in 2018 and data on follow-up measures were collected between 17and 24April 2020 (5weeks after the introduction of COVID-19 lockdown restrictions). Validated questionnaires were used to assess physical activity and sedentary behaviour.

Moderate-to-vigorous physical activities increased from 1.6 (0.9, 2.8) to 2.0 (1.0, 3.5) h/day [median (interquartile range)] (p < 0.001) during the COVID-19 lockdown, mainly due to an increase in time spent walking and doing odd jobs. In contrast, time spent exercising significanassociated with disease progression and mortality, we encourage CVD patients and their caregivers to explore novel solutions to increase physical activity levels and reduce sedentary time during (and beyond) the COVID-19 pandemic.Integral analysis of the development of the epithelium, mesenchyme, and smooth muscle cell (SMC) layers, i.e., the inner circular (IC) and outer longitudinal layers, as well as their relation with the mesentery is necessary to understand macroscopic gut development. We here focused on the proximal duodenum with the characteristic "C"-shaped loop and analyzed the duodenum down to the duodenojejunal flexure in C57BL/6J mouse embryos at embryonic days (E) 13.5, 15.5, and 17.5 by histomorphometric analysis. We examined the angle of the axis of the epithelial lumen, which was oval at E13.5 against the mesentery, along with the epithelial cell nuclear shape, the adjacent mesenchymal cell density in relation to the epithelial lumen axis, and the development of SMC layers. The luminal axis of the oval epithelial lumen at E13.5 rotated clockwise against the mesentery in the proximal duodenum. The shape of epithelial nuclei was longer and thinner at the long axis but shorter and broader at the short axis, whereas mesenchymal density was significantly lower in the area on the luminal long axis than that on the short axis. The number of SMC layers in the IC at E13.5, E15.5, and E17.5 showed a regional difference in relation to the mesentery, but no regional difference along the long axis of the duodenum. These findings suggest that epithelial lumen winding against the mesentery and the corresponding changes in the epithelial cell shape and surrounding mesenchymal density may be involved in the formation of the "C" loop of the proximal duodenum.

Understanding the durability of response to treatment and factors associated with failure to maintain response in a real-world setting can inform treatment decisions for patients with rheumatoid arthritis (RA). The aim of this study was to analyze durability of response to tocilizumab (TCZ) and factors associated with durability among US patients with RA in routine clinical practice.

TCZ initiators in the Corrona RA Registry were included. Durability of response was defined as maintaining continuous TCZ treatment and either an improvement of at least minimum clinically important difference (MCID) in Clinical Disease Activity Index (CDAI) score or low disease activity (LDA). Secondary analyses included patients treated with intravenous (IV) TCZ and excluded those who discontinued TCZ without reporting reasons for discontinuation. Durability was calculated with Kaplan-Meier survival analysis. Cox proportional hazards modeling identified factors associated with durability.

Among 1789 TCZ initiators, 466, 272, and 162 were persistent (with or without durable response) with follow-up visits at 1, 2, and 3years, respectively. Median MCID durability of response in CDAI was > 50% after 36months overall, 26months for TCZ-IV, and > 50% after 36months for those with known reasons for discontinuation; longer durability was associated with increased duration of RA and higher baseline CDAI score and shorter durability with history of malignancy and history of diabetes. Median LDA durability of response was 13.0months overall, for TCZ-IV, and for those with known reasons for discontinuation; shorter durability was associated with history of malignancy, history of diabetes, and higher baseline CDAI score.

Median durability of response to TCZ in RA was > 3years when defined as maintenance of MCID in CDAI score and > 1year with the more stringent criteria of maintenance of LDA.

ClinicalTrials.gov identifier, NCT01402661.

ClinicalTrials.gov identifier, NCT01402661.Recent advancements in sequencing and imaging technologies are providing new perspectives in solving the mystery of three-dimensional folding of genome in a nucleus. Chromosome conformation capture sequencing has discovered new chromatin structures such as topologically associated domains and loops in hundreds of kilobases. Super-resolution fluorescence microscopy with nanometer resolutions, in particular multiplexed approaches with sequence-specificity, has visualized chromatin structures from the rough folds of whole chromosomes to the fine loops of cis-regulatory elements in intact individual nuclei. Here, recent advancements in genome visualization tools with highly multiplexed labeling and reading are introduced. These imaging technologies have found ensemble behavior consistent to sequencing results, while unveiling single-cell variations. But, they also generated contradictory results on the roles of architectural proteins (like cohesion and CTCF) and enhancer-promoter interactions. Live-cell labeling methods for imaging specific genomic loci, especially the CRISPR/dCas9 system, are reviewed in order to give perspectives in the emergence of tools for visualizing genome structural dynamics.Hypertension is a major contributor to fatal/nonfatal cardiovascular diseases, and timely identification and appropriate management of factors affecting hypertension and its control are mandatory public health issues. By inducing neurohormonal alterations and metabolic impairment, sleep disorders have an impact on a variety of cardiovascular risk factors, including hypertension, and ultimately increase the risk of cardiovascular events. There is evidence that qualitative and quantitative sleep disorders are associated with resistant hypertension and with impaired circadian blood pressure variations. However, sleep disturbances are often unrecognized, or heterogeneity exists in their management by non-specialists in the field. This document by the Italian Society of Hypertension summarizes the updated evidence linking sleep disorders to hypertension and cardiovascular diseases, the major underlying mechanisms, and the possible management strategies. A simplified, evidence-based diagnostic and therapeutic algorithm for comorbid hypertension and common sleep disorders, namely obstructive sleep apnoea and insomnia, is proposed.