Whether noninvasive optimization of AV and VV delays improves the response to cardiac resynchronization therapy

Background: Device optimization is not routinely performed in patients who underwentcardiac resynchronization therapy (CRT) device implantation. Noninvasive optimization ofCRT devices by measurement of cardiac output (CO) can be used as a simple method to assessventricular systolic performance. The aim of this study was to assess whether optimization ofatrioventricular (AV) and interventricular (VV) delay can improve hemodynamic response toCRT and whether this optimization should be performed for each patient individually.Methods: Twenty patients with advanced heart failure New York Heart Association (NYHA)class III/IV, left ventricular ejection fraction ≤ 35% and left bundle branch block (QRS ≥ 120 ms)in sinus rhythm were evaluated from 24 h to 48 h after implantation of a CRT device by meansof impedance cardiography (ICG). CO was fi rst measured at each patient’s intrinsic rhythm.Patients then underwent adjustments of AV and VV delay from 80 ms to 140 ms and from–60 ms to +60 ms, respectively in 20 ms increment steps and CO at each setting was measuredby ICG. Both AV and VV delays were programmed according to the greatest improvement inCO compared to intrinsic rhythm.Results: There was a statistically signifi cant increase in CO measured at the intrinsic rhythmcompared to different AV delay by mean of 21% (3.8 ± 1.0 vs. 4.6 ± 0.1 L/min, p < 0.05).Optimal AV/VV delays with left ventricle-preexcitation or simultaneous biventricular pacingcaused additional increased CO from intrinsic rhythm by mean of 32.6% (3.8 ± 1.0 vs. 5.04 ±± 1.0 L/min, p < 0.05). Optimal AV/VV setting delays also resulted in improved hemodynamicresponses compared to VV factory setting delay.Conclusions: Both AV and VV delay optimization should be performed in clinical practice.Optimal AV delay improved outcome. However, combination of optimized AV/VV delays providedthe best hemodynamic response. Optimized AV/VV delays with left ventricle-preexcitationor simultaneous biventricular pacing increased hemodynamic output compared to intrinsicrhythm and VV factory setting delay

The current possible treatment approaches of Polycystic Ovary Syndrome (PCOS)

Introduction             Polycystic ovary syndrome (PCOS), first described by Stein and Leventhal in 1935, is one of the most prevalent endocrine system conditions affecting women of reproductive age. It affects between 6% and 13% of women and the majority of cases are identified between the ages of 20 and 30. Unfortunately, the disease is usually diagnosed only when bothersome symptoms such as hair loss, alopecia, acne, and infertility-related problems occur. Based on the Rotterdam criteria, four phenotypes of PCOS are distinguished. Aim of the study             This review aims to present the current state of knowledge about possible treatment approaches, both non-pharmacological and pharmacological. Materials and methods            The paper was created based on the Pubmed database. The literature was reviewed using the keywords: ”PCOS”, ”PCOS treatment” and “ PCOS medications “. The current state of knowledge           Treatments for PCOS must be tailored to the specific needs of each patient. In the management of PCOS, special attention is paid to diet, physical activity, and restoration of the Gut Microbiome. Medications used in therapy are oral contraceptives and anti-androgens, insulin sensitizers, ovulation inducers, calcium and vitamin D supplements, statins, Glucagon-like-peptide-1 (GLP-1) agonists, inositols and interleukin 22 (IL-22)  therapy. Summary            Treatment options for menstrual irregularities and hirsutism are based on the clinical goals and preferences of the patient. The ideal would be causal treatment, but due to the ongoing lack of full understanding of the pathogenesis of the syndrome, is not entirely feasible. The ideal would be causal treatment, but due to the ongoing lack of full understanding of the pathogenesis of the syndrome, is not entirely feasible. The most important is a multimodal approach to treat comorbid conditions such as diabetes mellitus type 2, obesity, hyperlipidemia, depression, and infertility

The multimodal approach to obesity treatment – current pharmacological and surgical methods and lifestyle changes

Introduction            Obesity is one of the major health problems of today’s population and is defined as a body mass index ≥ 30 kg/m2.  It is known that obesity may cause many complications such as type 2 diabetes, cardiovascular disease, osteoarthritis, obstructive sleep, apnoea, and several cancers. The only effective treatment of obesity can be pharmacological or surgical, especially when a years-long attempt to change habits has had no effects.  Aim of the study This review aims to present the current state of knowledge about non-pharmacological and pharmacological obesity treatment methods. Materials and methods            The paper was created based on the Pubmed database. The literature was reviewed using the keywords: ”obesity”, ”obesity treatment”, “ obesity lifestyle changes”, “obesity medications” and ”obesity surgery”. The current state of knowledge           The treatment of obesity requires a multimodal approach to treatment, including the addition of anti-obesity medications or bariatric surgery, or both, to assist people in reaching and sustaining sufficient weight loss to meet treatment goals. The 3 principal components of a comprehensive lifestyle intervention are diet, physical activity, and behavioral therapy. Among available anti-obesity medications include orlistat, phentermine, topiramate, naltrexone, bupropion, liraglutide, and semaglutide. Summary            The key challenge in the treatment of obesity is to maintain the effects obtained with multimodal therapy. Without proper motivation of patients and changes in eating and behavioral habits, it is impossible to achieve optimal results, therefore, in addition to medical interventions, more and more attention should be paid to psychological interventions

Immature platelet fraction in cardiovascular diagnostics and antiplatelet therapy monitoring

Immature platelet fraction (IPF), circulating platelets still containing RNA, can be easily calculated by automated flow cytometry, this makes them an accessible biomarker. Higher IPF concentrations were reported in patients with thrombocytopenia, patients who were smokers, and also those who were diabetics. Several studies have reported their diagnostic and prognostic importance in patients presenting with acute coronary syndromes, especially ST-segment myocardial infarction, where increased IPF level is an independent predictor of cardiovascular death. In addition, higher IPF were reported in patients with inadequate response to either clopidogrel or prasugrel, suggesting their potential role in antiplatelet therapy monitoring. Their prognostic significance was also observed in both coronary artery disease and postcardiac surgery status, where their higher levels correlated with the risk of major adverse cardiac events. The present review aims to present the current evidence on diagnostic, prognostic and potentially therapeutic roles of IPF in cardiovascular medicine

Pan-cancer analysis of whole genomes identifies driver rearrangements promoted by LINE-1 retrotransposition

About half of all cancers have somatic integrations of retrotransposons. Here, to characterize their role in oncogenesis, we analyzed the patterns and mechanisms of somatic retrotransposition in 2,954 cancer genomes from 38 histological cancer subtypes within the framework of the Pan-Cancer Analysis of Whole Genomes (PCAWG) project. We identified 19,166 somatically acquired retrotransposition events, which affected 35% of samples and spanned a range of event types. Long interspersed nuclear element (LINE-1; L1 hereafter) insertions emerged as the first most frequent type of somatic structural variation in esophageal adenocarcinoma, and the second most frequent in head-and-neck and colorectal cancers. Aberrant L1 integrations can delete megabase-scale regions of a chromosome, which sometimes leads to the removal of tumor-suppressor genes, and can induce complex translocations and large-scale duplications. Somatic retrotranspositions can also initiate breakage–fusion–bridge cycles, leading to high-level amplification of oncogenes. These observations illuminate a relevant role of L1 retrotransposition in remodeling the cancer genome, with potential implications for the development of human tumors

Comprehensive analysis of chromothripsis in 2,658 human cancers using whole-genome sequencing

Funder: Ludwig Center at HarvardFunder: National Cancer Institute: K22CA193848Funder: US National Institutes of Health Intramural Research Program Project Z1AES103266Abstract: Chromothripsis is a mutational phenomenon characterized by massive, clustered genomic rearrangements that occurs in cancer and other diseases. Recent studies in selected cancer types have suggested that chromothripsis may be more common than initially inferred from low-resolution copy-number data. Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA), we analyze patterns of chromothripsis across 2,658 tumors from 38 cancer types using whole-genome sequencing data. We find that chromothripsis events are pervasive across cancers, with a frequency of more than 50% in several cancer types. Whereas canonical chromothripsis profiles display oscillations between two copy-number states, a considerable fraction of events involve multiple chromosomes and additional structural alterations. In addition to non-homologous end joining, we detect signatures of replication-associated processes and templated insertions. Chromothripsis contributes to oncogene amplification and to inactivation of genes such as mismatch-repair-related genes. These findings show that chromothripsis is a major process that drives genome evolution in human cancer

Genomic footprints of activated telomere maintenance mechanisms in cancer

Abstract: Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer

Genomic footprints of activated telomere maintenance mechanisms in cancer

Abstract: Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer

Genomic footprints of activated telomere maintenance mechanisms in cancer

Abstract: Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer