Cardiac Dysfunction, Congestion and Loop Diuretics: their Relationship to Prognosis in Heart Failure

Background: Diuretics are the mainstay of treatment for congestion but concerns exist that they adversely affect prognosis. We explored whether the relationship between loop diuretic use and outcome is explained by the underlying severity of congestion amongst patients referred with suspected heart failure. Method and Results: Of 1190 patients, 712 had a left ventricular ejection fraction (LVEF) ≤50 %, 267 had LVEF >50 % with raised plasma NTproBNP (>400 ng/L) and 211 had LVEF >50 % with NTproBNP ≤400 ng/L; respectively, 72 %, 68 % and 37 % of these groups were treated with loop diuretics including 28 %, 29 % and 10 % in doses ≥80 mg furosemide equivalent/day. Compared to patients with cardiac dysfunction (either LVEF ≤50 % or NT-proBNP >400 ng/L) but not taking a loop diuretic, those taking a loop diuretic were older and had more clinical evidence of congestion, renal dysfunction, anaemia and hyponatraemia. During a median follow-up of 934 (IQR: 513–1425) days, 450 patients were hospitalized for HF or died. Patients prescribed loop diuretics had a worse outcome. However, in multi-variable models, clinical, echocardiographic (inferior vena cava diameter), and biochemical (NTproBNP) measures of congestion were strongly associated with an adverse outcome but not the use, or dose, of loop diuretics. Conclusions: Prescription of loop diuretics identifies patients with more advanced features of heart failure and congestion, which may account for their worse prognosis. Further research is needed to clarify the relationship between loop diuretic agents and outcome; imaging and biochemical measures of congestion might be better guides to diuretic dose than symptoms or clinical signs

Transanal division of the anorectal junction followed by laparoscopic low anterior resection and coloanal pouch anastomosis: A technique facilitated by a balloon port

We performed a laparoscopic ultra low anterior resection in two patients with low rectal cancers (3 cm from dentate line). A transanal division and continuous suture closure of anorectal junction was performed first followed by laparoscopic low anterior resection. A handsewn anastomosis between colonic pouch/transverse coloplasty and anal canal was facilitated by use of a transanal balloon port

Comparative evaluation of the antimicrobial susceptibility and cytotoxicity of husk extract of Cocos nucifera and chlorhexidine as irrigating solutions against Enterococcus Faecalis, Prevotella Intermedia and Porphyromonas Gingivalis – An in-vitro study

Aim and Background: The aim of the present study is to evaluate and compare the antimicrobial susceptibility and cytotoxicity of Cocos nucifera and chlorhexidine (CHX) as irrigating solutions against Enterococcus faecalis, Prevotella intermedia, and Porphyromonas gingivalis. Materials and Methods: The ethanolic extract of husk of C. nucifera was prepared. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the extract were determined using the serial broth dilution method and its cytotoxicity was evaluated against human periodontal fibroblasts using 3-(4,5-dimethyl-thiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay. Antibacterial susceptibility for two irrigating solutions, namely 2% CHX gluconate irrigant (Group I) and 1.5% C. nucifera husk irrigant (Group II), was tested against P. gingivalis, P. intermedia, and E. faecalis. Results: The MIC and MBC of C. nucifera husk extract for P. gingivalis were 468.75 μg/ml and 1562.5 μg/ml, for P. intermedia were 48.8 μg/ml and 1875 μg/ml, and for E. faecalis were 1562.5 μg/ml and 3750 μg/ml, respectively. The extract was nontoxic to the human periodontal fibroblast. Both the materials have shown similar antibacterial susceptibility and no difference was observed at baseline, 10, 30, and 60 min using two-way repeated measures of ANOVA. However, a statistically significant difference was observed between different time points for P. gingivalis and P. intermedia using Bonferroni multiple comparison test (f = 826.1390, P ≤ 0.05). Conclusion: 1.5% of ethanolic husk extract of C. nucifera has a significant antibacterial action against polymicrobial dental biofilm and its activity is comparable to that of 2% CHX which validates its use as a future irrigating solution for overcoming bacterial resistance with synthetic agents

Prevalence and Incidence of Atrial Fibrillation in Ambulatory Patients with Heart Failure

Heart failure (HF) and atrial fibrillation (AF) commonly co-exist. We aimed to determine the prevalence and incidence of AF in ambulatory patients with HF. HF was defined by the presence of symptoms or signs supported by objective evidence of cardiac dysfunction: either a left ventricular ejection fraction (LVEF) ≤45% (HFrEF), or LVEF >45% and a raised plasma concentration of amino-terminal pro-B type natriuretic peptide (NT-proBNP>220ng/L; HFpEF). Of 3,570 patients with HF, 1,164 were in AF at baseline (33%), with a higher prevalence among patients with HFpEF compared to HFrEF (40% vs 26%, respectively, p<0.001). Compared to patients with HF in sinus rhythm (SR), those in AF were older, had more severe symptoms and higher NT-proBNP, worse renal function and were more likely to receive loop diuretics, despite having a higher LVEF. Of those in SR, 1,372 patients had HFrEF and 1,034 had HFpEF. The incidence of AF at one year (3.0%) was similar for each phenotype (p=0.73). Increasing age, male sex, history of paroxysmal AF and higher plasma concentrations of NT-proBNP were independent predictors of incident AF during a median follow-up of 1,574 (IQR: 749-2,821) days; the predictors were similar for each phenotype. In conclusion, the prevalence of AF is high, especially in patients with HFpEF, but its incidence is modest. This may be because their onset is near simultaneous with the development of AF precipitating the onset of HF

Pharmacological and Non-pharmacological Treatment for Decompensated Heart Failure: What Is New?

Purpose of the Review: Acute heart failure (AHF) is a life-threatening clinical condition that requires prompt medical attention. The aim of the current review is to summarise the results of recent clinical trials conducted in patients with AHF. Recent Findings: Several novel compounds have apparently beneficial acute effects on cardiovascular haemodynamics and patients’ symptoms, but their administration has not yet translated into improved survival and has been deleterious in some cases. Summary: The management of patients with AHF is challenging and reflects the heterogeneity of patient’s presentation, the complexity and severity of a multi-organ syndrome, and the limited therapeutic options, usually restricted to a combination of diuretics and vasodilators. Ongoing trials of novel treatments may provide evidence of an effect on outcomes

Transcriptional mediators of treatment resistance in lethal prostate cancer

© 2021, The Author(s). Metastatic castration-resistant prostate cancer is typically lethal, exhibiting intrinsic or acquired resistance to second-generation androgen-targeting therapies and minimal response to immune checkpoint inhibitors1. Cellular programs driving resistance in both cancer and immune cells remain poorly understood. We present single-cell transcriptomes from 14 patients with advanced prostate cancer, spanning all common metastatic sites. Irrespective of treatment exposure, adenocarcinoma cells pervasively coexpressed multiple androgen receptor isoforms, including truncated isoforms hypothesized to mediate resistance to androgen-targeting therapies2,3. Resistance to enzalutamide was associated with cancer cell–intrinsic epithelial–mesenchymal transition and transforming growth factor-β signaling. Small cell carcinoma cells exhibited divergent expression programs driven by transcriptional regulators promoting lineage plasticity and HOXB5, HOXB6 and NR1D2 (refs. 4–6). Additionally, a subset of patients had high expression of dysfunction markers on cytotoxic CD8+ T cells undergoing clonal expansion following enzalutamide treatment. Collectively, the transcriptional characterization of cancer and immune cells from human metastatic castration-resistant prostate cancer provides a basis for the development of therapeutic approaches complementing androgen signaling inhibition