Safety and efficacy of soluble guanylate cyclase stimulators in patients with heart failure: A systematic review and meta-analysis

BACKGROUND The utility of novel oral soluble guanylate cyclase(sGC)stimulators(vericiguat and riociguat),in patients with reduced or preserved ejection fraction heart failure(HFrEF/HFpEF)is currently unclear.AIM To determine the efficacy and safety of sGC stimulators in HF patients.METHODS Multiple databases were searched to identify relevant randomized controlled trials(RCTs).Data on the safety and efficacy of sGC stimulators were compared using relative risk ratio(RR)on a random effect model.RESULTS Six RCTs,comprising 5604 patients(2801 in sGC stimulator group and 2803 placebo group)were included.The primary endpoint(a composite of cardiovascular mortality and first HF-related hospitalization)was significantly reduced in patients receiving sGC stimulators compared to placebo[RR 0.92,95%confidence interval(CI):0.85-0.99,P=0.02].The incidence of total HF-related hospitalizations were also lower in sGC group(RR 0.91,95%CI:0.86-0.96,P=0.0009),however,sGC stimulators had no impact on all-cause mortality(RR 0.96,95%CI:0.86-1.07,P=0.45)or cardiovascular mortality(RR 0.94,95%CI:0.83-1.06,P=0.29).The overall safety endpoint(a composite of hypotension and syncope)was also similar between the two groups(RR 1.50,95%CI:0.93-2.42,P=0.10).By contrast,a stratified subgroup analysis adjusted by type of sGC stimulator and HF(vericiguat vs riociguat and HFrEF vs HFpEF)showed near identical rates for all safety and efficacy endpoints between the two groups at a mean follow-up of 19 wk.For the primary composite endpoint,the number needed to treat was 35,the number needed to harm was 44.CONCLUSION The use of vericiguat and riociguat in conjunction with standard HF therapy,shows no benefit in terms of decreasing HF-related hospitalizations or mortality.

Medical therapy vs early revascularization in diabetics with chronic total occlusions:A meta-analysis and systematic review

BACKGROUND Management of chronic total occlusions(CTO)in diabetics is challenging,with a recent trend towards early revascularization[ER:Percutaneous coronary intervention(PCI)and bypass grafting]instead of optimal medical therapy(OMT).We hypothesize that ER improves morbidity and mortality outcomes in diabetic patients with CTOs as compared to OMT.AIM To determine the long term clinical outcomes and to compare morbidity and mortality between OMT and ER in diabetic patients with CTOs.METHODS Potentially relevant published clinical trials were identified in Medline,Embase,chemical abstracts and Biosis(from start of the databases till date)and pooled hazard ratios(HR)computed using a random effects model,with significant P value<0.05.Primary outcome of interest was all-cause death.Secondary outcomes included cardiac death,prompt revascularization(ER)or repeat myocardial infarction(MI).Due to scarcity of data,both Randomized control trials and observational studies were included.4 eligible articles,containing 2248 patients were identified(1252 in OMT and 1196 in ER).Mean follow-up was 45-60 mo.RESULTS OMT was associated with a higher all-cause mortality[HR:1.70,95%confidence interval(CI):0.80-3.26,P=0.11]and cardiac mortality(HR:1.68,95%CI:0.96-2.96,P=0.07).Results were close to significance.The risk of repeat MI was almost the same in both groups(HR:0.97,95%CI:0.61-1.54,P=0.90).Similarly,patients assigned to OMT had a higher risk of repeat revascularization(HR:1.62,95%CI:1.36-1.94,P<0.00001).Sub-group analysis of OMT vs PCI demonstrated higher all-cause(HR:1.98,95%CI:1.36-2.87,P=0.0003)and cardiac mortality(HR:1.87,95%CI:0.96-3.62,P=0.06)in the OMT group.The risk of repeat MI was low in the OMT group vs PCI(HR:0.53,95%CI:0.31-0.91,P=0.02).Data on repeat revascularization revealed no difference between the two(HR:1.00,95%CI:0.52-1.93,P=1.00).CONCLUSION In diabetic patients with CTO,there was a trend for improved outcomes with ER regarding all-cause and cardiac death as compared to OMT.These findings were reinforced with statistical significance on subgroup analysis of OMT vs PCI.

Effects of left ventricular assist device on pulmonary functions and pulmonary hemodynamics:A meta-analysis

BACKGROUND Given current evidence,the effect of left ventricular assist device(LVAD)implantation on pulmonary function tests remains controversial.AIM To better understand the factors contributing to the changes seen on pulmonary function testing and the correlation with pulmonary hemodynamics after LVAD implantation.METHODS Electronic databases were queried to identify relevant articles.The summary effect size was estimated as a difference of overall means and standard deviation on a random-effects model.RESULTS A total of four studies comprising 219 patients were included.The overall mean forced expiratory volume in one second(FEV1),forced vital capacity(FVC)and diffusion lung capacity of carbon monoxide(DLCO)after LVAD implantation were significantly lower by 0.23 L(95%CI:0.11-0.34,P=00002),0.18 L(95%CI:0.03-0.34,P=0.02),and 3.16 mmol/min(95%CI:2.17-4.14,P<0.00001),respectively.The net post-LVAD mean value of the cardiac index was significantly higher by 0.49 L/min/m2(95%CI:0.31-0.66,P<0.00001)compared to pre-LVAD value.The pulmonary capillary wedge pressure and pulmonary vascular resistance were significantly reduced after LVAD implantation by 8.56 mmHg(95%CI:3.78-13.35,P=0.0004),and 0.83 Woods U(95%CI:0.11-1.55,P=0.02),respectively.There was no significant difference observed in the right atrial pressure after LVAD implantation(0.61 mmHg,95%CI:-2.00 to 3.32,P=0.65).Overall findings appear to be driven by studies using HeartMateII devices.CONCLUSION LVAD implantation might be associated with a significant reduction of the spirometric measures,including FEV1,FVC,and DLCO,and an overall improvement of pulmonary hemodynamics.

Thrombocytopenia, an Overlooked Hematological Derangement in Hair Dye Poisoning

Thrombocytopenia is a common hematological disorder characterized by abnormally low number of platelets in circulating blood from multiple causes. The fundamental mechanisms involved are: ineffective production of platelets by the bone marrow, accerlated destruction of platelets or platelet splenic sequestration. Hair dye, containing Paraphenyllinediamaine has been linked to allergic reaction, nephrotoxicity, mutagenicity and hematological derangements as anemia. A female showed a clinical spectrum of decreasing platelet count along with anemia due to oral ingestion of hair dye. It is important to consider thrombocytopenia in management plan as it may impact the clinical outcome.

Examination of care processes and treatment optimization for head and neck cancer patients in a community setting"hub and hub"model

Objective:To examine referral pattern,the timing of diagnostic/staging processes,and treatment initiation for new head and neck cancer patients in a community setting.Methods:Patients with a newly diagnosed previously untreated diagnosis of head neck cancer managed at Asplundh Cancer Pavilion/Abington Memorial Hospital from October 2018 to March 2020.Source of referral and preceding workup were examined as well as intervals between initial head and neck consult and various timepoints of treatment initiation.Results:One hundred and five patients were included in the study.The primary referral sources were external general otolaryngology(56.3%).Oral surgery and dermatology obtained tissue biopsy approximately 80%of the time before referral.The average time from the ordering of initial staging positron emission tomography/computed tomography to finalized results was 14 days(range:10-25 days).Patients referred from dermatology and oral surgery were more likely to require single modality care,namely definitive surgical management.Time to treatment initiation average was 37 days(range:29-41 days).Patients with longer treatment times noted significantly higher times to both radiation and medical oncology consults(48.42 vs.18.13 days;P<0.001).Conclusions:No notable differences in treatment initiation times were identified based on referral source or extent of workup performed before head/neck surgery consult.It appears the largest opportunities for improvement in terms of reducing overall treatment length exist in the optimization of radiation initiation time.