Efficacy and safety of corticosteroids for the treatment of community-acquired pneumonia: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The role of corticosteroids in the treatment of community-acquired pneumonia (CAP) remains uncertain. We conducted an updated meta-analysis to investigate the effectiveness and potential effect modifiers of adjunctive corticosteroids in patients with CAP. METHODS: The protocol of this meta-analysis was registered with PROSPERO (CRD42022354920). We searched MEDLINE, Embase, the Cochrane Library and trial registers from inception till March 2023 to identify randomized controlled trials (RCTs) investigating corticosteroids in adult patients with CAP. Our primary outcome was the risk of all-cause mortality within 30 days after randomization (if not reported at day 30, we extracted the outcome closest to 30 days). Risk ratios (RR) and mean differences (MDs) were pooled under a random-effects model. RESULTS: Fifteen RCTs (n = 3252 patients) were included in this review. Corticosteroids reduced the risk of all-cause mortality in CAP patients (RR: 0.69, 95% CI: 0.53-0.89; high certainty). This significant result was restricted to hydrocortisone therapy and patients with severe CAP. Additionally, younger patients demonstrated a greater reduction in mortality. Corticosteroids reduced the incidence of shock and the need for mechanical ventilation (MV), and decreased the length of hospital and ICU stay (moderate certainty). CONCLUSIONS: Corticosteroids reduce the risk of all-cause mortality, especially in younger patients receiving hydrocortisone, and probably decrease the need for MV, the incidence of shock, and the length of hospital and ICU stay in patients with CAP. Our findings indicate that patients with CAP, especially severe CAP, will benefit from adjunctive corticosteroid therapy.

DOACs or VKAs or LMWH - What is the optimal regimen for cancer-associated venous thromboembolism? A systematic review and meta-analysis.

Background: Clinical guidelines have supported the use of direct anticoagulants (DOACs) for the treatment of cancer-associated venous thromboembolism (Ca-VTE). However, recent trials have reported increased bleeding risks associated with DOACs usage, raising concerns regarding its efficacy. Objectives: The authors conducted a meta-analysis to study the efficacy and safety of DOACs for the treatment of VTE in cancer patients, compared with Low-weight molecular heparin (LMWH) and Vitamin-K antagonists (VKAs). Methods: PubMed, EMBASE, Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL) were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines from inception to June 17th, 2021.The primary outcomes studied were VTE recurrence and major bleeding. Results: A total of 8 randomized controlled trials (RCTs) enrolling almost 7000 patients were included. Direct oral anticoagulants significantly reduced VTE Recurrence in cancer patients when compared to patients treated with LMWH or VKAs (Hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.46-0.83; P = 0.002; I2 = 26%). There were no statistically significant differences for major bleeding (HR 0.86, 95% confidence interval [CI] 0.56-1.33; P = 0.50; I2 = 34%), clinically relevant non-major bleeding (HR 1.23, 95% confidence interval [CI] 0.79-1.91; P = 0.35; I2 = 66%), pulmonary embolism (HR 0.71, 95% confidence interval [CI] 0.47-1.06; P = 0.10; I2 = 7%), and all-cause mortality (HR 0.98, 95% confidence interval [CI] 0.86-1.12; P = 0.78; I2 = 1%), between DOACs and LMWH. Conclusion: This analysis shows that DOACs are the optimal regimen to treat Ca-VTE. They have a similar to slightly increased bleeding risk compared with LMWH and are a safer alternative to VKAs.

Targeting Preload in Heart Failure: Splanchnic Nerve Blockade and Beyond.

Preload augmentation represents a critical mechanism for the cardiovascular system to increase effective circulating blood volume to increase cardiac filling pressures and, subsequently, for the heart to increase cardiac output. The splanchnic vascular compartment is the primary source of vascular capacity and thus the primary target for preload recruitment in humans. Under normal conditions, sympathetic stimulation of these primary venous vessels promotes the shift of blood from the splanchnic to the thoracic compartment and elevates preload and cardiac output. However, in heart failure, since filling pressures may be elevated at rest due to decreased venous capacitance, incremental recruitment of preload to enhance cardiac output may exacerbate congestion and limit exercise capacity. Accordingly, recent attention has focused on therapies designed to regulate splanchnic vascular redistribution to improve cardiac filling pressures and patient-centered outcomes such as quality of life and exercise capacity in patients with heart failure. In this review, we discuss the relevance of splanchnic circulation as a venous reservoir, the contribution of stressed blood volume to heart failure pathogenesis, and the implications for pharmacological therapeutic interventions to prevent heart failure decompensation. Further, we review emerging device-based approaches for cardiac preload reduction such as partial/complete occlusion of the superior vena cava or the inferior vena cava.

Efficacy of Sodium-Glucose Cotransporter-2 inhibitors in heart failure patients treated with dual angiotensin receptor blocker-neprilysin inhibitor: An updated meta-analysis.

BACKGROUND: Recent data suggest that the prevalence of heart failure has increased to approximately 23 million people globally. With increasing advancement in pharmacotherapeutics, Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i) have garnered attention among clinicians to treat Heart failure with reduced ejection fraction (HFrEF) in diabetic as well as non-diabetic patients. METHODS: MEDLINE, Scopus, Embase and Cochrane CENTRAL database were searched using relevant keywords and MeSH terms. Studies were considered only if they were randomized in nature and had a sample size >1000 HF patients. RESULTS: Our comprehensive search strategy yielded 864 articles, of which three RCTs met the inclusion criteria with a total population of 9696. Pooled analysis revealed an association between the use of SGLT2i and decreased frequency of primary outcome irrespective of background ARNI use (HR 0.73, 95% CI [0.58-0.93], p = 0.0106; HR 0.73, 95% CI [0.66-0.81], p < 0.0001). CONCLUSION: This meta-analysis provides substantial evidence, to safely use SGLT2i atop ARNI therapy in select HF patients to further improve outcomes.