A Meta-Analysis of Randomized Clinical Trials Assessing the Efficacy of PARP Inhibitors in Metastatic Castration-Resistant Prostate Cancer.

Prostate cancer ranks as the second most common malignancy in males. Prostate cancer progressing on androgen deprivation therapy (ADT) is castration-resistant prostate cancer (CRPC). Poly-ADP ribose polymerase (PARP) inhibitors (PARPis) have been at the forefront of the treatment of CRPC. We aim to better characterize the progression-free survival (PFS) and overall survival (OS) in metastatic CRPC patients treated with PARPis. A systemic review search was conducted using National Clinical Trial (NCT), PubMed, Embase, Scopus, and Central Cochrane Registry. The improvement in overall survival was statistically significant, favoring PARPis (hazard ratio (HR) 0.855; 95% confidence interval (CI) 0.752-0.974; p = 0.018). The improvement in progression-free survival was also statistically significant, with results favoring PARPis (HR 0.626; 95%CI 0.566-0.692; p = 0.000). In a subgroup analysis, similar results were observed where the efficacy of PARPis was evaluated in a subgroup of patients without homologous recombination repair (HRR) gene mutation, which showed improvement in PFS favoring PARPis (HR 0.747; 95%CI 0.0.637-0.877; p = 0.000). Our meta-analysis of seven RCTs showed that PARPis significantly increased PFS and OS when used with or without antihormonal agents like abiraterone or enzalutamide.

The Role and Efficacy of Vitamin C in Sepsis: A Systematic Review and Meta-Analysis.

Clinical rationale for study: Despite advancements in critical care, the mortality rate of sepsis remains high, with an overall poor prognosis. There is a complex pathophysiology of a lethal cascade of cytokines and inflammatory proteins underlying sepsis. The use of vitamin C can theoretically suppress the inflammatory cascade but remains a questionable practice due to a lack of conclusive evidence. Aims of the study: To appraise the therapeutic role of vitamin C in sepsis. Materials and methods: A systematic review was conducted on PubMed, Embase, and the Central Cochrane Registry. The study included randomized clinical trials (RCTs) with vitamin C as an intervention arm in the septic patient population. For continuous variables, the difference in means (MD) and for discrete variables, the odds ratio (OR) was used. For effect sizes, a confidence interval of 95% was used. A p-value of less than 0.05 was used for statistical significance. The analysis was performed using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. Results: 23 studies were included with the total sample size of 2712 patients. In patients treated with vitamin C, there was a statistically significant reduction in the mortality: OR = 0.778 (0.635 to 0.954), p = 0.016; the sequential organ failure assessment score (SOFA): MD = −0.749 (−1.115 to −0.383), p < 0.001; and the duration of vasopressor requirement: MD = −1.034 days (−1.622 to −0.445), p = 0.001. No significant difference was found in the hospital or ICU length of stay. Conclusions and clinical implications: Vitamin C treatment regimens were associated with reduced mortality, SOFA score, and vasopressor requirement compared to the control in sepsis. Given its low cost and minimal adverse effects, we strongly encourage further large, randomized trials to establish vitamin C as a standard of care in sepsis management.

Management of acute chest syndrome in patients with sickle cell disease: a systematic review of randomized clinical trials.

INTRODUCTION: Acute chest syndrome (ACS) accounts for the highest mortality in Sickle cell disease patients. Early diagnosis and timely management of ACS results in better outcomes. However, the effectiveness of most treatment modalities for ACS management has not been established. AREAS COVERED: To review the treatment modalities management protocols and highlight the effectiveness of each option a literature search was done. Randomized controlled trials that assessed the efficacy of different treatment modalities in ACS management in SCD patients were chosen and reviewed. EXPERT OPINION: 11 randomized controlled trials were found that evaluated the efficacy of incentive spirometry, positive expiratory pressure device, intravenous dexamethasone, oral vs. intravenous morphine, inhaled nitric oxide, unfractionated heparin, and blood transfusion in the prevention or treatment of ACS. Although there are guidelines for ACS treatment, the available evidence is very limited to delineating the effectiveness of various interventions in ACS management. More high-quality studies and trials with a larger patient population can benefit this area to support the recommendations with stronger evidence.

The Prognostic Significance of Peripheral Blood Biomarkers in Patients With Advanced Non-Small Cell Lung Cancer Treated With Pembrolizumab: A Clinical Study.

Systemic inflammation has long been associated with poor outcomes in many types of solid tumors. Peripheral blood biomarkers, such as absolute lymphocyte count (ALC) and the ratio of absolute neutrophil count to absolute lymphocyte count (ANC/ALC), have been shown to be immune-inflammatory parameters highlighting an individual's immune status. The prognostic role of ALC and ANC/ALC on overall survival (OS) was examined in patients with advanced non-small cell lung carcinoma (NSCLC) receiving pembrolizumab. Of a total of 239 patients, 52% were male, with a median age of 67 years (interquartile range [IQR], 59-73). Most patients had a diagnosis of adenocarcinoma (76%), with stage IV disease (82%). PD-L1 expression was >50% in 44% of the patients. The median time on treatment with pembrolizumab was 5.8 months (IQR, 2.9-12.7). An ANC/ALC <5 was associated with improved OS at initiation of pembrolizumab (P = .002), whereas an ALC >1.4 deciliter (dL) trended toward improved OS compared with ALC <1.4 dL (P = .053). After adjusting for potential cofounders with a multivariate analysis, a baseline ANC/ALC of 5 or higher was associated with a significantly increased risk of death (HR, 1.93; 95% CI, 1.27-2.93; P = .002). An ANC/ALC <5 at the time of initiation of treatment with pembrolizumab was associated with improved OS in patients with advanced NSCLC. The median ALC and ANC/ALC were significantly lower after 6 weeks of treatment with pembrolizumab.

Normal Saline Versus Low Chloride Solutions in Treatment of Diabetic Ketoacidosis: A Systematic Review of Clinical Trials.

Traditionally, normal saline solution (NSS) has been the fluid of choice in diabetic ketoacidosis (DKA) patients, but the NSS is an acidic fluid and may lead to the delayed resolution of DKA. A systemic review search was conducted on PubMed, Embase, and Central Cochrane Registry to compare the efficacy of low chloride solutions with normal saline solution in DKA resolution. Randomized clinical trials with normal saline as a control arm and low chloride solutions as an intervention arm were included. Four studies were included in the analysis. The investigated outcomes, including time to resolution for DKA and duration of insulin infusion, varied depending on the endpoint were reported in the studies. Overall, balanced solutions were generally associated with faster correction of pH. The time to reach overall DKA endpoints was comparable in both groups. We concluded that crystalloid solutions may be used as an initial resuscitation fluid in the DKA population and may lead to earlier resolution of acidosis. More clinical trial data is required to reach statistical significance for the hypothesis.

Efficacy of magnesium sulfate in the chronic obstructive pulmonary disease population: a systematic review and meta-analysis.

INTRODUCTION: Magnesium sulfate has been extensively used to treat asthma exacerbations, but its efficacy remains questionable in the chronic obstructive pulmonary disease (COPD) population. The aim of the study was to compare the efficacy of intravenous (IV) magnesium sulfate in COPD. A systemic review search was conducted on PubMed, Embase, and the Central Cochrane Registry. Randomized clinical trials were included with magnesium sulfate as an intervention arm in the COPD population. MATERIALS AND METHODS: For continuous variables, standardized mean difference (SMD) and difference in means (MD) were calculated. For discrete variables, the Mantel-Haenszel (MH) odds ratio was used. For effect sizes, a confidence interval of 95% was used. A p-value of less than 0.05 was used for statistical significance. Analysis was done using both random and fixed effect models. Heterogeneity was evaluated using the I² statistic. RESULTS: Seven studies were included in the final analysis. In patients with acute exacerbations of COPD treated with IV magnesium, a significant increase in forced expiratory volume in one second (FEV1) was observed (MD = 2.537 [0.717 to 4.357], p = 0.006), as well as in peak expiratory flow rate (PEFR) (SMD = 1.073 [0.748 to 1.397], p < 0.001) using the fixed model. Similarly, residual volume decreased significantly in the IV magnesium group (MD = -0.470 [-0.884 to -0.056], p = 0.026). The hospitalization rate was also lower in the magnesium group, (MH odds ratio 0.453 [0.233 to 0.882], p = 0.020). No statistically significant difference was noted in FEV1 in the stable COPD population. CONCLUSION: IV magnesium was associated with a favorable deviation of FEV1 and PEFR, decreased residual volume, and decreased odds of admission in the COPD exacerbation population. Therefore, magnesium sulfate can be used as an adjunctive therapy in the treatment of acute exacerbations of COPD.

Comparison of normal saline solution with low-chloride solutions in renal transplants: a meta-analysis.

BACKGROUND: Normal saline solution (NSS) has been the fluid of choice for renal transplant patients, but it can lead to hyperchloremic acidosis and hyperkalemia. This study was performed to compare the safety profile of low-chloride solutions with that of NSS in renal transplant patients. METHODS: We conducted a systemic review search on PubMed, Embase, and the Central Cochrane Registry. Randomized clinical trials (RCTs) and matched cohort studies involving NSS as the control arm and low-chloride solutions as an intervention arm were chosen. The standardized mean difference for continuous variables, the odds ratio (OR) for discrete variables, and a 95% confidence interval (CI) for effect sizes were used. A p-value of <0.05 was considered statistically significant. Analysis was performed using a random-effects model irrespective of heterogeneity, which was evaluated using I2 statistics. RESULTS: Nine RCTs and one cohort study with a total of 726 patients were included. After transplantation, serum potassium was significantly lower in the low-chloride group (standardized mean difference compared to NSS group, -0.38 mEq/L; 95% CI, -0.66 to -0.11; p = 0.007). Similarly, postoperative chloride was lower in the low-chloride group (-2.41 mEq/L [-3.34 to -1.48], p < 0.001). No statistically significance was observed in delayed graft function (OR, 0.98 [0.56-1.69], p = 0.93), day 3 creatinine (-0.14 mg/dL [-0.46 to 0.18], p = 0.38), or day 7 urine output (-0.08 L [-0.29 to 0.12], p = 0.43). CONCLUSION: Use of NSS during renal transplant leads to increased incidence of hyperchloremic acidosis with subsequent hyperkalemia, but clinical significance in the form of delayed graft function or postoperative creatinine remains comparable to that of low-chloride solutions.