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.

Risk of Nephrolithiasis in Patients with Inflammatory Bowel Disease Receiving Biologic Treatment.

INTRODUCTION: Inflammatory bowel disease is a chronic inflammatory disorder of the gastrointestinal tract. Biologic drugs target specific molecules in the body's immune system to control inflammation. Recent studies have suggested a potential link between their use and an increased risk of nephrolithiasis. We conducted a study to further investigate this association. METHODS: The study used multiple logistic regression analysis to assess the association between the use of biologic drugs and nephrolithiasis. A p-value of <0.05 was considered statistically significant. SAS 9.4 was used for statistical analysis. RESULTS: The final sample consisted of 22,895 cases, among which 5603 (24.51%) were receiving at least one biologic drug. The biologic drugs received were as follows: Adalimumab 2437 (10.66%), Infliximab 1996 (8.73%), Vedolizumab 1397 (6.11%), Ustekinumab 1304 (5.70%); Tofacitinib, 308 (1.35%); Certolizumab, 248 (1.08%); and Golimumab, 121 (0.53%). There were 1780 (7.74%) patients with Nephrolithiasis: 438 (8.0%) patients were receiving biologic treatment. We found that the use of Vedolizumab (OR = 1.307, 95% CI 1.076-1.588, p = 0.0071) increased the odds of Nephrolithiasis by 31%. CONCLUSION: Vedolizumab use was associated with an increased risk of nephrolithiasis. The use of two or more biologic drugs also increased the risk compared to no biologic treatment.

Granulocyte-colony stimulating factor in decompensated liver cirrhosis: a meta-analysis of four randomized controlled trials.

BACKGROUND: Decompensated liver cirrhosis (DC) has high mortality, but liver transplantation is limited due to organ scarcity and contraindications for transplantation. Granulocyte-colony stimulating factor (GCSF) shows potential for liver disease treatment with its regenerative and immunomodulatory properties. To assess the controversial use of GCSF in DC, a meta-analysis of randomized controlled trials (RCTs) compared survival benefits in patients receiving GCSF plus standard medical therapy (SMT) versus SMT alone. METHODS: A literature search was performed in four databases from data inception up to December 2022, and all registered randomized controlled (RCTs) evaluating GCSF-based therapies for cirrhotic patients were included. RESULTS: A study combining four RCTs assessed the impact of GCSF with SMT in 595 patients with decompensated cirrhosis. The results indicated that GCSF + SMT led to higher odds of survival compared to SMT alone [risk ratio 1.28, 95% CI (1.08-1.5)]. Heterogeneity existed among the studies, but overall, GCSF showed potential in improving survival. The intervention group exhibited improved Child-Pugh-Turcotte scores [-2.51, CI (-4.33 to -0.70)], and increased CD34 levels, but no significant improvement in MELD scores. These findings suggest GCSF may benefit patients with decompensated cirrhosis in terms of survival and liver function. CONCLUSION: These results suggest that the combination of GCSF and SMT may have a positive impact on the survival rate and improvement in CPT score in patients with DC. Further RCTs are needed to shed more light on this promising modality in end-stage liver disease.

Outcomes of Patients with Monoclonal Gammopathy of Undetermined Significance with and without Atrial Fibrillation: A Retrospective Cohort Analysis of the Nationwide Inpatient Sample Database.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) is a non-malignant precursor of multiple myeloma (MM). MGUS has been suggested to be associated with a higher risk of cardiovascular diseases, including AFIB, but it is still unclear whether this association is real. Studies are lacking on the impact of atrial fibrillation on health outcomes in this population. The association of AFIB in this population is lagging and merits further investigation. METHODS: The study conducted a retrospective analysis of the Nationwide Inpatient Sample (NIS) for 2018, including adult patients with primary diagnoses of MGUS and AFIB. Patients were divided into two groups based on AFIB presence. Outcomes assessed included complications, length of stay, mortality, hospital charges, and discharge disposition. RESULTS: The study included 9007 patients with MGUS of whom 2404 had AFIB. Patients with both MGUS and AFIB had higher rates of acute kidney injury [AKI] (31.5% vs. 27.5%; p = 0.002) and pericarditis (2% vs. 1.2%; p = 0.029). They also had longer hospital stays (5 vs. 4 days; p < 0.001) and higher hospitalization costs ($43,729 vs. $41,169; p < 0.001). CONCLUSIONS: The study showed that the prevalence of AFIB in MGUS patients is high. Patients with AFIB had increased rates of complications (AKI and pericarditis) and higher mortality compared to patients without AFIB. Further studies screening for AFIB in this patient population are warranted.

Heparin-Induced Thrombocytopenia in Chronic Hemodialysis Patients.

Heparin-induced thrombocytopenia (HIT) is a disorder originating from exposure to heparin and has a spectrum of presentation ranging from asymptomatic positive antibodies to thrombotic complications. When symptomatic, it is associated with morbidity and mortality. The incidence of HIT in the ESRD population is yet to be defined. End-stage renal disease (ESRD) patients are at particular risk due to constant exposure to heparin. The main treatment of HIT is to avoid heparin and pursue alternative anticoagulants. Since 1 of the main advantages of heparin in ESRD patients is the ease of its use due to non-renal clearance, the use of alternative anticoagulants poses yet another challenge for this population due to cost, availability, and adverse effects on ESRD patients. Argatroban seems like the best alternative to heparin in hemodialysis (HD) patients due to its liver clearance. Despite having limited studies in HIT, direct oral anticoagulants (DOACs) were added as a potential treatment for HIT, with apixaban favored in kidney dysfunction as it is the least dependent on kidney clearance. Other treatment modalities exist but are still being studied in ESRD patients. The presence of HIT antibodies is not always associated with clinical syndrome, and some studies suggested that heparin antibodies are transient, and the reintroduction of heparin is still being evaluated as a treatment option. Hence, HIT is a challenging diagnosis in ESRD patients, a population that has frequent exposure to anticoagulants, and a risk/benefit ratio should be weighed between the risk of progression to symptomatic HIT and the benefit of switching to a non-heparin anticoagulant bearing in mind the difficulties associated with the latter.