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.

Pharmacological options for Candida albicans Endocarditis at the roadblock with irrecoverable prosthetics and drug interactions: a case report and review of literature.

BACKGROUND: Candidemia is the fourth most common nosocomial bloodstream infection. Endocarditis from candidemia is a rare but possibly fatal complication. The efficacy of amphotericin and echinocandins for induction and azoles for suppression has been well studied. Source control of infection, including removal of foreign bodies, remains the cornerstone for the success of any antifungal therapy. CASE PRESENTATION: We are describing a case of a 63-years old patient with multiple comorbidities who developed candidemia secondary to Candida albicans. The prospect of curing the fungemia was made difficult by prosthetic devices, including prosthetic heart valves, intracardiac defibrillator, and inferior vena filter, which could not be extracted due to poor cardiovascular status and higher postoperative mortality risk. Combination therapy with amphotericin and 5-Flucytosine (5FC) was used with the first recurrence. Suppression with fluconazole was contraindicated due to prolonged corrected QT (QTc) interval. Isavuconazole was employed for chronic lifelong suppression. CONCLUSION: Retaining prosthetics in higher surgical risk patients presents us with unique clinical and pharmacological challenges regarding breakthrough infections, drug interaction, and side effects from prolonged suppressive therapies.

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.

Efficacy and Safety of Fevipiprant in Asthma: A Review and Meta-Analysis.

Fevipiprant is a non-steroidal oral prostaglandin D2 (PGD2) receptor 2 antagonist that reduces bronchial wall inflammation, possibly improving clinical outcomes in the asthmatic population. A systemic review search was conducted on PubMed, Embase, and Central Cochrane Registry. Randomized clinical trials were included with Fevipiprant as an intervention arm compared to placebo. For continuous variables, the standardized mean difference, and for discrete variables, Mantel-Haenszel Risk Ratio (MH Risk ratio) was used for analysis. Confidence interval of 95% and p-value < 0.05 was considered significant. The analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. A total of five articles, including seven trials, were included in the analysis. There was significant increase in post-bronchodilator forced expiratory volume in one second (FEV1) 0.249 (0.157-0.341), p<0.001 and pre-bronchodilator FEV1 0.115 (0.043 to 0.188), p=0.002. A decrease in asthma control questionnaire (ACQ) score of -0.124 (-0.187 to -0.062), p<0.001, was reported. Statistically significant asthma exacerbation reduction was reported in the high eosinophil count population with a daily dose of 450mg 0.77 relative risks (RR) (0.61-0.97). There was a positive deviation toward Fevipiprant 450mg dose for asthma reduction in the overall population, but it was not statistically significant. Fevipiprant produced a slight statistically significant reduction in asthma exacerbations in the high eosinophil count population with favorable deviation in the overall population. It significantly increased pre-and post-bronchodilator FEV1 and improved ACQ scores in treated patients. The benefits, though statistically significant, failed to translate into clinical importance.

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.

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.

An Unfortunate Case of Takotsubo Cardiomyopathy During Plasmapheresis for Myasthenia Crisis.

A literature review shows scarce reports of myasthenic crises (MC) complicated by Takotsubo cardiomyopathy (TC). This patient cohort (0.11%) has higher all-cause mortality and prolonged in-hospital course. We present a rare case of a 72-year-old man who developed cardiogenic shock post-plasmapheresis for myasthenia crisis. He became hemodynamically unstable and developed acute respiratory failure requiring intubation 30 minutes after completion of plasma exchange. Serum troponin peaked at 3.19 ng/mL while an emergent 12-lead electrocardiogram (EKG) showed new-onset diffuse ST-segment elevation. Hypokinesis of the entire apex, anterior septum, mid-and apical inferior septum, and mid-and apical inferior wall consistent with Takotsubo cardiomyopathy was seen on bedside echocardiogram. The patient received a continuous infusion of norepinephrine and vasopressin. The hospital course was complicated by multiorgan failure and eventual demise. This case highlights MC and the potential of plasma exchange therapy to induce TC.

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.

Clostridioides difficile infection in liver cirrhosis patients: A population-based study in United States.

BACKGROUND: Clostridioides (formerly Clostridium) difficile infection (CDI) is an increasingly frequent cause of morbidity and mortality in hospitalized patients. Multiple risk factors are documented in the literature that includes, but are not limited to, antibiotics use, advanced age, and gastric acid suppression. Several epidemiological studies have reported an increased incidence of CDI in advanced liver disease patients. Some have also demonstrated a higher prevalence of nosocomial infections in cirrhotic patients. AIM: To use a large nationwide database, we sought to determine CDI's risk among liver cirrhosis patients in the United States. METHODS: We queried a commercial database (Explorys IncTM, Cleveland, OH, United States), and obtained an aggregate of electronic health record data from 26 major integrated United States healthcare systems comprising 360 hospitals in the United States from 2018 to 2021. Diagnoses were organized into the Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) hierarchy. Statistical analysis for the multivariable model was performed using Statistical Package for Social Sciences (SPSS version 25, IBM CorpTM). For all analyses, a two-sided P value of < 0.05 was considered statistically significant. RESULTS: There were a total of 19387760 patients in the database who were above 20 years of age between the years 2018-2021. Of those, 133400 were diagnosed with liver cirrhosis. The prevalence of CDI amongst the liver cirrhosis population was 134.93 per 100.000 vs 19.06 per 100.000 in non-cirrhotic patients (P < 0.0001). The multivariate analysis model uncovered that cirrhotic patients were more likely to develop CDI (OR: 1.857; 95%CI: 1.665-2.113, P < 0.0001) compared to those without any prior history of liver cirrhosis. CONCLUSION: In this large database study, we uncovered that cirrhotic patients have a significantly higher CDI prevalence than those without cirrhosis. Liver cirrhosis may be an independent risk factor for CDI. Further prospective studies are needed to clarify this possible risk association that may lead to the implementation of screening methods in this high-risk population.

A Case of COVID-19-Associated Autoimmune Hemolytic Anemia With Hyperferritinemia in an Immunocompetent Host.

We report an interesting case of a middle-aged gentleman who presented with diabetic ketoacidosis (DKA) and tested polymerase chain reaction (PCR) positive for COVID-19 infection. His hospital stay was complicated by acute kidney injury, hematuria, and normocytic anemia. Initial chest x-ray demonstrated bibasilar opacities. D-dimer and C-reactive protein were elevated. During his hospital stay, his hemoglobin decreased from 13.4 g/dL to 9 g/dL, and further workup demonstrated ferritin of 49,081 ng/mL with lactate dehydrogenase of 1665 U/L. He was treated with prednisone and folic acid for autoimmune hemolytic anemia (AIHA). Ferritin was downtrended, and hemoglobin stabilized. As demonstrated by this case report and prior literature review, COVID-19 infection can be associated with AIHA.

Case report: aseptic meningitis secondary to varicella-zoster virus (VZV) without an exanthem post MMR vaccination.

BACKGROUND: Varicella-zoster virus (VZV) is a known cause of aseptic meningitis, with a predisposition for an immunocompromised population. A dermatomal rash usually accompanies aseptic meningitis secondary to VZV. CASE PRESENTATION: We report the case of a 31-year-old male with a history of chickenpox in childhood and recent shingles who presented with severe frontal headaches secondary to VZV meningitis. The patient had also recently received the measles-mumps-rubella (MMR) vaccine. He recovered without any neurological sequala. CONCLUSION: This case report describes an immunocompetent patient with recent MMR vaccination who developed aseptic meningitis secondary to VZV without any dermatomal involvement (Zoster Sine Herpete).

Can Clinicians Start Prescribing Inclisiran for Hypercholesterolemia Today? A Review of Clinical Studies for Internal Medicine Physicians and Endocrinologists.

The safety profile and efficacy margin of inclisiran as a lipid-lowering drug have been assessed in clinical trials and are underway in subgroups with relevant co-morbidities. This systematic review looks at the clinical trials that have been conducted to comment on its safety and efficacy. The conclusions can serve as a guide for practicing physicians and researchers for following current and future cohorts of patients. PubMed, Cochrane, Embase, Scopus, CINAHL, Web of Science, and Clinicaltrials.gov were searched comprehensively using the terms "Inclisiran", "ALN-PCSsc", and "ALN-PCS" using the Boolean operator "OR" with data cut-off date of June 28, 2020. The outcomes of safety and efficacy were collected and charted for the systematic review. In our study, eight clinical trials were included in the final study: the ORION (1,2,7,9-11) trials and two clinical trials (phase 1 randomized clinical trials) done before ORION trials. Favourable efficacy in terms of LDL levels and PSCK9 levels was observed across all eight clinical trials. No severe adverse effects, safety concerns, or fatalities attributable directly to inclisiran were reported. Therefore, our study results suggest a positive efficacy and safety profile of inclisiran as a lipid-lowering drug in clinical trials.

Catastrophic right-sided Candida empyema from spontaneous esophageal perforation.

Right-sided empyema secondary to esophageal rupture are rare but reported in the medical literature. We describe an atypical CASE of right-sided empyema with Candida Tropicalis, Candida Glabrata, and Staphylococcus lugdenensis leading to a diagnosis of spontaneous esophageal rupture. We concluded that pleural effusion with fungal and multi-organism growth should immediately raise suspicion for underlying missed esophageal perforation. Prompt diagnosis of esophageal perforation can prevent fatal complications like pleuritis, pneumothorax, hydrothorax, pneumomediastinum, mediastinitis, acute respiratory distress syndrome, and septic shock.

First case report of pulmonary embolism with Zoster Sine Herpete.

BACKGROUND: Varicella-Zoster Virus (VZV) infection is known to cause coagulation abnormalities leading to pulmonary embolism and ischemic strokes. The incidence of vascular and thrombotic complications with Zoster Sine Herpete has been reported very infrequently in the medical literature. CASE PRESENTATION: A 32-year-old man with no significant past medical history presented to Emergency Room with right-sided facial weakness and headache. We saw no rash on physical examination. A sub-segmental pulmonary embolus was found on C.T. angiography of the chest. VZV was detected on Lumbar Puncture studies. The patient responded well to anti-viral treatment and was discharged home without any complications. CONCLUSION: The suspicion of thrombo-embolic complications should be high with Zoster Sine Herpete. Screening for coagulopathies and timely initiation of anticoagulation should be carried out in appropriate clinical settings.

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.

Clinical and Microbiologic Efficacy and Safety of Imipenem/Cilastatin/Relebactam in Complicated Infections: A Meta-analysis.

BACKGROUND: Antimicrobial resistance is on the rise. The use of redundant and inappropriate antibiotics is contributing to recurrent infections and resistance. Newer antibiotics with more robust coverage for Gram-negative bacteria are in great demand for complicated urinary tract infections (cUTIs), complicated intra-abdominal infections (cIAIs), hospital-acquired bacterial pneumonia (HABP), and ventilator-associated bacterial pneumonia (VABP). MATERIALS AND METHODS: We performed this meta-analysis to evaluate the efficacy and safety profile of a new antibiotic, Imipenem/cilastatin/relebactam, compared to other broad-spectrum antibiotics for complicated infections. We conducted a systemic review search on PubMed, Embase, and Central Cochrane Registry. We included randomized clinical trials-with the standard of care as comparator arm with Imipenem/cilastatin/relebactam as intervention arm. For continuous variables, the mean difference was used. For discrete variables, we used the odds ratio. For effect sizes, we used a confidence interval of 95%. A P-value of less than 0.05 was used for statistical significance. Analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I² statistic. RESULTS: The authors observed similar efficacy at clinical and microbiologic response levels on early follow-up and late follow-up compared to the established standard of care. The incidence of drug-related adverse events, serious adverse events, and drug discontinuation due to adverse events were comparable across both groups. CONCLUSION: Imipenem/cilastatin/relebactam has a non-inferior safety and efficacy profile compared to peer antibiotics to treat severe bacterial infections (cUTIs, cIAIs, HABP, VABP).

Case report of peritoneal carcinomatosis of plasma cell origin in a patient with newly diagnosed HIV: A terminal event.

BACKGROUND: B-cell tumors and plasma cell malignancies have been identified in persons living with the human immunodeficiency virus (PLHIV). The literature review has revealed numerous reports of solitary plasmacytomas with metastasis in PLHIV. CASE REPORT: A young patient with no prior medical or surgical history presented with tumor lysis syndrome secondary to metastatic plasma cell Epstein-Baer virus (EBV) related malignancy with peritoneal carcinomatosis. The history and clinical picture promptly led to the diagnosis of HIV. The subsequent hospital course was dismal, and lifespan was cut short by multi-organ failure. CONCLUSION: This case is being reported to highlight the suspicion of HIV in patients presenting acutely with aggressive plasma cell malignancies.

First case report of acute cholangitis secondary to Cronobacter sakazakii.

INTRODUCTION: Cronobacter sakazakii is an opportunistic Gram-negative, rod-shaped bacterium which may be a causative agent of meningitis in premature infants and enterocolitis and bacteremia in neonates and adults. While there have been multiple cases of C. sakazakii infections, there have been no acute cholangitis cases reported in humans. CASE PRESENTATION: An 81-year-old male with a past medical history of basal cell carcinoma, alcoholic liver cirrhosis, transjugular intrahepatic portosystemic shunt procedure, complicated by staphylococcus bacteremia, pituitary tumor, glaucoma, and hypothyroidism presented to the emergency room with the complaint of diffuse and generalized 10/10 abdominal pain of 1 day's duration. There was a concern for pancreatitis, acute cholangitis, and possible cholecystitis, and the patient underwent a percutaneous cholecystostomy tube placement. Blood cultures from admission and biliary fluid cultures both grew C. sakazakii. The patient was treated with a carbapenem and clinically improved. CONCLUSIONS: The case study described a patient with multiple medical comorbidities that presented with C. sakazakii bacteremia and cholangitis. While this bacterium has been implicated in other infections, we believe this is the first time the bacteria is being documented to have caused acute cholangitis.

Antimicrobial Stewardship: A Review for Internal Medicine Physicians.

Antimicrobial stewardship is the need of the hour to prevent the collapse of our health care system at the hands of a pandemic of resistant pathogens. Inappropriate and indiscriminate abuse of antibiotics has left very few options for prescribing physicians as most of the pathogens, particularly gram-negative, are resistant to the major antibiotics. This article reviews the importance of Antimicrobial Stewardship Programs (ASP) for internal medicine physicians and residents. Commonly encountered clinical scenarios are discussed. Appropriate indications of antibiotics, pathogen-guided prescriptions, adverse effects of common antibiotics, and options to use newer antibiotics are reviewed. The role of a health care team is highlighted. The evidence-based steps taken to ensure ASPs implementation are reiterated to serve as an educational guide for medical residents and physicians.