Safety and efficacy of human serum albumin treatment in patients with cirrhotic ascites undergoing paracentesis: A systematic review and meta-analysis.

Ascites is the most common presentation of decompensated liver cirrhosis. It is treated with therapeutic paracentesis which is associated with several complications. The role of human albumin in patients with cirrhotic ascites remains elusive and has been extensively studied with conflicting results. Thus, in order to fully appraise the available data we sought to perform this systematic review and meta-analysis. Herein we included studies comparing the efficacy and safety of human albumin comparing with other volume expanders and vasoactive agents in patients undergoing paracentesis in cirrhotic ascites. Odds ratio (OR) and mean difference (MD) were used to estimate the outcome with a 95% confidence interval (CI). Albumin use reduced the odds of paracentesis induced circulatory dysfunction (PICD) by 60% (OR 0.40, 95% CI 0.27-0.58). While performing subgroup analysis, albumin use lowered the odds of PICD significantly (OR 0.34, 95% CI 0.22-0.52) in comparison to other colloid volume expanders, but did not lower the odds of PICD in comparison to vasoconstrictor therapy (OR 0.93, 95% CI 0.35-2.45). Albumin was associated with a statistically significant lower incidence of hyponatremia (OR 0.59, 95% CI 0.39-0.88). Albumin did not reduce the overall mortality, readmission rate, recurrence of ascites, mean arterial pressure, incidence of renal impairment, hepatic encephalopathy, and gastrointestinal (GI) bleeding. Thus, treatment with albumin in cirrhotic ascites reduced PICD and hyponatremia although there was no benefit in terms of mortality, readmission rate, recurrence of ascites, hepatic encephalopathy, and GI bleeding.

Patiromer and Sodium Zirconium Cyclosilicate in Treatment of Hyperkalemia: A Systematic Review and Meta-Analysis.

BACKGROUND: Patiromer and sodium zirconium cyclosilicate (SZC) are newer options for hyperkalemia treatment. This systematic review and meta-analysis were conducted to assess the safety and side effect profile of patiromer and SZC compared with placebo or other standards of care in the management of hyperkalemia. METHODS: We searched electronic databases for relevant articles. The screening was performed independently and data were extracted among the selected studies. We performed a statistical analysis on Revman 5.4 software. The odds ratio (OR) was used for outcome estimation with a 95% CI. RESULTS: Patiromer had lower rates of hyperkalemia (OR = 0.44; 95% CI, 0.22-0.89) compared with standard of care. The analysis showed no significant differences between the 2 groups in terms of overall adverse effects, any serious/specific adverse effects, or treatment discontinuation as a result of adverse effects. Comparing the SZC-10 group with standard of care showed no significant differences in the occurrence of hyperkalemia during treatment, overall adverse effects, any serious/specific adverse effects, or treatment discontinuation as a result of adverse effects but showed a higher rate of edema in the treatment group (OR = 6.77; 95% CI, 1.03-44.25). Similarly, no significant differences were seen between the 2 SZC doses for the occurrence of any adverse effects, hyperkalemia, constipation, diarrhea, or urinary tract infection, whereas edema was higher among patients receiving SZC-10 (OR = 3.13; 95% CI, 1.19-8.27). CONCLUSIONS: In patients with acute hyperkalemia, SZC is the drug of choice due to its more rapid reduction of serum potassium level, whereas in patients with chronic hyperkalemia, patiromer appears to be the drug of choice because SZC is associated with an increase in edema, likely due to an increase in sodium absorption, which could have important adverse consequences in patients with chronic kidney disease and or heart failure. Thus, both drugs were found to be safe while treating hyperkalemia. (Curr Ther Res Clin Exp. 2021; 82:XXX-XXX).

RBC Transfusion Strategies in the ICU: A Concise Review.

OBJECTIVES: To critically assess available high-level clinical studies regarding RBC transfusion strategies, with a focus on hemoglobin transfusion thresholds in the ICU. DATA SOURCES: Source data were obtained from a PubMed literature review. STUDY SELECTION: English language studies addressing RBC transfusions in the ICU with a focus on the most recent relevant studies. DATA EXTRACTION: Relevant studies were reviewed and the following aspects of each study were identified, abstracted, and analyzed: study design, methods, results, and implications for critical care practice. DATA SYNTHESIS: Approximately 30-50% of ICU patients receive a transfusion during their hospitalization with anemia being the indication for 75% of transfusions. A significant body of clinical research evidence supports using a restrictive transfusion strategy (e.g., hemoglobin threshold < 7 g/dL) compared with a more liberal approach (e.g., hemoglobin threshold < 10 g/dL). A restrictive strategy (hemoglobin < 7 g/dL) is recommended in patients with sepsis and gastrointestinal bleeds. A slightly higher restrictive threshold is recommended in cardiac surgery (hemoglobin < 7.5 g/dL) and stable cardiovascular disease (hemoglobin < 8 g/dL). Although restrictive strategies are generally supported in hematologic malignancies, acute neurologic injury, and burns, more definitive studies are needed, including acute coronary syndrome. Massive transfusion protocols are the mainstay of treatment for hemorrhagic shock; however, the exact RBC to fresh frozen plasma ratio is still unclear. There are also emerging complimentary practices including nontransfusion strategies to avoid and treat anemia and the reemergence of whole blood transfusion. CONCLUSIONS: The current literature supports the use of restrictive transfusion strategies in the majority of critically ill populations. Continued studies of optimal transfusion strategies in various patient populations, coupled with the integration of novel complementary ICU practices, will continue to enhance our ability to treat critically ill patients.

Endotracheal Tube Size Is Associated With Mortality in Patients With Status Asthmaticus.

BACKGROUND: There is limited evidence on the clinical importance of the endotracheal tube (ETT) size selection in patients with status asthmaticus who require invasive mechanical ventilation. We set out to explore the clinical outcomes of different ETT internal diameter sizes in subjects mechanically ventilated with status asthmaticus. METHODS: This was a retrospective study of intubated and non-intubated adults admitted for status asthmaticus between 2014-2021. We examined in-hospital mortality across subgroups with different ETT sizes, as well as non-intubated subjects, using logistic and generalized linear mixed-effects models. We adjusted for demographics, Charlson comorbidities, the first Sequential Organ Failure Assessment score, intubating personnel and setting, COVID-19, and the first PaCO2 . Finally, we calculated the post-estimation predictions of mortality. RESULTS: We enrolled subjects from 964 status asthmaticus admissions. The average age was 46.9 (SD 14.5) y; 63.5% of the encounters were women and 80.6% were Black. Approximately 72% of subjects (690) were not intubated. Twenty-eight percent (275) required endotracheal intubation, of which 3.3% (32) had a 7.0 mm or smaller ETT (ETT ≤ 7 group), 16.5% (159) a 7.5 mm ETT (ETT ≤ 7.5 group), and 8.6% (83) an 8.0 mm or larger ETT (ETT ≥ 8 group). The adjusted mortality was 26.7% (95% CI 13.2-40.2) for the ETT ≤ 7 group versus 14.3% ([(95% CI 6.9-21.7%], P = .04) for ETT ≤ 7.5 group and 11.0% ([95% CI 4.4-17.5], P = .02) for ETT ≥ 8 group, respectively. CONCLUSIONS: Intubated subjects with status asthmaticus had higher mortality than non-intubated subjects. Intubated subjects had incrementally higher observed mortality with smaller ETT sizes. Physiologic mechanisms can support this dose-response relationship.

Unrelated umbilical cord blood transplant for juvenile metachromatic leukodystrophy: a 5-year follow-up in three affected siblings.

Unrelated umbilical cord blood transplantation (UCBT) was used to treat three siblings with juvenile metachromatic leukodystrophy (jMLD). The efficacy of this therapy was measured over a 5-year period with serial neurological examinations, neuroimaging, nerve conduction studies (NCS), and neuropsychological evaluations (NPE). Outcomes were a function of disease stage at time of UCBT with alteration of disease course occurring in the first 2 years after UCBT and then subsequent halting of progression and stabilization of symptoms and disease.

Effect of thiamine supplementation in critically ill patients: A systematic review and meta-analysis.

INTRODUCTION: Several studies have previously shown the benefit of thiamine supplementation in critically ill patients. In order to fully appraise the available data, we performed a meta-analysis of 18 published studies. METHODS: A thorough systematic search was conducted. The studies enrolling critically ill patients receiving thiamine supplementation was compared with the standard of care (SOC) group. Data was analyzed using RevMan 5.4. Clinical outcomes were pooled using Odds Ratio (OR) and mean differences. RESULT: Eighteen studies (8 RCTs and 10 cohort studies) met the criteria for quantitative synthesis. In the analysis of RCTs, thiamine supplementation showed 42% lower odds of developing ICU delirium (OR 0.58, 95% CI, 0.34-0.98). A reduction in mortaliy was observed on performing fixed effect model analysis however, a level of statistical significance could not be reached on performing random effect model analysis (OR, 0.78; 95% CI, 0.59 to 1.04). Further sub-group analysis of 13 studies in patients with sepsis, there was no difference in mortality between the two groups (OR, 0.83; 95% CI, 0.63 to 1.09). CONCLUSION: Thiamine supplementation in critically ill patients showed a reduction in the incidence of ICU delirium among RCTs. However, there was no significant benefit in terms of overall mortality, and mortality in patients with sepsis. Further, large scale randomized prospective studies are warranted to investigate the role of thiamine supplementation in critically ill patients.

The Emerging Role of Vitamin C as a Treatment for Sepsis.

Sepsis, a life-threatening organ dysfunction due to a dysregulated host response to infection, is a leading cause of morbidity and mortality worldwide. Decades of research have failed to identify any specific therapeutic targets outside of antibiotics, infectious source elimination, and supportive care. More recently, vitamin C has emerged as a potential therapeutic agent to treat sepsis. Vitamin C has been shown to be deficient in septic patients and the administration of high dose intravenous as opposed to oral vitamin C leads to markedly improved and elevated serum levels. Its physiologic role in sepsis includes attenuating oxidative stress and inflammation, improving vasopressor synthesis, enhancing immune cell function, improving endovascular function, and epigenetic immunologic modifications. Multiple clinical trials have demonstrated the safety of vitamin C and two recent studies have shown promising data on mortality improvement. Currently, larger randomized controlled studies are underway to validate these findings. With further study, vitamin C may become standard of care for the treatment of sepsis, but given its safety profile, current treatment can be justified with compassionate use.

A 51-year-old man with seizures and progressive behavioral changes.

A 51-year-old man was admitted for evaluation of new-onset generalized seizures in the context of progressive and significant behavioral change. His medical history was only notable for previous outbreaks of genital herpes. He took no medications. He had occasional social alcohol use and no illicit drug use but was a 35-pack-year current smoker. The patient had no relevant occupational exposure history but had recently traveled to Panama. Initially, the patient's significant other noticed a progressive flattening of his affect. The patient then started to experience episodes of "passing out" that led to injuries prompting ED visits. He was prescribed antiseizure medications and scheduled for an outpatient workup. However, with progressive gait instability, lethargy, and an increase in frequency of generalized seizures, the patient was admitted for treatment of suspected viral encephalitis. Despite initiation of antimicrobial and antiviral therapy, the patient's level of alertness continued to decline, ultimately leading to intubation for airway protection.

The E3 ubiquitin ligase mind bomb 1 ubiquitinates and promotes the degradation of survival of motor neuron protein.

Spinal muscular atrophy is an inherited motor neuron disease that results from a deficiency of the survival of motor neuron (SMN) protein. SMN is ubiquitinated and degraded through the ubiquitin proteasome system (UPS). We have previously shown that proteasome inhibition increases SMN protein levels, improves motor function, and reduces spinal cord, muscle, and neuromuscular junction pathology of spinal muscular atrophy (SMA) mice. Specific targets in the UPS may be more efficacious and less toxic. In this study, we show that the E3 ubiquitin ligase, mind bomb 1 (Mib1), interacts with and ubiquitinates SMN and facilitates its degradation. Knocking down Mib1 levels increases SMN protein levels in cultured cells. Also, knocking down the Mib1 orthologue improves neuromuscular function in Caenorhabditis elegans deficient in SMN. These findings demonstrate that Mib1 ubiquitinates and catalyzes the degradation of SMN, and thus represents a novel therapeutic target for SMA.

Melatonin sensitizes human myometrial cells to oxytocin in a protein kinase C alpha/extracellular-signal regulated kinase-dependent manner.

CONTEXT: Studies have shown that labor occurs primarily in the night/morning hours. Recently, we identified the human myometrium as a target for melatonin (MEL), the neuroendocrine output signal coding for circadian night. OBJECTIVE: The purpose of this study was to determine the signaling pathway underlying the effects of MEL on contractility and the contractile machinery in immortalized human myometrial cells. DESIGN: To ascertain the signaling pathway of MEL leading to its effects on myometrial contractility in vitro, we performed gel retraction assays with cells exposed to iodo-MEL (I-MEL) with or without oxytocin and the Rho kinase inhibitor Y27632. I-MEL effects on inositol trisphosphate (IP(3))/diacylglycerol (DAG)/protein kinase C (PKC) signaling were also investigated. Additionally, we assayed for caldesmon phosphorylation and ERK1/2 activation. RESULTS: I-MEL was found to activate PKC alpha via the phospholipase C/IP(3)/DAG signaling pathway, which was confirmed by PKC enzyme assay. I-MEL did not affect myosin light chain phosphatase activity, and its effects on contractility were insensitive to Rho kinase inhibition. I-MEL did increase phosphorylation of ERK1/2 and caldesmon, which was inhibited by the MAPK kinase inhibitor PD98059 or the PKC inhibitor C1. CONCLUSIONS: MEL sensitizes myometrial cells to subsequent procontractile signals in vitro through activation of the phospholipase C/IP(3)/DAG signaling pathway, resulting in specific activation of PKC alpha and ERK1/2, thereby phosphorylating caldesmon, which increases actin availability for myosin binding and cross-bridging. In vivo, this sensitization would provide a mechanism for the increased nocturnal uterine contractility and labor that has been observed in late-term human pregnancy.