Assessing the efficacy of amyotrophic lateral sclerosis drugs in slowing disease progression: A literature review.

Amyotrophic lateral sclerosis (ALS) is a fatal and intricate neurodegenerative disease that impacts upper and lower motor neurons within the central nervous system, leading to their progressive destruction. Despite extensive research, the pathogenesis of this multifaceted disease remains elusive. The United States Food and Drug Administration (FDA) has granted approval for seven medications designed to address ALS and mitigate its associated symptoms. These FDA-sanctioned treatments are Qalsody, Relyvrio, Radicava, Rilutek, Tiglutik, Exservan, and Nuedexta. In this review, the effects of these seven drugs on ALS based on their mechanism of action, dosing, and clinical presentations are comprehensively summarized. Each medication offers a distinct approach to manage ALS, aiming to alleviate the burdensome symptoms and slow the disease's progression, thereby improving the quality of life for individuals affected by this neurological condition. However, despite these advancements in pharmaceutical interventions, finding a definitive cure for ALS remains a significant challenge. Continuous investigation into ALS pathophysiology and therapeutic avenues remains imperative, necessitating further research collaborations and innovative approaches to unravel the complex mechanisms underlying this debilitating condition.

Efficacy of Intravenous Colistin Monotherapy Versus Colistin Combined With Meropenem in Patients With Multidrug-Resistant Infections: A Retrospective Observational Study.

Background Intensive care units frequently contend with infections caused by highly drug-resistant organisms, particularly Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacterales (CRE), which often lead to high mortality rates. Colistin (colomycin) is employed to treat infections, notably extremely drug-resistant (XDR) bacteria. Antibiotic combination treatment is a frequently used tactic in this endeavour. However, the widespread use of antibiotics in synergy could result in the emergence of resistance and a rise in side effects, such as those linked to Clostridium difficile infection. The aim of the study was to assess and contrast the clinical results of intravenous colistin monotherapy with the combination of colistin and meropenem in patients experiencing MDR bacteremia resulting from Acinetobacter Baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacterales (CRE). Methods In this retrospective observational study, an analysis spanning two years, from June 2021 to June 2023, was conducted at a teaching hospital located in Karachi, Pakistan. The research involved the retrospective examination of medical records from 132 patients who had been diagnosed with MDR bacteremia. Patients were divided into two categories based on their treatment regimen, either intravenous colistin monotherapy or intravenous colistin combined with meropenem. Among the 132 patients included in the analysis, 66 underwent colistin monotherapy, while the other 66 received a combination of colistin and meropenem. The primary focus of evaluation in this study centered on the 14-day all-cause mortality, while secondary outcomes encompassed clinical success and microbiologic cure. Results The mean age of patients in both groups was comparable, and there were no noteworthy gender differences. Additionally, the distribution of infection types and the isolated pathogens showed no substantial distinctions between the two groups. The study revealed no statistically significant disparities in 14-day mortality, improvement in Sequential Organ Failure Assessment (SOFA) score, or the proportion of patients who were cured and survived between the two treatment groups. Conclusion The findings from this study lead to the conclusion that there exists no significant disparity in the efficacy of colistin monotherapy compared to the combination of colistin with meropenem in the treatment of MDR bacteremia stemming from Acinetobacter Baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Enterobacterales (CRE). The results provide a basis for future research and underscore the significance of ongoing endeavors to refine antibiotic treatment strategies in response to the worldwide issue of antibiotic resistance.

The Role of Sirtuin 1 (SIRT1) in Neurodegeneration.

Sirtuins (SIRT) are a class of histone deacetylases that regulate important metabolic pathways and play a role in several disease processes. Of the seven mammalian homologs currently identified, sirtuin 1 (SIRT1) is the best understood and most studied. It has been associated with several neurodegenerative diseases and cancers. As such, it has been further investigated as a therapeutic target in the treatment of disorders such as Parkinson's disease (PD), Huntington's disease (HD), and Alzheimer's disease (AD). SIRT1 deacetylates histones such as H1 lysine 26, H3 lysine 9, H3 lysine 56, and H4 lysine 16 to regulate chromatin remodeling and gene transcription. The homolog has also been observed to express contradictory responses to tumor suppression and tumor promotion. Studies have shown that SIRT1 may have anti-inflammatory properties by inhibiting the effects of NF-κB, as well as stimulating upregulation of autophagy. The SIRT1 activators resveratrol and cilostazol have been shown to improve Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores in AD patients. In this review, we aim to explore the various roles of SIRT1 with regard to neuroprotection and neurodegeneration.

Effect of Comorbidities on Inflammatory Bowel Disease-Related Colorectal Cancer: A Nationwide Inpatient Review.

Introduction  The risk of inflammatory bowel disease-associated colorectal cancer (IBD-CRC) is known to increase with primary sclerosing cholangitis (PSC) and a family history of CRC. However, the impact of comorbidities such as liver disease, obesity, diabetes, chronic lung, heart, and renal disease, and psychiatric illness on the risk of IBD-CRC remains unclear. We evaluated the effect of these comorbidities on the risk of IBD-CRC. Methods A retrospective review from 2009 to 2014 was conducted using the National Inpatient Sample data for adults 18 years and older. Patients with IBD (360,892), of whom 2,831 had CRC were identified using the International Classification of Diseases, Ninth Revision codes (ICD-9). Data on comorbidities were also obtained. Adjusted odds ratios (aOR) and confidence intervals (CI) were computed via logistic regression to evaluate the effect of comorbidities on the risk of IBD-CRC; the p-value was set at <0.05. Results The mean age of IBD patients in this study was 52.36±0.03. A majority of the patients with IBD-CRC were white and were significantly older compared to those without cancer (60 vs 52 years, p<0.05). The risk of colon cancer in IBD was increased by having a non-cholestatic liver disease (aOR 1.51, CI 1.23-1.86, p<0.01). Also, patients younger than 50 years with liver disease were at an increased risk of IBD-associated colon cancer in comparison to older patients (aOR 1.83 vs 1.34, p<0.05). Notably, diabetes, chronic pulmonary disease, renal failure, psychiatric illnesses, and rheumatoid diseases, were inversely associated with the risk of IBD-CRC (p<0.05). After stratifying by IBD subtypes, non-cholestatic liver disease was still independently associated with a higher risk for colon cancer in patients with ulcerative colitis or Crohn's disease (ulcerative colitis: aOR 1.43, CI 1.08-1.89; Crohn's disease: aOR 1.46, CI 1.10-2.00). Conclusions Patients with IBD who have non-cholestatic liver disease might have a higher risk for colon cancer, even at a younger age. These patients may require close colon cancer surveillance.

Decreasing Rates of Fracture-Related Hospitalization With Primary Biliary Cholangitis: Insights From the Nationwide Inpatient Sample.

Introduction Primary biliary cholangitis (PBC) is associated with an increased risk of developing fractures. Current guidelines recommend measures that can help prevent the development of fractures in these patients. The purpose of this study was to trend the rates of hospitalizations related to fractures and their burden on healthcare. Methods We performed a retrospective, cohort study of adults hospitalized in the United States with PBC between 2010 and 2014. Patients were identified using the Nationwide Inpatient Sample (NIS). Temporal analysis of PBC patients with a co-diagnosis of hip, vertebral, or wrist fractures (the study group) was performed with regards to the total number of inpatient admissions, inpatient mortality, length of stay, and total charges associated with hospitalization. Descriptive analyses were performed using the t-test for continuous data and the chi-square test for categorical data. Results During the five-year study period, there were 308,753 hospitalizations for PBC. There has been a downward trend (p=0.02) in fracture-related admissions among patients with PBC during this study period. Length of stay was higher in the PBC-fracture group (10.85 days vs 7.36 days; p<0.001). Total hospitalization charges were higher among the PBC-fracture patients when compared to the control group ($98,444 vs $72,964; p=0.004). Conclusion There has been a gradual reduction in the rate of fracture-related hospitalizations in patients with PBC. However, patients with PBC who have fractures have increased the utilization of health care resources as compared to their cohort admitted for reasons other than for a fracture.

Immunoglobulin G4 Cholangiopathy Masquerading as a Klatskin Tumor: An Interesting Case.

Immunoglobulin G4 (IgG4) cholangiopathy is used to describe regional biliary involvement in a systemic fibro-inflammatory and infiltrative disease, IgG4-related disease. Occasionally, it tends to present with localized disease leading to an extensive workup to rule out malignancy and infections, especially since IgG4-related disease is an uncommon entity. Herein, we present a case of a 68-year-old male who presented with pruritus and steatorrhea with imaging studies revealing a biliary hilar mass concerning for malignancy. Subsequent extensive testing was inconclusive of malignancy and finally noted to have elevated IgG4 levels as part of a broader workup. The patient was started on prednisone with the resulting improvement in his symptoms and the imaging findings.

Coaxial Double-Pigtail Stent Placement: A Simple Solution to Decrease Bleeding Risk Associated With Lumen-Apposing Metal Stent?

Endoscopic cystogastrostomy using lumen-apposing metal stent (LAMS) is considered the first-line therapy for symptomatic pancreatic fluid collections (PFCs). Routine coaxial placement of a double-pigtail stent (DPS) through LAMS is debated. We report the case of a patient with delayed massive gastrointestinal bleed eight weeks after LAMS placement due to splenic artery pseudoaneurysm leading to a complicated hospitalization. Theoretically, coaxial placement of DPS through LAMS can prevent the relatively sharp LAMS from eroding into the mucosa of the collapsed cavity of PFCs, decreasing the risk of bleeding. Our case adds to the growing need to further explore the utility of this combined intervention.

A Retrospective Review of Tumor Lysis Syndrome Associated With Colorectal Cancer.

Tumor lysis syndrome (TLS) is a life-threatening oncologic condition that is most commonly linked with hematologic malignancies and uncommonly seen in solid tumors, including colorectal cancer (CRC). Therefore, a lack of awareness regarding TLS in CRC could lead to significant morbidity and mortality. This study aims to explore the clinical characteristics and outcomes of TLS in patients with CRC. A systematic review of the literature was performed by searching PubMed using the keywords "tumor lysis syndrome" and "colorectal cancer". The English-language case reports and abstracts that the search results yielded were reviewed, and additional articles of interest were identified from reference lists. Information regarding the patients (age at diagnosis, presentation, and comorbidities), the tumors (histology, grade, and stage), radiologic investigations, treatment modalities (surgery, radiation, and systemic therapy), and the outcomes (response, adverse events) were recorded, when available. Descriptive statistics, such as frequency counts, medians, and ranges, were used to characterize the pooled sample. Nine case reports of TLS in CRC were identified in the literature; one additional case was added from our patient database. The median age of these patients was 58.5 years (range: 42-82 years) with 70% of these patients being male. Of note, 100% of these patients had metastatic colon cancer and 80% had metastatic involvement of the liver; 70% of these cases were associated with therapy-induced TLS with the median time-to-event being three days (range: 18 hours-30 days) after receiving chemotherapy. When looking at laboratory parameters, uric acid and lactate dehydrogenase (LDH) were consistently elevated in all the cases, but 50% of the cases had hyperkalemia and 50% had hyperphosphatemia. Treatment of TLS included supportive measures with IV hydration. Five out of 10 patients received urate oxidase and only one underwent hemodialysis. The overall mortality was 60%. TLS can occur with CRCs that demonstrate a high tumor burden. While most cases are associated with therapy, some cases are spontaneous in nature. Keeping in mind the high mortality associated with TLS, physicians should have a high degree of suspicion and should be aware of the fatal complications associated with TLS. Timely implementation of prophylactic and therapeutic measures including IV hydration as well as the use of xanthine oxidase inhibitors such as allopurinol can be life-saving in these cases.