A Systematic Review on Pulmonary Complications Secondary to Hematopoietic Stem Cell Transplantation.

The main purpose of this systematic review was to identify and synthesize evidence about pulmonary complications following stem cell transplantation to raise awareness among physicians since it is a lesser-known topic. Studies that included targeted pulmonary complications that occurred after stem cell transplantation; in humans; and were randomized controlled trials, cohort studies, and case studies between January 2011 and 2021. Fifteen intervention features were identified and analyzed in terms of their association with successful or unsuccessful interventions. Fifteen of 15 studies that met inclusion criteria had positive results. Features that appeared to have the most consistent positive effects included relevant information consisting of clinical presentations and management of complications.  Hematopoietic stem cell transplantation is a therapeutic method that has been introduced for various hematological diseases. Its main objective is to restore the hematopoietic function that has been eradicated or affected. The stem cell transplantation requires a period of administration of chemotherapeutic agents that may lead to infectious and/or non-infectious pulmonary complications that require follow-up. Noninfectious pulmonary complications include bronchiolitis obliterans, alveolar hemorrhage, fibroelastosis, pulmonary hypertension, and infections. Bronchiolitis obliterans syndrome is an obstructive lung disease that affects the small airways, reducing lung function, and it's the most frequent late-onset complication. Furthermore, diffuse pulmonary hemorrhage is a fatal adverse effect and the most common noninfectious pulmonary complication of acute leukemia, observed within the first weeks after the procedure. Pulmonary hypertension has multiple etiologies, mainly related to the pulmonary veno-occlusive disease. It carries a poor prognosis, with a 55% mortality rate. The area of hematology is very wide and prone to new development of treatments and procedures that could be available for new emerging diseases and improving survival rates.

Hyperinsulinemia Associated Depression.

Hyperinsulinemia promotes fat accumulation, causing obesity. Being an inflammatory state, obesity can induce further inflammation and is a risk factor for HPA (hypothalamic pituitary axis) dysregulation through hypercortisolism-related hyperglycemia. In another hypothesis, the sympathetic nervous system (SNS) plays a significant role in the regulation of hormone secretion from the pancreas such as an increase in catecholamines and glucagon as well as a decrease in plasma insulin levels, a disruption on SNS activity increases insulin levels, and induces glycogenolysis in the liver and lipolysis in adipose tissue during hypoglycemia. Hyperglycemia-hyperinsulinemia exacerbates inflammation and increases the oxidative stress along with regulating the levels of norepinephrine in the brain sympathetic system. Increased inflammatory cytokines have also been shown to disrupt neurotransmitter metabolism and synaptic plasticity which play a role in the development of depression via inhibiting serotonin, dopamine, melatonin, and glutamate signaling. An increased level of plasma insulin over time in the absence of exercising causes accumulation of lipid droplets in hepatocytes and striated muscles thus preventing the movement of glucose transporters shown to result in an increase in insulin resistance due to obesity and further culminates into depression. Further hyperinsulinemia-hyperglycemia condition arising due to exogenous insulin supplementation for diabetes management may also lead to physiological hyperinsulinemia associated depression. Triple therapy with SSRI, bupropion, and cognitive behavioral therapy aids in improving glycemic control, lowering fasting blood glucose, decreasing the chances of relapse, as well as decreasing cortisol levels to improve cognition and the underlying depression. Restoring the gut microbiota has also been shown to restore insulin sensitivity and reduce anxiety and depression symptoms in patients.

Tumor Necrosis Factor Alpha Blockade and Multiple Sclerosis: Exploring New Avenues.

Multiple sclerosis (MS) is the most common disabling disease of the central nervous system (CNS) with a progressive neurodegenerative pattern. It is characterized by demyelination of white matter in CNS and apoptosis of oligodendrocytes. Tumor necrosis factor (TNF) alpha is a major cytokine in the pathogenesis of MS. However, the failure of TNF alpha inhibitors in preclinical and clinical trials disapproved of their use in MS patients. Nevertheless, failures and misses sometimes open avenues for new hits. In the later years, it was discovered that TNF signaling is mediated via two different receptors, TNFR1 and TNFR2, both of which have paradoxical effects. TNFR1 mediates demyelination and apoptosis, while TNFR2 promotes remyelination and neuroprotection. This explained the cause of the failure of non-selective TNF alpha-blockers in MS. It also enlightened researchers that repurposing the previously formulated non-selective TNF alpha-blockers using a receptor-selective approach could lead to discovering novel biologic agents with a broader spectrum of indications and better safety profiles. This review focuses on a novel premier TNFR1 blocker, atrosab, which has been tested in animal models of MS, experimental autoimmune encephalomyelitis (EAE), where it demonstrated a reduction in symptom severity. The early promise shown by atrosab in preclinical studies has given us hope to find another revolutionary drug for MS in the future. Clinical trials, which will finally decide whether this drug can be used as a better therapeutic agent for MS or not, are still going on, but currently, there is no approved evidence regarding efficacy of these agents in treating MS.

Human Chorionic Gonadotropin and Related Peptides: Candidate Anti-Inflammatory Therapy in Early Stages of Sepsis.

Sepsis continues to be a major cause of morbidity, mortality, and post-recovery disability in patients with a wide range of non-infectious and infectious inflammatory disorders, including COVID-19. The clinical onset of sepsis is often marked by the explosive release into the extracellular fluids of a multiplicity of host-derived cytokines and other pro-inflammatory hormone-like messengers from endogenous sources ("cytokine storm"). In patients with sepsis, therapies to counter the pro-inflammatory torrent, even when administered early, typically fall short. The major focus of our proposed essay is to promote pre-clinical studies with hCG (human chorionic gonadotropin) as a potential anti-inflammatory therapy for sepsis.

The Efficacy of Probiotics in the Management of Helicobacter Pylori: A Systematic Review.

Helicobacter pylori is a Gram-negative microorganism that causes chronic dyspepsia, gastritis, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric adenocarcinoma. Various antibiotic regimens are employed to eradicate it; however, antibiotic resistance has skyrocketed in recent years, resulting in a reduction in eradication rates. As a result, numerous novel therapeutic approaches are being adopted in clinical practice, and probiotics are being extensively investigated. Probiotics are living bacteria that, when consumed, offer many medicinal advantages that may be accomplished by altering the amount or activity of gut flora. Their beneficial influence on gut health, immune system modulation, and cancer therapy is the subject of extensive investigation. This is owing to their perceived safety and simplicity of use. The primary objective of this review is to learn about and investigate the function of probiotics in the eradication of H. pylori, either alone or in conjunction with traditional treatments. Data have been collected from PubMed, PubMed Central, Medline, Cochrane, and Google Scholar, and relevant articles have been chosen following the PRISMA guidelines. Our search resulted in 2489 records, of which 123 full-text articles were screened for eligibility. Two reviewers independently performed the quality appraisal of 16 relevant articles, and ultimately 11 high-quality studies are included in this review. In conclusion, probiotic monotherapy does not have a significant effect on the eradication rates of H. pylori, but in conjunction with standard treatment regimens, there was mild improvement in the eradication rates but a significant reduction of side effects due to antibiotics.

Post-Marketing Experience of Edaravone in Amyotrophic Lateral Sclerosis: A Clinical Perspective and Comparison With the Clinical Trials of the Drug.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease that affects the upper and lower motor neurons. Currently, the only treatment for ALS is riluzole, which only has a limited effect on increasing survival from 3 to 6 months. New therapies are needed in the clinical setting for ALS. We aim to compare and contrast the clinical trials of edaravone and the post-marketing experience of the drug during this study. For the method, a search strategy was made using PubMed with the search terms "Amyotrophic lateral sclerosis" (MeSH) and "Edaravone" (MeSH). For inclusion criteria, we used full papers, studies involving humans, and studies published in the English language. We exclude meta-analyses, literature reviews, systematic reviews, studies involving animals, and studies not published in English. After close examination, 20 papers were used for the discussion in this review. The clinical trials showed efficacy in patients in reducing the revised ALS functional rating scale (ALSFRS-R) in patients with early ALS with selective criteria. We documented edaravone's post-marketing experience in six countries: Kuwait, South Korea, Argentina, United States, Israel, and Italy. During the study we analyzed, the forced vital capacity (FVC) and ALSFRS-R scored, together with edaravone's safety in the clinical trials and post-marketing experience. Edaravone seems to be more effective in Asia, where the ALSFRS-R scores and the FVC decline were similar to the clinical trial results in Japan. Studies in Europe did not find the drug clinically useful. At the same time, studies in United States and Argentina were mainly descriptive, so more information is needed to evaluate the drug's efficacy in that part of the world. The drug was well-tolerated in all studies. In conclusion, more studies need to be done worldwide to carry out and clarify the effectiveness of edaravone in the clinical setting.

How to Treat Asymptomatic and Symptomatic Urinary Tract Infections in the Kidney Transplant Recipients?

Patients with end-stage renal functions are treated with renal transplantation. After the transplantation, kidney transplant recipients (KTR) are at the risk of urinary tract infection (UTI). UTI in KTR may be symptomatic and asymptomatic. Asymptomatic UTI is the presence of the organisms without any signs and symptoms. There are various ways suggested in the published research papers to deal with UTI in the KTR. The goal of this literature review is to explore how to treat symptomatic and asymptomatic UTI in KTR. A PubMed search was conducted to identify the studies explaining the methods used to deal with UTI in KTR. A total number of 2158 articles were found while searching for regular keywords; however, we found 996 articles with the medical subject heading (Mesh) keywords. After applying the inclusion/ exclusion criteria, 56 articles with the regular keywords search and 29 articles with the Mesh keywords search were selected. These articles included 24 randomized clinical trials, 16 clinical trials, 7 review articles, 5 case reports, 2 controlled clinical trials, 2 observational studies, and 1 cross-sectional study. Our analysis has shown that the early removal of the stent after the transplantation and the use of antibiotics are beneficial in reducing the incidence of symptomatic UTI in the KTR; whereas, treating asymptomatic UTI in KTR has not been proven helpful in reducing the incidence of developing symptomatic UTI later on.

Fecal Microbiota Transplantation in Recurrent Clostridium Difficile Infection: Is it Superior to Other Conventional Methods?

Clostridium difficile (C. difficile) is a gram-positive species of spore-forming bacteria. C. difficile infection (CDI) is one of the most common hospital-acquired infections in the United States, mainly caused by the use of recent antibiotics that leads to intestinal dysbiosis. Recurrent C. difficile infection (rCDI) often occurs after the successful treatment of CDI. Approximately, 30% of patients experience a clinical recurrence of prior symptoms within eight weeks of antibiotic cessation. This present literature review covers the current pathophysiology of CDI, risk factors for infection, diagnostic methods, several treatment modalities, and the potential use of fecal microbial transplant (FMT) for patients with multiple recurrent CDIs. Recent studies have focused on FMT, with an efficacy rate of nearly 90% in multiple recurrent CDI settings. Despite its efficacy, it is not commonly used as first-line treatment. More studies are needed to establish this therapy as the first option in patients with rCDI.