Effectiveness of Novel Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Atrial fibrillation (AF) is a common cardiac arrhythmia associated with an increased risk of stroke and systemic embolism (SE). Anticoagulation therapy, particularly with vitamin K antagonists (VKA) or novel oral anticoagulants (NOACs), is essential for stroke prevention in patients with AF. However, the comparative effectiveness of NOACs and warfarin remains debatable. Of the 34 studies included, 14 studies involving 166,845 patients were included in the meta-analysis and 20 studies were included in the systematic review. Our findings indicate that NOACs were associated with a significantly lesser risk of stroke/SE with a relative risk (RR) of 0.84 and p=0.0005, and all-cause mortality RR=0.88 and p=0.006. There were no significant differences between major bleeding events with an RR of 0.87 and p=0.22, and serious adverse events (SAE) with RR=1.01 and p=0.35, compared to warfarin in patients with AF. Our meta-analysis demonstrates strong evidence for the superiority in reducing stroke/SE and all-cause mortality of NOACs compared to warfarin. However, no significant differences were identified in the bleeding outcomes or SAEs between the two groups.

Unraveling the Potential of Electroanalgesia: A Literature Review of Current Therapeutics.

Neuropathic pain (NP), arising from dysfunction in the neurological system, poses a significant challenge in pain management due to its intricate origin and unpredictable response to conventional treatments. Electroanalgesia, a collection of techniques such as transcutaneous electric nerve stimulation (TENS), peripheral electrical nerve stimulation (PENS), spinal cord stimulation (SCS), deep brain stimulation (DBS), and electroacupuncture (EA), presents a potential alternative or complementary approach. This review brings together evidence from 56 studies to evaluate the effectiveness and safety of electroanalgesia in chronic NP. It discusses the mechanisms underlying NP, the indications for electroanalgesia, and the techniques utilized, emphasizing the diverse applications and potential benefits. However, despite its potential uses, electroanalgesia has its limitations, including variable effectiveness and potential adverse effects. Furthermore, the review recognizes the limitations of the methodology and the need for further research to refine treatment protocols and enhance the understanding of electroanalgesia's role in comprehensive pain management strategies.

Non-Interferon-Dependent Role of STING Signaling in Pulmonary Hypertension.

BACKGROUND: Patients with constitutive activation of DNA-sensing pathway through stimulator of IFN (interferon) genes (STING), such as those with STING-associated vasculopathy with onset in infancy, develop pulmonary hypertension (PH). However, the role of STING signaling in general PH patients is heretofore undescribed. Here, we seek to investigate the role of STING in PH development. METHODS: STING expression in patient lung samples was examined. PH was induced in global STING-deficient mice and global type I IFN receptor 1-deficient mice using bleomycin or chronic hypoxia exposure. PH development was evaluated by right ventricular systolic pressure and Fulton index, with additional histological and flow cytometric analysis. VEGF (vascular endothelial growth factor) expression on murine immune cells was quantified and evaluated with multiplex and flow cytometry. Human myeloid-derived cells were differentiated from peripheral blood mononuclear cells and treated with either STING agonist or STING antagonist for evaluation of VEGF secretion. RESULTS: Global STING deficiency protects mice from PH development, and STING-associated PH seems independent of type I IFN signaling. Furthermore, a role for STING-VEGF signaling pathway in PH development was demonstrated, with altered VEGF secretion in murine pulmonary infiltrated myeloid cells in a STING-dependent manner. In addition, pharmacological manipulation of STING in human myeloid-derived cells supports in vivo findings. Finally, a potential role of STING-VEGF-mediated apoptosis in disease development and progression was illustrated, providing a roadmap toward potential therapeutic applications. CONCLUSIONS: Overall, these data provide concrete evidence of STING involvement in PH, establishing biological plausibility for STING-related therapies in PH treatment.

Evaluation of Efficacy of Bromocriptine as a Therapeutic Modality in the Treatment of Diabetes Mellitus: A Systematic Review.

Diabetes mellitus (DM), one of the oldest diseases known to mankind has always been difficult to treat even with the availability of a variety of medications. In such a scenario, the Food and Drug Administration (FDA) has approved a novel therapeutic, bromocriptine, with a different mechanism of action than the traditional medications since 2009 but has not been used as either first-line therapy or add-on therapy. In this systematic review, we searched databases like PubMed, Medline, PubMed Central, Cochrane Library, Clinicaltrials.gov, and Wiley Online Library. The selected articles were screened using inclusion and exclusion criteria and quality appraised; finally, 11 studies including eight clinical trials and three narrative reviews were included. It was found that an increase in dopamine and serotonin levels were hypothesized to convert the insulin-resistant (IR) state to an insulin-sensitive (IS) state. Hence in DM, as there is an IR state, the administration of dopamine was hypothesized to increase insulin sensitivity. In our study based on included studies, it was found that bromocriptine was superior as an add-on therapy to metformin compared to metformin alone, also it was found beneficial in people failing treatment with any one oral hypoglycemic agent. On the contrary, bromocriptine was found inferior to teneligliptin in treating DM. Still, more studies are required to make an accurate and reliable assessment of the efficacy of bromocriptine in treating DM.

The Associations of Auto-Brewery Syndrome and Diabetes Mellitus: A Literature Review and Clinical Perspective.

Endogenous production of alcohol without the external intake of alcohol is called auto-brewery syndrome (ABS), and to get its levels to rise to a level that it has physical symptoms of alcohol intake is rare. The most common cause of ABS is the metabolism of ingested carbohydrates by intestinal microflora. This occurrence does not happen in all normal individuals but only in some high-risk individuals. Patients with diabetes mellitus (DM) have been hypothesized to be at high risk for ABS. We searched databases, such as PubMed, Medline, and PubMed Central, to search for existing literature with relevant keywords. In the finalized review, we have included 30 relevant articles. Alcohol formed in the gut gets absorbed in the bloodstream and immediately gets metabolized, so usually it does not achieve a level in blood high enough to cause symptoms. In high-risk patients, there is an increase in the level of bloodstream alcohol above a certain level, so it shows symptoms. Because there is higher blood glucose in DM, the patients have been shown to be at increased risk for developing ABS. Similarly, obesity is also a risk factor for DM, making it a high-risk condition for ABS. The most involved pathogens are Candida and Saccharomyces.