Melatonin: Evolving Physiological Understanding and Potential Therapeutic Role in Pain Medicine Including Intervertebral Disc Degeneration.

BACKGROUND: Melatonin, one of the most versatile hormones in the body, is well appreciated in managing circadian rhythm and for antioxidant properties. Produced in the pineal gland and within mitochondria, melatonin influences many physiologic processes through receptor mediated and direct effects. OBJECTIVE: The present investigation explores the evolving pharmacologic properties of melatonin, as well as current therapeutic uses in areas where mitigating oxidative stress, inflammation, and cellular senescence. This review also delves into novel therapeutic potential of melatonin and how current research is revealing a wide array of therapeutic promise in pain medicine. STUDY DESIGN: A systematic review of randomized controlled trials (RCTs) and observational studies was performed using various search engines focused on melatonin and its role in pain medicine. METHODS: The available literature on melatonin and pain medicine was reviewed. A comprehensive literature search of multiple databases from 1966 to July 2024, including manual searches of the bibliography of known review articles was performed. Quality assessment of the included studies and best evidence synthesis were incorporated into qualitative and quantitative evidence synthesis. OUTCOME MEASURES: The primary outcome measure was the proportion of patients receiving melatonin with significant relief and functional improvement of greater than 50% of at least 3 months. Duration of relief was categorized as short-term (less than 6 months) and long-term (greater than 6 months). RESULTS: Melatonin can affect intervertebral disc (IVD) health through the enhancement of survival and function of nucleus pulposus cells, primarily through activation of the ERK1/2 signaling pathway. Melatonin also influences the biochemical environment of the IVD by modulating inflammation and oxidative stress, crucial factors in the pathogenesis of disc degeneration. Melatonin has been shown to reduce senescence and promote autophagy within disc cells, vital for clearing out damaged cellular components, preserving cellular function and preventing deterioration associated with aging and degenerative diseases. LIMITATIONS: Despite the availability of multiple studies, the paucity of clinical pain related literature is considered as the major drawback. CONCLUSION: Based on the present systematic review, melatonin plays a critical role in sleep, but evolving studies have demonstrated substantive roles in mitigating degenerative conditions in various tissues, including IVD degeneration. Ongoing studies will better clarify the role of melatonin as a potential therapeutic agent, including the targeted delivery to various body regions.

Fluoroquinolones: Neurological Complications and Side Effects in Clinical Practice.

Fluoroquinolones, a popular antibiotic class that inhibits nucleic acid synthesis of bacteria by disrupting the activity of the enzyme's topoisomerase IV and DNA gyrase, are used to treat bacterial infections. However, the widespread use of these drugs has allowed for the development of microbial resistance in recent years. Quinolones also have many clinically relevant side effects, including psychosis, confusion, seizures, headaches, dizziness, and nausea. Common side effects include tendinitis, myopathy, depression, and fatigue. Cardiovascular side effects include increased risk of aortic aneurysm, aortic dissection, and QT interval prolongation. Overall, quinolones can be an effective choice for treating bacterial infections. Still, the side effect profile and decreased efficacy secondary to microbial resistance no longer make the quinolone class an ideal choice for many types of infection. A better understanding of the role of quinolone-mediated or neurological damage, cardiovascular impairment, and musculoskeletal involvement is imperative to determine the risks/benefits for the clinician.

Spina Bifida Prevention: A Narrative Review of Folic Acid Supplements for Childbearing Age Women.

Neural tube defects (NTDs) are malformations that occur during embryonic development, and they account for most central nervous system birth anomalies. Genetic and environmental factors have been shown to play a role in the etiology of NTDs. The different types of NTDs are classified according to anatomic location and severity of the defect, with most of the neural axis anomalies occurring in the caudal spinal or cranial areas. Spina bifida is a type of NTD that is characterized by an opening in the vertebral arch, and the level of severity is determined by the extent to which the neural tissue protrudes through the opened arch(es). Prevention of NTDs by administration of folic acid has been studied and described in the literature, yet there are approximately 300,000 cases of NTDs that occur annually, with 88,000 deaths occurring per year worldwide. A daily intake of at least 400 µg of folic acid is recommended especially for women of childbearing age. To provide the benefits of folic acid, prenatal vitamins are recommended in pregnancy, and many countries have been fortifying foods such as cereal grain products with folic acid; however, not all countries have instituted folic acid fortification programs. The present investigation includes a description of the pharmacology of folic acid, neural tube formation, defects such as spina bifida, and the relevance of folic acid to developing spina bifida. Women's knowledge and awareness of folic acid regarding its importance in the prevention of spina bifida is a major factor in reducing incidence worldwide.

Cefiderocol (Fetroja) as a Treatment for Hospital-Acquired Pneumonia.

With increasing resistance to conventional antibiotic treatments, especially among gram-negative bacilli, the search for new antibiotics has become critical on a global scale. Among infections with multidrug-resistant bacteria is hospital-acquired pneumonia (HAP), which is nosocomial pneumonia in patients who have been hospitalized for more than 48 hours. HAP carries a high mortality rate and continues to be a challenge with regard to adequate treatment. The typical multidrug-resistant gram negatives found in HAP include Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii. Many new antibiotics have been studied and tested against these pathogens as possible solutions, and the search continues. Cefiderocol, a novel siderophore cephalosporin, is effective against these pathogens. Cefiderocol is an iron-chelating agent that makes use of iron pumps on the membrane of bacteria via a catechol moiety on the C3 side chain of the molecule. This allows for easy access into the cytoplasm, where it can inhibit peptidoglycan synthesis by binding to penicillin-binding proteins. Cefiderocol displays linear pharmacokinetics and is mainly excreted through the kidneys. It is well tolerated in healthy individuals but may need adjustments of dosage in patients with impaired renal function. Studies have shown that both healthy subjects and those with impaired renal function experienced some adverse effects, including nausea, diarrhea, abdominal pain, and increased creatinine kinase; however, these adverse effects were limited and experienced in placebo groups. It has demonstrated efficacy in treating infections caused by many multidrug-resistant gram-negative pathogens and has demonstrated high stability against many classes of b-lactamases. There have been multiple phase 3 trials, such as the CREDIBLE-CR trial and the APEKS-NP trial, that demonstrated efficacy in treated nosocomial pneumonia caused by multidrug-resistant gram negatives, such as carbapenem-resistant Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa, compared to the best available treatment. While clinical data remain limited, a few studies are showing clinical efficacy and few adverse effects. Cefiderocol demonstrated effectivity in treating multidrug-resistant gram-negative pneumonia in patients with multiple comorbidities, such as chronic kidney disease, chronic-obstructive pulmonary disease, and diabetes mellitus. Cefiderocol shows promise as a novel antimicrobial agent in treating multidrug-resistant gram-negative in HAP.

Posterior Sacroiliac Fusion Surgery: A Retrospective Single Center Study.

BACKGROUND: Chronic sacroiliitis has variable etiologies with numerous treatments of varying efficacy. In recent years, a novel posterior approach utilizing bone matrix has been developed although to date, there is limited data in the literature regarding efficacy and safety through this approach. Benefits described include reduced adverse outcomes and quicker recovery when compared to the lateral approach. OBJECTIVE: The present investigation focused on sacroiliac joint fusion through the posterior approach and outcomes including disability, pain, and use of analgesics post-surgery. STUDY DESIGN: This retrospective, single-center study was conducted evaluating safety and efficacy of sacroiliac fusion allograft implants (LinQ Implant System from PainTEQ; PsiF System from Omnia Medical). METHODS: A total of 72 posterior approach sacroiliac joint fusions were performed. Fifty-three individuals were enrolled and followed at LSU Health Shreveport as the sole investigational site between August 2020 and June 2024. Selected participant age ranged between 28 and 79 years, with a mean age of 53.4 years. The LinQ Implant System was the primary surgical hardware selected for implantation (83.0%), with the PsiF System chosen in the remaining cases. OUTCOME MEASURES: VAS Scores, disability changes, adverse outcomes, and analgesic use were compared after sacroiliac joint fusion via the posterior approach. RESULTS: Mean VAS Scores for SIJ Pain Intensity significantly decreased by 3.6 cm from a baseline score of 9.5 cm by the Specified End (June 1st, 2024). In this regard, 65.4% of patients experienced a 20% or greater improvement in pain, 38.5% of patients experienced a 50% or greater improvement in pain, and 26.9% of patients experienced a 70% or greater improvement in pain.  Zero (0) procedure-related adverse events nor intra- or post-operative complications occurred throughout the duration of the investigation. LIMITATIONS: Retrospective nature of the study without a control group. Fifty-four percent (39 of 72) completed minimum one year follow up. Further, the withdrawal rate was 26%. CONCLUSION: The results of the present investigation demonstrated effective outcomes with minimal adverse effects and improvements in disability over a three-year period in the largest single center study to date involving posterior approach sacroiliac joint fusion.

Palforzia for Peanut Allergy: A Narrative Review and Update on a Novel Immunotherapy.

With Palforzia appearing as the first oral immunotherapy for patients with peanut allergy, the present investigation aims to summarize recent clinical trials, the mechanism of dosing, and the real-world usage of this novel therapy. Palforzia offers a new avenue for treating the human allergic response in previous immune modulation refractory patients or patients who have undergone immune environment sensitivity testing, which allows for more specialized treatment. Current studies are focusing on certain age groups that have been shown to be more receptive to treatment. Further, studies are tailoring oral immunotherapy treatment alongside other immune modulators to elicit greater targeted immune tolerance. With an increasing prevalence of patient allergies, many questions remain surrounding the optimization of therapies in reaching therapeutic goals. Overall, Palforzia offers a hopeful treatment for peanut-allergic patients to attenuate their immune response while furthering research in related therapies.

Guselkumab, a Novel Monoclonal Antibody Inhibitor of the p19 Subunit of IL-23, for Psoriatic Arthritis and Plaque Psoriasis: A Review of Its Mechanism, Use, and Clinical Effectiveness.

Psoriatic arthritis and plaque psoriasis are autoimmune conditions affecting multiple organs, including the skin. The pathophysiology and etiology of these conditions are not fully understood; however, numerous factors are believed to play a critical role, including genetics and environmental risk factors. Furthermore, research suggests the IL-23/IL-17 pathway partially mediates these diseases. Once the IL-23 receptor is bound and activated, two subunits, p19, and p40, act through different signaling pathways. Ultimately, inflammation is produced through the effector molecule, IL-17, other cytokines, and tumor necrosis factor (TNF). Traditionally, these chronic conditions have been treated with TNF-α inhibitors and methotrexate, a dihydrofolate reductase inhibitor. Although successful in inhibiting the immune system, these drugs can have many adverse effects due to their broad targets. In recent years, more targeted therapy has become popular. Guselkumab is a monoclonal antibody that inhibits the p19 subunit of IL-23. It has been FDA-approved to treat both plaque psoriasis and psoriatic arthritis. Clinical trials showing guselkumab's efficacy have been promising, even showing improvement in symptoms of plaque psoriasis patients resistant to adalimumab, a TNF-α inhibitor. Guselkumab has also been shown to be well tolerated with a similar safety profile as other biologics inhibiting the immune system. In addition to its efficacy in treating plaque psoriasis and psoriatic arthritis, the mechanism of action offers a targeted approach that may minimize the broad immunosuppressive effects often associated with traditional therapies, providing a potential advantage in the long-term management of these autoimmune conditions.