Search

Bola-shaped diester dicarboxylic acid 2-({2-[(2-carboxybenzoyl)-xy]ethoxy}carbonyl)benzoic acid (L1H2)was synthesized by desymmetrizing phthalic anhydride using 1,2-ethane diol. The corresponding dinuclear copper(II)-tetracarboxylate complex[Cu2(L1)2·(DMF)2](1) has been synthesized. This paddle wheel complex was self-assembled with[15]-membered bis-chelate ring on either sides of the M–M axis. Upon treating with phenanthroline/bipyridine, the symmetrically formed bis-chelate rings in1were selectively desymmetrized into monochelate rings. The dinuclear association in1rearranged into mononuclear in [Cu(L1)·(bpy)](2) and [Cu(L1)·(phen)]·(DMF) (3), where bpy = bipyridine and phen = phenanthroline. The paddle wheel arrangement in1is very similar to that in dimeric Cu(II) acetate; the symmetric arrangement in1rearranged in its corresponding monomeric species on reacting with phen and bpy. The symmetric bis-chelate ring in1and the desymmetrized monochelate ring in2and3are discussed following their crystal structures. The crystal structures for all the complexes and the electronic and fluorescence properties are discussed. [ABSTRACT FROM AUTHOR]

The platelet count, mean platelet volume, and other hematological parameters were compared in blood samples anticoagulated with MgSO 4 and EDTA. A total of 15 samples were taken, and the platelet counts were observed to be significantly high in MgSO 4 -anticoagulated blood samples ranging from 53 × 10 3 to 499 × 10 3 /µL, whereas in EDTA-anticoagulated blood samples, the counts ranged from 10 × 10 3 to 353 × 10 3 /µL. This increased platelet count was also statistically significant with the P value being .005. The morphology of red blood cells and white blood cells in Leishman-stained smears from MgSO 4 -anticoagulated blood was below average. In conclusion, MgSO 4 can be used as an alternative anticoagulant only to estimate the platelet counts in EDTA-induced pseudothrombocytopenia.

Irritable bowel syndrome (IBS) is a highly prevalent and debilitating disorder of gut-brain interaction (DGBI) affecting millions globally. It imposes a significant burden on healthcare systems and is a leading cause of workplace absenteeism. IBS is classified into several subtypes based on predominant presenting symptoms, including IBS with constipation (IBS-C) and IBS with diarrhea (IBS-D), with each requiring targeted approaches to treatment. Some treatments, such as psychotherapy, dietary intervention, and medications like tricyclic antidepressants, are nonspecific and recommended for managing IBS symptoms across all subtypes. In contrast, therapies like secretagogues for IBS-C and eluxadoline or rifaximin for IBS-D are subtype-specific. However, many IBS treatments carry conditional recommendations and are based on low-certainty evidence, emphasizing the need for further research to expand the available treatment options. This review compares the latest IBS management guidelines from the American Gastroenterological Association (AGA), American College of Gastroenterology (ACG), British Society of Gastroenterology (BSG), and European Society for Neurogastroenterology and Motility (ESNM). Pharmacologic and non-pharmacologic therapies, including established and emerging interventions, will be explored to provide a comprehensive guide to management.

The prevalence of concomitant deep vein thrombosis (DVT) and its impact on 30-day outcomes in Hispanic patients with acute pulmonary embolism (PE) is unknown. We retrospectively studied a cohort of Hispanic patients admitted for acute PE to determine the relationship of concomitant DVT to clot burden on chest computer tomography (CT), right heart strain, and 30-day mortality. We identified 391 patients admitted with acute PE; 168 (42.9%) had concomitant DVTs on admission; 39 patients (9.9%) died during the 30-day follow-up: 12 patients without concomitant DVT and 27 with concomitant DVT, respectively ( p < .001). The presence of a proximal DVT independently predicted 30-day mortality even after adjusting for age, gender and admission PE severity index scores (PESI) (hazard ratio [HR] 2.0; 95% confidence interval [CI]: 1.4-3.0, p = .001). Proximal DVTs remained a significant predictor of 30-day mortality in patients with low and intermediate PESI scores (HR 2.5; 95% CI: 1.1-6.0, p = .035). The prevalence of concomitant DVT in Hispanic patients presenting with acute DVT is relatively lower than other ethnic groups. However, a proximal location of a DVT is of significant prognostic relevance. Hispanic patients with acute PE should routinely undergo compression doppler ultrasonography (CDUS) of the lower extremities., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The aim of this study was to identify the relationship between preventative dental practices and cardiometabolic health in adolescents., Method and Materials: Analysis included children aged 13 to 17 years enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 who completed an Oral Health Examination and Questionnaire. Deferred dental care was defined as not having a dental visit in the past year. Financial barriers to seeking dental care (vs no financial barriers) were assessed among those with deferred dental care in the past year. Primary cardiometabolic outcomes included obesity, elevated blood pressure, and hypertensive blood pressure. Secondary outcomes included dyslipidemia, glucose intolerance, uric acid, glomerular hyperfiltration, and albuminuria. Regression models adjusted for age, sex, race/ethnicity, household income, food insecurity, health insurance status, household education, and body mass index z-score examined associations using complex survey design procedures., Results: Of 2,861 adolescents, 17.6% (SE 0.9%) did not receive dental care in the past year and 20.2% (SE 1.9%) had a financial barrier to accessing dental care. In adjusted regression models, adolescents with deferred dental care had higher odds of dyslipidemia (odds ratio [OR]= 1.51, 95% CI 1.07 to 2.11, P = .020). Having a financial barrier was associated with lower odds of dyslipidemia (OR = 0.35, 95% CI 0.14 to 0.89, P = .03). Financial barriers were associated with lower non-high-density lipoprotein cholesterol (b = -7.95, 95% CI -14.87 to -1.05, P = .03) and higher high-density lipoprotein cholesterol (b = 3.06, 95% CI 0.37 to 5.75, P = .03) in adjusted models. Deferred dental care and financial barriers were not associated with any other cardiometabolic parameters., Conclusion: In this nationally representative cohort of adolescents, there was an association between lack of preventative dental care and the cardiometabolic health marker of dyslipidemia. However, financial barriers to dental care were surprisingly associated with higher high-density lipoprotein cholesterol levels and lower odds of dyslipidemia.

Background and Aims: To assess the association between dental caries and cardiometabolic risk in adolescents., Methods and Results: The analysis included adolescents aged 13-17 years enrolled in the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018 who completed an Oral Health Examination. Untreated caries was defined as having one or more decayed teeth. Caries experience was assessed by Decayed, Missing, Filled Teeth (DMFT) score. Primary cardiometabolic outcomes included elevated BP (defined as BP 120-129/<80 mmHg) and hypertensive BP (defined as BP ≥ 130/80 mmHg). Secondary cardiometabolic outcomes included obesity, dyslipidemia (defined as any abnormal lipid level), glucose intolerance (measured by HOMA-IR), and microalbuminuria (defined as urine albumin: creatinine ≥30 mg/mg). Adjusted linear and logistic models examined associations using complex survey design procedures. In the sample of 2861 adolescents, 25.6 % (1.3 %) had untreated caries. 55.4 % (1.3 %) had DMFT ≥1. In adjusted regression analyses, untreated caries status was not significantly associated with primary outcomes of elevated BP (OR = 1.04, 95 % CI 0.71, 1.52 p > 0.05), hypertensive BP (OR = 1.72, 95 % CI 0.71, 3.89 p > 0.05), nor secondary cardiometabolic outcomes. No statistically significant associations were found between DMFT score and primary outcomes of elevated BP (OR = 0.01, 95 % CI 0.34, 1.07 p > 0.05), hypertensive BP (OR = 0.91, 95 % CI 0.81, 1.08 p > 0.05), or secondary cardiometabolic outcomes., Conclusion: Although studies in other countries and in adults show associations between caries and cardiometabolic outcomes, this study did not find an association between caries and cardiometabolic markers., Competing Interests: Declaration of competing interest C.Sethna was on an advisory board for Travere Therapeutics., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Senescent cells, which accumulate in organisms over time, contribute to age-related tissue decline. Genetic ablation of senescent cells can ameliorate various age-related pathologies, including metabolic dysfunction and decreased physical fitness. While small-molecule drugs that eliminate senescent cells ('senolytics') partially replicate these phenotypes, they require continuous administration. We have developed a senolytic therapy based on chimeric antigen receptor (CAR) T cells targeting the senescence-associated protein urokinase plasminogen activator receptor (uPAR), and we previously showed these can safely eliminate senescent cells in young animals. We now show that uPAR-positive senescent cells accumulate during aging and that they can be safely targeted with senolytic CAR T cells. Treatment with anti-uPAR CAR T cells improves exercise capacity in physiological aging, and it ameliorates metabolic dysfunction (for example, improving glucose tolerance) in aged mice and in mice on a high-fat diet. Importantly, a single administration of these senolytic CAR T cells is sufficient to achieve long-term therapeutic and preventive effects., (© 2024. The Author(s).)

Cytarabine is an antimetabolite used in the treatment of acute myeloid leukemia which acts by inhibiting DNA synthesis and subsequently cell division. It works on rapidly dividing cells, for that reason, it affects cancer cells, bone marrow and skin cells. Cytarabine has variable cutaneous side effects, the most common one is palmar-plantar erythema which usually presents with a tingling sensation around 5-7 days after cytarabine initiation, followed by erythema and tenderness. Auricular erythema is a rare subtype involving bilateral ears which often presents as ear redness and tenderness as described in the presented case. It is unclear if the skin side effects are related to cytarabine dose or plasma concentration. Most cases of auricular erythema have a benign course and resolve spontaneously. Treatment is mainly conservative. Steroids and antihistamines can be used to speed up recovery given that the pathophysiology is thought to be immediate or due to a delayed hypersensitivity reaction to cytarabine., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Botros et al.)

Aims: To outline key factors that contribute to oral health issues of refugees and asylum seekers and provide management strategies for dental providers to teach desensitization and fear reduction for this special population., Methods and Results: We researched published literature in the PubMed database and incorporated lessons gained from treating refugee and asylee patients at a Vulnerable Populations Clinic (VPC) at an urban academic dental school. Refugees and asylees are at high risk for oral conditions due to a tendency to not seek routine dental treatment, psychological stressors, and various systemic factors. Oral health providers can teach patients desensitization and fear reduction by working to gain patients' trust by having effective communication and prioritizing comfort in the dental operatory. Providers should also utilize translation, psychological, and/or multicultural support services during their management of care., Conclusion: By having a stronger understanding of the key causes of oral health issues among refugees and asylees in the United States, dental providers can better approach managing care for this vulnerable patient population. The concepts of teaching desensitization and fear reduction utilized for this special population can be applied to managing care for the wider special needs patient community., (© 2022 Special Care Dentistry Association and Wiley Periodicals LLC.)

Senescent cells accumulate in organisms over time because of tissue damage and impaired immune surveillance and contribute to age-related tissue decline 1,2 . In agreement, genetic ablation studies reveal that elimination of senescent cells from aged tissues can ameliorate various age-related pathologies, including metabolic dysfunction and decreased physical fitness 3-7 . While small-molecule drugs capable of eliminating senescent cells (known as 'senolytics') partially replicate these phenotypes, many have undefined mechanisms of action and all require continuous administration to be effective. As an alternative approach, we have developed a cell-based senolytic therapy based on chimeric antigen receptor (CAR) T cells targeting uPAR, a cell-surface protein upregulated on senescent cells, and previously showed these can safely and efficiently eliminate senescent cells in young animals and reverse liver fibrosis 8 . We now show that uPAR-positive senescent cells accumulate during physiological aging and that they can be safely targeted with senolytic CAR T cells. Treatment with anti uPAR CAR T cells ameliorates metabolic dysfunction by improving glucose tolerance and exercise capacity in physiological aging as well as in a model of metabolic syndrome. Importantly, a single administration of a low dose of these senolytic CAR T cells is sufficient to achieve long-term therapeutic and preventive effects., Competing Interests: Competing Interests C.A., J.F., M.S. and S.W.L. are listed as the inventors of several patent applications (62/800,188; 63/174,277; 63/209,941; 63/209,940; 63/209,915; 63/209,924; 17/426,728; 3,128,368; 20748891.7; 2020216486) related to senolytic CAR T cells. C.A., M.S. and S.W.L. are advisors for Fate Therapeutics. S.W.L. also has provided consultancy for and had equity in Oric Pharmaceuticals, Blueprint Medicines, Mirimus Inc, Senecea Therapeutics, Faeth Therapeutics, and PMV Pharmaceuticals. D.A.T. is a member of the Scientific Advisory Board and receives stock options from Leap Therapeutics, Dunad Therapeutics, Cygnal Therapeutics and Mestag Therapeutics outside the submitted work. D.A.T. is scientific co-founder of Mestag Therapeutics. D.A.T. has received research grant support from Fibrogen, Mestag, and ONO Therapeutics. D.A.T. receives grant funding from the Lustgarten Foundation, the NIH, and the Thompson Foundation. None of this work is related to the publication. No other disclosures were reported. R.L.L. is on the supervisory board of Qiagen and is a scientific advisor to Imago, Mission Bio, Zentalis, Ajax, Auron, Prelude, C4 Therapeutics and Isoplexis. R.L.L. receives research support from Ajax, Zentalis and Abbvie and has consulted for Incyte, Janssen and Astra Zeneca and has received honoraria from Astra Zeneca for invited lectures. L.W.J owns stock in Pacyclex, Inc., and Illuminosonics, Inc. M.S. holds other unrelated patents on CAR technologies. S.W.L is an advisor for and has equity in the following biotechnology companies: ORIC Pharmaceuticals, Faeth Therapeutics, Blueprint Medicines, Geras Bio, Mirimus Inc., PMV Pharmaceuticals and Constellation Pharmaceuticals.

The clinical presentation and diagnosis of Tejocote root toxicity causing Mobitz Type 1 remains a scarcely clinical phenomenon, often resulting in delayed diagnosis and treatment. This case report highlights a 30-year-old female presenting with a constellation of symptoms, including fatigue, dizziness, chest pressure, myalgias, nausea, vomiting, and peripheral tingling. Significantly, the patient had been using Tejocote root as an over-the-counter laxative acquired from Mexico. Laboratory findings revealed detectable Digoxin levels in her bloodstream, while an electrocardiogram (EKG) indicated sinus bradycardia with Mobitz Type 1 heart block. The patient was treated with a single dose of atropine 0.5 mg IV push. A repeat EKG before discharge showed resolution of the Mobitz type 1. This case underscores the potential cardiovascular repercussions of Tejocote root consumption and emphasizes the importance of heightened clinical awareness, especially in regions where such herbal supplement usage is prevalent., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Assi et al.)

Neural progenitor cell (NPC) transplantation is a promising therapeutic strategy for replacing lost neurons following spinal cord injury (SCI). However, how graft cellular composition influences regeneration and synaptogenesis of host axon populations, or recovery of motor and sensory functions after SCI, is poorly understood. We transplanted developmentally-restricted spinal cord NPCs, isolated from E11.5-E13.5 mouse embryos, into sites of adult mouse SCI and analyzed graft axon outgrowth, cellular composition, host axon regeneration, and behavior. Earlier-stage grafts exhibited greater axon outgrowth, enrichment for ventral spinal cord interneurons and Group-Z spinal interneurons, and enhanced host 5-HT + axon regeneration. Later-stage grafts were enriched for late-born dorsal horn interneuronal subtypes and Group-N spinal interneurons, supported more extensive host CGRP + axon ingrowth, and exacerbated thermal hypersensitivity. Locomotor function was not affected by any type of NPC graft. These findings showcase the role of spinal cord graft cellular composition in determining anatomical and functional outcomes following SCI., (© 2023. The Author(s).)

Introduction: Inflammation is an inherently self-amplifying process, resulting in progressive tissue damage when unresolved. A brake on this positive feedback system is provided by the nervous system which has evolved to detect inflammatory signals and respond by activating anti-inflammatory processes, including the cholinergic anti-inflammatory pathway mediated by the vagus nerve. Acute pancreatitis, a common and serious condition without effective therapy, develops when acinar cell injury activates intrapancreatic inflammation. Prior study has shown that electrical stimulation of the carotid sheath, which contains the vagus nerve, boosts the endogenous anti-inflammatory response and ameliorates acute pancreatitis, but it remains unknown whether these anti-inflammatory signals originate in the brain., Methods: Here, we used optogenetics to selectively activate efferent vagus nerve fibers originating in the brainstem dorsal motor nucleus of the vagus (DMN) and evaluated the effects on caerulein-induced pancreatitis., Results: Stimulation of the cholinergic neurons in the DMN significantly attenuates the severity of pancreatitis as indicated by reduced serum amylase, pancreatic cytokines, tissue damage, and edema. Either vagotomy or silencing cholinergic nicotinic receptor signaling by pre-administration of the antagonist mecamylamine abolishes the beneficial effects., Discussion: These results provide the first evidence that efferent vagus cholinergic neurons residing in the brainstem DMN can inhibit pancreatic inflammation and implicate the cholinergic anti-inflammatory pathway as a potential therapeutic target for acute pancreatitis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Thompson, Tsaava, Rishi, Nadella, Mishra, Tuveson, Pavlov, Brines, Tracey and Chavan.)

As a global community, we have learned that the manifestations of severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2), infection, or coronavirus disease 2019 (COVID-19), extends far beyond respiratory compromise. Thrombocytopenia is thought to occur secondary to increased platelet consumption. Platelet activation and platelet-mediated immune inflammation contribute towards the thromboembolic complications seen in COVID-19 patients. In this report, the authors present the unusual case of a 75-year-old female with a history of COVID-19 infection who presented with a transient ischemic attack, thrombocytopenia, and amegakaryocytopenia., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Hassan et al.)

SCAMP (Social Causality using Agents with Multiple Perspectives) is one of four social simulators that generated socially realistic data for the Ground Truth program. Unlike the other three simulators, it is based on a computational principle, stigmergy, inspired by social insects. Using this approach, we modeled conflict in a nation-state inspired by the ongoing scenario in Syria. This paper summarizes stigmergy and describes the Conflict World we built in SCAMP., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021.)

High saturated fat diets have been shown to raise blood levels of cholecystokinin (CCK) and induce nonalcoholic steatohepatitis (NASH). CCK receptors are expressed on stellate cells and are responsible for hepatic fibrosis when activated. The purpose of this study was to test the safety and dose of a CCK receptor antagonist, proglumide, in human participants with NASH. An open-label single ascending dose study was conducted in 18 participants with clinical NASH based upon steatosis by liver ultrasound, elevated hepatic transaminases, and a component of the metabolic syndrome. Three separate cohorts (N = 6 each) were treated with oral proglumide for 12 weeks in a sequential ascending fashion with 800 (Cohort 1), 1,200 (Cohort 2), and 1,600 (Cohort 3) mg/day, respectively. Blood hematology, chemistries, proglumide levels, a biomarker panel for fibrosis, and symptom surveys were determined at baseline and every 4 weeks. Abdominal ultrasounds and transient elastography utilizing FibroScan were obtained at baseline and at Week 12. Proglumide was well tolerated at all doses without any serious adverse events. There was no change in body weight from baseline to Week 12. For Cohorts 1, 2, and 3, the median percent change in alanine aminotransferase was 8.42, -5.05, and -22.23 and median percent change in fibrosis score by FibroScan was 8.13, -5.44, and -28.87 (kPa), respectively. Hepatic steatosis as measured by controlled attenuation parameter score significantly decreased with proglumide, (P < 0.05). Blood microRNA biomarkers and serum 4-hydroxyproline were consistent with decreased fibrosis at Week 12 compared with baseline. These findings suggest proglumide exhibits anti-inflammatory and anti-fibrotic properties and this compound is well tolerated in participants with NASH., (© 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Statins constitute a cornerstone in the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). The routine use of these lipid-lowering agents may lead to unintentional neglect of their well-known myotoxic properties. We report the case of a 77-year-old female with a two-year history of rosuvastatin use who presented with progressive bilateral upper and lower extremity muscular weakness for one week, which improved upon discontinuation of her long-term statin therapy. The authors aim to draw attention to this potentially underdiagnosed cause of disability. It is imperative that clinicians are able to appreciate the myopathic spectrum of statin therapy, irrespective of the duration of use. Myonecrosis, in particular, can progress to rhabdomyolysis, leading to irreversible renal dysfunction, electrolyte abnormalities, and subsequent cardiac dysrhythmias. Ultimately, statin-induced myopathy may significantly hinder activities of daily living and impair quality of life. It is, however, a reversible condition if diagnosed and appropriately managed early on. Clinicians are encouraged to acquaint themselves with the symptomatology and relevant laboratory values that commonly accompany this acute condition., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Hassan et al.)

Objectives: To analyze whether use of proton pump inhibitors increase the risk for pancreatic cancer in a mouse model and human clinical cohorts., Methods: p48-Cre/LSL-KrasG12D mice that develop precancerous pancreatic intraepithelial neoplasia (PanINs) were treated with low- or high-dose proton pump inhibitors (PPIs) orally for 1 and 4 months. The mechanism for the cholecystokinin receptor 2 (CCK-2R) activation was investigated in vitro. Two resources were employed to analyze the risk of pancreatic cancer in human subjects with PPI use., Results: Serum gastrin levels were increased 8-fold (P < 0.0001) in mice treated with chronic high-dose PPIs, and this change correlated with an increase (P = 0.02) in PanIN grade and the development of microinvasive cancer. The CCK-2R expression was regulated by microRNA-148a in the p48-Cre/LSL-KrasG12D mice pancreas and in human pancreatic cancer cells in vitro. Proton pump inhibitor consumption in human subjects was correlated with pancreatic cancer risk (odds ratio, 1.54). A validation analysis conducted using the large-scale United Kingdom Biobank database confirmed the correlation (odds ratio, 1.9; P = 0.00761) of pancreatic cancer risk with PPI exposure., Conclusions: This investigation revealed in both murine models and human subjects, PPI use is correlated with a risk for development of pancreatic cancer., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Oral mucositis is a painful inflammatory response that can lead to infection, cachexia, and therapy termination. This immune-related adverse event (IRAE) has been well documented within the newly developing field of immunotherapy. This case series presents three patients, aged 73 to 81 years, who were undergoing treatment with programmed death-1 (PD-1) immunotherapy for cancer; each patient developed grade III mucositis, one after the fourth cycle and two after the seventh. All three patients had no prior history of oral pathology, yet each patient reported ulcerated and inflamed oral mucosa that was swollen and painful. These lesions involved various locations within the oral cavity and caused irritation to the point of dysphagia and odynophagia. Conservative treatments such as oral anesthetic and mouthwashes with antimicrobial properties had minimal effects. Each patient thereafter was started on systemic glucocorticoids in addition to the local treatments. The initiation of a systemic treatment resulted in a resolution of the oral lesions allowing each patient the option to return to their prior immunotherapy. Mucositis is uncommon and has no standardized treatment. This case series emphasizes the debilitative result of immunotherapy-induced mucositis and illustrates the need for systemic glucocorticoids. While conservative treatments such as oral mouthwashes can be effective in treating the symptoms of mucositis, the initiation of high-dose steroids with a prolonged taper has been shown to treat the condition at its source. Early recognition of mucositis with prompt initiation of steroids has proven to be the effective mainstay treatment to relieve mucositis while limiting pauses in cancer treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Foster et al.)

Importance: Male sex is associated with severe COVID-19. It is not known whether the risk of hospitalization differs between men with hypogonadism, men with eugonadism, and those receiving testosterone therapy (TTh)., Objective: To compare COVID-19 hospitalization rates for men with hypogonadism who were not receiving TTh, men with eugonadism, and men receiving TTh., Design, Setting, and Participants: This cohort study was conducted in 2 large academic health systems in St Louis, Missouri, among 723 men with a history of COVID-19 who had testosterone concentrations measured between January 1, 2017, and December 31, 2021., Exposures: The primary exposure was gonadal status (hypogonadism, eugonadism, and TTh). Hypogonadism was defined as a total testosterone concentration below the limit of normal provided by the laboratory (which varied from 175 to 300 ng/dL [to convert to nanomoles per liter, multiply by 0.0347])., Main Outcomes and Measures: The primary outcome was rate of hospitalization for COVID-19. Statistical adjustments were made for group differences in age, body mass index, race and ethnicity, immunosuppression, and comorbid conditions., Results: Of the 723 study participants (mean [SD] age, 55 [14] years; mean [SD] body mass index, 33.5 [7.3]), 116 men had hypogonadism, 427 had eugonadism, and 180 were receiving TTh. Men with hypogonadism were more likely than men with eugonadism to be hospitalized with COVID-19 (52 of 116 [45%] vs 53 of 427 [12%]; P < .001). After multivariable adjustment, men with hypogonadism had higher odds than men with eugonadism of being hospitalized (odds ratio, 2.4; 95% CI, 1.4-4.4; P < .003). Men receiving TTh had a similar risk of hospitalization as men with eugonadism (odds ratio, 1.3; 95% CI, 0.7-2.3; P = .35). Men receiving inadequate TTh (defined as subnormal testosterone concentrations while receiving TTh) had higher odds of hospitalization compared with men who had normal testosterone concentrations while receiving TTh (multivariable adjusted odds ratio, 3.5; 95% CI, 1.5-8.6; P = .003)., Conclusions and Relevance: This study suggests that men with hypogonadism were more likely to be hospitalized after COVID-19 infection compared with those with eugonadism, independent of other known risk factors. This increased risk was not observed among men receiving adequate TTh. Screening and appropriate therapy for hypogonadism need to be evaluated as a strategy to prevent severe COVID-19 outcomes among men.

Objective: The objective of this systematic review was to evaluate the risks of medication-related osteonecrosis of the jaw (MRONJ) in fibrous dysplasia (FD) and McCune-Albright syndrome (MAS) patients treated with bisphosphonates., Method and Materials: A systematic review of the literature was performed by searching PubMed and Embase databases using MeSH terms (fibrous dysplasia of bone, "fibrous dysplasia, polyostotic," osteonecrosis, jaw, therapeutics, diphosphonates, denosumab, teriparatide, estrogens, hormones, raloxifene hydrochloride, calcitonin, cathepsin K) and non-MeSH terms (antiresorptive therapy, antiresorptives, bisphosphonate, estrogen therapy, hormone therapy, bazedoxifene, cathepsin K inhibitor). Articles were limited to human studies, in English language, in which patients were on antiresorptives for at least 1 year. PRISMA statement guidelines were used to eliminate non-relevant studies. The PICOT question asked was, "Does exposure to bisphosphonates and other antiresorptives cause occurrence of MRONJ in fibrous dysplasia and fibrous dysplasia/McCune-Albright syndrome patients followed up for at least 1 year?", Results: Eight eligible articles were included in the quantitative synthesis after articles were screened using a PRISMA flowchart. There were 12 reported occurrences of MRONJ among a combined total of 312 fibrous dysplasia and fibrous dysplasia/McCune-Albright syndrome patients (3.85%)., Conclusion: Patients with fibrous dysplasia or fibrous dysplasia/McCune-Albright syndrome have a low incidence of MRONJ and may apparently have low susceptibility to spontaneous development of MRONJ.

Objective: We assessed whether famotidine improved inflammation and symptomatic recovery in outpatients with mild to moderate COVID-19., Design: Randomised, double-blind, placebo-controlled, fully remote, phase 2 clinical trial (NCT04724720) enrolling symptomatic unvaccinated adult outpatients with confirmed COVID-19 between January 2021 and April 2021 from two US centres. Patients self-administered 80 mg famotidine (n=28) or placebo (n=27) orally three times a day for 14 consecutive days. Endpoints were time to (primary) or rate of (secondary) symptom resolution, and resolution of inflammation (exploratory)., Results: Of 55 patients in the intention-to-treat group (median age 35 years (IQR: 20); 35 women (64%); 18 African American (33%); 14 Hispanic (26%)), 52 (95%) completed the trial, submitting 1358 electronic symptom surveys. Time to symptom resolution was not statistically improved (p=0.4). Rate of symptom resolution was improved for patients taking famotidine (p<0.0001). Estimated 50% reduction of overall baseline symptom scores were achieved at 8.2 days (95% CI: 7 to 9.8 days) for famotidine and 11.4 days (95% CI: 10.3 to 12.6 days) for placebo treated patients. Differences were independent of patient sex, race or ethnicity. Five self-limiting adverse events occurred (famotidine, n=2 (40%); placebo, n=3 (60%)). On day 7, fewer patients on famotidine had detectable interferon alpha plasma levels (p=0.04). Plasma immunoglobulin type G levels to SARS-CoV-2 nucleocapsid core protein were similar between both arms., Conclusions: Famotidine was safe and well tolerated in outpatients with mild to moderate COVID-19. Famotidine led to earlier resolution of symptoms and inflammation without reducing anti-SARS-CoV-2 immunity. Additional randomised trials are required., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Purpose: This study compared opioid prescription patterns among oral and maxillofacial surgeons (OMSs) treating Medicare beneficiaries in urban and rural settings, in an effort to identify avenues to further promote responsible opioid prescribing in a patient demographic vulnerable to opioid diversion., Materials and Methods: This study used Medicare Provider Utilization and Payment Data from 2014 to 2018, focusing on providers labeled as an OMS. Rural-urban commuting area codes were used to categorize each OMS as urban or rural. The demographic variables included total number of OMSs, provider gender, beneficiaries per provider, beneficiaries' age, and beneficiary hierarchal condition category (proxy for clinical complexity). The outcome variables included opioid prescribing rate, opioid claims per provider, opioid claims per beneficiary, and number of days' supply of opioids per claim. Descriptive statistics, χ 2 tests, 2-tailed t tests, and Wilcoxon rank-sum tests were used as appropriate., Results: Across all years, the data consisted of mostly urban and male OMSs. The mean number of Medicare beneficiaries prescribed opioids per OMS varied widely, and the mean age of beneficiaries was 70.4 ± 4.4 and 69.9 ± 4.1 years for urban and rural OMSs, respectively. Mean opioid claims per provider were higher among rural OMSs, with large standard deviations among both rural and urban OMSs. However, there were no significant differences in the opioid prescribing rate or in the mean opioid claims per beneficiary in all 5 years included in the study. There were also no clinically significant differences between urban and rural OMSs in the number of days' supply per claim (between 3 and 4 days in all periods). However, in each year, there was a significantly higher proportion of urban OMSs who prescribed more than 7 days' supply per claim., Conclusions: Opioid prescription practices were generally similar between rural and urban OMSs treating Medicare beneficiaries. The small subset of longer-term opioid prescribers, which were more prevalent in urban areas, warrants further investigation., (Copyright © 2021 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)