A beta-blocker, propranolol, decreases the efficacy from enzyme replacement therapy in Pompe disease.

UNLABELLED: Enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) fails to completely reverse muscle weakness in Pompe disease. ß2-agonists enhanced ERT by increasing receptor-mediated uptake of rhGAA in skeletal muscles. PURPOSE: To test the hypothesis that a ß-blocker might reduce the efficacy of ERT, because the action of ß-blockers opposes those of ß2-agonists. METHODS: Mice with Pompe disease were treated with propranolol (a ß-blocker) or clenbuterol in combination with ERT, or with ERT alone. RESULTS: Propranolol-treated mice had decreased weight gain (p<0.01), in comparison with clenbuterol-treated mice. Left ventricular mass was decreased (and comparable to wild-type) in ERT only and clenbuterol-treated groups of mice, and unchanged in propranolol-treated mice. GAA activity increased following either clenbuterol or propranolol in skeletal muscles. However, muscle glycogen was reduced only in clenbuterol-treated mice, not in propranolol-treated mice. Cell-based experiments confirmed that propranolol reduces uptake of rhGAA into Pompe fibroblasts and also demonstrated that the drug induces intracellular accumulation of glycoproteins at higher doses. CONCLUSION: Propranolol, a commonly prescribed ß-blocker, reduced weight, increased left ventricular mass and decreased glycogen clearance in skeletal muscle following ERT. ß-Blockers might therefore decrease the efficacy from ERT in patients with Pompe disease.

Non-Operative Approach to Contained Perforated Marginal Ulcers: A Systematic Review and Case Series.

BACKGROUND: Perforated marginal ulcers (PMUs) are a rare but known complication of bariatric surgery. Management typically involves prompt surgical intervention, but limited data exists on non-operative approaches. This study reviews published data on non-operative management of PMUs and presents a case series of patients who were managed non-operatively. Our hypothesis is that certain patients with signs of perforation can be successfully managed non-operatively with close observation. METHODS: We completed a systematic review searching PubMed, Embase, Web of Science, Cochrane, and clinicaltrials.gov. Ultimately 3 studies described the presentation and non-operative management of 5 patients. Additionally, we prospectively collected data from our institution on all patients who presented between Dec. 2022 and Dec. 2023 with PMUs confirmed on imaging and managed non-operatively. RESULTS: In our literature review, three patients had Roux-en-Y gastric bypass (RYGB), while two had one anastomosis gastric bypass. One patient required surgery two days after admission. Another underwent elective conversion surgery weeks later for a non-healing ulcer. Two received endoscopic interventions. One patient recovered with nil-per-os (NPO) status, and intravenous proton pump inhibitor (PPI) treatment. The patients in our case series presented with normal vital signs, an average of 30 months after RYGB, and with CT scan signs of perforation. None of these patients required surgical or endoscopic intervention. CONCLUSION: In conclusion, while perforated marginal ulcers have traditionally been considered a surgical emergency, some patients can be successfully treated with non-operative management. More research is needed to identify the clinical presentation features, comorbidities, and imaging findings of this group.

Platelet-rich plasma as a therapy for androgenic alopecia: a systematic review and meta-analysis.

OBJECTIVE: The past decade has seen platelet-rich plasma (PRP) become a popular therapy around the world as a treatment for androgenetic alopecia (AGA). These systematic review and meta-analyses assess the effectiveness and adverse effects of PRP to determine the role of PRP as a treatment for AGA among the other non-surgical treatment modalities. METHODS: This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and is registered under the PROSPERO ID CRD42019136329. Seven databases were searched from inception through May 2019. Meta-analyses of randomized controlled trials (RCTs) were performed to evaluate the effect of PRP treatments on hair density and hair thickness. RESULTS: Thirty studies, including 687 patients, met our inclusion criteria. Twenty-nine studies reported beneficial results, and 24 studies reached statistical significance on a measured outcome. Ten RCTs were included. Our meta-analyses show that PRP treatment increases hair density and hair thickness. CONCLUSIONS: PRP is an autologous treatment that lacks serious adverse effects and effectively improves hair density and hair thickness in men and women with AGA. Future research should include low risk-of-bias RCTs to optimize treatment protocols, investigate variability among studies, and to obtain more data on hair thickness changes.

Rejuvenating the periorbital area using platelet-rich plasma: a systematic review and meta-analysis.

Intradermal injection of autologous platelet-rich plasma (PRP) is a non-surgical cosmetic therapy to rejuvenate the periorbital area pathologies of wrinkles, periorbital hyperpigmentation (POH), and photoaging. The past decade has seen the adoption of this novel therapy around the world. This is the first systematic review and meta-analysis evaluating PRP treatment of periorbital pathologies. This is a PRISMA compliant review that includes a comprehensive search of the databases Cochrane Library, Ovid Medline, Ovid Embase, and clinicaltrials.gov. The search was performed in June 2019 to obtain all peer-reviewed articles published in English that describe the application of PRP to periorbital pathologies. A meta-analysis of patient satisfaction was performed for randomized controlled trials. Nineteen studies treating 455 patients (95% female, age range 28-60) were included. Studies were categorized based on reported outcomes: wrinkles (11 studies), POH (7 studies), and photoaging (6 studies). Patients were treated a mean of 3 times (range 1-8) in mean intervals of 23 days (range 14-56 days). Follow-up averaged 3 months (range 1-6 months). Meta-analysis of 3 randomized controlled clinical trials (RCTs) shows that patients treated with PRP have increased satisfaction above controls of saline, platelet-poor plasma, mesotherapy, and as an adjunct to laser therapy (overall effect p = 0.001, heterogeneity I2 = 64%). PRP treatment of periorbital area pathologies results in histologic improvements of photoaging, subjective satisfaction score increases, and blind evaluator assessments of rejuvenated skin appearance. Future studies are needed to address limitations of the current literature and should include long-term follow-up, delineation of the POH etiology that is treated, RCTs with low risk of bias, and be absent conflicts of interest or industry sponsors.Trial registration: Prospero Systematic Review Registration ID: CRD42019135968.

Treating hand and foot osteoarthritis using a patient's own blood: A systematic review and meta-analysis of platelet-rich plasma.

BACKGROUND: This study summarizes all literature investigating platelet-rich plasma (PRP) in the treatment of osteoarthritis of the hands and feet. MATERIALS & METHODS: This is a PRISMA compliant systematic review of 7 databases and includes a meta-analysis of randomized controlled trial (RCT) data on pain and function. RESULTS: Nine articles were included in the review. Meta-analysis of 4 RCTs shows PRP significantly improves pain and function versus control. More results are significant at longer duration follow-up. CONCLUSIONS: PRP improves pain and function of osteoarthritis. Heterogeneity and risk-of-bias limit current data, requiring more RCTs to determine any regenerative potential of PRP. PROSPERO SYSTEMATIC REVIEW REGISTRATION NUMBER: 136582.