Safety and efficacy of teplizumab in the treatment of type 1 diabetes mellitus: An updated systematic review and meta-analysis of randomized controlled trials.

AIM: To provide updated efficacy and safety information for teplizumab in the treatment of Stage 3 type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: The PubMed, Embase and Cochrane databases were searched for randomized controlled trials (RCTs) comparing teplizumab to placebo for T1DM that reported any of the following outcomes: (1) C-peptide area under the curve (AUC); (2) glycated haemoglobin (HbA1c) levels; (3) insulin requirements; and (4) adverse events. Heterogeneity was examined with I2 statistics. p values <0.05 were taken to indicate statistical significance. The continuous endpoints were compared through the pooled mean difference (MD) and binary endpoints were assessed using risk ratios, both with 95% confidence intervals (CIs). Statistical analyses were performed using Review Manager Web software. RESULTS: Eight RCTs with 1052 patients (754 receiving teplizumab) were included. Teplizumab significantly increased the AUC of C-peptide levels at 6 (MD 0.10 nmol/L, 95% CI 0.05, 0.16), 12 (MD 0.13 nmol/L, 95% CI 0.06, 0.20), 18 (MD 0.18 nmol/L, 95% CI 0.09, 0.27) and 24 months (MD 0.16 nmol/L, 95% CI 0.02, 0.31), significantly reduced HbA1c levels at 6 (MD -0.57%, 95% CI -1.07, -0.08) and 12 months (MD -0.31%, 95% CI -0.59, -0.02), and significantly reduced insulin requirements at 6 (MD -0.12 U/kg, 95% CI -0.16, -0.08), 12 (MD -0.11 U/kg, 95% CI -0.15, -0.07), 18 (MD -0.17 U/kg, 95% CI -0.26, -0.09) and 24 months (MD -0.11 U/kg, 95% CI -0.22, -0.01). CONCLUSION: Teplizumab increases AUC of C-peptide levels and decreases HbA1c levels and insulin use, without raising serious adverse event risk.

Standard medical therapy with vs. without nebulised magnesium for children with asthma decompensation.

Pediatric asthma is a common condition, and its exacerbations can be associated with significant morbidity and mortality. The role of nebulised magnesium as adjunct therapy for children with asthma exacerbations is still unclear. To compare clinical and functional outcomes for children with asthma exacerbation taking either nebulised magnesium sulfate added to standard medical therapy (SMT) versus SMT alone. PubMed, Embase, and Cochrane Library were systematically searched for randomised clinical trials (RCT) comparing the use of SMT with vs. without nebulised magnesium. The outcomes were respiratory rate, heart rate, % predicted peak expiratory flow rate (PEFR), % predicted forced expiratory volume (FEV1), peripheral O2 saturation, asthma severity scores, and need for intravenous (IV) bronchodilator use. Twelve RCTs and 2484 children were included. Mean age was 5.6 (range 2-17) years old, mean baseline % predicted FEV1 was 69.6%, and 28.66% patients were male. Children treated with magnesium had a significantly higher % predicted PEFR (mean difference [MD] 5.33%; 95% confidence interval [CI] 4.75 to 5.90%; p < 0.01). Respiratory rate was significantly lower in the magnesium group (MD -0.70 respirations per minute; 95% CI -1.24 to -0.15; p < 0.01). Need for IV bronchodilators, % predicted FEV1, heart rate, asthma severity scores, and O2 saturation were not significantly different between groups. CONCLUSION: In children with asthma exacerbation, treatment with nebulised magnesium and SMT was associated with a statistically significant, but small improvement in predicted PEFR and respiratory rate, as compared with SMT alone. WHAT IS KNOWN: • Magnesium sulfate has bronchodilating properties and aids in the treatment of asthma exacerbation when administered intravenously. • There is no significant evidence of benefit of nebulised magnesium as an adjunct therapy to the standard medical treatment for children with asthma exacerbations. WHAT IS NEW: • Our study suggests nebulised magnesium sulfate may have a statistically significant, but small benefit in respiratory rate and peak expiratory flow rate. The addition of nebulised magnesium does not seem to increase adverse events.

Continuation of Gender-Affirming Hormone Therapy in Transgender and Gender-Diverse Individuals: A Systematic Review.

OBJECTIVE: Gender-affirming hormone therapy (GAHT) is often used by transgender and gender-diverse individuals to align their physical appearance with their gender identity. Discontinuation rates and factors leading to discontinuation of GAHT are not fully understood. We aimed to assess the continuation and discontinuation rates of GAHT and the factors leading to discontinuation of GAHT in a systematic review of the literature. METHODS: We searched PubMed from 2009 until April 01, 2024, for all published studies that described initiation, discontinuation, and reasons for discontinuation of GAHT. Studies were screened by 2 authors independently. We included 6 studies that met the inclusion and exclusion criteria published between 2021 and 2024. RESULTS: Five studies reported GAHT discontinuation rates under 10%, whereas 1 study reported a discontinuation/lost to follow-up rate of 30.8%. Only 1 study was prospective, whereas all other studies were retrospective. Reasons for discontinuation of GAHT were described in only 2 studies. One study reported GAHT discontinuation primarily from external factors, whereas the other study suggested that GAHT discontinuation occurred due to change in gender identity. CONCLUSION: Current data on discontinuation of GAHT show that the rates of GAHT discontinuation appear to be low and the reasons include both external pressures and internal change of gender identity. A better understanding of the internal and external pressures that impact the decision to continue GAHT is needed in future studies.

Parasite DNA and Markers of Decreased Immune Activation Associate Prospectively with Cardiac Functional Decline over 10 Years among Trypanosoma cruzi Seropositive Individuals in Brazil.

Parasitemia and inflammatory markers are cross-sectionally associated with chronic Chagas cardiomyopathy (CCC) among patients with Trypanosoma cruzi. However, the prospective association of the parasite load and host immune response-related characteristics with CCC (that is, progressors) among T. cruzi seropositive individuals has only been partially defined. In a cohort of T. cruzi seropositive patients in Montes Claros and São Paulo, Brazil who were followed over 10 years, we identified the association of a baseline T. cruzi parasite load and systemic markers of inflammation with a decline in cardiac function and/or the presence of cardiac congestion 10 years later. The progressors (n = 21) were individuals with a significant decline in the left ventricular ejection fraction and/or elevated markers of cardiac congestion after 10 years. The controls (n = 31) had normal markers of cardiac function and congestion at the baseline and at the follow-up. They were matched with the progressors on age, sex, and genetic ancestry. The progressors had higher mean parasite loads at the baseline than the controls (18.3 vs. 0.605 DNA parasite equivalents/20 mL, p < 0.05). Of the 384 inflammation-related proteins analyzed, 47 differed significantly at a false discovery rate- (FDR-) corrected p < 0.05 between the groups. There were 44 of these 47 proteins that were significantly higher in the controls compared to in the progressors, including the immune activation markers CCL21, CXCL12, and HCLS1 and several of the tumor necrosis factor superfamily of proteins. Among the individuals who were seropositive for T. cruzi at the baseline and who were followed over 10 years, those with incident CCC at the 10-year marker had a comparatively higher baseline of T. cruzi parasitemia and lower baseline markers of immune activation and chemotaxis. These findings generate the hypothesis that the early impairment of pathogen-killing immune responses predisposes individuals to CCC, which merits further study.

Efficacy and safety of ruxolitinib vs best available therapy for polycythemia vera: An updated systematic review and meta-analysis.

Ruxolitinib, a JAK1/JAK2 inhibitor, has been shown to have lower thromboembolism rates compared to placebo in polycythemia vera (PV) patients. This meta-analysis evaluates ruxolitinib's efficacy and safety against best available therapy (BAT) in patients with PV and in hydroxyurea-resistant/intolerant PV patients. A comprehensive literature search was conducted up to November 2023. We compared ruxolitinib and BAT for efficacy and safety endpoints. Six studies involving 1061 patients were analyzed, with 620 on BAT and 441 on ruxolitinib. Ruxolitinib showed higher hematocrit control (p = 0.015) and treatment response (p = 0.04) compared to BAT. It also significantly improved Myeloproliferative Neoplasms-Symptom Assessment Form scores (MPN-SAF) (p < 0.01). Additionally, patients with PV treated with ruxolitinib had higher rates of nonmelanoma skin cancer (p < 0.01). In subgroup analyses focusing on patients resistant or intolerant to hydroxyurea, ruxolitinib maintained its efficacy, significantly improving treatment response (p < 0.01) and significant improvements in MPN-SAF (p = 0.02) score when compared to BAT. The safety profile was consistent with the overall analyses, showing significantly reduced thromboembolism rates (p = 0.04), increased rates of anemia (p = 0.01), and increased herpes zoster infections (p = 0.02). Ruxolitinib outperforms BAT in PV and patients with PV-resistant or intolerant to hydroxyurea, offering better hematocrit control and reducing symptomatic burden and thromboembolism risk. Yet, it is associated with higher rates of anemia, herpes infection, and skin cancer.

Shorter versus longer duration of antimicrobial therapy for early Lyme disease: A systematic review and meta-analysis.

BACKGROUND: Antibiotic therapy for patients with early Lyme disease is necessary to prevent later-stage Lyme disease complications. This systematic review and meta-analysis compares shorter versus longer antibiotic regimens in treating early Lyme disease. METHODS: A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was conducted up to November 2023. We examined treatment failure, complete response, and photosensitivity. Short vs. long therapy was defined as ≤10 days vs. >10 days. Subgroup analyses included antibiotic type and varying treatment durations. Analysis utilized RStudio 4.1.2. PROSPERO registration: CRD42023423876. RESULTS: Seven studies, encompassing 1,462 patients, were analyzed. No significant differences in treatment failure, 12-month complete response, final visit complete response were found between short and long durations of antibiotic therapy. Subgroup and sensitivity analyses corroborated these findings. CONCLUSION: Shorter and longer antibiotic regimens for early Lyme disease show similar efficacy, highlighting the potential of ≤10-day courses, as effective treatment options.

Incorporation of Black Soldier Fly (Hermetia illucens L.) larvae fat or extruded linseed in diets of growing rabbits and their effects on meat quality traits including detailed fatty acid composition.

The inclusion of Black Soldier Fly (BSF) fat or extruded linseed (LIN) in diets for growing rabbits on meat fatty acids (FA), dimethyl acetals (DMA), oxidative stability and color was evaluated. Forty-eight rabbits with 35 days of age were individually housed, fed one of 4 diets (LIN-Low, 30 g/kg of fat from LIN; LIN-High, 60 g/kg of fat from LIN; BSF-Low, 30 g/kg of BSF fat; BSF-High, 60 g/kg of BSF fat) and slaughtered after 5 weeks. Diets with BSF reduced the intramuscular FA but increased the 12:0 and 14:0 in meat compared to LIN, whereas LIN diets increased the 18:3n-3 deposition in meat. Regressions between FA intake and FA meat concentration indicate that the deposition of 12:0 and 14:0 in the meat of BSF-fed rabbits was lower than the deposition of n-3 PUFA in the meat of LIN-fed rabbits. Overall, lipid profiles of meat from BSF-fed rabbits were less healthy, but meat from LIN-fed rabbits was the more susceptible to oxidation.

[Schwannoma of the Upper Extremity: Retrospective Analysis of 17 Cases]. / Schwanoma do Membro Superior: Análise Retrospectiva de 17 Casos.

INTRODUCTION: Schwannoma or neurilemmoma is a benign peripheric nerve tumor that usually presents as a slow growing single lesion; it has origin in Schwann cells proliferation. Although it represents a small percentage of the benign tumors of the upper arm, it is the most frequent of neural origin. We present a retrospective study of upper limb schwannomas; our aim is establish the appropriate preoperative approach, to recognise the efficiency of the treatment and the pos-operative follow-up. MATERIAL AND METHODS: Review of 17 patients treated between 2007 and 2014 with upper limb schwannoma and characterization as to age, gender, location in the upper limb, signs and symptoms, pre-operative studies, histologic diagnosis and postoperative surveillance. RESULTS: In four of them the schwannoma was localized on the arm, three on the forearm, four on the wrist and 6 on the hand or fingers. We proceed to careful microsurgical dissection in a bloodless field to optimize the functional final result. The enucleation without fascicular lesion was achieved in 12 patients. In five patients we performed the excision of the fascicles involved by the mass. Nine patients developed paresthesias in the immediate postoperative period, with five of them improving in 12 months. One patient presented motor deficit of the radial nerve with partial recover at 12 monts. DISCUSSION: Schwannomas are rare tumours with well circumscribed morphology. Occasionally it appears in upper limb. The preoperative diagnosis is rarely, so normally the diagnosis is established only after excision and histologic study. CONCLUSION: Schwannoma should be considered as a diagnostic hypothesis when evaluating subcutaneous nodes associated with neurologic symptoms. It is important to query the presence of paresthesias and perform the Tinel sign, both typical of this condition. Imagiological exams have a scarce contribute in the diagnosis. To improve the final result, the preoperative study must be insightful, being advisable to consider the benefits of the surgery compared to the potential iatrogenic damage to the nerve.

Introdução: O schwanoma ou neurilemoma é um tumor benigno dos nervos periféricos e apresenta-se habitualmente como uma lesão única de crescimento indolente, com origem na proliferação das células de Schwann. Representa uma pequena percentagem dos tumores benignos do membro superior, contudo é o mais frequente de origem neural. Apresentamos um estudo retrospectivo de schwanomas do membro superior para estabelecer a abordagem pré-operatória adequada, avaliar a eficácia do tratamento e observar a evolução pós-operatória. Material e Métodos: Revisão de 17 doentes tratados desde 2007 a 2014 com schwanoma do membro superior e caracterização quanto à idade, sexo, localização no membro superior, sinais e sintomas, exames pré-operatórios, diagnóstico histológico e vigilância pós-operatória.Resultados: Observou-se que em quatro dos doentes, o schwanoma se localizava no braço, três no antebraço, quatro no punho e seis na mão ou dedos. Procedeu-se a excisão com ampliação óptica para optimização do resultado funcional final. A enucleação foi realizada sem lesão fascicular em 12 doentes. Por sua vez, em cinco doentes efectuou-se a excisão dos fascículos envolvidos pela massa. No pós-operatório imediato as parestesias surgiram em nove doentes, regredindo em cinco daqueles no período pósoperatório de 12 meses. Um doente evidenciou défice motor do nervo radial, com recuperação parcial aos 12 meses. Discussão: Os schwanomas são tumores raros, de morfologia bem delimitada, que atingem esporadicamente o membro superior. O diagnóstico pré operatório é pouco frequente, pelo que normalmente apenas se estabelece o diagnóstico após a excisão e o estudo histopatológico.Conclusão: Os schwanomas deverão ser equacionados nas hipóteses de diagnóstico dos nódulos subcutâneos associados a sintomas neurológicos. Assim, é importante investigar a presença de parestesias e o sinal de Tinel, característicos desta lesão. A imagiologiatem um contributo fruste no diagnóstico. Para melhorar o resultado final, o estudo pré-operatório deverá ser criterioso, sendo aconselhável ponderar o benefício da cirurgia face à potencial lesão iatrogénica do nervo.