Comparison of ciprofloxacin versus fosfomycin versus fosfomycin plus trimethoprim/sulfamethoxazole for preventing infections after transrectal prostate biopsy.

BACKGROUND: To evaluate antibiotic prophylaxis in transrectal prostate biopsies due to the recommendation of the European Medicines Agency (EMA): We describe our single center experience switching from ciprofloxacin to fosfomycin trometamol (FMT) alone and to an augmented prophylaxis combining fosfomycin and trimethoprim/sulfamethoxazole (TMP/SMX). METHODS: Between 01/2019 and 12/2020 we compared three different regimes. The primary endpoint was the clinical diagnosis of an infection within 4 weeks after biopsy. We enrolled 822 men, 398 (48%) of whom received ciprofloxacin (group-C), 136 (16.5%) received FMT (group-F) and 288 (35%) received the combination of TMP/SMX and FMT (group-BF). RESULTS: Baseline characteristics were similar between groups. In total 37/398 (5%) postinterventional infections were detected, of which 13/398 (3%) vs 18/136 (13.2%) vs 6/288 (2.1%) were detected in group-C, group-F and group-BF respectively. The relative risk of infectious complication was 1.3 (CI 0.7-2.6) for group-C vs. group-BF and 2.8 (CI 1.4-5.7) for group-F vs. group-BF respectively. CONCLUSION: The replacement of ciprofloxacin by fosfomycin alone resulted in a significant increase of postinterventional infections, while the combination of FMT and TMP/SMX had a comparable infection rate to FQ without apparent adverse events. Therefore, this combined regimen of FMT and TMP/SMX is recommended.

A case of acquired transient bleeding diathesis associated with acquired platelet storage pool deficiency and defective thromboxane A2 production.

Acquired disorders of platelet function are an underdiagnosed cause of bleeding tendency. A 14-year-old girl developed moderate mucocutaneous bleeding two weeks after a Mycoplasma pneumoniae infection successfully treated with clarithromycin. The patient was referred to us 7 months later for laboratory investigation of the persisting bleeding diathesis. The patient's personal and family histories were negative for bleeding disorders. Complete blood count, von Willebrand Factor levels and coagulation tests were normal; platelet aggregation, ATP secretion, δ-granules content and serum thromboxane B2 levels were defective. At follow-up visits, laboratory parameters and the bleeding diathesis progressively normalized within 2 years. The patient's condition is compatible with a diagnosis of acquired Storage Pool Deficiency (SPD), associated with defective thromboxane A2 production. To our knowledge, this is the first case of acquired, transient SPD with spontaneous remission. The pathogenic role of Mycoplasma pneumoniae infection or clarithromycin is possible, albeit uncertain.

What is the Injury Incidence and Profile in Professional Male Ice Hockey? A Systematic Review.

BACKGROUND: Professional male ice hockey is characterized by a congested in-season match schedule and by different scenarios where the whole body is exposed to great internal and external forces. Consequently, injuries occur from head to toe. However, there is a lack of data synthesis regarding the injury incidence and profile in this population. PURPOSE: The aim of this study was to conduct a systematic review to quantify the injury incidence rates in professional male ice hockey. STUDY DESIGN: Systematic Review. METHODS: The electronic databases PubMed, CINAHL, Web of Science, ProQuest-Sport medicine & Education Index, and Pro-Quest Dissertation and Thesis were searched utilizing terms related to ice hockey and injuries. Studies were included if they provided the incidence of injury in professional male hockey players and reported injuries in terms of time lost. The modified Newcastle Ottawa Scale for cohort studies and the Strengthening the Reporting of Observational Studies in Epidemiology - Sports Injury and Illness Surveillance Statement were used to assess the methodological quality of the studies. RESULTS: Eleven studies were included in the review. Match injury incidence ranged from 38 to 88.6 injuries/1000 hours of exposure, whereas training injury incidence varied from 0.4 to 2.6 injuries/1000 hours of exposure. Injuries of traumatic origin accounted for 76% to 96.6% of all injuries, with contusions and lacerations being the most common. Severe injuries accounted for 7.8% - 20% of all injuries. The lower extremities were the most susceptible to injury, comprising 27% to 53.7% of all reported injuries. CONCLUSION: Professional male ice hockey players are exposed to a substantial risk of injury during competitions, with lower extremities being the most commonly affected body part. The majority of injuries are traumatic and severe injuries account for a notable portion of overall injury cases.

Ultrasound-responsive microbubbles and nanodroplets: A pathway to targeted drug delivery.

Ultrasound-responsive agents have shown great potential as targeted drug delivery agents, effectively augmenting cell permeability and facilitating drug absorption. This review focuses on two specific agents, microbubbles and nanodroplets, and provides a sequential overview of their drug delivery process. Particular emphasis is given to the mechanical response of the agents under ultrasound, and the subsequent physical and biological effects on the cells. Finally, the state-of-the-art in their pre-clinical and clinical implementation are discussed. Throughout the review, major challenges that need to be overcome in order to accelerate their clinical translation are highlighted.

Blood donation for iron removal in individuals with HFE mutations: study of efficacy and safety and short review on hemochromatosis and blood donation.

Background: Elevated serum ferritin with/without HFE variants in asymptomatic persons leads frequently to referral for blood donation. Hemochromatosis (p.C282Y/p.C282Y) only requires treatment. We evaluated safety and feasibility of iron removal in healthy persons with elevated ferritin and HFE variants using blood donation procedures. Materials and methods: Thirty subjects with ferritin >200 ng/mL (women) or >300 ng/mL (men) with p.C282Y/p.C282Y, p.C282Y/p.H63D or p.H63D/p.H63D were randomized to weekly phlebotomy (removal of 450 mL whole blood) or erythrapheresis (removal of 360 mL red blood cells) every 14 days. The ferritin target was <100 ng/mL. A full blood count and ferritin were measured at each visit. Hemoglobin (Hb) ≥140 g/L was required at inclusion. If Hb dropped to <120 g/L (women) or <130 g/L (men), procedures were postponed (7 or 14 days). Primary endpoint was the number of procedures needed to the ferritin target; secondary objectives were duration of treatment and compliance. The treatment effect was tested with Poisson regression; number of procedures and treatment duration were compared between study arms with the Kruskal-Wallis test. Results: Twenty-five of 30 participants were men (83%); mean age was 47 years (SD 10.5), mean BMI 26.6 kg/m2 (SD 3.6); 17 had p.C282Y/p.C282Y, nine p.C282Y/p.H63D, four p.H63D/p.H63D. Median baseline Hb was 150 g/L (IQR 144, 1,559), median ferritin 504 ng/mL (IQR 406,620). Twenty-seven subjects completed the study. Treatment arm (p < 0.001) and HFE variant (p = 0.007) influenced the primary endpoint significantly. To ferritin levels <100 ng/mL, a median number of 7.5 (IQR 6.2, 9.8) phlebotomies and 4.0 (IQR 3.0, 5.8) erythraphereses (p = 0.001) was needed during a median of 66.5 days (IQR 49,103) and 78.5 days (IQR 46139), respectively (p = 0.448). Low Hb was the principal reason for protocol violation; anemia occurred in 13 participants (48%). Immediate complications were infrequent; fatigue was reported after 25% of phlebotomies and 45% of erythraphereses. Thirty-five procedures were postponed because of low Hb and 15 for non-medical reasons. The median interval was 7.0 (IQR 7.7) and 14.0 (IQR 14, 20) days between phlebotomies and erythraphereses, respectively. Conclusion: Blood donation procedures remove iron effectively in HC, but frequent treatments cause Hb decrease and fatigue that can impair feasibility.

FM19G11-loaded nanoparticles modulate energetic status and production of reactive oxygen species in myoblasts from ALS mice.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. Considerable evidence indicates that early skeletal muscle atrophy plays a crucial role in the disease pathogenesis, leading to an altered muscle-motor neuron crosstalk that, in turn, may contribute to motor neuron degeneration. Currently, there is no effective treatment for ALS, highlighting the need to dig deeper into the pathological mechanisms for developing innovative therapeutic strategies. FM19G11 is a novel drug able to modulate the global cellular metabolism, but its effects on ALS skeletal muscle atrophy and mitochondrial metabolism have never been evaluated, yet. This study investigated whether FM19G11-loaded nanoparticles (NPs) may affect the bioenergetic status in myoblasts isolated from G93A-SOD1 mice at different disease stages. We found that FM19G1-loaded NP treatment was able to increase transcriptional levels of Akt1, Akt3, Mef2a, Mef2c and Ucp2, which are key genes associated with cell proliferation (Akt1, Akt3), muscle differentiation (Mef2c), and mitochondrial activity (Ucp2), in G93A-SOD1 myoblasts. These cells also showed a significant reduction of mitochondrial area and networks, in addition to decreased ROS production after treatment with FM19G11-loaded NPs, suggesting a ROS clearance upon the amelioration of mitochondrial dynamics. Our overall findings demonstrate a significant impact of FM19G11-loaded NPs on muscle cell function and bioenergetic status in G93A-SOD1 myoblasts, thus promising to open new avenues towards possible adoption of FM19G11-based nanotherapies to slow muscle degeneration in the frame of ALS and muscle disorders.

High Residual Platelet Reactivity during Aspirin Therapy in Patients with Non-St Segment Elevation Acute Coronary Syndrome: Comparison Between Initial and Late Phases / Alta Atividade Plaquetária Residual em Resposta ao Ácido Acetilsalicílico na Síndrome Coronariana Aguda Sem Supra de ST: Comparação entre as Fases Aguda e Tardia

Abstract Background: High platelet reactivity (HPR) during therapy with acetylsalicylic acid (ASA) is a poor prognostic factor in acute coronary syndromes (ACS). The prevalence of HPR during ACS is greater than that reported in stable diseases. However, it is unclear whether this prevalence of HPR is a transient phenomenon or a characteristic of this high-risk population. Objective: The main objective is to compare the effects of ASA on platelet function in the initial and late phases of ACS in a single population. Secondary objectives are: correlation between the tests between themselves and the relationship between the tests and the variation of the inflammatory markers (C-reactive protein and interleukin-6). Methods: Seventy patients with non-ST segment elevation (NSTE) ACS in use of 100-200 mg of ASA per day for at least 7 days were prospectively studied. Platelet function was assessed in the first 48 hours and subsequently after 3 months using four methods: VerifyNow™ (VFN), whole blood platelet aggregation (WBPA) with arachidonic acid (AA) and collagen as agonists, and platelet function analyzer (PFA). The level of statistical significance considered was < 0.05. Results: According to the more specific methods (WBPA with AA and VFN), the incidence of HPR was significantly higher in the early phase than in the late phase: WBPA with AA: 31% versus 13%, p = 0.015; VFN: 32% versus 16%, p = 0.049. The other methods tested, which were less specific for ASA, did not show significant differences between phases. The correlation between the methods was weak or moderate (r ranging from 0.3 to 0.5, p < 0.05), and there were no significant associations between HPR and inflammatory markers. Conclusion: The prevalence of HPR during AAS therapy, assessed by specific methods for cyclooxygenase 1 (COX-1), is higher during the acute phase than in the late phase of NSTE ACS.

Resumo Fundamento: A alta atividade plaquetária (AAP) durante a terapia com ácido acetilsalicílico (AAS) é fator de mau prognóstico nas síndromes coronarianas agudas (SCA). A prevalência de AAP durante a SCA é maior do que a relatada na doença estável. No entanto, não está claro se esta prevalência de AAP é um fenômeno transitório ou característica dessa população de alto risco. Objetivo: O objetivo principal é comparar, em uma mesma população, os efeitos do AAS sobre a função plaquetária nas fases inicial e tardia da SCA. Os objetivos secundários são: correlação entre os testes entre si e a relação entre os testes e a variação dos marcadores inflamatórios (proteína C reativa e interleucina-6). Métodos: Foram estudados prospectivamente 70 pacientes com SCA sem elevação de ST (SCSST) em uso de 100 a 200 mg de AAS por dia por pelo menos 7 dias. A função plaquetária foi avaliada nas primeiras 48 horas e 3 meses após por quatro métodos: VerifyNow™ (VFN), agregometria de sangue total (AST) com ácido araquidônico (AA) e colágeno como agonistas, e analisador de função plaquetária (PFA). O nível de significância estatístico considerado foi < 0,05. Resultados: A média de idade foi de 65 ±9,7 anos e 54% da população eram do sexo feminino. De acordo com os métodos mais específicos (AST com AA e VFN), a incidência de AAP foi significativamente maior na fase inicial, em relação à tardia: AST com AA 31% versus 13%, p = 0,015; VFN 32% versus 16%, p = 0,049. Os outros métodos testados, menos específicos para o AAS, não mostraram diferenças significativas entre as fases. A correlação entre os métodos foi fraca ou moderada (r variando de 0,3 a 0,5, p < 0,05), e não houve associações significativas entre AAP e marcadores inflamatórios. Conclusão: A prevalência de AAP durante a terapia com AAS, avaliada por métodos específicos para cicloxigenase 1 (COX-1), é maior durante a fase aguda do que na tardia da SCASST.