BACKGROUND AND OBJECTIVE: Non-muscle-invasive bladder cancer (NMIBC) poses a significant clinical challenge, particularly when failing bacillus Calmette-Guérin (BCG) therapy, necessitating alternative treatments. Despite radical cystectomy being the recommended treatment, many patients are unfit or unwilling to undergo this invasive procedure, highlighting the need for effective bladder-sparing therapies. This review aims to summarize and report the evidence on the efficacy and to estimate the costs of bladder-preserving strategies used in NMIBC recurrence after failure of intravesical BCG therapy. METHODS: We systematically searched online databases for prospective studies investigating intravesical therapy, systemic therapy, or combination of both in patients treated previously with BCG. Owing to significant heterogeneity across the studies, a meta-analysis was inappropriate. A sensitivity analysis was performed in an exploratory manner. We used a decision-analytic Markov model to compare novel U.S. Food and Drug Administration-approved treatments with a 2-yr time horizon. KEY FINDINGS AND LIMITATIONS: A total of 57 studies published between 1998 and 2024, with 68 unique study arms and consisting of 2589 patients, were identified. The 3-mo overall response rate (ORR) across all studies, complete response rate (CRR) in concomitant carcinoma in situ (CIS) or CIS only disease, and recurrence-free rate (RFR) in papillary disease were estimated to be 52.4% (95% confidence interval [CI]: 45.4-59.2), 52.8% (95% CI: 42.9-62.6), and 26.4% (95% CI: 13.3-45.6), respectively. The 12-mo ORR, CRR, and RFR were estimated to be 78% (95% CI: 52.9-91.8), 27.8% (95% CI: 21.3-35.4), and 25.4% (95% CI: 18.2-34.2), respectively. The progression rate was estimated to be 13% (95% CI: 9-18.2). The mean proportion of patients treated with radical cystectomy was estimated to be 24.7 (range 0-85.7). The reported toxicity grades were overall mild, with a median of 3.4% (range 0-33.3%) participants experiencing a dose limiting toxicity. Compared with using radical cystectomy to treat patients failing BCG therapy, at a willingness-to-pay threshold of 100 000 USD, nadofaragene firadenovec was cost effective, with an incremental cost-effectiveness ratio (ICER) of 10 014 USD per quality-adjusted life year (QALY), while nogapendekin alfa inbakicept was less cost effective than nadofaragene firadenovec (ICER of 44 602 USD per QALY). Pembrolizumab, which dominated, was both less costly and more effective than the other strategies. CONCLUSIONS AND CLINICAL IMPLICATIONS: Salvage bladder-sparing therapies show a response rate of around 50% at 3 mo in patients with NMIBC failing BCG. However, long-term data are heterogeneous. Nevertheless, recently developed agents show promising tumor control activity. In the rapidly evolving landscape of urothelial cancer, some of these treatment strategies might be cost effective and improve patients' quality of life. The findings of our review highlight the need for novel, more effective therapeutic strategies. PATIENT SUMMARY: In this study, we reviewed the evidence on the efficacy of bladder-preserving strategies used in patients with bladder cancer recurrence after failing bacillus Calmette-Guérin (BCG) therapy. We found that these strategies show a response rate of around 50% at 3 mo. However, long-term data are heterogeneous. Nevertheless, recently developed agents show promising tumor control activity. In the rapidly evolving landscape of urothelial cancer, some of these treatment strategies might be cost effective and improve patients' quality of life.

• MeSH
• Adjuvants, Immunologic * therapeutic use   economics   MeSH
• Cost-Benefit Analysis * MeSH
• Administration, Intravesical MeSH
• BCG Vaccine * therapeutic use   economics   MeSH
• Neoplasm Invasiveness MeSH
• Humans MeSH
• Neoplasm Recurrence, Local MeSH
• Non-Muscle Invasive Bladder Neoplasms MeSH
• Urinary Bladder Neoplasms * drug therapy   pathology   therapy   economics   MeSH
• Treatment Failure MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Systematic Review MeSH

BACKGROUND: Head tremor poses diagnostic problems, especially when present as an isolated or predominant symptom. OBJECTIVES: To assess how maneuvers activating upper limb postural tremor can help differentiate head tremor in essential tremor (ET) from dystonic tremor (DT) in cervical dystonia. METHODS: 48 patients with head tremor (25 ET, 23 DT), underwent clinical examination and accelerometric evaluation of head and upper limb tremor during routine tremor-inducing tasks. RESULTS: While accelerometric power and clinical scores of head tremor did not significantly differ between patient groups, task-induced variations revealed distinctions. ET patients exhibited increased head tremor power and clinical scores during forward outstretched and lateral wing-beating arm positions, unlike DT patients. Coherence between head and upper limb tremor remained consistent. Tremor stability index showed no significant differences. CONCLUSIONS: Task-induced changes in head tremor could aid in distinguishing between ET and DT. Further research is needed to refine diagnostic approaches for head tremor.

• MeSH
• Accelerometry instrumentation   methods   MeSH
• Diagnosis, Differential MeSH
• Adult MeSH
• Dystonia diagnosis   physiopathology   MeSH
• Essential Tremor * diagnosis   physiopathology   MeSH
• Head * physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Arm * physiopathology   MeSH
• Posture physiology   MeSH
• Aged MeSH
• Torticollis diagnosis   physiopathology   MeSH
• Tremor * diagnosis   physiopathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

INTRODUCTION/AIMS: Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care. METHODS: Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs). RESULTS: The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death. DISCUSSION: Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.

• MeSH
• Autoantibodies blood   MeSH
• Activities of Daily Living MeSH
• Adult MeSH
• Double-Blind Method MeSH
• Immunologic Factors therapeutic use   adverse effects   administration & dosage   MeSH
• Immunoglobulins, Intravenous * therapeutic use   adverse effects   administration & dosage   MeSH
• Middle Aged MeSH
• Humans MeSH
• Myasthenia Gravis * drug therapy   MeSH
• Prospective Studies MeSH
• Receptors, Cholinergic * immunology   MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase II MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

BACKGROUND: Ice hockey is a dynamic game. We can observe collisions between the players that bring a risk of injury. There are many hockey clubs in the Czech Republic. These clubs raise great hockey players and many competing players in various levels of national leagues. The aim of this study was to map injuries in Czech hockey players and outline the situation of injury prevention and body care in ice hockey players. METHODS: We used a questionnaire survey method to obtain data. We received answers from 100 male active Czech ice hockey players, playing in the top three highest men's competitions (Extraleague - 2nd league). Individual injuries were analyzed according to specific body parts, injury type, playing position, level of competition using basic statistical characteristics and relative frequency analyses, including the recovery time, injury reason and the injury statistics per 1000 sporting performances in ice hockey. RESULTS: We found that 81% of participants suffered injuries with the overall incidence of injuries was 17.1 per 1000 sports performances and mainly happened during the match compared to training. The most common injuries were in the head and neck area (25%), often caused by a collision with another player, a stick or puck hit, or a collision with a board. Other frequently injured parts were the knees (21%), where internal ligament injuries predominate, and the shoulders (20%), where we recorded mainly ligament injuries. CONCLUSIONS: There is a high risk of various injury types of ice hockey players, that are developed accidentally in all body parts mostly in the match (mostly upper part of the body and knee) or by overloading (hip/groin area). We recommend strategies to avoid or minimize the injury risk of players. The hockey clubs, coaches, and players should extensively and regularly cooperate with physiotherapists, starting from the younger age of hockey groups, to prevent injuries and use regular strengthening of crucial muscle parts, regeneration, and compensatory exercises. We endorse adequately evaluating dangerous foul actions for referees and disciplinary officials also in minor competitions.

• MeSH
• Adult MeSH
• Hockey * injuries   MeSH
• Incidence MeSH
• Humans MeSH
• Young Adult MeSH
• Surveys and Questionnaires MeSH
• Athletic Injuries * epidemiology   prevention & control   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

BACKGROUND: Pulsed field ablation (PFA) of atrial fibrillation is a new method in clinical practice. Despite a favorable safety profile of PFA in atrial fibrillation ablation, rare cases of renal failure, probably due to hemolysis, have recently been reported. OBJECTIVE: The aim of this study was to determine the rate of hemolysis and cardiac cell death during in vitro PFA with different electric field intensities. METHODS: Blood samples from healthy volunteers and mouse HL-1 cardiomyocyte cell lines were subjected to in vitro irreversible electroporation using 216 bipolar pulses, each lasting 2 μs with intervals of 5 μs, repeated 20 times at a frequency of 1 Hz. These pulses varied from 500 V to 1500 V. Cell-free hemoglobin levels were assessed spectrophotometrically, and red blood cell microparticles were evaluated by flow cytometry. Cardiomyocyte death was quantified with propidium iodide. RESULTS: Pulsed field energy (1000 V/cm, 1250 V/cm, and 1500 V/cm) was associated with a significant increase in cell-free hemoglobin (0.32 ± 0.16 g/L, 2.2 ± 0.96 g/L, and 5.7 ± 0.39 g/L; P < .01) and similar increase in the concentration of red blood cell microparticles. Significant rates of cardiomyocyte death were observed at electric field strengths of 750 V/cm, 1000 V/cm, 1250 V/cm, and 1500 V/cm (26.5% ± 5.9%, 44.3% ± 6.2%, 55.5% ± 6.9%, and 74.5% ± 17.8% of cardiomyocytes; P < .01). CONCLUSION: The most effective induction of cell death in vitro was observed at 1500 V/cm. This intensity was also associated with a significant degree of hemolysis.

• MeSH
• Electroporation * methods   MeSH
• Atrial Fibrillation physiopathology   surgery   MeSH
• Hemolysis * physiology   MeSH
• Myocytes, Cardiac * metabolism   MeSH
• Cells, Cultured MeSH
• Humans MeSH
• Mice MeSH
• Flow Cytometry MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

This systematic literature review (SLR) aimed to comprehensively synthesize existing studies that have reported on TMG-derived parameters of lower extremities in soccer players. The PubMed, Web of Science, and EBSCOHost (including MEDLINE, SPORTDiscuss, ERIC, DOAJ, and SCOPUS) databases were searched from inception to the 31st of August, 2023. Reports were eligible if they satisfied the following criteria: recruited active soccer players, with no restriction on race, sex, age, level of expertise, or health status; studies utilizing TMG for measuring muscle contractile properties. In total, 25 published journal articles from 22 original studies were included in the current review, encompassing a total of 1224 participants (4% females). The analysis considered various muscles, with the biceps femoris (BF), rectus femoris (RF), vastus lateralis (VL), vastus medialis (VM), semitendinosus (ST), gastrocnemius lateralis (GL), and gastrocnemius medialis (GM) being investigated. Significant variations were observed in TMG parameters across different muscles, age categories, and levels of play. The quality of evidence varied from low to moderate for all analyses. The meta-regression analysis indicated that age moderated several TMG-derived parameters in lower limb muscles including BF Vc, RF Td and Vc, ST Dm and sustain time, VL Dm, Tc, Td and relaxation time (Tr), and VM Tc, Td and Tr, respectively. In conclusion, the current review illuminated the multifaceted applications of TMG in assessing lower extremity muscles in soccer players. Beyond evaluating muscle contractile properties in various superficial muscles of the lower limbs in soccer players, TMG-derived parameters may serve as potentially valuable markers in identifying neuromuscular risk factors for anterior cruciate ligament injuries and predicting hamstring-related injuries.

• Publication type
• Journal Article MeSH
• Review MeSH

Starting point: Cervical dystonia is a common form of focal dystonia, resulting in neck pain and the development of asymmetric neck and head postures. These abnormal postures contribute to muscular impairment, muscle imbalances, and, as a result, alteration in movement patterns. This study aimed to compare the asymmetry of cervical muscle activation pattern during cervical flexion movements between individuals with cervical dystonia and healthy young subjects. Methods: Eight individuals with cervical dystonia and eight healthy participants participated in this study. We recorded muscle activation from five pairs of cervical muscles (sternocleidomastoid, scalene, trapezius, suprahyoid, and infrahyoid) using surface electromyography. Normalized cross-correlation was used to analyze the symmetry of bilateral muscle activation. Results: The results showed significant differences in muscle activation symmetry between the cervical dystonia group and healthy subjects. Notably, patients with cervical dystonia exhibited less symmetric activation in the trapezius and sternocleidomastoid muscles compared to healthy controls (p < 0.01 and p < 0.05, respectively). Additionally, the trapezius muscle on the dystonic side lacked coordination with other cervical muscles, unlike in healthy individuals who displayed better coordination. Conclusions: These findings underline the challenges faced by individuals with cervical dystonia in achieving symmetric activation and coordination of cervical muscles. Evaluating cervical muscle activation symmetry may be a valuable approach for assessing motor impairments in these patients.

BACKGROUND: Preservation of mobility independence is a primary goal in older adults with physical frailty and sarcopenia (PF&S). Interventions based on the combination of physical activity (PA) and nutritional counselling have been indicated as strategies for the management of this condition, although their effectiveness is not confirmed in all investigations. A possible explanation for this uncertain scenario relies in the impact of the adherence to PA interventions. Hence, the present study investigated the impact of the adherence to PA sessions on the incidence of mobility disability in older adults with PF&S. METHODS: This is a secondary analysis of an evaluator blinded, randomised controlled trial, developed in 16 clinical sites across 11 European countries, from January 2016 to 31 October 2019. Participants were community-dwelling older adults (70+ years) with PF&S enrolled in the SPRINTT trial (NCT02582138). PF&S was operationalised as having a total score from 3 to 9 on the short physical performance battery (SPPB), low appendicular lean mass and ability to complete the 400-m walk test in < 15 min. Data from participants allocated to a multicomponent intervention (PA with technological support plus nutritional counselling) and a healthy ageing lifestyle education programme (control group) were analysed. Adherence to PA was assessed based on the number of weekly sessions attended. According to recommendations of the American College of Sports Medicine, adherence was categorised as below recommendations (< 2 sessions/week, BR), meeting recommendations (2-3 sessions/week, MR), and above recommendations (> 3 sessions/week, AR). The primary outcome was incident mobility disability, operationalised as incident inability to complete the 400-m walk test in < 15 min during up to 36 months of follow-up. RESULTS: Data of 1444 participants (mean age 79.3 years, 72.6% women) were analysed. In those with SPPB scores of 3-7, MR and AR groups had lower risk of mobility disability compared with controls [MR HR (95% CI): 0.57 (0.41-0.78), p = 0.001; AR HR (95% CI): 0.33 (0.23-0.46), p < 0.001] and BR groups [MR: HR (95% CI): 0.48 (0.34-0.69), p < 0.001; AR: HR (95% CI): 0.27 (0.18-0.38), p < 0.001] in a dose-dependent manner. In those with SPPB scores of 8 or 9, the BR group had a higher risk of mobility disability than controls. MR and AR groups had a lower risk of mobility disability than the BR group. CONCLUSIONS: In older adults with PF&S, adherence to PA recommendations is associated with lower incidence of mobility disability. This benefit depends on the degree of adherence as well as baseline physical performance. TRIAL REGISTRATION: ClinicalTrials.gov NCT02582138.

• MeSH
• Exercise * physiology   MeSH
• Humans MeSH
• Mobility Limitation * MeSH
• Persons with Disabilities MeSH
• Sarcopenia * physiopathology   therapy   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

Neurodegenerative motor disorders affect the neuromuscular system challenging daily life and normal activity. Parkinson's Disease (PD) is among the most prevalent ones, with a large impact and rising prevalence rates. Speech is most affected by PD as far as phonatory and articulatory performance is concerned. Neuromotor activity (NMA) alterations have an impact on larynx muscles responsible for vocal fold adduction and abduction, hampering phonation stability and regularity. The main muscular articulators involved in phonation control are the cricothyroid (tensor) and thyroarytenoid (relaxer) systems, regulated by two distinct direct neuromotor pathways, activated by the precentral gyrus laryngeal control areas. These articulations control the musculus vocalis, directly responsible for regular vocal fold vibration. An indirect estimation of the muscular tension produced by inverse filtering may split into two independent channels, assumed to be the tensor and relaxer neuromotor pathways such as the differential neuromotor activity (DNMA). The amplitude distributions of both DNMA channels allow comparing phonations from PD-affected persons (PDPs) and age-matched healthy control participants (HCPs) with respect to a set of reference mid-age normative participants (RSPs). The comparisons are carried out by Jensen-Shannon distributions of PDP and HCP phonations with respect to those of RSPs. A dataset of 96 phonation samples from participants balanced by gender is used to train a set of decision tree classifiers (DTCs) to distinguish PDP from HCP phonation. The best results from 10-fold cross-validation offered accumulated mismatches of 0.09 and 0.1292 for male and female subsets. The sensitivity, specificity, and accuracy of the classification results when separating PDP from HCP phonatios were 93.33%, 88.23%, and 90.63% (male PDP versus HCP) and 92.86%, 83.33%, and 87.50% (female PDP versus HCP), providing a stratification of PDPs and HCPs by objective disease grading from explainable AI (XAI) methods.

• MeSH
• Adult MeSH
• Phonation * physiology   MeSH
• Laryngeal Muscles * physiopathology   MeSH
• Larynx * physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Parkinson Disease * physiopathology   complications   MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Developmental remodeling shapes neural circuits via activity-dependent pruning of synapses and axons. Regulation of the cytoskeleton is critical for this process, as microtubule loss via enzymatic severing is an early step of pruning across many circuits and species. However, how microtubule-severing enzymes, such as spastin, are activated in specific neuronal compartments remains unknown. Here, we reveal that polyglutamylation, a post-translational tubulin modification enriched in neurons, plays an instructive role in developmental remodeling by tagging microtubules for severing. Motor neuron-specific gene deletion of enzymes that add or remove tubulin polyglutamylation-TTLL glutamylases vs. CCP deglutamylases-accelerates or delays neuromuscular synapse remodeling in a neurotransmission-dependent manner. This mechanism is not specific to peripheral synapses but also operates in central circuits, e.g., the hippocampus. Thus, tubulin polyglutamylation acts as a cytoskeletal rheostat of remodeling that shapes neuronal morphology and connectivity.

• MeSH
• Hippocampus metabolism   cytology   MeSH
• Polyglutamic Acid * metabolism   MeSH
• Microtubules * metabolism   MeSH
• Motor Neurons * metabolism   MeSH
• Mice MeSH
• Neuromuscular Junction metabolism   MeSH
• Synaptic Transmission MeSH
• Neurons * metabolism   MeSH
• Neuronal Plasticity * physiology   MeSH
• Peptide Synthases metabolism   genetics   MeSH
• Protein Processing, Post-Translational MeSH
• Spastin metabolism   MeSH
• Synapses metabolism   MeSH
• Tubulin metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH