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1.
J Neurosurg Sci ; 68(4): 482-491, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38949058

RESUMO

INTRODUCTION: Arachnoid cysts are primarily dysembryogenetic splitting or duplication of the embryonic meningeal mesenchyme, hence the paediatric preponderance. Neuroendoscopic cysto-cisternostomy is now the favoured treatment option. We pooled data on middle fossa arachnoid cysts (MCFAC) demographics, clinical presentations, cyst characteristics, neuro-endoscopic cysto-cisternostomy and its outcomes. EVIDENCE ACQUISITION: Using search words (from the keywords; 'endoscopic treatment' and 'middle fossa arachnoid cysts') combined using Boolean operators, a systematic review of the PubMed and Cochrane CENTRAL was started on 1st February 2023, as per protocol (PROSPERO CRD42023394345); 65 records and then 46 reports were screened, 169 cases were pooled from the 19 recruited reports for the qualitative and quantitative syntheses, after methodological assessment (significantly excellent 57.9% quality) using the Joanna Briggs Institute critical appraisal tools. EVIDENCE SYNTHESIS: The male-to-female ratio was 2.4:1, with a weighted average-age of 11.25 years in the modal childhood (32.0%) age-group. Headaches (53/29.3%), seizures (30/16.6%) and macrocephaly (25/13.8%) were the commonest presentations. Right-sided (30/55.6%) and Galassi II (55/48.3%) and III (53/46.5%) lesions were common. Rigid (124/93.9%) endoscopes aided cysto-cisternostomy using mostly bipolar diathermy (31/43.7%) and ventriculostomy forceps (18/25.4%); creating one (22/18.3%), two (14/11.6%) or more (78/65.0%) stomas. Fenestration sites were specifically CNIII&ICA (32/25.8%), CNII&ICA (27/21.8%), CNIII&tentorium cerebelli (23/18.6%), CNIII&PCA (1/0.8%) and through the side of CNVI (1/0.8%) into the pre-pontine cistern. Good clinical and radiological outcomes were reported. CONCLUSIONS: Largely excellent-to-good quality, low-level evidence reported MCFACs presenting in childhood with headaches, seizures and macrocephaly. At least two fenestrations using bipolar-diathermy/forceps and balloon-catheter expansion were used for cysto-cisternostomy, with good outcomes.


Assuntos
Cistos Aracnóideos , Fossa Craniana Média , Neuroendoscopia , Humanos , Cistos Aracnóideos/cirurgia , Neuroendoscopia/métodos , Fossa Craniana Média/cirurgia , Masculino , Feminino , Criança , Resultado do Tratamento
2.
Explor Target Antitumor Ther ; 5(3): 581-599, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966179

RESUMO

Passaged cell lines represent currently an integral component in various studies of malignant neoplasms. These cell lines are utilized for drug screening both in monolayer cultures or as part of three-dimensional (3D) tumor models. They can also be used to model the tumor microenvironment in vitro and in vivo through xenotransplantation into immunocompromised animals. However, immortalized cell lines have some limitations of their own. The homogeneity of cell line populations and the extensive passaging in monolayer systems make these models distant from the original disease. Recently, there has been a growing interest among scientists in the use of primary cell lines, as these are passaged directly from human tumor tissues. In this case, cells retain the morphological and functional characteristics of the tissue from which they were derived, an advantage often not observed in passaged cultures. This review highlights the advantages and limitations of passaged and primary cell cultures, their similarities and differences, as well as existing test systems that are based on primary and passaged cell cultures for drug screening purposes.

3.
J Phys Chem A ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968412

RESUMO

Kinetics of the lanthanide cations (Ln+ = La+-Lu+ excluding Pm+) reacting with molecular oxygen were measured in a selected-ion flow tube apparatus from 300 to 600 K. Where exothermic, these reactions occur efficiently, producing LnO+ + O. The reactions display positive temperature dependences consistent with Arrhenius equation behavior and show small activation energies (0-2 kJ mol-1) that are strongly correlated to promotion energies of the Ln+ atoms. Reanalysis of literature data on neutral Ln + O2 reactions show a similar correlation with slightly larger activation energies (0-10 kJ mol-1). The data are explained by a common mechanism controlling oxidation by molecular oxygen in these systems, as well as in gas-phase reactions of transition metal and posttransition metal cluster anions, neutral clusters deposited on surfaces, and for oxygen incident on metal surfaces. It is posited that across these systems, the height of an early barrier along the reaction coordinate is predictable based on knowledge of the electronic states of the reactants and may be used to either promote or inhibit oxygen activation.

4.
Microsc Microanal ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38973604

RESUMO

Atom probe tomography (APT) has been utilized to investigate the microstructure of two model borosilicate glasses designed to understand the solubility limits of phosphorous pentoxide (P2O5). This component is found in certain high-level radioactive defence wastes destined for vitrification, where phase separation can potentially lead to a number of issues relating to the processing of the glass and its long-term chemical and structural stability. The development of suitable focused ion beam (FIB)-preparation routes and APT analysis conditions were initially determined for the model glasses, before examining their detailed microstructures. In a 3.0 mol% P2O5-doped glass, both visual inspection and sensitive statistical analysis of the APT data show homogeneous microstructures, while raising the content to 4.0 mol% initiates the formation of phosphorus-enriched nanoscale precipitates. This study confirms the expected inhomogeneities and phase separation of these glasses and offers routes to characterizing these at near-atomic scale resolution using APT.

5.
Environ Sci Technol ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38952258

RESUMO

There is a notable lack of continuous monitoring of air pollutants in the Global South, especially for measuring chemical composition, due to the high cost of regulatory monitors. Using our previously developed low-cost method to quantify black carbon (BC) in fine particulate matter (PM2.5) by analyzing reflected red light from ambient particle deposits on glass fiber filters, we estimated hourly ambient BC concentrations with filter tapes from beta attenuation monitors (BAMs). BC measurements obtained through this method were validated against a reference aethalometer between August 2 and 23, 2023 in Addis Ababa, Ethiopia, demonstrating a very strong agreement (R2 = 0.95 and slope = 0.97). We present hourly BC for three cities in sub-Saharan Africa (SSA) and one in North America: Abidjan (Côte d'Ivoire), Accra (Ghana), Addis Ababa (Ethiopia), and Pittsburgh (USA). The average BC concentrations for the measurement period at the Abidjan, Accra, Addis Ababa Central summer, Addis Ababa Central winter, Addis Ababa Jacros winter, and Pittsburgh sites were 3.85 µg/m3, 5.33 µg/m3, 5.63 µg/m3, 3.89 µg/m3, 9.14 µg/m3, and 0.52 µg/m3, respectively. BC made up 14-20% of PM2.5 mass in the SSA cities compared to only 5.6% in Pittsburgh. The hourly BC data at all sites (SSA and North America) show a pronounced diurnal pattern with prominent peaks during the morning and evening rush hours on workdays. A comparison between our measurements and the Goddard Earth Observing System Composition Forecast (GEOS-CF) estimates shows that the model performs well in predicting PM2.5 for most sites but struggles to predict BC at an hourly resolution. Adding more ground measurements could help evaluate and improve the performance of chemical transport models. Our method can potentially use existing BAM networks, such as BAMs at U.S. Embassies around the globe, to measure hourly BC concentrations. The PM2.5 composition data, thus acquired, can be crucial in identifying emission sources and help in effective policymaking in SSA.

6.
Sci Adv ; 10(25): eadi0707, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905351

RESUMO

Ras is a small GTPase that is central to important functional decisions in diverse cell types. An important aspect of Ras signaling is its ability to exhibit bimodal or switch-like activity. We describe the total reconstitution of a receptor-mediated Ras activation-deactivation reaction catalyzed by SOS and p120-RasGAP on supported lipid membrane microarrays. The results reveal a bimodal Ras activation response, which is not a result of deterministic bistability but is rather driven by the distinct processivity of the Ras activator, SOS. Furthermore, the bimodal response is controlled by the condensation state of the scaffold protein, LAT, to which SOS is recruited. Processivity-driven bimodality leads to stochastic bursts of Ras activation even under strongly deactivating conditions. This behavior contrasts deterministic bistability and may be more resistant to pharmacological inhibition.


Assuntos
Transdução de Sinais , Proteínas ras , Proteínas ras/metabolismo , Proteínas Son Of Sevenless/metabolismo , Humanos
8.
AIMS Microbiol ; 10(2): 273-287, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38919722

RESUMO

Multidrug-resistant tuberculosis (TB) (MDR-TB), or TB that is simultaneously resistant to both isoniazid (INH) and rifampicin (RIF), is a barrier to successful TB control and treatment. Stratified data on MDR-TB, particularly in the high-burden western Kenya region, remain unknown. This data is important to monitor the efficacy of TB control and treatment efforts. Herein, we determined the molecular epidemiology of drug-resistant TB and associated risk factors in western Kenya. This was a non-experimental, population-based, cross-sectional study conducted between January and August 2018. Morning sputum samples of individuals suspected of pulmonary TB were collected, processed, and screened for Mycobacterium tuberculosis (Mtb) and drug resistance using line probe assay (LPA) and Mycobacterium growth indicator tubes (MGIT) culture. MGIT-positive samples were cultured on brain heart infusion (BHII) agar media, and the presence of Mtb was validated using Immunochromatographic assay (ICA). Drug sensitivity was performed on MGIT and ICA-positive but BHI-negative samples. Statistical significance was set at P < 0.05. Of the 622 Mtb isolates, 536 (86.2%) were susceptible to RIF and INH. The rest, 86 (13.83%), were resistant to either drugs or both. A two-sample proportional equality test revealed that the MDR-TB prevalence in western Kenya (5%) did not vary significantly from the global MDR-TB estimate (3.9%) (P = 0.196). Men comprised the majority of susceptible and resistant TB (75.9% and 77.4%%, respectively). Also, compared with healthy individuals, the prevalence of HIV was significantly higher in MDR-TB patients (35.9% vs 5.6%). Finally, TB prevalence was highest in individuals aged 25-44 years, who accounted for 58.4% of the total TB cases. Evidently, the prevalence of MDRTB in western Kenya is high. Particular attention should be paid to men, young adults, and those with HIV, who bear the greatest burden of resistant TB. Overall, there is a need to refine TB control and treatment programs in the region to yield better outcomes.

9.
Neurosurg Focus ; 56(6): E7, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38823058

RESUMO

OBJECTIVE: This study presents the results of an evaluation of the effectiveness of percutaneous thermal radiofrequency (RF) ablation of spinal nerve roots to reduce spasticity and improve motor function in children with cerebral palsy (CP). METHODS: A retrospective analysis was conducted on the surgical treatment outcomes of 26 pediatric patients with severe CP (Gross Motor Function Classification System levels IV-V). The assessment protocol included muscle tone assessment using the modified Ashworth scale (MAS), evaluation of passive and active range of motion, gait video recording, and locomotor status evaluation using the Gross Motor Function Measure (GMFM)-88 scale. Thermal RF rhizotomy (ablation of spinal nerve roots) was performed on all patients at the L2-S1 levels at 70°C for 90 seconds. The statistical data analysis was conducted using the t-test and Mann-Whitney U-test. A p value < 0.05 was considered statistically significant. RESULTS: Before the operation, the average level of spasticity in the lower-limb muscles of all patients was 3.0 ± 0.2 according to the MAS. In the early postoperative period, the spasticity level in all examined muscle groups significantly decreased to a mean of 1.14 ± 0.15 (p < 0.001). In the long-term postoperative period, the spasticity level in the examined muscle groups averaged 1.49 ± 0.17 points on the MAS (p < 0.001 compared to baseline, p = 0.0416 compared to the early postoperative period). Despite the marked reduction of spasticity in the lower limbs, no significant change in locomotor status according to the GMFM-88 scale was observed in the selected category of patients. In the long-term period, during the control examination of patients, the GMFM-88 level increased on average by 3.6% ± 1.4% (from 22.2% ± 3.1% to 25.8% ± 3.6%). CONCLUSIONS: The findings of this study offer preliminary yet compelling evidence that RF ablation of spinal nerve roots can lead to a significant and enduring decrease in muscle tone among children with severe spastic CP. Further studies and longer-term data of the impact on functionality and quality of life of patients with CP after spinal root RF ablation are needed.


Assuntos
Paralisia Cerebral , Rizotomia , Raízes Nervosas Espinhais , Humanos , Paralisia Cerebral/cirurgia , Rizotomia/métodos , Raízes Nervosas Espinhais/cirurgia , Masculino , Feminino , Criança , Estudos Retrospectivos , Pré-Escolar , Resultado do Tratamento , Espasticidade Muscular/cirurgia , Adolescente , Vértebras Lombares/cirurgia , Ablação por Radiofrequência/métodos
10.
Environ Pollut ; 357: 124439, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38942279

RESUMO

Emerging pollutants, such as pharmaceuticals and microplastics have become a pressing concern due to their widespread presence and potential impacts on ecological systems. To assess the ecosystem-level effects of these pollutants within a multi-stressor context, we simulated real-world conditions by exposing a near-natural multi-trophic aquatic food web to a gradient of environmentally relevant concentrations of fluoxetine and microplastics in large mesocosms over a period of more than three months. We measured the biomass and abundance of different trophic groups, as well as ecological functions such as nutrient availability and decomposition rate. To explore the mechanisms underlying potential community and ecosystem-level effects, we also performed behavioral assays focusing on locomotion parameters as a response variable in three species: Daphnia magna (zooplankton prey), Chaoborus flavicans larvae (invertebrate pelagic predator of zooplankton) and Asellus aquaticus (benthic macroinvertebrate), using water from the mesocosms. Our mesocosm results demonstrate that presence of microplastics governs the response in phytoplankton biomass, with a weak non-monotonic dose-response relationship due to the interaction between microplastics and fluoxetine. However, exposure to fluoxetine evoked a strong non-monotonic dose-response in zooplankton abundance and microbial decomposition rate of plant material. In the behavioral assays, the locomotion of zooplankton prey D. magna showed a similar non-monotonic response primarily induced by fluoxetine. Its predator C. flavicans, however, showed a significant non-monotonic response governed by both microplastics and fluoxetine. The behavior of the decomposer A. aquaticus significantly decreased at higher fluoxetine concentrations, potentially leading to reduced decomposition rates near the sediment. Our study demonstrates that effects observed upon short-term exposure result in more pronounced ecosystem-level effects following chronic exposure.

12.
J Vasc Interv Radiol ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38901491

RESUMO

Percutaneous transhepatic lymphatic embolization (PTLE) and peroral esophagogastroduodenoscopy (EGD) duodenal mucosal radiofrequency ablation (RFA) were performed to manage protein-losing enteropathy (PLE) in patients with congenital heart disease (CHD). Five procedures were performed in 4 patients (M/F = 3/1, median age: 49 years [range 31-71 years]). Transhepatic lymphangiography demonstrated abnormal peri-duodenal lymphatic channels. After methylene blue injection through transhepatic access, subsequent EGD evaluation showed methylene blue extravasation at various sites in the duodenal mucosa. Endoscopic RFA of the leakage sites followed by PTLE using 3:1 ethiodized oil to n-butyl cyanoacrylate glue resulted in improved symptoms and serum albumin (pre-procedure: 2.6 g/dL ± 0.2; post-procedure: 3.5 g/dL ± 0.4, p=0.004) over a median follow-up of 16 months (range 5-20). Transhepatic lymphangiography and methylene blue injection with EGD evaluation of the duodenal mucosa can help diagnose PLE. Combined PTLE and EGD-RFA can be considered to treat patients with PLE.

13.
Artigo em Inglês | MEDLINE | ID: mdl-38842372

RESUMO

BACKGROUND: Exposure to hypoxia immediately challenges a variety of physiologic systems that limit exercise capacity. Under normoxia, caffeine (CAFF) increases ventilation and subsequent oxygenation of hemoglobin (SpO2) and skeletal muscle (SmO2). CAFF improves exercise performance at altitude. However, little attention has been given to submaximal exercise in hypoxia, particularly regarding low CAFF consumers and female participants. The aim of this study was to determine the effect of CAFF on pulmonary, metabolic, and perceptual variables in response to submaximal running in hypoxia in low CAFF consuming males and females. METHODS: In a double blinded, counterbalanced design, 14 (6 females) individuals (24.1±5.1 years; VO2max: 40.6±5.6 mL × kg-1 × min-1; 20.8±8.0% body fat), who habitually consumed ≤150 mg/day of CAFF performed treadmill running at workloads of 25%, 40%, 60%, and 75% of sea level VO2max in normobaric hypoxia (FIO2=0.15) on two separate occasions: 1) 60 minutes after 6 mg/kg of CAFF; or 2) placebo. RESULTS: CAFF had no effect on any variable measured. Specifically, VE (condition: P=0.12; interaction: P=0.19), VT (condition: P=0.16; interaction: P=0.57), and Ve:VO2 (condition: P=0.07; interaction: P=0.69) were similar between groups. Further, CAFF had no effect on relative VO2 (condition: P=0.84; interaction: P=0.95), HR (condition: P=0.28; interaction: P=0.35), SmO2 (condition: P=0.66; interaction: P=0.82), or SpO2 (condition: P=0.16; interaction: P=0.97). Finally, rating of perceived exertion (RPE; P=0.92) and acute mountain sickness scores (P=0.29) were similar across conditions. CONCLUSIONS: These data demonstrate that CAFF provides no physiologic advantage to submaximal exercise in acute, normobaric hypoxia with low CAFF consuming males and females.

14.
bioRxiv ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38853984

RESUMO

Metabolic adaptations in response to changes in energy supply and demand are essential for survival. The mitochondrial calcium uniporter coordinates metabolic homeostasis by regulating TCA cycle activation, mitochondrial fatty acid oxidation and cellular calcium signaling. However, a comprehensive analysis of uniporter-regulated mitochondrial metabolic pathways has remained unexplored. Here, we investigate the metabolic consequences of uniporter loss- and gain-of-function, and identify a key transcriptional regulator that mediates these effects. Using gene expression profiling and proteomic, we find that loss of uniporter function increases the expression of proteins in the branched-chain amino acid (BCAA) catabolism pathway. Activity is further augmented through phosphorylation of the enzyme that catalyzes this pathway's committed step. Conversely, in the liver cancer fibrolamellar carcinoma (FLC)-which we demonstrate to have high mitochondrial calcium levels- expression of BCAA catabolism enzymes is suppressed. We also observe uniporter-dependent suppression of the transcription factor KLF15, a master regulator of liver metabolic gene expression, including those involved in BCAA catabolism. Notably, loss of uniporter activity upregulates KLF15, along with its transcriptional target ornithine transcarbamylase (OTC), a component of the urea cycle, suggesting that uniporter hyperactivation may contribute to the hyperammonemia observed in FLC patients. Collectively, we establish that FLC has increased mitochondrial calcium levels, and identify an important role for mitochondrial calcium signaling in metabolic adaptation through the transcriptional regulation of metabolism.

15.
Acta Med Philipp ; 58(1): 42-50, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38939853

RESUMO

Objectives: Perception about Physical and Rehabilitation Medicine provides information about awareness on identifying disabilities and managing their impact on activities of daily living; however, misconceptions about the field continue to exist among both students and physicians. This study aims to describe the perceptions of clinical clerks and interns towards the practice and role of Rehabilitation Medicine in management of patients. Methods: This is a descriptive cross-sectional study. Students from the Learning Unit 6 and 7 of UP College of Medicine answered adapted online survey forms from a previous study and participated in online focus group discussions. Qualitative data were used to infer the perception of medical students towards the specialty. The effect of the respondent's profile, background and affiliation on their knowledge, attitudes and perceptions were analyzed using One-Way ANOVA (α = 0.05). Qualitative data were analyzed using thematic analysis. Results: Learning Unit 6 and 7 students were found to have a perceived broad level of knowledge with regards the specialty. The students associated the specialty with focus on holistic care, quality of life, interdisciplinary collaboration, and diversity of cases managed. No statistically significant differences were found between the perception among: 1) Learning Unit 6 and 7, 2) those with or without a previous encounter with the specialty, 3) allied medical and non-allied medical undergraduate courses in terms of: a) confidence in the knowledge (p = 0.489), b) familiarity with conditions managed (p = 0.93) and c) interest towards the specialty (p = 0.693). The Organ System Integrated (OSI) curriculum, which promotes horizontal and vertical integration of concepts, provided a wide understanding of the basic concepts related to physiatry. The students' responses suggest a positive attitude towards Physical and Rehabilitation Medicine, as measured in their level of interest about knowing more regarding the specialty. Most common perceptions were that the specialty was multidisciplinary and holistic. However, the respondents' perceptions regarding the roles of the Rehabilitation team were limited. Conclusion: Learning unit level 6 and 7 students had a broad understanding of the practice and scope of the Physical and Rehabilitation Medicine specialty. Future researches can include other medical students in all year levels, including Learning Units 3, 4 and 5 of UPCM, to observe the development of their perceptions about the specialty throughout medical school.

16.
Acta Med Philipp ; 58(1): 79-83, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38939850

RESUMO

Looking along the physiological and physical changes in aging, in the light of a major burn, co-morbidities, surgical intervention and precaution, a geriatric burn patient requires a delicate balance of ideal burn care and rehabilitation to achieve functional independence. A 70-year-old patient, with 30% total body surface area flame burn injury, underwent bilateral partial calcanectomy secondary to calcaneus osteomyelitis, and Meek micrograft technique for burn injury on bilateral lower extremities, is presented in this case report. In order to ensure good graft take, her knees were immobilized causing bilateral soft tissue contractures. Subsequently, upon initiation of ambulation, gait abnormalities observed include absence of heel off and toe off, with heel walking. The patient was admitted for intensive inpatient rehabilitation, where significant improvement in the knee range of motion and ambulation were achieved. The patient was eventually discharged ambulatory with walker. Despite expected complications, rehabilitation management proved to be beneficial in improving function and ambulation in geriatric burn patient.

17.
Artigo em Inglês | MEDLINE | ID: mdl-38710768

RESUMO

BACKGROUND: On April 11th, 2023, the My Way Trading (MWT) recycling facility in Richmond, Indiana caught fire, mandating the evacuation of local residents and necessitating the U.S. Environmental Protection Agency (EPA) to conduct air monitoring. The EPA detected elevated levels of plastic combustion-related air pollutants, including hydrogen cyanide and benzene. OBJECTIVE: We aimed to identify these and other volatile organic compounds (VOCs) present as well as to identify the potential hazard of each compound for various human health effects. METHODS: To identify the VOCs, we conducted air monitoring at sites within and bordering the evacuation zone using proton transfer reaction mass spectrometry (PTR-MS) and non-targeted analysis (NTA). To facilitate risk assessment of the emitted VOCs, we used the EPA Hazard Comparison Dashboard. RESULTS: We identified 46 VOCs, within and outside the evacuation zone, with average detection levels above local background levels measured in Middletown, OH. Levels of hydrogen cyanide and 4 other VOCs were at least 1.8-fold higher near the incidence site in comparison to background levels and displayed unique temporal and spatial patterns. The 46 VOCs identified had the highest hazardous potential for eye and skin irritation, with approximately 45% and 39%, respectively, of the VOCs classified as high and very high hazards for these endpoints. Notably, all detected VOC levels were below the hazard thresholds set for single VOC exposures; however, hazard thresholds for exposure to VOC mixtures are currently unclear. IMPACT: This study serves as a proof-of-concept that PTR-MS coupled with NTA can facilitate rapid identification and hazard assessment of VOCs emitted following anthropogenic disasters. Furthermore, it demonstrates that this approach may augment future disaster responses to quantify additional VOCs present in complex combustion mixtures.

18.
N Engl J Med ; 390(20): 1849-1861, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38739079

RESUMO

BACKGROUND: One of the major determinants of exercise intolerance and limiting symptoms among patients with obstructive hypertrophic cardiomyopathy (HCM) is an elevated intracardiac pressure resulting from left ventricular outflow tract obstruction. Aficamten is an oral selective cardiac myosin inhibitor that reduces left ventricular outflow tract gradients by mitigating cardiac hypercontractility. METHODS: In this phase 3, double-blind trial, we randomly assigned adults with symptomatic obstructive HCM to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for 24 weeks, with dose adjustment based on echocardiography results. The primary end point was the change from baseline to week 24 in the peak oxygen uptake as assessed by cardiopulmonary exercise testing. The 10 prespecified secondary end points (tested hierarchically) were change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), improvement in the New York Heart Association (NYHA) functional class, change in the pressure gradient after the Valsalva maneuver, occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver, and duration of eligibility for septal reduction therapy (all assessed at week 24); change in the KCCQ-CSS, improvement in the NYHA functional class, change in the pressure gradient after the Valsalva maneuver, and occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver (all assessed at week 12); and change in the total workload as assessed by cardiopulmonary exercise testing at week 24. RESULTS: A total of 282 patients underwent randomization: 142 to the aficamten group and 140 to the placebo group. The mean age was 59.1 years, 59.2% were men, the baseline mean resting left ventricular outflow tract gradient was 55.1 mm Hg, and the baseline mean left ventricular ejection fraction was 74.8%. At 24 weeks, the mean change in the peak oxygen uptake was 1.8 ml per kilogram per minute (95% confidence interval [CI], 1.2 to 2.3) in the aficamten group and 0.0 ml per kilogram per minute (95% CI, -0.5 to 0.5) in the placebo group (least-squares mean between-group difference, 1.7 ml per kilogram per minute; 95% CI, 1.0 to 2.4; P<0.001). The results for all 10 secondary end points were significantly improved with aficamten as compared with placebo. The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS: Among patients with symptomatic obstructive HCM, treatment with aficamten resulted in a significantly greater improvement in peak oxygen uptake than placebo. (Funded by Cytokinetics; SEQUOIA-HCM ClinicalTrials.gov number, NCT05186818.).


Assuntos
Cardiomiopatia Hipertrófica , Fármacos Cardiovasculares , Teste de Esforço , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Benzilaminas , Miosinas Cardíacas/antagonistas & inibidores , Cardiomiopatia Hipertrófica/tratamento farmacológico , Cardiomiopatia Hipertrófica/fisiopatologia , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Uracila/análogos & derivados , Manobra de Valsalva , Obstrução do Fluxo Ventricular Externo/tratamento farmacológico , Obstrução do Fluxo Ventricular Externo/fisiopatologia , Obstrução do Fluxo Ventricular Externo/etiologia , Fármacos Cardiovasculares/farmacologia , Fármacos Cardiovasculares/uso terapêutico , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Administração Oral
19.
J Burn Care Res ; 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38702977

RESUMO

Burns affect 11 million people worldwide annually. Electrical burns are renowned for inflicting extensive harm and long-term consequences that can lead to severe illnesses and fatalities. People in both occupational and non-occupational settings may be exposed to electrical burns, leading to functional or anatomical consequences. We identified sociodemographic features related to electrical burns in both settings. A cross sectional design, using an open dataset of electrical shock injuries occurred in Colombia during 2010-2021 period, was carried out. Sociodemographic features of people injured in occupational and non-occupational settings were described in counts (%), incidence per 100.000 people (I0;95% CI). To identify related factors (age-sex adjusted) with injuries in occupational and non-occupational settings, we applied a Binary Logistic Regression. Over the 12-year period, there were 1.274 electrical burns (I0: 2.47;2.34-2.61), 287 in the occupational setting (I0: 1.35;1.20-1.51) and 987 in the non-occupational setting (I0: 3.25;3.05-3.46). Age median was 31 years, most cases distributed in middle adulthood (52.8%), males (88.1%), high school/technician (42.8%), urban location (73.7%), weekdays (95.3%), and daytime hours (85.5%). Factors related to electrical burns in the occupational setting were males, middle adulthood, high school/technician, Thursday, and daytime hours. Otherwise, factors related to electrical burns in the non-occupational setting were early childhood, primary school, urban location, and weekends. Both settings pose a risk of injuries to individuals. We have identified sociodemographic factors related to these injuries in both occupational and non-occupational settings, which could aid in preventing damages and long-term complications, especially among vulnerable subgroups such as determined above.

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