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Introduction: Rituximab (RTX) has been reported as an effective treatment alternative in primary forms of minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) associated with steroid dependence and frequent relapses. However, the optimal RTX regimen and the outcomes of further doses of RTX remain unclear. This study aimed to evaluate the use of induction and maintenance RTX therapy for adults with primary podocytopathies. Methods: We performed a retrospective case series on adult patients with steroid-dependent podocytopathies who received an induction RTX therapy. Maintenance therapy was performed at physician's discretion. Remission and relapse rates, concomitant corticosteroids and immunosuppressants use, B-cell depletion and adverse events were analyzed. Results: Fourteen patients (mean age at start of RTX 29.1 ± 21.9 years) with MCD (n = 7) or FSGS (n = 7) were treated with 2 doses of 1,000 mg 2 weeks apart (n = 13) or four doses of 375 mg/m2 (n = 1) of RTX. At last follow-up (mean 47.3 ± 101.7 months), 10 patients were in complete remission and two remained in partial remission. A reduction in the number of relapses, number of patients under corticosteroids and immunosuppressants, and dose of prednisolone was observed when compared to baseline (14 [100%] vs. 5 [35.7%]; 8/14 [57.1%] vs. 4/12 [33.3%]; 13/14 [92.9%] vs. 7/12 [58.3%]; 20 mg/day vs. 5.25 mg/day, respectively). Maintenance RTX therapy was used in 6 patients, with sustained complete remission. Infusion reactions were observed in 4 patients (one required treatment withdrawal). Conclusions: Our findings support the use of RTX for a steroid-free remission in podocytopathies and suggest that maintenance RTX is well-tolerated and associated with prolonged remission. Further studies are needed to confirm its efficacy and safety and establish the optimal induction and maintenance RTX regimen in steroid-dependent podocytopathies.
Rituximab (RTX) seems to be an effective treatment alternative in primary forms of MCD and FSGS, particularly in cases of steroid dependence and frequent relapses. Our findings support the use of RTX for a steroid-free remission in podocytopathies and suggest that maintenance RTX is well-tolerated and associated with prolonged remission. Further studies are needed to confirm its efficacy and safety and establish the optimal induction and maintenance RTX regimen in steroid-dependent podocytopathies.
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BACKGROUND: Swallowing is a complex process that requires the coordination of muscles in the mouth, pharynx, larynx, and esophagus. Dysphagia occurs when a person has difficulty swallowing. In the case of subjects with respiratory diseases, the presence of oropharyngeal dysphagia potentially increases lung disease exacerbations, which can lead to a rapid decline in lung function. This study aimed to analyze the swallowing of patients with idiopathic pulmonary fibrosis (IPF). METHODS: Patients with IPF were evaluated using the Eating Assessment Tool (EAT-10), tongue pressure, the Timed Water Swallow Test (TWST), and the Test of Mastication and Swallowing Solids (TOMASS). The findings were related to dyspnea severity assessed by the modified Medical Research Counsil (mMRC) score; the nutritional status screened with Mini Nutritional Assessment (MNA) tool; and pulmonary function tests, specifically spirometry and measurement of the diffusing capacity for carbon monoxide (DLCO), the maximal inspiratory pressure (PImax), and the maximal expiratory pressure (PEmax). RESULTS: The sample consisted of 34 individuals with IPF. Those who exhibited swallowing modifications scored lower on the MNA than those who did not (9.6 ± 0.76 vs. 11.64 ± 0.41 points; mean difference 1.98 ± 0.81 points; p = 0.02). They also showed poorer lung function when considering the predicted force vital capacity (FVC; 81.5% ± 4.61% vs. 61.87% ± 8.48%; mean difference 19.63% ± 9.02%; p = 0.03). The speed of liquid swallowing was altered in 31of 34 of the evaluated subjects (91.1%). The number of liquid swallows correlated significantly with the forced expiratory volume in 1 s (FEV1)/FVC ratio (r = 0.3; p = 0.02). Solid eating and swallowing assessed with the TOMASS score correlated with lung function. The number of chewing cycles correlated negatively with PImax% predicted (r = -0.4; p = 0.0008) and PEmax% predicted (r = -0.3; p = 0.02). FVC% predicted correlated with increased solid swallowing time (r = -0.3; p = 0.02; power = 0.6). Swallowing solids was also impacted by dyspnea. CONCLUSION: Patients with mild-to-moderate IPF can present feeding adaptations, which can be related to the nutritional status, lung function, and the severity of dyspnea.
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Trastornos de Deglución , Deglución , Fibrosis Pulmonar Idiopática , Lengua , Humanos , Masculino , Femenino , Anciano , Fibrosis Pulmonar Idiopática/fisiopatología , Fibrosis Pulmonar Idiopática/complicaciones , Deglución/fisiología , Trastornos de Deglución/fisiopatología , Trastornos de Deglución/etiología , Persona de Mediana Edad , Lengua/fisiopatología , Pruebas de Función Respiratoria , Presión , Estado Nutricional , Pulmón/fisiopatología , Disnea/fisiopatología , Disnea/etiología , Evaluación Nutricional , Anciano de 80 o más AñosRESUMEN
This study aimed to identify factors associated with colonization by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in adult patients admitted to a Brazilian hospital. This is a cross-sectional study, in which patients underwent a nasal swab and were asked about hygiene behavior, habits, and clinical history. Among the 702 patients, 180 (25.6%) had S. aureus and 21 (2.9%) MRSA. The factors associated with MRSA colonization were attending a gym (OR 4.71; 95% CI; 1.42 - 15.06), smoking habit in the last year (OR 2.37; 95% CI; 0.88 - 6.38), previous hospitalization (OR 2.18; CI 95%; 0.89 - 5.25), and shared personal hygiene items (OR 1.99; 95% CI; 0.71 - 5.55). At the time of admission, colonization by CA-MRSA isolates was higher than that found in the general population. This can be an important public health problem, already endemic in hospitals, whose factors such as those associated with habits (smoking cigarettes) and behaviors (team sports practice and activities in gyms) have been strongly highlighted. These findings may help developing infection control policies, allowing targeting patients on higher-risk populations for MRSA colonization.
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Infecciones Comunitarias Adquiridas , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Humanos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Estudios Transversales , Masculino , Femenino , Infecciones Estafilocócicas/microbiología , Infecciones Comunitarias Adquiridas/microbiología , Persona de Mediana Edad , Adulto , Factores de Riesgo , Brasil/epidemiología , Adulto Joven , Anciano , Factores Socioeconómicos , Portador Sano/microbiología , AdolescenteRESUMEN
INTRODUCTION: The study aim was to analyze the presentation, management, and follow-up of renal transplant patients developing bladder calculi. METHODS: Patients who underwent renal transplant with postoperative follow-up at our institution were retrospectively analyzed (1984-2023) to assess for the development of posttransplant bladder stones. All bladder stones were identified by computerized tomography imaging and stone size was measured using this imaging modality. RESULTS: The prevalence of bladder calculi post-renal transplantation during the study window was 0.22% (N = 20/8,835) with a median time to bladder stone diagnosis of 13 years posttransplant. Of all bladder stone patients, 6 (30%) received deceased donor and 14 (70%) living donor transplants. There were 11 patients with known bladder stone composition available; the most common being calcium oxalate (N = 6). Eleven (55%) patients had clinical signs or symptoms (most commonly microhematuria). Fourteen of the bladder stone cohort patients (70%) underwent treatment including cystolitholapaxy in 12 subjects. Of these 14 patients, 9 (64%) were found to have nonabsorbable suture used for their ureteroneocystostomy closure. CONCLUSIONS: The prevalence of bladder stones post-renal transplant is low. The utilization of nonabsorbable suture for ureteral implantation was the main risk factor identified in our series. This technique is no longer used at our institution. Other factors contributing to bladder stone formation in this population warrant identification.
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INTRODUCTION: The objective of this study was to stratify preoperative immune cell counts by cancer specific outcomes in patients with renal cell carcinoma (RCC) and a tumor thrombus after radical nephrectomy with tumor thrombectomy. METHODS: Patients with a diagnosis of RCC with tumor thrombus that underwent radical nephrectomy with thrombectomy across an international consortium of seven institutions were included. Patients who were metastatic at diagnosis and those who received preoperative medical treatment were also included. Retrospective chart review was performed to collect demographic information, past medical history, preoperative lab work, surgical pathology, and follow up data. Neutrophil counts, lymphocyte counts, monocyte counts, neutrophil to lymphocyte ratios (NLR), lymphocyte to monocyte ratios (LMR), and neutrophil to monocyte ratios (NMR) were compared against cancer-specific outcomes using independent samples t-test, Pearson's bivariate correlation, and analysis of variance. RESULTS: One hundred forty-four patients were included in the study, including nine patients who were metastatic at the time of surgery. Absolute lymphocyte count preoperatively was greater in patients who died from RCC compared to those who did not (2 vs 1.4; p < 0.001). Patients with tumor pathology showing perirenal fat invasion had a greater neutrophil count compared to those who did not (7.5 vs 5.5; p = 0.010). Patients with metastatic RCC had a lower LMR compared to those without metastases after surgery (2.5 vs 3.2; p = 0.041). Tumor size, both preoperatively and on gross specimen, had an interaction with multiple immune cell metrics (p < 0.05). CONCLUSIONS: Preoperative immune metrics have clinical utility in predicting cancer-specific outcomes for patients with RCC and a tumor thrombus. Additional study is needed to determine the added value of preoperative serum immune cell data to established prognostic risk calculators for this patient population.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/patología , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Neoplasias Renales/inmunología , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neutrófilos , Células Neoplásicas Circulantes , Trombectomía , Periodo Preoperatorio , Nefrectomía , Trombosis/inmunología , Trombosis/etiología , Recuento de Leucocitos , Recuento de Linfocitos , Monocitos/inmunologíaRESUMEN
BACKGROUND AND OBJECTIVES: Cardiopulmonary and skeletal muscle impairment and poor physical activity are potential contributors to reduced functional capacity in cystic fibrosis (CF). The Glittre-ADL test (TGlittre) has great potential for clinical use in adult CF adults, as it meets the need for a comprehensive assessment of physical function using tasks similar to activities of daily living. This study aimed to evaluate the performance of TGlittre in CF adults compared to the 6-min walk test (6MWT) and, secondarily, to quantify the associations of their results with pulmonary function, muscle strength, and health-related quality of life (HRQoL). METHODS: This cross-sectional study evaluated 34 CF adults and compared them with 34 subjects from a control group. The participants underwent the following assessments: functional capacity using TGlittre and 6MWT; spirometry; respiratory muscle strength; handgrip strength (HGS); and HRQoL using the Cystic Fibrosis Questionnaire-Revised (CFQ-R). RESULTS: While CF patients showed a longer time to perform TGlittre compared to controls (134 (119-150) versus 107 (95-126) % of the predicted time p = 0.0002), no difference between these groups was observed in the 6MWT. When the second TGlittre was compared to the first TGlittre, there was a significant decrease in total time for both CF patients (p < 0.0001) and controls (p = 0.0001). TGlittre time correlated with 6MWT distance (6MWD) (rs = -0.641, p < 0.0001), HGS (rs = -0.364, p = 0.034), peripheral oxygen saturation at the end of the test (rs = -0.463, p = 0.006) and the "digestive symptoms" domain of CFQ-R (rs = 0.376, p = 0.028). TGlittre time was shorter in patients who engaged in regular physical activity (3.10 (2.49-3.39) min versus 3.28 (2.95-3.53) min, p = 0.016). CONCLUSIONS: TGlittre is more effective than the 6MWT in detecting limitations during exercise. There is an important learning effect of TGlittre in adult CF patients. TGlittre time was correlated with 6MWD, HGS, oxygen saturation level, and the patient's level of physical activity.
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Fibrosis Quística , Prueba de Esfuerzo , Adulto , Humanos , Prueba de Esfuerzo/métodos , Actividades Cotidianas , Fuerza de la Mano , Fibrosis Quística/diagnóstico , Estudios Transversales , Calidad de VidaRESUMEN
Variations from classic bladder exstrophy (BE) are extremely uncommon, resulting in distinctive challenges in both diagnosis and management. The supravesical fissure variant of BE is exceptionally rare and has only been reported in male patients to date. Herein, we report the case and surgical management of a supravesical fissure variant of BE presentation in a newborn female patient and provide a literature review of this exstrophy variant.
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Extrofia de la Vejiga , Femenino , Humanos , Recién Nacido , Extrofia de la Vejiga/cirugíaRESUMEN
ABSTRACT This study aimed to identify factors associated with colonization by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in adult patients admitted to a Brazilian hospital. This is a cross-sectional study, in which patients underwent a nasal swab and were asked about hygiene behavior, habits, and clinical history. Among the 702 patients, 180 (25.6%) had S. aureus and 21 (2.9%) MRSA. The factors associated with MRSA colonization were attending a gym (OR 4.71; 95% CI; 1.42 - 15.06), smoking habit in the last year (OR 2.37; 95% CI; 0.88 - 6.38), previous hospitalization (OR 2.18; CI 95%; 0.89 - 5.25), and shared personal hygiene items (OR 1.99; 95% CI; 0.71 - 5.55). At the time of admission, colonization by CA-MRSA isolates was higher than that found in the general population. This can be an important public health problem, already endemic in hospitals, whose factors such as those associated with habits (smoking cigarettes) and behaviors (team sports practice and activities in gyms) have been strongly highlighted. These findings may help developing infection control policies, allowing targeting patients on higher-risk populations for MRSA colonization.
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BACKGROUND: Autologous hematopoietic stem cell transplant plays an important role in multiple myeloma (MM) treatment. Increasing incidence of MM and growing awareness of acute kidney injury (AKI) as a complication of hematopoietic stem cell transplant results in the need to better understand AKI in these patients. We aimed to evaluate incidence, risk factors and 5-year prognostic impact of AKI in MM patients undergoing autologous hematopoietic stem cell transplant. METHODS: Retrospective cohort study. AKI was defined by the KDIGO classification using creatinine and urinary output criteria. We used survival analysis methods considering competing events for risk factors and disease-free survival, Cox proportional regression for overall survival and stepwise regression methods for multivariable models. RESULTS: We analyzed data regarding 143 patients. The cumulative incidence of AKI and moderate-to-severe AKI was 49.7% and 14.1%, respectively. Factors with independent impact on AKI were obesity (HR: 1.83, 95% CI 1.07-3.11; p = 0.026), Hematopoietic cell transplantation-specific comorbidity index (HCT-CI) ≥ 2 (HR: 1.85, 95% CI 1.08-3.17), chronic kidney disease (CKD) (HR: 2.06, 95% CI 1.05-4.04), amyloidosis (HR: 2.25, 95% CI 1.25-4.06), mucositis grade 3-4 (HR: 2.19, 95% CI 1.25-3.86) and exposure to nephrotoxic drugs (HR: 2.0856, 95% CI 1.04-4.19). Moderate-to-severe AKI had an impact (HR: 1.62, 95% CI 1.15-2.31) on 5-year overall survival. CONCLUSION: Acute kidney injury affects almost half of MM patients undergoing autologous hematopoietic stem cell transplantation, and reduction in urinary output allows early diagnosis in almost a quarter of the patients. Obesity, HCT-CI ≥ 2, CKD, amyloidosis, mucositis grade 3-4 and exposure to nephrotoxic drugs are significant risk factors. Moderate-to-severe AKI is associated with lower 5-year overall survival.
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BACKGROUND: In rheumatoid arthritis (RA), the involvement of the pulmonary interstitium can lead to structural changes in the small airways and alveoli, leading to reduced airflow and maldistribution of ventilation. The single-breath nitrogen washout (SBN2W) test is a measure of the ventilatory distribution heterogeneity and evaluates the small airways. This study aimed to find out which clinical, serological, functional and radiological findings are useful to identify RA patients with pathological values of the phase III slope (SIII) measured by the SBN2W test. METHODS: This was a cross-sectional study in which RA patients were assessed using the Health Assessment Questionnaire-Disability Index (HAQ-DI) and the Clinical Disease Activity Index (CDAI) and underwent serological analysis of autoantibodies and inflammatory markers. In addition, they underwent pulmonary function tests (including the SBN2W test) and chest computed tomography (CT). RESULTS: Of the 60 RA patients evaluated, 39 (65%) had an SIII >120% of the predicted value. There were significant correlations between SIII and age (r = 0.56, p<0.0001), HAQ-DI (r = 0.34, p = 0.008), forced vital capacity (FVC, r = -0.67, p<0.0001), total lung capacity (r = -0.46, p = 0.0002), residual volume/total lung capacity (TLC) (r = 0.44, p = 0.0004), and diffusing capacity of the lungs for carbon monoxide (r = -0.45, p = 0.0003). On CT scans, the subgroup with moderate/severe disease had a significantly higher SIII than the normal/minimal/mild subgroup (662 (267-970) vs. 152 (88-283)% predicted, p = 0.0004). In the final multiple regression model, FVC, extent of moderate/severe involvement and age were associated with SIII, explaining 59% of its variability. CONCLUSIONS: In patients with RA, FVC, extent of lung involvement and age, all of which are easily obtained variables in clinical practice, identify poorly distributed ventilation. In addition, the presence of respiratory symptoms and deteriorated physical function are closely related to the distribution of ventilation in these patients.
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Artritis Reumatoide , Pulmón , Humanos , Estudios Transversales , Pulmón/diagnóstico por imagen , Capacidad Vital , Artritis Reumatoide/diagnóstico por imagen , Mediciones del Volumen PulmonarRESUMEN
In this work, blends based on poly (lactic acid) (PLA)/acrylonitrile-butadiene-styrene (ABS) compatibilized with maleic anhydride-grafted (SEBS-g-MA) were prepared in a co-rotational twin-screw extruder by varying the concentrations of the compatibilizing agent. The influence of the compatibilizing agent on the morphology, mechanical, thermal, thermomechanical, and rheological properties of the prepared materials was analyzed. The effect of annealing on the properties of the blends was also investigated using injection-molded samples. The X-ray diffraction (XRD) results proved that the increments in crystallinity were an effect of annealing in the PLA/ABS/SEBS-g-MA blends, resonating at higher heat deflection temperatures (HDTs). The impact strength of the PLA/ABS blends compatibilized with 10 wt% SEBS-g-MA was significantly increased when compared to the PLA/ABS blends. However, the hardness and elastic modulus of the blends decreased when compared to neat PLA. The refined morphology shown in the scanning electron microscopy (SEM) analyses corroborated the improved impact strength promoted by SEBS-g-MA. The torque rheometer degradation study also supported the increased compatibility between SEBS-g-MA, PLA, and ABS. The TGA results show that the PLA/ABS and PLA/ABS/SEBS-g-MA blends are more thermally stable than the neat PLA polymer at higher temperatures. The results showed that the ideal composition is the heat-treated PLA/ABS/SEBS-g-MA (60/30/10 wt%), given the high impact strength and HDT results. The results of this work in terms of mechanical improvement with the use of compatibilizers and annealing suggest that the PLA/ABS/SEBS-g-MA system can be used in the production of 3D-printing filaments.
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The nasal route has been investigated as a promising alternative for drug delivery to the central nervous system, avoiding passage through the blood-brain barrier and improving bioavailability. In this sense, it is necessary to develop and test the effectiveness of new formulations proposed for the management of neurological disorders. Thereby, the aim of this work was to develop and characterize an ion sensitive in situ hydrogel containing diazepam-loaded nanostructured lipid carriers (DZP-NLC) for nasal delivery in the treatment of epilepsy. Physical characterization of the developed formulations was performed and included the evaluation of rheological features, particle size, polydispersity index (PDI) and zeta potential (ZP) of an in situ hydrogel containing DZP-NLC. Afterwards, in vitro drug release, in vitro mucoadhesion and biocompatibility studies with RPMI 2650 nasal cells were performed. The in situ hydrogel containing DZP-NLC was aerosolized with a nasal spray device specifically designed for nose-to-brain delivery (VP7 multidose spray pump with a 232 N2B actuator) and characterized for droplet size distribution and spray cone angle. Finally, the deposition pattern of this hydrogel was evaluated in a 3D-printed human nasal cavity model. The developed in situ hydrogel containing DZP-NLC presented adequate characteristics for nasal administration, including good gelling ability, mucoadhesiveness and prolonged drug release. In addition, after inclusion in the hydrogel net, the particle size (81.79 ± 0.53 nm), PDI (0.21 ± 0.10) and ZP (-30.90 ± 0.10 mV), of the DZP-NLC remained appropriate for nose-to-brain delivery. Upon aerosolization in a nasal spray device, a suitable spray cone angle (22.5 ± 0.2°) and adequate droplet size distribution (Dv (90) of 317.77 ± 44.12 µm) were observed. Biocompatibility studies have shown that the developed formulation is safe towards RPMI 2650 cells in concentrations up to 100 µg/mL. Deposition studies on a 3D-printed human nasal cavity model revealed that the best nasal deposition profile was obtained upon formulation administration without airflow and at an angle from horizontal plane of 75°, resulting in 47% of administered dose deposited in the olfactory region and 89% recovery. The results of this study suggested that the intranasal administration of the developed in situ hydrogel containing DZP-NLC could be a promising alternative to the conventional treatments for epilepsy.
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Hidrogeles , Cavidad Nasal , Humanos , Rociadores Nasales , Encéfalo , Diazepam , Impresión Tridimensional , LípidosRESUMEN
INTRODUCTION: Dysgeusia may occur during conventional or target-therapies and affect patients adherence-to-treatment. Therefore, it should be monitored to improve clinical outcome. To date, available questionnaires on dysgeusia relate to traditional antineoplastics and do not apply to target-therapies as the pathogenetic mechanism and clinical expression differ. OBJECTIVES: To develop a patient-reported outcome measure (PROM) to screen for and monitor the occurrence and severity of dysgeusia in patients under Smoothened (SMO) inhibitors: the SMO-iD questionnaire. METHODS: Patients with locally advanced basal cell carcinomas referring dysgeusia under SMO inhibitors at the University Hospital of Naples Federico II, were enrolled between January-December 2020. The PROM was elaborated based on chemotherapy-induced dysgeusia (CiTas) scale (development phase) and then validated by measuring internal consistency and reliability (validation phase). RESULTS: Thirty-nine patients were enrolled and interviewed every 8 weeks. In the first phase, 160 CiTas questionnaires were collected, and the SMO-iD questionnaire was developed. In the second phase, 195 SMO-iD questionnaires were recorded, and reliability and validity assessed. Cronbach alpha was 0.89. CONCLUSIONS: The SMO-iD questionnaire is a validated questionnaire that shows high face and content validity as well as high internal consistency and reliability. Hence, it may be introduced in daily clinical setting to monitor dysgeusia in patients under SMO-inhibitors.
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OBJECTIVE: The purpose of this study was to establish the psychometric properties of the 9-Item Vestibular Activities Avoidance Instrument (VAAI-9), a patient-reported outcome measure developed to identify fear avoidance beliefs in persons with vestibular disorders. METHODS: This prospective cohort study included 100 participants 18 years and older seeking care at a balance disorders clinic for dizziness. Participants completed the VAAI-9, the Dizziness Handicap Inventory (DHI), and other patient-reported outcomes at the initial visit and the 3-month follow-up. To measure test-retest reliability, the VAAI-9 was completed again 5 days after the initial visit and was analyzed using a 2-way mixed ICC for absolute agreement. Internal consistency was determined using the Cronbach alpha. The Spearman correlation coefficient was used to assess convergent validity of the VAAI-9 with other outcomes. Receiver operating characteristic curves were used to identify baseline VAAI-9 cutoff scores for those who reported mild (DHI ≤ 30) or moderate or severe (DHI > 30) perceived disability at the 3-month follow-up. RESULTS: The mean age of the study cohort was 49 (SD = 16) years; 73 (73%) were women. Seventy-one participants completed the 5-day follow-up, and 68 completed the 3-month follow-up. The VAAI-9 demonstrated excellent internal consistency (α = 0.91) and test-retest reliability (ICC = 0.90). Baseline VAAI-9 scores had moderate to strong associations with other outcome measures at baseline and 3 months. A baseline VAAI-9 score of 26 or higher had a sensitivity of 80.6% and a specificity of 78.4% for identifying a DHI score of >30 at 3 months (area under the curve = 0.86). CONCLUSIONS: The results provide evidence of excellent reliability and validity for the 9-item VAAI in persons with vestibular disorders. A baseline VAAI-9 score of ≥26 identified individuals at risk of persistent moderate to severe disability due to dizziness. IMPACT: Initial levels of fear avoidance beliefs measured using the VAAI-9 provided important prognostic information about outcomes for persons with vestibular symptoms.
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Mareo , Enfermedades Vestibulares , Humanos , Femenino , Persona de Mediana Edad , Masculino , Mareo/diagnóstico , Psicometría , Reproducibilidad de los Resultados , Estudios Prospectivos , Evaluación de la Discapacidad , Vértigo/diagnóstico , Enfermedades Vestibulares/diagnóstico , Encuestas y CuestionariosRESUMEN
Hematopoietic stem cell transplant (HSCT) is an important treatment option for hematologic malignancies. Acute kidney injury (AKI) is a common complication in HSCTs and is related to worse outcomes. We aimed to create a predictive risk score for AKI in HSCT considering variables available at the time of the transplant. We performed a retrospective cohort study. AKI was defined by the KDIGO classification using creatinine and urinary output criteria. We used survival analysis with competing events. Continuous variables were dichotomized according to the Liu index. A multivariable analysis was performed with a backward stepwise regression. Harrel's C-Statistic was used to evaluate the performance of the model. Points were attributed considering the nearest integer of two times each covariate's hazard ratio. The Liu index was used to establish the optimal cut-off. We included 422 patients undergoing autologous (61.1%) or allogeneic (38.9%) HSCTs for multiple myeloma (33.9%), lymphoma (27.3%), and leukemia (38.8%). AKI cumulative incidence was 59.1%. Variables eligible for the final score were: hematopoietic cell transplant comorbidity index ≥2 (HR: 1.47, 95% CI: 1.08-2.006; p = 0.013), chronic kidney disease (HR: 2.10, 95% CI: 1.31-3.36; p = 0.002), lymphoma or leukemia (HR: 1.69, 95% CI: 1.26-2.25; p < 0.001) and platelet-to-lymphocyte ratio > 171.9 (HR: 1.43, 95% CI: 1.10-1.86; p = 0.008). This is the first predictive risk score for AKI in patients undergoing HSCTs and the first study where the platelet-to-lymphocyte ratio is independently associated with AKI.
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Nitric oxide (NO) is an important product of eosinophilic metabolism, and its increase is associated with bronchial remodeling and airway hyperresponsiveness. Fractional exhaled NO (FENO) in the expired air of patients with suspected or diagnosed asthma has been used as a marker for eosinophilic inflammation. This cohort study included asthmatic patients classified under steps 3, 4, or 5 of the global strategy for asthma management and prevention. In the morning of the same day, all patients underwent blood collection for eosinophil counts, followed by FENO measurement and spirometry. We considered 2 groups based on the bronchodilation (BD) response on spirometry (>10% of FVC or FEV1): positive (BD+) and negative (BD-). Differences between the 2 groups were analyzed for demographic features, FENO values, and predictive correlations between FENO and BD. Both groups of patients showed an increase in the eosinophil count (BD+, P = .03; BD-, P = .04) and FENO values (P = .015 for both) with an increase in the asthma severity from step 3 to step 5 of the global strategy for asthma management and prevention. The correlations of FENO and eosinophils as well as FENO values and BD + were 0.127 (95% confidence interval,-0.269 to -0.486) and 0.696 (95% confidence interval, 0.246-0.899; P = .007), respectively. Measuring FENO levels may be useful for identifying patients with BD+.
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Asma , Broncodilatadores , Humanos , Broncodilatadores/farmacología , Broncodilatadores/uso terapéutico , Prueba de Óxido Nítrico Exhalado Fraccionado , Estudios de Cohortes , Pruebas Respiratorias , Asma/diagnóstico , Asma/tratamiento farmacológico , Asma/metabolismo , Óxido Nítrico/metabolismo , EspiraciónRESUMEN
De novo variants (DNVs) analysis has proven to be a powerful approach to gene discovery in Autism Spectrum Disorder (ASD), which has not yet been shown in a Brazilian ASD cohort. The relevance of inherited rare variants has also been suggested, particularly in oligogenic models. We hypothesized that three-generation analyses of DNVs could provide new insights into the relevance of de novo and inherited variants across generations. To accomplish this goal, we performed whole-exome sequencing of 33 septet families composed of probands, parents, and grandparents (n = 231 individuals) and compared DNV rates (DNVr) between generations and those from two control cohorts. The DNVr in the probands (DNVr = 1.16) was marginally higher than in parents (DNVr = 0.60; p = 0.054), and in controls (DNVr = 0.68; p = 0.035, congenital heart disorder and DNVr = 0.70; p = 0.047, unaffected ASD siblings from Simons Simplex Collection). Moreover, most of the DNVs were found to have paternal origin in both generations (84.6%). Finally, we observed that 40% (6/15) of the DNVs in parents transmitted for probands are in ASD or ASD candidate genes, representing recently emerged risk variants to ASD in their families and suggest ZNF536, MSL2 and HDAC9 as ASD candidate genes. We did not observe an enrichment of risk variants nor sex bias of transmitted variants in the three generations, that can be due to sample size. These results further reinforce the relevance of de novo variants in ASD.