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PURPOSE: Axicabtagene ciloleucel (axi-cel) is an autologous CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for the treatment of relapsed or refractory large B-cell lymphoma. Little is known about the long-term survivorship after CAR T-cell therapy. METHODS: We previously reported the results of 298 patients who were leukapheresed with the intent to receive standard-of-care axi-cel (n = 275 infused) after two or more previous lines of therapy at a median follow-up of 12.9 months. Here, we report extended follow-up of this cohort to a median of 58 months, with a focus on late survivorship events. RESULTS: Among axi-cel-infused patients, progression-free survival at 5 years was 29% and overall survival (OS) at 5 years was 40%. The 5-year lymphoma-specific survival was 53% with infrequent late relapses. However, the 5-year nonrelapse mortality (NRM) was 16.2%, with over half of NRM events occurring beyond 2 years. Patients who were 60 years and older had a lower risk of relapse (P = .02), but a higher risk of NRM compared with patients younger than 60 years (NRM odds ratio, 4.5 [95% CI, 2.1 to 10.8]; P < .001). Late NRM was mainly due to infections and subsequent malignant neoplasms (SMNs). In total, SMNs occurred in 24 patients (9%), including therapy-related myeloid neoplasms (n = 15), solid tumors (n = 7), and unrelated lymphoid malignancies (n = 2). CONCLUSION: In the standard-of-care setting, axi-cel exhibits outcomes consistent with those reported in clinical trials, with sustained, durable responses observed at the 5-year time point. However, late infections and the development of SMN are key survivorship issues that reduce long-term survival after CAR T-cell therapy, particularly in the elderly.
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The Argus II retinal prosthesis restores visual perception to late blind patients. It has been shown that structural changes occur in the brain due to late-onset blindness, including cortical thinning in visual regions of the brain. Following vision restoration, it is not yet known whether these visual regions are reinvigorated and regain a normal cortical thickness or retain the diminished thickness from blindness. We evaluated the cortical thicknesses of ten Argus II Retinal Prostheses patients, ten blind patients, and thirteen sighted participants. The Argus II patients on average had a thicker left Cuneus Cortex and Lateral Occipital Cortex relative to the blind patients. The duration of the Argus II use (time since implant in active users) significantly partially correlated with thicker visual cortical regions in the left hemisphere. Furthermore, in the two case studies (scanned before and after implantation), the patient with longer device use (44.5 months) had an increase in the cortical thickness of visual regions, whereas the shorter-using patient did not (6.5 months). Finally, a third case, scanned at three time points post-implantation, showed an increase in cortical thickness in the Lateral Occipital Cortex between 43.5 and 57 months, which was maintained even after 3 years of disuse (106 months). Overall, the Argus II patients' cortical thickness was on average significantly rejuvenated in two higher visual regions and, patients using the implant for a longer duration had thicker visual regions. This research raises the possibility of structural plasticity reversing visual cortical atrophy in late-blind patients with prolonged vision restoration.
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Residual significant mitral regurgitation (MR) can increase the risk of adverse events after transcatheter aortic valve replacement (TAVR). The clinical benefits of staged transcatheter edge-to-edge repair (TEER) after TAVR remain underexplored. This study aimed to investigate the clinical outcomes of staged TEER for residual significant MR after TAVR. This observational study included 314 consecutive patients with chronic residual grade 3+ or 4+ MR at the 30-day follow-up after TAVR, with 104 patients (33.1%) treated with staged TEER (TEER group) and 210 (66.9%) with medical therapy alone. The primary composite outcomes were all-cause mortality and heart failure hospitalization at 2 years. Additional analysis, including changes in MR grade and the New York Association functional classification, and subgroup outcome comparisons based on MR etiology were also conducted. In our study, the rate of primary composite outcome was lower in the TEER group than in the medical therapy alone group (33.7% vs 48.1%, p = 0.015). Significant improvement in MR grade and New York Association class was observed in the TEER group after 2 years. The subgroup analysis demonstrated that in patients with degenerative MR, a lower incidence of composite outcome and heart failure hospitalization was observed in the TEER group (hazard ratio 0.35, 95% confidence interval 0.23 to 0.53, p <0.001). In conclusion, staged TEER after TAVR was associated with reduced MR and improved clinical outcomes. The clinical significance of MR after TAVR should be carefully evaluated, and TEER should be considered for patients with significant residual MR, particularly, those with degenerative MR.
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Estenosis de la Válvula Aórtica , Insuficiencia de la Válvula Mitral , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Masculino , Femenino , Insuficiencia de la Válvula Mitral/cirugía , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/cirugía , Resultado del Tratamiento , Anciano , Estudios de Seguimiento , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Válvula Mitral/cirugía , Válvula Mitral/diagnóstico por imagen , Insuficiencia Cardíaca , Factores de TiempoRESUMEN
BACKGROUND: Neck pain remains the fourth leading cause of disability and work loss, and a multimodal treatment approach is effective in reducing neck pain and disability. PURPOSE: The purpose of this study is to examine the use of cervical traction for managing neck pain by Physiotherapists in India, including how and when the traction is used, the modes and parameters of traction, any additional interventions given with traction, and the influence of professional demographic characteristics in decision making in traction usage. STUDY DESIGN: A cross-sectional survey. METHODOLOGY: A random sample of approximately 2500 musculoskeletal physiotherapists was surveyed, and the data was presented in a descriptive form. Chi-square analyses were used to identify the association between responders' qualifications and traction usage. RESULTS: From the total physiotherapist approached 18.52% (n = 463) responses were obtained, and 62% (n = 287) respondents reported that they would use traction in their clinical practice. Out of 92.3% of responders indicated using traction for radiculopathy, 78.7% of respondents used traction for patients with neck pain without radiculopathy. It is used as a combination therapy by 58.8% for radiculopathy and 52.2% for stiffness. There was no association between the responder's qualification and traction usage (χ2 = 0.707, p = 0.40). Traction is used in combination with other physiotherapeutic techniques. CONCLUSION: Traction use was consistent with the proposed criteria identifying patients likely to benefit. However, disregarding current guidelines, physiotherapists also use traction for non-radicular neck pain. Various traction delivery modes and parameters were used within a comprehensive plan of care incorporating multiple interventions.
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Dolor de Cuello , Fisioterapeutas , Tracción , Humanos , Dolor de Cuello/terapia , Tracción/métodos , Estudios Transversales , India , Fisioterapeutas/estadística & datos numéricos , Femenino , Masculino , Adulto , Modalidades de Fisioterapia/estadística & datos numéricos , Persona de Mediana Edad , Radiculopatía/terapiaRESUMEN
INTRODUCTION: Disturbances in potassium levels can induce ventricular arrhythmias and heighten mortality in patients with ST-elevation myocardial infarction (STEMI). This study evaluates the influence of sK levels on seven-day mortality and incidence of ventricular arrhythmias in STEMI patients to further improve clinical guidelines and outcomes. METHODS: This retrospective, propensity-matched study analyzed approximately 250,000 acute STEMI patients from 55 major academic medical centers/healthcare organizations (HCOs) in the US Collaborative Network of the TriNetX database. The sK levels recorded on the day of STEMI diagnosis were categorized into four cohorts: sK ≤ 3.4 (hypokalemia), 3.5 ≤ sK ≤ 4.5 (normal-control), 4.6 ≤ sK ≤ 5.0 (high-normal), and sK ≥ 5.1 (hyperkalemia). Patient cohorts were propensity-matched using linear and logistic regression for demographics. Outcomes of seven-day mortality, ventricular tachycardia (VT), and ventricular fibrillation (VF) were compared between these cohorts and the control group. RESULTS: The analysis showed hypokalemia was linked to significantly higher seven-day mortality (7.2% vs. 4.3%; RR 1.69; p<0.001), and increased rates of VT and VF. Similarly, hyperkalemia was associated with elevated mortality (12.7% vs. 4.6%; RR 2.76; p<0.001), VT, and VF rates. High-normal sK levels showed increased mortality (7.4% vs. 4.7%; RR 1.58; p<0.001), but unchanged VT or VF rates compared to the normal sK group. CONCLUSION: This comprehensive study highlights the correlation of sK levels with death in STEMI patients, revealing a nearly doubled risk of mortality with hypokalemia and almost triples with hyperkalemia. More notably, the mortality for STEMIs is higher for high-normal vs normal sK values. Additionally, hypokalemia and hyperkalemia were found to significantly elevate VT and VF risks.
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INTRODUCTION: The study aims to examine the disparities in mortality rates attributed to brain cancer between urban and rural areas over a 22-year period, totaling 315,538 deaths. This investigation serves as a crucial step in identifying areas within healthcare that require improvement. By pinpointing the variations in mortality rates between urban and rural settings, healthcare authorities can strategically implement necessary interventions. METHODOLOGY: A retrospective study was conducted by analyzing the death certificate available on the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database from 1999 to 2020 to evaluate the mortality rate trends of brain cancer ( International Classification of Diseases (ICD)-10 C71.0-71.9).The data was grouped based on rural and urban death rates according to the 2013 urbanization classification and the variables that were used were age, gender and race. Data was analyzed using Microsoft Excel and R Studio 4.3.1. Significant associations between demographic variables and mortality rates were identified via Binomial tests. RESULTS: From 1999 to 2020, urban areas recorded 259,402 deaths attributed to brain cancer, compared to 56,136 deaths in rural areas, indicating a higher mortality rate in urban settings. The mortality rate in both rural and urban areas exhibited an upward trend, except for a slight drop in 2010. The mortality rates were significantly higher in rural areas compared to urban areas for age groups 55-64 years and 65-74 years, males and caucasians. CONCLUSIONS: Our research underscores the differences in death rates from brain cancer between urban and rural areas, specifically among individuals aged 55-64 and 65-74, males and those of caucasian ethnicity. Future research must adopt a multifaceted approach, integrating more recent datasets and embracing a finer granularity of individual-level information. Moreover, there is a pressing need to explore the interplay of various factors such as access to healthcare, treatment modalities, genetic predispositions, and socioeconomic determinants on mortality outcomes.
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BACKGROUND: Over the years, strides in colon cancer detection and treatment have boosted survival rates; yet, post-colon cancer survival entails cardiovascular disease (CVD) risks. Research on CVD risks and acute cardiovascular events in colorectal cancer survivors has been limited. AIM: To compare the CVD risk and adverse cardiovascular outcomes in current colon cancer survivors compared to a decade ago. METHODS: We analyzed 2007 and 2017 hospitalization data from the National Inpatient Sample, studying two colon cancer survivor groups for CVD risk factors, mortality rates, and major adverse events like pulmonary embolism, arrhythmia, cardiac arrest, and stroke, adjusting for confounders via multivariable regression analysis. RESULTS: Of total colon cancer survivors hospitalized in 2007 (n = 177542) and 2017 (n = 178325), the 2017 cohort often consisted of younger (76 vs 77 years), male, African-American, and Hispanic patients admitted non-electively vs the 2007 cohort. Furthermore, the 2017 cohort had higher rates of smoking, alcohol abuse, drug abuse, coagulopathy, liver disease, weight loss, and renal failure. Patients in the 2017 cohort also had higher rates of cardiovascular comorbidities, including hypertension, hyperlipidemia, diabetes, obesity, peripheral vascular disease, congestive heart failure, and at least one traditional CVD (P < 0.001) vs the 2007 cohort. On adjusted multivariable analysis, the 2017 cohort had a significantly higher risk of pulmonary embolism (PE) (OR: 1.47, 95%CI: 1.37-1.48), arrhythmia (OR: 1.41, 95%CI: 1.38-1.43), atrial fibrillation/flutter (OR: 1.61, 95%CI: 1.58-1.64), cardiac arrest including ventricular tachyarrhythmia (OR: 1.63, 95%CI: 1.46-1.82), and stroke (OR: 1.28, 95%CI: 1.22-1.34) with comparable all-cause mortality and fewer routine discharges (48.4% vs 55.0%) (P < 0.001) vs the 2007 cohort. CONCLUSION: Colon cancer survivors hospitalized 10 years apart in the United States showed an increased CVD risk with an increased risk of acute cardiovascular events (stroke 28%, PE 47%, arrhythmia 41%, and cardiac arrest 63%). It is vital to regularly screen colon cancer survivors with concomitant CVD risk factors to curtail long-term cardiovascular complications.
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Anticoagulantes , Apéndice Atrial , Fibrilación Atrial , Humanos , Fibrilación Atrial/cirugía , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Apéndice Atrial/cirugía , Apéndice Atrial/diagnóstico por imagen , Anticoagulantes/uso terapéutico , Masculino , Femenino , Anciano , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & controlRESUMEN
BACKGROUND AND AIMS: This trial sought to assess the safety and efficacy of ShortCut, the first dedicated leaflet modification device, prior to transcatheter aortic valve implantation (TAVI) in patients at risk for coronary artery obstruction. METHODS: This pivotal prospective study enrolled patients with failed bioprosthetic aortic valves scheduled to undergo TAVI and were at risk for coronary artery obstruction. The primary safety endpoint was procedure-related mortality or stroke at discharge or 7 days, and the primary efficacy endpoint was per-patient leaflet splitting success. Independent angiographic, echocardiographic, and computed tomography core laboratories assessed all images. Safety events were adjudicated by a clinical events committee and data safety monitoring board. RESULTS: Sixty eligible patients were treated (77.0 ± 9.6 years, 70% female, 96.7% failed surgical bioprosthetic valves, 63.3% single splitting and 36.7% dual splitting) at 22 clinical sites. Successful leaflet splitting was achieved in all (100%; 95% confidence interval [CI] 94-100.0%, p<0.001) patients. Procedure time, including imaging confirmation of leaflet splitting, was 30.6 ± 17.9 min. Freedom from the primary safety endpoint was achieved in 59 (98.3%; 95% CI [91.1-100%]) patients, with no mortality and one (1.7%) disabling stroke. At 30 days, freedom from coronary obstruction was 95% (95% CI 86.1-99.0%). Within 90 days, freedom from mortality was 95% (95% CI 86.1-99.0%]), without any cardiovascular deaths. CONCLUSIONS: Modification of failed bioprosthetic aortic valve leaflets using ShortCut was safe, achieved successful leaflet splitting in all patients, and was associated with favorable clinical outcomes in patients at risk for coronary obstruction undergoing TAVI.
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Introduction: Paravalvular leak (PVL) is a severe complication of transcatheter aortic valve replacement (TAVR) that can lead to poor outcomes. TAVR-in-TAVR is a promising treatment for PVL; however, reports on its safety or efficacy are limited. In this study, we aimed to investigate the clinical outcomes of TAVR-in-TAVR using balloon-expandable prostheses for PVLs after TAVR. Methods: We retrospectively analyzed data from patients who underwent TAVR-in-TAVR using balloon-expandable Sapien prostheses for PVL after an initial TAVR at our institution. The procedural success, in-hospital complications, all-cause mortality, and echocardiographic data for up to 2 years post-surgery were evaluated. Results: In total, 31 patients with a mean age of 81.1 ± 7.9 years and mean Society of Thoracic Surgeons score of 8.8 ± 5.4% were identified. The procedural success rate of TAVR-in-TAVR was 96.8% (30/31). No in-hospital deaths, cardiac tamponade, or conversion to sternotomy occurred. Re-intervention was performed in only one patient (3.2%) during hospitalization. The all-cause mortality rates at 30 days and 2 years were 0% and 16.1%, respectively. A significant reduction in the PVL rate was observed at 30 days compared with that at baseline (p < 0.01). Discussion: Our findings suggest that TAVR-in-TAVR using balloon-expandable prostheses is safe and effective for PVL after TAVR with low complication rates and acceptable long-term outcomes. Further studies with larger sample sizes are needed to confirm our findings.
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AIMS: Left ventricular global longitudinal strain (LVGLS) is a known outcome predictor in transcatheter edge-to-edge repair (TEER) for functional mitral regurgitation (MR). We aimed to assess its prognostic yield in the setting of TEER for chronic primary MR. METHODS AND RESULTS: We conducted a single-centre, retrospective analysis of 323 consecutive patients undergoing isolated, first-time procedures. Stratified by baseline LVGLS quartiles (≤-19%, -18.9% to -16%, -15.9% to -12%, >-12%), the cohort was evaluated for the primary composite outcome of all-cause mortality or heart failure hospitalizations, as well as secondary endpoints consisting of mitral reinterventions and the persistence of significant residual MR and/or functional disability-all along the first year after intervention. Subjects with worse (i.e. less negative) LVGLS exhibited higher comorbidity, more advanced HF, and elevated procedural risk. Post-TEER, those belonging to the worst LVGLS quartile group sustained increased mortality (16.9% vs. 6.3%, Log-Rank P = 0.005, HR 1.75, 95% CI 1.08-4.74, P = 0.041) and, when affected by LV dysfunction/dilatation, more primary outcome events (21.1% vs. 11.5%, Log-Rank P = 0.037, HR 1.68, 95% CI 1.02-5.46, P = 0.047). No association was demonstrated between baseline LVGLS and other endpoints. Upon exploratory analysis, 1-month post-procedural LVGLS directly correlated with and was worse than its baseline counterpart by 1.6%, and a more impaired 1-month value-but not the presence/extent of deterioration-conferred heightened risk for the primary outcome. CONCLUSION: TEER for chronic primary MR is feasible, safe, and efficacious irrespective of baseline LVGLS. Yet, worse baseline LVGLS forecasts a less favourable post-procedural course, presumably reflecting a higher-risk patient profile.
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Cateterismo Cardíaco , Insuficiencia de la Válvula Mitral , Humanos , Insuficiencia de la Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Masculino , Femenino , Estudios Retrospectivos , Anciano , Pronóstico , Cateterismo Cardíaco/métodos , Enfermedad Crónica , Estudios de Cohortes , Resultado del Tratamiento , Medición de Riesgo , Persona de Mediana Edad , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatología , Anciano de 80 o más Años , Ecocardiografía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Índice de Severidad de la Enfermedad , Tensión Longitudinal GlobalRESUMEN
PURPOSE: Given the paucity of data on pediatric spontaneous pneumomediastinum (SPM), management is largely informed by extrapolation from adult studies or personal clinical experience, resulting in significant heterogeneity. The purpose of this study was to describe how pediatric patients with SPM are clinically managed at our institution and propose a treatment algorithm. METHODS: Retrospective chart review of pediatric patients with SPM from April 2002 to December 2021 at a single Canadian tertiary care center. Data on medical history, presentation characteristics, clinical management, and complications were gathered. Descriptive and inferential statistics were used to analyze data. RESULTS: We identified 63 patients for inclusion, median age was 15 years. Twenty-nine patients were transferred from another facility. Most common presenting symptoms were chest pain (72.3%), shortness of breath (44.6%), and subcutaneous emphysema (21.5%). Initial workup included chest x-ray (93.6%), CT scan (20.6%), and upper GI series (7.9%). There was no difference in the number of initial tests between admitted and discharged patients (p = 0.10). Of admitted patients (n = 35), 31.4% had primary SPM (no underlying comorbidity/inciting event) and 68.8% were secondary SPM (underlying comorbidity/inciting event). No patients with primary SPM developed complications or recurrences. In contrast, 16.7% of those with secondary SPM developed complications and 54.2% had at least one additional intervention after admission. DISCUSSION: There is significant variability in diagnostic investigation and treatment of pediatric SPM at our center. Amongst primary SPM, additional tests did not change complication rate or recurrence, including those transferred from another facility. An expeditious treatment algorithm is warranted. TYPE OF STUDY: Retrospective Cohort Study. LEVEL OF EVIDENCE: III.
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Enfisema Mediastínico , Adulto , Humanos , Niño , Adolescente , Estudios Retrospectivos , Enfisema Mediastínico/diagnóstico por imagen , Enfisema Mediastínico/etiología , Enfisema Mediastínico/terapia , Canadá , Tomografía Computarizada por Rayos X/métodos , RadiografíaRESUMEN
BACKGROUND: There are scarce data regarding mitral transcatheter edge-to-edge repair (TEER) in individuals aged 90 years and above. We aimed to evaluate patient characteristics, procedural aspects, and outcomes in this rapidly growing group. METHODS: We retrospectively studied a single-centre database of 967 isolated, first-time interventions, 103 (10.7%) of which were performed in nonagenarians. Outcomes included all-cause mortality, heart failure (HF) hospitalizations, and the persistence of significant mitral regurgitation (MR) or New York Heart Association functional class III/IV during the first postprocedural year. Analyses were repeated on a 204-patient, propensity score-matched subcohort, controlling for MitraScore elements, sex, race, MR etiology, functional status, atrial fibrillation/flutter, and procedural urgency. RESULTS: Compared with subjects below 90 years of age, nonagenarians were more likely to be white women of higher socioeconomic status; had a higher interventional risk, driven mainly by age and chronic kidney disease; presented more often with primary MR (71.8 vs 39.1%, P < 0.001); and exhibited less advanced biochemical/echocardiographic indices of cardiac remodelling. Further, their procedures were more commonly nonurgent and used fewer devices. A similarly high (> 97%) technical success rate was achieved in the 2 study groups. Likewise, no intergroup differences were observed in the rates or cumulative incidences of any of the explored endpoints, and neither of the outcomes' risks was associated with age 90 and above. Comparable outcomes were also noted in the propensity score-matched subgroups. CONCLUSIONS: In our experience, mitral TEER was equally feasible, safe, and efficacious in patients below and above 90 years of age.
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BACKGROUND: Limited data exist regarding the impact of mitral annular calcification (MAC) on outcomes of transcatheter edge-to-edge repair for mitral regurgitation (MR). METHODS: We retrospectively analyzed 968 individuals (median age, 79 [interquartile range, 70-86] years; 60.0% males; 51.8% with functional MR) who underwent an isolated, first-time intervention. Stratified by MAC extent per baseline transthoracic echocardiogram, the cohort was assessed for residual MR, functional status, all-cause mortality, heart failure hospitalizations, and mitral reinterventions post-procedure. RESULTS: Patients with above-mild MAC (n=101; 10.4%) were older and more likely to be female, exhibited a greater burden of comorbidities, and presented more often with severe, primary MR. Procedural aspects and technical success rate were unaffected by MAC magnitude, as was the significant improvement from baseline in MR severity and functional status along the first postprocedural year. However, the persistence of above-moderate MR or functional classes III and IV at 1 year and the cumulative incidence of reinterventions at 2 years were overall more pronounced within the above-mild MAC group (significant MR or functional impairment, 44.7% versus 29.9%, P=0.060; reinterventions, 11.9% versus 6.2%, P=0.033; log-rank P=0.035). No link was demonstrated between MAC degree and the cumulative incidence or risk of mortality and mortality or heart failure hospitalizations. Differences in outcomes frequencies were mostly confined to the primary MR subgroup, in which patients with above-mild MAC also experienced earlier, more frequent 2-year heart failure hospitalizations (20.8% versus 9.6%; P=0.016; log-rank P=0.020). CONCLUSIONS: Mitral transcatheter edge-to-edge repair in patients with and without above-mild MAC is equally feasible and safe; however, its postprocedural course is less favorable among those with primary MR.
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Calcinosis , Insuficiencia Cardíaca , Enfermedades de las Válvulas Cardíacas , Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Masculino , Humanos , Femenino , Anciano , Estudios Retrospectivos , Resultado del Tratamiento , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/cirugía , Calcinosis/diagnóstico por imagen , Calcinosis/cirugía , Cateterismo CardíacoRESUMEN
Purpose: The purpose of this study was to compare the efficacy, and ocular pharmacokinetics of a new 0.04% w/v bis in die means twice a day (BID) ophthalmic solution and marketed 0.05% w/v quater in die means four times a day (QID) ophthalmic emulsion of difluprednate in New Zealand white (NZW) rabbits. Methods: The preclinical proof of concept was established in paracentesis-induced acute inflammation, endotoxin-induced acute uveitis, and bovine serum albumin-induced chronic uveitis in NZW rabbit animal models. A comparison of clinical score, total cell count, and total protein was performed to determine efficacy. An ocular pharmacokinetic study was conducted to study the influence of the vehicle on the ocular absorption of the drug. Results: In both uveitis models, the new solution formulation and marketed emulsion formulation inhibited total clinical score, total cell count, PGE2, and total protein significantly more than the placebo and lipopolysaccharide (disease control) groups and were comparable. In an ocular pharmacokinetic study, the Cmax and AUC0-t of difluoroprednisolone 17-butyrate in humor were â¼2-fold higher after 14 days' instillation of new solution formulation (0.04% w/v, BID) compared with 14 days' instillation of marketed emulsion (0.05% w/v, QID). Conclusions: The study demonstrated that the efficacy of the solution formulation at a lower dose and reduced dosing regimen were comparable to that of the emulsion formulation. The reduction in strength and regimen may result in improved patient adherence and outcomes.
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Fluprednisolona , Uveítis , Animales , Conejos , Emulsiones , Fluprednisolona/análogos & derivados , Soluciones Oftálmicas , Uveítis/inducido químicamente , Uveítis/tratamiento farmacológicoRESUMEN
Asynchronous learning continues to gain popularity in medical education. One medium to facilitate asynchronous learning is the podcast. Currently, there are a limited number of hematology/oncology (H/O) podcasts geared towards residents and fellows ("trainees"). To address this need, we created a series of podcasts covering fundamental H/O topics for H/O fellows and internal medicine residents rotating on H/O services. We evaluate the effectiveness of this approach in this pilot study. Between September 2022 and February 2023, residents received recommended episodes via email prior to their rotation. Following their rotation, they received a survey. H/O fellows were encouraged to listen to any available episodes during the study period, after which they also received a survey. The survey collected baseline user information and included a 5-point Likert scale to determine if the podcast episodes were effective educational tools. Summary description was performed by the authors. In total 7 internal medicine residents (27 eligible) and 13 H/O fellows (18 eligible) completed the survey, for a total group of 20 respondents. The trainees found that the podcast helped with inpatient and outpatient management, was clinically relevant, and helped with clinical decision-making. They also agreed that the fundamentals of H/O are amenable to the podcast platform and are likely to continue to use podcasts as learning tools in H/O. This pilot study suggests that podcasts are an effective supplemental learning tool for the fundamentals of H/O in graduate medical education. The use of podcasts as educational tools should be encouraged for trainees.
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Educación Médica , Hematología , Humanos , Proyectos Piloto , Educación de Postgrado en Medicina , Oncología Médica , Encuestas y CuestionariosRESUMEN
INTRODUCTION AND OBJECTIVES: Limited data exist on the prognostic usefulness of transthoracic echocardiography preceding MitraClip for chronic primary mitral regurgitation (MR). We evaluated the predictive ability of transthoracic echocardiography in this setting. METHODS: A total of 410 patients (median age, 83 years, 60.7% males) were included in the study. The primary outcome was the 1-year composite of all-cause mortality or heart failure hospitalization. Secondary endpoints encompassed individual elements of the primary outcome, the persistence of significant functional impairment or above-moderate MR at 1 year, and above-mild MR at 1-month. RESULTS: The only parameter associated with the risk of the primary outcome was a ventricular end systolic diameter index of ≥2.1 cm/m2, corresponding to the cohort's 4th quartile (HR, 2.44; 95%CI, 1.09-4.68; P=.022). Concurrently, higher left atrial volume index (LAVi) and a mid-diastolic medial-lateral mitral annular diameter (MAD) equal to or above the cohort's median of 32.2mm were linked to a higher probability of death and heart failure hospitalization, respectively. LAVi of ≥ 60mL/m2, above-mild mitral annular calcification, and above-moderate tricuspid regurgitation conferred higher odds of functional class III-IV or above-moderate MR persistence. All variables except LAVi and MAD, as well as indexed mid-diastolic medial-lateral MAD of ≥ 20.2mm/m2 and mitral effective regurgitant orifice area of ≥ 0.40 cm2, were associated with greater-than-mild MR at 1 month. CONCLUSIONS: Preprocedural increased indexed left heart dimensions, mainly left ventricular end-systolic diameter index, MAD, mitral annular calcification, mitral effective regurgitant orifice area, and tricuspid regurgitation mark a less favorable course post-MitraClip for chronic primary MR.
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Cateterismo Cardíaco , Ecocardiografía , Insuficiencia de la Válvula Mitral , Humanos , Insuficiencia de la Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/diagnóstico , Masculino , Femenino , Anciano de 80 o más Años , Ecocardiografía/métodos , Enfermedad Crónica , Cateterismo Cardíaco/métodos , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Anciano , Pronóstico , Estudios Retrospectivos , Estudios de Seguimiento , Resultado del Tratamiento , Valor Predictivo de las PruebasRESUMEN
Athletic injuries are commonly implicated in the development of early osteoarthritic (EOA) changes in the knee. These changes have a significant impact on athletic performance, and therefore the early detection of EOA is paramount. The objective of the study is to assess the impact of different interventions on individuals with EOA, particularly focusing on recreational athletes. The study aims to evaluate the effectiveness of three treatment groups in improving various aspects related to knee EOA, including pain, range of motion, strength, and function. A study was undertaken with 48 recreational athletes with EOA who were assigned to one of three groups by the referring orthopedic surgeon: collagen (Col), exercise (Ex), or collagen and exercise (ColEx) groups. All the participants received their respective group-based intervention for 12 weeks. Visual analog scale (VAS), knee flexion range of motion (ROM) knee flexors and extensors strength, and KOOS were assessed at baseline, and after 4 weeks, 8 weeks, and 12 weeks of intervention. VAS for activity improved in all treatment groups, with no difference between groups. The between-group analysis for knee ROM revealed a significant difference (p = 0.022) in the Col vs. Ex group at 12 weeks. The knee flexor and extensor strength and the KOOS scores improved considerably in the Ex and the ColEx group (p < 0.05) at 12 weeks. Exercise therapy improved pain, strength and function in subjects with EOA, whereas the association of collagen seems to have accentuated the effects of exercise in bringing about clinical improvements.
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Terapia por Ejercicio , Osteoartritis de la Rodilla , Humanos , Dolor , Articulación de la Rodilla , Atletas , Suplementos Dietéticos , Resultado del Tratamiento , Rango del Movimiento ArticularRESUMEN
BACKGROUND: Little is known about mitral transcatheter edge-to-edge repair (TEER) in patients with mitral annular disjunction (MAD). OBJECTIVES: The authors sought to explore TEER for degenerative mitral regurgitation (MR) according to MAD status. METHODS: We retrospectively analyzed 271 consecutive patients (median age 82 [Q1-Q3: 75-88] years, 60.9% men) undergoing an isolated, first-ever TEER for whom there were viewable preprocedural echocardiograms. Stratified by MAD status at baseline, the cohort was evaluated for all-cause mortality, heart failure hospitalizations, and mitral reinterventions-the composite of which constituted the primary outcome-as well as functional capacity and residual MR, all along the first postprocedural year. RESULTS: Individuals with (n = 62, 22.9%) vs without MAD had more extensive prolapse and larger valve dimensions. Although the former's procedures were longer, utilizing more devices per case, technical success rate and residual MR were comparable. MAD presence was associated with higher mortality risk (HR: 2.64; 95% CI: 1.82-5.52; P = 0.014), and increased MAD length-with lower odds of functional class ≤II (OR: 0.65; 95% CI: 0.47-0.88; P = 0.006). Among 47 MAD patients with retrievable 1-month data, MAD regressed in 91.5% and by an overall 50% (Q1-Q3: 22%-100%) compared with baseline (P < 0.001). A greater MAD shortening conferred attenuated risk for the primary outcome. CONCLUSIONS: In our experience, TEER for degenerative MR accompanied by MAD was feasible and safe; however, its postprocedural course was somewhat less favorable. MAD shortening following TEER was observed in most patients and proved prognostically beneficial.
Asunto(s)
Implantación de Prótesis de Válvulas Cardíacas , Insuficiencia de la Válvula Mitral , Masculino , Humanos , Anciano de 80 o más Años , Femenino , Insuficiencia de la Válvula Mitral/diagnóstico por imagen , Insuficiencia de la Válvula Mitral/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Catéteres , Implantación de Prótesis de Válvulas Cardíacas/efectos adversosRESUMEN
In the present study, a comprehensive parametric analysis was carried out using the electrical discharge machining of Ti6Al4V, using pulse-on time, current, and pulse-off time as input factors with output measures of surface roughness and material removal rate. The present study also used two different nanopowders, namely alumina and nano-graphene, to analyze their effect on output measures and surface defects. All the experimental runs were performed using Taguchi's array at three levels. Analysis of variance was employed to study the statistical significance. Empirical relations were generated through Minitab. The regression model term was observed to be significant for both the output responses, which suggested that the generated regressions were adequate. Among the input factors, pulse-off time and current were found to have a vital role in the change in material removal rate, while pulse-on time was observed as a vital input parameter. For surface quality, pulse-on time and pulse-off time were recognized to be influential parameters, while current was observed to be an insignificant factor. Teaching-learning-based optimization was used for the optimization of output responses. The influence of alumina and nano-graphene powder was investigated at optimal process parameters. The machining performance was significantly improved by using both powder-mixed electrical discharge machining as compared to the conventional method. Due to the higher conductivity of nano-graphene powder, it showed a larger improvement as compared to alumina powder. Lastly, scanning electron microscopy was operated to investigate the impact of alumina and graphene powder on surface morphology. The machined surface obtained for the conventional process depicted more surface defects than the powder-mixed process, which is key in aeronautical applications.