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1.
Cureus ; 16(5): e60636, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38903301

RESUMO

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.

2.
World J Clin Oncol ; 15(4): 548-553, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38689632

RESUMO

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.

3.
Front Cardiovasc Med ; 11: 1374078, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38566964

RESUMO

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.

4.
J Pediatr Surg ; 59(5): 930-934, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38519387

RESUMO

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.


Assuntos
Enfisema Mediastínico , Adulto , Humanos , Criança , Adolescente , Estudos Retrospectivos , Enfisema Mediastínico/diagnóstico por imagem , Enfisema Mediastínico/etiologia , Enfisema Mediastínico/terapia , Canadá , Tomografia Computadorizada por Raios X/métodos , Radiografia
5.
Circ Cardiovasc Interv ; 17(2): e013424, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38235546

RESUMO

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.


Assuntos
Calcinose , Insuficiência Cardíaca , Doenças das Valvas Cardíacas , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Masculino , Humanos , Feminino , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Cateterismo Cardíaco
6.
J Cancer Educ ; 39(2): 106-110, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37950134

RESUMO

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.


Assuntos
Educação Médica , Hematologia , Humanos , Projetos Piloto , Educação de Pós-Graduação em Medicina , Oncologia , Inquéritos e Questionários
7.
Micromachines (Basel) ; 14(12)2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38138417

RESUMO

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.

8.
Am J Cardiol ; 207: 380-389, 2023 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-37778227

RESUMO

Few studies have compared the clinical outcomes between valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) with new-generation valves and re-operative surgical aortic valve replacement (Redo-SAVR). We compared the clinical outcomes of patients who underwent ViV-TAVR with those of patients who underwent Redo-SAVR at Cedars-Sinai Medical Center between 2015 and 2021. New-generation valves were used for ViV-TAVR. A propensity score-matched (PSM) analysis was performed to adjust for differences in baseline characteristics. The primary end point was all-cause mortality at 30 days and 2 years. In-hospital procedural and clinical outcomes were also compared between the groups. A total of 256 patients (140 who underwent ViV-TAVR and 116 who underwent Redo-SAVR) were eligible for PSM. In the unmatched cohort, patients in the ViV-TAVR group were older and had more co-morbidities than those in the Redo-SAVR group. After PSM, there were no significant differences in all-cause death between the ViV-TAVR and Redo-SAVR groups at 30 days (3.9% vs 2.6%, p = 0.65) or 2 years (6.5% vs 7.8%, p = 0.75). The incidences of stroke and heart failure rehospitalization were similar at 30 days and 2 years. The cumulative complication rates during hospitalization were significantly lower in the ViV-TAVR group than in the Redo-SAVR group (11.7% vs 28.6% p = 0.015). The long-term outcomes of ViV-TAVR using new-generation valves were similar to those of Redo-SAVR, although ViV-TAVR was associated with lower rates of in-hospital complications.


Assuntos
Estenose da Valva Aórtica , Bioprótese , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Humanos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Falha de Prótese , Reoperação , Resultado do Tratamento , Substituição da Valva Aórtica Transcateter/efeitos adversos , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/etiologia , Fatores de Risco
9.
Am J Cardiol ; 208: 101-110, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37827014

RESUMO

Multidetector computed tomography (MDCT) can provide valuable information for mitral assessment, but its role in transcatheter mitral edge-to-edge repair (TEER) planning has been poorly elucidated. We aimed to compare MDCT with 3-dimensional transesophageal echocardiography (3D-TEE) for TEER preprocedural evaluation. We analyzed the preprocedural MDCT and 3D-TEE of 108 consecutive patients with mitral regurgitation (MR) who underwent MitraClip implantation. The levels of agreement for the etiology and mechanism of MR, mitral calcification, mitral annulus, and mitral valve orifice area (MVOA) measurements were compared between MDCT and 3D-TEE data. Receiver-operating-characteristic curves were generated for mitral annulus area and MVOA using a low mean transmitral pressure gradient at discharge (<5 mm Hg) as the state variable, and the primary outcome of all-cause mortality or rehospitalization for heart failure at 1 year was compared between MDCT's and 3D-TEE's MVOA <4-cm2 cutoff. Good levels of agreement between MDCT and 3D-TEE were observed for determining the etiology (κ = 0.81) and mechanism (κ = 0.62) of MR but not for grading mitral calcification (κ = 0.31 to 0.35). The correlations between MDCT and 3D-TEE measurements were strong for mitral annulus area (r = 0.90) and good for MVOA (r = 0.73). Furthermore, no significant differences in the area under the receiver-operating-characteristic curve to predict low transmitral pressure gradient at discharge or the primary outcome at 1 year were detected between MDCT- and 3D-TEE-derived parameters (all p >0.05). In conclusion, in patients who underwent TEER with MitraClip, a high degree of agreement for comprehensive evaluation of MR and prediction of clinical outcomes between MDCT and 3D-TEE was observed.


Assuntos
Calcinose , Ecocardiografia Tridimensional , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Substituição da Valva Aórtica Transcateter , Humanos , Tomografia Computadorizada Multidetectores , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/cirurgia , Implante de Prótese de Valva Cardíaca/métodos , Ecocardiografia Tridimensional/métodos , Ecocardiografia Transesofagiana/métodos , Resultado do Tratamento
10.
N Am Spine Soc J ; 15: 100244, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37546166

RESUMO

Background Context: Both Transforaminal (TF) and Interlaminar (IL) endoscopic approaches are established techniques of decompression for lumbar compressive radiculopathy. In the absence of adequate literature, there is always some dilemma in selecting the approach for endoscopic decompression leading to long learning curves and high chances of inadequate decompression, iatrogenic instability, dural tear, or dysesthesia. Hence authors propose a new surgical nomenclature and algorithm for selection of endoscopic approach. Methods: This retrospective study included 396 of 626 consecutive patients who met the inclusion criteria, who underwent either TF (n=302) or IL (n=202) full endoscopic spine surgery. MRI findings of every patient were classified as per FAPDIS (Facet angle, Anterior pathology, Posterior pathology, Dorsal, Inferior, and Superior migration) algorithm. Inter-observer variations were calculated. The targeted nomenclature was used to define the selection of endoscopic TF or IL approach for symptomatic nerve root decompression. All patients were followed up for preop and postop 6 months VAS and Oswestry Disability Index score for validation of FAPDIS algorithm. Results: Median age: 46.8 years; Sides and levels operated 330 single-level ipsilateral, 54 multiple-level ipsilateral, 6 single-level bilateral, and 6 multiple-level bilateral. Interobserver agreement in the selection of TF approach was 0.873 and IL approach was 0.882. Interobserver variability was also calculated for each FAPDIS factor, selection of P3 and P4 pathology was the main reason for disagreement. All other FAPDIS factors show good to excellent correlation. The overall VAS score decreased from a preoperative value of 9 to 1 at 6 months follow-up (p-value < 0.001), and the overall Oswestry Disability Index score improved from 89 to 12 (p-value <.001). Conclusions: The author's new FAPDIS surgical nomenclature and algorithm is a reliable tool for describing the symptomatic nerve root compression for the selection of endoscopic surgical approach to achieve adequate decompression of offending neural structure with minimum challenges to minimize perioperative complication rate.

11.
Transplant Cell Ther ; 29(7): 449.e1-449.e7, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37120134

RESUMO

Tisagenlecleucel (tisa-cel) is an approved CD19-directed chimeric antigen receptor T cell (CAR-T) therapy for relapsed/refractory B cell malignancies. Given potentially life-threatening toxicities, including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, inpatient tisa-cel infusion and toxicity monitoring are often considered; however, the toxicity profile of tisa-cel may be conducive to outpatient administration. Here we review the characteristics and outcomes of tisa-cel recipients treated in the outpatient setting. Patients age ≥18 years with B cell non-Hodgkin lymphoma who received tisa-cel between June 25, 2018, and January 22, 2021, at 9 US academic medical centers were included in a retrospective analysis. Six of the 9 representative centers (75%) had an outpatient program in place. A total of 157 patients were evaluable, including 93 (57%) in the outpatient treatment group and 64 (43%) in the inpatient treatment group. Baseline characteristics, toxicity and efficacy, and resource utilization were summarized. The most common lymphodepletion (LD) regimen was bendamustine in the outpatient group (65%) and fludarabine/cyclophosphamide (91%) in the inpatient group. The outpatient group had more patients with a Charlson Comorbidity Index of 0 (51% versus 15%; P < .001), fewer patients with an elevated lactate dehydrogenase (LDH) level above the normal range at the time of LD (32% versus 57%, P = .003) compared to the inpatient group, and a lower Endothelial Activation and Stress Index score (.57 versus 1.4; P < .001). Any-grade CRS and ICANS were lower in the outpatient group (29% versus 56% [P < .001] and 10% versus 16% [P = .051], respectively). Forty-two outpatient tisa-cel recipients (45%) required an unplanned admission, with a median length of stay of 5 days (range, 1 to 27 days), compared to 13 days (range, 4 to 38 days) in the inpatient group. The median number of tocilizumab doses administered was similar in the 2 groups as were the rate of intensive care unit (ICU) transfer (5% versus 8%; P = .5) and median length of ICU stay (6 days versus 5 days; P = .7). There were no toxicity-related deaths in the 30 days post-CAR-T infusion in either group. Progression-free survival and overall survival were similar in the 2 groups. With careful patient selection, outpatient tisa-cel administration is feasible and associated with similar efficacy outcomes as inpatient treatment. Outpatient toxicity monitoring and management may help optimize healthcare resource utilization.


Assuntos
Carcinoma , Linfoma não Hodgkin , Receptores de Antígenos Quiméricos , Humanos , Adolescente , Pacientes Ambulatoriais , Estudos Retrospectivos , Recidiva Local de Neoplasia , Linfoma não Hodgkin/tratamento farmacológico
13.
Cardiovasc Drugs Ther ; 37(5): 1011-1019, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-36550349

RESUMO

Atrial fibrillation is associated with an increased risk of stroke secondary to thrombus formation in the left atrial appendage. Left atrial appendage occlusion (LAAO) is an effective method of reducing the risk of stroke in patients with atrial fibrillation. Although LAAO does not remove the requirement for anticoagulation, it reduces the risk of stroke when compared to anticoagulation alone. We critically analyze the data on LAAO in cardiac surgery. We also discuss the methods of LAAO, the risks of LAAO, and patient populations that could benefit from LAAO. We discuss high-level evidence that LAAO at the time of cardiac surgery reduces the risk of stroke in patients with a history of atrial fibrillation. In patients without a history of atrial fibrillation undergoing cardiac surgery, we suggest that LAAO should be considered in select patients at high risk of atrial fibrillation and stroke, when technically feasible.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicações , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Anticoagulantes , Resultado do Tratamento
14.
Blood Adv ; 7(17): 4765-4772, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36508286

RESUMO

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of many patients with aggressive relapsed or refractory large B-cell lymphoma (LBCL). Treatment can be complicated by clinically evident cytokine release syndrome (CRS), which is characterized by the development of fever, hypoxia, and hypotension, and can be life-threatening. Most patients treated with CAR-T cells develop CRS, which is thought to represent an immune phenomenon. It was previously unknown whether patients who did not develop CRS had reduced CAR-T cell activity and were therefore likely to have worse outcomes. We conducted a multicenter retrospective analysis of 352 adult patients treated at 8 academic medical centers in the United States who received axicabtagene ciloleucel or tisagenlecleucel for the treatment of LBCL. The outcomes of interest included progression-free survival, overall survival, complete response rate, and overall response rate. Of the included patients, 262 (74.4%) developed CRS. There was no significant difference in progression-free survival (P = .99) or overall survival (P = .16) between patients who developed CRS and those who did not develop CRS. Peak ferritin levels >5000 ng/mL during treatment and lactate dehydrogenase levels greater than the institutional upper limit of normal before lymphodepleting chemotherapy were associated with significantly worse progression-free and overall survival in the multivariate analysis. There was no significant difference in the complete response or overall response rates between patients who did and did not develop CRS. In this retrospective analysis, we report that patients who develop CRS have clinical outcomes similar to those of patients without CRS treated with commercial anti-CD19 CAR-T cells.


Assuntos
Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Adulto , Humanos , Estados Unidos , Receptores de Antígenos Quiméricos/uso terapêutico , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/terapia , Estudos Retrospectivos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Antígenos CD19 , Terapia Baseada em Transplante de Células e Tecidos
15.
Arch Orthop Trauma Surg ; 143(6): 3191-3199, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36305967

RESUMO

INTRODUCTION: Muscle fatigue is a leading cause of rotator cuff (RC) pathologies. Scapular orientation affected by changes in the thoracic spine account for differences in body postures leading to altered RC muscle activation. This posture-related alteration in RC muscle activation and its fatigue response needs to be analyzed. MATERIALS AND METHODS: This study included 50 healthy shoulders with no coexisting spine pathologies. Raw data were recorded using electromyography sensors for RC muscles during two isometric maneuvers of abduction and external rotation, performed at 30% maximum voluntary contraction at 30°, 45°, and 90° arm elevation in sitting and standing. The raw data were analyzed in DataLITE® software, and the mean power frequency (MPF) was extracted to analyze the fatigue response of RC muscles. The Wilcoxon signed-rank test and Kruskal-Wallis test with Bonferroni corrections analyzed fatigue differences between postures and various activities. P < 0.05 was considered significant for the results. RESULTS: Supraspinatus muscle demonstrated significant fatigue at 90° of arm elevation in standing as compared to sitting (MPF -5.40: -5.41; P = 0.03) posture. Between the three elevation angles, all the RC muscles showed increased fatigue at 90° (MPF range -5.22 to -6.64). When compared between abduction and external rotation, only infraspinatus showed fatigue in external rotation (MPF range -5.42 to -6.08). Among all the three RC muscles, infraspinatus showed the maximum fatigue of MPF -6.64 when compared to supraspinatus -5.22 and teres minor -5.36. CONCLUSION: The findings indicate that alterations in the body postures and different elevation angles affect the RC muscles' fatigue response.


Assuntos
Manguito Rotador , Articulação do Ombro , Humanos , Fadiga Muscular , Articulação do Ombro/fisiologia , Ombro/fisiologia , Postura , Eletromiografia , Amplitude de Movimento Articular/fisiologia
17.
JTCVS Tech ; 13: 92-100, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36466372

RESUMO

Objective: Robot-assisted coronary artery bypass (RCAB) is typically not offered to higher risk patients with reduced cardiopulmonary function, critical coronary artery disease, and challenging chest wall anatomy. In this study, we report the novel use of nonemergency intraoperative peripheral extracorporeal membrane oxygenation as partial cardiopulmonary support during RCAB for patients who were considered high-risk candidates for conventional CAB and at the same time not eligible for RCAB without cardiopulmonary support. Methods: Forty-five high risk patients (mean age, 68 years; Society of Thoracic Surgeons score, 6.27%; ejection fraction, 45%) underwent RCAB with nonemergency peripheral extracorporeal membrane oxygenation support for the following indications: inability to tolerate single-lung ventilation (n = 17; 38%), low ejection fraction <35% (n = 17; 38%), inadequate exposure of internal thoracic artery (n = 24; 53%), critical coronary artery disease (n = 16; 36%), and hemodynamic instability after anesthesia induction (n = 3; 7%). Following robotic internal thoracic artery takedown, all patients had beating heart minimally invasive direct CAB through a 2-inch minithoracotomy. Results: Up to 30 days, there were no strokes (0%), myocardial infarctions (0%), or access vessel complications (0%). One noncardiac related mortality (2.2%) was related to hemodialysis access issues in a patient with preexisting end-stage renal disease. One redo-CAB (2.2%) patient required sternotomy to locate the target vessel. Thirty-four (75.6%) patients were extubated within 6 hours of surgery. Conclusions: Our results examine the feasibility of using peripheral extracorporeal membrane oxygenation during RCAB for high-risk patients who otherwise had limited options. The use of peripheral extracorporeal membrane oxygenation in RCAB can potentially expand the surgical treatment options in high-risk coronary artery disease patients.

18.
FEBS J ; 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36471658

RESUMO

Lysine acetylation is a common reversible post-translational modification of proteins that plays a key role in regulating gene expression. Nuclear receptors (NRs) include ligand-inducible transcription factors and orphan receptors for which the ligand is undetermined, which together regulate the expression of genes involved in development, metabolism, homeostasis, reproduction and human diseases including cancer. Since the original finding that the ERα, AR and HNF4 are acetylated, we now understand that the vast majority of NRs are acetylated and that this modification has profound effects on NR function. Acetylation sites are often conserved and involve both ordered and disordered regions of NRs. The acetylated residues function as part of an intramolecular signalling platform intersecting phosphorylation, methylation and other modifications. Acetylation of NR has been shown to impact recruitment into chromatin, co-repressor and coactivator complex formation, sensitivity and specificity of regulation by ligand and ligand antagonists, DNA binding, subcellular distribution and transcriptional activity. A growing body of evidence in mice indicates a vital role for NR acetylation in metabolism. Additionally, mutations of the NR acetylation site occur in human disease. This review focuses on the role of NR acetylation in coordinating signalling in normal physiology and disease.

19.
Nanomaterials (Basel) ; 12(24)2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36558247

RESUMO

Nickel-based superalloys find their main use in missile engines, atomic devices, investigational aircraft, aerospace engineering, industrial applications, and automotive gas turbines, spacecraft petrochemical tools, steam power, submarines, and broader heating applications. These superalloys impose certain difficulties during the process fabrication owing to their levels of higher hardness. In the current study, the precise machining of Waspaloy was attempted through the wire electrical discharge machining (WEDM) technique. A multi-objective optimization has been performed, and the influence of multi-walled carbon nanotubes (MWCNTs) has been assessed using the passing vehicle search (PVS) algorithm. The effects of machining variables like current, Toff, and Ton were studied using the output measures of material removal rate (MRR), recast layer thickness (RLT), and surface roughness (SR). The Box-Behnken design was applied to generate the experimental matrix. Empirical models were generated which show the interrelationship among the process variables and output measures. The analysis of variance (ANOVA) method was used to check the adequacy, and suitability of the models and to understand the significance of the parameters. The PVS technique was executed for the optimization of MRR, SR, and RLT. Pareto fronts were derived which gives a choice to the user to select any point on the front as per the requirement. To enhance the machining performance, MWCNTs mixed dielectric fluid was utilized, and the effect of these MWCNTs was also analyzed on the surface defects. The use of MWCNTs at 1 g/L enhanced the performance of MRR, SR, and RLT by 65.70%, 50.68%, and 40.96%, respectively. Also, the addition of MWCNTs has shown that the machined surface largely reduces the surface defects.

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