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2.
Surg Neurol Int ; 14: 144, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37151449

RESUMO

Background: Myxofibrosarcoma (MFS) is a rare and locally infiltrative tumor that commonly occurs in extremities in older adults; however, truncal and head and neck cases have been reported. They are characterized by multinodular growth, incomplete fibrous septa, and myxoid stroma. Surgical resection is the mainstay of treatment. Case Description: The authors report a case of a combined, supraclavicular, infraclavicular, transaxillary, and posterior subscapular approaches for resection of giant MFS. Conclusion: The anatomical complexity and rarity of tumors involving the brachial plexus impose many challenges onto surgeons performing surgical resections. Treatment choices and surgical outcomes rely heavily on meticulous multidisciplinary planning, anatomical knowledge, careful dissection, and extent of resection. This case is unique in utilizing four different approaches to the brachial plexus to resect one tumor.

3.
J Thorac Dis ; 15(3): 1155-1162, 2023 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-37065555

RESUMO

Background: Primary spontaneous pneumomediastinum (PSPM) is a benign condition, but it can be difficult to discriminate from Boerhaave syndrome. The diagnostic difficulty is attributable to a shared constellation of history, signs, and symptoms combined with a poor understanding of the basic vital signs, labs, and diagnostic findings characterizing PSPM. These challenges likely contribute to high resource utilization for diagnosis and management of a benign process. Methods: Patients aged 18 years or older with PSPM were identified from our radiology department's database. A retrospective chart review was performed. Results: Exactly 100 patients with PSPM were identified between March 2001 and November 2019. Demographics and histories correlated well with prior studies: mean age (25 years); male predominance (70%); association with cough (34%), asthma (27%), retching or emesis (24%), tobacco abuse (11%), and physical activity (11%); acute chest pain (75%), and dyspnea (57%) as the first and second most frequent symptoms and subcutaneous emphysema (33%) as the most common sign. We provide the first robust data on presenting vital signs and laboratory values of PSPM, showing that tachycardia (31%) and leukocytosis (30%) were common. No pleural effusion was found in the 66 patients who underwent computed tomography (CT) of the chest. We provide the first data on inter-hospital transfer rates (27%). 79% of transfers were due to concern for esophageal perforation. Most patients were admitted (57%), with an average length of stay (LOS) of 2.3 days, and 25% received antibiotics. Conclusions: PSPM patients frequently present in their twenties with chest pain, subcutaneous emphysema, tachycardia, and leukocytosis. Approximately 25% have a history of retching or emesis and it is this population that must be discriminated from those with Boerhaave syndrome. An esophagram is rarely indicated and observation alone is appropriate in patients under age 40 with a known precipitating event or risk factors for PSPM (e.g., asthma, smoking) if they have no history of retching or emesis. Fever, pleural effusion, and age over 40 are rare in PSPM and should raise concern for esophageal perforation in a patient with a history of retching, emesis, or both.

4.
J Am Vet Med Assoc ; 261(7): 1-8, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36884382

RESUMO

OBJECTIVE: Patient factors may alter laser photon attenuation, but these factors have not been adequately evaluated in live dogs. Our objective was to evaluate class IV laser beam attenuation (LBA) by canine tissues using a colorimeter to evaluate melanin and erythema indices. We hypothesized that greater melanin and erythema indices and unclipped hair would increase LBA, and these properties would vary among tissues. ANIMALS: 20 client-owned dogs. PROCEDURES: Between October 1 and December 1, 2017, colorimeter measurements and LBA in various tissues before and after clipping overlying hair were evaluated. Data were analyzed using generalized linear mixed models. Statistical significance was set at P < .05. RESULTS: LBA was greater in unclipped (98.6 ± 0.4%) than clipped hair (94.6 ± 0.4%). The least LBA occurred in the pinna (93%) while the greatest occurred in the caudal vertebra (100%) and caudal semitendinosis muscles (100%). Each mm of tissue thickness resulted in LBA of 11.6%. Each unit increase in melanin index resulted in a 3.3% increase in LBA. There was no association of LBA with erythema index. CLINICAL RELEVANCE: To our knowledge, this is the first study that evaluated LBA by different tissues in live dogs using a colorimeter to evaluate melanin and erythema indices. We recommend clipping hair prior to photobiomodulation to decrease laser beam attenuation and using increased laser doses in thicker tissues and dogs with high melanin content. The colorimeter may be helpful in customizing patient treatment dosimetry. Future studies are necessary to determine therapeutic laser doses for adequate photobiomodulation effects.


Assuntos
Doenças do Cão , Melaninas , Cães , Animais , Eritema/veterinária , Lasers , Doenças do Cão/radioterapia , Doenças do Cão/cirurgia
5.
BMC Cancer ; 23(1): 99, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36709278

RESUMO

BACKGROUND: Both Red Blood Cell (RBC) transfusion and anemia are thought to negatively impact cancer survival. These effects have been reported with mixed findings in cancer of the esophagus. The potential impact of the application of restrictive transfusion strategies on this patient population has not been defined. MATERIALS AND METHODS: We conducted a retrospective study of esophagectomies and studied cases based on whether they were anemic or were transfused peri-operatively. Clinical characteristics and known clinicopathologic prognosticators were compared between these groups. Survival was compared by Cox proportional hazard modeling. Post-operative transfusions were assessed for compliance with restrictive transfusion thresholds. RESULTS: Three-hundred ninety-nine esophagectomy cases were reviewed and after exclusions 348 cases were analyzed. The median length of follow-up was 33 months (range 1-152 months). Sixty-four percent of patients were anemic pre-operatively and 22% were transfused. Transfusion and anemia were closely related to each other. Microcytic anemia was uncommon but was evaluated and treated in only 50% of cases. Most anemic patients had normocytic RBC parameters. Transfusion but not anemia was associated with a protracted/prolonged post-operative stay. Transfusion and anemia were both associated with reduced survival however only anemia was associated with decreased survival in multi-variable modeling. Sixty-eight percent of patients were transfused post-operatively and 11% were compliant with the restrictive threshold of 7 g/dL. CONCLUSIONS: Pre-operative anemia and transfusion are closely associated, however only anemia was found to compromise survival in our esophageal cancer cohort, supporting the need for more aggressive evaluation and treatment of anemia. Adherence to restrictive transfusion guidelines offers an opportunity to reduce transfusion rates which may also improve short-term outcomes.


Assuntos
Anemia , Neoplasias , Humanos , Estudos Retrospectivos , Anemia/etiologia , Anemia/terapia , Transfusão de Sangue , Neoplasias/complicações , Esôfago
6.
Surg Open Sci ; 11: 26-32, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36444286

RESUMO

Background: Anastomotic leak (AL) after minimally invasive esophagectomy (MIE) is a well-described source of morbidity for patients undergoing surgical treatment of esophageal neoplasm. With improved early recognition and endoscopic management techniques, the long-term impact remains unclear. Methods: A retrospective review was conducted of patients who underwent MIE for esophageal neoplasm between January 2015 and June 2021 at a single institution. Cohorts were stratified by development of AL and subsequent management. Baseline demographics, perioperative data, and post-operative outcomes were examined. Results: During this period, 172 MIEs were performed, with 35 of 172 (20.3%) complicated by an AL. Perioperative factors independently associated with AL were post-operative blood transfusion (leak rate 52.9% versus 16.8%; p = 0.0017), incompleteness of anastomotic rings (75.0% vs 19.1%; p = 0.027), and receiving neoadjuvant therapy (18.5% vs 30.8%; p < 0.0001). Inferior short-term outcomes associated with AL included number of esophageal dilations in the first post-operative year (1.40 vs 0.46, p = 0.0397), discharge disposition to a location other than home (22.9% vs 8.8%, p = 0.012), length of hospital stay (17.7 days vs 9.6 days; p = 0.002), and time until jejunostomy tube removal (134 days vs 79 days; p = 0.0023). There was no significant difference in overall survival between patients with or without an AL at 1 year (79% vs 83%) or 5 years (50% vs 47%) (overall log rank p = 0.758). Conclusions: In this large single-center series of MIEs, AL was associated with inferior short-term outcomes including hospital length of stay, discharge disposition other than to home, and need for additional endoscopic procedures, without an accompanying impact on 1-year or 5-year survival. Key message: In this large, single-center series of minimally invasive esophagectomies, anastomotic leak was associated with worse short-term outcomes including hospital length of stay, discharge disposition other than to home, and need for additional endoscopic procedures, but was not associated with worse long-term survival. The significant association between neoadjuvant therapy and decreased leak rates is difficult to interpret, given the potential for confounding factors, thus careful attention to modifiable pre- and peri-operative patient factors associated with anastomotic leak is warranted.

7.
Am Surg ; 89(6): 2427-2433, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35506914

RESUMO

INTRODUCTION: Resident physicians are uniquely at high financial risk given their long training programs, lack of financial education, and documented poor financial literacy. Budgeting for retirement savings is an important metric for financial literacy. METHODS: Semi-structured interviews were conducted with residents from two distinct surgery programs to assess their current financial status and their knowledge of and attitudes toward retirement savings strategies. Qualitative analysis was performed and the themes identified were examined in the context of previously reported quantitative survey data. RESULTS: As previously reported, 105 residents at Site 1 completed a comprehensive financial survey 56% of respondents reported having no retirement savings. On additional analysis, only 26% residents surveyed reported optimal savings habits defined as contributing $5000/year to a retirement account starting their first year of training. 23 residents from both sites and representing all post-graduate-year (PGY) levels then participated in the focused, semi-structured interviews. Site 2 residents were less likely to be female (P = .02) and carried a significantly larger debt burden (p < .01) but were otherwise comparable to residents from Site 1. On qualitative analysis three consistent themes emerged: (1) Resident understanding of strategies for retirement savings is poor; (2) Lack of knowledge is the primary barrier; (3) Surgical residents desire financial education. CONCLUSIONS: Surgery residents have a large debt burden, minimal retirement savings and an overall lack of understanding of savings strategies. Well-designed, early, and accessible educational interventions may improve the "financial vital signs" of surgical trainees and establish habits for long-term financial success.


Assuntos
Internato e Residência , Alfabetização , Humanos , Feminino , Masculino , Renda , Escolaridade , Inquéritos e Questionários
8.
Orphanet J Rare Dis ; 17(1): 377, 2022 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-36253825

RESUMO

BACKGROUND: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare, devastating blistering genodermatosis caused by mutations in the COL7A1 gene, which encodes for type VII collagen and is necessary for dermal-epidermal adhesion and integrity. Disease manifestations include severe and debilitating wounds, aggressive squamous cell carcinomas, and premature death; however, there are currently no approved therapies. This Phase 1/2a, open-label study evaluated the long-term efficacy and safety of gene-corrected autologous keratinocyte grafts (EB-101) for chronic RDEB wounds. METHODS: Autologous keratinocytes were harvested from participants with severe RDEB, transduced with a retrovirus containing the full-length COL7A1 gene, and grown into 5 × 7 cm (35 cm2) sheets. Gene-corrected keratinocyte sheets were then transplanted onto chronic RDEB wounds present for ≥ 12 weeks. RESULTS: Seven adult participants with severe RDEB were grafted with six sheets each (42 total sheets) onto wounds and followed for a mean of 5.9 years (range 4-8 years). Long-term improvements in wound healing and symptoms were observed. At year five, 70% (21/30) of treated sites demonstrated ≥ 50% wound healing compared to baseline by investigator global assessment. No sites with ≥ 50% wound healing were painful or pruritic, compared to 67% (6/9) of sites with < 50% wound healing (p < 0.001) at year five. Grafts were well-tolerated throughout long-term follow-up. No serious adverse events related to treatment were reported over a mean of 5.9 years of follow-up. No persistent systemic autoimmunity against type VII collagen or replication-competent retrovirus infections were identified, and no participants developed squamous cell carcinomas related to treatment during long-term follow-up. CONCLUSIONS: Treatment with EB-101 appears safe and efficacious, and produces long-term improvements in wound healing, pain, and itch for RDEB patients. Results from the Phase 3 randomized controlled trial are forthcoming. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01263379. Registered December 15, 2010. https://clinicaltrials.gov/ct2/show/NCT01263379.


Assuntos
Carcinoma de Células Escamosas , Epidermólise Bolhosa Distrófica , Adulto , Humanos , Colágeno Tipo VII/genética , Colágeno Tipo VII/metabolismo , Epidermólise Bolhosa Distrófica/genética , Epidermólise Bolhosa Distrófica/patologia , Queratinócitos/metabolismo , Cicatrização/genética
9.
J Card Surg ; 37(12): 5472-5474, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36150146

RESUMO

Aorto-tracheal fistulas are rare and highly lethal, with few reports of successful surgical intervention. We present a 48-year-old man with an aorto-tracheal fistula induced by radiation therapy for tracheal squamous cell carcinoma. He presented with hemoptysis and chest pain and workup revealed the aorta-tracheal fistula between the posterior aortic arch and anterior distal trachea. He was emergently taken to surgery. To our knowledge, this is the first report of an aorto-tracheal fistula successfully treated with a transverse aortic arch replacement and complex tracheal repair using autologous pericardium with an omental buttress.


Assuntos
Fístula , Procedimentos Cirúrgicos Torácicos , Masculino , Humanos , Pessoa de Meia-Idade , Traqueia/cirurgia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Aorta/patologia
10.
Vet Surg ; 51(1): 182-190, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34562025

RESUMO

OBJECTIVE: To improve the accuracy of drilling during the repair of sacroiliac luxations (SILs) with a 3D-printed patient-specific drill guide (3D-GDT) compared to free-hand drilling technique (FHDT). STUDY DESIGN: Blinded, randomized, prospective ex vivo study. SAMPLE POPULATION: Sixteen canine cadavers (20-25 kg). METHODS: Dorsal, bilateral SILs were created. Pelvic CT was performed pre- and post-drilling. The FHDT was drilled followed by 3D-GDT. CT and 3D measurements of craniocaudal and dorsoventral angles were compared between FHDT and 3D-GDT, as well as deviations of entry and exit points relative to optimal trajectory. RESULTS: Mean craniocaudal and dorsoventral angles for both CT- and 3D-measured 3D-GDT (CT 4.2 ± 3.9° and 3.9 ± 3.2°, respectively; 3D 5.1 ± 5.1° and 2.8 ± 2.3°, respectively p = .0006) were lower compared to FHDT (CT 11.8 ± 4.0°, p < .0001 and 8.9 ± 6.1°, p = .01; 3D 12.4 ± 5.9°, p = .0006 and 5.3 ± 5.24°, p = .05). Entry dorsoventral and end craniocaudal, dorsoventral, and 3D linear deviations were reduced with 3D-GDT. Sacral corridor disruption was present in 20% (3/15) for FHDT compared with 0% for 3D-GDT. CT and 3D analyses were in strong agreement (r = 0.77). CONCLUSION: Deviations of drill trajectories were minimized relative to optimal trajectories with 3D-GDT compared to FHDT in the dorsoventral and craniocaudal planes. CLINICAL SIGNIFICANCE: The use of 3D-GDT improves accuracy of sacral drilling compared with FHDT in canine cadavers. These results justify further evaluation in a clinical, prospective study.


Assuntos
Doenças do Cão , Luxações Articulares , Animais , Parafusos Ósseos/veterinária , Cadáver , Cães , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/cirurgia , Luxações Articulares/veterinária , Impressão Tridimensional , Estudos Prospectivos
11.
Ann Thorac Surg ; 114(1): e17-e19, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34748736

RESUMO

Lung transplantation has been well described for patients with coronavirus disease 2019 (COVID-19) in the acute setting, but less so for the resulting pulmonary sequelae. This report describes a case of lung transplantation for post-COVID-19 pulmonary fibrosis. A 52-year-old woman contracted COVID-19 in July 2020 and mounted a partial recovery, but she went on to have declining function over the ensuing 3 months, with development of fibrocystic lung changes. She underwent bilateral lung transplantation and recovered rapidly, was discharged home on postoperative day 14, and has done well in follow-up. This case report demonstrates that lung transplantation is an acceptable therapy for post-COVID-19 pulmonary fibrosis.


Assuntos
COVID-19 , Transplante de Pulmão , Fibrose Pulmonar , Feminino , Humanos , Pulmão , Pessoa de Meia-Idade , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/cirurgia
12.
J Thorac Dis ; 13(6): 3721-3730, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34277063

RESUMO

Primary spontaneous pneumomediastinum (PSPM) is a benign self-limited condition that can be difficult to discriminate from esophageal perforation. This may trigger costly work-up, transfers and hospital admissions. To better understand this diagnostic dilemma and current management, we undertook the most comprehensive and up to date review of PSPM. The PubMed database was searched using the MeSH term "Mediastinal Emphysema"[Mesh], to identify randomized controlled trials, meta-analyses and case series (including 10 or more patients) relevant to the clinical presentation and management of patients with PSPM. There were no relevant randomized controlled trials or meta-analyses. Nineteen case series met our criteria, including a total of 535 patients. The average mean age was 23 years with a 3:1 male predominance. Chest pain was the most common symptom, found in 70.9% of the patients. Dyspnea and neck pain were the second and third most common symptoms, found in 43.4% and 32% of the patients, respectively. Subcutaneous emphysema was the most common sign (54.2%). Common histories included smoking (29.6%), cough (27.7%), asthma (25.9%), physical exertion (21.1%) and recent retching or emesis (13%). Nearly all patients (96.9%) underwent chest X-ray (CXR). Other diagnostic studies included computed tomography (65%) and esophagram (35.6%). Invasive studies were common, with 13% of patients undergoing esophagogastroduodenoscopy and 14.6% undergoing bronchoscopy. The rate of hospital admission was 86.5%, with an average length of stay of 4.4 days. No deaths were reported. Notably, we identified a dearth of information regarding the vitals, laboratory values and imaging findings specific to patients presenting with PSPM. We conclude that PSPM is a benign clinical entity that continues to present a resource-intensive diagnostic challenge and that data on the vitals, labs, and imaging findings specific to PSPM patients is scant. An improved understanding of these factors may lead to more efficient diagnosis and management of these patients.

13.
Med Image Anal ; 73: 102154, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34280670

RESUMO

Simultaneous segmentation and detection of liver tumors (hemangioma and hepatocellular carcinoma (HCC)) by using multi-modality non-contrast magnetic resonance imaging (NCMRI) are crucial for the clinical diagnosis. However, it is still a challenging task due to: (1) the HCC information on NCMRI is insufficient makes extraction of liver tumors feature difficult; (2) diverse imaging characteristics in multi-modality NCMRI causes feature fusion and selection difficult; (3) no specific information between hemangioma and HCC on NCMRI cause liver tumors detection difficult. In this study, we propose a united adversarial learning framework (UAL) for simultaneous liver tumors segmentation and detection using multi-modality NCMRI. The UAL first utilizes a multi-view aware encoder to extract multi-modality NCMRI information for liver tumor segmentation and detection. In this encoder, a novel edge dissimilarity feature pyramid module is designed to facilitate the complementary multi-modality feature extraction. Secondly, the newly designed fusion and selection channel is used to fuse the multi-modality feature and make the decision of the feature selection. Then, the proposed mechanism of coordinate sharing with padding integrates the multi-task of segmentation and detection so that it enables multi-task to perform united adversarial learning in one discriminator. Lastly, an innovative multi-phase radiomics guided discriminator exploits the clear and specific tumor information to improve the multi-task performance via the adversarial learning strategy. The UAL is validated in corresponding multi-modality NCMRI (i.e. T1FS pre-contrast MRI, T2FS MRI, and DWI) and three phases contrast-enhanced MRI of 255 clinical subjects. The experiments show that UAL gains high performance with the dice similarity coefficient of 83.63%, the pixel accuracy of 97.75%, the intersection-over-union of 81.30%, the sensitivity of 92.13%, the specificity of 93.75%, and the detection accuracy of 92.94%, which demonstrate that UAL has great potential in the clinical diagnosis of liver tumors.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética
14.
Thorac Surg Clin ; 31(2): 119-128, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33926666

RESUMO

Publication of the National Emphysema Treatment Trial (NETT) in 2003 established lung volume reduction surgery (LVRS) as a viable treatment of select patients with moderate to severe emphysema, and the only intervention since the availability of ambulatory supplemental oxygen to improve survival. Despite these findings, surgical treatment has been underused in part because of concern for high morbidity and mortality. This article reviews recent literature generated since the original NETT publication, focusing on physiologic implications of LVRS, recent data regarding the safety and durability of LVRS, and patient selection and extension of NETT criteria to other patient populations.


Assuntos
Inflamação/metabolismo , Pneumonectomia/métodos , Doença Pulmonar Obstrutiva Crônica/cirurgia , Enfisema Pulmonar/cirurgia , Ensaios Clínicos como Assunto , Humanos , Segurança do Paciente , Seleção de Pacientes , Enfisema Pulmonar/mortalidade , Pneumologia/tendências , Qualidade de Vida , Risco , Resultado do Tratamento , Estados Unidos
15.
Semin Thorac Cardiovasc Surg ; 33(4): 1158-1168, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33711460

RESUMO

Duty-hour restrictions have implications on trainee operative exposure necessary to meet minimum case-volume requirements. We utilized a previously validated simulation model to evaluate the effect of program volume, trainee numbers and complement, and rotation schedule on the probability of achieving adequate esophagectomy case numbers for cardiothoracic surgery trainees. A ProModel simulator centered on probabilistic distributions of operative cases was utilized. Historical data from five 2-year cardiothoracic surgery training programs were obtained from 2016-2018 and used as inputs to the simulator that generated 10,000 "trainee 2-year periods" per program. Programs varied in annual average esophagectomy volume (12-91 per year), with 2-4 trainees graduating over a 2-year training period. If esophagectomy cases were distributed solely based on scheduling and institutional volume, only 60% of evaluated programs could adequately expose all trainees in esophagectomy to meet case requirements. The 3 programs with adequate esophagectomy volumes had averaged 3.3 times (range 3.0-3.6) the minimum number of board-required cases for their programs' trainees. The ability of programs to provide trainees with adequate esophagectomy volume is challenging based on institutional volume and scheduling. Through simulation, we demonstrate that programs need >2 times the expected minimum number of esophagectomies to ensure that >90% of trainees meet case-volume requirements. Programs may consider strategies such as allowing trainees to select cases based on personal need, train fewer fellows, or enable trainees to seek subspecialty exposure externally to achieve minimum esophagectomy case-load requirements.


Assuntos
Internato e Residência , Cirurgia Torácica , Competência Clínica , Educação de Pós-Graduação em Medicina , Esofagectomia/efeitos adversos , Humanos , Resultado do Tratamento
17.
Lancet Haematol ; 7(7): e511-e522, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32589977

RESUMO

BACKGROUND: Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer with a median overall survival of less than 6 months. We aimed to assess the response to single-agent selinexor, an oral selective inhibitor of nuclear export, in patients with relapsed or refractory DLBCL who had no therapeutic options of potential clinical benefit. METHODS: SADAL was a multicentre, multinational, open-label, phase 2b study done in 59 sites in 19 countries. Patients aged 18 years or older with pathologically confirmed diffuse large B-cell lymphoma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received two to five lines of previous therapies, and progressed after or were not candidates for autologous stem-cell transplantation were enrolled. Germinal centre B-cell or non-germinal centre B-cell tumour subtype and double or triple expressor status were determined by immunohistochemistry and double or triple hit status was determined by cytogenetics. Patients received 60 mg selinexor orally on days 1 and 3 weekly until disease progression or unacceptable toxicity. The study was initially designed to evaluate both 60 mg and 100 mg twice-weekly doses of selinexor; however, the 100 mg dose was discontinued in the protocol (version 7.0) on March 29, 2017, when an improved therapeutic window was observed at 60 mg. Primary outcome was overall response rate. The primary outcome and safety were assessed in all patients who received 60 mg selinexor under protocol version 6.0, or enrolled under protocol versions 7.0 or higher and received at least one dose of selinexor. This trial is registered at ClinicalTrials.gov, NCT02227251 (active but not enrolling). FINDINGS: Between Oct 21, 2015, and Nov 2, 2019, 267 patients were randomly assigned, with 175 allocated to the 60 mg group and 92 to the discontinued 100 mg group. 48 patients assigned to the 60 mg group were excluded due to enrolment before version 6.0 of the protocol; the remaining 127 patients received selinexor 60 mg and were included in analyses of primary outcome and safety. The overall response rate was 28% (36/127; 95% CI 20·7-37·0); 15 (12%) achieved a complete response and 21 (17%) a partial response. The most common grade 3-4 adverse events were thrombocytopenia (n=58), neutropenia (n=31), anaemia (n=28), fatigue (n=14), hyponatraemia (n=10), and nausea (n=8). The most common serious adverse events were pyrexia (n=9), pneumonia (n=6), and sepsis (n=6). There were no deaths judged as related to treatment with selinexor. INTERPRETATION: Single-drug oral selinexor induced durable responses and had a manageable adverse events profile in patients with relapsed or refractory DLBCL who received at least two lines of previous chemoimmunotherapy. Selinexor could be considered a new oral, non-cytotoxic treatment option in this setting. FUNDING: Karyopharm Therapeutics Inc.


Assuntos
Antineoplásicos/uso terapêutico , Hidrazinas/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Triazóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Carioferinas/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Proteína Exportina 1
19.
JTCVS Open ; 3: 128-135, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34173545

RESUMO

OBJECTIVE: The American Board of Thoracic Surgery-certifying examination is challenging for applicants. Single institutions have reported good results with a mock oral examination (MOE) for trainees. General surgery literature has demonstrated success with in-person multi-institutional MOE examinations. Due to small numbers of cardiothoracic training programs and significant geographic variability, we hypothesized that a multi-institutional, collaborative remotely administered MOE (mICMO) pairing faculty with trainees from different institutions would provide an important educational experience. METHODS: mICMOs were conducted via the Zoom virtual platform across 6 institutions. Descriptive results via post-experience survey were analyzed and reported. RESULTS: In total, 100% of trainees found mICMO useful. The majority would recommend to a peer, and 100% of faculty examiners found mICMO useful and would participate in another examination. CONCLUSIONS: Faculty and trainees found the experience to be effective with respect to creating a high-stakes environment, educationally beneficial, and productive. These results support the continued use of mICMO and encourage expansion and collaboration with additional institutions across the country.

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