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1.
Am Surg ; : 31348241241729, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38679964

RESUMO

INTRODUCTION: Identifying patients who can be safely managed in lower-level trauma centers is critical to avoid overburdening level I centers. This study examines the transfer patterns and outcomes of blunt splenic injury (BSI) patients cared for at 2 regional level III trauma centers as compared to an associated level I center. METHODS: A retrospective cohort study was conducted including all trauma patients with BSI admitted to 2 level III trauma centers (TC3) and a level I center (TC1) between 2012 and 2022. Patients were broken into 3 categories: TC1, TC3, and transfer patients (transferred from TC3 to TC1). RESULTS: A total of 1480 patients were admitted to TC1, 208 patients to TC3, and 128 were transferred. 22.7% of transfer patients were children. No difference in splenic injury grade was seen between patients managed at TC1 and TC3. Patients presenting to TC1 had more severe concomitant injuries. Patients underwent urgent splenectomy at similar rates at TC1 and TC3 (15.1 vs 18.7%, P = .1). Successful nonoperative management was achieved at similar rates (81.3 vs 75.5%, P = .1). When controlling for ISS and ED disposition, there was no significant difference in length of stay (LOS), ICU LOS, and inpatient mortality between TC1 and TC3. CONCLUSION: Level III centers effectively managed BSI achieving comparable outcomes to the level 1 center. Transfers commonly occurred in pediatric and multisystem trauma patients, though high-grade splenic injuries were not predictive of transfer. High-grade BSI can be safely managed at level III centers without need for transfer.

2.
J Trauma Acute Care Surg ; 96(4): 618-622, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37889926

RESUMO

BACKGROUND: Over the last two decades, the acute management of rib fractures has changed significantly. In 2021, the Chest Wall injury Society (CWIS) began recognizing centers that epitomize their mission as CWIS Collaborative Centers. The primary aim of this study was to determine the resources, surgical expertise, access to care, and institutional support that are present among centers. METHODS: A survey was performed including all CWIS Collaborative Centers evaluating the resources available at their hospital for the treatment of patients with chest wall injury. Data about each chest wall injury center care process, availability of resources, institutional support, research support, and educational offerings were recorded. RESULTS: Data were collected from 20 trauma centers resulting in an 80% response rate. These trauma centers were made up of 5 international and 15 US-based trauma centers. Eighty percent (16 of 20) have dedicated care team members for the evaluation and management of rib fractures. Twenty-five percent (5 of 20) have a dedicated rib fracture service with a separate call schedule. Staffing for chest wall injury clinics consists of a multidisciplinary team: with attending surgeons in all clinics, 80% (8 of 10) with advanced practice providers and 70% (7 of 10) with care coordinators. Forty percent (8 of 20) of centers have dedicated rib fracture research support, and 35% (7 of 20) have surgical stabilization of rib fracture (SSRF)-related grants. Forty percent (8 of 20) of centers have marketing support, and 30% (8 of 20) have a web page support to bring awareness to their center. At these trauma centers, a median of 4 (1-9) surgeons perform SSRFs. In the majority of trauma centers, the trauma surgeons perform SSRF. CONCLUSION: Considerable similarities and differences exist within these CWIS collaborative centers. These differences in resources are hypothesis generating in determining the optimal chest wall injury center. These findings may generate several patient care and team process questions to optimize patient care, patient experience, provider satisfaction, research productivity, education, and outreach. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level V.


Assuntos
Fraturas das Costelas , Traumatismos Torácicos , Parede Torácica , Humanos , Fraturas das Costelas/cirurgia , Parede Torácica/cirurgia , Assistência ao Paciente , Inquéritos e Questionários , Estudos Retrospectivos
3.
Am Surg ; 90(2): 303-305, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38124319

RESUMO

Early surgical stabilization of rib fracture (SSRF) improves outcomes in patients with flail physiology and severely displaced fractures. We present two cases of patients with severe chest injury and large flail segment who underwent SSRF while on veno-venous extracorporeal membrane oxygenation (VV-ECMO). The patients developed respiratory failure within 24 hours of admission requiring VV-ECMO. The extent of their chest wall injury limited pulmonary mechanics prohibiting transition off VV-ECMO. Therefore, SSRF was performed on hospital days 2 and 3 and while on VV-ECMO support. Stabilizing the chest wall allowed for improved ventilation and successful decannulation from VV-ECMO on postoperative days 3 and 4. Ultimately, both achieved a functional recovery and were discharged home. These cases demonstrate a unique thoracic damage control strategy wherein SSRF is performed while on VV-ECMO. Improving chest stability and pulmonary mechanics with SSRF allowed for safe transition off VV-ECMO and achieved a favorable long-term outcome.


Assuntos
Oxigenação por Membrana Extracorpórea , Tórax Fundido , Fraturas das Costelas , Traumatismos Torácicos , Ferimentos não Penetrantes , Humanos , Fraturas das Costelas/complicações , Fraturas das Costelas/cirurgia , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/cirurgia , Tórax Fundido/etiologia , Tórax Fundido/cirurgia , Estudos Retrospectivos
4.
J Shoulder Elbow Surg ; 33(1): 73-81, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37379964

RESUMO

BACKGROUND: Instability after reverse shoulder arthroplasty (RSA) is one of the most frequent complications and remains a clinical challenge. Current evidence is limited by small sample size, single-center, or single-implant methodologies that limit generalizability. We sought to determine the incidence and patient-related risk factors for dislocation after RSA, using a large, multicenter cohort with varying implants. METHODS: A retrospective, multicenter study was performed involving 15 institutions and 24 American Shoulder and Elbow Surgeons members across the United States. Inclusion criteria consisted of patients undergoing primary or revision RSA between January 2013 and June 2019 with minimum 3-month follow-up. All definitions, inclusion criteria, and collected variables were determined using the Delphi method, an iterative survey process involving all primary investigators requiring at least 75% consensus to be considered a final component of the methodology for each study element. Dislocations were defined as complete loss of articulation between the humeral component and the glenosphere and required radiographic confirmation. Binary logistic regression was performed to determine patient predictors of postoperative dislocation after RSA. RESULTS: We identified 6621 patients who met inclusion criteria with a mean follow-up of 19.4 months (range: 3-84 months). The study population was 40% male with an average age of 71.0 years (range: 23-101 years). The rate of dislocation was 2.1% (n = 138) for the whole cohort, 1.6% (n = 99) for primary RSAs, and 6.5% (n = 39) for revision RSAs (P < .001). Dislocations occurred at a median of 7.0 weeks (interquartile range: 3.0-36.0 weeks) after surgery with 23.0% (n = 32) after a trauma. Patients with a primary diagnosis of glenohumeral osteoarthritis with an intact rotator cuff had an overall lower rate of dislocation than patients with other diagnoses (0.8% vs. 2.5%; P < .001). Patient-related factors independently predictive of dislocation, in order of the magnitude of effect, were a history of postoperative subluxations before radiographically confirmed dislocation (odds ratio [OR]: 19.52, P < .001), primary diagnosis of fracture nonunion (OR: 6.53, P < .001), revision arthroplasty (OR: 5.61, P < .001), primary diagnosis of rotator cuff disease (OR: 2.64, P < .001), male sex (OR: 2.21, P < .001), and no subscapularis repair at surgery (OR: 1.95, P = .001). CONCLUSION: The strongest patient-related factors associated with dislocation were a history of postoperative subluxations and having a primary diagnosis of fracture nonunion. Notably, RSAs for osteoarthritis showed lower rates of dislocations than RSAs for rotator cuff disease. These data can be used to optimize patient counseling before RSA, particularly in male patients undergoing revision RSA.


Assuntos
Artroplastia do Ombro , Luxações Articulares , Osteoartrite , Articulação do Ombro , Humanos , Masculino , Idoso , Feminino , Artroplastia do Ombro/efeitos adversos , Artroplastia do Ombro/métodos , Articulação do Ombro/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Osteoartrite/cirurgia , Luxações Articulares/cirurgia , Amplitude de Movimento Articular
5.
J Shoulder Elbow Surg ; 32(12): 2483-2492, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37330167

RESUMO

BACKGROUND: Both patient and implant related variables have been implicated in the incidence of acromial (ASF) and scapular spine fractures (SSF) following reverse shoulder arthroplasty (RSA); however, previous studies have not characterized nor differentiated risk profiles for varying indications including primary glenohumeral arthritis with intact rotator cuff (GHOA), rotator cuff arthropathy (CTA), and massive irreparable rotator cuff tear (MCT). The purpose of this study was to determine patient factors predictive of cumulative ASF/SSF risk for varying preoperative diagnosis and rotator cuff status. METHODS: Patients consecutively receiving RSA between January 2013 and June 2019 from 15 institutions comprising 24 members of the American Shoulder and Elbow Surgeons (ASES) with primary, preoperative diagnoses of GHOA, CTA and MCT were included for study. Inclusion criteria, definitions, and inclusion of patient factors in a multivariate model to predict cumulative risk of ASF/SSF were determined through an iterative Delphi process. The CTA and MCT groups were combined for analysis. Consensus was defined as greater than 75% agreement amongst contributors. Only ASF/SSF confirmed by clinical and radiographic correlation were included for analysis. RESULTS: Our study cohort included 4764 patients with preoperative diagnoses of GHOA, CTA, or MCT with minimum follow-up of 3 months (range: 3-84). The incidence of cumulative stress fracture was 4.1% (n = 196). The incidence of stress fracture in the GHOA cohort was 2.1% (n = 34/1637) compared to 5.2% (n = 162/3127) (P < .001) in the CTA/MCT cohort. Presence of inflammatory arthritis (odds ratio [OR] 2.90, 95% confidence interval [CI] 1.08-7.78; P = .035) was the sole predictive factor of stress fractures in GHOA, compared with inflammatory arthritis (OR 1.86, 95% CI 1.19-2.89; P = .016), female sex (OR 1.81, 95% CI 1.20-2.72; P = .007), and osteoporosis (OR 1.56, 95% CI 1.02-2.37; P = .003) in the CTA/MCT cohort. CONCLUSION: Preoperative diagnosis of GHOA has a different risk profile for developing stress fractures after RSA than patients with CTA/MCT. Though rotator cuff integrity is likely protective against ASF/SSF, approximately 1/46 patients receiving RSA with primary GHOA will have this complication, primarily influenced by a history of inflammatory arthritis. Understanding risk profiles of patients undergoing RSA by varying diagnosis is important in counseling, expectation management, and treatment by surgeons.


Assuntos
Artrite , Artroplastia do Ombro , Fraturas de Estresse , Lesões do Manguito Rotador , Articulação do Ombro , Feminino , Humanos , Artrite/cirurgia , Artroplastia do Ombro/efeitos adversos , Fraturas de Estresse/diagnóstico por imagem , Fraturas de Estresse/etiologia , Amplitude de Movimento Articular , Estudos Retrospectivos , Fatores de Risco , Lesões do Manguito Rotador/complicações , Lesões do Manguito Rotador/diagnóstico por imagem , Lesões do Manguito Rotador/cirurgia , Escápula/diagnóstico por imagem , Escápula/cirurgia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia , Resultado do Tratamento , Masculino
6.
Am Surg ; 89(6): 2468-2475, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35575235

RESUMO

BACKGROUND: Resuscitative thoracotomy and clamshell thoracotomy are performed in the setting of traumatic arrest with the intent of controlling hemorrhage, relieving tamponade, and providing open chest cardiopulmonary resuscitation. Historically, return of spontaneous circulation rates for penetrating traumatic arrest as well as out of hospital survival have been reported as low as 40% and 10%. Vascular access can be challenging in patients who have undergone a traumatic arrest and can be a limiting step to effective resuscitation. Atrial cannulation is a well-established surgical technique in cardiac surgery. Herein, we present a case series detailing our application of this technique in the context of acute trauma resuscitation during clamshell thoracotomy for traumatic arrest in the emergency department. METHODS: A retrospective case series of atrial cannulation during traumatic arrest was conducted in Charlotte, NC at Carolinas Medical Center an urban level 1 trauma center. RESULTS: The mean rate of return of spontaneous circulation in our series, 60%, was greater than previously published upper limit of return of spontaneous circulation for penetrating causes of traumatic arrest. DISCUSSION: Intravenous access can be difficult to establish in the hypovolemic and exsanguinating patient. Traditional methods of vascular access may be insufficient in the setting of central vascular injury. Atrial appendage cannulation during atrial cannulation is a quick and reliable technique to achieve vascular access that employs common methods from cardiac surgery to improve resuscitation of traumatic arrest.


Assuntos
Fibrilação Atrial , Reanimação Cardiopulmonar , Humanos , Estudos Retrospectivos , Toracotomia/métodos , Ressuscitação/métodos , Cateterismo
7.
Am J Surg ; 224(6): 1409-1416, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36372581

RESUMO

BACKGROUND: The aim of this study was to evaluate the impact of the COVID-19 pandemic on volume and outcomes of Acute Care Surgery patients, and we hypothesized that inpatient mortality would increase due to COVID+ and resource constraints. METHODS: An American College of Surgeons verified Level I Trauma Center's trauma and operative emergency general surgery (EGS) registries were queried for all patients from Jan. 2019 to Dec. 2020. April 1st, 2020, was the demarcation date for pre- and during COVID pandemic. Primary outcome was inpatient mortality. RESULTS: There were 14,460 trauma and 3091 EGS patients, and month-over-month volumes of both remained similar (p > 0.05). Blunt trauma decreased by 7.4% and penetrating increased by 31%, with a concomitant 25% increase in initial operative management (p < 0.001). Despite this, trauma (3.7%) and EGS (2.9-3.0%) mortality rates remained stable which was confirmed on multivariate analysis; p > 0.05. COVID + mortality was 8.8% and 3.7% in trauma and EGS patients, respectively. CONCLUSION: Acute Care Surgeons provided high quality care to trauma and EGS patients during the pandemic without allowing excess mortality despite many hardships and resource constraints.


Assuntos
COVID-19 , Cirurgia Geral , Procedimentos Cirúrgicos Operatórios , Humanos , Centros de Traumatologia , Pandemias , Emergências , COVID-19/epidemiologia , Cuidados Críticos , Mortalidade Hospitalar , Estudos Retrospectivos
8.
Am J Surg ; 223(2): 410-416, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33814108

RESUMO

BACKGROUND: Surgical stabilization of rib fractures (SSRF) has been correlated with improved outcomes, including decreased length of stay (LOS). We hypothesized that an SSRF consultation service would increase the frequency of SSRF and improve outcomes. METHODS: A prospective observational study was performed to compare outcomes before and after implementing an SSRF service. Primary outcome was time from admission to surgery; secondary outcomes included LOS, mortality and morphine milligram equivalents (MME) prescribed at discharge. RESULTS: 1865 patients met consultation criteria and 128 patients underwent SSRF. Mortality decreased (6.3% vs. 3%) and patients were prescribed fewer MME at discharge (328 MME vs. 124 MME) following implementation. For the operative cohort, time from admission to surgery decreased by 1.72 days and ICU LOS decreased by 2.6 days. CONCLUSION: Establishment of an SSRF service provides a mechanism to maximize capture and evaluation of operative candidates, provide earlier intervention, and improve patient outcomes. Additional study to determine which elements and techniques are most beneficial is warranted. LEVEL OF EVIDENCE: III.


Assuntos
Fraturas das Costelas , Hospitalização , Humanos , Tempo de Internação , Encaminhamento e Consulta , Estudos Retrospectivos , Fraturas das Costelas/complicações , Fraturas das Costelas/cirurgia , Resultado do Tratamento
9.
Frontline Gastroenterol ; 12(6): 451-460, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712462

RESUMO

INTRODUCTION: The 2017 Joint Advisory Group on Gastrointestinal (GI) Endoscopy (JAG) census highlighted the pressure endoscopy services were under in meeting national targets and the factors behind this. In 2019, JAG conducted a further national census of endoscopy services to understand trends in activity, workforce and waiting time targets. METHODS: In April 2019, the census was sent to all eligible JAG-registered services. Collated data were analysed through various statistical methods. A further comparative dataset was created using available submissions from the 2017 census matched to services in the current census. RESULTS: There was a 68% response rate (322/471). There has been a 12%-15% increase in activity across all GI procedures with largest increases in bowel cancer screening. Fewer services are meeting waiting time targets compared with 2017, with endoscopist, nursing and physical capacity cited as the main reasons. Services are striving to improve capacity: 80% of services have an agreed business plan to meet capacity and the number using insourcing has increased from 13% to 20%. The workforce has increased, with endoscopist numbers increasing by 15%, nurses and allied health professionals by 14% and clerical staff by 30%. CONCLUSIONS: The 2019 JAG census is the most recent and extensive survey of UK endoscopy services. There is a clear trend of increasing activity with fewer services able to meet national waiting time targets than 2 years ago. Services have increased their workforce and improved planning to stem the tide but there remains a continued pressure to deliver high quality, safe endoscopy. In light of the COVID-19 pandemic, JAG recognises that these pressures will be severely exacerbated and waiting time targets for accreditation will need adjustment and tolerance during the evolution and recovery from the pandemic.

10.
Cochrane Database Syst Rev ; 3: CD010383, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33734432

RESUMO

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation positive (M+) non-small cell lung cancer (NSCLC) is an important subtype of lung cancer comprising 10% to 15% of non-squamous tumours. This subtype is more common in women than men, is less associated with smoking, but occurs at a younger age than sporadic tumours. OBJECTIVES: To assess the clinical effectiveness of single-agent or combination EGFR therapies used in the first-line treatment of people with locally advanced or metastatic EGFR M+ NSCLC compared with other cytotoxic chemotherapy (CTX) agents used alone or in combination, or best supportive care (BSC). The primary outcomes were overall survival and progression-free survival. Secondary outcomes included response rate, symptom palliation, toxicity, and health-related quality of life. SEARCH METHODS: We conducted electronic searches of the Cochrane Register of Controlled Trials (CENTRAL) (2020, Issue 7), MEDLINE (1946 to 27th July 2020), Embase (1980 to 27th July 2020), and ISI Web of Science (1899 to 27th July 2020). We also searched the conference abstracts of the American Society for Clinical Oncology and the European Society for Medical Oncology (July 2020); Evidence Review Group submissions to the National Institute for Health and Care Excellence; and the reference lists of retrieved articles. SELECTION CRITERIA: Parallel-group randomised controlled trials comparing EGFR-targeted agents (alone or in combination with cytotoxic agents or BSC) with cytotoxic chemotherapy (single or doublet) or BSC in chemotherapy-naive patients with locally advanced or metastatic (stage IIIB or IV) EGFR M+ NSCLC unsuitable for treatment with curative intent. DATA COLLECTION AND ANALYSIS: Two review authors independently identified articles, extracted data, and carried out the 'Risk of bias' assessment. We conducted meta-analyses using a fixed-effect model unless there was substantial heterogeneity, in which case we also performed a random-effects analysis as a sensitivity analysis. MAIN RESULTS: Twenty-two trials met the inclusion criteria. Ten of these exclusively recruited people with EGFR M+ NSCLC; the remainder recruited a mixed population and reported results for people with EGFR M+ NSCLC as subgroup analyses. The number of participants with EGFR M+ tumours totalled 3023, of whom approximately 2563 were of Asian origin. Overall survival (OS) data showed inconsistent results between the included trials that compared EGFR-targeted treatments against cytotoxic chemotherapy or placebo. Erlotinib was used in eight trials, gefitinib in nine trials, afatinib in two trials, cetuximab in two trials, and icotinib in one trial. The findings of FASTACT 2 suggested a clinical benefit for OS for participants treated with erlotinib plus cytotoxic chemotherapy when compared to cytotoxic chemotherapy alone, as did the Han 2017 trial for gefitinib plus cytotoxic chemotherapy, but both results were based on a small number of participants (n = 97 and 122, respectively). For progression-free survival (PFS), a pooled analysis of four trials showed evidence of clinical benefit for erlotinib compared with cytotoxic chemotherapy (hazard ratio (HR) 0.31; 95% confidence interval (CI) 0.25 to 0.39 ; 583 participants ; high-certainty evidence). A pooled analysis of two trials of gefitinib versus paclitaxel plus carboplatin showed evidence of clinical benefit for PFS for gefitinib (HR 0.39; 95% CI 0.32 to 0.48 ; 491 participants high-certainty evidence), and a pooled analysis of two trials of gefitinib versus pemetrexed plus carboplatin with pemetrexed maintenance also showed evidence of clinical benefit for PFS for gefitinib (HR 0.59; 95% CI 0.46 to 0.74, 371 participants ; moderate-certainty evidence). Afatinib showed evidence of clinical benefit for PFS when compared with chemotherapy in a pooled analysis of two trials (HR 0.42; 95% CI 0.34 to 0.53, 709 participants high-certainty evidence). All but one small trial showed a corresponding improvement in response rate with tyrosine-kinase inhibitor (TKI) compared to chemotherapy. Commonly reported grade 3/4 adverse events associated with afatinib, erlotinib, gefitinib and icotinib monotherapy were rash and diarrhoea. Myelosuppression was consistently worse in the chemotherapy arms; fatigue and anorexia were also associated with some chemotherapies. Seven trials reported on health-related quality of life and symptom improvement using different methodologies. For each of erlotinib, gefitinib, and afatinib, two trials showed improvement in one or more indices for the TKI compared to chemotherapy. The quality of evidence was high for the comparisons of erlotinib and gefitinib with cytotoxic chemotherapy and for the comparison of afatinib with cytotoxic chemotherapy. AUTHORS' CONCLUSIONS: Erlotinib, gefitinib, afatinib and icotinib are all active agents in EGFR M+ NSCLC patients, and demonstrate an increased tumour response rate and prolonged PFS compared to cytotoxic chemotherapy. We found a beneficial effect of the TKI compared to cytotoxic chemotherapy in adverse effect and health-related quality of life. We found limited evidence for increased OS for the TKI when compared with standard chemotherapy, but the majority of the included trials allowed participants to switch treatments on disease progression, which will have a confounding effect on any OS analysis. Single agent-TKI remains the standard of care and the benefit of combining a TKI and chemotherapy remains uncertain as the evidence is based on small patient numbers. Cytotoxic chemotherapy is less effective in EGFR M+ NSCLC than erlotinib, gefitinib, afatinib or icotinib and is associated with greater toxicity. There are no data supporting the use of monoclonal antibody therapy. Icotinib is not available outside China.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Afatinib/efeitos adversos , Afatinib/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Viés , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cetuximab/efeitos adversos , Cetuximab/uso terapêutico , Éteres de Coroa/efeitos adversos , Éteres de Coroa/uso terapêutico , Cloridrato de Erlotinib/efeitos adversos , Cloridrato de Erlotinib/uso terapêutico , Feminino , Gefitinibe/efeitos adversos , Gefitinibe/uso terapêutico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Pemetrexede/uso terapêutico , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Qualidade de Vida , Quinazolinas/efeitos adversos , Quinazolinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Clin Cancer Res ; 27(7): 2061-2073, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33355204

RESUMO

PURPOSE: Targeting RAF for antitumor therapy in RAS-mutant tumors holds promise. Herein, we describe in detail novel properties of the type II RAF inhibitor, LXH254. EXPERIMENTAL DESIGN: LXH254 was profiled in biochemical, in vitro, and in vivo assays, including examining the activities of the drug in a large panel of cancer-derived cell lines and a comprehensive set of in vivo models. In addition, activity of LXH254 was assessed in cells where different sets of RAF paralogs were ablated, or that expressed kinase-impaired and dimer-deficient variants of ARAF. RESULTS: We describe an unexpected paralog selectivity of LXH254, which is able to potently inhibit BRAF and CRAF, but has less activity against ARAF. LXH254 was active in models harboring BRAF alterations, including atypical BRAF alterations coexpressed with mutant K/NRAS, and NRAS mutants, but had only modest activity in KRAS mutants. In RAS-mutant lines, loss of ARAF, but not BRAF or CRAF, sensitized cells to LXH254. ARAF-mediated resistance to LXH254 required both kinase function and dimerization. Higher concentrations of LXH254 were required to inhibit signaling in RAS-mutant cells expressing only ARAF relative to BRAF or CRAF. Moreover, specifically in cells expressing only ARAF, LXH254 caused paradoxical activation of MAPK signaling in a manner similar to dabrafenib. Finally, in vivo, LXH254 drove complete regressions of isogenic variants of RAS-mutant cells lacking ARAF expression, while parental lines were only modestly sensitive. CONCLUSIONS: LXH254 is a novel RAF inhibitor, which is able to inhibit dimerized BRAF and CRAF, as well as monomeric BRAF, while largely sparing ARAF.


Assuntos
Sistema de Sinalização das MAP Quinases/fisiologia , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-raf/antagonistas & inibidores , Animais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Células HCT116 , Humanos , Camundongos , Mutação , Neoplasias/genética , Inibidores de Proteínas Quinases/farmacologia , Multimerização Proteica , Proteínas Proto-Oncogênicas B-raf/química , Proteínas Proto-Oncogênicas c-raf/química , Proteínas Proto-Oncogênicas p21(ras)/genética
12.
Cancer Res ; 80(19): 4278-4287, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32747364

RESUMO

Advanced ovarian cancers are a leading cause of cancer-related death in women and are currently treated with surgery and chemotherapy. This standard of care is often temporarily successful but exhibits a high rate of relapse, after which, treatment options are few. Here we investigate whether biomarker-guided use of multiple targeted therapies, including small molecules and antibody-drug conjugates, is a viable alternative. A panel of patient-derived ovarian cancer xenografts (PDX), similar in genetics and chemotherapy responsiveness to human tumors, was exposed to 21 monotherapies and combination therapies. Three monotherapies and one combination were found to be active in different subsets of PDX. Analysis of gene expression data identified biomarkers associated with responsiveness to each of the three targeted therapies, none of which directly inhibits an oncogenic driver. While no single treatment had as high a response rate as chemotherapy, nearly 90% of PDXs were eligible for and responded to at least one biomarker-guided treatment, including tumors resistant to standard chemotherapy. The distribution of biomarker positivity in The Cancer Genome Atlas data suggests the potential for a similar precision approach in human patients. SIGNIFICANCE: This study exploits a panel of patient-derived xenografts to demonstrate that most ovarian tumors can be matched to effective biomarker-guided treatments.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Biomarcadores Tumorais/genética , Neoplasias Ovarianas/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Antineoplásicos/farmacologia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Terapia de Alvo Molecular/métodos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Medicina de Precisão , Estudo de Prova de Conceito
13.
J Surg Educ ; 77(6): 1465-1472, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32646812

RESUMO

OBJECTIVE: After COVID-19 rendered in-person meetings for national societies impossible in the spring of 2020, the leadership of the Association of Program Directors in Surgery (APDS) innovated via a virtual format in order to hold its national meeting. DESIGN: APDS leadership pre-emptively considered factors that would be important to attendees including cost, value, time, professional commitments, education, sharing of relevant and current information, and networking. SETTING: The meeting was conducted using a variety of virtual formats including a web portal for entry, pre-ecorded poster and oral presentations on the APDS website, interactive panels via a web conferencing platform, and livestreaming. PARTICIPANTS: There were 298 registrants for the national meeting of the APDS, and 59 participants in the New Program Directors Workshop. The registrants and participants comprised medical students, residents, associate program directors, program directors, and others involved in surgical education nationally. RESULTS: There was no significant difference detected for high levels of participant satisfaction between 2019 and 2020 for the following items: overall program rating, topics and content meeting stated objectives, relevant content to educational needs, educational format conducive to learning, and agreement that the program will improve competence, performance, communication skills, patient outcomes, or processes of care/healthcare system performance. CONCLUSIONS: A virtual format for a national society meeting can provide education, engagement, and community, and the lessons learned by the APDS in the process can be used by other societies for utilization and further improvement.


Assuntos
Congressos como Assunto/organização & administração , Cirurgia Geral/educação , Internet , COVID-19/epidemiologia , Humanos , Pandemias , Distanciamento Físico , SARS-CoV-2 , Sociedades Médicas , Estados Unidos/epidemiologia
14.
J Surg Educ ; 77(6): e201-e208, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32703741

RESUMO

OBJECTIVE: Mobile phone-based paging systems have become increasingly common for communication within hospitals. Surgical interns receive the most pages, and our aim is to objectively quantify and evaluate this burden to allow for targeted improvement. DESIGN: We performed a retrospective review of our institutions mobile phone-based paging system data (Halo Health, Cincinnati, OH) from July 2019 to September 2019. SETTING: Carolinas Medical Center, Charlotte, NC, USA. PARTICIPANTS: Seven general surgery postgraduate year (PGY) 1 residents. RESULTS: Forty-five thousand eight hundred and one messages met inclusion criteria, with 27,397 messages received and 18,404 sent. PGY 1 residents each received an average of 48 ± 41 messages per shift, with 8 ± 17 messages per day while off-duty. Night shifts averaged more messages than day shifts (80 ± 39 vs 38 ± 32, p < 0.0001), and had more shifts with high message volume (30% vs 11%, p = 0.0005). Evaluating the total number of messages received per minute of the day, the largest number of high-volume message intervals (21) occurred during patient handoff (1700-1900 hours). Most messages were sent by nursing staff (55.8%), followed by medical providers (38.2%). CONCLUSIONS: PGY 1 residents receive a large number of pages using a messaging application, with many occurring at critical times. Residents received a higher volume of pages on night shifts, during patient handoff, and while off-duty. Since most pages are from nursing staff, targeted education and preventative actions may help decrease the volume of pages during these critical times.


Assuntos
Telefone Celular , Cirurgia Geral , Internato e Residência , Transferência da Responsabilidade pelo Paciente , Envio de Mensagens de Texto , Cirurgia Geral/educação , Pessoal de Saúde , Humanos , Estudos Retrospectivos
15.
Ann Surg ; 272(3): 469-478, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32657946

RESUMO

BACKGROUND AND OBJECTIVE: Reltecimod, a CD 28 T-lymphocyte receptor mimetic, inhibits T-cell stimulation by an array of bacterial pathogens. A previous phase 2 trial demonstrated improved resolution of organ dysfunction after NSTI. We hypothesized that early administration of reltecimod would improve outcome in severe NSTI. METHODS: Randomized, double-blind, placebo-controlled trial of single dose reltecimod (0.5 mg/kg) administered within 6 hours of NSTI diagnosis at 65 of 93 study sites. Inclusion: surgical confirmation of NSTI and organ dysfunction [modified Sequential Organ Failure Assessment Score (mSOFA) score ≥3]. Primary analysis was modified Intent-to-Treat (mITT), responder analysis using a previously validated composite endpoint, necrotizing infection clinical composite endpoint, defined as: alive at day 28, ≤3 debridements, no amputation beyond first operation, and day 14 mSOFA ≤1 with ≥3 point reduction (organ dysfunction resolution). A prespecified, per protocol (PP) analysis excluded 17 patients with major protocol violations before unblinding. RESULTS: Two hundred ninety patients were enrolled, mITT (Reltecimod 142, Placebo 148): mean age 55 ±â€Š15 years, 60% male, 42.4% diabetic, 28.6% perineal infection, screening mSOFA mean 5.5 ±â€Š2.4. Twenty-eight-day mortality was 15% in both groups. mITT necrotizing infection clinical composite endpoint success was 48.6% reltecimod versus 39.9% placebo, P = 0.135 and PP was 54.3% reltecimod versus 40.3% placebo, P = 0.021. Resolution of organ dysfunction was 65.1% reltecimod versus 52.6% placebo, P = 0.041, mITT and 70.9% versus 53.4%, P = 0.005, PP. CONCLUSION: Early administration of reltecimod in severe NSTI resulted in a significant improvement in the primary composite endpoint in the PP population but not in the mITT population. Reltecimod was associated with improved resolution of organ dysfunction and hospital discharge status.


Assuntos
Antígenos CD28/administração & dosagem , Desbridamento/métodos , Fasciite Necrosante/terapia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
16.
J Surg Educ ; 77(6): e237-e244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32654998

RESUMO

OBJECTIVE: Electronic health records (EHRs) are an integral part of the medical system and are used in all aspects of care. Despite multiple advantages of an EHR, concerns exist over the amount of time that residents spend on computers rather than in direct patient care. This study aims to quantify the time a general surgery resident spends on the EHR during their training. DESIGN/PARTICIPANTS: Active usage time data from our institution's EHR were extracted for 34 unique general surgery residents from October 2014 to June 2019. Career time on the EHR was calculated and a "work month" was defined as a 4-week period of 80 hours per week. SETTING: Carolinas Medical Center, Charlotte, NC. RESULTS: Total career EHR usage for a general surgery resident was 2512 continuous hours, corresponding to 31.4 work weeks or 7.9 work months. In total, 7133 charts were opened with an average of 20.5 minutes on the EHR per patient chart. Career time spent on specific tasks included: chart review 10.6 work weeks, documentation 10.4 work weeks, and order entry 5.4 work weeks. The total number of orders entered were 57,739 and total number of documents created were 9222. EHR time in all aspects, patient charts opened, documents created, and number of orders entered decreased as postgraduate year increased. CONCLUSIONS: This is the first study quantifying the total time a general surgery resident spends on the EHR during their clinical training. Total EHR time equated to nearly 8 work months. General surgery residents spend considerable time on the EHR and this underscores the importance of implementing methods to improve EHR efficiency and maximize time for clinical training.


Assuntos
Cirurgia Geral , Internato e Residência , Documentação , Registros Eletrônicos de Saúde , Cirurgia Geral/educação , Humanos , Fatores de Tempo
17.
J Surg Educ ; 77(5): 1056-1062, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32305335

RESUMO

OBJECTIVE: Time spent on the Electronic Health Record (EHR) influences surgical residents' clinical availability. Objective data assessing EHR usage among surgical residents are lacking and necessary. DESIGN/PARTICIPANTS: Active EHR usage data for 70 surgical residents were collected from April 2015 through April 2016. Active EHR usage was defined as more than 15 keystrokes, or 3 mouse clicks, or 1700 "mouse miles" per minute. Usage data of different specialties, interns (PGY 1), juniors (PGY 2, 3), and seniors (PGY 4, 5) were compared. SETTING: Carolinas Medical Center, Charlotte, NC. RESULTS: Interns spent more time than juniors on total EHR activities per day (134.5 vs 105.5 minutes, p < 0.001) and juniors spent more time per day than seniors (105.5 vs 78.7 minutes, p < 0.001). Among different EHR activities per patient, interns spent greater time than juniors on chart review (8.1 vs 6.2 minutes, p < 0.001), documentation (9.0 vs 6.5 minutes, p < 0.001), and orders (3.6 vs 3.0 minutes, p < 0.001). Juniors spent the same time as seniors on chart review (6.2 vs 6.5 minutes, p = 0.2). Juniors spent more time than seniors on documentation (6.5 vs 5.2 minutes, p < 0.001) and orders (3.0 vs 2.7 minutes, p < 0.05). Comparing EHR activities per patient among different specialties, General Surgery residents spent more time than Orthopedic residents on total EHR time (19.9 vs 15.9 minutes, p < 0.001), chart review (6.8 vs 5.7 minutes, p < 0.001), documentation (6.3 vs 5.6 minutes, p < 0.001), and orders (3.6 vs 2.6 minutes, p < 0.001). General Surgery residents spent less time than OB/GYN residents on total EHR time (19.9 vs 22 minutes, p < 0.01), chart review (6.8 vs. 7.5 minutes, p < 0.05), and documentation (6.3 vs 7.6 minutes, p < 0.001), but more time on orders (3.6 vs 2.9 minutes, p < 0.001). CONCLUSIONS: These are the first reported objective findings on surgical resident use of the EHR and may provide an opportunity for improvement in EHR training and usage.


Assuntos
Cirurgia Geral , Internato e Residência , Documentação , Registros Eletrônicos de Saúde , Cirurgia Geral/educação , Humanos , Fatores de Tempo
18.
J Am Coll Surg ; 230(6): 1080-1091.e3, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32240770

RESUMO

The novel coronavirus (COVID-19) was first diagnosed in Wuhan, China in December 2019 and has now spread throughout the world, being verified by the World Health Organization as a pandemic on March 11. This had led to the calling of a national emergency on March 13 in the US. Many hospitals, healthcare networks, and specifically, departments of surgery, are asking the same questions about how to cope and plan for surge capacity, personnel attrition, novel infrastructure utilization, and resource exhaustion. Herein, we present a tiered plan for surgical department planning based on incident command levels. This includes acute care surgeon deployment (given their critical care training and vertically integrated position in the hospital), recommended infrastructure and transfer utilization, triage principles, and faculty, resident, and advanced care practitioner deployment.


Assuntos
Infecções por Coronavirus/epidemiologia , Pneumonia Viral/epidemiologia , Centro Cirúrgico Hospitalar/organização & administração , Betacoronavirus , COVID-19 , Procedimentos Cirúrgicos Eletivos , Recursos em Saúde/provisão & distribuição , Humanos , Organizações sem Fins Lucrativos , Pandemias , Recursos Humanos em Hospital , SARS-CoV-2 , Sudeste dos Estados Unidos , Capacidade de Resposta ante Emergências , Telemedicina , Triagem
19.
J Am Coll Surg ; 231(1): 54-58, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32156654

RESUMO

BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) requires diversity in residency. The self-identified race/ethnicities of general surgery applicants, residents, and core teaching faculty were assessed to evaluate underrepresented minority (URM) representation in surgery residency programs and to determine the impact of URM faculty and residents on URM applicants' selection for interview or match. STUDY DESIGN: Data from the 2018 application cycle were collated for 10 general surgery programs. Applicants without a self-identified race/ethnicity were excluded. URMs were defined as those identifying as black/African American, Hispanic/Latino/of Spanish origin, and American Indian/Alaskan Native/Native Hawaiian/Pacific Islander-Samoan. Statistical analyses included chi-square tests and a multivariate model. RESULTS: Ten surgery residency programs received 9,143 applications from 3,067 unique applicants. Applications from white, Asian, Hispanic/Latino, black/African American, and American Indian applicants constituted 66%, 19%, 8%, 7% and 1%, respectively, of those applications selected to interview and 66%, 13%, 11%, 8%, and 2%, respectively, of applications resulting in a match. Among programs' 272 core faculty and 318 current residents, 10% and 21%, respectively, were identified as URMs. As faculty diversity increased, there was no difference in selection to interview for URM (odds ratio [OR] 0.83; 95% CI 0.54 to 1.28, per 10% increase in faculty diversity) or non-URM applicants (OR 0.68; 95% CI 0.57 to 0.81). Similarly, greater URM representation among current residents did not affect the likelihood of being selected for an interview for URM (OR 1.20; 95%CI 0.90 to 1.61) vs non-URM applicants (OR 1.28; 95% CI 1.13 to 1.45). Current resident and faculty URM representation was correlated (r = 0.8; p = 0.005). CONCLUSIONS: Programs with a greater proportion of URM core faculty or residents did not select a greater proportion of URM applicants for interview. However, core faculty and resident racial diversity were correlated. Recruitment of racially/ethnically diverse trainees and faculty will require ongoing analysis to develop effective recruitment strategies.


Assuntos
Educação de Pós-Graduação em Medicina/métodos , Etnicidade , Docentes de Medicina , Cirurgia Geral/educação , Internato e Residência/métodos , Grupos Minoritários , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos
20.
Toxicol Sci ; 174(1): 16-24, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31808915

RESUMO

1,3-Dichloropropene (1,3-D) showed a statistically increased incidence of bronchioloalveolar adenomas in male B6C3F1 mice at 60 ppm air concentration during previous chronic inhalation testing. No tumors were observed in female mice, nor in either sex of F344 rats up to 60 ppm, the highest dose tested. Therefore, to understand if lung tumors observed in high dose male mice are due to saturation of metabolic clearance, the linearity of 1,3-D concentrations in mouse blood was investigated on day 15 of repeated nose-only inhalation exposure to 0, 10, 20, 40, 60, 90, and 120 ppm (6 h/d, 7 d/week). Additional groups were included at 20, 60, and 120 ppm for blood collection at 1.5 and 3 h of exposure and up to 25 or 40 min post-exposure to determine area-under-the-curve. The data provide multiple lines of evidence that systemic exposures to 1,3-D in the mouse become nonlinear at inhalation exposure levels of 30 ppm or above. A reduction in minute volume occurred at the highest exposure concentration. The glutathione (GSH)-dependent metabolism of 1,3-D results in significant depletion of GSH at repeated exposure levels of 30 ppm and above. This loss of GSH results in decreased metabolic clearance of this test material, with a concomitant increase of the 1,3-D isomers in circulating blood at exposure concentrations ≥30 ppm. Shifts in the ratio of cis- and trans-1,3-D also support nonlinear toxicokinetics well below 60 ppm. Based on this data, a kinetically derived maximum dose for 1,3-D in mice for repeated exposures should be at or below 30 ppm. These results support non-relevance of 1,3-D-induced benign pulmonary tumorigenicity in mice for human health risk assessment.


Assuntos
Adenoma/induzido quimicamente , Compostos Alílicos/toxicidade , Carcinógenos/toxicidade , Hidrocarbonetos Clorados/toxicidade , Neoplasias Pulmonares/induzido quimicamente , Pulmão/efeitos dos fármacos , Modelos Teóricos , Adenoma/metabolismo , Compostos Alílicos/sangue , Compostos Alílicos/farmacocinética , Animais , Carcinógenos/metabolismo , Carcinógenos/farmacocinética , Transformação Celular Neoplásica/induzido quimicamente , Transformação Celular Neoplásica/metabolismo , Relação Dose-Resposta a Droga , Feminino , Hidrocarbonetos Clorados/sangue , Hidrocarbonetos Clorados/farmacocinética , Exposição por Inalação , Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Dinâmica não Linear , Ratos Endogâmicos F344 , Taxa Respiratória/efeitos dos fármacos , Medição de Risco , Fatores Sexuais , Distribuição Tecidual , Toxicocinética
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