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Drug sensitivity and resistance testing on diagnostic leukemia samples should provide important functional information to guide actionable target and biomarker discovery. We provide proof of concept data by profiling 60 drugs on 68 acute lymphoblastic leukemia (ALL) samples mostly from resistant disease in cocultures of bone marrow stromal cells. Patient-derived xenografts retained the original pattern of mutations found in the matched patient material. Stromal coculture did not prevent leukemia cell cycle activity, but a specific sensitivity profile to cell cycle-related drugs identified samples with higher cell proliferation both in vitro and in vivo as leukemia xenografts. In patients with refractory relapses, individual patterns of marked drug resistance and exceptional responses to new agents of immediate clinical relevance were detected. The BCL2-inhibitor venetoclax was highly active below 10 nM in B-cell precursor ALL (BCP-ALL) subsets, including MLL-AF4 and TCF3-HLF ALL, and in some T-cell ALLs (T-ALLs), predicting in vivo activity as a single agent and in combination with dexamethasone and vincristine. Unexpected sensitivity to dasatinib with half maximal inhibitory concentration values below 20 nM was detected in 2 independent T-ALL cohorts, which correlated with similar cytotoxic activity of the SRC inhibitor KX2-391 and inhibition of SRC phosphorylation. A patient with refractory T-ALL was treated with dasatinib on the basis of drug profiling information and achieved a 5-month remission. Thus, drug profiling captures disease-relevant features and unexpected sensitivity to relevant drugs, which warrants further exploration of this functional assay in the context of clinical trials to develop drug repurposing strategies for patients with urgent medical needs.
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Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Células Cultivadas , Técnicas de Cocultura , Xenoenxertos , Humanos , Células-Tronco Mesenquimais/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologiaRESUMO
BACKGROUND: Epiphysiodesis is well-established surgical treatment for the management of leg length discrepancy (LLD) in children; however, a variety of complications may occur. This study evaluates the nature, rate, and potential risk factors of complications associated with epiphysiodesis in a large patient population treated in 1 institution. METHODS: We evaluated the medical and radiographic records of 863 children who had lower extremity epiphysiodesis to manage LLD between 1980 and 2011. RESULTS: Sixty patients (7.0%) incurred complications of some type. Twenty-three patients (2.7%) had perioperative complications unrelated to physeal growth; all resolved without surgical treatment. These included 2 patients with transient intraoperative complications (laryngospasm and allergic rash), 7 with transient neurological symptoms (5 cutaneous nerve dysesthesia or numbness and 2 peroneal nerve neuropathies), and 14 with postoperative knee stiffness which resolved with therapy. Thirty-seven patients (4.3%) developed physeal growth-related complications, including 6 patients who developed overcorrection of leg length inequality (3 had contralateral epiphysiodesis to prevent overcorrection, while 3 declined), and 31 patients who developed angular deformity and/or continued growth of the physis. Of these 31 patients, 15 had reexploration of the epiphysiodesis site, 6 underwent corrective osteotomy, while in 10, no treatment was undertaken. Compared with patients who did not develop angular deformity, these 31 patients had significantly greater LLD (5.6 vs. 3.7 cm, respectively, P<0.01), were younger (10.7 vs. 11.7 in girls; 12.4 vs. 13.5 in boys; P<0.01), and were more likely to have a congenital etiology for their LLD (P<0.01). CONCLUSIONS: Epiphysiodesis is a safe and effective procedure for the correction of leg length inequality. The rate of complications in this study was 7.0%, the most prevalent being the development of angular deformity. Congenital etiology, younger age, and larger limb length inequalities were risk factors for the development of angular deformity. Both surgeons and families should be aware of nature and rate of complications associated with epiphysiodesis. LEVEL OF EVIDENCE: Level IV.
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Artrodese/efeitos adversos , Epífises/cirurgia , Desigualdade de Membros Inferiores/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Adolescente , Fatores Etários , Artrodese/métodos , Criança , Feminino , Humanos , Desigualdade de Membros Inferiores/diagnóstico por imagem , Masculino , Radiografia , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Fatores de RiscoRESUMO
Tracheoesophageal fistula is uncommon in adults but can cause devastating aspiration events. Herein, we report a unique case of a tracheoesophageal fistula in an adult that presented intraoperatively. The patient did not have any prior history of abdominal or thoracic surgery and was not intubated for a prolonged period of time. The diagnosis, subsequent hospital course, and recommendations for early recognition of this rare condition are discussed.
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PURPOSE: The impact of the COVID-19 pandemic on behavioral issues among those who have completed bariatric surgery (BS) is not well described in ethnically diverse populations. The aim of this study was to compare the impact of COVID-19 lockdown orders and after lockdown orders were lifted on substance use, mental health, and weight-related behaviors among a sample of post-BS adults. MATERIALS AND METHODS: A retrospective medical chart review identified BS patients from one university-based obesity medicine clinic and two BS practices. An online non-anonymous survey was implemented in two phases: during lockdown (April 1-May 31, 2020) and after lockdown orders were lifted (June 1, 2020-September 30, 2020) to obtain information about the COVID-19 pandemic's impact on BS patients. RESULTS: A total of 189 (during lockdown=39, post-lockdown=150) participants (90.4% female, mean age 52.4 years, SD 11.1, 49.8% non-Hispanic White, 30.6% non-Hispanic Black, 16.1% Hispanic) participated. Lockdown participants were more likely to have sleep problems (74.3% vs. 56.1%, P=.039) and feel anxious (82.0% vs. 63.0%, P=.024) versus post-lockdown participants. A majority (83.4%) reported depression in both lockdown/post-lockdown. Post-lockdown participants were more than 20 times more likely to report substance use compared those in lockdown (aOR 20.56, 95% CI 2.66-158.4). CONCLUSIONS AND RELEVANCE: The COVID-19 pandemic is having a substantial negative impact on substance use, mental health, and weight-related health behaviors in diverse BS patients. These findings have important implications for post-BS patient care teams and may suggest the integration of screening tools to identify those at high risk for behavioral health issues.
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Cirurgia Bariátrica , COVID-19 , Obesidade Mórbida , Transtornos Relacionados ao Uso de Substâncias , Adulto , Controle de Doenças Transmissíveis , Feminino , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
OBJECTIVE: To determine the surveillance impact of utilizing a discrete field in structured radiology reports in patients with incidental pancreatic findings. METHODS: We implemented a dictation template containing a discrete structured field element to auto-trigger listing of patients with incidental pancreatic findings on a pancreas clinic registry in the electronic health record. We isolated CT and MRI reports with incidental pancreatic findings over a 24-month period. We stratified patients by presence or absence of the discrete field element in reports (flagged versus unflagged) and evaluated the impact of report flagging on likelihood of clinic follow-up, follow-up imaging, endoscopic ultrasound, surgical intervention, genetics referral, obtaining pathologic diagnosis, and time interval between index imaging to various outcomes. RESULTS: Patients with flagged reports were more likely to be seen or discussed in a pancreas clinic compared with those with unflagged reports (189 of 376, 50.3% versus 79 of 474, 16.7%; P <. 001). Patients with flagged reports were more likely to get follow-up imaging than patients with unflagged reports (188 of 376, 50.0% versus 121 of 474, 25.5%; P < .001) and were more likely to undergo appropriate management of actionable findings compared with patients in the unflagged group (23 of 62, 37.1% versus 28 of 129, 21.7%; P = .036). DISCUSSION: Implementation of a structured discrete field element for reporting of patients with incidental pancreatic findings had positive impact on surveillance measures and can be applied in other organ systems with established surveillance guidelines to standardize patient care.
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Achados Incidentais , Tomografia Computadorizada por Raios X , Humanos , Imageamento por Ressonância Magnética , Pâncreas/diagnóstico por imagem , Estudos Retrospectivos , UltrassonografiaRESUMO
AbstractPellagra is a deficiency of niacin or its amino acid precursor, tryptophan, which presents with the classic four Ds: the characteristic dermatitis, diarrhea, dementia, and eventually death if left untreated. The incidence of pellagra is quite rare presently because of increased awareness and strategies such as vitamin fortification. However, the deficiency is still present in cultures that rely on maize as their primary source of sustenance. We report a recent outbreak in a catchment area in Kasese, Malawi, of 691 cases of pellagra which were successfully treated with niacin supplementation. We present this short report to highlight the importance of educating providers of at-risk populations about this diagnosis and to consider solutions for these populations to prevent further deficiencies.