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1.
J Sci Comput ; 100(2): 52, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966341

RESUMO

We introduce an hp-version discontinuous Galerkin finite element method (DGFEM) for the linear Boltzmann transport problem. A key feature of this new method is that, while offering arbitrary order convergence rates, it may be implemented in an almost identical form to standard multigroup discrete ordinates methods, meaning that solutions can be computed efficiently with high accuracy and in parallel within existing software. This method provides a unified discretisation of the space, angle, and energy domains of the underlying integro-differential equation and naturally incorporates both local mesh and local polynomial degree variation within each of these computational domains. Moreover, general polytopic elements can be handled by the method, enabling efficient discretisations of problems posed on complicated spatial geometries. We study the stability and hp-version a priori error analysis of the proposed method, by deriving suitable hp-approximation estimates together with a novel inf-sup bound. Numerical experiments highlighting the performance of the method for both polyenergetic and monoenergetic problems are presented.

2.
Int J Surg Case Rep ; 111: 108888, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37806030

RESUMO

INTRODUCTION AND IMPORTANCE: Roux-en-Y gastric bypass (RYGB) is one of the two most common weight loss surgeries. Surgical emergencies after gastric bypass can be complicated by devastating events that are often difficult to diagnose and manage. Perforated ulcers are a very rare complication after a RYGB. CASE PRESENTATION: In this report, the diagnosis and surgical management of a 59-year-old immunosuppressed male patient who presented with late perforation of a pre-pyloric ulcer in the gastric remnant after RYGB is presented. The perforation was repaired transversely in a running horizontal mattress fashion and patched with a piece of well-vascularized omentum. CLINICAL DISCUSSION: This case illustrates the potential for gastric remnant ulceration, even a decade after RYGB. A high degree of suspicion for the diagnosis of perforated remnant stomach is required, especially in the absence of pneumoperitoneum and free fluid. Patient-specific factors, such as immunosuppression in this case, may blunt normal physiologic response. CONCLUSION: Considering the location of the ulcer in the pre-pyloric area, we caution that the typical paradigm of marginal ulceration of the gastro-jejunal anastomosis does not always apply when evaluating gastric complications after RYGB.

3.
Ther Adv Chronic Dis ; 13: 20406223221099333, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35620185

RESUMO

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which may lead to uncontrolled immune activation and cytokine response in some. The pattern of pro-inflammatory cytokines is similar to that which has been observed to be involved in rheumatic diseases and target treatments. Viral arthritis is common with a wide variety in spectrum ranging from arthralgia to spurious and chronic arthritis. However, recent studies have demonstrated a correlation with endemic coronaviruses and increased risk of developing rheumatoid arthritis (RA). Cases are being identified that describe a post-COVID reactive; however, to date, no report has been published describing the onset of psoriasis and concomitant development of psoriatic arthritis after COVID-19 infection. We report an interesting case of psoriatic arthritis in a post-COVID-19 infection patient with review of the current literature.

4.
BMJ Case Rep ; 14(8)2021 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344646

RESUMO

De Garengeot hernia is a rare phenomenon describing the migration of the appendix into a femoral hernia sac. Many repair strategies have been described although an open inguinal approach with suture repair is the most common technique. Despite strong evidence that mesh limits recurrence, most forgo mesh use in the presence of appendicitis for fear of contamination. We report a case in a 68-year-old man managed completely with minimally invasive strategies. We performed a staged laparoscopic appendectomy followed by robotic hernia repair with polypropylene mesh. This is the first described two-stage minimally invasive approach and the first report demonstrating the feasibility of robotic hernia repair in the setting of de Garengeot hernia. It is our opinion that using a staged approach may encourage mesh repair by minimising the risk of implant contamination. Furthermore, we believe a fully minimally invasive technique may result in improved outcomes.


Assuntos
Apendicite , Hérnia Femoral , Procedimentos Cirúrgicos Robóticos , Idoso , Apendicectomia , Apendicite/cirurgia , Hérnia Femoral/cirurgia , Herniorrafia , Humanos , Masculino
5.
Math Biosci Eng ; 17(5): 4905-4941, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-33120534

RESUMO

Glioblastomas (GBMs) are the most aggressive primary brain tumours and have no known cure. Each individual tumour comprises multiple sub-populations of genetically-distinct cells that may respond differently to targeted therapies and may contribute to disappointing clinical trial results. Image-localized biopsy techniques allow multiple biopsies to be taken during surgery and provide information that identifies regions where particular sub-populations occur within an individual GBM, thus providing insight into their regional genetic variability. These sub-populations may also interact with one another in a competitive or cooperative manner; it is important to ascertain the nature of these interactions, as they may have implications for responses to targeted therapies. We combine genetic information from biopsies with a mechanistic model of interacting GBM sub-populations to characterise the nature of interactions between two commonly occurring GBM sub-populations, those with EGFR and PDGFRA genes amplified. We study population levels found across image-localized biopsy data from a cohort of 25 patients and compare this to model outputs under competitive, cooperative and neutral interaction assumptions. We explore other factors affecting the observed simulated sub-populations, such as selection advantages and phylogenetic ordering of mutations, which may also contribute to the levels of EGFR and PDGFRA amplified populations observed in biopsy data.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Neoplasias Encefálicas/genética , Glioblastoma/genética , Humanos , Mutação , Filogenia
6.
J Am Osteopath Assoc ; 120(12): 934-939, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33017462

RESUMO

In this case report, the authors discuss a patient with a rare entity, Kikuchi Fujimoto Disease, which exhibited unique osteopathic structural examination findings, including enlarged cervical lymph nodes in conjunction with a Chapman reflex (CR). This report highlights the critical importance of histological examination of the lymph nodes. Additionally, it reminds physicians to consider the ways in which CR can potentially contribute to the diagnostic process.


Assuntos
Linfadenite Histiocítica Necrosante , Lúpus Eritematoso Sistêmico , Linfadenite Histiocítica Necrosante/complicações , Linfadenite Histiocítica Necrosante/diagnóstico , Humanos , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Linfonodos/diagnóstico por imagem
7.
Laryngoscope ; 130(6): 1470-1478, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31433065

RESUMO

OBJECTIVES: The insulin-like growth factor-1 receptor (IGF1R) has been implicated in therapeutic resistance in head and neck squamous cell carcinoma (HNSCC), and small molecule tyrosine kinase inhibitors (TKIs) of IGF1R activity may have anticancer activity. Therefore, the relationship between survival and IGF1R expression was assessed for oral cavity (OC) cancer, and the antitumor effects of two IGF1R-TKIs, OSI-906 and BMS-754807, were evaluated in HNSCC cell lines in vitro. METHODS: Clinical outcome data and tissue microarray immunohistochemistry were used to generate IGF1R expression-specific survival curves. Immunoblot, alamarBlue proliferation assay, trypan blue exclusion viability test, clonogenic assay, flow cytometry, and reverse phase protein array (RPPA) were used to evaluate in vitro responses to IGF1R-TKIs. RESULTS: For patients with stage III/IV OCSCC, higher IGF1R expression was associated with poorer overall 5-year survival (P = 0.029). Both BMS-754807 and OSI-906 caused dose-dependent inhibition of IGF1R and Akt phosphorylation and inhibited proliferation; BMS-754807 was more potent than OSI-906. Both drugs reduced HNSCC cell viability; only OSI-906 was able to eliminate all viable cells at 10 µM. The two drugs similarly inhibited clonogenic cell survival. At 1 µM, only BMS-754807 caused a fourfold increase in the basal apoptotic rate. RPPA demonstrated broad effects of both drugs on canonical IGF1R signaling pathways and also inhibition of human epidermal growth factor receptor-3 (HER3), Src, paxillin, and ezrin phosphorylation. CONCLUSION: OSI-906 and BMS-754807 inhibit IGF1R activity in HNSCC cell lines with reduction in prosurvival and proliferative signaling and with concomitant antiproliferative and proapoptotic effects. Such antagonists may have utility as adjuvants to existing therapies for HNSCC. LEVEL OF EVIDENCE: NA Laryngoscope, 130:1470-1478, 2020.


Assuntos
Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Imidazóis/uso terapêutico , Fator de Crescimento Insulin-Like I/antagonistas & inibidores , Pirazinas/uso terapêutico , Pirazóis/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Triazinas/uso terapêutico , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Imidazóis/farmacologia , Fator de Crescimento Insulin-Like I/biossíntese , Neoplasias Bucais/tratamento farmacológico , Estadiamento de Neoplasias , Pirazinas/farmacologia , Pirazóis/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Resultado do Tratamento , Triazinas/farmacologia , Células Tumorais Cultivadas
8.
J Surg Res ; 245: 145-152, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31419639

RESUMO

BACKGROUND: Physicians are frequently called on to make medical decisions despite being uncertain about the outcomes of these choices. The psychological stress associated with these dilemmas, known as "Uncertainty Intolerance" (UI), can significantly impact the quality of a physician's practice as well as their own mental health. Coping with uncertainty is an important competency that all residents must master, and some residency programs are introducing new education initiatives aimed at improving UI. However, currently there is no standard protocol for measuring UI or the effectiveness of such interventions and there are no established methods for identifying the residents who would most benefit from the training. In this study, we aim to use the Physician Reaction to Uncertainty (PRU) and Physician Risk Attitude (PRA) scales as assessments for UI in surgical residents, and to determine if Myers-Briggs Type Indicator (MBTI) personality factors are associated with PRU and PRA scores and can be used to identify residents who are more likely to have higher UI. MATERIALS AND METHODS: The PRU and PRA scales, and the MBTI assessment were administered to a total pool of 71 general surgery residents. In addition to the survey questions, residents provided information regarding their gender (male or female), and stage of training (junior or senior). RESULTS: In total, 45 male residents and 25 female residents completed the PRA and PRU scales (98.6%). There were no statistically significant differences when comparisons were made between junior and senior residents or male and female residents. Thirty seven male residents and 18 female residents also completed the MBTI assessment (80.4% and 72%, respectively). PRU and PRA scores were analyzed with respect to personality factors to determine if certain dichotomies are associated with increased UI. There was a trend toward higher UI in individuals identifying with Judging. CONCLUSIONS: In this study, we have conducted a pilot study using the PRU and PRA scales to measuring the success of our new education initiatives aimed at improving uncertainty tolerance. We found that the PRU and PRA assessments were simple to administer and had a high completion rate. Our findings also suggest that individuals who identify with Judging may better tolerate the uncertainties associated with surgical practice, although larger studies will be required to determine if MBTI factors are linked to UI in surgical residents.


Assuntos
Internato e Residência/estatística & dados numéricos , Inventário de Personalidade/normas , Personalidade , Cirurgiões/psicologia , Incerteza , Adaptação Psicológica , Tomada de Decisão Clínica , Estudos de Viabilidade , Feminino , Humanos , Masculino , Inventário de Personalidade/estatística & dados numéricos , Projetos Piloto , Cirurgiões/educação , Cirurgiões/estatística & dados numéricos
9.
Obes Surg ; 29(6): 1990-1994, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30895505

RESUMO

BACKGROUND: Postoperative hemorrhage is a rare complication in bariatric surgery. We aim to determine if differences in blood pressure or perioperative medication administration contribute to postoperative bleeding in patients who were hemodynamically stable intraoperatively. METHODS: This was a retrospective case-control study of all bariatric surgery patients from 2014 to 2017 at a high volume academic center. We identified controls based on age, gender, ethnicity, type of procedure, and pre-operative blood pressure. RESULTS: Patients with postoperative hemorrhage had a significantly lower MAP during the portion of the surgery in which the abdominal contents were inspected for leaks and bleeds. The timing of enoxaparin or ketorolac administration was not associated with bleeding. CONCLUSION: Blood pressure lability, but not enoxaparin or ketorolac administration, is associated with postoperative hemorrhage.


Assuntos
Cirurgia Bariátrica , Pressão Sanguínea/fisiologia , Hipotensão/complicações , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Hemorragia Pós-Operatória/etiologia , Adulto , Idoso , Cirurgia Bariátrica/métodos , Pressão Sanguínea/efeitos dos fármacos , Transfusão de Sangue/estatística & dados numéricos , Estudos de Casos e Controles , Esquema de Medicação , Enoxaparina/administração & dosagem , Feminino , Humanos , Hipotensão/epidemiologia , Hipotensão/fisiopatologia , Hipotensão/cirurgia , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/fisiopatologia , Assistência Perioperatória/métodos , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/prevenção & controle , Hemorragia Pós-Operatória/terapia , Estudos Retrospectivos , Fatores de Risco
10.
Obes Surg ; 29(7): 2030-2036, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30903426

RESUMO

BACKGROUND: Excessive opioid prescribing creates risk for abuse and adverse effects, but must be balanced against individualized pain control. Minimal literature exists to guide providers in the postoperative bariatric surgical setting. STUDY DESIGN: We compare opioid prescribing practice for minimally invasive bariatric surgery in a university hospital with self-reported patient use and satisfaction. This data is used to create practice guidelines for postoperative prescriptions. A 10-question survey was administered at the first postoperative office visit. All patients at this visit were eligible. None declined or excluded. We analyzed 115 patients for 3 procedures: laparoscopic sleeve gastrectomy (LSG; n = 53), laparoscopic roux-en-Y gastric bypass (LRYGB; n = 50), and laparoscopic adjustable gastric band removal (LAGBR; n = 12). Outcomes included number of pills prescribed (verified), proportion used, duration of use, satisfaction with pain control, and non-narcotic analgesic use. RESULTS: An average of 27 ± 10 pills were dispensed for LSG, average 4.1 days of use; 28 ± 7 pills for LRYGB, 4.6 days; and16 ± 9 pills for LAGBR, 2.6 days. Fifty to 74% retained more than half or all of their opioids at 2 weeks. Fifty-four percent utilized non-narcotic analgesics. Overall, 91.3% reported adequate pain control. For each procedure, average number of pills used was calculated with representative values for "less than half left" (75% of average number of pills prescribed) and "more than half left" (25% of average number of pills prescribed). For LSG, an average of 9 pills were used; LRYGB 14 pills, and LAGBR 7 pills. CONCLUSIONS: Opioids are overprescribed following most common surgical procedures, but only one study has evaluated patterns after bariatric surgery. Our survey-based tool examines prescribing, utilization and satisfaction following common minimally invasive bariatric procedures. Opioid prescriptions were variable, and excessive for most patients. We now recommend prescribing no more than 15 pills after these operations.


Assuntos
Analgésicos Opioides/uso terapêutico , Cirurgia Bariátrica/efeitos adversos , Obesidade Mórbida/cirurgia , Dor Pós-Operatória/tratamento farmacológico , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos não Narcóticos/uso terapêutico , Cirurgia Bariátrica/métodos , Cirurgia Bariátrica/estatística & dados numéricos , Prática Clínica Baseada em Evidências/estatística & dados numéricos , Feminino , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Gastrectomia/estatística & dados numéricos , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Derivação Gástrica/estatística & dados numéricos , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Laparoscopia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/epidemiologia , Dor Pós-Operatória/epidemiologia , Satisfação do Paciente/estatística & dados numéricos , Período Pós-Operatório , Padrões de Prática Médica/normas , Padrões de Prática Médica/estatística & dados numéricos , Inquéritos e Questionários , Adulto Jovem
11.
Obes Surg ; 29(2): 593-600, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30353248

RESUMO

BACKGROUND: Sleeve gastrectomy with ileal transposition has been shown to be superior to sleeve gastrectomy alone for promoting weight loss in rat and porcine models. The absence of a mouse model for this procedure has impeded efforts to understand the molecular physiology underlying its efficacy. This study demonstrates the long-term survivability of sleeve gastrectomy with ileal transposition in mice. MATERIALS AND METHODS: In this study of technical feasibility, a sleeve gastrectomy with ileal transposition (SGIT), sleeve gastrectomy (SG), or sham surgery (SH) was performed on 7- to 8-week-old C57Bl/6J mice (n = 8 for each). To evaluate long-term survivability, mice were placed on an obesogenic diet and weighed weekly for 10 weeks. The intestinal identity of the transposed segment was assessed with gene expression analysis of duodenal-, jejunal-, and ileal-specific hormones using quantitative polymerase chain reaction. RESULTS: Overall, SGIT better prevented weight gain than the SG or sham procedures (10-week post-operative weight: SH 45.3 ± 1.0 g, SG 41.25 ± 1.6 g, SGIT 35.4 ± 0.8 g). Gene expression pattern analysis of three markers of intestinal identity (gastrin, cholecystokinin, and peptide YY) suggests that the ileal identity of the transposed segment is maintained 10 weeks after transposition. CONCLUSIONS: We demonstrate for the first time a reproducible mouse model of sleeve gastrectomy with ileal transposition. Future studies utilizing this model will expand our understanding of the molecular pathways through which the hindgut regulates satiety.


Assuntos
Gastrectomia/métodos , Íleo/cirurgia , Animais , Biomarcadores , Glicemia/análise , Colecistocinina/genética , Colecistocinina/metabolismo , Modelos Animais de Doenças , Estudos de Viabilidade , Gastrinas/genética , Gastrinas/metabolismo , Expressão Gênica , Camundongos Endogâmicos C57BL , Peptídeo YY/genética , Peptídeo YY/metabolismo , RNA/metabolismo , Distribuição Aleatória , Redução de Peso
12.
Prim Care ; 45(2): 289-303, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29759125

RESUMO

Soft tissue musculoskeletal pain disorders are common in the primary care setting. Early recognition and diagnosis of these syndromes minimizes patient pain and disability. This article gives a brief overview of the most common soft tissue musculoskeletal pain syndromes. The authors used a regional approach to organize the material, as providers will encounter these syndromes with complaints of pain referring to an anatomic location. The covered disorders include myofascial pain syndrome, rotator cuff tendinopathy, bicipital tendinopathy, subacromial bursitis, olecranon bursitis, epicondylitis, De Quervain disease, trigger finger, trochanteric bursitis, knee bursitis, pes anserine bursitis, Baker cyst, plantar fasciitis, and Achilles tendinopathy.


Assuntos
Doenças Reumáticas/diagnóstico , Doenças Reumáticas/terapia , Bursite/diagnóstico , Bursite/terapia , Diagnóstico Diferencial , Fibromialgia/diagnóstico , Fibromialgia/terapia , Articulação do Quadril , Humanos , Articulação do Joelho , Osteonecrose/diagnóstico , Osteonecrose/terapia , Distrofia Simpática Reflexa/diagnóstico , Distrofia Simpática Reflexa/terapia , Tendinopatia/diagnóstico , Tendinopatia/terapia
13.
Surg Obes Relat Dis ; 13(9): 1584-1589, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28663074

RESUMO

BACKGROUND: Few studies have examined whether preoperative period length, as defined by the amount of time from enrollment in a surgical weight loss program to the day of surgery, affects postoperative weight loss. OBJECTIVES: To identify associations between preoperative period length and postoperative weight loss. SETTING: Single surgeon at an academic medical center in the United States. METHODS: Retrospective chart review in 109 consecutive patients undergoing sleeve gastrectomy from 2014-2015. RESULTS: When patients were grouped based on postoperative percentage of total weight loss, greater weight loss was associated with shorter preoperative wait time. During the preoperative period, 72.2% of our patients achieved a net weight loss, but 34.6% had gained net weight until they started the preoperative "liver-shrinking" diet; 71.4±8.3% of the total preoperative weight loss occurred after initiating the preoperative diet, which accounted for approximately 15% of the whole preoperative period length. There was no correlation between the length of the preoperative diet and preoperative weight loss. CONCLUSIONS: Shorter preoperative periods and earlier initiation of liver reduction diets may increase postoperative weight loss, although ultimately there may be a limit to the weight loss that patients can achieve while adhering to highly restrictive lifestyle modifications.


Assuntos
Cirurgia Bariátrica/estatística & dados numéricos , Dietoterapia/estatística & dados numéricos , Gastrectomia/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Listas de Espera , Redução de Peso/fisiologia , Adulto , Dieta Redutora/estatística & dados numéricos , Feminino , Humanos , Cobertura do Seguro , Seguro Saúde , Masculino , Obesidade/cirurgia , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios , Estudos Retrospectivos , Programas de Redução de Peso
14.
Bull Math Biol ; 79(4): 939-974, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28290010

RESUMO

In this work, we present a pedagogical tumour growth example, in which we apply calibration and validation techniques to an uncertain, Gompertzian model of tumour spheroid growth. The key contribution of this article is the discussion and application of these methods (that are not commonly employed in the field of cancer modelling) in the context of a simple model, whose deterministic analogue is widely known within the community. In the course of the example, we calibrate the model against experimental data that are subject to measurement errors, and then validate the resulting uncertain model predictions. We then analyse the sensitivity of the model predictions to the underlying measurement model. Finally, we propose an elementary learning approach for tuning a threshold parameter in the validation procedure in order to maximize predictive accuracy of our validated model.


Assuntos
Teorema de Bayes , Calibragem , Neoplasias , Humanos , Modelos Teóricos , Prognóstico , Incerteza
15.
Otol Neurotol ; 37(10): 1577-1582, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27631831

RESUMO

OBJECTIVES: To compare speech/language development and academic progress between children with right versus left congenital aural atresia (CAA). STUDY DESIGN: Case control survey and review of audiometric data. SETTING: Tertiary care academic practice. PATIENTS: Children with unilateral CAA. MAIN OUTCOME MEASURES: Demographic and audiometric data; rates of grade retention, use of any hearing or learning resource, and behavioral problems. RESULTS: No significant differences in grade retention rate, utilization of amplification, speech language therapy, use of an individualized education program, or frequency modulated system were found between children with right versus left CAA. Children with left CAA were significantly more likely to be enrolled in special education programs (p = 0.026). Differences in reported communication problems approached significance with more difficulty noted in the right ear group (p = 0.059). Left CAA patients were also more likely to have reported behavioral problems (p = 0.0039). CONCLUSION: Contrary to the hypothesis that a normal hearing right ear confers a language advantage in patients with unilateral hearing loss, children with left CAA (normal right ear) were statistically more likely to be enrolled in a special education program and have behavioral problems. Reported communication problems were more common in right CAA patients, but this did not reach statistical significance. No differences were found in use of amplification, frequency modulated system, individualized education program, or grade retention. Further investigation of both the clinical implications and underlying psychoacoustics of unilateral hearing loss and the identification and habilitation of "at risk" unilateral hearing loss children is warranted.


Assuntos
Logro , Anormalidades Congênitas/fisiopatologia , Orelha/anormalidades , Lateralidade Funcional/fisiologia , Desenvolvimento da Linguagem , Fala/fisiologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Orelha/fisiopatologia , Escolaridade , Feminino , Perda Auditiva Unilateral , Humanos , Lactente , Aprendizagem/fisiologia , Masculino , Fonoterapia , Adulto Jovem
16.
Otolaryngol Head Neck Surg ; 151(1): 92-9, 2014 07.
Artigo em Inglês | MEDLINE | ID: mdl-24687941

RESUMO

OBJECTIVE: To demonstrate the feasibility of detecting and quantifying extracellular signal-related kinase (ERK) phosphorylation status using nanoimmunoassay (NIA). STUDY DESIGN: Analyses using Cal27, SCC25, and OSC19 head and neck squamous carcinoma cell lines in vitro and in a murine xenograft model. SUBJECTS AND METHODS: NIA and immunoblot were performed on whole-cell lysates, tumor lysates, and fine-needle aspirate biopsies to detect ERK phosphorylation states. RESULTS: Using NIA, all 6 isoforms of ERK1/2, including nonphosphorylated, monophosphorylated, and diphosphorylated species, could be reliably detected, distinguished, and quantified in a single assay using a single antibody. In vitro treatment of Cal27 cells with the epidermal growth factor receptor inhibitor gefitinib abolished phospho-ERK detection by immunoblot but resulted in residual detectable species by NIA. Residual phospho-ERK in gefitinib-treated cells could be further reduced by the addition of the insulin-like growth factor 1 receptor inhibitor OSI-906; this correlated with an additional decrease in proliferation over gefitinib alone. In a pilot study of 4 murine xenograft tumors, NIA performed on tumor lysates and fine-needle aspirate biopsies demonstrated altered ERK profiles after 2 days of gefitinib treatment compared with untreated mice. CONCLUSION: NIA offers a novel approach to quantitating the activation state of signaling molecules such as ERK in nanoscale in vitro and in vivo samples across a wide dynamic range. As such, it has potential to provide molecular diagnostic information before, during, and after treatment using a minimally invasive technique. Further study is warranted to determine its utility in assessing signaling proteins as biomolecular outcome predictors in clinical trials.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/enzimologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neoplasias de Cabeça e Pescoço/enzimologia , Imunoensaio , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Estudos de Viabilidade , Gefitinibe , Xenoenxertos , Imunoensaio/métodos , Técnicas In Vitro , Camundongos , Nanotecnologia , Quinazolinas/farmacologia
17.
Ann Allergy Asthma Immunol ; 111(4): 246-251.e2, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24054358

RESUMO

BACKGROUND: A number of factors are critical when considering the expected benefit of surgical intervention in patients with chronic rhinosinusitis (CRS) who have failed medical therapy. OBJECTIVE: To evaluate the Sino-nasal Outcome Test (SNOT-22) and other patient demographic characteristics as predictors of postsurgical improvement in patients with CRS. METHODS: Consecutive adult subjects presenting to the Otolaryngology Clinics at the University of Virginia with refractory CRS that required surgery were included. Patients were excluded if they had not completed both preoperative and postoperative SNOT-22 evaluations. Demographic and baseline measures, including asthma and smoking status, total immunuglobulin E (IgE), absolute eosinophil counts, and Lund-Mackay computed tomography (CT) scoring were also obtained for each subject. Regression analyses were performed. RESULTS: One hundred four subjects met criteria and were included. These subjects showed a 51% overall improvement in postsurgical SNOT-22 evaluations (95% confidence interval [CI]: [45, 57%], P < .001). Multivariate regression analysis revealed that SNOT-22 items related to "runny nose," "cough," and "sadness" were independent predictors of postsurgical SNOT-22 improvement (P < .05, for all). Although "runny nose" had a direct correlation with improvement, more severe "sadness" and "cough" scores had a negative impact on degree of improvement. Similarly, analyses indicated that questions categorized as pertaining to nasal or ear symptoms were uniquely associated with postsurgical improvement in SNOT-22 scores (P < .001 and P = .015, respectively). Neither Lund-Mackay CT scoring, total IgE, nor absolute eosinophil counts correlated with improvement in postsurgical SNOT-22 scores. CONCLUSION: Physicians can use components of the SNOT-22 to predict likelihood of symptom improvement after surgical intervention in subjects with CRS.


Assuntos
Avaliação de Resultados em Cuidados de Saúde/métodos , Rinite/cirurgia , Sinusite/cirurgia , Inquéritos e Questionários , Adulto , Afeto , Doença Crônica , Tosse/etiologia , Feminino , Humanos , Masculino , Período Pós-Operatório , Período Pré-Operatório , Rinite/complicações , Sinusite/complicações
18.
J Thorac Cardiovasc Surg ; 143(6): 1307-13, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22361247

RESUMO

OBJECTIVE: Five-year survival after the diagnosis of non-small cell lung cancer is the most common benchmark used to evaluate long-term survival. Data on survival beyond 5 years are sparse. We sought to elucidate variables affecting 10- to 18-year survival. METHODS: A total of 31,206 patients alive at least 5 years after diagnosis of non-small cell lung cancer who were registered in the Surveillance, Epidemiology, and End Results database from 1988 to 2001 were examined. Primary end points were disease-specific survival and overall survival. Survival analysis was performed with Kaplan-Meier estimates, multivariable Cox proportional hazards regression, and competing risk models. RESULTS: Overall survival at 10, 15, and 18 years was 55.4%, 33.1%, and 24.3%, respectively. Disease-specific survival at 10, 15, and 18 years was 76.6%, 65.4%, and 59.4%, respectively. In multivariable regression analysis, squamous cell cancers had a disease-specific survival advantage (hazard ratio, 0.88; P < .0001) but an overall survival disadvantage (hazard ratio, 1.082; P = .0002) compared with adenocarcinoma. Pneumonectomy (hazard ratio, 0.44) and lobectomy (hazard ratio, 0.474) had improved disease-specific survival compared with no surgery (P < .0001). Left-sided tumors (hazard ratio, 0.723; P = .036) and node-negative cancers (hazard ratio, 0.562; P < .001) also had a better disease-specific survival and, to a lesser extent, overall survival advantage. CONCLUSIONS: Five-year survivors of non-small cell lung cancer have a persistent risk of death from lung cancer up to 18 years from diagnosis. More than one half of all deaths in 5-year survivors are related to lung cancer. In multivariable regression analysis, age, node-negative disease, and lobar or greater resection were strong predictors of long-term survival (ie, 10-18 years).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Pneumonectomia/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Causas de Morte , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Programa de SEER , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
19.
Mol Cancer Ther ; 10(11): 2124-34, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21878657

RESUMO

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have poor efficacy in head and neck squamous carcinoma cells (HNSCC). Because the IGF-1 receptor (IGF1R) generates potent prosurvival signals and has been implicated in therapeutic resistance, its ability to induce resistance to EGFR-TKIs was studied in vitro. Five HNSCC cell lines showed reduced sensitivity to the EGFR-TKI gefitinib when the IGF1R was activated. In SCC-25 and Cal27 cells, gefitinib inhibited basal and EGF-stimulated EGFR, extracellular signal-regulated kinase (Erk), and Akt phosphorylation and reduced cell number. This correlated with initiation of apoptosis based on a 4-fold increase in PARP cleavage and a 2.5-fold increase in Annexin V positivity. The apoptotic response and reduction in cell number were blocked by IGF1R activation, which resulted in phosphorylation of both Erk and Akt. In both the cell lines, IGF1R-induced Erk, but not Akt, activation was eliminated by gefitinib. IGF1R-induced gefitinib resistance was unaffected by MAP/Erk kinase inhibition with U0126 but was partially impaired by inhibition of phosphoinositide-3-kinase with LY294002. The IGF1R-TKI PQ401 inhibited growth of SCC-25 and Cal27 cells alone and also acted synergistically with gefitinib. Thus, the IGF1R can make HNSCC cells resistant to EGFR-TKI treatment via a prosurvival mechanism. Of the 8 HNSCC tumor samples studied, all samples expressed the IGF1R and 5 showed detectable IGF1R phosphorylation, suggesting that this receptor may be relevant in vivo, and thus, combined EGFR/IGF1R inhibition may be necessary in some patients for effective targeted molecular therapy.


Assuntos
Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/metabolismo , Receptores ErbB/antagonistas & inibidores , Neoplasias de Cabeça e Pescoço/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Receptor IGF Tipo 1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Receptor IGF Tipo 1/antagonistas & inibidores , Receptor IGF Tipo 1/genética , Transdução de Sinais/efeitos dos fármacos , Carcinoma de Células Escamosas de Cabeça e Pescoço
20.
Surg Laparosc Endosc Percutan Tech ; 21(2): 111-5, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21471804

RESUMO

A retrospective review was performed of all patients with upper lobe non-small cell lung cancers to assess the use of thoracoscopy in determining chest wall invasion in patients with lung cancers abutting the first rib, but without overt radiographic invasion. Of the 12 patients with tumors abutting the first rib without overt radiographic invasion, thoracoscopy was able to correctly determine chest wall invasion in 8 patients. There was no significant morbidity related to thoracoscopy. Large tumor size did not preclude thoracoscopic staging, whereas dense adhesions did limit the use of staging thoracoscopy. Patients with invasion by thoracoscopy were able to begin radiation or chemotherapy much sooner (median 22.3 d) than patients requiring thoracotomy (median 60 d). The routine use of staging thoracoscopy in all tumors abutting the first rib without overt radiographic evidence of invasion accurately identified apical chest wall involvement in 8 of 12 patients. With this strategy, unnecessary neoadjuvant treatment and futile thoracotomy may be avoided.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/cirurgia , Síndrome de Pancoast/cirurgia , Parede Torácica/patologia , Toracoscopia/métodos , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Tempo de Internação , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Síndrome de Pancoast/patologia , Radiografia , Estudos Retrospectivos , Dor de Ombro/etiologia , Dor de Ombro/patologia , Parede Torácica/diagnóstico por imagem , Toracoscopia/instrumentação , Toracotomia/instrumentação , Toracotomia/métodos , Resultado do Tratamento
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