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1.
Adv Nutr ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31800007

RESUMO

Some evidence indicates that carotenoids may reduce the risk of bladder cancer (BC), but the association is unclear. We conducted a systematic review and meta-analysis of case-control and cohort studies investigating the relation between carotenoid intake or circulating carotenoid concentrations and BC risk in men and women. All relevant epidemiologic studies were identified by a search of PubMed and Scopus databases, and the Cochrane Library from inception to April 2019 with no restrictions. A random-effects model was used to calculate pooled RRs and their 95% CIs across studies for high compared with low categories of intake or circulating concentrations. We also performed a dose-response meta-analysis using the Greenland and Longnecker method and random-effects models. A total of 22 studies involving 516,740 adults were included in the meta-analysis. The pooled RRs of BC for the highest compared with the lowest category of carotenoid intake and circulating carotenoid concentrations were 0.88 (95% CI: 0.76, 1.03) and 0.36 (95% CI: 0.12, 1.07), respectively. The pooled RR of BC for the highest compared with lowest circulating lutein and zeaxanthin concentrations was 0.53 (95% CI: 0.33, 0.84). Dose-response analysis showed that BC risk decreased by 42% for every 1 mg increase in daily dietary ß-cryptoxanthin intake (RR: 0.58; 95% CI: 0.36, 0.94); by 76% for every 1 µmol/L increase in circulating concentration of α-carotene (RR: 0.24; 95% CI: 0.08, 0.67); by 27% for every 1 µmol/L increase in circulating concentration of ß-carotene (RR: 0.73; 95% CI: 0.57, 0.94); and by 56% for every 1 µmol/L increase in circulating concentrations of lutein and zeaxanthin (RR: 0.44; 95% CI: 0.28, 0.67). Dietary ß-cryptoxanthin intake and circulating concentrations of α-carotene, ß-carotene, and lutein and zeaxanthin were inversely associated with BC risk. The protocol was registered at PROSPERO as CRD42019133240.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31610232

RESUMO

In patients with alveolar-to-pleural air leak due to recent surgery or trauma, clinicians tend to manage chest tubes with suction therapy. Nonsuction therapy is associated with shorter chest tube duration but also a higher risk of pneumothorax. We sought to develop an intrapleural electrical impedance sensor for continuous, real-time monitoring of pneumothorax development in a porcine model of air leak as a means of promoting nonsuction therapy. Using thoracoscopy, 2 chest tubes and the pleural impedance sensor were introduced into the pleural space of 3 pigs. Continuous air leak was introduced through 1 chest tube by carbon dioxide insufflation. The second chest tube was placed to suction then transitioned to no suction at increasingly higher air leaks until pneumothorax developed. Simultaneously, real-time impedance measurements were obtained from the pleural sensor. Fluoroscopy spot images were captured to verify the presence or absence of pneumothorax. Statistical Analysis Software was used throughout. With the chest tube on suction, a fully expanded lung was identified by a distinct pleural electrical impedance respiratory waveform. With transition of the chest tube to water seal, loss of contact of the sensor with the lung resulted in an immediate measurement of infinite electrical impedance. Pneumothorax resolution by restoring suction therapy was detected in real time by a return of the normal respiratory impedance waveform. Pleural electrical impedance monitoring detected pneumothorax development and resolution in real time. This simple technology has the potential to improve the safety and quality of chest tube management.

3.
J Periodontol ; 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31380563

RESUMO

PURPOSE: The primary purpose of this study was to histologically determine if there is a significant difference in new bone formation, residual graft material, and connective tissue/other when ridge preservation is accomplished using a bovine versus a porcine xenograft. METHODS: Forty-four patients needing a single rooted tooth extraction and ridge preservation in preparation for dental implant placement were recruited in the study. After minimally traumatic tooth extraction, alveolar ridge dimensions were measured using a custom-fabricated acrylic stent. Patients were then randomized 1:1 to receive ridge preservation using either bovine or porcine xenograft material. A trimmed dense polytetrafluoroethylene (d-PTFE) membrane was overlaid on the graft material, the mucoperiosteal flaps were replaced, and the surgical site was sutured. After 18 to 20 weeks of wound healing, sites were surgically re-entered, ridge dimensions were again measured using the previously fabricated acrylic stents and a bone core sample of the grafted site was harvested for histomorphometric analysis. RESULTS: Thirty eight of the 44 enrolled patients completed the study, 17 from the bovine group and 21 from the porcine group. Histologically, there were no statistically significant differences between the groups for mean percentage of vital bone formation (bovine = 36.21%, porcine = 31.27%, P = 0.49), residual graft material (bovine = 20.47%, porcine = 19.52%, P = 0.82) and connective tissue/other (bovine = 43.32%, porcine = 49.21%, P = 0.19). For secondary outcomes, there were no significant differences between the groups for mean change in buccal ridge height, lingual ridge height, and ridge width. However, a higher number of patients in the porcine group had additional grafting at the time of implant placement, either because of thin buccal plate or failure of implant stability. CONCLUSION: The findings suggest that ridge preservation with porcine xenograft results in comparable histomorphometric outcomes and dimensional stability with bovine xenograft.

4.
BMC Cancer ; 19(1): 593, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31208434

RESUMO

BACKGROUND: Cancer patients with advanced disease routinely exhaust available clinical regimens and lack actionable genomic medicine results, leaving a large patient population without effective treatments options when their disease inevitably progresses. To address the unmet clinical need for evidence-based therapy assignment when standard clinical approaches have failed, we have developed a probabilistic computational modeling approach which integrates molecular sequencing data with functional assay data to develop patient-specific combination cancer treatments. METHODS: Tissue taken from a murine model of alveolar rhabdomyosarcoma was used to perform single agent drug screening and DNA/RNA sequencing experiments; results integrated via our computational modeling approach identified a synergistic personalized two-drug combination. Cells derived from the primary murine tumor were allografted into mouse models and used to validate the personalized two-drug combination. Computational modeling of single agent drug screening and RNA sequencing of multiple heterogenous sites from a single patient's epithelioid sarcoma identified a personalized two-drug combination effective across all tumor regions. The heterogeneity-consensus combination was validated in a xenograft model derived from the patient's primary tumor. Cell cultures derived from human and canine undifferentiated pleomorphic sarcoma were assayed by drug screen; computational modeling identified a resistance-abrogating two-drug combination common to both cell cultures. This combination was validated in vitro via a cell regrowth assay. RESULTS: Our computational modeling approach addresses three major challenges in personalized cancer therapy: synergistic drug combination predictions (validated in vitro and in vivo in a genetically engineered murine cancer model), identification of unifying therapeutic targets to overcome intra-tumor heterogeneity (validated in vivo in a human cancer xenograft), and mitigation of cancer cell resistance and rewiring mechanisms (validated in vitro in a human and canine cancer model). CONCLUSIONS: These proof-of-concept studies support the use of an integrative functional approach to personalized combination therapy prediction for the population of high-risk cancer patients lacking viable clinical options and without actionable DNA sequencing-based therapy.


Assuntos
Biologia Computacional/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Quimioterapia Combinada/métodos , Modelos Estatísticos , Medicina de Precisão/métodos , Rabdomiossarcoma Alveolar/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Cães , Sinergismo Farmacológico , Feminino , Xenoenxertos , Humanos , Estimativa de Kaplan-Meier , Camundongos , Camundongos Endogâmicos NOD
5.
Skelet Muscle ; 9(1): 12, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113472

RESUMO

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the pediatric cancer population. Survival among metastatic RMS patients has remained dismal yet unimproved for years. We previously identified the class I-specific histone deacetylase inhibitor, entinostat (ENT), as a pharmacological agent that transcriptionally suppresses the PAX3:FOXO1 tumor-initiating fusion gene found in alveolar rhabdomyosarcoma (aRMS), and we further investigated the mechanism by which ENT suppresses PAX3:FOXO1 oncogene and demonstrated the preclinical efficacy of ENT in RMS orthotopic allograft and patient-derived xenograft (PDX) models. In this study, we investigated whether ENT also has antitumor activity in fusion-negative eRMS orthotopic allografts and PDX models either as a single agent or in combination with vincristine (VCR). METHODS: We tested the efficacy of ENT and VCR as single agents and in combination in orthotopic allograft and PDX mouse models of eRMS. We then performed CRISPR screening to identify which HDAC among the class I HDACs is responsible for tumor growth inhibition in eRMS. To analyze whether ENT treatment as a single agent or in combination with VCR induces myogenic differentiation, we performed hematoxylin and eosin (H&E) staining in tumors. RESULTS: ENT in combination with the chemotherapy VCR has synergistic antitumor activity in a subset of fusion-negative eRMS in orthotopic "allografts," although PDX mouse models were too hypersensitive to the VCR dose used to detect synergy. Mechanistic studies involving CRISPR suggest that HDAC3 inhibition is the primary mechanism of cell-autonomous cytoreduction in eRMS. Following cytoreduction in vivo, residual tumor cells in the allograft models treated with chemotherapy undergo a dramatic, entinostat-induced (70-100%) conversion to non-proliferative rhabdomyoblasts. CONCLUSION: Our results suggest that the targeting class I HDACs may provide a therapeutic benefit for selected patients with eRMS. ENT's preclinical in vivo efficacy makes ENT a rational drug candidate in a phase II clinical trial for eRMS.

6.
Plast Reconstr Surg ; 143(6): 1589-1600, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30907803

RESUMO

BACKGROUND: Breast reconstruction plays a significant role in breast cancer treatment recovery. Introduction of the BREAST-Q questionnaire has facilitated quantifying patient-reported quality-of-life measures, promoting improved evidence-based clinical practice. Information regarding the effects of body mass index on patient-reported outcomes and health-related quality of life is significantly lacking. METHODS: Consecutive deep inferior epigastric perforator (DIEP) flap breast reconstruction patients prospectively completed BREAST-Q questionnaires preoperatively and at two points postoperatively. The first (postoperative time point A) and second (postoperative time point B) postoperative questionnaires were completed 1 month postoperatively and following breast revision, respectively. Postoperative flap and donor-site complications were recorded prospectively. BREAST-Q scores were compared at all time points and stratified by body mass index group (≤25, >25 to 29.9, 30 to 34.9, and ≥35 kg/m). RESULTS: Between July of 2012 and August of 2016, 73 patients underwent 130 DIEP flap breast reconstructions. Breast satisfaction and psychosocial and sexual well-being scores increased significantly postoperatively. Chest and abdominal physical well-being scores returned to baseline levels by postoperative point B. Preoperatively, stratified by body mass index, breast satisfaction and psychosocial well-being scores were significantly lower among patients with body mass index of 35 or higher and of more than 30, respectively. After reconstruction, not only were breast satisfaction, psychosocial, and sexual well-being scores significantly improved in all body mass index groups versus baseline, but also between-body mass index group differences were no longer present. Outcome satisfaction, flap, and donor-site morbidity were similar irrespective of body mass index. CONCLUSIONS: Patient-reported outcomes demonstrate significant improvements in breast satisfaction and psychosocial and sexual well-being among patients following DIEP flap reconstruction. Preoperative differences in quality-of-life scores were improved in patients with obesity (body mass index ≥30 kg/m). CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.


Assuntos
Neoplasias da Mama/cirurgia , Artérias Epigástricas/cirurgia , Mamoplastia/métodos , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Reto do Abdome/transplante , Adulto , Índice de Massa Corporal , Neoplasias da Mama/patologia , Diclofenaco/análogos & derivados , Intervalo Livre de Doença , Feminino , Sobrevivência de Enxerto , Humanos , Estudos Longitudinais , Mastectomia/métodos , Pessoa de Meia-Idade , Retalho Perfurante/irrigação sanguínea , Retalho Perfurante/transplante , Estudos Prospectivos , Reto do Abdome/irrigação sanguínea , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos
7.
Cancer Immunol Res ; 7(3): 466-475, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30563829

RESUMO

The mechanistic target of rapamycin (mTOR) integrates environmental inputs to regulate cellular growth and metabolism in tumors. However, mTOR also regulates T-cell differentiation and activation, rendering applications of mTOR inhibitors toward treating cancer complex. Preclinical data support distinct biphasic effects of rapamycin, with higher doses directly suppressing tumor cell growth and lower doses enhancing T-cell immunity. To address the translational relevance of these findings, the effects of the mTOR complex 1 (mTORC1) inhibitor, rapamycin, on tumor and T cells were monitored in patients undergoing cystectomy for bladder cancer. MB49 syngeneic murine bladder cancer models were tested to gain mechanistic insights. Surgery-induced T-cell exhaustion in humans and mice and was associated with increased pulmonary metastasis and decreased PD-L1 antibody efficacy in mouse bladder cancer. At 3 mg orally daily, rapamycin concentrations were 2-fold higher in bladder tissues than in blood. Rapamycin significantly inhibited tumor mTORC1, shown by decreased rpS6 phosphorylation in treated versus control patients (P = 0.008). Rapamycin reduced surgery-induced T-cell exhaustion in patients, evidenced by a significant decrease in the prevalence of dysfunctional programmed death-1 (PD-1)-expressing T cells. Grade 3 to 4 adverse event rates were similar between groups, but rapamycin-treated patients had a higher rate of wound complications versus controls. In conclusion, surgery promoted bladder cancer metastasis and decreased the efficacy of postoperative bladder cancer immunotherapy. Low-dose (3 mg daily) oral rapamycin has favorable pharmacodynamic and immune modulating activity in surgical patients and has the potential to decrease surgery-induced immune dysfunction.

8.
Sci Signal ; 11(557)2018 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-30459282

RESUMO

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood with an unmet clinical need for decades. A single oncogenic fusion gene is associated with treatment resistance and a 40 to 45% decrease in overall survival. We previously showed that expression of this PAX3:FOXO1 fusion oncogene in alveolar RMS (aRMS) mediates tolerance to chemotherapy and radiotherapy and that the class I-specific histone deacetylase (HDAC) inhibitor entinostat reduces PAX3:FOXO1 protein abundance. Here, we established the antitumor efficacy of entinostat with chemotherapy in various preclinical cell and mouse models and found that HDAC3 inhibition was the primary mechanism of entinostat-induced suppression of PAX3:FOXO1 abundance. HDAC3 inhibition by entinostat decreased the activity of the chromatin remodeling enzyme SMARCA4, which, in turn, derepressed the microRNA miR-27a. This reexpression of miR-27a led to PAX3:FOXO1 mRNA destabilization and chemotherapy sensitization in aRMS cells in culture and in vivo. Furthermore, a phase 1 clinical trial (ADVL1513) has shown that entinostat is tolerable in children with relapsed or refractory solid tumors and is planned for phase 1B cohort expansion or phase 2 clinical trials. Together, these results implicate an HDAC3-SMARCA4-miR-27a-PAX3:FOXO1 circuit as a driver of chemoresistant aRMS and suggest that targeting this pathway with entinostat may be therapeutically effective in patients.


Assuntos
DNA Helicases/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , MicroRNAs/metabolismo , Proteínas Nucleares/metabolismo , Proteínas de Fusão Oncogênica/metabolismo , Fatores de Transcrição Box Pareados/metabolismo , Rabdomiossarcoma Alveolar/metabolismo , Fatores de Transcrição/metabolismo , Animais , Antineoplásicos/farmacologia , Benzamidas/farmacologia , Linhagem Celular Tumoral , Biologia Computacional , Resistencia a Medicamentos Antineoplásicos , Epigênese Genética , Feminino , Transferência Ressonante de Energia de Fluorescência , Proteína Forkhead Box O1/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Camundongos , Transplante de Neoplasias , Fator de Transcrição PAX3/metabolismo , Piridinas/farmacologia , Análise de Sequência de RNA , Vincristina/farmacologia
9.
J Surg Res ; 231: 15-23, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30278922

RESUMO

BACKGROUND: Chest tube management protocols, particularly in patients with alveolar-pleural air leak due to recent surgery or trauma, are limited by concerns over safety, especially concerns about rapid and occult development of pneumothorax. A continuous, real-time monitor of pneumothorax could improve the quality and safety of chest tube management. We developed a rat model of pneumothorax to test a novel approach of measuring electrical impedance within the pleural space as a monitor of lung expansion. MATERIALS AND METHODS: Anesthetized Sprague-Dawley rats underwent right thoracotomy. A novel impedance sensor and a thoracostomy tube were introduced into the right pleural space. Pneumothorax of varying volumes ranging from 0.2 to 20 mL was created by syringe injection of air via the thoracostomy tube. Electrical resistance measurements from the pleural sensor and fluoroscopic images were obtained at baseline and after the creation of pneumothorax and results compared. RESULTS: A statistically significant, dose-dependent increase in electrical resistance was observed with increasing volume of pneumothorax. Resistance measurement allowed for continuous, real-time monitoring of pneumothorax development and the ability to track pneumothorax resolution by aspiration of air via the thoracostomy tube. Pleural resistance measurement demonstrated 100% sensitivity and specificity for all volumes of pneumothorax tested and was significantly more sensitive for pneumothorax detection than fluoroscopy. CONCLUSIONS: The electrical impedance-based pleural space sensor described in this study provided sensitive and specific pneumothorax detection, which was superior to radiographic analysis. Real-time, continuous monitoring for pneumothorax has the potential to improve the safety, quality, and efficiency of postoperative chest tube management.


Assuntos
Impedância Elétrica , Pneumotórax/diagnóstico , Animais , Fluoroscopia , Pleura/fisiologia , Ratos Sprague-Dawley , Respiração Artificial , Volume de Ventilação Pulmonar
10.
J Wound Care ; 27(Sup9): S30-S45, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30207844

RESUMO

OBJECTIVE: The aim of this study was to assess whether continuous diffusion of oxygen improves healing in people receiving treatment for diabetic foot ulcers (DFU). METHOD: A double-blind, placebo control randomised study to receive either active continuous diffusion of oxygen (CDO) therapy using an active CDO device, or a fully operational placebo device without delivering oxygen. Patients were followed until closure or 12 weeks. Patients, caretakers, treating physicians and independent evaluators were blinded to the study arm. All patients received identical offloading, debridement, dressings and follow-up. RESULTS: We enrolled 146 people with DFUs (77% male, aged 56.3±12.4 years). A significantly higher proportion (195%) of DFUs healed in the CDO arm compared with placebo (32.4% versus 16.7%, p=0.033). The time to 50% DFU closure was significantly shorter in patients that received CDO therapy (mean 18.4 versus 28.9 days, p=0.001). There were no differences in overall adverse events (p=0.66) or ulcer-related adverse events (p=0.30) in the active and placebo treatment groups. The relative performance of active CDO over placebo became greater when used in larger wounds (273%), in more chronic wounds (334%) and in weight bearing wounds (465%). CONCLUSION: The results of this study demonstrate that CDO leads to higher proportion of healed DFUs (p=0.033) and a faster time to closure compared with placebo in people with DFUs (p=0.015). Relative performance did not vary significantly with wound size (p=0.80), but revealed better relative performance in more chronic wounds (p=0.008) and in weight-bearing wounds (p=0.003).


Assuntos
Pé Diabético/terapia , Oxigênio/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bandagens , Desbridamento , Diabetes Mellitus Tipo 2 , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Estados Unidos , Cicatrização
11.
PLoS One ; 13(7): e0201273, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30024960

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0195827.].

12.
PLoS One ; 13(5): e0195827, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29734348

RESUMO

BACKGROUND: Recent interest in the study of concussion and other neurological injuries has heightened awareness of the medical implications of American tackle football injuries amongst the public. OBJECTIVE: Using the National Emergency Department Sample (NEDS) and the National Inpatient Sample (NIS), the largest publicly available all-payer emergency department and inpatient healthcare databases in the United States, we sought to describe the impact of tackle football injuries on the American healthcare system by delineating injuries, specifically neurological in nature, suffered as a consequence of tackle football between 2010 and 2013. METHODS: The NEDS and NIS databases were queried to collect data on all patients presented to the emergency department (ED) and/or were admitted to hospitals with an ICD code for injuries related to American tackle football between the years 2010 and 2013. Subsequently those with football-related neurological injuries were abstracted using ICD codes for concussion, skull/face injury, intracranial injury, spine injury, and spinal cord injury (SCI). Patient demographics, length of hospital stay (LOS), cost and charge data, neurosurgical interventions, hospital type, and disposition were collected and analyzed. RESULTS: A total of 819,000 patients presented to EDs for evaluation of injuries secondary to American tackle football between 2010 and 2013, with 1.13% having injuries requiring inpatient admission (average length of stay 2.4 days). 80.4% of the ED visits were from the pediatric population. Of note, a statistically significant increase in the number of pediatric concussions over time was demonstrated (OR = 1.1, 95% CI 1.1 to 1.2). Patients were more likely to be admitted to trauma centers, teaching hospitals, the south or west regions, or with private insurance. There were 471 spinal cord injuries and 1,908 total spine injuries. Ten patients died during the study time period. The combined ED and inpatient charges were $1.35 billion. CONCLUSION: Injuries related to tackle football are a frequent cause of emergency room visits, specifically in the pediatric population, but severe acute trauma requiring inpatient admission or operative interventions are rare. Continued investigation in the long-term health impact of football related concussion and other repetitive lower impact trauma is warranted.


Assuntos
Assistência à Saúde/estatística & dados numéricos , Futebol Americano/lesões , Doenças do Sistema Nervoso/etiologia , Adolescente , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Pacientes Internados/estatística & dados numéricos , Masculino , Estados Unidos
13.
Ann Surg Oncol ; 25(5): 1322-1328, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29497911

RESUMO

BACKGROUND: Accurate breast cancer staging is essential for optimal management of adjuvant therapies. While breast lymphatic drainage involves both axillary and internal mammary (IM) lymph node (LN) basins, IM LN sampling is not routinely advocated. The current study analyzes the incidence of IM LN metastases sampled during free flap breast reconstruction and subsequent changes in adjuvant treatment. METHODS: A retrospective analysis of patients with positive IM LN biopsies during free flap breast reconstruction was performed. Pre-reconstruction surgical and adjuvant therapies as well as staging and prognostic data were recorded. Change in adjuvant therapies based solely on IM LN positivity was determined. RESULTS: IM LN metastases were found on 28 (1.3%) out of 2057 patients and comprised the study population. Mean age was 49 years with pre-reconstruction chemotherapy or radiation administered in 50 or 54% of cases, respectively. Five (18%) patients had previously undergone lumpectomy with axillary sampling. Mean tumor size was 3.1 cm with tumor location evenly distributed among all four quadrants. Ten (36%) patients had isolated IM LN metastases Patients with both axillary and IM disease had larger lesions, increased prevalence of pre-reconstruction chemotherapy and radiation. Based exclusively on positive IM LN disease, 17 (63%) patients had a change in adjuvant therapy. CONCLUSION: Despite the low incidence of IM LN metastases, IM LN biopsy during free flap breast reconstruction is recommended. In 36% of cases, nodal metastases were isolated to the IM nodes. Identification of IM metastases influenced adjuvant therapies in a majority of cases.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Linfonodos/patologia , Adulto , Axila , Biópsia , Quimioterapia Adjuvante , Feminino , Humanos , Metástase Linfática , Mamoplastia , Glândulas Mamárias Humanas , Mastectomia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos Retrospectivos , Retalhos Cirúrgicos , Carga Tumoral
14.
J Vasc Surg ; 67(6): 1813-1820, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29452835

RESUMO

BACKGROUND: Duplex ultrasound (DUS) mapping of the veins and arteries of the upper extremity is a well-established practice in arteriovenous fistula creation for long-term hemodialysis access. Previous publications have shown that vein diameters varying from 2 to 3 mm are predictive of success. Regional anesthesia is known to result in vasodilation and thus to increase the diameter of upper extremity veins. This study compares the sizes of veins measured by preoperative DUS mapping with those obtained after regional anesthesia to determine whether intraoperative DUS results in increased vein diameters and thus changes in the operative plan. A second goal was to determine whether such changes resulted in functional access. METHODS: This was a prospective observational study conducted between July 2013 and December 2014. Consecutive patients were preoperatively mapped and then intraoperatively mapped after administration of a regional anesthetic. Comparison of vein mapping sizes and comparison of preoperative plan and operative procedure based on the preoperative and intraoperative DUS mapping, respectively, were analyzed with a repeated-measures linear model. Significance testing was two sided, with a significance level of 5%. RESULTS: Sixty-five patients with end-stage renal disease underwent placement of arteriovenous access with preoperative and intraoperative DUS mapping after regional anesthesia. Comorbidities were representative of the vascular population. After regional anesthesia, intraoperative mid forearm and distal forearm cephalic veins were significantly larger than their respective preoperative measurements. Average increase in diameter of the mid forearm cephalic vein and distal forearm was 0.96 mm (P < .001) and 0.50 mm (P = .04), respectively. There was a significant difference in the number and configuration of arteriovenous accesses (P < .0001). There was more than a twofold significant increase in radial artery-based access procedures concomitant with a significant reduction of brachial-based access procedures and a reduction in graft access procedures. Overall functional access rate was 63%, and patency rates were comparable to those reported in the literature. CONCLUSIONS: The routine use of intraoperative DUS mapping after regional anesthesia is recommended to determine the optimal access site for chronic hemodialysis access. Identifying additional access options not seen with physical examination and preoperative DUS mapping will provide end-stage renal disease patients with more fistula options and hence a longer access life span for a lifelong disease.


Assuntos
Derivação Arteriovenosa Cirúrgica/métodos , Falência Renal Crônica/terapia , Artéria Radial/cirurgia , Diálise Renal/métodos , Ultrassonografia Doppler Dupla/métodos , Veias/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Estudos Prospectivos , Artéria Radial/diagnóstico por imagem , Veias/diagnóstico por imagem , Adulto Jovem
15.
PLoS One ; 12(8): e0183161, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28817624

RESUMO

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma affecting children and is often diagnosed with concurrent metastases. Unfortunately, few effective therapies have been discovered that improve the long-term survival rate for children with metastatic disease. Here we determined effectiveness of targeting the receptor tyrosine kinase, EphB4, in both alveolar and embryonal RMS either directly through the inhibitory antibody, VasG3, or indirectly by blocking both forward and reverse signaling of EphB4 binding to EphrinB2, cognate ligand of EphB4. Clinically, EphB4 expression in eRMS was correlated with longer survival. Experimentally, inhibition of EphB4 with VasG3 in both aRMS and eRMS orthotopic xenograft and allograft models failed to alter tumor progression. Inhibition of EphB4 forward signaling using soluble EphB4 protein fused with murine serum albumin failed to affect eRMS model tumor progression, but did moderately slow progression in murine aRMS. We conclude that inhibition of EphB4 signaling with these agents is not a viable monotherapy for rhabdomyosarcoma.


Assuntos
Efrina-B2/metabolismo , Receptor EphB4/metabolismo , Rabdomiossarcoma/terapia , Animais , Linhagem Celular , Humanos , Camundongos , Camundongos Transgênicos , Prognóstico , Rabdomiossarcoma/metabolismo , Rabdomiossarcoma/patologia , Transdução de Sinais
16.
J Diabetes Sci Technol ; 11(5): 883-891, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28654304

RESUMO

BACKGROUND: Over the past generation, preclinical data have suggested that there is a potential physiologic benefit to applying oxygen topically to wounds. However, we are unaware of any studies in the literature that have robustly assessed whether this would lead to a higher proportion of healing in similarly treated people without oxygen. Therefore, the purpose of this study was to assess this in people being treated for chronic diabetic foot ulcers (DFUs). METHODS: We enrolled and randomized 100 subjects with DFUs (79% male, aged 58.3 ± 12.1 years) to receive either active continuous diffusion of oxygen (CDO) therapy using an active CDO device, or an otherwise fully operational sham device that provided moist wound therapy (MWT) without delivering oxygen. Patients were followed until closure or 12 weeks, whichever was sooner. Patients, treating physicians and independent evaluators were blinded to the study arm. All patients received identical offloading, dressings and follow-up. RESULTS: There were no significant differences in assessed descriptive characteristics between the treatment arms ( P > .05 for all). A significantly higher proportion of people healed in the active arm compared to sham (46% vs 22%, P = .02). This relative effect became greater in more chronic wounds (42.5% vs 13.5%, P = .006). Patients randomized to the active device experienced significantly faster rates of closure relative to the sham ( P < .001). CONCLUSIONS: The results of this study suggest that continuously diffused oxygen over a wound leads to significantly higher rates of closure, and faster time to closure, compared to similarly treated patients receiving standard therapy coupled with a sham device. Furthermore, the relative efficacy appears to improve the more the therapy may be needed (more chronic and larger wounds).


Assuntos
Pé Diabético/terapia , Oxigênio/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cicatrização
17.
World Neurosurg ; 105: 732-736, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28642182

RESUMO

OBJECTIVE: The association between obesity and nontraumatic subarachnoid hemorrhage (SAH) patient outcome is unclear. The aim of this study was to determine the impact of morbid obesity (body mass index ≥40 kg/m2) on nontraumatic SAH outcomes. METHODS: Using the Nationwide Inpatient Sample, we identified hospitalized, nontraumatic SAH patients who received their diagnoses from 2008 to 2013 and tested the effect of obesity on their mortality and clinical outcomes. Odds ratios were estimated with a mixed effects linear logistic model with adjustment for hospital clustering. All statistical testing was 2-sided, with a significance level of 5%. RESULTS: Out of 224,561 discharged patients with a diagnosis of nontraumatic SAH, 4714 (2.10%) were defined as morbidly obese. Patients with morbid obesity were younger (54.3 ± 0.44 vs. 59.5 ± 0.08 years; P < 0.001) and had longer length of stay (LOS) (13 ± 0.46 vs. 11.5 ± 0.06 days; P = 0.002). Morbid obesity was associated with significantly higher hospital costs (P < 0.001) and charges (P < 0.001). The risk of acute respiratory failure was higher in morbidly obese patients (odds ratio [OR] 1.49, 95% confidence interval [CI]: 1.3-1.71, P < 0.001). In a multivariate analysis of hospital mortality, obesity had a negative impact on mortality (OR 0.83, 95% CI: 0.74-0.92, P < 0.001). Overall, in-hospital mortality was associated with age, morbid obesity, LOS, clipping and coiling, and acute respiratory failure but not the symptomatic vasospasm. CONCLUSIONS: Morbid obesity is associated with increased LOS, hospital costs and charges and with acute respiratory failure. However, it is also associated with a decrease in hospital mortality.


Assuntos
Efeitos Psicossociais da Doença , Mortalidade Hospitalar/tendências , Obesidade Mórbida/diagnóstico , Obesidade Mórbida/mortalidade , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/mortalidade , Estudos de Coortes , Feminino , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Obesidade Mórbida/economia , Prognóstico , Hemorragia Subaracnóidea/economia , Estados Unidos/epidemiologia
18.
Br J Neurosurg ; 31(6): 714-717, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28618921

RESUMO

BACKGROUND: Elderly patients presenting with an acute subdural hematoma (aSDH) have historically had unfavorable outcomes. METHODS: We retrospectively reviewed patient records from 2005 through 2015 that were ≥80 years of age and underwent surgical evacuation of aSDH. RESULTS: Thirty-four patients met inclusion criteria, with a mean age of 84 years (range 80-91). Glascow Outcome Scale (GOS) of 4-5 was deemed a good outcome and a GOS 1-3 was deemed to be a poor outcome. Six patients had good outcome at last follow up and 27 patients had poor outcome. Patients with a higher presenting Glascow Coma Scale (GCS) trended towards better outcome [(good: mean 13.1, median 14.5, IQR 12.5-15) vs. (poor: mean 9.6, median 10, IQR 6-14) p = 0.06]. Patients with a higher in-hospital post-operative GCS score had significantly better overall outcome than patients who left the hospital with a lower GCS score [(good: mean 14.5, median 14.5, IQR 14-15) vs. (poor: mean 8.4, median 9, IQR 4-11) p = 0.001]. Patients with a good outcome had a median aSDH thickness of 17mm (IQR 12.75-19.75) while patients with a poor outcome had a median thickness of 20mm (IQR 16-24.5); p = 0.17. In addition, patients with a good outcome had a median midline shift of 10mm (IQR 6-12.5), while patients with a poor outcome had a median midline shift of 14mm (IQR 10-20); p = 0.07. CONCLUSIONS: The prognosis for elderly patients with large aSDH remains poor, but a subset of patients can benefit from surgical intervention.


Assuntos
Hematoma Subdural Agudo/diagnóstico , Acidentes por Quedas , Idoso de 80 Anos ou mais , Feminino , Escala de Resultado de Glasgow , Hematoma Subdural Agudo/diagnóstico por imagem , Hematoma Subdural Agudo/cirurgia , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Centros de Traumatologia , Resultado do Tratamento
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