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1.
Surg Endosc ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39060625

RESUMO

BACKGROUND: Bariatric surgery offers effective treatment for morbid obesity and associated medical comorbidities, with excellent short- and long-term outcomes. Although it has been well documented that racial minority bariatric patients have worse outcomes than White patients, it remains unclear whether this recognition has led to improvement. Herein, we assess recent trends in bariatric surgery among Black and White patients and compare early postoperative outcomes by race. METHODS: Primary sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) patients from 2015 to 2021 reported to the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program were studied. Bariatric patients were stratified by race (Black and White) and perioperative outcomes were compared between matched Black and White patients. Primary outcome was 30-day mortality. Secondary outcomes included hospital readmissions, hospital length of stay (LOS), reoperation, and postoperative complications. RESULTS: Overall, there were 193,071 Black and 645,224 White primary bariatric patients, with a higher volume of SG and RGYB performed among White patients. A total of 219,566 Black and White bariatric patients were matched and included in the case-control. Black patients were found to have higher rates of 30-day mortality (0.02% vs. 0.01%; p = 0.03) and readmissions (3.68% vs. 2.65%; p < 0.001). There were no significant differences in LOS, reoperations, or overall postoperative complications. However, there was a higher postoperative pulmonary thromboembolism rate (0.16% vs 0.08%; p < 0.001).). The differences in perioperative outcomes stratified by race persisted over the study period (Fig. 1). CONCLUSION: Black bariatric surgery patients continue to have worse perioperative outcomes compared with their White counterparts. Further work must be done to determine contributing factors in order to effect improvement in outcomes in bariatric surgical care for racial minority patients.

2.
J Surg Res ; 298: 81-87, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38581766

RESUMO

INTRODUCTION: Enhanced Recovery Programs (ERPs) mitigate racial disparities in postoperative length of stay (LOS) for colorectal populations. It is unclear, however, if these effects exist in the bariatric surgery population. Therefore, this study aimed to evaluate the racial disparities in LOS before and after implementation of bariatric surgery ERP. METHODS: A retrospective cohort study was performed using data from a single institution. Patients undergoing minimally invasive sleeve gastrectomy or Roux-en-Y gastric bypass from 2017 to 2019 (pre-ERP) or 2020-2022 (ERP) were included. Chi-square, Kruskal-Wallis, and analysis of variance were used to compare groups, and estimated LOS (eLOS) was assessed via multivariable regression. RESULTS: Seven hundred sixty four patients were identified, including 363 pre-ERPs and 401 ERPs. Pre-ERP and ERP cohorts were similar in age (median 44.3 years versus 43.8 years, P = 0.80), race (53.4% Black versus 56.4% Black, P = 0.42), and preoperative body mass index (median 48.3 versus 49.4, P = 0.14). Overall median LOS following bariatric surgery decreased from 2 days pre-ERP to 1 day following ERP (P < 0.001). Average LOS for Black and White patients decreased by 0.5 and 0.48 days, respectively. However, overall eLOS remained greater for Black patients compared with White patients despite ERP implementation (eLOS 0.21 days, P = 0.01). CONCLUSIONS: Implementation of a bariatric surgery ERP was associated with decreased LOS for both Black and White patients. However, Black patients did have slightly longer LOS than White patients in both pre-ERP and ERP eras. More work is needed to understand the driving mechanism(s) of these disparities to eliminate them.


Assuntos
Cirurgia Bariátrica , Recuperação Pós-Cirúrgica Melhorada , Tempo de Internação , Humanos , Masculino , Feminino , Tempo de Internação/estatística & dados numéricos , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Cirurgia Bariátrica/estatística & dados numéricos , Negro ou Afro-Americano/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Obesidade Mórbida/cirurgia , Obesidade Mórbida/etnologia , População Branca/estatística & dados numéricos
3.
Surg Endosc ; 37(8): 6519-6525, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37277519

RESUMO

INTRODUCTION: Bariatric surgery is a successful treatment for obesity, but barriers to surgery exist, including low health literacy. National organizations recommend patient education materials (PEM) not exceed a sixth-grade reading level. Difficult to comprehend PEM can exacerbate barriers to bariatric surgery, especially in the Deep South where high obesity and low literacy rates exist. This study aimed to assess and compare the readability of webpages and electronic medical record (EMR) bariatric surgery PEM from one institution. METHODS: Readability of online bariatric surgery and standardized perioperative EMR PEM were analyzed and compared. Text readability was assessed by validated instruments: Flesch Reading Ease Formula (FRE), Flesch Kincaid Grade Level (FKGL), Gunning Fog (GF), Coleman-Liau Index (CL), Simple Measure of Gobbledygook (SMOG), Automated Readability Index (ARI), and Linsear Write Formula (LWF). Mean readability scores were calculated with standard deviations and compared using unpaired t-tests. RESULTS: 32 webpages and seven EMR education documents were analyzed. Webpages were overall "difficult to read" compared to "standard/average" readability EMR materials (mean FRE 50.5 ± 18.3 vs. 67.4 ± 4.2, p = 0.023). All webpages were at or above high school reading level: mean FKGL 11.8 ± 4.4, GF 14.0 ± 3.9, CL 9.5 ± 3.2, SMOG 11.0 ± 3.2, ARI 11.7 ± 5.1, and LWF 14.9 ± 6.6. Webpages with highest reading levels were nutrition information and lowest were patient testimonials. EMR materials were sixth to ninth grade reading level: FKGL 6.2 ± 0.8, GF 9.3 ± 1.4, CL 9.7 ± 0.9, SMOG 7.1 ± 0.8, ARI 6.1 ± 1.0, and LWF 5.9 ± 0.8. CONCLUSION: Surgeon curated bariatric surgery webpages have advanced reading levels above recommended thresholds compared to standardized PEM from an EMR. This readability gap may unintentionally contribute to barriers to surgery and affect postoperative outcomes. Streamlined efforts are needed to create materials that are easier to read and comply with recommendations.


Assuntos
Cirurgia Bariátrica , Letramento em Saúde , Humanos , Compreensão , Smog , Educação de Pacientes como Assunto , Obesidade , Internet
4.
Am Surg ; 89(6): 2194-2199, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35726516

RESUMO

Over the past 5 years, The University of Alabama at Birmingham (UAB) Department of Surgery has taken a keen interest in the practice of surgery in rural Alabama and has established the UAB surgery community network. Our goal is to improve the delivery of surgical care in rural areas through active recruitment of rural surgeons, the development of research around rural surgery practice, and the expansion of a surgery network throughout the state. Here, we will present the challenges faced by rural surgery, our early work to address these challenges, and offer a plan for moving forward.


Assuntos
Redes Comunitárias , Cirurgiões , Humanos , Alabama , População Rural
6.
JAMA Netw Open ; 4(2): e210112, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33630087

RESUMO

Importance: Genetic disorders are historically defined through phenotype-first approaches. However, risk estimates derived from phenotype-linked ascertainment may overestimate severity and penetrance. Pathogenic variants in DICER1 are associated with increased risks of rare and common neoplasms and thyroid disease in adults and children. This study explored how effectively a genome-first approach could characterize the clinical traits associated with germline DICER1 putative loss-of-function (pLOF) variants in an unselected clinical cohort. Objective: To examine the prevalence, penetrance, and phenotypic characteristics of carriers of germline DICER1 pLOF variants via genome-first ascertainment. Design, Setting, and Participants: This cohort study classifies DICER1 variants in germline exome sequence data from 92 296 participants of the Geisinger MyCode Community Health Initiative. Data for each MyCode participant were used from the start of the Geisinger electronic health record to February 1, 2018. Main Outcomes and Measures: Prevalence of germline DICER1 variation; penetrance of malignant tumors and thyroid disease in carriers of germline DICER1 variation; structured, manual review of electronic health records; and DICER1 sequencing of available tumors from an associated cancer registry. Results: A total of 92 296 adults (mean [SD] age, 59 [18] years; 98% white; 60% female) participated in the study. Germline DICER1 pLOF variants were observed in 1 in 3700 to 1 in 4600 participants, more than double the expected prevalence. Malignant tumors (primarily thyroid carcinoma) were observed in 4 of 25 participants (16%) with DICER1 pLOF variants, which is comparable (by 50 years of age) to the frequency of neoplasms in the largest registry- and clinic-based (phenotype-first) DICER1 studies published to date. DICER1 pLOF variants were significantly associated with risks of thyroidectomy (odds ratio [OR], 6.0; 95% CI, 2.2-16.3; P = .007) and thyroid cancer (OR, 9.2; 95% CI, 2.1-34.7; P = .02) compared with controls, but there was not a significant increase in the risk of goiter (OR, 1.8; 95% CI, 0.7-4.9). A female patient in her 80s who was a carrier of a germline DICER1 hotspot variant was apparently healthy on electronic health record review. The term DICER1 did not appear in any of the medical records of the 25 participants with a pLOF DICER1 variant, even in those affected with a known DICER1-associated tumor or thyroid phenotype. Conclusions and Relevance: This cohort study was able to ascertain individuals with germline DICER1 variants based on a genome-first approach rather than through a previously established DICER1-related phenotype. Use of the genome-first approach may complement more traditional approaches to syndrome delineation and may be an efficient approach for risk estimation.


Assuntos
RNA Helicases DEAD-box/genética , Penetrância , Fenótipo , Ribonuclease III/genética , Doenças da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Genoma , Mutação em Linhagem Germinativa , Bócio Nodular/epidemiologia , Bócio Nodular/genética , Doença de Graves/epidemiologia , Doença de Graves/genética , Heterozigoto , Humanos , Hipotireoidismo/epidemiologia , Hipotireoidismo/genética , Neoplasias Renais/epidemiologia , Neoplasias Renais/genética , Mutação com Perda de Função , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Neoplasias/genética , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/genética , Prevalência , Blastoma Pulmonar/epidemiologia , Blastoma Pulmonar/genética , Sarcoma/epidemiologia , Sarcoma/genética , Tumor de Células de Sertoli-Leydig/epidemiologia , Tumor de Células de Sertoli-Leydig/genética , Tumores do Estroma Gonadal e dos Cordões Sexuais/epidemiologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/genética , Neoplasias Testiculares/epidemiologia , Neoplasias Testiculares/genética , Doenças da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/genética , Tireoidectomia/estatística & dados numéricos , Tireotoxicose/epidemiologia , Tireotoxicose/genética , Tumor de Wilms/epidemiologia , Tumor de Wilms/genética , Adulto Jovem
7.
Mucosal Immunol ; 11(6): 1694-1704, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30076393

RESUMO

Intestinal macrophages in healthy human mucosa are profoundly down-regulated for inflammatory responses (inflammation anergy) due to stromal TGF-ß inactivation of NF-κB. Paradoxically, in cytomegalovirus (CMV) intestinal inflammatory disease, one of the most common manifestations of opportunistic CMV infection, intestinal macrophages mediate severe mucosal inflammation. Here we investigated the mechanism whereby CMV infection promotes macrophage-mediated mucosal inflammation. CMV infected primary intestinal macrophages but did not replicate in the cells or reverse established inflammation anergy. However, CMV infection of precursor blood monocytes, the source of human intestinal macrophages in adults, prevented stromal TGF-ß-induced differentiation of monocytes into inflammation anergic macrophages. Mechanistically, CMV up-regulated monocyte expression of the TGF-ß antagonist Smad7, blocking the ability of stromal TGF-ß to inactivate NF-κB, thereby enabling MyD88 and NF-κB-dependent cytokine production. Smad7 expression also was markedly elevated in mucosal tissue from subjects with CMV colitis and declined after antiviral ganciclovir therapy. Confirming these findings, transfection of Smad7 antisense oligonucleotide into CMV-infected monocytes restored monocyte susceptibility to stromal TGF-ß-induced inflammation anergy. Thus, CMV-infected monocytes that recruit to the mucosa, not resident macrophages, are the source of inflammatory macrophages in CMV mucosal disease and implicate Smad7 as a key regulator of, and potential therapeutic target for, CMV mucosal disease.


Assuntos
Infecções por Citomegalovirus/imunologia , Citomegalovirus/fisiologia , Inflamação/imunologia , Mucosa Intestinal/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Proteína Smad7/metabolismo , Células Cultivadas , Anergia Clonal , Humanos , Macrófagos/virologia , Monócitos/virologia , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , RNA Interferente Pequeno/genética , Proteína Smad7/genética , Fator de Crescimento Transformador beta/metabolismo , Adulto Jovem
8.
Surg Obes Relat Dis ; 14(5): 631-636, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29454535

RESUMO

BACKGROUND: Despite a lack of demonstrated patient benefit, many insurance providers mandate a physician-supervised diet before financial coverage for bariatric surgery. OBJECTIVES: To compare weight loss between patients with versus without insurance mandating a preoperative diet. SETTING: University hospital, United States. METHODS: Retrospective study of all patients who underwent laparoscopic Roux-en-Y gastric bypass or sleeve gastrectomy over a 5-year period, stratified based on whether an insurance-mandated physician-supervised diet was required. Weight loss outcomes at 6, 12, and 24 months postoperation were compared. Linear mixed-models and backward-stepwise selection were used. P<0.05 was considered significant. RESULTS: Of 284 patients, 225 (79%) were required and 59 (21%) were not required to complete a preoperative diet by their insurance provider. Patients without the requirement had a shorter time to operation from initial consultation (P = .04), were older (P<.01), and were more likely to have government-sponsored insurance (P<.01). There was no difference in preoperative weight or body mass index or co-morbidities. In unadjusted models, percent excess weight loss was superior in the group without an insurance-mandated diet at 12 (P = .050) and 24 (P = .045) months. In adjusted analyses, this group also had greater percent excess weight loss at 6 (P<.001), 12 (P<.001), and 24 (P<.001) months; percent total weight loss at 24 months (P = .004); and change in body mass index at 6 (P = .032) and 24 (P = .007) months. There was no difference in length of stay or complication rates. CONCLUSIONS: Insurance-mandated preoperative diets delay treatment and may lead to inferior weight loss.


Assuntos
Cirurgia Bariátrica/estatística & dados numéricos , Dieta Redutora/estatística & dados numéricos , Seguro Saúde/estatística & dados numéricos , Adulto , Fatores Etários , Feminino , Gastrectomia/métodos , Gastrectomia/estatística & dados numéricos , Derivação Gástrica/estatística & dados numéricos , Humanos , Cobertura do Seguro/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Cuidados Pré-Operatórios/métodos , Cuidados Pré-Operatórios/estatística & dados numéricos , Estudos Retrospectivos , Tempo para o Tratamento , Resultado do Tratamento , Redução de Peso/fisiologia
9.
Surg Endosc ; 32(5): 2232-2238, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29067574

RESUMO

BACKGROUND: Strategies to address weight recidivism following Roux-en-Y gastric bypass (RYGB) could be developed if patients at risk were identified in advance. This study aimed to determine factors that predict weight regain. METHODS: Retrospective review was performed of patients who underwent laparoscopic RYGB at a single institution over 10 years. Group-based modeling was used to estimate trajectories of weight regain after nadir and stratify patients based on percent weight change (%WC). RESULTS: Three trajectories were identified from 586 patients: 121 had ongoing weight loss, 343 were weight stable, and 122 regained weight. Male sex (p = 0.020) and white race (p < 0.001) were associated with stable weight or weight regain. Being from a neighborhood of socioeconomic advantage (p = 0.035) was associated with weight regain. Patients with weight regain experienced improved percent weight loss (%WL) at nadir (p < 0.001) and ΔBMI (p = 0.002), yet they had higher weight and BMI and lower %WL and ΔBMI than the other two groups during long-term follow-up. On multivariate analyses, those who regained weight were more likely from socioeconomically advantaged neighborhoods (OR 1.82, CI 1.18-2.79). CONCLUSIONS: Several patient-related characteristics predicted an increased likelihood of weight regain. Further studies are needed to elucidate how these factors contribute to weight recidivism following bariatric surgery.


Assuntos
Derivação Gástrica , Laparoscopia , Obesidade Mórbida/cirurgia , Aumento de Peso , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos
10.
Lab Chip ; 16(17): 3304-16, 2016 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-27436197

RESUMO

Time-lapse imaging of biological samples is important for understanding complex (patho)physiological processes. A growing number of point-of-care biomedical assays rely on real-time imaging of flowing or migrating cells. However, the cost and complexity of integrating experimental models simulating physiologically relevant microenvironments with bulky imaging systems that offer sufficient spatiotemporal resolution limit the use of time-lapse assays in research and clinical settings. This paper introduces a compact and affordable lens-free imaging (LFI) device based on the principle of coherent in-line, digital holography for time-lapse cell migration assays. The LFI device combines single-cell resolution (1.2 µm) with a large field of view (6.4 × 4.6 mm(2)), thus rendering it ideal for high-throughput applications and removing the need for expensive and bulky programmable motorized stages. The set-up is so compact that it can be housed in a standard cell culture incubator, thereby avoiding custom-built stage top incubators. LFI is thoroughly benchmarked against conventional live-cell phase contrast microscopy for random cell motility on two-dimensional (2D) surfaces and confined migration on 1D-microprinted lines and in microchannels using breast adenocarcinoma cells. The quality of the results obtained by the two imaging systems is comparable, and they reveal that cells migrate more efficiently upon increasing confinement. Interestingly, assays of confined migration more readily distinguish the migratory potential of metastatic MDA-MB-231 cells from non-metastatic MCF7 cells relative to traditional 2D migration assays. Altogether, this single-cell migration study establishes LFI as an elegant and useful tool for live-cell imaging.


Assuntos
Adenocarcinoma/patologia , Neoplasias da Mama/patologia , Ensaios de Migração Celular/instrumentação , Dispositivos Lab-On-A-Chip , Análise de Célula Única , Imagem com Lapso de Tempo , Microambiente Tumoral , Adenocarcinoma/diagnóstico , Neoplasias da Mama/diagnóstico , Linhagem Celular Tumoral , Movimento Celular , Desenho de Equipamento , Feminino , Ensaios de Triagem em Larga Escala , Holografia , Humanos , Microscopia de Contraste de Fase , Testes Imediatos , Impressão Tridimensional , Reprodutibilidade dos Testes
11.
Surg Endosc ; 30(11): 5077-5083, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-26969666

RESUMO

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is an effective treatment for achieving and maintaining weight loss and for improving obesity-related comorbidities. As part of the approval process for bariatric surgery, many insurance companies require patients to have documented recent participation in a supervised weight loss program. The goal of this study was to evaluate the relationship of preoperative weight changes with outcomes following LRYGB. METHODS: A retrospective review was conducted of adult patients undergoing LRYGB between 2008 and 2012 at a single institution. Patients were stratified into quartiles based on % excess weight gain (0-4.99 % and ≥5 % EWG) and % excess weight loss (0-4.99 % and ≥5 % EWL). Generalized linear models were used to examine differences in postoperative weight outcomes at 6, 12, and 24 months. Covariates included in the final adjusted models were determined using backwards stepwise selection. RESULTS: Of the 300 patients included in the study, there were no significant demographic differences among the quartiles. However, there was an increased time to operation for patients who gained or lost ≥5 % excess body weight (p < 0.001). Although there was no statistical significance in postoperative complications, there was a higher rate of complications in patients with ≥5 % EWG compared to those with ≥5 % EWL (12.5 vs. 4.8 %, respectively; p = 0.29). Unadjusted and adjusted generalized linear models showed no statistically significant association between preoperative % excess weight change and weight loss outcomes at 24 months. CONCLUSION: Patients with the greatest % preoperative excess weight change had the longest intervals from initial visit to operation. No significant differences were seen in perioperative and postoperative outcomes. This study suggests preoperative weight loss requirements may delay the time to operation without improving postoperative outcomes or weight loss.


Assuntos
Obesidade Mórbida/cirurgia , Redução de Peso , Adulto , Feminino , Derivação Gástrica/métodos , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios , Estudos Retrospectivos , Resultado do Tratamento
12.
Obes Surg ; 25(4): 705-11, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25304222

RESUMO

BACKGROUND: Obesity poses serious health consequences, and bariatric surgery remains the most effective and durable treatment. The goal of this study was to identify the association of race and socioeconomic characteristics with clinical outcomes following laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: A retrospective review of all patients who underwent LRYGB between 2004 and 2010 was conducted. Outcomes analyzed included percent excess weight loss (%EWL), percent weight loss (%WL), change in body mass index (ΔBMI), and improvement or remission of obesity-associated medical conditions. RESULTS: In total, 663 patients met inclusion criteria with 170 (25.6%) African Americans and 493 (74.4%) European Americans. When compared to European Americans, the African American group included significantly more women and had a significantly higher preoperative BMI and lower socioeconomic status. In adjusted analyses, African Americans had significantly lower %EWL, %WL, and ΔBMI than the European Americans at 1-, 2-, and 5-year intervals of follow-up. Adjusted spline models including all follow-up visits for all patients also demonstrated a significant difference between the races in %EWL, %WL, and ΔBMI. Both races had similar improvement or remission of type 2 diabetes mellitus, obstructive sleep apnea, hyperlipidemia, and hypertension. CONCLUSION: Although African Americans had a statistically significant lower %EWL, %WL, and ΔBMI, both groups had durable weight loss and comparable rates of improvement or remission of obesity-associated comorbidities. Thus, both groups have significant improvement in their overall health after LRYGB.


Assuntos
Derivação Gástrica , Obesidade Mórbida/diagnóstico , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Grupos Raciais/estatística & dados numéricos , Classe Social , Adulto , Índice de Massa Corporal , Comorbidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/cirurgia , Feminino , Derivação Gástrica/reabilitação , Derivação Gástrica/estatística & dados numéricos , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/cirurgia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/etnologia , Estudos Retrospectivos , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/cirurgia , Resultado do Tratamento , Redução de Peso
13.
J Biol Chem ; 289(14): 10057-68, 2014 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-24550393

RESUMO

Elastin is the intrinsically disordered polymeric protein imparting the exceptional properties of extension and elastic recoil to the extracellular matrix of most vertebrates. The monomeric precursor of elastin, tropoelastin, as well as polypeptides containing smaller subsets of the tropoelastin sequence, can self-assemble through a colloidal phase separation process called coacervation. Present understanding suggests that self-assembly is promoted by association of hydrophobic domains contained within the tropoelastin sequence, whereas polymerization is achieved by covalent joining of lysine side chains within distinct alanine-rich, α-helical cross-linking domains. In this study, model elastin polypeptides were used to determine the structure of cross-linking domains during the assembly process and the effect of sequence alterations in these domains on assembly and structure. CD temperature melts indicated that partial α-helical structure in cross-linking domains at lower temperatures was absent at physiological temperature. Solid-state NMR demonstrated that ß-strand structure of the cross-linking domains dominated in the coacervate state, although α-helix was predominant after subsequent cross-linking of lysine side chains with genipin. Mutation of lysine residues to hydrophobic amino acids, tyrosine or alanine, leads to increased propensity for ß-structure and the formation of amyloid-like fibrils, characterized by thioflavin-T binding and transmission electron microscopy. These findings indicate that cross-linking domains are structurally labile during assembly, adapting to changes in their environment and aggregated state. Furthermore, the sequence of cross-linking domains has a dramatic effect on self-assembly properties of elastin-like polypeptides, and the presence of lysine residues in these domains may serve to prevent inappropriate ordered aggregation.


Assuntos
Tropoelastina/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Ressonância Magnética Nuclear Biomolecular , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Tropoelastina/genética , Tropoelastina/metabolismo
14.
Dig Endosc ; 26(3): 350-7, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23855514

RESUMO

BACKGROUND AND AIM: The 'bear-claw' or over-the-scope-clip system (OTSC; Ovesco Endoscopy, Tübingen, Germany) is a new clipping device developed for closure of large luminal gastrointestinal (GI) defects. The aim of the present study was to evaluate the clinical outcomes of patients treated with the OTSC. METHODS: The present study was an observational, open-label, retrospective, single-arm case series conducted at two hospitals with tertiary care endoscopy. It involved 20 clip applications in 16 patients (median age 65.8 years [range 51-90 years], seven women) with GI defects from fistulas and anastomotic dehiscence and peptic ulcer bleeding. RESULTS: The range of indications included gastrointestinal bleeding (n=6), gastrocutaneous fistulas (n=3), esophagotracheal and/or esophagopleural fistulae (n=3), resection ofsubmucosal tumor (n=2), stent fixation (n=1), and anastomotic leak after esophagectomy (n=1). The overall success rate for the OTSC device was 75% (12 out of 16 patients). The overall per case success rate was 70% (14 of 20 applications). Mean follow up was 10 months (range 1-10). There were no complications (0%) related to endoscopy, sedation or application of the clipping device. CONCLUSIONS: The OTSC system is a useful device in a variety of clinical scenarios including the management of larger GI leaks and fistulas, GI bleeding, full-thickness resection of tumors, and stent anchoring, even in very old and frail patients.


Assuntos
Endoscopia Gastrointestinal/instrumentação , Gastroenteropatias/diagnóstico , Gastroenteropatias/cirurgia , Instrumentos Cirúrgicos , Idoso , Idoso de 80 Anos ou mais , Angioplastia/instrumentação , Angioplastia/métodos , Estudos de Coortes , Endoscópios Gastrointestinais , Endoscopia Gastrointestinal/métodos , Desenho de Equipamento , Segurança de Equipamentos , Fístula Esofágica/diagnóstico , Fístula Esofágica/cirurgia , Feminino , Fístula Gástrica/diagnóstico , Fístula Gástrica/cirurgia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/cirurgia , Hemostasia Cirúrgica/instrumentação , Hemostasia Cirúrgica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Stents , Resultado do Tratamento
15.
J Gastrointest Surg ; 18(2): 250-5; discussion 255-6, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24101451

RESUMO

BACKGROUND: The goal of this study was to determine the impact of mesenteric defect closure and Roux limb position on the rate of internal hernia after laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: A retrospective review was conducted of all LRYGB patients from 2001 to 2011 who had all internal hernia (IH) defects closed (DC) or all defects not closed (DnC). RESULTS: Of 914 patients, 663 (72.5 %) had DC vs. 251 (27.5 %) with DnC, and 679 (74.3 %) had an ante-colic vs. 235 (25.7 %) with a retro-colic Roux limb. Forty-six patients (5 %) developed a symptomatic IH. Of these, 25 (3.8 %) were in the DC vs. 21 (8.4 %) in the DnC group (p = 0.005), and 26 (3.8 %) were in the ante-colic vs. 20 (8.5 %) in the retro-colic Roux limb position (p = 0.005). Data from 45 patients were available for further analysis. The most common symptom was chronic postprandial abdominal pain (53.4 %). All patients underwent CT scan consistent with IH in 26 patients (57.5 %), suggestive in 7 (15.6 %), showing small bowel obstruction in 4 (8.9 %), and negative in 8 (17.8 %). CONCLUSIONS: Closure of mesenteric defects and ante-colic Roux limb position result in a significantly lower IH rate. Furthermore, a high index of suspicion must be maintained since symptoms may be nonspecific and imaging may be negative in nearly 20 % of patients.


Assuntos
Derivação Gástrica/efeitos adversos , Hérnia/etiologia , Laparoscopia/efeitos adversos , Mesentério/cirurgia , Adolescente , Adulto , Idoso , Feminino , Derivação Gástrica/métodos , Hérnia/diagnóstico por imagem , Herniorrafia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Técnicas de Fechamento de Ferimentos , Adulto Jovem
16.
J Neurosci Res ; 91(11): 1419-28, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24038174

RESUMO

Many studies have shown that tetraspanins play important role in cell-cell and cell-extracellular matrix (ECM) interactions. The repertoire and functions of tetraspanins in Schwann cells, glial cells of the peripheral nervous system have remained largely uncharacterized. This study was undertaken to identify Schwann cell tetraspanins and to elucidate their possible functions. Microarray analysis revealed the expression of numerous tetraspanins in primary culture of Schwann cells. Expression of five of them, CD9, CD63, CD81, CD82, and CD151, and of tetraspanin-associated protein EWI-2 was also confirmed by immunofluorescence. Localization of CD9, CD63, CD81, and EWI-2 was largely confined to paranodes and Schmidt-Lanterman incisures, regions of noncompact myelin. Immunoprecipitation experiments showed that these four proteins form a complex in Schwann cells. siRNA silencing of individual components of the complex did not affect Schwann cell adhesion to ECM proteins or attachment to and alignment with axons. However, suppression of both CD63 and CD81 expression together significantly inhibited extension of Schwann cell processes along axons, without affecting initial attachment of the cells to the axonal surface. Adhesion, spreading, and migration of Schwann cells on ECM proteins also were not affected by double silencing of CD63 and CD81. Suppression of CD63 and CD81 expression did not affect the ability of Schwann cells to myelinate dorsal root ganglion neurons in vitro. These findings strongly suggest that CD63 and CD81 play an important role in Schwann cell spreading along axons but seem to be dispensable for Schwann cell myelination.


Assuntos
Axônios/metabolismo , Comunicação Celular/fisiologia , Células de Schwann/metabolismo , Tetraspanina 28/metabolismo , Tetraspanina 30/metabolismo , Animais , Western Blotting , Adesão Celular/fisiologia , Movimento Celular/fisiologia , Células Cultivadas , Imunofluorescência , Imunoprecipitação , Análise de Sequência com Séries de Oligonucleotídeos , RNA Interferente Pequeno , Ratos , Tetraspaninas/metabolismo , Transfecção
17.
J Immunol ; 190(12): 6626-34, 2013 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-23686492

RESUMO

Increased apoptotic death of gastric epithelial cells is a hallmark of Helicobacter pylori infection, and altered epithelial cell turnover is an important contributor to gastric carcinogenesis. To address the fate of apoptotic gastric epithelial cells and their role in H. pylori mucosal disease, we investigated phagocyte clearance of apoptotic gastric epithelial cells in H. pylori infection. Human gastric mononuclear phagocytes were analyzed for their ability to take up apoptotic epithelial cells (AECs) in vivo using immunofluorescence analysis. We then used primary human gastric epithelial cells induced to undergo apoptosis by exposure to live H. pylori to study apoptotic cell uptake by autologous monocyte-derived macrophages. We show that HLA-DR(+) mononuclear phagocytes in human gastric mucosa contain cytokeratin-positive and TUNEL-positive AEC material, indicating that gastric phagocytes are involved in AEC clearance. We further show that H. pylori both increased apoptosis in primary gastric epithelial cells and decreased phagocytosis of the AECs by autologous monocyte-derived macrophages. Reduced macrophage clearance of apoptotic cells was mediated in part by H. pylori-induced macrophage TNF-α, which was expressed at higher levels in H. pylori-infected, compared with uninfected, gastric mucosa. Importantly, we show that H. pylori-infected gastric mucosa contained significantly higher numbers of AECs and higher levels of nonphagocytosed TUNEL-positive apoptotic material, consistent with a defect in apoptotic cell clearance. Thus, as shown in other autoimmune and chronic inflammatory diseases, insufficient phagocyte clearance may contribute to the chronic and self-perpetuating inflammation in human H. pylori infection.


Assuntos
Apoptose/fisiologia , Células Epiteliais/patologia , Infecções por Helicobacter/imunologia , Leucócitos Mononucleares/imunologia , Macrófagos/imunologia , Citometria de Fluxo , Imunofluorescência , Mucosa Gástrica/citologia , Mucosa Gástrica/imunologia , Infecções por Helicobacter/patologia , Helicobacter pylori , Humanos , Marcação In Situ das Extremidades Cortadas , Fagocitose , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
PLoS One ; 7(9): e46130, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23049958

RESUMO

Elastin is a major structural component of elastic fibres that provide properties of stretch and recoil to tissues such as arteries, lung and skin. Remarkably, after initial deposition of elastin there is normally no subsequent turnover of this protein over the course of a lifetime. Consequently, elastic fibres must be extremely durable, able to withstand, for example in the human thoracic aorta, billions of cycles of stretch and recoil without mechanical failure. Major defects in the elastin gene (ELN) are associated with a number of disorders including Supravalvular aortic stenosis (SVAS), Williams-Beuren syndrome (WBS) and autosomal dominant cutis laxa (ADCL). Given the low turnover of elastin and the requirement for the long term durability of elastic fibres, we examined the possibility for more subtle polymorphisms in the human elastin gene to impact the assembly and long-term durability of the elastic matrix. Surveys of genetic variation resources identified 118 mutations in human ELN, 17 being non-synonymous. Introduction of two of these variants, G422S and K463R, in elastin-like polypeptides as well as full-length tropoelastin, resulted in changes in both their assembly and mechanical properties. Most notably G422S, which occurs in up to 40% of European populations, was found to enhance some elastomeric properties. These studies reveal that even apparently minor polymorphisms in human ELN can impact the assembly and mechanical properties of the elastic matrix, effects that over the course of a lifetime could result in altered susceptibility to cardiovascular disease.


Assuntos
Elastina/metabolismo , Peptídeos/metabolismo , Polimorfismo de Nucleotídeo Único/genética , Tropoelastina/genética , Tropoelastina/metabolismo , Humanos , Mutação , Peptídeos/genética
19.
Surg Endosc ; 26(12): 3515-20, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22684978

RESUMO

BACKGROUND: Bariatric surgery remains the most effective treatment for morbid obesity, and laparoscopic Roux-en-Y gastric bypass (LRYGB) continues to be the preferred operation. However, data for long-term outcomes are lacking. Our goal was to determine the long-term clinical outcomes after LRYGB. METHODS: Retrospective review of a prospectively maintained database was conducted on all patients who underwent LRYGB from 2001-2006. Only patients who had postoperative clinic visits both at ≤2 and ≥5 years were included. Data collected included patient demographics and postoperative clinical outcomes, including percent excess weight loss (%EWL), complications, and improvement or resolution of preoperative comorbidities (type 2 diabetes mellitus, hypertension, obstructive sleep apnea, and hyperlipidemia). Data were analyzed by using SAS (version 9.2) and SPSS (version 16) statistical software. RESULTS: There were 770 patients who underwent LRYGB at UAB from 2001-2006. Of these, 172 patients met inclusion criteria (148 women and 24 men) with a median age of 41 years and median body mass index of 46 kg/m(2). Median short- and long-term follow-up was 12 and 75 months, respectively. Mean %EWL was 69% for short-term and 65% for long-term follow-up (P = 0.0032). Of 172 patients, 66 experienced 81 complications at a median of 26 months after operation. The improvement or resolution of comorbidities was maintained in the long-term, and there was no statistically significant difference compared with improvement or resolution in the short-term. CONCLUSIONS: Although there was a statistically significant difference in %EWL between short- and long-term follow-up, both arms showed a clinically relevant %EWL (69 and 65%) and both were statistically significant compared with preoperative values. The improvement or resolution of comorbidities achieved with LRYGB was maintained in long-term follow-up. Thus, LRYGB resulted in significant improvement in clinical outcomes that were durable in the long term.


Assuntos
Derivação Gástrica/métodos , Laparoscopia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
Am Surg ; 78(6): 663-8, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22643261

RESUMO

Marginal ulcer is a significant complication of laparoscopic Roux-en-Y gastric bypass (LRYGB). Most marginal ulcers resolve with medical management, but nonhealing ulcers may require revision of the gastrojejunostomy, a procedure with significant morbidity and mortality. Traditionally, surgical therapy for refractory peptic ulcers includes a vagotomy. The current study evaluates the effectiveness of thoracoscopic truncal vagotomy (TTV) in the management of refractory marginal ulcers. All patients at two institutions with an intractable marginal ulcer after LRYGB treated with TTV between 2003 and 2010 were reviewed. Data were collected from chart review and telephone interview. Seventeen patients (mean age, 39 ± 13 years; 16 females) were diagnosed with marginal ulceration a median of 18 months after LRYGB and proceeded to TTV at a mean of 39 ± 43 weeks (range, 1 to 114 weeks) after the diagnosis. The median operative time was 89 ± 65 minutes (range, 45 to 318 minutes). Four patients had a complication (sympathetic contralateral pleural effusion, pneumothorax, operative bleeding, and readmission for emesis). Eleven patients had follow-up of 3 months to 6 years (median, 7 months). Nine patients (82%) had symptomatic improvement and/or endoscopic resolution, whereas two (18%) did not. No patient had endoscopic evidence of persistent or recurrent marginal ulcer. TTV achieves symptomatic improvement and/or endoscopic resolution of intractable marginal ulcers in over 80 per cent of patients status post gastric bypass and therefore offers a less morbid alternative to revision of the gastrojejunostomy.


Assuntos
Derivação Gástrica/efeitos adversos , Laparoscopia/efeitos adversos , Úlcera Péptica/cirurgia , Úlcera Gástrica/cirurgia , Toracoscopia/métodos , Vagotomia Troncular/métodos , Adulto , Feminino , Seguimentos , Derivação Gástrica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Morbidade/tendências , Obesidade Mórbida/cirurgia , Úlcera Péptica/epidemiologia , Úlcera Péptica/etiologia , Complicações Pós-Operatórias , Estudos Prospectivos , Úlcera Gástrica/epidemiologia , Úlcera Gástrica/etiologia , Tennessee/epidemiologia , Resultado do Tratamento , Adulto Jovem
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