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Macrophages, B cells, and adipocytes are among the adipose tissue (AT) APCs that differentiate and activate naive CD4+ T cells. Mice with adipocyte loss of MHC class II (MHC II) are more insulin sensitive. Because macrophages are professional APCs, mice with genetic myeloid MHC II depletion (myeloid MHC II knockout [mMHCII-/-]) were created and metabolically characterized. FITC+ glucan-coated particles (glucan-encapsulated small interfering RNA [siRNA] particles [GeRPs]) were also used to target MHC II knockout specifically in AT macrophages (ATMs). Mice with total body mMHCII-/- were generated by crossing LyzMCre with H2Ab1 floxed mice. For specific ATM depletion of H2Ab1, GeRPs containing H2Ab1 siRNA were administered to high-fat diet-fed C57BL/6 mice. Unexpectedly, mMHCII-/- mice had loss of both macrophage and adipocyte H2Ab1, one of only two Ag-presenting arms; thus, neither cell could present Ag and activate CD4+ T cells. This inability led to a reduction in AT immunosuppressive regulatory T cells, increased AT CD8+ T cells, and no improvement in systemic metabolism. Thus, with combined systemic myeloid and adipocyte MHC II loss, the impact of ATM-specific alterations in APC activity could not be delineated. Therefore, GeRPs containing H2Ab1 siRNA were administered to specifically reduce ATM H2Ab1 which, in contrast, revealed improved glucose tolerance. In conclusion, loss of either ATM or adipocyte APC function, but not both, improves systemic glucose metabolism because of maintenance of AT regulatory T cells.
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Adipócitos/imunologia , Tecido Adiposo/imunologia , Apresentação de Antígeno , Glucose/imunologia , Macrófagos/imunologia , Adipócitos/citologia , Tecido Adiposo/citologia , Animais , Apresentação de Antígeno/genética , Apresentação de Antígeno/imunologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Glucose/genética , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Macrófagos/citologia , Camundongos , Camundongos KnockoutRESUMO
BACKGROUND: Adipose tissue (AT) inflammation is linked to the development of type 2 diabetes (T2DM) and atherosclerosis in murine models of obesity. Reduced AT regulatory T cells (Tregs), which are anti-inflammatory immune cells, play an important part in this pathogenesis, and we have shown that AT-Tregs are inversely correlated to increasing body-mass-index. The purpose of this study was to evaluate the association between AT-Treg abundance and comorbidity status in patients undergoing bariatric surgery (BS). METHODS: Visceral (intra-abdominal) AT was harvested at that time of primary BS (n = 80) and collagenase digested. AT-Treg abundance (CD4+/CD25+/FOXP3+) was characterized using flow cytometry from the AT stromal vascular fraction. The median AT-Treg abundance (3.03%) was utilized to define high (High-Tregs, n = 39) and low AT-Treg (low-Tregs, n = 38) abundance within this cohort. These two groups were compared in terms of baseline demographic data, preoperative obesity-related comorbidities, glycemic parameters, including insulin resistance (HOMA-IR). RESULTS: Age, excess body weight, and sex were not different between groups. Prevalence of hypertension, hyperlipidemia, or T2DM preoperatively were not different between groups. Compared to High-Tregs, patients with low-Tregs were more likely to have insulin-dependent type 2 diabetes (12.5% vs 2.9%, p = 0.04). Within patients with T2DM, low-Treg patients had higher plasma insulin levels compared to high-Tregs (31.8 (28.4-56.5) vs 15.5 (10.1-23.1), p = 0.04) and trended towards higher insulin resistance (HOMA-IR) (9.0 (5.3-18.3) vs 3.5 (2.2-7.7), p = 0.08). Within those diagnosed with hyperlipidemia, preoperative statin use was higher in Low-Treg patients compared to the control cohort (91% vs 50%, p = 0.056). Low-Treg patients with hypertension were more likely to need 2 + anti-hypertensive agents preoperatively compared to their counterparts (71% vs 44%, p = 0.058). CONCLUSION: Within bariatric candidates, lower visceral AT-Treg abundance was associated with increased baseline medication requirements for type 2 diabetes, hypertension, and hyperlipidemia. This suggests that reduced AT-Tregs may be associated with higher obesity-related comorbidity severity.
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Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Animais , Comorbidade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Gordura Intra-Abdominal , Camundongos , Linfócitos T ReguladoresRESUMO
OBJECTIVES: The incidence rates of acute pancreatitis (AP) and the prevalence of class III obesity, and metabolic syndrome (MetS) are increasing in the US. Since class III obesity was associated with adverse clinical outcomes of AP, we sought to understand if the presence of metabolic comorbidities collectively recognized, as MetS were associated with worse clinical outcomes and increased health-care utilization. METHODS: The Nationwide Readmissions Database (NRD) (2010-2014) was reviewed to identify all adult subjects with a principal discharge diagnosis of AP. Inpatient mortality, severe AP (SAP), and 30-day readmissions were the primary outcomes analyzed. Propensity score weighted analyses were used to compare AP subjects with and without MetS and were further stratified by class III obesity status. RESULTS: MetS was associated with 12.91% (139,165/1,078,183) of all admissions with AP. Propensity score weighted analyses showed that MetS was associated with an increased proportion of SAP (OR 1.21, 95% CI 1.17, 1.25), but decreased mortality (OR 0.62, 95% CI 0.54, 0.70) and 30-day readmissions (OR 0.86, 95% CI 0.83, 0.89). Propensity score weighted analyses also revealed that class III obesity was independently associated with increased mortality in AP subjects with (OR 1.92, 95% CI 1.41, 2.61) and without MetS (OR 1.55, 95% CI 1.26, 1.92), and increased SAP in subjects with and without MetS. CONCLUSIONS: Class III obesity appears to be the primary factor associated with adverse clinical outcomes in subjects with MetS admitted with AP. This has significant implications for patient management and future research targeting AP.
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Síndrome Metabólica/complicações , Obesidade Mórbida/complicações , Pancreatite/complicações , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Comorbidade , Bases de Dados Factuais , Feminino , Custos Hospitalares , Mortalidade Hospitalar , Humanos , Masculino , Síndrome Metabólica/mortalidade , Pessoa de Meia-Idade , Obesidade Mórbida/mortalidade , Pancreatite/mortalidade , Readmissão do Paciente/estatística & dados numéricos , Pontuação de Propensão , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND AIMS: Previous studies have validated EUS-guided needle-based confocal laser endomicroscopy (nCLE) diagnosis of intraductal papillary mucinous neoplasms (IPMNs). We sought to derive EUS-guided nCLE criteria for differentiating IPMNs with high-grade dysplasia/adenocarcinoma (HGD-Ca) from those with low/intermediate-grade dysplasia (LGD). METHODS: We performed a post hoc analysis of consecutive IPMNs with a definitive diagnosis from a prospective study evaluating EUS-guided nCLE in the diagnosis of pancreatic cysts. Three internal endosonographers reviewed all nCLE videos for the patients and identified potential discriminatory EUS-guided nCLE variables to differentiate HGD-Ca from LGD IPMNs (phase 1). Next, an interobserver agreement (IOA) analysis of variables from phase 1 was performed among 6 blinded external nCLE experts (phase 2). Last, 7 blinded nCLE-naïve observers underwent training and quantified variables with the highest IOA from phase 2 using dedicated software (phase 3). RESULTS: Among 26 IPMNs (HGD-Ca in 16), the reference standard was surgical histopathology in 24 and cytology confirmation of metastatic liver lesions in 2 patients. EUS-guided nCLE characteristics of increased papillary epithelial "width" and "darkness" were the most sensitive variables (90%; 95% confidence interval [CI], 84%-94% and 91%; 95% CI, 85%-95%, respectively) and accurate (85%; 95% CI, 78%-90% and 84%; 95% CI, 77%-89%, respectively) with substantial (κ = 0.61; 95% CI, 0.51-0.71) and moderate (κ = 0.55; 95% CI, 0.45-0.65) IOAs for detecting HGD-Ca, respectively (phase 2). Logistic regression models were fit for the outcome of HGD-Ca as predictor variables (phase 3). For papillary width (cut-off ≥50 µm), the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.95, respectively. For papillary darkness (cut-off ≤90 pixel intensity), the sensitivity, specificity, and AUC for detection of HGD-Ca were 87.5% (95% CI, 62%-99%), 100% (95% CI, 69%-100%), and 0.90, respectively. CONCLUSIONS: In this derivation study, quantification of papillary epithelial width and darkness identified HGD-Ca in IPMNs with high accuracy. These quantifiable variables can be used in multicenter studies for risk stratification of IPMNs. (Clinical trial registration number: NCT02516488.).
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Microscopia Confocal , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Idoso , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Endossonografia , Feminino , Humanos , Lasers , Masculino , Microscopia Confocal/métodos , Pessoa de Meia-Idade , Neoplasias Intraductais Pancreáticas/diagnóstico por imagem , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Estudos ProspectivosRESUMO
Humoral alloimmunity negatively impacts both short- and long-term cell and solid organ transplant survival. We previously reported that alloantibody-mediated rejection of transplanted hepatocytes is critically dependent on host macrophages. However, the effector mechanism(s) of macrophage-mediated injury to allogeneic liver parenchymal cells is not known. We hypothesized that macrophage-mediated destruction of allogeneic hepatocytes occurs by cell-cell interactions requiring FcγRs. To examine this, alloantibody-dependent hepatocyte rejection in CD8-depleted wild-type (WT) and Fcγ-chain knockout (KO; lacking all functional FcγR) transplant recipients was evaluated. Alloantibody-mediated hepatocellular allograft rejection was abrogated in recipients lacking FcγR compared with WT recipients. We also investigated anti-FcγRI mAb, anti-FcγRIII mAb, and inhibitors of intracellular signaling (to block phagocytosis, cytokines, and reactive oxygen species [ROS]) in an in vitro alloantibody-dependent, macrophage-mediated hepatocytoxicity assay. Results showed that in vitro alloantibody-dependent, macrophage-mediated hepatocytotoxicity was critically dependent on FcγRs and ROS. The adoptive transfer of WT macrophages into CD8-depleted FcγR-deficient recipients was sufficient to induce alloantibody-mediated rejection, whereas adoptive transfer of macrophages from Fcγ-chain KO mice or ROS-deficient (p47 KO) macrophages was not. These results provide the first evidence, to our knowledge, that alloantibody-dependent hepatocellular allograft rejection is mediated by host macrophages through FcγR signaling and ROS cytotoxic effector mechanisms. These results support the investigation of novel immunotherapeutic strategies targeting macrophages, FcγRs, and/or downstream molecules, including ROS, to inhibit humoral immune damage of transplanted hepatocytes and perhaps other cell and solid organ transplants.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Rejeição de Enxerto/imunologia , Hepatócitos/imunologia , Macrófagos/imunologia , Receptores de IgG/metabolismo , ATPases Associadas a Diversas Atividades Celulares/genética , Animais , Células Cultivadas , Citotoxicidade Imunológica , DNA Helicases/genética , Humanos , Isoanticorpos/metabolismo , Transplante de Fígado , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo , Receptores de IgG/genética , Transdução de SinaisRESUMO
Filiform warts are commonly treated with surgical removal or cryotherapy, yet such treatment modalities may result in complications for darker skin types. We report a man successfully treated for more than 50 filiform facial warts using a combination of 5-fluorouracil 5% and salicylic acid 20%.
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Ácido Salicílico , Verrugas , Administração Tópica , Crioterapia , Fluoruracila/uso terapêutico , Humanos , Masculino , Ácido Salicílico/uso terapêutico , Verrugas/tratamento farmacológicoRESUMO
INTRODUCTION: Contrary to published literature, our institutional data demonstrated reduced weight loss following laparoscopic sleeve gastrectomy (LSG) compared to gastric bypass (LRYGB). The purpose of this study was to determine if known predictors of poor weight loss accounted for this discrepancy at a large volume center. METHODS: All patients undergoing primary LSG (n = 322) and LRYGB (n = 249), from 2014 to 2016, at a single institution were retrospectively reviewed. Baseline medical, socioeconomic, and follow-up data (6, 12, 24, and 36 months) were obtained. The first aim characterized differences in LSG and LRYGB. The second objective determined predictors of experiencing the lowest or highest quartile of excess body weight loss [(EBWL), (%EBWL-25th, %EBWL-75th)] at 12, 24, and 36 months. Thirdly, predictors of poor weight loss within sleeve gastrectomy were characterized. RESULTS: In comparison to patients undergoing LRYGB, LSG patients demonstrated lower baseline BMI (47.9 ± 8.2 vs. 51.5 ± 10.1, p < 0.0005), lower incidences of obesity-related comorbidities (p < 0.05), were more likely to have higher education (p = 0.02), and were associated with no-shows up to 2 years post-operatively. LSG remained a strong independent predictor of %EBWL-25th at 12 months (OR = 5.2, p < 0.005), 24 months (OR = 5.3, p < 0.005), and 36 months (OR = 7.3, p = 0.006), after adjusting for comorbidities, education, and no-shows. Predictors of poor weight loss after LSG included hypertension, African American race, major depression, no-shows at 6 and 12 months. Within patients associated with these characteristics, the relative risk of experiencing poor weight loss was significantly higher following LSG compared to LRYGB at 12 months (60% vs. 25.0%, p < 0.05), 24 months (43% vs. 18%, p < 0.05), and 36 months (70% vs. 21%, p < 0.05). CONCLUSIONS: LSG remained an independent predictor of poor weight loss at all post-operative time points. Furthermore, the risk of experiencing poor weight loss was significantly higher following LSG compared to LRYGB for patients with high-risk characteristics.
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Cirurgia Bariátrica/efeitos adversos , Derivação Gástrica/efeitos adversos , Laparoscopia/métodos , Obesidade Mórbida/cirurgia , Redução de Peso/fisiologia , Adulto , Cirurgia Bariátrica/métodos , Feminino , Seguimentos , Derivação Gástrica/métodos , Humanos , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE OF REVIEW: Pancreatic cystic lesions (PCLs) are increasingly identified on abdominal imaging. Given the malignant potential of certain cyst subtypes and the poor survival rates of pancreatic cancer, accurate diagnosis and appropriate management of these cysts are critical. RECENT FINDINGS: Advances in endoscopic ultrasound (EUS)-guided diagnostics have increased the accuracy of differentiating PCLs. These include cyst fluid molecular analysis, EUS-guided needle-based confocal laser endomicroscopy, and EUS-guided through the needle microforceps biopsy. This review encapsulates recent advances in the endoscopic management of PCLs with a specific focus on EUS-guided diagnosis. SUMMARY: It is important to accurately diagnose pancreatic cystic lesions with malignant potential where the definitive management is surgical resection. Misdiagnosis can result in inadvertent surgery of an otherwise benign lesion or malignant progression of a precancerous cyst. Moreover, pancreatic surgery is associated with significant morbidity and mortality. Recent advances in EUS-guided tissue acquisition, imaging, and molecular biomarkers have resulted in improved diagnostic accuracy of pancreatic cystic lesions. Future studies need to define efficient and accurate diagnostic algorithms for improved management of pancreatic cysts.
Assuntos
Endossonografia , Pâncreas/diagnóstico por imagem , Cisto Pancreático/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , HumanosRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis in part due to delayed diagnosis. Even with advances in cross-sectional imaging, small pancreatic malignancies can be missed. We sought to determine the performance of endoscopic ultrasound (EUS) in those without an obvious mass on multi-detector CT scan (MDCT), but with clinical suspicion for pancreatic malignancy. METHODS: Multiple databases were systematically searched to identify studies that assessed the diagnostic performance of EUS after negative or inconclusive pancreatic protocol MDCT for detection of pancreatic malignancy when clinically suspected. A total of four studies met the inclusion criteria. The point estimates in each study were compared to the summary pooled estimates of sensitivity and specificity with the aid of forest plots. Funnel plots and Egger's test were employed to evaluate possible publication bias. RESULTS: EUS-guided fine needle aspiration was performed in all studies. EUS was performed in 206 subjects with a clinical suspicion of a pancreatic mass but with an indeterminate MDCT. A pancreatic mass (mean size 21 ± 1.2 mm) was identified in 70% (n = 144) of the subjects, and 42.2% (n = 87) were diagnosed with PDAC. The pooled estimates of EUS for diagnosing pancreatic malignancy in the setting of an indeterminate MDCT were a sensitivity of 85% (95% CI 69-94%), specificity of 58% (95% CI 40-74%), positive predictive value of 77% (69-84%), negative predictive value of 66% (95% CI 53-77%), and an accuracy of 75% (95% CI 67-82). The summary area under the ROC curve was 0.80 (95% CI 0.52-0.89). The funnel plots and Egger's test did not show a significant publication bias. CONCLUSIONS: The yield of EUS is comparatively higher for the diagnosis of a pancreatic malignancy in patients with suspected cancer, but a non-diagnostic MDCT. Importantly, the majority of the lesions missed on CT represent PDAC, in which early diagnosis is essential.
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Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Endossonografia/métodos , Tomografia Computadorizada Multidetectores/métodos , Neoplasias Pancreáticas/diagnóstico por imagem , Feminino , Humanos , Masculino , Pâncreas/patologia , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Sensibilidade e Especificidade , Neoplasias PancreáticasAssuntos
Adalimumab/efeitos adversos , Betacoronavirus/imunologia , Infecções por Coronavirus/epidemiologia , Hidradenite Supurativa/tratamento farmacológico , Imunossupressores/efeitos adversos , Nasofaringite/epidemiologia , Pneumonia Viral/epidemiologia , Betacoronavirus/isolamento & purificação , COVID-19 , Ensaios Clínicos Fase III como Assunto , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Hidradenite Supurativa/imunologia , Humanos , Nasofaringite/imunologia , Pandemias/prevenção & controle , Placebos/efeitos adversos , Pneumonia Viral/imunologia , Pneumonia Viral/prevenção & controle , Fatores de Risco , SARS-CoV-2RESUMO
BACKGROUND: In the absence of a gold-standard diagnostic modality for cellulitis, sterile inflammatory disorders may be misdiagnosed as cellulitis. OBJECTIVE: To determine the utility of skin biopsy and tissue culture for the diagnosis and management of patients admitted with a diagnosis of presumed cellulitis. DESIGN: Pilot single-blind parallel group randomized controlled clinical trial in 56 patients with a primary diagnosis of presumed cellulitis. In the intervention group only, skin biopsy and tissue culture results were made available to the primary care team to guide diagnosis and management. Length of hospital stay and antibiotic use were evaluated as outcome measures. RESULTS: Length of stay showed the greatest opportunity for further study as a primary outcome (intervention: 4, IQR (2-6) vs. control: 5 IQR (3-8) days; p = 0.124). LIMITATIONS: The COVID-19 pandemic placed limitations on participant enrollment and study duration; in addition, data was collected from a single medical center. CONCLUSION: This study demonstrates that length of stay and anti-pseudomonal antibiotic de-escalation are endpoints that may be influenced by biopsy and tissue culture results in presumed cellulitis patients; these outcomes warrant further study.
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Antibacterianos , COVID-19 , Celulite (Flegmão) , Tempo de Internação , Humanos , Celulite (Flegmão)/diagnóstico , Celulite (Flegmão)/tratamento farmacológico , Celulite (Flegmão)/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Tempo de Internação/estatística & dados numéricos , Biópsia , Projetos Piloto , Antibacterianos/uso terapêutico , Método Simples-Cego , Adulto , Idoso , Pele/patologia , Pele/microbiologia , Técnicas de Cultura de Tecidos , SARS-CoV-2 , Pacientes Internados/estatística & dados numéricosRESUMO
Neutrophils are increasingly implicated in chronic inflammation and metabolic disorders. Here, we show that visceral adipose tissue (VAT) from individuals with obesity contains more neutrophils than in those without obesity and is associated with a distinct bacterial community. Exploring the mechanism, we gavaged microbiome-depleted mice with stool from patients with and without obesity during high-fat or normal diet administration. Only mice receiving high-fat diet and stool from subjects with obesity show enrichment of VAT neutrophils, suggesting donor microbiome and recipient diet determine VAT neutrophilia. A rise in pro-inflammatory CD4+ Th1 cells and a drop in immunoregulatory T cells in VAT only follows if there is a transient spike in neutrophils. Human VAT neutrophils exhibit a distinct gene expression pattern that is found in different human tissues, including tumors. VAT neutrophils and bacteria may be a novel therapeutic target for treating inflammatory-driven complications of obesity, including insulin resistance and colon cancer.
Assuntos
Dieta Hiperlipídica , Inflamação , Gordura Intra-Abdominal , Neutrófilos , Obesidade , Gordura Intra-Abdominal/imunologia , Gordura Intra-Abdominal/metabolismo , Animais , Obesidade/microbiologia , Obesidade/imunologia , Humanos , Neutrófilos/imunologia , Dieta Hiperlipídica/efeitos adversos , Camundongos , Inflamação/imunologia , Inflamação/microbiologia , Inflamação/patologia , Microbioma Gastrointestinal/imunologia , Masculino , Camundongos Endogâmicos C57BL , Feminino , Fezes/microbiologia , Microbiota/imunologia , Células Th1/imunologia , Infiltração de NeutrófilosRESUMO
Although some studies suggest that a linear dose-response relationship exists between exercise and insulin sensitivity, the exercise dose required to enhance pancreatic ß-cell function is unknown. Thirty-five older obese adults with prediabetes underwent a progressive 12-wk supervised exercise intervention (5 days/wk for 60 min at ~85% HRmax). Insulin and C-peptide responses to an OGTT were used to define the first- and second-phase disposition index (DI; ß-cell function = glucose-stimulated insulin secretion × clamp-derived insulin sensitivity). Maximum oxygen consumption (Vo2max) and body composition (dual-energy X-ray absorptiometry and computed tomography) were also measured before and after the intervention. Exercise dose was computed using Vo2/heart-rate derived linear regression equations. Subjects expended 474.5 ± 8.8 kcal/session (2,372.5 ± 44.1 kcal/wk) during the intervention and lost ~8% body weight. Exercise increased first- and second-phase DI (P < 0.05), and these changes in DI were linearly related to exercise dose (DIfirst phase: r = 0.54, P < 0.001; DIsecond phase: r = 0.56, P = 0.0005). Enhanced DI was also associated with increased Vo2max (DIfirst phase: r = 0.36, P = 0.04; DIsecond phase: r = 0.41, P < 0.02) but not lower body fat (DIfirst phase: r = -0.21, P = 0.25; DIsecond phase: r = -0.30, P = 0.10) after training. Low baseline DI predicted an increase in DI after the intervention (DIfirst phase: r = -0.37; DIsecond phase: r = -0.41, each P < 0.04). Thus, exercise training plus weight loss increased pancreatic ß-cell function in a linear dose-response manner in adults with prediabetes. Our data suggest that higher exercise doses (i.e., >2,000 kcal/wk) are necessary to enhance ß-cell function in adults with poor insulin secretion capacity.
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Exercício Físico/fisiologia , Células Secretoras de Insulina/fisiologia , Estado Pré-Diabético/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Educação Física e Treinamento/métodos , Estado Pré-Diabético/terapia , Fatores de Tempo , Redução de Peso/fisiologiaRESUMO
Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT, or IFG + IGT is unknown. Twenty-four older (66.7 ± 0.8 yr) obese (34.2 ± 0.9 kg/m(2)) adults were categorized as IFG (n = 8), IGT (n = 8), or IFG + IGT (n = 8) according to a 75-g oral glucose tolerance test (OGTT). Subjects underwent 12-wk of exercise (60 min/day for 5 days/wk at â¼85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic hyperinsulinemic clamp (40 mU·m(2)·min(-1)) with [6,6-(2)H]glucose was used to determine peripheral and hepatic insulin sensitivity. Nonoxidative glucose disposal and metabolic flexibility [insulin-stimulated respiratory quotient (RQ) minus fasting RQ] were also assessed. Glucose incremental area under the curve (iAUCOGTT) was calculated from the OGTT. Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than with IFG + IGT (P < 0.05). Exercise reduced glucose iAUCOGTT in IGT only (P < 0.05), and the decrease in glucose iAUCOGTT was inversely correlated with the increase in peripheral but not hepatic insulin sensitivity (P < 0.01). Increased clamp-derived peripheral insulin sensitivity was also correlated with enhanced metabolic flexibility, reduced fasting RQ, and higher nonoxidative glucose disposal (P < 0.05). Adults with IFG + IGT had smaller gains in clamp-derived peripheral insulin sensitivity and metabolic flexibility, which was related to blunted improvements in postprandial glucose. Additional work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training.
Assuntos
Exercício Físico/fisiologia , Intolerância à Glucose/metabolismo , Resistência à Insulina , Obesidade/metabolismo , Estado Pré-Diabético/metabolismo , Idoso , Glicemia/metabolismo , Jejum/sangue , Jejum/metabolismo , Feminino , Intolerância à Glucose/sangue , Teste de Tolerância a Glucose , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Fenótipo , Educação Física e Treinamento , Estado Pré-Diabético/sangueRESUMO
We report 2 patients who underwent Mohs micrographic surgery (MMS) and operative closure on the ear. Both cases were complicated by necrosis resulting in the formation of auricular defects. These cases highlight the importance of the auricular vasculature and the associated watershed regions during operative planning for MMS as well as the complications that can arise with vascular compromise. This case report also provides a review of the auricular vasculature with special attention to these vulnerable watershed regions.
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Orelha , Cirurgia de Mohs , Neoplasias Cutâneas , Orelha/patologia , Humanos , Cirurgia de Mohs/efeitos adversos , Necrose , Neoplasias Cutâneas/cirurgiaRESUMO
Decreased adipose tissue regulatory T cells contribute to insulin resistance in obese mice, however, little is known about the mechanisms regulating adipose tissue regulatory T cells numbers in humans. Here we obtain adipose tissue from obese and lean volunteers. Regulatory T cell abundance is lower in obese vs. lean visceral and subcutaneous adipose tissue and associates with reduced insulin sensitivity and altered adipocyte metabolic gene expression. Regulatory T cells numbers decline following high-fat diet induction in lean volunteers. We see alteration in major histocompatibility complex II pathway in adipocytes from obese patients and after high fat ingestion, which increases T helper 1 cell numbers and decreases regulatory T cell differentiation. We also observe increased expression of inhibitory co-receptors including programmed cell death protein 1 and OX40 in visceral adipose tissue regulatory T cells from patients with obesity. In human obesity, these global effects of interferon gamma to reduce regulatory T cells and diminish their function appear to instigate adipose inflammation and suppress adipocyte metabolism, leading to insulin resistance.
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Resistência à Insulina , Tecido Adiposo/metabolismo , Animais , Humanos , Interferon gama/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T Reguladores/metabolismoRESUMO
The role of adipose tissue (AT) inflammation in obesity and its multiple related-complications is a rapidly expanding area of scientific interest. Within the last 30 years, the role of the adipocyte as an endocrine and immunologic cell has been progressively established. Like the macrophage, the adipocyte is capable of linking the innate and adaptive immune system through the secretion of adipokines and cytokines; exosome release of lipids, hormones, and microRNAs; and contact interaction with other immune cells. Key innate immune cells in AT include adipocytes, macrophages, neutrophils, and innate lymphoid cells type 2 (ILC2s). The role of the innate immune system in promoting adipose tissue inflammation in obesity will be highlighted in this review. T cells and B cells also play important roles in contributing to AT inflammation and are discussed in this series in the chapter on adaptive immunity.
Assuntos
Imunidade Adaptativa/imunologia , Adipócitos/imunologia , Tecido Adiposo/imunologia , Imunidade Inata/imunologia , Obesidade/imunologia , Adipócitos/citologia , Adipócitos/metabolismo , Adipocinas/imunologia , Adipocinas/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Macrófagos/imunologia , Macrófagos/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
BACKGROUND: Adipose tissue has emerged as an important window into cancer pathophysiology, revealing potential targets for novel therapeutic interventions. The goal of this study was to compare the breast adipose tissue (BrAT) immune milieu surrounding breast carcinoma and contralateral unaffected breast tissue obtained from the same patient. MATERIALS AND METHODS: Patients undergoing bilateral mastectomy for unilateral breast cancer were enrolled for bilateral BrAT collection at the time of operation. After BrAT was processed, adipocyte and stromal vascular fraction (SVF) gene expression was quantified by PCR. SVF cells were also processed for flow cytometric immune cell characterization. RESULTS: Twelve patients underwent bilateral mastectomy for unilateral ductal carcinoma. BrAT adipocyte CXCL2 gene expression trended higher in the tumor-affected breast as compared to the unaffected breast. Macrophage MCP-1 and PPARγ gene expression also tended to be higher in the tumor-affected breasts. T cell gene expression of FOXP3 (p = 0.0370) were significantly greater in tumor-affected breasts than unaffected breasts. Affected BrAT contained higher numbers of Th2 CD4+ cells (p = 0.0165) and eosinophils (p = 0.0095) while trending towards increased macrophage and lower Th1 CD4+ cells infiltration than tumor-affected BrAT. CONCLUSION: This preliminary study aimed to identify the immunologic environment present within BrAT and is the first to directly compare this in individual patients' tumor-associated and unaffected BrAT. These findings suggest that cancer-affected BrAT had increased levels of T cell specific FOXP3 and higher levels of anti-inflammatory/regulatory cells compared to the contralateral BrAT.
Assuntos
Tecido Adiposo/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Inflamação/genética , Inflamação/patologia , Tecido Adiposo/imunologia , Adulto , Idoso , Carcinoma Ductal/patologia , Quimiocina CCL2/genética , Quimiocina CXCL2/genética , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , PPAR gama/genéticaRESUMO
BACKGROUND: Gastrointestinal (GI) and liver diseases contribute to substantial inpatient morbidity, mortality, and healthcare resource utilization. Finding ways to reduce the economic burden of healthcare costs and the impact of these diseases is of crucial importance. Thirty-day readmission rates and related hospital outcomes can serve as objective measures to assess the impact of and provide further insights into the most common GI ailments. AIM: To identify the thirty-day readmission rates with related predictors and outcomes of hospitalization of the most common GI and liver diseases in the United States. METHODS: A cross-sectional analysis of the 2012 National Inpatient Sample was performed to identify the 13 most common GI diseases. The 2013 Nationwide Readmission Database was then queried with specific International Classification of Diseases, Ninth Revision, Clinical Modification codes. Primary outcomes were mortality (index admission, calendar-year), hospitalization costs, and thirty-day readmission and secondary outcomes were predictors of thirty-day readmission. RESULTS: For the year 2013, the thirteen most common GI diseases contributed to 2.4 million index hospitalizations accounting for about $25 billion. The thirty-day readmission rates were highest for chronic liver disease (25.4%), Clostridium difficile (C. difficile) infection (23.6%), functional/motility disorders (18.5%), inflammatory bowel disease (16.3%), and GI bleeding (15.5%). The highest index and subsequent calendar-year hospitalization mortality rates were chronic liver disease (6.1% and 12.6%), C. difficile infection (2.3% and 6.1%), and GI bleeding (2.2% and 5.0%), respectively. Thirty-day readmission correlated with any subsequent admission mortality (r = 0.798, P = 0.001). Medicare/Medicaid insurances, ≥ 3 Elixhauser comorbidities, and length of stay > 3 d were significantly associated with thirty-day readmission for all the thirteen GI diseases. CONCLUSION: Preventable and non-chronic GI disease contributed to a significant economic and health burden comparable to chronic GI conditions, providing a window of opportunity for improving healthcare delivery in reducing its burden.
RESUMO
Introduction: Vitamin A deficiency (VAD) is an underreported micronutrient deficiency after bariatric surgery (BS). Objectives: The goal of this study was to characterize VAD prevalence in patients undergoing malabsorptive and restrictive procedures up to 2 years postoperatively. Methods: Primary sleeve gastrectomy (SG; n = 322) and gastric bypass (GB; n = 249) patients were reviewed. Levels for overall VAD (oVAD; retinol <39 mcg/dL) and moderate VAD (mVAD; retinol <30 mcg/dL) were reported preoperatively and 6, 12, and 24 months postoperatively. Differences in demographic, surgical, and postoperative data were tested between these groups. Settings: Single-center academic institution. Results: Serum retinol levels were documented for 56%, 74%, 61%, and 37% of patients for listed time points. Baseline retinol inversely correlated to preop body mass index (BMI) (R = -0.15, P = .007). Both oVAD and mVAD peaked 6 months postoperatively (33% vs. 15%, P < .005; 12% vs. 4%, P = .0004, respectively). oVAD remained elevated at 24 months (22% vs. 15%, P = .03). Compared to SG, oVAD was higher following GB at 6 months (39% vs. 28%, P = .001) and 12 months (26% vs. 17%, P = .04), and mVAD was greater with GB at 6 months (18% vs. 6%, P < .0005). African American patients had higher oVAD/mVAD preoperatively (26% vs. 13%, P = .02; 13% vs. 3%, P = .001, respectively) and at 6 months (19% vs. 10%, P = .04). Prior mild VAD (retinol 1.05-1.35 µM) was significantly associated with mVAD up to 12 months postoperatively. Conclusions: Although higher following LRYGB, VAD is prevalent following both malabsorptive and restrictive procedures. Preoperative serum retinol is inversely correlated to increasing BMI, and African American race and mild VAD are associated with moderate VAD.