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An amendment to this paper has been published and can be accessed via the original article.
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BACKGROUND: TREM-1 acts as an amplifier of inflammation expressed on macrophages. The objective of this study was to evaluate the relationship between TREM-1 and macrophage polarization, and association of TREM-1 and M1 macrophage polarization with insulin resistance (IR) in obese population compared to non-obese population. METHODS: We enrolled 38 patients after obtaining IRB approval for this study. We evaluated the mRNA and protein expression levels of general macrophage marker (CD68), M1 marker (CD86, CCR7, iNOS, IFNγ, TNF-α and IL-6,), M2 marker (CD206, CD163, IL-10, IL-4) and chemokine axis (MCP-1, CCR2 and CCR5) along with TREM-1 and TREM-2 in omentum fat, subcutaneous fat, and liver biopsy tissues of non-obese (N = 5), obese non-diabetics, (N = 16) and obese diabetics (N = 17). RESULTS: The results of our study showed over-expression of TREM-1, M1 markers and down-regulation of TREM-2 and M2 markers in the omentum, subcutaneous and liver biopsies of obese patients (diabetics and non-diabetics) compared to non-obese patients. Overall, the obese diabetic group showed a significant (p < 0.05) higher number of patients with over expression of M1 markers (TREM-1, CD68, CD86, CCR-7, iNOS, IFN-γ, TNF-α, IL-6, MCP-1, CCR-2 and CCR-5) and down-regulation of M2 markers (CD206, CD163 and IL-4) in liver biopsy compared to obese non-diabetics. CONCLUSIONS: TREM-1 expression is significantly increased along with the M1 markers in liver biopsy of obese diabetic (17/17) and obese non-diabetic patients (9/16). Our data suggests that TREM-1 overexpression and M1 macrophage polarization are associated with obesity-induced IR.
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Polaridade Celular , Resistência à Insulina , Macrófagos/patologia , Obesidade/patologia , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Adulto , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Biópsia , Comorbidade , Citocinas/metabolismo , Demografia , Diabetes Mellitus/genética , Diabetes Mellitus/patologia , Feminino , Fluorescência , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo II/metabolismo , Obesidade/genética , Omento/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Quimiocinas/metabolismoRESUMO
AIM: Atrial fibrillation (AF) has been associated with higher morbidity after esophagectomy. The objective of this study is to identify the surgical risk factors associated with new-onset atrial fibrillation after esophagectomy. METHODS: After Institutional Review Board approval, a prospectively maintained database was retrospectively queried to identify patients who underwent esophagectomy between 2003 and 2013. Data variables collected include pre-operative, intra-operative, and post-operative factors. Appropriate statistical analysis is performed utilizing Sigmaplot(®) version 12.3. RESULTS: From 2003 to 2013, 245 esophagectomies were performed at our institution, of these, 192 (147 males, mean age of 62 ± 11.12 years) were included in the final analysis and 53 were excluded [25 Roux-en-Y reconstruction (including three Merendino procedures), 20 had AF before surgery, and eight with staged esophagectomy]. Of 192 esophagectomies, 160 had malignancy (138 adenocarcinoma and 22 squamous cell carcinoma) and 106 (66.25%) received neo-adjuvant therapy. Esophagectomies were performed with Ivor Lewis Mckeown approach in 78 patients [34 Minimally Invasive (MIE), 37 open, and 7 Hybrid], Ivor Lewis approach in 56 patients (31 MIE, 10 Open, 15 Hybrid) and Transhiatal approach in 58 patients (16 MIE and 42 Open). Gastric conduit was used in 185 patients and colonic conduit in seven patients. Overall 30-day or in-hospital mortality was 3.6% (7/192). Forty-five (23.4%) patients with esophagectomy developed new-onset AF. Median onset of AF was post-op day 3 (0-32). They were older (65.7 vs. 61.3, p = 0.021), with medical comorbidities (thyroid disorder, hyperlipidemia, and coronary artery disease; p < 0.05) and lower diffusion capacity on Pulmonary function test (80.16 vs. 87.74%, p = 0.02) and stayed longer in hospital (19 vs. 14 days, p < 0.001) with severe post-operative complications (Clavien score ≥ III) (69 vs. 35.3%, p < 0.001). Multiple logistic regression analysis showed transthoracic approach (OR = 3.71, CI = 1.23-11.17, p = 0.02) and thyroid disorder (OR = 6.29, CI = 1.54-25.65, p = 0.01), and severe post-op complications (OR = 3.34, CI = 1.20-9.28, p = 0.02) were significantly associated with the development of new-onset AF. CONCLUSIONS: Transthoracic approach is an independent risk factor for the development of new-onset AF after esophagectomy. New-onset AF is associated with severe post-operative complications and longer hospital stay. Minimally invasive approach does not decrease the incidence of new-onset AF.
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Adenocarcinoma/cirurgia , Fibrilação Atrial/epidemiologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Fatores Etários , Idoso , Comorbidade , Doença da Artéria Coronariana/epidemiologia , Bases de Dados Factuais , Feminino , Mortalidade Hospitalar , Humanos , Hiperlipidemias/epidemiologia , Incidência , Laparoscopia/métodos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Análise Multivariada , Capacidade de Difusão Pulmonar , Estudos Retrospectivos , Fatores de Risco , Doenças da Glândula Tireoide/epidemiologiaRESUMO
BACKGROUND: Laparoscopic adrenalectomy (LA) has become the standard of care for many conditions requiring removal of the adrenal gland. Previous studies on outcomes after LA have had limitations. This report describes the 30-day morbidity and mortality rates after LA and analyzes factors affecting operative time, hospital length of stay (LOS), and postoperative morbidity. METHODS: Patients undergoing LA in 2007 and 2008 were identified from the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP). Using multivariate analysis of variance (ANOVA) and logistic regression, 52 demographic/comorbidity variables were analyzed to ascertain factors affecting operative time, LOS, and morbidity. RESULTS: The mean age of the 988 patients was 53.5 ± 13.7 years, and 60% of the patients were women. The mean body mass index (BMI) of the patients was 31.8 ± 7.9 kg/m(2). The 30-day morbidity and mortality rates were 6.8% and 0.5%, respectively. The mean and median operative times were 146.7 ± 66.8 min and 134 min, respectively. The mean and median hospital stays were 2.6 ± 3.1 days and 2 days, respectively. Compared with independent status, totally dependent functional status was associated with a 9.5-day increase in LOS (P = 0.0006) and an increased risk for postoperative morbidity (odds ratio [OR], 14.7; 95% confidence interval [CI], 2.4-91.9; P < 0.0001). Peripheral vascular disease (OR, 7.3; 95% CI, 1.7-31.7; P = 0.008) also was associated with increased 30-day morbidity. Neurologic and respiratory comorbidities were associated with increased LOS (P < 0.05). American Society of Anesthesiology (ASA) class 4 patients had a longer operative time than ASA class 1 patients (P = 0.002). CONCLUSIONS: The morbidity and mortality rates after LA are low. Dependent functional status and peripheral vascular disease predispose to postoperative morbidity. Dependent status, higher ASA class, and respiratory and neurologic comorbidities are associated with longer operative time and LOS.
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Adrenalectomia/métodos , Laparoscopia/estatística & dados numéricos , Doenças das Glândulas Suprarrenais/epidemiologia , Doenças das Glândulas Suprarrenais/cirurgia , Adrenalectomia/estatística & dados numéricos , Adulto , Idoso , Comorbidade , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação/estatística & dados numéricos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/cirurgia , Fatores de Risco , Resultado do TratamentoRESUMO
Recurrent dysphagia and/or gastroesophageal reflux (GER) are failures of treatment after Heller myotomy for achalasia. We present our single center experience with surgical interventions for these failures. We did a retrospective analysis of a prospectively collected database. Based on preoperative symptoms and endoscopy, esophagogram, and manometry results, patients were divided into three groups to guide management. Telephone follow-up was done using a structured foregut questionnaire. Between December 2003 and June 2009, 16 patients underwent operative interventions for disabling symptoms after previous Heller myotomy. Eight patients presented primarily with recurrent dysphagia and underwent transabdominal Heller myotomy with partial fundoplication. Seven patients reported good to excellent symptom relief at mean follow-up of 42 months. One patient reported no relief and eventually required esophageal bypass with retrosternal gastric pull-up. Four patients presented with uncontrolled GER. Two patients who underwent redo partial fundoplication reported poor symptomatic outcome and one patient has since undergone short limb Roux-en-y gastric bypass (SLRNYGB) with excellent symptom relief. The other two patients underwent SLRNYGB with excellent relief at 10 months. Four patients had end stage achalasia and underwent esophageal resection with reconstruction. All reported excellent symptom relief at mean follow-up of 36 months. Transabdominal redo Heller myotomy for dysphagia has good outcomes. Redo fundoplication for GER after previous myotomy has poor results and SLRNYGB is an effective option in these patients. Esophageal resection remains an effective, albeit morbid, option for end-stage achalasia.
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Procedimentos Cirúrgicos do Sistema Digestório , Acalasia Esofágica/cirurgia , Esfíncter Esofágico Inferior/cirurgia , Adulto , Idoso , Estudos de Coortes , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/cirurgia , Acalasia Esofágica/complicações , Acalasia Esofágica/patologia , Feminino , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Falha de TratamentoRESUMO
[This corrects the article on p. 3224 in vol. 9, PMID: 28804542.].
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Activated cell surface and intracellular receptors lead to insulin resistance in obesity. Among these receptors, triggering receptors expressed on myeloid cells (TREM)-1, toll like receptors (TLRs), and receptors for advanced glycation end products (RAGE) play a significant role in the induction of inflammatory response in innate immunity. TREM-1 potentially amplifies TLRs and RAGE synergistically with DNA-binding high-mobility group box 1 (HMGB-1). The objective of the study was to analyze the association between TREM-1/DAP12 and HMGB-1, RAGE and TLRs in obesity-induced insulin resistance. We examined the mRNA expression by RT-PCR and protein expression by Western blotting and immunofluorescence for TREM-1, TREM-2, DAP-12, HMGB-1, RAGE, TLR-4 and TLR-2 in omentum, subcutaneous and liver biopsy tissues of obese diabetic (n=22) and non-diabetic subjects (n=24) and compared with the non-obese non-diabetic controls (n=5). There was a significantly increased expression of TREM-1, DAP-12, HMGB-1, RAGE, TLR-4 and TLR-2 and decreased expression of TREM-2 in the omentum, subcutaneous and liver biopsy of obese diabetic subjects compared to obese non-diabetics and the non-obese population. Overall, obese diabetic subjects had high expression of TREM-1 in association with HMGB1 (100% vs 58.3%, P=0.003), RAGE (77.3% vs 41.7%, P=0.045), TLR4 (100% vs 58.3%, P=0.003), and TLR2 (100% vs 50%, P=0.003) in liver biopsy samples in comparison to obese non-diabetic subjects. Obese diabetics have significantly increased TREM-1, HMGB1, RAGE, and TLRs compared to obese non-diabetics. Our findings suggest a potential pathophysiological role of TREM-1 in conjunction with HMGB1 and inflammatory cell receptors (RAGE, TLR-4 and TLR-2) in obesity-induced insulin resistance.
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OBJECTIVE: Triggering receptor expressed on myeloid cells (TREM)-1 has recently been recognized as one of the potent amplifiers of acute and chronic inflammation. However, the exact role of TREM-1 in regard to insulin insensitivity is unknown. METHODS: mRNA transcripts and protein expression of TREM-1, TREM-2, and TREM-1/TREM-2 ratio were examined in the tissue biopsies (liver, omentum, and subcutaneous fat) and blood samples (neutrophils and monocytes) of subjects with obesity and diabetes (SO+ D+ ; n = 15), subjects with obesity but not diabetes (SO+ D- ; n = 7), and subjects without obesity (BMI < 30) and diabetes (SO- D- ; n = 5). RESULTS: The immunofluorescence and RT-PCR revealed significant increase in TREM-1, decrease in TREM-2, and increase in the TREM1/TREM2 ratio in SO+ D+ group compared with other groups. Overall, increased liver TREM-1 expression and soluble-TREM-1 were found in SO+ D+ group compared with SO+ D- group (100% vs. 57.14%, r = 0.582; P = 0.023). TREM-1 was significantly increased in all subjects with obesity and those with HOMA-IR index of >2. CONCLUSIONS: TREM-1 was found to be significantly higher in tissues biopsies and blood of subjects with obesity. Greater expression and activity of TREM-1 suggest a possible role in the underlying pathophysiology of obesity and associated comorbidities.
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Resistência à Insulina/fisiologia , Glicoproteínas de Membrana/metabolismo , Células Mieloides/metabolismo , Obesidade/metabolismo , Receptores Imunológicos/metabolismo , Adulto , Feminino , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/metabolismo , Neutrófilos , Omento/metabolismo , RNA Mensageiro/metabolismo , Gordura Subcutânea/metabolismo , Receptor Gatilho 1 Expresso em Células MieloidesRESUMO
BACKGROUND: Obesity has been implicated as an important risk factor for fundoplication failure. However, the mechanism of fundoplication in obese patients is not fully understood. Our objective is to evaluate the patterns of failure in relation to the body mass index (BMI) undergoing re-operative intervention after failed fundoplication. METHODS: After Institutional Review Board approval, the patients who underwent re-operative intervention for failed fundoplication between November 2008 and December 2013 were identified. Patients were classified into three groups: non-obese, obese, and morbidly obese (<30, 30-35, >35 BMI, respectively). Pre-operative assessment and operative procedure performed were compared between the groups. RESULTS: One hundred twenty-four patients satisfied study criteria. Non-obese patients (53.2 %) had significantly more dysphagia as an indication for re-operative procedure (obese 31.6 %, p < 0.05; morbidly 16.7 %, p < 0.05). Obese and morbidly obese patients had significantly higher incidence of recurrent hiatal hernia than non-obese patients (88.7 vs. 65.6 %, p < 0.05). Morbidly obese patients had significantly higher incidence of disrupted fundoplication than non-obese patients (41.7 vs. 19.4 %, p < 0.05). CONCLUSION: Similar anatomical failure patterns of state of fundoplication and recurrent hiatal hernia were noted between obese patients and morbidly obese patients and were distinct from non-obese patients.
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Fundoplicatura , Refluxo Gastroesofágico/cirurgia , Obesidade Mórbida/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Feminino , Refluxo Gastroesofágico/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Reoperação , Fatores de Risco , Falha de Tratamento , Adulto JovemRESUMO
BACKGROUND: The prevalence of gastroesophageal reflux disease (GERD) in the morbidly obese population is as high as 45%. The objective of this study was to compare the efficacy of various bariatric procedures in the improvement of GERD. METHODS: The Bariatric Outcomes Longitudinal Database is a prospective database of patients who undergo bariatric surgery by a participant in the American Society of Metabolic and Bariatric Surgery Center of Excellence program. GERD is graded on a 6-point scale, from 0 (no history of GERD) to 5 (prior surgery for GERD). Patients with GERD severe enough to require medications (grades 2, 3, and 4) from June 2007 to December 2009 are identified; the resolution of GERD is noted based on 6-month follow-up. RESULTS: Of a total of 116,136 patients, 36,938 patients had evidence of GERD preoperatively. After excluding patients undergoing concomitant hiatal hernia repair or fundoplication, there were 22,870 patients with 6-month follow-up. Mean age was 47.6±11.1 years, with an 82% female population. Mean BMI was 46.3±8.0 kg/m(2). Mean preoperative GERD score for patients with Roux-en-Y gastric bypass (RYGB) was 2.80±.56, and mean postoperative score was 1.33±1.41 (P<.0001). Similarly, adjustable gastric banding (AGB, 2.77±.57 to 1.63±1.37, P<.0001) and sleeve gastrectomy (SG, 2.82±.57 to 1.85±1.40, P<.0001) had significant improvement in GERD score. GERD score improvement was best in RYGB patients (56.5%; 7955 of 14,078) followed by AGB (46%; 3773 of 8207) and SG patients (41%; 240 of 585). CONCLUSION: All common bariatric procedures improve GERD. Roux-en-Y gastric bypass is superior to adjustable gastric banding and sleeve gastrectomy in improving GERD. Also, the greater the loss in excess weight, the greater the improvement in GERD score.