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1.
Nat Immunol ; 20(5): 581-592, 2019 05.
Article in English | MEDLINE | ID: mdl-30962591

ABSTRACT

Succinate is a signaling metabolite sensed extracellularly by succinate receptor 1 (SUNCR1). The accumulation of succinate in macrophages is known to activate a pro-inflammatory program; however, the contribution of SUCNR1 to macrophage phenotype and function has remained unclear. Here we found that activation of SUCNR1 had a critical role in the anti-inflammatory responses in macrophages. Myeloid-specific deficiency in SUCNR1 promoted a local pro-inflammatory phenotype, disrupted glucose homeostasis in mice fed a normal chow diet, exacerbated the metabolic consequences of diet-induced obesity and impaired adipose-tissue browning in response to cold exposure. Activation of SUCNR1 promoted an anti-inflammatory phenotype in macrophages and boosted the response of these cells to type 2 cytokines, including interleukin-4. Succinate decreased the expression of inflammatory markers in adipose tissue from lean human subjects but not that from obese subjects, who had lower expression of SUCNR1 in adipose-tissue-resident macrophages. Our findings highlight the importance of succinate-SUCNR1 signaling in determining macrophage polarization and assign a role to succinate in limiting inflammation.


Subject(s)
Inflammation/immunology , Macrophages/immunology , Obesity/immunology , Receptors, G-Protein-Coupled/immunology , Adipose Tissue/drug effects , Adipose Tissue/immunology , Adipose Tissue/metabolism , Animals , Cells, Cultured , Cytokines/genetics , Cytokines/immunology , Cytokines/metabolism , Gene Expression Profiling/methods , Humans , Inflammation/genetics , Inflammation/metabolism , Macrophages/metabolism , Male , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Obesity/genetics , Obesity/metabolism , Receptors, G-Protein-Coupled/deficiency , Receptors, G-Protein-Coupled/genetics , Succinic Acid/immunology , Succinic Acid/metabolism , Succinic Acid/pharmacology , THP-1 Cells
2.
Int J Mol Sci ; 25(3)2024 Jan 29.
Article in English | MEDLINE | ID: mdl-38338919

ABSTRACT

Pancreatic ductal adenocarcinoma contributes significantly to global cancer-related deaths, featuring only a 10% survival rate over five years. The quest for novel tumor markers is critical to facilitate early diagnosis and tailor treatment strategies for this disease, which is key to improving patient outcomes. In pancreatic ductal adenocarcinoma, these markers have been demonstrated to play a crucial role in early identification, continuous monitoring, and prediction of its prognosis and have led to better patient outcomes. Nowadays, biopsy specimens serve to ascertain diagnosis and determine tumor type. However, liquid biopsies present distinct advantages over conventional biopsy techniques. They offer a noninvasive, easily administered procedure, delivering insights into the tumor's status and facilitating real-time monitoring. Liquid biopsies encompass a variety of elements, such as circulating tumor cells, circulating tumor DNA, extracellular vesicles, microRNAs, circulating RNA, tumor platelets, and tumor endothelial cells. This review aims to provide an overview of the clinical applications of liquid biopsy as a technique in the management of pancreatic cancer.


Subject(s)
Carcinoma, Pancreatic Ductal , Neoplastic Cells, Circulating , Pancreatic Neoplasms , Humans , Endothelial Cells/pathology , Pancreatic Neoplasms/pathology , Liquid Biopsy/methods , Carcinoma, Pancreatic Ductal/pathology , DNA, Neoplasm/genetics , Neoplastic Cells, Circulating/pathology , Biomarkers, Tumor/genetics
3.
Langenbecks Arch Surg ; 408(1): 100, 2023 Feb 23.
Article in English | MEDLINE | ID: mdl-36813935

ABSTRACT

PURPOSE: The Clavien-Dindo Classification (CDC) and the Comprehensive Complication Index (CCI®) are both widely used methods for reporting postoperative complications. Several studies have compared the CCI® with the CDC in evaluating postoperative complications of major abdominal surgery. However, there are no published reports comparing both indexes in single-stage laparoscopic common bile duct exploration with cholecystectomy (LCBDE) for the treatment of common bile duct stones. This study aimed to compare the accuracy of the CCI® and the CDC in evaluating the complications of LCBDE. METHODS: In total, 249 patients were included. Spearman's rank test was used to calculate the correlation coefficient between CCI® and CDC with length of postoperative stay (LOS), reoperation, readmission, and mortality rates. Student t-test and Fisher's exact test were used to study, if higher ASA, age, larger surgical time, history of previous abdominal surgery, preoperative ERCP, and intraoperative cholangitis finding were associated with higher CDC grade or higher CCI® score. RESULTS: Mean CCI® was 5.17 ± 12.8. CCI® ranges overlap among three CDC grades: II (20.90-36.20), IIIa (26.20-34.60), and IIIb (33.70-52.10). Age > 60 years, ASA ≥ III, and intraoperative cholangitis finding were associated with higher CCI® (p = 0.010, p = 0.044, and p = 0.031) but not with CDC ≥ IIIa (p = 0.158, p = 0.209, and p = 0.062). In patients with complications, LOS presented a significantly higher correlation with CCI® than with CDC (p = 0.044). CONCLUSION: In LCBDE, the CCI® assesses better the magnitude of postoperative complications in patients older than 60 years, with a high ASA as well as in those who present intraoperative cholangitis. In addition, the CCI® correlates better with LOS in patients with complications.


Subject(s)
Cholecystectomy, Laparoscopic , Choledocholithiasis , Gallstones , Laparoscopy , Humans , Middle Aged , Choledocholithiasis/surgery , Laparoscopy/adverse effects , Postoperative Complications/etiology , Gallstones/surgery , Abdomen , Cholecystectomy, Laparoscopic/methods , Length of Stay , Retrospective Studies
4.
Int J Mol Sci ; 24(2)2023 Jan 06.
Article in English | MEDLINE | ID: mdl-36674640

ABSTRACT

There is a clear association between the molecular profile of colorectal cancer liver metastases (CRCLM) and the degree to which aggressive progression of the disease impacts patient survival. However, much of our knowledge of the molecular behaviour of colorectal cancer cells comes from experimental studies with, as yet, limited application in clinical practice. In this article, we review the current advances in the understanding of the molecular behaviour of CRCLM and present possible future therapeutic applications. This review focuses on three important steps in CRCLM development, progression and treatment: (1) the dissemination of malignant cells from primary tumours and the seeding to metastatic sites; (2) the response to modern regimens of chemotherapy; and (3) the possibility of predicting early progression and recurrence patterns by molecular analysis in liquid biopsy.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Humans , Follow-Up Studies , Colorectal Neoplasms/therapy , Colorectal Neoplasms/drug therapy , Liver Neoplasms/therapy , Liver Neoplasms/drug therapy , Molecular Biology
5.
HPB (Oxford) ; 25(8): 962-971, 2023 08.
Article in English | MEDLINE | ID: mdl-37183126

ABSTRACT

BACKGROUND: The clinical course of chronic pancreatitis is unpredictable and there is no globally accepted score to predict the disease course. We developed a clinical score to estimate pancreatitis-related hospitalisation in patients with newly diagnosed chronic pancreatitis. METHODS: We conducted a retrospective cohort study using two clinical chronic pancreatitis databases held in tertiary referral centres in Dublin, Ireland, and in Tarragona, Spain. Individuals diagnosed with chronic pancreatitis between 2007 and 2014 were eligible for inclusion. Candidate predictors included aetiology, body mass index, exocrine dysfunction, smoking and alcohol history. We used multivariable logistic regression to develop the model. RESULTS: We analysed data from 154 patients with newly diagnosed chronic pancreatitis. Of these, 105 patients (68%) had at least one hospital admission for pancreatitis-related reasons in the 6 years following diagnosis. Aetiology of chronic pancreatitis, body mass index, use of pain medications and gender were found to be predictive of more pancreatic-related hospital admissions. These predictors were used to develop a clinical score which showed acceptable discrimination (area under the ROC curve = 0.70). DISCUSSION: We developed a clinical score based on easily accessible clinical parameters to predict pancreatitis-related hospitalisation in patients with newly diagnosed chronic pancreatitis.


Subject(s)
Pancreatitis, Chronic , Humans , Retrospective Studies , Pancreatitis, Chronic/complications , Pancreatitis, Chronic/diagnosis , Pancreatitis, Chronic/therapy , Hospitalization , Hospitals
6.
Dig Surg ; 39(1): 6-16, 2022.
Article in English | MEDLINE | ID: mdl-34875657

ABSTRACT

INTRODUCTION: Most hepato-pancreato-biliary (HPB) procedures are still performed through open approach. Incisional hernia (IH) is one of the most common complications after open surgery. To date, published data on IH after HPB surgery are scarce; therefore, the aim of this study was to assess the current evidence regarding incidence, risk factors, and prevention. METHODS: Medline/PubMed (1946-2020), EMBASE (1947-2020), and the Cochrane library (1995-2020) were searched for studies on IH in open HPB surgery. Animal studies, editorials, letters, reviews, comments, short case series and liver transplant, laparoscopic, or robotic procedures were excluded. The protocol was registered with PROSPERO (CRD42020163296). RESULTS: A total of 5,079 articles were retrieved. Eight studies were finally included for the analysis. The incidence of IH after HPB surgery ranges from 7.7% to 38.8%. The identified risk factors were body mass index, surgical site infection, ascites, Mercedes or reversed T incisions, and previous IH. Prophylactic mesh might be safe and effective. CONCLUSIONS: IH after open HPB surgery is still an important matter. Some of the risk factors are specific for the HPB operations and the incision type should be carefully considered. Randomized controlled trials are required to confirm the role of prophylactic mesh after HPB operations.


Subject(s)
Biliary Tract Surgical Procedures , Incisional Hernia , Laparoscopy , Liver Transplantation , Biliary Tract Surgical Procedures/adverse effects , Humans , Incisional Hernia/etiology , Incisional Hernia/prevention & control , Laparoscopy/methods , Liver Transplantation/adverse effects , Surgical Wound Infection/etiology
7.
Eur Surg Res ; 63(4): 278-284, 2022.
Article in English | MEDLINE | ID: mdl-34875649

ABSTRACT

INTRODUCTION: Preoperative gastric ischemic conditioning (IC) improves the outcome of esophageal replacement gastroplasty and is associated with low morbidity. However, when the stomach cannot be used for esophageal replacement, a colonic replacement is required. The study aim was to assess the viability of right colon and terminal ileum IC in a rat model and the histological damage/recovery sequence and determine if neovascularization is a potential adaptive mechanism. METHODS: The study was conducted in Rattus norvegicus with ileocolic vascular ligation. Seven groups of animals were established (6 rats per group) with groups defined by the date of their post-IC euthanasia (+1, +3, +6, +10, +15, and +21 days). Comparisons were made with a sham group. Viability of the model was defined as <10% of transmural necrosis. The evaluation of histological damage used the Chiu score in hematoxylin and eosin sections of paraffin-embedded specimens with CD31 immunohistochemical assessment of neovascularization by the median of submucosal vessel counts in 5 high-magnification fields. RESULTS: Transmural colon necrosis occurred in 1/36 animals (2.78%) with no animal demonstrating transmural ileal necrosis. The maximum damage was observed in the colon on +1 day post-IC (average Chiu score 1.67, p = 0.015), whereas in the ileum, it was on days +1, +3, and +6 (average Chiu score 1.5, 1.3, and 1.17; p = 0.015, 0.002, and 0.015, respectively). In the +21-day group, histological recovery was complete in the colon in 4 (66.7%) of the 6 animals and in the ileum in 5 (83.3%) of 6 animals. There were no significant differences in quantitative neovascularization in any of the groups when compared with the sham group or when comparisons were made between groups. CONCLUSIONS: The tested animal model for IC of the colon and terminal ileum appeared to be feasible. Histological damage was maximal between the 1st and 3rd day following IC, but by day 21, recovery was complete in two-thirds of the rats. There was no evidence in this preliminary IC model that would suggest neovascularization as an adaptive mechanism.


Subject(s)
Ischemic Preconditioning , Rats , Animals , Ischemia , Ileum , Colon , Neovascularization, Pathologic , Necrosis
8.
Int J Mol Sci ; 23(15)2022 Jul 22.
Article in English | MEDLINE | ID: mdl-35897644

ABSTRACT

Nuclear magnetic resonance (NMR)-based advanced lipoprotein tests have demonstrated that LDL and HDL particle numbers (LDL-P and HDL-P) are more powerful cardiovascular (CV) risk biomarkers than conventional cholesterol markers. Of interest, in people living with HIV (PLHIV), predictors of preclinical atherosclerosis and vascular dysfunction may be associated with impaired immune function. We previously stated that immunological non-responders (INR) were at higher CV risk than immunological responders (IR) before starting antiretroviral therapy (ART). Using Liposcale® tests, we characterized the lipoprotein profile from the same cohort of PLHIV at month 12 and month 36 after starting ART, intending to explore what happened with these indicators of CV risk during viral suppression. ART initiation dissipates the differences in lipoprotein-based CV risk markers between INR and IR, and only an increase in the number of HDL-P was found in INR + IR when compared to controls (p = 0.047). Interestingly, CD4+ T-cell counts negatively correlated with medium HDL-P concentrations at month 12 in all individuals (ρ = -0.335, p = 0.003). Longitudinal analyses showed an important increase in LDL-P and HDL-P at month 36 when compared to baseline values in both IR and INR. A proper balance between a proatherogenic and atherogenic environment may be related to the reconstitution of CD4+ T-cell count in PLHIV.


Subject(s)
Anti-HIV Agents , Atherosclerosis , HIV Infections , Anti-HIV Agents/therapeutic use , Atherosclerosis/etiology , Biomarkers , Cholesterol/therapeutic use , HIV Infections/drug therapy , HIV Infections/pathology , Humans , Lipoproteins/blood
9.
Ann Surg ; 274(2): 255-263, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33196485

ABSTRACT

OBJECTIVE: To establish the optimal time to start oral refeeding in mild and moderate acute pancreatitis (AP) to reduce hospital length-of-stay (LOS) and complications. SUMMARY BACKGROUND DATA: Oral diet is essential in mild and moderate AP. The greatest benefits are obtained if refeeding starts early; however, the definition of "early" remains controversial. METHODS: This multicenter, randomized, controlled trial (NCT03829085) included patients with a diagnosis of mild or moderate AP admitted consecutively to 4 hospitals from 2017 to 2019. Patients were randomized into 2 treatment groups: immediate oral refeeding (IORF) and conventional oral refeeding (CORF). The IORF group (low-fat-solid diet initiated immediately after hospital admission) was compared to CORF group (progressive oral diet was restarted when clinical and laboratory parameters had improved) in terms of LOS (primary endpoint), pain relapse, diet intolerance, complications, and, hospital costs. RESULTS: One hundred and thirty one patients were included for randomization. The mean LOS for the IORF and CORF groups was 3.4 (SD ± 1.7) and 8.8 (SD ± 7.9) days, respectively (P < 0.001). In the CORF group alone, pain relapse rate was 16%. There were fewer complications (8% vs 26%) and health costs were twice as low, with a savings of 1325.7€/patient in the IORF than CORF group. CONCLUSIONS: IORF is safe and feasible in mild and moderate AP, resulting in significantly shorter LOS and cost savings, without causing adverse effects or complications.


Subject(s)
Enteral Nutrition/methods , Pancreatitis/diet therapy , Aged , Cost Savings , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Postoperative Complications/prevention & control , Spain
10.
Surg Endosc ; 35(9): 5024-5033, 2021 09.
Article in English | MEDLINE | ID: mdl-32968916

ABSTRACT

BACKGROUND: Concomitant gallstones and common bile duct stones (CBDS) is a relatively frequent presentation. The optimal treatment remains controversial and the debate persists between two strategies. The one-stage approach: laparoscopic cholecystectomy with laparoscopic common bile duct exploration (LCBDE) has been shown to be equally safe and more cost-effective than the more traditional two-stage approach: endoscopic retrograde cholangiography followed by laparoscopic cholecystectomy (ERCP + LC). However, many surgeons worldwide still prefer the two-stage procedure. This survey evaluated contemporary management of CBDS in Spain and assessed the impact of surgeon and hospital factors on provision of LCBDE. METHODS: A 25-item, web-based anonymous survey was sent to general surgeons members of the Spanish Surgeons Association. Descriptive statistics were applied to summarize results. RESULTS: Responses from 305 surgeons across 173 Spanish hospitals were analyzed. ERCP is the initial approach for preoperatively suspected CBDS for 86% of surgeons. LCBDE is the preferred method for only 11% of surgeons and only 11% treat more than 10 cases per year. For CBDS discovered intraoperatively, 59% of respondents attempt extraction while 32% defer to a postoperative ERCP. The main reasons cited for not performing LCBDE were lack of equipment, training and timely availability of an ERCP proceduralist. Despite these barriers, most surgeons (84%) responded that LCBDE should be implemented in their departments. CONCLUSIONS: ERCP was the preferred approach for CBDS for the majority of respondents. There remains limited use of LCBDE despite many surgeons indicating it should be implemented. Focused planning and resourcing of both training and operational demands are required to facilitate adoption of LCBDE as option for patients.


Subject(s)
Cholecystectomy, Laparoscopic , Choledocholithiasis , Gallstones , Surgeons , Cholangiopancreatography, Endoscopic Retrograde , Choledocholithiasis/surgery , Common Bile Duct , Gallstones/complications , Gallstones/diagnostic imaging , Gallstones/surgery , Humans , Surveys and Questionnaires
11.
J Minim Access Surg ; 17(3): 311-317, 2021.
Article in English | MEDLINE | ID: mdl-32964868

ABSTRACT

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) can be done as a day-case procedure and may have advantages over conventional laparoscopic cholecystectomy (LC). We present the results of our study looking at post-operative pain and post-operative recovery time. METHODS: This was a single-institution randomised double-blind controlled trial. Seventy-three patients with symptomatic cholelithiasis were randomized to SILC (n = 37) or LC (n = 36). The primary endpoint was to compare post-operative pain. We also compared surgical time, procedural difficulty, adverse events, additional ports used and conversion rate, success of day surgery process, return to work, aesthetic satisfaction, quality of life and 4-year incisional hernia rate. RESULTS: In the SILC group, post-operative analgesic requirements were lower on day 7, there was an earlier return to work and cosmetic satisfaction was significantly higher. The SILC procedure presented a higher technical difficulty. Operative time, surgical complications, post-operative pain, success of the day-case process, return to normal activity, quality of life scores and incisional hernia rates were similar for both the procedures. CONCLUSIONS: SILC has advantages over LC in terms of late post-operative analgesic requirements and aesthetic results; however, it is technically harder to perform. There was no benefit in terms of day surgery outcomes.

12.
HPB (Oxford) ; 22(9): 1339-1348, 2020 09.
Article in English | MEDLINE | ID: mdl-31899044

ABSTRACT

BACKGROUND: Hepatopancreatoduodenectomy (HPD) is an aggressive operation for treatment of advanced bile duct and gallbladder cancer associated with high perioperative morbidity and mortality, and uncertain oncological benefit in terms of survival. Few reports on HPD from Western centers exist. The purpose of this study was to evaluate safety and efficacy for HPD in European centers. METHOD: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients operated with HPD for bile duct or gallbladder cancer between January 2003 and January 2018. The patient and tumor characteristics, perioperative and survival outcomes were analyzed. RESULTS: In total, 66 patients from 19 European centers were included in the analysis. 90-day mortality rate was 17% and 13% for bile duct and gallbladder cancer respectively. All factors predictive of perioperative mortality were patient and disease-specific. The three-year overall survival excluding 90-day mortality was 80% for bile duct and 30% for gallbladder cancer (P = 0.013). In multivariable analysis R0-resection had a significant impact on overall survival. CONCLUSION: HPD, although being associated with substantial perioperative mortality, can offer a survival benefit in patient subgroups with bile duct cancer and gallbladder cancer. To achieve negative resection margins is paramount for an improved survival outcome.


Subject(s)
Bile Duct Neoplasms , Gallbladder Neoplasms , Bile Duct Neoplasms/surgery , Bile Ducts , Bile Ducts, Intrahepatic , Gallbladder Neoplasms/surgery , Hepatectomy , Humans , Pancreaticoduodenectomy/adverse effects
13.
Surgeon ; 17(6): 351-359, 2019 Dec.
Article in English | MEDLINE | ID: mdl-30704859

ABSTRACT

BACKGROUND: Current evidence shows that single-stage treatment of concomitant choledocholithiasis and cholelithiasis is as effective and safe as two-stage treatment. However, several studies suggest that single-stage approach requires shorter hospitalization time and is more cost-effective than the two-stage approach, even though it requires considerable training. This study aimed to evaluate the implementation of a protocol for managing concomitant choledocholithiasis and cholelithiasis using single-stage treatment. METHODS: A prospective cohort study of patients diagnosed with cholelithiasis and choledocholithiasis who were treated with the single-stage treatment - transcystic instrumentation, choledocotomy or intraoperative endoscopic retrograde cholangiopancreatography (ERCP) - between September 2010 and June 2017 was assessed. The primary outcomes were complications, hospital stay, operative time and recurrence rate. RESULTS: 164 patients were enrolled. 141 (86%) were operated laparoscopically. Preoperatively diagnosed stones were not found by intraoperative imaging or disappeared after "flushing" in 38 patients (23.2%). Surgical approach was transcystic in 45 patients (27.41%), choledochotomy in 74 (45.1%), intraoperative ERCP in 4 (2.4%), and bilioenteric derivation in 3 (1.8%). Mean hospitalization stay was 4.4 days. Mean operative time was 166 min 27 patients (16.5%) had complications and 1 patient was exitus (0.6%). Recurrence rate was 1.2%. CONCLUSIONS: Single-stage approach is a safe and effective management option for concomitant cholelithiasis and choledocolithiasis. Furthermore, a significant number of common bile duct stones pass spontaneously to duodenum or can benefit from a transcystic approach, with presumable low morbidity and cost-efficiency.


Subject(s)
Biliary Tract Surgical Procedures/methods , Choledocholithiasis/complications , Choledocholithiasis/surgery , Adult , Aged , Aged, 80 and over , Cholangiopancreatography, Endoscopic Retrograde , Choledocholithiasis/diagnosis , Clinical Protocols , Female , Humans , Length of Stay , Male , Middle Aged , Operative Time , Patient Selection , Prospective Studies , Treatment Outcome , Young Adult
14.
Int J Mol Sci ; 16(8): 17469-81, 2015 Jul 30.
Article in English | MEDLINE | ID: mdl-26263971

ABSTRACT

Data from recent studies conducted in rodent models and humans suggest that interleukin-17A (IL-17A) plays a role in the induction of inflammation in adipose tissue during obesity. The aim of this study was to assess the gene expression of IL-17A in adipose tissue of morbidly obese patients. We used RT-PCR to evaluate the expression of IL-17A and several adipo/cytokines in the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) of 10 normal-weight control women (BMI < 25 kg/m2) and 30 morbidly obese women (MO, BMI > 40 kg/m2). We measured serum levels of IL-17A and adipo/cytokines in MO and normal weight women. IL-17A expression was significantly higher in VAT than in SAT in MO patients (p = 0.0127). It was very low in normal-weight controls in both VAT and SAT tissues. We found positive correlations between IL-17A and IL-6, lipocalin-2 and resistin in VAT of MO patients. The circulating level of IL-17A was higher in the normal-weight group than the MO patients (p = 0.032), and it was significantly related to adiponectin and TNFRII levels. In conclusion, IL-17A expression in VAT is increased in morbidly obese women, which suggests a link between obesity and innate immunity in low-grade chronic inflammation in morbidly obese women.


Subject(s)
Immunity, Innate/genetics , Inflammation/genetics , Interleukin-17/biosynthesis , Obesity, Morbid/genetics , Adult , Body Mass Index , Female , Gene Expression Regulation , Humans , Inflammation/pathology , Interleukin-17/genetics , Interleukin-6/biosynthesis , Intra-Abdominal Fat/metabolism , Intra-Abdominal Fat/pathology , Middle Aged , Obesity, Morbid/pathology , Resistin/biosynthesis
15.
Int J Mol Sci ; 16(12): 29911-22, 2015 Dec 16.
Article in English | MEDLINE | ID: mdl-26694359

ABSTRACT

The purpose of this work was to evaluate the expression of fatty acid metabolism-related genes in human adipose tissue from moderately obese women. We used qRT-PCR and Western Blot to analyze visceral (VAT) and subcutaneous (SAT) adipose tissue mRNA expression involved in de novo fatty acid synthesis (ACC1, FAS), fatty acid oxidation (PPARα, PPARδ) and inflammation (IL6, TNFα), in normal weight control women (BMI < 25 kg/m², n = 35) and moderately obese women (BMI 30-38 kg/m², n = 55). In SAT, ACC1, FAS and PPARα mRNA expression were significantly decreased in moderately obese women compared to controls. The downregulation reported in SAT was more pronounced when BMI increased. In VAT, lipogenic-related genes and PPARα were similar in both groups. Only PPARδ gene expression was significantly increased in moderately obese women. As far as inflammation is concerned, TNFα and IL6 were significantly increased in moderate obesity in both tissues. Our results indicate that there is a progressive downregulation in lipogenesis in SAT as BMI increases, which suggests that SAT decreases the synthesis of fatty acid de novo during the development of obesity, whereas in VAT lipogenesis remains active regardless of the degree of obesity.


Subject(s)
Down-Regulation/genetics , Intra-Abdominal Fat/metabolism , Obesity/genetics , Subcutaneous Fat/metabolism , Cohort Studies , Fatty Acids/biosynthesis , Female , Glucose/metabolism , Humans , Inflammation/genetics , Intra-Abdominal Fat/enzymology , Intra-Abdominal Fat/pathology , Lipogenesis/genetics , Middle Aged , Oxidation-Reduction , RNA, Messenger/genetics , RNA, Messenger/metabolism , Subcutaneous Fat/enzymology , Subcutaneous Fat/pathology
16.
Ann Glob Health ; 90(1): 43, 2024.
Article in English | MEDLINE | ID: mdl-39036647

ABSTRACT

Background: Equatorial Guinea (EG) is located on the African west coast, with only 0.4 trained physicians per 1,000 resident population. The country has one medical school and there is no specialist training program. From 2000 to 2022, 524 doctors have received their medical degree. However, the number of national surgical specialists in the entire country is currently 42. Objective: Formación Especializada Sanitaria en Guinea Ecuatorial (FES Guinea) is a program specifically aimed at designing and implementing a long-term national surgical specialist training program. Methods: Más Que Salud (+QS), which means "More than Health" in Spanish, is a nonprofit organization leading the FES Guinea program. We used the theory of change (ToC) framework to evaluate the work accomplished and implement subsequent phases. The initial phase (A) included a needs assessment and mapping of available resources. An intermediate phase (B) started with a memorandum of understanding to implement a Train the Trainer program. The consolidation phase (C) consists of educational interventions and future advanced training projects. Findings: The ToC model allowed us an analyses of initial and intermediate phases. The needs assessments and resources mapping were executed while several scientific meetings and workshops were given. Scholarships to support specialist training abroad benefited six physicians in a diverse set of surgical disciplines. A regulatory commission to implement the FES Guinea program and the National Medical Council of EG were created. Working directly with the EG Ministry of Health, +QS codesigned a National Health Development Plan that began implementation in 2021 to continue until 2025. Conclusions: The ToC model allowed us to predict the current and future potential effects of FES Guinea on surgical workforce development in EG. This is a unique surgical training program, which combined effective initiatives spearheaded initially by an NGO that successfully incorporated both local health and academic authorities, ensuring sustainability.


Subject(s)
Specialties, Surgical , Humans , Equatorial Guinea , Specialties, Surgical/education , Program Development , Program Evaluation , Needs Assessment
17.
Cir Esp ; 91(7): 444-9, 2013.
Article in Spanish | MEDLINE | ID: mdl-23473433

ABSTRACT

INTRODUCTION: Patients with giant hernias with loss of domain require proper planning of surgical repair, because of the high associated comorbidity. The progressive preoperative pneumoperitoneum technique described by Goñi Moreno allows a more physiological adaptation of the patient and the abdominal cavity to the reinstatement of the viscera to the abdomen, enabling adequate surgical repair. The objective of this study was to analyze our experience in the treatment of this type of hernia. MATERIALS AND METHODS: We carried out a retrospective study that included 11 patients with major abdominal wall defects and loss of domain who were treated with this technique in 2 centers between 2005 and 2010. RESULTS: Eight patients had abdominal hernias and 3 had inguinal hernias. The average insufflation time was 2 weeks and the total amount of air was between 6.6 and 18 l. In 2 patients who showed pulmonary disease decompensation, insufflation had to be temporarily postponed. A further 2 patients had subcutaneous emphysema during the last few days of insufflation, which resolved spontaneously without sequelae. The open mesh repair technique was used in ventral hernias and the preperitoneal technique in all inguinal hernias. There was one recurrence during the 1-year follow-up. CONCLUSIONS: Goñi Moreno's technique remains safe to prepare patients with giant hernias with loss of domain. This procedure can reduce the morbidity caused by the increase in abdominal pressure after abdominal wall repair.


Subject(s)
Hernia, Inguinal/pathology , Hernia, Inguinal/surgery , Hernia, Ventral/pathology , Hernia, Ventral/surgery , Pneumoperitoneum, Artificial/methods , Preoperative Care/methods , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Retrospective Studies
18.
J Clin Med ; 12(14)2023 Jul 16.
Article in English | MEDLINE | ID: mdl-37510826

ABSTRACT

Sepsis of biliary origin is increasing worldwide and has become one of the leading causes of emergency department admissions. The presence of multi-resistant bacteria (MRB) is increasing, and mortality rates may reach 20%. This review focuses on the changes induced by the Tokyo guidelines and new concepts related to the early treatment of severe biliary disease. If cholecystitis or cholangitis is suspected, ultrasound is the imaging test of choice. Appropriate empirical antibiotic treatment should be initiated promptly, and selection should be performed while bearing in mind the severity and risk factors for MRB. In acute cholecystitis, laparoscopic cholecystectomy is the main therapeutic intervention. In patients not suitable for surgery, percutaneous cholecystostomy is a valid alternative for controlling the infection. Treatment of severe acute cholangitis is based on endoscopic or transhepatic bile duct drainage and antibiotic therapy. Endoscopic ultrasound and other new endoscopic techniques have been added to the arsenal as novel alternatives in high-risk patients. However, biliary infections remain serious conditions that can lead to sepsis and death. The introduction of internationally accepted guidelines, based on clinical presentation, laboratory tests, and imaging, provides a framework for their rapid diagnosis and treatment. Prompt assessment of patient severity, timely initiation of antimicrobials, and early control of the source of infection are essential to reduce morbidity and mortality rates.

19.
J Abdom Wall Surg ; 2: 11093, 2023.
Article in English | MEDLINE | ID: mdl-38312413

ABSTRACT

Purpose: The simultaneous repair of incisional hernias (IH) and the reconstruction of the intestinal transit may pose a challenge for many surgeons. Collaboration between units specialized in abdominal wall and colorectal surgery can favor simultaneous treatment. Methods: Descriptive study of patients undergoing simultaneous surgery of complex IH repair and intestinal transit reconstruction from the start of treatment in a joint team. All interventions were performed electively and with the collaboration of surgeons experts in abdominal wall and colorectal surgery. Results: 23 patients are included. 11 end colostomies, 1 loop colostomy, 6 end ileostomies and 5 loop ileostomies. Seven (30%) patients presented with a medial laparotomy incisional hernia, 3 (13%) with a parastomal incisional hernia, and 13 (56%) with a medial and parastomal incisional hernia. Closure of the hernial defect was achieved in 100% of cases, and reconstruction of the intestinal tract was achieved in 22 (95%). Component separation was required in 17 patients (74%), which were 11 (48%) posterior and 6 (26%) anterior. In-hospital morbidity was 9%, and only two patients presented Clavien-Dindo morbidity > III when requiring reoperation, one due to hemorrhage of the surgical bed and another due to dehiscence of the coloproctostomy. The mean follow-up was 11 months, with 20 (87%) patients having no complications. Mesh had to be removed in one patient with anastomotic dehiscence, no mesh had to be removed due to surgical site infection.

20.
Eur J Surg Oncol ; 49(3): 533-541, 2023 03.
Article in English | MEDLINE | ID: mdl-36631347

ABSTRACT

BACKGROUND: Today, there is still debate on the impact of neoadjuvant chemotherapy (NeoChem) on liver regeneration (LivReg). The objectives of this study were to assess the impact of NeoChem and its characteristics (addition of bevacizumab, number of cycles and time from end of NeoChem) on post-hepatectomy LivReg. MATERIAL & METHODS: Studies reporting LivReg in patients submitted to liver resection were included. Pubmed, Scopus, Web of Science, Embase, and Cochrane databases were searched. Only studies comparing NeoChem vs no chemotherapy or comparing chemotherapy characteristics from 1990 to present were included. Two researchers individually screened the identified records registered in a predesigned database. Primary outcome was future liver remnant regeneration rate (FLR3). Bias of the studies was evaluated with the ROBINS-I tool, and quality of evidence with the GRADE system. Data was presented as mean difference or standard mean difference. RESULTS: Eight studies with a total of 681 patients were selected. Seven were retrospective and one prospective comparative cohort studies. In patients submitted to major hepatectomy, NeoChem did not have an impact on LivReg (MD 3.12, 95% CI -2,12-8.36, p 0,24). Adding bevacizumab to standard NeoChem was associated with better FLR3 (SMD 0.45, 95% CI 0.19-0.71, p 0.0006). DISCUSSION: The main drawback of this review is the retrospective nature of the available studies. NeoChem does not have a negative impact on postoperative LivReg in patients submitted to liver resection. Regimens with bevacizumab seem to be associated with better postoperative LivReg rates when compared to standard NeoChem.


Subject(s)
Colorectal Neoplasms , Liver Neoplasms , Humans , Hepatectomy , Bevacizumab/therapeutic use , Retrospective Studies , Neoadjuvant Therapy , Prospective Studies , Colorectal Neoplasms/surgery , Liver Neoplasms/surgery , Liver Regeneration
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