Tumor necrosis factor-α serum levels in healthy smokers and nonsmokers

Florin Petrescu1, Sebastian Cosmin Voican1, Isabela Silosi21Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, Craiova, Romania; 2Department of Immunology, University of Medicine and Pharmacy of Craiova, Craiova, RomaniaBackground: Tobacco smoking is the most important risk factor for chronic obstructive pulmonary disease (COPD) development. Inhaled cigarette smoke can induce tumor necrosis factor-a (TNF-a) production by alveolar macrophages, which in turn may enhance the production of metalloproteinases (MMPs). MMPs have been involved in mediating airway inflammation and lung destruction.Objectives: We aimed to measure the TNF-a serum levels in healthy heavy smokers and healthy nonsmokers to determine the dose-response relationship based on the cigarette smoke exposure.Subjects and methods: We included in our study 43 healthy heavy smokers and 19 healthy nonsmokers (the control group). The smokers group was classified as less than one pack, one pack, and more than one pack per day. A clinical and paraclinical evaluation was performed in both groups, without any evidence of infection or COPD. The serum levels of TNF-a were assessed by ELISA.Results: The TNF-a serum levels were significantly higher for the group of smokers compared to the group of nonsmokers (P < 0.004). We also noticed an increased TNF-a concentration in the serum of smokers with more than one pack per day compared with those with less than one pack per day (P < 0.03). There was a positive correlation between the serum level of TNF-a and tobacco smoke exposure.Conclusions: The high levels of TNF-a in the serum of smokers suggest an imbalance between the proinflammatory and anti-inflammatory factors as a result of tobacco smoke exposure. The concentration of TNF-a is elevated in the serum of healthy heavy smokers in a cigarette dose-dependent manner. We speculate that the serum level of TNF-a might be a useful biomarker for the selection of heavy smokers with a high risk of developing smoke induced pulmonary diseases.Keywords: tobacco smoking, inflammation, chronic obstructive pulmonary disease, metalloproteinase

Computed tomography assessment of postoperative gastric vascular supply and staple-line leak development after sleeve gastrectomy

Background: Residual arterial supply of the gastric tube after sleeve gastrectomy (SG) can be damaged by surgery, which can reduce gastric tube perfusion and could promote postoperative leakage. Objective: To compare the postoperative vascularization of the gastric tube using early computed tomography (CT) scanning after SG in patients with or without postoperative staple-line leak. Setting: University hospital. Methods: A retrospective analysis of a prospective database was performed in consecutive patients undergoing SG. Patients who presented with a staple-line leak were matched (1:3) with a control group of patients who underwent surgery without postoperative morbidity during the same period. Gastric tube vascularization was studied on a postoperative day 2 CT scan in both groups of patients. Results: During the study period, 1826 patients underwent SG, including 42 patients (2.3%) who presented with a staple-line leak. Those 42 patients were successfully matched to 126 control patients. Global identification of residual gastric arterial supply in early postoperative CT scans was similar in patients with or without staple-line leak after SG. However, residual vascular supply of the gastroesophageal junction (i.e., terminal and anterior cardiotuberosity branches of the left gastric artery or left inferior phrenic artery) was more frequently interrupted by the staple line in the group of patients who developed a gastric leak. Conclusion: This study suggests a correlation between interruption of the main arteries supplying the gastroesophageal junction by the staple line on early postoperative CT scans and the development of gastric leak after SG. These results support the vascular theory as one of the causes of leak after SG

Multikinase inhibitor-induced liver injury in patients with cancer: A review for clinicians

International audienceBACKGROUND: Multikinase inhibitors (MKI) are targeted molecular agents that have revolutionized cancer management. However, there is a paucity of data concerning MKI-related liver injury risk and clinical guidelines for the management of liver toxicity in patients receiving MKI for cancer are scarce. DESIGN: We conducted a PubMed search of articles in English published from January 2000 to December 2018 related to hepatotoxicity of the 29 FDA-approved MKIs at doses used in clinical practice. The search terms were the international non-proprietary name of each agent cross-referenced with «hepatotoxicity», «hepatitis», «hepatic adverse event», or «liver failure», and «phase II clinical trial», «phase III clinical trial», or «case report». RESULTS: Following this search, 140 relevant studies and 99 case reports were considered. Although asymptomatic elevation of aminotransferase levels has been frequently observed in MKI clinical trials, clinically significant hepatotoxicity is a rare event. In most cases, the interval between treatment initiation and the onset of liver injury is between one week and two months. Liver toxicity is often hepatocellular and less frequently mixed. Life-threatening MKI-induced hepatic injury has been described, involving fulminant liver failure or death. Starting from existing data, a description of MKI-related liver events, grading of hepatotoxicity risk, and recommendations for management are also given for various MKI molecules. CONCLUSION: All MKIs can potentially cause liver injury, which is sometimes irreversible. As there is still no strategy available to prevent MKI-related hepatotoxicity, early detection remains crucial. The surveillance of liver function during treatment may help in the early detection of hepatotoxicity. Furthermore, the exclusion of potential causes of hepatic injury is essential to avoid unnecessary MKI withdrawal

Evolution of liver function tests in the 3 cases of antidepressant-induced liver injury.

<p>Evolution of liver function tests in the 3 cases of antidepressant-induced liver injury.</p

Characteristics of patients with normal and abnormal LFT.

<p>Characteristics of patients with normal and abnormal LFT.</p

Description of the 3 cases of antidepressant-induced liver injury.

<p>Description of the 3 cases of antidepressant-induced liver injury.</p

Predictive score of sarcopenia occurrence one year after bariatric surgery in severely obese patients.

BACKGROUND AND AIM:Sarcopenic obesity is a risk factor of morbidity and mortality. The aim of this study was to generate a predictive score of sarcopenia occurrence one year after bariatric surgery. PATIENTS AND METHODS:We conducted an observational prospective cohort study on a total of 184 severely obese patients admitted to our institution to undergo sleeve gastrectomy. Skeletal muscle cross-sectional area at the third lumbar vertebrae (SMA, cm2) was measured from the routinely performed computed tomography. The skeletal muscle index (SMI) was calculated as follows: SMA/height2 (cm2/m2). Sarcopenia was defined as an SMI < 38.5 cm2/m2 for women and < 52.4 cm2/m2 for men. Measurements were performed at surgery and one year later. RESULTS:Most of the included patients were female (79%), with a mean age of 42±0.9 years and body mass index of 43.2±0.5 kg/m2. Fifteen patients (8%) had sarcopenia before surgery and 59 (32%) at the one-year follow-up. Male gender (p<0.0001), SMA before surgery (p<0.0001), and SMI before surgery (p<0.0001) significantly correlated with the occurrence of sarcopenia one year after surgery by multivariate analysis. Two predictive sarcopenia occurrence scores were constructed using SMA and gender (SS1 score) or SMI and gender (SS2 score). The area under receiver operating characteristic (AUROC) curve of the SS2 score was significantly greater than that of the SS1 score for the diagnosis of postoperative sarcopenia occurrence (0.95±0.02 versus 0.90±0.02; p<0.01). A cut-off value for the SS2 score of 0.53 had a sensitivity of 90%, a specificity of 91%, a positive predictive value of 83%, and a negative predictive value of 95%. In the group of patients without baseline sarcopenia, the SS2 score had still an excellent AUROC of 0.92±0.02. A cut-off of 0.55 predicted development of sarcopenia one year after sleeve gastrectomy in these patients with a sensitivity of 87%, a specificity of 88%, and negative predictive value of 95%. CONCLUSION:The SS2 score has excellent predictive value for the occurrence of sarcopenia one year after sleeve gastrectomy. This score can be used to target early intensification of nutritional and dietetic follow-up to the predicted high-risk population

Adaptation of controlled attenuation parameter (CAP) measurement depth in morbidly obese patients addressed for bariatric surgery

International audienceBACKGROUND AND AIM: The controlled attenuation parameter (CAP) using FibroScan (Echosens, Paris, France) M or XL probe has been developed for liver steatosis assessment. However, CAP performs poorly in patients with high body mass index. The aim of our study was to assess whether CAP is overestimated using the standard XL probe in patients with morbid obesity, and in the case of an overestimation, to reprocess the data at a greater depth to obtain the appropriate CAP (CAPa).PATIENTS AND METHODS: We conducted an observational prospective cohort study on a total of 249 severely obese patients admitted to our institution to undergo sleeve gastrectomy. Patients had a liver biopsy performed during the surgery and a CAP measurement during the 15 days preceding biopsy. Patient files were reprocessed retrospectively by an algorithm, blinded to the patients' clinical data. The algorithm automatically assessed the probe-to-capsula distance (PCD) by analysing the echogenicity of ultrasound signals on the time-motion mode. In the case of a distance >35 mm, the algorithm automatically selected a deeper measurement for CAP (CAPa). When PCD was less than 35 mm, the measured CAP was considered as appropriated (CAPa) and no further reprocessing was performed.RESULTS: CAP recording was not performed at a sufficient depth in 130 patients. In these patients, the CAPa obtained at the adapted depth was significantly lower than CAP (298±3.9 versus 340±4.2 dB/m; p 35 mm, steatosis stage was the only parameter independently correlated with CAP values. For the diagnosis of steatosis (S≥1), moderate to severe steatosis (S≥2) and severe steatosis (S = 3), the AUROC curves of CAPa (measured CAP in patients with PCD35 mm) were 0.86, 0.83 and 0.79, respectively. The Obuchowski measure for the diagnosis of steatosis was 0.90±0.013.CONCLUSION: CAP was overestimated in a half of morbidly obese patients using an XL probe, but CAP can be performed correctly in these patients after adapting the measurement depth

Blood microbiota and metabolomic signature of major depression before and after antidepressant treatment: a prospective case–control study

International audienceBackground: The microbiota interacts with the brain through the gut-brain axis, and a distinct dysbiosis may lead to major depressive episodes. Bacteria can pass through the gut barrier and be found in the blood. Using a multiomic approach, we investigated whether a distinct blood microbiome and metabolome was associated with major depressive episodes, and how it was modulated by treatment.Methods: In this case-control multiomic study, we analyzed the blood microbiome composition, inferred bacterial functions and metabolomic profile of 56 patients experiencing a current major depressive episode and 56 matched healthy controls, before and after treatment, using 16S rDNA sequencing and liquid chromatography coupled to tandem mass spectrometry.Results: The baseline blood microbiome in patients with a major depressive episode was distinct from that of healthy controls (patients with a major depressive episode had a higher proportion of Janthinobacterium and lower levels of Neisseria) and changed after antidepressant treatment. Predicted microbiome functions confirmed by metabolomic profiling showed that patients who were experiencing a major depressive episode had alterations in the cyanoamino acid pathway at baseline. High baseline levels of Firmicutes and low proportions of Bosea and Tetrasphaera were associated with response to antidepressant treatment. Based on inferred baseline metagenomic profiles, bacterial pathways that were significantly associated with treatment response were related to xenobiotics, amino acids, and lipid and carbohydrate metabolism, including tryptophan and drug metabolism. Metabolomic analyses showed that plasma tryptophan levels are independently associated with response to antidepressant treatment.Limitations: Our study has some limitations, including a lack of information on blood microbiome origin and the lack of a validation cohort to confirm our results.Conclusion: Patients with depression have a distinct blood microbiome and metabolomic signature that changes after treatment. Dysbiosis could be a new therapeutic target and prognostic tool for the treatment of patients who are experiencing a major depressive episode