CHANGES IN SOME BIOPHYSICAL AND BIOCHEMICAL PARAMETERS IN BLOOD AND URINE OF WORKERS CHRONICALLY EXPOSED TO BENZENE

Objective: Benzene may occur naturally as a component of petroleum, or may be manufactured synthetically. It is found in the environment as a contaminant from both human activities and natural processes, posing serious bio-hazards from chronic exposure.Methods: A total of 330 individual were enrolled to study possible health hazards of benzene contamination; 265 males occupationally chronically exposed to low levels of benzene in their daily activity were compared to 65 healthy individuals of the same socio-economic standard. Benzene workers were divided between 45 workers in printing shops, 70 subjects dealing with benzene containing paints (painters), 75 subjects working in professions related to automotive work (autoworkers) and 75 car drivers.Results: benzene itself was not detected in blood or urine of all participants, but the levels of its metabolites; phenol and t,t-muconic acid, were higher in the blood and urine samples in the group of benzene-exposed workers. The results also indicate that individuals in this group are under oxidative stress. However, neither the determined liver function nor the kidney function tests showed significant deviation from controls. However, the results of the biophysical hematological parameters, including the degree of hemolysis, blood viscosity, RBCs aggregation and form factor were significantly deviated from normal.Conclusion: The deviation of the determined biochemical and biophysical parameters from normal may predispose such workers to a variety of health problems. Early correction of the oxidative stress and the hematological parameters and improvement of working conditions are necessary to prevent their progress to more serious health conditions, especially in children and young adolescents working under similar conditions.Running Title : Chronic exposure to benzene in work plac

Antibodies against a Surface Protein of Streptococcus pyogenes Promote a Pathological Inflammatory Response

Streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes is a clinical condition with a high mortality rate despite modern intensive care. A key feature of STSS is excessive plasma leakage leading to hypovolemic hypotension, disturbed microcirculation and multiorgan failure. Previous work has identified a virulence mechanism in STSS where M1 protein of S. pyogenes forms complexes with fibrinogen that activate neutrophils to release heparin-binding protein (HBP), an inducer of vascular leakage. Here, we report a marked inter-individual difference in the response to M1 protein–induced HBP release, a difference found to be related to IgG antibodies directed against the central region of the M1 protein. To elicit massive HBP release, such antibodies need to be part of the M1 protein–fibrinogen complexes. The data add a novel aspect to bacterial pathogenesis where antibodies contribute to the severity of disease by promoting a pathologic inflammatory response

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Prediction of pediatric PCNL outcomes using contemporary scoring systems

Purpose: To evaluate the applicability of contemporary percutaneous nephrolithotomy (PCNL) scoring systems in pediatric patients and to compare their predictive power for postoperative outcomes. Materials and methods: The records of 125 pediatric patients who were diagnosed with renal calculi and managed with PCNL between March 2011 and April 2016 were retrospectively analyzed. The predictive scoring systems; The Guy’s Stone Score (GSS), S.T.O.N.E. nephrolithometry and, Clinical Research Office of the Endourological Society (CROES) were calculated for all patients included in the study. Patient demographics, stone free rate (SFR), and complications were all reported and analyzed. Results: In patients with residual stones (group I) vs those who were (group II) stone free the median (IQR) of GSS was 2 (2-3) and 2 (1-2), CROES nomogram score was 215 (210-235) and 257 (240-264), and S.T.O.N.E. nephrolithometry score was 8 (7-9) and 5 (5-6), respectively (each <p0.0001). S.T.O.N.E. nephrolithometry score revealed the highest accuracy in predicting SFR. GSS was significantly correlated with complications but the CROES nomogram and S.T.O.N.E nephrolithometry were not significantly correlated with complications. Conclusion: The scoring systems could be used in predicting PCNL success in pediatric setting. However, further studies are required to make modifications in the scoring systems in pediatrics. The main variables in the scoring systems as stone burden, tract length and case volume were measured using records from adult patients. Besides these variables, the relatively small pelvicalyceal system and the higher incidence of anatomic malformations in pediatrics could potentially affect PCNL outcomes

Prediction of pediatric PCNL outcomes using contemporary scoring systems

Purpose: To evaluate the applicability of contemporary percutaneous nephrolithotomy (PCNL) scoring systems in pediatric patients and to compare their predictive power for postoperative outcomes. Materials and methods: The records of 125 pediatric patients who were diagnosed with renal calculi and managed with PCNL between March 2011 and April 2016 were retrospectively analyzed. The predictive scoring systems; The Guy’s Stone Score (GSS), S.T.O.N.E. nephrolithometry and, Clinical Research Office of the Endourological Society (CROES) were calculated for all patients included in the study. Patient demographics, stone free rate (SFR), and complications were all reported and analyzed. Results: In patients with residual stones (group I) vs those who were (group II) stone free the median (IQR) of GSS was 2 (2-3) and 2 (1-2), CROES nomogram score was 215 (210-235) and 257 (240-264), and S.T.O.N.E. nephrolithometry score was 8 (7-9) and 5 (5-6), respectively (each <p0.0001). S.T.O.N.E. nephrolithometry score revealed the highest accuracy in predicting SFR. GSS was significantly correlated with complications but the CROES nomogram and S.T.O.N.E nephrolithometry were not significantly correlated with complications. Conclusion: The scoring systems could be used in predicting PCNL success in pediatric setting. However, further studies are required to make modifications in the scoring systems in pediatrics. The main variables in the scoring systems as stone burden, tract length and case volume were measured using records from adult patients. Besides these variables, the relatively small pelvicalyceal system and the higher incidence of anatomic malformations in pediatrics could potentially affect PCNL outcomes

La médecine de précision en oncologie : challenges, enjeux et nouveaux paradigmes

International audienceL’oncologie médicale a pris, depuis quelques années, un tournant substantiel en intégrant la dimension génomique dans la prise de décision thérapeutique. En raison de l’accès aux technologies de séquençage (exome complet, séquençage ciblé du génome, séquençage de l’ARN, ADN circulant…) facilité par la mise en place de plateformes de biologie moléculaire et la diminution des coûts par échantillon, la caractérisation moléculaire est devenue un outil supplémentaire à la disposition du clinicien, s’ajoutant au diagnostic histologique et immunohistochimique et aux données d’imagerie radiologique. Cette approche moléculaire a permis d’identifier de nouvelles formes nosologiques et permet, au-delà de l’aspect cognitif, de renseigner sur les altérations qui sont à prendre en compte dans les décisions thérapeutiques (biomarqueurs prédictifs, activation de voies spécifiques, mutations de résistance). C’est dans ce contexte de profond et rapide changement de pratique médicale et scientifique qu’il a été proposé de réfléchir collectivement aux nouveaux enjeux sous la forme d’un workshop à l’occasion de Biovision qui s’est tenu à Lyon, du 4 au 6 avril 2017. Biovision est un forum international dédié à la Santé et aux Sciences de la vie, qui réunit sur quelques jours des communautés scientifiques, académiques et industrielles dans le but d’accélérer l’innovation. Lors de la 12e édition en avril 2017, le CLARA, l’Institut Roche ainsi que le SIRIC de Lyon ont donc organisé un workshop autour de la médecine de précision (« Precision medicine in oncology: challenges, stakes and new paradigms »). Des experts ainsi que des participants de différents horizons ont échangé sur le sujet afin de proposer des mesures clé

Detection of MDR1 single nucleotide polymorphisms C3435T and G2677T using real-time polymerase chain reaction: MDR1 single nucleotide polymorphism genotyping assay

The objective of this study was to develop a real-time polymerase chain reaction (PCR) method to detect MDR1 (human multidrug resistance gene) single nucleotide polymorphisms (SNPs) C3435T and G2677T. C3435T and G2677T are linked to MDR1*2, which is associated with enhanced efflux activity in vitro. Using the Smart Cycler, an allele-specific real-time PCR-based genotyping method was developed to detect C3435T and G2677T. The MDR1 genotype of human genomic DNA templates was determined by direct DNA sequencing. PCR reactions for genotyping C3435T and G2677T by using allele-specific primers were conducted in separate tubes. An additional nucleotide mismatch at the third position from the 3′ end of each allele-specific primer was used to abrogate nonspecific PCR amplification. The fluorescence emitted by SYBR Green I was monitored to detect formation of specific PCRproducts. PCR growth curves exceeding the threshold cycle were considered positive. Fluorescence melt-curve analysis was used to corroborate results from PCR growth curves. Using PCR growth curves, our assay accurately determined hetero- and homozygosity for C3435T and G2677T. Genotype assignments based on PCR growth curve, melt-curve analysis, agarose gel electrophoresis, and direct DNA sequencing results of PCR products were in perfect agreement. We have developed a rapid MDR1 genotyping method that can be used to assess the contribution of MDR1*2 to pharmacokinetic and pharmacodynamic variability of P-glycoprotein substrates