Pancreatic Cancer: Updates in Pathogenesis and Therapies

Despite the progress in pancreatic cancer (PC) chemo/radiotherapies, immunotherapies, and novel targeted therapies and the improvement in its peri-operative management policies, it still has a dismal catastrophic prognosis due to delayed detection, early neural and vascular invasions, early micro-metastatic spread, tumour heterogeneities, drug resistance either intrinsic or acquired, unique desmoplastic stroma, and tumour microenvironment (TME). Understanding tumour pathogenesis at the detailed genetic/epigenetic/metabolic/molecular levels as well as studying the tumour risk factors and its known precancerous lesions aggressively is required for getting a more successful therapy for this challenging tumour. For a better outcome of this catastrophic tumour, it should be diagnosed early and treated through multidisciplinary teams of surgeons, gastroenterologists/interventional upper endoscopists, medical/radiation oncologists, diagnostic/intervention radiologists, and pathologists at high-volume centres. Moreover, surgical resection with a negative margin (R0) is the only cure for it. In this chapter; we discuss the recently updated knowledge of PC pathogenesis, risk factors, and precancerous lesions as well as its different management tools (i.e. surgery, chemo/radiotherapies, immunotherapies, novel targeted therapies, local ablative therapies, etc.)

In-Plane Behavior of Cold-Formed Steel-Framed Shear Wall Panels Sheathed with Fibre Cement Board

Shear wall panels are commonly used as lateral load resisting elements to provide stability of the cold-formed steel-framed houses in Australia against wind and earthquake actions. The effectiveness of their lateral resistance behavior is obtained usually by experimental testing although it can also be done by analytical modeling. This paper presents racking test results of steelframed wall panels with different aspect ratios sheathed with fibre cement board subjected to monotonic and cyclic loading protocol. Performance parameters of the wall panels are obtained from the experimentally observed load-deflection curves using various existing methods and evaluation method is proposed. The evaluation method considers various performance characteristics including ductility modification factor, residual displacement recovery and load levels satisfying ultimate and serviceability limit state conditions

Fundamental Role of Neurochemicals Aberration in the Pathogenesis of Autism Spectrum Disorders

AIM: The aim of this research was to establish the perturbation of reliable biomarkers implicated in the pathophysiology of autism to help in the early diagnosis and to be as targets in the treatment of autism spectrum disorders (ASDs) in children and to spotlight into the complex crosstalk between these biomarkers. PATIENS AND METHODS: This study included 90 autistic children aged from 2 to 7 years old, who were classified into two groups, the atypical autism of 30 children and the childhood autism. The childhood autism group was further divided into mild-moderate autism group and severe autism group each of 30 children. The control group included 30 matched healthy children. All the participants were subjected to full psychiatric examinations, psychological investigations, and biochemical measurements, including gamma-aminobutaric acid (GABA), serotonin, dopamine (DA) in plasma, and brain-derived neurotrophic factor (BDNF) in serum. RESULTS: The autistic groups showed a highly significant increase in GABA, serotonin, DA, and BDNF levels compared to the control. Of note, the levels of GABA, DA, and BDNF were significantly increased with the increased disease severity. Furthermore, a significant positive correlation between BDNF levels and both GABA and DA levels in the childhood autism group has been recorded. CONCLUSION: The present clinical setting provides new insight into the fundamental role of BDNF in the brain of autistic children as any alterations of its level due to GABA increment cause change in serotonin and DA levels which have empirical evidence in the pathophysiology of ASD. The results received in this research, create a fertile base for the setup of particular targets in the intervention of this ailment

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication