One-Year Results of Simultaneous Topography-Guided Photorefractive Keratectomy and Corneal Collagen Cross-Linking in Keratoconus Utilizing a Modern Ablation Software

Purpose. To evaluate effectiveness of simultaneous topography-guided photorefractive keratectomy and corneal collagen cross-linking in mild and moderate keratoconus. Methods. Prospective nonrandomized interventional study including 20 eyes of 14 patients with grade 1-2 keratoconus that underwent topography-guided PRK using a Custom Ablation Transition Zone (CATz) profile with 0.02% MMC application immediately followed by standard 3 mw/cm2 UVA collagen cross-linking. Maximum ablation depth did not exceed 58 μm. Follow-up period: 12 months. Results. Progressive statistically significant improvement of UCVA from 0.83±0.37 logMAR preoperative, reaching 0.25±0.26 logMAR at 12 months (P<0.001). Preoperative BCVA (0.27±0.31 logMAR) showed a progressive improvement reaching 0.08±0.12 logMAR at 12 months (P=0.02). Mean Kmax reduced from 48.9±2.8 to 45.4±3.1 D at 12 months (P<0.001), mean Kmin reduced from 45.9±2.8 D to 44.1±3.2 D at 12 months (P<0.003), mean keratometric asymmetry reduced from 3.01±2.03 D to 1.25±1.2 D at 12 months (P<0.001). The safety index was 1.39 at 12 months and efficacy index 0.97 at 12 months. Conclusion. Combined topography-guided PRK and corneal collagen cross-linking are a safe and effective option in the management of mild and moderate keratoconus. Precis. To our knowledge, this is the first published study on the use of the CATz ablation system on the Nidek Quest excimer laser platform combined with conventional cross-linking in the management of mild keratoconus

Effects of administration of 10 nm or 50 nm gold nanoparticles (AuNPs) on blood profile, liver and kidney functions in male albino rats

This work aimed to investigate the effect of acute and chronic administration of gold nanoparticles (GNPs) on liver and kidney functions, blood glucose concentration, lipid profile, and haematological parameters in male albino rats. Two experiments were conducted. In acute study: Fifty-four adult mature male rats were randomly assigned into three equal groups (18 per group). Group 1 (control group): in which rats were received intramuscular (i.m) injection of 1 ml normal saline 0.9%. Group 2 (50 nm GNPs group): rats were i.m. injected with a single dose of 75 µg 50 nm GNPs/kg body weight (bwt). In Group 3 (10 nm GNPs group): rats were i.m. injected with a single dose of 75 µg 10 nm GNPs/kg bwt. In chronic study: Eighteen adult male rats were randomly divided into three equal groups (6 per group). Group І (control): rats were intramuscular (i.m) repeatedly injected with 1 ml normal saline 0.9% once/week 5 for weeks. Group 2 (50 nm GNPs): rats were i.m. injected with once/week with a dose of 75 µg 50 nm GNPs/kg bwt) for 5 weeks. In Group 3 (10 nm GNPs): male rats were i.m. injected with once/week with a dose of 75 µg 50 nm GNPs/kg bwt for 5 weeks, followed by 3 weeks washout period for all groups. Blood was collected at 3, 7, and 60 days in acute experiment, while, they were collected only before and after 2 months in chronic experiment. Acute and chronic administration of GNPs (10 or 50 nm size) in male albino rats induced no significant alterations for liver and kidney functions, lipid profile parameters and different haematological parameters at days 3 and 60 of the study. However, on day-7 post-treatment, GNPs-treated rats showed significantly (P &lt;0.05) higher serum ALT, AST, ALP, urea, creatinine, glucose, and different lipid profile and decreased HDL level. Chronic administration of 10 nm or 50 nm GNPs significantly (P &lt;0.05) decreased serum glucose levels. In conclusion acute or chronic administration of 10 nm or 50 nm GNPs could alter the liver, kidney functions and blood profile on day 7 post-treatment, however, these values returned to the normal levels on day 60 post- injection. Also, the chronic administration of GNPs induced a hypoglycemic effect in male albino rats

Effects of administration of 10 nm or 50 nm gold nanoparticles (AuNPs) on blood profile, liver and kidney functions in male albino rats

486-493This work aimed to investigate the effect of acute and chronic administration of gold nanoparticles (GNPs) on liver and kidney functions, blood glucose concentration, lipid profile, and haematological parameters in male albino rats. Two experiments were conducted. In acute study: Fifty-four adult mature male rats were randomly assigned into three equal groups  (18  per  group).   Group   1   (control   group):  in   which  rats   were  received   intramuscular   (i.m)   injection  of 1 ml normal saline 0.9%. Group 2 (50 nm GNPs group): rats were i.m. injected with a single dose of 75 µg 50 nm GNPs/kg body weight (bwt). In Group 3 (10 nm GNPs group): rats were i.m. injected with a single dose of 75 µg 10 nm GNPs/kg bwt. In chronic study: Eighteen adult male rats were randomly divided into three equal groups (6 per group). Group І (control): rats were intramuscular (i.m) repeatedly injected with 1 ml normal saline 0.9% once/week 5 for weeks. Group 2 (50 nm GNPs): rats were i.m. injected with once/week with a dose of 75 µg 50 nm GNPs/kg bwt) for 5 weeks. In Group 3 (10 nm GNPs): male rats were i.m. injected with once/week with a dose of 75 µg 50 nm GNPs/kg bwt for 5 weeks, followed by 3 weeks washout period for all groups. Blood was collected at 3, 7, and 60 days in acute experiment, while, they were collected only before and  after  2  months  in  chronic  experiment.  Acute  and  chronic  administration  of  GNPs  (10  or 50 nm size) in male albino rats induced no significant alterations for liver and kidney functions, lipid profile parameters and different haematological parameters at days 3 and 60 of the study. However, on day-7 post-treatment, GNPs-treated rats showed significantly (P P <0.05) decreased serum glucose levels. In conclusion acute or chronic administration of 10 nm or 50 nm GNPs could alter the liver, kidney functions and blood profile on day 7 post-treatment, however, these values returned to the normal levels on day 60 post- injection. Also, the chronic administration of GNPs induced a hypoglycemic effect in male albino rats

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

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

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

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&nbsp;years; 78.2% included were male with a median age of 37&nbsp;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

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity