1,722 research outputs found
Small extracellular vesicle targeting of hypothalamic AMPKα1 promotes weight loss in leptin receptor deficient mice
Background and aims: Leptin receptor (LEPR) deficiency promotes severe obesity and metabolic disorders. However, the current therapeutic options against this syndrome are scarce.
Methods: db/db mice and their wildtypes were systemically treated with neuronal-targeted small extracellular vesicles (sEVs) harboring a plasmid encoding a dominant negative mutant of AMP-activated protein kinase alpha 1 (AMPKα1-DN) driven by steroidogenic factor 1 (SF1) promoter; this approach allowed to modulate AMPK activity, specifically in SF1 cells of the ventromedial nucleus of the hypothalamus (VMH). Animals were metabolically phenotyped. Results: db/db mice intravenously injected with SF1-AMPKα1-DN loaded sEVs showed a marked feeding-independent weight loss and decreased adiposity, associated with increased sympathetic tone, brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT).Conclusion: Overall, this evidence indicates that specific modulation of hypothalamic AMPK using a sEV-based technology may be a suitable strategy against genetic forms of obesity, such as LEPR deficiencyMinisterio de Ciencia y Universidades co-funded by the FEDER Program of EU (CD: BFU2017-87721; RN: RTI2018-099413-B-I00 and RED2018-102379-T; ML: RTI2018-101840-B-I00, PID2021-128145NB-I00 and PDC2022-133958-I00). âla Caixaâ Foundation (ID100010434), under the agreement LCF/PR/HR19/52160022 (ML); EuroNanoMed III (RA & ML: EURONANOMED2019-050-ENAMEP); European Research Council (RN: ERC Synergy Grant-2019-WATCH-810331)S
Infected pancreatic necrosis : outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study
Peer reviewe
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
Timing of surgery following SARSâCoVâ2 infection: an international prospective cohort study
Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4â1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0â2 weeks, 3â4 weeks and 5â6 weeks of the diagnosis (odds ratio (95%CI) 4.1% (3.3â4.8), 3.9% (2.6â5.1) and 3.6% (2.0â5.2), respectively). Surgery performed â„ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5% (0.9â 2.1%)). After a â„ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2â8.7) vs. 2.4% (95%CI 1.4â3.4) vs. 1.3% (95%CI 0.6â2.0%), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms â„ 7 weeks from diagnosis may benefit from further delay
Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy
IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical
attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced
colorectal cancers at diagnosis.
OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced
oncologic stage and change in clinical presentation for patients with colorectal cancer.
DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all
17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December
31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period),
in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was
30 days from surgery.
EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery,
palliative procedures, and atypical or segmental resections.
MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer
at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as
cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding,
lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery,
and palliative surgery. The independent association between the pandemic period and the outcomes
was assessed using multivariate random-effects logistic regression, with hospital as the cluster
variable.
RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years)
underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142
(56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was
significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR],
1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic
lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03).
CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the
SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients
undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for
these patients
Diversity and ethics in trauma and acute care surgery teams: results from an international survey
Background Investigating the context of trauma and acute care surgery, the article aims at understanding the factors that can enhance some ethical aspects, namely the importance of patient consent, the perceptiveness of the ethical role of the trauma leader, and the perceived importance of ethics as an educational subject. Methods The article employs an international questionnaire promoted by the World Society of Emergency Surgery. Results Through the analysis of 402 fully filled questionnaires by surgeons from 72 different countries, the three main ethical topics are investigated through the lens of gender, membership of an academic or non-academic institution, an official trauma team, and a diverse group. In general terms, results highlight greater attention paid by surgeons belonging to academic institutions, official trauma teams, and diverse groups. Conclusions Our results underline that some organizational factors (e.g., the fact that the team belongs to a university context or is more diverse) might lead to the development of a higher sensibility on ethical matters. Embracing cultural diversity forces trauma teams to deal with different mindsets. Organizations should, therefore, consider those elements in defining their organizational procedures. Level of evidence Trauma and acute care teams work under tremendous pressure and complex circumstances, with their members needing to make ethical decisions quickly. The international survey allowed to shed light on how team assembly decisions might represent an opportunity to coordinate team member actions and increase performance
Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study
Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak.
Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study.
Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM.
Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide
Global disparities in surgeonsâ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study
: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSSŸ v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity > 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI
Elective surgery cancellations due to the COVID-19 pandemic: global predictive modelling to inform surgical recovery plans.
BACKGROUND: The COVID-19 pandemic has disrupted routine hospital services globally. This study estimated the total number of adult elective operations that would be cancelled worldwide during the 12âweeks of peak disruption due to COVID-19. METHODS: A global expert response study was conducted to elicit projections for the proportion of elective surgery that would be cancelled or postponed during the 12âweeks of peak disruption. A Bayesian ÎČ-regression model was used to estimate 12-week cancellation rates for 190 countries. Elective surgical case-mix data, stratified by specialty and indication (surgery for cancer versus benign disease), were determined. This case mix was applied to country-level surgical volumes. The 12-week cancellation rates were then applied to these figures to calculate the total number of cancelled operations. RESULTS: The best estimate was that 28â404â603 operations would be cancelled or postponed during the peak 12âweeks of disruption due to COVID-19 (2â367â050 operations per week). Most would be operations for benign disease (90·2 per cent, 25â638â922 of 28â404â603). The overall 12-week cancellation rate would be 72·3 per cent. Globally, 81·7 per cent of operations for benign conditions (25â638â922 of 31â378â062), 37·7 per cent of cancer operations (2â324â070 of 6â162â311) and 25·4 per cent of elective caesarean sections (441â611 of 1â735â483) would be cancelled or postponed. If countries increased their normal surgical volume by 20 per cent after the pandemic, it would take a median of 45âweeks to clear the backlog of operations resulting from COVID-19 disruption. CONCLUSION: A very large number of operations will be cancelled or postponed owing to disruption caused by COVID-19. Governments should mitigate against this major burden on patients by developing recovery plans and implementing strategies to restore surgical activity safely
It is time to define an organizational model for the prevention and management of infections along the surgical pathway : a worldwide cross-sectional survey
Background The objectives of the study were to investigate the organizational characteristics of acute care facilities worldwide in preventing and managing infections in surgery; assess participants' perception regarding infection prevention and control (IPC) measures, antibiotic prescribing practices, and source control; describe awareness about the global burden of antimicrobial resistance (AMR) and IPC measures; and determine the role of the Coronavirus Disease 2019 pandemic on said awareness. Methods A cross-sectional web-based survey was conducted contacting 1432 health care workers (HCWs) belonging to a mailing list provided by the Global Alliance for Infections in Surgery. The self-administered questionnaire was developed by a multidisciplinary team. The survey was open from May 22, 2021, and June 22, 2021. Three reminders were sent, after 7, 14, and 21 days. Results Three hundred four respondents from 72 countries returned a questionnaire, with an overall response rate of 21.2%. Respectively, 90.4% and 68.8% of participants stated their hospital had a multidisciplinary IPC team or a multidisciplinary antimicrobial stewardship team. Local protocols for antimicrobial therapy of surgical infections and protocols for surgical antibiotic prophylaxis were present in 76.6% and 90.8% of hospitals, respectively. In 23.4% and 24.0% of hospitals no surveillance systems for surgical site infections and no monitoring systems of used antimicrobials were implemented. Patient and family involvement in IPC management was considered to be slightly or not important in their hospital by the majority of respondents (65.1%). Awareness of the global burden of AMR among HCWs was considered very important or important by 54.6% of participants. The COVID-19 pandemic was considered by 80.3% of respondents as a very important or important factor in raising HCWs awareness of the IPC programs in their hospital. Based on the survey results, the authors developed 15 statements for several questions regarding the prevention and management of infections in surgery. The statements may be the starting point for designing future evidence-based recommendations. Conclusion Adequacy of prevention and management of infections in acute care facilities depends on HCWs behaviours and on the organizational characteristics of acute health care facilities to support best practices and promote behavioural change. Patient involvement in the implementation of IPC is still little considered. A debate on how operationalising a fundamental change to IPC, from being solely the HCWs responsibility to one that involves a collaborative relationship between HCWs and patients, should be opened.Peer reviewe
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