Global disparities in surgeons’ 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 (SPSS® 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

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Mechanics of Viral Chromatin Reveals the Pressurization of Human Adenovirus

Tight confinement of naked genomes within some viruses results in high internal pressure that facilitates their translocation into the host. Adenovirus, however, encodes histone-like proteins that associate with its genome resulting in a confined DNA–protein condensate (core). Cleavage of these proteins during maturation decreases core condensation and primes the virion for proper uncoating <i>via</i> unidentified mechanisms. Here we open individual, mature and immature adenovirus cages to directly probe the mechanics of their chromatin-like cores. We find that immature cores are more rigid than the mature ones, unveiling a mechanical signature of their condensation level. Conversely, intact mature particles demonstrate more rigidity than immature or empty ones. DNA-condensing polyamines revert the mechanics of mature capsid and cores to near-immature values. The combination of these experiments reveals the pressurization of adenovirus particles induced by maturation. We estimate a pressure of ∼30 atm by continuous elasticity, which is corroborated by modeling the adenovirus mini-chromosome as a confined compact polymer. We propose this pressurization as a mechanism that facilitates initiating the stepwise disassembly of the mature particle, enabling its escape from the endosome and final genome release at the nuclear pore

Methodology for the Absolute Configuration Determination of Epoxythymols Using the Constituents of <i>Ageratina glabrata</i>

A methodology to determine the enantiomeric excess and the absolute configuration (AC) of natural epoxythymols was developed and tested using five constituents of <i>Ageratina glabrata</i>. The methodology is based on enantiomeric purity determination employing 1,1′-bi-2-naphthol (BINOL) as a chiral solvating agent combined with vibrational circular dichroism (VCD) measurements and calculations. The conformational searching included an extensive Monte Carlo protocol that considered the rotational barriers to cover the whole conformational spaces. (+)-(8<i>S</i>)-10-Benzoyloxy-6-hydroxy-8,9-epoxythymol isobutyrate (<b>1</b>), (+)-(8<i>S</i>)-10-acetoxy-6-methoxy-8,9-epoxythymol isobutyrate (<b>4</b>), and (+)-(8<i>S</i>)-10-benzoyloxy-6-methoxy-8,9-epoxythymol isobutyrate (<b>5</b>) were isolated as enantiomerically pure constituents, while 10-isobutyryloxy-8,9-epoxythymol isobutyrate (<b>2</b>) was obtained as a 75:25 (8<i>S</i>)/(8<i>R</i>) scalemic mixture. In the case of 10-benzoyloxy-8,9-epoxythymol isobutyrate (<b>3</b>), the BINOL methodology revealed a 56:44 scalemic mixture and the VCD measurement was beyond the limit of sensitivity since the enantiomeric excess is only 12%. The racemization process of epoxythymol derivatives was studied using compound <b>1</b> and allowed the clarification of some stereochemical aspects of epoxythymol derivatives since their ACs have been scarcely analyzed and a particular behavior in their specific rotations was detected. In more than 30 oxygenated thymol derivatives, including some epoxythymols, the reported specific rotation values fluctuate from −1.6 to +1.4 passing through zero, suggesting the presence of scalemic and close to racemic mixtures, since enantiomerically pure natural constituents showed positive or negative specific rotations greater than 10 units

Current status of liver surgery for non-colorectal non-neuroendocrine liver metastases: the NON.LI.MET. Italian Society for Endoscopic Surgery and New Technologies (SICE) and Association of Italian Surgeons in Europe (ACIE) collaborative international survey

Despite the increasing trend in liver resections for non-colorectal non-neuroendocrine liver metastases (NCNNLM), the role of surgery for these liver malignancies is still debated. Registries are an essential, reliable tool for assessing epidemiology, diagnosis, and therapeutic approach in a single hub, especially when data are dispersive and inconclusive, as in our case. The dissemination of this preliminary survey would allow us to understand if the creation of an International Registry is a viable option, while still offering a snapshot on this issue, investigating clinical practices worldwide. The steering committee designed an online questionnaire with Google Forms, which consisted of 37 questions, and was open from October 5th, 2022, to November 30th, 2022. It was disseminated using social media and mailing lists of the Italian Society of Endoscopic Surgery and New Technologies (SICE), the Association of Italian Surgeons in Europe (ACIE), and the Spanish Chapter of the American College of Surgeons (ACS). Overall, 141 surgeons (approximately 18% of the total invitations sent) from 27 countries on four continents participated in the survey. Most respondents worked in general surgery units (62%), performing less than 50 liver resections/year (57%). A multidisciplinary discussion was currently performed to validate surgical indications for NCNNLM in 96% of respondents. The most commonly adopted selection criteria were liver resectability, RECIST criteria, and absence of extrahepatic disease. Primary tumors were generally of gastrointestinal (42%), breast (31%), and pancreaticobiliary origin (13%). The most common interventions were parenchymal-sparing resections (51% of respondents) of metachronous metastases with an open approach. Major post-operative complications (Clavien-Dindo &gt; 2) occurred in up to 20% of the procedures, according to 44% of respondents. A subset analysis of data from high-volume centers (&gt; 100 cases/year) showed lower post-operative complications and better survival. The present survey shows that NCNNLM patients are frequently treated by surgeons in low-volume hospitals for liver surgery. Selection criteria are usually based on common sense. Liver resections are performed mainly with an open approach, possibly carrying a high burden of major post-operative complications. International guidelines and a specific consensus on this field are desirable, as well as strategies for collaboration between high-volume and low-volume centers. The present study can guide the elaboration of a multi-institutional document on the optimal pathway in the management of patients with NCNNLM

The Power Board of the KM3NeT Digital Optical Module: Design, Upgrade, and Production

The KM3NeT Collaboration is building an underwater neutrino observatory at the bottom of the Mediterranean Sea, consisting of two neutrino telescopes, both composed of a three-dimensional array of light detectors, known as digital optical modules. Each digital optical module contains a set of 31 three-inch photomultiplier tubes distributed over the surface of a 0.44 m diameter pressure- resistant glass sphere. The module also includes calibration instruments and electronics for power, readout, and data acquisition. The power board was developed to supply power to all the elements of the digital optical module. The design of the power board began in 2013, and ten prototypes were produced and tested. After an exhaustive validation process in various laboratories within the KM3NeT Collaboration, a mass production batch began, resulting in the construction of over 1200 power boards so far. These boards were integrated in the digital optical modules that have already been produced and deployed, which total 828 as of October 2023. In 2017, an upgrade of the power board, to increase reliability and efficiency, was initiated. The validation of a pre-production series has been completed, and a production batch of 800 upgraded boards is currently underway. This paper describes the design, architecture, upgrade, validation, and production of the power board, including the reliability studies and tests conducted to ensure safe operation at the bottom of the Mediterranean Sea throughout the observatory’s lifespan

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P &lt; 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)