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  1. Zeng GH, Zhong W, Mazzon G, Zhu W, Lahme S, Khadgi S, et al.
    Mil Med Res, 2024 Oct 28;11(1):70.
    PMID: 39465407 DOI: 10.1186/s40779-024-00562-3
    Over the past three decades, there has been increasing interest in miniaturized percutaneous nephrolithotomy (mPCNL) techniques featuring smaller tracts as they offer potential solutions to mitigate complications associated with standard PCNL (sPCNL). However, despite this growing acceptance and recognition of its benefits, unresolved controversies and acknowledged limitations continue to impede widespread adoption due to a lack of consensus on optimal perioperative management strategies and procedural tips and tricks. In response to these challenges, an international panel comprising experts from the International Alliance of Urolithiasis (IAU) took on the task of compiling an expert consensus document on mPCNL procedures aimed at providing urologists with a comprehensive clinical framework for practice. This endeavor involved conducting a systematic literature review to identify research gaps (RGs), which formed the foundation for developing a structured questionnaire survey. Subsequently, a two-round modified Delphi survey was implemented, culminating in a group meeting to generate final evidence-based comments. All 64 experts completed the second-round survey, resulting in a response rate of 100.0%. Fifty-eight key questions were raised focusing on mPCNLs within 4 main domains, including general information (13 questions), preoperative work-up (13 questions), procedural tips and tricks (19 questions), and postoperative evaluation and follow-up (13 questions). Additionally, 9 questions evaluated the experts' experience with PCNLs. Consensus was reached on 30 questions after the second-round survey, while professional statements for the remaining 28 key questions were provided after discussion in an online panel meeting. mPCNL, characterized by a tract smaller than 18 Fr and an innovative lithotripsy technique, has firmly established itself as a viable and effective approach for managing upper urinary tract stones in both adults and pediatrics. It offers several advantages over sPCNL including reduced bleeding, fewer requirements for nephrostomy tubes, decreased pain, and shorter hospital stays. The series of detailed techniques presented here serve as a comprehensive guide for urologists, aiming to improve their procedural understanding and optimize patient outcomes.
  2. Godman B, Haque M, Leong T, Allocati E, Kumar S, Islam S, et al.
    Front Public Health, 2021;9:671961.
    PMID: 34249838 DOI: 10.3389/fpubh.2021.671961
    Background: Diabetes mellitus rates continue to rise, which coupled with increasing costs of associated complications has appreciably increased global expenditure in recent years. The risk of complications are enhanced by poor glycaemic control including hypoglycaemia. Long-acting insulin analogues were developed to reduce hypoglycaemia and improve adherence. Their considerably higher costs though have impacted their funding and use. Biosimilars can help reduce medicine costs. However, their introduction has been affected by a number of factors. These include the originator company dropping its price as well as promoting patented higher strength 300 IU/ml insulin glargine. There can also be concerns with different devices between the manufacturers. Objective: To assess current utilisation rates for insulins, especially long-acting insulin analogues, and the rationale for patterns seen, across multiple countries to inform strategies to enhance future utilisation of long-acting insulin analogue biosimilars to benefit all key stakeholders. Our approach: Multiple approaches including assessing the utilisation, expenditure and prices of insulins, including biosimilar insulin glargine, across multiple continents and countries. Results: There was considerable variation in the use of long-acting insulin analogues as a percentage of all insulins prescribed and dispensed across countries and continents. This ranged from limited use of long-acting insulin analogues among African countries compared to routine funding and use across Europe in view of their perceived benefits. Increasing use was also seen among Asian countries including Bangladesh and India for similar reasons. However, concerns with costs and value limited their use across Africa, Brazil and Pakistan. There was though limited use of biosimilar insulin glargine 100 IU/ml compared with other recent biosimilars especially among European countries and Korea. This was principally driven by small price differences in reality between the originator and biosimilars coupled with increasing use of the patented 300 IU/ml formulation. A number of activities were identified to enhance future biosimilar use. These included only reimbursing biosimilar long-acting insulin analogues, introducing prescribing targets and increasing competition among manufacturers including stimulating local production. Conclusions: There are concerns with the availability and use of insulin glargine biosimilars despite lower costs. This can be addressed by multiple activities.
  3. Rosenthal VD, Maki DG, Mehta Y, Leblebicioglu H, Memish ZA, Al-Mousa HH, et al.
    Am J Infect Control, 2014 09;42(9):942-56.
    PMID: 25179325 DOI: 10.1016/j.ajic.2014.05.029
    We report the results of an International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2007-December 2012 in 503 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study using the Centers for Disease Control and Prevention's (CDC) U.S. National Healthcare Safety Network (NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 605,310 patients hospitalized in the INICC's ICUs for an aggregate of 3,338,396 days. Although device utilization in the INICC's ICUs was similar to that reported from ICUs in the U.S. in the CDC's NHSN, rates of device-associated nosocomial infection were higher in the ICUs of the INICC hospitals: the pooled rate of central line-associated bloodstream infection in the INICC's ICUs, 4.9 per 1,000 central line days, is nearly 5-fold higher than the 0.9 per 1,000 central line days reported from comparable U.S. ICUs. The overall rate of ventilator-associated pneumonia was also higher (16.8 vs 1.1 per 1,000 ventilator days) as was the rate of catheter-associated urinary tract infection (5.5 vs 1.3 per 1,000 catheter days). Frequencies of resistance of Pseudomonas isolates to amikacin (42.8% vs 10%) and imipenem (42.4% vs 26.1%) and Klebsiella pneumoniae isolates to ceftazidime (71.2% vs 28.8%) and imipenem (19.6% vs 12.8%) were also higher in the INICC's ICUs compared with the ICUs of the CDC's NHSN.
  4. Kermansaravi M, Omar I, Mahawar K, Shahabi S, Bashir A, Haddad A, et al.
    Obes Surg, 2021 Dec;31(12):5303-5311.
    PMID: 34617207 DOI: 10.1007/s11695-021-05724-z
    BACKGROUND: Fasting during Ramadan is one of the five pillars of the Muslim faith. Despite the positive effects of fasting on health, there are no guidelines or clear recommendations regarding fasting after metabolic/bariatric surgery (MBS). The current study reports the result of a modified Delphi consensus among expert metabolic/bariatric surgeons with experience in managing patients who fast after MBS.

    METHODS: A committee of 61 well-known metabolic and bariatric surgeons from 24 countries was created to participate in the Delphi consensus. The committee voted on 45 statements regarding recommendations and controversies around fasting after MBS. An agreement/disagreement ≥ of 70.0% was regarded as consensus.

    RESULTS: The experts reached a consensus on 40 out of 45 statements after two rounds of voting. One hundred percent of the experts believed that fasting needs special nutritional support in patients who underwent MBS. The decision regarding fasting must be coordinated among the surgeon, the nutritionist and the patient. At any time after MBS, 96.7% advised stopping fasting in the presence of persistent symptoms of intolerance. Seventy percent of the experts recommended delaying fasting after MBS for 6 to 12 months after combined and malabsorptive procedures according to the patient's situation and surgeon's experience, and 90.1% felt that proton pump inhibitors should be continued in patients who start fasting less than 6 months after MBS. There was consensus that fasting may help in weight loss, improvement/remission of non-alcoholic fatty liver disease, dyslipidemia, hypertension and type 2 diabetes mellitus among 88.5%, 90.2%, 88.5%, 85.2% and 85.2% of experts, respectively.

    CONCLUSION: Experts voted and reached a consensus on 40 statements covering various aspects of fasting after MBS.

  5. Nasta AM, Goel R, Singhal R, Lemmens L, Baig S, Seki Y, et al.
    Obes Res Clin Pract, 2024;18(3):195-200.
    PMID: 38955573 DOI: 10.1016/j.orcp.2024.06.001
    INTRODUCTION: Revisional bariatric surgery (RBS) for insufficient weight loss/weight regain or metabolic relapse is increasing worldwide. There is currently no large multinational, prospective data on 30-day morbidity and mortality of RBS. In this study, we aimed to evaluate the 30-day morbidity and mortality of RBS at participating centres.

    METHODS: An international steering group was formed to oversee the study. The steering group members invited bariatric surgeons worldwide to participate in this study. Ethical approval was obtained at the lead centre. Data were collected prospectively on all consecutive RBS patients operated between 15th May 2021 to 31st December 2021. Revisions for complications were excluded.

    RESULTS: A total of 65 global centres submitted data on 750 patients. Sleeve gastrectomy (n = 369, 49.2 %) was the most common primary surgery for which revision was performed. Revisional procedures performed included Roux-en-Y gastric bypass (RYGB) in 41.1 % (n = 308) patients, One anastomosis gastric bypass (OAGB) in 19.3 % (n = 145), Sleeve Gastrectomy (SG) in 16.7 % (n = 125) and other procedures in 22.9 % (n = 172) patients. Indications for revision included weight regain in 615(81.8 %) patients, inadequate weight loss in 127(16.9 %), inadequate diabetes control in 47(6.3 %) and diabetes relapse in 27(3.6 %). 30-day complications were seen in 80(10.7 %) patients. Forty-nine (6.5 %) complications were Clavien Dindo grade 3 or higher. Two patients (0.3 %) died within 30 days of RBS.

    CONCLUSION: RBS for insufficient weight loss/weight regain or metabolic relapse is associated with 10.7 % morbidity and 0.3 % mortality. Sleeve gastrectomy is the most common primary procedure to undergo revisional bariatric surgery, while Roux-en-Y gastric bypass is the most commonly performed revision.

  6. Sartelli M, Di Bella S, McFarland LV, Khanna S, Furuya-Kanamori L, Abuzeid N, et al.
    World J Emerg Surg, 2019 02 28;14:8.
    PMID: 30858872 DOI: 10.1186/s13017-019-0228-3
    In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.
  7. Kermansaravi M, Chiappetta S, Shikora SA, Musella M, Kow L, Aarts E, et al.
    Obes Surg, 2024 Jul 24.
    PMID: 39046625 DOI: 10.1007/s11695-024-07395-y
    PURPOSE: With the global epidemic of obesity, the importance of metabolic and bariatric surgery (MBS) is greater than ever before. Performing these surgeries requires academic training and the completion of a dedicated fellowship training program. This study aimed to develop guidelines based on expert consensus using a modified Delphi method to create the criteria for metabolic and bariatric surgeons that must be mastered before obtaining privileges to perform MBS.

    METHODS: Eighty-nine recognized MBS surgeons from 42 countries participated in the Modified Delphi consensus to vote on 30 statements in two rounds. An agreement/disagreement among ≥ 70.0% of the experts was regarded to indicate a consensus.

    RESULTS: Consensus was reached on 29 out of 30 statements. Most experts agreed that before getting privileges to perform MBS, surgeons must hold a general surgery degree and complete or have completed a dedicated fellowship training program. The experts agreed that the learning curves for the various operative procedures are approximately 25-50 operations for the LSG, 50-75 for the OAGB, and 75-100 for the RYGB. 93.1% of experts agreed that MBS surgeons should diligently record patients' data in their National or Global database.

    CONCLUSION: MBS surgeons should have a degree in general surgery and have been enrolled in a dedicated fellowship training program with a structured curriculum. The learning curve of MBS procedures is procedure dependent. MBS surgeons must demonstrate proficiency in managing postoperative complications, collaborate within a multidisciplinary team, commit to a minimum 2-year patient follow-up, and actively engage in national and international MBS societies.

  8. Marcucci M, Painter TW, Conen D, Lomivorotov V, Sessler DI, Chan MTV, et al.
    Ann Intern Med, 2023 May;176(5):605-614.
    PMID: 37094336 DOI: 10.7326/M22-3157
    BACKGROUND: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively.

    OBJECTIVE: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery.

    DESIGN: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723).

    SETTING: 110 hospitals in 22 countries.

    PATIENTS: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications.

    INTERVENTION: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery.

    MEASUREMENTS: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment.

    RESULTS: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term.

    LIMITATION: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels.

    CONCLUSION: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications.

    PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong.

  9. Cali E, Quirin T, Rocca C, Efthymiou S, Riva A, Marafi D, et al.
    Genet Med, 2024 Sep 10.
    PMID: 39275948 DOI: 10.1016/j.gim.2024.101251
    PURPOSE: This study aims to comprehensively delineate the phenotypic spectrum of ACTL6B-related disorders, previously associated with both autosomal recessive and autosomal dominant neurodevelopmental disorders. Molecularly, the role of the nucleolar protein ACTL6B in contributing to the disease has remained unclear.

    METHODS: We identified 105 affected individuals, including 39 previously reported cases, and systematically analysed detailed clinical and genetic data for all individuals. Additionally, we conducted knockdown experiments in neuronal cells to investigate the role of ACTL6B in ribosome biogenesis.

    RESULTS: Biallelic variants in ACTL6B are associated with severe-to-profound global developmental delay/intellectual disability (GDD/ID), infantile intractable seizures, absent speech, autistic features, dystonia, and increased lethality. De novo monoallelic variants result in moderate-to-severe GDD/ID, absent speech, and autistic features, while seizures and dystonia were less frequently observed. Dysmorphic facial features and brain abnormalities, including hypoplastic corpus callosum, parenchymal volume loss/atrophy, are common findings in both groups. We reveal that in the nucleolus, ACTL6B plays a crucial role in ribosome biogenesis, in particular in pre-rRNA processing.

    CONCLUSION: This study provides a comprehensive characterization of the clinical spectrum of both autosomal recessive and dominant forms of ACTL6B-associated disorders. It offers a comparative analysis of their respective phenotypes provides a plausible molecular explanation and suggests their inclusion within the expanding category of 'ribosomopathies'.

  10. Abouelazayem M, Jain R, Wilson MSJ, Martinino A, Balasubaramaniam V, Biffl W, et al.
    Surg Endosc, 2024 Aug;38(8):4402-4414.
    PMID: 38886232 DOI: 10.1007/s00464-024-10881-0
    BACKGROUND: There is little international data on morbidity and mortality of surgery for perforated peptic ulcer (PPU). This study aimed to understand the global 30-day morbidity and mortality of patients undergoing surgery for PPU and to identify variables associated with these.

    METHOD: We performed an international study of adults (≥ 18 years) who underwent surgery for PPU from 1st January 2022 to 30th June 2022. Patients who were treated conservatively or had an underlying gastric cancer were excluded. Patients were divided into subgroups according to age (≤ 50 and > 50 years) and time from onset of symptoms to hospital presentation (≤ 24 and > 24 h). Univariate and Multivariate analyses were carried out to identify factors associated with higher 30-day morbidity and mortality.

    RESULTS:  1874 patients from 159 centres across 52 countries were included. 78.3% (n = 1467) of the patients were males and the median (IQR) age was 49 years (25). Thirty-day morbidity and mortality were 48.5% (n = 910) and 9.3% (n = 174) respectively. Median (IQR) hospital stay was 7 (5) days. Open surgery was performed in 80% (n = 1505) of the cohort. Age > 50 years [(OR = 1.7, 95% CI 1.4-2), (OR = 4.7, 95% CI 3.1-7.6)], female gender [(OR = 1.8, 95% CI 1.4-2.3), (OR = 1.9, 95% CI 1.3-2.9)], shock on admission [(OR = 2.1, 95% CI 1.7-2.7), (OR = 4.8, 95% CI 3.2-7.1)], and acute kidney injury [(OR = 2.5, 95% CI 1.9-3.2), (OR = 3.9), 95% CI 2.7-5.6)] were associated with both 30-day morbidity and mortality. Delayed presentation was associated with 30-day morbidity [OR = 1.3, 95% CI 1.1-1.6], but not mortality.

    CONCLUSIONS: This study showed that surgery for PPU was associated with high 30-day morbidity and mortality rate. Age, female gender, and signs of shock at presentation were associated with both 30-day morbidity and mortality.

  11. Global Burden of Disease 2019 Cancer Collaboration, Kocarnik JM, Compton K, Dean FE, Fu W, Gaw BL, et al.
    JAMA Oncol, 2022 Mar 01;8(3):420-444.
    PMID: 34967848 DOI: 10.1001/jamaoncol.2021.6987
    IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden.

    OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019.

    EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs).

    FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles.

    CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.

  12. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
  13. Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al.
    Autophagy, 2021 Jan;17(1):1-382.
    PMID: 33634751 DOI: 10.1080/15548627.2020.1797280
    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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