PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

The successful use of collagenase for Ledderhose disease (plantar fibromatosis) in a paediatric patient: a case report

AbstractLedderhose disease is a connective tissue disorder involving proliferation of fibrous tissue in the plantar fascia of the foot. Histologically identical manifestations exist in the hand (Dupuytren’s contracture) and penis (Peyronie’s disease), and collagenase injections are approved as a treatment in both, however not in Ledderhose, where the treatment of choice remains surgical resection. Surgery is associated with high rates of recurrence and need for further surgery, so alternative therapies should be sought. Due to their histological and physiological similarities, it is likely that therapies useful in Dupuytren’s and Peyronie’s would be useful in Ledderhose. Two previous case reports investigating collagenase injections for Ledderhose disease in adults have shown conflicting results; this study demonstrates the efficacy of collagenase injections in a paediatric patient at 1-year follow-up.</jats:p

Cervical Spine Pedicle Screw Accuracy in Fluoroscopic, Navigated and Template Guided Systems—A Systematic Review

Background: Pedicle screws provide excellent fixation for a wide range of indications. However, their adoption in the cervical spine has been slower than in the thoracic and lumbar spine, which is largely due to the smaller pedicle sizes and the proximity to the neurovascular structures in the neck. In recent years, technology has been developed to improve the accuracy and thereby the safety of cervical pedicle screw placement over traditional fluoroscopic techniques, including intraoperative 3D navigation, computer-assisted Systems and 3D template moulds. We have performed a systematic review into the accuracy rates of the various systems. Methods: The PubMed and Cochrane Library databases were searched for eligible papers; 9 valid papers involving 1427 screws were found. Results: fluoroscopic methods achieved an 80.6% accuracy and navigation methods produced 91.4% and 96.7% accuracy for templates. Conclusion: Navigation methods are significantly more accurate than fluoroscopy, they reduce radiation exposure to the surgical team, and improvements in technology are speeding up operating times. Significantly superior results for templates over fluoroscopy and navigation are complemented by reduced radiation exposure to patient and surgeon; however, the technology requires a more invasive approach, prolonged pre-operative planning and the development of an infrastructure to allow for their rapid production and delivery. We affirm the superiority of navigation over other methods for providing the most accurate and the safest cervical pedicle screw instrumentation, as it is more accurate than fluoroscopy and lacks the limitations of templates.</jats:p

Cervical Spine Pedicle Screw Accuracy in Fluoroscopic, Navigated and Template Guided Systems—A Systematic Review

Background: Pedicle screws provide excellent fixation for a wide range of indications. However, their adoption in the cervical spine has been slower than in the thoracic and lumbar spine, which is largely due to the smaller pedicle sizes and the proximity to the neurovascular structures in the neck. In recent years, technology has been developed to improve the accuracy and thereby the safety of cervical pedicle screw placement over traditional fluoroscopic techniques, including intraoperative 3D navigation, computer-assisted Systems and 3D template moulds. We have performed a systematic review into the accuracy rates of the various systems. Methods: The PubMed and Cochrane Library databases were searched for eligible papers; 9 valid papers involving 1427 screws were found. Results: fluoroscopic methods achieved an 80.6% accuracy and navigation methods produced 91.4% and 96.7% accuracy for templates. Conclusion: Navigation methods are significantly more accurate than fluoroscopy, they reduce radiation exposure to the surgical team, and improvements in technology are speeding up operating times. Significantly superior results for templates over fluoroscopy and navigation are complemented by reduced radiation exposure to patient and surgeon; however, the technology requires a more invasive approach, prolonged pre-operative planning and the development of an infrastructure to allow for their rapid production and delivery. We affirm the superiority of navigation over other methods for providing the most accurate and the safest cervical pedicle screw instrumentation, as it is more accurate than fluoroscopy and lacks the limitations of templates

MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca2+ overload and cell death

Early reperfusion of ischemic cardiac tissue remains the most effective intervention for improving clinical outcome following myocardial infarction. However, abnormal increases in intracellular Ca2+ during myocardial reperfusion can cause cardiomyocyte death and consequent loss of cardiac function, referred to as ischemia/reperfusion (IR) injury. Therapeutic modulation of Ca2+ handling provides some cardioprotection against the paradoxical effects of restoring blood flow to the heart, highlighting the significance of Ca2+ overload to IR injury. Cardiac IR is also accompanied by dynamic changes in the expression of microRNAs (miRNAs); for example, miR-214 is upregulated during ischemic injury and heart failure, but its potential role in these processes is unknown. Here, we show that genetic deletion of miR-214 in mice causes loss of cardiac contractility, increased apoptosis, and excessive fibrosis in response to IR injury. The cardioprotective roles of miR-214 during IR injury were attributed to repression of the mRNA encoding sodium/calcium exchanger 1 (Ncx1), a key regulator of Ca2+ influx; and to repression of several downstream effectors of Ca2+ signaling that mediate cell death. These findings reveal a pivotal role for miR-214 as a regulator of cardiomyocyte Ca2+ homeostasis and survival during cardiac injury

Global, regional, and national trends in routine childhood vaccination coverage from 1980 to 2023 with forecasts to 2030: a systematic analysis for the Global Burden of Disease Study 2023

Background: Since its inception in 1974, the Essential Programme on Immunization (EPI) has achieved remarkable success, averting the deaths of an estimated 154 million children worldwide through routine childhood vaccination. However, more recent decades have seen persistent coverage inequities and stagnating progress, which have been further amplified by the COVID-19 pandemic. In 2019, WHO set ambitious goals for improving vaccine coverage globally through the Immunization Agenda 2030 (IA2030). Now halfway through the decade, understanding past and recent coverage trends can help inform and reorient strategies for approaching these aims in the next 5 years. Methods: Based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2023, this study provides updated global, regional, and national estimates of routine childhood vaccine coverage from 1980 to 2023 for 204 countries and territories for 11 vaccine-dose combinations recommended by WHO for all children globally. Employing advanced modelling techniques, this analysis accounts for data biases and heterogeneity and integrates new methodologies to model vaccine scale-up and COVID-19 pandemic-related disruptions. To contextualise historic coverage trends and gains still needed to achieve the IA2030 coverage targets, we supplement these results with several secondary analyses: (1) we assess the effect of the COVID-19 pandemic on vaccine coverage; (2) we forecast coverage of select life-course vaccines up to 2030; and (3) we analyse progress needed to reduce the number of zero-dose children by half between 2023 and 2030. Findings: Overall, global coverage for the original EPI vaccines against diphtheria, tetanus, and pertussis (first dose [DTP1] and third dose [DTP3]), measles (MCV1), polio (Pol3), and tuberculosis (BCG) nearly doubled from 1980 to 2023. However, this long-term trend masks recent challenges. Coverage gains slowed between 2010 and 2019 in many countries and territories, including declines in 21 of 36 high-income countries and territories for at least one of these vaccine doses (excluding BCG, which has been removed from routine immunisation schedules in some countries and territories). The COVID-19 pandemic exacerbated these challenges, with global rates for these vaccines declining sharply since 2020, and still not returning to pre-COVID-19 pandemic levels as of 2023. Coverage for newer vaccines developed and introduced in more recent years, such as immunisations against pneumococcal disease (PCV3) and rotavirus (complete series; RotaC) and a second dose of the measles vaccine (MCV2), saw continued increases globally during the COVID-19 pandemic due to ongoing introductions and scale-ups, but at slower rates than expected in the absence of the pandemic. Forecasts to 2030 for DTP3, PCV3, and MCV2 suggest that only DTP3 would reach the IA2030 target of 90% global coverage, and only under an optimistic scenario. The number of zero-dose children, proxied as children younger than 1 year who do not receive DTP1, decreased by 74·9% (95% uncertainty interval 72·1-77·3) globally between 1980 and 2019, with most of those declines reached during the 1980s and the 2000s. After 2019, counts of zero-dose children rose to a COVID 19-era peak of 18·6 million (17·6-20·0) in 2021. Most zero-dose children remain concentrated in conflict-affected regions and those with various constraints on resources available to put towards vaccination services, particularly sub-Saharan Africa. As of 2023, more than 50% of the 15·7 million (14·6-17·0) global zero-dose children resided in just eight countries (Nigeria, India, Democratic Republic of the Congo, Ethiopia, Somalia, Sudan, Indonesia, and Brazil), emphasising persistent inequities. Interpretation: Our estimates of current vaccine coverage and forecasts to 2030 suggest that achieving IA2030 targets, such as halving zero-dose children compared with 2019 levels and reaching 90% global coverage for life-course vaccines DTP3, PCV3, and MCV2, will require accelerated progress. Substantial increases in coverage are necessary in many countries and territories, with those in sub-Saharan Africa and south Asia facing the greatest challenges. Recent declines will need to be reversed to restore previous coverage levels in Latin America and the Caribbean, especially for DTP1, DTP3, and Pol3. These findings underscore the crucial need for targeted, equitable immunisation strategies. Strengthening primary health-care systems, addressing vaccine misinformation and hesitancy, and adapting to local contexts are essential to advancing coverage. COVID-19 pandemic recovery efforts, such as WHO's Big Catch-Up, as well as efforts to bolster routine services must prioritise reaching marginalised populations and target subnational geographies to regain lost ground and achieve global immunisation goals

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit