Moritz Steinruecke’s research while affiliated with University of Cambridge and other places

BACKGROUND AND OBJECTIVES Traumatic brain injury (TBI) is a major public health challenge in India but there is a lack of high-quality data on its clinical characteristics and outcomes. We aimed to describe the TBI population of a tertiary care center in India, identify predictors of inpatient mortality, and assess the performance of existing prognostic tools. METHODS We conducted a prospective observational cohort study of patients admitted to a high-volume tertiary care center in Vellore, India, after a TBI between 2013 and 2019. RESULTS We identified 3172 patients (2667 males, 84%) admitted after a TBI (median age = 34 years [IQR 23-48]). Two-wheeler road traffic accidents caused 2259 (71%) injuries, in which 13 (0.6%) patients were wearing a helmet. There were 174 (5%) inpatient deaths (median length of stay = 6 days [IQR 4-10]) and overall mortality (median follow-up = 6 months [IQR 3-9]) was 17% (n = 540). Age, Glasgow Coma Scale motor score, systolic blood pressure ≤90 mm Hg, and key computed tomography imaging features were independently associated with inpatient mortality. Existing prognostic models predicted inpatient mortality with good performance (International Mission for Prognosis and Analysis of Clinical Trials in TBI: Brier = 0.0876, area under the curve (AUC) = 83% [95% CI 79%-87%]; Rotterdam CT: Brier = 0.0890, AUC 79% [95% CI 75%-83%]), but showed poorer performance for post-discharge mortality (International Mission for Prognosis and Analysis of Clinical Trials in TBI: Brier = 0.134, AUC = 75% [95% CI 72%-78%]; Rotterdam CT: Brier = 0.145, AUC 66% [95% CI 63%-69%]). CONCLUSION In a tertiary care center in India, we described a predominantly young male TBI population with a high contribution of 2-wheeler road traffic accidents and significant post-discharge mortality. Existing prognostic models showed poor performance when predicting which patients died after discharge. These findings should inform public health interventions to reduce the significant burden of TBI in India.

Delirium is a common acute onset neurological syndrome characterised by transient fluctuations in cognition. It affects over 20% of medical inpatients and 50% of those critically ill. Delirium is associated with morbidity and mortality, causes distress to patients and carers, and has significant socioeconomic costs in ageing populations. Despite its clinical significance, the pathophysiology of delirium is understudied, and many underlying cellular mechanisms remain unknown. There are currently no effective pharmacological treatments which directly target underlying disease processes. Although many studies focus on neuronal dysfunction in delirium, glial cells, primarily astrocytes, microglia, and oligodendrocytes, and their associated systems, are increasingly implicated in delirium pathophysiology. In this review, we discuss current evidence which implicates glial cells in delirium, including biomarker studies, post-mortem tissue analyses and pre-clinical models. In particular, we focus on how astrocyte pathology, including aberrant brain energy metabolism and glymphatic dysfunction, reactive microglia, blood-brain barrier impairment, and white matter changes may contribute to the pathogenesis of delirium. We also outline limitations in this body of work and the unique challenges faced in identifying causative mechanisms in delirium. Finally, we discuss how established neuroimaging and single-cell techniques may provide further mechanistic insight at pre-clinical and clinical levels.

Acknowledgments This study was supported by NIHR Global Health Research Unit Grant (NIHR16.136.79) and a project research grant from Portuguese Hernia and Abdominal Wall Society (Sociedade Portuguesa de Hernia e Parede Abdominal). The funders had no role in study design or writing of this report. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR or the UK Department of Health and Social Care. Background Technologies such as mesh and minimally invasive surgery (MIS) are recommended for inguinal hernia repair, but access and expertise varies significantly across different contexts. This study aimed to assess variability in the use of these two technologies, and evaluate their safety. Methods This was a pre-planned analysis of adults undergoing elective inguinal hernia repair in a prospective, international, cohort study between 30 January and 21 May 2023. Recurrent hernias and open midline approach were excluded. The primary outcome was the placement of mesh during open repair. The secondary outcome was adoption of MIS. A mixed-effects logistic regression model was used to identify factors associated with the adoption of these two technologies. Results This analysis included 14,768 patients from 612 hospitals in 81 countries: 8,916 (60.4%) from high-, 2,575 (17.4%) from upper-middle-, 2,642 (17.9%) from lower-middle and 635 (4.3%) from low-income countries. Mesh use in open surgery decreased from high- to low-income countries (98.9%, 94.4%, 82.3%, 72.1% respectively). MIS was adopted in less than a quarter of patients (3,661/14,768, 24.7%), and also decreased across income groups (29.3%, 27.6%, 12.5%, 1.1%). Surgery in a low-middle income country was associated with both lower mesh use (adjusted odds ratio 0.02, 0.01–0.06, p < 0.001) and lower MIS (0.11, 0.07–0.18, p < 0.001). Conclusion Global priority is to increase access and training programmes for mesh inguinal hernia repair in low-middle income countries. Expanding the role of MIS in well-resourced settings will require expansion of dedicated training programmes and a focus on patients who will have the most clinical benefit.

Background Multimorbidity poses a global challenge to healthcare delivery. This study aimed to describe the prevalence of multimorbidity, common disease combinations and outcomes in a contemporary cohort of patients undergoing major abdominal surgery. Methods This was a pre-planned analysis of a prospective, multicentre, international study investigating cardiovascular complications after major abdominal surgery conducted in 446 hospitals in 29 countries across Europe. The primary outcome was 30-day postoperative mortality. The secondary outcome measure was the incidence of complications within 30 days of surgery. Results Of 24,227 patients, 7006 (28.9%) had one long-term condition and 10,486 (43.9%) had multimorbidity (two or more long-term health conditions). The most common conditions were primary cancer (39.6%); hypertension (37.9%); chronic kidney disease (17.4%); and diabetes (15.4%). Patients with multimorbidity had a higher incidence of frailty compared with patients ≤ 1 long-term health condition. Mortality was higher in patients with one long-term health condition (adjusted odds ratio 1.93 (95%CI 1.16–3.23)) and multimorbidity (adjusted odds ratio 2.22 (95%CI 1.35–3.64)). Frailty and ASA physical status 3–5 mediated an estimated 31.7% of the 30-day mortality in patients with one long-term health condition (adjusted odds ratio 1.30 (95%CI 1.12– 1.51)) and an estimated 36.9% of the 30-day mortality in patients with multimorbidity (adjusted odds ratio 1.61 (95%CI 1.36–1.91)). There was no improvement in 30-day mortality in patients with multimorbidity who received pre-operative medical assessment. Conclusions Multimorbidity is common and outcomes are poor among surgical patients across Europe. Addressing multimorbidity in elective and emergency patients requires innovative strategies to account for frailty and disease control. The development of such strategies, that integrate care targeting whole surgical pathways to strengthen current systems, is urgently needed for multimorbid patients. Interventional trials are warranted to determine the effectiveness of targeted management for surgical patients with multimorbidity.

Background Timely and safe elective health care facilitates return to normal activities for patients and prevents emergency admissions. Surgery is a cornerstone of elective care and relies on complex pathways. This study aimed to take a whole-system approach to evaluating access to and quality of elective health care globally, using inguinal hernia as a tracer condition. Methods This was a prospective, international, cohort study conducted between Jan 30 and May 21, 2023, in which any hospital performing inguinal hernia repairs was eligible to take part. Consecutive patients of any age undergoing primary inguinal hernia repair were included. A measurement set mapped to the attributes of WHO’s Health System Building Blocks was defined to evaluate access (emergency surgery rates, bowel resection rates, and waiting times) and quality (mesh use, day-case rates, and postoperative complications). These were compared across World Bank income groups (high-income, upper-middle-income, lower-middle-income, and low-income countries), adjusted for hospital and country. Factors associated with postoperative complications were explored with a three-level multilevel logistic regression model. Findings 18 058 patients from 640 hospitals in 83 countries were included, of whom 1287 (7·1%) underwent emergency surgery. Emergency surgery rates increased from high-income to low-income countries (6·8%, 9·7%, 11·4%, 14·2%), accompanied by an increase in bowel resection rates (1·2%, 1·4%, 2·3%, 4·2%). Overall waiting times for elective surgery were similar around the world (median 8·0 months from symptoms to surgery), largely because of delays between symptom onset and diagnosis rather than waiting for treatment. In 14 768 elective operations in adults, mesh use decreased from high-income to low-income countries (97·6%, 94·3%, 80·6%, 61·0%). In patients eligible for day-case surgery (n=12658), day-case rates were low and variable (50·0%, 38·0%, 42·1%, 44·5%). Complications occurred in 2415 (13·4%) of 18 018 patients and were more common after emergency surgery (adjusted odds ratio 2·06, 95% CI 1·72–2·46) and bowel resection (1·85, 1·31–2·63), and less common after day-case surgery (0·39, 0·34–0·44). Interpretation This study demonstrates that elective health care is essential to preventing over-reliance on emergency systems. We identified actionable targets for system strengthening: clear referral pathways and increasing mesh repair in lower-income settings, and boosting day-case surgery in all income settings. These measures might strengthen non-surgical pathways too, reducing the burden on society and health services. Funding NIHR Global Health Research Unit on Global Surgery and Portuguese Hernia and Abdominal Wall Society (Sociedade Portuguesa de Hernia e Parede Abdominal).

Background Chronic subdural haematoma (CSDH) drainage is a common neurosurgical procedure. CSDHs cause excess mortality, which is exacerbated by frailty. Sarcopenia contributes to frailty – its key component, low muscle mass, can be assessed using cross‐sectional imaging. We aimed to examine the prognostic role of temporal muscle thickness (TMT) measured from preoperative computed tomography head scans among patients undergoing surgical CSDH drainage. Methods We retrospectively identified all patients who underwent CSDH drainage within 1 year of February 2019. We measured their mean TMT from preoperative computed tomography scans, tested the reliability of these measurements, and evaluated their prognostic value for postoperative survival. Results One hundred and eighty‐eight (122, 65% males) patients (median age 78 years, IQR 70–85 years) were included. Thirty‐four (18%) patients died within 2 years, and 51 (27%) died at a median follow‐up of 39 months (IQR 34–42 months). Intra‐ and inter‐observer reliability of TMT measurements was good‐to‐excellent (ICC 0.85–0.97, P < 0.05). TMT decreased with age (Pearson's r = −0.38, P < 0.001). Females had lower TMT than males (P < 0.001). The optimal TMT cut‐off values for predicting two‐year survival were 4.475 mm for males and 3.125 mm for females. TMT below these cut‐offs was associated with shorter survival in both univariate (HR 3.24, 95% CI 1.85–5.67) and multivariate (HR 1.86, 95% CI 1.02–3.36) analyses adjusted for age, ASA grade and bleed size. The effect of TMT on mortality was not mediated by age. Conclusions In patients with CSDH, TMT measurements from preoperative imaging were reliable and contained prognostic information supplemental to previously known predictors of poor outcomes.

Background Traumatic brain injury (TBI) is a common neurosurgical emergency but its epidemiological and clinical characteristics vary across country income levels. High-quality TBI data from low and lower-middle income countries are required to inform trials and public policy in these settings. Methods We performed a prospective cohort study of patients admitted to a high-volume tertiary hospital in Vellore, India following a TBI between 2013 and 2019. We collected data on patient characteristics and measured their outcomes using the Glasgow Outcome Scale-Extended (GOSE). Results We identified 3,172 patients (84% males) with a mean age of 35 years (SD = 18). Two-wheeler road traffic accidents caused 2,259/3,172 (71%) injuries, in which 13 (0.5%) patients were wearing a helmet. The median time from injury to admission was 3 hours (IQR = 2–7). 2,363/3,172 (75%) patients did not undergo surgery and 405/3,172 (13%) underwent decompressive craniectomy and haematoma evacuation. Inpatient mortality was 5.6% (median length of stay = 6 days [IQR = 4–10]) and overall mortality at discharge from follow-up (median = 6 months [IQR = 3–9]) was 18%. Inpatient deaths most frequently occurred within two days of admission (82/174 [47%]). 2,066/3,082 (67%) patients had upper- or lower-good recovery. The IMPACT (AUC = 83%, CI: 79–87%) and Rotterdam CT prognostic scores (AUC = 79%, CI: 75–83%) predicted inpatient mortality with good performance. Conclusions We describe the TBI population of a high-volume tertiary hospital in India, including inpatient mortality, medium-term functional status, and the performance of commonly used prognostic tools.

Background Functional neurological disorder (FND) is characterised by neurological symptoms, such as seizures and abnormal movements. Despite its significance to patients, the clinical features of chronic pain in people with FND, and of FND in people with chronic pain, have not been comprehensively studied. Methods We systematically reviewed PubMed, Embase and PsycINFO for studies of chronic pain in adults with FND and FND in patients with chronic pain. We described the proportions of patients reporting pain, pain rating and timing, pain-related diagnoses and responsiveness to treatment. We performed random effects meta-analyses of the proportions of patients with FND who reported pain or were diagnosed with pain-related disorders. Results Seven hundred and fifteen articles were screened and 64 were included in the analysis. Eight case–control studies of 3476 patients described pain symptoms in a higher proportion of patients with FND than controls with other neurological disorders. A random effects model of 30 cohorts found that an estimated 55% (95% CI 46% to 64%) of 4272 patients with FND reported pain. Random effects models estimated diagnoses of complex regional pain syndrome in 22% (95% CI 6% to 39%) of patients, irritable bowel syndrome in 16% (95% CI 9% to 24%) and fibromyalgia in 10% (95% CI 8% to 13%). Five studies of FND diagnoses among 361 patients with chronic pain were identified. Most interventions for FND did not ameliorate pain, even when other symptoms improved. Conclusions Pain symptoms and pain-related diagnoses are common in FND. Classification systems and treatments should routinely consider pain as a comorbidity in patients with FND.