Elective surgery system strengthening: development, measurement, and validation of the surgical preparedness index across 1632 hospitals in 119 countries

Background The 2015 Lancet Commission on global surgery identified surgery and anaesthesia as indispensable parts of holistic health-care systems. However, COVID-19 exposed the fragility of planned surgical services around the world, which have also been neglected in pandemic recovery planning. This study aimed to develop and validate a novel index to support local elective surgical system strengthening and address growing backlogs. Methods First, we performed an international consultation through a four-stage consensus process to develop a multidomain index for hospital-level assessment (surgical preparedness index; SPI). Second, we measured surgical preparedness across a global network of hospitals in high-income countries (HICs), middle-income countries (MICs), and low-income countries (LICs) to explore the distribution of the SPI at national, subnational, and hospital levels. Finally, using COVID-19 as an example of an external system shock, we compared hospitals' SPI to their planned surgical volume ratio (SVR; ie, operations for which the decision for surgery was made before hospital admission), calculated as the ratio of the observed surgical volume over a 1-month assessment period between June 6 and Aug 5, 2021, against the expected surgical volume based on hospital administrative data from the same period in 2019 (ie, a pre-pandemic baseline). A linear mixed-effects regression model was used to determine the effect of increasing SPI score. Findings In the first phase, from a longlist of 103 candidate indicators, 23 were prioritised as core indicators of elective surgical system preparedness by 69 clinicians (23 [33%] women; 46 [67%] men; 41 from HICs, 22 from MICs, and six from LICs) from 32 countries. The multidomain SPI included 11 indicators on facilities and consumables, two on staffing, two on prioritisation, and eight on systems. Hospitals were scored from 23 (least prepared) to 115 points (most prepared). In the second phase, surgical preparedness was measured in 1632 hospitals by 4714 clinicians from 119 countries. 745 (45·6%) of 1632 hospitals were in MICs or LICs. The mean SPI score was 84·5 (95% CI 84·1–84·9), which varied between HIC (88·5 [89·0–88·0]), MIC (81·8 [82·5–81·1]), and LIC (66·8 [64·9–68·7]) settings. In the third phase, 1217 (74·6%) hospitals did not maintain their expected SVR during the COVID-19 pandemic, of which 625 (51·4%) were from HIC, 538 (44·2%) from MIC, and 54 (4·4%) from LIC settings. In the mixed-effects model, a 10-point increase in SPI corresponded to a 3·6% (95% CI 3·0–4·1; p<0·0001) increase in SVR. This was consistent in HIC (4·8% [4·1–5·5]; p<0·0001), MIC (2·8 [2·0–3·7]; p<0·0001), and LIC (3·8 [1·3–6·7%]; p<0·0001) settings. Interpretation The SPI contains 23 indicators that are globally applicable, relevant across different system stressors, vary at a subnational level, and are collectable by front-line teams. In the case study of COVID-19, a higher SPI was associated with an increased planned surgical volume ratio independent of country income status, COVID-19 burden, and hospital type. Hospitals should perform annual self-assessment of their surgical preparedness to identify areas that can be improved, create resilience in local surgical systems, and upscale capacity to address elective surgery backlogs. Funding National Institute for Health Research (NIHR) Global Health Research Unit on Global Surgery, NIHR Academy, Association of Coloproctology of Great Britain and Ireland, Bowel Research UK, British Association of Surgical Oncology, British Gynaecological Cancer Society, and Medtronic.publishedVersio

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Genome-wide microarray expression and genomic alterations by array-CGH analysis in neuroblastoma stem-like cells.

Neuroblastoma has a very diverse clinical behaviour: from spontaneous regression to a very aggressive malignant progression and resistance to chemotherapy. This heterogeneous clinical behaviour might be due to the existence of Cancer Stem Cells (CSC), a subpopulation within the tumor with stem-like cell properties: a significant proliferation capacity, a unique self-renewal capacity, and therefore, a higher ability to form new tumors. We enriched the CSC-like cell population content of two commercial neuroblastoma cell lines by the use of conditioned cell culture media for neurospheres, and compared genomic gains and losses and genome expression by array-CGH and microarray analysis, respectively (in CSC-like versus standard tumor cells culture). Despite the array-CGH did not show significant differences between standard and CSC-like in both analyzed cell lines, the microarray expression analysis highlighted some of the most relevant biological processes and molecular functions that might be responsible for the CSC-like phenotype. Some signalling pathways detected seem to be involved in self-renewal of normal tissues (Wnt, Notch, Hh and TGF-β) and contribute to CSC phenotype. We focused on the aberrant activation of TGF-β and Hh signalling pathways, confirming the inhibition of repressors of TGF-β pathway, as SMAD6 and SMAD7 by RT-qPCR. The analysis of the Sonic Hedgehog pathway showed overexpression of PTCH1, GLI1 and SMO. We found overexpression of CD133 and CD15 in SIMA neurospheres, confirming that this cell line was particularly enriched in stem-like cells. This work shows a cross-talk among different pathways in neuroblastoma and its importance in CSC-like cells

Duloxetine plus exercise for knee osteoarthritis and depression: A feasibility study

Objective: To assess the feasibility of a 24-week, center-based, aerobic exercise program plus duloxetine to treat symptomatic knee osteoarthritis (OA) and major depression. Design: Patients with symptomatic knee OA and major depression were recruited between August 2021 and November 2022 from the University of Maryland and VA Maryland Health Care Systems and Baltimore metropolitan area using medical records and advertisements. The intervention included 1) supervised treadmill walking 3 times weekly and 2) duloxetine starting at 30 ​mg each day and titrating up to the optimal dosage of 60 ​mg daily. Data collection occurred at baseline and 12- and 24-weeks follow-up. Feasibility was evaluated from recruitment rates, reasons for drop out, and treatment adherence. Clinical measures included the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Hamilton Depression Rating Scale (HAM-D). Results: Among 377 interested participants, 9 patients were enrolled, and 1 completed treatment. The most common reason reported for not prescreening was time commitment (n ​= ​39), many patients did not satisfy depression screening criteria (n ​= ​45), and most enrolled participants were not experiencing a major depressive episode (n ​= ​6). The single treated participant was 100 ​% adherent to duloxetine and depression severity decreased (HAM-D ​= ​25 to 1), but compliance to supervised exercise was only 26 ​%, and knee pain severity changed little (KOOS ​= ​41.7 to 44.4). Conclusions: This intervention had low feasibility. Time commitment to supervised exercise sessions reduced accessibility, and depression defined by diagnostic criteria precluded knee OA patients with depressive symptoms not a meeting case-level diagnosis from receiving treatment. Clinical trial registration number: NCT04111627

Évaluation des besoins protéiques avant et 3 mois après chirurgie bariatrique chez des patients atteints d’obésité morbide

National audienceIntroduction : La chirurgie bariatrique chez les patients porteurs d’une obésité morbide permet une perte de poids durable, une réduction des comorbidités et une amélioration de la qualité de vie. Toutefois, elle s’accompagne de déficiences nutritionnelles, notamment d’une carence protéique capable d’engendrer une perte de la masse musculaire après la chirurgie. Cette perte protéique excessive peut limiter les effets bénéfiques du geste chirurgical. Or, le besoin protéique après chirurgie bariatrique n’est pas clairement défini. L’objectif de cette étude a donc été de déterminer le besoin en protéines de sujets obèses avant et après sleeve gastrectomie (SG) et by-pass gastrique (BPG), afin d’élaborer des recommandations précises et pratiques. Matériel & Méthodes : 19 patients obèses (IMC 43,2±1,2 kg/m²), âgés de 25 à 61 ans, ont été étudiés avant puis 3 mois après SG (n=13) ou BPG (n=6). Le besoin moyen en protéines (BMP) et l’apport protéique de sécurité (APS) de cette population ont été évalués par la mesure du bilan azoté avec 2 niveaux d’apports azotés, exprimés par kilogramme de poids corporel (kgPC) ou de masse maigre (kgMM) mesurée à l’aide de la dilution d’eau deutérée. Résultats : Le BMP de cette population avant opération est de 0,70±0.16 g/kg PC/j soit 1,38±0,31 g/kg MM/j, d’où un APS correspondant de 1,01 g/kg/j soit 2,00 g/kg MM/j. La perte de poids est de 19±1 kg 3 mois après la SG et de 19±2 kg après BPG, et les apports protéiques spontanés sont estimés à 0,39±0,04 g/kgPC/j et de 0,46±0,06 g/kgPC/j après BPG. Le calcul du BMP 3 mois après SG et BPG est de 0,60±0,15 g/kgPC/j et 0,50±0,18 g/kgPC/j respectivement, ou 1,07±0,27 g/kgMM/j et 0,89±0,18 g/kgMM/j. Les APS correspondant sont de 0,89 g/kgPoids/j et 0,85 g/kgPoids/j ou 1,60 g/kgMM/j et 1,51 g/kgMM/j. Conclusion : L’apport protéique de sécurité calculé pour les patients obèses morbides (1,01 g/kg/j) est plus élevé que pour les sujets adultes non-obèses (0,83 g/kg/j). Trois mois après la chirurgie, le besoin et l’apport protéique de sécurité diminuent quelle que soit le type de chirurgie mais les apports spontanés ne parviennent pas à couvrir les besoins en protéines. Ces résultats fournissent des arguments solides pour l’établissement de recommandations spécifiques pour les patients obèses morbides avant et après chirurgie bariatrique

PANTHER classification by signalling pathway.

<p>The differentially expressed genes in both SK-N-DZ and SIMA CSC-like cells were classified by PANTHER and graphed. The percentage represents the number of genes altered against total number of genes involved in each pathway.</p

Whole chromosome plots.

<p>Array-CGH from SK-N-DZ (A) and SIMA (B) cell lines. The X-axis represents the chromosomes while the Y-axis represent the normalize log2 ratio fluorescence intensity thresholds −1 (loss) and 1 (gain). The results show gains and losses of small chromosomal regions.</p

RT-qPCR for Sonic Hedgehog (A) and TGF-β pathways analysis (B) in SIMA CSC-like cells.

<p>The graphs represent the 2^−ΔΔCt values obtained by RT-qPCR for neurospheres. The dotted line indicates the 2^−ΔΔCt control (cell line) value equal to 1. Significance against control: p<0.05 (*); p<0.01 (**); p<0.001 (***) and p<0.0001 (****). Selected genes cover the most relevant components of each pathway. Results confirmed aberrant activation of Hh (A) and TGF-β (B) signalling pathways in CSC-like cells.</p

MicroRNA identified in array-CGH analysis.

<p>MicroRNA identified in array-CGH analysis.</p

Gene expression by RT-qPCR.

<p>The graphs represent the 2^−ΔΔCt values obtained by RT-qPCR for neurospheres. The dotted line indicates the 2^−ΔΔCt control (cell line) value equal to 1. Significance against control: p<0.05 (*); p<0.01 (**); p<0.001 (***) and p<0.0001 (****). <b>Corroboration of expression array (A).</b> Both SK-N-DZ (▪) and SIMA (▴) CSC-like cells showed a similar expression profile. <b>Stem Cell Markers expression (B).</b> Results confirmed a high overexpression of CSC markers in SIMA cell line after the neurosphere formation assay.</p