Estudo morfométrico da retina em doentes com formas precoces de degenerescência macular da idade : Integridade e quantificação das estruturas através da tomografia de coerência ótica de domínio espectral

RESUMO: Introdução A degenerescência macular da idade (DMI) é uma patologia ocular resultante da interação entre a componente genética e os fatores ambientais. O impacto direto que tem ao nível da cegueira, pelo envelhecimento da população mundial, e o impacto desafiante ao nível económico reveste esta patologia de um particular interesse em saúde pública. A contínua evolução da tomografia de coerência ótica (OCT), com a melhoria dos algoritmos utilizados, tem contribuído para uma melhor caracterização e monitorização da DMI. Esta técnica tem permitido, de forma não invasiva, a aquisição de imagens transversais e topográficas de alta resolução dos tecidos. No diagnóstico e monitorização da DMI é importante poder separar-se as primeiras alterações patológicas das alterações próprias do envelhecimento humano. E neste sentido, a constante evolução e melhoria da imagiologia ocular tem dado alguns contributos importantes. Uma aparente diminuição da espessura da retina em algumas localizações topográficas bem como algumas alterações ao nível das camadas externas têm sido tradicionalmente estudadas e associadas à DMI. No entanto, estas alterações não têm justificado por si só a totalidade das alterações que ocorrem e a procura de possíveis diferenças estruturais e morfológicas, possíveis de identificar e quantificar através de SDOCT, surgem como alternativa na melhoria de conhecimento nas formas precoces da DMI. Objetivo Descrever e estudar a espessura média de várias segmentações retinianas e da coroide, obtida de forma manual na região macular através da Tomografia de Coerência Ótica de domínio espectral (SD-OCT), entre participantes com DMI precoce/intermédia e participantes de um grupo de controlo. Métodos Estudo observacional, com metodologia transversal, em que se procedeu à avaliação e quantificação das várias estruturas retinianas e da coroide através do SD-OCT até 3mm do centro da fóvea. Apenas os participantes com diagnóstico médico de DMI confirmado (presença/ausência), seguidos no Instituto de Oftalmologia Dr. Gama Pinto, e com informação clinica essencial para o estudo (retinografia policromática, monocromática e infravermelho por SLO) foram considerados. De acordo com a classificação Age-Related Eye Disease Study (AREDS) e os mais recentes critérios de classificação clinica para a DMI precoce/intermédia foram criados dois grupos de estudo. O grupo de controlo (categoria 1 AREDS) constituído por um subgrupo de participantes sem alterações ligadas à idade (G1 – sem drusens nem alterações pigmentares por DMI) e por um subgrupo de participantes sem DMI mas com algumas alterações ligadas à idade (G2 - apenas alguns drusens <63 μm e sem alterações pigmentares por DMI). O grupo de DMI foi constituído por participantes com drusens intermédios (63-124 μm) ou pela presença de alterações pigmentares por DMI que constituem o grupo de DMI precoce (G3 – categoria 2 AREDS) e os participantes com vários drusens intermédios, pelo menos um drusen de grandes dimensões (≥125 μm de diâmetro), ou pela presença de atrofia geográfica sem envolvimento da fóvea constituem o grupo de DMI intermédia (G4 – categoria 3 AREDS). A análise e quantificação manual das várias camadas de retina e coroide foram baseadas na nomenclatura internacional para o OCT (IN•Consensus) e as diferenças encontradas entre os grupos em estudo descritas. A comparação entre os grupos e/ou subgrupos em estudo foi feita através da aplicação do teste qui-quadrado, ou teste exato de Fisher, para variáveis categóricas e nominais e do teste T-Student para as variáveis continuas. O teste não paramétrico Mann-Whitney foi utlizado para comparação da espessura média das várias estruturas segmentadas entre grupo de controlo e DMI precoce/intermédia. Para a comparação das diferenças encontradas na espessura das várias estruturas segmentadas, nos quatro subgrupos, foi utilizado o teste comparações múltiplas de Kruskal-Wallis. Por fim, e com ajuste para o sexo e idade, procedeu-se ao cálculo de estimativas dos coeficientes, Odds Ratio e valores p obtidos de modelos de regressão logística múltiplos de algumas características de maior interesse na DMI. Resultados: 450 participantes (38% do sexo masculino e 61,8% do sexo feminino) foram estudados. O grupo de controlo (n=204), constituído por 43,6% de participantes do sexo masculino e 56,4% de participantes do sexo feminino, apresentou uma idade média e desvio padrão de 71,5+/-9,5. Em relação ao grupo de DMI precoce/intermédia (n=246), constituído por uma menor percentagem do sexo masculino 33,7% e por uma maior percentagem do sexo feminino 66,3%, verificou-se um aumento da idade média e desvio padrão de 75,7+/-10,3 comparativamente ao grupo de controlo (p<0,001). Cerca de 62,6% dos participantes com DMI precoce/intermédia apresentaram mapas maculares considerados normais, segundo os valores normativos do SD-OCT, e obtiveram um menor numero médio de letras atingidas (p<0,001) comparativamente ao grupo de controlo. Variabilidade intraoperador: pode-se verificar que os maiores valores foram encontrados nas localizações de maior espessura. Variabilidade interoperador: excetuando os 0,826 (0,727;0,898) obtidos na camada plexiforme externa (T2,5) e os 0,634 (0,469;0,771) obtidos na camada plexiforme interna (N2) todos os restantes valores de correlação são superiores a 0,92. Com exceção da camada de fibras nervosas (CFN) todas as segmentações estudadas apresentam diferenças estatisticamente significativas espessuras médias entre grupos com doença comparativamente aos grupos de controlo. Entre Controlo e DMI precoce/intermédia foram encontrados os seguintes valores médios: Complexo das camadas de células ganglionares com camada plexiforme interna (75,2+/-6,7;72,1+/-6,6 p<0,001); camada de células ganglionares (49,3+/-5,6; 47,1+/-5,4 p<0,001); camada plexiforme interna (25,9+/-2,8; 25+/-2,7 p=0,001); camada nuclear interna (44,1+/-4,2; 41,2+/-4,1 p<0,001); camada plexiforme externa (15,1+/-2,1; 14,6+/-1,9 p=0,014); complexo camada plexiforme externa com camada nuclear externa (90,6+/-6,6; 87,9+/-7,7 p<0,001); camada nuclear externa (76,7+/-6,4; 74,5+/-7,7 p=0,002); zona mioide dos fotorrecetores (24,5+/-1,3; 22,9+/-2,2 p<0,001); segmentos externos dos fotorrecetores (22,7+/-1,9; 20,9+/-2,6 p<0,001); complexo epitélio pigmentar da retina com Membrana de Bruch (33,4+/-2,6; 40,5+/-9,7 p<0,001); Coroide (249,8+/-88,4; 200,2+/-76,9 p<0,001). Conclusão: As medições das várias camadas da retina e coroide, nas 13 localizações estudadas de forma manual pelo SD-OCT, apresentaram uma boa repetibilidade e reprodutibilidade. Foi demonstrado que com treino, e seguindo o protocolo desenvolvido, poderão ser atingidos valores de ICC bastante elevados através da quantificação manual. A utilização da espessura central macular para avaliar e monitorizar a patologia retiniana não pareceu ser o parâmetro mais adequado (cerca de 64% de casos de DMI precoce/intermédia são identificados como estando dentro dos valores normais). Com exceção da CFN, todas as segmentações da retina interna mostraram diferenças marcadas entre os subgrupos extremos (DMI intermedia com subgrupo sinais de envelhecimento e com subgrupo sem alterações). No entanto nem todas as segmentações foram sensíveis à presença de diferenças mais ténues na espessura média nos subgrupos. Foi no complexo CCG_CPI, em especial na região temporal, que foram encontradas maiores diferenças nos vários grupos etários. Foi nesta localização que maiores diferenças foram encontradas entre os vários subgrupos permitindo também encontrar diferenças entre os subgrupos onde as variações são mais ténues (como entre DMI precoce com sinais de envelhecimento). A camada nuclear interna (CNI) apresentou uma boa capacidade de discriminar diferenças entre subgrupos com diferenças mais ténues, no entanto as grandes diferenças encontradas entre sexos e nos grupos etários podem atenuar a sua utilidade na presença e ausência de doença. As segmentações ao nível da zona mioide dos fotorrecetores, dos segmentos externos dos fotorrecetores (SEF), do complexo epitélio pigmentar da retina com Membrana de Bruch (EPR_MB), e do complexo SEF com epitélio pigmentar da retina e Membrana de Bruch (SE_EPR_MB) apresentam grandes diferenças nos vários grupos etários sem aparentarem grandes diferenças entre sexos. Estas segmentações permitem encontrar grandes diferenças essencialmente entre subgrupos extremos (G1 com G4). Nestas segmentações não foram encontradas grandes diferenças entre ausência de doença com DMI precoce. Em relação à Coroide foram encontradas grandes diferenças ao longo dos grupos etários sendo mais diminuída no sexo feminino na presença de doença. Apresenta na globalidade boa capacidade de discriminação entre G4 com G1, G4 com G2, e G3 com G2.ABSTRACT: Introduction Age-related macular degeneration (AMD) is an ocular pathology resulting from the interaction between genetic and environmental factors. The direct impact it has in terms of blindness, the aging of the world population, or the impact and challenging economic level takes this pathology of a particular Interest in public health. The characterization and monitoring of AMD has been improved through the use of optical coherence tomography (OCT). This technique has allowed, noninvasively, the acquisition of transversal and topographic high resolution images of tissues. In the diagnosis and monitoring of AMD it is important to separate the first pathological changes of changes in human aging. In this sense, the constant evolution and improvement of imaging has given some important contributions. An apparent decrease in retinal thickness in some topographical locations in the early AMD and changes the level of the outer layers have traditionally been studied and associated with AMD. However, these changes have not justified itself all the changes that occur as the disturbance of VA and the search for possible structural and morphological differences, possible to Identify and quantify through SD-OCT emerge as an alternative to improve knowledge in the early forms of AMD. AIM Study the mean thickness of various retinal and choroidal segmentations, obtained manually in the macular region by Spectral Domain Optical Coherence Tomography, among participants with early/intermediate AMD and participants in a control group. Methods: A cross-sectional study in which the retinal and choroidal structures were evaluated and quantified through SD-OCT up to 3 mm from the center of the fovea. Only participantes with a confirmed AMD medical diagnosis (presence / absence), followed by the Dr. Gama Pinto Institute of Ophthalmology, and with essential clinical information for the study (polychromatic, monochromatic and infrared retinography by SLO) were included. According to the Age-Related Eye Disease Study (AREDS) and more recent clinical classification to define early and intermediate stages of AMD, two groups were Created. The early/intermediate AMD study group was formed by: cases with intermediate drusen (63-124μm in diameter) or mild RPE abnormalities designated by G3 (early AMD — AREDS category 2); and cases with numerous intermediate drusens, at least one large drusen (≥125μm in diameter), and geographic atrophy (area of RPE’s atrophy not involving the center of the fovea) designated by G4 (intermediate AMD — AREDS category 3). The control group (no AMD — AREDS category 1) was formed by: cases with no apparent aging changes designated by G1 (no drusen and no AMD pigmentary abnormalities) and others with normal aging changes designated by G2 (only small drusen ≤63 μm and no AMD pigmentary abnormalities). The manual analysis and quantification of the various layers of the retina and choroid will be based on the international nomenclature for the OCT (IN • Consensus) and the differences between the study groups described. The comparison between groups and / or subgroup in the study was made by applying the chi-square test or Fisher's exact test for categorical and nominal variables and the Student t-test for continuous variables. The nonparametric Mann-Whitney test it was used for comparing the mean thickness of the various segmented structures between the control group and early/intermediate AMD. To compare the differences in the thickness of the various segmented structures in four subgroups, it was used multiple comparisons of Kruskal-Wallis test. Finally, and adjusted for sex and age, estimates of the coefficients, Odds Ratio and p values, obtained from multiple logistic regression models of some characteristics of greater interest in AMD, were calculated. Results: 450 participants (38% of males and 61.8% of females) were studied. The control group, consisting of 43.6% male gender participants and 56.4% were female, had a mean age+/-standard deviation of 71.5 +/- 9.5. Regarding early/intermediate AMD group, consisting of a lower percentage of males 33.7% and a higher percentage of females 66.3%, there was an increase in mean age+/-standard deviation 75.7 +/- 10.3 compared with the control group (p <0.001). About 62.6% of participants with AMD have normal macular maps according to normative values SD-OCT and obtained a decreased number of letters (p <0.001) compared to the control group. Intraoperator variability: it can be verified that the highest values were found in the locations of greater thickness. Interoperator variability: except the 0.826 (0.727; 0.898) obtained in the outer plexiform layer (T2,5) and the 0.634 (0.469; 0.771) obtained in the inner plexiform layer (N2) all other correlation values are higher than 0.92. Except RNFL all structures studied have show thickness statistically significant differences between groups in disease compared to control groups. Between control and AMD group the following mean values were found: Ganglion cell complex (75.2 +/- 6.7, 72.1 +/- 6.6 p<0.001); ganglion cell layer (49.3 +/- 5.6, 47.1 +/- 5.4 p <0.001); inner plexiform layer (25.9+/- 2.8, 25 +/- 2.7 p = 0.001); inner nuclear layer (44.1 +/- 4.2, 41.2 +/- 4.1 p <0.001); outer plexiform layer (15.1 +/- 2.1, 14.6 +/- 1.9 p = 0.014); outer nuclear layer and outer plexiform layer complex (90.6 +/- 6.6, 87.9 +/- 7.7 p <0.001); outer nuclear layer (76.7 +/- 6.4, 74.5 +/-7.7 p = 0.002); myoid zone (24.5 +/- 1.3, 22.9 +/- 2.2 p <0.001); outer segments (22.7 +/- 1.9, 20.9 +/- 2.6 p <0.001); RPE_BM (33.4 +/- 2.6, 40.5 +/- 9.7 p <0.001); Choroid (249.8 +/-88.4; 200.2 +/- 76.9 p <0.001). Conclusion: The measurements of the various layers of the retina and choroid, studied in 13 locations manually by the SD-OCT, exhibit good repeatability and reproducibility. It has been shown that with training and following the protocol can be achieved ICC values quite high by manual quantification. The use of the total thickness of the retina to assess and monitor the retinal disease seems not to be sufficient (approximately 64% of cases of AMD are identified as being within the normal range). With the exception of RNFL, all segmentations of the inner retina clearly show marked differences between the extreme subgroups (G4 with G1). However, not all the segmentations appeared to be sensitive to the presence of smalls differences in mean thickness in the subgroups. It was in GCL_IPL complex, especially in the temporal region, which were found major differences between age groups, this location which is most discriminate differences between the various subgroups also possible to find differences between subgroups where the variations are slight. Inner nuclear layer has a good ability to find differences between subgroups with fainter differences however large differences between genders and slight differences in the age groups can attenuate their usefulness between presence and absence of disease. The myoid zone, outer segments, RPE_BM and OS_RPE_BM segmentations differ widely in age groups but no gender differences. These features allow find great differences between extreme subgroups. These segmentations were no major differences between the absences of disease with early/intermediate AMD. In choroid were found large differences across age groups being more decreased in females in the presence of disease. It has a good ability to discriminate between G4 with G1, G4 with G2, and G3 with G2

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Fish energy budget under ocean warming and flame retardant exposure

Climate change and chemical contamination are global environmental threats of growing concern for the scientific community and regulatory authorities. Yet, the impacts and interactions of both stressors (particularly ocean warming and emerging chemical contaminants) on physiological responses of marine organisms remain unclear and still require further understanding. Within this context, the main goal of this study was to assess, for the first time, the effects of warming (+ 5 °C) and accumulation of a polybrominated diphenyl ether congener (BDE-209, brominated flame retardant) through dietary exposure on energy budget of the juvenile white seabream (Diplodus sargus). Specifically, growth (G), routine metabolism (R), excretion (faecal, F and nitrogenous losses, U) and food consumption (C) were calculated to obtain the energy budget. The results demonstrated that the energy proportion spent for G dominated the mode of the energy allocation of juvenile white seabream (56.0-67.8%), especially under the combined effect of warming plus BDE-209 exposure. Under all treatments, the energy channelled for R varied around 26% and a much smaller percentage was channelled for excretion (F: 4.3-16.0% and U: 2.3-3.3%). An opposite trend to G was observed to F, where the highest percentage (16.0 ± 0.9%) was found under control temperature and BDE-209 exposure via diet. In general, the parameters were significantly affected by increased temperature and flame retardant exposure, where higher levels occurred for: i) wet weight, relative growth rate, protein and ash contents under warming conditions, ii) only for O:N ratio under BDE-209 exposure via diet, and iii) for feed efficiency, ammonia excretion rate, routine metabolic rate and assimilation efficiency under the combination of both stressors. On the other hand, decreased viscerosomatic index was observed under warming and lower fat content was observed under the combined effect of both stressors. Overall, under future warming and chemical contamination conditions, fish energy budget was greatly affected, which may dictate negative cascading impacts at population and community levels. Further research combining other climate change stressors (e.g. acidification and hypoxia) and emerging chemical contaminants are needed to better understand and forecast such biological effects in a changing ocean.info:eu-repo/semantics/publishedVersio

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)

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AimThe SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery.MethodsThis was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin.ResultsOverall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P ConclusionOne in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery