Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Physical activity program for patients with dementia and their relative caregivers: randomized clinical trial in Primary Health Care (AFISDEMyF study)

[ENG]Background: The aging of the population has led to the increase of chronic diseases, especially dementia and cardiovascular diseases, and it has become necessary for their relatives to dedicate more time in caregiving. The objective in the first phase of this study is to evaluate the effectiveness of a Primary Health Care procedure to increase the physical activity of people with dementia and their relative caregivers. Also the effect on the cognitive state and cardiovascular risk will be assessed. Methods/Design: Design: Clinical, multicentric and randomized trial. A simple random sampling to select 134 patients diagnosed with dementia will be carried out. After contacting their relatives, his/her participation in the trial will be requested. A basal assessment will be made and the participants will be asigned to control or intervention group (1:1). Variables: The main measure will be the assessment of physical activity (podometer and 7-PAR) in patients and caregivers. In patients with dementia: ADAS-cog, functional degree and cardiovascular risk. In caregivers: cardiovascular risk, general health and quality of life. Intervention: For 3 months, participants will receive instructions to do physical activity with an adapted program. This program will be designed and applied by Primary Health Care professionals in patients with dementia and their caregivers. The control group will receive regular care. Analysis: An intention-to-treat analysis will be carried out by comparing the observed differences between basal, 6 and 12 months measures. Change in the mean of daily steps assessed with the podometer and 7-PAR will be the main result. Discussion: If the main hypothesis is confirmed, it could be useful to improve the cognitive state of patients with dementia, as well as the cardiovascular risk of all of them. The results can be good to improve technical features of the devices that register the physical activity in the patients with dementia, and it could facilitate its commercialization. Trial registration: Clinical Trials.gov Identifier: NCT02044887

Physical activity program for patients with dementia and their relative caregivers: randomized clinical trial in Primary Health Care (AFISDEMyF study)

BACKGROUND: The aging of the population has led to the increase of chronic diseases, especially dementia and cardiovascular diseases, and it has become necessary for their relatives to dedicate more time in caregiving. The objective in the first phase of this study is to evaluate the effectiveness of a Primary Health Care procedure to increase the physical activity of people with dementia and their relative caregivers. Also the effect on the cognitive state and cardiovascular risk will be assessed. METHODS/DESIGN: Design: Clinical, multicentric and randomized trial. A simple random sampling to select 134 patients diagnosed with dementia will be carried out. After contacting their relatives, his/her participation in the trial will be requested. A basal assessment will be made and the participants will be asigned to control or intervention group (1:1). Variables: The main measure will be the assessment of physical activity (podometer and 7-PAR) in patients and caregivers. In patients with dementia: ADAS-cog, functional degree and cardiovascular risk. In caregivers: cardiovascular risk, general health and quality of life. Intervention: For 3 months, participants will receive instructions to do physical activity with an adapted program. This program will be designed and applied by Primary Health Care professionals in patients with dementia and their caregivers. The control group will receive regular care. Analysis: An intention-to-treat analysis will be carried out by comparing the observed differences between basal, 6 and 12 months measures. Change in the mean of daily steps assessed with the podometer and 7-PAR will be the main result. DISCUSSION: If the main hypothesis is confirmed, it could be useful to improve the cognitive state of patients with dementia, as well as the cardiovascular risk of all of them. The results can be good to improve technical features of the devices that register the physical activity in the patients with dementia, and it could facilitate its commercialization. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT02044887

Safety of primary anastomosis following emergency left sided colorectal resection: an international, multi-centre prospective audit.

This is the peer reviewed version of the following article: group, T. E. S. o. C. c. (2018). "Safety of primary anastomosis following emergency left sided colorectal resection: an international, multi-centre prospective audit." Colorectal Disease 20(S6): 47-57., which has been published in final form at https://doi.org/10.1111/codi.1437. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsINTRODUCTION: Some evidence suggests that primary anastomosis following left sided colorectal resection in the emergency setting may be safe in selected patients, and confer favourable outcomes to permanent enterostomy. The aim of this study was to compare the major postoperative complication rate in patients undergoing end stoma vs primary anastomosis following emergency left sided colorectal resection. METHODS: A pre-planned analysis of the European Society of Coloproctology 2017 audit. Adult patients (> 16 years) who underwent emergency (unplanned, within 24 h of hospital admission) left sided colonic or rectal resection were included. The primary endpoint was the 30-day major complication rate (Clavien-Dindo grade 3 to 5). RESULTS: From 591 patients, 455 (77%) received an end stoma, 103 a primary anastomosis (17%) and 33 primary anastomosis with defunctioning stoma (6%). In multivariable models, anastomosis was associated with a similar major complication rate to end stoma (adjusted odds ratio for end stoma 1.52, 95%CI 0.83-2.79, P = 0.173). Although a defunctioning stoma was not associated with reduced anastomotic leak (12% defunctioned [4/33] vs 13% not defunctioned [13/97], adjusted odds ratio 2.19, 95%CI 0.43-11.02, P = 0.343), it was associated with less severe complications (75% [3/4] with defunctioning stoma, 86.7% anastomosis only [13/15]), a lower mortality rate (0% [0/4] vs 20% [3/15]), and fewer reoperations (50% [2/4] vs 73% [11/15]) when a leak did occur. CONCLUSIONS: Primary anastomosis in selected patients appears safe after left sided emergency colorectal resection. A defunctioning stoma might mitigate against risk of subsequent complications

The impact of conversion on the risk of major complication following laparoscopic colonic surgery: an international, multicentre prospective audit.

This is the peer reviewed version of the following article: The and E. S. o. C. c. groups (2018). "The impact of conversion on the risk of major complication following laparoscopic colonic surgery: an international, multicentre prospective audit." Colorectal Disease 20(S6): 69-89., which has been published in final form at https://doi.org/10.1111/codi.14371. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.BACKGROUND: Laparoscopy has now been implemented as a standard of care for elective colonic resection around the world. During the adoption period, studies showed that conversion may be detrimental to patients, with poorer outcomes than both laparoscopic completed or planned open surgery. The primary aim of this study was to determine whether laparoscopic conversion was associated with a higher major complication rate than planned open surgery in contemporary, international practice. METHODS: Combined analysis of the European Society of Coloproctology 2017 and 2015 audits. Patients were included if they underwent elective resection of a colonic segment from the caecum to the rectosigmoid junction with primary anastomosis. The primary outcome measure was the 30-day major complication rate, defined as Clavien-Dindo grade III-V. RESULTS: Of 3980 patients, 64% (2561/3980) underwent laparoscopic surgery and a laparoscopic conversion rate of 14% (359/2561). The major complication rate was highest after open surgery (laparoscopic 7.4%, converted 9.7%, open 11.6%, P < 0.001). After case mix adjustment in a multilevel model, only planned open (and not laparoscopic converted) surgery was associated with increased major complications in comparison to laparoscopic surgery (OR 1.64, 1.27-2.11, P < 0.001). CONCLUSIONS: Appropriate laparoscopic conversion should not be considered a treatment failure in modern practice. Conversion does not appear to place patients at increased risk of complications vs planned open surgery, supporting broadening of selection criteria for attempted laparoscopy in elective colonic resection

An international multicentre prospective audit of elective rectal cancer surgery; operative approach versus outcome, including transanal total mesorectal excision (TaTME)

IntroductionTransanal total mesorectal excision (TaTME) has rapidly emerged as a novel approach for rectal cancer surgery. Safety profiles are still emerging and more comparative data is urgently needed. This study aimed to compare indications and short-term outcomes of TaTME, open, laparoscopic, and robotic TME internationally.MethodsA pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 audit was performed. Patients undergoing elective total mesorectal excision (TME) for malignancy between 1 January 2017 and 15 March 2017 by any operative approach were included. The primary outcome measure was anastomotic leak.ResultsOf 2579 included patients, 76.2% (1966/2579) underwent TME with restorative anastomosis of which 19.9% (312/1966) had a minimally invasive approach (laparoscopic or robotic) which included a transanal component (TaTME). Overall, 9.0% (175/1951, 15 missing outcome data) of patients suffered an anastomotic leak. On univariate analysis both laparoscopic TaTME (OR 1.61, 1.02-2.48, P=0.04) and robotic TaTME (OR 3.05, 1.10-7.34, P=0.02) were associated with a higher risk of anastomotic leak than non-transanal laparoscopic TME. However this association was lost in the mixed-effects model controlling for patient and disease factors (OR 1.23, 0.77-1.97, P=0.39 and OR 2.11, 0.79-5.62, P=0.14 respectively), whilst low rectal anastomosis (OR 2.72, 1.55-4.77, P<0.001) and male gender (OR 2.29, 1.52-3.44, P<0.001) remained strongly associated. The overall positive circumferential margin resection rate was 4.0%, which varied between operative approaches: laparoscopic 3.2%, transanal 3.8%, open 4.7%, robotic 1%.ConclusionThis contemporaneous international snapshot shows that uptake of the TaTME approach is widespread and is associated with surgically and pathologically acceptable results

Evaluating the incidence of pathological complete response in current international rectal cancer practice: the barriers to widespread safe deferral of surgery

This is the peer reviewed version of the following article: , which has been published in final form at https://doi.org/10.1111/codi.14361. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions."Colorectal Disease © 2018 The Association of Coloproctology of Great Britain and Ireland Introduction: The mainstay of management for locally advanced rectal cancer is chemoradiotherapy followed by surgical resection. Following chemoradiotherapy, a complete response may be detected clinically and radiologically (cCR) prior to surgery or pathologically after surgery (pCR). We aim to report the overall complete pathological response (pCR) rate and the reliability of detecting a cCR by conventional pre-operative imaging. Methods: A pre-planned analysis of the European Society of Coloproctology (ESCP) 2017 audit was performed. Patients treated by elective rectal resection were included. A pCR was defined as a ypT0 N0 EMVI negative primary tumour; a partial response represented any regression from baseline staging following chemoradiotherapy. The primary endpoint was the pCR rate. The secondary endpoint was agreement between post-treatment MRI restaging (yMRI) and final pathological staging. Results: Of 2572 patients undergoing rectal cancer surgery in 277 participating centres across 44 countries, 673 (26.2%) underwent chemoradiotherapy and surgery. The pCR rate was 10.3% (67/649), with a partial response in 35.9% (233/649) patients. Comparison of AJCC stage determined by post-treatment yMRI with final pathology showed understaging in 13% (55/429) and overstaging in 34% (148/429). Agreement between yMRI and final pathology for T-stage, N-stage, or AJCC status were each graded as ‘fair’ only (n = 429, Kappa 0.25, 0.26 and 0.35 respectively). Conclusion: The reported pCR rate of 10% highlights the potential for non-operative management in selected cases. The limited strength of agreement between basic conventional post-chemoradiotherapy imaging assessment techniques and pathology suggest alternative markers of response should be considered, in the context of controlled clinical trials

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic