The Diverticular Disease Registry (DDR Trial) by the Advanced International Mini-Invasive Surgery Academy Clinical Research Network: Protocol for a Multicenter, Prospective Observational Study

Diverticular disease is an increasingly common issue, with a variety of clinical presentations and treatment options. However, very few prospective cohort studies explore outcomes between the different presentations and treatments. The Diverticular Disease Registry (DDR Trial) is a multicenter, prospective, observational cohort study on behalf of the Advanced International Mini-Invasive Surgery (AIMS) academy clinical research network. The DDR Trial aims to investigate the short-term postoperative and long-term quality of life outcomes in patients undergoing surgery or medical treatments for diverticular disease. DDR Trial is open to participation by all tertiary-care hospitals. DDR Trial has been registered at ClinicalTriats.gou (NCT 04907383). Data collection will be recorded on Research Electronic Data Capture (REDCap) starting on June 1 , 2021 and will end after 5 years of recruitment. All adult patients with imaging-proven colonic diverticular disease (i.e., symptomatic colonic diverticulosis including diverticular bleeding, diverticulitis, and Symptomatic Uncomplicated Diverticular Disease) will be included. The primary outcome of DDR Trial is quality of life assessment at 12-month according to the Gastrointestinal Quality of Life Index (GIQLI). The secondary outcome is 30-day postoperative outcomes according to the Clavien-Dindo classification. DDR Trial will significantly advance in identifying the optimal care for patients with diverticular disease by exploring outcomes of different presentations and treatments

Anastomosis configuration and technique following ileocaecal resection for Crohn's disease: a multicentre study

A limited ileocaecal resection is the most frequently performed procedure for ileocaecal CD and different anastomotic configurations and techniques have been described. This manuscript audited the different anastomotic techniques used in a national study and evaluated their influence on postoperative outcomes following ileocaecal resection for primary CD. This is a retrospective, multicentre, observational study promoted by the Italian Society of Colorectal Surgery (SICCR), including all adults undergoing elective ileocaecal resection for primary CD from June 2018 May 2019. Postoperative morbidity within 30 days of surgery was the primary endpoint. Postoperative length of hospital stay (LOS) and anastomotic leak rate were the secondary outcomes. 427 patients were included. The side to side anastomosis was the chosen configuration in 380 patients (89%). The stapled anastomotic (n = 286; 67%), techniques were preferred to hand-sewn (n = 141; 33%). Postoperative morbidity was 20.3% and anastomotic leak 3.7%. Anastomotic leak was independent of the type of anastomosis performed, while was associated with an ASA grade ≥ 3, presence of perianal disease and ileocolonic localization of disease. Four predictors of LOS were identified after multivariate analysis. The laparoscopic approach was the only associated with a reduced LOS (p = 0.017), while age, ASA grade ≥ 3 or administration of preoperative TPN were associated with increased LOS. The side to side was the most commonly used anastomotic configuration for ileocolic reconstruction following primary CD resection. There was no difference in postoperative morbidity according to anastomotic technique and configuration. Anastomotic leak was associated with ASA grade ≥ 3, a penetrating phenotype of disease and ileo-colonic distribution of CD

National variations in perioperative assessment and surgical management of Crohn's disease: a multicentre study

Aim: Crohn's disease (CD) requires a multidisciplinary approach and surgery should be undertaken by dedicated colorectal surgeons with audited outcomes. We present a national, multicentre study, with the aim to collect benchmark data on key performance indicators in CD surgery, to highlight areas where standards of CD surgery excel and to facilitate targeted quality improvement where indicated. Methods: All patients undergoing ileocaecal or redo ileocolic resection in the participating centres for primary and recurrent CD from June 2018 to May 2019 were included. The main objective was to collect national data on hospital volume and practice variations. Postoperative morbidity was the primary outcome. Laparoscopic surgery and stoma rate were the secondary outcomes. Results: In all, 715 patients were included: 457 primary CD and 258 recurrent CD with a postoperative morbidity of 21.6% and 34.7%, respectively. Laparoscopy was used in 83.8% of primary CD compared to 31% of recurrent CD. Twenty-five hospitals participated and the total number of patients per hospital ranged from 2 to 169. Hospitals performing more than 10 primary CD procedures per year showed a higher adoption of laparoscopy and bowel sparing surgery. Conclusions: There is significant heterogeneity in the number of CD surgeries performed per year nationally in Italy. Our data suggest that high-volume hospitals perform more complex procedures, with a higher adoption of bowel sparing surgery. The rate of laparoscopy in high-volume hospitals is higher for primary CD but not for recurrent CD compared with low-volume hospitals

Exome-wide Rare Variant Analysis Identifies TUBA4A Mutations Associated with Familial ALS

Exome sequencing is an effective strategy for identifying human disease genes. However, this methodology is difficult in late-onset diseases where limited availability of DNA from informative family members prohibits comprehensive segregation analysis. To overcome this limitation, we performed an exome-wide rare variant burden analysis of 363 index cases with familial ALS (FALS). The results revealed an excess of patient variants within TUBA4A, the gene encoding the Tubulin, Alpha 4A protein. Analysis of a further 272 FALS cases and 5,510 internal controls confirmed the overrepresentation as statistically significant and replicable. Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability. These results further emphasize the role of cytoskeletal defects in ALS and demonstrate the power of gene-based rare variant analyses in situations where causal genes cannot be identified through traditional segregation analysis

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Predictive factors for drain placement after laparoscopic cholecystectomy

PURPOSE: Currently, surgical drainage during a laparoscopic cholecystectomy (LC) is still placed in selected patients. Evidence of the non-beneficial effect of the surgical drain comes from studies with a heterogeneous population. This preliminary study aims to identify any clinical, demographic, or intraoperative predictive factors for a surgical drain placement during LC as the first step to identify population for a prospective randomized study. METHOD: The study was conducted in a single referral center and academic hospital between 2014 and 2018. Patients who underwent unconverted LC were divided into two groups: Group A (drain) and Group B (no drain). We explored baseline, preoperative, intraoperative characteristics, and postoperative outcomes. RESULTS: Between 409 patients who underwent LC: 90 (22%) patients were in Group A (drain). Age >64 years, male sex, cholecystitis, Charlson comorbidity index (CCI) ≥ 1, experienced surgeon, intraoperative technical difficulties, need for an additional trocar, operative time >60 min, and estimated blood loss >10 ml were predictive factors at univariate analysis. While at multivariate analysis, cholecystitis (odds ratio [OR]: 2.8, 95% CI:1.5–5.1; p 10 ml (OR: 3.0, 95% CI:1.7–5.3; p < 0.0001) were predictive factors for a surgical drain placement during LC. CONCLUSIONS: This study identified predictive factors that currently drive the surgeons to a surgical drain placement after LC. Randomized prospective studies are needed to define the use of drain placement in these selected patients

Symptomatic Uncomplicated Diverticular Disease (SUDD): Practical Guidance and Challenges for Clinical Management

Symptomatic Uncomplicated Diverticular Disease (SUDD) is a syndrome within the diverticular disease spectrum, characterized by local abdominal pain with bowel movement changes but without systemic inflammation. This narrative review reports current knowledge, delivers practical guidance, and reveals challenges for the clinical management of SUDD. A broad and common consensus on the definition of SUDD is still needed. However, it is mainly considered a chronic condition that impairs quality of life (QoL) and is characterized by persistent left lower quadrant abdominal pain with bowel movement changes (eg, diarrhea) and low-grade inflammation (eg, elevated calprotectin) but without systemic inflammation. Age, genetic predisposition, obesity, physical inactivity, low-fiber diet, and smoking are considered risk factors. The pathogenesis of SUDD is not entirely clarified. It seems to result from an interaction between fecal microbiota alterations, neuro-immune enteric interactions, and muscular system dysfunction associated with a low-grade and local inflammatory state. At diagnosis, it is essential to assess baseline clinical and Quality of Life (QoL) scores to evaluate treatment efficacy and, ideally, to enroll patients in cohort studies, clinical trials, or registries. SUDD treatments aim to improve symptoms and QoL, prevent recurrence, and avoid disease progression and complications. An overall healthy lifestyle – physical activity and a high-fiber diet, with a focus on whole grains, fruits, and vegetables – is encouraged. Probiotics could effectively reduce symptoms in patients with SUDD, but their utility is missing adequate evidence. Using Rifaximin plus fiber and Mesalazine offers potential in controlling symptoms in patients with SUDD and might prevent acute diverticulitis. Surgery could be considered in patients with medical treatment failure and persistently impaired QoL. Still, studies with well-defined diagnostic criteria for SUDD that evaluate the safety, QoL, effectiveness, and cost-effectiveness of these interventions using standard scores and comparable outcomes are needed