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

Latent Tuberculosis Infection in Haematopoietic Stem Cell Transplant Recipients: A Retrospective Italian Cohort Study in Tor Vergata University Hospital, Rome

The results of tuberculosis (TB) screening and reactivation in a cohort of 323 adult patients undergoing haematopoietic stem cell transplantation (HSCT) from 2015 to 2019 at the University Hospital of Tor Vergata, Rome, Italy, were reported. A total of 260 patients, 59 (18.3%) autologous and 264 (81.7%) allogeneic transplants, underwent Interferon Release (IFN)-γ (IGRA) test screening: 228 (87.7%) were negative, 11 (4.2%) indeterminate and 21 (8.1%) positive. Most of the IGRA-positive patients were of Italian origin (95.2%) and significantly older than the IGRA-negative (p < 0.001); 22 (8.5%) patients underwent a second IGRA during the first year after transplantation, and 1 tested positive for IGRA. Significantly lower monocyte (p = 0.044) and lymphocyte counts (p = 0.009) were detected in IGRA negative and IGRA indeterminate patients, respectively. All latent TB patients underwent isoniazid prophylaxis, and none of them progressed to active TB over a median follow-up period of 63.4 months. A significant decline in TB screening practices was shown from 2015 to 2019, and approximately 19% of patients were not screened. In conclusion, 8.1% of our HSCT population had LTBI, all received INH treatment, and no reactivation of TB was observed during the follow-up period. In addition, 19% escaped screening and 8% of these came from countries with a medium TB burden, therefore at higher risk of possible development of TB

Inhibition of HECT E3 ligases as potential therapy for COVID-19

AbstractSARS-CoV-2 is responsible for the ongoing world-wide pandemic which has already taken more than two million lives. Effective treatments are urgently needed. The enzymatic activity of the HECT-E3 ligase family members has been implicated in the cell egression phase of deadly RNA viruses such as Ebola through direct interaction of its VP40 Protein. Here we report that HECT-E3 ligase family members such as NEDD4 and WWP1 interact with and ubiquitylate the SARS-CoV-2 Spike protein. Furthermore, we find that HECT family members are overexpressed in primary samples derived from COVID-19 infected patients and COVID-19 mouse models. Importantly, rare germline activating variants in the NEDD4 and WWP1 genes are associated with severe COVID-19 cases. Critically, I3C, a natural NEDD4 and WWP1 inhibitor from Brassicaceae, displays potent antiviral effects and inhibits viral egression. In conclusion, we identify the HECT family members of E3 ligases as likely novel biomarkers for COVID-19, as well as new potential targets of therapeutic strategy easily testable in clinical trials in view of the established well-tolerated nature of the Brassicaceae natural compounds.</jats:p

Impact of COVID-19 on the oncological outcomes of colorectal cancer surgery in northern Italy in 2019 and 2020: multicentre comparative cohort study

Abstract Background This study compared patients undergoing colorectal cancer surgery in 20 hospitals of northern Italy in 2019 versus 2020, in order to evaluate whether COVID-19-related delays of colorectal cancer screening resulted in more advanced cancers at diagnosis and worse clinical outcomes. Method This was a retrospective multicentre cohort analysis of patients undergoing colorectal cancer surgery in March to December 2019 versus March to December 2020. Independent predictors of disease stage (oncological stage, associated symptoms, clinical T4 stage, metastasis) and outcome (surgical complications, palliative surgery, 30-day death) were evaluated using logistic regression. Results The sample consisted of 1755 patients operated in 2019, and 1481 in 2020 (both mean age 69.6 years). The proportion of cancers with symptoms, clinical T4 stage, liver and lung metastases in 2019 and 2020 were respectively: 80.8 versus 84.5 per cent; 6.2 versus 8.7 per cent; 10.2 versus 10.3 per cent; and 3.0 versus 4.4 per cent. The proportions of surgical complications, palliative surgery and death in 2019 and 2020 were, respectively: 34.4 versus 31.9 per cent; 5.0 versus 7.5 per cent; and 1.7 versus 2.4 per cent. Cancers in 2020 (versus 2019) were more likely to be symptomatic (odds ratio 1.36 (95 per cent c.i. 1.09 to 1.69)), clinical T4 stage (odds ratio 1.38 (95 per cent c.i. 1.03 to 1.85)) and have multiple liver metastases (odds ratio 2.21 (95 per cent c.i. 1.24 to 3.94)), but were not more likely to be associated with surgical complications (odds ratio 0.79 (95 per cent c.i. 0.68 to 0.93)). Conclusion Colorectal cancer patients who had surgery between March and December 2020 had an increased risk of advanced disease in terms of associated symptoms, cancer location, clinical T4 stage and number of liver metastases. </jats:sec

Adapted Physical Activity for the Promotion of Health and the Prevention of Multifactorial Chronic Diseases: the Erice Charter

The Erice Charter was unanimously approved at the conclusion of the 47th Residential Course "Adapted Physical Activity in Sport, Wellness and Fitness: New Challenges for Prevention and Health Promotion", held on 20-24 April 2015 in Erice, Italy, at the "Ettore Majorana" Foundation and Centre for Scientific Culture, and promoted by the International School of Epidemiology and Preventive Medicine "G. D'Alessandro" and the Study Group on Movement Sciences for Health of the Italian Society of Hygiene, Preventive Medicine and Public Health.After an intense discussion the participants identified the main points associated with the relevance of physical activity for Public Health, claiming the pivotal role of the Department of Prevention in coordinating and managing preventive actions. The participants underlined the importance of the physicians specialized in Hygiene, Preventive Medicine and Public Health. The contribution of other operators such as physicians specialized in Sport Medicine was stressed. Further, the holders of the new degree in Human Movement and Sport Sciences were considered fundamental contributors for the performance of physical activity and their presence was seen as a promising opportunity for the Departments of Prevention. Primary prevention based on recreational physical activities should become easily accessible for the population, avoiding obstacles such as certification steps or complex bureaucracy. The Sport Doctor is recognized as the principal referent for preliminary physical evaluation and clinical monitoring in secondary and tertiary prevention actions based on adapted physical activities. Developing research in the field is essential as well as implementing higher education on physical activity management in Schools of Public Health

Adapted Physical Activity for the Promotion of Health and the Prevention of Multifactorial Chronic Diseases: the Erice Charter

The Erice Charter was unanimously approved at the conclusion of the 47th Residential Course "Adapted Physical Activity in Sport, Wellness and Fitness: New Challenges for Prevention and Health Promotion", held on 20-24 April 2015 in Erice, Italy, at the "Ettore Majorana" Foundation and Centre for Scientific Culture, and promoted by the International School of Epidemiology and Preventive Medicine "G. D'Alessandro" and the Study Group on Movement Sciences for Health of the Italian Society of Hygiene, Preventive Medicine and Public Health. After an intense discussion the participants identified the main points associated with the relevance of physical activity for Public Health, claiming the pivotal role of the Department of Prevention in coordinating and managing preventive actions. The participants underlined the importance of the physicians specialized in Hygiene, Preventive Medicine and Public Health. The contribution of other operators such as physicians specialized in Sport Medicine was stressed. Further, the holders of the new degree in Human Movement and Sport Sciences were considered fundamental contributors for the performance of physical activity and their presence was seen as a promising opportunity for the Departments of Prevention. Primary prevention based on recreational physical activities should become easily accessible for the population, avoiding obstacles such as certification steps or complex bureaucracy. The Sport Doctor is recognized as the principal referent for preliminary physical evaluation and clinical monitoring in secondary and tertiary prevention actions based on adapted physical activities. Developing research in the field is essential as well as implementing higher education on physical activity management in Schools of Public Health

Effect of centre volume on pathological outcomes and postoperative complications after surgery for colorectal cancer: results of a multicentre national study

Background: The association between volume, complications and pathological outcomes is still under debate regarding colorectal cancer surgery. The aim of the study was to assess the association between centre volume and severe complications, mortality, less-than-radical oncologic surgery, and indications for neoadjuvant therapy.Methods: Retrospective analysis of 16,883 colorectal cancer cases from 80 centres (2018-2021). Outcomes: 30-day mortality; Clavien-Dindo grade >2 complications; removal of >= 12 lymph nodes; non-radical resection; neoadjuvant therapy. Quartiles of hospital volumes were classified as LOW, MEDIUM, HIGH, and VERY HIGH. Independent predictors, both overall and for rectal cancer, were evaluated using logistic regression including age, gender, AJCC stage and cancer site.Results: LOW-volume centres reported a higher rate of severe postoperative complications (OR 1.50, 95% c.i. 1.15-1.096, P = 0.003). The rate of >= 12 lymph nodes removed in LOW-volume (OR 0.68, 95% c.i. 0.56-0.85, P = 12 lymph nodes removed was lower in LOW-volume than in VERY HIGH-volume centres (OR 0.57, 95% c.i. 0.41-0.80, P = 0.001). A lower rate of neoadjuvant chemoradiation was associated with HIGH (OR 0.66, 95% c.i. 0.56-0.77, P < 0.001), MEDIUM (OR 0.75, 95% c.i. 0.60-0.92, P = 0.006), and LOW (OR 0.70, 95% c.i. 0.52-0.94, P = 0.019) volume centres (vs. VERY HIGH).Conclusion: Colorectal cancer surgery in low-volume centres is at higher risk of suboptimal management, poor postoperative outcomes, and less-than-adequate oncologic resections. Centralisation of rectal cancer cases should be taken into consideration to optimise the outcomes