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Background: In Italy, the incidence of SARS-CoV-2 infection peaked in April and November 2020, defining two pandemic waves of coronavirus disease 2019 (COVID-19). This study compared the characteristics and outcomes of patients with inflammatory bowel disease (IBD) and SARS-CoV-2 infections between pandemic waves., Methods: Observational longitudinal study of IBD patients with SARS-CoV-2 infection. Patients with established diagnoses of IBD and of SARS-CoV-2 infection were consecutively enrolled in two periods: (i) first wave, from 1 March 2020 to 31 May 2020; and (ii) second wave, from 15 September to 15 December 2020., Results: We enrolled 937 IBD patients (219 in the first wave, 718 in the second wave). Patients of the first wave were older (mean ± SD: 46.3 ± 16.2 vs. 44.1 ± 15.4 years, p = 0.06), more likely to have ulcerative colitis (58.0% vs. 44.4%, p < 0.001) and comorbidities (48.9% vs. 38.9%; p < 0.01), and more frequently residing in Northern Italy (73.1% vs. 46.0%, p < 0.001) than patients of the second wave. There were no significant differences between pandemic waves in sex (male: 54.3% vs. 53.3%, p = 0.82) or frequency of active IBD (44.3% vs. 39.0%, p = 0.18). The rates of negative outcomes were significantly higher in the first than second wave: pneumonia (27.8% vs. 11.7%, p < 0.001), hospital admission (27.4% vs. 9.7%, p < 0.001), ventilatory support (11.9% vs. 5.4%, p < 0.003) and death (5.5% vs. 1.8%, p < 0.007)., Conclusion: Between the first and second SARS-CoV-2 pandemic waves, demographic, clinical and geographical features of IBD patients were different as were the symptoms and outcomes of infection. These differences are likely due to the different epidemiological situations and diagnostic possibilities between the two waves., (© 2023. The Author(s).)

Acute myeloid leukemia (AML) is a heterogeneous disease that accounts for ~20% of all childhood leukemias, and more than 40% of children with AML relapse within three years of diagnosis. Although recent efforts have focused on developing a precise medicine-based approach towards treating AML in adults, there remains a critical gap in therapies designed specifically for children. Here, we present ex vivo drug sensitivity profiles for children with de novo AML using an automated flow cytometry platform. Fresh diagnostic blood or bone marrow aspirate samples were screened for sensitivity in response to 78 dose conditions by measuring the reduction in leukemic blasts relative to the control. In pediatric patients treated with conventional chemotherapy, comprising cytarabine, daunorubicin and etoposide (ADE), ex vivo drug sensitivity results correlated with minimal residual disease (r = 0.63) and one year relapse-free survival (r = 0.70; AUROC = 0.94). In the de novo ADE analysis cohort of 13 patients, AML cells showed greater sensitivity to bortezomib/panobinostat compared with ADE, and comparable sensitivity between venetoclax/azacitidine and ADE ex vivo. Two patients showed a differential response between ADE and bortezomib/panobinostat, thus supporting the incorporation of ex vivo drug sensitivity testing in clinical trials to further evaluate the predictive utility of this platform in children with AML.

Objectives: Inflammatory bowel disease (IBD) can affect young and reproductively active patients. Our aim was to analyze pregnancy outcomes in a large cohort of women with IBD., Methods: All women with at least one pregnancy were given a questionnaire regarding the outcome of their pregnancy. They were divided into IBD pregnancies and controls depending on whether pregnancy occurred within or over 10 years prior to the diagnosis of IBD., Results: Three hundred questionnaires were analyzed for a total of 478 pregnancies that led to live-born babies. Age at conception was older in IBD women than in the controls. Active smoking was more frequent in the control group. The risk of intrauterine growth restriction (IUGR) was higher in IBD pregnancies (odds ratio [OR] 3.028, 95% confidence interval [CI] 1.245-7.370, P = 0.013). The week of gestation at delivery was lower in the IBD population. And the risk of cesarean section was higher in IBD pregnancies (OR 1.963, 95% CI 1.274-3.028, P = 0.002). Among women with IBD pregnancy, the risk of preterm birth was higher in patients with active disease at the time of conception (OR 4.088, 95% CI 1.112-15.025, P = 0.030), but lower in patients who continued regular therapy during pregnancy. Similarly, the risk of urgent cesarean section was reduced in the case of disease remission, while the risk of a planned cesarean delivery was higher in patients with perianal disease (OR 11.314, 95% CI 3.550-36.058, P < 0.01)., Conclusions: Our study shows a higher risk of IUGR, cesarean section, and poor blood pressure control in IBD pregnancies. We emphasize the importance of achieving disease remission before considering pregnancy., (© 2022 The Authors. Journal of Digestive Diseases published by Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background and Aims: Vedolizumab is a gut-selective anti-integrin (α4β7) antibody for the treatment of inflammatory bowel disease with a well-known optimal safety profile. We aimed to compare its risk of infections with that of anti-TNF drugs and ustekinumab in patients with both ulcerative colitis and Crohn's disease., Methods: All Crohn's disease and ulcerative colitis patients undergoing biological treatment at our centre between 2013 and 2019 were retrospectively included. All infectious complications were registered, considering both inpatient and outpatient events. A comparison of the exposure-adjusted infection rates of vedolizumab, anti-TNF drugs and ustekinumab was carried out, with a specific focus on the rate of gut infections. All infection rates were expressed in events per patient-years (PYs)., Results: The overall exposure-adjusted infection rate was 11.5/100 PYs. The most common infections were respiratory tract infections, cutaneous infections, HSV infections/reactivations and gut infections. The rate of serious infections was 1.3/100 PYs. The infection rate of vedolizumab was 17.5/100 PYs, with Crohn's disease patients having a lower infection risk compared with ulcerative colitis patients (P = 0.035). Gut infections were observed in 3.0% of the whole patient population (1.5/100 PYs) and were more common in the vedolizumab group (P = 0.0001)., Conclusions: Our study confirms the good safety profile of vedolizumab. Among patients treated with vedolizumab, those with ulcerative colitis have a higher risk of developing infectious complications. Patients treated with vedolizumab have a higher risk of gut infections compared with patients treated with anti-TNF drugs or ustekinumab. Presumably, this is due to the gut-selective mechanism of action of vedolizumab., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Capsule endoscopy has been considered the first-line approach for the investigation of obscure gastro-intestinal bleeding since its approval in 2001. Our study aims to evaluate the diagnostic yield of capsule endoscopy in the investigation of this condition. We also analyse the incidence of non-small-bowel lesions missed after conventional endoscopy and later detected by capsule endoscopy in patients with suspected obscure bleeding., Methods: A total of 290 patients with negative conventional endoscopy referred to our centre to undergo a capsule endoscopy examination for the investigation of obscure gastro-intestinal bleeding. We considered as non-small-bowel lesions those outside the tract between the second duodenal portion and the ileocecal valve. We also looked for actively bleeding lesions at the time of the exam., Results: Intestinal preparation was good, adequate or poor in 74.1%, 8.4%, and 17.5% of the tests, respectively. Caecum was reached in 92.4%. Capsule retention occurred in 0.7%. Mean small bowel transit time was 5hours and 13minutes. Diagnostic yield was 73.8%. An actively bleeding lesion was noticed in 39.3% of positive tests. Capsule endoscopy revealed clinically significant non-small-bowel lesions missed at gastroscopy or colonoscopy in 30.3% of patients, 43.2% of which were bleeding., Conclusions: Capsule endoscopy has high diagnostic yield and safety in the investigation of obscure gastro-intestinal bleedings. Given the high percentage of non-small-bowel lesions detected, it may be appropriate to consider an endoscopic second look before performing a capsule endoscopy study., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Background: Human telomerase reverse transcriptase (hTERT) and its components play a significant role in cancer progression, but recent data demonstrated that telomeres and telomerase alterations could be found in other diseases; increasing evidence suggests a key role of this enzyme in the fields of hepatobiliary and pancreatic diseases., Data Sources: We performed a PubMed search with the following keywords: telomerase, hepatocellular carcinoma, cholangiocarcinoma, pancreatic adenocarcinoma by December 2019. We reviewed the relevant publications that analyzed the correlation between telomerase activity and hepatobiliary and pancreatic diseases., Results: Telomerase reactivation plays a significant role in the development and progression of hepatobiliary and pancreatic tumors and could be used as a diagnostic biomarker for hepatobiliary and pancreatic cancers, as a predictor for prognosis and a promising therapeutic target., Conclusions: Our review summarized the evidence about the critical role of hTERT in cancerous and precancerous lesions of the alteration and its activity in hepatobiliary and pancreatic diseases., (Copyright © 2020 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Unlabelled: Direct-to-implant breast reconstruction can be achieved more easily by means of soft-tissue replacement devices such as dermal matrices and synthetic meshes. The feasibility of a subcutaneous approach has been recently investigated by some studies with different devices functioning as implant support. Aim of this study is to analyze the long-term results, both objective and subjective, of a previous nonrandomized trial comparing prepectoral (subcutaneous) and retropectoral breast reconstructions., Methods: Patients enrolled in a nonrandomized prospective trial, comparing the standard retropectoral reconstruction and the prepectoral subcutaneous approach, using a titanium-coated mesh in both techniques, were followed up and evaluated for long-term results. Cases were compared in terms of the causes and rate of reinterventions, of the postoperative BREAST-Q questionnaire results, and of an objective surgical evaluation., Results: The subcutaneous group had a rate of implant failure and removal of 5.1% when compared with 0% in the retropectoral group. Aesthetic outcome was significantly better for the subcutaneous group both at a subjective and at an objective evaluation. Capsular contracture rate was 0% in the subcutaneous group., Conclusions: A higher rate of implant failure and removal, although not significant, always because of skin flaps and wound problems, should be taken into account for a careful patients selection. The subcutaneous breast reconstruction shows good long-term results. A coherent subjective and objective cosmetic advantage of this approach emerges. Moreover, no capsular contracture is evident, albeit in a relatively limited number of cases.

Background: Immediate implant reconstruction after a conservative mastectomy is an attractive option made easier by prosthetic devices. Titanized polypropylene meshes are used as a hammock to cover the lower lateral implant pole. We conducted a prospective nonrandomized single-institution study of reconstructions using titanium-coated meshes either in a standard muscular mesh pocket or in a complete subcutaneous approach. The complete subcutaneous approach means to wrap an implant with titanized mesh in order to position the implant subcutaneously and spare muscles., Methods: Between November 2011 and January 2014, we performed immediate implant breast reconstructions after conservative mastectomies using TiLoop® Bra, either with the standard retropectoral or with a prepectoral approach. Selection criteria included only women with normal Body Mass Index (BMI), no large and very ptotic breasts, no history of smoking, no diabetes, and no previous radiotherapy. We analyzed short-term outcomes of such procedures and compared the outcomes to evaluate implant losses and surgical complications., Results: A total of 73 mastectomies were performed. Group 1 comprised 29 women, 5 bilateral procedures, 34 reconstructions, using the standard muscular mesh pocket. Group 2 comprised 34 women, 5 bilateral procedures, 39 reconstructions with the prepectoral subcutaneous technique. Baseline and oncologic characteristics were homogeneous between the two groups. After a median follow-up period of 13 and 12 months, respectively, no implant losses were recorded in group 1, and one implant loss was recorded in group 2. We registered three surgical complications in group 1 and two surgical complications in group 2., Conclusions: Titanium-coated polypropylene meshes, as a tool for immediate definitive implant breast reconstruction, resulted as safe and effective in a short-term analysis, both for a retropectoral and a totally subcutaneous implant placement. Long-term results are forthcoming. A strict selection is mandatory to achieve optimal results. Level of Evidence: Level II, therapeutic study.