Long-term continuous monitoring of the preterm brain with diffuse optical tomography and electroencephalography: A technical note on cap manufacturing

open12noDiffuse optical tomography (DOT) has recently proved useful for detecting whole-brain oxygenation changes in preterm and term newborns' brains. The data recording phase in prior explorations was limited up to a maximum of a couple of hours, a time dictated by the need to minimize skin damage caused by the protracted contact with optode holders and interference with concomitant clinical/nursing procedures. In an attempt to extend the data recording phase, we developed a new custom-made cap for multimodal DOT and electroencephalography acquisitions for the neonatal population. The cap was tested on a preterm neonate (28 weeks gestation) for a 7-day continuous monitoring period. The cap was well tolerated by the neonate, who did not suffer any evident discomfort and/or skin damage. Montage and data acquisition using our cap was operated by an attending nurse with no difficulty. DOT data quality was remarkable, with an average of 92% of reliable channels, characterized by the clear presence of the heartbeat in most of them.openopenAlfonso Galderisi; Sabrina Brigadoi; Simone Cutini; Sara Basso Moro; Elisabetta Lolli; Federica Meconi; Silvia Benavides-Varela; Eugenio Baraldi; Piero Amodio; Claudio Cobelli; Daniele Trevisanuto; Roberto Dell'AcquaGalderisi, Alfonso; Brigadoi, Sabrina; Cutini, Simone; BASSO MORO, Sara; Lolli, Elisabetta; Meconi, Federica; Silvia, Benavides-Varela; Baraldi, Eugenio; Amodio, Piero; Cobelli, Claudio; Trevisanuto, Daniele; Dell'Acqua, Robert

Silencing of anti-chondrogenic microRNA-221 in human mesenchymal stem cells promotes cartilage repair in vivo

There is a growing demand for the development of experimental strategies for efficient articular cartilage repair. Current tissue engineering-based regenerative strategies make use of human mesenchymal stromal cells (hMSCs). However, when implanted in a cartilage defect, control of hMSCs differentiation towards the chondrogenic lineage remains a significant challenge. We have recently demonstrated that silencing the anti-chondrogenic regulator microRNA-221 (miR-221) was highly effective in promoting in vitro chondrogenesis of monolayered hMSCs in the absence of the chondrogenic induction factor TGF-β. Here we investigated the feasibility of this approach first in conventional 3D pellet culture and then in an in vivo model. In pellet cultures, we observed that miR-221 silencing was sufficient to drive hMSCs towards chondrogenic differentiation in the absence of TGF-β. In vivo, the potential of miR-221 silenced hMSCs was investigated by first encapsulating the cells in alginate and then by filling a cartilage defect in an osteochondral biopsy. After implanting the biopsy subcutaneously in nude mice, we found that silencing of miR-221 strongly enhanced in vivo cartilage repair compared to the control conditions (untreated hMSCs or alginate-only). Notably, miR-221 silenced hMSCs generated in vivo a cartilaginous tissue with no sign of collagen type X deposition, a marker of undesired hypertrophic maturation. Altogether our data indicate that silencing miR-221 has a pro-chondrogenic role in vivo, opening new possibilities for the use of hMSCs in cartilage tissue engineering. This article is protected by copyright. All rights reserved

Mucinous and Signet-Ring Cell Colonic Adenocarcinoma in Inflammatory Bowel Disease: A Case-Control Study

Simple Summary Chronic active inflammation is a known risk factor for colorectal cancer (CRC) in inflammatory bowel disease (IBD), while the adenoma-carcinoma sequence appears to be associated with sporadic CRC. In the general population, mucinous and signet-ring cell adenocarcinomas are characterized by a worse prognosis. In IBD, a higher frequency of these CRC histotypes has been reported. In the present study, we investigated the frequency and characteristics of mucinous and signet-ring cell adenocarcinomas in patients with IBD versus age-matched non-IBD Controls. CRC was more frequently represented by mucinous/signet-ring cell adenocarcinoma in IBD than in Controls. In rectal CRC, there was a higher proportion of mucinous/signet-ring cell adenocarcinoma vs. standard adenocarcinoma in IBD but not in non-IBD Controls. No risk factors for these two CRC histotypes were identified in IBD. Present findings support that the frequency of mucinous/signet-ring cell colorectal adenocarcinoma is higher in IBD, being associated with rectal involvement of CRC. A higher frequency of mucinous and signet-ring cell colonic adenocarcinoma has been reported in inflammatory bowel disease (IBD). The primary aim was to investigate the frequency of mucinous and signet-ring cell colorectal adenocarcinoma in patients with IBD (Cases) versus age-matched non-IBD Controls. The secondary aims were to compare the characteristics of these two histotypes of colorectal cancer (CRC) in IBD patients vs. Controls and to search for specific risk factors in IBD. In a case-control study, all IBD patients with CRC diagnosed from 2000 to 2022 were enrolled and matched for age (1:2) with non-IBD Controls with CRC. The study population included 120 CRC patients (40 IBD, 80 Controls). In IBD, CRC included standard adenocarcinoma in 23 (57.5%) patients mucinous/signet-ring cell adenocarcinoma in 17 (42.5%) patients. The proportion of mucinous/signet-ring cell adenocarcinoma was higher in IBD than in Controls (17 [42.5%] vs. 18 [22.5%]; p = 0.03). In rectal CRC, the proportion of mucinous/signet-ring cell adenocarcinoma was higher than standard adenocarcinoma in IBD (8 [47.1%] vs. 4 [17.4%]; p = 0.04) but not in Controls (4 [22.2%] vs. 20 [32.2%]; p = 0.59). In rectal CRC, the proportion of these two histotypes was higher in Cases than in Controls (8/12 [66.6%] vs. 4/24 [16.6%]; p = 0.008), with no risk factors identified in IBD. CRC was more frequently represented by mucinous/signet-ring cell adenocarcinoma in IBD than in age-matched non-IBD Controls. In IBD, these two CRC histotypes were more frequent in the rectum

A Novel Smad7 Genetic Variant Mapping on the Genomic Region Targeted by Mongersen Is Associated with Crohn's Disease

Down-regulation of Smad7 with a specific Smad7 antisense (AS) oligonucleotide-containing oral drug (Mongersen) was effective in pre-clinical studies and initial clinical trials in Crohn's disease (CD) patients. A recent phase 3 trial was discontinued due to an apparent inefficacy of the drug, but factors contributing to the failure of this study remain unknown. Here, we analysed the frequency in CD of rs144204026 C/T single nucleotide polymorphism (SNP), which maps on the corresponding region targeted by the Smad7 AS contained in the Mongersen formulation and examined whether such a variant allele affects the ability of Smad7 AS to knockdown Smad7

Impact of the time interval between primary or interval surgery and adjuvant chemotherapy in ovarian cancer patients

IntroductionPrimary debulking surgery (PDS), interval debulking surgery (IDS), and platinum-based chemotherapy are the current standard treatments for advanced ovarian cancer (OC). The time to initiation of adjuvant chemotherapy (TTC) could influence patient outcomes.MethodsWe conducted a multicenter retrospective cohort study of advanced (International Federation of Gynecology and Obstetrics (FIGO) stage III or IV) OC treated between 2014 and 2018 to assess progression-free survival (PFS) and overall survival (OS) in relation to TTC. All patients underwent a germline multigene panel for BRCA1/2 evaluation.ResultsAmong the 83 patients who underwent PDS, a TTC ≥ 60 days was associated with a shorter PFS (hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.04–3.93, p = 0.038), although this association lost statistical significance when adjusting for residual disease (HR 1.52, 95% CI 0.75–3.06, p = 0.244, for TTC and HR 2.73, 95% CI 1.50–4.96, p = 0.001, for residual disease). Among 52 IDS patients, we found no evidence of an association between TTC and clinical outcomes. Ascites, type of chemotherapy, or germline BRCA1/2 mutational status did not influence TTC and were not associated with clinical outcomes in PDS or IDS patients.DiscussionIn conclusion, longer TTC seems to negatively affect prognosis in patients undergoing PDS, especially those with residual disease

Real-time Interobserver Agreement in Bowel Ultrasonography for Diagnostic Assessment in Patients With Crohn's Disease:An International Multicenter Study

Background The unavailability of standardized parameters in bowel ultrasonography (US) commonly used in Crohn's disease (CD) and the shortage of skilled ultrasonographers are 2 limiting factors in the use of this imaging modality around the world. The aim of this study is to evaluate interobserver agreement among experienced sonographers in the evaluation of bowel US parameters in order to improve standardization in imaging reporting and interpretation. Methods Fifteen patients with an established diagnosis of CD underwent blinded bowel US performed by 6 experienced sonographers. Prior to the evaluation, the sonographers and clinical and radiological IBD experts met to formally define the US parameters. Interobserver agreement was tested with the Quatto method (s). Results All operators agreed on the presence/absence of CD lesions and distinguished absence of/mild activity or moderate/severe lesions in all patients. S values were moderate for bowel wall thickness (s = 0.48, P = n.s.), bowel wall pattern (s = 0.41, P = n.s.), vascularization (s = 0.52, P = n.s.), and presence of lymphnodes (s = 0.61, P = n.s.). Agreement was substantial for lesion location (s = 0.68, P = n.s.), fistula (s = 0.74, P = n.s.), phlegmon (s = 0.78, P = 0.04), and was almost perfect for abscess (s = 0.95, P = 0.02). Poor agreement was observed for mesenteric adipose tissue alteration, lesion extent, stenosis, and prestenotic dilation. Conclusions In this study, the majority of the US parameters used in CD showed moderate/substantial agreement. The development of shared US imaging interpretation patterns among sonographers will lead to improved comparability of US results among centers and facilitate the development of multicenter studies and the spread of bowel US training, thereby allowing a wider adoption of this useful technique

INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors: a transversal challenge. The INVIDIa study

Aim: Considering the unmet need for the counseling of cancer patients treated with immune checkpoint inhibitors (CKI) about influenza vaccination, an explorative study was planned to assess flu vaccine efficacy in this population. Methods: INVIDIa was a retrospective, multicenter study, enrolling consecutive advanced cancer outpatients receiving CKI during the influenza season 2016-2017. Results: Of 300 patients, 79 received flu vaccine. The incidence of influenza syndrome was 24.1% among vaccinated, versus 11.8% of controls; odds ratio: 2.4; 95% CI: 1.23-4.59; p = 0.009. The clinical ineffectiveness of vaccine was more pronounced among elderly: 37.8% among vaccinated patients, versus 6.1% of unvaccinated, odds ratio: 9.28; 95% CI: 2.77-31.14; p < 0.0001. Conclusion: Although influenza vaccine may be clinically ineffective in advanced cancer patients receiving CKI, it seems not to negatively impact the efficacy of anticancer therapy

Complete heterotopic pancreas

A 43-year-old man presented to our hospital with acute abdominal pain and decreased bowel movements. Physical examination revealed a painful abdominal mass in mesogastrium. A small intestine contrast ultrasonography showed an ileal–ileal intussusception looked like a doughnut shape, with the telescoped part inside (“double cockade”, “bowel in the bowel”), created by the hyperechoic central core and mesentery surrounded by the hypoechoic outer oedematous bowel (Fig. 1, panel a), confirmed by MR-enterography (Fig. 1, panel b). Laparoscopy was performed and showed an intussusception of 10 cm length at about 80 cm from ileo-ciecal valve. A side-to-side anastomosis at ileal level was performed. Pathological examination revealed a polyp with a short peduncle (Fig. 2, panel a) diagnosed as complete heterotopic pancreas with both ductal–acinar and insular features. Antibodies to glucagon were used to identify alpha cells (Fig. 2, panel b). Postoperative course was uneventful