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Assessment of inflammatory bowel disease (IBD) currently relies on aspecific clinical signs of bowel inflammation. Specific imaging of the diseased bowel regions is still lacking. Here, we investigate mucosal addressin cell adhesion molecule 1 (MAdCAM-1) as a reliable and specific endothelial target for engineered nanoparticles delivering imaging agents to obtain an exact mapping of diseased bowel foci. We generated a nanodevice composed of PLGA-PEG coupled with anti-MAdCAM-1 antibody half-chains and loaded with quantum dots (P@QD-MdC NPs). Bowel localization and systemic biodistribution of the nanoconjugate were analyzed upon injection in a murine model of chronic IBD obtained through repeated administration of dextran sulfate sodium salt. Specificity for diseased bowel regions was also assessed ex vivo in human specimens from patients with IBD. Potential for development as contrast agent in magnetic resonance imaging was assessed by preliminary study on animal model. Synthesized nanoparticles revealed good stability and monodispersity. Molecular targeting properties were analyzed in vitro in a cell culture model. Upon intravenous injection, P@QD-MdC NPs were localized in the bowel of colitic mice, with enhanced accumulation at 24 h post-injection compared to untargeted nanoparticles (p<0.05). Nanoparticles injection did not induce histologic lesions in non-target organs. Ex vivo exposure of human bowel specimens to P@QD-MdC NPs revealed specific recognition of the diseased regions vs uninvolved tracts (p<0.0001). After loading with appropriate contrast agent, the nanoparticles enabled localized contrast enhancement of bowel mucosa in the rectum of treated mice. P@QD-MdC NPs efficiently detected bowel inflammation foci, accurately following the expression pattern of MAdCAM-1. Fine-tuning of this nanoconjugate with appropriate imaging agents offers a promising non-invasive tool for specific IBD diagnosis.

Ellis grade III coronary artery perforations (G3-CAP) remain a life-threatening complication of percutaneous coronary intervention (PCI), with high morbidity and mortality and lack of consensus regarding optimal treatment strategies. We reviewed all PCIs performed in 10 European centers from 1993 to 2019 recording all G3-CAP along with management strategies, in-hospital and long-term outcome according to Device-related perforations (DP) and Guidewire-related perforations (WP). Among 106,592 PCI (including 7,773 chronic total occlusions), G3-CAP occurred in 311 patients (0.29%). DP occurred in 194 cases (62.4%), more commonly in proximal segments (73.2%) and frequently secondary to balloon dilatation (66.0%). WP arose in 117 patients (37.6%) with chronic total occlusions guidewires involved in 61.3% of cases. Overall sealing success rate was 90.7% and usually required multiple maneuvers (80.4%). The most commonly adopted strategies to obtain hemostasis were prolonged balloon inflation (73.2%) with covered stent implantation (64.4%) in the DP group, and prolonged balloon inflation (53.8%) with coil embolization (41%) in the WP group.  Procedural or in-hospital events arose in 38.2% of cases: mortality was higher after DP (7.2% vs 2.6%, p = 0.05) and acute stent thrombosis 3-fold higher (3.1% vs 0.9%, p = 0.19). At clinical follow-up, median 2 years, a major cardiovascular event occurred in one-third of cases (all-cause mortality 8.2% and 7.1% respectively, without differences between groups). In conclusion, although rare and despite improved rates of adequate perforation sealing G3-CAP cause significant adverse events. DP and WP result in different patterns of G3-CAP and management strategies should be based on this classification.

Switching to bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) from other antiretroviral regimens is safe and effective for virologically suppressed people living with HIV (PLWH). The term virological suppression includes both low but detectable HIV viremia and undetectable HIV viremia, and the latter is possibly associated with a lower immune activation state. Herein, we describe a 24-month follow-up of experienced PLWH with plasma HIV RNA undetectable or detectable < 50 copies/ml switching to BIC/FTC/TAF. A previous 12-month monitoring was available, and the factors correlated with treatment efficacy. This retrospective multicenter study included PLWH who switched to BIC/FTC/TAF in the period of 2019–2022, and who were HBsAg and HCV RNA negative. The follow-up study times were 6 (T6), 12 (T12), 18 (T18), and 24 (T24) months after the switch (T0). Survival analysis with multiple-failure-per-subject design, Kaplan–Meier survival estimates, multivariate analysis of variance, multilevel linear regression, and a hierarchical ordered logistic model were applied. A total of 329 PLWH had plasma HIV RNA which was either undetectable or detectable at <50 copies/mL at T0, and 197 responded to all inclusion criteria: M/F 140/57; the median CD4+ cell count was 677 cells/mm3; and HIV RNA at T0 was undetectable in 108 patients. Most of the 197 patients (122, 61.9%) were on a previous INSTI-based regimen. HIV RNA undetectability was more frequent at each follow-up point in patients with HIV RNA that was undetectable at T0, and it showed a higher frequency throughout the follow-up period in patients with always-undetectable HIV RNA in the 12 months before the switch. A higher nadir CD4 cell count had a predictive role, and HBcAb positivity had no influence. In conclusion, the switch could be programmed and possibly delayed on a case-by-case basis in order to achieve persistent plasma HIV RNA undetectability. Undiagnosed loss of HBcAb has no detrimental consequences on the response to BIC/FTC/TAF.

Some evidence suggests a reduction in clinical and surgical recurrence after mesenteric resection in Crohn’s Disease (CD). The aim of the REsection of the MEsentery StuDY (Remedy) was to assess whether mesenteric removal during surgery for ileocolic CD has an impact in terms of postoperative complications, endoscopic and ultrasonographic recurrences, and long-term surgical recurrence. Among the 326 patients undergoing primary resection between 2009 and 2019 in two referral centers, in 204 (62%) the mesentery was resected (Group A) and in 122 (38%) it was retained (Group B). Median follow-up was 4.7 ± 3 years. Groups were similar in the peri-operative course. Endoscopic and ultrasonographic recurrences were 44.6% and 40.4% in Group A, and 46.7% and 41.2% in Group B, respectively, without statistically significant differences. The five-year time-to-event estimates, compared with the Log-rank test, were 3% and 4% for normal or thickened mesentery (p = 0.6), 2.8% and 4% for resection or sparing of the mesentery (p = 0.6), and 1.7% and 5.4% in patients treated with biological or immunosuppressants versus other adjuvant therapy (p = 0.02). In Cox’s model, perforating behavior was a risk factor, and biological or immunosuppressant adjuvant therapy protective for surgical recurrence. The resection of the mesentery does not seem to reduce endoscopic and ultrasonographic recurrences, and the five-year recurrence rate.

Colorectal cancer (CRC) remains challenging to diagnose, necessitating the identification of a noninvasive biomarker that can differentiate it from other conditions such as inflammatory bowel diseases (IBD) and diverticular disease (DD). Raman spectroscopy (RS) stands out as a promising technique for monitoring blood biochemical profiles, with the potential to identify distinct signatures identifying CRC subjects. We performed RS analysis on dried plasma from 120 subjects: 32 CRC patients, 37 IBD patients, 20 DD patients, and 31 healthy controls. We also conducted longitudinal studies of CRC patient's postsurgery to monitor the spectral changes over time. We identified six spectral features that showed significant differences between CRC and non‐CRC patients, corresponding to tryptophan, tyrosine, phenylalanine, lipids, carotenoids, and disulfide bridges. These features enabled the classification of CRC patients with an accuracy of 87.5%. Moreover, longitudinal analysis revealed that the spectral differences normalized over 6 months after surgery, indicating their association with the presence of the disease. Our study demonstrates the potential of RS to identify specific biomolecular signatures related to CRC. These results suggest that RS could be a novel screening and monitoring tool, providing valuable insights for the development of noninvasive and accurate diagnostic methods for CRC. Blood serves as a valuable repository of disease biomarkers, offering insights for diagnosis. Raman spectroscopy (RS) emerges as a promising technique, capable of discerning distinct molecular signatures in biological samples. This study demonstrates RS's efficacy in distinguishing dried plasma samples across various bowel diseases .

We investigated the spike IgG levels of HIV+ patients on antiretroviral therapy six months after they received their second dose (T2) and six months after the third dose (T3) of the BNT162b2 mRNA vaccine, as well as the influence of different levels of plasma HIV viremia of overall CD4+ cell count and nadir value on the humoral time course. One hundred eighty-four patients were enrolled. The median age was 55 years, the median CD4+ cell count was 639 cells/mm3 and the median nadir value was 258 cells/mm3. On the basis of all tests performed during the study period, persistently undetectable plasma HIV RNA (PUD) was found in 66 patients, low-level viremia (LLV) in 57 and ongoing viremia (OV) in 61. Serum levels of IgG antibodies against a trimeric S-protein antigen were tested with DiaSorin Liaison SARS-CoV-2 TrimericS IgG and the response was classified as optimal (>75th percentile), intermediate (50th–25th percentile) and low (<25th percentile). The frequencies of the three different patterns of plasma HIV viremia (PUD, LLV and OV) were comparable in patients with low, intermediate and optimal IgG response evaluated at T2, with no difference in overall CD4+ cell count or nadir count. At T3, 92.9% of patients achieved an optimal response: T2 response proved to be the most important factor in predicting T3 optimal response in patients with LLV and OV.A nadir value ≤ 330 cells/mm3 had 100% sensitivity in predicting a non-optimal response. In conclusion, we demonstrated the persistence of anti-spike IgG, with high serum levels occurring in most patients six months after the third dose of the BNT162b2 mRNA vaccine and a predictive role of humoral response at T2 in subjects with detectable plasma HIV viremia. Immunological alterations related to past immunodeficiency may persist despite immune reconstitution, and the nadir value could be a useful tool for elaborating personalized vaccine schedules.

A major concern in the management of Inflammatory Bowel Disease (IBD) is the absence of accurate and specific biomarkers to drive diagnosis and monitor disease status timely and non-invasively. Fibroblast activation protein (FAP) represents a hallmark of IBD bowel strictures, being overexpressed in stenotic intestinal myofibroblasts. The present study aimed at evaluating the potential of circulating FAP (cFAP) as an accessible blood biomarker of IBD. Quantitative determination of cFAP was performed by enzyme-linked immunosorbent assay on plasma samples prospectively collected from patients with IBD and control subjects. A discrimination model was established on a training set of 50% patients and validated on independent samples. Results showed that cFAP concentration was reduced in patients with IBD when compared to controls ( p < 0.0001). Age, sex, smoking, disease location and behavior, disease duration and therapy were not associated with cFAP. The sensitivity and specificity of cFAP in discriminating IBD from controls were 70 and 84%, respectively, based on the optimal cutoff (57.6 ng mL −1 , AUC = 0.78). Predictions on the test set had 57% sensitivity, 65% specificity, and 61% accuracy. There was no strong correlation between cFAP and routine inflammatory markers in the patients' population. A subgroup analysis was performed on patients with Crohn's disease undergoing surgery and revealed that cFAP correlates with endoscopic mucosal healing. In conclusion, cFAP deserves attention as a promising blood biomarker to triage patients with suspected IBD. Moreover, it might function as a biomarker of post-operative remission in patients with Crohn's disease.

Although the creation of a stoma reduces the risk of septic pouch complications following ileal pouch-anal anastomosis (IPAA), the stoma itself and its reversal can give rise to substantial morbidity during the two- or three-stage concept. Aim of study is to compare stoma-related complications in Ulcerative Colitis patients undergoing laparoscopic versus open IPAA. We collected data on 250 IPAA patients from two Italian Centres between 2005 and 2015. We compared perioperative and postoperative events in 150 open vs 100 laparoscopic IPAA. We performed a case-matched analysis based on baseline differences among groups to compare the rate of mechanical complications. There were no significant differences between open and laparoscopic IPAA in overall stoma complications (complications during ileostomy: 11.3% vs 12%,p = 0.8; early complications: 10% vs 8%,p = 0.5; late complications: 12.6% vs 6%,p = 0.08). The case-matched analysis found a slightly reduced incidence of obstructive complications at any stage with laparoscopy. Overall stoma related complications do not seem to be reduced by minimally-invasive approach itself, but patients might experience less mechanical problems with laparoscopy without conversion. •Stoma formation and reversal can contribute to substantial morbidity in UC surgery.•Laparoscopic approach might help reduce the stoma associated complications.•Slightly less obstructive complications were found in laparoscopic group.•Overall stoma related complications do not seem to be influenced by surgical technique.

Acute severe colitis is the major indication for surgery in inflammatory bowel diseases (IBD), and in particular, in ulcerative colitis (UC). A laparoscopic approach for abdominal colectomy is recommended, due to better perioperative and long-term outcomes. However, costs, time-spending, and outcomes are still a topic of improvement. We designed a standardized 10-steps, sequential approach to laparoscopic colectomy, based on the philosophy of the “critical view of safety”, with the aim to improve perioperative outcomes (operative duration, estimated blood loss, complications, readmissions, reoperations, and length of postoperative stay). We performed a retrospective cohort study using data from a prospectively maintained clinical database. We included all the consecutive, unselected patients undergoing laparoscopic subtotal colectomy (SCo) for IBD between 2008 and 2019 in a tertiary IBD Italian Centre. Starting from 2015, we regularly adopted the novel Sequential Approach for a Critical-View Colectomy (SACCo) technique. We included 59 (40.6%) patients treated with different laparoscopic approaches, and 86 patients (59.4%) operated on by the SACCo procedure. The mean operating time was significantly shorter for the SACCo group (144 vs. 224 min; p < 0.0001). The SACCo technique presented a trend to fewer major complications (6.8% vs. 8.3%), less readmissions (2.3% vs. 13.5%; p = 0.01), and shorter postoperative hospital stay (7.2 vs. 8.8 days; p = 0.003). Laparoscopic SACCo-technique is a safe and reproducible surgical approach for acute severe colitis and may improve the outcomes of this demanding procedure.