Textbook outcome in urgent early cholecystectomy for acute calculous cholecystitis: results post hoc of the S.P.Ri.M.A.C.C study

Introduction: A textbook outcome patient is one in which the operative course passes uneventful, without complications, readmission or mortality. There is a lack of publications in terms of TO on acute cholecystitis. Objetive: The objective of this study is to analyze the achievement of TO in patients with urgent early cholecystectomy (UEC) for Acute Cholecystitis. and to identify which factors are related to achieving TO. Materials and methods: This is a post hoc study of the SPRiMACC study. It ́s a prospective multicenter observational study run by WSES. The criteria to define TO in urgent early cholecystectomy (TOUEC) were no 30-day mortality, no 30-day postoperative complications, no readmission within 30 days, and hospital stay ≤ 7 days (75th percentile), and full laparoscopic surgery. Patients who met all these conditions were taken as presenting a TOUEC. Outcomes: 1246 urgent early cholecystectomies for ACC were included. In all, 789 patients (63.3%) achieved all TOUEC parameters, while 457 (36.6%) failed to achieve one or more parameters and were considered non-TOUEC. The patients who achieved TOUEC were younger had significantly lower scores on all the risk scales analyzed. In the serological tests, TOUEC patients had lower values for in a lot of variables than non-TOUEC patients. The TOUEC group had lower rates of complicated cholecystitis. Considering operative time, a shorter duration was also associated with a higher probability of reaching TOUEC. Conclusion: Knowledge of the factors that influence the TOUEC can allow us to improve our results in terms of textbook outcome

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p < 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p < 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p < 0.0001) or urgent (20.4% vs. 38.5%; p < 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p < 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice

L’approccio ambientale per gli interventi di building renovation dei quartieri Erp degli anni ’50-’80 in Italia. Indirizzi di supporto decisionale tra caratteristiche di “autorità” e obiettivi di transizione verde

Una percentuale consistente del patrimonio edilizio italiano, un tempo periferia, oggi fa parte di un più ampio assetto di aree metropolitane complesse ed estese il cui ruolo è stato recentemente ricollocato in una posizione di rilievo all’interno dell'agenda della politica tecnica europea e del dibattito nel nostro paese. In relazione alle nuove esigenze dettate dagli obiettivi della building renovation, è necessario individuare azioni appropriate che consentano di raggiungere elevate prestazioni degli ambienti urbani. Questo approccio rappresenta una particolare sfida rispetto agli interventi di riqualificazione dell’edilizia residenziale pubblica rappresentativa, anche in relazione al livello di qualità autoriale e di sperimentazione edilizia, dell’espansione urbana in Italia tra gli anni ‘50 e la metà degli anni ’80. In tali contesti il raggiungimento della neutralità carbonica non può prescindere dai valori progettuali che tali quartieri hanno avuto nell'evoluzione della cultura architettonica in Italia. Il riconoscimento identitario dei luoghi, infatti, gioca un ruolo non secondario nei processi di trasformazione, facendo della riconoscibilità un elemento fondamentale nel necessario passaggio da endemiche condizioni di marginalità verso nuove centralità urbane riferite alla trasformazione rigenerativa e di rinnovo delle aree metropolitane periurbane, come imposto dal contrasto del climate change e dai programmi di ripresa post Covid-19

IN-UP_INHABITING THE UPCYCLING. Regenerative strategies for inhabiting the process

The massive expansion of the suburbs in Italy between the 1950s and 1980s, characterised by the construction of subsidised public housing estates, has necessarily given way since the 1990s to physical and social redevelopment of large peripheral complexes. Starting from the project of technological, typological and energetic-environmental recovery of architectural artefacts and, more specifically, of public residential buildings, the contribution investigates the theme of regeneration by presenting the results of a project experience developed on the occasion of the RELIVE2020 design competition-workshop. The project proposal, through a systemic approach capable of providing a decisive contribution to regenerative processes, prefigures a replicable model of a resilient, inclusive and low environmental impact city

A decoy oligonucleotide to NF-κB delivered through inhalable particles inhibits the lung inflammation induced by LPS in rat

NF-kB plays a prominent role in orchestrating the airway inflammatory response in several diseases, including cystic fibrosis [1]. The specific inhibition of NF-kB by decoy oligonucleotides delivered in the lung may limit the progression of inflammation [2], although rationally designed systems are needed to control drug release and optimize pharmacological response. In this regard, here we have developed and tested in vivo an inhalable dry powder for prolonged delivery of a decoy oligodeoxynucleotide to NF-κB (dec-ODN), consisting of large porous particles (LPP) based on poly(lactic-coglycolic) acid (PLGA). First, LPP containing dec-ODN (dec-ODN LPP) have been engineered to meet aerodynamic criteria crucial for pulmonary delivery, to gain an effective loading of dec-ODN, to sustain its release and to preserve its structural integrity in lung lining fluids. Then, we have investigated the effects of dec-ODN LPP in a rat model of lung inflammation induced by intra-tracheal aerosolization of LSP from P. aeruginosa. The results show that a single intratracheal insufflation of dec-ODN LPP significantly prevented the neutrophil infiltration induced by LPS up to 72 hours, whereas naked dec-ODN was able to inhibit it only at 6 hours. The persistent inhibition of neutrophil infiltrate by dec-ODN LPP was associated with a significant reduction of NF-κB/DNA binding activity as well as interleukin-6, interleukin-8 and mucin-2 mRNA expression in lung homogenates. Taken together, our findings show that dec-ODN LPP may provide a new strategy for local treatment of inflammation associated with lung diseases. 1.Park GY and Christman JW. Nuclear factor kappa B is a promising therapeutic target in inflammatory lung disease. Curr Drug Targets. 2006 Jun;7(6):661-8. 2.Cabrini G et al., Targeting transcription factor activity as a strategy to inhibit pro-inflammatory genes involved in cystic fibrosis: decoy oligonucleotides and low-molecular weight compounds. Curr Med Chem. 2010;17(35):4392-404

Development of Potent Inhibitors of the Mycobacterium tuberculosis Virulence Factor Zmp1 and Evaluation of Their Effect on Mycobacterial Survival inside Macrophages

The enzyme Zmp1 is a zinc-containing peptidase that plays a critical role in the pathogenicity of Mycobacterium tuberculosis. Herein we describe the identification of a small set of Zmp1 inhibitors based on a novel 8-hydroxyquinoline-2-hydroxamate scaffold. Among the synthesized compounds, N-(benzyloxy)-8-hydroxyquinoline-2-carboxamide (1 c) was found to be the most potent Zmp1 inhibitor known to date, and its binding mode was analyzed both by kinetics studies and molecular modeling, identifying critical interactions of 1 c with the zinc ion and residues in the active site. The effect of 1 c on intracellular Mycobacterium survival was assayed in J774 murine macrophages infected with M. tuberculosis H37Rv or M. bovis BCG and human monocyte-derived macrophages infected with M. tuberculosis H37Rv. Cytotoxicity and genotoxicity were also assessed. Overall, inhibitor 1 c displays interesting in vitro antitubercular properties worthy of further investigation

Early Ultrasound Response and Progressive Transmural Remission After Treatment With Ustekinumab in Crohn’s Disease

Background & aims: In this STARDUST substudy, the effect of ustekinumab on transmural bowel inflammation was assessed in adults with moderate-to-severe Crohn's disease (CD) by using intestinal ultrasound (IUS), a noninvasive imaging procedure. Methods: STARDUST was an international, multicenter, phase 3b, interventional, randomized controlled trial specifically designed to compare treat-to-target and standard-of-care treatment strategies in ustekinumab-treated CD patients. In this substudy, the most affected bowel segment at baseline by IUS was used for all analyses. Key IUS endpoints (centrally read, parameter-blinded) were IUS response, transmural remission, bowel wall thickness (BWT), blood flow, bowel wall stratification, and inflammatory fat. Results: Seventy-seven patients were evaluated. IUS response could be determined 4 weeks after treatment initiation, with progressive improvement through week 48. IUS response and transmural remission rates at week 48 were 46.3% and 24.1%, respectively. IUS response, transmural remission, BWT, and blood flow normalization rates were more pronounced in the colon and biologic-naive patients. Fair/moderate reliability (κ = 0.21-0.51) was observed between week 4 IUS response and week 48 overall endoscopic response and fecal calprotectin/complete biomarker outcomes. Endoscopy and IUS baseline agreement was >90% in determining the terminal ileum as the most affected bowel segment. IUS response absence at week 4 was associated with no endoscopic response (based on the simplified endoscopic score for Crohn's disease terminal ileum subscore) at week 48 (negative predictive value = 73%). Conclusions: In this first international, multicenter, interventional study, IUS showed that ustekinumab-treated CD patients achieved progressive IUS response (46.3%) and transmural remission (24.1%) through week 48, with a more robust response in the colon and biologic-naive patients. Clinicaltrials: gov number: NCT03107793