Azienda Ospedaliera Universitaria Research Articles

Impact on global health status, quality-sexual life and chronic fatigue state of risk-reducing salpingo-oophorectomy in women who are BRCA1/2 mutation carriers: experience from a third level italian center.

Objective: BRCA 1 and 2 mutation carriers are invited to follow intensive clinical and instrumental surveillance programs or are offered prophylactic ovarian surgery. These recommendations impact many aspects of their lives. The primary objective of this study was to assess the overall quality of life (HRQoL) before and after prophylactic bilateral salpingo-oophorectomy (BSO). Secondary objectives were investigating sexual health (SH) and fatigue severity state (FSS). Design: This was a single-center, retrospective observational, study. Setting: Women who underwent surgical treatment of bilateral salpingo-oophorectomy between 2018 and 2024 at “DAI Materno Infantile” of Azienda Ospedaliera Universitaria “Federico II” of Naples were included. Methods: These patients were tracked down to undergo specific questionnaires, such as “Global Health Status and Quality of Life Scale (QOL) (EORTC QLQ-C30)”, “EORTC Sexual Health Questionnaire (QLQ-SH22), and “Fatigue Severity Scale (FSS)”, to evaluate their psychological, sexual and general physical condition impact before the surgery, 3 and 6 months later. Results: The overall mean QoL score was 88.3±29.8 (mean + standard deviation), and this score worsened when the surgery was performed at 3 months (p <.0001) with a score of 51.7±30.7 with a mean difference (MD) of 36.6 points; instead, when we evaluated at 6 months, the overall mean QoL score was 73.1±24.3 with an MD of 21.4 points. FSS reported a score of 2.7±1.15 vs 4.2±1.59 (p<.0001) vs 3.5±1.43 (p<.0001), respectively, before and 3-6 months after surgery. EORTC QLQ-SH22 before and after treatment showed statistically significant changes in sexual satisfaction (p<.0001). Conclusion: BSO may impact the quality of life regardless of the hormonal status of patients related to age or menopause, both about the functional evaluation and the psychological and emotional assessment report. The physical change related to the surgical procedure is associated with a mental shift that affects both the physical and sexual energy of our patients in the first 3 months postoperatively, with a slight improvement of these data at 6 months.

Eyelid Contact Dermatitis: 25-Year Single-Center Retrospective Study

Background/Objectives: Eyelid dermatitis is an inflammatory disease affecting the palpebral skin characterized by itching, edema, and scaling of the periorbital area. This entity can be a manifestation of various underlying dermatological diseases, but allergic contact dermatitis (ACD) is the predominant etiology of eyelid dermatitis among patients, being diagnosed in 43.4% of cases. The thin and highly permeable nature of eyelid skin increases its susceptibility to allergens, making it a distinct clinical entity. This study aimed to identify the primary haptens associated with eyelid ACD and compare these findings with the allergens implicated in non-eyelid ACD over a 25-year period in a large cohort of patients. Methods: We conducted a monocentric, retrospective study on a dataset of 7955 patients patch-tested for ACD at the Outpatient Allergy Dermatology Clinic of the Azienda Ospedaliera Universitaria Senese (AOUS) from 1997 to 2021. Eyelid ACD cases were identified based on clinical features and positive patch test results. Data on demographics, occupation, and personal history of atopy were collected. The statistical analyses assessed the associations between allergens and eyelid ACD. The trends in the sensitization rates for the most prevalent allergens were also evaluated. Results: Eyelid ACD was identified in 4.6% of the study population, predominantly affecting women (88.6%). Patients with eyelid ACD were more likely to exhibit single-hapten positivity (54.6%) and an atopic phenotype (52.3%) compared to non-eyelid ACD cases. Nickel sulfate (54%), cobalt chloride (13.4%), and thimerosal (12.6%) were the most common allergens associated with eyelid ACD. While thimerosal sensitization decreased significantly following its removal from topical products, nickel sensitization increased, likely due to exposure from electronic devices and hand–eye contact. Conclusions: The haptens identified in eyelid ACD largely overlap with those found in other body regions, including metals, fragrances, and preservatives. However, the unique characteristics of eyelid skin and hand–eye contact patterns play a significant role in sensitization. This study highlights the need for further investigation into the pathophysiology of eyelid allergic contact dermatitis, with particular emphasis on elucidating the mechanisms of hapten sensitization. Such insights could contribute to the development of effective strategies aimed at reducing allergen exposure.

In vitro effect of hCG on cryptorchid patients’ gubernacular cells: a predictive model for adjuvant personalized therapy

BackgroundCryptorchidism is the absence of one or both testicles in the scrotum at birth, being a risk factor for testis cancer and infertility. The most effective method to treat cryptorchidism is orchiopexy, followed by human chorionic gonadotropin (hCG) therapy; however, a portion of treated patients do not show a significant improvement in testis volume and vascularization after adjuvant therapy.MethodsIn this study, we generated an in vitro model to predict the patient response to hCG by cultivating and treating primary cells derived from five cryptorchid patients’ biopsies of gubernaculum testis, the ligament that connects the testicle to the scrotum. On these in vitro cultured cells, we analyzed the effect of hCG on cell proliferation, tubular structure formation, cellular respiration, reactive oxygen species content, and proteome.ResultsWe demonstrate that in vitro hCG stimulates gubernacular cells to proliferate and form vessel-like structures to a different extent among the five cryptorchid patients’ cells, with a decrease in oxygen consumption and reactive oxygen species generation. Furthermore, from the proteomic analysis, we show that hCG regulates the intra- and extra-cellular organization of gubernacular cells together with a massive regulation of the antioxidant response.ConclusionsHereby, we characterized the cellular and molecular effects of hCG, demonstrating that the diverse patient response to hCG may be ascribable to their age since young patients better respond in vitro to the hormone, supporting a prompt surgical procedure and subsequent therapy.Trial registrationThe study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Ethics Committee of “Azienda Ospedaliera Universitaria Integrata” (AOUI) of Verona, Italy (“ANDRO-PRO”, protocol code N. 4206 CESC of 26 April 2023).

Robotic-Assisted Surgical Staging with Sentinel Node Biopsy for Apparently Early-Stage Endometrial Cancer Using the Modular Multi-Arm Surgical Robot System Versius® (Cambridge Medical Robots): A Case Series

Objectives: The aim of the study was to report the first cases of surgical staging for apparently early-stage endometrial cancer performed using the Versius® next-generation robotic surgical system (Cambridge Medical Robots [CMR] Surgical, Cambridge, UK). Design: The study used a prospective case series. Participants/Materials: Women who underwent surgical staging, including total hysterectomy, bilateral adnexectomy, and sentinel lymph node (SLN) biopsy, for apparently early-stage endometrial cancer using the Versius® next-generation robotic surgical system (CMR Surgical, Cambridge, UK) were included. Setting: The study was conducted at a Gynecologic Oncology Referral Center. Methods: We prospectively recorded data of all consecutive women who underwent the investigated surgical procedure. Results: Fourteen endometrial cancer patients were treated between March and August 2024 at the Azienda Ospedaliera Universitaria Integrata of Verona. The mean age was 69.4 ± 8.7 years, and the average body mass index was 27.2 ± 4.8. SLN biopsy was performed on all patients: 5 patients had unilateral and 9 bilateral successful SLN detection; 6 women underwent systematic pelvic lymphadenectomy in the unmapped areas. The median operative time was 122 (min-max, 77–185) minutes, and the median hysterectomy time was 34 (min-max, 18–68) minutes. None of the surgical procedures required conversion to conventional laparoscopic or open surgery for technical reasons, and no intraoperative complications were recorded. No readmissions, reoperations, or deaths were observed during the follow-up (median 102 days, min-max 39–249). Limitations: The limitations of the study are the first experience in a limited study population and the use of methylene blue for SLN mapping. Conclusions: Our preliminary results with the Versius® platform appear encouraging regarding surgical time, blood loss, rate of completion of the robotic procedures, and complications risk. Further studies will confirm the indications, feasibility, and safety of the Versius® surgical robot system for treating apparently early-stage endometrial cancer.

Clinical Comparison of Decentration and Tilt Effects in Iris-Claw and Trans-scleral Plug Lenses: Wavefront Analysis With a Pyramidal Sensor Aberrometer.

To compare the aberrometric profile of the Artisan Aphakia lens (Opthec BV) and transscleral plug FIL-SSF lens (Soleko) and to assess the impact of tilt and decentration on their optical performance. This retrospective observational study was conducted at Azienda Ospedaliera Universitaria Careggi, Florence, Italy, with a consecutive cohort of aphakic eyes undergoing secondary lens implantation with an Artisan or FIL-SSF lens. Wavefront analysis was performed using a pyramidal wavefront-based aberrometer (Osiris-T; CSO). Tilt and decentration were calculated using anterior segment optical coherence tomography (MS-39; CSO). The study included 47 eyes from 45 patients: 24 eyes in the FIL-SSF group and 23 eyes in the Artisan group. Decentration was 0.39 ± 0.14 mm in the FIL-SSF group and 0.51 ± 0.16 mm in the Artisan group (P = .02). The mean tilt value was 6.6 ± 2.35 degrees in the FIL-SSF group and 5.9 ± 1.86 degrees in the Artisan group (P = .13). Internal higher order aberrations (HOAs) were 0.23 ± 0.07 μm in the FIL-SSF group and 0.29 ± 0.13 μm in the Artisan group (P = .02). The point spread function (PSF) Strehl ratio was 0.12 ± 0.05 in the FIL-SSF group and 0.10 ± 0.04 (P = .11) in the Artisan group. The PSF Strehl ratio without lower order aberration (PSFw2) was 0.28 ± 0.12 in the FIL-SSF group and 0.23 ± 0.09 in the Artisan group (P = .01). The Artisan and FIL-SSF lenses provide comparable optical performance in terms of the PSF Strehl ratio. However, the Artisan lens appears to be more susceptible to decentration, which may result in increased higher order aberrations and a consequently lower PSFw2 Strehl ratio. [J Refract Surg. 2024;40(12):e926-e933.].

Role of ultra-processed foods in modulating the effect of Mediterranean diet on human and planet health—study protocol of the PROMENADE randomized controlled trial

BackgroundThe Mediterranean diet (MD), globally recognized for its sustainability and health benefits, traditionally emphasizes the consumption of plant-based foods in raw or minimally processed forms. However, shifting lifestyles, even in Mediterranean regions, have led to an increasing consumption of ultra-processed foods (UPF). Epidemiological evidence suggests that UPF consumption may be detrimental to human health, but there is only one clinical trial on this topic which is largely debated in the scientific community. This study aims to investigate the impact of the inclusion of UPF within a Mediterranean-based dietary pattern on cardiometabolic markers, gut microbiota, and other markers of human and planet health.MethodsFifty clinically healthy individuals showing overweight and presenting a low-to-moderate cardiovascular risk profile will be recruited for a 7-month randomized, open, cross-over dietary trial. Eligible participants will be randomly assigned to a 3-month high-UPF MD (intervention group) or a low-UPF MD (control group), with a 1-month wash-out period. Both intervention diets will have identical food group compositions, with the intervention group consuming 5 servings/day of selected UPF items, and the control group consuming raw/minimally processed items from the same food group. Blood, urine, and fecal samples, alongside food/lifestyle diaries, will be collected from each participant before and after the dietary interventions. The primary endpoint will be the change in plasma LDL-cholesterol levels from baseline. Additional markers include blood pressure, anthropometric parameters, chemical parameters, glucose and lipid-related metabolic markers, incretins, inflammatory and oxidative stress markers, fecal microbiota composition, and short-chain fatty acids. Finally, food waste production will be evaluated through specific validated food diaries. The study has been approved by the Ethical Committee of the University of Milan and the Tuscany Regional Ethics Committee of the Azienda Ospedaliera Universitaria (AOU) - Careggi, Florence.DiscussionResults from the PROMENADE study will improve knowledge about the impact of UPF consumption on human and planet health and will contribute to the scientific debate on this topic.Trial registrationClinicalTrials.gov NCT06314932. Registered on March 13, 2024.

From applicator-based (Paris system) implantations to rhinoseptoplasty: the concept of anatomic implantation for interventional radiotherapy in squamous cell carcinoma of the nasal vestibule. Short term results in a monoinstitutional series

Aim: Interventional radiotherapy (IRT) is being increasingly advocated as the standard treatment for the primary lesion in nasal vestibule squamous cell carcinoma (NV-SCC). The respect of the anatomical planes of the nose tip during implantation has been hypothesized to reduce the classical IRT toxicities on the cartilages, such as septal and even alar perforations. The present work describes a monoinstitutional series of NV-SCC treated with an IRT technique that follows the above principle (anatomical implantation), with a focus on IRT toxicities. Methods: All consecutive patients with nasal vestibule (NV) carcinoma treated between March 2022 and October 2023 with IRT on the primary lesion at Azienda Ospedaliera Universitaria di Sassari and Mater Olbia Hospital were included. Results: A total of 15 patients were treated with IRT following the principles of anatomical implantation. The only treatment-related toxicity observed has been the mechanical damage to the skin from the buttons used to stabilize the plastic tubes. Conclusion: IRT with anatomical implantation allows a high nose preservation rate and very good cosmetic results, which appear to be decisive advantages in comparison with traditional surgery, while confirming comparable effectiveness from an oncological point of view. However, in the present series, we describe typical skin toxicity that may have a negative impact on cosmetic results. We propose a new strategy involving the use of a soft medium such as a sponge to protect the skin from damage.

Study protocol for Near-infrared molecular imaging for lung cancer detection and treatment during mini-invasive surgery (phase II Trial) - (the RECOGNISE study)

Introduction. To date, radical surgery remains the best curative option in patients with early-stage lung cancer. In patients with small lung lesions, video-assisted thoracic surgery (VATS) should be increasingly chosen as a fundamental alternative to thoracotomy as it is associated with less postoperative pain and better quality of life. This scenario necessarily increases the need for thoracic surgeons to implement new localization techniques. The conventional near-infrared (NIR) indocyanine green (ICG) method demonstrated a significant limitation in deep cancer recognition, principally due to its intrinsic low-depth tissue penetration. Similarly, the lymph-node sentinel approach conducted by the ICG method was demonstrated to be inefficient, mainly due to the non-specificity of the tracker and the irregular pathway of pulmonary lymph node drainage. Our study aims to evaluate the effectiveness of Cetuximab- IRDye800CW in marking lung nodules and mediastinal lymph nodes. Methods and analysis. This study is defined as an open-label, single-arm, single-stage phase II trial evaluating the effectiveness of Cetuximab-IRDye800CW in detecting tumors and lymph-node metastases in patients with lung cancer who are undergoing video-assisted thoracic surgery (VATS). Cetuximab is a monoclonal antibody that binds, inhibits, and degrade the EGFR. The IRDye® 800CW, an indocyanine-type NIR fluorophore, demonstrated enhanced tissue penetration compared to other NIR dyes. The combination with the clinical approved monoclonal antibody anti-epidermal growth factor EGFR Cetuximab (Cetuximab-IRDye800) has shown promising results as a specific tracker in different cancer types (i.e., brain, pancreas, head, and neck). The study’s primary outcome is focused on the proportion of patients with lung nodules detected during surgery using an NIR camera. The secondary outcomes include a broad spectrum of items, including the proportion of patients with detection of unexpected cancer localization during surgery by NIR camera and the proportion of patients with negative surgical margins, the evaluation of the time spawns between the insertion of the NIR camera and the visualization of the nodule and the possible morbidity of the drug assessed during and after the drug infusion. Ethics and dissemination. This trial has been approved by the Ethical Committee of Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino (Torino, Italy) and by the Italian Medicines Agency (AIFA). Findings will be written as methodology papers for conference presentations and published in peer-reviewed journals. The Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino, the University of Torino, and the AIRC Public Engagement Divisions will help identify how best to publicize the findings.Trial registration EudraCT 202,100,645,430. ClinicalTrials.gov NCT06101394 (October 23, 2023).

Convolutional Neural Network-Based Automated Segmentation of Skeletal Muscle and Subcutaneous Adipose Tissue on Thigh MRI in Muscular Dystrophy Patients.

We aim to develop a deep learning-based algorithm for automated segmentation of thigh muscles and subcutaneous adipose tissue (SAT) from T1-weighted muscle MRIs from patients affected by muscular dystrophies (MDs). From March 2019 to February 2022, adult and pediatric patients affected by MDs were enrolled from Azienda Ospedaliera Universitaria Pisana, Pisa, Italy (Institution 1) and the IRCCS Stella Maris Foundation, Calambrone-Pisa, Italy (Institution 2), respectively. All patients underwent a bilateral thighs MRI including an axial T1 weighted in- and out-of-phase (dual-echo). Both muscles and SAT were manually and separately segmented on out-of-phase image sets by a radiologist with 6 years of experience in musculoskeletal imaging. A U-Net1 and U-Net3 were built to automatically segment the SAT, all the thigh muscles together and the three muscular compartments separately. The dataset was randomly split into the on train, validation, and test set. The segmentation performance was assessed through the Dice similarity coefficient (DSC). The final cohort included 23 patients. The estimated DSC for U-Net1 was 96.8%, 95.3%, and 95.6% on train, validation, and test set, respectively, while the estimated accuracy for U-Net3 was 94.1%, 92.9%, and 93.9%. Both of the U-Nets achieved a median DSC of 0.95 for SAT segmentation. The U-Net1 and the U-Net3 achieved an optimal agreement with manual segmentation for the automatic segmentation. The so-developed neural networks have the potential to automatically segment thigh muscles and SAT in patients affected by MDs.

Interventional radiotherapy (brachytherapy) for re-irradiation of recurrent head and neck malignancies: oncologic outcomes and morbidity.

Management of recurrent head and neck cancer (HNC) is challenging. One option in previously irradiated patients is re-irradiation using interventional radiotherapy (IRT), the modern form of brachytherapy. Re-irradiation using IRT can be delivered as an exclusive strategy for salvage or through a postoperative or perioperative approach after salvage surgery. The aim of the present study is to analyse a bicentric Italian series focusing on the use of IRT as a re-irradiation modality and assess the resulting evidence concerning oncologic outcomes and morbidity. This is a retrospective study performed in two referral centres in Italy: Policlinico Universitario Agostino Gemelli in Rome and Azienda Ospedaliera Universitaria in Sassari. All patients who had previously received a full course of external beam RT and have been re-irradiated using high-dose-rate IRT between December 2010 and June 2023 were included. Patients were retreated either by a combination of surgery and perioperative (either endocavitary or interstitial) IRT or by exclusive interstitial IRT. Thirty-four patients were included in the present series, 2 of whom underwent more than one IRT re-irradiation. Notably, no patient reported specific IRT-related toxicities. Median follow-up, excluding patients who died of HNC, was 24.5 months. Two-year local relapse-free survival was 26%, disease-specific survival 39.1%, and overall survival 36.6%. The present series is the largest reported experience of re-irradiation by IRT for HNC in Italy. The very low rate of toxicity confirms IRT as the safest re-irradiation modality. It is noteworthy to underline that IRT is a multidisciplinary strategy based on the close cooperation between surgeons and radiation oncologists during every phase, from the recommendation of treatment and implantation in the operating theatre, to its prescription and dose painting.

Randomised controlled trial combining vitamin E-functionalised chocolate with physical exercise to reduce the risk of protein–energy malnutrition in predementia aged people: study protocol for Choko-Age

ObjectiveProtein–energy malnutrition and the subsequent muscle wasting (sarcopenia) are common ageing complications. It is knowing to be also associated with dementia. Our programme will test the cytoprotective functions of vitamin...

Prevalence and Shifts in Antibiotic Use in an Italian Hospital: A Comparison of 2016 and 2022 Data

Abstract Background Antibiotics are among the most commonly prescribed drugs, but inappropriate prescription rates (molecule, duration or dosage) remain high, leading to the selection of multidrug-resistant microorganisms. This study aims to describe the most commonly used antibiotics in our hospital and compare them to 2016 data. Methods Conducted in November 2022 at the Azienda Ospedaliera Universitaria delle Marche of Ancona (Italy), the study followed the protocol proposed by the European Center for Disease Prevention and Control (ECDC). Patients admitted to wards before 8 a.m. and not discharged at the time of the survey were included. Data from 2022 were compared to the 2016 study. Results In 2022, 41.7% (N = 284) of the 681 patients were taking at least one antibiotic, with 400 antibiotic therapies administered, of which 90.5% were given parenterally. Among the patients on antimicrobial therapy, 40% were being treated for a community infection, 27% for a hospital acquired infection and 19% for surgical prophylaxis. Among all the antimicrobial prescriptions used, the most used class of antibiotics in 2022 was penicillin / beta lactamase inhibitor (21.6%, N = 86), followed by third-generation cephalosporins (11.8%, N = 47), carbapenems (11.6%, N = 46), glycopeptides (8.8%, N = 35), first-generation cephalosporins (8.8%, N = 35) and fluoroquinolones (7.0%, N = 28). Data from 2016 registered a 21.2% prevalence of penicillin / beta lactamase inhibitor, 15.7% of fluoroquinolones, 14.7% of third-generation cephalosporins, 10.5% first-generation cephalosporins, 7.6% of carbapenems and 4.1% of glycopeptides. Conclusions The prevalence of antibiotics used in our hospital has changed after six years. This shift may be due to new patterns of bacterial resistance and new antimicrobial drugs (e.g. cefiderocol). Key messages • Our study found a shift in prevalence of antibiotic use in our hospital after six years. • Penicillin/beta lactamase inhibitors are still the most commonly used antibiotics in our hospital.

Advanced age is an independent prognostic factor of disease progression in high-risk prostate cancer: results in 180 patients treated with robot-assisted radical prostatectomy and extended pelvic lymph node dissection in a tertiary referral center

ObjectivesThis study aimed to assess more clinical and pathological factors associated with prostate cancer (PCa) progression in high-risk PCa patients treated primarily with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND) in a tertiary referral center.Materials and methodsIn a period ranging from January 2013 to October 2020, RARP and ePLND were performed on 180 high-risk patients at Azienda Ospedaliera Universitaria Integrata of Verona (Italy). PCa progression was defined as biochemical recurrence/persistence and/or local recurrence and/or distant metastases. Statistical methods evaluated study endpoints, including Cox’s proportional hazards, Kaplan-Meyer survival curves, and binomial logistic regression models.ResultsThe median age of included patients was 66.5 [62–71] years. Disease progression occurred in 55 patients (30.6%), who were more likely to have advanced age, palpable tumors, and unfavorable pathologic features, including high tumor grade, stage, and pelvic lymph node invasion (PLNI). On multivariate analysis, PCa progression was predicted by advanced age (≥ 70 years) (HR = 2.183; 95% CI = 1.089–4377, p = 0.028), palpable tumors (HR = 3.113; 95% CI = 1.499–6.465), p = 0.002), and PLNI (HR = 2.945; 95% CI = 1.441–6.018, p = 0.003), which were associated with clinical standard factors defining high-risk PCa. Age had a negative prognostic impact on elderly patients, who were less likely to have palpable tumors but more likely to have high-grade tumors.ConclusionsHigh-risk PCa progression was independently predicted by advanced age, palpable tumors, and PLNI, which is associated with standard clinical prognostic factors. Consequently, with increasing age, the prognosis is worse in elderly patients, who represent an unfavorable age group that needs extensive counseling for appropriate and personalized management decisions.

Evaluation of saliva and nasopharyngeal swab sampling for genomic detection of SARS-CoV-2 in children accessing a pediatric emergency department during the second pandemic wave.

SARS-CoV-2 infection is mainly detected by multiplex real-time RT-PCR from upper respiratory specimens, which is considered the gold-standard technique for SARS-CoV-2 infection diagnosis. A nasopharyngeal (NP) swab represents the clinical sample of choice, but NP swabbing can be uncomfortable to the patients, especially for pediatric-age participants, requires trained healthcare personnel, and may generate an aerosol, increasing the intrinsic exposure risk of healthcare workers. The objective of this study was to compare paired NP and saliva samples (SS) collected from pediatric patients to evaluate whether the saliva collection procedure may be considered a valuable alternative to the classical NP swab (NPS) sampling in children. In this study, we describe a SARS-CoV-2 multiplex real-time RT-PCR protocol for SS, comparing the results with the paired NPS specimens from 256 pediatric patients (mean age 4.24 ± 4.40 years) admitted to the hospital emergency room of Azienda Ospedaliera Universitaria Integrata (AOUI), Verona, and randomly enrolled between September 2020 and December 2020. The saliva sampling demonstrated consistent results when compared to NPS use. The SARS-CoV-2 genome was detected in 16 out of 256 (6.25%) NP samples, among which 13 (5.07%) were positive even when paired SS were analyzed. Moreover, SARS-CoV-2-negative NPS and SS were consistent, and the overall concordances between NPS and SS were detected in 253 out of 256 samples (98.83%). Our results suggest that saliva samples may be considered a valuable alternative to NPS for SARS-CoV-2 direct diagnosis with multiplex real-time RT-PCR in pediatric patients.

The humoral and cellular response to mRNA SARS-CoV-2 vaccine is influenced by HLA polymorphisms.

Host genetic variability contributes to susceptibility to SARS-CoV-2 infection and COVID-19 evolution and the role of HLA system has not clearly emerged, suggesting the involvement of other factors. Studying response to vaccination with Spyke protein mRNA represents an ideal model to highlight whether the humoral or cellular responses are influenced by HLA. Four hundred and sixteen workers, vaccinated with Comirnaty beginning 2021, were selected within the Azienda Ospedaliera Universitaria "Città della Salute e della Scienza di Torino." The humoral response was determined with the LIAISON® kit, while the analysis of the cellular response was performed with the Quantiferon SARS-CoV-2 assay, for the S1 (receptor-binding domain; Ag1) and S1 and S2 (Ag2) subunits of the Spyke protein. Six HLA loci were typed by next-generation sequencing. Associations between HLA and vaccine response were performed with univariate and multivariate analyses. An association was found between A*03:01, B*40:02 and DPB1*06:01 and high antibody concentration and between A*24:02, B*08:01 and C*07:01 and low humoral responses. The haplotype HLA-A*01:01 ~ B1*08:01 ~ C*07:01 ~ DRB1*03:01 ~ DQB1*02:01 conferred an increased risk of low humoral response. Considering cellular responses, 50% of the vaccinated subjects responded against Ag1 and 59% against Ag2. Carriers of DRB1*15:01 displayed a higher cellular response both to Ag1 and Ag2 compared to the rest of the cohort. Similarly, DRB1*13:02 predisposed to a robust cellular response to Ag1 and Ag2, while DRB1*11:04 showed an opposite trend. Cellular and humoral responses to Comirnaty are influenced by HLA. Humoral response is mainly associated to class I alleles, with A*03:01, previously associated to protection against severe COVID-19, and response to vaccination, standing out. Cellular response predominantly involves class II alleles, with DRB1*15:01 and DPB1*13:01 prevailing. Affinity analysis for Spyke peptides is generally in line with the association results.

Clinical characteristics and risk factors for mortality in COVID-19 patients during the first wave of the COVID-19 pandemic in Rome, Italy: a single-center retrospective study.

Since the beginning of 2020, the SARS-CoV-2 pandemic has become a serious public health problem. Numerous studies have highlighted the main clinical features of COVID-19, mainly the huge heterogeneity of the clinical manifestations that can vary from asymptomatic infection to serious viral pneumonia with a high mortality rate. The aim of this study was to analyze retrospectively the clinical characteristics and assess the risk factors for mortality in an Italian cohort of patients with COVID-19. Retrospective analysis including patients with COVID-19 admitted to the Infectious Diseases wards of Azienda Ospedaliera Universitaria Policlinico "Umberto 1", Rome, from March 2020 to May 2020. The data were part of an electronic anonymous web-based database processed by SIMIT (Italian Society of Infectious and Tropical Diseases). 258 patients were included in the analysis, and 34 (13.2%) died. The median age was 62 (IQR, 52-74), 106 (40%) were women, and 152 (60%) were males, 172 (66.7%) had at least one co-morbidity. The most common signs and symptoms were: fever [221 (85.6%)], cough [135 (52.3%)], and dyspnea [133 (51.5%)]. The PaO2/FiO2 ratio was often altered [352 (IQR, 308-424)]. Lymphopenia [lymphocyte counts, 875/μL (IQR, 640-1250)] and high levels of D-dimer [mg/dL, 874 (IQR, 484-1518)] were found. Non-survivors were older than survivors [median age, 74 (IQR, 67-85)] vs. 61 (QR, 51-72)], mostly men [25 (73.5%)] and more frequently with more than 2 comorbidities [21 (61.8%) vs. 94 (42.1%)]. In the multiple logistic regression model, the variables associated with in-hospital mortality were age [OR, 3.65 (95% CI, 1.22-10.89)], male gender [OR, 2.99 (95% CI, 1.18-7.54)], blood urea [OR, 2.76 (95% CI, 1.20-6.35)] and a low PaO2/FiO2 ratio [OR, 0.28 (95% CI, 0.12-0.62)]. The mortality rate in COVID-19 was 13,2%. The risk factors associated with in-hospital mortality were advanced age, male sex, increased blood urea, and the PaO2/FiO2 ratio reduction.

Clinical activity of regorafenib in elderly patients with recurrent glioblastoma.

Glioblastoma multiforme is one of the most frequent and aggressive primary tumors in the central nervous system, representing >60% of all brain tumors in adults. Despite treatment, prognosis remains poor with most if not all patients experiencing disease recurrence and a 2-year survival rate of 27%. At present, no confirmed standard treatment exists for recurrent glioblastoma. Regorafenib is one of the few options available, based on results from the REGOMA trial. In the present study, a real-life retrospective investigation on the role of regorafenib in patients with recurrent glioblastoma (>60 years old) from two main Oncological Units in South Italy (Azienda Ospedaliera Universitaria Luigi Vanvitelli, Naples, Italy and Ospedale Civile San Giovanni di Dio, Frattamaggiore, Naples, Italy), was performed. The primary endpoint was overall survival (OS), whereas progression-free survival (PFS), objective response rate and disease control were secondary endpoints. Survival was then analyzed according to age, isocitrate dehydrogenase (IDH) and methylated methylguanine-DNA-methyltransferase (MGMT) status. A total of 56 patients met the eligibility criteria. The intention to treat population median PFS (mPFS) was 4.1 months and median OS (mOS) was 6.8 months. Age did not appear to have a significant influence on mPFS. mOS in MGMT-methylated patients was improved compared with that of the unmethylated group (7.7 months vs. 5.6 months). Both mOS and mPFS were longer in IDH-mutant patients. The present study was one of the first real life analyses of regorafenib in recurrent glioblastoma. The results were in line with the REGOMA trial. Age did not appear to be a prognostic factor, thus suggesting that treatment choice should not be different in elderly. MGMT methylation appeared to influence OS. To the best of our knowledge, this was the first report of regorafenib activity in older patients and, while the results were statistically significant, these should be confirmed in further studies.

Recent Advances in the Management of Gastrointestinal Disease

Interdisciplinary sessions at the recent United European Gastroenterology (UEG) Week, held in Vienna, Austria, from 8th to 11th October 2022, covered new approaches to the diagnosis and treatment of gastrointestinal and hepatic disorders, with a focus on advances in the non-invasive management of these diseases. Abstract-based and poster sessions presented original research from Europe and other parts of the world. This review summarises selected data presented in the fields of inflammatory bowel disease (IBD), disorders of gut–brain interaction (DGBI), gastro-oesophageal reflux disease (GORD), and disorders of the pancreas. Previously termed functional gastrointestinal disorders, the Rome Foundation is gradually moving toward the use of DGBI in place of functional gastrointestinal disorders to avoid stigma. Cristina Rubín de Célix, Gastroenterology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-Princesa), Universidad Autónoma de Madrid (UAM), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Spain, described a systematic review and meta-analysis of real-world evidence for ustekinumab in the treatment of Crohn’s disease. Regarding irritable bowel syndrome (IBS), Salvatore Crucillà, Gastroenterology Unit, Azienda Ospedaliera Universitaria Integrata Verona, Italy, showed that following a Mediterranean diet resulted in symptom improvement and faecal microbiota changes in patients with constipation-predominant IBS. Fiona Kinnear, Novozymes A/S, Cork, Ireland, reported patients’ experiences of probiotics for IBS. Tatyana Kugler, Department of Internal Medicine, Donetsk National Medical University, Ukraine, discussed quality of life (QoL) in patients with functional dyspepsia (FD), and Ayesha Shah, Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, and Faculty of Medicine and Faculty of Health and Behavioural Sciences, University of Queensland, Brisbane, Australia, considered the impact of a diagnosis of more than one DGBI. James White, Medscape Global Education, London, UK, considered the impact of continuing medical education (CME) on confidence in the management of GORD. Additionally, Peter Macinga, Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague, Czechia, provided evidence that chronic pancreatitis is associated with an alteration in the gut microbiota, and Joakim Svahn, Viatris AB, Stockholm, Sweden, described the use of a patient support programme (PSP) in patients prescribed pancreatic enzyme replacement therapy (PERT) for pancreatic exocrine insufficiency (PEI).

Integrated system for the proactive analisys of risk infection in patient’s surgical route

Abstract Background The most common hospital safety incidents are Hospital-Acquired-Infections (HAI) and among these Surgical Site Infections (SSIs). Our study proposes the use of a proactive system to manage risk combining the new Risk Identification Framework by WHO (IPCAF), the Lean method and the hospital’s Procedure Analysis. Each of the methods has pros and cons, and there is no existing literature that researches the concurrent use of all three methods. We focused on analysing patients’ surgical route to demonstrate that using an integrated system for preventing SSIs delivers enhanced results and significantly contibutes to a reduction in occurence of SSIs. Methods We conducted a retrospective observational study from 18 March 2019 to 20 April 2019 at Azienda Ospedaliera Universitaria Federico II di Napoli, Italia (Europa). The study is structured in 3 phases: Phase 1- application of proactive risk management tools (18 March- 15 April 2019); Phase 2-integration of results with the elaboration of a single system for proactive risk management (15-20 April 2019); Phase 3- collection of epidemiologic data concerning SSI. We used the incidence of surgical site as efficiency indicator (1-10 March 2022). The endpoints identified were: Primary Endpoint: a reduction of infection occurrence in surgical sites Secondary Endpoint: identification of critical points and control points within the surgical process with relevant corrective measures Results The rate of incidence of SSIs was selected as the efficacy indicator for the system. Our study recorded a 2.40% incidence rate for SSIs in 2020, compared to an incidence rate of 3.80% in 2018 and of 3.5% in 2017. Conclusions Considering the economic impact of the infections, along with the increased incidence of mortality and morbidity, employing all available tools to try and reduce SSIs incidence becomes paramount. A small reduction can produce significant cost savings that can be invested in other prevention programs. Key messages • Integrated system in proactively and promptly identifying risks related to patients’ surgical routes is effectiveness. • The system can be adapted to different healthcare settings, to prevent adverse incidents by employing a risk management strategy, and to further enhance existing strategies.

MTOR Inhibitor Use Is Associated With a Favorable Outcome of COVID-19 in Patients of Kidney Transplant: Results of a Retrospective Study.

IntroductionIn solid organ transplant recipients, COVID-19 is associated with a poor prognosis because of immunosuppression. Some studies suggest a potential therapeutic role of mammalian Target of Rapamycin (mTOR) inhibitors in SARS-CoV-2 infection. This study aimed to assess the impact of mTOR employment on the evolution and outcome of SARS-CoV-2 infection in solid organ transplant recipients.MethodsWe enrolled kidney transplant patients attending the Azienda Ospedaliera Universitaria Federico II in Naples and followed up on these patients from March 2020 to June 2021. We evaluated the risk of acquiring the SARS-CoV-2 infection, the clinical presentation of the disease, and its outcome together with the type of immunosuppressive therapy. Finally, we assessed the impact of mTOR inhibitors on relevant clinical metrics of SARS-CoV-2 infection.ResultsWe enrolled 371 patients, of whom 56 (15.1%) contracted SARS-CoV-2 infection during the period of the study. There were no differences observed among the different immunosuppressive therapies concerning the risk of acquiring SARS-CoV-2 infection. In contrast, the type of immunosuppressive therapy had a significant impact on the outcome of the disease. In detail, patients who received mTOR inhibitors, as part of their immunosuppressive therapy, compared to other regimens had a lower chance of developing a moderate or severe form of the disease (OR = 0.8, 95, CI: (0.21–0.92), P = 0.041).ConclusionIn kidney transplant patients, the use of mTOR inhibitors as part of an immunosuppressive regimen is associated with a better prognosis in the case of COVID-19.