Azienda Ospedaliero-Universitaria Research Articles

Molecular Tumour Board (MTB): From Standard Therapy to Precision Medicine.

Background: In the metastatic setting, cancer patients may not benefit from standard care regimes and their diseases undergo drug resistance due to tumour cell heterogeneity and genomic landscape complexity. In recent years, there have been several attempts to personalise the diagnostic-therapeutic path and to propose novel strategies based on not only histological test results but also on each patient's clinical history and molecular biology. Profiling molecular tests allows physicians to investigate the single tumour genomic landscape and to promote targeted approaches. The Molecular Tumour Board (MTB) is a multidisciplinary committee dedicated to selecting individualised and targeted therapeutic strategies appropriate for patients suffering from diseases that present resistance to standard care. Materials and Methods: Our MTB settled in "Azienda Ospedaliero Universitaria delle Marche", Ancona (AN), Italy, and includes oncologists, molecular biologists, geneticists, and other specialists. Clinical cases are referred by physicians to the MTB, through the Cancer and Research Centre of the Marche Region (CORM), through a telemedicine platform. Four possible molecular profiles are available: FoundationOne® CDx e FoundationOne®Liquid CDx and two local Next Generation Sequencing (NGS) panels, with 16 DNA genes and 10 RNA genes respectively. The resulting genetic mutations and their analyses are evaluated by all the members of the Board and a report for each patient is provided with medical recommendations. Results: from June 2021 to May 2023, we collected data from 97 referral patients (M: 49, F: 48). The mean age was 60.6 years (range 22-83 years). 90 cases were approved for testing. Only seven patients were not eligible for genomic profiling. In two patients who were eligible, molecular profiling was not performed because a tissue sample was not available. Off-label therapy was recommended for three patients. 5% of cases (5/88) showed addressable driver mutations associated with an existing targeted therapy and were immediately enrolled. Conclusions: MTB presents a powerful tool for offering precise medical goals. Our Department of Clinical Oncology also takes advantage of the important role of multidisciplinary teams, through the establishment of CORM and MTB meetings, within which there is the chance to perform NGS-based analyses. It will be important in the future to implement the use of genomic profiling to improve personalised care and to guide the choice of suitable therapies and more appropriate management of patients.

Retrolental cohesive ophthalmic viscoelastic injection in severely subluxated cataracts: The "Viscolift technique".

To describe a novel surgical approach in the management of subluxated cataracts. A 70-year-old Caucasian male with a subluxated cataract in the left eye was referred to our clinic at the Azienda Ospedaliero-Universitaria di Bologna- Ophthalmology Unit. The ophthalmic examination revealed a best-corrected visual acuity (BCVA) of 20/200 in the left eye with monocular diplopia and a severely subluxated NO6/NC6 cataract and the fundus examination did not reveal any vitreoretinal abnormalities. The right eye had 20/20 BCVA and was pseudophakic. After a 300° conjunctival peritomy, a single 25-gauge valved trocar 4 mm was inserted from the limbus in the inferotemporal quadrant, where the cataract was mainly dislocated and a corneal paracentesis to reduce the anterior chamber intraocular pressure was performed. Subsequently cohesive viscoelastic was progressively injected in the retrolental space through the trocar, to recenter and elevate the subluxated cataract. Thereafter, a complete centered capsulorhexis was performed, four capsular hooks were inserted to stabilize the bag, and complete phacoemulsification was performed with intact posterior capsular support. In the end, given the lack of capsular support elements such as the Cionni ring or Ahmed segment, a sutureless scleral fixated intraocular lens was implanted. One week after surgery, the BCVA was 20/25, and the final BCVA at 6 months was 20/20, without any complications. Retrolental cohesive ophthalmic viscoelastic injection could represent a novel effective surgical approach in recentering and elevating subluxated cataracts, facilitating the capsulorhexis, and reducing the risk of a pars plana approach.

Does therapeutic drug monitoring (TDM) of trough concentrations suffice for optimizing preemptive therapy with ganciclovir of cytomegalovirus infections in non-renal solid organ transplant recipients?

The aim of this study is to explore the relationship between ganciclovir exposure and clinical efficacy and/or safety in non-renal solid organ transplant (SOT) recipients receiving preemptive therapy with ganciclovir/valganciclovir and undergoing therapeutic drug monitoring (TDM)-guided dosing optimization. Non-renal SOT recipients admitted to IRCCS Azienda Ospedaliero-Universitaria of Bologna receiving preemptive therapy with ganciclovir or valganciclovir for active cytomegalovirus (CMV) infection and who underwent at least one TDM were included. Desired ganciclovir Cmin range was set at 1-3mg/L, and average ganciclovir trough concentrations (Cmin ) were calculated for each patient. Reduced CMV viral load below the lower limit of quantification (LLQ) at 30 days and occurrence of myelotoxicity were selected as the primary outcome. Univariate analysis was performed by comparing patients with average Cmin below or above 1 or 3mg/L. Receiver operating characteristic (ROC) curve analysis was performed to identify the average ganciclovir Cmin cut-off predictive for clinical efficacy or toxicity. Twenty-nine out of 89 retrieved patients met the inclusion criteria, with a median (interquartile [IQR]) baseline CMV viral load of 27,163 copies/mL (IQR 13159.75-151340.25 copies/mL). Reduced CMV viral load below the LLQ at 30 days was found in 17 patients (58.6%). No difference was found in the primary outcome between patients showing average Cmin below or above 1mg/L (100.0%vs. 53.8%; p= .25) and/or 3mg/L (65.2%vs. 33.3%; p = .20). ROC analysis did not allow to identify an average Cmin cut-off predictive of clinical efficacy or toxicity. No clear relationship between ganciclovir Cmin and neither CMV eradication nor safety issues was identified.

Possible Use of Linear Echobronchoscope for Diagnosis of Peripheral Pulmonary Nodules.

Echobronchoscope-guided transbronchial needle aspiration (EBUS-TBNA) is mainly used as the transbronchial approach to hilar/mediastinal lymph nodes or lesions, for diagnostic or staging purposes. Moreover, the role of linear EBUS-TBNA as a diagnostic tool for central intrapulmonary lesions adjacent to the trachea or the major bronchi is also well established. However, since the tip of the ultrasound probe at the distal end of the echobronchoscope is very thin, it can be wedged through smaller peripheral bronchi, reaching the distal parenchyma and allowing for peripheral pulmonary lesion sampling. The main aim of this retrospective study was to evaluate the diagnostic yield and the safety of EBUS-TBNA in the diagnosis of pulmonary peripheral nodules. The database of the Interventional Pulmonology Unit of Azienda Ospedaliero-Universitaria delle Marche (Ancona, Italy) was evaluated to identify peripheral pulmonary nodules approached by EBUS-TBNA. Thirty patients with a single peripheral pulmonary nodule located peripherally to the subsegmental bronchi of the lower lobes and adjacent to a small bronchus greater than 3 mm in diameter were included in this study. The nodule was visible using endoscopic ultrasound in 28 patients and the diagnosis was obtained via EBUS-TBNA in 26 cases (12 adenocarcinoma, 5 typical carcinoid tumors, 4 hamartoma and 5 metastatic lesions). The diagnostic yield was 86.6% for all 30 patients and 92.8% if only the 28 patients in which the lesion was visualized via echobronchoscopy were considered. No relevant adverse events were observed. We conclude that EBUS-TBNA may be an effective and safe option to sample pulmonary peripheral nodules in selected patients with lower lobe peripheral pulmonary lesions adjacent to small bronchi greater than 3 mm in diameter and reachable with the EBUS-TBNA probe.

O-062 MicroRNAs in Blastocoel Fluid: a molecular signature for predicting human embryo implantation potential

Abstract Study question Can microRNA expression in blastocoel fluid (BF) predict embryo implantation potential? Summary answer Up-regulation of miR-106, miR-373, miR-301, miR-320 and miR-525-3p represents the molecular signature characterizing the embryos with high implantation capability. What is known already The discovery of DNA within the BF and in spent embryo culture media, has caused increased interest in the non-invasive preimplantation testing application for monogenic disorders and aneuploidies. Aneuploid embryos have a lower implantation potential, however, chromosomal abnormalities represent only a tiny percentage of the causes of implantation failure. MiRNAs can control all cellular pathways and are involved in pluripotency, self-renewal, and stemness, and their altered regulation affects different human diseases. Study design, size, duration From September 2018 to March 2022, 112 BFsampleswere collected from human embryos on the fifth day of development, before the blastocyst cryopreservation. The samples were classified according to blastocyst grade and the data on implantation outcome and term births were collected for the transferred embryos. We compared the expression profiles of 89 miRNAs, previously identified in BF, between 33 BF from implanted embryos and 30 from non-implanted ones, regardless of blastocyst grade. Participants/materials, setting, methods By custom-designed TaqMan Low-Density Array card (TLDA), we analyzed the expression of 89 miRNAs in 4 different BF samples simultaneously. Differentially expressed (DE) miRNAs were identified by Volcano plot and Significance Analysis of Microarrays (SAM) tests. Bioinformatic analysis was performed to identify the biological role of the DE miRNAs. To evaluate miRNA’s ability for predicting implantation, Pearson’s correlation analyses, classical univariate Receiver Operator Characteristic (ROC) curve analysis, and the optimal cut-off value determination were performed. Main results and the role of chance We found five miRNAs, miR-106, miR-373, miR-301, miR-320 and miR-525-3pup-regulated in BF from implanted blastocysts. The identified miRNAs perform an important role during the first phases of embryo development suggesting that their up-regulation may reflect embryo health. Moreover, four of the five miRNAs showed significant correlation coefficients in both implanted and non-implanted blastocysts, indicating that their expression changes in the same way in the single sample and reflects the potentiality of the embryo to implant. Finally, ROC curve analysis confirmed that our miRNAs could be considered potential biomarkers for implantation. Limitations, reasons for caution Successful implantation requires a close dialogue between the embryo and the endometrium, mediated by different proteins and miRNAs produced by both the embryo and maternal tissues. Determining the quality of the embryo and its implantation potential is not sufficient to predict successful pregnancy outcomes. Wider implications of the findings This study represents the first report correlating miRNA profiles in BFand implantation and suggests that miRNA signature could become an accurate tool to evaluate embryo quality. It could be associated or replaced with the PGT-A to choose the most competent embryo and improve the outcome of assisted reproduction cycles. Trial registration number The study has been approved by theEthical Committee of Azienda Ospedaliero Universitaria Policlinico "G.Rodolico -San Marco" Catania.

An Explainable Radiogenomic Framework to Predict Mutational Status of KRAS and EGFR in Lung Adenocarcinoma Patients.

The complex pathobiology of lung cancer, and its spread worldwide, has prompted research studies that combine radiomic and genomic approaches. Indeed, the early identification of genetic alterations and driver mutations affecting the tumor is fundamental for correctly formulating the prognosis and therapeutic response. In this work, we propose a radiogenomic workflow to detect the presence of KRAS and EGFR mutations using radiomic features extracted from computed tomography images of patients affected by lung adenocarcinoma. To this aim, we investigated several feature selection algorithms to identify the most significant and uncorrelated sets of radiomic features and different classification models to reveal the mutational status. Then, we employed the SHAP (SHapley Additive exPlanations) technique to increase the understanding of the contribution given by specific radiomic features to the identification of the investigated mutations. Two cohorts of patients with lung adenocarcinoma were used for the study. The first one, obtained from the Cancer Imaging Archive (TCIA), consisted of 60 cases (25% EGFR, 23% KRAS); the second one, provided by the Azienda Ospedaliero-Universitaria 'Ospedali Riuniti' of Foggia, was composed of 55 cases (16% EGFR, 28% KRAS). The best-performing models proposed in our study achieved an AUC of 0.69 and 0.82 on the validation set for predicting the mutational status of EGFR and KRAS, respectively. The Multi-layer Perceptron model emerged as the top-performing model for both oncogenes, in some cases outperforming the state of the art. This study showed that radiomic features can be associated with EGFR and KRAS mutational status in patients with lung adenocarcinoma.

#6073 MAGNETIC RESONANCE RADIOMIC ANALYSIS FOR THE PREDICTION OF GRAFT FAILURE IN PATIENTS WITH KIDNEY TRANSPLANTATION

Abstract Background and Aims Prediction of future graft failure with non-invasive investigations is a relevant objective for transplant clinicians. We previously demonstrated a promising discrimination capacity for interstitial fibrosis / tubular atrophy (IFTA) >50% in kidney biopsy of a machine learning (ML) based magnetic resonance imaging (MRI) radiomic algorithm. Aim of the present study is to evaluate accuracy of MRI radiomic-based ML algorithms in predicting future graft failure. Method Single-center retrospective observational cohort study on a previously characterized cohort of kidney transplant recipients who underwent graft biopsy and graft MRI imaging within 6 months from biopsy, both on clinical indication, at the “Azienda Ospedaliero-Universitaria di Modena”, Italy, from 1/1/2012 to 1/3/2021. The primary outcome was to identify the best combination of MRI radiomic features for the prediction of graft failure during follow-up. Segmentation of renal parenchyma, cortex and medulla on MRI sequences was performed using the 3DSlicer software. Radiomic features were then extracted using an in-house software based on pyradiomics applying Wavelet and Gaussian filters. LASSO algorithm was employed to select correlated features with outcome and summarize them in a radiomic signature. Using radiomic signature alone and then merged with meaningful clinical data we trained ML-algorithms using 70% of cases for training/validation, with a 10-fold internal cross-validation, and 30% for model testing. Model performance was assessed using AUC with a 95% confidence interval (CI). Results Seventy coupled tests (63 patients) were included and randomly subdivided into a training/validation cohort (n = 50) and a test cohort (n = 20). Median follow-up was 24.73 months (interquartile range 13.64-46.57). Radiomic model had an AUC of 0.88 (95%_CI 0.70-0.97) in training and 0.57 (95%_CI 0.23-0.86) in test cohort. Radiomic-clinical mixed model had an AUC of 0.90 (95%_CI 0.73-0.98) in training and 0.66 (95%_CI 0.33-0.88) in test cohort. Conclusion We produced an MRI radiomic-based ML algorithm with good prediction ability for future graft failure in patients with kidney transplant. Given the limited number of enrolled patients, validation in larger (and ideally prospective) cohorts is required to confirm our findings. Comparison of radiomic-based ML with histological parameters (i.e., IFTA) for the prediction of graft failure in our cohort is currently under assessment.

The decision-making process in out-of-hospital cardiac arrest: from complexity to opportunities.

Intensive Care Unit and Regional ECMO Referral Centre, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy Received 1 May 2023 Accepted 3 May 2023. Correspondence to Chiara Lazzeri, MD, Intensive Care Unit and Regional ECMO Referral Centre Emergency Department, Largo Brambilla 3, 50134, Florence, Italy, Tel: +39 55 7947823; fax: +39 55 7947821; e-mail: [email protected]

Comparing implications of cardiovascular risk of abacavir and integrase inhibitors: why scientific community is confused and timid?

aModena HIV Metabolic Clinic bDepartment of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia cDepartment of Infectious Diseases, Azienda Ospedaliero-Universitaria, Policlinico of Modena, Modena, Italy. Correspondence to Giovanni Guaraldi, MD, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Largo del Pozzo 71, 41124 Modena, Italy. Tel: +39 059 422 5318; fax: +39 335 33 34 34; e-mail: [email protected] Received 13 January, 2023 Accepted 8 February, 2023

A Case of Robot-Assisted Repair of Lymphatic Fistula with Chylous Ascites Following Robotic Retroperitoneal Lymph Node Dissection

Clinical History: A 47-year-old patient, with a history of testicular tumor treated with chemotherapy and robotic retroperitoneal lymph node dissection, experienced recurrent postoperative chylous ascites despite conservative management. Therefore, decision was made to perform robot-assisted exploration to find the source of chyle leakage and to repair it. Physical Examination: Shifting dullness refers to a sign elicited on abdominal examination for ascites, see: https://en.wikipedia.org/wiki/Shifting_dullness. The patient had this sign on abdominal examination at the time of the intervention, as explained in the video. Diagnosis: Inguinal intranodal lymphography was performed, showing an effusion at the level of the third lumbar vertebral body that was embolized. Intervention: On robot-assisted abdominal exploration, intraperitoneal lymphatic effusion was noted from the left para-aortic region, close to the left renal artery. The lymphatic vessels of greater caliber were then closed with metal clips, until all the major sources of lymph effusion were under control. Next, a continuous suture running over the remaining para-aortic lymphatic tissue was applied. Once the suture was completed, methylene blue was then introduced through the nasogastric tube, with no effusion resulting from the lymphatic tissue at any level in the abdomen. A layer of hemostatic matrix was then added and a tubular drain was placed in the retroperitoneum, with its tip laying on the effusion site. The peritoneum was closed and after a final check of the hemostasis, the robotic trocars were removed and the port sites closed. Follow-Up Outcomes: The drain was removed after 72 hours. Since the intervention, the patient did not experience any further recurrence. In this first description, robotic approach was feasible and efficient in management of postoperative chylous ascites not responding to conservative treatment. The authors have received and archived patient consent for video recording/publication in advance of video recording of procedure. The authors declare that they have not had any commercial associations during the past 3 years that might create a conflict of interest in connection with the video. This study is derived from the “IRCCS Azienda Ospedaliero-Universitaria di Bologna,” and there are no conflicts of interest or obligations resulting from it. Runtime of video: 4 mins 22 secs

Evaluation of the number of accesses with "codice rosa" to the emergency department of Azienda Ospedaliero-Universitaria Pisana (A.O.U.P.): a care path for victims of violence/abuse

Evaluation of the number of accesses with "codice rosa" to the emergency department of Azienda Ospedaliero-Universitaria Pisana (A.O.U.P.): a care path for victims of violence/abuse

From Leonardo to the Valsalva graft: the physics behind valve-sparing aortic root replacement.

Journal Article Accepted manuscript From Leonardo to the Valsalva graft: the physics behind valve-sparing aortic root replacement Get access Giacomo Murana, MD, PhD, Giacomo Murana, MD, PhD Division of Cardiac Surgery, Cardiac Surgery Department, IRCCS, Azienda Ospedaliero-Universitaria di Bologna Corresponding author: Dr. Giacomo Murana, Cardiac Surgery Department, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Via Massarenti 9, 40138, Bologna, Italy. Tel: 0039 051 2143361 Fax: 0039 051 345990. e-mail: g.murana@hotmail.com; giacomo.murana@aosp.bo.it Search for other works by this author on: Oxford Academic PubMed Google Scholar Davide Pacini, MD, PhD Davide Pacini, MD, PhD Division of Cardiac Surgery, Cardiac Surgery Department, IRCCS, Azienda Ospedaliero-Universitaria di BolognaDepartment of Experimental, Diagnostic and Specialty Medicine, DIMES, University of Bologna, Bologna Search for other works by this author on: Oxford Academic PubMed Google Scholar European Journal of Cardio-Thoracic Surgery, ezad094, https://doi.org/10.1093/ejcts/ezad094 Published: 13 March 2023 Article history Received: 06 March 2023 Accepted: 11 March 2023 Published: 13 March 2023

Evaluation, Description and Magnitude of Readmission Phenomenon in Azienda Ospedaliero Universitaria Pisana (AOUP) for Chronic-Degenerative Diseases in the Period 2018–2021

Readmissions are hospitalizations following a previous hospitalization (called index hospitalization) of the same patient that occurred in the same facility or nursing home. They may be a consequence of the progression of the natural history of a disease, but they may also reveal a previous suboptimal stay, or ineffective management of the underlying clinical condition. Preventing avoidable readmissions has the potential to improve both a patient's quality of life, by avoiding exposure to the risks of re-hospitalization, and the financial well-being of health care systems. We investigated the magnitude of 30 day repeat hospitalizations for the same Major Diagnostic Category (MDC) in the Azienda Ospedaliero Universitaria Pisana (AOUP) over the period from 2018 to 2021. Records were divided into only admissions, index admissions and repeated admission. The length of the stay of all groups was compared using analysis of variance and subsequent multi-comparison tests. Results showed a reduction in readmissions over the period examined (from 5.36% in 2018 to 4.46% in 2021), likely due to reduced access to care during the COVID-19 pandemic. We also observed that readmissions predominantly affect the male sex, older age groups, and patients with medical Diagnosis Related Groups (DRGs). The length of stay of readmissions was longer than that of index hospitalization (difference of 1.57 days, 95% CI 1.36-1.78 days, p < 0.001). The length of stay of index hospitalization is longer than that of single hospitalization (difference of 0.62 days, 95% CI 0.52-0.72 days, p < 0.001). A patient who goes for readmission thus has an overall hospitalization duration of almost two and a half times the length of the stay of a patient with single hospitalization, considering both index hospitalization and readmission. This represents a heavy use of hospital resources, about 10,200 more inpatient days than single hospitalizations, corresponding to a 30-bed ward working with an occupancy rate of 95%. Knowledge of readmissions is an important piece of information in health planning and a useful tool for monitoring the quality of models of patient care.

Effect of ospemifene on vaginal microbiome in postmenopausal women with vulvovaginal atrophy.

This study aimed (i) to compare the vaginal microbiome profiles of women suffering from vulvovaginal atrophy with that of healthy postmenopausal women and to (ii) assess the effect of ospemifene and systemic hormone treatment on the composition of the vaginal microbiome. Sixty-seven postmenopausal women attending the Gynecology Clinic of Azienda Ospedaliero-Universitaria of Bologna (Italy) were enrolled. Of them, 39 received a diagnosis of atrophy and 28 were considered healthy controls. In the group of atrophic women, 20 were prescribed ospemifene and 19 received hormone treatment. The vaginal health index was calculated, and a vaginal swab was collected for the assessment of vaginal maturation index and the analysis of vaginal microbiome through 16S rRNA gene sequencing. Clinical/microbiological analyses were repeated after 3 months of treatment. The vaginal microbiome of atrophic women was characterized by a significant reduction of Lactobacillus ( P = 0.002) and an increase of Streptococcus ( P = 0.008) and Sneathia ( P = 0.02). A positive correlation between vaginal health index/vaginal maturation index and Lactobacillus abundance was found ( P = 0.002 and P = 0.035, respectively). Both therapeutic approaches effectively improved vaginal indices. Systemic hormone treatment induced changes in minority bacterial groups of the vaginal microbiome, whereas ospemifene was able to eliminate specific bacterial taxa, such as Staphylococcus ( P = 0.04) and Clostridium ( P = 0.01). Both treatments induced a trend in the increase of bifidobacteria. The vaginal microbiome of atrophic women differs significantly from that of healthy postmenopausal women. Ospemifene may lead to a condition of vaginal health, likely characterized by the reduction of "potentially harmful" bacteria.

2300. Neonates born to mothers with SARS-CoV-2 infection in pregnancy: a follow-up and serological study

Abstract Background To evaluate the early and late clinical outcomes of neonates born to mothers with SARS-CoV-2 infection in pregnancy, the dynamics of maternal IgG trans placental transfer and its persistence during the first month of life. Methods Prospective study enrolling neonates born to mothers with SARS-CoV-2 infection in pregnancy at IRCCS Azienda Ospedaliero Universitaria di Bologna, Italy, between April 2020 and September 2021. Neonates born to women with infection onset before 2 weeks prior to delivery were enrolled in a 12-month follow-up, including clinical and laboratory evaluations, cranial ultrasound, fundoscopy evaluation. Quantitative IgG to S1/S2 subunits of spike protein were assessed in mother-neonate dyads within 48 hours post-delivery and during follow-up until negative. Transplacental IgG transfer ratio was assessed in relation to the type and trimester of maternal infection. Results One hundred and forty-five neonates were included. the rate of preterm delivery was similar between women with and without SARS-CoV-2 infection (6.2% versus 8.7%, P=0.53). No clinical, laboratory, cerebral and fundoscopy abnormalities were detected at birth or during follow-up, through 11 months (range 8–12). MedianIgG level at birth was not different between neonates born to asymptomatic or symptomatic mothers (18.5 AU/mL, IQR 12–49, versus 31.5 AU/mL, IQR 15–71, P=0.07) nor in relation to the trimester of maternal infection (Table 1), even though mothers with third trimester infections had higher IgG level at birth. Transplacental transfer ratio was higher following second trimester maternal infections and was the lowest following third trimester infections (Table 1). Maternally derived IgG were rapidly weaned, with most infants (115/140, 82%) seronegative by 4 months of age. Conclusion Early and later outcomes of infants born to SARS-CoV-2 infected mothers were favorable. IgG trans placental transfer was higher following second trimester maternal infections, which could be relevant to inform studies on appropriate vaccination strategies aimed at neonatal protection. Maternally derived IgG are rapidly weaned in the first months of life. Disclosures All Authors: No reported disclosures.

310 CLINICAL COURSE AND CHARACTERISTICS OF ADVANCED HEART FAILURE ASSOCIATED WITH ARRHYTHMOGENIC CARDIOMYOPATHY

Abstract Background The prevalence and course of heart failure (HF) in arrhythmogenic cardiomyopathy (ACM) is unresolved, and previous studies have mostly focused on the right-dominant variant of the disease, less prone to HF. Conversely, ACM variants with left ventricular (LV) involvement are now increasingly recognized, often initially ‘mis-diagnosed’ as dilated cardiomyopathy. Aim of this study was therefore to describe the prevalence and clinical course of advance HF in the full clinical spectrum of ACM. Methods We retrospectively reviewed records of all ACM patients diagnosed before 2021 from 3 Italian Cardiomyopathy Referral Centres (Azienda Ospedaliero Universitaria Careggi; Policlinico Sant’Orsola; Azienda Ospedaliero Universitaria Sant’Andrea). LV involvement was diagnosed in the presence of subepicardial late gadolinium enhancement (LGE) in at least 3 contiguous segments in the same short-axis slice at cardiac magnetic resonance, independent of whether it fulfilled the 2010 Task Force criteria for right-dominant ACM (biventricular ACM) or not (left-dominant ACM); in this latter case, diagnosis was reached after careful exclusion of other differential diagnosis, and only when at least one of the following features was present: likely pathogenic/pathogenic genetic variant associated with ACM; familial history of ACM; electrocardiographic abnormalities suggestive of ACM with LV involvement. Advanced HF was defined as NYHA functional class III/IV and/or referral for heart transplantation. Median follow-up was 6 years. Results Forty-four out of 174 ACM patients (25%) developed advanced HF: 10 right-dominant ACM and 34 with LV involvement. Twenty ACM patients were initially diagnosed with dilated cardiomyopathy; as such, development of advanced HF in 17 cases preceded the diagnosis of ACM. Five patients were diagnosed with ACM after heart transplantation, by histological examination. In the other 22, median time from ACM diagnosis to advanced HF development was 4 years. As compared to those without, advanced HF patients were more likely to present LV involvement. During clinical course, 20 (46%) advanced HF patients received at least one appropriate ICD intervention, with 13 experiencing an electrical storm. Twenty-six (59%) patients required HF-related hospitalization, and 32 (72%) were referred for heart transplantation with 25 ultimately receiving it. ACM patients with advanced HF, compared to those without, experienced a higher rate of mortality (36% vs. 6%; OR 3.5 [95%CI: 1.4-8.7], p=0.01) and ventricular arrhythmic events (41% vs. 11%; OR 2.4 [95%CI: 1.1-5.0], p=0.02). Conclusions Advanced HF progression in ACM is not rare, and occurs more frequently in variants with LV involvement. Advanced HF is associated with increased mortality and arrhythmic risk.

Transits in Oncology: A Protocol Study for a Therapy-Educational Training Built-In Intervention

The study “Transits in oncology” has been perfected with the collaboration of the UOC of Oncological Mammary Surgery of the Azienda Ospedaliero Universitaria Senese Siena, specifically by Prof. Donato Casella. The study means to analyze the impact of art-therapy interventions aimed at minimizing psychological distress in women with a diagnosis of breast cancer/mammary carcinoma (anxiety/depression), hence improving their psychophysical wellbeing. To this end, the study employs the evaluation of specific psychological parameters with the purpose of monitoring anxiety and depression levels, while investigating a potential correlation between the anxiety and depression levels and other psychological variables, such as alexithymia. The mammary carcinoma diagnosis, to all effects, constitutes an actual “disorienting dilemma” for the woman: it leads to questioning one’s way of life, and their past and future choices; the upheaval is conducive to a reflective phase that upsets one’s “expectations of meaningfulness”. The art-therapy intervention has been elaborated in a protocol that underscores its transformative methodology qualities: it aims to act on the regenerative potential of the turmoil, for an elaboration of trauma that does not negate it or further it (the feeling that nothing will change and everything will go back to the way it was before), but rather disrupts it. The final goal is to promote new existential practices, generating positive change towards self-awareness, stimulating the activation of one’s latent resources by accessing one’s symbolic world and one’s imagination.

The energy crisis in Europe 2022: new challenges ahead for rehabilitation

International Journal of Therapy and RehabilitationVol. 29, No. 10 EditorialThe energy crisis in Europe 2022: new challenges ahead for rehabilitationMassimiliano PolastriMassimiliano PolastriCorrespondence to: Massimiliano Polastri; E-mail Address: [email protected]Department of Continuity of Care and Integration, Physical Medicine and Rehabilitation, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, ItalySearch for more papers by this authorMassimiliano PolastriPublished Online:31 Oct 2022https://doi.org/10.12968/ijtr.2022.0134AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Chamber. The UK's first hospital to be completely powered by solar energy. 2022. https://tinyurl.com/5n962ws7 (accessed 4 October 2022) Google ScholarEuronews. UK consumers face 80% rise in energy bills from October as regulator raises price cap. 2022. https://tinyurl.com/3srpxu7x (accessed 4 October 2022) Google ScholarEuropean Central Bank. Natural gas dependence and risks to Euro area activity. 2022. https://tinyurl.com/5n7pmr75 (accessed 4 October 2022) Google ScholarEuropean Commission. New solar energy system at Potenza's San Carlo hospital. 2017. https://tinyurl.com/jmwxd9tw (accessed 4 October 2022) Google ScholarEurostat. Natural gas price statistics. 2022a. https://tinyurl.com/2f849ja4 (accessed 4 October 2022) Google ScholarEurostat. Electricity price statistics. 2022b. https://tinyurl.com/2md5ksv5 (accessed 4 October 2022) Google ScholarNHS England. Solar power sparks an electrical future for Milton Keynes University Hospital. 2021. https://tinyurl.com/mr32mead (accessed 4 October 2022) Google ScholarÖnal G, Güney G, Gün F, Huri M. Telehealth in paediatric occupational therapy: a scoping review. Int J Ther Rehabil. 2021;28(7):1–16. https://doi.org/10.12968/ijtr.2020.0070 Link, Google ScholarPanda S, Bali S, Kirubakaran B, Hagenberg A. Telerehabilitation and total knee arthroplasty: a systematic review and meta-analysis of randomised controlled trials. Int J Ther Rehabil. 2015;22(Suppl 8):S6. https://doi.org/10.12968/ijtr.2015.22.Sup8.S6 Link, Google ScholarPolastri M. Telerehabilitation in patients with COVID-19. Int J Ther Rehabil. 2022;29(5):1–3. https://doi.org/10.12968/ijtr.2022.0065 Google ScholarSkalamera M. The Ukraine crisis: the neglected gas factor. Orbis. 2015;59(3):398–410. https://doi.org/10.1016/j.orbis.2015.05.002 Crossref, Google ScholarTrading Economics. EU natural gas. 2022. https://tinyurl.com/584rj6j (accessed 4 October 2022) Google ScholarWorld Health Organization. Joint statement: working together towards COVID-19 and seasonal influenza vaccinations for this winter. https://tinyurl.com/4ezajy6u (accessed 24 October 2022) Google Scholar FiguresReferencesRelatedDetailsCited byThe ongoing energy crisis and the provision of electrophysical therapiesMassimiliano Polastri, Maurizio Borsari, Luca Macrelli25 January 2023 | International Journal of Therapy and Rehabilitation, Vol. 30, No. 1 2 October 2022Volume 29Issue 10ISSN (online): 1759-779X Metrics History Published online 31 October 2022 Published in print 2 October 2022 Information© MA Healthcare LimitedPDF download

Hormone therapy in postmenopausal women living with HIV: a view towards prevention of multiple metabolic conditions and improvement of quality of life.

aModena HIV Metabolic Clinic bDepartment of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia cDepartment of Infectious Diseases, Azienda Ospedaliero-Universitaria, Policlinico of Modena, Modena, Italy. Correspondence to Giovanni Guaraldi, MD, Associate Professor, Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Largo del Pozzo 71, 41124 Modena, Italy. Tel: +39 059 422 5318; Mob: +39 335 33 34 34; e-mail: [email protected] Received 8 June, 2022 Accepted 15 June, 2022

Real-World Comparison of Isavuconazole and Voriconazole in Terms of the Need for Dosage Adjustments Guided by Clinical Pharmacological Advice During Primary Prophylaxis of Invasive Fungal Infections in Pediatric Patients with Hemato-Oncological Malignancies.

Limited evidence concerning optimal azole dosing regimens currently exists for antifungal prophylaxis in hemato-oncological pediatric patients. Hemato-oncological children receiving intravenous or oral isavuconazole or voriconazole for primary antifungal prophylaxis at IRCCS Azienda Ospedaliero-Universitaria of Bologna during November 2020 to October 2021 and undergoing CPA programs based on real-time therapeutic drug monitoring (TDM) were retrospectively analyzed. CPAs for isavuconazole and voriconazole and the number of dosage adjustments were collected. Normalized trough concentrations [(C min )/dose/kg] were calculated for both drugs at each TDM assessment, and the coefficient of variation was determined. The efficacy and safety of the drugs were evaluated. Sixteen hemato-oncological pediatric patients received azole prophylaxis (mean age and weight: 9.1 ± 4.9 years and 32.6 ± 16.0 kg; 6 isavuconazole and 10 voriconazole). Sixty and 89 CPAs were delivered as isavuconazole and voriconazole, respectively. Dosage adjustments were needed in 3.3% of cases for isavuconazole and 53.9% of cases for voriconazole ( P < 0.001). At first TDM, achievement of the desired target during standard dosing regimens was higher for isavuconazole (83.3%) than for voriconazole (10.0%; P = 0.008). Dispersion of normalized concentrations was higher for voriconazole (CV = 139.1% vs. CV = 79.4%). Elevation of ALT and aspartate aminotransferase levels between baseline and the third month was higher in patients receiving voriconazole (median, 28 vs. 90 U/L; P = 0.038, and 19 vs. 65.5 U/L; P = 0.002). Our findings suggest that there is limited variability in isavuconazole exposure in hemato-oncological pediatric patients receiving azole prophylaxis , resulting in a low need for CPA-guided dosage adjustments.