Università Cattolica del Sacro Cuore

The new Cabotegravir + Rilpivirine long acting (CAB + RPV) is the injectable regimen for treatment-experienced people with HIV (PWH). Little data from real-world settings are available, particularly in more complex PWH. We aimed to investigate the effectiveness of CAB + RPV in our real-life cohort of experienced PWH. We conducted a prospective observational longitudinal study by enrolling PWH who switched to CAB + RPV. We recruited participants from our outpatient clinic and a lower percentage of complex PWH followed by our home-care assistance (HCA). We evaluated time to virological failure (VF) and time to treatment discontinuation (TD) for any cause using Cox regression analyses. In the subgroup followed by HCA we also analyzed the total HIV-DNA trend during the study period. We enrolled 62 participants: 52 were outpatients (83.9%) and 10 followed by HCA (16.1%). Mostly were males (66.1%), with a median age of 51 years (IQR 31–60). During a 31.5 person-years follow-up (PYFU), all participants maintained virological suppression (< 30cps/mL). We observed 9 discontinuations during follow-up, with a rate of discontinuation of 28.6 per 100 PYFU. The estimated probabilities of maintaining CAB + RPV at 24 and 48 weeks were 84.9% (SD: 0.5) and 79.2% (SD: 0.7), respectively. No significant predictors of discontinuations were found. In the subgroup, we found no significant changes in the HIV-DNA levels over time (p = 0.332). Our results confirm the efficacy of CAB + RPV as a switch strategy in virologically suppressed PWH and even in more complex individuals, encouraging its use in PWH in need, coupled with HCA home administration support.

Although foster care represents an essential practice for helping children and families in difficult situations, nowadays, in Italy, the number of people open to engaging in this kind of care is limited compared to the real need, and agencies have difficulties recruiting new foster parents. The present qualitative study is aimed at identifying the process that leads families to become foster parents and investigating how this decision has been put into practice, with the aim of improving practices in the foster care system. A constructivist grounded theory approach was used to study the experiences of foster parent dyads in Northern Italy. The basic social process of ‘acting generatively’ was identified. This represented the inner need to act experienced by the people who approach foster care and who are guided by the desire to go beyond the self, to serve others and to take care of future generations. Six axial codes representing the six main phases in this process, characterized from a sociorelational point of view, were identified: values awareness, generative ideation, generative agreement, evaluation, generative intention and generative action. This article describes a foster decision‐making model that may help social workers in recruiting foster families.

Cardiovascular disease (CVD) remains a significant global health concern for women, influenced by a complex interplay of social, economic, and environmental factors. This article examines cardiovascular risk through the lens of the exposome, which encompasses all environmental exposures from conception onward, including pollution, diet, and chronic stress. Social determinants such as socioeconomic status (SES), education, and stress management play crucial roles in shaping women’s cardiovascular health. Lower SES and education are associated with greater exposure to adverse living conditions, poor nutrition, and limited access to healthcare, increasing the risk of CVD. Environmental pollution, particularly air pollution and climate-related changes, further exacerbates cardiovascular risk by promoting oxidative stress and inflammation. Additionally, gender-specific factors, such as pregnancy and menopause, interact with the exposome, heightening the vulnerability of women to cardiovascular risks over their lifetime. Addressing these risk factors requires a comprehensive approach, incorporating public health strategies that focus on reducing pollution, improving food security, and mitigating social inequalities. By addressing the cumulative and interacting exposures that contribute to cardiovascular disease, especially in women, more effective prevention strategies can be developed to improve long-term health outcomes.

Recurrent pregnancy loss (RPL) represents a complication of pregnancy occurring in 1%–3% of all couples trying to conceive. About 50%–60% of RPL cases remain idiopathic, therefore therapeutic strategies seem empirical and based on unproven evidence. We investigated the efficacy of corticosteroids in women with RPL. We conducted a systematic review and meta‐analysis, up to August 2024, in the PubMed, Scopus, and Web of Science databases, including studies on idiopathic RPL women and comparing corticosteroids versus control treatment. Primary outcome was the ongoing pregnancy rate beyond 12 weeks of gestation; secondary outcomes were live birth rate (LBR), stillbirth, birth weight, incidence of preeclampsia and/or gestational diabetes, gestational age at delivery, and fetal abnormalities. Four studies comprising 417 RPL women randomly assigned to steroid or control treatment were included. We found that oral corticosteroids significantly increase the ongoing pregnancy rate beyond 12 weeks of gestation compared to the control group (log OR [odds ratio] = 1.49 [0.32, 2.67], p = 0.01), with high heterogeneity ( I ² = 75%), and improve LBR (log OR = 0.9 [0.11, 1.69], p = 0.03), with low heterogeneity ( I ² = 0.05%). However, the limited number of studies significantly limits the strength of the findings. Also, the benefit/risk assessment of the use of corticosteroids in early pregnancy for RPL is still unclear.

Background and Aims Presence of active hepatitis C virus (HCV) infection may influence the outcome of patients treated for hepatocellular carcinoma (HCC), although this issue has never been adequately assessed in a large series of patients. The aim of this study was to evaluate whether the presence of active HCV affects the survival of patients treated for HCC. Methods This study assessed the outcome of 3123 anti‐HCV‐positive patients with HCC, subdivided according to the presence of active HCV infection or previous sustained virological response (SVR). Comparisons were also carried out after propensity score matching (PSM) considering demographic, clinical and oncological characteristics. Results The median overall survival from HCC treatment was longer in patients with SVR than in those with active HCV infection both before ( n = 2118: 61.0 months [95% confidence internal (CI): 56.5–65.5] vs. n = 1005: 51.0 months [95% CI: 43.4–58.6]; p = 0.003) and after PSM ( n = 1285: 60.0 months [95% CI: 55.3–64.7] vs. n = 926: 54.0 months [95% CI: 46.7–61.3]; p = 0.030). Active HCV infection was associated with a greater risk of mortality (hazard ratio: 1.22–1.27, p = 0.001) independently of liver‐ and tumour‐related variables, and modality of HCC treatment. Death due to liver failure was more common in patients with active HCV infection (24.5% vs. 17.1%; p = 0.001), while non‐liver‐related causes of death were more common in patients with SVR (25.0% vs. 17.0%; p = 0.001). Conclusions SVR is associated with a better outcome in patients undergoing HCC treatment, thus suggesting that these patients may benefit from antiviral therapy for HCV independently of cure of HCC.

The aim of this study was to present a nationwide survey on the specialist’s attitudes towards stereotactic body radiotherapy (SBRT) combined with poly (ADP-ribose) polymerase inhibitors (PARPi) with oligometastatic/oligoprogressive/oligorecurrent ovarian cancer (oMPR-OC) patients. The 19-item questionnaire was developed by specialists and distributed online. Replies were stratified by categories and analyzed using descriptive statistics. Respondents ( N = 100) were radiation oncologists (57%), medical oncologists (32%), and gynecologic oncologists (11%). Fifty-four percent of respondents considered medical oncologists as the primary oncologists for oMPR-OC, while 23% preferred radiation oncologists and 15% favored gynecologic oncologists. Seventy-three percent discuss these cases in the Multidisciplinary Tumor Board, while 15, 6, and 2% send the patients straight to SBRT, surgery, or chemotherapy, respectively. Seventy-four percent of the experts interviewed were treated with SBRT less than 10 oMPR-OC patients. Concomitant treatment was highly heterogeneous, but it had little to no reported side effects. A significant variation in how PARPi is managed during SBRT was found: 34% do not interrupt the administration, while 52% pause and restart it later. Forty-three percent of respondents believe that the PARPi dosage should not be reduced when administered concurrently with SBRT. Sixty-nine percent of respondents believe that the SBRT dose should not be decreased while receiving PARPi if the constraints are met. The majority of respondents (40%) favored expert consensus for enhancing the clinical management of oMPR-OC, while 34% preferred clinical guidelines. A lack of or low toxicity with the combination of PARPi and SBRT was perceived, and a significant degree of heterogeneity concerning clinical protocols for their combination. Moreover, it emphasizes the low number of patients who have received this treatment approach nationwide.

Background Encorafenib plus cetuximab (EC) is the standard of care for pre-treated BRAF V600E mutated metastatic colorectal cancer (mCRC). Depth of response (DpR) and early tumour shrinkage (ETS) previously showed a strong correlation with survival outcomes of first-line chemotherapy ± biological agents. Objectives We aimed to assess potential predictors of primary resistance to EC ± binimetinib (B) and relationships of DpR/ETS with survival outcomes and clinical characteristics. Design This is a retrospective real-world cohort study of BRAF V600E mutated mCRC patients treated with second-line EC ± B at 20 Italian centres. Methods Measurable disease according to Response Evaluation Criteria In Solid Tumour (RECIST) 1.1 at baseline and at least one subsequent computed tomography (CT) scan were mandatory for inclusion. Clinical features associated with primary resistance, DpR and ETS were investigated. Relationships of DpR and ETS, both as binary, according to conventional (30% for DpR and 20% for ETS) and median cut-off values, and continuous variables, with progression-free (PFS), overall survival (OS) and duration of response (DoR) were assessed in non-primary resistant patients. Results A total of 105 patients were included. The primary resistance rate was 28% (29/105) and was associated with baseline peritoneal metastases (p = 0.04). Disease control and overall response rates were 72% (76/105) and 24% (25/105), respectively, with a median DpR of 15% and an ETS rate of 37% (28/76). Mucinous histology was associated with a significantly lower magnitude of DpR (p = 0.005) and a lower rate of ETS (p = 0.002). In the multivariable models, DpR significantly correlated with longer PFS as a dichotomous variable, according both to conventional (hazard ratio (HR)DpR ⩾30%: 0.52, 95% CI: 0.30–0.90, p = 0.02) and median cut-off values (HRDpR⩾15%: 0.55, 95% CI: 0.33–0.92, p = 0.03), and as a continuous variable (HR per 10% increment: 0.88, 95% CI: 0.78–0.98, p = 0.02), while correlations with OS were not confirmed. DpR was also significantly associated with longer DoR (pDpR⩾30% = 0.04; pDpR⩾15% = 0.04; pcont. = 0.02), whereas no relationships of ETS with PFS, OS or DoR were detected. Conclusion A DpR of at least 15% independently predicts PFS benefit in BRAF V600E mutated mCRC patients treated with second-line EC ± B.

Facioscapulohumeral dystrophy type 1 (FSHD1) displays prominent intra- and interfamilial variability, which complicates the phenotype-genotype correlation. In this retrospective study, we investigated FSHD1 patients classified as category D according to the Comprehensive Clinical Evaluation Form (CCEF), a category defined by FSHD patients showing uncommon clinical features, to identify genetic causes explaining these uncommon phenotypes. Demographics, clinical data and clinical scales of FSHD1 patients were retrospectively evaluated. Patients were divided into four CCEF categories, and comparisons between groups were performed. In category D, when uncommon features suggested the presence of an unrelated genetic disease, a more extensive collection of data was performed. 157 FSHD1 patients were included in the study (82 males, 75 females) with mean age of 52.1 ± 13.5 years at the time of the study. D4Z4 repeat sizes ranged between 2 and 10 RU. According to the CCEF, 114 patients were classified into category A, 8 into category B and C each, and 27 into category D. In category D, 9 patients presented uncommon features related to commonly acquired comorbidities, whereas in the remaining 18 patients, all but two with upper-sized FSHD1 D4Z4 repeats (7–10 RU), we suspected an unrelated genetic neurological disease based on clinical phenotype. In 14/18 patients, we identified FSHD-unrelated genetic causes, most often unrelated repeat expansion disorders. This emphasizes the need of careful clinical and genetic work-up to avoid confusion between FSHD-intrinsic clinical variability and clinical features unrelated to the disease.

Introduction: Complicated urinary tract infections (cUTIs) represent a significant clinical challenge due to their association with sepsis, high morbidity and mortality, and an increased risk of recurrence and chronic infection. Effective management requires prompt, targeted interventions. Areas covered: This review highlights the importance of early, targeted antibiotic therapy based on local resistance profiles, patient-specific factors, and pharmacokinetic/pharmacodynamic considerations. We examined emerging and existing antibiotics, including beta-lactams, fluoroquinolones, aminoglycosides, and beta-lactamase inhibitor combinations, which show potential against multidrug-resistant organisms (MDRO) linked to cUTI. Additionally, we propose revisiting the broad definition of cUTI to promote a more pragmatic approach that minimizes unnecessary antibiotic use and hospitalization. Expert opinion: Current evidence underscores the need for antimicrobial stewardship, precise diagnostics, and innovative therapies to address cUTI while mitigating antimicrobial resistance. A targeted, patient-centered approach is essential to optimize outcomes and reduce the burden of resistant infections.

To investigate whether 18F-fluorodeoxyglucose positron emission tomography-computed tomography ([18F]F-FDG PET/CT) metabolic parameters were associated with histology and to assess their prognostic role in patients with thymic lesions. In total, 116 patients (49/67 M/F; mean age 59.5 years) who underwent preoperative [18F]F-FDG PET/CT and thymectomy from 2012 to 2022 were retrospectively analyzed. Associations between histology and metabolic parameters (maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), peak standardized uptake value (SUVpeak), total lesion glycolysis (TLG), metabolic tumor volume (MTV), ratio between target lesion and liver SUVmax (rPET), quotient of SUVpeak in the tumor residual and SUVmean in a 20-cm3 volume of interest (qPET), and tumor-to-mediastinum (T/M) were analyzed. Freedom from recurrence (FFR) was determined and compared using the Kaplan–Meier and the log-rank test. The median follow-up was 38 months (range 14–72 months). In total, 27 thymic hyperplasia, 41 low-risk thymomas (LRT) (types A, AB, and B1), and 48 high-risk thymomas (HRT) (B2, B3 thymoma, and carcinoma) were included. SUVmax, SUVmean, SUVpeak, rPET, qPET, and T/M were significantly higher in HRT than LRT and hyperplasia (p < 0.001). TLG and MTV were significantly higher in patients with LRT (p < 0.001). Only rPET, qPET, and T/M remained significantly higher in HRT than in LRT subgroups (p = 0.042, p = 0.049, and p = 0.028, respectively). SUVmax, SUVmean, and SUVpeak cutoffs of < 4.3, < 2.87, and 4.03, respectively, significantly distinguished patients with longer FFR (p = 0.009, p = 0.05, and p = 0.05). Positron emission tomography (PET) metabolic parameters could help to differentiate thymic histotypes. Standardized uptake value (SUV)-based parameters appear promising to predict recurrent disease.

This clinical consensus statement of the European Association of Percutaneous Cardiovascular Interventions was developed in association with the European Society of Cardiology Working Group on Cardiovascular Surgery. It aims to define procedural and contemporary technical requirements that may improve the efficacy and safety of percutaneous coronary intervention (PCI), both in the acute phase and at long-term follow-up, in a high-risk cohort of patients on optimal medical therapy when clinical and anatomical high-risk criteria are present that entail unacceptable surgical risks, precluding the feasibility of coronary artery bypass grafting (CABG). This document pertains to patients with surgical contraindication according to the Heart Team, in whom medical therapy has failed (e.g., residual symptoms), and for whom the Heart Team estimates that revascularisation may have a prognostic benefit (e.g., left main, last remaining vessel, multivessel disease with large areas of ischaemia); however, there is a lack of data regarding the size of this patient population. This document aims to guide interventional cardiologists on how to proceed with PCI in such high-risk patients with reduced left ventricular ejection fraction after the decision of the Heart Team is made that CABG - which overall is the guideline-recommended option for revascularisation in these patients - is not an option and that PCI may be beneficial for the patient. Importantly, when a high-risk PCI is planned, a multidisciplinary decision by interventional cardiologists, cardiac surgeons, anaesthetists and non-invasive physicians with expertise in heart failure management and intensive care should be agreed upon after careful consideration of the possible undesirable consequences of PCI, including futility, similar to the approach for structural interventions.

Background Rimegepant, a novel oral calcitonin gene-related peptide receptor antagonist, has been recently approved for the acute migraine treatment. While its efficacy was confirmed in randomized clinical trials, no data is available regarding real-life effectiveness and tolerability. GAINER, a prospective, multicentric study, aimed to evaluate rimegepant effectiveness and tolerability in the real-world setting. Methods Our study involved 16 headache centers across Italy. The main outcomes were: i) 2 h pain freedom, and ii) occurrence of treatment-emergent adverse events after administration. Participants were instructed to treat one migraine attack with rimegepant 75 mg orally disintegrating tablet. Using an ad hoc diary, participants prospectively collected migraine attack features at baseline and every 30 min after rimegepant administration, up to 2 h post dose. A 24 h follow up was also collected. Results We enrolled 103 participants with migraine (74.8% female, mean age 44.4 [42.0-46.7] years, 24.3% with chronic migraine of whom 44.0% presented a concomitant diagnosis of medication overuse headache). The number of previously failed preventive classes was 2.7 [2.3-3.2]. Participants presented a mean of 9.6 [8.2-10.9] monthly migraine days at baseline. At rimegepant intake, 40.8% of patients rated migraine intensity as severe. Pain freedom 2 h post dose was reported in 44.7% (46/103) of individuals. Pain freedom 2 h post dose was not influenced by baseline pain severity (p = 0.316), but it was associated with timing of intake (p = 0.032) with a higher rate of 2 h pain freedom when rimegepant was taken within 1 h from pain onset. Mild adverse events were reported in 15.5% total attacks (16/103), predominantly fatigue (n = 6), gastrointestinal symptoms (n = 6), somnolence (n = 4), and transient cognitive difficulties (n = 3). Tolerability was rated as good-to-excellent in 85.4% cases (88/103). † Luigi Francesco Iannone and Gloria Vaghi contributed equally to this work. Conclusions Our data confirms rimegepant effectiveness and safety in the acute migraine treatment in a real-world setting in a cohort of participants that includes subjects with episodic or chronic migraine, medication overuse and a high number of prior preventive treatment failures. Trial registration The study was preregistered on clinicaltrial.gov, NCT05903027.

Introduction/Objective Data on long-term treatment with Esketamine Nasal Spray (ESKNS) in real-world patients with treatment resistant depression (TRD) is scarce. The primary aim of the study is to evaluate the effectiveness and tolerability of ESK-NS treatment at 6 and 12-month follow-ups. Methods This is part of an observational, retrospective, multicentric Italian study (REAL-ESK study). Subjects for the present study underwent psychiatric assessments after 6 and 12 months from the start of ESK-NS treatment. Repeated measures analysis of variance (ANOVA) was used to assess changes in continuous variables, such as scores on psychometric scales from baseline to follow-up time points. Results Of 63 patients who maintained ESK-NS treatment for at least 6 months, 48 were responders or remitters (76.2%). Among 15 non-responders at 6 months, 4 significantly improved at 12-month follow-up. At least one side effect was reported by 71.8% of subjects with a 6-month follow-up assessment. An overall reduction of side effects was noticed as treatment progressed (42% of patients who continued the treatment reported side effects at 12 months). The most common side effects were sedation (31.7%) and dissociation (28.6%) during ESK-NS sessions. Only 2 patients discontinued ESK-NS for tolerability reasons. Conclusion The results support the effectiveness and safety of esketamine in the mid and long-term treatment of TRD patients. The late clinical response of a subgroup of patients represents a novel finding. Data needs to be confirmed in larger samples and longer observation periods.

Objective Epilepsy surgery outcomes tend to be judged by the percentage in seizure reduction without considering the effect on specific seizure types, particularly tonic–clonic seizures, which produce the greatest morbidity and mortality. We assess how often focal to bilateral tonic–clonic seizures (BTCS) stop and how often they appear de novo after epilepsy surgery. Methods Analysis of a prospectively maintained epilepsy surgery database between 1986 and 2022 that characterizes the burden of BTCS after resective epilepsy surgery. Patients were stratified according to presence or absence of preoperative BTCS and whether these were active (defined as ≥1 BTCS/year prior to surgery) or remote. Results A total of 804 patients were followed for a median of 7 years (interquartile range [IQR] = 3–13 years) after epilepsy surgery, most being temporal lobe resections (91%, 95% confidence interval [CI] = 89–93%). At last visit, 72% of patients (95% CI = 69–75%) were seizure‐free for 1 year or more. Of 521 patients with preoperative BTCS, 300 (58%, 95% CI = 53%–61%) no longer had them after surgery. BTCS recurred in 221 patients, but 128 of them (58%, 95% CI = 51%–64%) had no BTCS in the last year of follow‐up. Those patients who continued to experience BTCS after surgery had a median reduction of 92% in yearly BTCS frequency (IQR = 65%–98%, p < .001). Of 283 patients with no preoperative BTCS, 17 developed de novo BTCS (6%, 95% CI = 4%–9%), with a median of 2 BTCS during the entire follow‐up period. Forty‐seven percent (95% CI = 42%–53%) of patients without preoperative BTCS became seizure‐free after surgery, compared with 33% (95% CI = 29–37, p < .001) of patients with preoperative BTCS. Significance Epilepsy surgery markedly reduces or eliminates BTCS, which should have a potential positive impact on morbidity and mortality. This favors offering surgery even if the chance of seizure freedom is not high and calls for a new surgical outcome scale to factor in seizure severity reduction.

Trigonocephaly as well as uni- and bicoronal synostosis are rare pathologies that are nonetheless common in pediatric setting. In this chapter, the authors will describe the principal of anterior vault remodeling as well as the more common procedures reported in the literature. While all surgical techniques share common goals (ICP increase prevention; cranial morphology normalization; prevention of neurodevelopmental injury; prevention of ocular movement disturbances), they differ mostly in the way of dealing with cranial reconstruction. Surgical techniques can then be divided into open field surgery, device-assisted procedures, and endoscopy-assisted suturectomy followed by postoperative cranial orthotic therapy or mini-invasive microscope-assisted suturectomy. In order to better describe the aforementioned techniques, in this chapter each of the surgical steps will be described from positioning to dressing.