Stigma and mental health among people living with HIV across the COVID-19 pandemic: a cross-sectional study.

BACKGROUND: Mental health (MH) is extremely relevant when referring to people living with a chronic disease, such as people living with HIV (PLWH). In fact - although life expectancy and quality have increased since the advent of antiretroviral therapy (ART) - PLWH carry a high incidence of mental disorders, and this burden has been exacerbated during the COVID-19 pandemic. In this scenario, UNAIDS has set new objectives for 2025, such as the linkage of at least 90% of PLWH to people-centered, context-specific MH services. Aim of this study was to determine the prevalence of MD in PLWH followed at the Clinic of Infectious Diseases of the University of Bari, Italy. METHODS: From January 10th to September 10th, 2022, all PLWH patients accessing our outpatient clinic were offered the following standardized tools: HAM-A for anxiety, BDI-II for depression, PC-PTSD-5 for post-traumatic stress disorder, CAGE-AID for alcohol-drug abuse. Factors associated with testing positive to the four MD were explored with a multivariable logistic regression model. RESULTS: 578 out of 1110 HIV-patients agreed to receive MH screening, with 141 (24.4%) people resulting positive to at least one MH disorder. HAM-A was positive in 15.8% (n = 91), BDI-II in 18% (n = 104), PC-PTSD-5 in 5% (n = 29) and CAGE in 6.1% (n = 35). The multivariable logistic regression showed a higher probability of being diagnosed with anxiety, depression and post-traumatic stress disorder for PLWH who reported severe stigma, social isolation, psychological deterioration during the COVID-19 pandemic and for those receiving a dolutegravir (DTG)-based regimen. Moreover, history of drug use (OR 1.13; [95% CE 1.06-4.35]), family stigma (2.42 [1.65-3.94]) and social isolation (2.72 [1.55;4.84]) were found to be associated to higher risk for substance use disorder. CONCLUSIONS: In this study, stigma was a strong predictor for being diagnosed of a MH disorder among PLWH. Also, the possible role of dolutegravir as a risk factor for the onset of MH disorders should be considered in clinical practice, and MH of patients receiving DTG-containing regimens should be constantly monitored.

Loading dose plus continuous/extended infusion versus intermittent bolus of ß-lactams for the treatment of Gram-negative bacteria bloodstream infections: a propensity score-adjusted retrospective cohort study.

BACKGROUND: Optimal ß-lactam dosing for the treatment of Gram-negative bacteria bloodstream infections (GNB-BSIs) remains a debated issue. Herein, the efficacy and safety of a loading dose (LD) followed by extended/continuous infusion (EI/CI) versus intermittent bolus (IB) of these drugs for the treatment of GNB-BSIs was evaluated. METHODS: This is a retrospective observational study enrolling patients with GNB-BSIs treated with ß-lactams from 1 October 2020 to 31 March 2022. The 30 day infection-related mortality rate was assessed with Cox regression, while mortality risk reduction was evaluated by an inverse probability of treatment weighting regression adjustment (IPTW-RA) model. RESULTS: Overall, 224 patients were enrolled: 140 and 84 in the IB and EI/CI groups, respectively. ß-Lactam regimens were chosen according to pathogen antibiogram, clinical judgement and current guidelines. Interestingly, the LD + EI/CI regimen was associated with a significant lower mortality rate (17% versus 32%, P = 0.011). Similarly, ß-lactam LD + EI/CI was significantly associated with a reduced risk of mortality at multivariable Cox regression [adjusted HR (aHR) = 0.46; 95%CI = 0.22-0.98; P = 0.046]. Finally, the IPTW-RA (adjusted for multiple covariates) was performed, showing a significant risk reduction in the overall population [-14% (95% CI = -23% to -5%)]; at the subgroup restricted analysis, a significant risk reduction (>15%) was observed in the case of GNB-BSI in severely immunocompromised patients (P = 0.003), for SOFA score > 6 (P = 0.014) and in septic shock (P = 0.011). CONCLUSIONS: The use of LD + EI/CI of ß-lactams in patients with a GNB-BSI may be associated with reduced mortality; also in patients with severe presentation of infection or with additional risk factors, such as immunodepression.

Correlation of radiological and histopathological response after neoadjuvant radiotherapy in soft tissue sarcoma.

BACKGROUND: The aim of this study was to assess the association between radiological and histopathological response after neoadjuvant radiotherapy (nRT) in soft tissue sarcoma (STS), as well as the prognostic value of the different response evaluation methods on the oncological outcome. METHODS: A retrospective cohort of patients with localized STS of the extremity and trunk wall, treated with nRT followed by resection were included. The radiological response was assessed by RECIST 1.1 (RECIST) and MR-adapted Choi (Choi), histopathologic response was evaluated according to the EORTC-STBSG recommendations. Oncological outcome parameters of interest were local recurrence-free survival (LRFS), disease metastases-free survival (DMFS), and overall survival (OS). RESULTS: For 107 patients, complete pre- and postoperative pathology and imaging datasets were available. Most tumors were high-grade (77%) and the most common histological subtypes were undifferentiated pleomorphic sarcoma/not otherwise specified (UPS/NOS, 40%), myxoid liposarcoma (MLS, 21%) and myxofibrosarcoma (MFS, 16%). When comparing RECIST to Choi, the response was differently categorized in 58%, with a higher response rate (CR + PR) with Choi. Radiological responders showed a significant lower median percentage of viable cells (RECIST p = .050, Choi p = .015) and necrosis (RECIST p < .001), and a higher median percentage of fibrosis (RECIST p = .005, Choi p = .008), compared to radiological non-responders (SD + PD). RECIST, Choi, fibrosis, and viable cells were not significantly associated with altered oncological outcome, more necrosis was associated with poorer OS (p = .038). CONCLUSION: RECIST, Choi and the EORTC-STBSG response score show incongruent results in response evaluation. The radiological response was significantly correlated with a lower percentage of viable cells and necrosis, but a higher percentage of fibrosis. Apart from necrosis, radiological nor other histopathological parameters were associated with oncologic outcomes.

Impact of active cancer on COVID-19 survival: a matched-analysis on 557 consecutive patients at an Academic Hospital in Lombardy, Italy.

BACKGROUND: The impact of active cancer in COVID-19 patients is poorly defined; however, most studies showed a poorer outcome in cancer patients compared to the general population. METHODS: We analysed clinical data from 557 consecutive COVID-19 patients. Uni-multivariable analysis was performed to identify prognostic factors of COVID-19 survival; propensity score matching was used to estimate the impact of cancer. RESULTS: Of 557 consecutive COVID-19 patients, 46 had active cancer (8%). Comorbidities included diabetes (n = 137, 25%), hypertension (n = 284, 51%), coronary artery disease (n = 114, 20%) and dyslipidaemia (n = 122, 22%). Oncologic patients were older (mean age 71 vs 65, p = 0.012), more often smokers (20% vs 8%, p = 0.009), with higher neutrophil-to-lymphocyte ratio (13.3 vs 8.2, p = 0.046). Fatality rate was 50% (CI 95%: 34.9;65.1) in cancer patients and 20.2% (CI 95%: 16.8;23.9) in the non-oncologic population. Multivariable analysis showed active cancer (HRactive: 2.26, p = 0.001), age (HRage>65years: 1.08, p < 0.001), as well as lactate dehydrogenase (HRLDH>248mU/mL: 2.42, p = 0.007), PaO2/FiO2 (HRcontinuous: 1.00, p < 0.001), procalcitonin (HRPCT>0.5ng/mL: 2.21, p < 0.001), coronary artery disease (HRyes: 1.67, p = 0.010), cigarette smoking (HRyes: 1.65, p = 0.041) to be independent statistically significant predictors of outcome. Propensity score matching showed a 1.92× risk of death in active cancer patients compared to non-oncologic patients (p = 0.013), adjusted for ICU-related bias. We observed a median OS of 14 days for cancer patients vs 35 days for other patients. CONCLUSION: A near-doubled death rate between cancer and non-cancer COVID-19 patients was reported. Active cancer has a negative impact on clinical outcome regardless of pre-existing clinical comorbidities.

The What, the Why, and the How of Liver Ablations: A Practical Guide for the Medical Oncologist.

Interventional oncology plays a major role within modern oncological patient management. Image-guided thermal ablation has been recognized as a successful local therapeutic option in patients with primary and secondary malignant liver diseases, as also recalled by the recent European Society of Medical Oncology (ESMO) guidelines on colorectal metastases. As image-guided treatments may be as effective as surgery in selected patients with liver lesions, the clinical oncologist should be familiar with the indications, risks, and technical aspects of liver ablation in order to provide their patients with the best outcomes. This article provides a broad overview of the most commonly used ablation techniques and highlights the most relevant technical aspects such as the ideal setting in the operating theatre; which image-guided methods are available, including the growing application of fusion imaging; or contrast-enhanced ultrasound for guiding/monitoring the procedure. A further aim is to expand the knowledge among medical oncologists about liver ablation procedures and to provide insights into the future perspectives of percutaneous minimally invasive procedures in the liver.

Real-time US/cone-beam CT fusion imaging for percutaneous ablation of small renal tumours: a technical note.

INTRODUCTION: Fusion imaging is gaining attention as an imaging technique to assist minimally invasive tumour ablation. Ultrasound (US) and computed tomography (CT) are the most common imaging modalities to guide thermal ablation of renal tumours, yet cone-beam CT (CBCT) has recently been described to successfully assist percutaneous renal interventions. Our goal was to evaluate primary technical success and correct lesion targeting of US/CBCT fusion imaging to guide the ablation of kidney masses < 2 cm in a small group of patients. MATERIAL AND METHODS: Six renal lesions (maximum diameter 11-17 mm) were treated with RFA in 5 different patients using real-time US/CBCT. Fusion imaging was used to identify and monitor tumour ablation. Demographics, tumour characteristics and mean serum creatinine levels were recorded before and after the procedure. Primary technical success and correct lesion targeting represented the main endpoints of the study. Primary technique efficacy was confirmed at 1-month and 3-month contrast-enhanced CT follow-ups. RESULTS: In all cases, a confident US/CBCT synchronisation was reached and allowed for a correct targeting and a successful percutaneous ablation. Primary technique efficacy was 100%. No recurrence was observed at the follow-up that ranged from 8 to 26 months (mean 16 months). CONCLUSIONS: US/CBCT fusion proved to be a viable method to precisely guide safe and effective percutaneous thermal ablation in patients with small renal tumours, especially when hardly detectable on US. KEY POINTS: • US/CBCT fusion imaging for renal ablation is safe and feasible. • US/CBCT fusion imaging allows for an improved targeting and complete ablation of small RCC with poor US-conspicuity.

Stroke management during the COVID-19 outbreak: challenges and results of a hub-center in Lombardy, Italy.

PURPOSE: We describe the reorganization carried out during the COVID-19 outbreak at one of the stroke centers in Italy and report on the clinical features and procedural variables of stroke patients in need of endovascular treatment. METHODS: From 1 March to 10 May 2020, we retrospectively analyzed data from stroke patients in need of urgent neurointerventional treatment. Clinical presentation, demographics, and clinical history were collected along with procedural variables (door-to-needle time, needle-to-mTiCi time). Each patient underwent a nasal swab (polymerase chain reaction test), clinical screening, and chest CT scan to assess the risk of SARS-CoV-2 infection. Technical success, procedural safety (including staff SARS-CoV-2 infection), and clinical outcome at discharge were retrieved. A comparison was made with the same patient population treated between 1 March and 10 May 2019 to highlight possible differences in the characteristics or outcomes of the patients. RESULTS: One hundred thirty-six ischemic stroke patients were admitted to our facility from 1 March to 10 May 2020. Of these, 12 patients (9%) were classified as "high risk" for SARS-CoV-2 infection. Radiological suspicion of COVID-19 was confirmed in all cases by pharyngeal swab. Five SARS-CoV-2 patients (42%) needed endovascular therapy. None of the staff members tested positive for IgG against SARS-CoV-2. Compared to the same period in 2019, an increase in the mean interval from the first symptoms to hospital arrival was observed (p < 0.05). CONCLUSION: Endovascular treatment of stroke presented several challenges during the COVID-19 outbreak. Within the hospital, special pathways can be used to maintain both procedural safety and procedural times.

Efficacy and tolerability of DAAs in HCV-monoinfected and HCV/HIV-coinfected patients with psychiatric disorders.

BACKGROUND: Few data are available regarding the use of direct antiviral agents (DAAs) for chronic hepatitis C in psychiatric patients. The aim of the study is to assess safety and outcome of DAAs in patients with psychiatric comorbidities. METHODS: This retrospective, observational, single-centre study enrolled patients treated with psychiatric drugs who initiated DAAs between 2015 and 2018. Patients were classified into two groups: A (on anxiolitycs/antidepressant) and B (on antipsychotics). Week-12 sustained virological response (SVR-12) and adverse events (AEs) were evaluated. RESULTS: One hundred forty-four patients were included (A:101; B:43). Patients were 49.3% males, mean age 60 years (SD ± 13.5); 31.9% cirrhotic; 125 (86.8%) HCV-monoinfected and 19 (13.2%) HCV /HIV-coinfected. Twenty patients (13.8%) required a change of psychiatric therapy before initiation of DAA. Overall, SVR-12 was achieved in 88.2% of subjects in intention-to-treat(ITT)-analysis. Lower SVR rates were observed in group B vs A (79% vs 92%, p = 0.045) and in those changing psychiatric drugs vs others (8% vs 30%, p = 0.015). According to per-protocol (PP)-analysis, SVR-12 was achieved in 93/95 (97.9%) in group A versus 34/36 (94.4%) in group B (p = 0.30). At least one AE occurred in 60 patients (41.6%), including 10 severe AEs, leading to 3 discontinuations. AEs were more frequently reported in group A (p = 0.015). CONCLUSIONS: The study confirms effectiveness and safety of DAA-based treatment also in this special population, even if a careful evaluation of history and drug-drug interactions is warranted.

Percutaneous radiofrequency ablation of HCC: reduced ablation duration and increased ablation size using single, internally cooled electrodes with an optimized pulsing algorithm.

PURPOSE: To assess the use of optimized radiofrequency (RF) to achieve larger, spherical ablation volumes with short application duration for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty-two patients (M:F = 17:5, median age 69.6 year, range 63-88) with 28 HCCs due to HCV + liver cirrhosis underwent RFA. 20/28 (71.4%) were tumors ≤3cm diameter, and 8/28 (28.6%) ranged from 3.2 to 4.2 cm. RF was applied using up to 2500mA via an optimized pulsing algorithm with real-time ultrasound monitoring to detect hyperechogenic changes. Single insertions of an internally cooled electrode were performed using exposed tips of 2 or 3 cm for 13 HCCs and 4 cm for 15 HCCs. All patients were followed-up for a minimum of 5 years with contrast-enhanced computed tomography (CECT). RESULTS: Technical success was achieved without adverse events in all cases. The mean ablation time was 8.5 ± 2.6 min. In 21/28 (75%), ablation duration ranged from 3 to 9 min, with 12 min duration applied in only 7/28 (25%). Mean coagulation diameters were 2.4 ± 0.14, 3.3 ± 0.62, and 4.4 ± 1.0, for 2, 3 and 4 cm electrodes, respectively (p < 0.01). The sphericity index was 74.9 ± 12.8 for 4 cm electrodes and 81.9 ± 8.0 for shorter electrodes (p = 0.091). At 5-year follow-up, no tumor ≤3 cm had recurrence and only 2/8 (25%) >3 cm tumors developed local progression. One patient had multifocal disease with no local progression. CONCLUSION: Efficient delivery of RF energy can considerably decrease the ablation time in many instances while achieving larger, relatively spherical, and reproducible areas of ablation with extremely low rates of local tumor progression and adverse events.

Computed tomography (CT)-derived radiomic features differentiate prevascular mediastinum masses as thymic neoplasms versus lymphomas.

OBJECTIVES: We aimed to assess the ability of radiomics, applied to not-enhanced computed tomography (CT), to differentiate mediastinal masses as thymic neoplasms vs lymphomas. METHODS: The present study was an observational retrospective trial. Inclusion criteria were pathology-proven thymic neoplasia or lymphoma with mediastinal localization, availability of CT. Exclusion criteria were age < 16 years and mediastinal lymphoma lesion < 4 cm. We selected 108 patients (M:F = 47:61, median age 48 years, range 17-79) and divided them into a training and a validation group. Radiomic features were used as predictors in linear discriminant analysis. We built different radiomic models considering segmentation software and resampling setting. Clinical variables were used as predictors to build a clinical model. Scoring metrics included sensitivity, specificity, accuracy and area under the curve (AUC). Wilcoxon paired test was used to compare the AUCs. RESULTS: Fifty-five patients were affected by thymic neoplasia and 53 by lymphoma. In the validation analysis, the best radiomics model sensitivity, specificity, accuracy and AUC resulted 76.2 ± 7.0, 77.8 ± 5.5, 76.9 ± 6.0 and 0.84 ± 0.06, respectively. In the validation analysis of the clinical model, the same metrics resulted 95.2 ± 7.0, 88.9 ± 8.9, 92.3 ± 8.5 and 0.98 ± 0.07, respectively. The AUCs of the best radiomic and the clinical model not differed. CONCLUSIONS: We developed and validated a CT-based radiomic model able to differentiate mediastinal masses on non-contrast-enhanced images, as thymic neoplasms or lymphoma. The proposed method was not affected by image postprocessing. Therefore, the present image-derived method has the potential to noninvasively support diagnosis in patients with prevascular mediastinal masses with major impact on management of asymptomatic cases.

Clusterization of co-morbidities and multi-morbidities among persons living with HIV: a cross-sectional study.

BACKGROUND: Among people living with HIV (PLWH), the prevalence of non-HIV related co-morbidities is increasing. Aim of the present study is to describe co-morbidity and multi-morbidity, their clustering mode and the potential disease-disease interactions in a cohort of Italian HIV patients. METHODS: Cross-sectional analysis conducted by the Coordinamento Italiano per lo Studio di Allergia e Infezioni da HIV (CISAI) on adult subjects attending HIV-outpatient facilities. Non-HIV co-morbidities included: cardiovascular disease, diabetes mellitus, hypertension, oncologic diseases, osteoporosis, probable case of chronic obstructive pulmonary disease (COPD), hepatitis C virus (HCV) infection, psychiatric illness, kidney disease. Multi-morbidity was defined as the presence of two or more co-morbidities. RESULTS: One thousand and eighty-seven patients were enrolled in the study (mean age 47.9 ± 10.8). One hundred-ninety patients (17.5%) had no co-morbidity, whereas 285 (26.2%) had one condition and 612 (56.3%) were multi-morbid. The most recurrent associations were: 1) dyslipidemia + hypertension (237, 21.8%); 2) dyslipidemia + COPD (188, 17.3%); 3) COPD + HCV-Ab+ (141, 12.9%). Multi-morbidity was associated with older age, higher body mass index, current and former smoking, CDC stage C and longer ART duration. CONCLUSIONS: More than 50% of PLHW were multi-morbid and about 30% had three or more concurrent comorbidities. The identification of common patterns of comorbidities address the combined risks of multiple drug and disease-disease interactions.

Laser and radiofrequency ablations for benign and malignant thyroid tumors.

A growing body of evidence is being published regarding the safety and efficacy of minimally invasive image-guided ablation techniques. While clinical applications of these techniques are increasing, international societies have started to publish treatment guidelines and to make efforts to standardize both terminology and reporting criteria for image-guided thyroid ablations. Laser ablation and radiofrequency ablation (RFA) are among the most common ablation techniques either for benign and malignant thyroid nodules. Unlike laser ablation and RFA in the treatment of benign thyroid nodules, where safety and efficacy have been widely demonstrated, evidence regarding local tumor control of thyroid malignancies is still limited. However, preliminary results are encouraging and image-guided thermal ablation techniques can be considered a valid alternative to surgery for the treatment of benign thyroid nodules and recurrent thyroid cancers. This review evaluates the basic concept of RFA and laser ablations, their techniques, clinical outcomes, and complications based on the suggestions of several society guidelines. Multidisciplinary collaboration remains critical to identify patients which may benefit from minimally invasive image-guided thermal ablations, especially if surgery or radioiodine therapy are not feasible options.

Thermal ablation to relieve pain from metastatic bone disease: a systematic review.

OBJECTIVE: To review the efficacy of percutaneous thermal ablation (TA) of bone metastases (radiofrequency ablation [RFA], microwave ablation [MWA], cryoablation [CA], and MR-guided focused ultrasound [MRgFUS]) in reducing pain in patients with advanced stage cancer. MATERIALS AND METHODS: We searched MEDLINE/PubMed, MEDLINE In-Process, BIDS ISI, Embase, CINAHL, and the Cochrane database using the keywords "ablation," "painful," "bone," and "metastases" combined in multiple algorithms. Inclusion criteria were: original clinical studies published between 2001 and 2018; performance of RFA, MWA, CA or MRgFUS; and quantitative pain assessment before/after TA of bone metastasis. RESULTS: Eleven papers (3 on RFA, 1 on MWA, 2 on CA, and 5 on MRgFUS) involving 364 patients were reviewed. A technical success rate of 96-100% was reported, with follow-up for up to 6 months. At baseline, pain scores ranged from 5.4 to 8, at 1-4 weeks from 0.5 to 5, and at 12 weeks from 0.3 to 4.5. Mean pain reduction compared with baseline ranged from 26 to 91% at 4 weeks and from 16% to 95% at 12 weeks. MWA treatments caused no complications, whereas MRgFUS showed the highest complication rate. The number of minor complications observed ranged from 0 to 59 (complication ratio 0-1.17), whereas the number of significant adverse effects ranged from 0 to 4 (complication ratio 0-0.04). CONCLUSION: All techniques achieved pain relief after 1 and 3 months, in up to 91% and 95% of patients respectively. MWA showed a negligible complication rate, whereas MRgFUS is associated with a noteworthy rate of adverse events. Future studies should adopt a standardized pain reporting scale to allow for meta-analysis.

Prognostic value of mitotic count in leiomyosarcoma: A comprehensive monocentric retrospective study.

BACKGROUND: Leiomyosarcomas (LMSs) include heterogeneous entities with different clinical courses not entirely predicted by known prognostic factors. In particular, the value of mitotic count as independent prognostic factor in LMS has been poorly investigated. METHODS: We retrospectively analyzed all patients with a diagnosis of LMS who accessed to our Institution from June 1999 to May 2022 for which mitotic count was numerically expressed within the pathology report. Univariate and multivariate analyses were conducted to explore the prognostic value of mitotic count along with other clinical and histological variables. RESULTS: We identified 121 eligible patients, with a median follow-up of 91.03 months (range 0.62-275.2 months). Median progression-free survival (mPFS) was 16.7 months, and median overall survival (mOS) was 105.6 months. In univariate analysis, mitotic count showed a significant impact on PFS and OS, with an hazard ratio per mitotic unit of 1.03 (1.01-1.04, p < 0.001) and 1.03 (1.01-1.04, p = 0.007), respectively. Similar results were found for locally advanced and metastatic patients, separately. Other significant prognostic factors for PFS were stage at diagnosis, performance status, tumor size and Ki-67, while differentiation, necrosis, grade, stage at diagnosis, tumor size, performance status and age at diagnosis were identified for OS. In multivariate analysis, the only significant factors were mitotic count and the presence of metastases at diagnosis for PFS, whereas the same two factors plus age at diagnosis were identified for OS. CONCLUSION: Mitotic count represented the most important histological prognostic factor for OS and PFS in localized and metastatic LMS.

Intravenous Fosfomycin as Adjunctive Therapy for Gram-Negative Bacteria Bloodstream Infections: A Propensity Score Adjusted Retrospective Cohort Study.

BACKGROUND: The role of intravenous fosfomycin (iv-FOS) as a part of combination therapy for Gram-negative bacteria bloodstream infections (GNB-BSI) needs to be evaluated in clinical practice, as in vitro data show potential efficacy. METHODS: All consecutive patients with a GNB-BSI from 01 January 2021 to 01 April 2023 were included. Primary outcome was 30-day mortality. A Cox regression analysis was used to identify predictors of mortality; an inverse-probability of treatment-weighting (IPTW) analysis was also performed. RESULTS: Overall, 363 patients were enrolled: 211 (58%) males, with a median (q1-q3) age of 68 (57-78) years, and a median Charlson comorbidity index of 5 (3-7). At GNB-BSI onset, the median SOFA score was 5 (2-7) and 122 patients (34%) presented with septic shock. Pathogens were principally Klebsiella pneumoniae (42%), Escherichia coli (28%) and Pseudomonas aeruginosa (17%); of them, 36% were carbapenem-resistant. The therapy included carbapenems (40%), cephalosporins (37%) and beta-lactams/beta-lactamases-inhibitors (19%); a combination with iv-FOS was used in 98 (27%) cases at a median dosage of 16 (16-18) g/daily. The use of iv-FOS was not associated with reduced crude mortality (21% vs 29%, P = 0.147). However, on multivariable Cox-regression, combination therapy with iv-FOS resulted in protection for mortality (aHR 0.51, 95% CI 0.28-0.92), but not other combo-therapies (HR 0.69, 95% CI 0.44-1.16). This result was also confirmed with the IPTW-adjusted Cox model (aHR 0.52, 95% CI 0.31-0.91). Subgroup analysis suggested a benefit in severe infections (SOFA > 6, PITT ≥ 4) and when iv-FOS was initiated within 24 hours of GNB-BSI onset. CONCLUSIONS: Fosfomycin in combination therapy for GNB-BSI may have a role in improving survival. These results justify the development of further clinical trials.

Overcoming data scarcity in radiomics/radiogenomics using synthetic radiomic features.

PURPOSE: To evaluate the potential of synthetic radiomic data generation in addressing data scarcity in radiomics/radiogenomics models. METHODS: This study was conducted on a retrospectively collected cohort of 386 colorectal cancer patients (n = 2570 lesions) for whom matched contrast-enhanced CT images and gene TP53 mutational status were available. The full cohort data was divided into a training cohort (n = 2055 lesions) and an independent and fixed test set (n = 515 lesions). Differently sized training sets were subsampled from the training cohort to measure the impact of sample size on model performance and assess the added value of synthetic radiomic augmentation at different sizes. Five different tabular synthetic data generation models were used to generate synthetic radiomic data based on "real-world" radiomics data extracted from this cohort. The quality and reproducibility of the generated synthetic radiomic data were assessed. Synthetic radiomics were then combined with "real-world" radiomic training data to evaluate their impact on the predictive model's performance. RESULTS: A prediction model was generated using only "real-world" radiomic data, revealing the impact of data scarcity in this particular data set through a lack of predictive performance at low training sample numbers (n = 200, 400, 1000 lesions with average AUC = 0.52, 0.53, and 0.56 respectively, compared to 0.64 when using 2055 training lesions). Synthetic tabular data generation models created reproducible synthetic radiomic data with properties highly similar to "real-world" data (for n = 1000 lesions, average Chi-square = 0.932, average basic statistical correlation = 0.844). The integration of synthetic radiomic data consistently enhanced the performance of predictive models trained with small sample size sets (AUC enhanced by 9.6%, 11.3%, and 16.7% for models trained on n_samples = 200, 400, and 1000 lesions, respectively). In contrast, synthetic data generated from randomised/noisy radiomic data failed to enhance predictive performance underlining the requirement of true signal data to do so. CONCLUSION: Synthetic radiomic data, when combined with real radiomics, could enhance the performance of predictive models. Tabular synthetic data generation might help to overcome limitations in medical AI stemming from data scarcity.

Real life experience on the use of Remdesivir in patients admitted to COVID-19 in two referral Italian hospital: a propensity score matched analysis.

Remdesivir (RDV) was the first Food and Drug Administration (FDA)-approved medication for COVID-19, with discordant data on efficacy in reducing mortality risk and disease progression. In the context of a dynamic and rapidly changing pandemic landscape, the utilization of real-world evidence is of utmost importance. The objective of this study is to evaluate the impact of RDV on patients who have been admitted to two university referral hospitals in Italy due to COVID-19. All patients older than 18 years and hospitalized at two different universities (Bari and Palermo) were enrolled in this study. To minimize the effect of potential confounders, we used propensity score matching with one case (Remdesivir) and one control that never experienced this kind of intervention during hospitalization. Mortality was the primary outcome of our investigation, and it was recorded using death certificates and/or medical records. Severe COVID-19 was defined as admission to the intensive care unit or a qSOFAscore ≥ 2 or CURB65scores ≥ 3. After using propensity score matching, 365 patients taking Remdesivir and 365 controls were included. No significant differences emerged between the two groups in terms of mean age and percentage of females, while patients taking Remdesivir were less frequently active smokers (p < 0.0001). Moreover, the patients taking Remdesivir were less frequently vaccinated against COVID-19. All the other clinical, radiological, and pharmacological parameters were balanced between the two groups. The use of Remdesivir in our cohort was associated with a significantly lower risk of mortality during the follow-up period (HR 0.56; 95% CI 0.37-0.86; p = 0.007). Moreover, RDV was associated with a significantly lower incidence of non-invasive ventilation (OR 0.27; 95% CI 0.20-0.36). Furthermore, in the 365 patients taking Remdesivir, we observed two cases of mild renal failure requiring a reduction in the dosage of Remdesivir and two cases in which the physicians decided to interrupt Remdesivir for bradycardia and for QT elongation. Our study suggests that the use of Remdesivir in hospitalized COVID-19 patients is a safe therapy associated with improved clinical outcomes, including halving of mortality and with a reduction of around 75% of the risk of invasive ventilation. In a constantly changing COVID-19 scenario, ongoing research is necessary to tailor treatment decisions based on the latest scientific evidence and optimize patient outcomes.

Case Report: Should Regorafenib be prescribed as a continuous schedule in gastrointestinal stromal tumors? Three case reports on Regorafenib personalized schedule.

Introduction: Regorafenib is a tyrosine kinase inhibitor (TKI) approved in metastatic gastrointestinal stromal tumor (GIST), colorectal cancer, and hepatocarcinoma. Anyway, the toxicity profile of Regorafenib standard schedule is associated with poor compliance and a high rate of discontinuation. For this reason, there is a growing need for a Regorafenib personalized schedule emerging from the scientific community. Objective: The aim of this case series was to describe the experience of our sarcoma referral center with the continuous administration of Regorafenib as an alternative regimen to treat metastatic GIST patients. Methods: We retrospectively collected clinical, pathological, and radiological data of patients with metastatic GIST treated with daily personalized Regorafenib at a single tertiary referral center from May 2021 to December 2022. Results: We identified three patients fulfilling the inclusion criteria. The average follow-up since the start of Regorafenib was 19.1 months (12-25 months). All three patients had started a standard third-line Regorafenib schedule according to guidelines. The reasons for switching to a continuous schedule were as follows: exacerbation of symptoms during week-off treatment in the first patient, a serious adverse event (AE) in the second patient, and a combination of both conditions in the third. After switching, none of the patients reported severe AEs, and they improved control of tumor-related symptoms. Two of the patients experienced disease progression after 16 months (9 months of which is continuous schedule) and 12 months (8.1 months of which is continuous schedule) of Regorafenib, respectively; the third patient is still receiving continuous Regorafenib at the time of writing, with a progression-free survival of 25 months (14 months after the modified schedule start). Conclusion: With a similar efficacy and lower toxicities, a daily, personalized Regorafenib schedule seems to be a promising alternative to the standard regimen for metastatic GIST patients, including the frail ones. Further prospective analyses are needed to confirm the safety and efficacy of such regimen.