Azienda Ospedaliera G. Brotzu

Evidence from rheumatology supports a within-class treatment switch for JAK-inhibitors (JAKi), but data in ulcerative colitis (UC) remain limited. We aimed to assess the effectiveness and safety of initiating a second JAKi in patients with UC previously treated with another JAKi. We conducted a multicenter retrospective study, including patients with UC starting a second JAKi after prior JAKi exposure. The primary endpoint was Week 12 steroid-free clinical remission (SFCR-rectal bleeding subscore = 0, stool frequency subscore ≤ 1, and no steroids). We included 243 patients (median follow-up: 38 [21-57] weeks). At Weeks 12, 26, and 52, SFCR was achieved in 116/243 (48%), 120/243 (49%), and 69/243 (28%), respectively. Secondary loss of response to the first JAKi was associated with higher SFCR at Week 12 compared to primary failure (odds ratio [OR] = 1.92, 95% confidence interval [CI] = 1.11-3.30, P = 0.02). Higher baseline disease activity (OR = 0.68, 95% CI = 0.68-0.55, P < 0.01) and steroid use (OR = 0.23, 95% CI = 0.13-0.42, P < 0.01) had lower odds of Week 12 SFCR. Endoscopic remission occurred in 22/243 (9%) (<Week 26) and 27/243 (11%) (26-78 weeks), and endoscopic improvement in 53/243 (22%) and 45/243 (19%), respectively. Sixty-seven (28%) patients discontinued the second JAKi, mostly due to primary (36/67) or secondary failure (22/67). Sixty-six adverse events (mostly acne and infections) occurred in 56 (23%) patients, without major thromboembolic or cardiovascular events. Treatment with a second JAKi is effective and safe in patients with UC already exposed to JAKi. Primary failure to a first JAKi and steroid use at initiation of the second JAKi might reduce the likelihood of success with the second JAKi.

Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) relapse is the most frequent cause of allogeneic stem cell transplantation (allo-SCT) failure. The utility of post-relapse therapy is controversial due to the high incidence of toxicity and the low efficacy. This sub-analysis of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) AML/MDS relapse study focuses on 647 AML/MDS relapsing after allo-SCT performed between 2015 and 2021. Following the relapse, these patients were treated with either hypomethylating agents (HMAs)-based therapy (n = 308) or other treatments (n = 339), including intensive chemotherapy, FLT3-inhibitors, and second allo-SCT. HMAs-based therapies were more frequently used in older patients, transplanted not in CR following a reduced-intensity conditioning regimen. The overall response rate (ORR) with or without HMA-based salvage treatment was 33% and 40%, respectively (P = .006). The complete remission (CR) rate was 23% and 33% in the two groups, respectively (P < .001). The long-term OS and TRM of the two groups were superimposable. Independently from the type of salvage, an advantage in OS was observed when donor lymphocytes infusion (DLI) was included (P < .001). Relapse within 12 months after SCT, low disease burden at relapse, and the CR status at transplant confirmed their independent strong prognostic impact on both HMA and non-HMA-based group (HR 0.05, 0.44, and 0.49 and HR 0.19, 0.32, and 0.53, respectively). Despite the lower ORR observed with HMA-based therapy, the long-term OS was comparable to that observed with other therapies. The immune control of the disease relapse with DLI is of benefit, independently from the salvage therapy. .

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The management of chronic lymphocytic leukemia (CLL) in older patients requires careful balancing of therapeutic efficacy with the risks of treatment intolerance. Frailty assessment is increasingly recognized as a critical determinant of clinical outcomes, but its specific role in guiding therapy with second-generation Bruton tyrosine kinase inhibitors remains poorly defined. We conducted a prospective, multicenter investigation of 326 consecutive CLL patients aged 65years or older who received zanubrutinib across 52 Italian centers, aiming to evaluate whether the Clinical Frailty Scale (CFS) could predict treatment discontinuation in real-world practice. The cohort was characterized by advanced age (median 78.1years, range 65.1-94.5), with over half of the patients presenting with Binet stage C disease. Two-thirds were treated in the frontline setting, while the remainder received zanubrutinib as salvage therapy. After a median follow-up of 8 months, 48 patients (14.7%) discontinued treatment, most commonly due to toxicity or disease progression. Receiver operating characteristic curve analysis identified a CFS of 3 as the optimal threshold for predicting discontinuation, with an area under the curve of 0.65 (95% CI 0.56-0.73, p<0.001). At 12months, the discontinuation rate was significantly higher among patients with a CFS >3 (29.2%) compared with those with a CFS ≤3 (8.8%) (p<0.001); among conventional prognostic variables, only relapsed/refractory disease demonstrated an independent association with TTD. These findings highlight the CFS as a simple yet powerful clinical tool that provides incremental prognostic information beyond standard disease-related factors. Incorporating frailty assessment into treatment planning may enhance patient selection and optimize therapeutic strategies for elderly CLL patients in daily practice.

Despite national and international guidelines on Helicobacter pylori management, limited evidence exists on how these recommendations are applied in routine clinical practice. This nationwide survey, conducted by the Italian Association of Hospital Gastroenterologists and Endoscopists and the Italian Federation of General Practitioners (FIMMG), aimed to identify the empirical first- and second-line treatments most commonly recommended in Italy. Members of societies were invited via email to anonymously complete an original 20-item questionnaire. Ten therapeutic regimens were proposed, with treatment durations classified as 7, 10, or 14 days. Respondents reported the type of proton-pump inhibitor (PPI) used, total daily dose (mg/day), and whether probiotics and/or lactoferrin were recommended. PPI doses were standardized according to acid inhibition potency and categorized as low, standard, or high. Among the 1262 respondents [358 gastroenterologists (GEs) and 904 general practitioners (GPs)], the first-line regimen most frequently prescribed was the triple therapy with PPI, clarithromycin and amoxicillin (35.2%; 12% of GEs vs. 44.4% of GPs; P < 0.0001), followed by bismuth quadruple therapy - three-in-one capsule (BQT-TSC: 31.2%; 51.4 vs. 23.3%, P < 0.001), and sequential therapy (21.7%; 26.8 vs. 19.7%, P < 0.001). For second-line, BQT-TSC was the most prescribed regimen (53.1%; GEs versus GSs: not statistically significant). 10-day courses and low-dose PPIs predominated, and approximately 1/3 of respondents recommended probiotics. Empirical regimen selection, PPI dosing, and probiotic use frequently diverged from guideline recommendations. These findings highlight the need to align clinical practice with evidence-based standards to improve eradication rates, optimize cost-effectiveness, and preserve healthcare resources.

Current guidelines for managing infections in pediatric patients with cancer do not recommend routine antibiotic prophylaxis (AP). However, several aspects of AP, including the role of diagnosis, the impact of neutropenia duration, screening for resistant bacterial colonization, and antibiotic stewardship, remain a matter of debate. To address these issues, a panel of experts from the Italian Association of Pediatric Hematology and Oncology (AIEOP) and the Italian Society of Pediatric Infectious Diseases (SITIP) conducted a Delphi consensus. A comprehensive literature review and a national survey of pediatric oncology centers identified clinically relevant topics that are not fully covered by current guidelines. Based on this, the expert panel developed and voted on 14 statements covering eight key areas: the role of diagnosis, duration of neutropenia, screening for colonization with antibiotic resistant bacteria, use of validated risk scores, implementation of antimicrobial stewardship programs, periodic monitoring of local epidemiology, choice of antibiotic for prophylaxis, and the risk of resistance following prophylaxis. The panel reached a consensus against prophylaxis in patients receiving monoclonal antibody therapy and advised against using the duration of neutropenia alone as a criterion to initiate prophylaxis, recommending it only for severe neutropenia (< 500/mm³). They also emphasized the importance of screening for multidrug resistant bacteria and implementing antimicrobial stewardship supported by specialist consultation. These recommendations provide guidance for clinicians on the selective use of AP, supporting informed decision making while ensuring appropriate treatment and reducing the emergence of multidrug resistant bacterial infections.

The epidemiological transition has led to an increase in life expectancy and to a growing population of chronic patients, often with heart failure. These patients are frequently affected by comorbidities and frailty, which in turn increase the risk of disability and worsening quality of life, requiring an accurate multidimensional assessment (MDA). In this context, MDA is crucial for integrated and holistic management of elderly patients, considering not only the pathology but the patient in his complexity. MDA requires a multidisciplinary team to ensure a comprehensive and integrated assessment of the elderly patient. MDA tools assess various domains of health, using scales and validated tools to explore physical, functional, mental and socio-economic status. MDA is applied in two phases: an initial screening procedure and an in-depth analysis of individual problems for targeted interventions. MDA can be performed in various care settings, including outpatient clinics, hospitals, nursing homes, home care, and rehabilitation centers. Several studies show that MDA improves survival as well as functional and mental status, reducing hospitalization times and the frequency of institutionalization. This ANMCO position paper discusses MDA tools of older adults with chronic heart disease, highlighting the need for a holistic approach to address comorbidities and frailty in a growing population.

The Census carried out by the Italian Society of Nephrology's Peritoneal Dialysis (PD) Project Group has been following the evolution of PD for 20 years. For the first time, the latest edition in 2024 was followed up by an on-line audit conducted between 28/04/2025 and 09/05/2025. With 185 of the 228 Centers which used PD in 2024 taking part, the Audit investigated a number of questions which are controversial or relatively unexplored: 1) the incremental dialysis prescription in CAPD; 2) empiric peritonitis therapy; 3) the prophylaxis of exit site infections (ESI); 4) types of peritoneal catheter used; 5) the use of telemedicine. There is no consensus on the incremental prescription in CAPD. Most start with a single exchange, and in the event of two exchanges the majority keep the abdomen empty for part of the day. However, 37.4% of the 162 Centers using incremental PD begin from 2+ exchanges, while 26.5% in two-exchange CAPD keep the abdomen always full. A fair degree of variation was also observed regarding the type of catheter used, although 75.7% of the Centers use only one type in their Center. Almost all the Centers follow ISPD recommendations on empiric peritonitis therapy and ESI/TI prophylaxis, the validity of which is confirmed by the constant reduction in the drop-out rate for peritonitis recorded over the last 20 years. Finally, Telemedicine data show the ever-increasing use of this tool, notably Telemonitoring, whereas only a minority of the Centers use Teleassistance - in particular Televisits - which is particularly useful in Assisted PD.

Abstract Background and Aims Chronic kidney disease (CKD) and acute kidney injury (AKI) are among the most significant long-term complications following radical nephrectomy (RN) for renal masses. In clinical practice, precise renal function assessment is crucial to minimize these risks, particularly for patients with an oncological solitary kidney (SK), where management largely depends on glomerular filtration rate (GFR) values. While estimated GFR (eGFR) is the most commonly used method to assess renal function, it carries a notable margin of error compared to the gold standard, measured GFR (mGFR). This study aimed to quantify the discrepancy between eGFR most used formulas and mGFR in a cohort of patients with oncological solitary kidneys to enhance accuracy in clinical decision-making and postoperative care. Method We retrospectively analyzed a cohort of 170 patients with a solitary kidney (SK), of whom 79.4% (n = 135) had an oncological SK. Renal function was assessed using measured GFR (mGFR) via Iohexol clearance, considered the gold standard, and compared with estimated GFR (eGFR) calculated using multiple formulas. To evaluate the agreement between mGFR and eGFR methods, we computed the Concordance Correlation Coefficient (CCC), Total Deviation Index (TDI), and Coverage Probability (CP). Histograms were generated to visualize the distribution of absolute differences between Iohexol clearance and eGFR, while scatter plots were used to compare individual eGFR methods against mGFR. All statistical analyses and visualizations were performed using R (version 4.4.2). The following packages were used: ggplot2 for scatter plots, epiR for CCC, TDI, and CP calculations, and dplyr/tidyr for data preprocessing. Results Descriptive analysis is shown in Table 1. Agreement between mGFR and eGFR varied across formulas (Tables 2, 3). EKFC showed the highest concordance, while CKD-EPI 2012 (cystatin C) and Cockcroft-Gault performed worst (Fig. 1). Histograms (Fig. 2) and scatter plots confirmed these discrepancies. Conclusion In daily clinical practice, a tailored nephrological follow-up based on measured GFR (mGFR) is essential for radical nephrectomy (RN) patients with a solitary kidney. Reliance on estimated GFR (eGFR) alone can lead to significant clinical errors, either underestimating or overestimating actual renal function, potentially resulting in critical medical consequences.

SummaryUnderstanding bloodstream infection (BSI) epidemiology is crucial for optimizing antibiotic therapy in paediatric haematology–oncology patients undergoing chemotherapy or haematopoietic cell transplantation (HCT). However, updated paediatric data remain scarce. This multicentre retrospective study analysed BSI epidemiology across 22 Italian centres (2018–2019), assessing pathogens, resistance profiles, empirical antibiotic therapy (EAT) and clinical course with outcomes. Mortality risk factors were evaluated using a Cox regression model. A total of 510 BSI episodes occurred in 396 patients (median age 6.4 years), with an incidence of 2.9 and 5.1 per 1000 inpatient days for chemotherapy and HCT respectively. Multidrug‐resistant (MDR), third to fourth generation cephalosporin‐ and carbapenem‐resistant, account for 18.3%, 29.3% and 8.2% of Gram‐negative infections respectively. 42.2% of Klebsiella pneumoniae isolates were MDR. Combination EAT was used in 269/510 episodes, with piperacillin–tazobactam+amikacin being most common. Microbiological appropriateness was 82%. Infection‐related and 30‐day mortality rates were 4.1% and 5.29%, respectively, with appropriate EAT significantly reducing mortality. Our findings highlight the burden of resistant pathogens in paediatric BSIs and emphasize the importance of appropriate EAT in improving outcomes, underscoring the need for treatment strategies tailored to local resistance patterns.