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In a recent article titled "Embracing Cancer Complexity: Hallmarks of Systemic Disease" published in Cell, Swaton et al. propose the idea of cancer as a guest that develops within a host. They discuss the possible causes and events of neoplastic cell dysregulations within an organism, highlighting events such as cachexia and thrombosis. However, we believe that to understand cancer-associated phenomena better, cancer cannot be considered a guest. In reality, cancer is born, develops, and spreads within its environment. It does not come from outside but instead uses the same system in which it lives to promote its death plan. Indeed, today we know that cancer not only causes local symptoms in the affected organ but also leads to systemic symptoms, which are evidence of inflammation associated with cancer. Inflammation is vital in controlling oncogenesis and neoplastic proliferation during the resistance phase, which is a critical moment for the immune system to demonstrate its effectiveness. However, if the immune system causes immunopathological damage, it may lead to necrosis and eventually to the tolerance phase, which can result in systemic symptoms. Understanding these phenomena thoroughly explains thrombophilia, anemia, sarcopenia, and iron metabolism disruption in advanced-stage neoplastic patients. The concept of the microenvironment takes on a different meaning in this context. The same cells that should oppose cancer in the tolerance phase now participate in a process that self-maintains, favoring the growth of the cancer and its death plan. The exact knowledge of these mechanisms is a more modern translational approach to treating cancer and its related symptoms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Potassium is the most represented intracellular electrolyte in the human body. Its extracellular levels are maintained within strict limits through different mechanisms, which constitute the homeostasis of potassium. Hyperkalemia is the most common electrolyte disorder in patients with cardiovascular disease. Although with different levels of severity, it carries an increased risk of hospitalization, cardiovascular morbidity and mortality. Hyperkalemia may also be an important cause of discontinuation or impossibility of titration of fundamental therapies in the cardiology patient. The principal aim of this review is to analyze the mechanisms underlying hyperkalemia, as well as to summarize its epidemiology, risk factors, monitoring methodologies and electrophysiological and electrocardiographic effects, providing just only few essential elements of therapy. In this way the physician, and especially the cardiologist, can have an adequate knowledge for its management in clinical practice.

Background and Aim: Suboptimal disease control (SDC) and its contributing factors in IBD according to STRIDE-II criteria is unclear. IBD-PODCAST was a non-interventional, international, multicenter real-world study to assess this., Methods: Data from the Italian IBD cohort (N=220) are presented here. Participants aged ≥19 with confirmed IBD diagnosis of ≥1 year were consecutively enrolled. A retrospective chart review and cross-sectional assessment by physicians and patients within the past 12 months were performed. SDC or optimal disease control was assessed using adapted STRIDE-II criteria., Results: At the index date, 53.4 % of 116 CD patients and 49.0 % of 104 UC patients had SDC, mainly attributed to a Short Inflammatory Bowel Disease Questionnaire score <50, failure to achieve endoscopic remission, and the presence of active extra-intestinal manifestations in both diseases. Disease monitoring with imaging and/or endoscopy during the previous year was conducted in ∼50 % of patients, with endoscopy performed in ∼40 %. Potential therapeutic adjustments were reported for half of the patients., Conclusions: This study highlights SDC in a significant portion of IBD Italian patients. These results emphasize the need for more proactive management strategies in both CD and UC patients., Competing Interests: Competing interests, (Copyright © 2024. Published by Elsevier Ltd.)

Cisplatin is a nephrotoxic agent able to damage renal function both in acute and chronic phases. Radiotherapy concomitant with cisplatin 100 mg/m 2 given once every 3 weeks is the curative standard of care for locally advanced head and neck cancer. A prospective evaluation of a wide range of biochemical and anthropometrical parameters, handgrip strength, risk of malnutrition, visual analogue scale of appetite, and body composition was performed before, during, and after concomitant chemoradiotherapy in 60 consecutive patients affected by locally advanced head and neck cancer. The treatment dramatically influenced every clinical and laboratory parameter, especially regarding nutritional status despite a high protein intake. In terms of medium eGFR decay, chemoradiotherapy reduced the renal function of about 8 ml/min/1.73m 2 in 6 weeks, harboring some cases of mild acute kidney injury and acute kidney disease. Furthermore, patients with eGFR < 60 mL/min/1.73m 2 pre-treatment were just 3 (5%), becoming 5 (8.3%) at the end despite the high-protein diet implemented following ESPEN guidelines. The drop in eGFR did not correlate with weight loss during treatment or with anthropometric parameters pre and post. Nutritional counselling pre-, during, post-treatments plays a crucial role in preventing malnutrition and sarcopenia, leading to better oncological and nephrological outcomes too., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Individuals with celiac disease (CD) often report the persistence of gastrointestinal symptoms despite adherence to a gluten-free diet (GFD). A diet rich in fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) could cause symptoms in CD on a GFD, and conversely a low-FODMAP diet could positively influence the therapeutic management of CD and non-celiac gluten sensitivity (NCGS). The aim of this review was to explore the hypothetical impact of the FODMAD diet and the low-FODMAP diet (LFD) in CD and gluten-related disorders., Methods: A complete online search for FODMAP related to CD, NCGS, and the GFD was carried out using the Pubmed, Medline, and Cochrane databases., Results: Indeed, an LFD could successfully provide symptom relief in GFD-treated CD patients. Fructans, typical components of FODMAPs, have been associated with digestive symptoms in NCGS, and an LFD could improve the clinical picture. According to some evidence, an LFD could also improve the psychological status both in celiac patients on a GFD and in NCGS. However, an LFD should not have a significant impact on gut microbiota., Conclusions: Recent evidence supports the role of FODMAP restriction in CD patients with persistent symptoms on a GFD and in decreasing gastrointestinal disturbances in NCGS, although the GFD still represents the first-line therapy.

Aims: Electrical storm (ES) is a life-threatening condition requiring a rapid management. Percutaneous stellate ganglion block (PSGB) is proved to be safe and effective on top of standard therapy, but no data are available about its early use., Methods and Results: We considered all patients enrolled from 1 July 2017 to 30 April 2024 in the STAR registry (STellate ganglion block for Arrhythmic stoRm), a multicentre, international, observational, prospective registry. We aimed to assess the effectiveness of the first PSGB only. Patients were divided into two groups depending on whether they received PSGB before [early PSGB, often due to antiarrhythmic drug (AAD) contraindication] or after (delayed PSGB) intravenous AADs (AADs other than beta-blockers). We considered 180 PSGB (26 early PSGB and 154 AAD first). In the early PSGB group, we observed a statistically significant reduction of treated arrhythmic events in the hour after PSGB compared with the hour before: 0 (0-0) vs. 4.5 (1-10), P < 0.001, and the extent of the reduction was similar in the early PSGB and delayed PSGB groups [-4.5 (-7 to -2) vs. -2.5 (-3.5 to -1.5), P = ns]. The percentage of patients free from arrhythmias was similar in the two groups up to 12 h after PSGB (81 vs. 84%, P = 0.6, after 1 h; 77 vs. 79%, P = 0.8, at 3 h; and 65 vs. 69%, P = 0.7, after 12 h)., Conclusion: Percutaneous stellate ganglion block is proved to be effective also when used early in the treatment of ES. Due to its rapidity of action, our results may suggest its early use to reduce the number of defibrillations and possibly to reduce the likelihood of a refractory ES., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Semaglutide, a glucagon-like peptide-1 receptor agonist, has emerged as a pivotal therapeutic agent in the management of the cardio-renal-metabolic continuum. Initially developed for glycemic control in type 2 diabetes mellitus, its benefits extend far beyond glucose regulation. Clinical trials have demonstrated semaglutide's potential to reduce major adverse cardiovascular events, particularly in overweight/obese patients with high cardiovascular risk, as well as improving functional capacity in patients suffering from heart failure with preserved left ventricular function. Additionally, it has shown promise in improving renal outcomes, such as slowing the progression of albuminuria and reducing the risk of chronic kidney disease in diabetic populations. These effects are likely due to its multifaceted mechanisms, including anti-inflammatory properties, weight reduction, blood pressure lowering, and direct renal protection. This review synthesizes current evidence on semaglutide's role in the interrelated domains of cardiovascular, renal, and metabolic health.

Objectives: Patients with chronic limb-threatening ischemia (CLTI) have a high risk of lower limb amputation and loss of walking independence. Minor amputations play a key role in ensuring walking independence and they represent a challenge in terms of timing and level for vascular surgeons. A major cause of re-amputation is a defect in wound healing and a possible predictor of re-amputation for non-healing wounds could be the incorrect timing of minor amputation after revascularization. The lack of evidence in the literature leads to a wide variability of choices in clinical practice. The purpose of this study was to try to find the optimal timing analysing the risk of re-amputation in CLTI patients who have undergone successful revascularization and minor amputation focussing on timing of minor amputation., Methods: We conducted a single centre retrospective analysis on a cohort of 151 patients consecutively admitted to our hospital for CLTI (Rutherford 5) between January 2014 and April 2022. All the enrolled patients underwent successful revascularization of lower limbs and a minor amputation for dry acral necrosis. The characteristics of the patients and the revascularization procedures were collected and analysed. Patients were divided into two groups based on the timing of minor amputation performed before (group 1) or after the day (group 2) that best predicts the risk of re-amputation according to a Receiver Operating Characteristic (ROC) curve analysis. The primary outcome of this study was the risk of re-amputation during the first 60 days of follow-up after a primary minor amputation, with revascularization still effective. The impact of the timing of minor amputation after revascularization, the type of revascularization and the presence of risk factors known to prolong the wound healing process were evaluated in a uni- and multi-variable logistic regression model., Results: Systemic hypertension, and type of revascularization (i.e. open vs endovascular) were independent predictors of the risk of re-amputation at 60 days (HR 4.26, 95% CI 1.30-14.04, p = .017 and HR 2.35, 95% CI 1.16-4.78, p = .018, respectively). Moreover, time ≤14 days between revascularization and first amputation was associate with a clear, albeit not statistically significant, trend toward increased risk of re-amputation (HR 2.09, 95% CI 0.97-4.51, p = .06)., Conclusions: In a cohort of patients who underwent a successful revascularization for CLTI and a minor amputation for dry gangrene in the first 14 days after revascularization, a higher -although not significant-risk of re-amputation was reported. In this cohort of patients, a delayed demolitive procedure should be considered to allow better tissue perfusion and to reduce the risk of re-amputation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: Paolo Ghia received honoraria from AbbVie, AstraZeneca, BeiGene, BMS, Galapagos, Janssen, Lilly/LoxoOncology, MSD, and Roche, and research funding from AbbVie, AstraZeneca, BMS, and Janssen, and is an Editor of HemaSphere. Marzia Varettoni received honoraria from AbbVie, AstraZeneca, BeiGene, and Janssen. The remaining authors declare no conflict of interest.

The absence of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is commonly used to distinguish takotsubo syndrome (TTS) from other myocardial diseases. However, case series have reported the presence of LGE in TTS. This study aimed to summarize the evidence on the frequency of LGE in TTS and identify potential variables that may influence the detection of LGE. Electronic databases were systematically searched for studies reporting LGE frequency in patients with TTS. The overall frequency was estimated using the inverse variance method and a random-effects model for a single proportion. Factors influencing LGE detection were analyzed. Of 490 studies screened, 21 were included (703 patients, 90% women). The estimated overall frequency of LGE was 22.4% (95% confidence interval [CI] 8.7% to 39.6%). In patients with TTS who underwent CMR within 3 days of symptom occurrence, the frequency of LGE was 40.7% (95% CI 18.8% to 64.5%), which was significantly higher than in those who performed CMR after 3 days (3.9%, p <0.010). The sensitivity threshold used in the imaging protocols had a statistically significant impact on the frequency of LGE detection (p = 0.030). A total of 10 studies performed a follow-up CMR after at least 3 months, reporting a frequency of LGE of 1.7% (95% CI 0.0% to 8.9%). In conclusion, published studies report the presence of LGE in TTS at presentation in a significant proportion of patients. However, its detection is strongly influenced by the duration between symptom onset and CMR acquisition and by the sensitivity threshold used for the imaging protocol. LGE is rarely present at follow-up., Competing Interests: Declaration of competing interest The authors have no competing interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: The most frequent consequence of elevated uric acid (UA) levels is the development of gout and urate kidney disease. Besides these effects, several studies have investigated the association between hyperuricemia and cardiovascular (CV) disease. High serum UA has been identified as an important determinant of all-cause and CV mortality and CV events (acute and chronic coronary syndrome, stroke and peripheral artery disease). Despite the high number of publications on this topic, there are two questions that are still unanswered: do we need a specific CV cut-off of serum UA to better refine the CV risk? Is urate lowering treatment (ULT) able to reduce CV risk in asymptomatic patients? In this review, we will focus on these two points., Data Synthesis: Although no doubt exists that the relationship between CV events starts at lower levels than the actually used cut-off, different papers found dissimilar cut-offs. Furthermore, heterogeneity is present depending on the specific CV events evaluated and none of the found cut-off have been tested in external populations (in order to confirm its discriminatory capacity). Furthermore, only few randomized clinical trials on the role of hypouricemic agents in reducing the CV risk have been published giving heterogeneous results. The last published one (ALL-HEART) has strong limitations, that we will deeply discuss., Conclusions: A definitive answer to the two questions is impossible with the actually published paper but, over identifying current gaps in knowledge we try to individuate how they can be overruled., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Data on the predictors of percutaneous stellate ganglion block (PSGB) efficacy in electrical storm are scanty., Objective: We aimed to assess whether PSGB efficacy is influenced by the arrhythmia type and cycle length before the procedure., Methods: This is a subanalysis of the multicenter STAR study. The population was stratified into 3 groups according to the median cycle length of the latest ventricular arrhythmia before PSGB: ventricular fibrillation (VF), fast ventricular tachycardia (VT), and slow VT. The primary outcome was the number of treated arrhythmic episodes (with antitachycardia pacing or direct current shocks) in the hour immediately after PSGB compared with the hour before., Results: We considered 139 PSGBs from 112 patients divided into VF (51 procedures), fast VT (44 procedures, VT cycle <375 ms), and slow VT (44 procedures, VT cycle ≥375 ms). The number of treated arrhythmic episodes in the hour after every PSGB was significantly lower compared with the hour before in all groups (VF: 0 [0-1] vs 5 [2-8], P < .001; fast VT: 0 [0-0] vs 1 [0-6.5], P < .001; slow VT: 0 [0-0] vs 1 [0-4.5], P = .001). In analyzing the reduction of the number of antitachycardia pacing sequences or direct current shocks from the hour before to the hour after PSGB, a significant trend was observed across the groups (Jonckheere-Terpstra trend P < .001), and a significant difference was observed in comparing slow VT vs VF and fast VT vs VF but not in comparing slow VT vs fast VT. VF was independently associated with the probability of reduction of treated events after PSGB., Conclusion: PSGB is an effective treatment of electrical storm in patients with all types of ventricular arrhythmias. However, its effectiveness was more pronounced in patients with VF., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: The optimal mechanical thrombectomy technique for distal, medium vessel occlusion (DMVO) stroke remains unknown. We aimed to compare the safety and efficacy of 2 thrombectomy first-line approaches, direct aspiration (DA), and combined technique (CT) in patients with DMVOs., Methods: We conducted a retrospective review of a prospectively collected multicenter database of patients with DMVOs (at or distal to M2 and A1), who underwent mechanical thrombectomy with JET D reperfusion catheters between January 2020 and December 2021. The primary end point was the rate of first-pass complete recanalization, defined as modified treatment in cerebral infarction (mTICI) 3. The hemorrhagic complications, the 90 days functional independence rate (modified Rankin Scale 0-2), and mortality were also evaluated., Results: A total of 171 consecutive patients were enrolled (95 in DA and 76 in CT cohort). The 2 groups had comparable demographics and baseline characteristics. The DA group had a higher rate of first-pass effect (40.0% vs 10.5%, P < .001), final mTICI 2b-3 (89.5% vs 71.1%, P = .003) and final mTICI 3 (58.9% vs 28.9%, P < .001), shorter groin to reperfusion time (65 ± 43 min vs 101 ± 60 min, P < .001), and higher rate of 90-day functional independence (63.7% vs 36.1%; P = .001) compared with the CT group. There were no significant differences in hemorrhagic complications between the 2 groups. The DA group showed a lower rate of 90-day mortality (9.9% vs 27.8%; P = .004)., Conclusion: In patients with DMVOs, DA with a distal dedicated reperfusion catheter appears to demonstrate better safety and efficacy when compared with the CT using the same catheter., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: Antibody-mediated rejection is a significant cause of kidney transplant failure. Recent studies have shown that the MHC class I MICA gene influences the transplantation outcome. However, the role of the primary MICA receptor, NKG2D, has yet to be explored., Aim: We aimed to investigate the correlation between recipient/donor MICA allele matching and NKG2D genotype with the risk of antibody-mediated rejection and their potential clinical effects and implications for organ maintenance therapy., Methods: Of the 524 patients who underwent transplantation, 387 were eligible for the study. Complete MICA allele and two functional polymorphisms of NKG2D ( rs1049174C>G and rs2255336G>A ) were analyzed in 148 transplanted patients and 146 controls., Results: Increased recipient/donor MICA allele mismatches correlate with an elevated risk of antibody-mediated rejection (X 2 = 6.95; Log-rank=0.031). Notably, the rs1049174[GG] genotype contributes to a significantly increased risk of antibody-mediated rejection (X 2 = 13.44; Log-rank=0.001 and X 2 = 0.34; Log-rank=0.84). The combined effect of two MICA allele mismatches and rs1049174[GG] genotype shows the highest risk (X 2 = 23.21; Log-rank<0.001). Most importantly, patients with rs1049174[GG] and rs2255336[ AA ] genotypes may respond less to mTOR inhibitor immunosuppressive therapy than Calcineurin inhibitors ( rs1049174[GG]; P=0.035; and rs2255336[AA] ; P=0.002)., Conclusion: Recipient/donor MICA allele mismatches and specific NKG2D variants, as well as their combinations, influence kidney transplant outcomes, providing insights for personalized treatment and enhancing graft survival., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Littera, Mocci, Argiolas, Littarru, Lai, Melis, Sanna, Mereu, Lorrai, Mascia, Angioi, Mascia, Matta, Lepori, Floris, Manieli, Bianco, Onnis, Rassu, Deidda, Carta, Giuressi, Perra, Chessa, Giglio and Pani.)

Background: Tracheobronchial injury is a life-threatening condition with a considerable missed diagnosis rate. The larger the tracheal lesion the more difficult it is to heal. Both conservative and non-conservative treatments are used to treat tracheal injury. This article reports a clinical scenario in which conservative treatment was successfully used to manage a severe tracheal tear., Case Description: We present the case of a 63-year-old male with a cough for over a year who suffered from a 4-cm tracheobronchial injury (level IIIA, Cardillo classification) after endotracheal intubation for right lower bilobectomy. This injury showed full-layer tissue tearing of the tracheal wall, without esophageal injury or mediastinitis. The tracheal tear was discovered during the bronchoscopy examination on postoperative day one. The patient's vital signs were almost stable, including body temperature, blood pressure, heart rate, and oxygen saturation. We adopted a conservative treatment approach, including oxygen administration, painkillers, broad-spectrum antibiotics therapy, and nutritional support. Using this treatment, the 4-cm long tracheal rupture healed within four weeks. No tracheal tear was found in the bronchoscopy re-examination. The computed tomography scan showed that the mediastinal and subcutaneous emphysema had disappeared entirely. The patient fully recovered well without any complaints of discomfort., Conclusions: Conservative treatment provides a valuable strategy for treating patients with massive tracheal lesions, representing an effective approach, especially in older patients with underlying diseases whose conditions are not suitable for operative treatments., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1288/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background and Hypothesis : Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) are significant risks for kidney cancer (KC) patients undergoing partial (PN) or radical nephrectomy (RN) and for living kidney donors (LKD). This study compares AKI and CKD incidence in these groups with a pre-operative glomerular filtration rate (GFR) over 60 mL/min/1.73 m 2 . Methods : This study included 465 KC patients with cT1-2N0M0 kidney mass and 256 LKD who underwent nephrectomy at four Italian institutions from 2014 to 2021. Data on demographics, comorbidities, and therapies were analyzed. Serum creatinine and estimated GFR (eGFR) were measured before and after surgery. Outcomes were AKI (per KDIGO guidelines) and CKD stage progression. Analyses included descriptive statistics, ANOVA, logistic regression, and Kaplan-Meier survival. Results : Among 721 patients, significant age and gender differences were noted. Hypertension (41%) and diabetes (7.1%) were prevalent in RN and PN groups. Post-surgery AKI was more common in donors (84%), while CKD stage progression varied by surgery type (CKD stage G3 after 60 months: RN 48.91%, PN 18.22%, LKD 26.56%). Age, pre-surgery CKD, and surgery type predicted CKD progression. Limitations include retrospective design and bias. Conclusions : Both LKD and KC patients face similar AKI and CKD risks. Surgery type significantly influences AKI and CKD incidence, highlighting the importance of approach.

The clinical safety and efficacy of rituximab biosimilars compared to the reference rituximab (Mabthera) have been well established in randomized trials. However, concerns persist regarding the safety of changing from the reference product to biosimilars, and particularly between different biosimilars. This prospective multicenter observational study was conducted in 13 oncohematology units of eight Italian regions. The study included 800 patients with non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) who received rituximab between March 2018 and June 2022. To minimize survivorship bias, only newly diagnosed patients (i.e., those without prior rituximab treatment) were included in the analysis of adverse drug reactions (ADRs). Thus, this study focused on 505 incident cases (79.8% of the initial cohort) from 13 centers. A total of 3681 rituximab infusions were administered, and 16.8% of the patients experienced at least one ADR. These were observed most frequently during the first infusion (44 patients, 52%) and the second infusion (17 patients, 20%). The most frequent reactions were general disorders and administration site conditions (n. 50, 8% serious). These findings support the clinical safety of rituximab biosimilars and suggest that switching between biosimilars does not increase the risk of adverse events. This evidence may alleviate concerns about biosimilar use, potentially leading to broader acceptance and reduced healthcare costs.

Aim: To provide guidance for follow-up and monitoring of children and adolescents identified as positive to islet autoantibodies (IA) in the general population screening for type 1 diabetes (T1D) in Italy., Methods: Detection of IA helps to diagnose pre-symptomatic T1D, prevent diabetic ketoacidosis (DKA) and identify persons for new therapies to delay symptomatic diabetes. Italy recently became the first country to approve by law a general autoantibody screening program for T1D and celiac disease in all children and adolescents (age 1-17yr). A pilot study is currently underway in four Italian regions addressing feasibility issues to be used in the scale up to nationwide screening. Meanwhile, a group of experts developed guidance recommendations for follow-up and monitoring of identified IA positive persons., Results: Ten key components have been identified: establishment of a registry for children and adolescents at risk; close collaboration with the national network of family paediatricians; creation of T1D centers with expertise in follow-up and monitoring; educational measures; assurance of solid IA tests; identification of appropriate metabolic tests; feed-back feasibility and acceptability questionnaires; potential access to available therapeutic interventions; valuable outcome measures including DKA incidence; costs monitoring. Distinctive features of this program include single (in addition to multiple) IA antibody-positive persons in follow-up and the use of CGM to assess risk progression, rather than the cumbersome OGTT., Conclusion: It is expected that the proposed follow-up and monitoring program will be effective, affordable and acceptable to children and families identified in general T1D screening in Italy., (© 2024 John Wiley & Sons Ltd.)

Purpose: Advances in surgical procedures and immunosuppressive therapies have considerably improved the outcomes of patients who have undergone liver transplantation in the past few decades. In 2020, the Italian Liver Transplant Working Group published practice-oriented algorithms for immunosuppressive therapy (IT) in adult liver transplant (LT) recipients. Due to the rapidly evolving LT field, regular updates to the recommendations are required. This review presents a consensus- and evidence-based update of the 2020 recommendations., Methods: The Italian Liver Transplant Working Group set out to address new IT issues, which were discussed based on supporting literature and the specialists' personal experiences. The panel deliberated on and graded each statement before consensus was reached., Results: A series of consensus statements were formulated and finalized on: (i) oncologic indications for LT; (ii) management of chronic LT rejection; (iii) combined liver-kidney transplantation; (iv) immunosuppression for transplantation with an organ donated after circulatory death; (v) transplantation in the presence of frailty and sarcopenia; and (vi) ABO blood group incompatibility between donor and recipient. Algorithms were updated in the following LT groups: standard patients, critical patients, oncology patients, patients with specific etiology, and patients at high immunologic risk. A steroid-free approach was generally recommended, except for patients with autoimmune liver disease and those at high immunologic risk., Conclusion: The updated consensus- and evidence-based 2024 recommendations for immunosuppression regimens in adult patients with ABO-compatible LT address a range of clinical variables that should be considered to optimize the choice of the immunosuppression treatment in clinical practice in Italy., (© 2024. The Author(s).)

The clinical case presented refers to a woman suffering from metastatic breast cancer treated with sacituzumab govitecan (SG) who has a long progression-free survival. The case is characterized by the extreme aggressiveness of the neoplastic disease that relapses during adjuvant hormonal treatment with a metastatic disease that presents immunohistochemical characteristics different from the primary tumor. After first-line therapy with nabpaclitaxel and atezolizumab and the subsequent one with carboplatin and gemcitabine, both characterized by short PFS, the third line with SG is characterized by obtaining a complete response and a prolonged PFS as well as extreme tolerability that continues to this day after 15 months of treatment.

Objective: Rare and complex epilepsies encompass a diverse range of disorders characterized by seizures. We aimed to establish a consensus on key issues related to these conditions through collaboration among experienced neurologists, neuropediatricians, and patient advocacy representatives., Methods: Employing a modified Delphi method, a scientific board comprising 20 physicians and 4 patient advocacy representatives synthesized existing literature with their expertise to formulate statements on contentious topics. A final 32-member expert panel, representing diverse regions of Italy, validated these statements through a two-round voting process, with consensus defined as an average score ≥7., Results: Sixteen statements reached a consensus, emphasizing the necessity for epidemiological studies to ascertain the true prevalence of rare epilepsies. Etiology emerged as a crucial factor influencing therapeutic strategies and outcome prediction, with particular concern regarding prolonged and tonic-clonic seizures. The importance of early implementation of specific drugs and non-pharmacological interventions in the treatment algorithm for developmental and epileptic encephalopathies (DEEs) was underscored. Multidisciplinary care involving experts with diverse skills was deemed essential, emphasizing non-seizure outcomes in adolescence and adulthood., Significance: This national consensus underscores the imperative for personalized, comprehensive, and multidisciplinary management of rare epilepsies/DEEs. It advocates for increased research, particularly in epidemiology and therapeutic approaches, to inform clinical decision-making and healthcare policies, ultimately enhancing patients' outcomes., Plain Language Summary: The modified Delphi method is broadly used to evaluate debated topics. In this work, we sought the consensus on integrated and social care in epilepsy management. Both representatives of high-level epilepsy centers and patients' caregivers were directly involved., (© 2024 The Author(s). Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Description of the Work: Leptin is a reliable predictive and surrogate marker of the efficacy of multitargeted treatment of cancer cachexia., Purpose: To the best of our knowledge, no study has assessed the predictive role of biomarkers in establishing the effectiveness of anti-cachectic treatment, which remains a complex issue. Herein, we aimed to find a marker that can detect early response to anti-cachectic treatment., Patients and Methods: From January 2012 to December 2022, all consecutive eligible advanced cancer patients with cachexia were prospectively enrolled in an exploratory and validation cohort according to eligibility criteria. All patients received a combined anti-cachectic treatment consisting of megestrol acetate plus celecoxib plus l-carnitine plus antioxidants that showed efficacy in a previous phase III randomized study. Primary endpoints were an increase in lean body mass (LBM), a decrease in resting energy expenditure (REE), a decrease in fatigue, and improvement in global quality of life., Results: A total of 553 consecutive patients were recruited. Twenty patients dropped out, equally distributed over the exploratory (11 patients) and validation (9 patients) cohorts, for early death due to disease progression. Then, 533 patients were deemed assessable. Leptin level changes inversely correlated with circulating levels of inflammatory mediators and reflected the improvement of body composition, energy metabolism, functional performance, and quality of life. At multivariate regression analysis, at week 8, leptin change was an independent predictor of LBM, skeletal muscle index (SMI), grip strength increase, and REE; at week 16, leptin change was an independent predictor of the same parameters and improvement in Eastern Cooperative Oncology Group performance status. The ability of leptin to predict changes in LBM, SMI, REE, and grip strength was superior to that of other inflammatory markers when comparing the receiver operating curves. Moreover, increasing delta leptin values were associated with significantly better outcomes in LBM, SMI, REE, grip strength, and fatigue., Conclusions: Leptin is a reliable predictive marker for multitargeted anti-cachectic treatment outcomes. Thus, it can be an ideal candidate for monitoring and predicting the effects of anti-cachectic treatment and a surrogate marker of the immune-metabolic actions of the selected drugs., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that echocardiography-derived phenotypes, depicting different degrees of RV remodeling and dysfunction, may provide additional prognostic information to current risk stratification tools., Methods: Consecutive incident PAH patients aged ≥18 years, diagnosed between January 2005 and December 2021, underwent clinical assessment, right heart catheterization, standard echocardiography. Simple echocardiographic variables were combined in order to define a priori four phenotypes representing different degrees of RV dilatation and RV-pulmonary arterial (PA) coupling: Phenotype 1 with mildy dilated right ventricle and preserved RV-PA coupling (n = 152 patients); phenotype 2 with mildly dilated right ventricle and poor RV-PA coupling (n = 143 patients); phenotype 3 with severely dilated right ventricle and preserved RV-PA coupling (n = 201 patients); phenotype 4 with severely dilated right ventricle and poor RV-PA coupling, with or without severe tricuspid regurgitation (n = 519 patients). Risk stratification was based on the European Society of Cardiology/European Respiratory Society (ESC/ERS) 3-strata model and Registry to Evaluate Early and Long-Term PAH disease Management (REVEAL) 2.0 score., Results: These phenotypes were present in all risk groups. Notably, regardless of the ESC/ERS risk stratum assigned to the patient, phenotype 4 was associated with a 2-fold increase of the odds of death (HR 2.1, 95% CI 1.6-2.8, p < 0.001), while phenotype 1 was associated with a 71% reduction in the odds of dying (HR 0.29, 95% CI 0.18-0.47, p < 0.001)., Conclusions: Echocardiography-derived phenotypes describing RV remodeling and dysfunction may provide prognostic information which is independent of and additional to the clinically defined risk in incident PAH patients., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Acute central nervous system (CNS) complications are common and well described among pediatric patients undergoing haematopoietic cell transplantation (HCT). However, their long-term outcomes are not known. The aim of this study is to describe the incidence, characteristics, and risk factors of long-term epilepsy in pediatric patients with acute CNS complications of HCT., Methods: This retrospective study included pediatric patients who developed acute CNS complications from autologous or allogeneic HCT between 2000 and 2022. Clinical, therapeutic and prognostic data including long-term outcomes were analyzed. A diagnosis of epilepsy was provided if unprovoked seizures occurred during follow-up., Results: Ninety-four patients (63 males, 31 females, median age 10 years, range 1-21 years) were included. The most common acute CNS complications were posterior reversible encephalopathy syndrome (n = 43, 46 %) and infections (n = 15, 16 %). Sixty-five patients (69 %) had acute symptomatic seizures, with 14 (16 %) having one or more episodes of status epilepticus (SE). Nine patients (9.6 %) were diagnosed with long-term focal epilepsy during the follow-up (5-year cumulative incidence from the acute complication, 13.3 %). Acute symptomatic SE during neurological complications of HCT was associated with an increased risk of long-term epilepsy (OR=14, 95 % CI 2.87-68.97)., Conclusions: A higher occurrence of epilepsy has been observed in our cohort compared to the general population. Acute symptomatic SE during HCT was associated with a higher risk of long-term epilepsy. Pediatric patients with CNS complications during HCT could benefit from specific neurological follow-up. Further studies are needed to characterize mechanisms of epileptogenesis in pediatric patients undergoing HCT., Competing Interests: Declaration of competing interest The Authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Thomas Chatzikonstantinou received honoraria from AbbVie. Lydia Scarfò received honoraria from AbbVie, AstraZeneca, BeiGene, Lilly, Janssen, Octapharma. Gloria Iacoboni received honoraria and travel support from Novartis, Kite/Gilead, Bristol‐Myers Squibb, Abbvie, Autolus, Miltenyi, and AstraZeneca. Rosa Collado received support for attending meetings from Janssen‐Cilag and S.A. Sara Galimberti received honoraria support for attending meetings from AbbVie, AstraZeneca, Jazz, Novartis, and Incyte, honoraria from Roche, Celgene, Pfizer, and Janssen, and support for attending meetings from Jazz, AstraZeneca, and Roche. Romain Guieze received honoraria, consulting fees, and support for attending meetings from AbbVie, Beigene, Roche, Janssen, and AstraZeneca. Eleftheria Hatzimichael received honoraria from AbbVie, Janssen‐Cilag, AstraZeneca, and Roche. Yair Herishanu received honoraria from Janssen, AbbVie, Roche, AstraZeneca, Medion, and Lilly. José‐Ángel Hernández‐Rivas received honoraria as a consultant from Janssen, AbbVie, AstraZeneca, Lilly, and BeiGene and support for attending meetings from Janssen, AbbVie, AstraZeneca, and BeiGene. Ozren Jaksic received honoraria from Johnson and Johnson, AstraZeneca, and Lilly, honoraria from Johnson and Johnson, AbbVie, AstraZeneca, and Lilly, and support for attending meetings from Johnson and Johnson, and AbbVie. Kamel Laribi received consulting fees from AbbVie, AstraZeneca, Janssen, Beigene, Takeda, and Novartis. Maya Koren‐Michowitz received honoraria from Novartis, Pfizer, and Gad Medical LTD. and support for attending meetings from Novartis. Arnon P. Kater received advisory board fees and research money from Janssen, AbbVie, BMS, AstraZeneca, and Roche/Genentech, and support for attending meetings from Janssen and AbbVie. Ioannis Kotsianidis received honoraria and consulting fees from AbbVie and Janssen. Ivana Milosevic received honoraria from AbbVie, Roche, Sandoz, AstraZeneca, and Janssen, and support for attending meetings from AbbVie, Roche, and Takeda. Almudena Navarro‐Bailón received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, Takeda, Janssen, and Beigene. Jacopo Olivieri received honoraria from AbbVie, AstraZeneca, and Janssen. Gianluigi Reda received consulting fees from AbbVie, AstraZeneca, Janssen, and Beigene, and is currently employed by AstraZeneca. Gian M. Rigolin received honoraria for participation in speaker's bureau from AbbVie, Astra Zeneca, Beigene, and Janssen, and support for attending meetings from Janssen. Mattia Schipani received honoraria and support for attending meetings from AstraZeneca, AbbVie, and Janssen‐Cilag and owns shares of stock in AbbVie, AstraZeneca, Merck, Eli Lilly, Sanofi, Johnson and Johnson, Pfizer, Gilead, and GSK. Tereza Shokralla and Stephan Stilgenbauer reports research funding from, consultancy or advisory role for, honoraria from, speakers' bureau participation for, and travel support from AbbVie, Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Celgene, Gilead, GlaxoSmithKline, Hoffmann‐La Roche, Incyte, Infinity, Janssen, Novartis, and Sunesis. Eric Tse received support for attending meetings from Takeda. Theodoros Vassilakopoulos received honoraria from Takeda, Roche, Genesis Pharma, Merck, Novartis, Gilead, Sandoz, AstraZeneca, Integris, and Servier, and support for attending meetings from Takeda, Roche, Genesis Pharma, Merck, Pfizer, and Winmedica. Candida Vitale received honoraria from AbbVie, consulting fees from AstraZeneca, and support for attending meetings from AstraZeneca, Takeda, and Janssen. Renata Walewska received honoraria from AbbVie, AstraZeneca, and Beigene, support for attending meetings from Janssen, AbbVie, and AstraZeneca, and advisory board fees from AbbVie, AstraZeneca, Janssen, Beigene, and SecuraBio. Lucrecia Yañez received honoraria from AbbVie, AstraZeneca, Novartis, Gilead, Janssen, Jazz, MSD, and Pfizer, support for attending meetings from AbbVie, AstraZeneca, Gilead, Janssen, and Pfizer, and advisory board fees from AbbVie, AstraZeneca, Jazz, Janssen, Beigene, and Celgene. Francesc Bosch received consulting fees, honoraria, and payment for expert testimony from AbbVie, Genentech, Novartis, Takeda, Janssen, Roche, Mundipharma, Celgene/BMS, AstraZeneca, Lilly, Beigene, Gilead and TG Therapeutics, Advantage Allogene, Lava Therapeutics, and Enterome. Stephen Mulligan received advisory board fees from AbbVie, AstraZeneca, Janssen, Roche, and BeiGene. Maria Angelopoulou received consulting fees from AbbVie, Takeda, Janssen, Roche, Genesis, Gilead, and Amgen and honoraria from AbbVie, Takeda, Roche, Genesis, Gilead, and Novartis. Fatih Demirkan received support for attending meetings from Janssen and AbbVie. Tomas Papajík received honoraria and advisory board fees from AbbVie, Janssen‐Cilag, and AstraZeneca, and support for attending meetings from AstraZeneca. Marta Coscia received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, and Janssen. Constantine Tam received honoraria from AbbVie, Beigene, Janssen, and LOXO. Antonio Cuneo received honoraria, advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, Beigene, Janssen, and Lilly. Gianluca Gaidano received honoraria from Abbvie, AstraZeneca, BeiGene, Hikma, Incyte, Janssen, and Lilly. Niki Stavroyianni received honoraria from Janssen, AbbVie, AstraZeneca, and Lilly, and support for attending meetings from Janssen and AstraZeneca. Lukas Smolej received consulting fees, honoraria, and support for attending meetings from AbbVie, AstraZeneca, and Janssen and advisory board fees from AbbVie and AstraZeneca. Martin Spacek received honoraria and consulting and advisory board fees, and support for attending meetings from AbbVie, AstraZeneca, and Janssen. Michael Doubek received research support and honoraria from AbbVie, AstraZeneca, and Janssen. Eugene Nikitin received honoraria from AbbVie. Kostas Stamatopoulos received research support from AbbVie, AstraZeneca, Janssen, Novartis, and Roche; honoraria from AbbVie, AstraZeneca, Bristol Myers Squibb, Lilly, and Janssen. Paolo Ghia received research support from AbbVie, AstraZeneca, BMS, Janssen and honoraria from AbbVie, AstraZeneca, BeiGene, BMS, Galapagos, Genmab, Janssen, Loxo Oncology @Lilly, MSD, Roche, and is an Editor of HemaSphere. Georgios Karakatsoulis, Eva Minga, Dimitra Chamou, Jana Kotaskova, Christos Demosthenous, Elisa Albi, Miguel Alcoceba, Salem Al‐Shemari, Thérèse Aurran‐Schleinitz, Francesca Bacchiarri, Sofia Chatzileontiadou, Zadie Davis, Marcos Daniel de Deus Santos, Maria Dimou, Elena Dmitrieva, David Donaldson, Gimena Dos Santos, Barbara Dreta, Maria Efstathopoulou, Shaimaa El‐Ashwah, Alicia Enrico, Andrzej Frygier, Andrea Galitzia, Eva Gimeno, Valerio Guarente, Sean Harrop, Elżbieta Kalicińska, Volkan Karakus, Bonnie Kho, Maria Kislova, Εliana Konstantinou, Zuzana Kubova, Jorge Labrador, Deepesh Lad, Luca Laurenti, Thomas Longval, Alberto Lopez‐Garcia, Juan Marquet, Stanislava Maslejova, Carlota Mayor‐Bastida, Biljana Mihaljevic, Fatima Miras, Riccardo Moia, Marta Morawska, Uttam K. Nath, Irina Panovska‐Stavridis, Maria Papaioannou, Cheyenne Pierie, Anna Puiggros, Rosa Ruchlemer, Annett Schiwitza, Yandong Shen, Tereza Shokralla, Martin Simkovic, Svetlana Smirnova, Dina S. A. Soliman, Tamar Tadmor, Kristina Tomic, Andrea Visentin, George Vrachiolias, Vojin Vukovic, Zhenshu Xu, Munci Yagci, Mohamed Yassin, Jana Zuchnicka, David Oscier, Alessandro Gozzetti, Panagiotis Panagiotidis, Blanca Espinet, Paolo Sportoletti, Gerassimos A. Pangalis, Viola M. Popov, Bella Biderman, Roberta Murru, Rainer Claus, Livio Trentin, Darko Antic, Olga B. Kalashnikova, Mark Catherwood, Sarka Pospisilova, and Anastasia Chatzidimitriou have no conflict of interest to disclose.

In patients at high cardiovascular risk, a low-density lipoprotein cholesterol (LDL-C) reduction of ≥50% from baseline and an LDL-C goal of <70 mg/dL (or <55 mg/dL in very high-risk patients) are recommended. Multiple registry and retrospective studies have shown that patients with high atherosclerotic cardiovascular risk often do not reach the targets defined by the European Society of Cardiology guidelines as a result of suboptimal management of LDL-C. Here, we report the data on lipid-lowering therapy and lipid targets from the Survey on Risk FactOrs and CardiovascuLar secondary prEvention and drug strategieS (SOFOCLES), an observational, prospective study designed to collect data on patients with ischemic heart disease treated at cardiac outpatient clinics across the Italian national territory. We included patients with known coronary heart disease (CHD) who underwent follow-up visits at various outpatient cardiology clinics. A total of 2532 patients were included (mean age: 67±17 years, 80% male). Among patients with available laboratory data (n=1712), 995 (58%) had LDL-C<70 mg/dL, 717 (42%) had LDL-C≥70 mg/dL, and 470 (27%) had LDL-C<55 mg/dL. Patients who more frequently achieved the recommended LDL-C levels were male, had diabetes, had a higher educational level, and performed intense physical activity. Statins were used in 2339 (92%) patients, high-intensity statins (e.g., rosuvastatin 20/40 mg or atorvastatin 40/80 mg) in 1547 patients (61% of the whole population and 66% of patients on statins), and ezetimibe in 891 patients (35%). Patients receiving high-intensity statins tended to be younger, not to have diabetes, and to have been included in a cardiac rehabilitation program. In a real-world sample of Italian patients with CHD, adherence to lipid-lowering therapy fell markedly short of optimal levels. Many patients did not achieve the LDL-C target of 70 mg/dL, and even fewer reached the LDL-C target of 55 mg/dL. Notably, patients with a lower educational level had a greater likelihood of being undertreated. Strategies aimed at improving preventive interventions for CHD and overcoming social disparities should be evaluated and optimized.

Background: Continence issues due to organic causes including previous colorectal surgery or neurological issues might benefit from Transanal irrigation (TAI) that proved to be highly effective but with a number of limitations including a relatively high discontinuation rates. Our study was aimed at evaluating the efficacy of an advanced protocol tailored to each patient to prevent dropout and increase satisfaction, independence, and quality of life., Materials and Methods: This was a prospective, interventional, multicenter, nonrandomized study involving children aged 4-18 years with bowel dysfunction unresponsive to conventional treatments who required TAI. TAI was performed in accordance to the best standards of care with a total irrigation volume that was determined based on low emission X-Ray barium enemas performed at the very beginning of the study. All patients underwent training and assessments of continence, patients' perspectives and quality of life were performed at different timepoints from enrollment (T0) up to 6 months since TAI was introduced (T3)., Results: A total of 78 patients were enrolled. Male to female ratio was 1.4:1. Mean age at enrollment was 106.1 ± 42.8 months. Discontinuation was reported by 3 patients (3.8 %). Continence, satisfaction and a number of other outcome measures increased from baseline (T0) to the last visit (T3). In particular, mean Rintala total score increased linearly from 7.8 to 14.8 during the study period (T0 to T3 timepoints). On a multivariate analysis, the only parameter that proved to be inversely associated with continence as well as with other outcome measures was the use of laxatives at enrollment and during the study., Conclusions: This study has demonstrated the high efficacy of this innovative patient-tailored TAI protocol across all assessed scores. Of note, given the negative impact of laxatives, our findings suggest limiting their use in this patient population to further increase the efficacy of the procedure., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Mesenchymal-epithelial transition (MET) exon 14 (METex14) skipping mutation is a rare alteration in non-small-cell lung cancer (NSCLC), occurring in about 3%-4% of cases. Here we report disease and patient characteristics, and efficacy and tolerability of MET inhibitors among advanced METex14 NSCLC patients from the Italian real-world registry ATLAS., Materials and Methods: Clinical-pathological and molecular data, and treatment efficacy/tolerability outcomes were retrospectively collected from the ATLAS registry., Results: From July 2020 to July 2023 a total of 146 METex14 advanced NSCLC patients were included across 27 Italian centers. Median age was 74 years, and most patients were male (52%), with an Eastern Cooperative Oncology Group performance status < 2 (72%) and adenocarcinoma subtype (83%). One hundred and twenty-five out of 146 (86%) patients received at least one line of systemic anticancer therapy. Fifty-six (38%) were treated with capmatinib and 34 (23%) with tepotinib. 29% and 52% of them received targeted treatment in the first and second line, respectively. In the cohort of patients treated with MET inhibitors, the response rate (RR) was 37% (33% in previously treated patients and 46% in treatment-naïve) with a disease control rate of 62%. With a median follow-up of 10.8 months, progression-free survival was 6.6 months [95% confidence interval (CI) 4.3-8.3 months] and overall survival was 10.7 months (95% CI 7.2-19.3 months). In patients with measurable brain metastases (17 cases), the intracranial RR was 41%. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 12% of patients with grade 3 peripheral edema in 7% of cases. A fatal adverse reaction occurred in one patient due to pneumonitis. TRAEs-related dose reduction and discontinuation were reported in 6% and 8% of cases, respectively., Conclusion: Capmatinib and tepotinib represent an effective treatment option in NSCLC patients with METex14. Real-world efficacy outcomes are worse than those reported in prospective clinical trials. Their activity is more pronounced in the treatment-naïve population, suggesting that this is the right setting in the management of patients with METex14., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction and importance: Large retroperitoneal schwannomas are rare and present significant challenges in surgical management, particularly when located in the pelvic region. Gynecologists can encounter rare problems when a pelvic schwannoma is mistaken for an adnexal pathology. Case Presentation: A 62-year-old woman presented with a giant retroperitoneal mass suspected of a potentially malignant ovarian tumor preoperatively. Computed tomography revealed a large mixed solid-cystic mass near the right adnexa measuring 118 × 100 × 80 mm. The cancer antigen 125 level was 196 U/mL. We performed a diagnostic-operative laparoscopy, which showed a retroperitoneal neoformation below the cava and aortic bifurcation adherent to the sacrum, right pelvic vessels, and hypogastric nerve up to the vagina. We carefully detached the mass from the nearby tissues using the most appropriate laparoscopic devices. The entire neoplasm was removed through the vagina into a surgical bag. The surgery lasted 180 min without complications. Histology revealed a grade I benign schwannoma. At the 12-month follow-up, the patient was asymptomatic without signs of recurrence. Clinical Discussion: Pelvic retroperitoneal schwannomas can mimic ovarian carcinomas; misdiagnosis may occur due to their rarity and the difficulty of interpreting preoperative imaging. In case of unexpected giant presacral schwannomas surgical management is challenging due to their peculiar location. Conclusion: This case underscores the need for a skilled, experienced team of gynecological oncologists to achieve favorable outcomes when performing laparoscopic surgery of giant pelvic retroperitoneal schwannoma. Adequate knowledge of the complex pelvic anatomy, careful surgical planning, and familiarity with the most appropriate surgical tools are critical points., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Contraception, pregnancy and fertility are seldom discussed with women receiving dialysis and the medical staff of dialysis centres. Since the majority of women on dialysis are past childbearing age, these themes are not always given proper consideration and this category of patients may be missing important information. Young women of childbearing age who are on dialysis frequently experience sexual dysfunction and hormonal disorders of the hypothalamic-pituitary-gonadal axis. In addition, dialysis often has a relevant psychological impact and affects the person's social role. Physical changes may accompany kidney failure, including the presence of a vascular or peritoneal access. The dialysis ward is not a place that facilitates privacy, and discussing contraception is not always easy, particularly in some cultural contexts, or between a male doctor and a young woman. While pregnancy and contraception are routinely addressed with women waiting for a kidney transplant, they are less frequently discussed with women on dialysis. Numerous studies have found that over half of the pregnancies in women on dialysis are unplanned. How frequently patients are seen (at each dialysis session, or during periodic visits) does not necessarily make things better, as often some issues are taken for granted or discussing them is postponed. In our centre, over 160 patients are on chronic hemodialysis (HD) and 20 are on peritoneal or home HD. Only nine women were of childbearing age in our center, all on HD. We discussed with them on counselling about pregnancy, and to ensure that all women of childbearing age would be offered counselling on contraception and pregnancy, we designed simple leaflets and an infographic, in collaboration with our nursing team and residents, as a guide and a reminder for our staff to discuss these topics with the patients., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Atrial fibrillation and heart failure are two common cardiovascular conditions that frequently coexist, and it has been widely demonstrated that in patients with chronic heart failure, atrial fibrillation is associated with a significant increase in the risk of all-cause death and all-cause hospitalization. Nevertheless, there is no unanimous consensus in the literature on how to approach this category of patients and which therapeutic strategy (rhythm control or frequency control) is the most favorable in terms of prognosis; moreover, there is still a lack of data comparing the different ablative techniques of atrial fibrillation in terms of efficacy, and many of the current trials do not consider current ablative techniques such as high-power short-duration ablation index protocol for radiofrequency pulmonary vein isolation. Eventually, while several RCTs have widely proved that in patients with heart failure with reduced ejection fraction, ablation of atrial fibrillation is superior to medical therapy alone, there is no consensus regarding those with preserved ejection fraction. For these reasons, in this review, we aim to summarize the main updated evidence guiding clinical decision in this complex scenario, with a special focus on the most recent trials and the latest meta-analyses that examined the role of catheter ablation (CA) in rhythm control in patients with AF and HF.

Background: The optimal strategy during percutaneous coronary intervention (PCI) of aneurysmatic right coronary artery (ARCA) remains uncertain and has never been tested in the acute setting., Objectives: To compare the in-hospital and long-term outcomes of immediate and staged PCI strategies for ARCA as culprit lesions during acute coronary syndrome (ACS)., Methods: Among 102.376 PCIs performed in 18 European centers, a total of 85 patients presenting with acute coronary syndrome undergoing ARCA PCI were finally included in the analysis. PCI strategy (stenting performed during the immediate vs staged procedure) and pharmacological approach adopted were collected. The primary outcome was procedural success (technical success without in-hospital MACE)., Results: The primary outcome occurred in 48.2 % of cases, with no significant differences observed between the immediate and staged PCI groups (50.9 % vs 43.3 %, p = 0.504). Patients in the staged-PCI group had a significantly higher rate of intravenous anticoagulant use (83.3 % vs 48.1 %, p = 0.002), BARC type 3 and 5 bleedings (12.9 % vs 1.9 %, p = 0.037), and longer in-hospital stay (7.40 ± 5.11 vs 9.5 ± 5.25 days, p = 0.049). After multivariate analysis, no independent predictors for procedural success were found in either group. Target lesion failure occurred in 24.1 % of cases without differences between groups at a median follow-up of three years., Conclusions: Among patients undergoing ARCA PCI in the setting of ACS, immediate or staged PCI were associated with similar in-hospital and long-term outcomes. However, staged PCI was associated with a higher risk of major bleeding events and longer length of stay compared to immediate PCI strategy., Competing Interests: Declaration of competing interest Dr. Azzalini received consulting fees from Abiomed, Teleflex, GE Healthcare, Philips, Abbott Vascular, Asahi Intecc, and Cardiovascular Systems, Inc.; Corrado Tamburino is a consultant for Medtronic and received speaker honoraria from Meril. Ferdinando Varbella receives consulting fees from Amgen, Sanofi, Pfizer, Astra Zeneca, Daichi Sankyo and Bayer; Alessio La Manna is a proctor for Kardia srl, Terumo Italia and GADA spa. Jose Maria De La Torre Hernandez received consulting fees from Boston Scientific, Medtronic, Abbot, Biotronik and Daichii Sankyo. Massimo Leoncini speaker honoraria from Boston Scientific, Terumo, Shockwave Medical, Penumbra and Daichii Sankyo. The other coauthors do not have any conflict of interest related to this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Concomitant aortic stenosis and coronary artery disease in the elderly population is frequent and the proper therapeutic approach is a matter of debate. We present 2 challenging cases of patients affected by severe aortic stenosis and chronic total occlusion of the left main, demonstrating the safety and feasibility of transcatheter aortic valve replacement, performed both with balloon-expandable and self-expanding valves., Competing Interests: Prof Flavio Ribichini is a physician proctor for Medtronic and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Renal failure is one of the most important manifestations of multiple myeloma. It is caused by renal lesions such as cast nephropathy, immunoglobulin deposition disease, AL amyloidosis or other glomerular and/or tubular diseases, mostly due to the toxic effect of free light chains in serum. Renal failure can represent a clinical emergency and is associated with poor outcome in newly diagnosed and relapsed/refractory multiple myeloma patients. Although progression-free survival and overall survival have improved with the introduction of novel agents, renal failure remains a challenge for the treatment of patients with multiple myeloma. Monoclonal antibodies are a component of therapy for newly diagnosed and relapsed/refractory patients and, based on clinical trials and real-world experience, are also safe and effective for subjects with renal failure, even if they are on dialysis. Most of the data are on anti-CD38 and anti-SLAM7 antibodies, but new antibody-drug conjugates such as belantamab mafodotin and bispecific antibodies also appear to be effective in myeloma kidney disease. In the future, we will have to face some challenges, such as defining new criteria for renal response to treatment, defining specific trials for these difficult-to-treat patients and integrating different therapeutic options.

Introduction: The underdiagnosis of chronic kidney disease (CKD) remains a significant public health concern. The Early chroNic kiDney disease pOint of caRe Screening (ENDORSE) project aimed to evaluate the clinical and economic implications of a targeted training intervention for general practitioners (GPs) to enhance CKD awareness and early diagnosis., Methods: Data on estimated Glomerular Filtration Rate (eGFR) and Urinary Albumin-Creatinine Ratio (uACR) were collected by 53 Italian GPs from 112,178 patients at baseline and after six months. The intervention involved six months of hybrid training provided by 11 nephrologists, which included formal lectures, instant messaging support, and joint visits for complex cases., Results: The results demonstrated a substantial increase in the use of eGFR (+44.7%) and uACR (+95.2%) tests. This led to a 128.9% rise in the number of individuals screened for CKD using the KDIGO classification, resulting in a 62% increase in CKD diagnoses. The intervention's impact was particularly notable in high-risk groups, including patients with type 2 diabetes, hypertension, and heart failure., Discussion: A budget impact analysis projected cumulative five-year savings of €1.7 million for the study cohort. When these findings were extrapolated to the entire Italian CKD population, potential savings were estimated at €106.6 million, highlighting significant cost savings for the national health service. The clinical simulation assumed that early diagnosed CKD patients would be treated according to current indications for dapagliflozin, which slows disease progression., Conclusion: The ENDORSE model demonstrated that targeted training for GPs can significantly improve early CKD detection, leading to better patient outcomes and considerable economic benefits. This approach shows promise for broader implementation to address the underdiagnosis of CKD on a national and potentially international scale., Competing Interests: FP received fees from AstraZeneca and GSK for lectures. LDN received fees from AstraZeneca, Astellas, Bayer and NovoNordisk for lectures and scientific consultations. GG received fees from AstraZeneca, Astellas, Alexion, GSK, Boehringer, Novartis and Bayer for lectures and scientific consultation. MB received fees from Astellas, AstraZeneca, GSK, Nipro and Travere Therapeutics for lectures and scientific consultations. GLM received payment or honoraria for lectures, presentation, speakers bureaus, eduational events - Support for attending meetings or and/or travel from Astellas, Hansa Biopharma, Travere, Vifor, Eli-Lily, GlaxoSmithKline, Alexion, Braun, and Boehringer Ingelheim. LG received research grants from Abionyx, Sanofi; consultancy fees from Baxter, Travere, AstraZeneca, GSK, Novartis, Chinook, Roche, Reata, Nestle, Otsuka, Gilead Science, Bayer, Vifor Fresenius; speaker fees from Bayer and Werfen. The authors report no other conflicts of interest in this work., (© 2024 Pesce et al.)

The consumption of energy drinks (ED) has become a growing public health issue, since potentially ED-related serious adverse cardiovascular events, including arrhythmias, myocardial infarction, cardiomyopathies, and sudden cardiac death, have been reported in recent years. The substances contained in ED include caffeine, taurine, sugars, B group vitamins and phyto-derivatives, which, especially if taken in large quantities and in a short amount of time, could cause serious side effects through various mechanisms of action, such as increased blood pressure and QT interval prolongation. Although there are still many open questions on ED that require further specific investigations, there is an urgent need for information and educational plans to the population, as well as for regulatory actions, particularly regarding transparency of substances and possible adverse effects.

Competing Interests: The authors declare no conflict of interest.

Anaemia is common in chronic kidney disease (CKD) and has a significant impact on quality of life (QoL), work productivity and outcomes. Current management includes oral or intravenous iron and erythropoiesis-stimulating agents (ESAs), to which hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been recently added, increasing the available therapeutic options. In randomised controlled trials, only intravenous iron improved cardiovascular outcome, while some ESAs were associated with increased adverse cardiovascular events. Despite therapeutic advances, several challenges and unmet needs remain in the current management of anaemia of CKD. In particular, clinical practice does not include an assessment of QoL, which prompted a group of European nephrologists and representatives of patient advocacy groups to revisit the current approach. In this consensus document, the authors propose a move towards a more holistic, personalised and long-term approach, based on existing evidence. The focus of treatment should be on improving QoL without increasing the risk of adverse cardiovascular events, and tailoring management strategies to the needs of the individual. In addition, the authors discuss the suitability of a currently available anaemia of CKD-specific health-related QoL measure for inclusion in the routine clinical management of anaemia of CKD. The authors also outline the logistics and challenges of incorporating such a measure into electronic health records and how it may be used to improve QoL for people with anaemia of CKD., Competing Interests: I.D. has received research grants from Baxter, Medtronic and Sanofi and honoraria for advisory boards and speaker meetings from AstraZeneca, Bayer, GSK, Sanofi and Vifor Pharma. M.F. has received consultancy fees from AstraZeneca and GSK. H.F. has received consultancy and speaker fees from AstraZeneca, BMS, Sanofi, GSK and Vifor Pharma. L.G.’s university department (DIMEPRE-J) received research grants from Abionyx and Sanofi; he has received consultancy and speaker fees from AstraZeneca, Baxter, Chinook, GSK, Medtronic, Mundipharma, Novartis, Pharmadoc, F. Hoffmann-La Roche Ltd, Sandoz, Sanofi, Travere, Vifor Pharma, Astellas Pharma, Estor, Fresenius Kabi and Werfen. N.H. is an employee of GSK. R.M. has been a member of advisory boards for Amgen, Astellas Pharma and GSK; has received consultancy fees from Bayer and GSK and has been an invited speaker at meetings supported by Amgen, Astellas Pharma, AstraZeneca and Vifor Pharma. A.P. has received consultancy fees from AstraZeneca and GSK. J.P. has received consultancy and speaker fees from Astellas Pharma, GSK and Vifor Pharma. C.R. has received consultancy and speaker fees from Akebia, Astellas Pharma, AstraZeneca, Boehringer Ingelheim, GSK, Otsuka and Vifor Pharma. J.E.S.A. has received consultancy and speaker fees from Astellas Pharma, Baxter, GSK and Vifor Pharma. P.U.T. has received honoraria for advisory boards and speaker meetings from Amgen, Astellas Pharma, AstraZeneca, Baxter, GSK, Théradial and Vifor Pharma. R.C.V. is an advisor to AstraZeneca, Baxter, Fresenius Kabi, Fresenius Medical Care, GSK, Kibow Biotech, Nextkidney, Nipro and Novartis. C.W. has received consultancy fees from Amgen, Amicus, Astellas Pharma, AstraZeneca, Bayer, Boehringer Ingelheim, Vifor Pharma, Chiesi, Chugai, Fresenius Medical Care, GSK, Idorsia, Eli Lilly, MSD, Novartis and Novo Nordisk and grants and consultancy fees from Boehringer Ingelheim and Sanofi. C.I.B. and D.G.Z. have nothing to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background & Aims: International consensus has recently introduced a new definition of metabolic dysfunction-associated steatotic liver disease (MASLD). We sought to analyse epidemiological trends, prognostic features, and transplant survival benefits of patients with MASLD and without MASLD waiting for liver transplantation (LT) in Italy., Methods: Using the Italian Liver Transplant Registry database, we analysed data from adult patients listed for primary LT attributable to end-stage chronic liver disease between January 2012 and December 2022. Independent multivariable waiting lists and post-transplant survival models were developed for patients with and without hepatocellular carcinoma (HCC). A Monte Carlo simulation was used to create 5-year transplant benefit distributions based on the presence of MASLD, HCC, and model for end-stage liver disease (MELD)-sodium values., Results: A total sample of 1,941 patients with MASLD and 11,201 patients without MASLD was considered. A significant increase in the prevalence of MASLD as an indication for LT was observed from 2012 to 2022, for both cohorts with HCC (from 17.7 to 30%) and without HCC (from 9.5 to 11.8%) cohorts. Projections suggest that, as early as next year, MASLD will overcome HCV as the second most common indication for transplantation after alcoholic liver disease in Italy. According to univariate and multivariate analyses, MASLD was not an independent predictive factor for patient survival after transplantation. However, it increased the risk of death for patients on the waiting list without HCC (hazard ratio 1.62, p <0.001). At the same MELD-sodium, the 5-year transplant benefit was higher in patients with non-HCC MASLD, followed by patients with HCC, whereas it was lower in patients without HCC and without MASLD., Conclusions: Patients with non-HCC MASLD had an increased waitlist mortality and 5-year transplant survival benefit compared with other candidates., Impact and Implications: The present research addresses the critical need to understand the evolving landscape of liver transplantation indications, mainly focusing on metabolic dysfunction-associated steatotic liver disease (MASLD) in Italy. Given the significant rise in MASLD cases, these findings highlight that patients with non-HCC MASLD face increased waitlist mortality and benefit more from liver transplantation within 5 years compared with other candidates. The significance of these results lies in their emphasis on the necessity of focusing on patients with MASLD on waiting lists to improve outcomes. By tailoring transplant eligibility criteria and resource allocation, the study provides actionable insights to improve patient survival and optimise liver transplantation practices., (© 2024 The Author(s).)

The treatment landscape for CLL has undergone a profound transformation with the advent of targeted agents (TAs) like Bruton's Tyrosine Kinase inhibitors (BTKis) and BCL-2 inhibitors (BCL-2is). These agents target crucial cellular pathways in CLL, offering superior efficacy over traditional chemo-immunotherapy, which has led to improved progression-free and overall survival rates. This advancement promises enhanced disease control and potentially normal life expectancy for many patients. However, the journey is not without challenges, as these TAs are associated with a range of adverse events (AEs) that can impact treatment efficacy and patient quality of life. This review focuses on detailing the various AEs related to TA management in CLL, evaluating their frequency and clinical impact. The aim is to present a comprehensive guide to the effective management of these AEs, ensuring optimal tolerability and efficacy of TAs. By reviewing the existing literature and consolidating findings, we provide insights into AE management, which is crucial for maximizing patient outcomes in CLL therapy.

The issue of suboptimal drug regimen adherence in secondary cardiovascular prevention presents a significant barrier to improving patient outcomes. To address this, the utilization of drug combinations, specifically single pill combinations (SPCs) and polypills, was proposed as a strategy to simplify treatment regimens. This approach aims to enhance treatment accessibility, affordability, and adherence, thereby reducing healthcare costs and improving patient health. The document is an Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) scientific statement on simplifying drug regimens for secondary cardiovascular prevention. It discusses the underuse of treatments despite available, effective, and accessible options, highlighting a significant gap in secondary prevention across different socio-economic statuses and countries. The statement explores barriers to implementing evidence-based treatments, including patient, healthcare provider, and system-related challenges. The paper also reviews international guidelines, the role of SPCs and polypills in clinical practice, and their economic impact, advocating for their use in secondary prevention to improve patient outcomes and adherence., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

In recent decades, an incredible evolution in antithrombotic therapies used for treating patients with atherosclerosis, atrial fibrillation, and venous thromboembolism has been observed, leading to the availability of increasingly safe drugs. Nonetheless, bleeding complications remain a significant concern, with considerable health, social, and economic implications. To improve the acute management of patients experiencing or at risk for major bleeding events, specific reversal agents for antithrombotic drugs have been recently developed. While these agents demonstrate effectiveness in small-scale pharmacodynamic studies and clinical trials, it is imperative to balance the benefits of reversing antiplatelet or anticoagulant therapy against the risk of prothrombotic effects. These risks include the potential loss of antithrombotic protection and the prothrombotic tendencies associated with bleeding, major surgery, or trauma. This joint document of the Italian Association of Hospital Cardiologists ( Associazione Nazionale Medici Cardiologi Ospedalieri ) and the Italian Society of Emergency Medicine ( Società Italiana di Medicina d'Emergenza-Urgenza ) delineates the key features and efficacy of available reversal agents. It also provides practical flowcharts to guide their use in patients with active bleeding or those at elevated risk of major bleeding events., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Obesity is a chronic and relapsing disease characterized by the interaction between individual predispositions and an obesogenic environment. Recent advances in understanding the mechanisms of energetic homoeostasis paved the way to more effective therapeutic approaches compared with traditional treatments. Since obesity is a complex disease, it necessitates a multi-disciplinary approach whose implementation remains challenging. Nonetheless, emerging pharmacological interventions appear promising. Currently, therapeutic success is discreet in the short term but often fails to maintain long-term weight loss due to a high likelihood of weight regain. Cardiologists play a key role in managing patients with obesity, yet often lack familiarity with its comprehensive management. The aim of this document is to summarize knowledge to consolidate essential knowledge for clinicians to effectively treat patients living with obesity. The paper emphasizes the pivotal role of a strong patient-clinician relationship in navigating successful treatment. We analyse the criteria commonly used to diagnose obesity and point out the strengths and limitations of different criteria. Furthermore, we discuss the role of obesiologists and the contributions of cardiologists. In addition, we detail key components of effective therapeutic strategies, including educational aspects and pharmacological options., Competing Interests: Conflict of interest: Authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Individuals who experienced severe Traumatic Brain Injury (sTBI) are often characterized by relevant motor dysfunctions which are likely to negatively affect activities of daily living and quality of life and often persist for years. However, detailed objective information about their magnitude are scarce. The aim of this study was to quantitatively assess the extent of motor deficits in terms of postural control effectiveness under static and dynamic conditions and to investigate the existence of possible correlations between the results of clinical tests and instrumental measures. Postural sway and functional mobility (i.e., instrumented Timed Up and Go test, iTUG) were objectively measured in 18 individuals with sTBI and 18 healthy controls using a pressure plate and a wearable inertial sensor. Additionally, participants with history of sTBI completed the Rivermead Mobility Index (RMI). One-way ANOVA and Spearman's rank correlation analysis were employed to examine differences between the two groups and determine potential correlations between the instrumental tests and clinical scales. The results show that people with sTBI were characterized by larger sway area and longer iTUG walking sub-phase. Significant correlations were also detected between RMI scores and iTUG total duration, as well as the walking phase. Taken together, these findings suggest that, even years after the initial injury, individuals with sTBI appear characterized by impaired postural control and functional mobility, which appears correlated with the RMI score. The integration of instrumental measures with clinical scales in the routine assessment and treatment of individuals with sTBI would result in more comprehensive, objective, and sensitive evaluations, thus improving precision in treatment planning, enabling ongoing progress monitoring, and highlighting the presence of motor deficits even years after the initial injury. Such integration is of importance for enhancing the long-term quality of life for individuals with sTBI., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Federico Arippa reports financial support was partially provided by Sardegna Ricerche, I FAIR Program, and by the 10.13039/501100009873Regione Autonoma della Sardegna. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Nutritional therapy (NT) based on a controlled protein intake represents a cornerstone in managing chronic kidney disease (CKD). However, if a CKD patient is at the same time affected by cancer, oncologists and nutritionists tend to suggest a dietary regimen based on high protein intake to avoid catabolism and malnutrition. International guidelines are not clear when we consider onco-nephrological patients and, as a consequence, no clinical shared strategy is currently applied in clinical practice. In particular, no precise nutritional management is established in nephrectomized patients for renal cell carcinoma (RCC), a specific oncological cohort of patients whose sudden kidney removal forces the remnant one to start a compensatory mechanism of adaptive hyperfiltration. Our study aimed to investigate the efficacy of a low-normal-protein high-calorie (LNPHC) diet based on a Mediterranean model in a consecutive cohort of nephrectomized RCC patients using an integrated nephrologist and nutritionist approach. A consecutive cohort of 40 nephrectomized RCC adult (age > 18) patients who were screened for malnutrition (malnutrition screening tool, MST < 2) were enrolled in a tertiary institution between 2020 and 2022 after signing a specific informed consent form. Each patient underwent an initial nephrological and nutritional evaluation and was subsequently subjected to a conventional CKD LNPHC diet integrated with aproteic foods (0.8 g/Kg/die: calories: 30-35 kcal per kg body weight/die) for a period of 6 months (±2 months). The diet was structured after considering eGFR (CKD-EPI 2021 creatinine formula), comorbidities, and nutritional status. MST, body mass index (BMI), phase angle (PA), fat mass percentage (FM%), fat-free mass index (FFMI), body cell mass index (BCMI), extracellular/intracellular water ratio (ECW/ICW), extracellular matrix/body cell mass ratio (ECM/BCM), waist/hip circumference ratio (WHC), lab test exams, and clinical variables were examined at baseline and after the study period. Our results clearly highlighted that the LNPHC diet was able to significantly improve several nutritional parameters, avoiding malnutrition and catabolism. In particular, the LNPHC diet preserved the BCM index (delta on median, ΔM + 0.3 kg/m 2 ) and reduced the ECM/BCM ratio (ΔM - 0.03 *), with a significant reduction in the ECW/ICW ratio (ΔM - 0.02 *), all while increasing TBW (ΔM + 2.3% *). The LNPHC diet was able to preserve FFM while simultaneously depleting FM and, moreover, it led to a significant reduction in urea (ΔM - 11 mg/dL **). In conclusion, the LNPHC diet represents a new important therapeutic strategy that should be considered when treating onco-nephrological patients with solitary kidney due to renal cancer.

Introduction/aims: The global incidence and prevalence of myasthenia gravis (MG) range between 6-31/million and 10-37/100,000, respectively. Sardinia is a high-risk region for different immune-mediated disorders, but the epidemiology of MG remains unclear. We determined the epidemiology of MG with acetylcholine receptor (AChR)-immunoglobulin G (IgG) and muscle-specific tyrosine kinase (MuSK)-IgG in the district of Sassari (North-Western Sardinia; population, 325,288)., Methods: From the laboratory of the University Hospital of Sassari (reference for AChR/MuSK-IgG testing in Sardinia since 1998) and the main neurology units in Sardinia, we retrospectively identified MG patients with (1) AChR-IgG and/or MuSK-IgG positivity by radioimmunoprecipitation assay; and (2) residency in the district of Sassari. Incidence (January 2010-December 2019) and prevalence (December 31, 2019) were calculated., Results: A total of 202 patients were included (incident, 107; prevalent, 180). Antibody specificities were AChR (n = 187 [93%]) and MuSK (n = 15 [7%]). The crude MG incidence (95% confidence interval) was 32.6 (26.8-39.2)/million, while prevalence was 55.3 (47.7-63.9)/100,000. After age-standardization to the world population, incidence decreased to 18.4 (14.3-22.5)/million, while prevalence decreased to 31.6 (26.1-37.0)/100,000. Among incident cases, age strata (years) at MG onset were: <18 (2%), 18-49 (14%), 50-64 (21%), and ≥65 (63%)., Discussion: Sardinia is a high-risk region for MG, with a prevalence that exceeds the European threshold for rare disease. Identification of the environmental and genetic determinants of this risk may improve our understanding of disease pathophysiology., (© 2024 Wiley Periodicals LLC.)