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Background: Islet transplantation has the potential to cure type 1 diabetes by restoring endogenous insulin production. However, its success relies on balancing improved glycaemic control with the risks of immunosuppressive therapy. This study aimed to evaluate long-term outcomes of islet transplantation alone for type 1 diabetes, focusing on the effects of islet mass and immunosuppressive regimens on graft survival and insulin independence, and weighing glycaemic control benefits against the risks of immunosuppressive therapy., Methods: This cohort study retrospectively analysed individuals aged 18-67 years with type 1 diabetes who received intraportal islet transplantation alone at IRCCS Ospedale San Raffaele, Milan, Italy. Inclusion criteria comprised adults with type 1 diabetes diagnosed before the age of 55 years with severe recurrent hypoglycaemia or glycaemic instability. Major exclusion criteria included a HbA 1c of more than 12·5%, a BMI of more than 30 kg/m 2 , and insulin requirements exceeding 1·2 IU/kg per day, along with contraindications to immunosuppressive therapy. Participants were recruited from the hospital's islet transplant registry. Follow-up was conducted through regular clinical visits, with data collected retrospectively. Outcomes assessed included patient survival, graft survival, insulin independence, glycaemic control, and adverse events. Data were analysed using an intention-to-treat method, mixed-effects models, Kaplan-Meier estimates, and Cox and logistic regression to identify factors linked to metabolic success and reduced risks., Findings: 79 patients underwent intrahepatic or intraportal islet transplantation alone between Feb 16, 2001, and June 1, 2023, and received a total of 159 islet infusions, with a median total islet mass of 9637 islet equivalents (IEQ) per kg. Complications were infrequent and mostly involved minor bleeding, with only 3% (two of 79) of patients requiring surgical intervention. Glycaemic control improved significantly after infusion, with a reduction of HbA 1c by -10·04 mmol/mol (-13·63 to -6·46), and a decrease in daily insulin requirements by -13·35 units per day (-17·04 to -9·65). The intention-to-treat analysis showed a median graft survival (fasting C peptide ≥0·3 ng/mL) of 3·9 years (95% CI 1·6 to 6·2) and 44% (35/79) insulin independence for a median of 6 years (95% CI 2·88 to 9·08). Patients receiving more than 10 000 IEQ/kg with BAS, FK506, and Rapa therapy had a median graft survival of 9·7 years (3·1-16·0) and 73% (16 of 22) insulin independence. Kaplan-Meier estimates indicated graft survival rates of 86% at 1 year, 65% at 5 years, 47% at 10 years, 47% at 15 years, and 40% at 20 years. Overall survival was 92% (73 of 79) over a median follow-up of 13·1 years, with a 20-year survival probability of 84%. Adverse events related to immunosuppressive therapy were reported in 44% (35 of 79) of patients, with allosensitisation rates increasing from 6% at baseline to 42% after therapy discontinuation., Interpretation: This analysis of a large islet transplantation alone cohort provides valuable insights into factors influencing outcomes and highlights potential risks, supporting informed clinical decision making and the optimisation of future β-cell replacement strategies., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Type 1 diabetes (T1D) presents a persistent medical challenge, demanding innovative strategies for sustained glycemic control and enhanced patient well-being. Beta cells are specialized cells in the pancreas that produce insulin, a hormone that regulates blood sugar levels. When beta cells are damaged or destroyed, insulin production decreases, which leads to T1D. Allo Beta Cell Transplantation has emerged as a promising therapeutic avenue, with the goal of reinstating glucose regulation and insulin production in T1D patients. However, the path to success in this approach is fraught with complex immunological hurdles that demand rigorous exploration and resolution for enduring therapeutic efficacy. This exploration focuses on the distinct immunological characteristics inherent to Allo Beta Cell Transplantation. An understanding of these unique challenges is pivotal for the development of effective therapeutic interventions. The critical role of glucose regulation and insulin in immune activation is emphasized, with an emphasis on the intricate interplay between beta cells and immune cells. The transplantation site, particularly the liver, is examined in depth, highlighting its relevance in the context of complex immunological issues. Scrutiny extends to recipient and donor matching, including the utilization of multiple islet donors, while also considering the potential risk of autoimmune recurrence. Moreover, unanswered questions and persistent gaps in knowledge within the field are identified. These include the absence of robust evidence supporting immunosuppression treatments, the need for reliable methods to assess rejection and treatment protocols, the lack of validated biomarkers for monitoring beta cell loss, and the imperative need for improved beta cell imaging techniques. In addition, attention is drawn to emerging directions and transformative strategies in the field. This encompasses alternative immunosuppressive regimens and calcineurin-free immunoprotocols, as well as a reevaluation of induction therapy and recipient preconditioning methods. Innovative approaches targeting autoimmune recurrence, such as CAR Tregs and TCR Tregs, are explored, along with the potential of stem stealth cells, tissue engineering, and encapsulation to overcome the risk of graft rejection. In summary, this review provides a comprehensive overview of the inherent immunological obstacles associated with Allo Beta Cell Transplantation. It offers valuable insights into emerging strategies and directions that hold great promise for advancing the field and ultimately improving outcomes for individuals living with diabetes., 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 © 2023 Caldara, Tomajer, Monti, Sordi, Citro, Chimienti, Gremizzi, Catarinella, Tentori, Paloschi, Melzi, Mercalli, Nano, Magistretti, Partelli and Piemonti.)

Background: Periodic surges of COVID-19 patients seeking care in the hospital environment overwhelm systems reduce the availability of resources for treatment of non-COVID-19 cases (Zheng et al. in J Hosp Infect 106:325-329, 2020). Hospital flow and resource management could be greatly enhanced by differentiating patients who are likely at risk of adverse clinical outcomes from those who could safely be discharged after evaluation and managed outside of the hospital setting (Sun et al. in J Infect Dis 223:38-46, 2021). Herein, we propose a prognostic score named PEGALUS (Predictivity of Elderly age, arterial blood Gas Analysis and Lung UltraSound) that could potentially help clinicians properly and rapidly choose the appropriate allocation of COVID-19 patients admitted to the emergency department (ED)., Methods: This observational prospective study enrolled COVID-19 patients who were admitted to the ED of IRCCS San Raffaele Hospital (HSR)., Results: 230 COVID-19 patients were enrolled and 30-day follow-up data was collected. Composite outcome was death or need for oro-tracheal intubation (OTI). 50 patients (21.5%) reached the outcome during the observational period. In multivariate Cox analysis, age, PO 2 /FiO 2 ratio, pCO 2 , duration of symptoms, and lung ultrasound evaluation were significantly associated with the adverse outcome. We obtained a new scorecard (PEGALUS) according to the hazard ratio of the identified predictors. PEGALUS score performed well in predicting the composite outcome (AUC 0.866, 95% IC 0.812-0.921; p < 0.001). Kaplan-Meier showed that a PEGALUS score < 7 was associated with a good 30-day prognosis (survival rate 97.5%), compared to a PEGALUS score of 7-11 (survival rate 85.9%; p log-rank 0.009) and PEGALUS score > 11 (survival rate 49.3%; p log-rank < 0.001)., Conclusions: PEGALUS score performed at the admission can predict adverse outcomes in patients with COVID-19. The systematic application of this score might permit a more accurate and rapid treatment allocation in this setting., (© 2022. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Background: There is no information on acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) among invasively ventilated coronavirus disease 2019 (COVID-19) patients in Western healthcare systems., Objective: To study the prevalence, characteristics, risk factors and outcome of AKI and CRRT among invasively ventilated COVID-19 patients., Methods: Observational study in a tertiary care hospital in Milan, Italy., Results: Among 99 patients, 72 (75.0%) developed AKI and 17 (17.7%) received CRRT. Most of the patients developed stage 1 AKI (33 [45.8%]), while 15 (20.8%) developed stage 2 AKI and 24 (33.4%) a stage 3 AKI. Patients who developed AKI or needed CRRT at latest follow-up were older, and among CRRT treated patients a greater proportion had preexisting CKD. Hospital mortality was 38.9% for AKI and 52.9% for CRRT patients., Conclusions: Among invasively ventilated COVID-19 patients, AKI is very common and CRRT use is common. Both carry a high risk of in-hospital mortality., (© 2020 S. Karger AG, Basel.)

Objective: In the setting of normal sodium (Na) intake, many patients with hypertension have inappropriately elevated plasma aldosterone (Aldo) levels and may be at increased risk for tissue damage. Moreover, other adrenocortical steroids, including endogenous ouabain can stimulate tissue damage. As endogenous ouabain is often elevated in chronically Na-loaded states, is a vasoconstrictor, raises blood pressure (BP), and also promotes tissue fibrosis, we investigated the extent to which plasma Aldo and endogenous ouabain were coelevated among naïve hypertensive patients (NHP). We also investigated the impact of an acute salt load on these steroids, BP, and renal function., Methods: NHP (590) were grouped in tertiles based on their baseline plasma Aldo (mean ± SEM first 7.59 ± 0.18, versus third 24.15 ± 0.31 ng/dl). Baseline plasma renin activity (2.4 ± 0.1 versus 1.2 ± 0.1 ng/ml per h, P < 0.001), endogenous ouabain (268 ± 14.9 pmol/l versus 239.0 ± 13.6 pmol, P < 0.01) and DBP (91.9 ± 0.76 versus 89.6 ± 0.71 mmHg, P = 0.017) were higher in NHP in the third versus the first Aldo tertile, respectively., Results: Acute Na loading showed that the BP of the third Aldo tertile NHP was especially salt-sensitive (slope of pressure-natriuresis relationship 0.015 ± 0.002 versus 0.003 ± 0.001 μEq/mmHg per min, P = 0.00024 after adjustment for sex, BMI, and age). Regression analyses showed that plasma Aldo and endogenous ouabain were linearly related (β = 0.181, P = 0.0003)., Conclusion: Among patients with essential hypertension, circulating endogenous ouabain and Aldo are typically coelevated and their BP is salt-sensitive. In conditions where Aldo is inappropriately elevated, both Aldo and endogenous ouabain may contribute to adverse cardiovascular and renal outcomes.