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Filomena Russo,1 Marco Galluzzo,2,3 Luca Stingeni,4 Severino Persechino,5 Leonardo Zichichi,6 Andrea Conti,7 Claudia Giofrè,8 Valentina Dini,9 Martina Vispi,10 Laura Atzori,11 Angelo Cattaneo,12 Aurora Parodi,13 Federico Bardazzi,14 Giuseppe Stinco,15 Paolo Dapavo,16 Giampiero Girolomoni,17 Maria Letizia Musumeci,18 Manuela Papini,19 Marina Venturini,20 Stefano Dastoli,21 Sergio Di Nuzzo,22 Maria Concetta Fargnoli,23 Gianluca Pagnanelli,24 Nicoletta Bernardini,25 Daniele Mario Gambini,26 Piergiorgio Malagoli,27 Carlo Mazzatenta,28 Ketty Peris,29 Iris Zalaudek,30 Gabriella Fabbrocini31 ,† Francesco Loconsole,32 Camilla Vassallo,33 Lucia Pietroleonardo,34 Francesca Prignano,35 Chiara Franchi,36 Anna Maria Offidani,37 Claudio Bonifati,38 Vito Di Lernia,39 Giovanni Gigante,40 Marta Silvia Bartezaghi,40 Matteo Franchi,41,42 Paola Ursoleo,40 Elisabetta Aloisi40 1Dermatology Section, Department of Medical, Surgical and Neurological Science, University of Siena, S. Maria Alle Scotte Hospital, Siena, Italy; 2Department of Systems Medicine, University of Rome “Tor Vergata”, Rome, Italy; 3Dermatology Unit, Fondazione Policlinico “Tor Vergata”, Rome, Italy; 4Section of Dermatology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy; 5Dermatology Unit, NESMOS Department, Faculty of Medicine & Psychology, Sapienza University of Rome, Sant’Andrea University Hospital, Rome, Italy; 6Unit of Dermatology, San Antonio Abate Hospital, Trapani, Italy; 7Section of Dermatology, Department of Specialized Medicine, University of Modena and Reggio Emilia, Modena, Italy; 8U.O.C. Dermatologia, A.O. Papardo, Messina, Italy; 9Section of Dermatology, Department of Medicine and Oncology, University of Pisa, Pisa, Italy; 10Dermatology Unit, Misericordia Hospital, Grosseto, Italy; 11Dermatology Unit, Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy; 12Dermatology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Italy; 13Section of Dermatology, DiSSal University of Genoa, Ospedale-Policlinico San Martino IRCCS, Genova, Italy; 14Dermatology Division, Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy; 15Section of Dermatology, Department of Medicine, University of Udine, Udine, Italy; 16Section of Dermatology, Department of Medical Sciences, University of Turin, Turin, Italy; 17Section of Dermatology, Department of Medicine, University of Verona, Verona, Italy; 18Section of Dermatology, Department of Medical and Surgical Specialties, University of Catania, Catania, Italy; 19Dermatology Clinic of Terni, University of Perugia, Perugia, Italy; 20Section of Dermatology, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; 21Department of Health Sciences, Magna Graecia University, Catanzaro, Italy; 22Department of Medicine and Surgery, University of Parma, Parma, Italy; 23Section of Dermatology, Department of Biotechnological and Applied Clinical Science, University of L’Aquila, L’Aquila, Italy; 24Department of Dermatology, Istituto Dermopatico dell’Immacolata - IRCCS, Roma, Italy; 25Department of Medical-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Dermatology Unit, “Daniele Innocenzi”, Asl Latina, Italy; 26Dermatology Unit, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy; 27Dermatology Unit, Azienda Ospedaliera San Donato Milanese, Milan, Italy; 28Dermatology Unit, Lucca Azienda USL Toscana Nord Ovest, Pisa, Italy; 29Department of Translational Medicine and Surgery, IRCCS A. Gemelli University Polyclinic Foundation, Sacred Heart Catholic University, Rome, Italy; 30Department of Dermatology, University of Trieste, Trieste, Italy; 31Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; 32Department of Dermatology, University of Bari, Bari, Italy; 33Institute of Dermatology, IRCCS Policlinico San Matteo Foundation and University of Pavia, Pavia, Italy; 34Dermatology Unit, Vito Fazzi Hospital, Lecce, Italy; 35Dermatology Clinic, Department of Health Sciences, University of Florence, Florence, Italy; 36Dermatology Unit, IRCCS IO Galeazzi, Milan, Italy; 37Dermatological Clinic, Polytechnic University of the Marche Region, Ancona, Italy; 38Department of Dermatology, Istituto Dermatologico San Gallicano - IRCCS, Roma, Italy; 39Dermatology Unit, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy; 40Novartis Farma SpA, Origgio, Italy; 41National Centre for Healthcare Research and Pharmacoepidemiology, Milan, Italy; 42Laboratory of Healthcare Research and Pharmacoepidemiology, Department of Statistics and Quantitative Methods, University of Milano Bicocca, Milan, Italy†Gabriella Fabbrocini passed away on 3 March 2023Correspondence: Filomena Russo, Dermatology Section, Department of Medical, Surgical and Neurological Science, University of Siena, S. Maria Alle Scotte Hospital, Siena, Italy, Email file.russo@libero.itPurpose: SUPREME, a phase IIIb study conducted in Italy, demonstrated safety and high efficacy of secukinumab for up to 72 weeks in patients with moderate-to-severe plaque-type psoriasis. SUPREME 2.0 study aimed to provide real-world data on the long-term drug survival and effectiveness of secukinumab beyond 72 weeks.Patients and Methods: SUPREME 2.0 is a retrospective observational chart review study conducted in patients previously enrolled in SUPREME study. After the end of the SUPREME study, eligible patients continued treatment as per clinical practice, and their effectiveness and drug survival data were retrieved from medical charts.Results: Of the 415 patients enrolled in the SUPREME study, 297 were included in SUPREME 2.0; of which, 210 (70.7%) continued secukinumab treatment throughout the 42-month observation period. Patients in the biologic-naïve cohort had higher drug survival than those in the biologic-experienced cohort (74.9% vs 61.7%), while HLA-Cw6–positive and HLA-Cw6–negative patients showed similar drug survival (69.3% and 71.9%). After 42 months, Psoriasis Area and Severity Index (PASI) 90 was achieved by 79.6% of patients overall; with a similar proportion of biologic-naïve and biologic-experienced patients achieving PASI90 (79.8% and 79.1%). The mean absolute PASI score reduced from 21.94 to 1.38 in the overall population, 21.90 to 1.24 in biologic-naïve and 22.03 to 1.77 in biologic-experienced patients after 42 months. The decrease in the absolute PASI score was comparable between HLA-Cw6–positive and HLA–Cw6-negative patients. The baseline Dermatology Life Quality Index scores also decreased in the overall patients (10.5 to 2.32) and across all study sub-groups after 42 months. Safety was consistent with the known profile of secukinumab, with no new findings.Conclusion: In this real-world cohort study, secukinumab showed consistently high long-term drug survival and effectiveness with a favourable safety profile.Keywords: psoriasis, secukinumab, real-world evidence, drug survival, SUPREME

Marina Talamonti,1 Filomena Russo,2 Giovanna Malara,3,4 Katharina Hansel,5 Manuela Papini,6 Angelo Cattaneo,7 Aurora Parodi,8 Andrea Chiricozzi,9,10 Piergiorgio Malagoli,11 Federico Bardazzi,12 Valeria Brazzelli,13 Paolo Dapavo,14 Paolo Gisondi,15 Cristina Zane,16 Concetta Potenza,17 Franca Cantoresi,18 Maria Concetta Fargnoli,19 Sara Trevisini,20 Pina Brianti,21 Leonardo Pescitelli,22 Giovanni Gigante,23 Marta Bartezaghi,23 Luisa Caputo,23 Elisabetta Aloisi,23 Antonio Costanzo24,25 On behalf of the SUPREME Study Group1Dermatology, University of Rome Tor Vergata, Rome, Italy; 2Department of Medical, Surgical and Neurological Science, Dermatology Section, University of Siena, S. Maria alle Scotte Hospital, Siena, Italy; 3Dermatology Unit, Hospital “Bianchi Melacrino Morelli”, Reggio, Calabria, Italy; 4Department of Dermatology, Papardo Hospital, Messina, Italy; 5Section of Dermatology, Department of Medicine and Surgery, University of Perugia, Perugia, Italy; 6Dermatologic Clinic of Terni, Department of Medicine and Surgery, University of Perugia, Perugia, Italy; 7U.O. Dermatologia, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Milano, Italy; 8Di.S.Sal. Section of Dermatology, Ospedale Policlinico San Martino, University of Genova, Genova GE, 16132, Italy; 9UOC di Dermatologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli - IRCCS, Rome, Italy; 10Dermatologia, Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy; 11Psocare Unit, I.R.C.C.S Policlinico San Donato, Milano, Italy; 12Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 13Dermatology, Fondazione IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy; 14Department of Biomedical Science and Human Oncology, Second Dermatologic Clinic, University of Torino, Torino, Italy; 15Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy; 16Dermatology Department, ASST Spedali Civili di Brescia, University of Brescia, Brescia, Italy; 17Dermatology Unit “Daniele Innocenzi”, Department of Medico-Surgical Sciences and Biotechnologies, Faculty of Pharmacy and Medicine, Sapienza University of Rome – Polo Pontino, Latina, Italy; 18Dermatology Unit, Department of Medicine, University of Roma, Roma, Italy; 19Dermatology, Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy; 20Department of Dermatology, University of Trieste, Trieste, Italy; 21Dermatology and Cosmetology Unit - San Raffaele Hospital, Milan, Italy; 22Department of Health Sciences, Dermatology Clinic, University of Firenze, Firenze, Italy; 23Novartis Farma SpA, Origgio, Italy; 24Unit of Dermatology, IRCCS Humanitas Research Hospital, Milano, Italy; 25Department of Biomedical Sciences, Humanitas University, Milano, ItalyCorrespondence: Marina Talamonti, Dermatology-Department of Systems Medicine, University of Rome Tor Vergata, PTV – Policlinico Tor Vergata, V.le Oxford 81, Rome, 00133, Italy, Tel +39 0620902743, Fax +39 0620902742, Email talamonti.marina@gmail.comPurpose: Secukinumab is a fully human monoclonal antibody that inhibits interleukin (IL)-17A approved for the treatment of moderate to severe plaque psoriasis in adults and children. We compared the efficacy and safety of secukinumab in patients aged < 65 years (adult patients) versus patients aged ≥ 65 years (elderly patients) in a post-hoc analysis of the SUPREME study.Patients and Methods: Patients with moderate to severe plaque psoriasis received subcutaneous secukinumab 300 mg per week for the first 5 weeks, then 300 mg per month. We compared the following outcomes in patients aged ≥ 65 years vs < 65 years: baseline characteristics; PASI50/75/90/100 response rates (improvements ≥ 50%/75%/90%/100% in Psoriasis Area and Severity Index (PASI) from baseline); changes in Dermatology Life Quality Index (DLQI); Hospital Anxiety and Depression Scale (HAD-A, HAD-D) score changes; treatment-emergent adverse events (TEAEs).Results: Secukinumab was slightly less effective in elderly patients than in adult patients (response rates at week 16: PASI90, 69.4% vs 80.9%, p = 0.4528; PASI100, 44.4% vs 56.7%, p = 0.8973). Elderly and adult patients showed a similar time course of changes in absolute PASI scores. Patients aged ≥ 65 years had a statistically significantly lower improvement in quality of life (mean DLQI reduction) than patients aged < 65 years at week 16 [− 5.4 (± 4.3) vs − 8.8 (± 6.9), p = 0.0065] and at week 24 [− 5.3 (± 4.4) vs − 9.2 (± 7.1), p = 0.0038]. Secukinumab treatment resulted in comparable mean reductions in anxiety and depression scores in both cohorts at 24 weeks [HAD-A, − 1.3 (± 3.3) vs − 2.1 (± 3.8), p = 0.9004; HAD-D, − 1.0 (± 3.3) vs − 1.5 (± 3.1), p = 0.4598]. The frequency of TEAEs in the two cohorts was similar (16.7% vs 14.6%, p = 0.7391).Conclusion: Secukinumab is a valid option for the management of moderate to severe psoriasis in elderly patients.Keywords: psoriasis, biologics, interleukin-17A, secukinumab, elderly

Luca Stingeni,1 Giovanna Malara,2,3 Andrea Conti,4 Luisa Di Costanzo,5 Carlo Giovanni Carrera,6 Martina Burlando,7 Piergiorgio Malagoli,8 Maria Letizia Musumeci,9 Federico Bardazzi,10 Valeria Brazzelli,11 Paolo Amerio,12 Clara De Simone,13,14 Sara Trevisini,15 Anna Balato,16 Matteo Megna,17 Francesco Loconsole,18 Catia De Felice,19 Marta Bartezaghi,20 Alice Rausa,20 Elisabetta Aloisi,20 Roberto Orsenigo,20 Antonio Costanzo21,22 On behalf of the SUPREME Study Group1Dermatology Section, Medical and Surgical Department, University of Perugia, Perugia, Italy; 2Dermatology Unit, Hospital “Bianchi Melacrino Morelli”, Reggio Calabria, Italy; 3Department of Dermatology, Papardo Hospital, Messina, Italy; 4Dermatologic Unit, Department of Surgery, Infermi Hospital, AUSL Romagna, Rimini, Italy; 5Department of Dermatology, “Gaetano Rummo” Hospital, Benevento UOC Dermatologia, AO G. Rummo, Benevento, Italy; 6U.O. Dermatologia, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Milano, Italy; 7IRCCS San Martino Polyclinic Hospital, Di.S.Sal. Section of Dermatology, Genoa, Italy; 8Dermatology Unit IRCCS Policlinico San Donato, Milan, Italy; 9Dermatology Clinic, University of Catania, Catania, Italy; 10Division of Dermatology, University Hospital Policlinico “S. Orsola-Malpighi”, Bologna, Italy; 11Institute of Dermatology, Foundation IRCCS Policlinico San Matteo and University of Pavia, Pavia, Italy; 12Dermatologic Clinic, G. D’Annunzio University, Chieti, Italy; 13Istituto di Dermatologia, Università Cattolica del Sacro Cuore, Rome, Italy; 14Fondazione Policlinico Universitario A. Gemelli – IRCCS, Rome, Italy; 15Dermatology Department, University of Trieste, Trieste, Italy; 16Dermatology Unit, University of Campania “Luigi Vanvitelli”, Naples, Italy; 17Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; 18Department of Biomedical Sciences and Human Oncology, University of Bari, Bari, Italy; 19Department of Clinical Dermatology, Centre for the Study and Treatment of Psoriasis, San Gallicano Dermatological Institute, IRCCS, Rome, Italy; 20Novartis Farma SpA, Origgio, Italy; 21Unit of Dermatology, IRCCS Humanitas Research Hospital, Milan, Italy; 22Department of Biomedical Sciences, Humanitas University, Milan, ItalyCorrespondence: Luca Stingeni, Dermatology Section, Medical and Surgical Department, University of Perugia, Perugia, Italy, Tel +39075-5783881, Email luca.stingeni@unipg.itPurpose: Psoriasis, a common systemic inflammatory disorder, presents with gender-related differences in the quality of life (QoL) and treatment outcomes. This post hoc analysis from the Phase 3b SUPREME study explored gender-related differences in patient characteristics and efficacy of secukinumab 300 mg on Psoriasis Area and Severity Index (PASI) 75/90/100 and impact on QoL using the Dermatology Life Quality Index (DLQI) in patients with moderate to severe psoriasis through week 24.Patients and Methods: The proportion of patients achieving PASI 75/90/100 was computed using a nonresponder imputation approach. Differences between cohorts were analyzed using a logistic regression model. The mean change from baseline in DLQI was computed using the Wilcoxon test.Results: Among the 433 patients (males: 71.6%), females had a higher DLQI than males at baseline (13.1 vs 9.5; P< 0.0001). Males had a slightly higher response for PASI 90 than females at week 16 (80.7% vs 78.1%; P=0.0779) and 24 (83.2% vs 79.7%; P=0.0319). No differences were observed between genders in PASI 100/75 responses at week 24. Both genders showed an improvement in DLQI with secukinumab at week 24 (− 10.9 vs − 8.1, respectively, in females vs males; P=0.0004).Conclusion: In summary, secukinumab was effective in the treatment of psoriasis, irrespective of gender.Keywords: plaque psoriasis, PASI, patient-reported outcomes, Dermatology Quality of Life Index, Hospital Anxiety and Depression Scale

Cyclosporine A (CsA) is one of the systemic therapeutic options for moderate-to-severe psoriasis, based on its efficacy and rapidity of action. The current study investigated the response to CsA in patients with moderate-to-severe plaque psoriasis. TRANSITION was an observational, cross-sectional, multicentre study which evaluated the proportion of partial- and suboptimal-responders among patients with moderate-to-severe plaque psoriasis treated with continuous CsA for ≥12 weeks. Patients demonstrating a Psoriasis Area and Severity Index (PASI) response of ≥90, ≥75 and <90, ≥50 and <75 and <50 were defined as responders, suboptimal-responders, partial-responders, and non-responders, respectively. A total of 196 patients (mean age, 46.6 years; 62.8% males) from 14 sites in Italy were evaluated. At the study visit, the mean (SD) PASI score was 4.2(5.5) compared with 15.3(7.1) prior to the last CsA cycle. For response categories, 39.8%, 22.4%, 16.8%, and 20.9% of patients were responders, suboptimal-responders, partial-responders, and non-responders to CsA treatment. Overall, 28.6% of patients permanently discontinued treatment with CsA (lack of efficacy [10.2%], poor tolerability and voluntary discontinuation [3.6% each], and other [11.7%]). Patients were only partially satisfied with CsA treatment, reporting measurable impact on quality of life. Only 40% patients showed a satisfactory response to CsA. [ABSTRACT FROM AUTHOR]

Background: Recent developments improved outcomes in patients with autoimmune diseases. Biologics were approved as first-line treatment in selected naïve patients with plaque psoriasis (PsO), psoriatic arthritis (PsA), ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). Among them, secukinumab was most recently approved for treatment of active nr-axSpA in adults. In this work, we assessed the budget impact of new secukinumab treatment options in the Italian market., Methods: A cross-indication budget impact model was designed to estimate the effects of adding secukinumab in the Italian market from the National Health System perspective over a 3-year period. The model included all adults with PsO, PsA, AS and nr-axSpA, treated with biologics or biosimilars. It compared costs between two scenarios, secukinumab availability or absence, for the four diseases combined and taken individually. A sensitivity analyses was conducted., Results: There were 68,121 adult patients treated with biologics in 2021 and 68,341 in 2023. The budget impact analysis (BIA) on all indications showed a cost reduction of €33.7 million (- 1.5%) over 3 years with the introduction of secukinumab. PsA patients had the highest saving (- €34.9 million), followed by PsO patients (- €7.8 million). Cost saving in PsO patients was balanced by increased budget reported in AS patients (+ €8.0 million). In nr-axSpA patients, secukinumab reported no significant budget increase (+ 1.0%)., Conclusion: This BIA accounted for the new indication of secukinumab in nr-axSpA patients, reporting no significant changes in the required budget and adding an effective treatment option. Considering all indications, secukinumab is a sustainable treatment option., (© 2023. The Author(s).)

Secukinumab, a fully human monoclonal antibody, neutralizes interleukin-17A, a cornerstone cytokine driving the multiple manifestations of psoriasis. This post-hoc analysis of the SUPREME study was performed to determine the sustainability of response to secukinumab in terms of Psoriasis Area and Severity Index (PASI) 90 in patients with moderate-to-severe plaque psoriasis. Based on PASI 90 response at week 16, patients were stratified as PASI 90 responders (PASI90R, n = 337) or non-responders (PASI90NR, n = 72). At week 20, 94.2% (n = 295/313) achieved PASI 90/100 response in PASI90R, with response maintained through week 48 (89.6%, n = 189/211). An increased proportion of patients achieved PASI 90/100 response in PASI90NR (week 20: 29.9%, n = 20/67; week 48: 57.1%, n = 20/35). Overall, 64.4% patients achieved absolute PASI score = 0 at week 24 with response sustained to week 48 (66.9%). Secukinumab showed sustained and stable efficacy in maintaining PASI 90 response in patients with moderate-to-severe plaque psoriasis up to week 48.

In fragile X syndrome (FXS), sensory hypersensitivity and impaired habituation is thought to result in attention overload and various behavioral abnormalities in reaction to the excessive and remanent salience of environment features that would normally be ignored. This phenomenon, termed sensory defensiveness, has been proposed as the potential cause of hyperactivity, hyperarousal, and negative reactions to changes in routine that are often deleterious for FXS patients. However, the lack of tools for manipulating sensory hypersensitivity has not allowed the experimental testing required to evaluate the relevance of this hypothesis. Recent work has shown that BMS-204352, a BK Ca channel agonist, was efficient to reverse cortical hyperexcitability and related sensory hypersensitivity in the Fmr1-KO mouse model of FXS. In the present study, we report that exposing Fmr1-KO mice to novel or unfamiliar environments resulted in multiple behavioral perturbations, such as hyperactivity, impaired nest building and excessive grooming of the back. Reversing sensory hypersensitivity with the BK Ca channel agonist BMS-204352 prevented these behavioral abnormalities in Fmr1-KO mice. These results are in support of the sensory defensiveness hypothesis, and confirm BK Ca as a potentially relevant molecular target for the development of drug medication against FXS/ASD.

Intellectual disability (ID) and autism are present in several neurodevelopmental disorders and are often associated in genetic syndromes, such as Fragile X and Rett syndromes. While most evidence indicates that a genetic component plays an important role in the aetiology of both autism and ID, a number of studies suggest that immunological dysfunctions may participate in the pathophysiology of these disorders. Brain-specific autoantibodies have been detected in the sera of many autistic children and autoimmune disorders are increased in families of children with autism. Furthermore, cytokine imbalance has been reported in children with autism. These results may reflect an inappropriate immune response to environmental factors, such as infectious or toxic exposure. The role of microglia as sensors of pre- and post-natal environmental stimuli and its involvement in the regulation of synaptic connectivity, maturation of brain circuitry and neurogenesis has recently emerged. An abnormal immune response during critical windows of development and consequent abnormal production of neuro-inflammatory mediators may have an impact on the function and structure of brain and can play a role in the pathogenesis of non syndromic autism. Recent evidence suggests an involvement of neuro-inflammation also in syndromic forms of autism and ID. Immune dysregulation has been found in children with Fragile X syndrome and an intrinsic microglia dysfunction has been recently reported in Rett syndrome. The present review summarizes the current literature suggesting that neuro-inflammatory mechanisms may contribute to the pathogenesis of different ID- and autism-associated disorders, thus representing common pathophysiological pathways and potential therapeutic targets.

Dramatic removal of potassium during hemodialysis sessions can induce changes in the electrical properties of nerve cells or muscle fibers, which may underlie neuromuscular symptoms referred by end-stage renal disease patients. The primary aim of our study was to investigate the effects of acetate-free biofiltration (AFB) on the amplitude of compound motor action potential (cMAP) obtained after stimulation of the ulnar nerve at the wrist. The secondary aim was to compare the effect of two different potassium removal modalities on cMAP amplitude and to analyze the effects on muscular force by specific dynamometric tests. Twenty-eight patients received dialysis for 4 h, 3 times per week, first with standard AFB with constant potassium (AFB) and then with AFB with a variable concentration of potassium in the dialysis bath (AFB(K)). The amplitude of cMAP was determined after ulnar nerve stimulation at the wrist at different time intervals: at the start of dialysis; at 15, 45, 90, and 120 min after beginning the session; and at the end of treatment. At the same time intervals, muscle force generation was determined using a dynamometer. Finally, we measured plasma electrolytes, intraerythrocytic potassium, and the electrical membrane potential at rest (REMP) of the erythrocytic membrane. The main finding of this study was a significant reduction of cMAP amplitude in the first 45 min after AFB, which paralleled the reduction in serum potassium levels. Moreover, there was a reduction of muscular strength determined with dynamometric measurements. Potassium removal induced by the two different modalities of AFB may significantly affect myocardial and fibromuscular cells by modulating the electrochemical balance of cell membranes. The transient alteration of the electrical properties on voluntary striated muscle fibers may contribute to the brief reduction in muscular strength we detected in patients who underwent AFB. AFB(K) can minimize the negative effects of standard AFB treatment on neuromuscular excitability, most likely through a more gentle variation of potassium levels during dialysis.

Background: The risk of developing cardiovascular diseases is higher in patients on haemodialysis than in the general population. These patients may develop arrhythmias that depend on the extra- and intracellular concentrations of potassium. ECG findings, particularly the QT interval and its dispersion (QT(d)) and the QT(c) (QT interval corrected for heart rate according to Bazett's formula) and its dispersion (QT(cd)), may be direct indicators of the risk of developing arrhythmia., Methods: Our cohort comprised 28 patients who were dialysed for 3.5-4 h three times per week, first with haemodiafiltration with a constant potassium concentration (HDF) in the dialysis bath then with haemodiafiltration with variable concentrations of potassium (HDF(k)). ECGs were done at different time intervals: at the start of dialysis (T(0)), at 15 (T(15)), 45 (T(45)), 90 (T(90)) and 120 min (T(120)) after the beginning of the session, and at the end of treatment (T(end)). ECG-derived data (QT, QT(d), QT(c) and QT(cd)) were measured. At the same time points, plasma electrolytes, intra-erythrocytic potassium and the electrical membrane potential at rest (REMP) of the erythrocytic membrane were measured., Results: Plasma potassium concentration diminished more gradually in HDF(k) than in HDF, the difference being statistically significant at T(15) and T(45) (P<0.05), and T(90) (P<0.01). The intra-erythrocytic potassium concentration remained constant throughout the observation period. In both HDF and HDF(k), REMP was lower at all points after T(0) (P<0.05), but the reduction was greater and more significant in HDF than in HDF(k) at T(15) and T(120) (P<0.05). ECG revealed a statistically significant diminution in HDF(k) vs HDF in the measures of dispersion of QT and QT(c) at T(15), T(90), T(120) and T(end) (P<0.01) and of QT(cd) at T(45) (P<0.05). The mean of QT(d), adjusted for plasma potassium, increased over time in HDF with large alternate mean increase and decrease peaks and error intervals. In HDF(k), instead, there was a progressive and constant diminution with minor error intervals. QT(cd) adjusted for plasma potassium had the same trend. A marked difference was found between the final values in standard HDF and those in HDF(k)., Conclusions: HDF and HDF(k) have significantly different effects on QT(c). ECG data demonstrate that the risk of arrhythmia could be lower, with a variable removal of potassium during haemodialysis. With HDF but not HDF(k), hyperpolarization of the cell membrane is detected, and this could have a destabilizing effect on different types of cardiac cell, giving rise to retrograde circuits.

Background and Aim: Our aim was to evaluate QTc interval and QTc dispersion in 27 end-stage renal disease (ESRD) patients undergoing Acetate Free Biofiltration (AFB) in order to ascertain any correlations between the electrrocardiographic (ECG) parameters, serum Na+, K+, Ca++, Mg++ and intraerythrocytic Mg++ (Mg++e) concentrations. All measures were made at t0 (session beginning), t1 (first hour), t2 (second hour), t3 (third hour), and t4 (session end)., Results: Blood pressure, heart rate, bodyweight and total ultrafiltration in the three dialysis sessions were constant. A significant progressive increase occurred in serum Ca++ during the sessions, while there was a significant diminution in serum K+. The pattern for Mg++ concentrations in serum and erythrocytes differed: in serum it decreased, whereas Mg++e increased. At t4, the QTc interval was reduced to a significant extent with respect to the baseline value. QTc dispersion significantly increased at t1 without there being significant variations at other times with respect to t0. At t2, t3 and t4, values promptly returned to baseline levels. QTc had a negative correlation with serum Ca++ levels at t4. In contrast, an inverse correlation was found between QTc dispersion and serum K+ at t1. No other correlations could be found between any other electrolytes, QTc interval or QTc dispersion., Conclusion: In conclusion, the decrease observed in the QTc interval at the end of an AFB session was inversely related to serum Ca++ concentrations. Moreover, an increase in QTc dispersion occurred during the first hour of the session, and was negatively correlated with serum K+.

Colon diverticular disease is a very common pathology in western countries and represents a risk factor for septic-type complications, especially in peritoneal dialysis patients. We examined both diagnostic procedure and therapeutics options, either pharmacological or surgical. Ultrasonography, which is useful for the diagnosis of diverticulosis and diverticular disease, has been supported in the last few years by new imaging techniques, such as NMR and CT, that also find applications in the treatment of diverticulitis complications like peritoneal abscesses. Our emphasis is on the therapeutic perspective, either dietetic - based on the use of a fibre-rich diet and the infusion of liquids by intravenous injection - or surgical, such as the Hartmann procedure, single anastomosis with stomia conservation and laparoscopic and endoscopic treatment. These therapeutic approaches have reduced both morbidity and mortality rate and have emphasized how the reduction of surgical stress on the mesothelium promotes the recovery of the functional integrity and, consequently, faster resumption of peritoneal dialysis. In conclusion, diverticulosis alone is not a contraindication for peritoneal dialysis, but constitutes a risk factor for the continuation of this alternative treatment.