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Objective: The present systematic review and meta-analysis aims to determine the difference in the interdialytic weight gain (IDWG) between low salt intake diet and normal/high salt intake diet or between nutritional counseling aimed at reducing diet salt intake and no nutritional counseling in patients on chronic hemodialysis., Methods: Medline, PubMed, Web of Science, and the Cochrane Library were searched. Randomized, crossover or parallel studies and observational studies were considered for inclusion and: 1) included adult patients on chronic hemodialysis since at least 6 months; 2) compared normal salt intake diet with low salt intake diet on IDWG; 3) compared nutritional counseling aimed at reducing diet salt intake with no intervention on IDWG; 4) reported on IDWG., Results: Eight articles (783 patients) were fully assessed for eligibility and included in the investigation. Meta-analysis showed frequencies of patients that increased their weight after dialysis more than 2.5 Kg (events) over total enrolled subjects for each group (control and experimental). As no significant heterogeneity was observed (I 2  = 8%; p = 0.36), the pooled analysis was performed using a fixed-effect model. Funnel plot was generated and no obvious asymmetry was observed. The Overall Odds Ratio to get an event in the experimental group, in respect to controls, is 0.57 (0.33-0.97) (p = 0.04] with single studies OR ranging between 0.11 and 1.08., Conclusion: The present systematic review and meta-analysis suggest that the use of a low salt diet sodium or a nutritional counseling aimed at reducing diet salt intake is associated with a statistically significant reduction of the IDWG in patients on chronic hemodialysis., Competing Interests: Declaration of competing interest None., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Objectives : The aim of this study is to compare data from two cohorts separated by a 17-year interval. We assessed the prevalence and severity of symptoms with the "dialysis symptom index" in these two groups, recruited in 2007 and 2024, to determine how advancements in dialysis therapy have influenced the symptom burden's prevalence and severity. Methods : End-stage renal diseases patients receiving maintenance hemodialysis three times a week in the hemodialysis unit of the university hospital were recruited between February and March 2007. In May 2024, in the same unit, another population sample was recruited and studied, as in 2007. The Dialysis Symptom Index (DSI) was administered to each patient, during the dialysis treatment. The DSI is made up of 30 questions, each of which addresses a specific physical or emotional symptom. The total symptom burden score, representing the total number of symptoms reported as being present, and the total symptom severity score, which represents the sum of individual severity scores, were generated for each patient. Results : We studied 71 patients in 2007 and 61 patients in 2024. The demographic, clinical and laboratory characteristics of the two study populations did not differ significantly. The total symptom burden score did not differ significantly between 2007 and 2024. The prevalence of most symptoms was similar in the two groups. The prevalence of constipation, decreased interest in sex and difficulty in becoming sexually aroused was higher in 2024 than in 2007. The total symptom severity was similar in the two periods. The severity of most symptoms was similar in the two groups. The severity of decreased interest in sex and difficulty in becoming sexually aroused was higher in 2024 than in 2007. Conclusions : The present study shows that, 17 years apart, the prevalence and severity of the symptom burden in patients on maintenance hemodialysis did not change significantly. These results suggest that studies investigating the causes and the pathogenesis of symptoms of patients on maintenance hemodialysis are urgently needed in the next future, as well as studies on therapeutic strategies.

Purpose: Heart failure (HF) is a major health problem affecting millions of people worldwide. In the latest years, many efforts have been made to identify predictors of poor prognosis in these patients. The aim of this systematic review and meta-analysis was to enlighten the correlation between liver stiffness (LS), assessed by Shear Wave Elastography techniques, and HF, particularly focusing on the prognostic value of LS on cardiovascular outcomes., Methods: We searched the PUBMED databases (up to May 1st, 2023) for studies that enlightened the correlation between LS and cardiovascular outcomes in patients hospitalized for acute decompensated heart failure (ADHF). We performed a meta-analysis to estimate the efficacy of LS in predicting the prognosis of patients with ADHF., Results: We analyzed data from 7 studies, comprising 677 patients, that assessed the prognostic value of LS in predicting cardiovascular outcomes in patients hospitalized for ADHF. The pooled analysis showed that increased liver stiffness was associated with higher risk of adverse cardiac events (hazard ratio 1.07 [1.03, 1.12], 95% CI)., Conclusion: Increased LS is associated with poor prognosis in patients hospitalized for HF and might help effectively identify those patients at high risk for worse outcomes., (© 2024. The Author(s).)

The present systematic review and meta-analysis aims to compare the effect of bicarbonate hemodialysis and HDF on quality of life (QoL), fatigue, and time to recovery in end-stage renal disease (ESRD) patients. Searches were run on January 2024 and updated on 3 March 2024 in the following databases: Ovid MEDLINE (1985 to present); Ovid EMBASE (1985 to present); Cochrane Library (Wiley); PubMed (1985 to present). Ten articles were fully assessed for eligibility and included in the investigation. Compared to HD, online HDF had a pooled MD of the mental component score (MCS) of the SF-36 of 0.98 (95% CI - 0.92, 2.87; P = 0.31). and of the physical component score (PCS) of 0.08 (95% CI - 1.32, 1.48; P = 0.91). No significant heterogeneity was observed (Chi 2  = 4.85; I 2  = 38%; P = 0.18 and Chi 2  = 3.85; I 2  = 22%; P = 0.28, respectively). Studies that compared the QoL assessed through the Kidney Disease Questionnaire or KDQOL-SF and show that HDF does not improve QoL when compared with HD, in most studies. In five out of seven studies, HDF was not significantly more effective than HD in improving fatigue. The length of the recovery time resulted in similar in patients receiving HDF and HD in all studies included in the present review. HDF is not more effective than HD in improving QoL and fatigue and in reducing the length of time of recovery after dialysis., (© 2024. The Author(s).)

Background/Objectives: Although depression and anxiety are found to be affected by temperaments, little research has studied these relationships in pregnancy. The present study explored the associations among perinatal depression (PD), anxiety dimensions (state, trait, and generalized anxiety disorder (GAD)), and temperaments between women in the three trimesters of pregnancy through a network analysis approach. Moreover, differences in the severity of PD and anxiety between women in the three trimesters were evaluated. Methods: Women in first (N = 31), second (N = 184), and third (N = 54) trimesters of pregnancy were recruited in the present cross-sectional study. The network analysis included PD, anxiety dimensions, and temperaments. Three network models were estimated, and ANOVAs evaluated the differences in the severity of PD and anxiety, including trimesters as a between-subject factor. Results: PD and GAD were the nodes most strongly connected across the three groups. Cyclothymic, depressive, and anxious temperaments were most frequently associated with PD and GAD. Hyperthymic temperament was in the periphery of the three networks. Lastly, women in the first trimester had the highest severity of PD and GAD. Conclusions: PD and GAD showed the strongest associations. Anxiety dimensions had positive associations with PD and GAD, suggesting their role as possible risk factors. Temperaments were differently associated within the network between the three groups. Clinical interventions during pregnancy should target the central variables, considering their direct and indirect relationships.

Purpose: The aim of our study was to evaluate changes in the retinal and choriocapillaris circulations in patients with hypothalamic amenorrhea., Methods: Prospective, cross-sectional observational study on 25 patients (50 eyes) diagnosed with hypothalamic amenorrhea and 25 age-matched healthy women. Optical coherence tomography angiography (OCTA) was used to evaluate the vessel density (VD) of superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris VD layers in whole 6.4 × 6.4-mm image and in fovea grid-based image. In patients' group, systemic parameters were collected: body mass index (BMI), endometrial rhyme thickness, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, insulin, and cortisol., Results: SCP and DCP did not show any statistical difference when comparing patients and controls (all p > 0.05). Differently, choriocapillaris VD in the whole region showed a non-significant tendency toward higher values in the patients group in both eyes (p = 0.038 for right eye [RE], p = 0.044 for left eye [LE]). Foveal choriocapillaris VD was higher in hypothalamic amenorrhea women vs. healthy controls (66.0 ± 2.4 vs. 63.7 ± 6.6%, p = 0.136 for RE; 65.0 ± 2.4 vs. 61.6 ± 7.0%, p = 0.005 for LE). Focusing on correlation with systemic parameters, SCP and DCP foveal density had a medium/high effect size with endometrial rhyme, along with DCP in the fovea area vs. cortisol and SCP in the whole area vs. FSH., Conclusion: When comparing hypothalamic amenorrhea patients to healthy subjects, OCTA detected changes in the choriocapillaris layer, showing increased VD in the early stage of the systemic pathology, suggesting that microvascular "compaction" could be a first phase of hypoestrogenism adaptation., (© 2024. The Author(s).)

Purpose: The present systematic review and meta-analysis aimed at evaluating the effect of low dialysate sodium concentration on interdialytic weight gain (IDWG) in chronic hemodialysis patients., Methods: Studies were eligible for inclusion if they were English language papers published in a peer-reviewed journal and met the following inclusion criteria: (1) studies in adult patients (over 18 years of age), (2) included patients on chronic hemodialysis since at least 6 months; (3) compared standard (138-140 mmol/l) or high (> 140 mmol/l) dialysate sodium concentration with low (< 138 mmol/l) dialysate sodium concentration; (4) Included one outcome of interest: interdialytic weight gain. Medline, PubMed, Web of Science, and the Cochrane Library were searched for the quality of reporting for each study was performed using the Quality Assessment Tool of Controlled Intervention Studies of the National Institutes of Health. The quality of reporting of each cross-over study was performed using the Revised Cochrane Risk of Bias (RoB) tool for cross-over trials as proposed by Ding et al. RESULTS: Nineteen studies (710 patients) were included in the analysis: 15 were cross-over and 4 parallel randomized controlled studies. In cross-over studies, pooled analysis revealed that dialysate sodium concentration reduced IDWG with a pooled MD of - 0.40 kg (95% CI - 0.50 to - 0.30; p < 0.001). The systematic review of four parallel, randomized, studies revealed that the use of a low dialysate sodium concentration was associated with a significant reduction of the IDWG in two studies, sustained and almost significant (p = 0.05) reduction in one study, and not significant reduction in one study., Conclusion: Low dialysate sodium concentration reduces the IDWG in prevalent patients on chronic hemodialysis., (© 2024. The Author(s).)

Objective: The use of selective serotonin reuptake inhibitors (SSRIs) is common among hemodialysis patients who receive treatment for depression. However, studies on the efficacy of SSRIs in patients on chronic hemodialysis are few and have led to conflicting results. The present systematic review aims to evaluate, in randomized, controlled studies (RCSs), the efficacy of SSRI administration in reducing symptoms of depression in patients on chronic hemodialysis when compared with placebo or psychological interventions. Method : Research was run on December 2023 in the following databases: Ovid MEDLINE (1985 to present); Ovid EMBASE (1985 to present); Cochrane Library (Wiley); and PubMed (1985 to present). The primary outcome was the frequency and severity of the symptoms of depression assessed through the Beck Depression Inventory (BDI) or the Hamilton Depression Rating Scale (HAMD). The secondary outcome was the prevalence of adverse events. Results : Seven studies totaling 433 patients were included. The number of patients in each individual study ranged from 13 to 120. The length of studies ranged from 8 weeks to 6 months. Heterogeneous data precluded informative meta-analysis. Three studies compared sertraline with a placebo. Of these, two demonstrated that sertraline was better than the placebo in reducing the symptoms of depression while one showed no statistically significant differences between sertraline and the placebo. One study, comparing fluoxetine with a placebo showed that the symptoms of depression did not differ significantly at 8 weeks. In another study, escitalopram administration led to a significantly greater reduction in the Hamilton Depression Rating Scale score compared to a placebo, as well as in the Hamilton Anxiety Rating Scale score. In one study, citalopram and psychological interventions were both effective in reducing the symptoms of depression and anxiety and, in another study, sertraline was modestly more effective than CBT at 12 weeks in reducing the symptoms of depression. Conclusions : SSRIs may be effective in reducing the symptoms of depression in patients on chronic hemodialysis. SSRI administration, at the dosage used in the studies included in the present systematic review, seems safe in most hemodialysis patients. However, the paucity of studies and the limited number of patients included in the trials may suggest that further randomized, controlled studies are needed to determine if SSRIs may be used routinely in daily clinical practice in such a population.

Introduction: This study aims to evaluate the effectiveness and reliability of the utilization for clinical reporting of the evaluation of digital images of bone marrow aspirates by morphologists and their comparability with the classic microscopic morphological evaluation., Methods: We scanned 180 consecutive bone marrow needle aspirates smears using the "Metafer4 VSlide" whole slide imaging (WSI) digital scanning system. We evaluated the statistical comparability and the risk of bias of the microscopic readings with those performed on the screen on the digitized medullary images., Results: The evaluation of cellularity on the screen was equivalent, with a higher frequency of "normal" than the analysis of digital preparations. The means and medians of the percentage values obtained on the different cell populations with the microscopic and digital reading were comparable as the main categories are concerned, with an average difference equal to 0 for the neutrophilic and eosinophilic granulocytic series, at -0.2% for the total myeloid cells, at 1.2% for the erythroid series, at -0.4% for the lymphocytes and at -0.4% for the blasts. Dysplastic features were consistently identified in 69/71 cell lineages., Conclusion: Our study demonstrated that screen evaluation of digitized bone marrow needle aspirates provides quantitative and qualitative results comparable to traditional microscopic analysis of the corresponding slide smears. Digital images offer significant benefits in reducing the workload of experienced operators, reproducibility and sharing of observations, and image preservation. Even in routine diagnostic activities, their use does not alter the quality of the results obtained in evaluating bone marrow needle aspirates., (© 2024 John Wiley & Sons Ltd.)

Objectives : To define if the use of proton pump inhibitors (PPI) is associated with PDF prevalence and characteristics and with time of recovery after dialysis in patients on maintenance hemodialysis. Methods : Patients were defined as experiencing PDF if they spontaneously offered this complaint when asked the open-ended question: "Do you feel fatigued after dialysis?". Time of recovery after dialysis (TIRD) was also assessed for each patient. Each patient was invited to rate the intensity, duration and frequency of PDF from 1 to 5. We defined if patients used PPI (no PPI use or PPI use), the type of used PPI, the dose of used PPI, and the duration of the use of PPI (<1 year or ≥1 year). Results : A total of 346 patients were studied: 259 used PPI (55 used omeprazole, 63 esomeprazole, 54 pantoprazole, 87 lansoprazole, and 7 rabeprazole) and 87 did not. Two hundred and thirty-two patients declared PDF and 114 did not. The median [min-max] TIRD was 210 min [0-1440]. The prevalence of PDF in PPI users and PPI non-users was 67% and 68%, respectively ( p = 0.878). The median [min-max] TIRD did not differ significantly between PPI users and PPI non-users (180 [0-1440] and 240 [0-1440], respectively; p = 0.871). Median PDF intensity, duration, frequency, and severity did not differ significantly between PPI use and no use. The prevalence of PDF was similar among the different types of PPI use and did not differ with respect to PPI non-users. Duration of PPI exposure was <1 year in 40 patients and ≥1 year in 219 patients. The prevalence of PDF did not differ between the two exposures. The correlation matrix between PPI equivalent dose, PPI treatment duration and PDF frequency, PDF characteristics, and TIRD showed whether there was statistical significance. Conclusions : The use of PPI is not associated with PDF and time of recovery after dialysis in patients on maintenance hemodialysis.

Microbial-based biostimulants, functioning as biotic and abiotic stress protectants and growth enhancers, are becoming increasingly important in agriculture also in the context of climate change. The search for new products that can help reduce chemical inputs under a variety of field conditions is the new challenge. In this study, we tested whether the combination of two microbial growth enhancers with complementary modes of action, Azotobacter chroococcum 76A and Trichoderma afroharzianum T22, could facilitate tomato adaptation to a 30% reduction of optimal water and nitrogen requirements. The microbial inoculum increased tomato yield (+48.5%) under optimal water and nutrient conditions. In addition, the microbial application improved leaf water potential under stress conditions (+9.5%), decreased the overall leaf temperature (-4.6%), and increased shoot fresh weight (+15%), indicating that this consortium could act as a positive regulator of plant water relations under limited water and nitrogen availability. A significant increase in microbial populations in the rhizosphere with applications of A. chroococcum 76A and T. afroharzianum T22 under stress conditions, suggested that these inoculants could enhance soil microbial abundance, including the abundance of native beneficial microorganisms. Sampling time, limited water and nitrogen regimes and microbial inoculations all affected bacterial and fungal populations in the rhizospheric soil. Overall, these results indicated that the selected microbial consortium could function as plant growth enhancer and stress protectant, possibly by triggering adaptation mechanisms via functional changes in the soil microbial diversity and relative abundance., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Cirillo, Romano, Woo, Di Stasio, Lombardi, Comite, Pepe, Ventorino and Maggio.)

Introduction: The aim of this study was to determine if the Geriatric Depression Scale (GDS) was predictor of mortality in elderly patients on chronic hemodialysis (HD)., Methods: A total of 140 HD patients ≥65 years were studied. Symptoms of depression were assessed through GDS and cognitive function through the Mini Mental State Examination (MMSE). GDS scores 0-9 are considered normal (Group 1); scores of 10-20 (Group 2) and 21-30 (Group 3) indicate mild and severe depression., Results: Median GDS was 13 (11-15): 54 patients in Group 1, 49 in Group 2, and 37 in Group 3. After a follow-up of 58.85 ± 38.8 months, 94 patients died and 46 were alive. Kaplan-Meier survival was significantly lower in patients of Groups 2 and 3 than in Group 1 (log-rank χ 2 : 101.9; DF: 2; p < 0.0001). According to Cox regression analysis, mortality was associated with age and GDS, and inversely associated with MMSE and Kt/V., Conclusion: GDS predicts mortality in elderly HD patients., (© 2023 International Society for Apheresis and Japanese Society for Apheresis.)

Importance: Postoperative delirium (POD) is a common and serious complication after surgery. Various predisposing factors are associated with POD, but their magnitude and importance using an individual patient data (IPD) meta-analysis have not been assessed., Objective: To identify perioperative factors associated with POD and assess their relative prognostic value among adults undergoing noncardiac surgery., Data Sources: MEDLINE, EMBASE, and CINAHL from inception to May 2020., Study Selection: Studies were included that (1) enrolled adult patients undergoing noncardiac surgery, (2) assessed perioperative risk factors for POD, and (3) measured the incidence of delirium (measured using a validated approach). Data were analyzed in 2020., Data Extraction and Synthesis: Individual patient data were pooled from 21 studies and 1-stage meta-analysis was performed using multilevel mixed-effects logistic regression after a multivariable imputation via chained equations model to impute missing data., Main Outcomes and Measures: The end point of interest was POD diagnosed up to 10 days after a procedure. A wide range of perioperative risk factors was considered as potentially associated with POD., Results: A total of 192 studies met the eligibility criteria, and IPD were acquired from 21 studies that enrolled 8382 patients. Almost 1 in 5 patients developed POD (18%), and an increased risk of POD was associated with American Society of Anesthesiologists (ASA) status 4 (odds ratio [OR], 2.43; 95% CI, 1.42-4.14), older age (OR for 65-85 years, 2.67; 95% CI, 2.16-3.29; OR for >85 years, 6.24; 95% CI, 4.65-8.37), low body mass index (OR for body mass index <18.5, 2.25; 95% CI, 1.64-3.09), history of delirium (OR, 3.9; 95% CI, 2.69-5.66), preoperative cognitive impairment (OR, 3.99; 95% CI, 2.94-5.43), and preoperative C-reactive protein levels (OR for 5-10 mg/dL, 2.35; 95% CI, 1.59-3.50; OR for >10 mg/dL, 3.56; 95% CI, 2.46-5.17). Completing a college degree or higher was associated with a decreased likelihood of developing POD (OR 0.45; 95% CI, 0.28-0.72)., Conclusions and Relevance: In this systematic review and meta-analysis of individual patient data, several important factors associated with POD were found that may help identify patients at high risk and may have utility in clinical practice to inform patients and caregivers about the expected risk of developing delirium after surgery. Future studies should explore strategies to reduce delirium after surgery.

Background: and Sex and cognitive profile may be related to the laterality of motor symptoms in idiopathic Parkinson's disease., Introduction: Parkinson's disease (PD) is well recognised as an inherently asymmetric disease with unilateral onset of motor symptoms. The laterality of motor symptoms may be linked to sex, clinical and demographic variables, and neuropsychological disorders. However, the available data are inconsistent. This study aimed to explore the potential association between the laterality of motor symptoms and clinical and demographic variables and deficits in specific cognitive domains., Material and Methods: We retrospectively recruited 97 participants with idiopathic PD without dementia; 60 presented motor symptoms on the left side and 37 on the right side. Both groups were comparable in terms of age, age at disease onset, disease duration, and severity of the neurological deficits according to the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale., Results: Participants with left-side motor symptoms scored lower on the Schwab and England Activities of Daily Living scale. Our sample included more men than women (67% vs. 33%). Both sexes were not equally represented in the 2 groups: there were significantly more men than women in the group of patients with left-side motor symptoms (77% vs. 23%), whereas the percentages of men and women in the group of patients with right-side motor symptoms were similar (51% vs. 49%). Both groups performed similarly in all neuropsychological tasks, but women, independently of laterality, performed better than men in the naming task., Conclusion: We found a clear prevalence of men in the group of patients with left-side motor symptoms; this group also scored lower on the Schwab and England Scale. Female sex was predictive of better performance in the naming task. Sex should always be considered in disorders that cause asymmetric involvement of the brain, such as PD., (Copyright © 2021 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Aim: To evaluate predisposition to eating disorders (ED) or body dissatisfaction in adults with type 1 diabetes mellitus (T1DM); to further investigate any differences in ED predisposition between subjects with T1DM on multiple daily injections (MDI) or insulin pumps (CSII) and in respect to control healthy subjects., Methods: We conducted a monocentric, cross-sectional, observational study. We enrolled subjects with T1DM, aged ≥ 18 years, and healthy subjects (HS) as control group. All participants completed two questionnaires to detect possible predisposition to ED: 34-items Body Shape Questionnaire (BSQ) and Eating Disorder Inventory-3 (EDI-3). HS only filled BSQ. For subjects with T1DM data about glycated hemoglobin and duration of disease were also collected., Results: 162 subjects with T1DM (age 41 ± 12 years, 77 [47%] males) and 50 HS (age 38 ± 13 years, 18 (36%) males) were enrolled. 87 subjects with T1DM (54%) were on MDI and 75 (46%) were on CSII. No significant difference in the distribution of BSQ scores between subjects with T1DM and HS was observed (p = 0.551), although 16% of subjects with T1DM scored BSQ class 1 points while 8% of HS scored a BSQ class 1 points. No significant difference in BSQ scores was observed between subjects with T1DM on MDI or CSII. Between these two groups, no differences in EDI-3 scores were observed except for perfectionism score: subjects on MDI present more frequently a predisposition for perfectionism (p < 0.05) and, at a trend level, for bulimia., Conclusion: A non -significant higher percentage of BSQ class 1 was detected in subjects T1DM compared to healthy controls. Among subjects with T1DM, no differences between MDI and CSII were observed in ED predisposition. A more perfectionist personality has been detected among subjects on MDI., 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 © 2023. Published by Elsevier B.V.)

Prolonged B cells stimulation due to the Hepatitis C virus (HCV) can result in autoimmunity, stigmatized by rising levels of cryoglobulins (CGs), the rheumatoid factor (RF), and free light chains (FLC) of immunoglobulins (Ig) associated with a range of symptoms, from their absence to severe cryoglobulinemic vasculitis and lymphoma. Here, we aimed to identify an immunological signature for the earliest stages of vasculitis when cryoprecipitate is still not detectable. We firstly analyzed the IgG subclasses, FLC, and RF in 120 HCV-RNA-positive patients divided into four groups according to the type of cryoprecipitate and symptoms: 30 asymptomatic without cryoprecipitate (No Cryo), 30 with vasculitis symptoms but without CGs that we supposed were circulating but still not detectable (Circulating), 30 type II and 30 type III mixed cryoglobulinemia (Cryo II and Cryo III, respectively). Our results revealed that patients with supposed circulating CGs displayed a pattern of serological parameters that closely resembled Cryo II and Cryo III, with a stronger similarity to Cryo II. Accordingly, we analyzed the groups of Circulating and Cryo II for their immunoglobulin heavy chain (IgH) and T-cell receptor (TCR) gene rearrangements, finding a similar mixed distribution of monoclonal, oligoclonal, and polyclonal responses compared to a control group of ten HCV-RNA-negative patients recovered from infection, who displayed a 100% polyclonal response. Our results strengthened the hypothesis that circulating CGs are the origin of symptoms in HCV-RNA-positive patients without cryoprecipitate and demonstrated that an analysis of clonal IGH and TCR rearrangements is the best option for the early diagnosis of extrahepatic complications.

Purpose: Little is known about the relationships between apathy, depressive symptoms and interdialytic weight gain (IDWG) in patients on chronic hemodialysis. Aim of the present study is to investigate the association between IDWG and symptoms of depression and apathy in hemodialysis patients., Methods: A total of 139 chronic patients of the HD units between January 2020 and December 2021 were included in the present cross-sectional study. IDWG was calculated as the difference between the pre-HD weight and the weight registered after the previous session; the average of the sessions in a month was registered. Apathy Evaluation Scale (AES) was adopted to evaluate apathy. Depression was assessed by Beck Depression Inventory (BDI)., Results: Ninety-three patients had IDWG% ≤ 4 and 46 had an IDWG% > 4. Correlation between IDWG% and BDI as well that between IDWG% and AES were not statistically significant. Median BDI and mean AES did not differ significantly between the groups. In addition, 104 patients had a BDI < 16 and 35 had a BDI ≥ 6. Seventy-five patients had an AES score ≤ 35 and 63 had a AES score > 35. The IDWG (kg) and the IDWG% did not differ significantly between the two groups., Conclusion: IDWG is not associated with symptoms of depression or apathy in hemodialysis patients. Thus, these results may question if the use of behavioral intervention aimed at improving motivation is warranted in the hemodialysis population to reduce the IDWG., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Aim of the present study was to assess whether post-dialysis fatigue (PDF) may be related to pre- or post-dialysis levels of serum S100B protein. Hemodialysis patients (HD) who answered to be fatigued after their hemodialysis sessions when asked: "Do you feel worse after dialysis? if they answered yes" were considered to suffer from PDF. Serum Interleukins (IL-1β, IL-6, IL-10), TNF-α and S100B were assessed by ELISA kit., Results: Thirty HD patients were studied: 22 (73.4%) reported to suffer from PDF. Serum S100B post-dialysis levels (median [IQR] = 17.4 μg [7.1 to 30.9]) were significantly higher than serum S100B pre-dialysis levels (median [IQR] = 5 μg [1.4 to 22.1]; p = 0.0001). S100B post-dialysis was significantly higher than S100B pre-dialysis either in patients with PDF or without PDF., Conclusions: Pre- and post-dialysis values of serum S100B and its delta did not differ significantly between patients with and without PDF and were not associated with the length of the TIRD in patients on chronic hemodialysis., (© 2022 International Society for Apheresis and Japanese Society for Apheresis.)

Objective: Preeclampsia (PE) is the major cause of maternal morbidity and mortality and the leading cause of premature delivery worldwide. As well as intrauterine growth restriction (IUGR), PE is associated with pathogenic evidence of placental malperfusion and ischemia. Recent literature has highlighted the potential of pravastatin in the prevention and treatment of these conditions. Aim of this study is to describe perinatal outcomes and placental histopathological findings in a small series of pregnant women with severe PE and IUGR treated with pravastatin on compassionate grounds. Two-year follow up of these babies is provided., Study Design: Between October 2017 and October 2019 in Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy, women with singleton pregnancy between 19.6 and 27.6 gestational weeks, who presented with severe PE and IUGR were counselled for a compassionate treatment with Pravastatin 40 mg a day. Treated women were compared with controls identified with similar data in terms of gestational age at diagnosis, clinical maternal data, Doppler severity findings. Neonates were followed up for two years., Results: The median time from diagnosis to delivery was 39 days (IQR 20) for women in the pravastatin group and 20 days (IQR 20.5) for controls. Looking to maternal blood exams, in the group of women treated with pravastatin, maximum transaminase, creatinine levels were lower than in controls, where the minimum platelet count was higher. Placenta examination did not reveal any significant differences in placental histopathological findings. No significant differences were observed in the investigated perinatal data, as well as in infant follow-up, although an increased prenatal weight gain was found in treated pregnancies in comparison to controls., Conclusions: Our data did not allow us to find significant differences in pregnancy outcome and infant follow-up, as well as in placental histological picture in preeclamptic patients when pravastatin is administered in the late second trimester. However, we suggest its possible role in stabilizing the disease, increasing the prenatal weight gain and prolonging the duration of pregnancy, thus preventing the progression to a more severe maternal disease., 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 © 2023 Elsevier B.V. All rights reserved.)

Sleep deprivation is a significant risk to the health and judgment of physicians. We wanted to investigate whether anesthesiology residents (ARs) who work only one night shift per week have different physical and mental health from occupational medicine residents (OMRs) who do not work at night. A total of 21 ARs and 16 OMRs attending a university general hospital were asked to wear an actigraph to record sleep duration, heart rate and step count and to complete a questionnaire for the assessment of sleep quality, sleepiness, fatigue, occupational stress, anxiety, depression and happiness. ARs had shorter sleep duration than OMRs; on average, they slept 1 h and 20 min less ( p < 0.001). ARs also had greater daytime sleepiness, a higher heart rate and lower happiness than OMRs. These results should be interpreted with caution given the cross-sectional nature of the study and the small sample size, but they are an incentive to promote sleep hygiene among residents.

Botulinum toxin A (BoNT/A) is the first-line treatment for idiopathic cervical dystonia (ICD) and is widely used in the clinical setting. To date, scanty data are available on the effectiveness of BoNT in treating acquired cervical dystonia (ACD). Here we present a long-term follow-up of ACD patients treated with BoNT/A that focused on safety and efficacy. The study included subjects who had received at least six treatments of three commercially available BoNT/A drugs [abobotulinumtoxinA (A/Abo), incobotulinumtoxinA (A/Inco) and onabotulinumtoxinA (A/Ona)]. Safety and efficacy were assessed based on patients' self-reports regarding adverse effects (AE), duration of improvement of dystonia and/or pain relief. Global clinical improvement was measured on a six-point scale. 23 patients with ACD were administered 739 treatments (A/Abo in 235, A/Inco in 72, A/Ona in 432) with a mean number of treatments of 31 ± 20 (range 6-76) and duration of 10 ± 6 weeks (range 2-25). The mean dose was 737 ± 292 U for A/Abo, 138 ± 108 U for A/Inco and 158 ± 80 U for A/Ona. The average benefit duration was 89 ± 26 (A/Abo), 88 ± 30 days (A/Inco), and 99 ± 55 days (A/Ona) (p = 0.011); global clinical improvement for all sessions was 4 ± 1. ANOVA one-way analysis indicated that A/Ona had the best profile in terms of duration (p < 0.05), whereas A/Abo had the best pain relief effect (p = 0.002). Side effects were reported in 9% of treatments (67/739), with ten treatments (1%) complicated by two side effects. Most side effects were rated mild to moderate; severe side effects occurred following three treatments with the three different BoNT; two required medical intervention. No allergic reactions were reported. Even after 25 years of repeated treatments, all serotypes of BoNT demonstrate positive effects in treating ACD with long-lasting efficacy and safety., (© 2022. The Author(s).)

Background: No available and easy to administer cognitive test has been evaluated for the prediction of mortality in prevalent patients on chronic hemodialysis. The aim of the present study was to determine if the Mini-Mental State Examination (MMSE) was predictor of mortality in patients on chronic hemodialysis., Methods: One hundred twenty-seven prevalent patients on chronic hemodialysis were studied. All patients underwent assessment of cognitive function through the MMSE. The MMSE was administered during a midweek hemodialysis session, avoiding the beginning and the end of each treatment to minimize the effects of fluctuations in uremic syndrome or blood pressure in accordance with a previous study. An MMSE score ≤23 was used as indicative of cognitive impairment. Demographic, clinical, and laboratory parameters were recorded for each patient., Results: Mean (SD) MMSE was 23.2 ± 4.1. Median MMSE was 24 (min-max: 2-30). MMSE was ≤23 in 72 patients and >23 in 55. With data updated in March 2021, after a mean follow-up of 58.8 ± 41 months (range: 2-156 months), 75 patients died, and 17 were transplanted. None was lost to follow-up or was transferred to another unit. Dead participants, as compared with alive ones, were significantly older, had a higher Charlson Index score, had lower Activities daily living and Instrumental activities daily living, and had a lower MMSE score and lower serum albumin levels. Kaplan-Meier analysis showed that survival was significantly lower in patients with MMSE ≤23 than in those with MMSE >23 (log-rank χ 2 : 8.825, p = 0.003). According to Cox regression analysis, mortality was associated with age and inversely associated with MMSE., Conclusion: We show that the MMSE predicts mortality in prevalent patients on chronic hemodialysis., (© 2022 Wiley Periodicals LLC.)

Introduction: The present cross-sectional study aimed to compare the prevalence, the characteristics of post-dialysis fatigue and the length of recovery time after hemodialysis in prevalent end-stage renal disease patients (ESRD) receiving bicarbonate hemodialysis (HD) or hemodiafiltration (HDF)., Methods: Patients were suffering from post-dialysis fatigue if they spontaneously offered this complaint when asked the open-ended question: "Do you feel fatigued after dialysis?". Moreover, each patient was invited to rate the intensity, duration, and frequency of post-dialysis fatigue from 1 to 5. In order to assess RECOVERY TIME AFTER DIALYSIS, patients were invited to answer to the following single open-ended question: "How long does it take you to recover from a dialysis session?", Findings: We included 335 patients: 252 received HD and 83 received HDF. Post-dialysis fatigue was present in 204 patients (60.9%). Prevalence of post-dialysis fatigue did not differ significantly between patients on HD (62.3%) and on HDF (56.6%; p = 0.430). Median recovery time after dialysis was 180 min [180-240] and did not differ significantly between the two subgroups (180 min [130-240] and 240 min [120-332] p = 0.671, respectively). Median post-dialysis fatigue intensity, duration, and frequency were 3 [1-5], 3 [1-5], and 4 [1-5] and did not differ significantly between patients on HD and on HDF. At the multivariate analysis, age, ADL and hemoglobin levels were the independent predictors of the HDF treatment., Discussion: Prevalence and characteristics of post-dialysis fatigue do not differ significantly between patients receiving bicarbonate HD or HDF., (© 2022 The Authors. Hemodialysis International published by Wiley Periodicals LLC on behalf of International Society for Hemodialysis.)

The aim of this study was to analyse the cytocompatibility of Surefil One (SuO) with respect to the release of monomers from the material. The following reference materials were chosen: SDR Flow Plus (SDR, Dentsply Sirona, Konstanz, Germany), One Q Bond (Q, Dentalica, Milan, Italy), and Ketac (K, 3M-ESPE, USA). Fifteen dentin discs (2 mm thickness and diameter) were obtained from 15 third molars and were used in this study. After dentin disc permeability measurement, murine fibroblasts were grown, and the pulp surface of the dentinal disc was placed in direct contact with the cells immersed in DMEM. The experimental materials were positioned on the occlusal side of each dentinal disc until a uniform thickness of 2 mm was obtained. Then, the discs were inserted into an artificial pulp chamber for 24 hours to assess the cytocompatibility. Afterwards, the moles of monomers leached from the specimens in DMEM were determined using HPLC. Statistical analysis was performed using ANOVA ( p < 0.05). Under the experimental conditions, the toxic effect induced by all tested materials was slight or absent. Diurethane dimethacrylate and acrylic acid were not found in the culture media. It is concluded that all materials have good cytocompatibility consistent with the nondeterminability of the monomers released after polymerization., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022 Luca Marigo et al.)

Background: This work aimed to shed light on the notorious debate over the role of an educational/cognitive/behavioral or psychological approach in the reduction of interdialytic weight gain (IDWG) in patients on chronic hemodialysis., Methods: Searches were run from 1975 to January 2022 on Medline, PubMed, Web of Science, and the Cochrane Library. The search terms included "hemodialysis/haemodialysis" AND "adherence" AND ("fluid intake" OR "water intake") AND ("weight gain" OR "interdialytic weight gain" OR "IDWG") AND "patient-level interventions. Randomized controlled studies were eligible if they were in English, published in a peer-reviewed journal and regarded adults patients with on chronic hemodialysis for at least 6 months; compared educational/cognitive and/or counseling/behavioral or psychological interventions to no intervention on interdialytic weight gain. Outcome of interest was interdialytic weight gain. The review was registered on the International Prospective Register of Systematic Reviews in Health and Social Care (PROSPERO, ID number CRD42022332401)., Results: Eighteen studies (1759 patients) were included in the analysis. Compared to the untreated group, educational/cognitive and/or counseling/behavioral interventions significantly reduced interdialytic weight gain with a pooled mean difference of - 0.15 kg (95% CI - 0.26, 30-0.05; P = 0.004). On the other hand, psychological/affective interventions reduced interdialytic weight gain with a pooled mean difference of - 0.26 kg (95% CI - 0.48, - 0.04; P = 0.020)., Conclusions: Educational/cognitive, counseling/behavioral or psychological/affective interventions significantly reduced the interdialytic weight gain in patients on chronic hemodialysis, although such reduction did not appear to be clinically relevant on hard outcomes., (© 2022. The Author(s).)

Introduction: This study explores the link between fatigue and apathy in patients on chronic hemodialysis (HD)., Methods: One hundred thirty-nine chronic HD patients underwent the assessment of fatigue, apathy, depression, and their functional status, with the fatigue severity scale (FSS), the Apathy Evaluation Scale (AES), the beck depression inventory (BDI), the activity of daily living (ADL), and instrumental activity of daily living (IADL)., Results: Patients with high FSS had a significantly lower ADL and IADL score, higher BDI, Charlson Comorbidity Index, and AES score, and lower serum levels of creatinine, compared to low FSS patients. FSS was highly correlated with the AES, as well as with the BDI and the AES correlates with the BDI. At multiple regression analyses, only apathy and IADL were independent predictor variables of fatigue in HD population., Conclusion: Future longitudinal studies could determine if apathy is a causative factor for fatigue manifestation and development in HD patients., (© 2021 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Cryoglobulinemic Vasculitis (CV) is an autoimmune/lymphoproliferative disorder associated with HCV infection that in 5%-10% of cases evolves into a B cell Non-Hodgkin's Lymphoma (NHL). B-cell activating factor (BAFF) is a key regulator in B-cell development and survival. Particular genetic variants are responsible for BAFF signaling impairment in autoimmune and neoplastic diseases. We evaluated BAFF and BAFF-receptor (BAFF-R) polymorphisms in order to determine if they predispose to HCV-related CV and NHL. The analysis was performed on 416 HCV-chronically infected patients: 136 HCV without signs/symptoms of lymphoproliferations/autoimmunity (HCV), 166 HCV with CV (HCV-CV) and 114 HCV with NHL (HCV-NHL). Rs9514828 SNP on BAFF promoter, rs61756766 on BAFF-R and rs12428930 on the BAFF gene were evaluated by Real-Time PCR. Concerning rs9514828, the frequency of C/T genotype was significantly higher in HCV-CV than in HCV. The difference in the distribution of the T/T mutant genotype in HCV-CV compared to HCV was significant as well as the distribution of C/T and T/T genotype in HCV-NHL versus HCV. T minor allele was more frequent in HCV-NHL and HCV-CV than in HCV. The distribution of C/T + T/T (for the dominant model of penetrance C/T + T/T vs. C/C) was significantly higher in HCV-CV and HCV-NHL than in HCV. Genotyping of rs61756766 on BAFF-R coding gene, revealed C/T heterozygosis at a frequency of 11% in HCV-NHL versus 3% in HCV. The T minor allele frequency was higher in HCV-NHL than in HCV. No differences emerged by genotyping rs12428930 SNP on BAFF coding gene. Our results reinforce the hypothesis that BAFF/BAFF-R genetic pattern has a role in the pathogenesis of HCV-related lymphoproliferations. BAFF/BAFF-R variants could identify a risk haplotype for HCV related CV and NHL and a BAFF/BAFF-R genetic profile assessment could potentially contribute to tailoring anti-BAFF therapy by identifying patients with BAFF alterations in which the treatment could be more beneficial., (© 2022 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.)

Triple-negative breast cancer (TNBC) is characterized by earlier recurrence and shorter survival compared with other types of breast cancer. Moreover, approximately 15 to 25% of all TNBC patients harbor germline BRCA (gBRCA) 1/2 mutations, which confer a more aggressive phenotype. However, TNBC seems to be particularly sensitive to chemotherapy, the so-called 'triple negative paradox'. Therefore, Neoadjuvant chemotherapy (NACT) is currently considered the preferred approach for early-stage TNBC. BRCA status has also been studied as a predictive biomarker of response to platinum compounds. Although several randomized trials investigated the addition of carboplatin to standard NACT in early-stage TNBC, the role of BRCA status remains unclear. In this retrospective analysis, we evaluated data from 136 consecutive patients with Stage I-III TNBC who received standard NACT with or without the addition of carboplatin, in order to define clinical features and outcomes in BRCA 1/2 mutation carriers and non-carrier controls. Between January 2013 and February 2021, 67 (51.3%) out of 136 patients received a standard anthracyclines/taxane regimen and 69 (50.7%) patients received a platinum-containing chemotherapy regimen. Deleterious germline BRCA1 or BRCA2 mutations were identified in 39 (28.7%) patients. Overall, patients with deleterious gBRCA1/2 mutation have significantly higher pCR rate than non-carrier patients (23 [59%] of 39 vs. 33 [34%] of 97; p = 0.008). The benefit of harboring a gBRCA mutation was confirmed only in the subset of patients who received a platinum-based NACT (17 [65.4%] of 26 vs. 13 [30.2%] of 43; p = 0.005) while no differences were found in the platinum-free subgroup. Patients who achieved pCR after NACT had significantly better EFS (OR 4.5; 95% CI 1.9-10.7; p = 0.001) and OS (OR 3.3; 95% CI 1.3-8.9; p = 0.01) than patients who did not, regardless of BRCA1/2 mutation status and type of NACT received. Our results based on real-world evidence show that TNBC patients with the gBRCA1/2 mutation who received platinum-based NACT have a higher pCR rate than non-carrier patients, supporting the use of this chemotherapy regimen in this patient population. Long-term follow-up analyses are needed to further define the role of gBRCA mutation status on clinical outcomes in patients with early-TNBC.

Red blood cells (RBCs) are characterized by a remarkable elasticity, which allows them to undergo very large deformation when passing through small vessels and capillaries. This extreme deformability is altered in various clinical conditions, suggesting that the analysis of red blood cell (RBC) mechanics has potential applications in the search for non-invasive and cost-effective blood biomarkers. Here, we provide a comparative study of the mechanical response of RBCs in patients with Alzheimer's disease (AD) and healthy subjects. For this purpose, RBC viscoelastic response was investigated using atomic force microscopy (AFM) in the force spectroscopy mode. Two types of analyses were performed: (i) a conventional analysis of AFM force-distance (FD) curves, which allowed us to retrieve the apparent Young's modulus, E; and (ii) a more in-depth analysis of time-dependent relaxation curves in the framework of the standard linear solid (SLS) model, which allowed us to estimate cell viscosity and elasticity, independently. Our data demonstrate that, while conventional analysis of AFM FD curves fails in distinguishing the two groups, the mechanical parameters obtained with the SLS model show a very good classification ability. The diagnostic performance of mechanical parameters was assessed using receiving operator characteristic (ROC) curves, showing very large areas under the curves (AUC) for selected biomarkers (AUC > 0.9). Taken all together, the data presented here demonstrate that RBC mechanics are significantly altered in AD, also highlighting the key role played by viscous forces. These RBC abnormalities in AD, which include both a modified elasticity and viscosity, could be considered a potential source of plasmatic biomarkers in the field of liquid biopsy to be used in combination with more established indicators of the pathology., 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 © 2022 Nardini, Ciasca, Lauria, Rossi, Di Giacinto, Romanò, Di Santo, Papi, Palmieri, Perini, Basile, Alcaro, Di Stasio, Bizzarro, Masullo and De Spirito.)

Down Syndrome (DS) is a neurodevelopmental disorder that is characterized by an accelerated aging process, frequently associated with the development of Alzheimer's disease (AD). Previous studies evidenced that DS patients have various metabolic anomalies, easily measurable in their serum samples, although values that were found in DS patients were compared with those of age-matched non-DS patients, thus hampering to discriminate the physiologic age-related changes of serum metabolites from those that are truly caused by the pathologic processes associated with DS. In the present study we performed a targeted metabolomic evaluation of serum samples from DS patients without dementia of two age classes (Younger DS Patients, YDSP, aging 20-40 years; Aged DS Patients, ADSP, aging 41-60 years), comparing the results with those that were obtained in two age classes of non-DS patients (Younger non-DS Patients, YnonDSP, aging 30-60 years; Aged-nonDS Patients, AnonDSP, aging 75-90 years). Of the 36 compounds assayed, 30 had significantly different concentrations in Pooled non-DS Patients (PnonDSP), compared to Pooled DS Patients (PDSP). Age categorization revealed that 11/30 compounds were significantly different in AnonDSP, compared to YnonDSP, indicating physiologic, age-related changes of their circulating concentrations. A comparison between YDSP and ADSP showed that 19/30 metabolites had significantly different values from those found in the corresponding classes of non-DS patients, strongly suggesting pathologic, DS-associated alterations of their serum levels. Twelve compounds selectively and specifically discriminated PnonDSP from PDSP, whilst only three discriminated YDSP from ADSP. The results allowed to determine, for the first time and to the best of our knowledge, the true, age-independent alterations of metabolism that are measurable in serum and attributable only to DS. These findings may be of high relevance for better strategies (pharmacological, nutritional) aiming to specifically target the dysmetabolism and decreased antioxidant defenses that are associated with DS.