Chorioretinal biomarkers in hypothalamic amenorrhea.

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.

Mini-Mental State Examination predicts mortality in patients on chronic hemodialysis.

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 χ2 : 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.

Serological and Molecular Characterization of Hepatitis C Virus-Related Cryoglobulinemic Vasculitis in Patients without Cryoprecipitate.

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.

B-cell activating factor (BAFF), BAFF promoter and BAFF receptor allelic variants in hepatitis C virus related Cryoglobulinemic Vasculitis and Non-Hodgkin's Lymphoma.

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.

Correlation Between QElaXto Techniques and Supersonic Imagine for Liver Stiffness Quantification in Chronic Liver Disease.

OBJECTIVES: Intersystem variability in liver stiffness (LS) quantification with ultrasound shear wave elastography (SWE) precludes direct comparison of results obtained with different equipment. The aim of this study was to investigate the agreement between point-SWE and 2-dimensional-SWE with Esaote-MyLab 9 (p-QElaXto and 2D-QElaXto, respectively) and 2D-SWE with SuperSonic Imagine (SSI) in order to assess specific LS thresholds for fibrosis staging with QElaXto techniques, using SSI as a reference standard. METHODS: A total of 235 compensated chronic liver disease (CLD) patients without comorbidities potentially affecting LS were enrolled in the study. Among them, 101 patients underwent also liver biopsy. Agreement between the equipment was assessed with Pearson coefficient and Bland-Altman analysis, while cut-off values were calculated with receiver operating characteristics analysis. RESULTS: Correlation between 2D-QElaXto and p-QElaXto with SSI resulted very good (r = 0.898 and r = 0.866), especially in precirrhotic stages, with a mean difference between LS values of -1.3 kPa for 2D-QElaXto and -0.6 kPa for p-QElaXto compared with SSI. Cut-off thresholds for diagnosing fibrosis ≥F2, ≥F3, and F4 in non-HBV-related CLD were, respectively, 5.5, 8.0, and 10.6 kPa for 2D-QElaXto and 6.1, 8.1, and 11.7 kPa for p-QElaXto. All three SWE techniques were effective in differentiating significant fibrosis ≥F2 from mild or absent fibrosis in the subgroup of patients submitted to biopsy and showed good feasibility. CONCLUSIONS: Correlation between QElaXto techniques and SSI in LS measurements is very good. Our study identifies for the first time cut-off thresholds for fibrosis staging in non-HBV-related CLD using two QElaXto techniques.

What about the caregiver? A journey into Parkinson's disease following the burden tracks.

OBJECTIVES: To investigate caregivers and patients characteristics related to different dimensions of burden in Parkinson's disease (PD). METHODS: 55 pairs of PD patients and caregivers were recruited. The burden was evaluated with the Caregiver Burden Inventory (CBI). Multivariate analysis was applied to evaluate the impact of caregivers' and patients' characteristics on the varying aspects of burden. RESULTS: ADL score was the dominant predictor for the total score and all dimensions of CBI, except for the social burden, which is strongly predicted by the motor severity of PD. As one can easily imagine, the Total CBI decreases as the ADL score increases. DISCUSSION: An increased appreciation for characteristics of caregiver burden is a fundamental aspect of the patient's global evaluation. Clinicians may need to directly probe for these factors in the caregiver as they may not be elicited routinely.

Serum interleukin-6 and endotoxin levels and their relationship with fatigue and depressive symptoms in patients on chronic haemodialysis.

BACKGROUND: Little is known about the underlying aetiology of fatigue in haemodialysis (HD) patients apart from a significant association and overlapping symptomatology with depressive symptoms. Growing evidence exists for the involvement of the immune system, by pro-inflammatory cytokines, in the development of fatigue in other inflammatory diseases. In HD patients, increased exposure to bacterial endotoxins may contribute to an inflammatory response and may potentially lead to fatigue. We therefore aimed (i) to assess the interrelationship between serum endotoxin (EA) levels, interleukin-6 (IL-6) levels and fatigue in HD patients; (ii) to evaluate whether there is a relationship between depressive symptoms and inflammation as well and (iii) to what extent depressive symptoms and fatigue are related to each other. METHODS: Fatigue and depressive symptoms in daily life were assessed in 59 individuals using the SF-36 vitality subscale and the Geriatric Depression Scale. Blood samples were collected on a mid-week dialysis session to determine EA levels, through the Endotoxin Activity Assay (EAA™), and IL-6 concentrations, through the commercially available Abcam ELISA (Enzyme-Linked Immunosorbent Assay) kit. RESULTS: EA, IL-6 levels and depressive symptoms were significantly correlated with fatigue. EA levels and depressive symptoms were significant predictors of fatigue, explaining 31% of its variance. However, EA and IL-6 were not significantly associated with depression. CONCLUSIONS: Fatigue in HD patients may be related to endotoxemia and inflammation through IL-6. Furthermore, fatigue is significantly associated with depressive symptoms. Future research into the causal interrelationship of inflammation, fatigue and depression in HD patients might lead to potential targets for therapeutic strategies.

Assessing Baveno VI criteria with liver stiffness measured using a new point-shear wave elastography technique (BAVElastPQ study).

BACKGROUND AND AIMS: To date, no study has explored the potential role of ElastPQ, a novel point-SWE technique, in the assessment of clinically significant portal hypertension. The aim of our study was to determine a liver stiffness (LS) cut-off value measured by ElastPQ and laboratory parameters that could help to identify those patients who can safely avoid screening endoscopy. METHODS: Data were collected on 1422 patients who underwent ElastPQ measurement from January 2013 to January 2016 in our Department. Inclusion criteria were a LS value of ≥7 kPa, an upper gastrointestinal endoscopy within 12 months and a diagnosis of compensated chronic liver disease. Exclusion criteria were history of decompensated liver disease, evidence of porto-spleno-mesenteric vein thrombosis and non-cirrhotic portal hypertension. Varices were graded as low-risk varices (grade <2) or varices needing treatment (VNT, grade ≥2). RESULTS: The study included 195 patients (120 [61%] HCV, 171 [88%] Child-Pugh A). Varices were present in 35% cases, with 10% prevalence of VNT. According to ROC curve analysis, LS measurement and platelet count were evaluated as predictors of VNT. Overall, 75/195 (38%) met the 'BAVElastPQ' criteria (that is, LS < 12 kPa and platelet count >150 000/µL). Within this group, 11/75 (15%) had any grade of varices and only 1/75 (1%) had VNT. The BAVElastPQ criteria gave sensitivity of 0.95, specificity of 0.42, positive predictive value of 0.15 and negative predictive value of 0.99. CONCLUSIONS: The BAVElastPQ criteria correctly identified 99% of patients without VNT. By applying such criteria, we could have potentially avoided 38% of surveillance endoscopies in our cohort.

Prevalence of Obsessive-Compulsive Symptoms in Elderly Parkinson Disease Patients: A Case-Control Study.

BACKGROUND: The clinical picture of obsessive-compulsive disorder encompasses a broad range of symptoms that are related to multiple psychological domains, including perception, cognition, emotion, and social relatedness. As obsessive-compulsive symptoms (OCS) frequently have an early onset, there are limited data about OCS in older populations (≥65 years) and, in particular, in elderly subjects with Parkinson disease (PD). OBJECTIVE: This study aimed to estimate the prevalence of OCS using a self-report measure (Obsessive-Compulsive Inventory-Revised) and to identify associated sociodemographic and clinical factors in a sample of elderly PD patients compared to a comparison group of similarly aged healthy volunteers. RESULTS: The mean age was 74 ± 6 years in the PD patients and 73 ± 7 years in the comparison group. The mean disease duration was 9.6 ± 5.8 years. Among the PD patients, 30.7% reported at least one OCS or a related disorder compared to 21.1% in the comparison group. Hoarding was significantly more common in PD patients than in the comparison group. CONCLUSIONS: Subclinical OCS were present at a high percentage in both PD patients and comparison group. The OCS phenotype in PD may present differently, as hoarding was more common in PD patients.

Contrast-Enhanced Ultrasound in the Short-Term Evaluation of Hepatocellular Carcinoma after Locoregional Treatment.

BACKGROUND: Contrast-enhanced ultrasound (CEUS) with second-generation contrast agents performed 1 month after hepatocellular carcinoma (HCC) treatment is almost as sensitive as contrast-enhanced computed tomography (CECT) in depicting the residual tumor. However, the efficacy of CEUS performed early after the procedure is still debated. AIM: We evaluated the diagnostic accuracy (DA) of CEUS for the assessment of tumor response shortly after locoregional therapy in patients with unresectable HCC. METHODS: Ninety-four patients with 104 HCC lesions who were scheduled to receive percutaneous ethanol injection, radiofrequency ablation, transcatheter arterial chemoembolization, or combined treatment were enrolled in this study. With CECT at 1-month as the reference standard, the DA of CEUS performed 48-h after the procedure was evaluated. Patients were followed-up to look for tumor or disease progression. RESULTS: Based on CECT findings, 43/104 lesions were diagnosed as having residual viability after 1 month. CEUS performed 48 h after treatment detected residual tumor in 34/43 nodules with treatment failure at CECT with a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 79.1, 96.7, 94.4, 86.8, and 89%, respectively. There was a high degree of concordance between CEUS and CECT (kappa coefficient = 0.78). A hyperemic halo was detectable in 35 lesions without a statistically significant difference between concordant and discordant cases. In patients with uninodular disease responders according to 48 h CEUS had a significantly longer mean overall survival and time to progression compared to nonresponders. CONCLUSION: CEUS performed 48 h after treatment can be considered a reliable modality for the evaluation of the real extent of necrosis and has prognostic value in the assessment of HCC.

Safinamide as an adjunct therapy in older patients with Parkinson's disease: a retrospective study.

BACKGROUND: Safinamide, as a levodopa adjunct, is effective in reducing motor fluctuations in Parkinson's disease (PD) patients; however, scarce evidence is available regarding its use in older PD patients. AIM: To evaluate the safety and tolerability of safinamide as an adjunct therapy in patients aged ≥ 60 years with advanced PD. METHODS: A retrospective study including 203 PD patients admitted to a geriatric day hospital, who were evaluated following an extensive clinical protocol. Safinamide use was categorized as never used, ongoing, and withdrawn. Potential correlations of Safinamide withdrawal were investigated in stepwise backward logistic regression models. RESULTS: A total of 44 out of 203 participants were current or former users of Safinamide. Overall, 14 (32%) patients discontinued due to treatment-emergent adverse events (TEAEs). Withdrawal was not associated with older age. CONCLUSIONS: Safinamide as an adjunct therapy in patients aged ≥ 60 years with advanced PD was found to be safe and well-tolerated in older patients. There were no specific demographic or clinical characteristics associated with suspension.

Comorbidities rather than age affect medium-term outcome in octogenarian patients after total knee arthroplasty.

PURPOSE: As the population ages, it is important to determine whether total knee arthroplasties (TKA)s are safe and beneficial in the octogenarian population. The aims of the present study were: (1) to assess the effect of comorbidities and age on the incidence of postoperative complications following TKA and (2) to evaluate the mid-term outcome of octogenarian patients. METHODS: A retrospective matched-paired analysis by gender, BMI and duration of follow-up was conducted on 206 patients older than 80 years and younger than 75 years between 2009 and 2016, undergoing primary TKA. The mean follow-up was 5 years. Outcome measures including Oxford Knee Score (OKS), Knee Society Score (KSS), Knee Society Function Score (KSFS), postoperative complications, length of stay (LOS) and survivorship were analysed. The association between complications and comorbidities was assessed using multivariable logistic regression after adjusting for age, Deyo-Charlson Comorbidity Index (D-CCI) and the American Society of Anesthesiologist's (ASA) physical status classification. RESULTS: In the multivariable models, D-CCI class is an independent predictor for postoperative cardiac complications, delirium and transfusion rate (OR ranging from 1.2 to 69.5 in respect to D-CCI reference class 0). Being ≥ 80 years old was associated with an increased risk of transfusion (OR 3.4; 95% CI 1.7-6.8) and 1.7-day increase in LOS (p < 0.001). Both groups showed significant improvement in postoperative knee scores following TKA. CONCLUSION: Octogenarians experienced good clinical results when compared to their younger counterparts. Comorbidities, rather than age itself, are responsible for the increase in postoperative morbidity. Preoperative risk assessment has to be optimized in order to reduce complications.

Reward (BIS/BAS) mechanisms and fatigue in patients on chronic hemodialysis.

Recently, it has been demonstrated that chronic inflammation could have a role on fatigue onset in chronic hemodialysis (HD). Research on neuro-immune interactions highlighted that an alteration of basal ganglia functioning, secondary to chronic inflammation, may translate in a reduced motivation and altered reward processes in chronic diseases. This study investigated a possible correlation between fatigue severity and reward mechanisms, that regulate motivational dispositions, in HD patients. Evaluation scales were administered to ninety-four patients on HD (54 Male, 40 Female; Mdage = 67±26.5; Dialytic Mdage in years = 4±6.3. Fatigue was assessed by using Fatigue Severity Scale (FSS). Behavioural Inhibition System (BIS) and Behavioural Activation System (BAS) Scale was administered to investigate approach/avoidance behaviours. Anxiety and depression were measured by State-Trait Anxiety Inventory (STAI-Y) and Beck Depression Inventory (BDI-II). Results show that the distribution of HD patients for FSS score did not show a normal pattern. FSS score was significantly higher in patients with high BIS Z-score than in patients with low and medium BIS Z-score. BDI score and STAI-Y scores were similar among BIS Z-score groups of patients. Findings suggest that in patients on chronic hemodialysis there is a correlation between fatigue severity symptoms and motivational disposition mechanisms that predispose to action inhibition.

Stress-related vulnerability and usefulness of healthcare education in Parkinson's disease: The perception of a group of family caregivers, a cross-sectional study.

Parkinson's Disease is associated with a high assistive complexity, thus generating in caregivers a burden proportional to the intensity of the care provided. This study aims to evaluate whether the stress-related level of caregivers is related to their perception of the need for healthcare education. A cross-sectional study was conducted on 69 family caregivers that completed the Stress-related Vulnerability Scale (SVS scale) with a tool of proposed interventions stratified according to caregivers' need as "nothing", "somewhat", "moderately" and "extremely". A direct association between the SVS scale and the perception of the usefulness of interventions was detected, and significant differences were observed for "Caregivers tele-support group" and "Peer-led support group" interventions, thus suggesting an important role for caregivers' emotional status in considering of training courses. Caregivers are split between low vulnerability, with minimal perception of training need, and high burden state with the acute necessity of support to manage patients.

Recovery Time after Hemodialysis Is Inversely Associated with the Ultrafiltration Rate.

INTRODUCTION: The present study aimed to determine the variables that are associated with a longer dialysis recovery time (DRT) and to define the relationship that exists between DRT and the ultrafiltration rate (UFR) in prevalent chronic hemodialysis (CHD) patients. METHODS: We studied 210 prevalent CHD of 5 hemodialysis units in Central Italy. Patients were invited to answer to the question: "How long does it take you to recover from a dialysis session?" Answers to this question were subsequently converted into minutes. Demographic, clinical and laboratory parameters were recorded for each patient as well as the UFR (mL/kg/h), the dialysate sodium concentration and temperature. RESULTS: Median DRT was 180 min (60-420). Ninety five (45%) patients had a DRT ≥ the median value. Mean UFR was 9.2 ± 3.0 mL/kg/h. Patients with a lower DRT had a less prevalent disability in the instrumental activities daily living, had a higher UFR, and a lower dialysate temperature, as compared with subjects with higher DRT. According to the logistic regression model, UFR was associated with a DRT below the median (i.e., 180) in the unadjusted model (OR 1.12; 95% CI 1.02-1.23; p = 0.019), after adjusting for age and sex (OR 1.11; 95% CI 1.01-1.22; p = 0.025), and in the fully adjusted model (OR 1.11; 95% CI 1.04-1.22; p = 0.040). UFR increase was associated with increasing probability of DRT below the median (p for trend = 0.035). The highest tertile of DRT was associated with UFR below the mean value (i.e., 9.2 mL/kg/h) in multinomial logistic regression having the lowest DRT tertile as reference. DRT was significantly lower in patients with UFR > 13 mL/kg/h than in patients with UFR 10-13 or < 10 mL/kg/h. CONCLUSION: DRT is inversely associated with UFR in CHD patients. Whether a high UFR should be recommended to reduce the DRT needs to be elucidated through an adequate prospective randomized study.

Low-molecular weight compounds in human seminal plasma as potential biomarkers of male infertility.

STUDY QUESTION: Is the determination of antioxidants, oxidative/nitrosative stress-related compounds, purines, pyrimidines and energy-related metabolites in human seminal plasma of utility to evidence biomarkers related to male infertility? SUMMARY ANSWER: The determination of 26 metabolites in seminal plasma allowed to evidence that 21/26 of them are biomarkers of male infertility, as well as to calculate a cumulative index, named Biomarker Score, that fully discriminates fertile controls from infertile patients and partially differentiates infertile without from infertile with spermiogram anomalies. WHAT IS KNOWN ALREADY: Epidemiological studies indicated that a male factor is involved in ~50% of cases of pregnancy failure, with a significant percentage of infertile males having no alterations in the spermiogram. Further laboratory analyses of male infertility are mainly dedicated only to gross evaluations of oxidative stress or total antioxidant capacity. STUDY DESIGN, SIZE, DURATION: Seminal plasma of 48 fertile controls and 96 infertile patients (master group), were collected from September 2016 to February 2018. A second group of 44 infertile patients (validation group) was recruited in a second, independent centre from September 2017 to March 2018. Samples were analysed in blind using a 'Redox Energy Test' to determine various low-molecular weight compounds, with the aim of finding metabolic profiles and biomarkers related to male infertility. PARTICIPANTS/MATERIALS, SETTING, METHODS: In all seminal plasma, 26 water- and fat-soluble compounds (related to antioxidant defences, oxidative/nitrosative stress, purine, pyrimidine and energy metabolism) were analysed using high-performance liquid chromatographic methods. According to spermiogram, infertile patients of both groups were also categorized into normozoospermic (N, no anomalies in the spermiogram), or into the subgroup including all patients with anomalies in the spermiogram (asthenoteratooligozoospermic ATO + asthenozoospermic A + teratozoospermic T + oligozoospermic O). MAIN RESULTS AND THE ROLE OF CHANCE: In the master group, results indicated that 21/26 compounds assayed in seminal plasma of infertile males were significantly different from corresponding values determined in fertile controls. These 21 compounds constituted the male infertility biomarkers. Similar results were recorded in patients of the validation group. Using an index cumulating the biochemical seminal plasma anomalies (Biomarker Score), we found that fertile controls had mean Biomarker Score values of 2.01 ± 1.42, whilst infertile patients of the master and of the validation group had mean values of 12.27 ± 3.15 and of 11.41 ± 4.09, respectively (P < 0.001 compared to controls). The lack of statistical differences between the master and the validation groups, in both the metabolic profiles and the Biomarker Score values, allowed to pool patients into a single cohort of infertile males. The Biomarker Score values showed that fertile controls and infertile males clustered into two distinct groups. Infertile patients without (N, n = 42) or with (ATO + A + T + O, n = 98) spermiogram anomalies differed in some biomarkers (ascorbic acid, all-trans retinol, α-tocopherol, cytidine, uridine, guanine). These differences were reinforced by distribution frequencies and posterior probability curves of the Biomarker Score in the three groups. LIMITATIONS, REASONS FOR CAUTION: Results were obtained in relatively limited number of human seminal plasma samples. Using the 'Redox Energy Test' it was possible to associate specific metabolic profiles and values of the Biomarker Score to fertile controls or infertile males. However, it was not possible to evaluate whether the different anomalies of the spermiogram are associated with specific metabolic profiles and values of the Biomarker Score. WIDER IMPLICATIONS OF THE FINDINGS: The 'Redox Energy Test', coupled with the Biomarker Score that cumulates the biochemical characteristics of seminal plasma into a single index, evidenced a set of low-molecular weight biomarkers potentially useful in the laboratory management of male infertility. STUDY FUNDING/COMPETING INTEREST(S): The study was partly funded with research grants from the University of Catania. None of the authors have any conflicting interests to declare.

Prevalence and associated variables of post-dialysis fatigue: Results of a prospective multicentre study.

AIM: The study aims to determine prevalence and severity of PDF and to define its associated variables. METHODS: In five haemodialysis units of northern-centre Italy, patients were regarded to suffer from PDF if they spontaneously offered this complaint when asked the open-ended question: Do you feel better or worse after dialysis? If worse, please specify in which way. A complaint of fatigue would be probed further with questions directed at its duration, frequency and intensity, allowing creation of a fatigue index of severity (one third of the sum of these three parameters, each rated from 1 to 5). Patients were stratified into three groups according the severity of PDF: 1) score = 0; 2) score = 1-3; 3) score > 3. RESULTS: We studied 271 patients: 164 had PDF and 107 did not. PDF patients had significantly longer time of recovery after dialysis (TIRD). TIRD was significantly associated with PDF duration, intensity, and frequency. Patients with PDF were older and had a lower ADL score. At multivariate analysis, PDF was significantly associated with TIRD. In a multivariate model that did not include TIRD, PDF was independently associated with age and ADL. Sixty patients had moderate PDF and 104 had severe PDF. In patients with severe PDF, age and dialytic age were higher, ADL and IADL scores were lower, TIRD was longer and the ultrafiltration rate was lower. At multivariate analysis, PDF severity was independently associated with TIRD. In the model without TIRD, PDF severity was associated with ADL only. CONCLUSION: Post-dialysis fatigue is frequent and associated with age and ADL. Dialytic variables seem unrelated to PDF.

The effects of a multidisciplinary education course on the burden, health literacy and needs of family caregivers.

Chronic diseases are mostly managed by family caregivers that often face the "caregiver burden". This study aimed to understand whether a multidisciplinary theoretical-practical training course could influence the burden, health literacy and needs of caregivers. Seventy-six familial caregivers were asked to complete the Caregiver Burden Inventory-CBI, Caregiver Needs Assessment-CNA, and Health Literacy Questionnaire-HLQ, before and after the course. A significant decrease in CBI and an increase of CNA were observed. However, a significantly higher rate of CBI decrease and a lower increase of CNA were detected in the neurological compared to the oncological group (p = 0.001). Moreover, the ability of the participants to look for and find health information significantly improved. The course contrasted caregivers' burden, increased their search for health information, and revealed their requiring of training and emotional and social support. Caregiver education plays a pivotal role in the management of chronic patients, enhancing the quality of life of both patients and caregivers.

Liver Stiffness in Pediatric Patients with Fatty Liver Disease: Diagnostic Accuracy and Reproducibility of Shear-Wave Elastography.

Purpose To evaluate the diagnostic accuracy of shear-wave elastography (SWE) in identifying different degrees of fibrosis in a cohort of consecutive children and adolescents with nonalcoholic steatohepatitis (NASH). Materials and Methods Consecutive pediatric patients scheduled to undergo liver biopsy were studied with an ultrasonography-based SWE system. Elastography was performed in 68 of 69 patients with biopsy-proved NASH (37 boys and 31 girls; mean age, 12.6 years ± 2.48; age range, 8-17 years). The correlations among laboratory findings, liver stiffness, and fibrosis score were analyzed, and the area under the receiver operating characteristic curve (AUC) was used to assess the presence of any fibrosis (score ≥F1) or significant fibrosis (score ≥F2). Findings from histologic examination were used as the standard of reference. Results SWE showed a very high correlation with liver fibrosis (P < .001) at univariate and multivariate analyses. The AUCs for the association of any and significant fibrosis were 0.92 (95% confidence interval [CI]: 0.86, 0.98) and 0.97 (95% CI: 0.95, 0.99), respectively. The intraclass correlation coefficient for absolute agreement was 0.95 (95% CI: 0.90, 0.97). Conclusion SWE is an accurate and reproducible noninvasive technique that efficiently depicts the presence of significant liver fibrosis and, less accurately, mild liver fibrosis in pediatric patients with nonalcoholic fatty liver disease. Larger clinical prospective studies are warranted to confirm SWE accuracy and establish threshold values for fibrosis grading in comparison or in combination with other noninvasive methods. © RSNA, 2016.

Autoantibodies to post-translationally modified type I and II collagen in Charcot neuroarthropathy in subjects with type 2 diabetes mellitus.

AIMS: Charcot neuroarthropathy (CN) is a disabling complication, culminating in bone destruction and involving joints and articular cartilage with high inflammatory environment. Its real pathogenesis is as yet unknown. In autoinflammatory diseases, such as rheumatoid arthritis, characterized by inflammation and joint involvement, autoantibodies against oxidative post-translationally modified (oxPTM) collagen type I (CI) and type II (CII) were detected. Therefore, the aim of our study was to assess the potential involvement of autoimmunity in charcot neuroarthropathy, investigating the presence of autoantibodies oxPTM-CI and oxPTM-CII, in participants with charcot neuroarthropathy. METHODS: In this case-control study, we enrolled 124 participants with type 2 diabetes mellitus (47 with charcot neuroarthropathy, 37 with diabetic peripheral neuropathy without charcot neuroarthropathy, and 40 with uncomplicated diabetes), and 32 healthy controls. The CI and CII were modified with ribose and other oxidant species, and the modifications were evaluated with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Binding of sera from the participants was analyzed with enzyme-linked immunosorbent assay. RESULTS: Age, body mass index, waist and hip circumferences, and lipid profile were similar across the 4 groups, as well as glycated hemoglobin and duration of diabetes among people with diabetes. An increased binding to both native and all oxidation-modified forms of CII was found in participants with CN and diabetic neuropathy. Conversely, for CI, an aspecific increased reactivity was noted. CONCLUSIONS: Our results detected the presence of autoantibodies against oxidative post-translational modified collagen, particularly type 2 collagen, in participants with charcot neuroarthropathy and diabetic neuropathy, suggesting the possible involvement of autoimmunity. Further studies are required to understand the role of autoimmunity in the pathogenesis of charcot neuroarthropathy.