Prognostic value of liver stiffness in patients hospitalized for acute decompensated heart failure: a meta-analysis.

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.

Interdialytic weight gain and low dialysate sodium concentration in patients on chronic hemodialysis: a systematic review and meta-analysis.

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.

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.

Perioperative Factors Associated With Postoperative Delirium in Patients Undergoing Noncardiac Surgery: An Individual Patient Data Meta-Analysis.

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.

Predisposition to eating disorders in adults with type 1 diabetes: Comparison between multiple daily injections and continuous subcutaneous insulin infusion.

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.

Geriatric Depression Scale predicts mortality in elderly patients on chronic hemodialysis.

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 χ2 : 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.

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.

Pravastatin for severe preeclampsia with growth restriction: Placental findings and infant follow-up.

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.

Sleep in Residents: A Comparison between Anesthesiology and Occupational Medicine Interns.

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.

Interdialytic weight gain is not associated with symptoms of depression or apathy in patients on chronic hemodialysis.

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.

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.

Post-dialysis fatigue: Comparison of bicarbonate hemodialysis and online hemodiafiltration.

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.

Post-dialysis fatigue and serum S100B protein in patients on chronic hemodialysis. A pilot study.

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-1ß, 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.

Efficacy and safety of long-term botulinum toxin treatment for acquired cervical dystonia: a 25-year follow-up.

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.

Cytotoxic Evaluation of the New Composite Resin through an Artificial Pulp Chamber.

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.

Sensing red blood cell nano-mechanics: Toward a novel blood biomarker for Alzheimer's disease.

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.

BRCA Mutation Status in Triple-Negative Breast Cancer Patients Treated with Neoadjuvant Chemotherapy: A Pivotal Role for Treatment Decision-Making.

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.

Interdialytic weight gain and educational/cognitive, counseling/behavioral and psychological/affective interventions in patients on chronic hemodialysis: a systematic review and meta-analysis.

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.

Biochemical Discrimination of the Down Syndrome-Related Metabolic and Oxidative/Nitrosative Stress Alterations from the Physiologic Age-Related Changes through the Targeted Metabolomic Analysis of Serum.

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.