Red blood cells membrane micropolarity as a novel diagnostic indicator of type 1 and type 2 diabetes

Classification of the category of diabetes is extremely important for clinicians to diagnose and select the correct treatment plan. Glycosylation, oxidation and other post-translational modifications of membrane and transmembrane proteins, as well as impairment in cholesterol homeostasis, can alter lipid density, packing, and interactions of Red blood cells (RBC) plasma membranes in type 1 and type 2 diabetes, thus varying their membrane micropolarity. This can be estimated, at a submicrometric scale, by determining the membrane relative permittivity, which is the factor by which the electric field between the charges is decreased relative to vacuum. Here, we employed a membrane micropolarity sensitive probe to monitor variations in red blood cells of healthy subjects (n=16) and patients affected by type 1 (T1DM, n=10) and type 2 diabetes mellitus (T2DM, n=24) to provide a cost-effective and supplementary indicator for diabetes classification. We find a less polar membrane microenvironment in T2DM patients, and a more polar membrane microenvironment in T1DM patients compared to control healthy patients. The differences in micropolarity are statistically significant among the three groups (p<0.01). The role of serum cholesterol pool in determining these differences was investigated, and other factors potentially altering the response of the probe were considered in view of developing a clinical assay based on RBC membrane micropolarity. These preliminary data pave the way for the development of an innovative assay which could become a tool for diagnosis and progression monitoring of type 1 and type 2 diabetes. Keywords: Diabetes mellitus, Membrane micropolarity, Red blood cells, Fluorescence lifetime microscopy, Metabolic imaging, Personalized medicin

Functional impairment is associated with an increased risk of mortality in patients on chronic hemodialysis

Background: Functional impairment is associated with adverse outcomes in older people, as well as in patients on chronic hemodialysis. The aim of the present study was to determine the characteristics associated with functional impairment in chronic hemodialysis, and to evaluate if functional impairment represents a risk factor for reduced survival in chronic hemodialysis. Methods: All 132 chronic hemodialysis referring to the Hemodialysis Service of the Catholic University, Rome, Italy between November 2007 and May 2015 were included. All patients underwent comprehensive geriatric assessment; functional ability was estimated using two questionnaires exploring independency in bathing, dressing, toileting, transferring, continence, feeding (ADLs), and independency in using the telephone, shopping, food preparation, housekeeping, laundering, traveling, taking medications, and handling finances (IADLs). Functional impairment was diagnosed in presence of dependence in one or more ADLs/IADLs. Mood was assessed using the 30-item Geriatric Depression Scale. Logistic regression was used to evaluate factors associated with functional impairment. The association between functional impairment and survival was assessed by Cox regression. Results: ADLs impairment was present in 34 (26 %) participants, while IADLs impairment was detected in 64 (48 %) subjects. After a follow up of 90 months, 55 (42 %) patients died. In logistic regression, depressive symptoms were associated with ADLs and IADLs impairment (OR 1.12; 95 % CI = 1.02-1.23; OR 1.16; 95 % CI = 1.02-1.33; respectively). In Cox regression, ADLs impairment was associated with mortality (HR 2.47; 95 % CI-1.07-5.67) while IADLs impairment was not associated with reduced survival (HR .80; 95 % CI-.36-1.76). Conclusions: Functional impairment is associated with depressive symptoms; also, impairment in the ADLs represents a risk factor of reduced survival in chronic hemodialysis. These associations and their potential implication should be assessed in dedicated studies

Outcomes and Risk Factors for Complications of Laser Ablation for Thyroid Nodules: A Multicenter Study on 1531 Patients

Image-guided laser ablation therapy (LAT) of benign thyroid nodules demonstrated favorable results in randomized trials with fixed modalities of treatment. The aim of this retrospective multicenter study was to assess the effectiveness, tolerability, and complications of LAT in a large consecutive series of patients from centers using this technique in their routine clinical activity

Subclinical atherosclerosis is linked to small intestinal bacterial overgrowth via vitamin K2-dependent mechanisms

Aim To assess the rate of matrix Gla-protein carboxylation in patients with small intestinal bacterial overgrowth (SIBO) and to decipher its association with subclinical atherosclerosis. METHODS Patients with suspected SIBO who presented with a low risk for cardiovascular disease and showed no evidence of atherosclerotic plaques were included in the study. A glucose breath test was performed in order to confirm the diagnosis of SIBO and vascular assessment was carried out by ultrasound examination. Plasma levels of the inactive form of MGP (dephosphorylateduncarboxylated matrix Gla-protein) were quantified by ELISA and vitamin K2 intake was estimated using a food frequency questionnaire. RESULTS Thirty-nine patients were included in the study. SIBO was confirmed in 12/39 (30.8%) patients who also presented with a higher concentration of dephosphorylated-uncarboxylated matrix Gla-protein (9.5 \u3bc g/L vs 4.2 \u3bc g/L; P = 0.004). Arterial stiffness was elevated in the SIBO group (pulse-wave velocity 10.25 m/s vs 7.68 m/s; P = 0.002) and this phenomenon was observed to correlate linearly with the levels of dephosphorylated-uncarboxylated matrix Gla-protein ( f = 0.220, R 2 = 0.366, P = 0.03). Carotid intima-media thickness and arterial calcifications were not observed to be significantly elevated as compared to controls. CONCLUSION SIBO is associated with reduced matrix Gla-protein activation as well as arterial stiffening. Both these observations are regarded as important indicators of subclinical atherosclerosis. Hence, screening for SIBO, intestinal decontamination and supplementation with vitamin K2 has the potential to be incorporated into clinical practice as additional preventive measures

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

Simple Summary In this retrospective observational study, we evaluated data from patients with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NACT) in order to better define the impact of germline BRCA1/2 (gBRCA1/2) mutation status on outcomes in this patient population. Our results show that patients with BRCA1/2 mutation had a higher pathologic complete response (pCR) rate than non-mutated patients; nevertheless, the benefit was confirmed only in the subset of patients who received a platinum-based NACT. Furthermore, pCR was associated with improved Event Free Survival (EFS) and Overall Survival (OS), regardless of BRCA1/2 mutation status and type of NACT received. Long-term follow-up analyses are needed to further define the impact of gBRCA mutation status in patients with early-TNBC. 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

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 &gt;85 years, 6.24; 95% CI, 4.65-8.37), low body mass index (OR for body mass index &lt;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 &gt;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.</p

Biodiversity’s contributions to sustainable development

International concern to develop sustainably challenges us to act upon the inherent links between 23 our economy, society and environment, and is leading to increasing acknowledgement of 24 biodiversity’s importance. This Review discusses the breadth of ways in which biodiversity can 25 support sustainable development. It uses the Sustainable Development Goals (SDGs) as a basis for 26 exploring scientific evidence of the benefits delivered by biodiversity. It focuses on papers that 27 provide examples of how biodiversity components (i.e. ecosystems, species and genes) directly 28 deliver benefits that may contribute to the achievement of individual SDGs. It also considers how 29 biodiversity’s direct contributions to fulfilling some SDGs may indirectly support the achievement of 30 other SDGs to which biodiversity does not contribute directly. How the attributes (e.g. diversity, 31 abundance or composition) of biodiversity components influence the benefits delivered is also 32 presented, where described by the papers reviewed. While acknowledging potential negative 33 impacts and trade-offs between different benefits, the study concludes that biodiversity may 34 contribute to fulfilment of all SDGs

Steroid and cyclosporine therapy in idiopathic membranous nephropathy. monocentric experience and literature review

Immunosuppressive treatment of patients with idiopathic membranous nephropathy (IMN) is debated due to its possible side effects. The 2012 KDIGO guidelines suggest alkylating agents as first choice therapy. The aim of the study is to retrospectively evaluate the induction and maintenance of clinical remission in patients with histological diagnosis of IMN undergoing steroid and/or cyclosporine therapy at the Nephrology Unit of the Sant'Andrea Hospital in Rome

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 &lt; 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