Healthy Matched Subjects Research Articles

Red blood cell distribution width: a promising index for estimating disease activity of Systemic lupus erythematosus

Background: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease and is associated with considerable morbidity. Elevation in red cell distribution width (RDW), a simple routinely done investigation, could be a prognostic marker in SLE patients. Objective: To assess red blood cell distribution width for estimating disease activity in patients with SLE. Methods: This cross-sectional study was conducted in the Department of Physiology, Dhaka Medical College, Dhaka from July 2016 to June 2017. For this study, 30 SLE patients, aged 18 to 55 years, were considered as the study group and 30 aged matched healthy subjects were considered as control group. SLE Disease Activity Index (SLEDAI) score was used to assess disease activity. RDW and ESR were also estimated. Independent samples t-test, Chi Square test, Pearson’s correlation co-efficient (r) test, Regression analysis, Diagnostic accuracy test and ROC curve analysis were performed as applicable.. Results: In this study, RDW and ESR was significantly (p=0.000) higher in SLE patients in comparison to that of control. A significant association was observed among RDW, ESR and active disease (OR; 5.33, 95% CI; 0.78 to 36.33 and OR; 5.66, 95% CI; 0.75 to 42.36, p=0.001). RDW was positively correlated with SLEDAI score and ESR in patients with SLE. It was 84.2% sensitive and 72.7% specific for diagnosing active disease. Conclusion: This study concludes that RDW is increased in SLE patients and can be served as a useful index to estimate the disease activity. J Bngladesh Soc Physiol 2021;16(1): 95-103

Noninvasive biomarkers of non-alcoholic fatty liver disease in patients with metabolic syndrome: insights from the RESOLVE Study.

The aim of the present study was to evaluate: 1) the presence of liver steatosis using Fatty Liver Index (FLI), Hepatic Steatosis Index (HSI) and Liver Fat Score (LFS) in patients suffering from metabolic syndrome (MS); and 2) the association of FLI, HSI and LFS with the cardiometabolic risks. A total of 91 patients with MS (39 men, 52 women) and 44-age matched healthy subjects (control; 23 men and 21 women) were enrolled in the study. A continuous cardiometabolic score (MetsScore) and the noninvasive tests of hepatic steatosis were calculated for comparison and association analysis. Liver steatosis was detected in 86%, 84% and 80% of people diagnosed with MS using FLI, HSI and LFS respectively and MetsScore increases with FLI severity (P<0.05). Also, FLI and LFS were positively associated with MetsScore (P<0.01 and P<0.05 respectively) but not HSI. Multivariate linear regression models revealed that FLI has a stronger association with MetsScore compared with HSI and LFS (P<0.001). FLI is associated with the severity of MS and represent a good indicator to assess the relation between liver steatosis and a cardiometabolic disorders in clinical routine.

982. Effect of Hepatic Impairment on the Safety and Pharmacokinetics of Rezafungin

BackgroundRezafungin (RZF) is a novel echinocandin antifungal being developed for treatment of candidemia and invasive candidiasis, and for prevention of invasive fungal diseases among immunosuppressed patients. In the Phase 2 and Phase 3 treatment trials of rezafungin compared with caspofungin (STRIVE [NCT02734862] and ReSTORE [NCT03667690], respectively), patients with severe hepatic impairment (HI) were not included due to lack of caspofungin data in this population. Rezafungin was previously evaluated in patients with moderate hepatic impairment. Here we report an open-label, single-dose study on rezafungin in patients with HI (Child-Pugh class C).MethodsTo investigate the safety, tolerability, and pharmacokinetics (PK) of RZF in subjects with HI and healthy subjects (HS), 8 subjects with HI and 8 HS matched for age, sex, and body mass index (BMI) were enrolled and received a single 400-mg intravenous 1-hour infusion of RZF. Plasma PK sampling was performed at various time points through 336 hours postdose. RZF PK parameters were derived using non-compartmental analysis. Safety was assessed throughout the study. ResultsThe majority of the HI subjects were White (87.5%) and male (75%) while equal distribution between White and Black or African American was observed among HS (50%) and 75% were male. The mean age of HI subjects was 58 years (range, 41–68 years) and 56.6 years (range, 50–61 years) for the HS. Mean BMI was 29.7 kg/m2 (range, 24.5–34.3 kg/m2) for HI subjects and 29.7 kg/m2 (range, 25.4–34.2 kg/m2) for the HS. RZF exposure (Cmax and AUC) in subjects with HI was ~30% lower than that in HS (Table 1), while half-life was generally similar (HI: 121 h, HS:124 h; Figure 1). Three HI subjects had one adverse event (AE) each (bronchitis, worsening hepatic encephalopathy, hyponatremia), all moderate in severity; one HS had 1 AE of infusion site infiltration mild in severity. No AEs were considered related to RZF, and all were resolved or resolving by the end of the study.Table 1. Plasma Rezafungin PK Parameter Estimates in Subjects with Severe Hepatic Impairment or Normal Hepatic Function After a Single 400 mg IV Infusion of Rezafungin Figure 1. Mean (+SD) Plasma Rezafungin Concentration-Time Profiles in Subjects with Severe Hepatic Impairment or Normal Hepatic Function After a Single 400-mg IV Infusion of Rezafungin (Semi-Logarithmic Scale)ConclusionRZF was well tolerated in HI subjects and showed modestly reduced exposure that was within the range observed in matched HS. These findings support no RZF dose adjustment in subjects with severe hepatic impairment. Disclosures Voon Ong, PhD, Cidara Therapeutics (Employee, Shareholder) Taylor Sandison, MD, MPH, Cidara Therapeutics (Employee, Shareholder) Rebeca M. Melara, M.S., Altasciences (contract research organization) (Employee) Thomas C. Marbury, MD, Orlando Clinical Research Center (Employee, Other Financial or Material Support, Equity owner of Orlando Clinical Research Center) Alena Jandourek, MD, Cidara therapeutics (Consultant) Shawn Flanagan, PhD, Cidara Therapeutics (Employee, Shareholder)

Atrial function analysis after percutaneous umbrella device and suture-mediated patent fossa ovalis closure.

Atrial fibrillation is an undesirable event following percutaneous patent fossa ovalis (PFO) closure with metallic occluders, suggesting that implanting a rigid closure device could alter atrial function. Suture-mediated PFO closure is a new technique, achieving closure of the PFO by means of a simple suture. Aim of this study was to evaluate left atrial function after closure of PFO by direct suture and traditional occluders. We studied 40 age and sex homogeneous patients, 20 undergoing PFO closure by device (OCL) and 20 by suturing (NS). Twenty healthy sex-age matched subjects made up the control group (CT). Left atrial function was evaluated by using volumetric and speckle-tracking analysis assessing the following parameters: total emptying fraction (EF), Expansion Index (EI), active emptying fraction (AEF), strain values of the reservoir (r-ED), conduit (cd-ED) and contraction phase (ct-ED). Compared to CT and NS, OCL patients had significantly worst indices of left atrial reservoir function (EF P=0.001, EI P=0.003, r-ED P<0.001), conduit function (cd-ED P=0.018) and contraction function (AEF P=0.010; ct-ED P<0.001). No significant differences were observed in left atrial function indices between CT and NS patients. Suture-mediated PFO closure does not alter left atrial function. Conversely, metallic occluder is associated with worse left atrium function. This detrimental effect on atrial function could favor the development of atrial arrhythmias.

Prevalence, Prognosis, and Outcome in Egyptian Children with Primary Immune Thrombocytopenia: A Single-Center Experience

Background: Idiopathic (immune) thrombocytopenic purpura (ITP) is a heterogeneous clinical disorder characterized by immune-mediated platelet destruction. ITP is usually a benign, self-limiting disease in children. Objective: To assess prevalence, prognosis, and outcome of Egyptian children with primary immune thrombocytopenia. Patients and Methods: This cross-sectional study was carried on 80 children (1-13 years) with primary ITP who presented to the Pediatric Hematology Unit and outpatient clinic of Zagazig University Hospitals, during the period from April 2020 to June 2021. Patients were divided into two groups; Group (1): included 20 healthy matched subjects (control), Group (2): included 60 patients with primary ITP. The group was subdivided into 3 subgroups, Subgroup (2A) included 20 patients with newly diagnosed ITP, Subgroup (2B) included 20 patients with persistent ITP, and Subgroup (2C) included 20 patients with chronic ITP. Results: There were significant differences between the studied groups in age, sex, and weight. There was a statistically significant association between prognosis and general characteristics of the studied ITP patients. Conclusion: primary ITP in children is a nonthreatening and self-limited disease, usually lasting less than one year, and chronic form has different prognostic parameters. The use of these parameters can early distinguish children who are expected to have short and uneventful disease duration, to minimize their exposure to pharmaceutical intervention.

Vitamin D Receptor Gene Polymorphisms and Risk of Knee Osteoarthritis: Possible Correlations with TNF-α, Macrophage Migration Inhibitory Factor, and 25-Hydroxycholecalciferol Status.

Osteoarthritis (OA) etiology and pathogenesis not yet fully understood. We studied the role of vitamin D receptor single-nucleotide polymorphisms (VDR-SNPs), vitamin D3, serum and synovial macrophage migration inhibitory factor (MIF), and tumor necrosis factor-α (TNF-α) in the development and progression of knee OA (KOA). This study included 205 Egyptian subjects (105 patients with KOA and 100 unrelated, healthy matched subjects selected as controls). The patient group was divided into three groups according to KOA severity (mild, moderate, and severe), with 35 patients in each group. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used for the ApaI and TaqI SNPs. Vitamin D, serum and synovial TNF-α, and MIF assays were performed using ELISA kits. There were significantly lower serum levels of 25-hydroxycholecalciferol with significant increasing TNF-α and MIF levels in relation to disease severity among the cases (all: p˂0.05).Wild homozygous and heterozygous mutant genotypes (GG+GT) and G allele of ApaI demonstrated risk for KOA development, with odds ratio OR = 6.313 (95% confidence interval (CI) 2.074-19.210) and OR = 1.532 (95%CI 1.013-2.317), respectively. Homozygous mutant CC genotype and C allele of TaqI could be considered a risk factor associated with KOA development, with OR = 2.667 (95%CI 1.270-5.601) and OR = 0.737 (95%CI 0.496-1.095), respectively. VDR-SNPs, vitamin D3, TNF-α, and MIF could play an essential role in the pathogenesis and progression of KOA with mechanistic associations.

Wall shear stress angle determines aortic growth in patients with bicuspid aortic valves

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The Dutch Heart Foundation Background Patients with bicuspid aortic valve (BAV) have altered flow velocity patterns with different wall shear stress (WSS) distributions in the ascending aorta compared to patients with tricuspid aortic valves. These WSS distributions are associated with aortic dilatation in cross sectional studies, however, longitudinal data demonstrating a potential causative role is missing. Purpose The aim of this study was to assess the differences in WSS distributions between BAV patients and healthy subjects and to determine the predictive value of WSS for aortic growth in patients with a BAV. Methods Forty patients with a BAV and 32 healthy matched subjects were prospectively studied by 4D-flow cardiovascular magnetic resonance (CMR). Peak velocity, pulse wave velocity, aortic distensibility, peak systolic WSS (magnitude), the different WSS components (axial and circumferential), and WSS angle were assessed in the proximal ascending aorta. WSS angle was defined as the angle between the WSSmagnitude and WSSaxial component. In the BAV patients, aortic volumetric growth over three years was determined in the proximal ascending aorta (first 5cm) based on CT angiography. Multivariate linear regression analysis was used to identify independent predictors of aortic volumetric growth. Results Of the BAV patients, 21 (53%) had a left-right fusion pattern and eight patients had Turner syndrome. WSSaxial was significantly lower in BAV patients compared to healthy subjects (p = 0.008) and WSScircumferential and WSS angle were significantly higher (both p &amp;lt; 0.001, see Figure). WSSmagnitude, pulse wave velocity, and aorta distensibility were not statistically significant different. WSSmagnitude (0.69 N/m² [0.51-0.81] vs 1.08 N/m² [0.89-1.24], p = 0.005), WSSaxial (0.50 N/m² [0.39-0.61] vs 0.72 N/m² [0.54-0.94], p = 0.015) and WSScircumferential (0.34 N/m² [0.32-0.46] vs 0.64 N/m² [0.47-0.81], p = 0.008) were significantly lower in BAV Turner patients compared to BAV non-Turner patients, while WSS angle (40° [34-41] vs 40° [32-48], p = 0.607) was not statistically significant different. During a follow-up of three years, there was a significant growth of the proximal ascending aorta in the BAV patients (1.2 cm3 [-0.2-2.5], p = 0.001). In multivariate analysis corrected for baseline aortic volume and diastolic blood pressure, WSS angle was the only independent predictor for proximal aortic volume growth (β=0.108, p = 0.030). Conclusions Increased WSScircumferential and especially WSS angle are present in patients with BAV. WSS angle was the only independent predictor of aortic growth. These findings highlight the potential role of WSS measurements in patients with BAV to stratify patients at risk for aortic dilation.

FcγRIIa and FcγRIIIa genes polymorphism in Egyptian children with primary immune thrombocytopenia

IntroductionPhagocytosis of autoantibody-sensitized coated platelets through Fc gamma receptors on phagocytic cells is an important mechanism of thrombocytopenia in primary immune thrombocytopenia (ITP). ObjectiveWe aimed to investigate the contribution of the FcγRIIa and FcγRIIIa genes polymorphism to the risk of ITP and their association with disease characteristics in Egyptian children. MethodsA case control study was conducted on eighty children with primary ITP and eighty age and sex healthy matched subjects as a control group. The FcγRIIa and FcγRIIIa genes polymorphism was detected using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). ResultsWe found that the FcγRIIa‐131H and ‐131R allele frequencies were 51.3 % and 48.7%, respectively, in children with ITP, versus 75% and 25%, respectively, in controls (p = 0.002). The compound heterozygous HR genotype was significantly higher in ITP patients (p < 0.05). The FcγRIIIa-158F and ‐158V allele frequencies were 46.3% and 53.7%, respectively, in children with ITP, versus 70% and 30%, respectively, in controls (p = 0.002). The compound heterozygous VF genotype was significantly higher in ITP patients (p < 0.05). The combined HR/FV genotype was 47.5% in ITP patients, versus 10% in controls (p < 0.001). No significant difference was found between children with newly diagnosed ITP and those who developed chronic ITP, regarding the frequency distribution of the FcγRIIa and FcγRIIIa alleles and genotypes (p > 0.05). ConclusionThere is a possible association of the FcγRIIa and FcγRIIIa genes polymorphism with the risk for, and genetic susceptibility to ITP in Egyptian children, but large-scale studies are still needed to support our findings.

POS0835 DECLINE IN FORCED VITAL CAPACITY (FVC) IN SUBJECTS WITH SYSTEMIC SCLEROSIS-ASSOCIATED INTERSTITIAL LUNG DISEASE (SSC-ILD) IN THE SENSCIS TRIAL VERSUS HYPOTHETICAL REFERENCE SUBJECTS WITHOUT LUNG DISEASE

Background:In the randomized SENSCIS trial in subjects with SSc-ILD, nintedanib reduced the rate of decline in FVC over 52 weeks (mL/year) by 44% compared to placebo. Healthy individuals have varied FVC depending on age, sex, ethnicity and height; expected values can be determined using internationally recognised reference equations.Objectives:To provide further context to the FVC declines observed in the SENSCIS trial, we compared the decline in FVC observed in subjects with SSc-ILD in the SENSCIS trial with the decline in FVC that would be expected in hypothetical subjects without ILD matched for age, sex, ethnicity and height.Methods:The SENSCIS trial enrolled subjects with SSc-ILD aged ≥18 years with first non-Raynaud symptom ≤7 years before screening, extent of fibrotic ILD ≥10% on HRCT, FVC ≥40% predicted and DLco 30–89% predicted. Baseline FVC (mL) and changes in FVC (mL) at week 52 were assessed in the nintedanib and placebo groups, with missing values at week 52 imputed using predictions from the primary analysis model (random slope and intercept model). Changes in FVC in the SENSCIS trial were compared to values in hypothetical healthy reference subjects matched to the SENSCIS subjects for age, sex, ethnicity and height. FVC values in these healthy reference subjects were derived from the equations published by the European Respiratory Society Global Lung Function Initiative in 2012, which were derived from data from over 70,000 subjects.1Results:In the nintedanib and placebo groups of the SENSCIS trial, respectively, mean (SD) time since onset of first non-Raynaud symptom was 3.5 (1.6) and 3.5 (1.8) years. In the nintedanib group, mean (SD) FVC at baseline was 2460 (737) mL, compared with 3403 (787) mL in the healthy reference subjects. In the placebo group, mean (SD) FVC at baseline was 2544 (817) mL compared with 3516 (887) mL in the healthy reference subjects. The difference in the change from baseline in FVC at week 52 between the nintedanib-treated subjects in the SENSCIS trial (n=287) and the healthy reference subjects was 26.6 mL ([95% CI: 1.2, 52.0]; p=0.04). The difference in the change from baseline in FVC at week 52 between the placebo-treated subjects in the SENSCIS trial (n=286) and the reference subjects was 77.5 mL ([95% CI: 51.4, 103.7]; p&lt;0.001) (Figure 1).Conclusion:Subjects with SSc-ILD who participated in the SENSCIS trial had marked lung function impairment at baseline compared with healthy matched reference subjects, despite a mean duration of SSc of 3.5 years. Over 52 weeks, the decline in FVC in subjects with SSc-ILD who received placebo was 4-fold greater than in healthy reference subjects. Subjects with SSc-ILD who were treated with nintedanib had a decline in FVC that was only slightly greater than the decline observed in the matched healthy subjects. These data support the clinical relevance of the reduction in the rate of FVC decline provided by nintedanib in patients with SSc-ILD.

Ability of a Set of Trunk Inertial Indexes of Gait to Identify Gait Instability and Recurrent Fallers in Parkinson's Disease.

The aims of this study were to assess the ability of 16 gait indices to identify gait instability and recurrent fallers in persons with Parkinson’s disease (pwPD), regardless of age and gait speed, and to investigate their correlation with clinical and kinematic variables. The trunk acceleration patterns were acquired during the gait of 55 pwPD and 55 age-and-speed matched healthy subjects using an inertial measurement unit. We calculated the harmonic ratios (HR), percent recurrence, and percent determinism (RQAdet), coefficient of variation, normalized jerk score, and the largest Lyapunov exponent for each participant. A value of ≤1.50 for the HR in the antero-posterior direction discriminated between pwPD at Hoehn and Yahr (HY) stage 3 and healthy subjects with a 67% probability, between pwPD at HY 3 and pwPD at lower HY stages with a 73% probability, and it characterized recurrent fallers with a 77% probability. Additionally, HR in the antero-posterior direction was correlated with pelvic obliquity and rotation. RQAdet in the antero-posterior direction discriminated between pwPD and healthy subjects with 67% probability, regardless of the HY stage, and was correlated with stride duration and cadence. Therefore, HR and RQAdet in the antero-posterior direction can both be used as age- and-speed-independent markers of gait instability.

Serotonin transporter availability increases in patients recovering from a depressive episode

Molecular imaging studies have shown low cerebral concentration of serotonin transporter in patients suffering from depression, compared to healthy control subjects. Whether or not this difference also is present before disease onset and after remission (i.e. a trait), or only at the time of the depressive episode (i.e. a state) remains to be explored. We examined 17 patients with major depressive disorder with positron emission tomography using [11C]MADAM, a radioligand that binds to the serotonin transporter, before and after treatment with internet-based cognitive behavioral therapy. In all, 17 matched healthy control subjects were examined once. Cerebellum was used as reference to calculate the binding potential. Differences before and after treatment, as well as between patients and controls, were assessed in a composite cerebral region and in the median raphe nuclei. All image analyses and confirmatory statistical tests were preregistered. Depression severity decreased following treatment (p < 0.001). [11C]MADAM binding in patients increased in the composite region after treatment (p = 0.01), while no change was observed in the median raphe (p = 0.51). No significant difference between patients at baseline and healthy controls were observed in the composite region (p = 0.97) or the median raphe (p = 0.95). Our main finding was that patients suffering from a depressive episode show an overall increase in cerebral serotonin transporter availability as symptoms are alleviated. Our results suggest that previously reported cross-sectional molecular imaging findings of the serotonin transporter in depression most likely reflect the depressive state, rather than a permanent trait. The finding adds new information on the pathophysiology of major depressive disorder.

The Frequency of Tumor Necrosis Factor-alpha Gene Polymorphism in Patients with Chronic Immune Thrombocytopenia.

Background: The aim of this study was to reveal the frequency of Necrosis Factor _Alpha Gene Polymorphism in evaluation of severity and outcome of chronic immune thrombocytopenia in pediatric department of Zagazig University hospitals. Methods: We conduct a retrospective case control on 40 children diagnosed with chronic ITP and 40 age and sex healthy matched subjects as a control recruited from outpatient hematology clinic Faculty of Medicine, Zagazig University. Results: We found a highly significant difference between ITP group and control group as regarding TNF-α alleles where A allele was expressed in 43.7% of cases versus 17.5% 0f control, P value

Assessment of INPP4B Expression Level in Acute Myeloid Leukemia Patients and Its Prognostic Significance. An Egyptian Study

Background: Acute myeloid leukemia (AML) is a complex and heterogeneous hematopoietic tissue neoplasm caused by gene mutations, chromosomal rearrangement and deregulation of gene expression. Inositol polyphosphate 4-phosphatase type II (INPP4B) is a clinically relevant factor in the phosphoinositide 3 kinase (PI3K) pathway- associated cancers, has been found to have a bad prognostic role in AML. However, the exact mechanism is still unclear. Objective: We aimed in this study to investigate the prognostic role of INPP4B overexpression in Egyptian AML patients. Patients and methods: A total of 80 patients with newly diagnosed AML were included in the study. In addition, 40 apparently healthy, age and sex matched subjects served as control group. Immunophenotyping, cytogenetic analysis and quantitative assessment of INPP4B gene transcript were performed using real time PCR. Results: INPP4B overexpression was detected in 27.5 % of newly diagnosed AML patients. There was a statistically significant decrease in the probability of achieving complete remission (CR) with shorter overall survival (OS), event free survival (EFS) and disease-free survival (DFS) in the INPP4B high expression group compared with the low expression group (p=0.003, 0.03, 0.02 and <0.001; respectively). Conclusion: We can conclude thatINPP4B overexpression is associated with poor response to therapy with poor outcome, and add prognostic value in patients with AML. INPP4B overexpression could be a valuable tool for making therapeutic decisions.

Evaluation of Oxidative Stress and Antioxidant Status in Beta Thalassemia Major Patients: A Single-Center Study

Abstract Background: Regular blood transfusion in children with beta thalassemia major lead toperoxidative tissue injury secondary to iron overload, increased oxidative stress and disturbance of oxidant anti-oxidantstatus of patients. Aim of Study: The present study aimed to assessoxidative stress, trace elements and oxidant-antioxidants status of beta thalassemia-major (b-TM) patients on regular blood trans-fusion. Patients and Methods: A case-control study included 35 beta thalassemic patients attending the pediatric Haematolo-gyclinic of El-Galaa Teaching Hospital and 35 age sex healthy matched subjects as control group. Serumzinc (Zn), copper (Cu), magnesium (Mg), serum Malondialdehyde (MDA), Superoxide Dismutase (SOD), serum catalase (CAT), Total Antioxidant Capacity (TAC) were performed for both patients and control. Results: Meanserum iron, ferritin, Alanine Transaminase (ALT), Aspartate Transaminase (AST) and total bilirubin levels were significantly higher in the b-TM group while mean hemoglobin, hematocritand total iron binding capacity were lower in the b-TM group. A significant increase in the levels of MDA, SOD whereas significant decrease in the levels of serum Zn, Mg. TAC and CAT was observed in the b-TM group. No significant difference in serum Cu between patients and control. Serum ferritin was found to have positive correlation with patients' age, weight, height, ALT, AST and total bilirubin, MDA, serum iron while significant negative correlation with total iron binding capacity, serum Zn and Mg levels whereas no significant correlation with serum Cu, SOD, CAT, TAC. Conclusion: Childrenwith beta thalassemia major suffering from oxidative stress, deficiency of some micronutrients and endogenous antioxidants. Selected trace elements and antioxi-dants supplementation require further studies for their eva-luation.

Comprehensive amino acid flux analysis in the post-acute phase of critically ill post-surgery patients, compared to healthy matched subjects

Rationale: ESPEN guidelines recommend administering 1.3 g/kg /d protein to stabilized critically ill patients, although insight in the specific perturbations in protein and amino acid metabolism of this population remain underexplored. Comprehensive metabolic flux analysis is a novel approach to perform metabolic phenotyping of ICU patients.

Trabecular Bone Score and Bone Quality in Systemic Lupus Erythematosus Patients

Background: Systemic lupus erythematosus (SLE) patients run a higher risk of having low bone mass due to multifactorial events that include physical inactivity, persistent inflammation, low vitamin D levels, and glucocorticoid treatment. This study aimed at obtaining a comparison between bone involvement in SLE patients and healthy matched subjects (HS).Methods: A total of 40 SLE females (average age 54.1 ± 16.3 years) and 40 age–gender matched HS (average age 54.2 ± 15.9 years) were enrolled after having obtained informed written consent. Bone mineral density (BMD, g/cm2) of the lumbar spine (L1–L4) was analyzed by a dual-energy X-ray absorptiometry (DXA) scan (GE, Lunar Prodigy). The lumbar spine trabecular bone score (TBS) was derived for each spine DXA examination by the TBS index (TBS iNsight Medimaps).Results: The lumbar spine TBS score was statistically significantly lower in SLE patients than in HS (0.797 ± 0.825 vs. 1.398 ± 0.207, p < 0.001, as was BMD (p < 0.001) in all areas examined.Conclusions: SLE is associated with significant low bone mass as evidenced by DXA and TBS. This study emphasizes the importance of using DXA and TBS in the evaluation of the different aspects of bone architecture.

T1 mapping and cardiac magnetic resonance feature tracking in mitral valve prolapse.

T1 mapping (T1-map) and cardiac magnetic resonance feature tracking (CMR-FT) techniques have been introduced for the early detection of interstitial myocardial fibrosis and deformation abnormalities. We sought to demonstrate that T1-map and CMR-FT may identify the presence of subclinical myocardial structural changes in patients with mitral valve prolapse (MVP). Consecutive MVP patients with moderate-to-severe mitral regurgitation and comparative matched healthy subjects were prospectively enrolled and underwent CMR-FT analysis to calculate 2D global and segmental circumferential (CS) and radial strain (RS) and T1-map to determine global and segmental native T1 (nT1) values. Seventy-three MVP patients (mean age, 57 ± 13 years old; male, 76%; regurgitant volume, 57 ± 21 mL) and 42 matched control subjects (mean age, 56 ± 18 years; male, 74%) were included. MVP patients showed a lower global CS (- 16.3 ± 3.4% vs. - 17.8 ± 1.9%, p = 0.020) and longer global nT1 (1124.9 ± 97.7 ms vs. 1007.4 ± 26.1 ms, p < 0.001) as compared to controls. Moreover, MVP patients showed lower RS and CS in basal (21.6 ± 12.3% vs. 27.6 ± 8.9%, p = 0.008, and - 13.0 ± 6.7% vs. - 14.9 ± 4.1%, p = 0.013) and mid-inferolateral (20.6 ± 10.7% vs. 28.4 ± 8.7%, p < 0.001, and - 12.8 ± 6.3% vs. - 16.5 ± 4.0%, p < 0.001) walls as compared to other myocardial segments. Similarly, MVP patients showed longer nT1 values in basal (1080 ± 68 ms vs. 1043 ± 43 ms, p < 0.001) and mid-inferolateral (1080 ± 77 ms vs. 1034 ± 37 ms, p < 0.001) walls as compared to other myocardial segments. Of note, nT1 values were significantly correlated with CS (r, 0.36; p < 0.001) and RS (r, 0.37; p < 0.001) but not with regurgitant volume. T1-map and CMR-FT identify subclinical left ventricle tissue changes in patients with MVP. Further studies are required to correlate these subclinical tissue changes with the outcome. • T1 mapping (T1-map) and cardiac magnetic resonance feature tracking (CMR-FT) techniques have been introduced for the early detection of interstitial myocardial fibrosis and deformation abnormalities. • In MVP patients, we demonstrated a longer global nT1 with associated reduced global circumferential (CS) and radial strain (RS) as compared to control subjects. • Among MVP patients, the mid-basal left ventricle inferolateral wall showed longer nT1 with reduced CS and RS as compared to other myocardial segments. Further studies are required to correlate these subclinical tissue changes with the outcome.

Identification of a Signaling Mechanism by Which the Microbiome Regulates Th17 Cell-Mediated Depressive-Like Behaviors in Mice.

Microbiota dysbiosis has been linked to major depressive disorder, but the mechanisms whereby the microbiota modulates mood remain poorly understood. The authors tested whether specific changes in the microbiome modulate depressive-like behaviors. Stools from learned helpless, non-learned helpless, and non-shocked mice were analyzed by V4 16S RNA sequencing to identify gut bacteria associated with learned helplessness and to quantify the level of the quorum-sensing molecule autoinducer-2 (AI-2). T cells were analyzed by flow cytometry, and serum amyloid proteins (SAA) were analyzed by quantitative real-time polymerase chain reaction. Fecal transfer approach and administration of oleic acid and AI-2 were used to determine the effects of the microbiome and quorum-sensing molecules on depressive-like behaviors. Mice deficient in segmented filamentous bacteria (SFB) were resilient to the induction of depressive-like behavior, and were resensitized when SFB was reintroduced in the gut. SFB produces the quorum-sensing AI-2 and promotes the production of SAA1 and SAA2 by the host, which increases T helper 17 (Th17) cell production. Th17 cells were required to promote depressive-like behaviors by AI-2, as AI-2 administration did not promote susceptibility to depressive-like behaviors or SAA1 and SAA2 production in Th17-deficient mice after stress. Oleic acid, an AI-2 inhibitor, exhibited antidepressant properties, reducing depressive-like behavior, intestinal SAA1 and SAA2 production, and hippocampal Th17 cell accumulation. Stool samples from 10 people with current depressive symptoms and 10 matched healthy control subjects were analyzed as well. Patients with current major depressive disorder exhibited increased fecal interleukin 17A, SAA, and SFB levels. The study results reveal a novel mechanism by which bacteria alter mood.

Diagnostic validity of optic nerve head colorimetric assessment and optical coherence tomography angiography in patients with glaucoma

Background/AimsThe aim of this study was to assess the optic nerve head (ONH) and macular vessel density with optical coherence tomography angiography (OCT-A) and the ONH haemoglobin (ONH Hb) amount...

The circular RNA landscape in specific peripheral blood mononuclear cells of critically ill patients with sepsis

BackgroundDysregulation of the host immune response is a pathognomonic feature of sepsis. Abnormal physiological conditions are understood to shift efficient linear splicing of protein-coding RNA towards non-canonical splicing, characterized by the accumulation of non-coding circularized (circ)RNA. CircRNAs remain unexplored in specific peripheral blood mononuclear cells (PBMCs) during sepsis. We here sought to identify and characterize circRNA expression in specific PBMCs of patients with sepsis due to community-acquired pneumonia (CAP) relative to healthy subjects.MethodsThe study comprised a discovery cohort of six critically ill patients diagnosed with sepsis due to community-acquired pneumonia and four (age, gender matched) healthy subjects. PBMCs were isolated, and fluorescence-activated cell sorting was used to purify CD14+ monocytes, CD4+, CD8+ T cells, and CD19+ B cells for RNA sequencing. CD14+ monocytes from independent six healthy volunteers were purified, and total RNA was treated with or without RNase R.ResultsRNA sequencing of sorted CD14+ monocytes, CD4+, CD8+ T cells, and CD19+ B cells from CAP patients and healthy subjects identified various circRNAs with predominantly cell-specific expression patterns. CircRNAs were expressed to a larger extent in monocytes than in CD4+, CD8+ T cells, or B cells. Cells from CAP patients produced significantly higher levels of circRNA as compared to healthy subjects. Considering adjusted p values, circVCAN (chr5:83519349-83522309) and circCHD2 (chr15:93000512-93014909) levels in monocytes were significantly altered in sepsis. Functional inference per cell-type uncovered pathways mainly attuned to cell proliferation and cytokine production. In addition, our data does not support a role for these circRNAs in microRNA sequestration. Quantitative PCR analysis in purified monocytes from an independent group of healthy volunteers confirmed the existence of circVCAN and circCHD2.ConclusionsWe provide a benchmark map of circRNA expression dynamics in specific immune cell subsets of sepsis patients secondary to CAP. CircRNAs were more abundant in immune cells of sepsis patients relative to healthy subjects. Further studies evaluating circRNA expression in larger cohorts of sepsis patients are warranted.