Combined Group Of Patients Research Articles

DNA Damage in Moderate and Severe COVID-19 Cases: Relation to Demographic, Clinical, and Laboratory Parameters.

The ability of the SARS-CoV-2 virus to cause DNA damage in infected humans requires its study as a potential indicator of COVID-19 progression. DNA damage was studied in leukocytes of 65 COVID-19 patients stratified by sex, age, and disease severity in relation to demographic, clinical, and laboratory parameters. In a combined group of COVID-19 patients, DNA damage was shown to be elevated compared to controls (12.44% vs. 5.09%, p < 0.05). Severe cases showed higher DNA damage than moderate cases (14.66% vs. 10.65%, p < 0.05), and males displayed more damage than females (13.45% vs. 8.15%, p < 0.05). DNA damage is also correlated with international normalized ratio (INR) (r = 0.471, p < 0.001) and creatinine (r = 0.326, p < 0.05). In addition to DNA damage, severe COVID-19 is associated with age, C-reactive protein (CRP), and creatinine. Receiver operating characteristic analysis identified age, INR, creatinine, DNA damage, and CRP as significant predictors of disease severity, with cut-off values of 72.50 years, 1.46 s, 78.0 µmol/L, 9.72%, and 50.0 mg/L, respectively. The results show that DNA damage correlates with commonly accepted COVID-19 risk factors. These findings underscore the potential of DNA damage as a biomarker for COVID-19 severity, suggesting its inclusion in prognostic assessments to facilitate early intervention and improve patient outcomes.

Morbidity and mortality in premature or low birth weight patients with congenital heart disease in three European pediatric heart centers between 2016 and 2020.

The treatment of preterm and low birth weight (LBW) neonates born with congenital heart disease (CHD) requiring early cardiac intervention remains challenging. We aimed to analyze morbidity and mortality in this combined high-risk patient group. A retrospective cohort study was conducted of preterm [<37 weeks gestational age (GA)] and/or LBW neonates (<2,500 g) born with a diagnosis of CHD, which requires invasive cardiac intervention (surgery or catheter) within their first year of life. Patients born between 2016 and 2020 and treated in three European pediatric heart centers were included. A total of 308 neonates (51% male) with CHD were included. Of those, 237 (77%) were born preterm, 259 (84%) were LBW, and 188 (61%) were both. The median GA was 35.4 weeks (interquartile range 33.3-36.9) and the mean birth weight was 2,016 ± 580 g. CHD was categorized as simple (12%), moderate (64%), or severe (24%). The overall complication rate was 45% and was highest in patients with severe CHD (p = 0.002). One-year mortality (19%) was associated with severe CHD, low relative birth weight in patients with genetic diagnoses, and low GA at birth, whereas GA at birth significantly impacted survival only after 3 months of life. The high morbidity and mortality in preterm and LBW neonates with CHD reflect their complexity and consequent limited treatment feasibility.

Multifractal organization of EEG signals in multiple sclerosis

Quantifying the complex/multifractal organization of the brain signals is crucial to fully understanding the brain processes and structure. In this contribution, we performed the multifractal analysis of the electroencephalographic (EEG) data obtained from a controlled multiple sclerosis (MS) study, focusing on the correlation between the degree of multifractality, disease duration, and disability level. Our results reveal a significant correspondence between the complexity of the time series and multiple sclerosis development, quantified respectively by scaling exponents and the Expanded Disability Status Scale (EDSS). Namely, for some brain regions, a well-developed multifractality and little persistence of the time series were identified in patients with a high level of disability, whereas the control group and patients with low EDSS were characterized by persistence and monofractality of the signals. The analysis of the cross-correlations between EEG signals supported these results, with the most significant differences identified for patients with EDSS >1 and the combined group of patients with EDSS ≤1 and controls. No association between the multifractality and disease duration was observed, indicating that the multifractal organization of the data is a hallmark of developing the disease. The observed complexity/multifractality of EEG signals is hypothetically a result of neuronal compensation – i.e., of optimizing neural processes in the presence of structural brain degeneration. The presented study is highly relevant due to the multifractal formalism used to quantify complexity and due to scarce resting-state EEG evidence for cortical reorganization associated with compensation.

Cerebral blood flow in striatum is increased by partial dopamine agonism in initially antipsychotic-naïve patients with psychosis.

Resting cerebral blood flow (rCBF) in striatum and thalamus is increased in medicated patients with psychosis, but whether this is caused by treatment or illness pathology is unclear. Specifically, effects of partial dopamine agonism, sex, and clinical correlates on rCBF are sparsely investigated. We therefore assessed rCBF in antipsychotic-naïve psychosis patients before and after aripiprazole monotherapy and related findings to sex and symptom improvement. We assessed rCBF with the pseudo-Continuous Arterial Spin Labeling (PCASL) sequence in 49 first-episode patients (22.6 ± 5.2 years, 58% females) and 50 healthy controls (HCs) (22.3 ± 4.4 years, 63% females) at baseline and in 29 patients and 49 HCs after six weeks. RCBF in striatum and thalamus was estimated with a region-of-interest (ROI) approach. Psychopathology was assessed with the positive and negative syndrome scale. Baseline rCBF in striatum and thalamus was not altered in the combined patient group compared with HCs, but female patients had lower striatal rCBF compared with male patients (p = 0.009). Treatment with a partial dopamine agonist increased rCBF significantly in striatum (p = 0.006) in the whole patient group, but not significantly in thalamus. Baseline rCBF in nucleus accumbens was negatively associated with improvement in positive symptoms (p = 0.046), but baseline perfusion in whole striatum and thalamus was not related to treatment outcome. The findings suggest that striatal perfusion is increased by partial dopamine agonism and decreased in female patients prior to first treatment. This underlines the importance of treatment effects and sex differences when investigating the neurobiology of psychosis.

Association between prediabetes and cognitive function in Parkinson's disease.

It remains largely unknown whether prediabetes is related to cognitive impairment in Parkinson's disease (PD). This study aimed to assess the association between prediabetes and cognitive function in PD patients. In this cross-sectional study, 262 PD patients (age, 69.8±10.3 years; Hoehn-Yahr stage, 2.3±0.8) were classified into diabetes (glycated hemoglobin [HbA1c] ≥6.5% or previously diagnosed, n=76), prediabetes (5.7%-6.4%, n=90), or diabetes free (≤5.6%, n=96) groups. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) test. Both the diabetes and prediabetes groups had significantly lower MoCA scores (17.0±6.6 and 18.0±6.1, respectively) than the diabetes free group (20.0±5.7), even after adjusting for potential confounders (p=.002 and p=.008, respectively). In the combined group of prediabetes and diabetes free patients, higher HbA1c levels significantly correlated with lower MoCA scores (p=.031). There was a significant interaction of diabetes status with age, but not with the duration of PD, on cognitive function. In addition to diabetes, prediabetes may negatively affect cognitive function in PD patients. Further prospective longitudinal studies are necessary to clarify the impact of prediabetes on the cognitive trajectory of these patients.

Outcomes 12 Months After Temperature-Controlled Radiofrequency Device Treatment of the Nasal Valve for Patients With Nasal Airway Obstruction

Nasal valve collapse is a primary cause of nasal airway obstruction (NAO). Patients with NAO and nasal valve collapse experience a variety of symptoms that lower their quality of life, such as nasal congestion, headache, sleep disturbance, daytime sleepiness, and snoring. To determine if active treatment of the nasal valve with a temperature-controlled radiofrequency (TCRF) device, previously demonstrated superior to a sham procedure at 3 months, was safe and associated with sustained improvements in symptoms of NAO through 12 months. In a prospective, multicenter, single-blinded, randomized clinical trial, patients in 16 centers in the US with index procedures between August and December 2020 were assigned to TCRF device treatment of the nasal valve or a sham control procedure (no RF energy). Patients had a baseline Nasal Obstruction Symptom Evaluation (NOSE) Scale score of 55 or greater with nasal valve collapse as the primary or substantial contributor to NAO. After primary end point evaluation at 3 months, eligible patients in the sham control arm crossed over to active treatment. Data analysis was performed between April and May 2022. Patients were treated bilaterally with the TCRF device at 4 or fewer nonoverlapping areas on the nasal mucosa at the junction of the upper and lower lateral cartilage on the lateral nasal wall. The primary end point measure was responder rate, defined as 20% or greater reduction in NOSE Scale score or 1 or greater reduction in NOSE Scale clinical severity category. A total of 108 patients received active treatment (77 as index active treatment, 31 after crossover). The mean (SD) age of patients was 48.5 (12.3) years; 66 (61.1%) were women. The combined group of patients receiving active treatment had a mean baseline NOSE Scale score of 76.3 (95% CI, 73.6-79.1). At 12 months (n = 88), the responder rate was 89.8% (95% CI, 81.7%-94.5%). The NOSE Scale score improved from baseline (mean change, -44.9 [95% CI, -52.1 to -37.7]). No device/procedure-related serious adverse events were reported. In this follow-up of a cohort from a randomized clinical trial, the minimally invasive TCRF device, previously demonstrated to be superior to a sham procedure, was safe and associated with improvement in symptoms of NAO through 12 months postprocedure. ClinicalTrials.gov Identifier: NCT04549545.

Awake Surgery for Arteriovenous Malformations in Eloquent Areas Does Not Increase Intraoperative Risks and Allows for Shorter-Term Recovery and Improved Status

Arteriovenous malformations (AVMs) located in eloquent areas are associated with a significant risk of neurologic deterioration. Awake surgery applied to intracranial AVMs could better identify eloquent areas, but its feasibility and application are controversial and limited to small case series. We retrospectively reviewed a group of 59 brain AVMs located in eloquent areas surgically treated with asleep craniotomy and compared it with a combined group of patients treated with awake craniotomy. Patients were stratified into 2 groups: patients who underwent asleep surgery and patients who underwent awake surgery. With this study, we aimed to perform a complete analysis of surgical risks and outcomes for this subgroup of patients in order to provide a basis for a future prospective study. We compared the asleep group of 25 patients and the awake group of 34 patients. No statistically significant differences were identified regarding the risk of postoperative complications, surgical radicality, presence of residual, and need for adjuvant treatment (P= 1.00). The improvement in Karnofsky Performance Status (KPS) was more rapid and effective during follow-up in patients treated with awake surgery compared with asleep surgery (KPS at day 30 >70%-80% versus 87.2%, P= 0.01 and at 1year KPS >70%-80% vs. 96.9%, P= 0.02). In contrast to what is commonly believed, applying awake surgery to this lesion does not involve increased intraoperative risks. Still, it seems to determine a significant improvement in the outcome of patients from postoperative day 30 onwards.

COVID-19 outbreak response at a nursing hospital in South Korea in the post-vaccination era, including an estimation of the effectiveness of the first shot of the Oxford-AstraZeneca COVID-19 vaccine (ChAdOx1-S).

ObjectivesWe descriptively reviewed a coronavirus disease 2019 (COVID-19) outbreak at a nursing hospital in Gyeonggi Province (South Korea) and assessed the effectiveness of the first dose of the Oxford-AstraZeneca vaccine in a real-world population.MethodsThe general process of the epidemiological investigation included a public health intervention. The relative risk (RR) of vaccinated and unvaccinated groups was calculated and compared to confirm the risk of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, and vaccine effectiveness was evaluated based on the calculated RR.ResultsThe population at risk was confined to ward E among 8 wards of Hospital X, where the outbreak occurred. This population comprised 55 people, including 39 patients, 12 nurses, and 4 caregivers, and 19 cases were identified. The RR between the vaccinated and unvaccinated groups was 0.04, resulting in a vaccine effectiveness of 95.3%. The vaccination rate of the non-patients in ward E was the lowest in the entire hospital, whereas the overall vaccination rate of the combined patient and non-patient groups in ward E was the third lowest.ConclusionThe first dose of the Oxford-AstraZeneca vaccine (ChAdOx1-S) was effective in preventing SARS-CoV-2 infection. To prevent COVID-19 outbreaks in medical facilities, it is important to prioritize the vaccination of healthcare providers.

The role of the Royal Air Force Deployed Readiness Preparation Team in the UK.

Royal Air Force (RAF) Waddington and Cranwell are both based in Lincolnshire and have Defence Primary Health Care Dental Centres on Station to provide dental care to service personnel. The facility at RAF Waddington was temporarily closed for refurbishment early 2020 and this saw the amalgamation of the two Dental Centres. This, alongside COVID, significantly impacted on the ability to deliver dental care to a combined patient group. Military dental teams are routinely deployed overseas to provide care for patients; however, the Deployed Readiness Preparation Team (DRPT) had not previously been activated in the UK in support of RAF Dental Centres. This UK-based deployment was to be innovative and able to demonstrate the wider utility of the military dental teams and portable equipment, to expand the facility at RAF Cranwell.The aim of this paper is to highlight the key principles and utility of deployable Defence dentistry by discussing the establishment and use of portable dental equipment to facilitate the increased clinical output of a dental centre. Through energetic and focused leadership, training and assurance, dentistry can be delivered with an occupational focus to provide a responsive and deployable care capability in a UK setting.

The Relationship Between and Correlates of Problematic Sexual Behavior and Major Mental Illness.

While research has consistently found that general distress and psychopathology are not predictive of sexual recidivism, examination of specific syndromes and their relationship to offending has revealed a potentially more complicated relationship. One proposed mechanism for the mixed findings with respect to major mental illness and sexual offending may be the confound of neurological injury. As identified in Mann et al. (2010) work on psychologically meaningful risk factors, mental illness represents an area in need of more study given the indirect influence it may exert on risk. To this end, the current paper summarizes the study of the relationship between neurological injury, psychosis and problematic sexual behavior among two Canadian samples of forensic and civil psychiatric patients. In the first study we observed higher than expected rates of sexually-themed psychotic symptoms (45%) and problematic sexual behavior (PSB; 40%) among a combined group of forensic and civil psychiatric patients (n = 109). Indeed 70 percent of those individuals who engaged in PSB endorsed sexually-themed psychotic symptoms. While comorbidity is common amongst this group, brain injury appeared to represent a specific liability. Compared to those who did not engage in PSB, those who did were almost 4x (OR = 3.83) more likely to have a documented history of brain injury (e.g., traumatic and acquired brain injury, including fetal alcohol syndrome). In the second study we sought to replicate this finding in a larger forensic sample of 1,240. However, the recorded rates of brain injury were significantly less, such that no relationship to PSB was observed. Based on the mixed findings to date, including our own data, questions remain about the nature of a potential shared vulnerability for psychosis and PSB previously postulated. Among psychiatrically complex individuals who engage in PSB, understanding etiology and links to risk are helpful, but perhaps more importantly is attention to the mechanisms through which symptoms confer risk (e.g., problem solving, sexual disinhibition, social/intimacy deficits) and how best to treat and manage them.

Peculiarities of Restoration of the Functional Condition of the Kidney Parenchyma in Children with Congenital Defects of the Ureterovesical Segment Depending on Methods of Its Operative Correction (According to Cytokine-enzymological Criteria)

Peculiarities of Restoration of the Functional Condition of the Kidney Parenchyma in Children with Congenital Defects of the Ureterovesical Segment Depending on Methods of Its Operative Correction (According to Cytokine-enzymological Criteria)

Comparative investigation of cell cycle and immunomodulatory genes in mucosal and cutaneous melanomas: Preliminary data suggest a potential promising clinical role for p16 and the PD-1/PD-L1 axis

Mucosal melanomas arise from the mucosal lining of various organs. Their etiology is currently unknown and there are no tissue-based methods to differentiate it from cutaneous melanomas. Furthermore, prognostic and predictive markers (e.g. for immune checkpoint inhibition) are lacking. In this study, we aimed to assess the protein expression levels of cell cycle-associated proteins and immune checkpoint markers in a cohort of mucosal melanomas in comparison to cutaneous melanomas and evaluated the effect of potential regulatory mechanisms. We performed immunohistochemistry, DNA methylation analysis and copy number profiling of 47 mucosal and 28 cutaneous melanoma samples. Protein expression of CD117, Ki67 and p16 was higher in mucosal melanomas, while BCL2, Cyclin D1, PD-1 and PD-L1 were overexpressed in cutaneous melanomas. CDKN2A deletions were the most prevalent numeric chromosomal alterations in both mucosal and cutaneous melanoma and were associated with decreased p16 expression. KIT was frequently amplified in mucosal melanomas, but not associated with CD117 expression. On the other hand, amplification of CCND1 lead to Cyclin D1 overexpression. In mucosal melanoma patients high PD-1 expression and high PD-L1 promoter methylation levels were associated with improved survival. PD-L1 expression correlated with response to immune checkpoint inhibitor therapy in the combined group of melanoma patients. Mucosal and cutaneous melanomas show different expression levels of cell cycle-associated and immunomodulatory proteins that are partially regulated by DNA methylation and copy number alterations. PD-1 expression and PD-L1 promoter methylation levels might be a prognostic marker for mucosal melanomas.

Identification of potential metabolic biomarkers in predicting esophageal varices needing treatment in patients with liver cirrhosis

The goal of this study was to determine the diagnostic performance of in vivo quantitative proton magnetic resonance spectroscopy (1H-MRS) to identify the presence of esophageal varices needing treatment (VNT), as well as investigate its correlation with clinical characteristics in patients with liver cirrhosis. Forty cirrhotic patients without VNT showing the negative red color sign, and 40 cirrhotic patients with VNT showing positive red color sign underwent laboratory tests, esophago-gastro-duodenoscopy, and 1H-MRS with single-voxel localization in the cirrhotic liver parenchyma. The levels of lactate + triglyceride (TG) and choline in cirrhotic patients with VNT were significantly higher than those in cirrhotic patients without VNT. In multivariate analysis, spleen diameter, platelet count, and platelet count/spleen diameter ratio, as well as lactate + TG, and choline were associated with the presence of VNT. Moreover, lactate + TG and choline levels were positively correlated with spleen diameter and negatively correlated with platelet count in the combined group of cirrhotic patients with and without VNT. Our study demonstrated that higher hepatic lactate + TG and choline levels in cirrhotic patients in conjunction with longer spleen diameter, lower platelet counts, and lower ratios of platelet count to spleen diameter were associated with the presence of esophageal VNT and the risk of developing variceal bleeding. Therefore, in vivo 1H-MRS might be an effective tool for diagnosing and predicting esophageal VNT in patients with liver cirrhosis.

Type 1 Diabetic Patients After Simultaneous Pancreas and Kidney Transplantation Have Less Intense Periodontal Inflammation Compared to Kidney Recipients Treated with Insulin.

BackgroundLong-term diabetes predisposes to pathological changes in periodontal tissues. Improvement in this respect can be expected in patients after pancreas transplantation.The aim of this study was to assess and compare the intensity of periodontium pathological lesions and inflammation markers concentration in gingival crevicular fluid (GCF) in patients with type 1 diabetes (T1D) after kidney (KTx) or simultaneous pancreas and kidney transplantation (SPK).Material/MethodsThe study included 20 T1D patients after SPK and 16 after KTx, and 15 non-diabetic kidney recipients (control). Periodontal clinical parameters and concentration of selected biochemical markers of inflammation in GCF were assessed. The following tests were used in statistical data analysis: Shapiro-Wilk test, the t test, the Mann-Whitney U tests, one-way ANOVA with Tukey’s post hoc test, and χ2 test (also with Yate’s correction). Moreover, linear regression and Pearson or Spearman correlation coefficient was used.ResultsThere were no differences in modified Sulcus Bleeding Index (mSBI) and GCF volume between the SPK group and control group, whereas values of these parameters in the KTx group were higher than in the SPK and control groups. Maximal clinical attachment loss and pocket depth and Periotest values were higher in diabetic recipients compared to controls, and did not differ between SPK and KTx.The concentration of IL-1β, MMP-8, resistin, TNFα, and YKL40 in the GCF in the KTx group was higher than in the SPK and control groups.In the combined group of T1D patients, there was a correlation between blood HbA1c and mSBI, GCF volume, and resistin, TNF-α and YKL40 concentrations, and between resistin concentration and mSBI.ConclusionsT1D patients after SPK show lower levels of inflammatory markers in GCF and present reduced intensity of periodontitis compared to kidney recipients treated with insulin.The severity of morphological changes in periodontium in T1D patients after KTx or SPK is higher than in non-diabetic kidney recipients.

Thoracoscopic surgical atrial fibrillation ablation in patients with an extremely enlarged left atrium

PurposeEfficacy of pulmonary vein isolation (PVI) for atrial fibrillation (AF) decreases as left atrial (LA) volume increases. However, surgical AF ablation with unknown efficacy is being performed in patients with a giant LA (GLA). We determined efficacy of thoracoscopic AF ablation in patients with compared to without a GLA.MethodsPatients underwent thoracoscopic PVI with additional left atrial ablations lines (in persistent AF) and were prospectively followed up. GLA was defined as LA volume index (LAVI) ≥ 50 ml/m2. Follow-up was performed with ECGs and 24-h Holters every 3 months. After a 3-month blanking period, all antiarrhythmic drugs were discontinued. The primary outcome was freedom of any atrial tachyarrhythmia ≥ 30 s during 2 years of follow-up.ResultsAt baseline, 68 (15.4%) patients had a GLA (LAVI: 56.7 [52.4–62.8] ml/m2), while 374 (84.6%) had a smaller LA (LAVI: 34.8 [29.2–41.3] ml/m2). GLA patients were older (61.9 ± 6.9 vs 59.4 ± 8.8 years, p = 0.02), more often diagnosed with persistent AF (76.5% vs 58.6%, p = 0.008). Sex was equally distributed (with approximately 25% females). GLA patients had more recurrences compared to non-GLA patients at 2-year follow-up (42.6% vs 57.2%, log rank p = 0.02). Freedom of AF was 69.0% in non-GLA paroxysmal AF patients compared to 43.8–49.3% in a combined group of GLA and/or persistent AF patients(log rank p < 0.001). Furthermore, freedom was 62.4% in non-GLA male patients, compared to 43.8–47.4 in a combined group of GLA and/or female sex(log rank p = 0.02).ConclusionThoracoscopic AF ablation is an effective therapy in a substantial part of GLA patients. Thoracoscopic AF ablation may serve as a last resort treatment option in these patients.

Increased right ventricular uptake on (99m Tc)-sestamibi SPECT myocardial perfusion imaging as a marker of elevated pulmonary artery systolic pressure measured by Doppler echocardiography

Abstract Funding Acknowledgements Type of funding sources: None. Background Though prior work has been done, the significance of the not uncommon finding of increased right ventricular (RV) tracer uptake in patients undergoing (99m Tc)-sestamibi SPECT myocardial perfusion imaging remains poorly defined and this finding not been systemically integrated into the interpretation of the study, despite likely carrying both diagnostic and prognostic relevance for the patient. Purpose To examine if the presence of increased RV tracer uptake in patients undergoing myocardial perfusion imaging with same-day protocol (99m Tc)-sestamibi SPECT is associated with a higher pulmonary artery systolic pressure (PASP) measured non-invasively with transthoracic Doppler echocardiography Methods Patients who underwent myocardial perfusion imaging with same-day protocol (99m Tc)-sestamibi SPECT at a single academic health system between 2017-2020 were retrospectively enrolled. Those patients who had a transthoracic echocardiogram performed within 60 days of the nuclear study with sufficient Doppler data to estimate pulmonary artery systolic pressure(PASP) using the tricuspid regurgitation peak velocity method were included. A right atrial pressure of either 3 mmHg, 8 mmHg, or 15 mmHg was used in the calculation of PASP in keeping with the 2015 American Society of Echocardiography guidelines. The rest images for each nuclear study were reviewed and analyzed for the presence of RV tracer uptake. RV uptake was graded as either 0 or "no RV uptake", 1+ or "partial RV uptake", or 2+ or "complete RV uptake". The nuclear studies were grouped accordingly and the mean PASP for each group was computed. The mean PASP was also computed for a combined group of patients who demonstrated either 1+ or 2+ RV uptake. Statistical analysis using a t-test was performed to compare the mean PASP of each patient group. Results 193 patients were included in the analysis. Of those, 123(63%) demonstrated "no RV uptake", 58(31%) demonstrated 1+ or "partial RV uptake", and 12(6%) demonstrated 2+ or "complete RV uptake". 70 patients(36%) had either 1+ or 2 + RV uptake. The mean PASP was 27.2 ± 7 mmHg for the "no RV uptake" group, 28.3 ± 9 mmHg for the 1+ RV uptake group and 41. 6 ± 14 mmHg for the 2+ RV uptake group. When combined, patients demonstrating 1+ or 2+ RV uptake had a mean PASP of 30.6 ± 11 mmHg. There was no statistical difference in the mean PASP of the "no RV uptake" group and the 1+ or "partial RV uptake group" (p = 0.434). The difference in mean PASP between the "no RV uptake" group and the combined 1+ or 2+ RV uptake group was statistically significant(p = 0.028). Conclusion In a small single health system sample, patients undergoing (99m Tc)-sestamibi SPECT myocardial perfusion imaging who have either partial or complete RV uptake on rest images have an increased pulmonary artery systolic pressure compared to patients who do not exhibit this finding.

A novel approach to rapid induction of remission in primary membranous nephropathy

То evaluate the effectiveness of a novel multi-targeted treatment approach including rituximab (RTX), cyclophosphamide (CPH) and steroids (S) to the induction of remission in patients with primary membranous nephropathy (PMN) compared to standard immunosuppression (IST). An open-label prospective comparative study included 56 PMN patients (pts) with nephrotic syndrome (NS) and high serum level of antibodies to the phospholipase A2 receptor anti-PLA2R (mean age 5112 years, men 70%). We recorded demographic and clinical parameters at the time of kidney biopsy, data from light-optical and immunomorphological studies. All pts were on stable doses of the renin-angiotensin systems blockers. We compared the effectiveness of different treatments in the inductions of clinical and immunological remissions in pts who received experimental treatment with RTX, CPH and S (RTX+CPH+S group, n=14) and two control groups: high-dose RTX therapy (group RTX, n=12), cyclosporine and steroids (group CsA+S, n=30). In the RTX+CPH+S group, remission was achieved in 100% of cases (of which complete remissions CR in 21.4%). The median time-to-remission (2.5 [1.0; 3.5] months) was significantly lower compared to both control groups: RTX (8.7 [6.6; 14.0] months, p=0.005) and CsA+S (12.4 [6.5; 19.9] months, p0.001). The cumulative incidence of clinical and immunological remissions was also significantly higher in the RTX+CPH+S group than in the control groups. These results were confirmed in comparative analyzes in the same treatment groups after propensity score matching. The cumulative incidence of clinical and immunological remissions in the RTX+CPH+S group was higher than in the combined group of patients who received other therapies (p0.001). The incidence of serious adverse events was low and did not differ between groups. The use of multi-targeted therapy with rituximab, cyclophosphamide, and steroids seems to be an effective approach for the rapid induction of PMN remission and prevention of NS complications.

FC 086GLOMERULI PROTEOME ANALYSIS REVEALS EARLY DIFFERENCES BETWEEN PRE-EXISTING AND DE-NOVO TYPE 2 DIABETES IN HUMAN RENAL ALLOGRAFTS

Abstract Background and Aims Diabetes mellitus, either preexisting or developing after kidney transplantation remains a crucial clinical problem. The aim of this study is to compare the proteome of histologically normal glomeruli from normoglycemic (NG), T2DM, and PTDM patients one year after kidney transplantation to identify novel early biomarkers detectable prior to the development of histologically visible diabetic nephropathy. Method We comparatively analyzed the proteome of histologically normal glomeruli from normoglycemic (NG) recipients, and recipients with pre-existing type 2 diabetes mellitus (T2DM), or post-transplant diabetes mellitus (PTDM), in protocol biopsies obtained one year after kidney transplantation. Glomerular cross-sections were microdissected in core biopsies from 8 NG, 8 PTDM and 8 T2DM kidney transplant recipients. Proteome was determined by liquid chromatography-tandem mass spectrometry. Relative differences in protein abundance and significantly dysregulated pathways were analyzed. Results Proteins related to immune response and inflammation, transport regulation and cell organization and communication, including the nephrin family, were more abundant in NG, as compared to the combined groups of diabetic patients. Proteins involved in cell morphogenesis and adhesion were less abundant in PTDM, as compared to T2DM. In contrast, CCT3, CCT4 and CNDP2 diabetic nephropathy markers, LDHB and tacrolimus binding protein FKBP1A were significantly overrepresented in glomeruli from PTDM, as compared to T2DM patients. Conclusion These data suggest that glomerular proteome profile differentiates PTDM from NG and T2DM, and disruption of cell-cell interactions at molecular level represents an early event in PTDM development.

Differential expression of long noncoding RNAs in patients with metastatic and nonmetastatic colorectal cancer.

e15023 Background: Long non-coding RNAs (lncRNA) play an important role in many biological processes, and their dysregulation can lead to various diseases, including colorectal cancer (CRC). In recent years, interactions between lncRNA, miRNA and mRNAs in development of CRC have attracted more and more attention. However, the currently obtained data on the complex regulatory interactions between lncRNA and microRNA during metastasis in patients with CRC are fragmentary, often contradictory and obtained on samples that are not significant in size. Therefore, the aim of the study was to analyze the features of lncRNA expression in CRC patients without metastases, with lymph nodes metastases and with liver metastases. Methods: The study included 200 patients with colon adenocarcinoma. The patients were divided into 3 groups: without metastases (T2N0MO, group 1, n = 100), with lymph node metastases (T2-3N1-2M0, group 2, n = 60) and with liver metastases (T3N2M1-2, group 3, n = 40). RNA isolation was performed by guanidine-thiocyanate-phenol-chloroform extraction. The lncRNA list was generated based on bioinformatic analysis. The relative expression of 20 lncRNAs (NEAT1, HELLPAR, AP000766.1, LINC00265, MIRLET7BHG, OLMALINC, AC245884.8, MEOX2-AS1, MEG3, NORAD, HCG11, WASIR2, AC005332.7, PURLN, OIP5-AS1, SNHG14, TUG1, XIST, MALAT1, FAM66E) was evaluated by RT-qPCR method. Differences were assessed using the Mann-Whitney test, and the Bonferroni correction was used to correct multiple comparisons. Results: Differential expression of 5 lncRNA (MALAT1, TUG1, XIST, LINC00265, HELLPAR) was found between CRC patients without metastases and patients with metastases to lymph nodes and liver. Thus, in group 1, expressions of MALAT1, TUG1 and HELLPAR were lower by 2.5, 4.0 and 5.5 times (p &lt; 0.005) than in combined group of patients with metastases to lymph nodes and liver, and XIST and LINC00265 expressions were higher by 2.2 and 3.4 times (p &lt; 0.05), respectively. Differential expression of 2 lncRNA (NORAD, WASIR2) was also found between group 2 and group 3. The NORAD expression in patients in group 3 was 5.5 times (p &lt; 0.05) lower than in patients in group 2, and WASIR2 expression, on the contrary, was 2.5 times (p &lt; 0.05) higher in patients in group 3. Conclusions: Thus, differential expression of lncRNA (MALAT1, TUG1, XIST, LINC00265, HELLPAR, NORAD and WASIR2), associated with regulation of proliferation and invasive ability of tumor cells, was found in 3 groups of CRC patients.

MiR-126, IL-7, CXCR1/2 receptors, inflammation and circulating endothelial progenitor cells: The study on targets for treatment pathways in a model of subclinical cardiovascular disease (type 1 diabetes mellitus)

BackgroundType 1 diabetes (T1DM) is associated with premature cardiovascular disease (CVD) and a pro-inflammatory state whilst the proangiogenic miR-126-3p/-5p may play a role in CVD. Animal studies established miR-126 to be pro-angiogenic. We hypothesised miR-126-3p/-5p are reduced in T1DM whilst pro-inflammatory cytokines are increased.Methods29 well controlled, T1DM patients without CVD and 20 healthy controls (HCs) were studied. MiR-126-3p/-5p were assayed in plasma and peripheral blood mononuclear cells (PBMCs) whilst Chemokine C-X-C Receptor 1/2 (CXCR1/2) mRNA in PBMCs by real-time quantitative PCR. Cytokines were assayed by the Mesoscale Discovery. Ingenuity Pathway Analysis (IPA) was used to predict target genes, cellular functions and pathological states regulated by miR-126-3p/-5p. IPA generated both direct and indirect causations between different targets and analysed whether these effects would be inhibitory or stimulatory based on the published evidence.ResultsT1DM patients had a relatively good diabetic control (HbA1c = 7.4 ± 0.7% or 57.3 ± 7.6 mmol/mol). Homeostatic cytokine IL-7, pro-inflammatory cytokines IL-8 and TNF-α, and vascular endothelial growth factor-C (VEGF-C) were increased in T1DM, versus HCs; p = 0.008, p = 0.003, p = 0.041 and p = 0.013 respectively. MiR-126-5p was significantly upregulated in PBMCs in T1DM versus HCs; p = 0.01, but not in plasma. MiR-126-3p was unchanged. CXCR1/2 were elevated in T1DM versus HCs; p = 0.009 and p < 0.001 respectively. MiR-126-5p was positively correlated with CXCR1/2, and with HbA1c whilst negatively correlated with circulating endothelial progenitor cells (CD34+CD133+CD45dim) and fibronectin adhesion assay in a combined group of T1DM patients and HCs; p = 0.028 p = 0.049 p = 0.035 p = 0.047 and p = 0.004 respectively. IPA predicted miR-126-5p to be anti-inflammatory through the inhibition of chemokine C–C motif ligand 27, chymotrypsin-like elastase 2A and IL-7, whilst miR-126-3p had no direct anti-inflammatory effect. Simultaneously IPA predicted IL-7 as the most upstream cytokine target.ConclusionsT1DM without apparent CVD or diabetic complications is an inflammatory state characterised not only by raised pro-inflammatory cytokines but also by increased receptor CXCR1/2 and miR-126-5p. MiR-126-5p upregulation may represent a compensatory response. Pro-miR-126-5p therapies or anti-IL-7 therapies may be a new option to reduce both inflammation and CVD risk in T1DM. Further research is required in a large prospective study in patients with T1DM.