Category: Nevin Manimala

Circ Cardiovasc Qual Outcomes. 2023 Oct 18:e009938. doi: 10.1161/CIRCOUTCOMES.123.009938. Online ahead of print.

ABSTRACT

BACKGROUND: High-quality research in cardiovascular prevention, as in other fields, requires inclusion of a broad range of data sets from different sources. Integrating and harmonizing different data sources are essential to increase generalizability, sample size, and representation of understudied populations-strengthening the evidence for the scientific questions being addressed.

METHODS: Here, we describe an effort to build an open-access repository and interactive online portal for researchers to access the metadata and code harmonizing data from 4 well-known cohort studies-the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study, FHS (Framingham Heart Study), MESA (Multi-Ethnic Study of Atherosclerosis), and ARIC (Atherosclerosis Risk in Communities) study. We introduce a methodology and a framework used for preprocessing and harmonizing variables from multiple studies.

RESULTS: We provide a real-case study and step-by-step guidance to demonstrate the practical utility of our repository and interactive web page. In addition to our successful development of such an open-access repository and interactive web page, this exercise in harmonizing data from multiple cohort studies has revealed several key themes. These themes include the importance of careful preprocessing and harmonization of variables, the value of creating an open-access repository to facilitate collaboration and reproducibility, and the potential for using harmonized data to address important scientific questions and disparities in cardiovascular disease research.

CONCLUSIONS: By integrating and harmonizing these large-scale cohort studies, such a repository may improve the statistical power and representation of understudied cohorts, enabling development and validation of risk prediction models, identification and investigation of risk factors, and creating a platform for racial disparities research.

REGISTRATION: URL: https://precision.heart.org/duke-ninds.

PMID:37850400 | DOI:10.1161/CIRCOUTCOMES.123.009938

Int J Lab Hematol. 2023 Oct 18. doi: 10.1111/ijlh.14188. Online ahead of print.

ABSTRACT

INTRODUCTION: Detection of iron deficiency (ID) remains challenging. We aimed to evaluate the performance of reticulocyte hemoglobin equivalent (Ret-He) as a potential diagnostic marker to assess ID and iron deficiency anemia (IDA) in a large pediatric cohort.

METHODS: A total of 3158 patients (aged 15 days to 19 years with a median age of 8.5 years; 60.2% female) were retrospectively studied. Statistical analysis was performed (a) to evaluate relationship of Ret-He with other relevant complete blood count and iron panel parameters; (b) to compare the levels of Ret-He in ID and IDA groups to a control group; and (c) to assess sensitivity and specificity of Ret-He in ID, IDA, and anemia without ID groups.

RESULTS: Ret-He values were significantly positively correlated to ferritin and transferrin saturation (TSAT). The median Ret-He was significantly lower in ID. A Ret-He cutoff of ≤30.0 pg distinguished cases of ID from the control group with a sensitivity of 90.2%, specificity of 59.5%, and area under curve (AUC) of 0.88. Ret-He showed better diagnostic performance in the IDA group and acceptable performance for ID without anemia. The sensitivity, specificity, and AUC were 90.1%, 80.9%, and 0.93 for IDA at cutoff value of ≤27.4 pg, and 80.8%, 51.1%, and 0.70 for ID without anemia at cutoff value of ≤30.8 pg, respectively.

CONCLUSION: Our large pediatric tertiary care hospital study demonstrates that Ret-He is a reliable marker to help confirm IDA in pediatric population. However, further studies are needed for its use to capture the early stages of ID.

PMID:37850393 | DOI:10.1111/ijlh.14188

J Genet. 2023;102:49.

ABSTRACT

Ancestry inference of admixed populations is an important issue in anthropology and studies of gene discovery, and characterization. Usually, local ancestor inference (LAI) methods use fixed-length windows to divide chromosomes into smaller blocks. The accuracy of LAI algorithms will decrease if a window with an inappropriate length is used to infer the ancestry of admixed individuals. In this study, we first present a heuristic function to determine a proper window length for LAI methods. This heuristic is based on the distance between the ancestral populations of admixed individuals. Then we introduce a method for ancestry inference of admixed population with deep conditional random field (AICRF). AICRF uses a conditional random field (CRF) parameterized by probable extreme learning machines (PELMs) trained on reference panels where PELM is a novel probabilistic ELM classifier. This method does not require many statistical or biological parameters. We evaluate the performance of AICRF in comparison with RFMix. Experimental results show that AICRF is more accurate than RFMix with increasing admixture times.

PMID:37850385

Circulation. 2023 Oct 18. doi: 10.1161/CIRCULATIONAHA.122.063460. Online ahead of print.

ABSTRACT

BACKGROUND: Homozygous familial hypercholesterolemia is a genetic disease characterized by extremely high levels of low-density lipoprotein cholesterol (LDL-C) and a high risk of premature cardiovascular events. Phase 2 of ORION (A Study of Inclisiran in Participants With Homozygous Familial Hypercholesterolemia) showed that inclisiran, a small interfering RNA that prevents production of the hepatic PCSK9 protein (proprotein convertase subtilisin/kexin type 9), could lead to durable reductions in LDL-C levels when added to statins and ezetimibe in patients with homozygous familial hypercholesterolemia.

METHODS: ORION-5 was a phase 3, 2-part, multicenter study in 56 patients with homozygous familial hypercholesterolemia and elevated LDL-C levels despite maximum tolerated doses of LDL-C-lowering therapies with or without lipoprotein apheresis. Patients eligible for part 1 (double-blind, 6 months) were randomized 2:1 to receive either 300 mg of inclisiran sodium (equivalent to 284 mg of inclisiran) or placebo. Placebo-treated patients from part 1 were transitioned to inclisiran in part 2 (open-label, 18 months). The primary end point was the percentage change in LDL-C levels from baseline to day 150.

RESULTS: The mean age of the patients was 42.7 years, and 60.7% were women. The mean baseline LDL-C levels were 294.0 mg/dL and 356.7 mg/dL in the inclisiran and placebo groups, respectively. The placebo-corrected percentage change in LDL-C level from baseline to day 150 was -1.68% (95% CI, -29.19% to 25.83%; P=0.90), and the difference was not statistically significant between the inclisiran and placebo groups. The placebo-corrected percentage change in PCSK9 levels from baseline to day 150 was -60.6% with inclisiran treatment (P<0.0001); this was sustained throughout the study, confirming the effect of inclisiran on its biological target of PCSK9. No statistically significant differences between the inclisiran and placebo groups were observed in the levels of other lipids and lipoproteins (apolipoprotein B, total cholesterol, and non-high-density lipoprotein cholesterol). Adverse events and serious adverse events did not differ between the inclisiran and placebo groups throughout the study.

CONCLUSIONS: Inclisiran treatment did not reduce LDL-C levels in patients with homozygous familial hypercholesterolemia despite substantial lowering of PCSK9 levels. Inclisiran was well-tolerated, and the safety findings were consistent with previously reported studies and the overall safety profile.

REGISTRATION: URL: https://www.

CLINICALTRIALS: gov; Unique identifier: NCT03851705.

PMID:37850379 | DOI:10.1161/CIRCULATIONAHA.122.063460

J Enzyme Inhib Med Chem. 2023 Dec;38(1):2269613. doi: 10.1080/14756366.2023.2269613. Epub 2023 Oct 18.

NO ABSTRACT

PMID:37850334 | DOI:10.1080/14756366.2023.2269613

Urologiia. 2023 Sep;(4):105-112.

ABSTRACT

AIM: To evaluate the possibilities of textural analysis of 3D models in differentiating the degree of nuclear dysplasia of the clear cell renal cell carcinoma (ccRCC).

MATERIALS AND METHODS: The specimens after surgical treatment of 190 patients with ccRCC were analyzed. In all cases, nephron-sparing surgery (NSS) was performed through laparoscopic access. The clinical characteristics were evaluated, including age, gender, tumor localization (side, surface and segments), absolute tumor volume, Charlson comorbidity index, body mass index, nephrometry scores (RENAL, PADOVA, C-index). Patients were divided into 2 groups. In group 1, there were 119 patients with the ccRCC of Grade 1 or 2, while group 2 consisted of 71 patients with ccRCC of Grade 3 and 4. All patients underwent 3D virtual planning of procedure using the 3D modeling program “Amira”. At the first stage, two experienced radiologists performed manual segmentation of 3D models of kidney parenchyma tumors. At the second stage, the tumor shape was analyzed with a mathematical calculation of three indicators and more than 300 textural features of statistics of types 1-2 were extracted. Further, an intellectual analysis was carried out. For the evaluation of tumor grade according to Furman system, the classification problem was solved using the machine learning algorithm Stochastic Gradient Descent and cross-validation k=5.

RESULTS: The accuracy of classification for the two groups of Grade 1 or 2 and Grade 3 or 4 on the F1 metric was 72.2. To build the model, the following parameters were selected: the absolute tumor volume, the Charlson comorbidity index, “Energy”, the first quartile and the second decile of the pixel intensity distribution.

CONCLUSION: The texture analysis of 3D models for the prediction of Fuhrman grade in ccRCC demonstrated satisfactory quality for two groups of Grade 1 or 2 and Grade 3 or 4 nuclear dysplasia.

PMID:37850289

Urologiia. 2023 Sep;(4):75-81.

ABSTRACT

INTRODUCTION: Renal cysts are a common disease that occurs at a rate of 7-10%. Currently there are no clinical recommendations for the treatment of patients with simple renal cysts. In the current literature there is some evidence that a simple renal cyst has negative effects on renal function. Decreased renal function occurs due to partial atrophy and loss of the renal parenchyma (in the “crater” area at the base of the cyst) caused by compression. Therefore, the efforts to analyze the effect of simple kidney cysts on kidney function and identify the characteristics of the cyst that affect renal function to determine the indications for surgical treatment remains a substantial task. The aim of the study was to analyze the effect of simple renal cysts on renal function, to investigate the relationship between cyst size, atrophied parenchyma volume, and renal function, and to determine indications for surgical treatment of simple renal cysts.

MATERIALS AND METHODS: We conducted a prospective cohort study. The study included 109 patients with simple renal cysts. Patients with a solitary cyst of the right or left renal kidney, grade I-II according to Bosniak classification, were included in the study. The estimated glomerular filtration rate (eGFR) of the patients was calculated using various formulas. A contrast CT scan of the urinary tract was also performed to determine the maximum size of the cyst, calculate the volume of the renal parenchyma, and the volume of the lost (atrophied) parenchyma. Patients underwent renal scintigraphy with calculation of total GFR and split renal function. We analyzed the symmetry of the function of both kidneys by comparing the GFR of the affected and healthy kidneys, analyzed the relationship between the presence of a kidney cyst and a decrease in GFR, between the maximum size of a renal cyst and a decrease in its function compared with that of a healthy kidney. We also analyzed the correspondence of total GFR values obtained in renal scintigraphy and GFR values calculated according to the formulas.

RESULTS: Data from 109 patients were available for analysis; the mean blood creatinine was 87.4 mol/L. The median maximum cyst size was 80 mm. The median baseline volume of the affected kidney parenchyma was 174 ml, the median volume of the lost parenchyma was 49 ml, and the median proportion of the lost parenchyma was 28%. The median total GFR was 77.07 ml/min. The median GFR of the healthy kidney was 45.49 mL/min, and the median GFR of the kidney affected by the cyst was 34.46 mL/min. The median difference in GFR of the healthy and affected kidney units was 11 mL/min and was statistically significant. Comparison of the eGFR values obtained by the formulas with the reference values of GFR obtained by scintigraphy showed that the Cockcroft-Gault formula with standardization on the body surface area calculated closest eGFR values to the reference ones. Correlation analysis revealed a statistically significant association between the proportion of lost parenchyma volume and the maximum cyst size: =0.37 with 95% CI [0.20; 0.52] (p-value = 0). A multivariate logistic regression model revealed that a statistically significant factor influencing the probability of a significant decrease in GFR was the percent of lost renal parenchyma volume (OR=1,13; =0).

CONCLUSIONS: Our study showed that growth of renal cysts associated with renal parenchyma atrophy and decrease of GFR of the affected kidney. An increase in the volume of atrophied parenchyma leads to the decrease in GFR of the affected kidney. The obtained data suggest that performing dynamic renal scintigraphy to assess the decrease in affected renal function and determine the indications for surgical treatment of renal cysts is a reasonable recommendation. According to the results of the study, the loss of 20% of the renal parenchyma can be considered an indication for renal scintigraphy. The Cockcroft-Gault formula with standardization on the body surface area allows to calculate closest GFR values to those obtained by scintigraphy and, therefore, can be recommended as the optimal formula for calculating eGFR in daily clinical practice.

PMID:37850285

Urologiia. 2023 Sep;(4):31-39.

ABSTRACT

AIM: To perform language and cultural adaptation and validation of the OABSS (Overactive Bladder Symptom Score) questionnaire among patients with overactive bladder (OAB), proposed as an effective tool for assessing the severity of symptoms and the efficiency of treatment in clinics of the Russian Federation.

MATERIALS AND METHODS: In accordance with the protocols for carrying out such studies, the procedure of standardized forward-backward translation of the OABSS questionnaire was performed. Further, the intermediate Russian-language version was applied to 15 patients with subsequent correction of deficiencies and approval of the final Russian-language version of the questionnaire. In total, the study group included 176 patients of both sexes with OAB symptoms who filled out the questionnaire twice (test-retest) with an interval of 10-14 days.

RESULTS: Based on the statistical analysis (Cronbach’s alpha = 0.961), there was a significant degree of internal consistency of the sample. This fact is also supported by the very high retest reliability of the questionnaire (ICC >0.9).

CONCLUSION: Our data showed that the Russian version of the OABSS questionnaire is a reliable and valid tool for subjective assessment of the severity of OAB symptoms.

PMID:37850278

HLA. 2023 Oct 18. doi: 10.1111/tan.15251. Online ahead of print.

ABSTRACT

Extreme polymorphism of HLA and killer-cell immunoglobulin-like receptors (KIR) differentiates immune responses across individuals. Additional to T cell receptor interactions, subsets of HLA class I act as ligands for inhibitory and activating KIR, allowing natural killer (NK) cells to detect and kill infected cells. We investigated the impact of HLA and KIR polymorphism on the severity of COVID-19. High resolution HLA class I and II and KIR genotypes were determined from 403 non-hospitalized and 1575 hospitalized SARS-CoV-2 infected patients from Italy collected in 2020. We observed that possession of the activating KIR2DS4*001 allotype is associated with severe disease, requiring hospitalization (OR = 1.48, 95% CI 1.20-1.85, p_c = 0.017), and this effect is greater in individuals homozygous for KIR2DS4*001 (OR = 3.74, 95% CI 1.75-9.29, p_c = 0.003). We also observed the HLA class II allotype, HLA-DPB1*13:01 protects SARS-CoV-2 infected patients from severe disease (OR = 0.49, 95% CI 0.33-0.74, p_c = 0.019). These association analyses were replicated using logistic regression with sex and age as covariates. Autoantibodies against IFN-α associated with COVID-19 severity were detected in 26% of 156 hospitalized patients tested. HLA-C*08:02 was more frequent in patients with IFN-α autoantibodies than those without, and KIR3DL1*01502 was only present in patients lacking IFN-α antibodies. These findings suggest that KIR and HLA polymorphism is integral in determining the clinical outcome following SARS-CoV-2 infection, by influencing the course both of innate and adaptive immunity.

PMID:37850268 | DOI:10.1111/tan.15251

J Clin Periodontol. 2023 Oct 18. doi: 10.1111/jcpe.13890. Online ahead of print.

ABSTRACT

AIM: To investigate the association between periodontal diseases, airflow limitation and incident chronic obstructive pulmonary disease (COPD) in a large-scale prospective UK Biobank cohort.

MATERIALS AND METHODS: Our approach comprised a cross-sectional study and a prospective cohort. Periodontal diseases were determined based on the participants’ self-reported dental symptoms, including painful gums, bleeding gums and loose teeth. Logistic regression and Cox proportional hazards models were used to evaluate the association of periodontal diseases with airflow limitation and incident COPD in the cross-sectional study and the prospective cohort, respectively.

RESULTS: The cross-sectional study involved 495,610 participants. Multivariable analysis found that periodontal diseases were significantly associated with airflow limitation (odds ratio = 1.036, 95% confidence interval [CI]: 1.015-1.059). The cohort study included 379,266 participants with a median follow-up period of 12.68 years. An elevated risk of incident COPD was associated with the presence of periodontal diseases (hazard ratio: 1.248, 95% CI: 1.174-1.326). The effect was consistent among subgroups, including baseline age (≤65 or >65 years), sex, smoking status and diabetes mellitus.

CONCLUSIONS: Periodontal diseases are associated with airflow limitation and elevated COPD incidence. Maintaining good periodontal health in patients with chronic bronchitis and emphysema may help prevent the onset of COPD.

PMID:37850252 | DOI:10.1111/jcpe.13890