MATERIALS AND METHODS: The study group included 105 patients with CP, with the age of the disease onset under 40 years old (the average age of onset was 26.9 years). The control group consisted of 76 persons without clinical signs of pancreatitis. The diagnosis of chronic pancreatitis in patients was made on the basis of clinical manifestations and the results of laboratory and instrumental investigations. Genetic examination of patients was conducted using the next-generation sequencing (NGS) technology and included targeted sequencing of all exons and exon-intron boundaries of the PRSS1, SPINK1, CTRC, CFTR, and CPA1 genes. The genotyping of the rs61734659 locus of the PRSS2 gene was also conducted.
RESULTS: Genetic risk factors of the CP development were found in 61% of patients. Pathogenic and likely-pathogenic variants associated with the risk of CP development were identified in the following genes: CTRC (37.1% of patients), CFTR (18.1%), SPINK1 (8.6%), PRSS1 (8.6%), and CPA1 (6.7%). The frequent gene variants in Russian patients with CP were as follows: CTRC gene - c.180C>T (rs497078), c.760C>T (rs121909293), c.738_761del24 (rs746224507); cumulative odds ratio (OR) for all risk alleles was 1.848 (95% CI: 1.054-3.243); CFTR gene - c.3485G>T (rs1800120), c.1521_1523delCTT (p.Phe508del, rs113993960), and c.650A>G (rs121909046); OR=2.432 (95% CI: 1.066-5.553). In the SPINK1, PRSS1, and CPA1 genes, pathogenic variants were found only in the group of patients with CP. The frequent variants of the SPINK1 gene include c.101A>G (p.Asn34Ser, rs17107315) and c.194+2T>C (rs148954387); of the PRSS1 gene - c.86A>T (p.Asn29Ile, rs111033566); of the CPA1 gene - c.586-30C>T (rs782335525) and c.696+23_696+24delGG. The OR for the CP development for the c.180TT genotype (rs497078) CTRC according to the recessive model (TT vs. CT+CC) was 7.05 (95% CI: 0.86-263, p=0.011). In the CTRC gene, the variant c.493+49G>C (rs6679763) appeared to be benign, the c.493+51C>A (rs10803384) variant was frequently detected among both the diseased and healthy persons and did not demonstrate a protective effect. The protective factor c.571G>A (p.Gly191Arg, rs61734659) of the PRSS2 gene was detected only in the group of healthy individuals and confirmed its protective role. 12.4% of the patients with CP had risk factors in 2 or 3 genes.
CONCLUSION: Sequencing of the coding regions of the PRSS1, SPINK1, CTRC, CFTR, and CPA1 genes allowed to identify genetic risk factors of the CP development in 61% of cases. Determining the genetic cause of CP helps to predict the disease course, perform preventive measures in the proband's relatives, and facilitate a personalized treatment of the patient in future.
METHODS: Three-week-old weanling NRs were fed either a high-carbohydrate diet (%En from carbohydrate/fat/protein = 70:10:20, 16.7 kJ/g; n = 8) or the same high-carbohydrate diet supplemented with PFJ (415 ml of 13,000-ppm gallic acid equivalent (GAE) for a final concentration of 5.4 g GAE per kg diet or 2.7 g per 2000 kcal; n = 8). Livers were obtained from these NRs for microarray gene expression analysis using Illumina MouseRef-8 Version 2 Expression BeadChips. Microarray data were analysed along with the physiological parameters of diabetes.
RESULTS: Compared to the control group, 71 genes were up-regulated while 108 were down-regulated in the group supplemented with PFJ. Among hepatic genes up-regulated were apolipoproteins related to high-density lipoproteins (HDL) and genes involved in hepatic detoxification, while those down-regulated were related to insulin signalling and fibrosis.
CONCLUSION: The results obtained suggest that the anti-diabetic effects of PFJ may be due to mechanisms other than an increase in insulin secretion.
METHODS: Consecutive NAFLD patients who underwent liver biopsy were enrolled in this study and had two sets each of pSWE and TE examinations by a nurse and a doctor on the same day of liver biopsy procedure. The medians of the four sets of pSWE and TE were used for evaluation of diagnostic accuracy using area under receiver operating characteristic curve (AUROC). Intra-observer and inter-observer variability was analyzed using intraclass correlation coefficients.
RESULTS: Data for 100 NAFLD patients (mean age 57.1 ± 10.2 years; male 46.0%) were analyzed. The AUROC of TE for diagnosis of fibrosis stage ≥ F1, ≥ F2, ≥ F3, and F4 was 0.89, 0.83, 0.83, and 0.89, respectively. The corresponding AUROC of pSWE was 0.80, 0.72, 0.69, and 0.79, respectively. TE was significantly better than pSWE for the diagnosis of fibrosis stages ≥ F2 and ≥ F3. The intra-observer and inter-observer variability of TE and pSWE measurements by the nurse and doctor was excellent with intraclass correlation coefficient > 0.96.
CONCLUSION: Transient elastography was significantly better than pSWE for the diagnosis of fibrosis stage ≥ F2 and ≥ F3. Both TE and pSWE had excellent intra-observer and inter-observer variability when performed by healthcare personnel of different backgrounds.
METHODS: Shear wave elastography assessments were performed in 75 CKD patients who underwent renal biopsy. The SWE-derived estimates of the tissue Young's modulus (YM), given as kilopascals (kPa), were measured. YM was correlated to patients' renal histological scores, broadly categorized into glomerular, tubulointerstitial and vascular scores.
RESULTS: Young's modulus correlates significantly with tubulointerstitial score (ρ = 0.442, P
METHODS: The review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Literature search was conducted in Pubmed, Web of Science and Scopus database up to 23 October 2021. To evaluate risk and bias applicability, the Cochrane risk-of bias tool and GRADE was used. The review was registered under PROSPERO CRD42021265303.
RESULTS: A total of 2921 articles were identified. 104 full texts were examined and 26 studies included in systematic review. 11 studies performed on native kidneys and 15 studies on transplanted kidney. A wide range of impact factors was found that affect the accuracy of SWE of renal fibrosis in adult patients.
CONCLUSIONS: Compared to point SWE, two-dimensional SWE with elastogram could enable better selection of the region of interest in kidneys, leading to reproducible results. Tracking waves were attenuated as the depth from skin to region of interest increased, therefore, SWE is not recommended for overweight or obese patients. Variable transducer forces might also affect SWE reproducibility, thus, training of operators to ensure consistent operator-dependent transducer forces may be helpful.
ADVANCES IN KNOWLEDGE: This review provides a holistic insight on the efficiency of using SWE in evaluating pathological changes in native and transplanted kidneys, thereby contributing to the knowledge of its utilisation in clinical practice.
OBJECTIVE: To evaluate the efficacy of palivizumab in reducing the incidence of RSV hospitalization in children with CF who are younger than 2 years.
METHODS: Four electronic databases (PubMed, Embase, CINAHL, and CENTRAL) were searched from inception until January 31, 2017, for clinical studies investigating the use of palivizumab in infants with CF aged less than 2 years. The primary outcome was hospitalization rate due to RSV infection. Secondary outcomes included hospitalization for respiratory illness, length of hospital stay, safety (adverse effects), and cost-effectiveness of palivizumab prophylaxis.
RESULTS: The review included a total of 10 studies (six cohort studies, two before-and-after studies, one cross-sectional study, and one randomized controlled trial) involving 3891 patients with CF. Seven studies reported that palivizumab prophylaxis had a positive impact on the rate of RSV hospitalization. Five studies (n=3404) reported that palivizumab prophylaxis significantly reduced the rate of hospitalization due to RSV infection compared to no prophylaxis. One study (n=5) demonstrated patients with CF who received palivizumab had no RSV hospitalization. Another study showed infants with CF receiving palivizumab (n=117) had a lower risk of hospitalization for RSV infection compared with premature infants (gestational age < 35 completed weeks) who received palivizumab (n=4880).
CONCLUSIONS: Evidence from the literature suggests that palivizumab may have a potential role in reducing RSV hospitalization in children aged less than 2 years with CF. Given the lack of overall data, additional research is warranted to better understand the efficacy and safety of prophylactic palivizumab in infants with CF.