A New, Safe, and Effective Technique for Percutaneous Insertion of a Peritoneal Dialysis Catheter.

A properly functioning peritoneal catheter is an essential element of effective peritoneal dialysis (PD). Currently, there are three techniques available for PD catheter placement, which include open surgery, laparoscopic surgery, and percutaneous catheter placement (PCP). Currently, no particular catheter placement approach has been proven with certainty to provide superior outcomes. We present a new modified PCP method with the use of the Veress needle covered with an intravascular catheter (IC) and preliminary clinical results of PD catheter placements with this new technique. The endpoints used in the study were 1-year technical survival of the catheter, and the incidence of early (1 month) mechanical as well as infection complications. The catheter was implanted in 24 patients. The catheter survival rate was 100%; however, in two cases, the catheters were removed due to complications not associated with PD treatment. No early mechanical complications such as bleeding, hematoma, perforations, internal organ damage, exit site leaks, or hernia in the place of insertion were observed. Similarly, no early infectious complications were observed. During the 1-year follow-up, no catheter migration occurred. Our results showed that the new PCP technique is a safe and easy procedure that minimizes the occurrence of both mechanical and infectious complications and ensures good catheter survival.

The RdRp genotyping of SARS-CoV-2 isolated from patients with different clinical spectrum of COVID-19.

BACKGROUND: The evolution of SARS-CoV-2 has been observed from the very beginning of the fight against COVID-19, some mutations are indicators of potentially dangerous variants of the virus. However, there is no clear association between the genetic variants of SARS-CoV-2 and the severity of COVID-19. We aimed to analyze the genetic variability of RdRp in correlation with different courses of COVID-19. RESULTS: The prospective study included 77 samples of SARS-CoV-2 isolated from outpatients (1st degree of severity) and hospitalized patients (2nd, 3rd and 4th degree of severity). The retrospective analyses included 15,898,266 cases of SARS-CoV-2 genome sequences deposited in the GISAID repository. Single-nucleotide variants were identified based on the four sequenced amplified fragments of SARS-CoV-2. The analysis of the results was performed using appropriate statistical methods, with p < 0.05, considered statistically significant. Additionally, logistic regression analysis was performed to predict the strongest determinants of the observed relationships. The number of mutations was positively correlated with the severity of the COVID-19, and older male patients. We detected four mutations that significantly increased the risk of hospitalization of COVID-19 patients (14676C > T, 14697C > T, 15096 T > C, and 15279C > T), while the 15240C > T mutation was common among strains isolated from outpatients. The selected mutations were searched worldwide in the GISAID database, their presence was correlated with the severity of COVID-19. CONCLUSION: Identified mutations have the potential to be used to assess the increased risk of hospitalization in COVID-19 positive patients. Experimental studies and extensive epidemiological data are needed to investigate the association between individual mutations and the severity of COVID-19.

NOS2 Polymorphism in Aspect of Left and Right-Sided Colorectal Cancer.

Background: The NOS2 gene polymorphism rs2297518 is associated with an increased level of NO, which could contribute to colorectal cancer (CRC) development. We hypothesized that the potential influence of the NOS2 gene polymorphism on cancer development may vary between right-sided and left-sided colon cancers, and rectal cancers. The aim of this study was to determine the rs2297518 polymorphism influence on colorectal cancer development with regard to tumor localization. Methods: This case-control study included 199 patients with CRC and 120 controls. The qPCR endpoint genotyping was conducted using the TaqMan® genotyping assay. Results: This study revealed significant differences in tumor characteristic and in the minor alelle A frequency in the NOS2 genotype between colorectal cancers with different localizations. The mucinous adenocarcinoma was diagnosed significantly more often in right-sided cancers than in left-sided (30.6% vs. 10.9%, p = 0.009) and rectal cancers (30.6% vs. 7.1%, p = 0.0003). The minor allele A of the NOS2 genotype was observed more frequently in right-sided cancers than in left-sided cancers (44.9% vs. 23.1%, p = 0.0137) and more frequently in rectal cancers than in left-sided cancers (40.0% vs. 23.1%, p = 0.0285). Conclusions: In conclusion, the results support the hypothesis that the SNP rs2297518 of the NOS2 gene influences colorectal cancer development with regard to tumor localization.

Hospital mortality rate and predictors in acute pancreatitis in Poland: A single-center experience.

BACKGROUND: Despite advances in medicine, acute pancreatitis remains a disorder that is associated with a high mortality rate. The objective of this study was to analyze in-hospital mortality in patients hospitalized with acute pancreatitis. METHODS: A prospective analysis of patients hospitalized with acute pancreatitis in a single surgical center was performed. Etiological factors, concomitant diseases, age, and intensive care unit treatment status were assessed to determine their impact on the cause and time of patient death. In addition, conventional laboratory tests performed in the emergency ward were evaluated for their potential as predictors of mortality. RESULTS: The study included 476 (n) patients hospitalized with acute pancreatitis in a single surgical center. The presentations included mild disease in 261 (54.8%) patients, moderate disease in 132 (27.7%) patients, and severe disease in 83 (17.5%) patients. The overall mortality rate was 7.14% (n = 34), including 41% in the severe disease group. The mean and median hospitalization times for these patients were 13.9 and 7 days, respectively. Respiratory failure is the main cause of patient death. CONCLUSIONS: Acute pancreatitis remains one of the most common gastroenterological diseases that may lead to death. Acute pancreatitis-related respiratory failure is the most common cause of death among patients with alcohol etiology of the disease. Moreover, the mortality rate was higher among older patients. Therefore, actions should be taken to discover prognostic factors of the severe form and initiate appropriate treatment.

Comparative study of virulence potential, phylogenetic origin, CRISPR-Cas regions and drug resistance of Escherichia coli isolates from urine and other clinical materials.

Introduction: Urinary tract infections (UTI), among which the main etiological factor is uropathogenic Escherichia coli (UPEC, E. coli), remain an important issue for clinicians. The aim of the study was to demonstrate clear differences in the pathogenic properties of urine-derived E. coli compared to other extraintestinal E. coli clinical isolates (derived from: blood, lower respiratory tracts, sputum, reproductive tract, body fluids, perianal pus, other pus, wound, postoperative wound and other sources). Methods: The collection of 784 E. coli isolates was collected from various materials of hospitalized patients. They were analyzed in terms of virulence-associated genes (papC, sfaD/sfaE, cnf1, usp., fimG/H, hlyA), belonging to phylogenetic groups and the presence of CRISPR-Cas regions using PCR. In addition, the epidemiological data and the antibiotic resistance profiles provided by the hospital's microbiology department were included for statistical analyses. Results: Urine-derived E. coli showed significantly greater virulence potential compared to other isolates, but they were generally unremarkable in terms of drug resistance. The isolates most often belonged to phylogenetic group B2. Drug resistance was negatively correlated with CRISPR 2 presence and high average virulence score, but positively correlated with CRISPR 4 presence. To the best of our knowledge, we are the first to report significant differences in sputum-derived isolates-they revealed the lowest virulence potential and, at the same time, the highest drug resistance. Discussion: In conclusion, we demonstrated significant differences of urinary-derived E. coli compared to other clinical E. coli isolates. We would like to suggest excluding penicillins from use in E. coli infection at this time and monitoring strains with a high pathogenicity potential.

The internment of patients undergoing treatment for alcohol addiction as a result of a specific interpretation of legal provisions by some judicial authorities. / Internowanie pacjentów leczacych sie odwykowo jako skutek okreslonej wykladni przepisów prawa przez niektóre organy wymiaru sprawiedliwosci.

In the Polish legal system, each medical procedure requires patient's consent. Exemptions from the obligation to obtain such a consent are limited by the legislator to exceptional situations, i.e., when the delay caused by the procedure for obtaining consent would pose a threat to patient's life, serious injury, or serious health impairment. Undergoing addiction treatment is also voluntary. Exceptions to this principle are stipulated by a legal act. People who abuse alcohol and therefore break down family life, demoralize minors, avoid the obligation to meet the needs of their families, or systematically disturb peace or public order, may be obliged to undergo addiction treatment in an inpatient or outpatient treatment centre on condition that they are addicted to alcohol. A patient who fails to report to the medical entity designated by the court to execute the decision on the obligation to undertake addiction treatment may be brought to this entity by the police. In the context of the obligation to obtain a consent for treatment by a person against whom a court decision containing an obligation in this respect has been issued, there are discrepancies in the application of law provisions. In some medical entities, this results in the forced continuation of addiction treatment by a given patient in hospital, as discharge from the hospital depends on a court order issued in this regard, not on the consent of the patient himself/herself. In other medical entities, patients are not admitted for treatment due to the lack of such a consent, despite the court's obligation in this respect. The article confirms that a specific practice of applying the law, which downgrades the role of the patient's consent in the therapeutic process, has negative consequences for the effectiveness of the therapy.

Long-Term Effect of SARS-CoV-2 Infection on the Retinal and Choroidal Microvasculature.

The purpose of this study was to evaluate the persistent changes in microvascular parameters based on optical coherence tomography angiography (OCTA) in patients hospitalized due to COVID-19 bilateral pneumonia. The case-control prospective study was carried out among 49 patients with COVID-19 and 45 healthy age- and gender-matched 2 and 8 months after hospital discharge. We found a significantly decreased vessel density (VD) in superficial capillary plexus (SCP) in COVID-19 patients. Significantly decreased vessel density (VD) in the superficial capillary plexus (SCP), the deep capillary plexus (DCP), and choriocapillaris (CC), with significantly increased vessel density observed in the choriocapillaris in the foveal area (FCC). The foveal avascular zone in DCP (FAZd) was significantly increased in the COVID-19 group. We found differences between OCTA parameters according to gender. The foveal VD in SCP and DCP was significantly decreased in women compared to men. The FAZ area in SCP (FAZs) and superior VD in the choriocapillaris (SCC) were significantly increased in women. In conclusion, we noticed persistent changes in the ocular parameters of OCTA in COVID-19 patients. At the second follow-up visit, we observed a widened FAZ zone in SCP and decreased VD in some regions of the retina and choroid.

Could pelvic floor sonography be a standalone method for excluding genuine stress urinary incontinence in women?

OBJECTIVES: Determine whether introital pelvic floor sonography with transvaginal probe (PFS-TV) can be an independent method in the diagnosis of genuine stress urinary incontinence (SUI) and to create a ultrasonographic diagnostic model to objectify diagnostic process. MATERIAL AND METHODS: The study involved 315 patients with a history of urinary incontinence problems. Based on the clinical examination and urodynamic examination, the final diagnosis was made. Patients were divided into two groups. Group I included women with SUI and Group II included patients without SUI (OAB and no-UI). Each patient underwent PFS-TV at rest and during straining. The groups were compared in terms of ultrasound parameters. RESULTS: Patients from both groups differed statistically in a significant way (p < 0.05) in terms of mean distance between the lower edge of the pubic symphysis at rest 19 mm vs 22 mm (Group I vs Group II) and during straining (D1 and D2) 22 mm vs 26 mm, the average value of the γ angle (at rest (γ1) 37.5° vs 40° and during straining (γ2) and 66° vs 58.5°, average difference value of angle γ during straining and at rest (γ2-γ1) 29° vs 14°, and frequency of urethral funneling 89% vs 17%. Two parameters studied during PFS-TV were included in the logistic regression model used to exclude the stress component of urinary incontinence. Diagnostic test parameters of model were sensitivity 86.6%, specificity 90.4%, accuracy 93.1%. CONCLUSIONS: PFS-TV makes it possible to exclude the stress component of urinary incontinence. The developed logistic regression model allows for the objectification of the results of ultrasound examination in patients with urinary incontinence.

Glutathione S-Transferase P1 Genetic Variant's Influence on the HbA1c Level in Type Two Diabetic Patients.

GST (glutathione S-transferases) are capable of influencing glucose homeostasis, probably through regulation of the response to oxidant stress. The aim of our study was to investigate the relationship between GSTP1 gene polymorphism and glycated hemoglobin (HbA1c) levels in type two diabetic (T2D) patients. A total of 307 T2D patients were included. Analysis of the GSTP1 gene polymorphism (rs1695) was conducted using the TaqMan qPCR method endpoint genotyping. HbA1c was determined using a COBAS 6000 autoanalyzer. A univariable linear regression and multivariable linear regression model were used to investigate the association between mean HbA1c level and GSTP1 gene polymorphism, age at T2D diagnosis, T2D duration, therapy with insulin, gender, BMI, smoking status. GSTP1 Val/Val genotype, age at T2D diagnosis, T2D duration and therapy with insulin were statistically significant contributors to HbA1c levels (p < 0.05). Multivariable regression analysis revealed that GSTP1 (Val/Val vs. Ile/Ile) was associated with higher HbA1c even after adjustment for variables that showed a statistically significant relationship with HbA1c in univariable analyses (p = 0.024). The results suggest that GSTP polymorphism may be one of the risk factors for higher HbA1c in T2D patients. Our study is limited by the relatively small sample size, cross-sectional design, and lack of inclusion of other oxidative stress-related genetic variants.

The Levels of Anti-SARS-CoV-2 Spike Protein IgG Antibodies Before and After the Third Dose of Vaccination Against COVID-19.

Purpose: The COVID-19 pandemic has been going on for almost three years, and so far, many preventive and therapeutic strategies have been developed. The issue of subsequent booster vaccinations is currently being discussed. We aimed to analyze how the third dose of vaccination against COVID-19 correlates with the dynamics of IgG anti-SARS-CoV-2 spike protein antibody levels in a group of healthy people. Patients and Methods: The prospective study included 93 participants before and after a second booster of COVID-19 vaccination, from whom 4 blood samples were collected at intervals. The levels of IgG anti-SARS-CoV-2 in serum were identified using the chemiluminescent immunoassay specific for the receptor-binding domain (RBD) of the S1 protein. The analysis of the results was performed using appropriate statistical methods, considering p <0.05 as a statistically significant value. Results: The IgG levels were significantly higher and less diverse after the same follow-up time from the second booster vaccination compared to the first booster. The antibody levels were positively correlated with female, healthcare workers, the elderly and participants with a negative COVID-19 history. Furthermore, the increase in IgG antibodies after the second booster vaccination correlated inversely with the baseline level of antibodies before the vaccination. The latest results showed that antibody levels dropped 1.5-fold after approx. 10 months from the second booster vaccination but still remained at a protective level. Conclusion: Booster vaccinations seem to better stimulate immune memory, and in the case of borderline IgG level induces the greatest increase in antibodies. It is worth considering the individual parameters of patients and measuring antibodies before vaccination.

Endoscopic changes in patients diagnosed with acute pancreatitis.

BACKGROUND: There have been long debates on the introduction of proton pump inhibitors into acute pancreatitis therapy as standard treatment. The aim of the study was to assess endoscopic lesions of the upper gastrointestinal tract in patients hospitalized for acute pancreatitis. METHODS: We carried out a prospective analysis of patients hospitalized in one surgical center who had an upper gastrointestinal tract endoscopic examination performed during the first 48 hours of hospitalization. We performed analysis of basic descriptive statistics along with the Shapiro-Wilk Test, logistic order regression analysis, One-Way Analysis of Variance, and Student's t-test for independent trials. RESULTS: From January 2016 to December 2019, 476 patients were hospitalized because of acute pancreatitis. The upper gastrointestinal tract endoscopic examination was performed in 85 patients (N.) in the first 48 hours. From the examined group 45 patients (52.94%) developed mild acute pancreatitis, 28 (32.94%) moderate pancreatitis, and 12 (14.12%) severe pancreatitis. Lesions in the endoscopic imaging were observed in 80 patients (94.12%). CONCLUSIONS: A very high percentage of patients hospitalized for acute pancreatitis present lesions in the endoscopic imaging of the upper gastrointestinal tract. The standard treatment of AP is the administration of non-steroidal anti-inflammatory drugs, which themselves can cause gastric and duodenal mucosal defects. All these factors indicate the need for standard use of proton pump inhibitors in patients hospitalized for acute pancreatitis.

Closing A Temporary Stoma - The Procedure Tactics.

The paper presents the results of clinical trials and meta-analyses regarding the closing time of: ileostomy (protective) after primary colorectal resection with anastomosis and colostomy - after Hartman's surgery. Rectal cancer surgery and ileal pouch-anal anastomosis (IPAA) in inflammatory bowel diseases often involves an ileostomy (temporary protective, preventive), which in a significant proportion of cases is eliminated at different times from the initial surgery. There is a discussion in the literature regarding the selection of the appropriate time of stoma closure, taking into account the experience of many clinical centers. An ileostomy is performed when the entire colon and rectum must be removed, or to protect the colon or ileorectal anastomosis. The creation of a protective stoma reduces the frequency of clinically significant anastomotic leakages and the need for surgical revisions in patients at increased risk of leakage. Also, the time of digestive system reconstruction, i.e., colostomy elimination, after Hartman's surgery depends on many factors, including the stage of disease and indications for adjuvant treatment. Should it be standard practice to close the stoma early? Based on previous studies and meta-analyses, as well as own experience - it is advisable to individualize the procedure, taking into account many factors that determine the clinical and oncological status (selection of the date - early or deferred, but not as a standard [!]).

Reproducibility of the German and Slovakian Versions of the Dietary Habits and Nutrition Beliefs Questionnaire (KomPAN).

PURPOSE: The aim of this study was to assess the reproducibility and reliability of the KomPAN questionnaire among two groups of university students from Germany and Slovakia. METHODS: A total of 422 individuals (mean age 21.4 years, SD 4.0), including 197 from Slovakia (men 26.2%) and 225 from Germany (men 22.3%), were tested using the self-administered (SA-Q) version of the KomPAN questionnaire and then retested two weeks later. A cross-classification analysis, kappa coefficients, Cronbach's ɑ coefficients, and a test-retest result comparison were conducted separately for each group of students to assess the reproducibility and reliability of the questionnaire. RESULTS: The cross-classification values were higher than 46.2% among the German students and higher than 55.8% among the Slovakian students. The kappa coefficients ranged from 0.21 to 0.90 in the German students and from 0.38 to 0.94 in the Slovakian students. Cronbach's ɑ ranged from 0.58 to 0.78. CONCLUSION: The questionnaire displayed a moderate to very good reproducibility, which was slightly higher in the Slovakian group than in the German group. Therefore, the questionnaire can be recommended for further analysis and comparison of the dietary habits among Germans and Slovakians on a larger scale.

Nano-Ag Particles Embedded in C-Matrix: Preparation, Properties and Application in Cell Metabolism.

The application of nano-Ag grains as antiviral and antibacterial materials is widely known since ancient times. The problem is the toxicity of the bulk or big-size grain materials. It is known that nano-sized silver grains affect human and animal cells in some medical treatments. The aim of this study is to investigate the influence of nano-Ag grains embedded in a carbonaceous matrix on cytotoxicity, genotoxicity in fibroblasts, and mutagenicity. The nanocomposite film is composed of silver nanograins embedded in a carbonaceous matrix and it was obtained via the PVD method by deposition from two separated sources of fullerenes and silver acetate powders. This method allows for the preparation of material in the form of a film or powder, in which Ag nanograins are stabilized by a carbon network. The structure and morphology of this material were studied using SEM/EDX, XRD, and Raman spectroscopy. The toxicology studies were performed for various types of the material differing in the size of Ag nanograins. Furthermore, it was found that these properties, such as cell viability, genotoxicity, and mutagenicity, depend on Ag grain size.

Lifestyle elements and risk of metabolic syndrome in adults.

BACKGROUND: The aim of the study was to investigate which elements of lifestyle are associated with metabolic health in adults, defined as the absence of components of metabolic syndrome (MetS) based on the International Diabetes Federation criteria. METHODS: Data from 10,277 individuals aged 40-65 years constituted the material of this study. Univariate and multivariate analyses with backward stepwise selection were carried out to identify the factors associated with the absence of metabolic disorders. RESULTS: No family history of cardiovascular disease increased the odds of being metabolically healthy 1.5-2-fold. Furthermore, the following factors were associated with higher odds of being metabolically healthy in men: abstinence from alcohol (healthy individuals vs. those with ≥3 [OR = 5.49 (2.23-13.52); p<0.001], ≥2 [OR = 4.52 (1.87-10.91); p = 0.001], and ≥1 components of MetS [OR = 3.04 (1.41-6.56); p = 0.005]), moderate alcohol use (healthy individuals vs. those with ≥3 [OR = 3.36 (1.54-7.32); p = 0.002], ≥2 [OR = 3.28 (1.52-7.10); p = 0.002], and ≥1 components of MetS [OR = 3.93 (1.64-9.42); p = 0.002]), moderate-to-vigorous physical activity (MVPA) >2 hours/day and sitting time of 3-6 hours/day. Drinking >2 cups of coffee per day (healthy vs. those with ≥3 [OR = 2.00 (1.47-2.71)], ≥2 [OR = 1.84 (1.38-2.45)], and ≥1 components of MetS [OR = 1.72 (1.30-2.28); all p<0.001]), limiting animal fats to <2 servings/day, MVPA >2 hours/day, and 7-8 hours of sleep per day were associated with higher odds of being metabolically healthy in women. CONCLUSIONS: A healthy lifestyle increased the odds of being metabolically healthy. Some lifestyle modifications may appear effective in prevention of not only MetS, but also single metabolic risk factors.

Retinal Microvascular Changes in COVID-19 Bilateral Pneumonia Based on Optical Coherence Tomography Angiography.

The purpose of this study was to evaluate retinal and choroidal microvascular alterations with optical coherence tomography angiography (OCTA) in COVID-19 patients hospitalized because of bilateral pneumonia caused by SARS-CoV-2. The vessel density (VD) and foveal avascular zone (FAZ) of 63 patients with SARS-CoV-2 pneumonia who had positive polymerase chain reaction (PCR) tests and who recovered after receiving treatment and 45 healthy age- and gender-matched controls were evaluated and compared using OCTA in the superficial capillary plexus (SCP) and deep capillary plexus (DCP). The VD was also estimated in both groups in the choriocapillaris (CC). In COVID-19 patients, there was a statistically significant difference between the patients and a control group in both superficial (FAZs) and deep (FAZd) avascular zone (p = 0.000). The VD was significantly lower in the foveal area in choriocapillaris (p = 0.046). There were no statistically significant changes in the VD in the superior, inferior, nasal, and temporal quadrants in superficial and deep plexus, or in the choriocapillaris. The VD was not significantly lower in the foveal area in superficial or deep plexus. COVID-19 may affect the retinal vasculature, causing ischemia, enlargement of the FAZ, and lowering of the VD in the choriocapillaris area. Routine ophthalmic examination after SARS-CoV-2 infection should be considered in the course of post-infectious rehabilitation.

Loss-of-function variant in chymotrypsin like elastase 3B (CELA3B) is associated with non-alcoholic chronic pancreatitis.

BACKGROUND: Genetic alterations in digestive enzymes have been associated with chronic pancreatitis (CP). Recently, chymotrypsin like elastase 3B (CELA3B) emerged as a novel risk gene. Thus, we evaluated CELA3B in two European cohorts with CP. METHODS: We analyzed all 8 CELA3B exons in 550 German non-alcoholic CP (NACP) patients and in 241 German controls by targeted DNA sequencing. In addition, we analyzed exons 6 and 7 by Sanger sequencing and the c.129+1G>A variant by melting curve analysis in 1078 further German controls. As replication cohort, we investigated up to 243 non-German European NACP patients and up to 1665 controls originating from Poland, Hungary, and Sweden. We assessed the cellular secretion and the elastase activity of recombinant CELA3B variants. RESULTS: In the German discovery cohort, we detected a splice-site variant in intron 2, c.129+1G>A, in 9/550 (1.64%) CP patients and in 5/1319 (0.38%) controls (P=0.007, OR=4.4, 95% CI=1.5-13.0). In the European replication cohort, this variant was also enriched in patients (9/178 [5.06%]) versus controls (13/1247 [1.04%]) (P=0.001, OR=5.1, 95% CI=2.1-12.0). We did not find the two previously reported codon 90 variants, p.R90C and p.R90L. CONCLUSIONS: Our data indicate that CELA3B is a susceptibility gene for CP. In contrast to previous reports suggesting that increased CELA3B activity is associated with CP risk, the splice-site variant identified here is predicted to cause diminished CELA3B expression. How reduced CELA3B function predisposes to pancreatitis remains to be elucidated.

Risk of chronic pancreatitis in carriers of loss-of-function CTRC variants: A meta-analysis.

The digestive protease chymotrypsin C (CTRC) protects the pancreas against pancreatitis by degrading potentially harmful trypsinogen. Loss-of-function genetic variants in CTRC increase risk for chronic pancreatitis (CP) with variable effect size, as judged by the reported odds ratio (OR) values. Here, we performed a meta-analysis of published studies on four variants that alter the CTRC amino-acid sequence, are clinically relatively common (global carrier frequency in CP >1%), reproducibly showed association with CP and their loss of function phenotype was verified experimentally. We found strong enrichment of CTRC variants p.A73T, p.V235I, p.K247_R254del, and p.R245W in CP cases versus controls, yielding OR values of 6.5 (95% confidence interval (CI) 2.4-17.8), 4.5 (CI 2.2-9.1), 5.4 (CI 2.6-11.0), and 2.6 (CI 1.6-4.2), respectively. Subgroup analysis demonstrated disease association of variants p.K247_R254del and p.R245W in alcoholic CP with similar effect sizes as seen in the overall CP group. Homozygosity or compound heterozygosity were rare and seemed to be associated with higher risk. We also identified a so far unreported linkage disequilibrium between variant p.K247_R254del and the common c.180C>T (p.G60 =) haplotype. Taken together, the results indicate that heterozygous loss-of-function CTRC variants increase the risk for CP approximately 3-7-fold. This meta-analysis confirms the clinical significance of CTRC variants and provides further justification for the genetic screening of CP patients.

Variants in the pancreatic CUB and zona pellucida-like domains 1 (CUZD1) gene in early-onset chronic pancreatitis - A possible new susceptibility gene.

OBJECTIVE: Non-alcoholic chronic pancreatitis (NACP) frequently develops in the setting of genetic susceptibility associated with alterations in genes that are highly expressed in the pancreas. However, the genetic basis of NACP remains unresolved in a significant number of patients warranting a search for further risk genes. DESIGN: We analyzed CUZD1, which encodes the CUB and zona pellucida-like domains 1 protein that is found in high levels in pancreatic acinar cells. We sequenced the coding region in 1163 European patients and 2018 European controls. In addition, we analyzed 297 patients and 1070 controls from Japan. We analyzed secretion of wild-type and mutant CUZD1 from transfected cells using Western blotting. RESULTS: In the European cohort, we detected 30 non-synonymous variants. Using different prediction tools (SIFT, CADD, PROVEAN, PredictSNP) or the combination of these tools, we found accumulation of predicted deleterious variants in patients (p-value range 0.002-0.013; OR range 3.1-5.2). No association was found in the Japanese cohort, in which 13 non-synonymous variants were detected. Functional studies revealed >50% reduced secretion of 7 variants, however, these variants were not significantly enriched in European CP patients. CONCLUSION: Our data indicate that CUZD1 might be a novel susceptibility gene for NACP. How these variants predispose to pancreatitis remains to be elucidated.

Dietary Patterns and Metabolic Disorders in Polish Adults with Multiple Sclerosis.

Diet plays a major role in the aetiopathogenesis of many neurological diseases and may exacerbate their symptoms by inducing the occurrence of metabolic disorders. The results of research on the role of diet in the course of multiple sclerosis (MS) are ambiguous, and there is still no consensus concerning dietary recommendations for patients with MS. The aim of this study was to analyse the dietary patterns (DPs) of patients with MS and to assess the relationships between these DPs and the metabolic disorders. The study participants were comprised of 330 patients aged 41.9 ± 10.8 years. A survey questionnaire was used to collect data related to diet, lifestyle and health. The DPs were identified using a principal component analysis (PCA). Three DPs were identified: Traditional Polish, Prudent and Fast Food & Convenience Food. An analysis of the odds ratios adjusted for age, gender, smoking and education showed that a patient's adherence to the Traditional Polish and the Fast Food & Convenience Food DPs increased the likelihood of abdominal obesity and low HDL-cholesterol concentration. Conversely, adherence to the Prudent DP was not significantly associated with any metabolic disorder. The results of this study confirmed that an unhealthy diet in patients with MS is connected with the presence of some metabolic risk factors. There is also an urgent need to educate patients with MS on healthy eating, because the appropriate modifications to their diet may improve their metabolic profile and clinical outcomes.