Alcoholic Liver Disease Is Associated with Elevated Plasma Levels of Novel Advanced Glycation End-Products: A Preliminary Study.

Elucidating the biochemical mechanisms associated with the progression of alcoholic liver disease (ALD) to more advanced stages such as alcoholic hepatitis (AH) remains an important clinical and scientific challenge. Several hypotheses point to the involvement of advanced glycation end-products (AGEs) in alcohol-associated liver injuries. Recently, we determined the structure of a synthetic, melibiose-derived AGE (MAGE), which was an analog of the novel AGE subgroup AGE10. The primary objective of our study was to determine whether AGE10 was associated with alcoholic hepatitis. The secondary objective was to provide a diagnostic accuracy of AGE10 in AH. To achieve this objective, we examined the plasma levels of AGE10 in 65 healthy individuals and 65 patients with AH. The AGE10 level was measured using a competitive ELISA. Our study confirmed that patients with AH had significantly higher plasma concentrations of AGE10 compared with healthy controls (184.5 ± 71.1 µg/mL and 123.5 ± 44.9 µg/mL, respectively; p < 0.001). In addition, AGE10 showed an acceptable performance as a diagnostic marker of AH, with an AUC of 0.78. In conclusion, AH was associated with elevated levels of novel advanced glycation end-product AGE10.

Bayesian network meta-analysis of face masks' impact on human physiology.

Several concerns regarding the safety of face masks use have been propounded in public opinion. The objective of this review is to examine if these concerns find support in the literature by providing a comprehensive overview of physiological responses to the use of face masks. We have performed a systematic review, pairwise and network meta-analyses to investigate physiological responses to the use of face masks. The study has been registered with PROSPERO (C RD42020224791). Obtained results were screened using our exclusion and inclusion criteria. Meta-analyses were performed using the GeMTC and meta R packages. We have identified 26 studies meeting our inclusion and exclusion criteria, encompassing 751 participants. The use of face masks was not associated with significant changes in pulsoxymetrically measured oxygen saturation, even during maximal-effort exercises. The only significant physiological responses to the use of face masks during low-intensity activities were a slight increase in heart rate, mildly elevated partial pressure of carbon dioxide (not meeting criteria for hypercarbia), increased temperature of facial skin covered by the mask, and subsequent increase of the score in the rating of heat perception, with N95 filtering facepiece respirators having a greater effect than surgical masks. In high-intensity conditions, the use of face masks was associated with decreased oxygen uptake, ventilation, and RR. Face masks are safe to use and do not cause significant alterations in human physiology. The increase in heart rate stems most likely from increased respiratory work required to overcome breathing resistance. The increase in carbon dioxide is too small to be clinically relevant. An increased rating of heat perception when using face masks results from higher temperature of facial skin covered by the mask.

Advanced Glycation End-Products in Common Non-Infectious Liver Diseases: Systematic Review and Meta-Analysis.

BACKGROUND: Excessive intake of fructose, glucose and alcohol is associated with the development of non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD). At the same time, these dietetic factors create an environment favorable for the generation of advanced glycation end-products. For this reason, advanced glycation end-products (AGEs) are hypothesized to play role in the development of NAFLD and ALD. In this systematic review and meta-analysis, we explore the relationship between NAFLD and ALD with AGE levels, including their diagnostic accuracy. METHODS: The systematic review and meta-analysis has been pre-registered with PROSPERO (CRD42021240954) and was performed in accordance with the PRISMA guidelines. Meta-analyses were performed using the meta R package. RESULTS: We have obtained 11 studies meeting our inclusion criteria, reporting data on 1844 participants (909 with NAFLD, 169 with ALD and 766 healthy controls). NAFLD was associated with significantly higher AGE fluorescence and serum N-(carboxyethyl)lysine (CEL) levels. Patients with alcoholic cirrhosis had significantly higher levels of N-(carboxymethyl)lysine (CML). Only individual studies examined AGEs in the context of their diagnostic accuracy. AGE fluorescence distinguished low and moderate steatosis with an AUC of 0.76. The ratio of CML, CEL and pentosidine to a soluble variant of the AGE receptor differentiated patients with NAFLD from healthy controls with high AUC (0.83-0.85). Glyceraldehyde-derived AGE separated non-alcoholic fatty liver (NAFL) from non-alcoholic steatohepatitis (NASH) with acceptable performance (AUC 0.78). CONCLUSIONS: In conclusion, NAFLD and ALD are associated with significantly higher levels of several AGEs. More research is needed to examine the diagnostic accuracy of AGEs, however individual studies show that AGEs perform well in distinguishing NAFL from NASH.

Changes in the composition of the human intestinal microbiome in alcohol use disorder: a systematic review.

Background: A growing body of evidence highlights the role of the intestine in the development of various alcohol use disorder (AUD) complications. The intestinal microbiome has been proposed as an essential factor in mediating the development of AUD complications such as alcoholic liver disease.Objectives: To provide a comprehensive description of alcohol-induced intestinal microbiome alterations.Methods: We conducted a systematic review of studies investigating the effect of alcohol on the intestinal microbiome using the PRISMA checklist. We searched the Medline database on the PubMed platform for studies determining the effect of alcohol on microbiota in individuals with AUD. The manual search included references of retrieved articles. Only human studies examining the intestinal bacterial microbiome using 16S ribosomal RNA sequencing were included. Data comparing relative abundances of bacteria comprising intestinal microbiota was extracted.Results: We retrieved 17 studies investigating intestinal microbiome alterations in individuals with AUD. Intestinal microbiome alterations in individuals with AUD included depletion of Akkermansia muciniphila and Faecalibacterium prausnitzii and an increase of Enterobacteriaceae. At the phylum level, a higher abundance of Proteobacteria and lower of Bacteroidetes were found. Mixed results regarding Bifidobacterium were obtained. Several species of short-chain fatty acids producing bacteria had a lower abundance in individuals with alcohol use disorder.Conclusion: Intestinal microbiome alterations associated with dysbiosis in individuals with AUD are generally consistent across studies, making it a promising target in potential AUD complications treatment.

Can we better protect patients with inflammatory bowel disease against infections - patient attitude and personal immunization knowledge.

BACKGROUND AND STUDY AIMS: Inflammatory bowel disease (IBD) predisposes patients to a severe course of infections yet adherence to vaccination guidelines is low. Little is known about IBD patient attitude towards immunizations. We aimed to investigate patient attitude towards vaccinations and its influence on personal immunization coverage. PATIENTS AND METHODS: A self-completed survey was completed by 195 IBD patients. The author-designed questionnaire comprised: demographic data, IBD medical history, vaccination history, reasons of influenza vaccine refusal, and the most reliable source of information about immunizations. Moreover, patients were asked if they agree with the statement that immunizations are beneficial for a person with IBD. RESULTS: 99 patients (50%) claimed that prevention of infectious diseases is beneficial for a person with IBD but this opinion had no influence on recommended vaccination uptake. There was suboptimal vaccination coverage : hepatitis B (55%); diphteria, pertussis, tetanus (12%); hepatitis A (7%); annual influenza (6%); varicella-zoster (3%), and pneumococcal vaccine (2%). Top reasons for nonvaccination were: lack of information from a physician (47,5%), unawareness (35%), perceived lack of benefit (33%) and concerns about adverse events (26%). The most reliable source of information concerning immunizations was a gastroenterologist for the majority of IBD patients (58%) while more than 35% chose their general practitioner. CONCLUSIONS: Active promotion and information regarding beneficial role of immunizations among IBD patients and other chronically ill individuals significantly improves the quality of care. It is important to explain misconceptions about vaccines by the most reliable sources. We propose implementing an uniformed "immunization chart" for every chronically ill individual.

Women with inflammatory bowel diseases have a suboptimal cervical cancer screening rate and are not aware of the recommended human papilloma virus vaccine.

The aim of the study was to assess the self-reported cervical cancer screening rate among patients with inflammatory bowel diseases (IBD) and patient attitude towards human papilloma virus (HPV) vaccination. A self-designed survey was conducted in hospitalized IBD patients. The survey comprised demographic data, questions regarding cervical smear test frequency and vaccinations recommended for an IBD patient. Randomly, patients completed the survey with a physician present to determine question comprehension. In order to provide test-retest reliability a group of 10 patients completed it twice. Survey data from 150 IBD patients (mean age: 36 years, SD ± 13; mean IBD duration: 10 years, SD ± 6.5) were analyzed. Fifteen percent of the patients reported irregular cervical testing and 15% do not remember when having had a previous cervical testing performed. Only 69% of the patients undergo testing regularly; 30% annually, 32% every 2-3 years; 7% every 5 years. The mean age of patients tested regularly was 22 years, vs. 32 years tested irregularly (p < .001). Only 10% of women claimed that HPV vaccine is recommended for an IBD patient. There is a low adherence to the recommendations regarding cervical cancer screening and prophylaxis. Better multi-disciplinary cooperation between patients and physicians is required to improve patient education and outcomes.

Serotonin-Related Gene Variants in Patients with Irritable Bowel Syndrome and Depressive or Anxiety Disorders.

AIM: To assess the association of six polymorphisms in serotonin-related genes with depressive or anxiety disorders in patients with irritable bowel syndrome (IBS). METHODS: The lifetime prevalence of depressive and anxiety disorders was assessed in 95 IBS patients (85% women) using the Munich version of the Composite International Diagnostic Interview (CIDI). IBS was diagnosed according to the Rome III criteria. SCL6A4 HTTLPR polymorphism (rs4795541) was determined using PCR-based method. Single-nucleotide polymorphisms in HTR1A (rs6295), HTR2A (rs6313 and rs6311), HTR2C (rs6318), and TPH1 (rs1800532) were detected by minisequencing method. RESULTS: IBS patients with depressive disorders were characterized by higher frequency of 5-HTTLPR L allele in comparison to IBS patients with anxiety disorders. The lower frequency of 1438 A allele in HTR2A was found in IBS patients with depressive disorders in comparison to IBS patients without mental disorders. The lower G allele frequency in HTR2C rs6318 polymorphism among IBS patients with anxiety disorders was also observed. CONCLUSIONS: Our results provide further evidence for the involvement of SLC6A4 rs4795541 and HTR2A rs6311 polymorphisms in the pathophysiology of depressive disorders in IBS patients. The new findings indicate that HTR2C rs6318 polymorphism may be associated with the susceptibility to anxiety disorders in IBS patients.

Inadequate seroprotection against hepatitis B virus and one detected case of hepatitis C virus infection among patients with inflammatory bowel disease.

OBJECTIVES: The prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among patients with inflammatory bowel disease (IBD) from central and eastern European countries is unknown. Postvaccination HBV immunity in an immunocompromised host may wane. The aims of the study were as follows: to assess the immune status for HBV and HCV among IBD patients, the level of HBV seroprotection, and to compare the immune status of patients who received mandatory versus recommended HBV vaccination. MATERIALS AND METHODS: Serological markers of HBV and HCV (anti-HBs, anti-HBc, HBsAg, and anti-HCV) were determined in 147 consecutive IBD patients. An anti-HBs of 10 IU/l or more was considered as immunity to HBV infection. RESULTS: HBV infection was detected in 21 patients, whereas 11 of them recalled previous HBV vaccination. Sixty-eight noninfected patients had a level of anti-HBs 10 IU/l or more and only 29% reached the cut-off level of 100 IU/l. Among patients vaccinated obligatorily, two patients had previous HBV infection and 15% did not have an adequate seroprotection against HBV. Patients who received a mandatory HBV vaccine more frequently had a protective anti-HBs level than those vaccinated voluntarily (P<0.001). One positive anti-HCV result was found. CONCLUSION: A mandatory HBV vaccination significantly increased the number of patients effectively protected against HBV; however, a remarkable number of vaccinated IBD patients had inadequate HBV seroprotection. All IBD patients should be screened for HBV and HCV infections and monitored for anti-HBs titers.

Genetic polymorphism of ABCB1 gene (C3435T) in patients with inflammatory bowel diseases. Is there any gender dependency?

BACKGROUND: In recent years, an increasing incidence of inflammatory bowel disease (IBD) has been reported, mainly as Crohn's disease (CD) and ulcerative colitis (UC). The individual susceptibility, the disease's course and response to the applied therapy is likely due to genetic factors such as ABCB1 gene mutations, exemplified by C3435T polymorphism. The aim of the study was to evaluate the distribution of C3435T polymorphism regarding the gender in IBD patients and control subjects from Lower Silesia region and its possible association with IBD susceptibility. METHODS: The research was conducted in groups of 61 IBD patients and 101 healthy subjects from the Lower Silesia region. Polymorphism of C3435T was determined using PCR-RFLP method. RESULTS: Frequency distributions of C3435T genotype and of 3435T or 3435C gene alleles of IBD, CD or UC patients were compared to control group; each treated as a whole or split further by gender. The statistically significant correlation was discovered between gender and C3435T genotype both for IBD and CD patients, with 3435CT heterozygote prevailing in IBD and CD males. Odds ratio calculations revealed statistically significant difference for the 3435CT genotype between control and: IBD group considered as a whole; IBD males; CD males; and for 3435TT variant between control and IBD males. Conclusions. The 3435CT genotype could be a risk factor for IBD and CD in men. The 3435TT genotype in males seems to be associated with the lower chance of IBD presence.

A 'cocoon immunization strategy' among patients with inflammatory bowel disease.

BACKGROUND AND AIMS: A 'cocoon strategy' is defined as the strategy of protecting vulnerable patients from infectious diseases by vaccinating those in close contact with them. In our study, we evaluate the vaccination status among children living with patients with inflammatory bowel disease (IBD) to determine the realization of the cocoon strategy and to identify characteristics associated with pediatric vaccine refusal. PATIENTS AND METHODS: A self-completed survey was conducted on 136 hospitalized patients with IBD. The survey comprised questions about household child vaccination coverage, the reasons for vaccine refusal, and the history of infectious diseases among the patients. RESULTS: Fifty-six patients reported living with children. Forty percent of children were vaccinated with at least one of the recommended vaccines. Most frequently, children received pneumococcal (26%) and rotaviruses (22%) vaccines. The most common reason for nonimmunization was patients' opinion that immunizations are not necessary for them (52%). There was a statistically significant association between the nonreimbursed vaccines coverage and the educational level of the patients (P<0.0001). Despite the fact that 28% of the patients could not definitively recall varicella infection, none of them and none of the children in their household had been vaccinated against chickenpox. CONCLUSION: The use of nonmandatory vaccines recommended in family members of patients with IBD is insufficient. Further vaccine promotion and education of patients as well as their healthcare providers is required. A particular concern is associated with the pneumococcal, influenza, rotaviruses, and varicella infections. Nonimmunized and varicella-zoster virus-seronegative patients should be vaccinated, and in case of immunosuppression, vaccination of children in the household is required.

The lifetime prevalence of anxiety disorders among patients with irritable bowel syndrome.

BACKGROUND: The prevalence of irritable bowel syndrome (IBS), the most common functional gastrointestinal disorder, ranges from 10% to 20% in the general population. It is estimated that from 40% to 90% of persons with a diagnosis of IBS suffer from mental disorders, mainly anxiety and depressive disorders. OBJECTIVES: The aim of the study was to assess the lifetime prevalence of anxiety disorders in IBS patients and to compare it with the prevalence of these disorders in a control group of patients with gastroesophageal reflux disease (GERD). MATERIAL AND METHODS: The study included 106 patients with IBS and 53 patients with GERD. IBS was diagnosed according to the Rome II criteria after a basic evaluation to exclude an organic disease. Anxiety disorders were diagnosed using the Composite International Diagnostic Interview (CIDI) in accordance with ICD-10 diagnostic criteria. RESULTS: Anxiety disorders during the patient's lifetime were diagnosed in 50 IBS patients (47%). Specific phobias occurred in 23.5% of them, social phobias in 10.4%, generalized anxiety disorder in 10.4%, panic disorder in 3.8% and agoraphobia in 8.5%. In the control group with GERD, anxiety disorders during the subject's lifetime were diagnosed in 30% of the group. The difference in the prevalence of anxiety disorders between patients with IBS and GERD was statistically significant (p<0.05). CONCLUSIONS: The lifetime prevalence of anxiety disorders in IBS patients was higher than in the control group with GERD (47% vs. 30%). The prevalence rate of anxiety disorders in the control group with GERD was similar to the prevalence rate in the general population.

Subclinical Cushing's syndrome in adrenal incidentalomas--possible metabolic consequences.

INTRODUCTION: The presence of subclinical Cushing's syndrome (SCS) and some features of the metabolic syndrome were evaluated in adrenal incidentaloma patients. MATERIAL AND METHODS: 165 patients were studied. Plasma cortisol, ACTH, DHEA-S, 17-OH-P, aldosterone, renin activity and 24-h urinary methoxycatecholamines were measured. Fasting concentrations of glucose, insulin, triglycerides, T-chol., HDL-chol. and LDL-chol. were determined and the FIRI and QUICKI indices were calculated. Blood pressure, WHR and BMI were determined in all patients. Forty healthy volunteers were the controls. RESULTS: 133 patients had unchanged endocrine function, 32 demonstrated hormonal disturbances without clinical symptoms (in 26 nonclinical hypercortisolism). The WHR and blood pressure in the SCS group were significantly higher than in the patients with nonfunctioning adenoma (NA). T-chol and LDL-chol were significantly higher, but HDL-chol was significantly lower, in the SCS than in the NA patients. Fasting insulin level was significantly higher in the SCS than in the NA patients and controls, while fasting glucose level was comparable. QUICKI was significantly lower in the SCS and NA patients than in the controls, while FIRI was significantly higher in the SCS group. CONCLUSIONS: In incidentaloma patients, hormonal function of the adrenal gland should be estimated because some of them present subclinical hyperfunction. These patients frequently display features of metabolic syndrome such as insulin resistance, hypertension, high triglycerides, T-chol and LDL-chol levels. Subtle autonomous cortisol secretion may be the cause of these features.

Low bone mineral density in adult patients with coeliac disease.

INTRODUCTION: Calcium and vitamin D malabsorption in coeliac disease (CD) predispose to skeletal demineralisation. The aim of this study was to evaluate the prevalence of bone mineral density (BMD) and calcium deficiencies in adult patients with CD and assess whether a gluten-free diet is sufficiently effective for BMD restoration. MATERIAL AND METHODS: BMD and biochemical parameters of bone and mineral metabolism were measured in 35 adult CD patients receiving (19) or not receiving (16) a gluten-free diet (GFD) and in 36 controls. Then the CD patients were treated with a GFD and calcium (1.0 g/day) plus alfacalcidol (0.25-1 µg/day) for one year. RESULTS: Reduced BMD was diagnosed in 57-77% of the patients. Mean calcaemia, calciuria, and 25(OH) vitamin D were lower, but serum PTH and bone-turnover markers (ALP, osteocalcin, ICTP) were significantly higher in the CD patients than in the controls. In the patients on the diet (GFD(+)), BMD was higher than in the GFD(-) patients, but lower than in the controls. The biochemical parameters were normal in the GFD(+) patients except for diminished calciuria. Mean BMD after one year of treatment significantly increased (p < 0.05), mostly in the lumbar spine (mean: 7.3%), but decreased in five patients who did not strictly adhere to the GFD. CONCLUSIONS: Deficiencies in calcium, vitamin D, and BMD are very common in adult CD patients. Gluten avoidance increased BMD, although the values remained markedly lower in several patients. Because of chronic calcium deficiency despite GFD, calcium and vitamin D supplementation in most adult CD patients is proposed.

Anorectal function and visceral hypersensitivity in celiac disease.

OBJECTIVE: To evaluate anorectal function and rectal sensitivity thresholds in patients with celiac disease (CD). METHODS: In 25 unselected patients with CD (16 female, 9 male; mean age 45, range 24 to 75 y) and 20 controls (12 female, 8 male; mean age 41, range 20 to 65 y) anorectal manometry and rectal balloon distension test were conducted using a 4 lumen water perfused catheter with a polyethylene balloon (Zinectics Manometric Catheter, Medtronic). RESULTS: In celiac patients the maximal anal resting pressure, reflecting the internal anal sphincter function, was significantly higher than that in the controls: 87.8±21.7 mm Hg versus 66.7±15.2 mm Hg (P<0.001). There were no considerable differences between both the groups neither in the maximal anal squeeze nor in the cough pressures. Celiac patients had significantly lower first sensation threshold: 25.6±10.8 mL versus 37.5±12.5 mL (P<0.05). Visceral hypersensitivity (rectal pain/discomfort threshold ≤100 mL) was observed in 36% of celiac patients and in none of the controls (P<0.01). CONCLUSIONS: The increased anal resting pressure and rectal hypersensitivity are observed in CD. Disturbances in gastrointestinal motility and visceral perception in the course of CD may occur at different levels of the brain-gut axis including direct changes in the enteric nervous system.