Prevalence and Risk Factors of Gastroesophageal Reflux Disease in Bulgaria: An Internet-Based Survey.

BACKGROUND: The global pooled prevalence of gastroesophageal reflux disease (GORD) is approximately 14% and varies significantly according to the country. More population-based studies are needed in regions lacking epidemiological data on the prevalence of GORD, such as Eastern Europe, particularly Bulgaria. This current study aimed to evaluate the prevalence of GORD in Bulgaria and assess the risk factors associated with this disorder. METHODS: An internet-based health survey was sent to Bulgarian adults. Individuals were invited to complete an online questionnaire on general and gastrointestinal health. The aim of the study was not explicitly stated. The survey collected data on sociodemographic and behavioral characteristics, validated questions to assess GORD, diagnostic questions based on Rome IV criteria to assess irritable bowel syndrome (IBS) and functional dyspepsia (FD), and questions about antisecretory drugs usage. RESULTS: Data were collected from 1,896 individuals (mean age = 35.5 years, SD = 11.7, 73.1% females). The prevalence of GORD in the study population was 27.5%, while 57.29% of all GORD patients taking PPIs had PPI-refractory GORD. Age (p = 0.02), body mass index (BMI) (p < 0.001), marital status (p = 0.03), occupation (p < 0.001), sexual problems (p < 0.001), FD (p < 0.001), and IBS (p < 0.001) were significantly associated with GORD prevalence. Patients with FD (p < 0.001; OR 5.38), IBS (p = 0.03; OR 1.07), and with higher BMI (p < 0.001, OR 1.05) were at an increased risk of having GORD. CONCLUSIONS: The first data on GORD prevalence in the adult population in Bulgaria have been reported. Disorders of gut-brain interaction have a significant impact on the prevalence of GORD.

Diagnosis and management of irritable bowel syndrome-like symptoms in ulcerative colitis.

Both ulcerative colitis (UC) and irritable bowel syndrome (IBS) are chronic gastrointestinal (GI) conditions that show some typical features. Persistent GI symptoms typical for IBS are observed in patients with diagnosed UC. Both IBS and UC are characterised by dysregulation of the enteric nervous system, alterations in the gut flora, low-grade mucosal inflammation, and activation of the brain-gut axis. Therefore, it appears that there may be some overlap between the two conditions. It is rather difficult to tell if the lower gastrointestinal symptoms are secondary to coexisting IBS or a hidden UC condition.

Increased prevalence of gastrointestinal symptoms and disorders of gut-brain interaction during the COVID-19 pandemic: An internet-based survey.

BACKGROUND: Quarantine with social distancing has reduced transmission of COVID-19; however, fear of the disease and these remedial measures cause anxiety and stress. It is not known whether these events have impacted the prevalence of gastrointestinal (GI) symptoms and disorders of brain-gut interaction (DGBI). METHODS: An online platform evaluated the prevalence of GI symptoms during the COVID-19 pandemic. Data collection utilized validated questionnaires and was fully anonymized. Findings were compared with identical data acquired in 2019. The association of results with stress and anxiety was analyzed. RESULTS: Data were collected from 1896 subjects May - August 2019 to 980 non-identical subjects May - June 2020. GI symptoms were reported by 68.9% during the COVID-19 lockdown compared with 56.0% the previous year (p < 0.001). The prevalence of irritable bowel syndrome (26.3% vs. 20.0%; p < 0.001), functional dyspepsia (18.3% vs. 12.7%; p < 0.001), heartburn (31.7% vs. 26.2%, p = 0.002), and self-reported milk intolerance (43.5% vs. 37.8% p = 0.004) was higher during the pandemic. Many individuals reported multiple symptoms. Anxiety was associated with presence of all GI symptoms. High levels of stress impacted functional dyspepsia (p = 0.045) and abdominal pain (p = 0.013). The presence of DGBI (p < 0.001; OR 22.99), self-reported milk intolerance (p < 0.001; OR 2.50), and anxiety (p < 0.001; OR 2.18) was independently associated with increased GI symptoms during COVID-19 pandemic. CONCLUSIONS: The prevalence of GI symptoms was significantly higher during the COVID-19 lockdown than under normal circumstances the previous year. This increase was attributable to increased numbers of patients with DGBI, an effect that was associated with anxiety.

Coordinated Multi-Language Translation of A Validated Symptom Questionnaire for Carbohydrate Intolerances: A Practical Structured Procedure.

BACKGROUND AND AIMS: Validated questionnaires help to minimize diagnostic bias, to standardize symptom assessment and to achieve comparability between studies and centers. In a recent European guideline the adult and the pediatric carbohydrate perception questionnaires (aCPQ and pCPQ), were recommended to be used for the diagnosis of carbohydrate intolerances in adult and pediatric patients. The implementation of this guideline into clinical practice makes availability of validated translations a necessity. METHODS: Clinical experts who recognized the need for these questionnaires to be available in their own language participated in the translation process. The tasks were assigned and a workflow following a predefined procedure based on recommendations of the Rome foundation was developed. The procedure had 5 phases: foundation, nomination, translation, revision, cognitive debriefing. RESULTS: Within eight months the aCPQ was translated into Bulgarian, French, Hungarian, Italian, Polish, Romanian, Russian and Slovenian language and the pCPQ into Dutch, French and Romanian. This expands the population which can be served with the aCPQ from 160 million to over 500 million Europeans. The reach of pCPQ expanded from 92 million to 193 million Europeans. CONCLUSIONS: We report the development and implementation of a centrally organized process of translation of validated questionnaires, following a predefined procedure based on recommendations of the Rome foundation. This structured procedure may aid future efforts to standardize and harmonize the translation of validated questionnaires.

Young age and short duration of the disease are associated with more frequent relapses in inflammatory bowel disease patients.

AIMS: To evaluate the effects of the clinical predictors such as age, duration of disease, sex, and smoking on the frequency of relapses in IBD patients. METHODS: This study recruited 289 IBD (133 with CD and 156 with UC) patients. All were followed-up for 36 months for relapses of the disease. We defined as frequently relapsing (≥1/year) patients with at least one relapse per year and as infrequently relapsing those with less than one relapse per year (<1/year). We assessed the effect of the clinical predictors: age, duration of disease, sex, and smoking on the frequency of relapses in IBD patients. RESULTS: Sixty-four (48.1%) of the CD patients were frequently relapsing and 69 (51.9%) were infrequently relapsing. There was a significant association between the age and the frequency of relapse (p=0.001; OR 0.964; 95% CI 0.941-0.987, p=0.002) and between the duration of the disease and frequency of relapse (p<0.001; OR 0.740, 95% CI 0.655-0.837, p<0.001). Seventy-two (46.2%) of the UC patients were frequently relapsing and 84 (53.8%) were infrequently relapsing. There was a significant association between the age and the frequency of relapse (p=0.001; OR 0.964, 95% CI 0.941-0.987, p=0.002) and between the duration of the disease and frequency of relapse (p<0.001; OR 0.740, 95% CI 0.655-0.837, p<0.001). CONCLUSION: We demonstrate in a relatively significant cohort of IBD patients that young age and short duration of the disease are associated with more frequent relapses.

Screening for hereditary transthyretin amyloidosis in Bulgaria.

Transthyretin amyloid (ATTR) amyloidosis is a rare disorder with an adult-onset defined by the accumulation of misfolded fibrils predominantly in peripheral nerves, the heart, and the digestive tract. The disease is characterized by two forms - hereditary (ATTRv) or acquired (ATTRwt). Various point mutations in the transthyretin gene induce the hereditary form of the disease. For finding new cases of ATTR amyloidosis and proper screening, the establishment of a multidisciplinary team and a Centre of Excellence (CoE) is essential. CoE provides regular education and training for better diagnosis and treatment. In the current review, we focus on the importance of having a multidisciplinary team and CoE, the screening strategy for ATTR amyloidosis in Bulgaria, and assessments performed when a patient is first suspected of having this rare disease.

Recommendations for the diagnosis and management of transthyretin amyloidosis with gastrointestinal manifestations.

Transthyretin amyloid (ATTR) amyloidosis is an adult-onset, rare systemic disorder characterized by the accumulation of misfolded fibrils in the body, including the peripheral nerves, the heart and the gastrointestinal tract. Gastrointestinal manifestations are common in hereditary (ATTRv) amyloidosis and are present even before the onset of the polyneuropathy in some cases. Delays in diagnosis of ATTRv amyloidosis with gastrointestinal manifestations commonly occur because of fragmented knowledge among gastroenterologists and general practitioners, as well as a shortage of centers of excellence and specialists dedicated to disease management. Although the disease is becoming well-recognized in the societies of Neurology and Cardiology, it is still unknown for most gastroenterologists. This review presents the recommendations for ATTRv amyloidosis with gastrointestinal manifestations elaborated by a working group of European gastroenterologists and neurologists, and aims to provide digestive health specialists with an overview of crucial aspects of ATTRv amyloidosis diagnosis to help facilitate rapid and accurate identification of the disease by focusing on disease presentation, misdiagnosis and management of gastrointestinal symptoms.

Lactobacilli Supplemented with Larch Arabinogalactan and Colostrum Stimulates an Immune Response towards Peripheral NK Activation and Gut Tolerance.

Probiotics possibly affect local and systemic immune reactions and maintain the intestinal immune homeostasis in healthy individuals and patients with diseases such as irritable bowel syndrome (IBS). In this single-center, blinded trial, we enrolled 40 individuals (20 patients with IBS and 20 healthy individuals) whose blood and fecal samples were collected before and after a 21-day administration of a product comprising Lactobacillus spp., larch arabinogalactan, and colostrum. The percentage of HLA-DR+ natural killer (NK) cells was higher in healthy individuals (p = 0.03) than in patients with IBS after product supplementation. In the fecal samples of patients with IBS, we observed a decline in IL-6, IFN-γ, TNF-α, and secretory IgA levels and, simultaneously, an increase in IL-10 and IL-17A levels after supplementation, although non-significant, whereas, in healthy individuals, we observed a significant decline in IL-6 and IFN-γ levels after supplementation (p < 0.001). Nevertheless, we observed a clinical improvement of symptoms in 65-75% of patients with IBS and the complete resolution of the initial symptoms in five of the 20 patients. We also observed a possible prophylactic effect by the inducing system antiviral impact accompanied by a trend for local immune tolerance in the gut in healthy individuals, where it is the desirable state.

Fecal calprotectin levels are elevated in transthyretin amyloidosis patients with gastrointestinal manifestations.

Transthyretin amyloid (ATTR) amyloidosis is a rare systemic disorder characterized by amyloid deposits formed by misfolded monomers of the transthyretin. Gastrointestinal (GI) manifestations are common in ATTR amyloidosis; however, their pathogenesis is not fully elucidated. In the present study, we aim to evaluate the diagnostic role of fecal calprotectin (FC) in ATTR amyloidosis patients with GI manifestations.We recruited 21 consecutive ATTR amyloidosis patients and 42 sex and age-matched healthy controls. The presentation of GI symptoms and the severity of peripheral neuropathy were evaluated. Colonoscopy and FC assessment were performed in all subjects.Mean levels of FC in ATTR amyloidosis patients (184 µg/g [30-430]) were significantly higher thаn those of controls (40 µg/g [30-70]), P < .001. Receiver operating characteristic curve analysis indicated a FC cut-off level of 71 µg/g, which differentiates ATTR amyloidosis with GI manifestations from healthy subjects with 91% sensitivity, 100% specificity, 100% positive predictive value, 95% negative predictive value and 97% overall accuracy. FC values were significantly associated with the presence of neutrophilic granulocytic infiltration in the colonic mucosa (P = .002), with the presence of amyloid deposits in rectal mucosa (P = .007) and the presence of diarrhea (P = .046).FC levels are elevated in patients with ATTR amyloidosis with GI manifestations, which suggests an inflammatory component in the pathogenesis of the disease. The presence of elevated FC concentrations could help gastroenterologists to include ATTR amyloidosis in their diagnostic work-up.

Prevalence of Irritable Bowel Syndrome, Functional Dyspepsia and their Overlap in Bulgaria: a Population-Based Study.

AIMS: We aimed to evaluate the prevalence of irritable bowel syndrome (IBS), functional dyspepsia (FD), and their overlap syndrome (OS) in the Bulgarian population and to assess the risk factors associated with these disorders. METHODS: We sent an internet-based survey to Bulgarian adults. The survey collected data on socio- demographic, behavioral and lifestyle characteristics, and diagnostic questions following the Rome IV criteria to assess IBS, FD and their overlap occurrence. RESULTS: Data was collected from 1,896 individuals (mean age = 35.5 years, 18-65, SD=11.7), 73.1% females. The prevalence of IBS was 20% (14% were with predominant constipation, 32% with predominant diarrhea, 52% had IBS with mixed bowel habits, and 2% unclassified IBS). Gender (p=0.005), age (p<0.001), marital status (p=0.009), occupation (p=0.001), alcohol consumption (p=0.013), sexual problems (p<0.001), FD (p<0.001), and milk intolerance (p<0.001) were significantly associated with IBS. Females (p=0.032; OR: 1.50), patients with FD (p<0.001; OR: 104.98), sexual problems (p= 0.001; ОR: 1.55 ), and milk intolerance (p<0.001; OR: 2.22) are at a higher risk of having IBS. The prevalence of FD was 12.7% (39% had postprandial distress syndrome, 33% epigastric pain syndrome, and 28% had the overlapping variant). Patients with IBS (p<0.001; OR: 127.88) and milk intolerance (p<0.001) were significantly associated with FD prevalence. The prevalence of OS was 11.7%. Gender (p=0.013), milk intolerance (p<0.001, OR: 1.65), urinary (p=0.035) and sexual problems (p<0.001, ОR: 1.80) were associated with OS prevalence. CONCLUSION: This is the first study to estimate the prevalence of IBS, FD, and their OS and assess the behavioral and demographic risk factors associated with these disorders in the Bulgarian population. Our results are valuable in filling in the epidemiological data gap regarding IBS, FD, and OS in Eastern Europe.

Trefoil Factor 3 is Highly Predictive of Complete Mucosal Healing Independently and in Combination with C-Reactive Protein in Patients with Ulcerative Colitis.

AIM: In the current study we aimed to evaluate the role of trefoil factor 3 (TFF3) as a marker for complete mucosal healing (MH) in patients with ulcerative colitis (UC). METHODS: We enrolled 116 consecutive UC patients. Trefoil factor 3 levels were measured by ELISA and were compared to the clinical activity, assessed by Lichtiger Index, fecal calprotectin (FCP) and C-reactive protein (CRP) levels. Colonoscopy was performed in all the patients and the findings were graded according to Mayo endoscopic score (EMS) and UC endoscopic index of severity (UCEIS). RESULTS: Trefoil factor 3 levels were significantly correlated with Lichtiger Index (r=0.736, p<0.001), EMS (r=0.811, p<0.001), UCEIS (r=0.820, p<0.001), FCP (r=0.696, p<0.001) and CRP (r=0.405, p<0.001). The TFF3 cut-off level of 6.74 ng/ml indicated complete MH (EMS=0; UCEIS=0) with a sensitivity and specificity of 0.879 and 0.869, respectively (area under the curve, AUC 0.927; 95% confidence interval, 0.877-0.976). The DeLong's test revealed no significant difference between the AUC of TFF3+CRP and the AUC of FCP (Z=1.717, p=0.086), AUC of TFF3+FCP (Z=1.908, p=0.056), and AUC of TFF3+CRP+FCPP (Z=1.915, p=0.056). However, the AUC of TFF3+CRP showed significant difference compared with the AUC of TFF3 (Z=2.210, p=0.027) and the AUC of CRP (Z=3.145, p=0.002) for predicting complete MH. CONCLUSIONS: Trefoil factor 3 levels correlated significantly with clinical activity, endoscopic indices, CRP and FCP in our patients. TFF3 is a highly predictive marker of complete MH independently and in combination with CRP in patients with UC.

Role of Fecal Calprotectin as a Noninvasive Indicator for Ulcerative Colitis Disease Activity.

BACKGROUND: It is essential in clinical management to determine the disease activity in ulcerative colitis (UC) patients. At present, the most accurate way of evaluating the UC severity is endoscopy with biopsy. Fecal calprotectin (FCP) is a non-invasive biomarker that is frequently used for monitoring of intestinal inflammation. AIMS: The purpose of our study was to assess the role of FCP as a noninvasive indicator for UC disease activity. MATERIALS AND METHODS: This prospective study enrolled 116 patients with UC (56 with quiescent UC and 60 with active UC) and 36 controls, referred for colonoscopy to our Center. Colonoscopy was performed in all the patients and the findings were graded according to Mayo endoscopic score (EMS) and UC endoscopic index of severity (UCEIS). FCP was analyzed in stool samples by means of point-of-care desk-top Quantum Blue® method. RESULTS: There was no significant difference between mean FCP levels in controls and UC patients in remission (р=0.205). Mean FCP in patients with active UC was significantly higher than that in controls (p<0.001) and in patients in remission (p<0.001). FCP significantly correlated with UCEIS (r = 0.869, p<0.001) and EMS (r = 0.814, p<0.001). CONCLUSION: The strong correlation with endoscopic disease activity suggests that FCP is a useful biomarker for noninvasive diagnosis and monitoring of disease activity in UC patients.

Gastrointestinal Manifestations in Hereditary Transthyretin Amyloidosis associated with Glu89Gln Mutation.

AIMS: In the current study we aimed to explore the prevalence of gastrointestinal (GI) manifestations in hereditary transthyretin amyloid (hATTR) amyloidosis associated with Glu89Gln mutation. METHODS: We recruited 78 patients with hATTR amyloidosis associated with Glu89Gln mutation. The diagnosis of hATTR was defined by a documented transthyretin mutation through DNA analysis. Symptoms were recorded as present or absent at the time of enrollment into the study. The gastrointestinal (GI) symptoms checklist included the following items: early satiety, nausea, vomiting, constipation, alternating diarrhea/ constipation, diarrhea, fecal incontinence and unintentional weight loss. RESULTS: Forty-two patients (53.8%) reported at least one GI symptom or sign. Diarrhea was the most frequently reported (30.8%), followed by unintentional weight loss (28.2%) and nausea (21.8%). Fecal incontinence (3.8%) was the least common one. No significant gender related difference in overall GI symptom prevalence was found (females 52.16%, males 55%, p = 0.834). Type of disease onset was not related to GI prevalence (earlyonset 50%, late-onset 55.6%, p=0.650). After dividing the patients into groups with a disease duration of <5 years, 5-10 years and >10 years, respectively, the prevalence of GI symptoms was found to be significantly higher in later stages (26.3% vs. 55.0% vs. 78.9%, p = 0.005; OR 2.450, 95% CI 1.084-5.538). Gastrointestinal manifestations had no impact on survival (p=0.193). CONCLUSIONS: Gastrointestinal manifestations are very common in hATTR patients with Glu89Gln mutation and increase with disease duration. They are not associated with gender and onset of the disease and have no impact on patient survival. These results highlight the importance of a thorough evaluation of the GI function in patients with ATTR amyloidosis and should stimulate further studies on the phenotypic differences related to genotype and geographic origin.

Transthyretin Amyloidosis with Gastrointestinal Manifestation: a Case Report.

Transthyretin amyloidosis (ATTR) is a rare, progressive, life-threatening, hereditary disorder caused by mutations in the transthyretin gene. Due to the phenotypic heterogeneity, ATTR is difficult to recognize and it is often diagnosed very late. In ATTR gastrointestinal (GI) disorders play an important role in the patients' morbidity and mortality. In some cases, GI symptoms are present even before the onset of the peripheral polyneuropathy. However, the complaints are various and it is really difficult to differentiate them from other GI disorders. We present a 61-year old male referred for diarrhea, unintentional weight loss and early satiety. He had hypotension after longstanding hypertension, numbness and tingling in the feet. We considered a broad differential diagnosis spectrum of chronic diarrhea syndrome and performed numerous laboratory, biochemical, imaging, endoscopic, histological and genetic tests. Transthyretin amyloidosis with a Glu89Gln mutation was diagnosed. Transthyretin amyloidosis is frequently misdiagnosed, representing a diagnostic challenge in GI practice. The presence of certain clinical combinations could help gastroenterologists to include ATTR in their diagnostic work-up.