Search

Monogenic mutations of the hepatocyte nuclear factor 1 homeobox A maturity onset diabetes of the young (HNF1A-MODY) is characterized by early onset, typically before the age of 25 years. Patients are often not clinically recognized; however, the identification of HNF1A-MODY patients is crucial because they require different antihyperglycemic medical treatment than patients with type 1 or type 2 diabetes mellitus. We describe two adult patients with monogenic diabetes, both identified as HNF1A-MODY, genetically c.815G>A, p.Arg272His and c675delC, p.Ser225Argfs*8, respectively. They were misdiagnosed as having type 1 diabetes mellitus, and consequently, initiating insulin therapy led to hypoglycemia and unstable blood glucose control. Usually, sulfonylureas represent the basis of antidiabetic treatment in patients with HNF1A-MODY; however, all medical personnel involved in diabetes care should be aware of monogenic diabetes mellitus and the possibilities for genetic testing. The patients observed have shown the necessity of the identification and appropriate genetic diagnosis of HNF1A-MODY in order to discontinue insulin therapy and to initiate adjusted diabetes management.

In westernized countries, adverse reactions to ingested foods are reported to affect up to 20% of the population. Functional, nonspecific, non-allergic gastrointestinal complaints are mainly due to the intolerance/malabsorption of carbohydrates (lactose and fructose), proteins (gluten), and biogenic amines (histamine). Food intolerance/malabsorption is defined by one or several of the above mentioned food components not being degraded and/or absorbed properly within the gastrointestinal tract. Food intolerance/malabsorption causes variable, functional, nonspecific, non-allergic gastrointestinal and extra-intestinal complaints, and a detailed diagnostic workup for all possible etiologic factors in individual patients is essential. Usually, evaluation for histamine intolerance is not included in differential diagnoses of patients with functional, nonspecific, non-allergic gastrointestinal complaints. A targeted dietary intervention for single or possibly combined intolerance/malabsorption is required. In this article, we review currently discussed differential diagnoses and available tests for intolerance/malabsorption. Accordingly, we aim to outline why including histamine and, histamine intolerance, should be considered in differential diagnoses of patients with functional, nonspecific, non-allergic gastrointestinal complaints.

Background Acute myocardial infarction is not only a somatic disease but potentially triggers psychological effects, too. Post-traumatic stress disorder (PTSD) is a common stress-related disorder. It is characterized by numerous symptoms, such as flashbacks, intrusions, nightmares and severe anxiety, as well as uncontrollable, intense and disturbing thoughts and feelings related to the traumatic experience. However, with regard to the development of PTSD, individual stress perception might be crucial since not every serious traumatic experience leads to PTSD. To date, almost no biological correlates of an individual's perception of stress have been identified as being associated with the long-term development of PTSD. Objective The aim of the study was to determine whether blood levels of TMAO vary immediately after AMI (1) in patients with or without depression, and (2) in patients with AMI induced PTSD symptomatology (subsyndromal PTSD and full PTSD). Furthermore, we investigated whether TMAO is a potential biomarker that might be useful in the prediction of PTSD symptomatology in the long term. Method A total of 114 AMI patients were assessed with standardized clinical psychiatric interviews based on the Hamilton Depression Scale (HAMD-17) after admission to the hospital and 6 months later. In addition, the CAPS-5 was used to explore PTSD symptoms (subsyndromal PTSD and full PTSD) 6 months after AMI. To assess patients' TMAO status, serum samples were collected at hospitalization and 6 months after AMI. Results Study participants with post-myocardial infarction PTSD symptomatology (subsyndromal PTSD and full PTSD) had significantly higher TMAO levels immediately after AMI than patients without PTSD symptoms (ANCOVA: TMAO (PTSD x time), F = 4.544, df = 1, p=0.035). In contrast, depressive symptomatology 6 months after AMI had no influence on TMAO levels (TMAO (depression x time), F = 0.083, df = 1, p=0.774). With the inclusion of additional clinical predictors in a hierarchical logistic regression model, TMAO becomes a significant predictor of PTSD symptomatology. Conclusions An elevated TMAO level immediately after AMI might reflect severe stress in PTSD-vulnerable patients, which might also lead to a short-term increased gut permeability to trimethylamine (TMA), the precursor of TMAO. Thus, elevated TMAO might be a biological correlate for stress that is associated with vulnerability to PTSD and might help to identify patients at increased risk. Funding Acknowledgement Type of funding sources: None.

Objectives In-house developed liquid-chromatography mass spectrometry (LC-MS/MS) methods are used more and more frequently for the simultaneous quantification of vitamin D metabolites. Among these, 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) is of clinical interest. This study assessed the agreement of this metabolite in two validated in-house LC-MS/MS methods. Methods 24,25(OH)2D3 was measured in 20 samples from the vitamin D external quality assurance (DEQAS) program and in a mixed cohort of hospital patients samples (n=195) with the LC-MS/MS method at the Medical University of Graz (LC-MS/MS 1) and at the University of Liège (LC-MS/MS 2). Results In DEQAS samples, 24,25(OH)2D3 results with LC-MS/MS 1 had a proportional bias of 1.0% and a negative systemic difference of −0.05%. LC-MS/MS 2 also showed a proportional bias of 1.0% and the negative systemic bias was −0.22%. Comparing the EQA samples with both methods, no systemic bias was found (0.0%) and the slope was 1%. The mean difference of 195 serum sample measurements between the two LC-MS/MS methods was minimal (−0.2%). Both LC-MS/MS methods showed a constant bias of 0.31 nmol/L and a positive proportional bias of 0.90%, respectively. Conclusions This study is the first to assess the comparability of 24,25(OH)2D3 concentrations in a mixed cohort of hospitalized patients with two fully validated in-house LC-MS/MS methods. Despite different sample preparation, chromatographic separation and ionization, both methods showed high precision measurements of 24,25(OH)2D3. Furthermore, we demonstrate the improvement of accuracy and precision measurements of 24,25(OH)2D3 in serum samples and in the DEQAS program.

Background/Aims Food intolerance/malabsorption, particularly histamine intolerance (HIT), may cause nonspecific functional gastrointestinal and extraintestinal symptoms. We evaluated gastrointestinal and extraintestinal symptoms in patients with HIT. Methods In an analysis of outpatients’ charts we identified 133 patients, who presented with recurring nonspecific functional gastrointestinal, extraintestinal symptoms, and a diamine oxidase value

Histamine intolerance (HIT) is thought to be caused by a disproportionate amount of histamine in the body. The enzyme diamine oxidase (DAO) is considered for the gastrointestinal degradation of histamine. For this open-label interventional pilot study, we identified 28 patients with HIT. For 4 weeks, they were instructed to take DAO capsules before meals. Then, throughout a follow-up period, they were instructed not to take the DAO. We used a questionnaire that included 22 symptoms, which were divided into 4 categories, as well as a symptom severity score. All symptoms improved significantly during the oral supplementation of DAO. During the follow-up period, without DAO supplementation, the symptoms sum scores increased again. The symptom intensity score was reduced for all symptoms. We have demonstrated, a significant reduction of every HIT-related symptom and its intensity due to DAO oral supplements. The ClinicalTrials.gov identifier (NCT number) is NCT03298568.

Background Helicobacter pylori has been associated with iron deficiency (ID). This study is aimed at investigating ID with conventional (ferritin, transferrin saturation [TSAT]) and new biomarkers (soluble transferrin receptor [sTfR], sTfR/log ferritin, reticulocyte hemoglobin content [CHr], hepcidin-25) in patients sub-grouped by the presence or absence of H. pylori infection. Methods In total, 200 consecutive outpatients, who were referred for the H. pylori 13C-urea breath test (13C-UBT), underwent blood testing for ID. Additionally, Thomas-plot (TP)-analyses (sTfR/log ferritin, CHr) were calculated. Results Fifty-three and 147 individuals were found with and without H. pylori infection, respectively. Patients with H. pylori infection showed a higher sTfR concentration (pH. pylori infection and 63/147 (42.9%) without H. pylori infection showed ID. Based on TP-analyses, 10/53 (18.9%) patients with and 17/147 (11.6%) without H. pylori infection were identified with ID. Completed eradication therapy tended to be associated with functional ID. Conclusions Helicobacter pylori infection was associated with significantly higher plasma sTfR concentrations and sTfR/log ferritin ratios. Patients with H. pylori eradication therapy were more often detected with functional ID compared to patients without eradication therapy, when using the new biomarkers.

Background: Posttraumatic stress disorder (PTSD) is a frequently observed stress-related disorder after acute myocardial infarction (AMI) and it is characterized by numerous symptoms, such as flashbacks, intrusions and anxiety, as well as uncontrollable thoughts and feelings related to the trauma. Biological correlates of severe stress might contribute to identifying PTSD-vulnerable patients at an early stage. Objective: Aims of the study were (1) to determine whether blood levels of trimethylamine N-oxide (TMAO) vary immediately after AMI in patients with/without AMI-induced PTSD symptomatology, (2) to investigate whether TMAO is a potential biomarker that might be useful in the prediction of PTSD and the PTSD symptom subclusters re-experiencing, avoidance and hyperarousal, and (3) to investigate whether TMAO varies immediately after AMI in patients with/without depression 6 months after AMI. Method: A total of 114 AMI patients were assessed with the Hamilton-Depression Scale after admission to the hospital and 6 months later. The Clinician Administered PTSD Scale for DSM-5 was used to explore PTSD-symptoms at the time of AMI and 6 months after AMI. To assess patients’ TMAO status, serum samples were collected at hospitalization and 6 months after AMI. Results: Participants with PTSD-symptomatology had significantly higher TMAO levels immediately after AMI than patients without PTSD-symptoms (ANCOVA: TMAO(PTSD x time), F = 4.544, df = 1, p = 0.035). With the inclusion of additional clinical predictors in a hierarchical logistic regression model, TMAO became a significant predictor of PTSD-symptomatology. No significant differences in TMAO levels immediately after AMI were detected between individuals with/without depression 6 months after AMI. Conclusions: An elevated TMAO level immediately after AMI might reflect severe stress in PTSD-vulnerable patients, which might also lead to a short-term increase in gut permeability to trimethylamine, the precursor of TMAO. Thus, an elevated TMAO level might be a biological correlate for severe stress that is associated with vulnerability to PTSD., HIGHLIGHTS An elevated TMAO level might be a biological correlate for severe stress that is associated with vulnerability to PTSD.

Histamine intolerance (HIT) is assumed to be due to a deficiency of the gastrointestinal (GI) enzyme diamine oxidase (DAO) and, therefore, the food component histamine not being degraded and/or absorbed properly within the GI tract. Involvement of the GI mucosa in various disorders and diseases, several with unknown origin, and the effects of some medications seem to reduce gastrointestinal DAO activity. HIT causes variable, functional, nonspecific, non-allergic GI and extra-intestinal complaints. Usually, evaluation for HIT is not included in differential diagnoses of patients with unexplained, functional GI complaints or in the here-listed disorders and diseases. The clinical diagnosis of HIT is challenging, and the thorough anamnesis of all HIT-linked complaints, using a standardized questionnaire, is the mainstay of HIT diagnosis. So far, DAO values in serum have not been established to correlate with DAO activity in the gut, but the diagnosis of HIT may be supported with determination of a low serum DAO value. A targeted dietary intervention, consisting of a histamine-reduced diet and/or supplementation with oral DAO capsules, is helpful to reduce HIT-related symptoms. This manuscript will present why histamine should also be taken into account in the differential diagnoses of patients with various diseases and disorders of unknown origin, but with association to functional gastrointestinal complaints. In this review, we discuss currently increasing evidence that HIT is primarily a gastrointestinal disorder and that it originates in the gut.

Single and/or combined food intolerance/malabsorption may cause nonspecific, functional gastrointestinal (GI) complaints. In lactose-intolerant patients we evaluated the influence of additional food intolerance/malabsorption with hydrogen (H2) breath tests. In a retrospective analysis of charts from 279 lactose-intolerant patients, we found 128 patients with only lactose intolerance (LIT). Then, we identified 106 LIT patients with additional histamine intolerance (HIT). Additionally, 45 LIT and HIT patients also had fructose malabsorption (FM). A hydrogen (H2) breath test was performed to evaluate LIT and FM. A serum diamine oxidase value of &lt, 10 U/mL and a response to a histamine-reduced diet was used to identify HIT. Using pairwise comparison with the Kruskal&ndash, Wallis test to associate the area under the curve (AUC) of LIT patients and, LIT with HIT, to LIT with HIT and FM it was found, that the exhaled hydrogen values were significantly higher in patients with two-fold and triple combined food intolerance/malabsorption (p &lt, 0.004 and p &lt, 0.001, respectively). Within the pool of 170 LIT patients with &gt, 20 ppm increase of expiratory H2 from baseline, there were 74 LIT-only patients, 60 LIT with HIT patients, and 36 LIT patients with additional HIT and FM. With the Kruskal&ndash, Wallis test AUCs demonstrated a significant difference between all three groups (p = 0.024). In patients with LIT, the presence of additional food intolerance/malabsorption, significantly increases expiratory H2 values. We demonstrate evidence, which may suggest HIT to embody an own GI disorder as food intolerance/malabsorption.

Objectives Recently, the fully automated flow cytometry-based UF-5000 (Sysmex Corboration, Kobe, Japan) urine sediment analyzer was developed providing bacteria (BACT) info flags for more accurate bacterial discrimination of urinary tract infections (UTIs). This study aimed to compare the reliability of the UF-5000 BACT-info flags with manual Gram stain and urine culture as the gold standard method. Methods A total of 344 urine samples were analyzed on the UF-5000 and compared with manual microscopic Gram stain and urine cultures. Agreement was assessed by Cohen’s kappa (κ) analysis. The Youden index was used to determine the optimal BACT and white blood cell (WBC) cut-off points for discriminating positive and negative urine cultures. Results Overall 98/344 (28.5%) samples were urine culture positive at a cut-off of ≥105 CFU/mL. “Gram-negative?” UF-5000 BACT-Info flags showed a better concordance of 25/40 (62.5%) with urine culture compared to Gram stain with 30/50 (60%). The results for UF-5000 discrimination of Gram-positive and Gram-negative microorganisms demonstrated a substantial (κ = 0.78) and fair (κ = 0.40) agreement with urine culture. Optimal cut-off points detecting positive urine cultures were 135 BACT/µL (sensitivity [SE]: 92.1%, specificity [SP]: 85.4%, positive predictive value [PPV]: 71%, negative predictive value [NPV]: 96%) and 23 WBC/µL (SE: 73.5%, SP: 84.1%, PPV: 65%, NPV: 89%). Conclusions The UF-5000 analyzer (Sysmex) is a reliable diagnostic tool for UTI screening. The displayed BACT-Info flags allow a quick diagnostic orientation for the clinician. However, the authors suggest verifying the automated Gram categories with urine culture.

Objectives The mucoprotein uromodulin is considered to correlate with glomerular filtration rates (GFR) in patients with chronic kidney disease (CKD). Here we investigated how serum uromodulin is associated with measured GFR using inulin-clearance and GFR estimated by CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation in healthy subjects. Methods We assessed possible correlations between uromodulin serum concentrations, inulin-GFR and CKD-EPI-GFR in a well characterized study cohort of 112 healthy living kidney donors with two kidneys before and 64 with one kidney after kidney donation. A subgroup of 32 individuals, which presented data before and after nephrectomy, was assessed separately. Results All 112 healthy living kidney donors with two kidneys revealed individual serum uromodulin concentrations between 60.1 and 450.5 µg/L. Sixty-four healthy kidney donors after nephrectomy had significantly lower median (interquartile range) serum uromodulin concentrations (124 [101–166] vs. 185 [152–238] µg/L), inulin-GFR (67.3 [60.6–74.6] vs. 93.5 [82.1–104.4] mL/min/1.73 m2), and CKD-EPI-GFR (61.2 [53.1–69.7] vs. 88.6 [80.0–97.1] mL/min/1.73 m2) as compared to the 112 donors before donation (p Conclusions These novel findings indicate that – in contrast to patients with CKD – serum uromodulin concentrations are not correlated with measured and estimated GFR in healthy individuals.

Sugars including lactose and fructose, or proteins (gluten), or biogenic amines (histamine), and combinations thereof may cause food intolerance/malabsorption. However, in usually asymptomatic patients with rare diseases, who present with functional, non-specific, non-allergic gastrointestinal (GI) complaints the etiologic factors of food intolerance/malabsorption need to be evaluated. We summarize patients with rare diseases, such as primary epiploic appendagitis, beta-thalassemias minor, Gullo syndrome and anomaly of the inferior vena cava, who presented functional, non-specific, non-allergic GI complaints. As conclusion, these GI symptoms in patients with otherwise asymptomatic, rare diseases were due to fructose malabsorption, histamine-, lactose intolerance and Helicobacter pylori (H.p.) infection. A registered and experienced dietician was employed to design an individually-tailored diet which ensured effective treatments and H.p. infection was accordingly eradicated.

Background.The microbiome-derived trimethylamine-N-oxide (TMAO) and the intestinal permeability marker zonulin are considered to be linked with depression. Moreover, carbohydrate malabsorption (CMA) was shown to be associated with signs of depression. This study is aimed at investigating possible sex-specific associations between TMAO and zonulin and the presence of depressive signs in individuals with and without CMA.Methods.Serum concentrations of TMAO and zonulin were determined in 115 and 136 individuals with the presence or absence of CMA. All 251 study participants underwent lactase gene C/T-13910polymorphism genotyping and fructose H2/CH4breath testing. Additionally, they filled in the Beck Depression Inventory (BDI-II) questionnaire.Results.The median TMAO and zonulin serum concentrations were 2.66 (1.93–4.14)μmol/L and 40.83 (34.73–47.48) ng/mL. Serum TMAO levels were positively correlated with depressive symptoms (P=0.011,ρ=0.160). The strongest correlations were observed in 87 females (P=0.010,ρ=0.274) and 49 males (P=0.027,ρ=0.315) without CMA, whereas 115 patients with CMA showed no significant correlations. Zonulin tended to be negatively correlated with the BDI-II score in 49 males without CMA (P=0.062,ρ=−0.269).Conclusion.This study demonstrates a positive correlationship between the serum TMAO concentrations and the severity of depressive symptoms in females and males without CMA. Serum zonulin levels were negatively correlated with signs of depression in males without CMA. These findings suggest a gender-specific relationship between the serum TMAO and zonulin concentrations, depression, and CMA.

This work aimed at investigating demographic, clinical, and genetic characteristics of individuals experiencing their first familial Mediterranean fever (FMF) attack at age ≥40 years in a very large cohort of Armenian FMF patients. In total, 10,370 Armenian patients diagnosed with FMF based on the Tel Hashomer criteria and carrying at least one MEFV mutant allele were included in this study. A total of 354 (3.40%) patients had late-onset FMF. Of these, 194 (54.80%) were female and 160 (45.20%) were male. The following genotypes were significantly associated with the late-onset variant: M680I/E148Q (P = 0.004), M694V/E148Q (P

This prospective cross-sectional study aimed to investigate the potential association between primary-adult lactose malabsorption, fructose malabsorption, tryptophan (TRP) metabolism and the presence of depressive signs. Overall 251 patients, who were referred for lactase gene C/T-13910 polymorphism genotyping and fructose hydrogen/methane breath testing, were included. All participants filled out the Beck Depression Inventory (BDI II). Serum concentrations of tryptophan (TRP), kynurenine (KYN), kynuric acid (KYNA), and TRP competing amino acids (leucine, isoleucine, valine, phenylalanine, tyrosine) were measured by high-pressure liquid-chromatography. Logistic regression analysis was performed with lactose malabsorption, fructose malabsorption and all potential biomarkers of TRP metabolism to assess the effect on signs of depression, defined as a BDI II score > 13. Primary-adult lactose malabsorption and fructose malabsorption was detected in 65 (25.90%) and 65 (25.90%) patients, respectively. Fructose malabsorption was significantly associated with BDI II score, whereas no such relationship was found for lactose malabsorption. Serum levels of TRP and TRP metabolites were no predictors of depression. The authors suggest to conduct further prospective longitudinal studies in order to get further insight of associations between carbohydrate malabsorption, biomarkers and mood disorders.

Food intolerance/malabsorption is caused by food ingredients, carbohydrates (mainly lactose and fructose), proteins (gluten), and biogenic amines (histamine) which cause nonspecific gastrointestinal and extra-intestinal symptoms. Here we focus on possible etiologic factors of intolerance/malabsorption especially in people with non-celiac gluten sensitivity (NCGS) or the so-called people without celiac disease avoiding gluten (PWCDAG) and histamine intolerance. Recognizing the recently described symptoms of NCGS (PWCDAG) we review correlations and parallels to histamine intolerance (HIT). We show that intestinal and extra-intestinal NCGS (PWCDAG) symptoms are very similar to those which can be found in histamine intolerance. After a detailed diagnostic workup for all possible etiologic factors in every patient, a targeted dietary intervention for single or possibly combined intolerance/malabsorption might be more effective than a short-term diet low in fermentable oligo-, di- and monosaccharides and polyols (FODMAP) or the untargeted uncritical use of gluten-free diets.

Introduction: The aim of this study was to assess pneumatic tube system (PTS) alteration on platelet function by the light transmission aggregometry (LTA) and whole blood aggregometry (WBA) method, and on the results of platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), and fibrinogen. Materials and methods: Venous blood was collected into six 4.5 mL VACUETTE® 9NC coagulation sodium citrate 3.8% tubes (Greiner Bio-One International GmbH, Kremsmünster, Austria) from 49 intensive care unit (ICU) patients on dual anti-platelet therapy and immediately hand carried to the central laboratory. Blood samples were divided into 2 Groups: Group 1 samples (N = 49) underwent PTS (4 m/s) transport from the central laboratory to the distant laboratory and back to the central laboratory, whereas Group 2 samples (N = 49) were excluded from PTS forces. In both groups, LTA and WBA stimulated with collagen, adenosine-5’-diphosphate (ADP), arachidonic acid (AA) and thrombin-receptor-activated-peptide 6 (TRAP-6) as well as platelet count, PT, APTT, and fibrinogen were performed. Results: No statistically significant differences were observed between blood samples with (Group 1) and without (Group 2) PTS transport (P values from 0.064 – 0.968). The AA-induced LTA (bias: 68.57%) exceeded the bias acceptance limit of ? 25%. Conclusions: Blood sample transportation with computer controlled PTS in our hospital had no statistically significant effects on platelet aggregation determined in patients with anti-platelet therapy. Although AA induced LTA showed a significant bias, the diagnostic accuracy was not influenced.

Diagnosis of histamine intolerance (HIT) has been based on low serum diamine oxidase (DAO) values, functional gastrointestinal disorders and improvement of symptoms with a histamine-reduced diet (HRD). In a retrospective analysis of outpatients' charts we identified 101 patients with HIT. After a median of 13 months, a questionnaire was distributed to the patients so that they could be classified into four diet-compliance groups. Calculated with all 101 patients we found an increase of serum DAO values due to a HRD. In the 63 patients that completed the questionnaire, we found that 50 patients had improvement of symptoms or no continuing symptoms. A significant increase of serum DAO levels was found in the patients with strict and occasional diet compliance. Therefore, we demonstrate that a HRD is not only improving symptoms in HIT, but is causing an increase in serum DAO values that correlates with the degree of diet compliance.

Background Recently, several manufacturers have launched automated urinalysis platforms. This study aimed to compare the diagnostic performance of the UF-5000 (Sysmex Corporation, Kobe, Japan) and the cobas® u 701 (Roche Diagnostics, Rotkreuz, Switzerland) urine sediment analyzers with manual phase-contrast microscopy as the reference method. Methods A total of 195 urine samples were analyzed on both automated platforms and subjected to manual microscopic examination. Agreement was assessed by Cohen’s kappa (κ) analysis. Sensitivities and specificities were calculated. Results The agreement of the UF-5000 with manual microscopy was almost perfect (κ > 0.8) for red (RBC) and white blood cells (WBC), renal tubular epithel cells, hyaline casts, bacteria (BACT) and yeast (YLC), substantial (κ = 0.61–0.80) for squamous epithel cells (SEC) and pathologic casts, and moderate (κ = 0.41–0.60) for transitional epithel cells. The cobas® u 701 showed substantial agreement (κ = 0.61–0.80) for WBC, moderate agreement (κ = 0.41–0.60) for hyaline casts, and fair agreement (κ = 0.21–0.40) for RBC, SEC, non-squamous epithel (NEC), pathologic casts, BACT and YLC. The UF-5000 sensitivities ranged between 98.5% for RBC and 83.3% for pathological casts. The cobas® u 701 showed sensitivities between 83.0% for WBC and 31.6% for YLC. Conclusions The UF-5000 (Sysmex) analyzer showed a better diagnostic agreement with manual phase-contrast microscopy compared to the cobas® u 701 (Roche) module. The Sysmex platform showed reliable results for urine sediment analysis. However, pathological samples should be verified with manual microscopy.

Healthy human blood contains only a trace amount of methemoglobin (Hb M), less than 1%. In Hb M iron is present in the oxidized ferric state (Fe3+) not in the reduced ferrous form (Fe2+) and this reduces the ability of hemoglobin to bind oxygen. The described rare hemoglobin variant Hb M‑Hyde Park (also known as Hb M-Akita) results from the substitution of amino acid tyrosine by histidine at position 93 of the beta-globin chain of hemoglobin. The rare Hb variant Hb M‑Hyde Park (Hb M‑Akita) is mainly inherited autosomal dominant and causes methemoglobinemia. Due to the low frequency of inherited Hb M variants, the diagnosis is challenging. Here, we here report on a family with Hb M‑Hyde Park (Hb M‑Akita) whose members demonstrated Hb M > 10%, but were, asymptomatic except for chronic cyanosis. Due to human mobility and migration other hemogobin variants, such as beta-thalassemia minor have spread to Austria . A genetic combination of two different hemoglobin variants may result in severe anemia. Genetic counseling for patients with hemoglobin variants, including Hb M‑Hyde Park (Hb M‑Akita) and beta-thalassemia minor, is essential.

Background and pilot study Celiac disease (CD) or gluten malabsorption is a well-defined autoimmune disorder characterized by mucosal gastrointestinal reaction to ingested gluten proteins. The necessary treatment for CD is a gluten-free diet. However, up to 30% of celiac patients experience persistent or recurring abdominal complaints despite following an exact gluten-free diet. This condition was named refractory, non-responsive celiac disease. Other food ingredients, such as carbohydrates and biogenic amines, also influence and impair digestion, and may cause these abdominal symptoms. In this retrospective pilot study, we have reported on 20 non-responsive, celiac disease patients, with persistent abdominal complaints, for longer than 6 months. These patients were evaluated for extra food intolerance/malabsorption, including fructose malabsorption, histamine-, lactose intolerance, and Helicobacter pylori (H.p.) infection. Results and conclusions The results demonstrate that 18 of the 20 refractory, non-responsive celiac disease patients presented various, additional food intolerance/malabsorption and/or H.p. infection. Seven NRCD patients demonstrated lactose intolerance, 7 showed fructose malabsorption, 11 had additional histamine intolerance and 6 had signs of H.p. infection or combinations thereof. If present, then eradication of H.p. was performed. Histamine intolerance, was found in more than 50% of patients, and it seems to play an important role in non-responsive celiac disease. A registered dietician continued to help with, and to improve, the patients’ gluten-free diet. Furthermore, additional food intolerance/malabsorption considerations were included in the individual, dietary recommendations.

Background So far, studies on possible association of plasma lipid levels and depressive disorder are contradictory. This prospective work aimed at assessing a plasma lipid profile in individuals with major depression and healthy controls. Methods In total, 94 patients with major depression and 152 healthy controls were included in this prospective study. After an overnight fasting state of 12 h they underwent blood drawing for triglyzerides (TG), total cholesterol, low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol measurements. All participants were evaluated in a clinical interview and filled out the self-rating Beck Depression Inventory (BDI-II) scale to identify depressive symptomatology. Results Ninety-four patients with major depression showed significantly higher median (interquartile range) plasma TG levels (108.0 [75.8–154.1] vs. 84.0 [63.0–132.2] mg/dL, P = 0.014) and significantly lower HDL-cholesterol levels (55.0 [46.9–123.0] vs. 61.5 [47.4–72.6] mg/dL, P = 0.049) compared to 152 individuals without depression, respectively. Total and LDL-cholesterol concentrations were observed slightly higher in patients with major depression. Significant positive correlation was found between TG, total cholesterol and LDL-cholesterol concentrations and the BDI-II score (p = 0.027, 0.048 and 0.018), and in tendency negative correlation between HDL-cholesterol levels and the BDI-II score (P = 0.091), respectively. Conclusions Depressive individuals were found with adverse plasma lipid patterns of higher TG and lower HDL-cholesterol levels compared to healthy controls. On this basis, the authors would suggest the implementation of routine lipid measurements in order to stratify these patients by their cardiovascular risk.

Background Current literature proposes associations between homocysteine (HCY), folic acid (FA), vitamin B12 metabolism and depression. However, the exact underlying biological mechanisms remain unclear. This study aimed at evaluating a possible link between primary adult-type lactose malabsorption (PALM), HCY, FA and vitamin B12 metabolism and depressive disorder. Methods Plasma levels of HCY, FA and vitamin B12 were determined in 78 patients with PALM and 160 individuals with lactase persistence sub-grouped by the presence or absence of major depression. Results In 78 patients with PALM, the subgroup of 22 individuals with major depression showed significantly higher median (interquartile range) HCY (10.10 [8.46–12.03] vs. 8.9 [7.54–9.86] μmol/L, p = 0.029) and lower plasma FA levels (5.7 [4.68–9.14] vs. 6.95 [5.24–10.56] μmol/L, p = 0.272) compared to the subgroup of 56 individuals without depression, respectively. No such associations could be observed for those 160 individuals without PALM (i.e., lactase persistence) Plasma HCY levels were positively correlated with depressive symptoms (p = 0.052), and showed negative correlations with FA (p = < 0.001) and vitamin B12 (p = 0.029), respectively. Conclusion Depressed individuals with PALM were found with significantly higher HCY and lower FA levels compared to non-depressed individuals with PALM, however, this association was absent in the subgroup of lactase persistent individuals. These findings suggest an association between increased HCY levels, lactose malabsorption and depression.

No full international consensus exists on disease markers to be used for assessing the human iron status. Therefore this study was conducted to compare performances of serum ferritin and transferrin saturation (TSAT) versus soluble transferrin receptor (sTfR)/log ferritin and reticulocyte hemoglobin content (CHr), also known as Thomas-plot, in the diagnosis of iron deficiency (ID).A total of 445 consecutive hospitalized patients, referred for routine testing of the actual iron status, were included. Logistic regression models for the probability of functional ID (CHr28pg) were constructed for all 445 patients, for 225 patients without (C-reactive protein [CRP]≤0.5mg/dL) and 220 patients with acute-phase reaction (CRP0.5mg/dL).Based on the Thomas-plot analyses, 153/445 (34.38%) patients were identified with ID. When ID was diagnosed by means of serum ferritin levels30ng/mL and TSAT levels20%, 105/445 (23.60%) and 215/445 (48.31%) patients were identified with ID, respectively. The sTfR/log ferritin ratio showed the best positive predictive values (PPV) (62.50 and 64.41%) to indicate functional ID in patients without as well as with acute-phase reaction compared to sTfR (58.14 and 61.67%), ferritin (32.50 and 32.86%) and TSAT (26.74 and 42.86%).In clinical practice, the prevalence of ID and the accuracy to detect functional ID are dependent on marker selection and its definition. Regarding the results of this work, for laboratory investigation of ID, however, we suggest using Thomas-plot analyses in combination with ferritin single-marker measurements to efficiently identify patients with ID.

Background/Aims: While lactose malabsorption is a well-investigated condition, few epidemiologic data are available for fructose and sorbitol malabsorption. The aim of this study was to assess the prevalence rates for primary lactose malabsorption, fructose and sorbitol malabsorption, and carbohydrate-specific small intestinal bacterial overgrowth (cs-SIBO) in an Austrian outpatient center. Methods: In total, 306 adult patients, who were primarily referred with suspected carbohydrate malabsorption by general practitioners to our outpatient clinic, underwent genetic testing (C/T-13910 polymorphism) for primary lactose malabsorption, and a combined hydrogen (H2)/methane (CH4) breath test for fructose (25 g) and sorbitol (12.5 g) malabsorption. Cohen's kappa (κ) was calculated for agreement between positive breath test results and self-reported symptoms during the test. Results: Seventy-eight (25.49%) patients were C/C-13910 homozygotes, indicating primary lactose malabsorption. Thirty-four (11.11%) and 57 (18.63%) patients were classified as fructose and sorbitol malabsorbers. Cohen's κ measuring agreements between positive fructose and sorbitol breath test results and self-reported symptoms during the test were 0.33 and 0.49, respectively. Twenty-nine (9.50%) patients with an early H2/CH4 peak (i.e. within 60 minutes after fructose and/or sorbitol ingestion) were diagnosed with cs-SIBO. Conclusion: In Austria, carbohydrate malabsorption is a frequent condition in patients referred by general practitioners to carbohydrate malabsorption testing.

Beta-trace protein (BTP) is a low-molecular-weight glycoprotein, which may serve as an endogenous biomarker of kidney function and cardiovascular risk.We examined cardiovascular and all-cause mortality according to BTP concentrations in 2962 individuals referred for coronary angiography from the Ludwigshafen Risk and Cardiovascular Health study and in 907 patients with Type 2 diabetes mellitus undergoing haemodialysis from the German Diabetes and Dialysis (4D) study.Haemodialysis patients had considerably higher median (interquartile range) BTP concentrations [6.00 (4.49-7.96) mg/L] and experienced a 4-fold increased mortality rate compared with coronary angiography patients [BTP concentration: 0.55 (0.44-0.67) mg/L]. After adjustment for age, sex, cardiovascular risk factors and creatinine, 4D patients in the highest quartile (7.96 mg/L) had a 1.6-fold increased rate of all-cause mortality [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.19-2.20] compared with the lowest quartile (4.49 mg/L) (P = 0.002) In patients undergoing coronary angiography, the adjusted HRs (95% CI) for all-cause and cardiovascular mortality were 1.23 (1.0-1.51) and 1.27 (0.99-1.63) in the highest (0.67 mg/L) compared with the lowest (0.44 mg/L) quartile (P = 0.043 and 0.062). In both cohorts, the BTP/creatinine ratio was a stronger predictor of all-cause and cardiovascular mortality compared with BTP.BTP was associated with all-cause mortality independently of renal function in haemodialysis patients. The BTP/creatinine ratio was more predictive for all-cause and cardiovascular mortality in haemodialysis patients and individuals referred for angiography compared with BTP as single marker.

Benign pancreatic hyperenzymemia (Gullo syndrome) is characterized by a more than threefold increase of the pancreatic enzymes lipase and amylase in the absence of a pancreatic disease over a period of more than 1 year, with elevations and significant undulations of pancreatic enzyme serum concentrations occurring on a day-to-day basis for 5 consecutive days. Nonspecific abdominal complaints may be caused by carbohydrate and/or protein malabsorption. We report a patient with benign pancreatic hyperenzymemia with lactose and histamine malabsorption; the symptoms of gastrointestinal malabsorption were treated successfully with an individually tailored lactose- and histamine-free diet.

Essentials In platelet function testing, standardized internal controls (IQC) are not commercially provided. Platelet function testing was performed daily on aliquoted pooled platelet concentrates. Pooled platelet concentrates showed stability for control purposes from Monday to Friday. Pooled platelet concentrates provide the necessary steadiness to serve as IQC material. SummaryBackground Standardized commercially available control material for internal quality control (IQC) of light transmission aggregometry (LTA) is still lacking. Moreover, the availability of normal blood donors to provide fresh platelets is difficult in small laboratories, where ‘volunteers’ may be in short supply. Objectives To evaluate the implementation of buffy-coat-derived pooled platelet concentrates (PCs) for IQC material for LTA. Methods We used buffy-coat-derived pooled PCs from the blood bank as IQC material for LTA. On each weekend one PC was prepared (> 200 mL) and aliquoted from the original storage bag on a daily basis in four baby bags (40–50 mL), which were delivered from Monday to Friday to our laboratory. The IQC measurements of at least 85 work-weeks (from Monday to Friday) were evaluated with this new IQC material. LTA was performed on a four-channel Chronolog 700 Aggregometer (Chronolog Corporation, Havertown, PA, USA) (agonists: collagen, adenosine diphosphate [ADP], arachidonic acid [AA] and thrombin receptor activator peptide-6 [TRAP-6]). Results The medians of platelet aggregation from IQC measurements with collagen, ADP and AA from Monday to Friday were 68.0–59.5, 3.0–2.0 and 51.0–50.0%, respectively, and the mean of platelet aggregation with TRAP-6 was 71.2–66.4%. Conclusions Buffy-coat-derived pooled PCs serve as a reliable and robust IQC material for LTA measurements and would be beneficial for the whole laboratory procedure and employees’ safety.

Primary Epiploic Appendagitis (PEA) is a rare cause of acute or subacute abdominal complaints and non-migratory pain. Usually the diagnosis of PEA is made when Computed Tomography (CT) reveals characteristic figures. Nonspecific abdominal complaints including diffuse abdominal pain may be caused by carbohydrate and/or protein malabsorption. We report a case of a patient with PEA who recovered without medication or surgical treatment within a few days. Eight months later, he was diagnosed with lactose- and histamine malabsorption and Helicobacter pylori infection. The malabsorption was treated successfully with an individually-tailored diet free of culprit triggers and the Helicobacter pylori infection was eradicated. A localized non-migratory abdominal pain caused by PEA needs to be differentiated from nonspecific abdominal complaints due to malabsorption and Helicobacter pylori infection.

The aim of this study was to establish a retrospective evaluation and comparison of the hydrogen/methane (H2/CH4) breath test and genetic test (C/T−13910polymorphism) results in lactose malabsorption testing. In total 263 consecutive patients with suspected lactose malabsorption were included in this study. They underwent the H2/CH4breath test following the ingestion of 50 g lactose and were tested for the C/T−13910polymorphism. In total 51 patients (19.4%) had a C/C−13910genotype, indicating primary lactose malabsorption. Only 19 patients (7.2%) also had a positive H2/CH4breath test. All in all 136 patients (51.69%) had a C/T−13910and 76 patients (28.91%) a T/T−13910genotype, indicating lactase persistence. Four patients (1.5%) with the C/T−13910genotype and one patient (0.4%) with the T/T−13910genotype had a positive H2/CH4breath test result, indicating secondary lactose malabsorption. Cohen's Kappa measuring agreement between the two methods was 0.44. Twenty patients (7.6%) with a positive H2/CH4peak within 60 minutes after lactose ingestion were classified as patients with lactose-dependent small intestinal bacterial overgrowth (SIBO). In conclusion, only moderate agreement between the breath test and the genetic test was shown. Secondary lactose malabsorption as well as preanalytical limitations of the combined H2/CH4breath test procedure can cause discrepant results. This trial is registered with K-42-13.

To the Editor: During the last decade the interest in using circulating cell-free DNA (ccfDNA)1 as a biomarker for the early diagnosis, prognosis, and monitoring of a variety of clinical conditions has increased rapidly. In daily clinical practice, it has been shown that preanalytical variables such as blood sampling, handling-procedurevariations, and blood storage conditions affect the ccfDNA concentration in human plasma (1). In this respect, optimal handling of blood samples between venipuncture and plasma preparation may be considered essential for downstream processes (1, 2) since time delay and/or agitation could trigger the release of genomic DNA from white blood cells (1). To reduce laboratory turnaround time, sample transport by pneumatic tube systems (PTS) has been established in many hospitals. However, rapid accelerations and decelerations during the PTS transport may cause shear stress and can potentially affect various laboratory measurements for coagulation, clinical chemistry, hematology, or blood gas analyses (3). At present, the literature lacks studies investigating the impact of PTS transport on quantitative ccfDNA measurements. Therefore, we compared ccfDNA plasma concentrations between paired whole …

BACKGROUND Genetic testing is a standard technique for the diagnosis of primary adult-type hypolactasia, also referred to as lactase non-persistence. The aim of this study was to compare the lactase gene (LCT) C/T-13910 polymorphism genotyping results of two commercially available real-time (RT)-PCR assays in patients referred to our outpatient clinic for primary lactose malabsorption testing. Furthermore, concomitant conditions of fructose/sorbitol malabsorption were assessed. METHODS Samples obtained from 100 patients were tested in parallel using the LCT T-13910C ToolSet for Light Cycler (Roche, Rotkreuz, Switzerland) and the LCT-13910C>T RealFast Assay (ViennaLab Diagnostics GmbH, Vienna, Austria). Additionally, patients were also screened for the presence of fructose/sorbitol malabsorption by functional hydrogen (H2)/methane (CH4) breath testing (HMBT). Cohen's Kappa (κ) was used to calculate the agreement between the two genotyping methods. The exact Chi-Square test was performed to compare fructose/sorbitol HMBT with LCT genotyping results. RESULTS Twenty-one (21.0%) patients had a LCT C/C-13910 genotype suggestive of lactase non-persistence, and 79 (79.0%) patients were identified with either a LCT T/C-13910 or T/T-13910 genotype (i.e., lactase persistence). In all genotype groups, concordance between the two RT-PCR assays was 100%. Cohen's κ demonstrated perfect observed agreement (p < 0.001, κ = 1). Fructose and sorbitol malabsorption was observed in 13/100 (13.0%) and 25/100 (25.0%) individuals, respectively. CONCLUSIONS Both RT-PCR assays are robust and reliable LCT genotyping tools in a routine clinical setting. Concomitant fructose and/or sorbitol malabsorption should be considered in individuals with suspected lactase-non-persistence. However, standardization of clinical interpretation of laboratory HMBT results is required.

Background: Diagnosis of small intestinal bacterial overgrowth (SIBO) remains challenging. This study aimed at proving the diagnostic concept of carbohydrate-specific SIBO (cs-SIBO) using glucose, fructose and sorbitol hydrogen (H2)/methane (CH4) breath testing (HMBT). Methods: In this study 125 patients referred to our outpatient clinic for SIBO testing were included. All individuals underwent glucose (50 g), fructose (25 g) and sorbitol (12.5 g) HMBT at 3 consecutive days. Patients with cs-SIBO (i.e. early H2/CH4 peak) were given rifaximin (600 mg/day) in a 10-day treatment. HMBT results were reassessed in a subset of patients 3–6 months after antibiotic therapy. In view of cs-SIBO diagnosis, agreements between HMBT results obtained for different sugars were calculated using Cohen’s kappa (κ) with 95% confidence intervals (CIs). Results: A total of 59 (47.2%) patients presented an early H2/CH4 peak with one or more sugars. Among these, 21 (16.8%), 10 (8.0%) and 7 (5.6%) individuals had a positive HMBT result with either glucose, fructose or sorbitol, respectively. Another 21 (16.8%) patients with a positive glucose HMBT result were also found positive with an early H2/CH4 peak obtained after ingestion of fructose and/or sorbitol. Fair agreement was observed between glucose and fructose (κ = 0.26, p = 0.0018) and between glucose and sorbitol (κ = 0.18, p = 0.0178) HMBT results. Slight agreement was observed between fructose and sorbitol (κ = 0.03, p = 0.6955) HMBT results only. Successful antibiotic therapy with rifaximin could be demonstrated in 26/30 (86.7%) of patients as indicated by normal HMBT results and symptom remission. Conclusions: Combined glucose, fructose and sorbitol HMBT has the potential to optimize cs-SIBO diagnosis. Furthermore, the majority of patients with cs-SIBO seem to benefit from rifaximin therapy regardless of its carbohydrate specificity.

Primary adult-type lactose malabsorption (PALM) is a widespread inherited autosomal recessive condition, which is considered to be associated with osteoporosis. This prospective study aimed at assessing the 25-hydroxy-vitamin D (25(OH)D) status and serum CrossLaps levels in individuals with PALM and normal controls.All participants (n=210) underwent genotyping for the LCT C/T-13910 polymorphism, 25(OH)D and CrossLaps measurements and clinical examinations. In addition, the anthropometric data (that is, height, weight and body mass index) were determined.Fifty-five individuals with PALM (that is, LCT C/C-13910 homozygotes) showed lower 25(OH)D (mean: 24.95±10.04 vs 28.59±9.56 ng/ml, P=0.018) and higher CrossLaps serum levels (mean: 0.46±0.31 vs 0.43±0.49 ng/ml, P=0.251) compared with 155 normal controls (that is, LCT C/T-13910 hetero- or T/T-13910 homozygotes). Anthropometric data were similar between PALM probands and controls.Individuals with PALM were found to have lower 25(OH)D and higher CrossLaps serum levels compared with normal controls. In order to preserve life-long bone health, routine 25(OH)D and CrossLaps serum measurements should be performed in individuals with PALM.

The aim of this retrospective study was to analyze the concomitant prevalence rates for lactose malabsorption (LM), fructose malabsorption (FM), and histamine intolerance (HI) in patients with so far unexplained gastrointestinal (GI) symptoms. A total of 439 outpatients, who presented unclear abdominal discomfort, underwent lactose (50 g) and fructose (25 g) hydrogen (H2) breath tests. Additionally, serum diamine oxidase (DAO) measurements were performed. Individuals with low serum DAO activity (

The aim of this study was to determine the frequencies and specificities of “enzyme-only” detected red blood cell (RBC) alloantibodies in the routine antibody screening and antibody identification in patients hospitalized in Austria. Routine blood samples of 2420 patients were investigated. The antibody screening was performed with a 3-cell panel in the low-ionic strength saline- (LISS-) indirect antiglobulin test (IAT) and with an enzyme-pretreated (papain) 3-cell panel fully automated on the ORTHO AutoVue Innova System. The antibody identification was carried out manually with an 11-cell panel in the LISS-IAT and with an enzyme-pretreated (papain) 11-cell panel. In total 4.05% (n=98) of all patients (n=2420) had a positive RBC antibody screening result. Of them 25.51% (25/98) showed “enzyme-only” detected specific or nonspecific RBC alloantibodies. Rhesus and Lewis system antibodies were found the only specificities of “enzyme-only” RBC alloantibodies: all in all 4.8% (4/98) were detected with anti-E, 3.06% (3/98) with anti-Lea, 3.06% (3/98) with anti-D after anti-D prophylaxis and 1.02% (1/98) with anti-e. In total, 14.29% (14/98) showed a nonspecific RBC alloantibody result with the enzyme test. The results of the present study demonstrate that a high number of unwanted positive reactions with the enzyme technique overshadows the detection of “enzyme-only” RBC alloantibodies. (Trial Registration: K-37-13).

The aim of this study was to evaluate a laboratory-guided therapeutic algorithm of preoperative anemia. 335 patients with elective hip or knee arthroplasty were included in this retrospective before-after study. Group I (n= 101) underwent conventional preoperative procedures before algorithm implementation. Group II (n= 234) underwent algorithm-guided preoperative anemia management. A hemoglobin-level of 13 g/dL was the therapeutic cut-off for men and women. Reticulocyte hemoglobin content (CHr) and soluble transferrin receptor (sTfR)/log ferritin ratio were used in the form of the Thomas plot. Iron deficiency (ID) was substituted with 1000 mg iron intravenous (i.v.) and 10000 international units (I.U.) of erythropoiesis-stimulating agent (ESA) subcutaneous (s.c.) or i.v., anemia of chronic disease (ACD) (without functional ID) with 40000 I.U. ESA s.c. or i.v and additionally 200 mg iron i.v. Substituted anemic patients in Group II (n=32) showed a distinctly higher preoperative (Hb-median 13 versus 11.95 g/dL) (P<0.01) and postoperative (Hb-median 9.75 versus 9.0 g/dL) (P<0.05) Hb level compared with untreated anemic patients in Group I (n=24). In Group II red blood cell (RBC) units (35 units/234 patients) were reduced by 44% compared with Group I (27 units/101 patients). Algorithm-guided preoperative anemia management raises perioperative Hb-level and reduces blood use.