Performance evaluation of a smartphone-based home test for fecal calprotection.

OBJECTIVES: Fecal calprotectin (FC) serves as a non-invasive marker for the assessment of gut inflammation in patients with inflammatory bowel disease (IBD). Laboratory measurements are usually performed with immunologic methods like enzyme-linked immunosorbent assay. Recently, quantitative home tests based on the lateral flow technology with smartphones as read-out devices have been developed. We compared the quantitative and qualitative performance of the quantitative lateral flow home test Preventis SmarTest® Calprotectin Home and the immunological test used in our laboratory (Eurospital Calprest® Turbo). METHODS: Fourty-five routine samples were analyzed in parallel with both tests according to the manufacturer's instructions. The read-out of the home test was performed with two smartphones (Apple iPhone 14 Pro and Samsung Galaxy XCover 5). The qualitative interpretation (positive, negative, borderline) was conducted using the cut-offs provided by the manufacturers. RESULTS: Statistically significant correlations with the laboratory standard method were observed for both smartphones (Spearman's rho 0.703 and 0.715, all p<0.005). The home test showed systematically higher concentrations compared to the routine assay. We found minimal qualitative agreement between the two tests (Cohen's kappas (κ)=0.323 and 0.300; p=0.003 and 0.005) showing a lower rate of positives with the home test. Both used smartphones showed good quantitative and qualitative agreement. CONCLUSIONS: The tests are quantitatively not interchangeable. However, the home test may be applicable for the serial follow-up management of patients with IBD. The higher rate of samples classified as negative with the home test may lead to an underestimation of affected patients.

The role of functional vitamin D deficiency and low vitamin D reservoirs in relation to cardiovascular health and mortality.

OBJECTIVES: The role of vitamin D deficiency in cardiovascular disease (CVD) is controversial. Inherent biological and analytical limitations compromise the specificity of widely used 25-hydroxyvitamin D [25(OH)D] cut-offs. Simultaneous determination of 25(OH)D and 24,25-dihydroxyvitamin D [24,25(OH)2D] permits a functional assessment of vitamin D metabolism. The present study compared the associations of functional vitamin D deficiency and low vitamin D reservoirs with CVD mortality and CVD burden. METHODS: 25(OH)D, 24,25(OH)2D, the degree of coronary obstruction on angiography, high-sensitive cardiac troponin T (hs-cTnT), N-terminal brain natriuretic peptide (NT-proBNP), and 10-year CVD mortality were obtained from 2,456 participants of the LURIC (Ludwigshafen Risk and Cardiovascular Health) study. RESULTS: Neither low 25(OH)D concentrations nor functional vitamin D deficiency were associated with the number of atherosclerotic coronary arteries or the degree of coronary obstruction. Over a median follow-up of 9.9 years, 454 participants died (23.6 %) due to CVD. CVD mortality was doubled in individuals with 25(OH)D concentrations below the widely used cut-off for deficiency of <50 nmol/L [20 ng/mL] (21.6 vs. 11.5 %). In individuals with and without functional vitamin D deficiency, CVD mortality was 25.0 and 16.7 %, respectively. NT-proBNP and heart failure prevalence were also higher in vitamin D deficient individuals. CONCLUSIONS: Vitamin D deficient individuals have markedly higher CVD mortality, but only marginally higher hs-cTnT concentrations. A higher prevalence of heart failure and higher NT-proBNP concentrations suggest a link between vitamin D deficiency and cardiac function. The traditional and metabolic assessment of vitamin D status showed comparable associations for the different parameters of cardiac health.

Association of Serum Trimethylamine-N-Oxide Concentration from Childhood to Early Adulthood with Age and Sex.

BACKGROUND: Primary prevention is the cornerstone of cardiometabolic health. In the randomized, controlled Special Turku Coronary Risk Factor Intervention Project (STRIP), dietary counseling intervention was given to children from infancy to 20 years of age and a follow-up was completed at age 26 years. We investigated the associations of age, sex, gut microbiome, and dietary intervention with the gut metabolite and the cardiac biomarker trimethylamine-N-oxide (TMAO). METHODS: Overall, 592 healthy participants (females 46%) from STRIP were investigated. Compared to the control group, the intervention group had received dietary counseling between ages 7 months and 20 years focused on low intakes of saturated fat and cholesterol and the promotion of fruit, vegetable, and whole-grain consumption. TMAO serum concentrations were measured by a liquid chromatography-tandem mass spectrometry method at ages 11, 13, 15, 17, 19, and 26 years. Microbiome composition was assessed using 16S rRNA gene sequencing at 26 years of age. RESULTS: TMAO concentrations increased from age 11 to 26 years in both sexes. At all measurement time points, males showed significantly higher serum TMAO concentrations compared to females, but concentrations were similar between the intervention and control groups. A direct association between TMAO concentrations and reported fiber intake was found in females. Gut microbiome analysis did not reveal associations with TMAO. CONCLUSIONS: TMAO concentration increased from childhood to early adulthood but was not affected by the given dietary intervention. In females, TMAO concentrations could be directly associated with higher fiber intake suggesting sex-specific differences in TMAO metabolism.

One sip of water with LT-4 supplementation-a key to euthyroidism in Hashimoto's thyroiditis.

PURPOSE: Recommended pharmacotherapy for hypothyroidism in Hashimoto's thyroiditis (HT) is oral supplementation with levothyroxine (LT-4). However, serum thyrotropin (TSH) levels within normal range are not consistently achieved with LT-4 medication. PATIENTS AND METHODS: We report on 35 HT patients with LT-4 therapy in this retrospective evaluation. In general, we recommend that a maximum of two sips of water, which would then amount to < 50 mL, be ingested at the same time as LT-4. We report on follow up examinations measuring TSH and antibodies against thyroid peroxidase (TPOAb) after 6 months to five years. RESULTS: After median time of 643 days (range 98-1825) we found in 35 HT patients a statistical significant reduction of serum TSH (p < 0.001) and TPOAb (p = 0.006). The patients median body weight was 71 kg (range 48-98) and a daily LT-4 dosage was used with median 69.1 µg (range 25-150). This results in a daily LT-4 dose of median 1.01 µg/kg bodyweight (range 0.3-2.3). CONCLUSIONS: The reduction of water ingestion to a maximum of two sips, which is <50 mL, combined with LT-4 supplementation helps to achieve euthyroidism in HT. In addition, it reduces the L-T4 medication dosage needed to lower TSH serum levels and decreases TPO antibodies in HT.

Classification of Vitamin D Status Based on Vitamin D Metabolism: A Randomized Controlled Trial in Hypertensive Patients.

Circulating 25-hydroxyvitamin D (25(OH)D) is the generally accepted indicator of vitamin D status. Since hydroxylation of 25(OH)D to 24-25-dihydroxyvitamin D (24,25(OH)2D) is the first step of its catabolism, it has been suggested that a low 24,25(OH)D level and a low vitamin D metabolite ratio (VMR), i.e., 24,25(OH)2D divided by 25(OH)D, may indicate high vitamin D requirements and provide additional diagnostic information beyond serum 25(OH)D. We, therefore, evaluated whether the classification of "functional vitamin D deficiency", i.e., 25(OH)D below 50 nmol/L, 24,25(OH)2D below 3 nmol/L and a VMR of less than 4%, identifies individuals who benefit from vitamin D supplementation. In participants of the Styrian Vitamin D Hypertension trial, a randomized controlled trial (RCT) in 200 hypertensive patients with serum 25(OH)D below 75 nmol/L, who received either 2.800 international units of vitamin D per day or placebo over 8 weeks, 51 participants had functional vitamin D deficiency. In these individuals, there was no treatment effect of vitamin D supplementation on various parameters of bone metabolism and cardiovascular risk except for a significant effect on parathyroid hormone (PTH) and expected changes in vitamin D metabolites. In conclusion, a low vitamin D metabolite profile did not identify individuals who significantly benefit from vitamin D supplementation with regard to bone markers and cardiovascular risk factors. The clinical significance of functional vitamin D deficiency requires further evaluation in large vitamin D RCTs.

Vitamin D and vitamin K status in postmenopausal women with normal and low bone mineral density.

OBJECTIVES: Vitamin D and K are believed to promote bone health, but existing evidence is controversial. This study aimed to measure several metabolites of both vitamins by liquid chromatography tandem mass spectrometry (LC-MS/MS) in a cohort of postmenopausal women with low and normal bone mineral density (BMD). METHODS: Vitamin metabolites (25-hydroxyvitamin D (25[OH]D), 24,25-dihydroxyvitamin D (24,25(OH)2D), phylloquinone (K1), menaquinone-4 (MK-4) and MK-7) were measured in 131 serum samples by LC-MS/MS. The vitamin D metabolite ratio (VMR) was calculated. Parathyroid hormone (PTH), type I procollagen-N-terminal-peptide (PINP) and C-terminal telopeptides of type I collagen (CTX-I) were measured by immunoassay. Dual X-ray absorptiometry was performed to identify participants with normal (T-score>-1) and low (T-score<-1) BMD. RESULTS: Mean age was 58.2±8.5 years. BMD was normal in 68 and low in 63 women. Median (interquartile range) for 25(OH)D and total vitamin K concentrations were 53.5 (39.6-65.9) nmol/L and 1.33 (0.99-2.39) nmol/L. All vitamin metabolites were comparable in individuals with normal and low BMD. Furthermore, BMD and trabecular bone score were comparable in participants with adequate and inadequate vitamin status (at least one criterion was met: 25(OH)D <50 nmol/L, 24,25(OH)2D <3 nmol/L, VMR <4 %, total vitamin K <0.91 nmol/L). PTH, but not PINP or CTX-I, was inversely correlated with 25(OH)D, 24,25(OH)2D and VMR. Synergistic effects between vitamin D and K were not observed. CONCLUSIONS: Vitamin D and K status is not related to BMD and trabecular bone quality in postmenopausal women. Inverse associations were only seen between vitamin D metabolites and PTH.

Functional Assessment of Vitamin D Status by a Novel Metabolic Approach: The Low Vitamin D Profile Concept.

BACKGROUND: Determining serum 25-hydroxyvitamin D [25(OH)D], 24,25-dihydroxyvitamin D [24,25(OH)2D] and the vitamin D metabolite ratio (VMR) allows the identification of individuals with a low vitamin D metabolite profile. Here, we evaluated if such a functional approach provides superior diagnostic information to serum 25(OH)D alone. METHODS: 25(OH)D, 24,25(OH)2D, and the VMR were determined in participants of the DESIRE (Desirable Vitamin D Concentrations, n = 2010) and the LURIC (Ludwigshafen Risk and Cardiovascular Health, n = 2456) studies. A low vitamin D metabolite profile (vitamin D insufficiency) was defined by a 24,25(OH)2D concentration <1.2 ng/mL (<3 nmol/L) and a VMR <4%. Parathyroid hormone (PTH) and bone turnover markers were measured in both cohorts, whereas 10-year mortality data was recorded in LURIC only. RESULTS: The median age in DESIRE and LURIC was 43.3 and 63.8 years, respectively. Median 25(OH)D concentrations were 27.2 ng/mL (68.0 nmol/L) and 15.5 ng/mL (38.8 nmol/L), respectively. Serum 25(OH)D deficiency, defined as <20.2 ng/mL (<50 nmol/L), was present in 483 (24.0%) and 1701 (69.3%) participants of DESIRE and LURIC, respectively. In contrast, only 77 (3.8%) and 521 (21.2%) participants had a low vitamin D metabolite profile. Regardless of the serum 25(OH)D concentration, a low vitamin D metabolite profile was associated with a significantly higher PTH, accelerated bone metabolism, and higher all-cause mortality than an unremarkable vitamin D metabolite profile. CONCLUSIONS: The personalized assessment of vitamin D status using a functional approach better identifies patients with accelerated bone metabolism and increased mortality than the use of a fixed 25(OH)D cutoff of 20 ng/mL (50 nmol/L).

The possible role of quinolinic acid as a predictive marker in patients with SARS-CoV-2.

BACKGROUND AND AIMS: Quinolinic acid (QA) is a metabolite of the kynurenine pathway, which is activated by inflammatory stimuli during viral infection. We investigated the role of QA in patients infected with SARS-CoV-2, particularly its prognostic value for survival. METHODS: Overall, 104 unvaccinated inpatients were included, divided into a survival (N = 80) and a deceased group (N = 24). Plasma levels of tryptophan, kynurenine, QA, C-reactive protein (CRP) and procalcitonin (PCT) were measured on admission and after seven days. The QA/TRP ratio and the relative differences between the measurements for QA (QA-Diff) and QA/TRP (Diff-QA/TRP) were calculated. RESULTS: Among the kynurenine pathway markers, QA-Diff showed the highest discriminatory power for the survival prognosis (Youden index 0.467, cut-off -1.3 %, AUC 0.733, p < 0.001, sensitivity 0.79, specificity 0.675). Among the inflammatory markers, CRP showed the highest discriminatory power (Youden index 0.533, cut-off 25.0 mg/L, AUC 0.794, p < 0.001, sensitivity 0.958, specificity 0.575). A significant correlation between QA and PCT was found on admission and after one week (Spearman's rho 0.455 and 0.539, all p-values < 0.001). CONCLUSIONS: QA may serve as prognostic marker for survival in patients with SARS-CoV-2. The repeated measurements during the first week of the disease may enhance the prognostic power.

A personalized management approach in disorders of the irritable bowel syndrome spectrum.

Symptoms of the disorders across the irritable bowel syndrome (IBS) spectrum include several different, usually postprandial, abdominal complaints. Up to date, dietary treatments of the IBS have neither been personalized nor diagnosed with sufficient scientific evidence. They have mostly been treated using 'one-size-fits-all' approaches. Such include exclusion diets, a low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet, and gluten-free diets, lactose-free diets, a diet recommended by the UK National Institute for Health and Care Excellence, and a wheat-free diet. The exact pathophysiology of IBS disorders across the spectrum is still unclear. However, the symptom profile of IBS spectrum disorders seems similar to that of food intolerance/malabsorption syndromes. Celiac disease, fructose malabsorption, histamine intolerance and lactose intolerance represent food intolerance/malabsorption disorders based on the indigestion of sugars and/or proteins. Helicobacter pylori infection may potentially promote the development of IBS and, when facing a case of IBS-like symptoms, a search for intolerance/malabsorption and H. pylori should be added to find the correct treatment for the respective patient. This review will discuss why the 'one-size-fits-all' dietary approach in the treatment of complaints across the IBS spectrum cannot be successful. Hence, it will provide an overview of the most common overall dietary approaches currently used, and why those should be discouraged. Alternatively, a noninvasive diagnostic workup of the pathophysiologic factors of food intolerance/malabsorption in each patient with symptoms of the IBS spectrum is suggested. Additionally, if H. pylori is found, eradication therapy is mandatory, and if food intolerance/malabsorption is detected, an individual and personalized dietary intervention by a registered dietician is recommended.

Functional Abdominal Pain Disorders in Children May Be Associated with Food Intolerance/Malabsorption.

Functional abdominal pain disorders (FAPDs) are among the most common types of chronic pain disorders in children. FAPD symptoms are characterized by chronic abdominal pain and changed bowel movements. The pathophysiology of FAPDs in children is unknown, but these conditions may have an imprecise clinical overlap to food intolerance/malabsorption. We report on 51 consecutive children (23/28 males/females; median age 15.3 years) with investigated FAPDs from 2017 to 2022 in this retrospective pilot study. Small intestinal biopsies in children demonstrated the association of lactase and diamine oxidase (DAO), which prompted us to perform hydrogen (H2) breath tests for lactose intolerance (LIT) and determine serum DAO for the evaluation of histamine intolerance (HIT) in pediatric patients with FAPDs. To complete the food intolerance/malabsorption evaluation tests, we included a search for antibodies against tissue transglutaminase to find celiac disease (CD), performed H2 breath tests to detect fructose malabsorption (FM), and conducted a search for IgA antibodies against H. pylori infection. The results demonstrate that all 51 children evaluated were diagnosed with food intolerance/malabsorption and/or various combinations thereof. Seven children showed FM, eight of the children had HIT, and eight children had LIT. The other children had combinations: thirteen children (25.5%) had HIT and LIT, seven children (9.8%) had FM with HIT, five children (13.7%) had FM and LIT, and three children (5.9%) had a triple combination of FM, HIT, and LIT. By describing this method of personalized investigation for food intolerance/malabsorption in children with FAPDs, we demonstrate that functional abdominal pain disorders may be associated with food intolerance/malabsorption. After such diagnosis in this pediatric population, a registered dietitian helped to establish a reduction and/or exclusion diet individually tailored to their symptomatology.

The Use of Next-Generation Sequencing in Pharmacogenomics.

BACKGROUND: Next-generation sequencing (NGS) methods have become more commonly performed in clinical and research laboratories. METHODS: This review summarizes the current laboratory NGS-based diagnostic approaches in pharmacogenomics including targeted multi-gene panel sequencing, whole-exome sequencing (WES), and whole-genome sequencing (WGS). RESULTS: Clinical laboratories perform multiple non-uniform types of pharmacogenetic panels, which can reduce the overall number of single-gene tests to be more cost-efficient. Compared to the targeted multi-gene panels, which are not typically designed to detect novel variants, WES and WGS have a greater potential to identify secondary pharmacogenomic findings, which might be predictive for the pharmacotherapy outcome of different patient settings. WGS overcomes the limitations of WES enabling a more accurate exome-sequencing at appropriate coverage and the sequencing of non-coding regions. Different NGS-based study designs with different test strategies and study populations, varying sample sizes, and distinct analytical and interpretation procedures lead to different identification results of pharmacogenomic variants. CONCLUSIONS: The rapid progress in gene sequencing technologies will overcome the clinical and laboratory challenges of WES and WGS. Further high throughput NGS-based pharmacogenomics studies in different populations and patient settings are necessary to expand knowledge about rare functional variants and to enhance translation in clinical practice.

[Clinical Application Examples of a Next-Generation Sequencing based Multi-Genepanel Analysis]. / Klinische Anwendungsbeispiele einer Next-Generation-Sequencing-basierten Multi-Genpanel-Analyse.

This review provides an overview of clinically useful applications of a next-generation sequencing (NGS)-based multi-gene panel testing strategy in the areas of oncology, hereditary tumor syndromes, and hematology. In the case of solid tumors (e.g. lung carcinoma, colon-rectal carcinoma), the detection of somatic mutations contributes not only to a better diagnostic but also therapeutic stratification of those affected. The increasing genetic complexity of hereditary tumor syndromes (e.g. breast and ovarian carcinoma, lynch syndrome/polyposis) requires a multi-gene panel analysis of germline mutations in affected families. Another useful indication for a multi-gene panel diagnostics and prognosis assessment are acute and chronic myeloid diseases. The criteria of the WHO-classification and the European LeukemiaNet-prognosis system for acute myeloid leukemia can only be met by a multi-gene panel test strategy.

Fecal Calprotectin Elevations Associated with Food Intolerance/Malabsorption Are Significantly Reduced with Targeted Diets.

Inflammatory bowel disease (IBD) involves two clinically defined entities, namely Crohn's disease and ulcerative colitis. Fecal calprotectin (FCAL) is used as a marker to distinguish between organic IBD and functional bowel disease in disorders of the irritable bowel syndrome (IBS) spectrum. Food components may affect digestion and cause functional abdominal disorders of the IBS spectrum. In this retrospective study, we report on FCAL testing to search for IBD in 228 patients with disorders of the IBS spectrum caused by food intolerances/malabsorption. Included were patients with fructose malabsorption (FM), histamine intolerance (HIT), lactose intolerance (LIT), and H. pylori infection. We found elevated FCAL values in 39 (17.1%) of 228 IBS patients with food intolerance/malabsorption and H. pylori infection. Within these, fourteen patients were lactose intolerant, three showed fructose malabsorption, and six had histamine intolerance. The others had combinations of the above conditions: five patients had LIT and HIT, two patients had LIT and FM, and four had LIT and H. pylori. In addition, there were individual patients with other double or triple combinations. In addition to LIT, IBD was suspected in two patients due to continuously elevated FCAL, and then found via histologic evaluation of biopsies taken during colonoscopy. One patient with elevated FCAL had sprue-like enteropathy caused by the angiotensin receptor-1 antagonist candesartan. When screening for study subjects concluded, 16 (41%) of 39 patients with initially elevated FCAL agreed to voluntarily control FCAL measurements, although symptom-free and -reduced, following the diagnosis of intolerance/malabsorption and/or H. pylori infection. After the initiation of a diet individualized to the symptomatology and eradication therapy (when H. pylori was detected), FCAL values were significantly lowered or reduced to be within the normal range.

ABCB1 Gene Variants and Antidepressant Treatment Outcomes: A Systematic Review and Meta-Analysis Including Results from the CAN-BIND-1 Study.

The P-glycoprotein efflux pump, encoded by the ABCB1 gene, has been shown to alter concentrations of various antidepressants in the brain. In this study, we conducted a systematic review and meta-analysis to investigate the association between six ABCB1 single-nucleotide polymorphisms (SNPs; rs1045642, rs2032582, rs1128503, rs2032583, rs2235015, and rs2235040) and antidepressant treatment outcomes in individuals with major depressive disorder (MDD), including new data from the Canadian Biomarker and Integration Network for Depression (CAN-BIND-1) cohort. For the CAN-BIND-1 sample, we applied regression models to investigate the association between ABCB1 SNPs and antidepressant treatment response, remission, tolerability, and antidepressant serum levels. For the meta-analysis, we systematically summarized pharmacogenetic evidence of the association between ABCB1 SNPs and antidepressant treatment outcomes. Studies were included in the meta-analysis if they investigated at least one ABCB1 SNP in individuals with MDD treated with at least one antidepressant. We did not find a significant association between ABCB1 SNPs and antidepressant treatment outcomes in the CAN-BIND-1 sample. A total of 39 studies were included in the systematic review. In the meta-analysis, we observed a significant association between rs1128503 and treatment response (T vs. C-allele, odds ratio = 1.30, 95% confidence interval = 1.15-1.48, P value (adjusted) = 0.024, n = 2,526). We did not find associations among the six SNPs and treatment remission nor tolerability. Our findings provide limited evidence for an association between common ABCB1 SNPs and antidepressant outcomes, which do not support the implementation of ABCB1 genotyping to inform antidepressant treatment at this time. Future research, especially on rs1128503, is recommended.

Myeloperoxidase as a Potential Biomarker of Acute-Myocardial-Infarction-Induced Depression and Suppression of the Innate Immune System.

While myeloperoxidase (MPO) serves as an indicator of both neutrophil and innate-immune-system function, the potential suppression of the innate immune system in patients with acute myocardial infarction (AMI)-induced depression might be evidenced by a decrease in MPO serum levels. The aim of this prospective study was to (1) determine whether serum concentrations of MPO vary immediately and 6 months after AMI and (2) to investigate whether MPO concentrations at the time of the AMI are significant predictors of AMI-induced depression and the depression-associated suppression of the innate immune system. A total of 109 AMI patients were assessed with the Hamilton Depression Scale (HAMD-17) immediately after admission to the hospital and 6 months later. The MPO status was assessed with serum samples, which were also collected immediately and 6 months after AMI. The depressive patients showed significantly lower MPO blood levels immediately and 6 months after the AMI compared to the patients without depression (ANCOVA: MPO (depression) F = 4.764, df = 1, p = 0.031). The baseline MPO was observed as a significant predictor (p = 0.027) of AMI-induced depression 6 months after AMI. MPO is a potential biomarker for AMI-induced depression, indicating a depression-associated suppression of the innate immune system.

Alteration of the kynurenine pathway is inversely associated with the humoral immune response in patients with SARS-CoV-2.

BACKGROUND: The scale and the course of antibody production in patients with SARS-CoV-2 is highly variable. Factors involved in the immune regulation during the infection may play a major role in the antibody response. We investigated the relationship between the inflammatory markers of the kynurenine pathway and the concentration of antibodies against SARS-CoV-2 in infected patients 8 - 11 days after admission. METHODS: The study included 72 SARS-CoV-2 - positive inpatients hospitalized between August 2020 and April 2021. The plasma concentrations of tryptophan, kynurenine, anti-SARS-CoV-2 antibodies and the leucocyte count were measured 8 - 11 days after admission. The kynurenine/tryptophan ratio (KYN/TRP ratio) was calculated. Tertiles based on the values for tryptophan, kynurenine, KYN/TRP ratio and the leucocytes were generated. RESULTS: Statistically significant correlations were observed between anti-SARS-CoV-2 antibodies and tryptophan, kynurenine, KYN/TRP ratio and the leucocytes (p-values < 0.001-0.007). The high kynurenine and KYN/TRP ratio tertiles showed significantly lower antibody titers compared to the low tertiles (p-values 0.017 and < 0.001). The low tryptophan and leucocytes tertiles showed significantly lower antibody titers compared to the high tertiles (p-values 0.001 and 0.008). CONCLUSION: Patients with higher activation levels of the kynurenine pathway tended to develop lower anti-SARS-CoV-2 antibody titers.

[The Impact of Next-Generation Sequencing on Medical Genetic Diagnostics and Counseling]. / Die Bedeutung der Hochdurchsatz-Sequenzierung in der medizinisch genetischen Diagnostik und Beratung.

Next-generation sequencing is a modern diagnostic high-throughput method (multi-gene analysis) that can be used to better diagnose both hereditary cancers (tumor disposition syndromes, germline diagnostics) and somatic mutations in tumors. The broad usage of this technology in daily clinical practice demonstrates the real interindividual genetic variability. This method has great importance for the investigation of heterogeneous genetic diseases (e. g. tumors, neurodegenerative and neuromuscular diseases). Further indications are pharmacogenetics and non-invasive prenatal diagnosis. It can be expected that this diagnostic tool will find wide clinical application. With the rapid increase and complexity of genetic data information, the correct interpretation and transmission of the results in the human genetic counseling (germline diagnostics) is of great importance. The genetic counseling must be realigned and adapted accordingly in daily clinical practice.

Tryptophan recovery index as a new biomarker for fitness.

The maximal oxygen uptake (VO2max) and maximal power output (Pmax) are commonly used parameters to evaluate the endurance fitness status. A connection between exercise and the kynurenine pathway (KP), which describes the metabolism of unused tryptophan, has already been reported. However, a potential association of the KP with endurance fitness levels remains unknown. In this study, adolescent competitive athletes performed an exhaustive incremental exercise test. Blood samples were taken before, directly after, and 30 minutes after the end of exercise. Tryptophan (Trp), kynurenine (Kyn) and kynurenic acid (KA) serum levels were determined by high-performance liquid chromatography (HPLC). Forty-four male and 27 female athletes (median age: 16 years) were recruited. During exhaustive exercise tests, Trp initially declined and then increased 30 minutes after discontinuing exercise. Similar findings were observed for Kyn, whereas KA levels behaved inversely. After incremental exhaustive exercise the relative increase of Trp concentrations, termed the tryptophan-recovery-index (TRI), showed a highly significant positive correlation with VO2max and Pmax (r=0.468 and 0.491, p-values <0.001). There was a significant gender-difference with higher levels of all metabolites at all measured time points in male participants. In the present study, a highly significant correlation was found between the TRI and the maximal oxygen uptake in well-trained athletes. The implementation of TRI can therefore be suggested as a biomarker for physical fitness.