Incorporation of CAD (computer-aided detection) with thin-slice lung CT in routine 18F-FDG PET/CT imaging read-out protocol for detection of lung nodules.

OBJECTIVE: To evaluate the detection rate and performance of 18F-FDG PET alone (PET), the combination of PET and low-dose thick-slice CT (PET/lCT), PET and diagnostic thin-slice CT (PET/dCT), and additional computer-aided detection (PET/dCT/CAD) for lung nodules (LN)/metastases in tumor patients. Along with this, assessment of inter-reader agreement and time requirement for different techniques were evaluated as well. METHODS: In 100 tumor patients (56 male, 44 female; age range: 22-93 years, mean age: 60 years) 18F-FDG PET images, low-dose CT with shallow breathing (5 mm slice thickness), and diagnostic thin-slice CT (1 mm slice thickness) in full inspiration were retrospectively evaluated by three readers with variable experience (junior, mid-level, and senior) for the presence of lung nodules/metastases and additionally analyzed with CAD. Time taken for each analysis and number of the nodules detected were assessed. Sensitivity, specificity, positive and negative predictive value, accuracy, and Receiver operating characteristic (ROC) analysis of each technique was calculated. Histopathology and/or imaging follow-up served as reference standard for the diagnosis of metastases. RESULTS: Three readers, on an average, detected 40 LN in 17 patients with PET only, 121 LN in 37 patients using ICT, 283 LN in 60 patients with dCT, and 282 LN in 53 patients with CAD. On average, CAD detected 49 extra LN, missed by the three readers without CAD, whereas CAD overall missed 53 LN. There was very good inter-reader agreement regarding the diagnosis of metastases for all four techniques (kappa: 0.84-0.93). The average time required for the evaluation of LN in PET, lCT, dCT, and CAD was 25, 31, 60, and 40 s, respectively; the assistance of CAD lead to average 33% reduction in time requirement for evaluation of lung nodules compared to dCT. The time-saving effect was highest in the less experienced reader. Regarding the diagnosis of metastases, sensitivity and specificity combined of all readers were 47.8%/96.2% for PET, 80.0%/81.9% for PET/lCT, 100%/56.7% for PET/dCT, and 95.6%/64.3% for PET/CAD. No significant difference was observed regarding the ROC AUC (area under the curve) between the imaging methods. CONCLUSION: Implementation of CAD for the detection of lung nodules/metastases in routine 18F-FDG PET/CT read-out is feasible. The combination of diagnostic thin-slice CT and CAD significantly increases the detection rate of lung nodules in tumor patients compared to the standard PET/CT read-out. PET combined with low-dose CT showed the best balance between sensitivity and specificity regarding the diagnosis of metastases per patient. CAD reduces the time required for lung nodule/metastasis detection, especially for less experienced readers.

Which irrigating provides a better bond strength in glass fiber posts: Chlorhexidine or Sodium Hypochlorite? A systematic review with meta-analysis.

Background: The aim of this systematic review and meta-analysis was to evaluate the influence of the use of chlorhexidine on endodontic instrumentation on the bond strength of glass fiber posts with resin cements. The guiding question of the study was: "Is the bond strength of glass fiber posts greater when using chlorhexidine as an irrigator in endodontic treatment instead of sodium hypochlorite?". Material and Methods: This study was conducted according to Guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). In vitro studies were included that have compared chlorhexidine and sodium hypochlorite as an endodontic irrigator in the chemical-mechanical preparation. Results: Eight studies were included in the qualitative analysis and seven in the meta-analysis. Both the analysis by subgroups and the total analysis, using a random effect model, showed no statistically significant differences between the groups (p> 0.05), either in the specific analysis for cervical root third (p = 0.30; 95% CI = -2.11, 6.91) or medium (p = 0.05; 95% CI = -0.03, 4.56), or nonspecific regarding the third to the root third (p = 0.48; 95% CI = -4.00, 1.86). Conclusions: There are no statistically significant differences in the bond strength of glass fiber posts and resin cements in teeth endodontically treated under irrigation by both chlorhexidine and sodium hypochlorite. Key words:Chlorhexidine, sodium hypochlorite, bond strength, glass fiber post.

The value of bone SPECT/CT in evaluation of foot and ankle arthrodesis and adjacent joint secondary osteoarthritis.

OBJECTIVE: To evaluate the value of SPECT/CT (single photon emission computed tomography/computed tomography) in foot and ankle arthrodesis and development of secondary osteoarthritis in the adjacent joints. MATERIALS AND METHODS: SPECT/CT of 140 joints in the foot and ankle (34 upper ankle (UA), 28 lower ankle (LA), 27 talonavicular (TN), 12 calcaneo-cuboidal (CC), and 39 other smaller joints after arthrodesis in 72 patients were evaluated retrospectively regarding fusion grade in CT (0 = no fusion, 1 = < 50% fusion, 2 = > 50% fusion, 3 = complete fusion) and radiotracer uptake (0 = no uptake, 1 = mild uptake, 2 = moderate uptake, 3 = high uptake) on SPECT/CT. Severity of osteoarthritis (1 = mild, 2 = moderate, 3 = severe) and radiotracer uptake grade in adjacent joints was also assessed. In 54 patients, clinical information about interventions in the follow-up was available. RESULTS: According to the SPECT/CT, arthrodesis was successful (grade 2 or 3 CT fusion and grade 0 or 1 uptake) in 73% (25/34) of UA joints, 71% (20/28) of LA joints, 67% (18/27) TN, 100% (12/12) CC joints, and 62% (24/39) of other smaller joints. In 12 joints, there were discrepant findings in SPECT/CT (fusion grade 2 and uptake grade 2 or 3 (n = 9); or, fusion grade 0 or 1 and uptake grade 1 (n = 3)). The fusion rate 6-12 months after arthrodesis was 42% (14/33), 59% (20/34) after 13-24 months, and 89% (65/73) after more than 24 months, respectively. Average radiotracer uptake in arthrodesis decreased with age: 6-12 months: 1.60, 12-24 months: 1.32, > 24 months: 0.38. There was a significant negative correlation between radiotracer uptake grade and CT fusion grade. Osteoarthritis was observed in 131 adjacent joints. During the post scan follow-up, additional arthrodeses were performed in 33 joints, of which 11 joints were re-arthrodesis and 22 were new arthrodeses in osteoarthritic adjacent joints. All these 11 joints with failed arthrodesis had grade 0 of CT fusion and grade 2 or 3 of radiotracer uptake. All 22 adjacent joints with osteoarthritis, which subsequently underwent arthrodesis, had grade 2 or 3 radiotracer uptake, and the primary arthrodesis joints were healed and fused in all these cases. CONCLUSION: Bone SPECT/CT is a valuable hybrid imaging tool in the evaluation of foot and ankle arthrodesis and gives additional useful information about the development of secondary osteoarthritis in the adjacent joints with higher value for the assessment of secondary osteoarthritis. A practical four-type classification ('Lucerne Criteria') combining metabolic and morphologic SPECT/CT information for evaluation of arthrodesis joints has been proposed.

An unbiased AAV-STARR-seq screen revealing the enhancer activity map of genomic regions in the mouse brain in vivo.

Enhancers are important cis-regulatory elements controlling cell-type specific expression patterns of genes. Furthermore, combinations of enhancers and minimal promoters are utilized to construct small, artificial promoters for gene delivery vectors. Large-scale functional screening methodology to construct genomic maps of enhancer activities has been successfully established in cultured cell lines, however, not yet applied to terminally differentiated cells and tissues in a living animal. Here, we transposed the Self-Transcribing Active Regulatory Region Sequencing (STARR-seq) technique to the mouse brain using adeno-associated-viruses (AAV) for the delivery of a highly complex screening library tiling entire genomic regions and covering in total 3 Mb of the mouse genome. We identified 483 sequences with enhancer activity, including sequences that were not predicted by DNA accessibility or histone marks. Characterizing the expression patterns of fluorescent reporters controlled by nine candidate sequences, we observed differential expression patterns also in sparse cell types. Together, our study provides an entry point for the unbiased study of enhancer activities in organisms during health and disease.

Increased 18F-PSMA and 18F-FDG Uptake in Lipomatous Hypertrophy of the Interatrial Septum.

ABSTRACT: Lipomatous hypertrophy of the interatrial septum (LHIS) is a benign anomaly with low prevalence. Lipomatous hypertrophy of the interatrial septum is asymptomatic in most of the cases and rarely leads to atrial arrhythmias, obstructive flow symptoms, or sudden death. It is mostly diagnosed as an incidental finding in cross-sectional imaging and echocardiography, and increased 18F-FDG uptake on LHIS has been described. We present a case of repeated increased 18F-PSMA uptake in LHIS. Although very rare, familiarity with the typical features and prevalence of LHIS in PET/CT can avoid misinterpretation for metastatic disease.

Changes in Radiosensitivity to Gamma-Rays of Lymphocytes from Hyperthyroid Patients Treated with I-131.

This study investigated the peripheral blood lymphocytes (PBL) response to a dose of γ-rays in patients treated with radioiodine (I-131) for hyperthyroidism vs. healthy controls, to gain information about the individual lymphocytes' radio-sensitivity. Blood samples were taken from 18 patients and 10 healthy donors. Phosphorylated histone variant H2AX (γ-H2AX) and micronuclei (MN) induction were used to determine the change in PBL radio-sensitivity and the correlations between the two types of damage. The two assays showed large inter-individual variability in PBL background damage and in radio-sensitivity (patients vs. healthy donors). In particular, they showed an increased radio-sensitivity in 36% and 33% of patients, decrease in 36% and 44%, respectively. There was a scarce correlation between the two assays and no dependence on age or gender. A significant association was found between high radio-sensitivity conditions and induced hypothyroidism. PBL radio-sensitivity in the patient group was not significantly affected by treatment with I-131, whereas there were significant changes inter-individually. The association found between clinical response and PBL radio-sensitivity suggests that the latter could be used in view of the development of personalized treatments.

Novel Pyridazin-3(2H)-one-Based Guanidine Derivatives as Potential DNA Minor Groove Binders with Anticancer Activity.

Novel aryl guanidinium analogues containing the pyridazin-3(2H)-one core were proposed as minor groove binders (MGBs) with the support of molecular docking studies. The target dicationic or monocationic compounds, which show the guanidium group at different positions of the pyridazinone moiety, were synthesized using the corresponding silyl-protected pyridazinones as key intermediates. Pyridazinone scaffolds were converted into the adequate bromoalkyl derivatives, which by reaction with N,N'-di-Boc-protected guanidine followed by acid hydrolysis provided the hydrochloride salts 1-14 in good yields. The ability of new pyridazin-3(2H)-one-based guanidines as DNA binders was studied by means of DNA UV-thermal denaturation experiments. Their antiproliferative activity was also explored in three cancer cell lines (NCI-H460, A2780, and MCF-7). Compounds 1-4 with a bis-guanidinium structure display a weak DNA binding affinity and exhibit a reasonable cellular viability inhibition percentage in the three cancer cell lines studied.

ID2 controls differentiation of enteroendocrine cells in mouse small intestine.

AIMS: The mammalian gut is the largest endocrine organ. Dozens of hormones secreted by enteroendocrine cells regulate a variety of physiological functions of the gut but also of the pancreas and brain. Here, we examined the role of the helix-loop-helix transcription factor ID2 during the differentiation of intestinal stem cells along the enteroendocrine lineage. METHODS: To assess the functions of ID2 in the adult mouse small intestine, we used single-cell RNA sequencing, genetically modified mice, and organoid assays. RESULTS: We found that in the adult intestinal epithelium Id2 is predominantly expressed in enterochromaffin and peptidergic enteroendocrine cells. Consistently, the loss of Id2 leads to the reduction of Chromogranin A-positive enteroendocrine cells. In contrast, the numbers of tuft cells are increased in Id2 mutant small intestine. Moreover, ablation of Id2 elevates the numbers of Serotonin+ enterochromaffin cells and Ghrelin+ X-cells in the posterior part of the small intestine. Finally, ID2 acts downstream of BMP signalling during the differentiation of Glucagon-like peptide-1+ L-cells and Cholecystokinin+ I-cells towards Neurotensin+ PYY+ N-cells. CONCLUSION: ID2 plays an important role in cell fate decisions in the adult small intestine. First, ID2 is essential for establishing a differentiation gradient for enterochromaffin and X-cells along the anterior-posterior axis of the gut. Next, ID2 is necessary for the differentiation of N-cells thus ensuring a differentiation gradient along the crypt-villi axis. Finally, ID2 suppresses the commitment of secretory intestinal epithelial progenitors towards tuft cell lineage and thus controls host immune response to commensal and parasitic microbiota.

Does flossing before or after brushing influence the reduction in the plaque index? A systematic review and meta-analysis.

OBJECTIVES: The purpose of this systematic review was to assess whether flossing before or after influences plaque index reduction. METHODS: This systematic review was conducted according to the guidelines of the preferred reporting items for systematic reviews and meta-analyses and registered with the International prospective register of systematic reviews under number CRD42019126239. The PICO question was, 'does flossing before or after brushing have any effect on reducing dental plaque?'. An electronic search was performed until April 2020 in the following databases: PubMed/MEDLINE, Scopus Web of Science and Cochrane Library. The initial database search resulted in 9679 references, and after detailed analysis of the titles and abstracts of the selected studies, the inclusion/exclusion criteria were applied, and 06 complete articles were downloaded and selected for further analysis. After the complete 02 articles were selected, 60 patients with a mean age of 23.1 years were studied and compared dental flossing before or after dental brushing. RESULTS: The results showed that there was no statistical difference between brush-floss and floss-brush in reducing plaque index (p = 0.91, RR: 0.01, 95% CI: -0.16, 0.18). CONCLUSIONS: Flossing before or after brushing has no significant effect on reducing dental plaque index. However, more clinical studies should be conducted.

Phosphatidylethanol in patients with liver diseases of different etiologies: Analysis of six homologues and comparison with other alcohol markers.

BACKGROUND AND AIMS: Phosphatidylethanol (PEth) is a direct alcohol biomarker. Aim of the study was to evaluate the performance of six homologues of PEth in comparison to other alcohol markers in patients with liver diseases. METHODS: The study included 234 patients with liver disease, who gave statements about alcohol consumption during the three months prior to the doctor's appointment. Ethylglucuronide in urine (uEtG) and in hair (hEtG) and carbohydrate-deficient transferrin (CDT) were analyzed in addition to PEth. RESULTS: Of all patients 47% stated to have drunk alcohol during the past three months. UEtG, hEtG and CDT showed a sensitivity of 29% and a specificity of 92% together for ingestion of at least two standard drinks (24 g) per week. With PEth 16:0/18:1 in addition, sensitivity increased to 59%. For consumption in the last week uEtG's sensitivity and specificity was 28% and 100%, respectively. PEth's was 75% and 93%. When looking at patients who consumed at least two standard drinks per week during the past three months and of which a hair sample could be obtained, hEtG's sensitivity was 37% and specificity 90%. PEth had a sensitivity of 53% and specificity of 100%. Quotients of PEth 16:0/18:1 with 16:0/18:2, 16:0/20:4 and 18:0/18:2 were smaller when alcohol had been consumed more recently. CONCLUSION: Despite the rather poor overall sensitivity of alcohol biomarkers in this study, PEth showed best sensitivity for all time periods of alcohol consumption.

Pyridazinones containing dithiocarbamoyl moieties as a new class of selective MAO-B inhibitors.

A novel class of potential MAO-B inhibitors was designed and synthesized in good yield by combining the pyridazinone moiety with the dithiocarbamate framework, two relevant pharmacophores for drug discovery. The biological results obtained for the different pyridazinone/dithiocarbamate hybrids (compounds 8-14) indicated that most of them reversibly and selectively inhibit the hMAO-B in vitro with IC50 values in the µM range and exhibit not significant cellular toxicity. The analogues 9a1, 11a1, 12a2, 12b1 and 12b2, which present the dithiocarbamate fragment derivatized with a piperidin-1-yl or pyrrolidin-1-yl group and placed at C3 or C4 of the diazine ring, were the most attractive compounds of these series. Molecular modeling studies were performed to analyze the binding mode to the enzyme and the structure activity relationships of the titled compounds, as well as to predict their drug-like properties.

The value of intravenous contrast medium in PSMA PET/CT imaging in patients with biochemical recurrence of prostate cancer.

PURPOSE: To investigate the added value of diagnostic abdominal contrast-enhanced computed tomography (ceCT) in Ga-68 PSMA PET/CT in prostate cancer patients with biochemical recurrence (BCR). METHODS: Eighty-two consecutive patients (median age, 69 years; range, 45-86 years) with BCR underwent Ga-68 PSMA PET/CT with low-dose nonenhanced (ne) whole-body CT and diagnostic ceCT. Imaging results were retrospectively reviewed by two readers (R1, R2) for diagnostic certainty, local recurrence, lymph node metastasis (LNM) and bone metastasis. Interobserver agreement was assessed. Histopathology served as reference standard in 7, imaging and clinical follow-up in 65 and clinical follow-up alone in 10 patients. RESULTS: Certain local recurrence, LNM and bone metastasis diagnoses increased substantially from ceCT (R1: 5%/18%/32%; R2: 37%/50%/82%) to nePET/CT (R1: 78%/87%/93%; R2: 81%/87%/95%) for both readers, but the difference between nePET/CT and cePET/CT (R1: 77%/96%/92%; R2: 89%/94%/96%) was marginal. Interobserver agreement was minimal with ceCT (Krippendorff's alpha: 0.04-0.26), substantial with nePET/CT (0.60-0.86) and best with cePET/CT (0.76-0.86). The areas under the receiver operating characteristic curve (AUCs) for local recurrence for R1/R2 were 0.60/0.65 for ceCT, 0.81/0.79 for nePET/CT and 0.81/0.82 for cePET/CT. AUCs for LNMs for R1/R2 were 0.67/0.77 for ceCT, 0.91/0.82 for nePET/CT and 0.92/0.87 for cePET/CT. AUCs for BMs for R1/R2 were 0.60/0.53 for ceCT, 0.93/0.84 for nePET/CT and 0.93/0.86 for cePET/CT. CONCLUSION: Diagnostic abdominal ceCT increases the diagnostic certainty and interobserver agreement in Ga-68 PSMA PET/CT in BCR of prostate cancer. The diagnostic performance of cePET/CT is significantly better than ceCT alone but not nePET/CT.

Surgical Trauma in Mice Modifies the Content of Circulating Extracellular Vesicles.

Surgical interventions rapidly trigger a cascade of molecular, cellular, and neural signaling responses that ultimately reach remote organs, including the brain. Using a mouse model of orthopedic surgery, we have previously demonstrated hippocampal metabolic, structural, and functional changes associated with cognitive impairment. However, the nature of the underlying signals responsible for such periphery-to-brain communication remains hitherto elusive. Here we present the first exploratory study that tests the hypothesis of extracellular vesicles (EVs) as potential mediators carrying information from the injured tissue to the distal organs including the brain. The primary goal was to investigate whether the cargo of circulating EVs after surgery can undergo quantitative changes that could potentially trigger phenotypic modifications in the target tissues. EVs were isolated from the serum of the mice subjected to a tibia surgery after 6, 24, and 72 h, and the proteome and miRNAome were investigated using mass spectrometry and RNA-seq approaches. We found substantial differential expression of proteins and miRNAs starting at 6 h post-surgery and peaking at 24 h. Interestingly, one of the up-regulated proteins at 24 h was α-synuclein, a pathogenic hallmark of certain neurodegenerative syndromes. Analysis of miRNA target mRNA and corresponding biological pathways indicate the potential of post-surgery EVs to modify the extracellular matrix of the recipient cells and regulate metabolic processes including fatty acid metabolism. We conclude that surgery alters the cargo of circulating EVs in the blood, and our results suggest EVs as potential systemic signal carriers mediating remote effects of surgery on the brain.

Extensive nuclear gyration and pervasive non-genic transcription during primordial germ cell development in zebrafish.

Primordial germ cells (PGCs) are the precursors of germ cells, which migrate to the genital ridge during early development. Relatively little is known about PGCs after their migration. We studied this post-migratory stage using microscopy and sequencing techniques, and found that many PGC-specific genes, including genes known to induce PGC fate in the mouse, are only activated several days after migration. At this same time point, PGC nuclei become extremely gyrated, displaying general broad opening of chromatin and high levels of intergenic transcription. This is accompanied by changes in nuage morphology, expression of large loci (PGC-expressed non-coding RNA loci, PERLs) that are enriched for retro-transposons and piRNAs, and a rise in piRNA biogenesis signatures. Interestingly, no nuclear Piwi protein could be detected at any time point, indicating that the zebrafish piRNA pathway is fully cytoplasmic. Our data show that the post-migratory stage of zebrafish PGCs holds many cues to both germ cell fate establishment and piRNA pathway activation.

Monitoring jaw osteomyelitis therapy with single-photon emission computed tomography/computed tomography.

OBJECTIVE: The aim of the study was to evaluate the value of single-photon emission computed tomography/computed tomography (SPECT/CT) for therapy response assessment of jaw osteomyelitis. MATERIALS AND METHODS: Thirty-four baseline and 74 follow-up SPECT/CT examinations for therapy response assessment were performed in 34 patients with jaw osteomyelitis. SPECT/CT and planar late-phase bone scintigraphy images were assessed at baseline and follow-up, according to the following criteria: tracer uptake grade (0 = no uptake, 1 = low uptake, 2 = moderate uptake and 3 = high uptake); and morphologic signs (osteolysis, sequestration, sclerosis, periosteal reaction and pathologic fracture). RESULTS: At baseline, SPECT/CT showed marked (grade 2 or 3) uptake in 91% (31/34) of the patients, osteolysis in 85% (29/34), sclerosis in 71% (24/34), periosteal reaction in 44% (15/34) and a sequestrum in 24% (8/34). In 24 patients with clinically complete remission during or after at least 12 months' therapy, bone scintigraphy showed grade 0 or 1 uptake in 100% (24/24) and SPECT/CT in 91% (22/24) of the patients. Sclerosis with the disappearance of osteolysis, sequestration and periosteal reactions was the predominant morphologic finding in complete responders (68%; 16/24). In 10 patients with symptoms of exacerbation of the osteomyelitis, 80% (8/10) showed increasing uptake, 90% (9/10) sclerosis, 80% osteolysis (8/10) and 40% (4/10) osteolysis and periosteal reactions. CONCLUSION: SPECT/CT is a valuable tool to accurately assess therapy response, disease exacerbation and complications of jaw osteomyelitis. Low-grade (grade 1) residual tracer uptake is common in patients with clinically complete remission and is suggestive of ongoing bone remodeling and healing.

[Modern diagnosis and therapy of benign thyroid diseases]. / Moderne Abklärung und Therapie benigner Schilddrüsenerkrankungen.

Modern diagnosis and therapy of benign thyroid diseases Abstract. Benign thyroid diseases continue to be widespread endocrine disorders. Early recognition of their symptoms and exact diagnosis are the prerequisite of targeted therapy and minimal impairment of the patient's well-being. Drug treatment, radioiodine therapy, thermal ablation procedures and surgery have been shown to be successful treatment options. As guidelines for diagnosis and treatment of patients continue to evolve, an interdisciplinary approach ensures optimal diagnosis and management on every step in the care for these patients. We present three clinical scenarios for benign thyroid disease: the symptomatic goitre, the painful thyroid and the thyroid with hyperthyroidism.

Impaired diagnostic accuracy of hair ethyl glucuronide testing in patients with renal dysfunction.

The impact of renal impairment and hemodialysis on ethyl glucuronide concentrations in hair (hEtG) is not well known. Here, hEtG levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in patients presenting to the transplant outpatient clinic and compared with the self-reported alcohol consumption in an anonymous validated questionnaire. Estimated daily alcohol intake (EDI) was calculated. A total of 94 patients with varying renal function (Glomerular filtration rate (GFR) > 60 mL/min: group 1 (n = 47); GFR 30-60 ml/min: group 2 (n = 29); GFR < 30 mL/min: group 3 (n = 18)) were included in the study. Fifteen of 18 (83.3%) patients in group 3 were on dialysis. Altogether, hEtG tested positive (> 5 pg/mg) in 25.5% (n = 24) of patients, while 36.2% (n = 34) and 14.9% (n = 14) of patients reported any or regular (> 10 g/d) alcohol consumption, respectively. The median hEtG concentration of positive samples was much higher in patients in group 3 with advanced renal dysfunction or on dialysis than in patients in group 1 or 2 (group 1, 2, 3 dialysis patients: 74, 52, 145 and 155 pg/mg, respectively), although they consumed on average much less alcohol per day (median EDI group 1, 2, 3, dialysis patients: 16, 17, 3 and 3 g/d, respectively). Also, there was a significant correlation between the hEtG concentration and EDI for patients in group 1 (ρ = 0.84; p = 0.01), but not for patients in group 2 (ρ = -0.35, p = 0.39) or 3 (ρ = 0.02, p = 0.96). Furthermore, the ability of hEtG to correctly identify abstainers as such was lower for patients with advanced renal dysfunction than for the remaining patients (specificity for group 1, 2, 3: 92%, 87%, 82%, respectively). So, monitoring hEtG concentration was less reliable in patients with advanced renal dysfunction or on hemodialysis and by far overestimated the amount of alcohol consumed.