Ultrasound grading of thyroid nodules using the BTA U-scoring guidelines – Is there evidence of intra-and interobserver variability?

IntroductionU-score ultrasound classification (graded U1-U5) is widely used to grade thyroid nodules based on benign and malignant sonographic features. It is well established that ultrasound is an operator-dependent imaging modality and thus more susceptible to subjective variances between operators when using imaging-based scoring systems. We aimed to assess whether there is any intra- or interobserver variability when U-scoring thyroid nodules and whether previous thyroid ultrasound experience has an effect on this variability.MethodsA total of 14 ultrasound operators were identified (five experienced thyroid operators, five with intermediate experience and four with no experience) and were asked to U-score images from 20 thyroid cases shown as a single projection, with and without Doppler flow. The cases were subsequently rescored by the 14 operators after six weeks. The first and second round U-scores for the three operator groups were then analysed using Fleiss’ kappa to assess interobserver variability and Cochran’s Q test to determine any intraobserver variability.ResultsWe found no significant interobserver variability on combined assessment of all operators with fair agreement in round 1 (Fleiss’ kappa = 0.30, p <0.0001) and slight agreement in round 2 (Fleiss’ kappa = 0.19, p < 0.0001). Cochran’s Q test revealed no significant intraobserver variability in all 14 operators between round 1 and round 2 (all p>0.05).ConclusionsWe found no statistically significant inter- or intraobserver variability in the U-scoring of thyroid nodules between all participants reinforcing the validity of this scoring method in clinical practice, allaying concerns regarding potential subjective biases in reporting.     

Systemic immune-inflammation index is a promising non-invasive biomarker for predicting the survival of urinary system cancers: a systematic review and meta-analysis

ObjectiveSystemic immune-inflammation index (SII) has been reported in numerous studies to effectively predict the survival outcomes of urinary system cancers; however no agreement has been reached. This meta-analysis aimed to explore the prognostic significance of pre-treatment SII in tumours of the urinary system.MethodsRelevant published articles were selected from Web of Science, PubMed, Embase, and the Cochrane Library up to 30 August 2020. The hazard ratios (HRs) with 95% confidence intervals (CIs) were computed to estimate the associations of pre-treatment SII with overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS) in urinary system cancers.Results13 papers were included in our meta-analysis. From the combined data, we found that a high pre-treatment SII indicated a markedly worse OS (HR = 1.98; 95% CI: 1.75–2.23; p < .001), PFS (HR: 2.08; 95% CI: 1.32–3.26; p = .002), and CSS (HR: 2.41, 95% CI: 1.73–3.35, p < .001). Additionally, patients with an elevated SII value might have undesirable pathological characteristics, including a large tumour size, a poor differentiation grade, and an advanced tumour stage (all p < .001).ConclusionsPre-treatment SII could be used as a non-invasive and promising biomarker to indicate the prognosis of urinary system cancer patients.

KEY MESSAGES:

• This meta-analysis evaluates the predictive value of systemic immune-inflammation index (SII) for patients with urinary system cancer.
• A high pre-treatment SII indicates a poor prognosis.
• SII can serve as a promising non-invasive biomarker to help clinicians assess the prognosis and develop treatment strategies for urinary system cancer patients.

     

Performance and user evaluation of a novel capacitance-based automatic urinometer compared with a manual standard urinometer after elective cardiac surgery

IntroductionIn the intensive care setting, most physiologic parameters are monitored automatically. However, urine output (UO) is still monitored hourly by manually handled urinometers. In this study, we evaluated an automatic urinometer (AU) and compared it with a manual urinometer (MU).MethodsThis prospective study was carried out in the intensive care unit of a cardiothoracic surgical clinic. In postoperative patients (n = 34) with indwelling urinary catheters and an expected stay of 24 hours or more, hourly UO samples were measured with an AU (Sippi, n = 220; Observe Medical, Gothenburg, Sweden) or an MU (UnoMeter™ 500, n = 188; Unomedical, Birkerød, Denmark) and thereafter validated by cylinder measurements. Malposition of the instrument at the time of reading excluded measurement. Data were analyzed with the Bland-Altman method. The performance of the MU was used as the minimum criterion of acceptance when the AU was evaluated. The loss of precision with the MU due to temporal deviation from fixed hourly measurements was recorded (n = 108). A questionnaire filled out by the ward staff (n = 28) was used to evaluate the ease of use of the AU compared with the MU.ResultsBland-Altman analysis showed a smaller mean bias for the AU (+1.9 ml) compared with the MU (+5.3 ml) (P <0.0001). There was no statistical difference in measurement precision between the two urinometers, as defined by their limits of agreement (±15.2 ml vs. ±16.6 ml, P = 0.11). The mean temporal variation with the MU was ±7.4 minutes (±12.4%), and the limits of agreement were ±23.9 minutes (±39.8%), compared with no temporal variation with the AU (P <0.0001). The ward staff considered the AU easy to learn to use and rated it higher than the MU (P <0.0001).ConclusionsThe AU was not inferior to the MU and was significantly better in terms of bias, temporal deviation and staff opinion, although the clinical relevance of these findings may be open to discussion.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-0899-4) contains supplementary material, which is available to authorized users.     

The inter-rater reliability of clinical tests that best predict the subclassification of lumbar segmental instability: structural,functional and combined instability

ObjectivesThis study investigated the inter-rater reliability of three structural end range lumbar segmental instability tests with the highest positive likelihood ratio (+ LR) against flexion–extension radiographs, and three functional mid-range clinical tests that predict the success of lumbar stabilisation exercises in patients with recurrent or chronic low-back pain (R/CLBP). The study also investigated the reliability of lumbar segmental instability, subclassification as: functional, structural and combined instability.MethodForty adults with R/CLBP (30 men and 10 women), aged 21–71 years, underwent repeated measurements of specific clinical tests for structural or functional lumbar segmental instability.ResultsAll functional-instability tests: the prone instability test (PIT), the aberrant motion test and the average passive straight-leg raise (PSLR>91°) test showed a high percentage agreement (90, 97·5 and 95%, respectively) and a high kappa coefficient (0·71, 0·79 and 0·77, respectively). In addition, two structural tests: the lumbar flexion range of motion (ROM) >53° and the passive lumbar extension test (PLET) showed a high percentage agreement (82 and 73%, respectively), and a moderate kappa coefficient (0·48 and 0·46, respectively). The lack of hypomobility with the posteroanterior (PA) glide test was found to be unreliable (agreement = 25%; k = − 0·02). Locating the pain-provoking segment, as the first portion of PIT, was found to be moderately reliable (k = 0·41). The subclassification categories of lumbar segmental instability (functional, structural and combined) were found to be significantly reliable (PABAK) 0·90, 0·70 and 0·95, respectively).DiscussionAll investigated tests (except the lack of hypomobility with the PA glide test), in addition to subclassifying the categories of lumbar segmental instability, were significantly reliable in the assessment of lumbar instability.     

Free breathing contrast-enhanced time-resolved magnetic resonance angiography in pediatric and adult congenital heart disease

Background

Contrast enhanced magnetic resonance angiography (MRA) is generally performed during a long breath-hold (BH), limiting its utility in infants and small children. This study proposes a free-breathing (FB) time resolved MRA (TRA) technique for use in pediatric and adult congenital heart disease (CHD).

Methods

A TRA sequence was developed by combining spiral trajectories with sensitivity encoding (SENSE, x4 kx-ky and x2 kz) and partial Fourier (75% in kz). As no temporal data sharing is used, an independent 3D data set was acquired every ~1.3s, with acceptable spatial resolution (~2.3x2.3x2.3mm). The technique was tested during FB over 50 consecutive volumes. Conventional BH-MRA and FB-TRA data was acquired in 45 adults and children with CHD. We calculated quantitative image quality for both sequences. Diagnostic accuracy was assessed in all patients from both sequences. Additionally, vessel measurements were made at the sinotubular junction (N = 43), proximal descending aorta (N = 43), descending aorta at the level of the diaphragm (N = 43), main pulmonary artery (N = 35), left pulmonary artery (N = 35) and the right pulmonary artery (N = 35). Intra and inter observer variability was assessed in a subset of 10 patients.

Results

BH-MRA had significantly higher homogeneity in non-contrast enhancing tissue (coefficient of variance, P <0.0001), signal-to-noise ratio (P <0.0001), contrast-to-noise ratio (P <0.0001) and relative contrast (P = 0.02) compared to the FB-TRA images. However, homogeneity in the vessels was similar in both techniques (P = 0.52) and edge sharpness was significantly (P <0.0001) higher in FB-TRA compared to BH-MRA. BH-MRA provided overall diagnostic accuracy of 82%, and FB-TRA of 87%, with no statistical difference between the two sequences (P = 0.77). Vessel diameter measurements showed excellent agreement between the two techniques (r = 0.98, P <0.05), with no bias (0.0mm, P = 0.71), and clinically acceptable limits of agreement (-2.7 to +2.8mm). Inter and intra observer reproducibility showed good agreement of vessel diameters (r>0.988, P<0.0001), with negligible biases (between -0.2 and +0.1mm) and small limits of agreement (between -2.4 and +2.5mm).

Conclusions

We have described a FB-TRA technique that is shown to enable accurate diagnosis and vessel measures compared to conventional BH-MRA. This simplifies the MRA technique and will enable angiography to be performed in children and adults whom find breath-holding difficult.

Electronic supplementary material

The online version of this article (doi:10.1186/s12968-015-0138-9) contains supplementary material, which is available to authorized users.     

Comparison of two- and three-dimensional transvaginal ultrasound in the visualisation of intrauterine devices

The aims of the study were to evaluate whether three-dimensional transvaginal ultrasound (3D TV US) is superior to two-dimensional transvaginal ultrasound (2D TV US) at visualising intrauterine devices and determining their position. This prospective study included 52 participants with an intrauterine device fitted, who underwent 2D TV US and 3D TV US. 2D TV US and 3D-reconstructed coronal images were reviewed by two gynaecological radiologists to assess ease of visualisation and position of the intrauterine devices. Statistical analysis was performed using Wilcoxon signed-rank, McNemar and Chi-squared tests. The inter-observer agreement was measured using Cohen’s Kappa. Intrauterine device visualisation scores were significantly higher with 2D TV US compared with 3D TV US (Radiologist 1 p = <0.001, Radiologist 2 p = 0.007). A significant number of T-arms appeared to perforate into the adjacent myometrium on the 3D-reconstructed coronal image, but were normal on the 2D images (Radiologist 1 p = <0.001, Radiologist 2 p = 0.008). Radiologist 1 found 19 perforated T-arms on 3D TV US compared with four on 2D TV US. Radiologist 2 found 13 perforated T-arms on 3D TV US compared with five on 2D TV US. Both radiologists agreed on the positions of the intrauterine devices substantially with 3D TV US (Kappa = 0.69) and moderately with 2D TV US (Kappa = 0.55). The 3D TV US did not visualise an intrauterine device better than 2D TV US. The 3D-reconstructed coronal image of the uterus can reliably display cases of T-arm perforation into the adjacent myometrium, which could be missed on 2D TV US images. The 3D TV US should be used in addition to 2D TV US in all cases where an intrauterine device is under evaluation.     

The pattern of human papillomavirus infection and genotypes among Nigerian women from 1999 to 2019: a systematic review

BackgroundThere are no robust national prevalence of Human Papillomavirus (HPV) genotypes in Nigerian women despite the high burden of cervical cancer morbidity and mortality.The objective of studyThis study aims to determine the pooled prevalence and risk factors of genital HPV infection in Nigeria through a systemic review protocol.MethodsDatabases including PubMed, Scopus, Google Scholar and AJOL were searched between 10 April to 28 July 2020. HPV studies on Nigerian females and published from April 1999 to March 2019 were included. GRADE was used to assess the quality of evidence.ResultsThe pooled prevalence of cervical HPV was 20.65% (95%CI: 19.7–21.7). Genotypes 31 (70.8%), 35 (69.9%) and 16 (52.9%) were the most predominant HPV in circulation. Of the six geopolitical zones in Nigeria, northeast had the highest pooled prevalence of HPV infection (48.1%), while the least was in the north-west (6.8%). After multivariate logistic regression, duration (years) of sexual exposure (OR = 3.24, 95%CI: 1.78–9.23]), history of other malignancies (OR = 1.93, 95%CI: 1.03–2.97]), history of sexually transmitted infection (OR = 2.45, 95% CI: 1.31–3.55]), coital frequency per week (OR = 5.11, 95%CI: 3.86–14.29), the status of circumcision of the sexual partner (OR = 2.71, 95%CI: 1.62–9.05), and marital status (OR = 1.72, 95%CI: 1.16–4.72), were significant risk factors of HPV infection (p < 0.05). Irregular menstruation, post-coital bleeding and abdominal vaginal discharge were significantly associated with HPV infection (p < 0.05).ConclusionHPV prevalence is high in Nigeria and was significantly associated with several associated risk factors. Rapid screening for high-risk HPV genotypes is recommended and multivalent HPV vaccines should be considered for women.     

Predictors for mechanical ventilation and short-term prognosis in patients with Guillain-Barré syndrome

IntroductionGuillain-Barré syndrome (GBS) is an immune-mediated disorder of the peripheral nervous system. Respiratory failure requiring mechanical ventilation (MV) is a serious complication of GBS. Identification of modifiable risk factors for MV and poor short-term prognosis in mechanically ventilated patients with GBS may contribute to the individualized management and may help improve the outcome of the patients.MethodsWe retrospectively analyzed the clinical data of 541 patients who were diagnosed with GBS from 2003 to 2014. Independent predictors for MV and short-term prognosis in mechanically ventilated patients were identified via multivariate logistic regression analysis.ResultsThe mean age was 41.6 years with a male predilection (61.2 %). Eighty patients (14.8 %) required MV. Multivariate analysis revealed that shorter interval from onset to admission (p < 0.05), facial nerve palsy (p < 0.01), glossopharyngeal and vagal nerve deficits (p < 0.01) and lower Medical Research Council (MRC) sum score at nadir (p < 0.01) were risk factors for MV; disease occurrence in summer (p < 0.01) was a protective factor. As to prognostic factors, absence of antecedent infections (p < 0.01) and lower MRC sum score at nadir (p < 0.01) were predictors of poor short-term prognosis in mechanically ventilated patients regardless of treatment modality. We further investigated the predictors of poor short-term prognosis in patients requiring MV with different nadir MRC sum scores. Combined use of intravenous corticosteroids with intravenous immunoglobulin (odds ratio 10.200, 95 % confidence interval 1.068–97.407, p < 0.05) was an independent predictor of poor short-term prognosis in mechanically ventilated patients with a nadir MRC sum score from 0 to 12 points, regardless of existence of antecedent infection.ConclusionsClinical predictors of MV and poor short-term prognosis in mechanically ventilated GBS patients were distinct. Add-on use of intravenous corticosteroids was a risk factor for poor short-term prognosis in mechanically ventilated patients with a nadir MRC sum score from 0 to 12 points.     

Mild traumatic brain injury affects the features of migraine

BackgroundHeadache is one of the most common symptoms after concussion, and mild traumatic brain injury (mTBI) is a risk factor for chronic migraine (CM). However, there remains a paucity of data regarding the impact of mTBI on migraine-related symptoms and clinical course.MethodsOf 2161 migraine patients who participated in the American Registry for Migraine Research between February 2016 and March 2020, 1098 completed questions assessing history of TBI (50.8%). Forty-four patients reported a history of moderate to severe TBI, 413 patients reported a history of mTBI. Patients’ demographics, headache symptoms and triggers, history of physical abuse, allodynia symptoms (ASC-12), migraine disability (MIDAS), depression (PHQ-2), and anxiety (GAD-7) were compared between migraine groups with (n = 413) and without (n = 641) a history of mTBI. Either the chi-square-test or Fisher’s exact test, as appropriate, was used for the analyses of categorical variables. The Mann-Whitney test was used for the analyses of continuous variables. Logistic regression models were used to compare variables of interest while adjusting for age, gender, and CM.ResultsA significantly higher proportion of patients with mTBI had CM (74.3% [307/413] vs. 65.8% [422/641], P = 0.004), had never been married or were divorced (36.6% [147/402] vs. 29.4% [187/636], P = 0.007), self-reported a history of physical abuse (24.3% [84/345] vs. 14.3% [70/491], P <  0.001), had mild to severe anxiety (50.5% [205/406] vs. 41.0% [258/630], P = 0.003), had headache-related vertigo (23.0% [95/413] vs. 15.9% [102/640], P = 0.009), and difficulty finding words (43.0% [174/405] vs. 32.9% [208/633], P <  0.001) in more than half their attacks, and headaches triggered by lack of sleep (39.4% [155/393] vs. 32.6% [198/607], P = 0.018) and reading (6.6% [26/393] vs. 3.0% [18/607], P = 0.016), compared to patients without mTBI. Patients with mTBI had significantly greater ASC-12 scores (median [interquartile range]; 5 [1–9] vs. 4 [1–7], P < 0.001), MIDAS scores (42 [18–85] vs. 34.5 [15–72], P = 0.034), and PHQ-2 scores (1 [0–2] vs. 1 [0–2], P = 0.012).ConclusionPatients with a history of mTBI are more likely to have a self-reported a history of physical abuse, vertigo, and allodynia during headache attacks, headaches triggered by lack of sleep and reading, greater headache burden and headache disability, and symptoms of anxiety and depression. This study suggests that a history of mTBI is associated with the phenotype, burden, clinical course, and associated comorbid diseases in patients with migraine, and highlights the importance of inquiring about a lifetime history of mTBI in patients being evaluated for migraine.     

Clinical relevance of depressed kynurenine pathway in episodic migraine patients: potential prognostic markers in the peripheral plasma during the interictal period

BackgroundAltered glutamatergic neurotransmission and neuropeptide levels play a central role in migraine pathomechanism. Previously, we confirmed that kynurenic acid, an endogenous glutamatergic antagonist, was able to decrease the expression of pituitary adenylate cyclase-activating polypeptide 1–38, a neuropeptide with known migraine-inducing properties. Hence, our aim was to reveal the role of the peripheral kynurenine pathway (KP) in episodic migraineurs. We focused on the complete tryptophan (Trp) catabolism, which comprises the serotonin and melatonin routes in addition to kynurenine metabolites. We investigated the relationship between metabolic alterations and clinical characteristics of migraine patients.MethodsFemale migraine patients aged between 25 and 50 years (n = 50) and healthy control subjects (n = 34) participated in this study. Blood samples were collected from the cubital veins of subjects (during both the interictal/ictal periods in migraineurs, n = 47/12, respectively). 12 metabolites of Trp pathway were determined by neurochemical measurements (UHPLC-MS/MS).ResultsPlasma concentrations of the most Trp metabolites were remarkably decreased in the interictal period of migraineurs compared to healthy control subjects, especially in the migraine without aura (MWoA) subgroup: Trp (p < 0.025), L-kynurenine (p < 0.001), kynurenic acid (p < 0.016), anthranilic acid (p < 0.007), picolinic acid (p < 0.03), 5-hydroxy-indoleaceticacid (p < 0.025) and melatonin (p < 0.023). Several metabolites showed a tendency to elevate during the ictal phase, but this was significant only in the cases of anthranilic acid, 5-hydroxy-indoleaceticacid and melatonin in MWoA patients. In the same subgroup, higher interictal kynurenic acid levels were identified in patients whose headache was severe and not related to their menstruation cycle. Negative linear correlation was detected between the interictal levels of xanthurenic acid/melatonin and attack frequency. Positive associations were found between the ictal 3-hydroxykynurenine levels and the beginning of attacks, just as between ictal picolinic acid levels and last attack before ictal sampling.ConclusionsOur results suggest that there is a widespread metabolic imbalance in migraineurs, which manifests in a completely depressed peripheral Trp catabolism during the interictal period. It might act as trigger for the migraine attack, contributing to glutamate excess induced neurotoxicity and generalised hyperexcitability. This data can draw attention to the clinical relevance of KP in migraine.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01239-1.     

InterMiG: international differences in the therapeutic approach to migraine patients in specialized headache centers

BackgroundThere is currently a wide therapeutic arsenal for migraine patients, without a single first-line preventive drug and we choose the different available alternatives taking into account comorbidities, national guidelines, previous treatments and personal experiences.Our objective was to evaluate the differences in the use of migraine treatments between neurologists from different countries.MethodsThis is a multi-centre observational study carried out by neurologists from specialized headache units in seven countries, retrospective with consecutive inclusion of all patients presenting with a migraine diagnosis, over a period of three months.ResultsA total of 734 patients were recruited but only 600 were considered in the analysis in order to homogenize the patient cohorts from countries: 200 Spain (ES), 100 Italy (IT), 85 Russia (RUS), 80 Germany (DE), 60 Portugal (PT), 45 Poland (PL) and 30 Australia (AU). 85.4 % of patients were women with a mean age of 42.6 ± 11.8 years. Considering previous and current preventive treatment, the order of use was: antidepressants (69.3 %), antiepileptic drugs (54.7 %), beta-blockers and antihypertensive drugs (49.7 %), OnabotulinumtoxinA (44.0 %) and others (36.2 %).Statistically significant differences were found between all pharmacological classes: antidepressants were commonly used in all countries, with the exception of Poland (AU: 76.7 %, IT: 71.0 %, DE: 60.0 %, PL: 31.1 %, PT: 71.7 %, RUS: 70.6 %, ES: 78.5 %; p < 0.0001); antiepileptic drugs were more frequently prescribed in Portugal, Australia and Spain (AU: 73.3 %, IT: 40.0 %, DE: 37.5 %, PL: 48.9 %, PT: 85.0 %, RUS: 29.4 % and ES: 69.0 %; p < 0.0001); beta-blockers and antihypertensive drugs were frequently used in all countries except Italy (AU: 60.0 %, IT: 14.0 %, DE: 53.8 %, PL: 48.9 %, PT: 68.3 %, RUS: 49.4 % and ES: 59.0 %; p < 0.0001); BTX-A were predominately used in Spain, Italy and Australia (AU:56.7 %, IT:58.0 %, DE:20.0 %, PL: 42.2 %, PT: 26.7 %, RUS: 24.7 % and ES: 58.5 %; p < 0.0001) and others were most frequently used in Poland (AU: 0.0 %, IT: 19.0 %, DE: 42.5 %, PL: 95.6 %, PT: 31.7 %, RUS: 3.5 % and ES: 49.5 %; p < 0.0001). If only patients without comorbidities are considered (200/600), statistically differences between countries persist in all preventive treatments.ConclusionsThere is heterogeneity in the choice of preventive treatment between different countries. Prospective comparative studies of the different oral and subcutaneous alternatives would help to create a global therapeutic algorithm that would guarantee the best option for our patients.     

Functional Testing for Tranexamic Acid Duration of Action Using Modified Viscoelastometry

IntroductionTranexamic acid (TXA) is the standard medication to prevent or treat hyperfibrinolysis. However, prolonged inhibition of lysis (so-called “fibrinolytic shutdown”) correlates with increased mortality. A new viscoelastometric test enables bedside quantification of the antifibrinolytic activity of TXA using tissue plasminogen activator (TPA).Materials and MethodsTwenty-five cardiac surgery patients were included in this prospective observational study. In vivo, the viscoelastometric TPA test was used to determine lysis time (LT) and maximum lysis (ML) over 96 h after TXA bolus. Additionally, plasma concentrations of TXA and plasminogen activator inhibitor 1 (PAI-1) were measured. Moreover, dose effect curves from the blood of healthy volunteers were performed in vitro. Data are presented as median (25–75th percentile).ResultsIn vivo TXA plasma concentration correlated with LT (r = 0.55; p < 0.0001) and ML (r = 0.62; p < 0.0001) at all time points. Lysis was inhibited up to 96 h (LT_TPA-test: baseline: 398 s [229–421 s] vs. at 96 h: 886 s [626–2,175 s]; p = 0.0013). After 24 h, some patients (n = 8) had normalized lysis, but others (n = 17) had strong lysis inhibition (ML <30%; p < 0.001). The high- and low-lysis groups differed regarding kidney function (cystatin C: 1.64 [1.42–2.02] vs. 1.28 [1.01–1.52] mg/L; p = 0.002) in a post hoc analysis. Of note, TXA plasma concentration after 24 h was significantly higher in patients with impaired renal function (9.70 [2.89–13.45] vs.1.41 [1.30–2.34] µg/mL; p < 0.0001). In vitro, TXA concentrations of 10 µg/mL effectively inhibited fibrinolysis in all blood samples.ConclusionsDetermination of antifibrinolytic activity using the TPA test is feasible, and individual fibrinolytic capacity, e.g., in critically ill patients, can potentially be measured. This is of interest since TXA-induced lysis inhibition varies depending on kidney function.     

Alanine aminotransferase and spleno-portal dynamics affect spleen stiffness measured by point shear-wave elastography in patients with chronic hepatitis C in the absence of significant liver fibrosis

BackgroundSpleen stiffness (SS) has gained a lot of interest in the context of liver cirrhosis and portal hypertension stratification. However, there is a paucity of data on confounding factors that may alter SS values.MethodsBetween January 2018 and October 2019, we enrolled 120 healthy subjects and 117 patients with hepatitis C virus (HCV) infection who did not have significant liver fibrosis (i.e., F0–1). Abdominal ultrasound evaluation was performed on each individual to measure portal vein diameter, portal flow velocity, spleen bipolar diameter, and splenic area. We also performed liver and spleen elastography.ResultsHCV patients had higher SS (p < 0.001), portal vein diameter (p = 0.031), portal flow velocity (p = 0.035), spleen bipolar diameter (p = 0.042) and area (p = 0.025), and ALT levels (p < 0.001). Linear regression models showed that SS increased by 3.220 kPa for each mm of portal vein diameter, by 0.7 kPa for each cm/s of portal flow velocity, by 2.239 kPa for each cm of spleen bipolar diameter, and by 0.233 kPa for each cm² of spleen area. Patients with HCV infection were stratified according to median ALT levels (i.e. 32 IU/L). SS and spleno-portal axis parameters were significantly higher in patients with an ALT level > 32 IU/L. Besides, the relationship between SS and ALT was described by cubic polynomial regression according to the following equation: 11.735 + 0.404 (ALT)¹ − 0.002 (ALT)² + 4.26 × 10^–6 (ALT)³.ConclusionsOur results bring new light to the role of inflammation as a confounding factor for SS measurement. Therefore, particular attention should be paid to serum transaminase for a correct evaluation of spleen elastography.     

Clinical symptoms of androgen deficiency in men with migraine or cluster headache: a cross-sectional cohort study

BackgroundTo compare symptoms of clinical androgen deficiency between men with migraine, men with cluster headache and non-headache male controls.MethodsWe performed a cross-sectional study using two validated questionnaires to assess symptoms of androgen deficiency in males with migraine, cluster headache, and non-headache controls. Primary outcome was the mean difference in androgen deficiency scores. Generalized linear models were used adjusting for age, BMI, smoking and lifetime depression. As secondary outcome we assessed the percentage of patients reporting to score below average on four sexual symptoms (beard growth, morning erections, libido and sexual potency) as these items were previously shown to more specifically differentiate androgen deficiency symptoms from (comorbid) anxiety and depression.ResultsThe questionnaires were completed by n = 534/853 (63%) men with migraine, n = 437/694 (63%) men with cluster headache and n = 152/209 (73%) controls. Responders were older compared to non-responders and more likely to suffer from lifetime depression.Patients reported more severe symptoms of clinical androgen deficiency compared with controls, with higher AMS scores (Aging Males Symptoms; mean difference ± SE: migraine 5.44 ± 0.90, p <  0.001; cluster headache 5.62 ± 0.99, p <  0.001) and lower qADAM scores (quantitative Androgen Deficiency in the Aging Male; migraine: − 3.16 ± 0.50, p <  0.001; cluster headache: − 5.25 ± 0.56, p <  0.001). Additionally, both patient groups more often reported to suffer from any of the specific sexual symptoms compared to controls (18.4% migraine, 20.6% cluster headache, 7.2% controls, p = 0.001).ConclusionMen with migraine and cluster headache more often suffer from symptoms consistent with clinical androgen deficiency than males without a primary headache disorder.     

Supplementation of EPA and DHA in pregnant women with type 1 diabetes mellitus

Background/objectiveLower proportions of n-3 PUFAs have been observed in neonates born to diabetic mothers. We aimed to investigate the association between DHA and EPA supplementation during pregnancy complicated with type 1 diabetes on concentration and proportion of fatty acids in maternal and foetal blood.Subjects and methodsWe conducted a prospective randomized, single-blinded, placebo-controlled trial of 111 eligible pregnant women with type 1 diabetes and presented the results of 84 (intervention arm and control arm comprised 42 participants each) of them who successfully finished the trial in an academic hospital. The initiation of EPA and DHA supplementation or placebo started at randomization visit on gestational week 11–12. Blood samples were taken on the first (screening) visit to the clinic (1st trimester, between 8th and 10th gestational week, GW), then in the second trimester (19–24th GW) and third trimester (30th–33rd GW). On the delivery day, a blood sample was taken on fasting just before birth. The umbilical vein blood sample was taken shortly after the delivery.ResultsWe found a significant increase in the intervention group when compared the first and the third trimester for n-3 PUFAs concentration, 4.3 mg/L (3.3–7.6): 10.0 mg/L (7.1–13.7), p < .001. In the intervention group, the concentration of DHA in maternal vein serum was 11.4 mg/L (7.7–17.5), and in umbilical vein serum, it was 5.1 mg/L (3.0–7.7), which was significantly higher than that in the control group, maternal vein serum: median 9.2 mg/L(6.0–12.3), p = .03 and umbilical vein serum: median 3.4 mg/L (2.1–5.6), p = .009.ConclusionThe increased weight gain in pregnancy and concentration and proportions of DHA, n-3 PUFAs with a decreased proportion of AA, n-6 PUFAs, and AA/DHA ratio in maternal and umbilical vein serum summarize the effect of supplementation with EPA and DHA.     

A polymorphism in the 3′-untranslated region of the matrix metallopeptidase 9 gene is associated with susceptibility to idiopathic calcium nephrolithiasis in the Chinese population

ObjectiveTo investigate whether single nucleotide polymorphisms (SNPs) in the 3′ untranslated region (UTR) of the matrix metallopeptidase 9 gene (MMP9) are associated with susceptibility to calcium oxalate stones.MethodsA total of 428 patients with kidney stone disease (KSD) and 450 control individuals were enrolled. Three MMP9 SNPs (rs20544, rs9509, and rs1056628) were genotyped, and MMP9 mRNA and protein expression was determined in patients and controls. The dual luciferase reporter gene assay was conducted by transfecting HEK293 cells with miR-491-5p mimics and plasmids containing MMP9 with rs1056628 AA/CC genotypes.ResultsThe rs1056628 CC genotype was significantly increased in KSD patients compared with controls (CC vs AA: odds ratio [OR] = 2.279, 95% confidence interval [CI] = 1.048–4.956). The rs1056628 C allele frequency was higher in KSD patients than controls. The increased KSD risks associated with rs1056628 were more evident in individuals aged <30 years (OR = 3.504, 95% CI = 1.102–11.139) and men (OR = 2.522, 95% CI = 1.004–6.334). mRNA and protein levels of MMP9 were significantly higher in KSD patients with the CC genotype than in those with the AA genotype.ConclusionThis study demonstrates that MMP9 SNP rs1056628 is associated with a significant KSD risk in Chinese Han individuals.     

Influence of iron deficiency anemia on glycated hemoglobin levels in non-diabetic Saudi women

ObjectiveStudies of patients with iron deficiency anemia (IDA) have shown a relationship between high glycated hemoglobin (HbA1c) and low hemoglobin (Hb) concentration. The present study was conducted to determine the influence of IDA on HbA1c in non-diabetic women.MethodsFifty-nine Saudi women (20 to 50 years old) were enrolled and categorized into groups according to their circulating hemoglobin concentration: Non-IDA (Hb ≥7.45 mmol/L; n = 38) and IDA (Hb ≤7.44 mmol/L; n = 21). The IDA group was further subdivided according to the severity of the IDA, as follows: mild (Hb 6.83 to 7.44 mmol/L; n = 9) and moderate–severe (Hb <6.83 mol/L; n = 12). HbA1c, Hb, ferritin, fasting blood glucose, and red blood cell (RBC) count were measured in each participant.ResultsHbA1c did not significantly differ between the groups, but the absolute HbA1c level was significantly lower in the mild and moderate–severe anemia groups than the non-anemic group, and was positively associated with Hb, ferritin, and RBC count. In addition, the HbA1c level was inversely associated with the Hb concentration.ConclusionsHbA1c is significantly associated with parameters related to IDA in non-diabetic Saudi women. Therefore, assessment of IDA-related parameters is recommended prior to making a diagnosis of diabetes.     

Advanced interatrial block predicts ineffective cardioversion of atrial fibrillation: a FinCV2 cohort study

AimsRhythm control using electrical cardioversion (CV) is a common treatment strategy for patients with symptomatic atrial fibrillation (AF). To guide clinical decision making, we sought to assess if electrocardiographic interatrial blocks could predict CV failure or AF recurrence as the phenomenon is strongly associated with atrial arrhythmias.MethodsThis study included 715 patients who underwent a CV for persistent AF lasting >48 h. P-wave duration and morphology were analyzed in post-procedure or the most recent sinus rhythm electrocardiograms and compared with rates of CV failure and AF recurrence within 30 days after CV as well as their combination (ineffective CV).ResultsCV was unsuccessful in 63 out of 715 patients (8.8%) and AF recurred in 209 out of 652 (29.2%) patients within 30 days after CV. Overall, 272 (38.0%) CVs turned out ineffective. Advanced interatrial block (AIAB) defined as P-wave duration ≥120 ms and biphasic morphology in inferior leads (II, III and aVF) was diagnosed in 72 (10.1%) cases. AIAB was an independent predictor for CV failure (OR 4.51, 95%CI 1.76–11.56, p = .002), AF recurrence (OR 2.93, 95%CI 1.43–5.99, p = .003) and ineffective CV (OR 3.87, 95%CI 2.04–7.36, p < .001).ConclusionAIAB predicted CV failure, AF recurrence as well as their composite. This study presents an easy electrocardiographic tool for the identification of patients with persistent AF who might not benefit from an elective CV in the future.

KEY MESSAGES

• Interatrial blocks are very common in patients with atrial fibrillation.
• Advanced interatrial block predicts ineffective cardioversion.

     

Risk profile,antithrombotic treatment and clinical outcomes of patients in Nordic countries with atrial fibrillation – results from the GARFIELD-AF registry

AimsThe objective was to evaluate the clinical characteristics, management and two-year outcomes of patients with newly diagnosed non-valvular atrial fibrillation at risk for stroke in Nordic countries.MethodsWe examined the baseline characteristics, antithrombotic treatment, and two-year clinical outcomes of patients from four Nordic countries.ResultsA total of 52,080 patients were enrolled in the GARFIELD-AF. Out of 29,908 European patients, 2,396 were recruited from Nordic countries. The use of oral anticoagulants, alone or in combination with antiplatelet (AP), was higher in Nordic patients in all CHA₂DS₂-VASc categories: 0–1 (72.8% vs 60.3%), 2–3 (78.7% vs 72.9%) and ≥4 (79.2% vs 74.1%). In Nordic patients, NOAC ± AP was more frequently prescribed (32.0% vs 27.7%) and AP monotherapy was less often prescribed (10.4% vs 18.2%) when compared with Non-Nordic European patients. The rates (per 100 patient years) of all-cause mortality and non-haemorrhagic stroke/systemic embolism (SE) were similar in Nordic and Non-Nordic European patients [3.63 (3.11–4.23) vs 4.08 (3.91–4.26), p value = .147] and [0.98 (0.73–1.32) vs 1.02 (0.93–1.11), p value = .819], while major bleeding was significantly higher [1.66 (1.32–2.09) vs 1.01 (0.93–1.10), p value < .001].ConclusionNordic patients had significantly higher major bleeding than Non-Nordic-European patients. In contrast, rates of all-cause mortality and non-haemorrhagic stroke/SE were comparable. Clinical Trial RegistrationUnique identifier: NCT01090362. URL: http://www.clinicaltrials.gov. Key MessageNordic countries had significantly higher major bleeding than Non-Nordic-European countries. Rates of mortality and non-haemorrhagic stroke/SE were similar .