Fast and accurate Slicewise OutLIer Detection (SOLID) with informed model estimation for diffusion MRI data

The accurate characterization of the diffusion process in tissue using diffusion MRI is greatly challenged by the presence of artefacts. Subject motion causes not only spatial misalignments between diffusion weighted images, but often also slicewise signal intensity errors. Voxelwise robust model estimation is commonly used to exclude intensity errors as outliers. Slicewise outliers, however, become distributed over multiple adjacent slices after image registration and transformation. This challenges outlier detection with voxelwise procedures due to partial volume effects. Detecting the outlier slices before any transformations are applied to diffusion weighted images is therefore required. In this work, we present i) an automated tool coined SOLID for slicewise outlier detection prior to geometrical image transformation, and ii) a framework to naturally interpret data uncertainty information from SOLID and include it as such in model estimators. SOLID uses a straightforward intensity metric, is independent of the choice of the diffusion MRI model, and can handle datasets with a few or irregularly distributed gradient directions. The SOLID-informed estimation framework prevents the need to completely reject diffusion weighted images or individual voxel measurements by downweighting measurements with their degree of uncertainty, thereby supporting convergence and well-conditioning of iterative estimation algorithms. In comprehensive simulation experiments, SOLID detects outliers with a high sensitivity and specificity, and can achieve higher or at least similar sensitivity and specificity compared to other tools that are based on more complex and time-consuming procedures for the scenarios investigated. SOLID was further validated on data from 54 neonatal subjects which were visually inspected for outlier slices with the interactive tool developed as part of this study, showing its potential to quickly highlight problematic volumes and slices in large population studies. The informed model estimation framework was evaluated both in simulations and in vivo human data.Peer reviewe

Efficacy of salbutamol via Easyhaler®unaffected by low inspiratory flow

AbstractThe fine particle dose delivered via dry powder inhalers (DPIs) is often affected by the inspiratory flow rate generated during inhalation. This has clinical implications, since the fine particle dose determines the amount of drug reaching the lungs. With Easyhaler®DPI the fine particle dose remains relatively constant over the range of inspiratory flow rates from 30–60 l min−1. The aim of this study was to confirm that clinical efficacy is maintained even at low flow rates by comparing the bronchodilating effect of salbutamol (100 μ g) delivered via Easyhaler®at a target inspiratory flow of 30 l min−1with the same dose of salbutamol via pressurised metered-dose inhaler (pMDI) plus spacer.This was a double-blind, randomized, cross-over study with double-dummy technique. Twenty-one paediatric and adult asthmatic patients completed the study, which was conducted over 2 study days. The main outcome parameter was forced expiratory volume in 1 sec (FEV1). The patients were trained to generate a low peak inspiratory flow rate (PIFR) of 30 l min−1, and the actual PIFR through Easyhaler®was recorded.The average PIFR through Easyhaler®was 28·7 l min−1. The difference in the maximum value of FEV1(FEV1max) between the treatments after drug inhalation was 0·01 l. The mean of FEV1maxwas 2·67 l after pMDI plus spacer compared to 2·69 l after Easyhaler®. Improvements in FEV1were clinically significant. No significant differences between treatments were found.A reasonably low inspiratory flow rate through Easyhaler®produces an equivalent improvement in lung function to a correctly used pMDI plus spacer. Hence, Easyhaler®can be used with confidence in patients who may have difficulty in generating a high inspiratory flow rate, such as children and the elderly

Prediction of neo-adjuvant chemotherapy response in bladder cancer : the impact of clinical parameters and routine biomarkers

Purpose To investigate the role of clinical parameters and immunohistochemical (IHC) biomarkers in their feasibility to predict the effect of neo-adjuvant chemotherapy (NAC) in patients with muscle-invasive urothelial bladder cancer (MIBC). Materials and methods The first 76 consecutive patients with MIBC treated with NAC and radical cystectomy in two University hospitals in Finland between 2008 and 2013 were chosen for this study. After excluding patients with non-urothelial cancer, less than two cycles of chemotherapy, no tissue material for IHC analysis or non-muscle-invasive bladder cancer in re-review, 59 patients were included in the final analysis. A tissue microarray block was constructed from the transurethral resection samples and IHC stainings of Ki-67, p53, Her-2 and EGFR were made. The correlations between histological features in transurethral resection samples and immune-histochemical stainings were calculated. The associations of clinicopathological parameters and IHC stainings with NAC response were evaluated. Factors affecting survival were estimated. Results The complete response rate after NAC was 44%. A higher number of chemotherapy cycles was associated with better response to neo-adjuvant chemotherapy. No response to neo-adjuvant chemotherapy and female gender was associated with decreased cancer-specific survival. The IHC stainings used failed to show an association with neo-adjuvant chemotherapy response and overall or cancer specific survival. Conclusions Patients who do not respond to neo-adjuvant chemotherapy do significantly worse than responders. This study could not find clinical tools to distinguish responders from non-responders. Further studies preferably with larger cohorts addressing this issue are warranted to improve the selection of patients for neo-adjuvant chemotherapy.Peer reviewe

Late gadolinium enhancement (LGE) progresses with right ventricle volume in children after repair of tetralogy of fallot

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Prevalence of autoimmune disorders among bladder pain syndrome patients' relatives

Purpose Possible genetic background and autoimmune etiology of Bladder Pain Syndrome (BPS, formerly Interstitial Cystitis, IC) has been suggested. We studied whether familial clustering of BPS, other autoimmune diseases or fibromyalgia exist among BPS patients' genetically close relatives; possibly reflecting some common predisposing genetic background of these diseases. Materials and methods Altogether 420 first- or second-degree relatives of 94 BPS patients fulfilling the NIDDK criteria were asked to fill in a survey on the self-reported diagnosis of urinary tract diseases, fibromyalgia and 23 autoimmune diseases, together with filling the O'Leary-Sant symptom score. The ones with high symptom scores were interviewed and, if necessary, referred to a further clinical consultation. The prevalence of other diseases was compared to previously published prevalence percentages. Results 334 (80%) of 420 family members returned the questionnaire. Only one of the relatives fulfilled the NIDDK criteria, and one sibling pair among the original BPS patients was found. Asthma, ulcerative colitis, fibromyalgia, iritis and rheumatoid arthritis were more common in the study population than in the reference populations. The reported prevalence of atopic dermatitis and rhinoconjunctivitis causing allergies were lower. In addition, the results show that the O'Leary-Sant symptom score is not reliable in screening for new BPS cases. Conclusions Our study suggests that in BPS patients' families, fibromyalgia and autoimmune diseases including asthma, and especially the non-allergic form of asthma, may be over-represented.Peer reviewe

Interstitial cystitis: a rare manifestation of primary Sjögren’s syndrome, successfully treated with low dose cyclosporine

Chronic interstitial cystitis (IC), mostly affecting middle-aged women, is a very rare manifestation of primary Sjögren’s syndrome (pSS). Hereby, we report a 42-year-old woman with pSS, presenting with dysuria, urinary frequency, and suprapubic pain. She was diagnosed to have chronic IC, based upon the cystoscopic biopsy finding of chronic inflammation in the bladder wall. Systemic corticosteroid and azathioprine treatments together with local intravesical therapies were not effective. Therefore, cyclosporine (CSA) therapy was initiated. Initial low dose of CSA (1.5 mg/kg/d) improved the symptoms of the patient, with no requirement for dose increment. After 4 months of therapy, control cystoscopic biopsy showed that bladder inflammation regressed and IC improved. This case suggests that even low doses of CSA may be beneficial for treating chronic IC associated with pSS syndrome

Evaluation of Circulating Cardiovascular Biomarker Levels for Early Detection of Congenital Heart Disease in Newborns in Sweden

Congenital heart disease (CHD) is the most common congenital malformation in humans worldwide. Circulating cardiovascular biomarkers could potentially improve the early detection of CHD, even in asymptomatic newborns.\nTo assess the performance of a dried blood spot (DBS) test to measure the cardiovascular biomarker amino terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) levels in newborns and to compare DBS with standard EDTA analysis in control newborns during the first week of life.\nThis diagnostic study was conducted in a single regional pediatric service in southern Sweden. Healthy, term neonates born between July 1, 2018, and May 31, 2019, were prospectively enrolled and compared against retrospectively identified newborns with CHD born between September 1, 2003, and September 30, 2019. Neonates who required inpatient treatment beyond the standard postnatal care were excluded.\nNew DBS test for NT-proBNP quantification in newborns that used 3 μL of blood vs the current screening standard.\nPerformance of the new test and when combined with pulse oximetry screening was measured by receiver operating characteristic curve analysis. Performance of the new test and EDTA screening was compared using Pearson linear correlation analysis.\nThe DBS samples of 115 neonates (81 control newborns and 34 newborns with CHD, of whom 63 were boys [55%] and the mean [SD] gestational age was 39.6 [1.4] weeks) were analyzed. The new NT-proBNP test alone identified 71% (n = 24 of 34) of all CHD cases and 68% (n = 13 of 19) of critical CHD cases as soon as 2 days after birth. Detection of any CHD type improved to 82% (n = 28 of 34 newborns) and detection of critical CHD improved to 89% (n = 17 of 19 newborns) when combined pulse oximetry screening and NT-proBNP test results were used. Performance of the NT-proBNP test was excellent when control newborns were matched to newborns with CHD born between July 1, 2018, and May 31, 2019 (area under the curve, 0.96; SE, 0.027; 95% CI, 0.908-1.0; asymptotic P < .05).\nThis study found that NT-proBNP assay using minimal DBS samples appears to be timely and accurate in detecting CHD in newborns and to discriminate well between healthy newborns and newborns with various types of CHD. This finding warrants further studies in larger cohorts and highlights the potential of NT-proBNP to improve neonatal CHD screening.\nImportance\nObjectives\nDesign, Setting, and Participants\nExposure\nMain Outcomes and Measures\nResults\nConclusions and Relevanc

The Effects of Acceptance and Commitment Therapy (ACT) Intervention on Inflammation and Stress Biomarkers: a Randomized Controlled Trial

Background Psychological processes can be manifested in physiological health. We investigated whether acceptance and commitment therapy (ACT), targeted on psychological flexibility (PF), influences inflammation and stress biomarkers among working-age adults with psychological distress and overweight/obesity. Method Participants were randomized into three parallel groups: (1) ACT-based face-to-face (n = 65; six group sessions led by a psychologist), (2) ACT-based mobile (n = 73; one group session and mobile app), and (3) control (n = 66; only the measurements). Systemic inflammation and stress markers were analyzed at baseline, at 10 weeks after the baseline (post-intervention), and at 36 weeks after the baseline (follow-up). General PF and weight-related PF were measured with questionnaires (Acceptance and Action Questionnaire, Acceptance and Action Questionnaire for Weight-Related Difficulties). Results A group x time interaction (p = .012) was detected in the high-sensitivity C-reactive protein (hsCRP) level but not in other inflammation and stress biomarkers. hsCRP decreased significantly in the face-to-face group from week 0 to week 36, and at week 36, hsCRP was lower among the participants in the face-to-face group than in the mobile group (p = .035, post hoc test). Age and sex were stronger predictors of biomarker levels at follow-up than the post-intervention PF. Conclusion The results suggest that ACT delivered in group sessions may exert beneficial effects on low-grade systemic inflammation. More research is needed on how to best apply psychological interventions for the health of both mind and body among people with overweight/obesity and psychological distress.Peer reviewe

Sequential induction of auxin efflux and influx carriers regulates lateral root emergence

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