Anatomy-Driven Pathology Detection on Chest X-rays

Pathology detection and delineation enables the automatic interpretation of medical scans such as chest X-rays while providing a high level of explainability to support radiologists in making informed decisions. However, annotating pathology bounding boxes is a time-consuming task such that large public datasets for this purpose are scarce. Current approaches thus use weakly supervised object detection to learn the (rough) localization of pathologies from image-level annotations, which is however limited in performance due to the lack of bounding box supervision. We therefore propose anatomy-driven pathology detection (ADPD), which uses easy-to-annotate bounding boxes of anatomical regions as proxies for pathologies. We study two training approaches: supervised training using anatomy-level pathology labels and multiple instance learning (MIL) with image-level pathology labels. Our results show that our anatomy-level training approach outperforms weakly supervised methods and fully supervised detection with limited training samples, and our MIL approach is competitive with both baseline approaches, therefore demonstrating the potential of our approach.Comment: Accepted at MICCAI 202

Stiripentol fails to lower plasma oxalate in a dialysis-dependent PH1 patient

Background: Primary hyperoxaluria type 1 (PH1) is a multisystemic metabolic disorder caused by an excessive production of oxalate by the liver. The majority of patients presenting in early infancy have end-stage renal disease (ESRD). While awaiting the results of sRNAi trials, the current standard treatment is combined liver-kidney transplantation. Recently, Stiripentol has been reported as a promising drug in the treatment of primary hyperoxaluria by reducing urinary oxalate (UOx). Stiripentol is an anti-convulsive drug used in the treatment of children suffering from Dravet syndrome. It causes blockage of the last step in oxalate production by inhibition of hepatic lactate dehydrogenase 5 (LDH5). Case: We administered Stiripentol as compassionate use in an anuric infant with dialysis-dependent PH1 over a period of 4 months. Although achieving plasma concentrations of Stiripentol that were recently reported to lower UOx excretion, we did not observe significant reduction to plasma oxalate concentrations (POx). Conclusion: We conclude that Stiripentol may not be useful to reduce POx in PH patients with advanced chronic kidney disease (CKD), but larger studies are needed to confirm this finding

Overexpression of eIF3a in Squamous Cell Carcinoma of the Oral Cavity and Its Putative Relation to Chemotherapy Response

The eukaryotic translation initiation factor eIF3a is one of the core subunits of the translation initiation complex eIF3, responsible for ribosomal subunit joining and mRNA recruitment to the ribosome. It is known to play an important role in general translation initiation as well as in the specific translational regulation of various gene products, among which many influence tumour development, progression, and the therapeutically important pathways of DNA damage repair. Therefore, beyond its role in protein synthesis, eIF3a is emerging as regulator in tumour pathogenesis and therapy response and, therefore, a potential tumor marker. By means of a tissue microarray (TMA) for histopathological and statistical assessment, we here show eIF3a expression in 103 cases of squamous cell carcinoma of the oral cavity (OSCC), representing tissues from 103 independent patients. A subset of the study cohort was treated with platinum based therapy. Our results show that the 170 kDa protein is upregulated in OSCC and correlates with good overall survival. Overexpressing tumors respond better to platinum-based chemotherapy, suggesting eIF3a as a putative predictive as well as prognostic tumor marker in OSCC

High prevalence of anti-HCV antibodies in two metropolitan emergency departments in Germany : a prospective screening analysis of 28,809 patients

Background and Aims: The prevalence of hepatitis C virus (HCV) antibodies in Germany has been estimated to be in the range of 0.4–0.63%. Screening for HCV is recommended in patients with elevated ALT levels or significant risk factors for HCV transmission only. However, 15–30% of patients report no risk factors and ALT levels can be normal in up to 20–30% of patients with chronic HCV infection. The aim of this study was to assess the HCV seroprevalence in patients visiting two tertiary care emergency departments in Berlin and Frankfurt, respectively. Methods: Between May 2008 and March 2010, a total of 28,809 consecutive patients were screened for the presence of anti-HCV antibodies. Anti-HCV positive sera were subsequently tested for HCV-RNA. Results: The overall HCV seroprevalence was 2.6% (95% CI: 2.4–2.8; 2.4% in Berlin and 3.5% in Frankfurt). HCV-RNA was detectable in 68% of anti-HCV positive cases. Thus, the prevalence of chronic HCV infection in the overall study population was 1.6% (95% CI 1.5–1.8). The most commonly reported risk factor was former/current injection drug use (IDU; 31.2%) and those with IDU as the main risk factor were significantly younger than patients without IDU (p<0.001) and the male-to-female ratio was 72% (121 vs. 46 patients; p<0.001). Finally, 18.8% of contacted HCV-RNA positive patients had not been diagnosed previously. Conclusions: The HCV seroprevalence was more than four times higher compared to current estimates and almost one fifth of contacted HCV-RNA positive patients had not been diagnosed previously

Neonatal screening: identification of children with 11β-hydroxylase deficiency by second-tier testing

21-Hydroxylase deficiency (21-OHD) is the target disease of newborn screening for congenital adrenal hyperplasia (CAH). We describe the additional detection of patients suffering from 11β-hydroxylase deficiency (11-OHD) by second-tier testing.Over a period of 5 years, screening for CAH was done in a total of 986,098 newborns by time-resolved immunoassay (DELFIA®) for 17α-hydroxyprogesterone (17-OHP). Positive samples were subsequently analyzed in an LC-MS/MS second-tier test including 17-OHP, cortisol, 11-deoxycortisol, 4-androstenedione and 21-deoxycortisol.In addition to 78 cases of 21-OHD, 5 patients with 11-OHD were identified. Diagnostic parameters were a markedly elevated concentration of 11-deoxycortisol in the presence of a low level of cortisol. Androstenedione was also increased. In contrast to 21-OHD, concentrations of 21-deoxycortisol were normal.Steroid profiling in newborn blood samples showing positive results in immunoassays for 17-OHP allows for differentiating 21-OHD from 11-OHD. This procedure may not detect all cases of 11-OHD in the newborn population because there may be samples of affected newborns with negative results for 17-OHP in the immunoassay

Atorvastatin added to interferon beta for relapsing multiple sclerosis: a randomized controlled trial

Statins have anti-inflammatory and immunomodulatory properties in addition to lipid-lowering effects. The present study evaluated the effect of atorvastatin added to interferon beta-1b in multiple sclerosis (MS) in a multicenter, randomized, parallel-group, rater-blinded study performed in eight Swiss hospitals. Seventy-seven patients with relapsing-remitting MS started interferon beta-1b every other day. After 3months, they were randomized 1:1 to receive atorvastatin 40mg/day or not in addition to interferon beta-1b until month 15. The primary endpoint was the proportion of patients with new lesions on T2-weighted images at month 15 compared to baseline at month three. At study end, the proportion of patients with new lesions on T2-weighted images was equal in both groups (odds ratio 1.14; 95% CI 0.36-3.56; p=0.81). All predefined secondary endpoints including number of new lesions and total lesion volume on T2-weighted images, total number of new Gd-enhancing lesions on T1-weighted images, total brain volume, volume of grey matter, volume of white matter, EDSS, MSFC, relapse rate, time to first relapse, number of relapse-free patients and neutralizing antibodies did not show any significant differences (all p values >0.1). Transient elevations of liver enzymes were more frequent with atorvastatin (p=0.02). In conclusion, atorvastatin 40mg/day in addition to interferon beta-1b did not have a beneficial effect on relapsing-remitting MS compared to interferon beta-1b monotherapy over a 12-month perio

Patient Perspective in Obesity Surgery: Goals for Weight Loss and Improvement of Body Shape in a Prospective Cohort Study

Objective: Obesity surgery provides sustainable weight loss, improvement of comorbidities, and improved quality of life (QOL). There is few evidence on the patient perspective and goals. This study compared expected and achieved weight loss, body shape, and QOL. Methods: Patients completed the Moorehead-Ardelt QOL questionnaire (MAQOL) and questionnaires on actual and expected weight loss and body shape, comorbidities, and goals of obesity surgery preoperatively and within 24 months postoperatively. Results: 44 patients completed questionnaires pre- and postoperatively. BMI, MAQOL and comorbidities significantly improved postoperatively. Patients’ expected weight loss goal corresponded to a postoperative BMI of 32.6 ± 5.6 kg/m2 and was not different from their achieved BMI within 24 months after surgery (33.9 ± 6.3 kg/m2, p = 0.276). Self-reported body shape improved but did not reach preoperatively expected goals. During the weight loss period, patients adapted their weight loss and body shape goals to higher levels. Patients attributed a higher part of their success in weight loss to surgery postoperatively (79.5 ± 22.0 vs. 89.1 ± 18.4%, p = 0.028). Conclusion: Patients lost as much weight as they had expected and later modified the goals to even greater weight loss. Body shape improved but did not reach expected levels. QOL improved independently from weight loss and body shape. Patients attributed successful weight loss predominantly to surgery

How can Brewer–Dobson circulation trends be estimated from changes in stratospheric water vapour and methane?

The stratospheric meridional overturning circulation, also referred to as the Brewer–Dobson circulation (BDC), controls the composition of the stratosphere, which, in turn, affects radiation and climate. As the BDC cannot be directly measured, one has to infer its strength and trends indirectly. For instance, trace gas measurements allow the calculation of average transit times. Satellite measurements provide information on the distributions of trace gases for the entire stratosphere, with measurements of particularly long temporal and dense spatial coverage available for stratospheric water vapour (H2O). Although chemical processes and boundary conditions confound interpretation, the influence of methane (CH4) oxidation on H2O in the stratosphere is relatively straightforward, and thus H2O is an appealing tracer for transport analysis despite these caveats. In this work, we explore how mean age of air trends can be estimated from the combination of stratospheric H2O and CH4 data, by carrying out a proof of concept within the model environment of the Chemical Lagrangian Model of the Stratosphere (CLaMS). In particular, we assess the methodological uncertainties related to the two commonly used approximations of (i) instantaneous stratospheric entry mixing ratio propagation and (ii) constant correlation between mean age and the fractional release factor of CH4. Performing various sensitivity studies with CLaMS, we test different methods of the mean age of air trend estimation, and we aim to provide simple and practical advice on the adjustment of the used approximations for obtaining more reliable mean age of air trends from the measurements of H2O and CH4. Our results show that the estimated mean age of air trends from the combination of stratospheric H2O and CH4 changes may be significantly affected by the assumed approximations. Depending on the investigated stratospheric region and the considered period, the error in estimated mean age of air trends can be large, especially in the lower stratosphere. For particular periods, the errors from the two approximations can lead to opposite effects, which may even cancel out. Finally, for a more reliable estimate of the mean age of air trends, we propose adjusting the approximation method by using an idealized age spectrum to propagate stratospheric entry mixing ratios. The findings of this work can be used for assessing the uncertainties in stratospheric BDC trend estimation from global satellite measurements

Collaborative nowcasting of COVID-19 hospitalization incidences in Germany

Real-time surveillance is a crucial element in the response to infectious disease outbreaks. However, the interpretation of incidence data is often hampered by delays occurring at various stages of data gathering and reporting. As a result, recent values are biased downward, which obscures current trends. Statistical nowcasting techniques can be employed to correct these biases, allowing for accurate characterization of recent developments and thus enhancing situational awareness. In this paper, we present a preregistered real-time assessment of eight nowcasting approaches, applied by independent research teams to German 7-day hospitalization incidences during the COVID-19 pandemic. This indicator played an important role in the management of the outbreak in Germany and was linked to levels of non-pharmaceutical interventions via certain thresholds. Due to its definition, in which hospitalization counts are aggregated by the date of case report rather than admission, German hospitalization incidences are particularly affected by delays and can take several weeks or months to fully stabilize. For this study, all methods were applied from 22 November 2021 to 29 April 2022, with probabilistic nowcasts produced each day for the current and 28 preceding days. Nowcasts at the national, state, and age-group levels were collected in the form of quantiles in a public repository and displayed in a dashboard. Moreover, a mean and a median ensemble nowcast were generated. We find that overall, the compared methods were able to remove a large part of the biases introduced by delays. Most participating teams underestimated the importance of very long delays, though, resulting in nowcasts with a slight downward bias. The accompanying prediction intervals were also too narrow for almost all methods. Averaged over all nowcast horizons, the best performance was achieved by a model using case incidences as a covariate and taking into account longer delays than the other approaches. For the most recent days, which are often considered the most relevant in practice, a mean ensemble of the submitted nowcasts performed best. We conclude by providing some lessons learned on the definition of nowcasting targets and practical challenges

'Fat mass and obesity associated' gene (FTO): No significant association of variant rs9939609 with weight loss in a lifestyle intervention and lipid metabolism markers in German obese children and adolescents

<p>Abstract</p> <p>Background</p> <p>We have previously identified strong association of six single nucleotide polymorphisms (SNPs) in <it>FTO </it>(fat mass and obesity associated gene) to early onset extreme obesity within the first genome wide association study (GWA) for this phenotype. The aim of this study was to investigate whether the obesity risk allele of one of these SNPs (rs9939609) is associated with weight loss in a lifestyle intervention program. Additionally, we tested for association of rs9939609 alleles with fasting blood parameters indicative of glucose and lipid metabolism.</p> <p>Methods</p> <p>We initially analysed rs9939609 in a case-control study comprising 519 German overweight and obese children and adolescents and 178 normal weight adults. In 207 of the obese individuals who took part in the outpatient obesity intervention program 'Obeldicks' we further analysed whether carrier status of the obesity risk A-allele of rs9939609 has a differential influence on weight loss after the intervention program. Additionally, we investigated in 480 of the overweight and obese patients whether rs9939609 is associated with fasting blood levels of glucose, triglycerides and HDL and LDL-cholesterol. Genotyping was performed using allele specific polymerase chain reaction (ARMS-PCR). For the association study (case-control approach), the Cochran-Armitage trend test was applied. Blood parameters were analysed using commercially available test kits and the log10-transformed blood parameters and changes in BMI-standard deviation scores (BMI-SDS) were analysed by linear regression with sex and age as covariates under an additive mode of inheritance with the rs9939609 A-allele as risk allele.</p> <p>Results</p> <p>We confirmed the association of the risk A-allele of rs9939609 with overweight and early onset obesity (one sided p = 0.036). However, we observed no association of rs9939609 alleles with weight loss or fasting levels of blood glucose, triglycerides and cholesterol.</p> <p>Conclusion</p> <p>We confirmed the rs9939609 A-allele as a risk factor for early onset obesity whereas its impact on weight loss or on serum levels of glucose, triglycerides and cholesterol could not be detected in our samples.</p> <p>Trial Registration</p> <p><b>This study is registered </b>at clinicaltrials.gov (NCT00435734).</p