Deep learning body-composition analysis of clinically acquired CT-scans estimates creatinine excretion with high accuracy in patients and healthy individuals.

Assessment of daily creatinine production and excretion plays a crucial role in the estimation of renal function. Creatinine excretion is estimated by creatinine excretion equations and implicitly in eGFR equations like MDRD and CKD-EPI. These equations are however unreliable in patients with aberrant body composition. In this study we developed and validated equations estimating creatinine production using deep learning body-composition analysis of clinically acquired CT-scans. We retrospectively included patients in our center that received any CT-scan including the abdomen and had a 24-h urine collection within 2 weeks of the scan (n = 636). To validate the equations in healthy individuals, we included a kidney donor dataset (n = 287). We used a deep learning algorithm to segment muscle and fat at the 3rd lumbar vertebra, calculate surface areas and extract radiomics parameters. Two equations for CT-based estimate of RenAl FuncTion (CRAFT 1 including CT parameters, age, weight, and stature and CRAFT 2 excluding weight and stature) were developed and compared to the Cockcroft-Gault and the Ix equations. CRAFT1 and CRAFT 2 were both unbiased (MPE = 0.18 and 0.16 mmol/day, respectively) and accurate (RMSE = 2.68 and 2.78 mmol/day, respectively) in the patient dataset and were more accurate than the Ix (RMSE = 3.46 mmol/day) and Cockcroft-Gault equation (RMSE = 3.52 mmol/day). In healthy kidney donors, CRAFT 1 and CRAFT 2 remained unbiased (MPE = - 0.71 and - 0.73 mmol/day respectively) and accurate (RMSE = 1.86 and 1.97 mmol/day, respectively). Deep learning-based extraction of body-composition parameters from abdominal CT-scans can be used to reliably estimate creatinine production in both patients as well as healthy individuals. The presented algorithm can improve the estimation of renal function in patients who have recently had a CT scan. The proposed methods provide an improved estimation of renal function that is fully automatic and can be readily implemented in routine clinical practice.

Deep Learning-Based Data-Point Precise R-Peak Detection in Single-Lead Electrocardiograms.

Low-cost wearables with capability to record electrocardiograms (ECG) are becoming increasingly available. These wearables typically acquire single-lead ECGs that are mainly used for screening of cardiac arrhythmias such as atrial fibrillation. Most arrhythmias are characteruzed by changes in the RR-interval, hence automatic methods to diagnose arrythmia may utilize R-peak detection. Existing R-peak detection methods are fairly accurate but have limited precision. To enable data-point precise detection of R-peaks, we propose a method that uses a fully convolutional dilated neural network. The network is trained and evaluated with manually annotated R-peaks in a heterogeneous set of ECGs that contain a wide range of cardiac rhythms and acquisition noise. 700 randomly chosen ECGs from the PhysioNet/CinC challenge 2017 were used for training (n=500), validation (n=100) and testing (n=100). The network achieves a precision of 0.910, recall of 0.926, and an F1-score of 0.918 on the test set. Our data-point precise R-peak detector may be important step towards fully automatic cardiac arrhythmia detection.Clinical relevance- This method enables data-point precise detection of R-peaks that provides a basis for detection and characterization of arrhythmias.

Effect of weight change on progression of knee OA structural features assessed by MRI in overweight and obese women.

OBJECTIVE: To evaluate the effects of weight change on progression of knee osteoarthritis (OA) structural features by magnetic resonance imaging (MRI) in overweight and obese women without clinical knee OA. DESIGN: 347 participants from the Prevention of Knee Osteoarthritis in Overweight Females (PROOF) study were classified with latent class growth analysis into a subgroup with steady weight (n = 260; +0.1 ± 4.0 kg, +0.2 ± 4.4%), weight gain (n = 43; +8.6 ± 4.0 kg, +9.8 ± 4.1%) or weight loss (n = 44; -9.0 ± 7.2 kg, -9.8 ± 7.5%) over 2.5 years. Baseline and follow-up 1.5T MRIs were scored with MRI Osteoarthritis Knee Score (MOAKS) for progression of bone marrow lesions (BMLs), cartilage defects, osteophytes, meniscal abnormalities, meniscal extrusion and synovitis. Associations between subgroups and change in MRI features at knee-level were assessed using adjusted Generalized Estimating Equations. RESULTS: 687 knees from 347 women (median age 55.2 years, interquartile range (IQR) 5.5, median body mass index (BMI) 31.2 kg/m2, IQR 5.3) were analyzed. Progression of synovitis was 18% in the weight gain vs 7% in the stable weight subgroup (OR 2.88; 95%CI 1.39-5.94). The odds for progression of patellofemoral (PF) BMLs and cartilage defects increased with 62% (OR 1.62; 95%CI 0.92-2.84) and 53% (OR 1.53; 95%CI 0.92-2.56) in the weight gain vs the stable weight subgroup. CONCLUSIONS: In overweight and obese women, progression of synovitis increased more than 2.5 times in a weight gain compared to a stable weight subgroup over 2.5 years. Large effect sizes were also found for the difference in progression of PF BMLs and PF cartilage defects between the weight gain and stable weight subgroup.

A novel succinate dehydrogenase subunit B germline variant associated with head and neck paraganglioma in a Dutch kindred: A family-based study.

OBJECTIVE: In the Netherlands, the majority of hereditary head and neck paragangliomas (HNPGL) are caused by germline variants in the succinate dehydrogenase genes (SDHD, SDHB, SDHAF2). Here, we evaluate a four-generation family linked to a novel SDHB gene variant with the manifestation of a HNPGL. DESIGN: A family-based study. SETTING: The VU University Medical Center (VUmc) Amsterdam, a tertiary clinic for Otolaryngology and Head and Neck Surgery. PARTICIPANTS AND MAIN OUTCOME MEASURES: The index patients presented with an embryonic rhabdomyosarcoma and a non-Hodgkin lymphoma. Array-based comparative genomic hybridisation (aCGH) analysis and multiplex ligation-dependent probe amplification (MLPA) revealed a novel deletion of exon 1-3 in the SDHB gene, suspected to predispose to paraganglioma (PGL)/pheochromocytoma (PHEO) syndrome type 4. Subsequently, genetic counselling and DNA testing were offered to all family members at risk. Individuals that tested positive for this novel SDHB gene variant were counselled and additional clinical evaluation was offered for the identification of HNPGL and/or PHEO. RESULTS: The DNA of 18 family members was tested, resulting in the identification of 10 carriers of the exon 1-3 deletion in the SDHB gene. One carrier was diagnosed with a carotid body PGL and serum catecholamine excess, which was surgically excised. Negative SDHB immunostaining of the carotid body tumour confirmed that it was caused by the SDHB variant. The remaining 9 carriers showed no evidence of PGL/PHEO. CONCLUSION: Deletion of exon 1-3 in the SDHB gene is a novel germline variant associated with the formation of hereditary HNPGL.

Sources of errors and uncertainties in the assessment of forest soil carbon stocks at different scales-review and recommendations.

Spatially explicit knowledge of recent and past soil organic carbon (SOC) stocks in forests will improve our understanding of the effect of human- and non-human-induced changes on forest C fluxes. For SOC accounting, a minimum detectable difference must be defined in order to adequately determine temporal changes and spatial differences in SOC. This requires sufficiently detailed data to predict SOC stocks at appropriate scales within the required accuracy so that only significant changes are accounted for. When designing sampling campaigns, taking into account factors influencing SOC spatial and temporal distribution (such as soil type, topography, climate and vegetation) are needed to optimise sampling depths and numbers of samples, thereby ensuring that samples accurately reflect the distribution of SOC at a site. Furthermore, the appropriate scales related to the research question need to be defined: profile, plot, forests, catchment, national or wider. Scaling up SOC stocks from point sample to landscape unit is challenging, and thus requires reliable baseline data. Knowledge of the associated uncertainties related to SOC measures at each particular scale and how to reduce them is crucial for assessing SOC stocks with the highest possible accuracy at each scale. This review identifies where potential sources of errors and uncertainties related to forest SOC stock estimation occur at five different scales-sample, profile, plot, landscape/regional and European. Recommendations are also provided on how to reduce forest SOC uncertainties and increase efficiency of SOC assessment at each scale.

Intra- and inter-annual variation of Cd, Zn, Mn and Cu in foliage of poplars on contaminated soil.

The uptake of trace metals in the leaves of fast-growing woody species is a crucial factor in ecological risk assessment and in the evaluation of phytoextraction potentials. In this study, we present a long-term data series of foliar Cd, Zn, Mn and Cu concentrations in poplar (Populus trichocarpa x P. deltoides). Leaves were collected every three weeks from 2001 until 2007 on three sites, (i) a new plantation on an alluvial soil polluted by river sediments, (ii) a new plantation on an unpolluted soil and (iii) a 10-year old plantation on a polluted dredged sediment soil. In addition, tree rings were measured on the alluvial soil in order to better assess growth over the past seven years. Foliar concentrations of Cd, Zn and Mn decreased considerably with time in the new plantation on polluted soil. Concentrations of Zn and Mn decreased in the new plantation on unpolluted soil as well. The older plantation on polluted soil did not show changes in foliar concentrations for Cd, Zn or Mn. Foliar Cu concentrations slightly increased for all sites. Within one growing season, foliar concentrations of Cd, Zn, Cu and Mn increased towards the end of the season. The tree ring data of the poplars on the alluvial soil indicated a strong decrease in growth due to declining tree condition from 2005 onwards, the same year that foliar Cd and Zn concentrations markedly decreased. Lower transpiration rates probably induced a lower uptake of dissolved trace metals. It is concluded that stand health and growth rate have a strong impact on the variation of foliar trace metal concentrations over time.

Comparison of 2 different regimens for reactogenicity, safety, and immunogenicity of the live attenuated oral rotavirus vaccine RIX4414 coadministered with oral polio vaccine in South African infants.

BACKGROUND: A phase II, randomized, double-blind, placebo-controlled study was conducted in South Africa during 2003-2004 to evaluate the safety, reactogenicity, and immunogenicity of 2 regimens of the live attenuated oral human rotavirus vaccine RIX4414 when coadministered with the Expanded Program on Immunization childhood vaccines, including oral polio vaccine. METHODS: Healthy infants were randomized (2:2:1) to receive either 2 doses of RIX4414 (n = 190; at 10 and 14 weeks, with placebo at 6 weeks), 3 doses of RIX4414 (n = 189; at 6, 10, and 14 weeks), or 3 doses of placebo (n = 96), all with concomitant routine vaccinations. The antirotavirus IgA seroconversion rate was assessed using enzyme-linked immunosorbent assay at 2 months after the last dose of RIX4414 or placebo. Antipolio types 1, 2, and 3 antibodies were measured using a virus neutralization assay. Solicited symptoms were recorded for 15 days after each dose. RESULTS: The antirotavirus IgA seroconversion rates were similar in the RIX4414 2- and 3-dose groups (44.3% and 44.4%, respectively; P = .544, by 1-sided Fisher exact test) and antirotavirus IgA geometric mean concentrations were also comparable. Seroprotection rates for antipolio types 1, 2, and 3 antibodies were high (93%-100%) and were not significantly different among groups. Solicited symptoms reported within 15 days after vaccination were similar in all groups. CONCLUSIONS: The immune seroconversion response to the RIX4414 vaccine with 3 doses was not superior to the 2-dose regimen. There was no interference by either regimen with antibody response to oral polio vaccine, and RIX4414 was well tolerated when given with routine vaccinations.

Breast MRI in clinically and mammographically occult breast cancer presenting with an axillary metastasis: a systematic review.

BACKGROUND: Axillary metastatic lymphadenopathy with no primary tumour identified in the breast on physical examination, mammography or ultrasound is referred to as occult breast cancer. The goal of this systematic review is to give an overview of the value and additional considerations of using breast MRI in occult breast cancer. METHODS: The databases of Pubmed, Embase, CINAHL and the Cochrane library were searched for studies addressing the use of breast MRI in occult breast cancer. Cross-referencing was used to find additional articles. RESULTS: 8 retrospective studies were included. Breast MRI can detect an otherwise occult breast cancer in more than two thirds of patients with a high sensitivity but lower specificity. In 80% of patients MRI detected lesions could be localized again by using ultrasound. Furthermore the size and localization of the lesions found on MRI most often correlated closely with findings at pathology. Breast MRI also provided the possibility of breast conserving surgery in one thirds of patients. CONCLUSION: Breast MRI can result in additional detection of otherwise occult lesions in occult breast cancer. Because of low specificity of malignant lesion detection by breast MRI, lesions should be histologically confirmed. This can be achieved either by MRI or ultrasound guided biopsy, as long as all MRI detected lesions are histologically checked. Routine application of breast MRI in occult breast cancer may also alter locoregional treatment by offering the possibility of breast conserving surgery in one thirds of patients.

Co-administration study in South African infants of a live-attenuated oral human rotavirus vaccine (RIX4414) and poliovirus vaccines.

A double-blind, placebo-controlled phase II trial (e-Track 444563-014/NCT00346892) was conducted in South Africa to evaluate the co-administration of RIX4414 (live-attenuated human G1P[8] rotavirus vaccine) and oral poliovirus vaccine (OPV) administered simultaneously. Healthy infants (n=450) were randomized into three groups (RIX4414+OPV, RIX4414+IPV or Placebo+OPV) to receive two oral doses of RIX4414/placebo with OPV or IPV using two vaccination schedules (6-10 weeks and 10-14 weeks). Serum anti-rotavirus IgA antibodies (ELISA) and neutralizing antibodies (micro-neutralization assay) to poliovirus serotypes 1, 2 and 3 were measured. Co-administration of RIX4414 with OPV did not result in a decrease in the high sero-protection rates against poliovirus serotypes 1, 2 and 3 detected after the third OPV dose (98-100%). The anti-rotavirus IgA antibody sero-conversion rates were higher for the 10-14 weeks schedule (55-61%) compared to the 6-10 weeks schedule (36-43%). Solicited symptoms were reported at similar rates between RIX4414 and placebo groups and no serious adverse events related to RIX4414 were reported. This study provided evidence that RIX4414 can be co-administered with routine EPI immunizations including OPV and that two doses of RIX4414 were well tolerated and immunogenic in South African infants.

Do surgical distal bypasses still play a role in the treatment of critical limb ischemia?

AIM: The treatment of critical limb ischemia is at present very controversial. In fact surgery using different grafts (venous or prosthetic) is in competition with percutaneous angioplasty. Progresses of endoluminal techniques brought certain authors to think that angioplasty is now the first treatment of critical limb ischemia. The aim of the study hereby is to compare our results of distal venous bypasses to the results obtained in literature with venous or other grafts and to those of the percutaneous angioplasty. MATERIAL AND METHOD: In this retrospective study of 113 operated cases between January 2003 and December 2006 by four surgeons, 21 cases are excluded considering the lack of data. Among the remaining 92 cases, the average age is 68.1 years. Men represent 79.4%. Comorbidities include: COPD 55.4%, coronary artery disease 60.9%, diabetes 44.6%, dyslipidemia 66.3% and dialysis 9.8%. Surgical revision was necessary in 29.4%. There were 30.4% stage III limb ischemia and 62% stage IV. Acute ischemia was present in 7.6% of patients. The proximal anastomosis of the bypass is femoral except for 13 cases. The outflow artery is always sural or even more distal. RESULTS: Perioperative mortality is of 2.2% (two cases). The average follow up was of 26.2 months (0.16-64). Eleven patients required subsequent amputation. The primary patency at 1, 3 and 5 years was respectively of 82.1%, 70.6% and 55.9% while limb salvage was respectively of 87.4%, 85.9% and 85.9% at the same intervals. CONCLUSION: Comparing our results to those of the literature for venous or prosthetic bypasses and distal angioplasties, we remain convinced of the high efficiency, on the long run, of infra-popliteal venous bypass grafts. Meanwhile, recent data on distal angioplasties are promising and in constant progress.

[Competent and diverse. Portrayal of older adults in Dutch television commercials ten years later]. / Competent en veelzijdig. Representatie van ouderen in de ster-reclame tien jaar later.

The present study replicates our study of older adults' portrayal in Dutch television commercials conducted in 1993. The central question is whether older adults are being portrayed more visibly in Dutch television commercials and whether this portrayal has become more diverse compared to ten years ago. Based on a list of descriptions of all commercials broadcasted by public television channels in 2003 (N= 4767) 117 commercials featuring older adults were selected. By means of a quantitative content analysis it was examined whether and how older men and women are portrayed. It was concluded that although older adults are not more prevalent compared to ten years ago, their portrayal is more diverse with respect to their roles and the advertised products. Older adults were portrayed as more competent and less age-stereotypical in television commercials.

A short report on highlights of worldwide development of RIX4414: a Singaporean experience.

In Singapore, we conducted a phase II randomized, double-blind, placebo-controlled dose ranging study using an attenuated human rotavirus vaccine, RIX4414. Altogether, 2464 healthy infants were recruited. Two oral doses of vaccine at 104.7, 105.2 or 106.1 ffu or placebo were administered with routine immunizations at 3 and 4 months of age. Seroconversion and 'vaccine take' in the vaccine groups 1-month post dose 2 varied from 76 to 91% and 98 to 100% respectively. Vaccine was well tolerated and did not interfere with response of concomitantly administered vaccines.

A rotavirus vaccine for infants: the Asian experience.

INTRODUCTION: Severe rotavirus gastroenteritis in children causes significant morbidity worldwide and substantial deaths in developing countries. Hence, a live attenuated vaccine Rotarix was developed with human strain RIX4414 of G1P1A P[8] specificity. RIX4414 trials in infants have begun in developed and developing countries worldwide. An overview of RIX4414 in developed and developing countries and prospects with this vaccine in Asia are presented. METHODS: Completed RIX4414 trials have been reviewed. RESULTS: Two oral doses of RIX4414 were well tolerated with a reactogenicity profile similar to placebo. RIX4414 was also highly immunogenic, e.g., in a dose-ranging study conducted in Singapore, 98.8% to 100% of infants had a vaccine take after 2 doses. RIX4414 did not affect the immune response of simultaneously administered routine infant vaccines. RIX4414 significantly reduced severe rotavirus gastroenteritis in settings where multiple serotypes including the emerging G9 type co-circulated. CONCLUSION: These encouraging results warrant further evaluation of the vaccine worldwide and especially in developing countries with the highest need. Therefore, evaluation of the Rotarix vaccine is continuing in large phase III trials in Asia and worldwide.

A short report on highlights of world-wide development of RIX4414: a Latin American experience.

An oral, human-derived monovalent (G1P1A) rotavirus vaccine, strain RIX4414, has been developed by GlaxoSmithKline, Rixensart, Belgium. The safety, immunogenicity and efficacy of this vaccine were evaluated in a randomized, double-blind, placebo-controlled, phase IIb trial conducted in Brazil, Mexico and Venezuela. Healthy infants were given two doses of vaccine (104.7, 105.2 or 105.8 ffu) or placebo at age 2 and 4 months, with routine DTPw-HBV and Hib vaccines. OPV was given separately, at least 2 weeks before or after administration of the study vaccine. A total of 2155 infants were enrolled, of whom 1618 received one of the three vaccine viral concentrations and 537 were given placebo. Analysis of efficacy included diarrheal episodes occurring from 2 weeks after second dose until one year of age. Efficacy rates against any rotavirus gastroenteritis, severe rotavirus gastroenteritis and hospitalizations for rotavirus disease were as high as 70% (46-84%; 95%CI), 86% (63-96%; 95%CI), and 93% (54-100%; 95%CI), respectively. For non-G1 (mainly G9) serotypes, RIX4414 vaccine conferred protection as high as 83% (40-97%; 95%CI) against severe gastroenteritis. A decrease was noted in the incidence of severe rotavirus-related gastroenteritis after first dose. It is demonstrated that two doses of RIX4414 are highly efficacious against severe rotavirus gastroenteritis and hospitalization, including disease caused by non-G1 strains, namely G9 serotypes.

Safety and immunogenicity of RIX4414 live attenuated human rotavirus vaccine in adults, toddlers and previously uninfected infants.

A live attenuated human rotavirus (HRV) vaccine, strain RIX4414, was tested sequentially in adults, previously infected toddlers, and previously uninfected infants. A single dose was given to adults and toddlers and found well tolerated. Next, a dose ranging (three different viral concentrations) safety and immunogenicity study was conducted in rotavirus IgA antibody negative infants (N= 192), who received two doses of RIX4414 vaccine or placebo at 2 and 4 months of age. No side effects were seen after vaccination. Specifically, administration of RIX4414 vaccine was not temporally associated with fever, diarrhea, or increase in liver transaminases. Rotavirus IgA seroconversion ranged from 50 to 88% after one dose and from 73 to 96% after two doses, depending on vaccine titer. After the first dose, on days 7-9 post vaccination, between 38 and 60% of the infants shed the vaccine virus, whereas after the second dose only 0 to 13% of the vaccinees shed the vaccine virus. It is concluded that RIX4414 strain HRV vaccine is virtually non-reactogenic and, at high titer, highly immunogenic in susceptible infants.