The parkin V380L variant is a genetic modifier of Machado-Joseph disease with impact on mitophagy.

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative spinocerebellar ataxia caused by a polyglutamine-coding CAG repeat expansion in the ATXN3 gene. While the CAG length correlates negatively with the age at onset, it accounts for approximately 50% of its variability only. Despite larger efforts in identifying contributing genetic factors, candidate genes with a robust and plausible impact on the molecular pathogenesis of MJD are scarce. Therefore, we analysed missense single nucleotide polymorphism variants in the PRKN gene encoding the Parkinson's disease-associated E3 ubiquitin ligase parkin, which is a well-described interaction partner of the MJD protein ataxin-3, a deubiquitinase. By performing a correlation analysis in the to-date largest MJD cohort of more than 900 individuals, we identified the V380L variant as a relevant factor, decreasing the age at onset by 3 years in homozygous carriers. Functional analysis in an MJD cell model demonstrated that parkin V380L did not modulate soluble or aggregate levels of ataxin-3 but reduced the interaction of the two proteins. Moreover, the presence of parkin V380L interfered with the execution of mitophagy-the autophagic removal of surplus or damaged mitochondria-thereby compromising cell viability. In summary, we identified the V380L variant in parkin as a genetic modifier of MJD, with negative repercussions on its molecular pathogenesis and disease age at onset.

B7-1 and PlGF-1 are two possible new biomarkers to identify fracture-associated trauma patients at higher risk of developing complications: a cohort study.

BACKGROUND: Around 10% of fractures lead to complications. With increasing fracture incidences in recent years, this poses a serious burden on the healthcare system, with increasing costs for treatment. In the present study, we aimed to identify potential 'new' blood markers to predict the development of post-surgical complications in trauma patients following a fracture. METHODS: A total of 292 trauma patients with a complete three-month follow-up were included in this cohort study. Blood samples were obtained from 244 of these patients. Two complication groups were distinguished based on the Clavien-Dindo (CD) classification: CD grade I and CD grade III groups were compared to the controls (CD 0). The Mann-Whitney U test was used to compare the complication groups to the control group. RESULTS: Analysis of the patients' data revealed that risk factors are dependent on sex. Both, males and females who developed a CD III complication showed elevated blood levels of B7-1 (p = 0.015 and p = 0.018, respectively) and PlGF-1 (p = 0.009 and p = 0.031, respectively), with B7-1 demonstrating greater sensitivity (B7-1: 0.706 (male) and 0.692 (female), PlGF-1: 0.647 (male) and 0.615 (female)). Further analysis of the questionnaires and medical data revealed the importance of additional risk factors. For males (CD 0: 133; CD I: 12; CD III: 18 patients) alcohol consumption was significantly increased for CD I and CD III compared to control with p = 0.009 and p = 0.007, respectively. For females (CD 0: 107; CD I: 10; CD III: 12 patients) a significantly increased average BMI [kg/m2] from 25.5 to 29.7 with CD III was observed, as well as an elevation from one to three comorbidities (p = 0.003). CONCLUSIONS: These two potential new blood markers hold promise for predicting complication development in trauma patients. Nevertheless, further studies are necessary to evaluate the diagnostic utility of B7-1 and PlGF-1 in predicting complications in trauma patients and consider sex differences before their possible use as routine clinical screening tools.

Impact of keratoconus stage on outcome after corneal crosslinking.

BACKGROUND: This study aimed to analyze if the outcome after corneal crosslinking (CXL) in progressive keratoconus patients depends on the stage at which the procedure is performed. This knowledge would help to improve success of CXL and to define surgery indications in those patients. METHODS: In this retrospective study, 124 consecutive eyes of 100 patients with progressive keratoconus undergoing corneal CXL at the University Eye Hospital Tübingen were included. The eyes were graded according to modified Krumeich stages depending on induced myopia or astigmatism, corneal radii, minimum corneal thickness, and morphological changes. The observation period covered November 2008 to September 2018. Preoperatively, 12 and 24 months after CXL, the best corrected visual acuity (BCVA) was determined and astigmatism as well as tomographic parameters (Kmax, Kmin, central corneal thickness (CCT), minimum corneal thickness (MCT)) were measured by means of a Scheimpflug camera system. RESULTS: BCVA results showed significant differences between the modified Krumeich stages at 12 months (p = 0.014) and at 24 months postoperatively (p = 0.032). Also, astigmatism differed significantly among the stages at 24 months after CXL (p = 0.023). However, no significant differences regarding astigmatism were detectable after 12 months. In terms of Kmax, Kmin, CCT, and MCT, no significant differences between the Krumeich stages were observed. CONCLUSIONS: BCVA showed a significantly higher improvement after CXL in the early stage of keratoconus compared to a higher stage. However, the postinterventional tomographic values did not differ significantly between the different modified Krumeich stages. The significantly higher improvement in BCVA after CXL in the early stage might indicate that earlier intervention provides a higher subjective benefit to the individual. Further studies with larger sample sizes are needed to confirm these findings.

Local Tumor Infiltration and Locoregional Recurrence in Desmoplastic Cutaneous Squamous Cell Carcinoma.

BACKGROUND: Perusal of the literature of cutaneous squamous cell carcinoma (SCC) reveals that the role of the desmoplastic subtype is indistinct. Data on local infiltration and recurrence are inconsistent dependent on surgical technique, histological method, and investigated collective. OBJECTIVE: The aim of the study was to analyze local infiltration and locoregional recurrence of the desmoplastic subtype under a uniform procedure. METHODS AND MATERIALS: Between 2005 and 2015, 320 SCCs were analyzed and histological sections of all tumors were examined. Data collection included locoregional recurrence, metastasis rate, and tumor-specific death. The median follow-up was 36.5 months. RESULTS: The desmoplastic subtype required significant more re-excisions (70.0% vs 23.9%, p < .001), more interventions until tumor-free margins were achieved (maximal 6 vs 2; p < .001), showed more widespread tumor infiltration with larger excisional margins (median 9 mm, 2-51 mm vs median 4 mm, 1-10 mm; p < .001), and a 5-fold higher local recurrence rate (26.7% vs 5.0%, p < .001). The metastasis rate (16.6% vs 2.3%, p < .001) was increased. CONCLUSION: The desmoplastic subtype is characterized by a widespread local infiltration associated with perineural infiltration. It seems to be a marker for decreased histological detectability with a high rate of locoregional recurrence and metastasis.

Prevalence of Candida species in Psoriasis.

BACKGROUND: Psoriasis patients are more frequently colonised with Candida species. The correlation between fungal colonisation and clinical severity is unclear, but may exacerbate psoriasis and the impact of antipsoriatic therapies on the prevalence of Candida is unknown. OBJECTIVES: To examine the prevalence of C species in psoriasis patients compared to an age- and sex-matched control population, we investigated the influence of Candida colonisation on disease severity, immune cell activation and the interplay on psoriatic treatments. METHODS: The prevalence of C species was examined in 265 psoriasis patients and 200 control subjects by swabs and stool samples for fungal cultures. Peripheral mononuclear blood cells (PBMCs) were collected from 20 fungal colonised and 24 uncolonised patients and stimulated. The expression of interferon (IFN)-γ, IL-17A, IL-22 and tumour necrosis factor (TNF)-α from stimulated PBMCs was measured by quantitative real-time polymerase chain reaction (qPCR). RESULTS: A significantly higher prevalence for Candida was detected in psoriatic patients (p ≤ .001) compared to the control subjects; most abundant in stool samples, showing Candida albicans. Older participants (≥51 years) were more frequent colonised, and no correlation with gender, disease severity or systemic treatments like IL-17 inhibitors was found. CONCLUSIONS: Although Candida colonisation is significantly more common in patients with psoriasis, it does not influence the psoriatic disease or cytokine response. Our study showed that Candida colonisation is particularly more frequent in patients with psoriasis ≥51 years of age. Therefore, especially this group should be screened for symptoms of candidiasis during treatment with IL-17 inhibitors.

Evaluation of bowel wall thickness by ultrasound as early diagnostic tool for therapeutic response in Crohn's disease patients treated with ustekinumab.

BACKGROUND: Ustekinumab was approved for the treatment of patients with moderate to severe CD 2. Development of predictors for selecting patients responding to ustekinumab has to be the next step. US offers a noninvasive method with great sensitivity in detecting CD activity 11. AIM: To evaluate BWT by BS as early diagnostic tool for treatment response in CD patients treated with ustekinumab at week 8. METHODS: This is a prospective monocentric study. Twenty-three CD patients had BS at the time of first and second application. BS was performed by one of 2 experienced DEGUM certificated sonographers, with evaluation by both independently and blindly. Primary endpoint was substantial sonographic response defined as decrease of BWT ≥ 1 mm. Secondary endpoint was concordance between sonographic and clinical response, defined as decrease of CDAI ≥ 70 points and sonographic and biochemical response defined as decrease of CRP ≥ 0.5 mg/dl. RESULTS: At week 8, BS detected in 10 of 23 patients a substantial decrease of BWT ≥ 1 mm; in 7, a decrease < 1 mm. Compared to baseline, all 17 patients showed generally improved blood data and 16/17 generally improved clinical data. Of those with a decrease of BWT ≥ 1 mm, we observed a substantial decrease of CDAI ≥ 70 points in 9/10 patients and a substantial decrease of CRP ≥ 0.5 mg/dl in 8/10 patients. CONCLUSION: Our study suggests that sonographic measurement of BWT can be a helpful parameter for selecting patients responding early to ustekinumab and for providing assistance in terms of further treatment interval at week 8.

Neurocognitive development in isolated Robin sequence treated with the Tuebingen palatal plate.

OBJECTIVES: We aimed to determine the neurocognitive development of cleft palate patients with and without Robin sequence (RS). MATERIALS AND METHODS: Children with isolated RS with cleft palate and children with cleft palate only (CPO) were contacted at the age of 5-6 years. All RS children had undergone initial polygraphic sleep study (PG) with a mixed-obstructive apnea index (MOAI) of ≥ 3/h and were consequently treated with the Tuebingen palatal plate. A standardized clinical examination as well as a neuropediatric and neuropsychological examination included the Wechsler Pre-school and Primary Scale of Intelligence (WPPSI-III), Kaufman Assessment Battery for Children (K-ABC), and an assessment of developmental milestones. RESULTS: In total, 44 children (22RS, 22CPO) were included. RS children were younger at study (70.5 ± 7.3 and 75.2 ± 7.5 months; P = .035). Both groups achieved the evaluated milestones within the normed time frame. WPPSI-III and K-ABC results showed no group differences. Mean values for Verbal IQ (101.8 ± 11.1 vs. 97.1 ± 15.7), Performance IQ (102.9 ± 12.1 vs. 99.6 ± 14.5), Processing Speed Quotient (98.9 ± 15.6 vs. 94.5 ± 15.7), Full-Scale IQ (103.2 ± 12.1 vs. 98.4 ± 15.3), and Sequential Processing Scale (102.1 ± 13.1 vs. 94.2 ± 17.3) were within the reference range (IQ 85-115) for RS and CPO children, respectively, indicating average performance of both groups. CONCLUSION: No neurocognitive, physical, or mental impairments were detected suggesting that RS children having upper airway obstruction (UAO) treated early and effectively may use their potential for an age-appropriate neurocognitive development. CLINICAL RELEVANCE: Tuebingen palatal plate treatment successfully releases UAO. Thus, isolated RS does not necessarily result in developmental delay or an impaired neurocognitive outcome. TRIAL REGISTRATION: Deutsches Register Klinischer Studien, DRKS00006831, https://www.drks.de/drks_web/.

Adolescent boys with constitutional delay of growth and puberty grow faster than patients with organic growth hormone deficiency.

OBJECTIVE: Constitutional delay of growth and puberty (CDGP) is a tempo variant with a good prognosis. Healthy late-maturing adolescents grow slower than postulated by age-related references, and therefore, CDGP is frequently confused with growth hormone deficiency (GHD). For differential diagnosis, height velocity references for CDGP are needed. DESIGN AND PATIENTS: Here, we provide height velocity data for late-maturing boys based on mixed longitudinal and cross-sectional observations in a group of 38 German adolescents with proven CDGP and compare them with cross-sectional observations in a group of 164 adolescents with organic GHD from the National Cooperative Growth Study registry. RESULTS: In the critical age interval from 13.4 to 14.9 years, the growth of prepubertal adolescents with CDGP was faster (mean/median height velocity, 5.2/5.4 cm/years; quartiles, 4.4-6.2 cm/years) than that of prepubertal adolescents with organic GHD (3.5/3.2 cm/years; quartiles, 2.0-4.4 cm/years) in the cross-sectional analysis (p < .0001). Based on our mixed longitudinal and cross-sectional analysis, the height velocity of adolescent boys with CDGP exceeded previous model calculations on average by 1.0 cm. CONCLUSIONS: In conclusion, prepubertal adolescents with CDGP grow faster than patients with organic GHD. Previous model estimates underestimated height velocity of boys with CDGP.

Outcomes after Descemet membrane endothelial keratoplasty over a period of 7 years at a tertiary referral center: endothelial cell density, central corneal thickness, and visual acuity.

PURPOSE: To better assess clinical trajectories of patients with or without ocular comorbidity after Descemet membrane endothelial keratoplasty. BACKGROUND: To report on the outcomes of eyes with differing starting conditions following surgery. DESIGN: Retrospective study at a University Eye Hospital. PARTICIPANTS: 361 eyes separated into group 1 (n=229; eyes with endothelial disease only) and group 2 (n=132; eyes with additional ocular comorbid conditions, such as herpetic eye disease 18/132 (13.6%), glaucoma 16/132 (12.1%), dry age-related macular degeneration 14/132 (10.6%), epiretinal membranes 10/132 (7.6%), and wet age-related macular degeneration 9/132 (6.8%)). METHODS: Consecutive eyes that underwent Descemet membrane endothelial keratoplasty over a follow-up period of up to 7 years at a tertiary referral center were reviewed. Main outcome measures were best-corrected visual acuity, postoperative complications, graft survival, central corneal thickness, and endothelial cell density. RESULTS: Postoperative best-corrected visual acuity at year 1 improved in both groups significantly (Wilcoxon signed rank test: group 1, p =.002; .63 to .23 logMAR; group 2, p <.001; 1.15 to .87 logMAR) with a group difference in favor of group 1 (p =.009, Mann-Whitney-Wilcoxon). A decrease of the endothelial cell density and central corneal thickness was noted at postoperative year 1 for both groups (paired t-tests (group 1, p <.001; group 2, p =.045) and paired t-tests (group 1, p <.001; group 2, p =.003). Complications were less common, and graft longevity was superior in group 1. CONCLUSION: Eyes with different starting conditions might experience a visual improvement and benefit from surgery. Descemet membrane endothelial keratoplasty is a valid treatment for endothelial disorders in manifold of eyes. Further long-term studies are required.

Successful Regression in Patients with Progressive Keratoconus by Corneal Crosslinking. / Erfolgreiche Regression durch Crosslinking bei Patienten mit fortschreitendem Keratokonus.

BACKGROUND: Since 2019, corneal collagen crosslinking (CXL) is included in the catalog of procedures covered by statutory health insurance in Germany. CXL is an established ophthalmological procedure for the last 20 years. The aim of this investigation was the measurement of progression before and after CXL. MATERIAL UND METHODS: 65 consecutive eyes with progressive keratoconus from 53 patients were included in the retrospective study, which were observed at the University Eye Hospital Tübingen at least two years before and at least two years after CXL. The time of observation took place from October 2009 until March 2018. Parameters of interest had been the best corrected visual acuity (BCVA) and the keratometric values from the elevation maps measured by a Scheimpflug camera. RESULTS: 65 eyes of 53 patients had been documented. The study population included 46 (86.8%) male and 7 (13.2%) female subjects. The mean age was 24 ± 8 years. The averaged observation time between the primary consultation and CXL showed 25 ± 15 months. Preoperatively the mean BCVA pointed out in a significant increase (0.13 ± 0.17 [first visit] vs. 0.23 ± 0.22 [preOP], p < 0.0001) while the mean Kmax resulted in a statistically significant increase (46.34 ± 3.33 dpt [first visit] vs. 48.78 ± 4.17 dpt [preOP], p < 0.0001). The mean thinnest point of the cornea showed a significant decrease (490.48 ± 34.23 µm [first visit] vs. 468.62 ± 29.84 µm [preop], p < 0.0001). Postoperatively the mean BCVA resulted in a significant improvement at the 12th postoperative month in comparison to the preoperative measurement (0.23 ± 0.22 [preOP] vs. 0.16 ± 0.14 [12 months], p = 0.04 respectively 0.17 ± 0.17 [24 months], p = 0.0006). The mean Kmax demonstrated in the 12th postoperative month a significant reduction (48.78 ± 4.17 dpt [preOP] vs. 47.91 ± 3.41 dpt [12 months], p = 0.0009 respectively 48 ± 4.56 dpt [24 months], p = 0.0051). The mean thinnest point of the cornea indicated a decrease at the 12th postoperative month (468.62 ± 29.84 µm [preOP] vs. 459.82 ± 35.88 µm [12 months], p = 0.0078 respectively 453.47 ± 43.39 µm [24 months], p = 0.0227). CONCLUSION: CXL is a successful procedure for the therapy of progressive keratoconus.

The Role of Reconstructive Surgery and Brachytherapy in Pediatric Bladder/Prostate Rhabdomyosarcoma.

PURPOSE: The surgical approach to localized bladder/prostate rhabdomyosarcoma in children may change due to a new radiotherapeutic modality. We assessed the impact of brachytherapy following surgery for local tumor control, and report surgical techniques and outcomes. MATERIALS AND METHODS: We retrospectively analyzed the records of all children who underwent surgery for bladder/prostate rhabdomyosarcoma, including tumor relapse, at our institution from 2009 onward. RESULTS: A total of 38 patients with a median age of 29 months (range 10 to 134) met inclusion criteria. Five-year overall survival was 92.8% (95% CI 72.9 to 98.1), and event-free survival at a median followup of 12 months (range 3 to 111) was 73.7% (95% CI 53.4 to 86.2). Three treatment groups were defined, ie bladder preserving surgery combined with brachytherapy, bladder preserving surgery alone and cystectomy. Five-year event-free survival rates for the 3 groups were 85.6% (95% CI 61.2 to 95.2), 66.7% (95% CI 27.2 to 88.2) and 50% (95% CI 5.8 to 84.5), respectively. Bladder preserving surgery was performed in 33 patients (87%), of whom 23 (70%) also underwent brachytherapy, while cystectomy was performed in 5 (13%). Reconstructive procedures varied depending on tumor location and spread. CONCLUSIONS: Combining brachytherapy with surgery results in a high bladder preservation rate and improves event-free survival compared to surgery alone in children with bladder/prostate rhabdomyosarcoma. The combination is also effective in treating local tumor relapse, and is associated with less extensive reconstructive procedures due to exclusion of tumors of unfavorable size and location for brachytherapy.

Diagnosis of severe growth hormone deficiency in the newborn.

OBJECTIVE: Severe neonatal growth hormone deficiency (GHD) can cause recurrent hypoglycaemia. Early diagnosis is warranted. The aim of the study was to analyse the GH content in screening cards of 25 affected and 281 healthy newborns. PATIENTS AND MEASUREMENTS: A total of 110 screening cards from ill newborns were sent to us for measuring GH content by a highly sensitive GH ELISA. Clinical information was obtainable in 61 cases. Severe GHD was defined by the presence of recurrent hypoglycaemia with a significant pituitary malformation or two additional pituitary hormone deficiencies. Screening cards from 281 healthy newborns (34.0-37.9 weeks) were prospectively analysed. RESULTS: In 25 newborns (5 preterm), the definition of severe GHD was fulfilled based on recurrent hypoglycaemia in combination with malformation of the pituitary or midline structures in 21 cases and combined TSH and ACTH deficiency in four cases. The median GH concentration of those affected with severe GHD was 3.9 µg/L (range: 1.1-11.8), significantly below the previously reported reference range (P < .001). A GH concentration of 7 µg/L was confirmed as the cut-off for term newborns with the best accuracy (90.0% sensitivity and 98.7% specificity). The 95% reference range for healthy preterm newborns (n = 151) was 7.6-47.1 µg/L (median: 20.3 µg/L). CONCLUSIONS: A GH content <7.0 µg/L in the newborn screening card confirms severe GHD with high accuracy. In preterm newborns, the lower limit of the reference interval was 0.6 µg/L higher than in term newborns. The newborn screening card is a valuable source for the very early diagnosis of GH deficiency.

The Kids Obesity Prevention Program: Cluster Randomized Controlled Trial to Evaluate a Serious Game for the Prevention and Treatment of Childhood Obesity.

BACKGROUND: Health games provide opportunities for the treatment and prevention of childhood obesity. We developed a motion-controlled serious game for children that addresses 3 core topics of nutrition, physical activity, and stress coping. It is the first serious game that extensively targets the dietary energy density principle (DED-P) in relation to nutrition. The game is intended to provide an additional educational component for the prevention and treatment of obesity in children. OBJECTIVE: The Kids Obesity Prevention study aimed to evaluate the newly developed game and to evaluate how well children are able to understand and apply the DED-P. METHODS: This cluster randomized controlled trial collected data from 82 primary school children aged 9 to 12 years and their parents at baseline (T0), at 2 weeks after study commencement (T1), and at the 4-week follow-up (T2). The dropout rate was 3.6%. The intervention group (IG) played the game within 2 weeks (2 sessions with different game modules). One part of the game involves selection of food with the lower energy density when presented with a pair of foods. This allows assessment of whether the children have understood the DED-P and whether they can apply it to unknown foods under time pressure. The control group (CG) received a brochure about the food pyramid concept and physical activity. The primary outcome was the gain in knowledge (nutrition and stress coping) and measured with a pretested questionnaire. The secondary outcomes were the maintenance of knowledge, application of the DED-P, feelings during game play, game acceptance, and behavioral measures (physical activity, media consumption, and dietary intake). RESULTS: The knowledge score ranging from 0 to 100 increased from T0 (IG: 53 [SD 10], CG: 50 [SD 11]) to T1 (IG: 69 [SD 11], CG: 52 [SD 12]) in IG versus CG (P<.001). At T2, the knowledge score of IG remained at the same level as that of T1. Game data showed that after DED-P education, the classification under time pressure of unknown versus known food pairs according to their DED category was similar (hit rate around 70%). Overall, 95% of the children liked the game very much or much. No group changes were observed at the behavioral level. CONCLUSIONS: The Kids Obesity Prevention program sustainably increased knowledge in the areas of nutrition and stress coping, and children were able to apply the DED-P. TRIAL REGISTRATION: ClinicalTrials.gov NCT02551978; https://clinicaltrials.gov/ct2/show/NCT02551978.

Treatment and outcome of the patients with rhabdomyosarcoma of the biliary tree: Experience of the Cooperative Weichteilsarkom Studiengruppe (CWS).

BACKGROUND: Biliary rhabdomyosarcoma (RMS) is the most common biliary tumor in children. The management of affected patients contains unique challenges because of the rarity of this tumor entity and its critical location at the porta hepatis, which can make achievement of a radical resection very difficult. METHODS: In a retrospective chart analysis we analysed children suffering from biliary RMS who were registered in three different CWS trials (CWS-96, CWS-2002P, and SoTiSaR registry). RESULTS: Seventeen patients (12 female, 5 male) with a median age of 4.3 years were assessed. The median follow-up was 42.2 months (10.7-202.5). The 5-year overall (OS) and event free survival (EFS) rates were 58% (45-71) and 47% (34-50), respectively. Patients > 10 years of age and those with alveolar histology had the worst prognosis (OS 0%). Patients with botryoid histology had an excellent survival (OS 100%) compared to those with non-botryoid histology (OS 38%, 22-54, p = 0.047). Microscopic complete tumor resection was achieved in almost all patients who received initial tumor biopsy followed by chemotherapy and delayed surgery. CONCLUSION: Positive predictive factors for survival of children with biliary RMS are age ≤ 10 years and botryoid tumor histology. Primary surgery with intention of tumor resection should be avoided.

Calcification of the iliac arteries: a marker for leakage risk in rectal anastomosis-a blinded clinical trial.

PURPOSE: Anastomotic leakage (AL) is associated with increased morbidity and mortality after colorectal surgery. Calcification of the arteries has been identified as a risk factor for cardiovascular events and can be reliably measured on computed tomography using software assistance. The aim of this prospective study was to prove the value of calcium scoring of the iliac arteries as a predictor of AL after rectal anastomosis. METHODS: Consecutive patients who underwent colorectal resection with rectal anastomosis were analyzed. Diagnostic computed tomography images were used to detect calcification of the arteries supplying the rectal anastomosis. Logistic regression analysis was used to determine the relationship between vascular calcification and AL. RESULTS: Of 139 included and analyzed patients, AL occurred in 15 (11%). The volume and calcium scores were significantly higher in the infrarenal aorta, the left and right common iliac artery, and the left internal iliac artery. In univariate analysis, calcification of the left internal iliac artery and both internal iliac arteries combined correlated with the occurrence of the primary endpoint. A receiver operating curve analysis led to the cut-off values of 30 and 6 for the volume score and calcium score, respectively. They provide a negative predictive value of 0.97 and a positive predictive value of 0.19. CONCLUSIONS: Calcification in the iliac arteries appears to be a good marker for the risk of leakage after rectal anastomosis. The calcification scoring system is easy to calculate after computed tomography and may aid in patient selection to create a protective ileostomy.

Interview based malnutrition assessment can predict adverse events within 6 months after primary and revision arthroplasty - a prospective observational study of 351 patients.

BACKGROUND: Being at risk for malnutrition can be observed among hospitalized patients of all medical specialties. There are only few studies in arthroplasty dealing with defining and assessing malnutrition as such a potentially risk. This study aims to identify the risk for malnutrition following primary (pAP) and revision arthroplasty (rAP) (1) using non-invasive interview based assessment tools and to analyze effects on clinical outcome (2) and quality of life (3). METHODS: A consecutive series of hospitalized patients of a Department of Arthroplasty at a Level 1 Trauma Center in Western Europe was observed between June 2014 and June 2016. Patients were monitored for being at risk for malnutrition at hospital admission (T1) and 6 months post surgery (T2) by non-invasive interview based assessment tools (NRS 2002, SF-MNA, MNA). Adverse events, length of hospital stay and quality of life (HRQL, SF-36) were monitored. RESULTS: 351 (283 pAP/ 68 rAP) patients were included. At T1, 13.4% (47) / 23.9% (84) / 27.4% (96) and at T2 7.3% (18) / 17.1% (42) / 16.0% (39) of all patients were at risk for malnutrition regarding NRS/SF-MNA/MNA. Prevalence of malnutrition risk was higher in rAP (22.1-29.4%) compared to pAP (11.3-26.9%). Patients being at risk for malnutrition showed prolonged hospitalization (NRS 14.5 to 12.5, SF-MNA 13.7 to 12.4, MNA 13.9 to 12.3 days, p < 0.05), delayed mobilization (NRS 2.1 to 1.7, SF-MNA 1.8 to 1.7, MNA 1.9 to 1.7 days), lower values in HRQL and more adverse events. CONCLUSIONS: There is a moderate to high prevalence of risk for malnutrition in arthroplasty that can easily be assessed through interview based screening tools. Being at risk for malnutrition can reduce the clinical outcome following pAP and rAP. Patients with an impaired nutritional status show reduced values in physical and mental aspects of HRQL. Non-invasive interview-based nutritional assessment can predict adverse events in primary and revision total arthroplasty and can therefore help identifying patients at risk before surgery. TRIAL REGISTRATION: The study protocol was approved by the local ethics committee (193/2014BO2) and registered at the German Clinical Trials Register according to WHO standard ( DKRS00006192 ).

Attitudes Toward e-Health: The Otolaryngologists' Point of View.

INTRODUCTION: Online communication and the number of e-health applications have noticeably increased. However, little is known about the otolaryngologists' use behavior and their attitudes toward the potential of e-health. The aims of the study were to evaluate the documentation, information, and communication technologies used by otolaryngologists and to get a better understanding of their attitudes toward the potential of e-health for cross-sectoral patient care. METHODS: A survey was developed and tested by otolaryngologists, healthcare-information technology experts, and health services researchers. A total of 334 otolaryngologists in private practice were asked to participate in this cross-sectional study. In total, 234 of them took part in the study, and 157 returned completed questionnaires. Statistical analysis was performed by using crosstabs, including chi-square tests, and multivariate logistic regressions. Results and Materials: Digital technologies are widely used by otolaryngologists (e.g., 89.6% use an electronic health record). However, the majority of intersectoral communication is still based on analogue techniques (e.g., fax use in 63.7%). From the otolaryngologists' perspectives, the potential of e-health for intersectoral care is mostly in appointment scheduling, further referrals to hospitals, and automated appointment reminders. The physicians' attitudes toward e-health are associated with their Internet use behavior in daily life (odds ratio = 4.30, confidence interval 1.11-16.64, p = 0.035) but not with their demographics. DISCUSSION: The otolaryngologists are well prepared and have an overall positive attitude toward e-health for deeper use in cross-sectoral care. Therefore, e-health in otolaryngology needs more attention and resources for further studies, especially with a focus on quality and safety of care.

Emergency Coagulation Assessment During Treatment With Direct Oral Anticoagulants: Limitations and Solutions.

BACKGROUND AND PURPOSE: In patients receiving direct oral anticoagulants (DOACs), emergency treatment like thrombolysis for acute ischemic stroke is complicated by insufficient availability of DOAC-specific coagulation tests. Conflicting recommendations have been published concerning the use of global coagulation assays for ruling out relevant DOAC-induced anticoagulation. METHODS: Four hundred eighty-one samples from 96 DOAC-treated patients were tested using prothrombin time (PT), activated partial thromboplastin time (aPTT) and thrombin time (TT), DOAC-specific assays (anti-Xa activity, diluted TT), and liquid chromatography-tandem mass spectrometry. Sensitivity and specificity of test results to identify DOAC concentrations <30 ng/mL were calculated. Receiver operating characteristic analyses were used to define reagent-specific cutoff values. RESULTS: Normal PT and aPTT provide insufficient specificity to safely identify DOAC concentrations <30 ng/mL (rivaroxaban/PT: specificity, 77%/sensitivity, 94%; apixaban/PT: specificity, 13%/sensitivity, 94%, dabigatran/aPTT: specificity, 49%/sensitivity, 91%). Normal TT was 100% specific for dabigatran, but sensitivity was 26%. In contrast, reagent-specific PT and aPTT cutoffs provided >95% specificity and a specific TT cutoff enhanced sensitivity for dabigatran to 84%. For apixaban, no cutoffs could be established. CONCLUSIONS: Even if highly DOAC-reactive reagents are used, normal results of global coagulation tests are not suited to guide emergency treatment: whereas normal PT and aPTT lack specificity to rule out DOAC-induced anticoagulation, the low sensitivity of normal TT excludes the majority of eligible patients from treatment. However, reagent-specific cutoffs for global coagulation tests ensure high specificity and optimize sensitivity for safe emergency decision making in rivaroxaban- and dabigatran-treated patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT02371044 and NCT02371070.

POST-TEXT III and IV Hepatoblastoma: Extended Hepatic Resection Avoids Liver Transplantation in Selected Cases.

OBJECTIVE: To analyze the outcome of hepatoblastoma (HB) patients presenting with post treatment extent of disease (POST-TEXT) stages III and IV after neoadjuvant chemotherapy. BACKGROUND: Primary liver transplantation has been advocated as surgical treatment for children with HB involving 3 or 4 sectors at diagnosis. However, in some cases, tumors seem resectable after chemotherapy through aggressive use of nontransplant surgical procedures. METHODS: Data of 27 HB patients were reviewed, undergoing extended liver resection for POST-TEXT III or IV tumors after chemotherapy between 1992 and 2015. Median follow-up was 58 months (range 9-188). RESULTS: Median age at surgery was 18.2 months (interquartile range 10.8-32.5). Staging of the children after chemotherapy revealed POST-TEXT III in 21 and POST-TEXT IV in 6 cases. In 2 children, the hepatic resection was performed under cardiopulmonary bypass because of extended vena cava thrombosis; in 2 patients, a simultaneous sternotomy was performed for resection of bilateral lung metastases. The 5-year overall survival rate was 80.7%. CONCLUSIONS: Aggressive surgical resection is a successful approach in some patients with POST-TEXT III and IV HB who otherwise would be candidates for liver transplantation. These children should undergo central review and should be surgically managed at centers of excellence for pediatric liver surgery. Despite challenging surgical procedures and complex clinical courses, the patients benefit from avoidance of morbidities of organ transplant. However, preparation of backup liver transplantation should be considered in selected cases.

Low association between fasting and OGTT stimulated glucose levels with HbA1c in overweight children and adolescents.

BACKGROUND: Diabetes and prediabetes are defined based on different methods such as fasting glucose, glucose at 2-hour in oral glucose tolerance test (OGTT), and glycated hemoglobin A1c (HbA1c). These parameters probably describe different deteriorations in glucose metabolism limiting the exchange between each other in definitions of diabetes. OBJECTIVE: To investigate the relationship between OGTT and HbA1c in overweight and obese children and adolescents living in Germany. METHODS: Study population: Overweight and obese children and adolescents (n = 4848; 2668 female) aged 7 to 17 years without known diabetes. The study population was stratified into the following subgroups: normal glucose tolerance, prediabetes, diabetes according to OGTT and/or HbA1c categories, confirmed diagnosis of diabetes. RESULTS: In the entire study group fasting plasma glucose (FPG) correlated weakly to 2-hour glucose (r = 0.26), FPG correlated weakly to HbA1c (r = 0.18), and 2-hour glucose correlated weakly to HbA1c (r = 0.17, all P < .001). Patients with confirmed diabetes showed a very high correlation between FPG and 2-hour glucose (r = 0.73, n = 50). Moderate correlations could be found for patients with impaired fasting glucose (2-hour glucose vs HbA1c: r = 0.30, n = 436), for patients with diabetes according to OGTT and/or HbA1c (FPG vs 2-hour glucose: r = 0.43; 2-hour glucose vs HbA1c: r = -0.30, n = 115) and for patients with confirmed diabetes (2-hour glucose vs HbA1c: r = -0.47, all P < .001). CONCLUSIONS: Because FPG, 2-hour glucose, and HbA1c correlated only weakly we propose that these parameters, particularly in the normal range, might reflect distinct aspects of carbohydrate metabolism.