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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/m 2 ] 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., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Smoking is the most significant and modifiable risk factor for a range of conditions, including cancer, cardiovascular and respiratory diseases. Furthermore, it significantly reduces bone mass and increases the risk of fragility fractures due to its detrimental effects on bone metabolism and regeneration. Moreover, smoking is a known cause of chronic systemic inflammation, leading to an imbalance of cytokines. Comprehending the pathological mechanisms that underlie cytokine production and its impact on post-surgical healing is essential to prevent post-surgical complications. The present study recruited a total of 1144 patients, including 897 patients, among them non-smokers ( N = 413 ), current smokers ( N = 201 ) and ex-smokers ( N = 283 ). Human proteome profiler arrays were used to screen for smoking-dependent differences in the serum cytokine and protein profiles, after matching samples for age, gender, body mass index (BMI), alcohol use, and diabetes risk. Cytokines and immune checkpoint proteins such as CD28, B7-1, MIG, TGFβ2 and IL-1α/β were quantified by ELISA. Our study demonstrates a comprehensive understanding of the relationship between smoking, the development of complications, the systemic immune inflammation index (SII) and cytokine/protein levels. We found that a comparison of non-smokers, former smokers, and active smokers in our study cohort did not exhibit significantly altered cytokine and protein serum levels although other studies reported differences between smokers and non-smokers. We were unable to identify single blood circulating markers that could predict complications in smokers after trauma. However, we found the ratio of women to men to be inverted between non-smokers and active smokers resulting in a ratio of 0.62 in smokers. Furthermore, we demonstrate a higher complication rate, longer hospitalizations and elevated SII values among smokers, indicating an involvement of the immune system. See also the graphical abstract(Fig. 1)., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2024 Tümen et al.)

Objectives: Generative Adversarial Networks (GANs) can produce synthetic images free from personal data. They hold significant value in medical research, where data protection is increasingly regulated. Panoramic radiographs (PRs) are a well-suited modality due to their significant level of standardization while simultaneously displaying a high degree of personally identifiable data., Methods: We produced synthetic PRs (syPRs) out of real PRs (rePRs) using StyleGAN2-ADA by NVIDIA©. A survey was performed on 54 medical professionals and 33 dentistry students. They assessed 45 radiological images (20 rePRs, 20 syPRs, and 5 syPRcontrols) as real or synthetic and interpreted a single-image syPR according to the image quality (0-10) and 14 different items (agreement/disagreement). They also rated the importance for the profession (0-10). A follow-up was performed for test-retest reliability with >10 % of all participants., Results: Overall, the sensitivity was 78.2 % and the specificity was 82.5 %. For professionals, the sensitivity was 79.9 % and the specificity was 82.3 %. For students, the sensitivity was 75.5 % and the specificity was 82.7 %. In the single syPR-interpretation image quality was rated at a median of 6 and 11 items were considered as agreement. The importance for the profession was rated at a median score of 7. The Test-retest reliability yielded a value of 0.23 (Cohen's kappa)., Conclusions: The study marks a comprehensive testing to demonstrate that GANs can produce synthetic radiological images that even health professionals can sometimes not differentiate from real radiological images, thereby being genuinely considered authentic. This enables their utilization and/or modification free from personally identifiable information., Clinical Significance: Synthetic images can be used for university teaching and patient education without relying on patient-related data. They can also be utilized to upscale existing training datasets to improve the accuracy of AI-based diagnostic systems. The study thereby supports clinical teaching as well as diagnostic and therapeutic decision-making., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors Rouven Schönhof and Raoul Schönhof are first-degree relatives. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background and Aims: Postpolypectomy syndrome (PPS) is a relevant adverse event that can appear after polypectomy. Several publications mention postpolypectomy syndrome using different criteria to define it. The aim of this study is to detect potential risk factors and predictors for developing PPS and to define the main criteria of PPS., Methods: In this retrospective monocentric study, 475 out of 966 patients who underwent colonoscopy with polypectomy from October 2015 to June 2020 were included. The main criterion of PPS is defined as the development of postinterventional abdominal pain lasting more than six hours., Results: A total of 9.7% of the patients developed PPS, which was defined as local abdominal pain around the polypectomy area after six hours. A total of 8.6% of the study population had abdominal pain within six hours postintervention. A total of 3.7% had an isolated triad of fever, leukocytosis, and increased CRP in the absence of abdominal pain. Increased CRP combined with an elevated temperature over 37.5 °C seems to be a positive predictor for developing PPS. Four independent risk factors could be detected: serrated polyp morphology, polypoid configurated adenomas, polyp localization in the cecum, and the absence of intraepithelial neoplasia., Conclusions: Four independent risk factors for developing PPS were detected. The combination of increased CRP levels with elevated temperature seems to be a predictor for this pathology. As expected, the increasing use of cold snare polypectomies will reduce the incidence of this syndrome. Key summary: Our monocentric study on 966 patients detected four independent risk factors for developing PPS: pedunculated polyp, resected polyps in the cecum, absence of IEN, and serrated polyp morphology. The combination of increased CRP levels with elevated temperature seems to be a predictor for this pathology.

Early and reliable detection of infection is vital for successful treatment. Serum markers such as C-reactive protein (CRP) and procalcitonin (PCT) are known to increase with a time lag. Azurocidin 1 (AZU1) has emerged as a promising marker for septic patients, but its diagnostic value in orthopedic and trauma patients remains unexplored. Between July 2020 and August 2023, all patients necessitating inpatient treatment for periprosthetic joint infection (PJI), peri-implant infection (II), soft tissue infection, chronic osteomyelitis, septic arthrodesis, bone non-union with and without infection were enrolled. Patients undergoing elective total joint arthroplasty (TJA) served as the control group. Blood samples were collected and analyzed for CRP, white blood cell count (WBC), PCT, and AZU1. Based on the inclusion and exclusion criteria 222 patients were included in the study (trauma = 38, soft tissue infection = 75, TJA = 33, PJI/II = 39, others = 37). While sensitivity and specificity were comparably high for AZU1 (0.734/0.833), CRP and PCT had higher specificity (0.542/1 and 0.431/1, respectively), and WBC a slightly higher sensitivity (0.814/0.455) for septic conditions. Taken together, the area under the curve (AUC) showed the highest accuracy for AZU1 (0.790), followed by CRP (0.776), WBC (0.641), and PCT (0.656). The Youden-Index was 0.57 for AZU1, 0.54 for CRP, 0.27 for WBC, and 0.43 for PCT. Elevated AZU1 levels effectively distinguished patients with a healthy condition from those suffering from infection. However, there is evidence suggesting that trauma may influence the release of AZU1. Additional research is needed to validate the diagnostic value of this new biomarker and further explore its potential clinical applications., Competing Interests: All authors declare that they have no conflict of interest., (Copyright © 2024 Hemmann et al.)

Introduction:  Inguinal procedures in children are frequent and typically performed in an outpatient setting. We aimed to analyze whether there is a difference in postoperative pain scores and setup time (start of anesthesia management to incision time) when comparing caudal block (CB) with local wound infiltration., Materials and Methods:  We enrolled pediatric outpatients scheduled for inguinal procedures. Patients were randomized to receive either preincision CBs or end-of-procedure local wound infiltration. Postoperative pain scores until 24 hours postoperatively and setup time were analyzed., Results:  Fifty-two patients were included in the study. Thirty patients received a CB, and 22 patients received local infiltration (LI). There was no significant difference in postoperative pain scores. Setup time was significantly higher in the CB group: median 22.5 minutes IQR (16-46 minutes) compared with 17 minutes in the LI group IQR (10-35 minutes), p -value of 0.0026., Conclusion:  Both CB and LI result in good postoperative pain control after inguinal procedures in pediatric outpatients. Since LI is less time consuming and has lower risks for complications, we recommend this technique for inguinal procedures in pediatric outpatients. Our findings will need to be confirmed in larger cohorts, but we believe the evidence generated with this study has the potential to positively influence patient care, operating room efficiency, and costs., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Spinal injuries are difficult injuries to assess yet can be associated with significant neurological damage. To avoid secondary damage, immobilization is considered state of the art trauma care. The indication for spinal immobilization must be assessed, however, for potential complications as well as its advantages and disadvantages., Methods: This systematic review addressing the question of the correct indication for spinal immobilization in trauma patients was compiled on the basis of our previously published analysis of possible predictors from the Trauma Registry of the German Society for Trauma Surgery. A Delphi procedure was then used to develop suggestions for action regarding immobilization based on the results of this review., Results: The search of the literature yielded 576 publications. The 24 publications included in the qualitative analysis report of 2 228 076 patients. A decision tool for spinal immobilization in prehospital trauma care was developed (Immo traffic light system) based on the results of the Delphi procedure. According to this system, severely injured patients with blunt trauma, severe traumatic brain injury, peripheral neurological symptoms, or spinal pain requiring treatment should be immobilized. Patients with a statistically increased risk of spinal injury as a result of the four cardinal features (fall >3m, severe trunk injury, supra clavicular injury, seniority [age >65 years]) should only have their spinal motion restricted after weighing up the pros and cons. Isolated penetrating trunk injuries should not be immobilized., Conclusion: High-quality studies demonstrating the benefit of prehospital spinal immobilization are still lacking. Decision tools such as the Immo traffic light system can help weigh up the pros and cons of immobilization.

This cross-sectional study explored factors associated with the corona virus disease 2019 (COVID-19) vaccination acceptance among higher education students in southwestern Germany. We conducted a cross-sectional online survey at six state-approved higher education institutions (HEIs) between July and November 2021. In addition to descriptive analyses, univariate as well as multivariate binary logistic regression analyses were conducted. A total of 6556 higher education students aged 18 years and older participated in our survey; 91.4% of participating students had been vaccinated against COVID-19 at least once. The factors that significantly contributed to the explanation of higher education students' vaccination status in the multivariate analysis (area under curve-AUC = 0.94) were variables on the perception of the virus SARS-CoV-2 (affective risk perception: Adjusted odds ratio-aOR = 1.2; perception of the outbreak as a media-hype: aOR = 0.8), attitudes towards personal (aOR = 0.7) and study-related (aOR = 0.8) health and safety measures to prevent transmission of SARS-CoV-2, and attitudes towards COVID-19 vaccination (preservation of own health: aOR = 1.3; confidence in vaccine safety: aOR = 1.7; supporting higher education through vaccination: aOR = 1.2; own contribution to the containment of the pandemic: aOR = 1.7). The findings target assisting HEIs in returning to face-to-face teaching after previous semesters of online teaching.

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., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Hematopoietic stem cell transplantation (HSCT) is associated with severe medical complications and variable outcomes depending on the recipient's disease stage and health condition. Biomarkers predicting outcome may have therapeutic relevance in pediatric cancer care. Insulin-like growth factor 1 (IGF-1), a mitogenic and anabolic peptide hormone expressed in almost all tissues, is the major growth factor in childhood. Decreased IGF-1 concentration in conditions that cause catabolic metabolism may reflect a patient's degree of physical robustness and serve as a predictive biomarker for transplantation outcome. We evaluated the impact of pretransplantation serum IGF-1 level on both survival and adverse events in 587 pediatric cancer patients who underwent autologous or allogeneic HSCT between 1987 and 2014 at the University Children's Hospital Tübingen. Survival probabilities of the entire cohort and of defined subgroups according to pretransplantation serum IGF-1 level were estimated using the Kaplan-Meier method. The mean pretransplantation IGF-1 level (n = 498) was low: -1.67 SDS (SD, 1.54). Completeness of follow-up was 96% at 3 years post-HSCT and 83% at 10 years. Overall survival (OS) at 10 years was 44.8% (95% confidence interval, 40.6% to 48.9%). Decreasing IGF-1 SDS was associated with significant increases in transplantation-related mortality (P = .027), sinusoidal obstruction syndrome (quartiles 4 to 1: 3%, 1%, 12%, and 12%; P < .001), and thrombotic microangiopathy (quartiles 4 to 1: 0%, 0%, 2%, and 5%; P = .004). Compared with patients in IGF-1 deciles 2 to 10, patients in IGF-1 decile 1 had significantly poorer outcome (P = .042) with lower median survival (12 months versus 68 months) and 10-year OS (37% versus 52%). This retrospective study suggests that pretransplantation serum IGF-1 level has utility as a predictor of survival and selected vascular adverse events that may have diagnostic and therapeutic relevance in pediatric cancer care., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

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&#95;web/., (© 2022. The Author(s).)

Background: The methylation of IGF1 promoter P2 was reported to negatively correlate with serum IGF-1 concentration and rhGH treatment response in children with idiopathic short stature. These findings have not yet been confirmed., Objective: This study aimed to determine IGF1 promoter P2 methylation in short children treated with rhGH and correlate clinical parameters with the methylation status. In addition, long-term stability of methylation during rhGH treatment was studied., Design: This was a single tertiary center study analyzing clinical GH response and IGF-1 serum concentration changes in patients with GHD (n=40), SGA short stature (n=36), and Turner syndrome (n=16) treated with rhGH. Data were correlated to the methylation of two cytosine residues (-137, +97) of the P2 promoter of IGF1 in blood cells measured by pyrosequencing in 443 patient samples., Results: Basal and stimulated IGF-1 concentrations, first year increment in height velocity and studentized residuals of a prediction model did not correlate to the methylation of -137 und +97 in IGF1 P2 promoter. The methylation of these two sites was relatively stable during treatment., Conclusions: This study did not confirm IGF1 P2 promotor being a major epigenetic locus for GH responsiveness in patients treated with a normal dose of rhGH. Additional studies are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Apel, Iliev, Urban, Weber, Schweizer, Blumenstock, Pasche, Nieratschker and Binder.)

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., (© 2022. The Author(s).)

Purpose: Autosomal recessive retinitis pigmentosa (arRP) can be caused by mutations in the phosphodiesterase 6A (PDE6A) gene. Here, we describe the natural course of disease progression with respect to central retinal function (i.e., visual acuity, contrast sensitivity, and color vision) and establish a detailed genotype--phenotype correlation., Methods: Forty-four patients (26 females; mean age ± SD, 43 ± 13 years) with a confirmed genetic diagnosis of PDE6A-associated arRP underwent comprehensive ophthalmological examinations including best-corrected visual acuity (BCVA) with Early Treatment Diabetic Retinopathy Study charts, contrast sensitivity (CS) with Pelli-Robson charts at distances of 3 m and 1 m, and color vision testing using Roth 28-Hue and Panel D-15 saturated color cups., Results: The most frequently observed variants were c.998+1G>A/p.?, c.304C>A/p.R102S, and c.2053G>A/p.V685M. Central retinal function in patients homozygous for variant c.304C>A/p.R102S was better when compared to patients homozygous for variant c.998+1G>A/p.?, although the former were older at baseline. Central retinal function was similar in patients homozygous for variant c.304C>A/p.R102S and patients heterozygous for variants c.304C>A/p.R102S and c.2053G>A/p.V685M, although the latter were younger at baseline. Annual decline rates in central retinal function were small., Conclusions: We conclude that the severity of the different disease-causing PDE6A mutations in humans with respect to central visual function may be ranked as follows: c.2053G>A/p.V685M in homozygous state (most severe) > c.998+1G>A/p.? in homozygous state > c.304C>A/p.R102S and c.2053G>A/p.V685M in compound-heterozygous state > c.304C>A/p.R102S in homozygous state (mildest). The assessment of treatment efficacy in interventional trials will remain challenging due to small annual decline rates in central retinal function.

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., (Copyright © 2022 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

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., (© 2021 The Authors. Mycoses published by Wiley-VCH GmbH.)

Background: Robin sequence is defined as the triad of micrognathia, glossoptosis, and upper airway obstruction. In up to 85 percent, it is associated with cleft palate. Many studies have reported worse speech development in Robin sequence children after cleft palate repair. The authors investigated speech development in isolated Robin sequence with cleft palate versus children with cleft palate only at the age of 5 to 6 years., Methods: All Robin sequence children were treated with the Tübingen palatal plate after birth. Data were collected using the German version of the Great Ormond Street Speech Assessment. Audio and video recordings were reviewed and analyzed separately by two blinded senior phoniatricians based on the German version of the Universal Reporting Parameters for Cleft Palate Speech, and scored to enable comparability of speech outcomes., Results: Forty-four children (Robin sequence, n = 22; cleft palate only, n = 22) were included. Robin sequence children were significantly older at surgery (11.8 months versus 7.1 months; p < 0.001) but younger at study (70.5 months versus 75.2 months; p = 0.035). They also had more severe cleft of the palate (p = 0.006). All children studied showed good to very good speech development without serious impairment. None of the reported parameters on the German version of the Universal Reporting Parameters for Cleft Palate Speech showed significant group differences; the median total score in the Robin sequence group was 23 (interquartile range, 16.5 to 27.5) versus 19 (interquartile range, 17 to 23) in the cleft palate-only group. Statistical analysis revealed no significant effect of group (Z = -1.47; p = 0.14)., Conclusions: No group differences in speech development were found at age 5 to 6 years. Isolated Robin sequence does not necessarily represent a risk for impaired speech development., Clinical Question/level of Evidence: Risk, II., (Copyright © 2021 by the American Society of Plastic Surgeons.)

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., Competing Interests: The authors declare that they have no conflict of interest./Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Purpose: To evaluate whether there is a change in findings of coronavirus disease 2019 patients in follow up lung ultrasound and to determine whether these findings can predict the development of severe disease., Materials and Methods: In this prospective monocentric study COVID-19 patients had standardized lung ultrasound (12 area evaluation) at day 1, 3 and 5. The primary end point was detection of pathologies and their change over time. The secondary end point was relationship between change in sonographic results and clinical outcome. Clinical outcome was assessed on development of severe disease defined as need for intensive care unit., Results: Data of 30 patients were analyzed, 26 patients with follow-up lung ultrasound. All of them showed lung pathologies with dynamic patterns. 26,7% developed severe disease tending to have an ubiquitous lung involvement in lung ultrasound. In patients with need for intensive care unit a previously developed increase in B-lines, subpleural consolidations and pleural line irregularities was more common. A statistically significant association between change in B-lines as well as change in pleural line irregularities and development of severe disease was observed (p<0,01)., Conclusion: The present study demonstrates that follow up lung ultrasound can be a powerful tool to track the evolution of disease and suggests that lung ultrasound is able to indicate an impending development of severe disease in COVID-19 patients., Competing Interests: The authors have declared that no competing interests exist.

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., (© 2021. The Author(s).)

Background and Purpose:  Accurate and rapid assessment of coagulation status is necessary to guide thrombolysis or reversal of anticoagulation in stroke patients, but commercially available point-of-care (POC) assays are not suited for coagulation testing in patients treated with direct oral anticoagulants (DOACs). We aimed to evaluate the direct thrombin monitoring (DTM) test card by Helena Laboratories (Texas, United States) for anti-IIa-specific POC coagulation testing, hypothesizing that its POC-ecarin clotting time (POC-ECT) accurately reflects dabigatran plasma concentrations., Methods:  A prospective single-center diagnostic study (ClinicalTrials.gov-identifier: NCT02825394) was conducted enrolling patients receiving a first dose of dabigatran and patients already on dabigatran treatment. Blood samples were collected before drug intake and 0.5, 1, 2, 8, and 12 hours after intake. POC-ECT was performed using whole blood (WB), citrated blood (CB), and citrated plasma (CP). Dabigatran plasma concentrations were determined by mass spectrometry., Results:  In total, 240 blood samples from 40 patients contained 0 to 275 ng/mL of dabigatran. POC-ECT with WB/CB/CP ranged from 20 to 186/184/316 seconds. Pearson's correlation coefficient showed a strong correlation between dabigatran concentrations and POC-ECT with WB/CB/CP ( R2  = 0.78/0.90/0.92). Dabigatran concentrations >30 and >50 ng/mL (thresholds for thrombolysis, surgery, and reversal therapy according to clinical guidelines) were detected by POC-ECT with WB/CB/CP (>36/35/45 and >43/45/59 seconds) with 95/97/97 and 96/98/97% sensitivity, and 81/87/94 and 74/60/91% specificity., Conclusion:  This first study evaluating DOAC-specific POC coagulation testing revealed an excellent correlation of POC-ECT with actual dabigatran concentrations. Detecting clinically relevant dabigatran levels with high sensitivity/specificity, the DTM assay represents a suitable diagnostic tool in acute stroke, hemorrhage, and urgent surgery., Competing Interests: F.H. reports nonfinancial support from Helena Laboratories, during the conduct of the study; other from Bayer, other from Daiichi Sankyo, outside the submitted work. I.B. reports personal fees and other from Bristol-Myers Squibb/Pfizer, grants and personal fees from Siemens Healthcare, personal fees from CSL Behring, other from Aspen, other from LFB Biomedicaments, outside the submitted work. H.R. reports nonfinancial support from Helena Laboratories, during the conduct of the study. U.Z. reports nonfinancial support from Helena Laboratories, during the conduct of the study; grants and personal fees from Biogen Idec, personal fees from Bayer Vital, personal fees from Bristol-Myers Squibb/Pfizer, personal fees from CorTec, personal fees from Medtronic, grants from Servier, grants from Janssen Pharmaceutica NV, outside the submitted work. S.P. reports nonfinancial support from Helena Laboratories, during the conduct of the study; personal fees from Bayer, grants and personal fees from Boehringer-Ingelheim, grants and personal fees from Bristol-Myers Squibb/Pfizer, grants and personal fees from Daiichi Sankyo, personal fees from Werfen, outside the submitted work., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Medication-related osteonecrosis of the jaw (MRONJ) is a severe side effect of antiresorptive (AR) drugs such as bisphosphonates (BP) and denosumab (Dmab). Although several risk factors are described, the etiology of MRONJ is still not fully elucidated. Bone-strengthening is the primary aim of antiresorptive therapy; however, overly increased bone mass and microcrack accumulation are also discussed in MRONJ etiologies. The aim of this study is to evaluate the microarchitecture of jaw bones with micro-computed tomography (micro-CT) in AR-treated patients with or without MRONJ. Human jaw bone samples of AR-treated patients were separated into 11 groups by AR treatment bisphosphonate (BP), denosumab (Dmab), both (M) and control groups. Subgroups were divided according to the clinical localization as AR-exposed vital jaw bone (BP exp , Dmab exp , M exp ), osteonecrosis-margin of a sequestrum (BPO mar , DmabO mar , MO mar ) and osteonecrosis-sequestrum (BPO seq , DmabO seq , MO seq ). Healthy jaw bone (C HB ) and osteoporotic jaw bone (C OP ) represent control groups. Samples underwent retrospective micro-CT and morphometric analysis in representative units by bone volume fraction (BV/TV), bone surface density (BS/BV), trabecular thickness (Tr.Th.), trabecular number (Tr.N.), trabecular space (Tr.Sp.), Euler characteristic for bone connectivity, bone mineral density (BMD) and tissue mineral density (TMD). A total of 141 samples from 78 patients were analyzed. BV/TV of M exp group (mean: 0.46 ± 0.27) was significantly higher than in the C OP group (mean: 0.14 ± 0.05; p = 0.0053). Tr.Th. differed significantly between the BP exp group (mean: 0.32 ± 0.15) and the M exp group (mean: 0.57 ± 0.20; p = 0.0452) as well as between the BPO seq group (mean: 0.25 ± 0.10) and the MO seq group (mean: 0.39 ± 0.18; p = 0.0417). Signs of trabecular thickening and unorganized trabecular microarchitecture from AR-exposed- to sequestrum groups, were analyzed in 3D reconstructions. However, BS/BV, Tr.N., and Tr.Sp. showed no significant differences. Euler characteristic of the BPO seq group (median: 7.46) doubled compared to that of the BP exp group (median: 14.97; p = 0.0064). Mineralization parameters BMD and TMD were similar in all groups. Findings show evidence of enhanced bone mass and suspect microarchitecture in some AR-treated jaw bone compared to osteoporotic jaw bone. Despite increased bone mass, some MRONJ samples showed decreased trabecular connectivity by Euler characteristic compared to AR-treated jaw bone. These samples may indicate extensive ossification and ineffective bone mass with superficially higher bone mass without existing or even reduced mechanical stability, indicated by connectivity loss. This result might also suggest a high risk to microcrack accumulation. At some point, possibly some kind of over-ossification could lead to under-nourishment and microarchitectural weakness, creating instability, subsequently increasing vulnerability to MRONJ., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2021 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

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., (© 2020 John Wiley & Sons Ltd.)

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.

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., (© 2020 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Background and Purpose: The corneal collagen crosslinking procedure has been clinically performed worldwide for approximately 20 years. The aim of the study was to analyze the long-term outcomes of corneal crosslinking at the University Eye Hospital in Tübingen., Methods: In this retrospective study 136 consecutive eyes with progressive keratoconus from 107 patients were included. The observational period was from December 2008 to March 2018. The parameters analyzed were best corrected visual acuity (BCVA) and the keratometry values from elevation maps measured using a Scheimpflug camera., Results: The study population of 107 patients included 96 (90%) male and 11 (10%) female subjects and the mean age was 23 ± 8 years. The mean observation time between corneal collagen crosslinking and the last follow-up examination was 42 ± 29 months. The mean postoperative BCVA showed a significant improvement from baseline at each point of postoperative measurement. The mean astigmatism and the mean Kmax showed a statistically significant reduction in the first 6 postoperative months. The mean thinnest point of the cornea showed a significant reduction in the first 6 months, after which the cornea thickness stabilized. No serious adverse events relating to the treatment were registered., Conclusion: Long-term outcomes after corneal collagen crosslinking showed a significant reduction of the keratometry values and the BCVA was significantly higher compared to the preoperative value at all times of observation. In conclusion, corneal collagen crosslinking was shown to be an effective and safe treatment for progressive keratoconus.

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., (©Isabelle Mack, Nadine Reiband, Carolin Etges, Sabrina Eichhorn, Norbert Schaeffeler, Guido Zurstiege, Caterina Gawrilow, Katja Weimer, Riyad Peeraully, Martin Teufel, Gunnar Blumenstock, Katrin Elisabeth Giel, Florian Junne, Stephan Zipfel. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 24.04.2020.)

Background: Overriding the differentiation blockage in acute myeloid leukemia (AML) is the most successful mode-of-action in leukemia therapy - now curing the vast majority of patients with acute promyelocytic leukemia (APL) using all-trans retinoic acid (ATRA)-based regimens. Similar approaches in other leukemia subtypes, such as IDH1/2-mutated AML, are under active investigation. We herein present successful release of the differentiation blockage upon treatment with the natural (-)-Δ 9 -Tetrahydrocannabinol isomer dronabinol in vitro and in vivo., Methods: Cellular maturation and differentiation were followed in two patients employing whole genome methylation profiling, proteome analyses, NGS deep sequencing and multispectral imaging flow cytometry. For functional studies lentiviral OGT knock-down in vitro and ex vivo cell models were created to evaluate proliferative, apoptotic and differentiating effects of OGT in acute leukemia., Findings: In here, we provide molecular evidence that dronbinol is capable to override the differentiation blockage of acute leukemia blasts at the state of the leukemia-initiating clone. We further identify the O-linked β-N-acetyl glucosamine (O-GlcNAc) transferase (OGT) to be crucial in this process. OGT is a master regulator enzyme adding O-GlcNAc to serine or threonine residues in a multitude of target proteins. Aberrant O-GlcNAc modification is implicated in pathologies of metabolic, neurodegenerative and autoimme diseases as well as cancers. We provide evidence that dronabinol induces transcription of OGT via epigenetic hypomethylation of the transcription start site (TSS). A lentiviral OGT-knock out approach proves the central role of OGT exerting antileukemic efficacy via a dual-mechanism of action: High concentrations of dronabinol result in induction of apoptosis, whereas lower concentrations drive cellular maturation. Most intriguingly, overriding of the differentiation blockage of acute leukemia blasts is validated in vivo following two patients treated with dronabinol., Interpretation: In conclusion, we provide evidence for overcoming the differentiation blockage in acute leukemia in subentities beyond promyelocytic and IDH1/2-mutated leukemia and thereby identify O-GlcNAcylation as a novel (drugable) field for future leukemia research., Funding: Unrestricted grant support by the IZKF Program of the Medical Faculty Tübingen (MMS) and Brigitte Schlieben-Lange Program as well as the Margarete von Wrangell Program of the Ministry of Science, Research and the Arts, Baden-Württemberg, Germany (KKS) and Athene Program of the excellence initiative University of Tübingen (KKS)., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of the study was to evaluate predictable parameters with the highest sensitivity used in the diagnosis of children septic shoulder arthritis., Methods: All children treated in our paediatric orthopaedic hospital between 2000 and 2017 with intraoperative verified septic arthritis of the shoulder were included in this retrospective study. Diagnostic procedures e.g. ultrasound, MRI, radiograph or blood samples as well as typical clinical symptoms were evaluated as predictable parameters for septic shoulder arthritis in paediatric patients. Descriptive statistics as well as sensitivity analysis were performed., Results: In all, 25 children, 20 boys and five girls, aged from eight days to 15 years, were included for further statistical analysis. All parameters included were tested for sensitivity with binomial confidence intervals (Cis) of 95%. Predictive parameters with highest sensitivity were pseudo paralysis (100%, CI 0.86 to 1.00) and C-reactive protein (CRP) (96%, CI 0.79 to 0.99) superior to temperature (52%, CI 0.3 to 0.73), white blood count (11%, CI 0.01 to 0.34), radiograph (21%, CI 0.04 to 0.50), ultrasound (71%, CI 0.47 to 0.88) or MRI (100%, CI 0.78 to 1.00)., Conclusion: The diagnosis of a septic arthritis of the shoulder in children can be challenging for the clinician and especially for the resident doctor. Clinical symptoms such as pseudo paralysis and increased CRP level must be considered as predictive markers not to delay further diagnostics and treatment., Level of Evidence: IV., (Copyright © 2020, The author(s).)

Purpose : To assess the efficacy and safety of systemic interferon alpha-2a (IFN) for refractory pseudophakic cystoid macular edema (PCME). Methods : Retrospective observational study. The primary outcome was the decrease of central retinal thickness (CRT). Secondary endpoints were the improvement of best-corrected visual acuity (BCVA) and the assessment of IFN-related side effects. Results : Twenty-four eyes of 20 patients were included. The median CRT was 513 µm (range 220-980 µm) at baseline and decreased to 190 µm (range 140-520 µm) at the last follow-up visit (p < 0.001). Reduction of CRT greater than 100 µm was observed in 22 eyes (92%). The median BCVA (logMAR) increased statistically significant from 0.5 (range 0.2-1.5) at baseline to 0.3 (0-0.8) at the last follow-up (p < 0.001). The BCVA improved in 18 eyes (75%) and remained stable in five eyes (21%). No severe treatment-related side effects occurred. Conclusion : IFN is a very effective agent for treatment of refractory PCME.

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.

Background: We evaluated a magnetic resonance (MR)-conditional high-power microwave ablation system., Methods: An ex vivo 1.5-T evaluation was conducted by varying the sequence (T1-weighted volume interpolated breath-hold examination, T1w-VIBE; T1-weighted fast low-angle shot, T1w-FLASH; T2-weighted turbo spin-echo, T2w-TSE), applicator angulation to B 0 (A-to-B 0 ), slice orientation, and encoding direction. Tip location error (TLE) and artefact diameters were measured, and influence of imaging parameters was assessed with analysis of variance and post hoc testing. Twenty-four ex vivo ablations were conducted in three bovine livers at 80 W and 120 W. Ablation durations were 5, 10, and 15 min. Ablation zones were compared for short-axis diameter (SAD), volume, and sphericity index (SI) with unpaired t test., Results: The artefact pattern was similar for all sequences. The shaft artefact (4.4 ± 2.9 mm, mean ± standard deviation) was dependent on the sequence (p = 0.012) and the A-to-B 0 (p < 0.001); the largest shaft diameter was measured with T1w-FLASH (6.3 ± 3.4 mm) and with perpendicular A-to-B 0 (6.7 ± 2.4 mm). The tip artefact (1.6 ± 0.7 mm) was dependent on A-to-B 0 (p = 0.001); TLE was -2.6 ± 1.0 mm. Ablation results at the maximum setting (15 min, 120 W) were SAD = 42.0 ± 1.41 mm; volume = 56.78 ± 3.08 cm 3 , SI = 0.68 ± 0.05. In all ablations, SI ranged 0.68-0.75 with the smallest SI at 15 min and 120 W (p = 0.048)., Conclusion: The system produced sufficiently large ablation zones and the artefact was appropriate for MR-guided interventions.

BACKGROUND This study investigated the effect of donor-dependent factors on contamination rates of conjunctival swabs of human donor eyes. MATERIAL AND METHODS From July 2015 to September 2017 a total of 1008 conjunctival swabs from 504 consecutive human donor eyes were analyzed. Cross-tabulation, chi-squared tests, and Fisher's exact tests were used to evaluate the effect of donor-dependent factors on contamination rates of conjunctival swabs. RESULTS The mean conjunctival swabs contamination rate was 28.4%. Donors with the diagnosis of carcinoma or metastases were associated with an increased conjunctival swab contamination rate [odds ratio (OR)=1.8, 95% confidence interval (CI)=1.2-2.6, p=0.007; OR=1.7, 95% CI=1.1-2.6, p=0.016; respectively]. However, the age, sex, diagnosis of diabetes mellitus, and donors who received chemotherapy did not significantly increase the conjunctival swab contamination risk. CONCLUSIONS Donors with the diagnosis of a carcinoma or metastases seemed to be predisposed to increased conjunctival swab contamination risk.

OX40 and its ligand are members of the TNF/TNF receptor superfamily, which includes various molecules influencing cellular signaling and function of both tumor and immune cells. The ability of OX40 to promote proliferation and differentiation of activated T cells fueled present attempts to modulate this immune checkpoint to reinforce antitumor immunity. While we recently found evidence for the involvement of OX40 in pathophysiology of acute myeloid leukemia including natural killer (NK) cell immunosurveillance, less is known on its role in acute lymphoblastic leukemia (ALL). In the present study, OX40 expression on ALL cells was significantly associated with positivity for the adverse risk factor BCR-ABL. In line, signaling via OX40 increased metabolic activity of primary ALL cells and resulted in release of cytokines involved in disease pathophysiology. Furthermore, interaction of ALL-expressed OX40 with its cognate ligand on NK cells stimulated ALL cell lysis. The data presented thus not only identify the yet unknown involvement of OX40/OX40L in ALL pathophysiology and NK cell immunosurveillance but also point to the necessity to thoroughly consider the consequences of modulating the OX40/OX40L molecule system beyond its effects on T cells when developing OX40-targeting approaches for cancer immunotherapy., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Early orchidopexy (OP) around the age of 1 year is recommended in boys with congenital undescended testis (UDT) worldwide since decades. Former retrospectives studies did not distinguish congenital from acquired UDT with a consecutive negative bias concerning the age at surgery., Methods: In a retrospective analysis, data of all boys who underwent OP in eight pediatric surgery institutions from 2009 to 2015 were analyzed. Congenital or acquired UDT were differentiated. Patients were categorized into 3 groups of age at surgery: (1) <12 months, (2) 12-24 months, (3) >24 months. Data of one institution were analyzed in detail: exact age of first referral, exact age at surgery, intraoperative findings., Results: Out of 4448 boys, 3270 boys had congenital UDT. In 81% (2656 cases) surgery was performed beyond the age of 1 year, in 54.4% (1780) beyond the age of 2 years. chi-Square statistics showed a higher rate of early operations in hospitals compared to outpatient services and in Germany compared to Switzerland. In 694 congenital detailed cases, median age at referral was 13 months [range 0-196], median age at surgery was 15 months [range 0-202]., Conclusion: Delayed referral is the main reason for guideline non-conform delayed surgery in UDT., Type of Study: Clinical Research paper., Level of Evidence: Level III: Treatment Study., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background During treatment with direct oral anticoagulants ( DOAC ), coagulation assessment is required before thrombolysis, surgery, and if anticoagulation reversal is evaluated. Limited data support the accuracy of DOAC -specific coagulation assays around the current safe-for-treatment threshold of 30 ng/ mL . Methods and Results In 481 samples obtained from 96 patients enrolled at a single center, DOAC concentrations were measured using Hemoclot direct thrombin inhibitor assay, Biophen direct thrombin inhibitor assay or ecarin clotting time for dabigatran, chromogenic anti-Xa assay ( AXA ) for factor Xa inhibitors (rivaroxaban, apixaban) and ultraperformance liquid chromatography-tandem mass spectrometry as reference. All dabigatran-specific assays had high sensitivity to concentrations >30 ng/ mL , but specificity was lower for Hemoclot direct thrombin inhibitor assay (78.2%) than for Biophen direct thrombin inhibitor assay (98.9%) and ecarin clotting time (94.6%). AXA provided high sensitivity and specificity for rivaroxaban, but low sensitivity for apixaban (73.8%; concentrations up to 82 ng/ mL were misclassified as <30 ng/ mL ). If no DOAC -specific calibration for AXA is available, results 2-fold above the upper limit of normal indicate relevant rivaroxaban concentrations. For apixaban, all elevated results should raise suspicion of relevant anticoagulation. Conclusions DOAC -specific tests differ considerably in diagnostic performance for concentrations close to the currently accepted safe-for-treatment threshold. Compared with Biophen direct thrombin inhibitor assay and ecarin clotting time, limited specificity of Hemoclot direct thrombin inhibitor assay poses a high risk of unnecessary anticoagulation reversal or treatment delays in patients on dabigatran. While AXA accurately detected rivaroxaban, the impact of low apixaban levels on the assay was weak. Hence, AXA results need to be interpreted with extreme caution when used to assess hemostatic function in patients on apixaban. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Unique identifiers: NCT 02371044, NCT 02371070.

This study assessed the influence of donor, environmental, and logistical factors on the contamination rates of the conjunctival swabs and organ culture media of human donor eyes.In total, 1008 conjunctival swabs and 418 organ culture media samples from 504 consecutive human donor eyes were analyzed. Cross-tabulation, chi-squared tests, and Fisher's exact tests were used to assess the influence of the different factors on the contamination rates of the conjunctival swabs and organ culture media.The overall contamination rates were 28.4% for the conjunctival swabs and 1.0% for the organ culture media. A prolonged time between death and the conjunctival swab collection was associated with an increased conjunctival swab contamination rate [odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.2-3.0, P = .007]. The highest conjunctival swab contamination rate was found in the corneas procured in external institutions (outside the university hospital) (44.1%, OR = 3.6, 95%CI = 1.5-8.4, P = .003). Hospitalization times of 2 to 7 days prior to death were associated with an increased conjunctival swab contamination risk (OR = 2.6, 95%CI = 1.1-5.8, P = .021). However, the sex, age, cause of donor death, differentiation between septic and aseptic donors, differentiation between heart-beating brain-dead multiorgan donors and cadaveric donors, a warmer mean monthly temperature, and death to corneoscleral disc excision time did not significantly increase the conjunctival swab contamination risk. In addition, none of these factors affected the organ culture media contamination risk. Moreover, a positive conjunctival swab did not significantly increase the media contamination risk (P = .08). Surprisingly, the microorganisms causing media contamination were present at 50% of the amount detected on the conjunctival surface of the respective donor eye.A prolonged time between death and the conjunctival swab collection, a hospitalization time of 2 to 7 days prior to death, and corneal collection outside the university hospital seemed to be the main factors responsible for an increased conjunctival swab contamination risk. In addition, our investigation illustrated that a positive conjunctival swab is not a strong indicator for organ culture media contamination. Critical discussion is necessary regarding the validity of conjunctival swabs as prognostic parameters for organ culture media contamination.

Objectives: To study the lengths and diameters of aortic segments in healthy and diseased aortas and to assess the role of aortic elongation in Type A aortic dissection (TAD) prediction., Methods: Ectasia and aneurysm were defined by ascending aorta diameters of 45-54 mm and ≥55 mm, respectively. Computed tomography angiography studies of 256 healthy, 102 ectasia, 38 aneurysm, 17 pre-TAD and 166 TAD aortas were analysed using curved multiplanar reformats., Results: The study groups were structurally equal. The diameter of the ascending aorta was 35 mm in the control group and was larger (P < 0.001) in the pre-TAD (43 mm) and TAD (56 mm) groups. The length of the ascending aorta from the aortic annulus to the brachiocephalic trunk was 92 mm in the control group, 113 mm in the ectasia group, 120 mm in the aneurysm group and 111 mm and 118 mm in the pre-TAD and TAD groups (all P < 0.001 compared with the control group). An ascending aorta length of 120 mm was exceeded in 2% of the control group, 31% of the ectasia group, 50% of the aneurysm group, 24% of the pre-TAD group and 48% of the TAD group. The correlation between the diameter and the length of the ascending aorta was r = 0.752; therefore, both parameters must be examined separately. A score considering both parameters identified 23.5% of pre-TAD patients, significantly more than the diameter alone, and 31.4% of ectasia aortas were elongated., Conclusions: Patients with ectatic (45-54 mm diameter) and elongated (≥120 mm) ascending aortas represent a high-risk subpopulation for TAD.

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.

Purpose: Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma. In 7% of the cases it is localized at the chest wall or intrathoracically. The aim of this study was to analyze the multimodal treatment concepts and outcomes of children suffering from intrathoracic and chest wall RMS treated within three different Cooperative Soft Tissue Sarcoma (CWS) trials and one registry (Soft Tissue Sarcoma Registry, SoTiSaR)., Methods: Data of 51 patients with thoracic RMS enrolled in three different CWS trials (CWS-86, -91, -2002P) and one registry (SoTiSaR) were analyzed retrospectively. Surgery and its influence on outcome were assessed. Median follow-up was 37.5 months (0.9-152.5)., Results: Median age of the patients was 8.8 years (range 0-19 years). The 5-year overall survival rate (OS) was 57% (95%-CI 49-65) and the 5-year event-free survival rate (EFS) was 45% (38-52). Thirty-five patients had tumors located at the chest wall (EFS: 51%, 43-59), and 16 patients had intrathoracic tumors (EFS: 26%, 13-39). Seventeen patients with tumors ≤ 5 cm had a better outcome (EFS: 64%, 52-76) compared to patients with tumors larger than 5 cm (EFS: 36%, 27-45). Radiotherapy (RT) significantly improved the survival of patients with alveolar RMS compared to patients with embryonal histology (EFS: 66%, 52-80 vs. 32%, 21-43 p = 0.02). Complete tumor excision during delayed surgery was the main prognostic factor for survival (p = 0.045)., Conclusion: Thoracic RMS is a rare tumor entity. Completeness of tumor resection significantly improved survival of the 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 ).

Purpose: The purpose of this study is to analyze the combined approach of endovascular and open surgical procedures for insertion of permanent central venous catheters in children with intestinal failure and end-stage venous access., Methods: Data of 14 children (16 interventions) with intestinal failure and end-stage venous access, treated within the pediatric intestinal rehabilitation program at our institution between September 2011 and November 2016, were retrospectively reviewed. The patients underwent hybrid endovascular/open surgical approaches for insertion of central venous catheters. Access to central veins was established through endovascular intervention; catheter placement was achieved with combined interventional and surgical measures depending on the individual vascular conditions., Results: Median age at intervention was 47months (interquartile range (IQR),29-74), median time for interventions was 66min (IQR,42-111). Catheter placement was successfully achieved in all patients. The median dose of irradiation during angiography was 0.2Gy*cm 2 (IQR, 0.2-0.6), no complications occurred during or after interventions., Conclusions: Hybrid endovascular/open surgical procedures can be successfully applied for restoring or maintaining permanent central venous catheters in children with intestinal failure and end-stage venous access. These approaches are a valuable contribution in intestinal rehabilitation programs contributing to a further decrease of the need for intestinal transplantation in affected patients., Type of Study: Treatment Study., Level of Evidence: Level IV., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Acute respiratory distress syndrome (ARDS) is associated with high mortality rates. ARDS patients suffer from severe hypoxemia, and extracorporeal membrane oxygenation (ECMO) therapy may be necessary to ensure oxygenation. ARDS has various etiologies, including trauma, ischemia-reperfusion injury or infections of various origins, and the associated immunological responses may vary. To support the immunological response in this patient collective, we used intravenous IgM immunoglobulin therapy to enhance the likelihood of pulmonary recovery., Methods: ARDS patients admitted to the intensive care unit (ICU) who were placed on ECMO and treated with (IVIG group; n  = 29) or without (control group; n  = 28) intravenous IgM-enriched immunoglobulins for 3 days in the initial stages of ARDS were analyzed retrospectively., Results: The baseline characteristics did not differ between the groups, although the IVIG group showed a significantly reduced oxygenation index compared to the control group. We found no differences in the length of ICU stay or ventilation parameters. We did not find a significant difference between the groups for the extent of inflammation or for overall survival., Conclusion: We conclude that administration of IgM-enriched immunoglobulins as an additional therapy did not have a beneficial effect in patients with severe ARDS requiring ECMO support., Trial Registration: Clinical Trials: NCT02961166; retrospectively registered., Competing Interests: The ethics committee of the University Hospital Tuebingen (Eberhard-Karls Universität Tübingen; Ethik-Kommission; Gartenstraße 47;72074 Tübingen, Germany) approved the study. The project number is 370/2017/BO2. Informed consent was not required from the patients involved into this retrospective analysis. This proceeding was approved by the local ethics committee (project number 370/2017/BO2) of Eberhard Karls University Tuebingen since extraction of pseudonymous medical records provides structured data and therefore legally permits evaluation of the data for research.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Purpose: To assess the long-term results and complications of scleral-fixated posterior chamber intraocular lenses (PC IOLs) with the knotless Z-suture technique., Setting: University Eye Hospital, Tübingen, Germany., Design: Retrospective case series., Methods: Records of consecutive patients who had implantation of scleral-fixated PC IOLs with the knotless Z-suture technique with a minimum follow-up of 3 years were reviewed., Results: Sixty-six eyes of 62 patients were included. The mean preoperative corrected distance visual acuity (CDVA) was 0.71 logarithm of the minimum angle of resolution (logMAR) ± 0.58 (SD). The mean CDVA was 0.67 ± 0.54 logMAR (P = .257; n = 66) after 3 years, 0.73 ± 0.55 logMAR (P = .399; n = 60) after 5 years, 0.8 ± 0.68 logMAR (P = .348; n = 30) after 8 years, and 1.09 ± 0.76 logMAR (P = .069; n = 13) after 10 years. Failure because of suture breakage was observed in 11 eyes (16.7%) after a mean of 7.5 years. Kaplan-Meier time-to-event analysis showed a 40% failure probability after 10 years. Traumatic aphakia was the only risk factor for failure (odds ratio 4.1; 95% confidence interval, 1.0-18.3; P = .049). Complications included retinal detachment (15%), cystoid macular edema (9%), increased intraocular pressure requiring surgical intervention (7.6%), corneal edema (4.5%), and posterior iris-chafing syndrome with microhyphema (3%)., Conclusions: Implantation of scleral-fixated PC IOLs using the knotless Z-suture was a safe technique resulting in good visual outcomes. The long-term success of the procedure was dependent on the material properties of the suture., (Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

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.