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Background: Borna disease virus 1 (BoDV-1) causes rare human infections within endemic regions in southern and eastern Germany. The infections reported to date have been linked to severe courses of encephalitis with high mortality and mostly irreversible symptoms. Whether BoDV-1 could act as a trigger for other neurological conditions, is, however, incompletely understood. Objectives and methods: In this study, we addressed the question of whether the presentation of a clinically isolated syndrome (CIS) or of multiple sclerosis (MS) might be associated with a milder course of BoDV-1 infections. Serum samples of 100 patients with CIS or MS diagnosed at a tertiary neurological care center within an endemic region in southern Germany and of 50 control patients suffering from headache were retrospectively tested for BoDV-1 infections. Results: In none of the tested sera, confirmed positive results of anti-BoDV-1-IgG antibodies were retrieved. Our results support the conclusion that human BoDV-1 infections primarily lead to severe encephalitis with high mortality. [ABSTRACT FROM AUTHOR]

Purpose: The epidemiology of HIV-infected individuals on the Medical Intensive Care Units (MICU) has changed after profound progress in treatment of AIDS-defining illnesses and anti-retroviral therapy (ART). Changes of MICU utilization of Hepatitis C (HCV) patients following roll-out of direct-acting antivirals (DAA) are yet to evaluate. Methods: We performed a retrospective study on all patients with HIV, HIV/HCV and HCV admitted to the MICU of University Hospital Bonn 2014–2019. We assessed sociodemographic data, available clinical data from HIV patients (CDC stage, CD4 + lymphocyte cell count, HIV-1-RNA, ART) and HCV patients (HCV-RNA, stage of liver cirrhosis, treatment history) and outcome. Results: 237 patients (46 HIV, 22 HIV/HCV, 169 HCV; 168 male, median age 51.3 years) with 325 MICU admissions were included. Admission criteria for HIV patients were infections (39.7% AIDS-associated, 23.8% with controlled HIV-infection) and cardiopulmonary diseases (14.3%). HIV/HCV coinfected patients had infections in controlled/uncontrolled HIV-infection (46.4%), cardiopulmonary diseases and intoxication/drug abuse (17.9% each). Reasons for HCV-mono-infected patients were infections (24.4%), sequelae of liver disease (20.9%), intoxication/drug abuse (18.4%) and cardiopulmonary diseases (15%). 60 patients deceased; most important risk factor was need for mechanical ventilation. The number of HCV-patients admitted to MICU with chronic active disease and sequelae of liver disease decreased while the proportion of patients with completed DAA-treatment increased. Conclusion: Infections remain the most important reason for MICU admission in patients with HIV and/or HCV infection while non-AIDS related conditions increased. DAA roll-out has a beneficial effect on liver-associated morbidity in HCV patients admitted to MICU. [ABSTRACT FROM AUTHOR]

Human Papilloma Virus (HPV)-associated oropharyngeal squamous cell cancer (OPSCC) represents an OPSCC subgroup with an overall good prognosis with a rising incidence in Western countries. Multiple lines of evidence suggest that HPV-associated tumors are not a homogeneous tumor entity, underlining the need for accurate prognostic biomarkers. In this retrospective, multi-institutional study involving 906 patients from four centers and one database, we developed a deep learning algorithm (OPSCCnet), to analyze standard H&E stains for the calculation of a patient-level score associated with prognosis, comparing it to combined HPV-DNA and p16-status. When comparing OPSCCnet to HPV-status, the algorithm showed a good overall performance with a mean area under the receiver operator curve (AUROC) = 0.83 (95% CI = 0.77-0.9) for the test cohort (n = 639), which could be increased to AUROC = 0.88 by filtering cases using a fixed threshold on the variance of the probability of the HPV-positive class - a potential surrogate marker of HPV-heterogeneity. OPSCCnet could be used as a screening tool, outperforming gold standard HPV testing (OPSCCnet: five-year survival rate: 96% [95% CI = 90–100%]; HPV testing: five-year survival rate: 80% [95% CI = 71–90%]). This could be confirmed using a multivariate analysis of a three-tier threshold (OPSCCnet: high HR = 0.15 [95% CI = 0.05–0.44], intermediate HR = 0.58 [95% CI = 0.34–0.98] p = 0.043, Cox proportional hazards model, n = 211; HPV testing: HR = 0.29 [95% CI = 0.15–0.54] p < 0.001, Cox proportional hazards model, n = 211). Collectively, our findings indicate that by analyzing standard gigapixel hematoxylin and eosin (H&E) histological whole-slide images, OPSCCnet demonstrated superior performance over p16/HPV-DNA testing in various clinical scenarios, particularly in accurately stratifying these patients. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the incidence and risk factors of preoperative DVT in elderly patients with intertrochanteric fracture of the femur and determine the optimal preoperative time. Methods: Electronic medical records of 358 patients over 60 years of age with intertrochanteric fractures from May 1, 2016, to May 1, 2019, were retrospectively analyzed. The preoperative group was divided into DVT and non-DVT. Univariate analysis was used for preliminary comparison, and multivariate logistic regression analysis was used to identify independent risk factors associated with DVT development. ROC curve was drawn to analyze the specificity and sensitivity of risk factors for DVT diagnosis. The diagnostic value of the model was analyzed by the ROC curve of multivariable combined diagnosis. Results: A total of 358 patients who met the criteria were enrolled. The total prevalence of DVT before surgery was 8.38%. Multivariate logistic regression analysis showed that smoking status, preoperative time, albumin (ALB), D-dimer level, diabetes mellitus, and hypertension were independent risk factors for preoperative DVT. Preoperative time has the best sensitivity and specificity for diagnosing the occurrence of preoperative DVT. The ROC curve analysis model of multivariable combined diagnosis has a better diagnostic value. Conclusions: In this study, elderly patients with intertrochanteric femur fracture had a higher incidence of deep vein thrombosis before surgery. Early identification of DVT-related risk factors may contribute to individualized risk assessment and preventing adverse outcomes in patients with intertrochanteric fractures. [ABSTRACT FROM AUTHOR]

Purpose: Isolated clavicle fractures (CF) rarely show complications, but their influence in the thorax trauma of the seriously injured still remains unclear. Some authors associate CF with a higher degree of chest injuries; therefore, the clavicle is meant to be a gatekeeper of the thorax. Methods: A retrospective analysis of the TraumaRegister DGU® (project 2017-10) was carried out involving the years 2009–2016 (ISS ≥ 16, primary admission to a trauma center). Cohort formation: unilateral and bilateral flail chest injuries (FC), respectively, with and without a concomitant CF. Results: 73,141 patients (26.5% female) met the inclusion criteria and 12,348 had flail chest injuries (FC; 20.0% CF; 67.7% monolateral FC), 25,425 other rib fractures (17.7% CF), and 35,368 had no rib fractures (6.5% CF). On average, monolateral FC patients were 56.0 ± 17.9 years old and bilateral FC patients were 57.7 ± 19 years old. The ISS in unilateral and bilateral FC were 29.1 ± 11.7 and 42.2 ± 12.9 points, respectively. FC with a CF occurred more frequently with bicycle and motorbike injuries in monolateral FC and pedestrians in bilateral FC injuries and less frequently due to falls. Patients with a CF in addition to a FC had longer hospital and ICU stays, underwent artificially respiration for longer periods, and died less often than patients without a CF. The effects were highly significant in bilateral FC. CF indicates more relevant concomitant injuries of the lung, scapula, and spinal column. Moreover, CF was associated with more injuries of the extremities in monolateral CF. Conclusion: Due to the relevance of a concomitant CF fracture in FC, diagnostics should focus on finding CFs or rule them out. Combined costoclavicular injuries are associated with a significantly higher degree of thoracic injuries and longer hospital stays. [ABSTRACT FROM AUTHOR]

Purpose: In patients with pyogenic spondylodiscitis, surgery is considered the treatment of choice to conduct proper debridement, stabilise the spine and avoid extended bed rest, which in turn is a risk factor for complications such as deep vein thrombosis and pulmonary embolism. Methods: We conducted a retrospective clinical study with analysis of a group of 99 patients who had undergone treatment for pyogenic discitis at our institution between June 2012 and August 2017. Included parameters were age, sex, disease pattern, the presence of deep vein thrombosis, resuscitation, in-hospital mortality, present anticoagulation, preexisting comorbidities, tobacco abuse, body mass index, microbiological germ detection and laboratory results. Results: Among the analysed cohort, 12% of the treated patients for pyogenic spondylodiscitis suffered from a radiologically confirmed pulmonary embolism. Coronary heart disease (p < 0.01), female sex (p < 0.01), anticoagulation at admission (p < 0.01) and non-O blood type (p < 0.001) were associated with development of pulmonary embolism. Pulmonary embolism was significantly associated with resuscitation (p < 0.005) and deep vein thrombosis (p < 0.001). Neurosurgery was not associated with increased risk for pulmonary embolism compared to conservative-treated patients (p > 0.05). Conclusion: Surgery for pyogenic spondylodiscitis was not associated with an elevated risk of pulmonary embolism in our analysis. However, we describe several risk factors for pulmonary embolism in this vulnerable cohort. Prospective studies are necessary to improve prevention and postoperative management in patients with pyogenic spondylodiscitis. [ABSTRACT FROM AUTHOR]

Purpose: Concomitant chest injury is known to negatively affect bone metabolism and fracture healing, whereas traumatic brain injury (TBI) appears to have positive effects on bone metabolism. Osteogenesis can also be influenced by the timing of fracture stabilization. We aimed to identify how chest injuries, TBI and fracture stabilization strategy influences the incidence of non-union. Methods: Patients with long bone fractures of the lower extremities who had been treated between 2004 and 2014 were retrospectively analysed. Non-union was defined as fracture healing not occurring in the expected time period and in which neither progression of healing nor successful union is expected without intervention. Diverse clinical and radiological parameters were statistically analysed using the Statistical Package for the Social Sciences (SPSS). Results: The total number of operations before consolidation was an independent predictor (odds ratio [OR] = 6.416, p < 0.001) for the development of non-union in patients with long bone fractures. More specifically, patients treated according to the damage control orthopaedics (DCO) principle had a significantly higher risk of developing a non-union than patients treated according to the early total care (ETC) principle (OR = 7.878, p = 0.005). Concomitant chest injury and TBI could not be identified as influencing factors for non-union development. Conclusion: Our results indicate that the number of operations performed in patients with long bone fractures should be kept as low as possible and that the indication for and the timing of DCO treatment should be meticulously noted to minimize the risk of non-union development. [ABSTRACT FROM AUTHOR]

Purpose: Novel oral anticoagulants are increasingly replacing vitamin K antagonists in the prophylaxis of thromboembolism as they are associated with lower incidence of spontaneous intracerebral hematomas and they do not require drug level monitoring. However, management dilemmas are apparent in patients on novel oral anticoagulants who have developed intracerebral hematomas after traumatic brain injury, since clinical experience with their reversal strategies is limited. Methods: We retrospectively studied 90 patients with traumatic intracerebral hematomas undergoing treatment at the surgical intensive care unit of the BG University Clinic Bergmannsheil in Bochum between 2015 and 2018. We analyzed potential prognostic factors for their radiological (expansion of intracerebral hematoma) and clinical (patients' outcome) course, in particular the role of novel oral anticoagulants. Results: 71.1% of patients were male; mean age was 67.3 years. Hematoma's expansion occurred in 35.9% of our patients, whereas 62.2% of our cohort showed a favorable outcome, defined as Glasgow Outcome Scale 4 and 5. Intake of novel oral anticoagulants was associated with a higher rate of hematoma's expansion compared to patients on vitamin K antagonists (p = 0.05) or to patients with normal coagulation status (p = 0.002). A younger age (p < 0.001) was identified as the sole independent prognostic factor for a more favorable outcome, after excluding our cases, who underwent a cardiopulmonary resuscitation. Conclusions: Our data showed a higher rate of hematoma's expansion in patients with traumatic intracerebral hematomas on novel oral anticoagulants vs. vitamin K antagonists and recommend the consideration of prophylactic reversal of the novel oral anticoagulants at admission. Larger prospective trials are warranted to conclude whether the current specific reversal protocols are safe and effective. [ABSTRACT FROM AUTHOR]

Summary: Knowledge about risk factors of mortality after hip fracture might encourage prevention and further improvements in care. This study identified patient risk factors as well as hospital and regional characteristics associated with a decreased risk. Variation of mortality was largest on patient level and modest on hospital and regional level. Introduction: Among numerous studies analyzing mortality as worst consequence after hip fracture, the majority focused on patient level and fewer on hospital and regional level. Comprehensive knowledge about contributing factors on all levels might help to reveal relevant inequalities, which would encourage prevention and further improvements in care. This study aimed at investigating variation of mortality after hip fracture on patient, hospital, and regional level in Germany. Methods: We performed a retrospective cohort study on hip fracture patients aged 65 and older using statutory health insurance claims data from Jan 2009 through Dec. 2012 and additional information from the Federal Statistical Office Germany. Regions were classified based on two-digit postal code. We applied a multilevel Cox proportional hazard model with random intercepts on hospital and regional level to investigate the risk factors for mortality within 6 and 12 months after hip fracture. Results: The dataset contained information on 123,119 hip fracture patients in 1014 hospitals in 95 German regions. Within 6/12 months, 20.9%/27.6% of the patients died. On patient level, male sex, increasing age, increased pre-fracture care level, and increasing comorbidity were associated with an increased hazard of mortality. Hospitals with increasing hip fracture volume or with orthogeriatric co-management and regions with increased population density were associated with a decreased hazard. Variation was largest on patient level and rather modest on hospital and regional level. Conclusions: The identification of patient-related risk factors enables prognosticating mortality after hip fracture. After adjusting for those, variation seemed to be attributable rather to hospitals than to regions. [ABSTRACT FROM AUTHOR]

Purpose: To determine the impact of depression, epilepsy and drug abuse during pregnancy on delivery and fetal outcome. Due to the worldwide increasing prevalence of neurological and psychiatric diseases and drug abuse, the number of affected pregnant women is increasing.Methods: A large-scale retrospective case-control analysis of pregnancies affected by depression, epilepsy or drug abuse with and without medication was conducted in two German perinatal centres between 2013 and 2017. The case group consisted of 706 pregnant women who had a diagnosis of depression, epilepsy or drug abuse vs. 12,574 pregnant women without neuropsychiatric diagnosis (control group). The analysis included the rate of intrauterine growth restriction, birth weight and length, neonatal head circumference.Results: Significant differences in the subgroups were found in the parameters intrauterine growth restriction, birth weight, length and head circumference. Women with epilepsy were affected less often than women with depression and substance abuse. Major differences were found in the group of women with substance abuse. Negative associations were found within the non-pharmacologically managed disease group itself compared to women exposed to medication.Conclusion: The present results demonstrated a negative association between maternal neurological or psychiatric disease and pregnancy outcome in the examined parameters. However, the non-pharmacologically treated maternal disease was identified as a risk factor itself. [ABSTRACT FROM AUTHOR]

Background: Hantavirus infections are endemic worldwide, and its incidence in Europe has been steadily increasing. In Western Europe, hantavirus infections are typically caused by Puumala hantavirus and cause nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome. Up to now, there is only little data about the course of acute NE in children, but it has been suggested that hantavirus infections take a lighter course in children when compared to adults. We performed a retrospective analysis of adults and children diagnosed with acute NE in two counties in South-Western Germany to investigate if there are differences in the course of the disease. Methods: We reviewed the medical records of 295 adults and 22 children with acute NE regarding clinical presentation, laboratory findings, complications and outcome. Results: Acute kidney injury (AKI) and thrombocytopenia occurred at similar frequencies and severity in both groups. Sudden onset of fever and back/loin pain were two of the three most common symptoms in both adults and children. However, adults presented more frequently with arthralgia and visual disturbances, whereas abdominal pain and nausea/vomiting could be detected more often in children. No significant differences were found in the incidence of complications (haemodialysis, long-term outcome of kidney function, length of hospital stay). Conclusions: The clinical course of acute NE was similar in adults and children with high frequency of AKI as well as thrombocytopenia, but with full recovery of all patients. [ABSTRACT FROM AUTHOR]

Purpose: We have recently shown that uncomplicated phlegmonous appendicitis is characterized by independent inflammatory patterns based on significant eosinophilia in children aged 7-17 years. However, clinical decision-making based on inflammatory values is not easy, especially due to the dynamics of inflammation over time. The present study was performed to evaluate the basic distinguishability of the inflammatory entities by laboratory values over time based on an extended patient number with children aged 0-17 years.Methods: All patients aged 0-17 years, who underwent appendectomy from January 2008 until June 2016, were retrospectively reviewed. Special attention was paid to cellular subpopulations within full blood counts within compartments of time (onset of symptoms - blood sampling): 0-12 , > 12-24 , > 24-36 , > 36-48 , > 48-72 , > 72 h.Results: 1041 appendectomies were included in the study. The inflammatory course in patients with complicated appendicitis (n = 369) was characterized by continuously increased mean leukocytes, neutrophil and monocyte counts compared with patients with phlegmonous appendicitis (n = 489). In contrast, continuous relative eosinophilia was found in uncomplicated appendicitis within the inflammatory process. In cases of negative appendectomies (n = 183), again, distinct independent inflammatory patterns were found.Conclusion: Eosinophilia is a constant and independent pattern in children with uncomplicated appendicitis, which, thus, can be distinguished throughout the inflammatory process. [ABSTRACT FROM AUTHOR]

Background: Malignant ascites often develops in patients with ovarian cancer, but there is a lack of more detailed characterization of the different histological subtypes.Methods: Ascites specimens from patients with ovarian cancer who were treated at Bayreuth Hospital from 2006 to 2015, with follow-up until December 2016, were reevaluated retrospectively.Results: A total of 191 women (mean age 64 years, range 48-79) were included, of whom 180 (94.2%) had carcinoma, three (1.6%) had malignant mixed müllerian tumors (MMMTs), four (2.1%) had sex cord-stromal tumors (SCSTs), three (1.6%) had germ cell tumors (GCTs), and one (0.5%) had a sarcoma. The carcinoma group comprised 134 (70.1%) patients with high-grade serous papillary ovarian cancer, 17 (8.9%) with low-grade serous papillary ovarian cancer, 10 (5.3%) with mucinous carcinomas, nine (4.7%) with endometrioid carcinomas, six (3.1%) with clear cell carcinomas, and four (2.1%) with neuroendocrine tumors. The latter group consisted of two patients with mixed neuroendocrine-nonneuroendocrine tumors (MiNENs), one with only a small cell carcinoma (SCCO), and one with a mucinous carcinoid. The noncarcinomatous group of eight patients (4.2%) included three (1.6%) with Sertoli-Leydig cell tumor and mature cystic teratoma (MCT), one (0.5%) with a granulosa cell tumor, and one with a leiomyosarcoma. A statistically significant difference in the proportion of patients with malignant ascites was observed, at 17.7% (3/17) in those with low-grade serous papillary ovarian cancer and 91.8% (123/134) in those with high-grade serous papillary ovarian carcinomas. In both patients with MiNEN, the glandular tumor cell component was found in the ascites. Tumor cells were found in the ascitic fluid in 50% (5/10) of patients with mucinous ovarian carcinomas, 16.7% (1/6) of those with clear cell carcinomas, and 33.3% (1/3) of those with MMMTs. The two patients (2/3; 66.7%) with neoplastic squamous cell components in MCT and the only patient with a granulosa cell tumor in the SCST group (1/4; 25%) had malignant cell populations in the ascites, whereas patients with endometrioid cell carcinoma and leiomyosarcoma lacked tumor cells in the ascites. The malignant ascites was detected at the initial diagnosis in all 138 (100%) patients with ovarian neoplasms.Conclusions: High-grade serous papillary ovarian cancer was the main histological subtype most frequently found in ascites fluid in this series. The significant difference (P < 0.00001) in the malignancy rate in comparison with low-grade serous papillary carcinoma confirms the histological distinction between the two entities. Initial evidence of ovarian cancer in ascites fluid allows correct primary diagnosis in cytology specimens and is important for staging and prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Dysplasia of the hip is a well known cause of secondary osteoarthritis of the hip. The triple pelvic osteotomy (TPO), according to the technique described by Toennis and Kalchschmidt, is a well established procedure to address dysplasia of the hip joint. Non-unions after triple pelvic osteotomies are rare and can occur at each of these osteotomies. The literature is lacking in studies investigating larger group of patients with non-unions after triple pelvic osteotomy. The aim of this study is to evaluate risk factors leading to a non-union after triple pelvic osteotomy.Methods: A total of 53 patients with a non-union after triple pelvic osteotomy were included in this retrospective case-control. In addition, we identified a cohort of randomly selected patients undergoing hardware removal after triple pelvic osteotomy ("union" group) but had not developed non-union as the control group. This control group underwent the same procedure by the same group of surgeons in the same time period. The variables obtained from the review of the two groups were analyzed using appropriate statistical methods including Bivariable Analysis (p < 0.005) and Multivariable logistic regression analysis (p < 0.015).Results: We identified a total of 53 patients out of the 3269 who had undergone TPO and had developed a non-union. The control group consisted of 117 patients who did not experience a non-union. Bivariable analysis of basic demographic characteristics demonstrated that gender, BMI, smoking, preoperative CE angle and degree of surgical correction did not differ significantly between the groups. There was a statistically significant (p < 0.05) difference between age (31.5 ± 9.4 vs. 27.5 ± 9.0 in the non-union and union groups, respectively; p = < 0.001) and postoperative CE angle (34.4 ± 5.0 vs. 32.8 ± 3.5 in the non-union and union groups, respectively; p = 0.02). Multivariable analysis demonstrated that an age over 30 was significantly associated with non-union (p = 0.01, OR 2.6, 95% CI 1.3-5.3).Conclusion: Non-unions after TPO are rare. A higher age and higher degree of surgical correction might be associated risk factors for developing a non-union. Furthermore, smoking, obesity and previous hip surgeries might also contribute to developing a non-union after triple pelvic osteotomy. [ABSTRACT FROM AUTHOR]

Purpose: Escherichia coli urine isolates from patients presenting to the emergency department at a German tertiary care hospital were retrospectively analyzed from January 2015-March 2017 to determine antibiotic resistance patterns and patient risk factors for resistance.Methods: Uncomplicated urinary tract infection (UTI) was defined as UTI in the otherwise healthy patient without relevant co-morbidities and complications. Patients were assumed to have UTI if diagnosis was made by the attending physician with conclusive dipstick results. For subgroup analysis, only patients with symptoms suggestive for UTI documented in their records were included.Results: 228 patients with a UTI diagnosed by the attending physician with E. coli isolated in urine culture were included. 154/228 patients had documented symptomatic UTI, 57/154 had uncomplicated infection, 76/154 patients had cystitis, and 124/154 were female. Resistance rates of uncomplicated UTI in symptomatic patients were: ciprofloxacin 10.5%, cotrimoxazole 15.8%, amoxicillin/clavulanic acid 5.3%, nitrofurantoin 0% (CLSI MICs). Previous hospitalization in the last 3 months (including patients living in a long-term care facility) was significantly correlated with resistance to ciprofloxacin, cotrimoxazole and amoxicillin/clav. Previous hospitalization was a strong predictor of resistance to ciprofloxacin and cotrimoxazole in multivariate analysis also. Other risk factors correlated with resistance were hematological malignancy (for cotrimoxazole) and renal transplantation (for ciprofloxacin).Conclusions: Cotrimoxazole is still an alternative for treating uncomplicated cystitis. Previous hospitalization in the last 3 months was a strong predictor of resistance to cotrimoxazole and ciprofloxacin. Other risk factors which might help guide empirical therapy are hematological malignancy and renal transplantation. [ABSTRACT FROM AUTHOR]

We assessed the dynamics in the prevalence of children with congenital heart disease (CHD) and Down syndrome in Germany with regard to phenotype, severity, and gender. Data from patients with CHD and Down syndrome born between 1980 and 2014 were analyzed, who are registered with the German National Register for Congenital Heart Defects. One thousand six hundred eighteen CHD patients with Down syndrome were identified. The prevalence of children born with both Down syndrome and CHD was constant from 2005 to 2009 but increased from 2010 to 2014. Regarding CHD groups, complex and simple lesions have become more equal since 2005. The number of simple lesions with shunt has a peak prevalence in the period of 2010-2014. Atrioventricular septal defect was the most common CHD phenotype, but temporal changes were found within the group of CHD phenotypes over the observation period.Conclusion: Our findings suggest a growing number of CHD and Down syndrome, which may be the result of improved medical management and progress in educational, social, and financial support. This development is noteworthy as it adds new aspects to present discussions in the media and political settings. What is known: • Congenital heart disease is regarded to be the most important clinical phenomenon in children with Down syndrome, due to its significant impact on morbidity and mortality. • New developments in prenatal diagnostic and therapy management of congenital heart disease continue to influence the number of patients diagnosed with congenital heart disease and Down syndrome. What is New: • This study provides essential data giving the first overview of the dynamics in the prevalence of congenital heart disease and Down syndrome over an extended length of time up to 2015 in a large patient cohort, taking recent developments into account. • Our data suggest a growing prevalence of congenital heart disease and Down syndrome, which may be the result of improved medical management for Down syndrome patients and progress in educational, social, and financial support for their families; this development is noteworthy as it adds new aspects to the present discussion in the media and political settings. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to evaluate the current state of treatment in traumatic anterior shoulder dislocation in Germany and to detect changes over the last 12 years. Methods: Seven hundred ninety-six trauma and/or orthopaedic departments were found in the German hospital directory 2012. The websites of each department were searched for the email address of the responsible shoulder surgeon (if applicable) or the head of the department. Seven hundred forty-six email addresses were found, and emails with the request to participate in an online survey were sent in January 2013. Six hundred seventy-five emails probably reached the correct addressee. Seventy-one emails were rejected, and no contact could be made. One-hundred ninety-one (28 %) participated in the study. The data were compared to similar data from a survey on shoulder dislocation performed in the same department and published in 2001. Results: After the first-time traumatic shoulder dislocation in patients aged younger than 30 years participating in sports, 14 % of the participants would prefer conservative treatment, 83 % arthroscopic, and 3 % open surgery. When surgery was indicated, arthroscopic Bankart repair was the treatment of choice for 93 % of the participants. In 2001, 27 % had indicated conservative treatment after the first-time shoulder dislocation in active patients younger than 30 years. When surgery was indicated, 66 % had performed arthroscopic and 34 % open stabilization. For the standard arthroscopic Bankart repair without concomitant injuries, 41 % of the participants use two and 54 % three suture anchors. Knotless anchors were preferred by 72 %. In the case of glenoid bone loss greater than 25 %, only 46 % perform a procedure for glenoid bone augmentation. Fifteen percent of the participants always recommended immobilization in external rotation after traumatic first-time shoulder dislocation. Conclusions: The majority of participants recommend arthroscopic Bankart repair with two or three suture anchors in young persons with the first-time dislocations. Compared to 2001 less recommend conservative treatment, complex "open" surgical procedures are no longer used. The knowledge that a Bankart procedure likely fails in significant glenoid bone loss is not implemented in the clinical practice. Thus, there is a need to educate surgeons on this topic. [ABSTRACT FROM AUTHOR]

Unlabelled: The aim of this study was to characterize the phenotype and treatment of young patients (manifestation <30 years) with diabetes of mitochondrial origin (DMO), based on the German/Austrian DPV (Diabetes Patienten Verlaufsdokumentation) registry. Only 13 (0.02 %) of all patients with diabetes in this cohort were identified with DMO, mainly due to the Kearns-Sayre (n = 5), Pearson (n = 3), or mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome (n = 2). The onset of DMO (14.2, interquartile range (IQR) 7.1-16 years) was later than diabetes onset in individuals with T1D but earlier than in T2D. At manifestation, patients exhibited a mild elevation of blood glucose concentrations (251, IQR 178-299 mg/dl) without ketoacidosis. They had lower body mass index (BMI) values (-1.39 ± 0.28 kg/m(2)) than peers with T1D or T2D (p < 0.0001) and higher triglycerides (211, IQR 134-574 mg/dl) than in T1D (p = 0.04) while there was a high rate of dyslipidemia (86 %). Insulin requirements (0.58, IQR 0.37-0.90 U/kg/d) were between T1D and T2D while glucometabolic control (glycated hemoglobin A1c (HbA1c) 7.4 ± 0.52 %) in DMO was comparable to age-matched T2D and stable over a 5-year follow-up.Conclusion: Primary mitochondrial disorders are a rare cause of juvenile diabetes and likely to be underdiagnosed. As there is clinical overlap with T1D and T2D, dyslipidemia and low body weight may help to identify further DMO cases.What Is Known: • In adults diabetes of mitochondrial origin (DMO) is a rare cause of non-autoimmune diabetes, affecting about 0.8 % of diabetes cases. • Common features are a maternal family history of diabetes, hearing loss and neurological abnormalities. What is New: • In our juvenile cohort 0.02 % of diabetes patients (age < 30 years) were affected by DMO, while Kearns Sayre, MELAS and Pearson syndrome were the most frequent entities. • Juvenile DMO patients exhibited dyslipidemia, higher triglycerides and a lower BMI than peers with T1D or T2D, while some patients also showed retinal changes. [ABSTRACT FROM AUTHOR]

Purpose: Animal and human studies suggest that vitamin D regulates functions of the reproductive system. Vitamin D deficiency is prevalent in women of reproductive age. Vitamin D status has been associated with in vitro fertilisation outcome, features of polycystic ovarian syndrome (PCOS) and endometriosis. The aims of our study were to investigate the prevalence of vitamin D deficiency of infertile women living in central Germany, to identify risk factors for vitamin D deficiency and to specify seasonal variations of vitamin D status.Methods: This was a retrospective cohort study at an academic tertiary care centre (N = 113) and an Outpatient Centre for Reproductive Medicine (N = 193) of women presenting for infertility treatment. The statistical evaluation was descriptive and explorative. Possible risk factors associated with an increased risk for vitamin D deficiency were assessed using multiple logistic regression models. Variables with p value less than 0.05 were further assessed in a multivariable logistic regression model.Results: Overall, 98.2 % of patients at centre 1 and 81.3 % of women with impaired fertility at centre 2 had deficient or insufficient vitamin D levels. Overweight BMI and limited exposure to sun (winter, spring and autumn trimester) were associated with an increased risk of vitamin D deficiency. Vitamin D levels did not vary according to age or infertility associated disorders (e.g. endometriosis, PCOS).Conclusion: The rate of vitamin D deficiency among women with impaired fertility is alarming. Prospective studies are pressingly needed to confirm a causal relationship and to investigate the potential therapeutic benefits of vitamin D supplementation in this population. [ABSTRACT FROM AUTHOR]

Background: Steroid-resistant nephrotic syndrome (SRNS) is still regarded as a serious disease although treatment with cyclosporine (CSA) has improved outcome. However, the duration of treatment in responders is unclear, and treatment of patients with genetic causes is a matter of debate. Methods: Thirty-six patients with SRNS were studied retrospectively. Median age at presentation was 3.2 (range, 0.06-15.0) and median follow-up 15.5 years (range, 1.8-27.7), respectively; 23 (64 %) had focal segmental glomerulosclerosis (FSGS) on biopsy. In 33/36 patients (92 %), genetic testing was performed for at least three most common genes known to be mutated in SRNS. Results: Nineteen patients (53 %), especially those with minimal change nephrotic syndrome (MCNS) at initial biopsy ( p < 0.002), entered complete remission with CSA monotherapy, including one patient with compound heterozygous NPHS1 and dominant ACTN4 mutation, respectively. Ten patients entered partial remission (28 %, all FSGS), including two with NPHS2 mutations. Seven patients (six FSGS, one MCNS) did not respond to treatment. In 15 of 19 responders to CSA, treatment was stopped after a median of 3.1 years (range, 0.5-14) and no further relapses occurred in 11/15 (73 %) patients with median follow-up of 9.7 years. Conclusions: CSA monotherapy is effective in SRNS. Discontinuation of CSA is possible in many patients with complete remission. [ABSTRACT FROM AUTHOR]

Introduction: Intoxications involving prescription opioids are a major public health problem in many countries. When taken with opioids, alcohol can enhance the effects of opioids, particularly in the central nervous system. However, data quantifying the impact of alcohol involvement in opioid-related intoxications are limited.Methods: Using claims data from the German Pharmacoepidemiological Research Database (GePaRD), we conducted a retrospective cohort study based on users of high-potency opioid (HPO) analgesics during the years 2005-2009. HPO use was classified as extended-release, immediate-release or both. We calculated incidence rates (IRs) for opioid intoxications or related events as well as adjusted IR ratios (aIRR) comparing HPO-treated patients with alcohol-related disorders (ARDs) to those without ARDs overall and within each HPO category.Results: During the study period, 308,268 HPO users were identified with an overall IR of 340.4 per 100,000 person-years [95 % confidence interval (CI) 325.5-355.7]. The risk was highest when patients received concomitant treatment with extended- and immediate-release HPOs (IR 1093.8; 95 % CI 904.6-1310.9). ARDs increased the risk during HPO use by a factor of 1.7 and the highest aIRR was seen when comparing patients simultaneously exposed to extended- and immediate-release HPOs with ARDs to those without ARD also after excluding patients with potential improper/non-medical HPO use.Conclusions: Physicians should be aware of these elevated risks in HPO patients with ARDs. Active patient education by healthcare providers regarding the risk of opioid intoxications or related events due to alcohol in conjunction with HPOs is warranted. [ABSTRACT FROM AUTHOR]

Study Design:Retrospective study.Objectives:This study was implemented to detect risk factors for the developing of heterotopic ossifications (HOs) in spinal cord injury (SCI) patients.Setting:This study was conducted in Murnau, Germany.Methods:All patients from 2008-2012 with acute SCI were routinely examined by ultrasound of the hips every 2 weeks. The sub group of SCI patients suffering of HO of the hips were extracted and the incidence of developing an HO was calculated. Parameters like age, level of injury, ASIA Impairment Scale (AIS), duration time of accident until diagnosis of HO, Brooker stage, localization of HO (magnetic resonance imaging (MRI)) and symptoms like thrombosis, emboli, decrease of range of motion (ROM), dermal symptoms, swelling, increase in D-Dimere level, were evaluated. Also accompanying injuries of the brain, lung and extremities were recorded.Results:From January 2008 until January 2012, 575 patients with an acute and traumatic SCI were treated in our Department. During this period 32 HOs were detected in the muscles surrounding the hip. In 10 cases a single side and in 22 cases both sides were affected. A total of 26 patients were detected showing up a Brooker 0, two patients Brooker 1, and five patients a Brooker stage >2. The adductor muscles showed an edema in 19 cases and the quadriceps muscles were affected in 15 cases. 26% of all SCI patients showed AIS A status, but in patients who developed HO, 64% have had an AIS A status. 19% of patients with a HO were AIS B and 9.5% showed an AIS C and D. Regarding the level of injury the distribution of patients suffering of HO was comparable to the distribution of SCI patients without HO. In mean HO were detected 9 weeks after SCI and no new HO were found after the 22nd (n=1) week of injury. Clinical symptoms such as swelling, pain, redness or decrease in ROM or increase in D-Dimere levels were seen in 24 cases. Accompanying injuries like brain injury and lung contusions were found in 83% of patients developing HO. The incidence of thrombosis was comparable to SCI patients without HO. One patient with no accompanying injuries or clinical symptoms was detected by routinely performed ultrasound.Conclusions:The risk of developing HO in patients with traumatic SCI is 5.5% but increases when accompanying injuries of the brain and lung occur. Patients with a neurological status of AIS A must also be quoted as risk patients. When considering the described risk factors and clinical symptoms, 96% of all HO can be detected. [ABSTRACT FROM AUTHOR]

Introduction: Superficial siderosis is presumably a consequence of recurrent bleeding into the subarachnoid space. The objective of this study was to assess the prevalence of superficial siderosis after singular, aneurysmal subarachnoid hemorrhage (SAH) in the long term. Methods: We retrospectively identified all patients who presented with a singular, acute, aneurysmal SAH at our institution between 2010 and 2013 and in whom a magnetic resonance imaging (MRI) including T2*-weighted imaging was available at least 4 months after the acute bleeding event. MRI scans were judged concerning the presence and distribution of superficial siderosis. Influence of clinical data, Fisher grade, localization, and cause of SAH as well as the impact of neurosurgical interventions on the occurrence of superficial siderosis was tested. Results: Seventy-two patients with a total of 117 MRIs were included. Mean delay between SAH and the last available MRI was 47.4 months (range 4-129). SAH was Fisher grade 1 in 2 cases, 2 in 4 cases, 3 in 10 cases, and 4 in 56 cases. Superficial siderosis was detected in 39 patients (54.2 %). In all patients with more than one MRI scan, localization and distribution of superficial siderosis did not change over time. Older age ( p = 0.02) and higher degree of SAH ( p = 0.03) were significantly associated with the development of superficial siderosis. Conclusion: Superficial siderosis develops in approximately half of patients after singular, aneurysmal SAH and might be more common in patients with an older age and a greater amount of blood. However, additional factors must play a role in whether a patient is prone to develop superficial siderosis or not. [ABSTRACT FROM AUTHOR]

Background: To investigate the long-term neurodevelopmental outcome in children after hemolytic uremic syndrome (HUS) and to compare outcome dependent on central nervous system (CNS) involvement during HUS. Methods: A single-center retrospective cohort of 47 children was examined at a median age of 10.6 (range 6-16.9) years and a median follow-up of 7.8 (range 0.4-15.3) years after having had HUS. Intellectual performance was assessed with the German version of the Wechsler Intelligence Scale 4th version and neuromotor performance with the Zurich Neuromotor Assessment (ZNA). The occurrence of neurological symptoms during the acute phase of HUS was evaluated retrospectively. Results: Mean IQ of the whole study population fell within the normal range (median full scale IQ 104, range 54-127). Neuromotor performance was significantly poorer in the domains 'adaptive fine,' 'gross motor,' 'static balance' (all p < 0.05) and 'associated movements' ( p < 0.001); only the 'pure motor' domain was within the normal reference range. Neurological findings occurred in 16/47 patients (34 %) during acute HUS. Neurodevelopmental outcome was not significantly different between children with or without CNS involvement. Conclusions: Our follow-up of children after HUS showed a favorable cognitive outcome. However, neuromotor outcome was impaired in all study participants. Neurological impairment during acute HUS was not predictive of outcome. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to analyze the neurological involvement and outcome in pediatric patients with hemolytic uremic syndrome (HUS) during the 2011 epidemic caused by Escherichia coli O104:H4. Methods: Clinical data and data from magnetic resonance imaging (MRI) scans and electroencephalography (EEG) during the acute phase of the disease and during follow-up at 3 and 6 months were analyzed in 50 patients. Twenty-five of these patients underwent neuropsychological testing (WISC IV) during follow-up. Results: Neurological involvement (stupor or coma, seizures, visual disturbances, paresis, myocloni) was initially observed in 14/50 (28 %) patients. One patient died. EEG abnormalities were more frequent in patients with neurological involvement than in those without (12/14 vs. 13/25, respectively). Cranial MRI scans were analyzed in nine patients with neurological involvement, of whom five showed abnormal findings. At the 3- and 6-month follow-ups, EEG abnormalities were found in 14/40 (35 %) and 7/36 (19 %) patients, respectively, whereas 28/42 (67 %) and 17/39 (44 %) patients, respectively, complained about on-going reduced performance. Neuropsychological testing showed a slightly lower global intelligence quotient in patients with neurological involvement versus those without (113.4 ± 2.8 vs. 119.4 ± 1.8, respectively). Conclusions: Neurological involvement was frequent in our cohort. Accordingly, the incidence of pathological EEG findings was high, even in patients without clinical signs of neurological involvement. Nevertheless, major neurological sequelae were rare, and neuropsychological outcome was favorable after 6 months. [ABSTRACT FROM AUTHOR]

Aim: During a large outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 in Germany 2011 caused by Fenugreek sprouts, 56 cases of haemolytic uraemic syndrome (HUS) and 124 cases of STEC were notified in Hesse. Almost 50 % of these cases were linked to six clusters. Timely identification of vehicles was warranted to halt the outbreak. Subject and methods: A retrospective cohort study was conducted. The description of this cluster investigation exemplarily addresses short-comings and obstacles to the prompt identification of outbreak sources. Results: The only uncooked food item which could explain all cases was a salad containing radish sprouts. A second cluster probably related to the consumption of radish sprouts was discovered, raising the count to 4 HUS and 3 STEC-cases for both clusters. The backtracking of the radish sprouts shortly after the source farm had been publicly mentioned, as probably implicated in the outbreak, provided an early support of this hypothesis. Conclusion: In contrast to the Fenugreek sprouts mentioned with other clusters, Radish sprouts were identified as the most probable source of the two clusters, indicating cross contamination at production. This investigation revealed several hitherto known but still not sufficiently addressed deficits such as a need for earlier mobilization of additional laboratory capacities, better documentation and sharing of information, better use of modern communication systems and data sources, clear responsibilities, early indication if support is needed, structured and intensified retrieval of possible common exposures, more resources to follow all traces at short notice. [ABSTRACT FROM AUTHOR]

Study design:A retrospective study reporting specific complications of certain skin flaps for treating pressure ulcers.Objectives:To describe the rate and type of complications after pressure ulcer surgery in patients with spinal cord injury.Setting:Germany, Rheinland Pfalz.Methods:We collected data from 352 patients treated with 421 skin flaps to determine the rate and type of complications of each skin flap used.Results:In this study, we analyzed the results of 421 skin flaps in 352 patients with a total of 657 pressure ulcers from January 2006 to December 2010. Our patients had ischial, pelvic, sacral, trochanteric and lower extremity ulcers. Ischial ulcers were most common, followed by sacral and trochanteric ulcers. There were 87 complications in 421 flaps, which was an overall rate of 21%. Suture line dehiscence was the most common complication with 27 cases (31%), followed by 22 cases of infection (25.2%), 17 cases of hematoma (19.5%), 12 cases of partial necrosis (13.7%) and 9 cases of total flap necrosis (10.3%).Conclusion:Pressure ulcers in spinal cord-injured patients are very common and difficult and expensive to treat. The high rate of complications and the associated costs suggest the importance of evaluating the efficacy of treatment options. Conservative procedures have been standardized, but there still has been limited success in establishing guidelines on how to manage complications arising from flap surgery. Our extensive documentation of flap plastics will be useful managing complications after the surgical treatment of pressure ulcers in spinal cord-injured patients. [ABSTRACT FROM AUTHOR]

Background: Anaemia is a frequently diagnosed condition which can develop as a consequence of numerous factors, including infectious diseases (IDs). Travelling, especially in sub-/tropical regions, leads to an elevated risk of contracting IDs. The aim of our study was to assess the epidemiological significance of IDs in inducing anaemia among a large cohort of returned travellers. Methods: This was a cross-sectional study in which data on 17,009 returned travellers aged 20–49 years who consulted the travel medicine clinic of the University of Munich between 1999 and 2011 were retrieved and analysed. Results: Of the returned travellers, 8.3 % (6.0 % of males/10.4 % of females) were diagnosed with anaemia. The prevalence of anaemia was significantly elevated among patients of African (21.4/28.3 %) and Asian (11.6/15.7 %) origin. When the study population was restricted to the 14,636 travellers of German origin, 7.1 % of the returned travellers (4.6/9.6 %) were diagnosed with anaemia. The prevalence was significantly elevated among patients who travelled for >30 days (5.7 of males/10.6 % of females) and for male travellers visiting friends and relatives (7.7 %). However, these correlations were confounded by malaria. The prevalence of anaemia was significantly elevated only among returned travellers diagnosed with malaria (36.1 of males/26.9 % of females) and with symptomatic intestinal Entamoeba histolytica infections (30.0/33.3 %). Conclusion: Following the exclusion of confounding by malaria from the statistical analysis, the prevalence of anaemia was found to be significantly elevated among patients of African and Asian origin, and among patients of German origin who had travelled for >30 days, it could be mainly attributable to chronic, long-lasting causes. Although more than 550 travel-associated IDs were assessed in our study, only symptomatic intestinal Entamoeba histolytica infections and, to an even larger extent, malaria were determined to be of epidemiological significance for inducing anaemia among travellers. [ABSTRACT FROM AUTHOR]

Purpose: Before elective operations, particularly orthopaedic surgery, national guidelines in Germany recommend testing for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) to reduce the risk of transmission of the virus through a needlestick or cutting injury. Such testing is expensive. The number of new and unknown diagnoses of viral infections that can be detected by routine screening has not yet been evaluated. Methods: The aim of our department of orthopaedic surgery is to screen every adult patient listed for an operation for HBV, HCV and HIV. We retrospectively analysed the number of operations in this single centre from 2001 to 2010, correlated this number with the total number of screens and calculated the number of newly diagnosed infections. An additional cost:benefit ratio was calculated. Results: A total of 20,869 operations were performed by the department between 2001 and 2010. After exclusion of all interventions in children and all patients who had multiple operations, 15,482 patients remained. Test results were found for 10,011 of these patients during this period (screening rate 65 %). Of those screened, in only four cases (0.4 ‰) was a previously unknown infection detected. Conclusions: Two-thirds of the patients included in our study actually underwent screening; this rate was lower than expected. The incidence of newly detected infections was low, putting the benefit of a routine preoperative screening for HBV, HCV and HIV into question. From an economic point of view the low detection rate is a strong argument in favour of omitting routine preoperative screening. Screening only those patients with risk factors may be as safe as screening every patient and would help reduce costs. [ABSTRACT FROM AUTHOR]

Varicella (chickenpox) has traditionally been regarded as a benign, inevitable disease of childhood. In Germany information on the clinical and economic impact of varicella is limited. This study assessed the health risks and economic burden of varicella with a special focus on the relevance of complications as a cost driver. We used an age-structured, dynamic infectious disease model for the spread of infection in the German population combined with a module modeling the course of disease and medical management in the case of infection. Model input data were derived mainly from a retrospective epidemiological survey of 1,334 varicella cases in Germany. This survey included detailed information on outpatient care, complications, inpatient treatment, and sick leave. In the base case analysis the model predicted approx. 740,000 varicella cases per year. Some 40,000 experienced complications, of which 5,700 required inpatient care. Total annual costs for payers, i.e., sickness funds, was 78 million euro, the largest portion of which was due to the significant coverage of work loss costs incurred by parents caring for their sick children ("Kinderpflegekrankengeld"). For the society total annual costs were 187.5 million euro, 82% of which was indirect. Complications account for disproportionate 32% (25%) of cost from the payers' (societal) perspective. However, the vast majority of costs are due to uncomplicated cases. The burden of varicella in Germany is thus significant, not only in terms of morbidity but also from an economic viewpoint. Vaccination strategies targeting groups with high risk of complications might fail to reduce the considerable burden of varicella substantially. Routine vaccination against varicella would be a meaningful measure to reduce the burden of VZV infection in Germany. [ABSTRACT FROM AUTHOR]