Supplementary orthopaedic screening for children and adolescents to prevent permanent skeletal deformities - protocol for the "OrthoKids" study.

BACKGROUND: Skeletal deformities (SD) in children and adolescents can lead to arthritic conditions, impairment of quality of life, and high treatment costs in the long term. However, comprehensive data on the prevalence of SDs in children and adolescents are limited and it remains therefore unclear whether there is a healthcare gap. "OrthoKids" is a project that addresses this evidence gap by implementing an orthopaedic screening for children and adolescents that supplements existing detection examinations within statutory standard care in Germany. OBJECTIVE: To detect SDs so that they can be treated as needed at an early stage. METHODS: The implementation of the supplementary orthopaedic screening will be evaluated through an exploratory cohort study that is set up in the German state Baden-Wuerttemberg. 20,000 children and adolescents aged 10 to 14 years will be recruited as a prospective cohort. A retrospective control cohort will be formed based on claims data provided by two cooperating statutory health insurances (SHIs). Participating children and adolescents receive a one-time orthopaedic screening. If at least one SD is diagnosed, treatment will be provided as part of the statutory standard care. Within the scope of the project, a follow-up examination will be performed after one year. An IT-platform will complement the study. The primary outcome measure is the point prevalence of scoliosis, genu varum/valgum, hip dysplasia, and flat feet. Secondary outcome measures are (i) the point prevalence of further less common SDs, (ii) health-related quality of life (HRQoL), (iii) sports ability based on activity (physical/athletic), physical constraints, and (sports) injuries, as well as (iv) monetary consequences of the orthopaedic screenings' implementation. Implementation determinants will be evaluated, too. DISCUSSION: If the supplementary orthopaedic screening proves to be viable, it could be considered as a supplementary examination for children and adolescents within the frame of SHI in Germany. This could relieve the burden of disease among children and adolescents with SDs. In addition, it could disburden SHIs in the medium to long term. TRIAL REGISTRATION: The OrthoKids study was registered in the German Clinical Trials Registry (Deutsches Register Klinischer Studien (DRKS)) on 26th July 2022 under the number 00029057.

Relevant factors in the diagnosis of concomitant osteomyelitis in pediatric hip septic arthritis. A series of 41 cases treated by hip arthroscopy.

INTRODUCTION: Septic arthritis of the hip can appear isolated or concomitant with pelvic osteomyelitis. Delay in the diagnosis of a concomitant osteomyelitis increases the number of required surgeries and of possible complications. PURPOSE: This study aims to establish relevant factors in the diagnosis of concomitant osteomyelitis in cases with septic arthritis of the hip among paediatric patients. METHODS: The data were collected between 2005 and 2020. 41 pediatric patients with suspicion of septic arthritis of the hip joint, treated arthroscopically, were included. The following diagnostic test parameters were collected: ultrasound, MRI, X-Rays, blood samples, temperature, and incapacity to bear weight. The data were analysed with the sensitive analysis method using descriptive statistic. RESULTS: 41 patients were analyzed, with an average age of 6.04 y (7 months to 14 years), of which ten patients (24.39%) presented concomitant osteomyelitis. 6 out of ten patients needed secondary surgery. Regarding age, concomitant osteomyelitis was most common in the age group 4-14 years old. Average number of days of clinical symptoms before admission was 6.2 days. 36/41 cases showed CRP values higher than 2 mg/dl. 9/10 cases with concomitant osteomyelitis showed a CRP > 2 mg/dl, with an average value of 8.9 mg/dl. 22/41 patients underwent an MRI, of which nine cases presented a concomitant osteomyelitis. The probability of a child to have septic arthritis of the hip with adjacent osteomyelitis was analysed through a score based on four factors: impossibility to bear weight and/or hip pain in children in the non-walking age category, CRP > 2 mg/dl, age older than > 4 y, symptoms longer than 4 days. CONCLUSIONS: Children at the age of walking, with incapacity to bear weight, presenting symptoms longer than 4 days and a CRP > 2 mg/dl, should receive an MRI before surgery to exclude adjacent osteomyelitis. LEVEL OF EVIDENCE: IV.

Early hyperdopaminergic state following sub-thalamic nucleus deep brain stimulation in Parkinson disease.

BACKGROUND: Hyperdopaminergic state (HS), especially impulse control behaviors (ICBs), are not rare in Parkinson's disease (PD). Controversial data regarding HS prevalence one year following sub-thalamic nucleus deep brain stimulation (STN-DBS) are reported. OBJECTIVE: Our objectives were to describe early postoperative HS (PoOHS) including ICBs, hypomania and psychotic symptoms during the first 3 months following STN-DBS (V1) and their prognosis at 1 year (V2). METHODS: This descriptive study included 24 PD patients treated successively with bilateral STN-DBS between 2017 and 2019. The primary endpoint was prevalence of PoOHS at V1 according to the Ardouin Scale of Behaviour in Parkinson's Disease. RESULTS: Prior to STN-DBS (V0), 25% patients had HS (only ICBs) whereas at V1 (during the 3 first months), 10 patients (41.7%) had one or several HS (P=0.22) (de novo in 29.2%): 7 (29.2%) ICBs, 4 (16.7%) hypomanic mood, 1 (4.7%) psychotic symptoms. At V2, all V0 and V1 HS had disappeared, while 1 patient (4.2%) presented de novo HS (P<0.01). No correlation was found between the occurrence of PoOHS at V1 and any V0 data. Higher levodopa equivalent dose of dopamine agonists at V1 was correlated with ICB at V1 (P=0.04). CONCLUSION: We found that early PoOHS are frequent in PD after STN-DBS, mostly de novo, with ICBs and hypomania being the most frequent. Despite a good prognosis of PoOHS at one year, our work emphasizes the importance of both a cautious adjustment of dopamine agonist doses and a close non-motor monitoring pre- and post-STN-DBS in PD.

Feasibility of changing for a rechargeable constant current neurostimulator in Parkinson's disease.

BACKGROUND: Little is known about outcome and settings adaptations after replacement of constant-voltage non-rechargeable implantable pulse generator (CV-nrIPG) by constant-current rechargeable IPG (CC-rIPG). OBJECTIVE: To determine the feasibility and safety of replacing a CV-nrIPG by a CC-rIPG in Parkinson's disease (PD) and the subsequent outcome. METHODS: A prospective cohort of thirty PD patients, whose CV-nrIPG was replaced by a CC-rIPG in University Hospital of Lyon between January 2017 and December 2018 (rIPG group) and 39 PD patients, who underwent the replacement of a CV-nrIPG by the same device in 2016 (nrIPG group), were enrolled in this study. Three surgeons performed the operations. Duration of hospitalization for the replacement as well as the number of in or outpatient visits during the first 3 months after the surgery were recorded. In the rIPG group, we compared preoperative DBS settings and the theoretical amplitude estimated using Ohm's law to the amplitude used at the end of follow-up. We assessed patients' and clinicians' opinion on the patient global functioning after the replacement using Clinical Global Impression score. RESULTS: Duration of hospitalization (P=0.47) and need for additional hospitalizations (P=0.73) or consultations (P=0.71) to adapt DBS parameters did not differ between the two groups. Neurological condition (CGI score) was considered as unchanged by both patients and neurologists. Final amplitude of stimulation using CC-rIPG was not predicted by Ohm's law in most cases. CONCLUSIONS: Replacing CV-nrIPG by CC-rIPG is safe and well tolerated but require neurological expertise to set the new parameters of stimulation.

[Multimodal treatment of hepatocellular carcinoma]. / Multimodale Therapie des hepatozellulären Karzinoms.

Hepatocellular carcinoma (HCC) is one of the most common and most lethal cancers worldwide. Treatment of patients with HCC is complicated by the underlying liver disease in up to 80% of all cases. Interdisciplinary and multimodal treatment strategies are essential for successful therapy. Established therapies include surgical interventions (liver transplantation, resection), local ablative therapies (e.g., microwave or radiofrequency ablation), and locoregional therapies (e.g., transarterial chemoembolization [TACE] and selective internal radiotherapy [SIRT/TARE]). Moreover, there are emerging opportunities for systemic therapies. While the multityrosine kinase inhibitor sorafenib has been the only agent approved for patients with unresectable HCC for almost a decade, there are now additional systemic treatment options including the tyrosine kinase inhibitors (TKIs) lenvatinib, regorafenib, and cabozantinib as well as the VEGF-receptor inhibitor ramucirumab. To date, immune checkpoint inhibitor monotherapies have failed to show an overall survival benefit, but according to recent data combined immunotherapy/VEGF inhibition has shown superior activity in first-line treatment compared with sorafenib. The advent of numerous novel systemic agents offers a variety of combination opportunities. Combinations of systemic agents with locoregional treatments in palliative and potentially curative settings are currently being investigated. Today, treatment of patients with HCC is more challenging than ever owing to the multiple therapeutic options available, demanding strict multidisciplinary cooperation in the treatment selection process. There is an urgent need for clinical studies in order to further optimize the therapy sequence and to identify efficacious mono- and combination therapies.

[Management of benign liver tumors]. / Management benigner Lebertumoren.

Benign liver tumors form a heterogeneous group. The most frequent forms include simple cysts, hemangiomas, focal nodular hyperplasia and hepatocellular adenomas. They are often incidentally detected during routine sonography. The diagnosis of a liver tumor not uncommonly causes anxiety and insecurity in those affected, which is why a rapid and reliable diagnostic procedure should be carried out. Because some tumors, particularly hepatocellular adenomas, are of prognostic relevance due to the potential risk of malignant transformation, a correct classification should always be strived for. The type and extent of diagnostic clarification depend on the clinical and patient-related risk factors. This article describes the most important benign space-occupying lesions. The etiology, clinical manifestations and diagnostics as well as possible necessary treatment measures are presented.

Immunophenotyping of cerebrospinal fluid cells in ischaemic stroke.

BACKGROUND AND PURPOSE: Post-ischaemic immune cell invasion into the brain is well characterized in animal stroke models and contributes to neuronal damage. Therefore, it represents a promising therapeutic target. Cerebrospinal fluid (CSF) is easily accessible and may reflect cellular events within the parenchyma. However, comprehensive studies on CSF immune cells in patients with stroke are lacking. METHODS: In a retrospective cohort study, we performed extensive immune-cell profiling in CSF and peripheral blood of patients with acute ischaemic stroke and healthy controls. In patients with stroke, infarct size was quantified on follow-up imaging. RESULTS: Overall, 90 patients with ischaemic stroke and 22 controls were included in our study. After stroke, the total protein was increased (537.3 vs. 353.2 mg/L, P = 0.008) and the mean total white cell count was slightly but non-significantly elevated (1.76 vs. 0.50 cells/µL, P = 0.059). Proportions of CSF lymphocytes, monocytes and granulocytes and their respective subsets did not differ between patients with stroke and controls. In addition, there were no associations between proportions of major leukocyte subsets in CSF and the time from symptom onset to CSF sampling, infarct size or infarct localization. CONCLUSIONS: Ischaemic stroke induces only a very slight increase of CSF immune cells without changes in the composition of immune cell subsets, thus indicating that parenchymal inflammation is not sufficiently reflected in the CSF. Our findings suggest that CSF is not a major invasion route for immune cells and that CSF cell analyses are not suitable as biomarkers to guide future immune therapies for stroke.

[Hip dysplasia-new and proven methods]. / Hüftdysplasie ­ Neues und Bewährtes.

BACKGROUND: Hip dysplasia is one of the most common disorders in paediatric orthopedics. With the development of ultrasound techniques treatment has changed, and earlier diagnosis and treatment is possible. So, for more than 20 years diagnosis and treatment has been focused on ultrasound. Many papers reporting new diagnostic techniques like MRI have been published. Arthroscopic reduction is a new surgical procedure. However, established surgical procedures continue to play an important role in the treatment. CURRENT TREATMENT: This paper presents new and established diagnostic techniques, conservative and surgical treatment options. Unfortunately, due to the great number of publications, not all aspects could be taken into account. In particular, we describe the diagnostic and treatment standards in German-speaking countries based on ultrasound hip screening. However, also international aspects of diagnostic and treatment options have been included.

[Early and late complications and their management in slipped capital femoral epiphysis]. / Früh- und Spätkomplikationen sowie deren Management bei der ECF.

BACKGROUND: Slipped capital femoral epiphysis (SCFE) remains a challenge for the treating surgeon. First of all, SCFE should be diagnosed as early as possible. The earlier the diagnosis is made in adolescents, the lower the slip angle will be. Mild slips show more favourable long-term courses than moderate and severe SCFE. COMPLICATIONS: With increasing slip angle, the risk of complications increases. The complications of SCFE are diverse, the most severe of which are avascular necrosis (AVN) and chondrolysis. AVN is more common in surgically treated than in non-operatively managed patients and unstable SCFE bears the highest risk of AVN. THERAPY: Adequate treatment of AVN is still controversial. For surgical treatments, variable rates of AVN have been reported. There is a wide spectrum of surgeries for treating AVN, from hip joint-preserving techniques to total hip replacement. In central Europe there is wide consensus in favour of treating the contralateral side, but this is not without complications. Surgical treatment with in-situ pinning must be carried out with great care to take into consideration the morphology of the femoral head and not to perforate it. It should always be ensured that no osteosynthesis material penetrates the hip joint.

[Specific cases of slipped capital femoral epiphysis : Endocrinopathies, hormone therapy and other rare causes]. / Besondere Fälle der Epiphyseolysis capitis femoris : Endokrinopathien, Hormontherapie und andere seltene Ursachen.

In slipped capital femoral epiphysis (SCFE) atypical causes can be found in about 5% of cases. The patients' age differs from the typical age of SCFE patients of between age 10 and 16. There are numerous causes of atypical SCFE: different endocrine disorders, sequelae of chronic renal failure and effects of radiation and chemotherapy on the proximal femoral physis. The diagnostic and therapeutic procedures must be expanded to the search for and treatment of endocrinological disorders. Orthopaedic treatment follows the principles applied to patients with idiopathic SCFE. However, the specific treatment modalities which arise from different patient ages and bone qualities are taken into account.

[Psychosocial burden and strains in geriatric nursing: comparison of nursing personnel with and without migration background]. / Psychosoziale Belastungen und Beanspruchungen in der Altenpflege: Vergleich zwischen Pflegekräften mit und ohne Migrationshintergrund.

BACKGROUND: Because of demographic changes the nursing care sector is faced with a lack of qualified employees in the medium and long term. The shortage in the work force is caused by high workloads and unfavorable working conditions. In response to this shortage, there have been attempts to recruit qualified nursing staff from abroad and also to improve the integration of people with a migration background living in Germany into the job market. METHODOLOGY: Based on a quantitative cross-sectional study of 366 nurses, the psychosocial burden and strains among employees with a migration background (n = 112) and without a migration background (n = 254) were examined. For this purpose, 13 scales of the German version of the Copenhagen Psychosocial Questionnaire (COPSOQ) were used for the assessment of psychosocial factors at work. The results were compared with professional group-specific reference values (geriatric care) from the COPSOQ database. RESULTS: The comparison of nursing staff with and without a migration background revealed that the emotional demands, work-privacy conflict and role conflicts factors received a significantly better rating among nursing staff with a migration background, while development opportunities were rated worse by this population group. The surveyed nursing staff exhibited higher stress values compared to the COPSOQ reference group in almost all scales. CONCLUSION: Nursing staff with a migration background need to be supported with respect to development opportunities. Suitable education and training measures may offer adequate career perspectives and may encourage employees to stay in their jobs.

The impact of the revolution in hepatitis C treatment on hepatocellular carcinoma.

Hepatitis C infection represents a global health problem affecting ∼200 million chronically infected patients worldwide. Owing to the development of a fibrogenic and inflammatory micromilieu in the liver, hepatitis C virus (HCV)-infected patients are at a high risk of developing fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The advent of direct-acting antiviral agents (DAAs), however, has spurred a revolution in the treatment of HCV patients with sustained viral response (SVR) rates exceeding 90% in real-life settings. Recent clinical trials suggest that these novel treatments will not only alter the epidemiology of HCV infection but also the incidence of HCV-induced complications including hepatic decompensation, liver transplantation and hepatocarcinogenesis. Here, we summarize data from clinical trials carried out in HCV patients with compensated and decompensated cirrhosis and analyze the impact of viral clearance on HCC development and treatment. Finally, we review and discuss current and future treatment options of HCV patients with HCC in pre- and post-transplantation settings.

[Apophyseal Avulsions of the Hip Region in Adolescents]. / Avulsionsverletzungen der Hüftregion des Jugendlichen.

BACKGROUND: In daily practice apophyseal avulsions of sportive adolescents are frequently being diagnosed with a time delay and treated heterogeneously. GOAL: Using the most actual literature and the own experience the current diagnostic and therapeutic strategies are put into perspective with regards of the needs of the adolescent athlete. MATERIAL AND METHODS: The apophyseal lesions of the hip area in adolescence are separated in those at the pelvis and those at the proximal femur. They are reviewed according to its frequency and relevance using the most updated literature. The treatment methods reported focus on the degree of dislocation and level of sports activity. RESULTS: The most frequent apophyseal avulsion of the pelvis is the avulsion of the tuber ischiadicum, followed by the inferior anterior iliac spine the superior anterior iliac spine and the apophysis of the ilium. The most affected structure at the proximal femur is the lesser trochanter, lesions of the greater trochanter are rare. The cause of injury is a specific acute contracture of the muscle inserting at the affected apophysis during different sporting activities. The treatment of pelvic apophyseal injuries is surgical only in cases with considerable fragment dislocation and in high level athletes. At the femoral side the patients are treated almost always conservatively. DISCUSSION: Despite of modern and efficient osteosynthetic techniques the treatment of avulsion lesions of the hip region is mainly conservative, even in athletes. By applying consequent diagnostic and therapeutic principles the development of pseudarthroses and heteropic ossifications can be minimised.

[Sternal fracture in growing children : A rare and often overlooked fracture? Documentation of four cases]. / Sternumfraktur im Wachstumsalter : Eine seltene oder häufig übersehene Fraktur? Dokumentation von 4 Fällen.

BACKGROUND: Sternal fractures in childhood are rare. The aim of the study was to investigate the accident mechanism, the detection of radiological and sonographical criteria and consideration of associated injuries. METHOD: In the period from January 2010 to December 2012 all inpatients and outpatients with sternal fractures were recorded according to the documentation. RESULTS: A total of 4 children aged 5-14 years with a sternal fracture were treated in 2 years, 2 children were hospitalized for pain management and 2 remained in outpatient care. CONCLUSION: Isolated sternal fractures in childhood are often due to typical age-related traumatic incidents. Ultrasonography is a useful diagnostic tool for fracture detection and radiography is the method of choice for visualization of the extent of the dislocation.

Conservatism and novelty in the genetic architecture of adaptation in Heliconius butterflies.

Understanding the genetic architecture of adaptive traits has been at the centre of modern evolutionary biology since Fisher; however, evaluating how the genetic architecture of ecologically important traits influences their diversification has been hampered by the scarcity of empirical data. Now, high-throughput genomics facilitates the detailed exploration of variation in the genome-to-phenotype map among closely related taxa. Here, we investigate the evolution of wing pattern diversity in Heliconius, a clade of neotropical butterflies that have undergone an adaptive radiation for wing-pattern mimicry and are influenced by distinct selection regimes. Using crosses between natural wing-pattern variants, we used genome-wide restriction site-associated DNA (RAD) genotyping, traditional linkage mapping and multivariate image analysis to study the evolution of the architecture of adaptive variation in two closely related species: Heliconius hecale and H. ismenius. We implemented a new morphometric procedure for the analysis of whole-wing pattern variation, which allows visualising spatial heatmaps of genotype-to-phenotype association for each quantitative trait locus separately. We used the H. melpomene reference genome to fine-map variation for each major wing-patterning region uncovered, evaluated the role of candidate genes and compared genetic architectures across the genus. Our results show that, although the loci responding to mimicry selection are highly conserved between species, their effect size and phenotypic action vary throughout the clade. Multilocus architecture is ancestral and maintained across species under directional selection, whereas the single-locus (supergene) inheritance controlling polymorphism in H. numata appears to have evolved only once. Nevertheless, the conservatism in the wing-patterning toolkit found throughout the genus does not appear to constrain phenotypic evolution towards local adaptive optima.

Musculoskeletal pain: a new algorithm for differential diagnosis of a cardinal symptom in pediatrics.

Musculoskeletal pain (MSP) is a common childhood complaint associated with multiple differential diagnoses, including cancer. Considering the expanding spectrum of diagnostics, evaluat-ing a young patient with MSP is a challenge today, particularly for non-specialists in a primary care setting. Since childhood cancer is rare and most cardinal symptoms mimic rather non-serious diseases, misdiagnosis is not uncommon, but of significant prognostic relevance. To build the appropriate bridge between primary and secon-dary care for a child presenting with MSP, thereby preventing treatment delay and longterm sequelae, initial evaluation should follow a comprehensive, multidisciplinary, systematic and stepwise approach, which unites the patient's individual anamnestic, psychosocial, and clinical charac-teristics. After a systematic review of the literature, we generated multidisciplinarily quality-assured recommendations for efficient, rational and cost-effective primary care assessment of pediatric MSP. The algorithm promotes the identification and structured interpretation of the patient's individual clinical clues. It should serve the primary care physician to recognize when further intervention, rather than reassurance and follow-up, is needed using the minimum amount of testing to make an appropriate, prompt diagnosis in the clinical situation "child presenting with MSP". A German version of this algorithm has been published in the Guideline-Portal of The Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF) in November 2013.

A role for nuclear NF-kappaB in B-cell-specific demethylation of the Igkappa locus.

The immunoglobulin kappa gene is specifically demethylated during B-cell maturation in a process which utilizes discrete cis-acting modules such as the intronic kappa enhancer element and the matrix attachment region (MAR). While any MAR sequence is sufficient for this reaction, mutation analysis indicates that tissue specificity is mediated by kappaB binding sequences within the kappa intronic enhancer. The plasmacytoma cell line S107 lacks kappaB binding activity and fails to demethylate the kappa locus. However, B-cell specific demethylation is restored by the introduction of an active kappaB binding protein gene relB. This represents the first demonstration of a trans-acting factor involved in cell-type-specific demethylation, and suggests that the same protein-DNA recognition system used for transcription may also contribute to the earlier developmental events that bring about activation of the kappa locus.