Pulsed electromagnetic fields after arthroscopic treatment for osteochondral defects of the talus: double-blind randomized controlled multicenter trial

Background. Osteochondral talar defects usually affect athletic patients. The primary surgical treatment consists of arthroscopic debridement and microfracturing. Although this is mostly successful, early sport resumption is difficult to achieve, and it can take up to one year to obtain clinical improvement. Pulsed electromagnetic fields (PEMFs) may be effective for talar defects after arthroscopic treatment by promoting tissue healing, suppressing inflammation, and relieving pain. We hypothesize that PEMF-treatment compared to sham-treatment after arthroscopy will lead to earlier resumption of sports, and aim at 25% increase in patients that resume sports. Methods/Design. A prospective, double-blind, randomized, placebo-controlled trial (RCT) will be conducted in five centers throughout the Netherlands and Belgium. 68 patients will be randomized to either active PEMF-treatment or sham-treatment for 60 days, four hours daily. They will be followed-up for one year. The combined primary outcome measures are (a) the percentage of patients that resume and maintain sports, and (b) the time to resumption of sports, defined by the Ankle Activity Score. Secondary outcome measures include resumption of work, subjective and objective scoring systems (American Orthopaedic Foot and Ankle Society Ankle-Hindfoot Scale, Foot Ankle Outcome Score, Numeric Rating Scales of pain and satisfaction, EuroQol-5D), and computed tomography. Time to resumption of sports will be analyzed using Kaplan-Meier curves and log-rank tests. Discussion. This trial will provide level-1 evidence on the effectiveness of PEMFs in the management of osteochondral ankle lesions after arthroscopy. Trial registration. Netherlands Trial Register (NTR1636)

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

A novel Alzheimer disease locus located near the gene encoding tau protein

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted

The global retinoblastoma outcome study : a prospective, cluster-based analysis of 4064 patients from 149 countries

DATA SHARING : The study data will become available online once all analyses are complete.BACKGROUND : Retinoblastoma is the most common intraocular cancer worldwide. There is some evidence to suggest that major differences exist in treatment outcomes for children with retinoblastoma from different regions, but these differences have not been assessed on a global scale. We aimed to report 3-year outcomes for children with retinoblastoma globally and to investigate factors associated with survival. METHODS : We did a prospective cluster-based analysis of treatment-naive patients with retinoblastoma who were diagnosed between Jan 1, 2017, and Dec 31, 2017, then treated and followed up for 3 years. Patients were recruited from 260 specialised treatment centres worldwide. Data were obtained from participating centres on primary and additional treatments, duration of follow-up, metastasis, eye globe salvage, and survival outcome. We analysed time to death and time to enucleation with Cox regression models. FINDINGS : The cohort included 4064 children from 149 countries. The median age at diagnosis was 23·2 months (IQR 11·0–36·5). Extraocular tumour spread (cT4 of the cTNMH classification) at diagnosis was reported in five (0·8%) of 636 children from high-income countries, 55 (5·4%) of 1027 children from upper-middle-income countries, 342 (19·7%) of 1738 children from lower-middle-income countries, and 196 (42·9%) of 457 children from low-income countries. Enucleation surgery was available for all children and intravenous chemotherapy was available for 4014 (98·8%) of 4064 children. The 3-year survival rate was 99·5% (95% CI 98·8–100·0) for children from high-income countries, 91·2% (89·5–93·0) for children from upper-middle-income countries, 80·3% (78·3–82·3) for children from lower-middle-income countries, and 57·3% (52·1-63·0) for children from low-income countries. On analysis, independent factors for worse survival were residence in low-income countries compared to high-income countries (hazard ratio 16·67; 95% CI 4·76–50·00), cT4 advanced tumour compared to cT1 (8·98; 4·44–18·18), and older age at diagnosis in children up to 3 years (1·38 per year; 1·23–1·56). For children aged 3–7 years, the mortality risk decreased slightly (p=0·0104 for the change in slope). INTERPRETATION : This study, estimated to include approximately half of all new retinoblastoma cases worldwide in 2017, shows profound inequity in survival of children depending on the national income level of their country of residence. In high-income countries, death from retinoblastoma is rare, whereas in low-income countries estimated 3-year survival is just over 50%. Although essential treatments are available in nearly all countries, early diagnosis and treatment in low-income countries are key to improving survival outcomes.The Queen Elizabeth Diamond Jubilee Trust and the Wellcome Trust.https://www.thelancet.com/journals/langlo/homeam2023Paediatrics and Child Healt

Deformation of aluminium cylindrical cups formed under gas detonation and theoritical modelling

Bu çalışmada, hava-yakıt hacimsel oranı 1 (bir) alınarak Asetilen($C_2H_2$)-Oksijen($O_{2}$) karışımıyla detonasyon (şok hız) elde edilerek, alüminyum levhaların (Etial 5) silindirik kap biçiminde şekillendirilmesi çalışması yapılmıştır. Çalışma için çift kademeli bir detonasyonla şekillendirme düzeneği tasarlanarak imal edilmiştir. Detonasyonun elde edilmesinde Çift Kademeli Detonasyon Tüp (ÇKDT) hacminin %100 oranında gönderilen reaktant (Oksijen-asetilen karışımı) miktarı, manometre ve debi metrelerle bilgisayar kontrollü olarak yapılmıştır. Detonasyonun hızı ve basıncıda bilgisayar kontrollü olarak ölçülmüştür.. Silindirik kalıplar içinde biçimlendirilen alüminyum levhaların şekillenebilirlik miktarları ölçülerek analiz edilmiştir. Detonasyonla şekillendirmenin teorik modeli eksplisit dinamik analiz kodu kullanan ANSYS/LS-DYNA yazılımı kullanılarak oluşturulmuş ve model çözümlenmiştir. Deneysel ve teorik sonuçların birim uzama, kalınlık değişimleri ve şekillendirme miktarlarının karşılaştırılması yapılmıştır. Geliştirilen teorik ve deneysel modelin birbiriyle %80-90 oranında uyumlu olduğu gözlemlenmiş uyumsuzluğun nedenleri araştırılmıştır.In this study, cylindrical cups formation of Aluminum alloy sheets (Etial 5) has been researched by using detonation forming. The detonation has been achieved by acetylene ($C_2H_2$)-Oxygen ($O_{2}$) mixture accepting the volume ratio of the mixture as 1, with this respect double staged detonation forming apparatus has been designed and manufactured. Volume of the reactant (mixture of $C_2H_2$-$O_{2}$), 100%, allowed to the Double Staged Detonation Tube (DSDT) has been controlled by manometer and flow meter in conjunction with a computer programme. Shock speed and detonation pressure recorded by computer controlled system. Volume of cup shape formability of the sheets has been evaluated. Detonation forming system has been modeled and analyzed by ANSYS/LS-DYNA computer software which uses explicit dynamic analysis code. Comparison of experimental and theoretical results were obtained from unit strain, thickness variation and volume of formability have been carried out. Experimental results approximately 80%-90% agreement with the theoretical results

The theoretical and experimental investigation of blank holder forces plate effect in deep drawing process of AL 1050 material

The plastic forming process of sheet plate takes an important place in forming metals. The traditional sheet plate forming techniques used in industry are experimental and expensive methods. Prediction of the forming results, determination of the punching force, blank holder forces and the thickness distribution of the sheet metal will decrease the production cost and time of the material to be formed. With this aim, firstly simulation was realized with taking the contact model, material specifications into consideration by using non-linear explicit finite elements method (ANSYS LS-DYNA). In the analysis, the effects of fixed blank holder forces on the wall thickness distribution and wrinkles were examined. As a result of the analysis, without the sheet metal wrinkling or exceeding the tearing limits, for smooth drawings of blank holder the required forces were determined. The results were evaluated and experiments were done with the forces which were determined earlier. As a result of the experiments, which were done with the results obtained with finite elements method, 90% consistency between the experimental and theoretic results was seen. © 2007 Elsevier Ltd. All rights reserved

Drug exposure in early pregnancy might be related to the effects of increased maternal progesterone in implantation period

Aim: This short communication aims to evaluate the relation in between drug exposure time and early pregnancy regarding gestational weeks. Methods: The study covers the referrals made to the Department of Pharmacology for a teratogenic consultation in a 3-year period. From the recordings of pregnant women, the last menstrual period and the starting date of medication were used to determine the time of prescription with regard to gestational weeks. Results: In all of the three years, potentially teratogenic medication was prescribed more frequently in the 3rd, 4th and 5th gestational weeks (in between 15–35 days of pregnancy). Approximately 75% of the pregnant women in the study were prescribed with drugs, most frequently with analgesics, antibiotics, gastrointestinal drugs and antidepressants, in these gestational weeks. Conclusions: The timing of prescriptions in early pregnancy frequently coincides with the increased levels of maternal progesterone in implantation period. Progesterone may lead to negative mood symptoms of an increased pain perception, anxiety, irritability and aggression in some of the pregnant women and therefore causes an increased stress condition which in turn may result in pain, infection and inflammation in the individual. Taking the frequently used medications into consideration, the reason for prescriptions in this period might be related to the symptoms originating from the effects of progesterone. Future studies are needed to better demonstrate this association of drug exposure and effects of maternal progesterone in early pregnancy

A Comparison of Various Vascularization-Perfusion Venous Nerve Grafts with Conventional Nerve Grafts in Rats

Demirci, Mehmet/0000-0002-7316-3877; Erdem Ozdamar, Sevim/0000-0001-9348-6457WOS: 000269719700005PubMed: 19472105Peripheral nerves with defective segments can only be repaired using nerve grafts. Among the various nerve graft options, the outcome of vascularized grafts has been shown to be better, especially when used in the hypovascular and scarred recipient bed. The purpose of this study was to compare the regeneration capacities of various types of venous nerve grafts in a rat model. Forty adult male Wistar albino rats were divided Into four groups. A 2-cm-long segment of femoral sheath was isolated from the surrounding tissue without disturbing the unity, of the femoral sheath contents. Four different nerve graft models were applied: flow-through venous, arterialized venous, prefabricated venous, and conventional nerve graft (control). All nerve grafts were closed with silicone sheets. These neurovascular segments were reopened in postoperative week 10 to determine the viability of the grafted nerves and to assess the degree of nerve healing. Histopathologic C examinations, morphometric analysis, and electrophysiological measurements were performed. The degree of nerve healing in the flow-through venous nerve grafts was similar to that observed in the arterialized nerve grafts. Prefabricated flow-through venous grafts were not as successful as flow-through Venous grafts or arterialized nerve grafts. All of the vascularized nerve grafts showed better results than the conventional nerve grafts