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Objective: Rupture of the anterior cruciate ligament (ACL) in childhood and adolescence is a serious injury. It is now known that conservative therapy of an unstable knee joint in childhood or adolescence under can lead to poor subjective and objective results. The aim of this study is to record long-term results after transepiphyseal ACL reconstruction using autologous hamstring tendons and extracortical fixation in childhood and adolescence with open physes - at least 15 years after surgery., Methods: Our internal registry was used to identify all patients who received surgical treatment of an acl tear during childhood and adolescence by transepiphyseal acl reconstruction more than 15 years previously. In these patients, the International Knee Documentation Committee for Subjective Knee Form (IKDCsubj.), Knee Injury and Osteoarthritis Outcome Score (KOOS), Tegner Activity Score (TAS) and Lysholm Score were collected, and clinical and magnetic resonance imaging (MRI) examinations were performed., Results: A total of 22 patients were identified, 5 of whom could not be contacted. The mean age at the time of surgery was 13.1 years, and the mean follow-up time was 17.4 years. In 3 patients, a traumatic tear was observed with subsequent reconstruction of the ACL. None of the included patients showed a growth disorder during the course of the study. The IKDC subj. was 92.4 ± 14.7 (48 - 100), the Lysholm score was 87.9 ± 16.9 (34 - 100), the TAS was 5.7 ± 2.3 (3 - 9) and the pain level based on VAS was 3.5 ± 2.6 (1 - 8) points. The values showed subjective and objective deterioration compared to the 10-year results, with no statistical significance. The following subscores were reported for the KOOS: KOOS pain 90.9 ± 17.6 (28 - 100); KOOS symptom 82.9 ± 22.6 (11 - 100); KOOOS ADL 94.3 ± 13.7 (44 - 100); KOOS Sport 80.3 ± 26.4 (15 - 100); KOOS QOL 80.9 ± 25.8 (0 - 100). 13 of the 17 patients could also be clinically and radiologically examined. In 92% of patients, an intact acl reconstruction was found without evidence of cartilage or meniscus damage. The mean lateral difference in the KT-1000 measurement was 1.5 mm., Conclusion: ACL reconstruction in childhood and adolescence provides good functionality and stability of the knee joint over the long term. Secondary signs of osteoarthritis can only be detected in isolated cases by MRI. ACL reconstruction using the transepiphyseal technique can be considered the method of choice for open growth plate knee joints., Competing Interests: The authors declare that they have no conflict of interest./Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: The Mayo Elbow Performance Score (MEPS) is a rating system consisting of four dimensions to evaluate elbow performance. It is a common tool for assessment of elbow impairments worldwide. We determined the validity and reliability of its German version (MEPS-G) after cross-cultural adaptation., Methods: Six investigators examined 57 patients with elbow pathologies. The MEPS-G was compared to validated elbow scores such as the German versions of DASH, the Oxford Elbow Score, pain level and subjective elbow performance on a VAS. Inter-rater reliability (IRR) and validity of the score and its dimensions were also reviewed. Verification was performed using the intraclass correlation coefficient (ICC), the prevalence and bias with adjusted Kappa (PABAK) and the Spearman correlation., Results: The IRR of the MEPS-G score was moderate (ICC (2.1) = 0.65). The IRR of the four individual dimensions was moderate to high (K PABAK  = 0.55 -0.81). Validity for the sum score (r = 0.52-0.65) and the dimensions pain (r = 0.53-0.62), range of motion (r = 0.7) and stability (r = - 0.61) was verified. The function subscale reached insufficient validity (r = 0.15-0.39)., Conclusion: The MEPS-G is not sufficiently valid, which is consistent with its English version. The patient-based dimensions were a weakness, demonstrating high risk of bias. There is no general recommendation for the utilization of the MEPS-G as outcome measurement for patients with elbow pathologies., (© 2022. The Author(s).)

Recent efforts in understanding the course and severity of SARS-CoV-2 infections have highlighted both potentially beneficial and detrimental effects of cross-reactive antibodies derived from memory immunity. Specifically, due to a significant degree of sequence similarity between SARS-CoV-2 and other members of the coronavirus family, memory B-cells that emerged from previous infections with endemic human coronaviruses (HCoVs) could be reactivated upon encountering the newly emerged SARS-CoV-2, thus prompting the production of cross-reactive antibodies. Determining the affinity and concentration of these potentially cross-reactive antibodies to the new SARS-CoV-2 antigens is therefore particularly important when assessing both existing immunity against common HCoVs and adverse effects like antibody-dependent enhancement (ADE) in COVID-19. However, these two fundamental parameters cannot easily be disentangled by surface-based assays like enzyme-linked immunosorbent assays (ELISAs), which are routinely used to assess cross-reactivity. Here, we have used microfluidic antibody affinity profiling (MAAP) to quantitatively evaluate the humoral immune response in COVID-19 convalescent patients by determining both antibody affinity and concentration against spike antigens of SARS-CoV-2 directly in nine convalescent COVID-19 patient and three pre-pandemic sera that were seropositive for common HCoVs. All 12 sera contained low concentrations of high-affinity antibodies against spike antigens of HCoV-NL63 and HCoV-HKU1, indicative of past exposure to these pathogens, while the affinity against the SARS-CoV-2 spike protein was lower. These results suggest that cross-reactivity as a consequence of memory reactivation upon an acute SARS-CoV-2 infection may not be a significant factor in generating immunity against SARS-CoV-2.

Background: In patients with chronic lateral epicondylitis who have failed nonoperative treatment, open or percutaneous release of the common extensor origin (CEO) without subsequent reconstruction tends to result in good clinical outcomes. However, surgery can lead to iatrogenic injuries of the lateral collateral ligamentous complex, causing posterolateral rotatory instability (PLRI)., Purpose: To determine the clinical outcomes of lateral ulnar collateral ligament (LUCL) reconstruction using a triceps tendon graft after failed open CEO surgery., Study Design: Case series; Level of evidence, 4., Methods: A total of 103, patients underwent revision surgery at a single institution because of PLRI after failed open release of the CEO (Hohmann procedure) between January 2007 and October 2016. The primary surgery had been performed at other institutions in all cases. Of these patients, 72 were available for follow-up (49 by clinical examination, 23 by telephone interview). Standardized clinical examination; Mayo Elbow Performance Score (MEPS); 11-item version of the Disabilities of the Arm, Shoulder and Hand Score (QuickDASH); subjective elbow value (SEV); and patient satisfaction were assessed at least 2 years after LUCL reconstruction., Results: The mean age of patients in the study was 46.9 years (range, 21-74 years), and the mean follow-up was 2.8 years after revision surgery. The mean MEPS was 78.9, and the mean QuickDASH score reached 20.4. The mean SEV was 78.6%, and 75% of the patients rated the surgery as good to excellent. Complications were detected in 14% of the patients, and 9 needed revision surgery, primarily owing to graft failure with recurrent instability (n = 5)., Conclusion: LUCL reconstruction in patients with PLRI after release of the CEO can restore elbow stability and achieve high patient satisfaction. However, outcome scores and revision rates in this cohort were inferior to published outcomes of primary LUCL reconstruction for treatment of noniatrogenic or traumatic PLRI., Competing Interests: The authors declared that there are no conflicts of interest in the authorship and publication of this contribution. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2022.)

Objective: Latissimus dorsi transfer aims to reduce pain and improve function for irreparable tears of the posterosuperior rotator cuff by restoring the transversal force couple to improve external rotation and delaying superior migration of the humeral head., Indications: Surgery is advocated in patients with unbearable shoulder pain and limited external rotation caused by an irreparable posterosuperior rotator cuff tear. Usually, a latissimus transfer is recommended in the presence of superior migration of the humeral head, higher grade fatty infiltration of the rotator cuff and a restriction of range of motion and strength for abduction and external rotation. Advantages of the arthroscopically assisted technique are the missing need of detaching the deltoid from its origin, smaller incisions and therapy of concomitant intraarticular lesions., Contraindications: Little pain and sufficient shoulder function in massive posterosuperior rotator cuff tears do not necessitate latissimus transfer. In the presence of subscapularis tears, osteoarthritis and deltoid dysfunction as well as shoulder stiffness tendon transfer are associated with inferior clinical outcomes., Surgical Technique: Surgery is performed in prone position. The incision is made about 5 cm caudal of the posterolateral corner of the acromion and extends over 6 cm at the inferior border of the deltoid muscle. After exploration and protection of the axillary and radial nerve the latissimus tendon is peeled off of the humerus. The medial part of the latissimus is then mobilized to gain length for the later transfer. Afterwards the footprint of the infraspinatus is visualized and debrided. Two or three suture anchors are placed into the posterosuperior aspect of the greater tuberosity. The sutures are stitched through the tendon in a horizontal mattress stitch configuration and the tendon tied onto the bone. In arthroscopic advancement, the patient is placed in an upright beach-chair position with the arm attached to an arm holder. After debridement of the supraspinatus and infraspinatus footprint, arthroscopic preparation at the anterior border of the subscapularis tendon is performed. The latissimus tendon is visualized and detached with electrocautery. Afterwards the interval between posterior rotator cuff and deltoid muscle is prepared to allow the transfer of the latissimus tendon to the posterosuperior footprint. This marks the transition to the open approach, in which the arm is placed in a flexed and internally rotated position., Postoperative Management: Immobilization in a shoulder sling for 3 weeks. Early passive range of motion (ROM: flexion 30°, internal rotation 60°, abduction 0°, external rotation 0°) was immediately allowed. After 3 weeks, passive ROM was increased to 90° of flexion, 60° of abduction, whereas external rotation was still restricted. After 7 weeks, free passive ROM and after 8 weeks active ROM (assisted) were allowed., Results: In all, 67 patients (mean age 63 years) were examined 54 months (± 28) after open transfer of the latissimus dorsi tendon. Constant score improved from 24 (± 6) points to 68 (± 17) points. Active flexion increased from 83° (± 47°) to 144° (± 35°), abduction from 69° (± 33°) to 134° (± 42°) and external rotation from 24° (± 18°) to 35° (± 21°). The VAS score decreased from 6.3 (± 1.1) to 1.8 (± 2). However, osteoarthritis worsened over time and the Hamada-Fukuda stage increased from 1.4 to 2.1 and the acromihumeral distance decreased from 7.9 (± 2.6) to 5.1 (± 2.2) at final follow-up., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: A cause of groin pain after total hip arthroplasty (THA) is mechanical irritation or impingement of the iliopsoas tendon. The incidence is about 4%. If conservative therapy fails, an arthroscopic release of the iliopsoas tendon can be performed. The aim of the study was to assess the mid-term clinical outcome after arthroscopic release. We hypothesize that good results can be achieved by a minimally invasive endoscopic procedure., Methods: Using our in-house database, all patients who received an endoscopic release of the iliopsoas tendon due to mechanical irritation after THA were identified. Inclusion criteria were mechanical irritation of the iliopsoas tendon after cementless THA with minimal acetabular component prominence. Exclusion criteria were marked prominence of the acetabular component and groin pain after THA for any other reason. In these patients, the modified Harris Hip Score (mHHS), the pain level using the numerical analogue scale and the UCLA Activity Score were measured. The mean follow-up period was 7 ± 3.8 (2.6-11.7) years., Results: 25 patients were identified in whom an arthroscopic release of the iliopsoas tendon had been performed since 2007. The data of 20 patients were available at follow-up. The gender ratio was 1:1, the average age at the time of arthroscopy was 59 ± 27.7 (52-78) years. The average interval between THA and arthroscopy was 6.3 ± 4.0 (1.7-15) years. The mHHS showed a significant improvement from preoperative 31.2 ± 9.8 (17.6-47.3) to 82.0 ± 9.8 (46.2-100) points (p = 0.001). The pain level on the NAS decreased significantly from 8.5 ± 1.2 (7-10) to 2.5 ± 1.8 (0-6) points (p = 0.001). The activity level based on the UCLA Activity Score raised from 4.0 ± 2.7 (0-7) to 6.5 ± 1.8 (3-9) (p = 0.09)., Conclusion: Mechanical irritation and impingement of the iliopsoas tendon is an important diagnosis to be considered in persistent groin pain after total hip arthroplasty. In failure of non-operative treatment, good clinical results can be achieved with arthroscopic release and the pain level can be significantly reduced., Level of Evidence: IV., (© 2020. The Author(s).)

Stroke is the leading cause of neurological disability in people over 40 years of age and the fourth leading cause of death in Argentina. In the last ten years, the indexed publications related to the treatment of ischemic stroke were more numerous than those of hemorrhagic stroke. The objective of this material is to provide local and updated recommendations for the management of patients with spontaneous intracerebral hemorrhage during hospitalization. For the writing of this manuscript, diferent specialists were convened to form working groups. Ten central topics expressed as epidemiology, initial care, imaging, blood pressure treatment, reversal of antithrombotics, indication for surgery, seizure prophylaxis, prognosis, prevention of complications and resumption of antithrombotics were raised. For each topic, the most frequent questions of daily practice were raised through PICO questions. After a systematic review of the literature, recommendations were generated, evaluated using the GRADE system and agreed between authors and patients.

Purpose: To investigate whether the use of an erector spinae plane block (ESPB) would reduce perioperative pain after arthroscopic therapy for femoroacetabular impingement syndrome (FAIS) and to examine the amount of additional opioids and postoperative nausea and vomiting (PONV)., Methods: From October 2019 to October 2020, 68 patients undergoing arthroscopic therapy for FAIS were randomly allocated into 2 groups. The first group received an ultrasound-guided ESPB preoperatively with 30 mL of 0.375% ropivacaine and standard postoperative oral medication. The second group received a sham block preoperatively with 30 mL of 0.9% saline and standard postoperative oral medication. The primary endpoint was pain scores (numeric pain score out of 10) during the first 24 hours postoperatively. Secondary outcomes were opioid consumption during the first 24 hours (converted to morphine equivalents) and the incidence of PONV. Demographic and clinical characteristics were recorded for all patients. Categorial data were compared with chi-squared and Fisher's exact tests. Continuous data were compared with 2-sided t tests and Wilcoxon rank-sum tests., Results: Sixty-eight subjects consented and were successfully randomized. Reported postoperative pain was significantly lower in the ESPB group than in the control group during the first 24 hours. The opioid amount (P = .865) and postoperative nausea (P = .642) did not differ significantly between groups. No associated complications such as falls, hematomas, or muscular weakness occurred in either group., Conclusion: This study demonstrates that ESPB significantly decreases pain in the first 24 hours after arthroscopic therapy for FAIS. However, there was no evidence of lower opioid consumption compared with the control group. Overall, a low and comparable rate of PONV was present. Therefore, the ESPB seems to complement a multimodal approach to perioperative pain management in hip arthroscopy., Level of Evidence: 1, randomized controlled trial., (Copyright © 2021 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

The clinical outcome of SARS-CoV-2 infections, which can range from asymptomatic to lethal, is crucially shaped by the concentration of antiviral antibodies and by their affinity to their targets. However, the affinity of polyclonal antibody responses in plasma is difficult to measure. Here we used microfluidic antibody affinity profiling (MAAP) to determine the aggregate affinities and concentrations of anti-SARS-CoV-2 antibodies in plasma samples of 42 seropositive individuals, 19 of which were healthy donors, 20 displayed mild symptoms, and 3 were critically ill. We found that dissociation constants, K d , of anti-receptor-binding domain antibodies spanned 2.5 orders of magnitude from sub-nanomolar to 43 nM. Using MAAP we found that antibodies of seropositive individuals induced the dissociation of pre-formed spike-ACE2 receptor complexes, which indicates that MAAP can be adapted as a complementary receptor competition assay. By comparison with cytopathic effect-based neutralisation assays, we show that MAAP can reliably predict the cellular neutralisation ability of sera, which may be an important consideration when selecting the most effective samples for therapeutic plasmapheresis and tracking the success of vaccinations., (© 2021 Schneider et al.)

Molecular chaperones contribute to the maintenance of cellular protein homoeostasis through assisting de novo protein folding and preventing amyloid formation. Chaperones of the Hsp70 family can further disaggregate otherwise irreversible aggregate species such as α-synuclein fibrils, which accumulate in Parkinson's disease. However, the mechanisms and kinetics of this key functionality are only partially understood. Here, we combine microfluidic measurements with chemical kinetics to study α-synuclein disaggregation. We show that Hsc70 together with its co-chaperones DnaJB1 and Apg2 can completely reverse α-synuclein aggregation back to its soluble monomeric state. This reaction proceeds through first-order kinetics where monomer units are removed directly from the fibril ends with little contribution from intermediate fibril fragmentation steps. These findings extend our mechanistic understanding of the role of chaperones in the suppression of amyloid proliferation and in aggregate clearance, and inform on possibilities and limitations of this strategy in the development of therapeutics against synucleinopathies., (© 2021. The Author(s).)

While the initial pathology of Parkinson's disease and other α-synucleinopathies is often confined to circumscribed brain regions, it can spread and progressively affect adjacent and distant brain locales. This process may be controlled by cellular receptors of α-synuclein fibrils, one of which was proposed to be the LAG3 immune checkpoint molecule. Here, we analysed the expression pattern of LAG3 in human and mouse brains. Using a variety of methods and model systems, we found no evidence for LAG3 expression by neurons. While we confirmed that LAG3 interacts with α-synuclein fibrils, the specificity of this interaction appears limited. Moreover, overexpression of LAG3 in cultured human neural cells did not cause any worsening of α-synuclein pathology ex vivo. The overall survival of A53T α-synuclein transgenic mice was unaffected by LAG3 depletion, and the seeded induction of α-synuclein lesions in hippocampal slice cultures was unaffected by LAG3 knockout. These data suggest that the proposed role of LAG3 in the spreading of α-synucleinopathies is not universally valid., (© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

The humoral immune response plays a key role in suppressing the pathogenesis of SARS-CoV-2. The molecular determinants underlying the neutralization of the virus remain, however, incompletely understood. Here, we show that the ability of antibodies to disrupt the binding of the viral spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell, the key molecular event initiating SARS-CoV-2 entry into host cells, is controlled by the affinity of these antibodies to the viral antigen. By using microfluidic antibody-affinity profiling, we were able to quantify the serum-antibody mediated inhibition of ACE2-spike binding in two SARS-CoV-2 seropositive individuals. Measurements to determine the affinity, concentration, and neutralization potential of antibodies were performed directly in human serum. Using this approach, we demonstrate that the level of inhibition in both samples can be quantitatively described using the dissociation constants ( K D ) of the binary interactions between the ACE2 receptor and the spike protein as well as the spike protein and the neutralizing antibody. These experiments represent a new type of in-solution receptor binding competition assay, which has further potential applications, ranging from decisions on donor selection for convalescent plasma therapy, to identification of lead candidates in therapeutic antibody development, and vaccine development.

Scanning transmission electron microscopy (STEM) allows for imaging, diffraction, and spectroscopy of materials on length scales ranging from microns to atoms. By using a high-speed, direct electron detector, it is now possible to record a full two-dimensional (2D) image of the diffracted electron beam at each probe position, typically a 2D grid of probe positions. These 4D-STEM datasets are rich in information, including signatures of the local structure, orientation, deformation, electromagnetic fields, and other sample-dependent properties. However, extracting this information requires complex analysis pipelines that include data wrangling, calibration, analysis, and visualization, all while maintaining robustness against imaging distortions and artifacts. In this paper, we present py4DSTEM, an analysis toolkit for measuring material properties from 4D-STEM datasets, written in the Python language and released with an open-source license. We describe the algorithmic steps for dataset calibration and various 4D-STEM property measurements in detail and present results from several experimental datasets. We also implement a simple and universal file format appropriate for electron microscopy data in py4DSTEM, which uses the open-source HDF5 standard. We hope this tool will benefit the research community and help improve the standards for data and computational methods in electron microscopy, and we invite the community to contribute to this ongoing project.

Robust atomic-to-meso-scale chirality is now observed in the one-dimensional form of tellurium. This enables a large and counter-intuitive circular-polarization dependent second harmonic generation response above 0.2 which is not present in two-dimensional tellurium. Orientation variations in 1D tellurium nanowires obtained by four-dimensional scanning transmission electron microscopy (4D-STEM) and their correlation with unconventional non-linear optical properties by second harmonic generation circular dichroism (SHG-CD) uncovers an unexpected circular-polarization dependent SHG response from 1D nanowire bundles - an order-of-magnitude higher than in single-crystal two-dimensional tellurium structures - suggesting the atomic- and meso-scale crystalline structure of the 1D material possesses an inherent chirality not present in its 2D form; and which is strong enough to manifest even in the aggregate non-linear optical (NLO) properties of aggregates.

Objectives: Stroke knowledge is poor in the general population worldwide. Yet, data from Spanish-Speaking populations, particularly in Latin America, are scant. We aim to evaluate stroke awareness using personal interviews in a population-based study., Materials and Methods: A questionnaire of stroke awareness was administered to a randomly selected sample of households. "Good stroke knowledge for action" was defined as recognition of impaired strength, sensation and language plus intention to seek urgent medical attention in a hypothetical stroke situation. Demographics, the term to name stroke, recognition of warning signs and attitude towards seeking medical attention were compared between individuals with and without "good stroke knowledge for action"., Results: From 1986 respondents (87%, median age 59 years [IQR 23], 50.7% female), most recognized stroke as ACV (cerebrovascular accident, [63%]). Weakness/decreased sensation were recognized as stroke warning signs by 83.5% of respondents, followed by aphasia (77.9%), incoordination (71.6%) and headache (70.5%). Chest pain was misclassified as stroke warning sign by 25% of subjects. In a hypothetical stroke situation, most respondents would go to the hospital (52.3%), or activate the EMS (39%). Individuals with a good stroke knowledge for action (63.5%) recognized visual symptoms (60.4% vs 43.8, p<0.0001), incoordination (78.8% vs 34.4%, p<0.0001) and headache (70.5% vs. 57.8%, p<0.0001) more frequently, and were less likely to misrecognize chest pain as stroke warning sign (23.8% vs. 28.9%, p=0.015). Neither, age (OR 1 CI 0.99-1.00, p=0.94), gender (OR 0.95, CI 0.79-1.16, p=0.61) or race (OR 1.17, CI 0.97-1.42, p=0.097) predicted good stroke knowledge for action., Conclusions: Most people recognize stroke as ACV. The recognition of stroke warning signs and the attitude towards seeking emergent medical attention appears acceptable. Yet, most respondents would go directly to the hospital avoiding the EMS., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The Mayo Elbow Performance Score is a clinical assessment to rate the performance of the elbow from a medical and/or therapeutic perspective. It is simple and efficient to operate and therefore frequently used in research as well as in clinics. However, an adequate translation of the MEPS into the German language and a verification of the quality criteria for the use in the German health system are currently lacking., Goal of the Study: The aim of this study is to translate the MEPS and to review the applicability of the German version (MEPS-G) in Germany., Materials and Methods: The translation was undertaken on the basis of a guideline for cultural adaptation. Two independent translations were created, combined and translated back into English by two native speakers. The back translations were reviewed and the German version was amended accordingly. The suitability of the final questionnaire was verified in a pretest with 73 participants., Results: The MEPS was converted into the German version MEPS-G and was tested. Apart from minor adjustments, the questionnaire was translated into German without difficulty. The time to complete the assessment was on average 2.5 min (± 1.6)., Conclusion: First analyses of the psychometric properties of the German MEPS showed identical values as the English version. The detailed quality criteria will be reviewed in a subsequent study., Competing Interests: The authors declare that they have no conflict of interest./Die Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The biological function of proteins is dictated by the formation of supra-molecular complexes that act as the basic machinery of the cell. As such, measuring the properties of protein species in heterogeneous mixtures is of key importance for understanding the molecular basis of biological function. Here, we describe the combination of analytical microfluidic tools with liquid chromatography for multidimensional characterisation of biomolecules in complex mixtures in the solution phase. Following chromatographic separation, a small fraction of the flow-through is distributed to multiple microfluidic devices for analysis. The microfluidic device developed here allows the simultaneous determination of the hydrodynamic radius, electrophoretic mobility, effective molecular charge and isoelectric point of isolated protein species. We demonstrate the operation principle of this approach with a mixture of three unlabelled model proteins varying in size and charge. We further extend the analytical potential of the presented approach by analysing a mixture of interacting streptavidin with biotinylated BSA and fluorophores, which form a mixture of stable complexes with diverse biophysical properties and stoichiometries. The presented microfluidic device positioned in-line with liquid chromatography presents an advanced tool for characterising multidimensional physical properties of proteins in biological samples to further understand the assembly/disassembly mechanism of proteins and the nature of complex mixtures.

The mechanism of amyloid co-aggregation and its nucleation process are not fully understood in spite of extensive studies. Deciphering the interactions between proinflammatory S100A9 protein and Aβ 42 peptide in Alzheimer's disease is fundamental since inflammation plays a central role in the disease onset. Here we use innovative charge detection mass spectrometry (CDMS) together with biophysical techniques to provide mechanistic insight into the co-aggregation process and differentiate amyloid complexes at a single particle level. Combination of mass and charge distributions of amyloids together with reconstruction of the differences between them and detailed microscopy reveals that co-aggregation involves templating of S100A9 fibrils on the surface of Aβ 42 amyloids. Kinetic analysis further corroborates that the surfaces available for the Aβ 42 secondary nucleation are diminished due to the coating by S100A9 amyloids, while the binding of S100A9 to Aβ 42 fibrils is validated by a microfluidic assay. We demonstrate that synergy between CDMS, microscopy, kinetic and microfluidic analyses opens new directions in interdisciplinary research., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Recent studies have shown that assessment of the lateral center-edge angle (LCEA) between 18° and 25° is not sufficient to adequately classify mildly dysplastic hips and that further radiological features should be considered. However, no correlation between different morphologic features and clinical outcomes has been investigated so far., Purpose: To analyze the clinical outcomes of patients with different subtypes of borderline dysplastic hips who underwent arthroscopic surgery., Study Design: Cohort study; Level of evidence, 3., Methods: We examined patients with an LCEA between 18° and 25° who underwent arthroscopic treatment for femoroacetabular impingement syndrome between January 2015 and December 2016. A hierarchical cluster analysis was performed to identify hip morphologic subtypes according to radiographic parameters, including the LCEA, femoro-epiphyseal acetabular roof (FEAR) index, anterior and posterior wall indices (AWI and PWI), Tönnis angle, alpha angle, and femoral neck-shaft angle. In addition, the International Hip Outcome Tool 12 (iHOT-12) and a visual analog scale (VAS) for pain were applied preoperatively and at follow-up, and the results were compared among the different clusters. Previously reported minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) values were used to determine clinically significant improvements., Results: A total of 40 patients were identified. Of these, 36 patients were available for evaluation at a mean follow-up of 43.8 months. In total, 4 sex-independent clusters with different morphologic patterns of the hip were identified: cluster 1, unstable anterolateral deficiency (FEAR index >2°, AWI <0.35); cluster 2, stable anterolateral deficiency (FEAR index <2°, AWI <0.35); cluster 3, stable lateral deficiency (FEAR index >2°, normal AWI and PWI); and cluster 4, stable posterolateral deficiency (FEAR index <2°, PWI <0.85). At follow-up, clusters 1, 2, and 3 showed significantly improved iHOT-12 ( P < .0001) and VAS pain ( P < .0001) scores, and cluster 4 showed no significant improvements. The MCID of 15.2 points was achieved by all patients in clusters 2 and 3, by 63% of patients in cluster 1, and by 23% of patients in cluster 4. Clusters 2 and 3 differed significantly from clusters 1 and 4 ( P = .02). A postoperative PASS score of 60 was achieved by all patients in cluster 3, by 86% of patients in cluster 2, by 63% of patients in cluster 1, and by 20% of patients in cluster 4. The differences between the groups were statistically significant ( P = .01)., Conclusion: Arthroscopic surgery yielded good results in the treatment of stable borderline hip dysplasia with anterolateral and lateral deficiency. In contrast, borderline hip dysplasia with acetabular retroversion showed no improvements after arthroscopic therapy. This study underlines the need for an accurate analysis of all possible radiological signs to adequately classify borderline dysplastic hips., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: W.M. has received consulting fees from Arthrex and Richard Wolf. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2020.)

Introduction: Shoulder arthroplasty for proximal humerus fracture sequelae is known to provide significant patient improvement, yet this outcome varies with time, prosthesis type, and fracture sequelae. We outline the expected course of postoperative shoulder pain and function in patients with anatomical (ASA) or reverse (RSA) shoulder arthroplasty following different fracture sequelae., Materials and Methods: Of 111 consecutive patients from our local shoulder arthroplasty registry, 32 underwent ASA for Boileau type 1 sequelae and 77 RSA patients were identified with Boileau types I, III, and IV. By 5 year post-surgery, there were 72 patients available. All patients underwent standardised ASA or RSA procedures with anatomical (Promos Standard; Lima SMR™; Arthrex Eclipse™; Univers™ II) or reverse prostheses (Promos Reverse ® ; Lima SMR™ Reverse; Univers Revers™; Aequalis ® Reversed). Range of motion, Constant-Murley, Disability of the Arm, Shoulder and Hand (DASH), and Shoulder Pain and Disability Index (SPADI) scores were compared at 6, 12, 24, and 60 months postoperatively. We used generalised linear mixed models or random-effects ordered logistic regression to investigate postoperative changes of outcome parameters from baseline to follow-up time points for each group as well as for group comparisons., Results: Range of motion and clinical scores improved until 24 months postoperatively and did not deteriorate thereafter, except for internal rotation of Boileau type III and IV patients and external rotation of RSA patients with type I and IV sequelae. At all follow-ups, ASA patients with Boileau type I sequelae had significantly better internal and external rotation versus patients with RSA and/or other Boileau types (p < 0.001), while Constant, DASH, and SPADI scores were not significantly different between groups., Conclusion: In humeral fracture sequelae, ASA and RSA lead to sustained clinical improvements. Surgeons may primarily consider implantation of ASA in type I sequelae.

Background and Objective: Posttraumatic or postoperative movement restrictions in elbow joints can often occur (including capsular contracture) and can generate everyday limitations. In persistent elbow stiffness, arthroscopic arthrolysis with removal of the dorsal and ventral capsule portions can be carried out. The purpose of this study was to assess the efficacy of arthroscopic capsulectomy by means of an in vitro anatomical study., Methods: A standardized elbow arthroscopy with ventral and dorsal capsulectomy was performed and image-documented in five fresh-frozen elbow specimens. Subsequently, open dissection of the elbow joint was performed to analyze the amount of residual capsule by means of photodocumentation of the specimens., Results: Regardless of the surgeon and surgical experience, anterior and posterior remnants of the capsule remained in all specimens. Dorsal capsule strands around the standard arthroscopy portals were noticed particularly more often in the area of the high dorsolateral camera portal. An incomplete capsulectomy was seen on the ulnar side at the level of the posterior medial ligament (PML) in the immediate vicinity of the ulnar nerve. Ventrally, a capsulectomy was performed from the radial side and also the ulnar side until the brachialis muscle and additionally a complete capsulectomy as far as the anterior medial ligament (AML) and radial collateral ligament (RCL) was achieved. The capsule was completely resected in a proximal direction. Distally, irrelevant capsular remnants were found in the region of the annular ligament and distal of the tip of the coronoid process., Conclusion: Arthroscopic arthrolysis can be performed with a high degree of radicality. The radicality must be self-critically taken into account in one's own action. The radicality of the portal change may even be higher ventrally than with an isolated column procedure. On the other hand, it must be critically considered that posteriorly, the PML cannot be adequately addressed by means of arthroscopy due to the risk of ulnar nerve injury. Portal changes might help to enable a more complete visualization of the joint capsule and may avoid leaving possibly relevant remnants of the capsule. If a release of the PML is required, this may have to be carried out in combination with an ulnar nerve release in a mini-open technique.

A body-centered cubic W-based refractory high entropy alloy with outstanding radiation resistance has been developed. The alloy was grown as thin films showing a bimodal grain size distribution in the nanocrystalline and ultrafine regimes and a unique 4-nm lamella-like structure revealed by atom probe tomography (APT). Transmission electron microscopy (TEM) and x-ray diffraction show certain black spots appearing after thermal annealing at elevated temperatures. TEM and APT analysis correlated the black spots with second-phase particles rich in Cr and V. No sign of irradiation-created dislocation loops, even after 8 dpa, was observed. Furthermore, nanomechanical testing shows a large hardness of 14 GPa in the as-deposited samples, with near negligible irradiation hardening. Theoretical modeling combining ab initio and Monte Carlo techniques predicts the formation of Cr- and V-rich second-phase particles and points at equal mobilities of point defects as the origin of the exceptional radiation tolerance.

Background: Arthroscopic and open debridement arthroplasty for elbow arthrosis produce excellent results. Resection of the tip of the olecranon and coronoid, as well as debridement of the associated fossae, is frequently described as sufficient for restoring range of motion and reducing pain., Objectives: The purpose of this study was to demonstrate that medial and lateral osteophytes of the olecranon and the coronoid usually mark the first bony contact and may, therefore, restrict range of motion., Material and Methods: 11 fresh-frozen elbows were dissected. The fossae were coated with Optosil P Plus (C-silicone), and maximal flexion and extension was simulated. The distribution of C‑silicone impressions was documented. 6/7 donors were male. The mean age at the time of death was 82 ., Results: Out of 11 elbows, 4 exhibited arthritic changes. All arthritic elbows showed marginal osteophytes of the olecranon without characteristic dipping of the olecranon into its fossa. In 1/4 cases, additional osteophytes at the side of the coronoid were detected (in comparison to 1/7 in healthy elbows)., Conclusion: The distribution of osteophytes in elbow arthrosis may be underestimated. Many clinicians describe a resection of the tip of the olecranon and the coronoid and debridement of the related fossa as sufficient. Our study supports the theory that marginal osteophytes, especially of the olecranon, should be resected during debridement arthroplasty, since the distribution of bony contact differs in arthritic and healthy elbows.

Background: Epidemiological data on stroke is scarce in Latin America. Estudio Epidemiológico Poblacional sobre Accidente Cerebrovascular (EstEPA) is a population-based program planned to assess prevalence, incidence, mortality, and burden of disease for stroke in the Department of General Villegas, province of Buenos Aires, Argentina., Methods and Design: Prevalence study will consist of a two-phase survey approach in the urban area of General Villegas. First, trained social workers with a structured questionnaire will collect data in 2000 randomly selected housing units. Those subjects screened positive for possible strokes will be interviewed and examined by stroke neurologists to confirm diagnosis. The incidence study will be performed according to the methodology of WHO STEPS stroke surveillance manual and will detect all new strokes in the department during a 5-year period. General and disease-specific mortality rates will be assessed monthly during a 5-year period, using different sources of information. To assess the overall burden of cerebrovascular disease, disability adjusted life years will be calculated., Discussion: EstEPA will assess for the first time all aspects of stroke epidemiology in Argentina. Its results will help to implement population-based interventions and to properly allocate public health resources., (Copyright © 2018. Published by Elsevier Inc.)

Introduction: Incidences of scapular notching (SN) in reverse shoulder arthroplasty (RSA) range between 0% and 96%, and controversy remain as to its relevance for patient outcome. We assessed the reliability of scapular notching (SN) grading based on the Sirveaux classification system using anteroposterior radiographs., Materials and Methods: 206 RSA procedures with 5-year postoperative anteroposterior shoulder radiographs were classified independently by seven assessors according to Sirveaux (session 1). After a review meeting, three assessors re-classified the radiographs along with quality criteria (session 2). SN grading by the majority of assessors was taken as the reference. Classification interobserver reliability was analyzed using Kappa statistics., Results: The incidence of SN was estimated at 53% and 37% at the first and second sessions, respectively. Interobserver reliability Kappa coefficients resulting from the first and second sessions were 0.27 and 0.43, respectively. Case selection based on radiographic quality criteria did not improve SN grading reliability in the second session., Conclusion: Agreement between individual surgeons was low when grading SN in RSA according to Sirveaux using anteroposterior radiographs. Consensus among several assessors may increase reliability in research settings.

Background: The Barrow Neurological Institute (BNI) scale is a novel quantitative scale measuring maximal subarachnoid hemorrhage (SAH) thickness to predict delayed cerebral ischemia (DCI). This scale could replace the Fisher score, which was traditionally used for DCI prediction., Objective: To validate the BNI scale., Methods: All patient data were obtained from the prospective aneurysmal SAH multicenter registry. In 1321 patients, demographic data, BNI scale, DCI, and modified Rankin Scale (mRS) score up to the 1-yr follow-up (1FU) were available for descriptive and univariate statistics. Outcome was dichotomized in favorable (mRS 0-2) and unfavorable (mRS 3-6). Odds ratios (OR) for DCI of Fisher 3 patients (n = 1115, 84%) compared to a control cohort of Fisher grade 1, 2, and 4 patients (n = 206, 16%) were calculated for each BNI grade separately., Results: Overall, 409 patients (31%) developed DCI with a high DCI rate in the Fisher 3 cohort (34%). With regard to the BNI scale, DCI rates went up progressively from 26% (BNI 2) to 38% (BNI 5) and corresponding OR for DCI increased from 1.9 (1.0-3.5, 95% confidence interval) to 3.4 (2.1-5.3), respectively. BNI grade 5 patients had high rates of unfavorable outcome with 75% at discharge and 58% at 1FU. Likelihood for unfavorable outcome was high in BNI grade 5 patients with OR 5.9 (3.9-8.9) at discharge and OR 6.6 (4.1-10.5) at 1FU., Conclusion: This multicenter external validation analysis confirms that patients with a higher BNI grade show a significantly higher risk for DCI; high BNI grade was a predictor for unfavorable outcome at discharge and 1FU.

Background: Restoration of the mechanical axis is a main objective in total knee replacement (TKR). Aim of this study was to analyse the verification tool of a pinless navigation system in conventional TKR (cTKR)., Methods: In a prospective study, 147 TKR were performed by conventional technique. Using the "pinless verification" mode of a smartphone based navigation system, the cutting block position and final resection plane for distal femur and proximal tibial resection were measured. If necessary, the block position or resection level were optimized, corrections were protocolled. Postoperatively, standardized radiographs were performed., Results: In 65.3%, intraoperative measurements changed the surgical procedure (corrections: 20.4% femoral, 25.9% tibial, 19% both). The additional time for surgery compared to cTKR averaged 6 minutes (79 ± 15 versus 73 ± 17 minutes). Using navigation data, the final femoral and tibial axes were in 93% within a range of ±2°. A mean difference of 1.4° and 1.6° could be shown between the final measurement of the navigation system and the postoperative mLDFA and mMPTA., Conclusion: Intraoperative pinless navigation has impact on the surgical procedure in the majority of cTKR. It represents a less time-consuming tool to improve implant position while maintaining the routine of conventional technique.

Background and purpose Identifying embolic strokes of undetermined source (ESUS) patients likely to harbor atrial fibrillation may have diagnostic and therapeutic implications. Our aim was to examine differences between ESUS and cardioembolic strokes, to evaluate stroke recurrence rate among ESUS and to identify baseline characteristics of ESUS patients who were later diagnosed with atrial fibrillation. Materials and methods We assessed all ischemic stroke patients admitted between June 2012 and November 2013. ESUS were compared to cardioembolic strokes at discharge. After at least 12-month follow-up, ESUS patients diagnosed with atrial fibrillation were compared to those who remained as ESUS. Results There were 236 ischemic strokes, 32.6% were ESUS. Compared to cardioembolic strokes, ESUS were younger (p < 0.0001), had milder strokes (p < 0.05), less prevalence of hypertension (p < 0.05), peripheral vascular disease (p < 0.05), and previous ischemic stroke (p < 0.05). After follow-up, 15% of ESUS patients had stroke recurrences and 12% evidenced paroxysmal atrial fibrillation. ESUS patients diagnosed with atrial fibrillation in the follow-up were older (p < 0.0001), had higher erythrocyte sedimentation rate (p < 0.05), and were more likely to have ≥2 infarcts in the same arterial territory in the initial magnetic resonance imaging (p < 0.05). Conclusions Older age, small-scattered infarcts on initial magnetic resonance imaging and high erythrocyte sedimentation rate levels appear to identify ESUS patients more likely to be diagnosed of atrial fibrillation during follow-up.

Objective: To determine the effectiveness of achieving pregnancy with focused intercourse in the fertile window identified using natural fertility indicators., Methods: 24-cycle prospective effectiveness study., Setting: A North American web-based fertility monitoring service., Participants: 256 North American women aged 20-43 (mean age 29.2 years) seeking to achieve pregnancy., Intervention: Participants identified their fertile window with either electronic hormonal fertility monitoring or cervical mucus monitoring, or both, and recorded their observations on an online fertility tracking system., Main Outcome Measures: Pregnancies were validated by nurses with an online self-assessed pregnancy evaluation form. Survival analysis was used to determine pregnancy rates., Results: There were 150 pregnancies among the 256 participants with an overall pregnancy rate of 78 per 100 women over 12 menstrual cycles. There were 54 pregnancies (68%) among the 80 women using the fertility monitor, 11 pregnancies (46%) among the 24 women using mucus monitoring, and 90 (63%) among the 143 women using both mucus and monitor. The 12-cycle pregnancy rates per 100 women were 83 (monitor group), 72 (mucus group), and 75 (mucus and monitor group). Pregnancy rates reached 100% at 24 cycles of use for those women using the hormonal fertility monitor., Conclusion: Use of the hormonal fertility monitor alone seems to offer the best natural estimate of the fertile phase of the menstrual cycle for women wishing to achieve a pregnancy. Focusing intercourse through 24 menstrual cycles can be beneficial for achieving pregnancy.

Purpose: To investigate the 2-year postoperative clinical and subjective outcomes after arthroscopic rotator cuff repair (ARCR) with xenologous porcine dermal patch augmentation compared with ARCR alone., Methods: Patients aged 60 years or older with a complete supraspinatus (SSP) tendon tear underwent primary ARCR with a transosseous-equivalent technique. By use of a matched-pair comparative trial design, a consecutive series of 20 patients receiving additional xenologous porcine dermal patch augmentation (patch group) was matched by tear location with 20 patients who received ARCR only (control group). Prior conservative treatment failed in all patients. Patients with concomitant pathologies precluding accurate repair assessment, partial or open reconstruction, or a latissimus dorsi and/or pectoralis major muscle transfer were excluded. Patients reported daily pain levels for 10 days after surgery. Clinical parameters and various patient-reported outcome scores were documented preoperatively and at 3, 6, and 24 months after surgery. Repair integrity was determined by magnetic resonance imaging or ultrasound at 24 months. Adverse events were recorded. Group outcome differences were analyzed with t tests, Fisher exact tests, and mixed models., Results: Patients in both groups were aged 67 years on average (range, 60-74 years), and 70% of patients were men. Patients in the patch group had slightly more SSP fatty infiltration preoperatively. Patch surgical procedures were on average 22 minutes longer than control interventions (P = .003). At 24 months, 4 patients and 9 patients were diagnosed with a recurrent SSP tendon defect in the control group (n = 20) and patch group (n = 19), respectively (relative risk, 2.4; P = .096). Of 11 defects (85%) identified as medial cuff failure, 8 occurred in the patch group. Pain rated by all patients decreased from postoperative day 1 to day 10 without any significant group difference (P = .348). No significant group differences were noted for other outcome parameters, and recurrent defects had no relevant effect on functional outcomes. Local complications (including recurrent defects) occurred in 8 patients in the control group and 12 in the patch group (P = .343)., Conclusions: Our pilot study supports the view that an SSP tear repair with porcine dermal xenograft augmentation does not benefit patients in terms of reducing the risk of a recurrent tendon defect or improving shoulder function up to 24 months after surgical repair., Level of Evidence: Level III, therapeutic study, retrospective comparative trial., (Copyright © 2017 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Background: An inadequate clinical outcome after conservatively treated radial head fractures is not uncommon. We analyzed the subjective limitations, objective complaints, and surgical procedures for radial head fractures initially treated conservatively., Patients and Method: Between 2007 and 2016, 70 patients (42 men, 28 women) who suffered from fracture sequelae after conservatively treated radial head fractures were examined. Demographic (age, 41.8 years, range, 16-75 years) and clinical data (pain, range of motion, instability) were retrospectively evaluated., Results: The average time to surgery after trauma was 50 months (range, 5-360 months). In 38 cases, radial head fractures were initially treated with immobilization for 3.4 weeks (range, 1-8 weeks). Physiotherapeutic treatment was performed in 39 cases. In only half of the cases was retrospective Mason classification possible: 20 type I, 8 type II, 5 type III, and 2 type IV. Of the 70 patients, 53 had posttraumatic elbow stiffness; 34 had isolated lateral and four patients isolated medial ligament instability. There were eight cases with a combination of lateral and medial ligament instability and 27 cases of elbow stiffness combined with instability. An average of 1.2 (range, 1-4) surgical procedures per patient were performed. In all, 64 patients underwent elbow arthroscopy with arthrolysis and additional treatment depending on other injuries. The range of motion improved on average from preoperative flexion/extension of 131-15-0° to postoperative flexion/extension of 135-5-0° (gain in flexion: 4.2° and extension: 10.6°)., Conclusion: Conservative treatment of radial head fractures does not always yield good results. Reasons for a poor outcome include chronic instability, cartilage damage, stiffness, or a combination thereof. Improved outcomes can be achieved via arthroscopic arthrolysis., Competing Interests: Compliance with ethical guidelinesR. Nietschke, K.J. Burkhart, B. Hollinger, F.I. Dehlinger, A. Zimmerer, and M.M. Schneider declare that they have no competing interests. This article does not contain any studies with human participants or animals performed by any of the authors.

Background: Radiocapitellar arthritis or defects most often result from trauma. Most of the patients are young and have high functional demands with high load capacities. Therefore, endoprosthetic options should be postponed for as long as possible. If conservative treatment cannot relieve symptoms sufficiently, radial head preservation, resection or replacement options are at the surgeon's disposal. In early stages of radiocapitellar arthritis, radial head preservation options can be taken into account. The chances ofgood results decrease with increasing cartilage damage., Treatment Options: In addition to radial head preservation options this article discusses radial head resection with and without anconeus interposition and radial head as well as radiocapitellar replacement. Clinical data are rare. The advantages and disadvantages of each option must be discussed with the patient and the decision should be made individually on the basis of patient specific factors. The aim must be to postpone endoprosthetic options - especially total elbow arthroplasty - for as long as possible, while assuring a functional range of motion with an acceptable pain level.

Background and Objectives: Marijuana is the most commonly used illicit drug among college students, with heavy use leading to negative outcomes. Use of marijuana for medical and recreational purposes in select U.S. states has been controversial, with concerns surrounding increased prevalence rates and harm. The current exploratory study aimed to assess marijuana use in college students in Colorado, demographic differences in frequency of use, and motives for using., Methods: College students (N = 300; 61% female) were recruited through introductory psychology courses and completed a series of questionnaires and a marijuana urine screen., Results: Almost three-fourths of the sample reported lifetime use of marijuana. Sixty-five percent used marijuana within the last year and 29% tested positive on the urine screen. Hurdle Poisson regression models with a subset of participants (n = 117) showed non-Greek and freshman status were associated with increased number of days participants used marijuana in the last month. Problem marijuana use was positively associated with a range of motives-of note-motives focused on coping, boredom, alcohol, and food., Conclusions and Scientific Significance: Prevalence rates of marijuana use were high in this sample of college students in a state with legal recreational marijuana use. Particular students (eg, students who use marijuana to cope) may be at higher risk for problem marijuana use. Developing effective, tailored interventions for university students is warranted. (Am J Addict 2017;26:830-837)., (© 2017 American Academy of Addiction Psychiatry.)

Objective: To develop an educational intervention that targets residents' beliefs and attitudes to quality Improvement (QI) and leadership in order to demonstrate proactive behaviour., Design: Theory-driven, mixed methods study including document analysis, interviews, observations and open-ended questionnaires., Setting: Six Dutch teaching hospitals., Intervention: Using expertise from medicine, psychology, organizational and educational sciences we developed a situated learning programme named Ponder and IMProve (PIMP). The acronym PIMP reflects the original upbeat name in Dutch, Verwonder & Verbeter. It has a modern, positive meaning that relates to improving your current circumstances. In quarterly 1-h sessions residents are challenged to identify daily workplace frustrations and translate them into small-scale QI activities., Main Outcome Measures: Organizational awareness, beliefs and attitudes to QI and organizational responsibilities, resident behaviour, barriers and facilitators to successful learning and the programme's potential impact on the organization., Results: Overall, 19 PIMP meetings were held over a period of 3 years. Residents defined 119 PIMP goals, resolved 37 projects and are currently working on another 39 projects. Interviews show that PIMP sessions make residents more aware of the organizational aspects of their daily work. Moreover, residents feel empowered to take up the role of change agent. Facilitators for success include a positive cost-benefit trade-off, a valuable group process and a safe learning environment., Conclusion: This article demonstrates the added value of multidisciplinary theory-driven research for the design, development and evaluation of educational programmes. Residents can be encouraged to develop organizational awareness and reshape their daily frustrations in QI work., (© The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com)

Background: The exact role of platelet-rich plasma (PRP) in rotator cuff tendon reconstruction remains unclear., Purpose/hypothesis: This study investigated whether an intraoperative pure PRP injection, compared with a local anesthetic injection, improves patient-reported outcomes at 3 and 6 months after arthroscopic rotator cuff repair. The hypothesis was that pure PRP improves patient-reported outcomes (Oxford Shoulder Score [OSS]) at 3 and 6 months after surgery and has the same pain-reducing effect compared with a postoperative subacromial local anesthetic (ropivacaine) injection., Study Design: Randomized controlled trial; Level of evidence, 1., Methods: Between January 2011 and November 2012, a total of 120 patients who underwent arthroscopic double-row repair of a supraspinatus tendon rupture were randomized to receive either pure PRP by an injection at the footprint (PRP group; n = 60) or ropivacaine injected in the subacromial region (control group; n = 60). Seventy-eight percent of patients had other concomitant tears. All patients, surgeons, and follow-up investigators were blinded. Clinical parameters and various outcome scores (Constant-Murley shoulder score; OSS; patient American Shoulder and Elbow Surgeons score; quick Disabilities of the Arm, Shoulder and Hand score; EuroQol 5 dimensions) were documented preoperatively and at 3, 6, and 24 months postoperatively. The repair integrity was assessed by magnetic resonance imaging or ultrasound at 24 months. Furthermore, a pain diary was completed within the first 10 postoperative days, and adverse events were recorded. Group outcome differences were analyzed using t tests, Fisher exact tests, and mixed models., Results: The final follow-up rate was 91%. An associated tear of the subscapularis tendon was diagnosed in 23% of PRP-treated patients and 36% of control patients. Three months after surgery, the mean (±SD) OSS was 32.9 ± 8.6 in PRP-treated patients and 30.7 ± 10.0 in control patients (P = .221). No significant differences were noted for other outcome parameters as well as at 6 and 24 months postoperatively. Smoking was a significant effect modifier. Pain for both groups decreased from postoperative day 1 to 10 without any significant group difference (P = .864). Six (12.2%) and 11 (20.8%) patients were diagnosed with a recurrent supraspinatus tendon defect in the PRP and control groups, respectively (P = .295). Twenty-two (40.7%) and 18 (30.5%) PRP-treated and control patients, respectively, experienced a local adverse event within 24 months (P = .325)., Conclusion: Patients treated with pure PRP showed no significantly improved function at 3, 6, and 24 months after arthroscopic repair compared with control patients receiving ropivacaine; however, a similar pain reduction was documented in both groups. The negative influence of smoking on the effect of pure PRP requires further investigation., Registration: NCT01266226 (ClinicalTrials.gov)., (© 2016 The Author(s).)

Purpose: The reliability of the Rockwood classification, the gold standard for acute acromioclavicular (AC) joint separations, has not yet been tested. The purpose of this study was to investigate the reliability of visual and measured AC joint lesion grades according to the Rockwood classification., Methods: Four investigators (two shoulder specialists and two second-year residents) examined radiographs (bilateral panoramic stress and axial views) in 58 patients and graded the injury according to the Rockwood classification using the following sequence: (1) visual classification of the AC joint lesion, (2) digital measurement of the coracoclavicular distance (CCD) and the horizontal dislocation (HD) with Osirix Dicom Viewer (Pixmeo, Switzerland), (3) classification of the AC joint lesion according to the measurements and (4) repetition of (1) and (2) after repeated anonymization by an independent physician. Visual and measured Rockwood grades as well as the CCD and HD of every patient were documented, and a CC index was calculated (CCD injured/CCD healthy). All records were then used to evaluate intra- and interobserver reliability., Results: The disagreement between visual and measured diagnosis ranged from 6.9 to 27.6 %. Interobserver reliability for visual diagnosis was good (0.72-0.74) and excellent (0.85-0.93) for measured Rockwood grades. Intraobserver reliability was good to excellent (0.67-0.93) for visual diagnosis and excellent for measured diagnosis (0.90-0.97). The correlations between measurements of the axial view varied from 0.68 to 0.98 (good to excellent) for interobserver reliability and from 0.90 to 0.97 (excellent) for intraobserver reliability., Conclusion: Bilateral panoramic stress and axial radiographs are reliable examinations for grading AC joint injuries according to Rockwood's classification. Clinicians of all experience levels can precisely classify AC joint lesions according to the Rockwood classification. We recommend to grade acute ACG lesions by performing a digital measurement instead of a sole visual diagnosis because of the higher intra- and interobserver reliability., Level of Evidence: Case series, Level IV.

Background: Osteochondrosis dissecans is a disorder of the subchondral bone potentially affecting the adjacent articular cartilage. There remains disunity with regard to treatment methods., Case Presentation: We present the case of a 21-year-old Swiss woman who presented with clinically symptomatic bilateral osteochondrosis dissecans lesions at both medial femoral condyles. She underwent sequential surgical intervention and was prospectively monitored using clinical scores and magnetic resonance imaging. Her left knee was treated with an open refixation of the osteochondrosis dissecans lesion with two 2.0 mm screws in combination with a cancellous bone graft and subchondral drilling since the cartilage of the osteochondrosis dissecans lesion was intact. On her right knee, she underwent open removal of the defective bone and cartilage, cancellous bone graft with subchondral drilling and coverage with a bilayered collagenous membrane (autologous matrix-induced chondrogenesis technique) since the cartilage of the osteochondrosis dissecans lesion was not intact. At final follow-up 12 months after surgery her Lysholm score had improved from 79 to 95 on her left side and from 74 to 78 on her right. Magnetic resonance imaging displayed good integration of the cancellous bone graft with a slight irregularity at the articular surface on her left side (magnetic resonance observation of cartilage repair tissue (MOCART) 75). The magnetic resonance imaging of her right knee depicted satisfying bony reconstitution with yet more irregularity at the joint surface (magnetic resonance observation of cartilage repair tissue 65) in comparison to her left femoral condyle., Conclusions: In cases of failed conservative treatment of osteochondrosis dissecans lesions of the knee joint surgery should be taken into consideration. Considering this case, we believe that the focus should be the preservation of the cartilaginous layer whenever possible or at least replacement with high quality replacement tissue, such as autologous chondrocyte implantation.

Axial alignment is one of the main objectives in total knee arthroplasty (TKA). Computer-assisted surgery (CAS) is more accurate regarding limb alignment reconstruction compared to the conventional technique. The aim of this study was to analyse the precision of the innovative navigation system DASH® by Brainlab and to evaluate the reliability of intraoperatively acquired data. A retrospective analysis of 40 patients was performed, who underwent CAS TKA using the iPod-based navigation system DASH. Pre- and postoperative axial alignment were measured on standardized radiographs by two independent observers. These data were compared with the navigation data. Furthermore, interobserver reliability was measured. The duration of surgery was monitored. The mean difference between the preoperative mechanical axis by X-ray and the first intraoperatively measured limb axis by the navigation system was 2.4°. The postoperative X-rays showed a mean difference of 1.3° compared to the final navigation measurement. According to radiographic measurements, 88% of arthroplasties had a postoperative limb axis within ±3°. The mean additional time needed for navigation was 5 minutes. We could prove very good precision for the DASH system, which is comparable to established navigation devices with only negligible expenditure of time compared to conventional TKA.

Background: The goal of the present study was to summarize current treatment for acute acromioclavicular (AC) joint dislocations., Method: In all, 796 orthopedics and/or trauma departments in Germany were identified in the national hospital directory (www.dka.de). Using the respective hospital web sites, the email addresses of the responsible shoulder/sports surgeon or, if not available, the head of department (successful in 746 cases) were identified. Emails with a link to an online survey with 36 questions and two reminders were sent; 60 were undeliverable. Thus, 686 emails probably reached the addressee. A total of 203 colleagues (30%) participated in the survey. Findings were compared to results of the survey published by Bäthis et al. in 2001., Results: More than 90% treat Rockwood I or II injuries conservatively and Rockwood IV to VI injuries surgically. However, 34% answered having never seen a Rockwood VI injury. Of those replying, 73% prefer surgical treatment for Rockwood III injuries. Favored surgical techniques were the hook plate in 44% and the arthoscopic TightRope® in 27%, while 11% prefer coracoclavicular cerclage, 6% AC joint transfixation, 3% minimally invasive AC joint reconstruction (MINAR), 1% coracoclavicular screw fixation, and 8% a completely different procedure. Concerning acute Rockwood III injuries, orthopedics and/or trauma surgeons still prefer surgical treatment but less often than 10 years ago (84%)., Conclusions: Favored techniques have completely changed since 2001 when the majority of physicians preferred AC joint transfixation or coracoclavicular cerclages, both techniques that are hardly used today. The hook plate appears to have become "standard therapy". The arthroscopic TightRope® is the second most common despite being the newest technique.

Background: Contrast-enhanced magnetic resonance imaging (MRI) is highly sensitive for assessing temporomandibular joint (TMJ) involvement in juvenile idiopathic arthritis (JIA), but only sparse data exist on normal TMJ appearance in children., Purpose: To determine normal MRI appearance and enhancement pattern of pediatric TMJ as basis for diagnosing early arthritis., Material and Methods: In 27 children (age range, 1.2-16.8 years) without TMJ pathology undergoing head MRI, fat-saturated T2-weighted (T2W) and postcontrast fat-saturated T1-weighted (T1W) images sagittally aligned to the 54 TMJs, besides standard T1W and T2W images, were assessed for bony and soft tissue signal intensity (SI), the amount of perceptible joint fluid, and contrast enhancement (CE)., Results: Bone marrow SI and CE of the mandible were consistent with varying degrees of residual red marrow in 96% of joints. The mandibular condyles were mostly isointense to the ramus, but in 9% showed mild edema-like bone marrow SI and CE. Small amounts of intraarticular fluid were detected in 31% on T2W images without fat saturation and in 83% on T2W images with fat saturation as fine lines in the upper or lower joint compartment or as small dots in an articular recess. Seventy-nine percent of all TMJs showed intense joint enhancement on early images restricted to areas of intraarticular fluid., Conclusion: Small amounts of joint fluid with intense CE are a common MRI finding in TMJs of children without JIA and therefore should not be considered diagnostic for early arthritis., (© The Foundation Acta Radiologica 2014.)

Background: Hardware removals are among the most commonly performed surgical procedures worldwide. Current literature offers little data concerning postoperative patient satisfaction. The purpose of our study was to evaluate the patients' point of view on implant removal., Methods: We surveyed patients of a German level one trauma center, who underwent hardware removal in 2009 and 2010, with regard to their personal experiences on implant removal. Exclusively, data obtained out of the survey were analyzed., Results: In 332 patients surveyed, most hardware removals were performed at the ankle joint (21%) followed by the wrist (15%). The most frequent indication was a doctor's recommendation (68%), followed by pain (31%) and impaired function (31%). Patient reported complication rate of implant removal was 10%. Importantly, after implant removal because of pain or impaired function patients reported an improvement in function (72%) as well as decreased pain (96%). 96% of all responding patients and 66% of the patients who suffered from subsequent complications would opt for surgical implant removal again., Conclusion: In summary, despite the challenging and frequently troublesome nature of surgical hardware removal our data contradicts the widely held view that implant removal is often without a positive effect on the patients. These findings may influence the surgeons' attitude towards implant removal and their day-to-day routine in patient counseling.

Sentinel lymph node biopsy (SLNB) is a critical component of melanoma management. Extensive prior surgery at the site of a primary melanoma is considered a relative contraindication for SLNB. While evidence suggests that SLNB may be performed accurately even in those patients who have undergone prior wide local excision, it is less clear whether patients who have undergone more extensive surgical procedures, particularly flap reconstructions, can benefit from this procedure. We report a case of a patient who had undergone surgical removal of a primary melanoma and subsequent reconstruction with a rotational flap in whom a SLNB was performed successfully, which revealed nodal metastasis, suggesting that SLNB may remain an appropriate option in carefully selected patients who have previously undergone extensive surgery at site of primary disease., (2015 BMJ Publishing Group Ltd.)

Unlabelled: Triple-negative breast cancers (TNBCs) are highly aggressive cancers that lack targeted therapies. However, EGFR is frequently activated in a subset of TNBCs and represents a viable clinical target. Because the endocytic adaptor protein Endophilin A2 (SH3GL1/Endo II) has been implicated in EGFR internalization, we investigated Endo II expression and function in human TNBCs. Endo II expression was high in several TNBC cells compared with normal breast epithelial cells. Stable knockdown (KD) of Endo II was achieved in two TNBC cell lines, and although cell viability was unaffected, defects in receptor-mediated endocytosis were observed. EGFR signaling to Erk and Akt kinases was impaired in Endo II KD cells, and this correlated with reduced rates of EGFR internalization and cell motility. Endo II KD cells also displayed defects in three dimensional (3D) cell invasion, and this correlated with impaired extracellular matrix degradation and internalization of MT1-MMP. Endo II silencing also caused a significant reduction in TNBC tumor growth and lung metastasis in mammary orthotopic tumor xenograft assays. In human breast tumor specimens, Endo II expression was highest in TNBC tumors compared with other subtypes, and at the level of gene expression, high Endo II was associated with reduced relapse-free survival in patients with basal-like breast cancers. Together, these results identify a positive role for Endo II in TNBC tumor metastasis and a potential link with poor prognosis., Implications: Endophilin A2 and related adaptor proteins represent important signaling hubs to target in metastatic cancers., (©2015 American Association for Cancer Research.)

Purpose: The purpose of this study was to evaluate currently preferred treatment strategies as well as the acceptance of new arthroscopic techniques among German orthopaedic surgeons. We assumed that surgeons specialized in shoulder surgery and arthroscopy would treat acute acromioclavicular joint dislocations different to non-specialized surgeons., Methods: Seven hundred and ninety-six orthopaedic and/or trauma departments were found through the German hospital directory of 2012. Corresponding websites were searched for the email address of the chair of shoulder surgery (if applicable) or the department. Seven hundred forty-six emails with the request for study participation including a link to an online survey of 36 questions were sent. In 60 emails, the recipient was unknown., Results: Two hundred and three (30 %) surgeons participated in the survey. one hundred and one were members of the AGA (German-speaking Society for Arthroscopy and Joint-Surgery) and/or of the DVSE (German Association of Shoulder and Elbow Surgery) and regarded as specialists, while 102 were non-members and regarded as non-specialists. According to the treatment of Rockwood I/II and IV-VI injuries, no significant differences were found. Seventy-four % of non-specialists and 67 % of specialists preferred surgical treatment for Rockwood III injuries (P = 0.046). Non-specialists would use the hook plate in 56 % followed by the TightRope in 16 %; specialists would use the TightRope in 38 % followed by the hook plate in 32 % (P = 0.004)., Conclusions: The majority of German orthopaedic and trauma surgeons advise surgical treatment for Rockwood III injuries. Specialists recommend surgery less often. Non-specialists prefer the hook plate, whereas specialists prefer the arthroscopic TightRope technique., Level of Evidence: Observational survey, Level IV.

Background: Among women worldwide, breast cancer is the most commonly diagnosed cancer, and the second leading cause of cancer-related deaths. Improved understanding of breast tumourigenesis may facilitate the development of more effective therapies. Peroxisome proliferator-activated receptor (PPAR)γ is a transcription factor that regulates genes involved in insulin sensitivity and adipogenesis. Previously, we showed, using 7,12-dimethylbenz [a] anthracene (DMBA)-treated haploinsufficient PPARγ mice, that PPARγ suppresses breast tumour progression; however, the PPARγ expressing cell types and mechanisms involved remain to be clarified. Here, the role of PPARγ expression and activation in mammary epithelial cells (MG) with respect to DMBA-mediated breast tumourigenesis was investigated., Methods: PPARγ MG knockout (PPARγ-MG KO) mice and their congenic, wild-type controls (PPARγ-WT) were treated once a week for six weeks by oral gavage with 1 mg DMBA dissolved in corn oil and maintained on a normal chow diet. At week 7, mice were randomly divided into those maintained on a normal chow diet (DMBA Only; PPARγ-WT: n = 25 and PPARγ-MG KO: n = 39) or those receiving a diet supplemented with the PPARγ ligand, rosiglitazone (ROSI, 4 mg/kg/day) (DMBA + ROSI; PPARγ-WT: n = 34 and PPARγ-MG KO: n = 17) for the duration of the 25-week study., Results: Compared to DMBA Only-treated PPARγ-WTs, both breast tumour susceptibility and serum levels of proinflammatory and chemotactic cytokines, namely IL-4, eotaxin, GM-CSF, IFN-γ, and MIP-1α, were decreased among PPARγ-MG KOs. Cotreatment with ROSI significantly reduced breast tumour progression among PPARγ-WTs, correlating with increased BRCA1 and decreased VEGF and COX-2 protein expression levels in breast tumours; whereas, surprisingly DMBA + ROSI-treated PPARγ-MG KOs showed increased breast tumourigenesis, correlating with activation of COX-2., Conclusion: These novel data suggest MG-specific PPARγ expression and signaling is critical during breast tumourigenesis, and may serve as a strong candidate predictive biomarker for response of breast cancer patients to the use of therapeutic strategies that include PPARγ ligands.