Cas12a2 elicits abortive infection through RNA-triggered destruction of dsDNA.

Bacterial abortive-infection systems limit the spread of foreign invaders by shutting down or killing infected cells before the invaders can replicate1,2. Several RNA-targeting CRISPR-Cas systems (that is, types III and VI) cause abortive-infection phenotypes by activating indiscriminate nucleases3-5. However, a CRISPR-mediated abortive mechanism that leverages indiscriminate DNase activity of an RNA-guided single-effector nuclease has yet to be observed. Here we report that RNA targeting by the type V single-effector nuclease Cas12a2 drives abortive infection through non-specific cleavage of double-stranded DNA (dsDNA). After recognizing an RNA target with an activating protospacer-flanking sequence, Cas12a2 efficiently degrades single-stranded RNA (ssRNA), single-stranded DNA (ssDNA) and dsDNA. Within cells, the activation of Cas12a2 induces an SOS DNA-damage response and impairs growth, preventing the dissemination of the invader. Finally, we harnessed the collateral activity of Cas12a2 for direct RNA detection, demonstrating that Cas12a2 can be repurposed as an RNA-guided RNA-targeting tool. These findings expand the known defensive abilities of CRISPR-Cas systems and create additional opportunities for CRISPR technologies.

No effect of dislocation status at arrival in emergency department on outcome of knee joint dislocations.

PURPOSE: Knee dislocation is a rare but severe injury of the lower extremities. The aim of this study was to report on the epidemiology, diagnostics and treatment of such injuries and to identify negative predictors of clinical outcomes. METHODS: This retrospective analysis included all knee dislocations treated at a Level I Trauma Centre in Germany between 2009 and 2021. Medical records were categorised, collected and analysed in a standardised manner. A follow-up visit 1 year after the injury focused on limitations in knee mobility. RESULTS: A total of 120 knee dislocations were included in the study. 29.3% of patients presented to the emergency department with a dislocated joint, and 17.5% (n = 21) had a neurovascular lesion. At follow-up 12 months after the injury, 65.8% of the patients reported limitations in the range of motion, and 11.7% (n = 14) reported severe limitations in daily activities. Site infections due to surgery occurred in 3.3% of patients. Increased body weight (r = 0.294; p < 0.001 and r = 0.259; p = 0.004), an increased body mass index above 25 kg/m2 (body mass index, r = 0.296; p < 0.001 and r = 0.264; p = 0.004) and deficits in peripheral perfusion as well as sensory and motor function (r = 0.231; p = 0.040 and r = -0.192; p = 0.036) were found to be negative predictive factors for clinical outcome. For posttraumatic neurovascular injury, lack of peripheral perfusion, insufficient sensory and motor function (r = -0.683; p < 0.0001), as well as a higher Schenck grade (r = 0.320; p = 0.037), were identified as independent risk factors. The status of dislocation at the site of the accident and on arrival at the emergency department had no impact on the outcome or neurovascular injury. CONCLUSION: Knee dislocation is a rare injury with a high rate of severe complications such as neurovascular lesions. In particular, the initial status of neurovascular structures and injury classification showed a relevant negative correlation with the posttraumatic status of nerves and vessels. In particular, patients with these characteristics need close monitoring to prevent negative long-term consequences. LEVEL OF EVIDENCE: Level III.

A Multicenter Longitudinal MRI Study Assessing LeMan-PV Software Accuracy in the Detection of White Matter Lesions in Multiple Sclerosis Patients.

BACKGROUND: Detecting new and enlarged lesions in multiple sclerosis (MS) patients is needed to determine their disease activity. LeMan-PV is a software embedded in the scanner reconstruction system of one vendor, which automatically assesses new and enlarged white matter lesions (NELs) in the follow-up of MS patients; however, multicenter validation studies are lacking. PURPOSE: To assess the accuracy of LeMan-PV for the longitudinal detection NEL white-matter MS lesions in a multicenter clinical setting. STUDY TYPE: Retrospective, longitudinal. SUBJECTS: A total of 206 patients with a definitive MS diagnosis and at least two follow-up MRI studies from five centers participating in the Swiss Multiple Sclerosis Cohort study. Mean age at first follow-up = 45.2 years (range: 36.9-52.8 years); 70 males. FIELD STRENGTH/SEQUENCE: Fluid attenuated inversion recovery (FLAIR) and T1-weighted magnetization prepared rapid gradient echo (T1-MPRAGE) sequences at 1.5 T and 3 T. ASSESSMENT: The study included 313 MRI pairs of datasets. Data were analyzed with LeMan-PV and compared with a manual "reference standard" provided by a neuroradiologist. A second rater (neurologist) performed the same analysis in a subset of MRI pairs to evaluate the rating-accuracy. The Sensitivity (Se), Specificity (Sp), Accuracy (Acc), F1-score, lesion-wise False-Positive-Rate (aFPR), and other measures were used to assess LeMan-PV performance for the detection of NEL at 1.5 T and 3 T. The performance was also evaluated in the subgroup of 123 MRI pairs at 3 T. STATISTICAL TESTS: Intraclass correlation coefficient (ICC) and Cohen's kappa (CK) were used to evaluate the agreement between readers. RESULTS: The interreader agreement was high for detecting new lesions (ICC = 0.97, Pvalue < 10-20 , CK = 0.82, P value = 0) and good (ICC = 0.75, P value < 10-12 , CK = 0.68, P value = 0) for detecting enlarged lesions. Across all centers, scanner field strengths (1.5 T, 3 T), and for NEL, LeMan-PV achieved: Acc = 61%, Se = 65%, Sp = 60%, F1-score = 0.44, aFPR = 1.31. When both follow-ups were acquired at 3 T, LeMan-PV accuracy was higher (Acc = 66%, Se = 66%, Sp = 66%, F1-score = 0.28, aFPR = 3.03). DATA CONCLUSION: In this multicenter study using clinical data settings acquired at 1.5 T and 3 T, and variations in MRI protocols, LeMan-PV showed similar sensitivity in detecting NEL with respect to other recent 3 T multicentric studies based on neural networks. While LeMan-PV performance is not optimal, its main advantage is that it provides automated clinical decision support integrated into the radiological-routine flow. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Diagnostic imaging strategies of acute intracerebral hemorrhage in European academic hospitals-a decision-making analysis.

PURPOSE: To evaluate and compare which factors are relevant to the diagnostic decision-making and imaging workup of intracerebral hemorrhages in large, specialized European centers. METHODS: Expert neuroradiologists from ten large, specialized centers (where endovascular stroke treatment is routinely performed) in nine European countries were selected in cooperation with the European Society of Neuroradiology (ESNR). The experts were asked to describe how and when they would investigate specific causes in a patient who presented with an acute, atraumatic, intracerebral hemorrhage for two given locations: (1) basal ganglia, thalamus, pons or cerebellum; (2) lobar hemorrhage. Answers were collected, and decision trees were compared. RESULTS: Criteria that were considered relevant for decision-making reflect recommendations from current guidelines and were similar in all participating centers. CT Angiography or MR angiography was considered essential by the majority of centers regardless of other factors. Imaging in clinical practice tended to surpass guideline recommendations and was heterogeneous among different centers, e.g., in a scenario suggestive of typical hypertensive hemorrhage, recommendations ranged from no further follow-up imaging to CT angiography and MR angiography. In no case was a consensus above 60% achieved. CONCLUSION: In European clinical practices, existing guidelines for diagnostic imaging strategies in ICH evaluation are followed as a basis but in most cases, additional imaging investigation is undertaken. Significant differences in imaging workup were observed among the centers. Results suggest a high level of awareness and caution regarding potentially underlying pathology other than hypertensive disease.

Reduced performance after return to competition in ACL injuries: an analysis on return to competition in the 'ACL registry in German Football'.

PURPOSE: ACL injuries are one of the most severe injuries in football, but medical consequences and performance outcomes after return to competition are only rarely investigated. Aim of this study was to analyse the time of return to competition (RTC) in German professional, semi-professional and amateur football. Also, this investigation highlights the rate of career ending and performance outcome after RTC in different playing levels by the measurement of playing level, performed matches and played minutes. METHODS: Database of this investigation is the 'ACL registry in German Football' with prospectively collected injury data. Between 2014 and 2018, four seasons in professional (1st-3rd league), semi-professional (4th-6th league) and amateur leagues (7th league) were analysed regarding the return to competition period and performance parameters. Data were collected for three subsequent seasons after injury and compared with the pre-injury and injury season. Data collection was performed using standardized methods. RESULTS: A total of 607 ACL injuries were registered during the 4-year period with a mean RTC time of 337.1 day (SD: 183). After primary ACL ruptures, the fastest RTC was found in professional football (247.3 days), while in semi-professional (333.5 d; p < 0.0001) and amateur football (376.2 d; p < 0.0001) a prolonged absence was detected. Re-ruptures occurred in 17.8% (n = 108) and showed similar trend with fastest RTC in professionals (289.9 days; p = 0.002). Within the first three seasons after injury, 92 players (36.7%) in semi-professional and 24 (20%) in professionals had to end their career. Keeping the level of play was only possible for 48 (47.5%) of professionals, while only 47 (29.6%) of semi-professionals and 43 (28.1%) of amateurs were able to. Only in professional football, no significant difference could be seen in the played minutes and games after 2 years compared to the pre-injury season. CONCLUSION: Lower playing levels and re-ruptures are the main factors for a prolonged return to competition after ACL rupture in German football. Significant reduction in playing level and a high rate of career endings were found for all levels of play. However, only professional players were able to regain their playing minutes and games 2 years after injury, while lower classed athletes did not reach the same amount within 3 years. LEVEL OF EVIDENCE: Level III.

Incidence and treatment of intracapsular femoral neck fractures in Germany.

INTRODUCTION: Intracapsular femoral neck fractures are one of the most common fractures in Germany. Nevertheless, the epidemiology and treatment modalities are not described comprehensively. For this reason, this study highlights the epidemiology of femoral neck fractures in different age groups and summarizes treatment strategies within the period from 2009 to 2019 based on nationwide data. MATERIALS AND METHODS: In this retrospective cohort study all cases of intracapsular femoral neck fractures (ICD-10: S72.0) between 2009 and 2019 in Germany were analyzed with regard to epidemiology, incidence and treatment. Operation and procedure classification system (OPS)- codes in combination with intracapsular femoral neck fracture as main diagnosis were taken to investigation. Data was provided by the Federal Statistical Office of Germany (Destatis). RESULTS: A total of 807,834 intracapsular femoral neck fractures with a mean incidence of 110.0 per 100,000 inhabitants annually was detected within eleven years. In 68.8% of all fractures patients were female. Most patients were older than 70 years (82.4%), and 56.7% were older than 80 years. The overall increase of fracture numbers between 2009 and 2019 was 23.2%. Joint replacement has been most often performed (80.4%). Hemiarthroplasty (56.8%) and total hip arthroplasty (22.8%) were the most common procedures with an increase of 27.1 and 38.6%, respectively. The proportion of cemented hemiarthroplasties was 86.2% while 51.3% of all total hip arthroplasties were totally or partially cemented. Osteosyntheses were mainly conducted using dynamic compression screws (34.0%), conventional screws (31.3%) and nails (22.2%). CONCLUSION: The incidence of intracapsular femoral neck fractures in Germany has been increasing continuously within the last decade. In particular, patients over 80 years suffered predominantly from this type of fracture. The majority was treated with a joint replacement procedure, mainly cemented hemiarthroplasty.

Endovascular Treatment for Acute Ischemic Stroke With or Without General Anesthesia: A Matched Comparison.

BACKGROUND: Endovascular treatment in large artery occlusion stroke reduces disability. However, the impact of anesthesia type on clinical outcomes remains uncertain. METHODS: We compared consecutive patients in the Swiss Stroke Registry with anterior circulation stroke receiving endovascular treatment with or without general anesthesia (GA). The primary outcome was disability on the modified Rankin Scale after 3 months, analyzed with ordered logistic regression. Secondary outcomes included dependency or death (modified Rankin Scale score ≥3), National Institutes of Health Stroke Scale after 24 hours, symptomatic intracranial hemorrhage with ≥4 points worsening on National Institutes of Health Stroke Scale within 7 days, and mortality. Coarsened exact matching and propensity score matching were performed to adjust for indication bias. RESULTS: One thousand two hundred eighty-four patients (GA: n=851, non-GA: n=433) from 8 Stroke Centers were included. Patients treated with GA had higher modified Rankin Scale scores after 3 months than patients treated without GA, in the unmatched (odds ratio [OR], 1.75 [1.42-2.16]; P<0.001), the coarsened exact matching (n=332-524, using multiple imputations of missing values; OR, 1.60 [1.08-2.36]; P=0.020), and the propensity score matching analysis (n=568; OR, 1.61 [1.20-2.15]; P=0.001). In the coarsened exact matching analysis, there were no significant differences in National Institutes of Health Stroke Scale after 1 day (estimated coefficient 2.61 [0.59-4.64]), symptomatic intracranial hemorrhage (OR, 1.06 [0.30-3.75]), dependency or death (OR, 1.42 [0.91-2.23]), or mortality (OR, 1.65 [0.94-2.89]). In the propensity score matching analysis, National Institutes of Health Stroke Scale after 24 hours (estimated coefficient, 3.40 [1.76-5.04]), dependency or death (OR, 1.49 [1.07-2.07]), and mortality (OR, 1.65 [1.11-2.45]) were higher in the GA group, whereas symptomatic intracranial hemorrhage did not differ significantly (OR, 1.77 [0.73-4.29]). CONCLUSIONS: This large study showed worse functional outcome after endovascular treatment of anterior circulation stroke with GA than without GA in a real-world setting. This finding appears to be independent of known differences in patient characteristics between groups.

Higher risk of ACL rupture in amateur football compared to professional football: 5-year results of the 'Anterior cruciate ligament-registry in German football'.

PURPOSE: Anterior cruciate ligament (ACL) injuries are a common severe type of football injury at all levels of play. A football-specific ACL registry providing both prospective ACL injury data according to the skill level and risk factors for ACL injury is lacking in the literature. METHODS: This study is based on the prospective 'ACL registry in German Football' implemented in the 2014-15 season. Professional (1st-3rd league), semi-professional (4th-6th league) and amateur leagues (7th league) were analysed regarding the incidence and risk factors for ACL injuries. Injuries were registered according to the direct reports of the injured players to the study office and double-checked via media analysis. After injury registration, the players received a standardised questionnaire. Data were analysed from the 2014-15 to the 2018-19 football season. RESULTS: Overall, 958 ACL injuries were registered during the 5-year study period. The incidence of ACL injuries was highest in amateur football (0.074/1000 h football exposure) compared to professional (0.058/1000 h; p < 0.0001) and semi-professional football (0.043/1000 h; p < 0.0001). At all skill levels, match incidence (professional: 0.343; semi-professional: 0.249; amateur: 0.319) was significantly higher than training incidence (professional: 0.015; semi-professional: 0.004; amateur: 0.005). Major risk factors were previous ACL injury (mean: 23.3%), other knee injuries (mean: 19.3%) and move to a higher league (mean: 24.2%). CONCLUSION: This sports-specific ACL registry provides detailed information on the incidence and risk factors for ACL injuries in football over five years. Risk factors are skill level, match exposure, move to a higher league and previous knee injury. These factors offer potential starting points for screening at-risk players and applying targeted prevention. LEVEL OF EVIDENCE: II.

Do directional deep brain stimulation leads rotate after implantation?

BACKGROUND: The two middle contacts of directional leads (d-leads) for deep brain stimulation are split into three segments, allowing current steering toward desired axial directions. To facilitate programming, their final orientation needs to be reliably determined. However, it is currently unclear whether d-leads rotate after implantation. Our objective was to assess the degree of d-lead rotation after implantation. METHODS: We retrospectively analyzed d-lead orientation on intraoperative X-rays, postoperative CT scans (latencies to surgery: 108-189 min postoperatively), and rotational fluoroscopies (4-9 days postoperatively) for a consecutive series of 32 implanted d-leads. For five d-leads, a CT scan with a mean follow-up of 57 days (range 28-182) was available. All d-leads were implanted with the marker facing anterior and the intention to hit an "iron sight" (ISi) on the X-ray, indicating anterior orientation (i.e., 0° ± 6°). RESULTS: In nine d-leads, an ISi was visible on the final X-ray; median orientation was 1.5° (range 0.5-6.0°) at the first follow-up CT, confirming anterior orientation. In d-leads without ISi or where ISi was not evaluable, the median rotation was 15.5° (9.5-35.0°) and 26.5° (5.5-62.0°), respectively. The orientation of the initial CT was comparable with the orientation determined by the postoperative rotational fluoroscopy and second CT in all d-lead groups. CONCLUSION: D-lead orientation does not change within the first week after implantation. We provide first indications that d-lead orientation remains stable for several weeks after surgery. Determination of lead orientation using marker-based X-ray alone seems too imprecise; adding the ISi method can increase determination of intraoperative orientation.

Large Hemorrhagic Extrascleral Ciliary Body Melanoma Recurrence Treated With Transarterial Embolization and Coiling Followed by Exenteration.

A 59-year-old male patient who suffered from a systemically metastasized, large extrascleral uveal melanoma recurrence of the left eye presented with active hemorrhage from the tumor. He had undergone proton beam irradiation for an epithelioid ciliary body melanoma 4 years before presentation and was lost to follow-up. Magnetic resonance angiography showed vascularization of the lesion via the ophthalmic and maxillary artery. Selective transarterial embolization of the tumor was conducted with polyvinyl alcohol microparticles followed by coiling of the supplying arteries. The bleeding stopped after 2 days and the tumor started to become necrotic. As tumor removal was the primary wish of the patient at this point in time, exenteration was carried out a week later without significant blood loss, intraoperative or postoperative complications. Socket healing was adequate, and the patient reported improved quality of life. He refused systemic palliative treatment and died 3 months after the intervention.

Changes of Material Elastic Properties during Healing of Ruptured Achilles Tendons Measured with Shear Wave Elastography: A Pilot Study.

Therapy options for ruptured Achilles tendons need to take into account the right balance of timing, amount and intensity of loading to ensure a sufficient biomechanical resilience of the healing tendon on the one hand, and to enable an adequate tensile stimulus on the other hand. However, biomechanical data of human Achilles tendons after rupture during the separate healing stages are unknown. Shear wave elastography is an ultrasound technique that measures material elastic properties non-invasively, and was proven to have a very good correlation to biomechanical studies. Taking advantage of this technology, 12 patients who suffered from an acute Achilles tendon rupture were acquired and monitored through the course of one year after rupture. Nine of these patients were treated non-operatively and were included for the analysis of biomechanical behaviour. A significant increase of material elastic properties was observed within the first six weeks after trauma (up to 80% of baseline value), where it reached a plateau phase. A second significant increase occurred three to six months after injury. This pilot study suggests a time correlation of biomechanical properties with the biological healing phases of tendon tissue. In the reparative phase, a substantial amount of biomechanical resilience is restored already, but the final stage of biomechanical stability is reached in the maturation phase. These findings can potentially be implemented into treatment and aftercare protocols.

Feasibility, safety, and outcome of recanalization treatment in childhood stroke.

OBJECTIVE: Intravenous thrombolysis and endovascular therapy (IVT/EVT) are evidence-based treatments for adults with arterial ischemic stroke (AIS). However, randomized controlled trials in pediatric patients are lacking. This study aimed to describe feasibility, safety, and outcome of IVT/EVT in children with AIS. METHODS: This retrospective study (01/2000-12/2015) included a multicenter, population-based consecutive cohort of patients aged 1 month to 16 years, diagnosed with AIS and presenting with pediatric National Institutes of Health Stroke Scale (pedNIHSS) ≥ 4. Clinical and radiological data of patients receiving IVT/EVT were compared to those receiving standard care (SC) using linear regression to adjust for potential confounders. EVT included intra-arterial thrombolysis and/or mechanical thrombectomy. Outcome was assessed 6 months after stroke using the pediatric stroke outcome measure (PSOM). RESULTS: Overall, 150 patients (age 7.1 ± 4.9 years, 55 [37%] females) presented with pedNIHSS ≥ 4. Recanalization treatment was performed in 16 (11%), of whom 5 (3%) were treated with IVT and 11 (7%) with EVT. Patients receiving recanalization treatment were older (mean age = 11.0 vs 6.9 years, p = 0.01) and more severely affected (median pedNIHSS = 13.5 vs 8.0, p < 0.001). Death and bleeding complications did not differ between the 2 groups. Median (interquartile range) PSOM 6 months after AIS was 2.5 (1-4.3) and 1 (0-2) in the IVT/EVT and SC groups, respectively (p = 0.014). However, after multiple linear regression analysis, only higher baseline pedNIHSS remained associated with an unfavorable outcome (p < 0.001). INTERPRETATION: Recanalization treatment is feasible and seems to be safe in severely affected pediatric AIS patients. The assessment of efficacy of IVT/EVT in pediatric stroke patients requires larger studies. Ann Neurol 2018;83:1125-1132.

Interleukin 1 Receptor Antagonist Anakinra, Intravenous Immunoglobulin, and Corticosteroids in the Management of Critically Ill Adult Patients With Hemophagocytic Lymphohistiocytosis.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) causes multiple organ dysfunction frequently leading to intensive care unit (ICU) referral and/or death. We report on a series of critically ill adult patients treated with a non-etoposide-based regimen including interleukin 1 antagonist anakinra, intravenous immunoglobulin (IVIG), and/or corticosteroids (CS) for HLH. METHODS: Eight adult (≥18 years) ICU patients having received treatment with anakinra ± IVIG ± CS for HLH between March 2014 and March 2016 at a large tertiary care university hospital (Medical University of Vienna, Vienna, Austria) were retrospectively analyzed. RESULTS: Eight patients (median age: 38 years; range: 20-58 years; 4 males and 4 females) received anakinra together with IVIG (n = 7) and/or high-dose CS (n = 5) for suspected reactive HLH (median H-score: 214; range: 171-288). Seven (88%) patients required vasopressors and invasive mechanical ventilation and 6 (75%) patients required renal replacement therapy (median Sequential Organ Failure Assessment [SOFA] score at HLH diagnosis: 9.5; range: 6-14). Six patients showed a significant decline in the SOFA score at 1 and 2 weeks following treatment initiation (P = .03), and the remainder 2 patients experienced early death. Five patients survived to ICU discharge, 4 of them could further be discharged from hospital (hospital survival rate: 50%). No overt treatment-related toxicity was noted. CONCLUSION: Anakinra in combination with IVIG and/or CS resulted in a hospital survival rate of 50% in 8 critically ill adult patients with HLH despite a vast degree of organ dysfunction and the need for aggressive ICU treatment. Further research on non-etoposide-based treatment strategies for HLH in critically ill adults is warranted.

Risk factor analysis for delayed union after subtrochanteric femur fracture: quality of reduction and valgization are the key to success.

BACKGROUND: Subtrochanteric femur fractures (SFF) are uncommon, but have a high complication rate concerning non-union and mechanical complications. There is ongoing discussion about risk factors for delayed fracture healing after SFF. The purpose of this study was to evaluate potential risk factors for delayed fracture healing after SFF. METHODS: This retrospective radio-morphometric case control study compares 61 patients after SFF in two groups (uncomplicated healing within 6 months postoperatively vs. delayed union) concerning radiographical properties. The patients were analyzed concerning the following parameter: Quality of the reduction according to Baumgaertner, CCD-angle, Tip-Apex Distance, leg-length shortening and fracture healing according to the RUSH Score. RESULTS: The mean RUSH-Score at 6 months postoperatively was 21.32(±4.57). At that point of time, only 29/61 fractures were radiographically fully consolidated (timely fracture healing) and 32 patients were rated as delayed union. The total revision rate was 9/61 (14.7%), whereof four patients required revision for symptomatic non-union of the SFF. The results of the radio-morphometric measurement showed a significant difference between both groups concerning the degree of reduction measured according to Baumgaertner (p = 0.022). The postoperative ipsilateral CCD-angle was different between the two groups (p = 0.019). After 12 months postoperatively, 48/61 (78.6%) of fractures were rated healed without any further intervention. CONCLUSIONS: Delayed union after SFF occurs frequently. In our patient population, the quality of reduction and the postoperative CCD-angle were the key factors to avoid delayed union. LEVEL OF EVIDENCE: Level III, Therapeutic study. TRIAL REGISTRATION: Clinical Trial Registry University of Regensburg Z-2018-1074-1. Registered 04. Aug 2018. https://studienanmeldung.zks-regensburg.de.

Bone Marrow Aspirate Concentrate for the Treatment of Avascular Meniscus Tears in a One-Step Procedure-Evaluation of an In Vivo Model.

Avascular meniscus tears show poor intrinsic regenerative potential. Thus, lesions within this area predispose the patient to developing knee osteoarthritis. Current research focuses on regenerative approaches using growth factors or mesenchymal stem cells (MSCs) to enhance healing capacity within the avascular meniscus zone. The use of MSCs especially as progenitor cells and a source of growth factors has shown promising results. However, present studies use bone-marrow-derived BMSCs in a two-step procedure, which is limiting the transfer in clinical praxis. So, the aim of this study was to evaluate a one-step procedure using bone marrow aspirate concentrate (BMAC), containing BMSCs, for inducing the regeneration of avascular meniscus lesions. Longitudinal meniscus tears of 4 mm in size of the lateral New Zealand White rabbit meniscus were treated with clotted autologous PRP (platelet-rich plasma) or BMAC and a meniscus suture or a meniscus suture alone. Menisci were harvested at 6 and 12 weeks after initial surgery. Macroscopical and histological evaluation was performed according to an established Meniscus Scoring System. BMAC significantly enhanced regeneration of the meniscus lesions in a time-dependent manner and in comparison to the PRP and control groups, where no healing could be observed. Treatment of avascular meniscus lesions with BMAC and meniscus suturing seems to be a promising approach to promote meniscus regeneration in the avascular zone using a one-step procedure.

Investigation of Bistetramethylammonium Hydrogencyclotriphosphate-A Molecular Rotor?

The crystalline phase ß-[N(CH3 )4 ]2 HP3 O9 undergoes a reversible phase transition to γ-[N(CH3 )4 ]2 HP3 O9 , which was studied by dynamic scanning calorimetry and X-ray diffraction. The rotational dynamics of the anion [P3 O9 ]3- were evident from variable temperature 31 P magic angle spinning (MAS) NMR spectroscopy. The rotational dynamics could be simulated with a 3-site jump model, which yields spectra in good agreement with experiment. An activation energy of 0.6 eV could be estimated from line shape analysis. Impedance spectra reflect a bulk proton conductivity of γ-[N(CH3 )4 ]2 HP3 O9 of 6.9×10-5  S cm-1 at 240 °C and an activation energy of approximately 1.0 eV. Thus this salt features bulk protonic motion, while local rotational anionic motion happens with activation energies of the same order, as suggested by the paddle-wheel mechanism.

Injury mechanism of midfacial fractures in football causes in over 40% typical neurological symptoms of minor brain injuries.

PURPOSE: The injury mechanisms of midfacial fractures may be typical causes of concussion, but hardly any scientific data on midfacial injuries sustained in football are available. Head and brain trauma represent frequent injuries in athletes of different sports that require appropriate treatment by sports and trauma physicians. This study investigated the management of midfacial fractures in football and the association of such fractures with concomitant brain injury. METHODS: In a prospective cohort study lasting 24 months (2012 to 2013), midfacial injuries of football players were analysed with regard to the injury mechanisms, first aid procedures on the field, treatment and return-to-play. To analyse concomitant and potentially overlooked minor brain injuries due to the trauma, we retrospectively investigated the neurological symptoms of the study population. RESULTS: The study included 132 football players (37 semi-professionals and 95 amateurs) with midfacial fractures. The main injury mechanisms were head-to-head and head-to-elbow trauma. The mean period of return-to-play after trauma was 33.5 days, which was significantly shortened if a protective face mask was worn (mean 10.4 days earlier, p = 0.0006). Semi-professional football players returned to play earlier (p = 0.009) and more often used protective face masks (p = 0.001). 55 players (41.6%) had neurological symptoms immediately after trauma as a possible sign of concomitant minor brain injury. 5 of 132 players with concussion had been hospitalised for 24 h, but no persistent neurological symptoms were detected. CONCLUSION: In football, midfacial fractures represent moderate-to-severe injuries with time away from sports of more than 4 weeks. Over 40% of athletes with a midfacial fracture showed concomitant neurological symptoms as a sign of minor brain injury. Therefore, sports physicians and other staff supervising athletes in daily practice should be aware of the presence of neurological symptoms. LEVEL OF EVIDENCE: Level III.

Neuromuscular exercises prevent severe knee injury in adolescent team handball players.

PURPOSE: Team handball is associated with a high risk of severe knee injury that needs to be reduced, particularly at the youth level. The purpose of this study was to show how an injury-prevention programme effectively reduces severe knee injury in adolescent team handball players. METHODS: Of 23 adolescent handball teams of both sexes, 13 were randomly allocated into the intervention group (168 players) and 10 into the control group (111 players). Players of the intervention group regularly participated in an injury-prevention programme for one season. Handball exposure and sustained injuries were documented for both groups on a monthly basis. The primary outcome parameter of the injury-prevention programme was the incidence of severe knee injury. RESULTS: Of the 279 included players, 68 (24%) sustained 82 injuries yielding an overall incidence of 1.85 injuries per 1000 h handball exposure (intervention group: 50 injuries/incidence: 1.90/1000 h; control group: 32 injuries/incidence: 1.78/1000 h). Knee injury was the second most frequent injury in adolescent team handball. The primary outcome parameter, severe knee injury occurred significantly more often in the control group [mean age (SD) 15.1 (1.0), injury incidence 0.33/1000 h] than in the intervention group [mean age (SD) 14.9 (0.9), injury incidence 0.04/1000 h]. The odds ratio was 0.11 (95% CI 0.01-0.90), p = 0.019. Other injuries to the lower extremities showed no significant difference between the two groups. CONCLUSIONS: Frequent neuromuscular exercises prevent severe knee injury in adolescent team handball players and should thus be included in the practical routine as well as in the education of team coaches.

Diverging lesion and connectivity patterns influence early and late swallowing recovery after hemispheric stroke.

Knowledge about the recovery of oral intake after hemispheric stroke is important to guide therapeutic decisions, including the administration of enteral tube feeding and the choice of the appropriate feeding route. They aimed to determine the localization and connectivity of lesions in impaired recovery versus recovered swallowing after initially dysphagic stroke. Sixty-two acute ischemic hemispheric stroke patients with impaired oral intake were included in a prospective observational cohort study. Voxel-based lesion-symptom mapping and probabilistic tractography were used to determine the association of lesion location and connectivity with impaired recovery of oral intake ≥7 days (indication for early tube feeding) and ≥4 weeks (indication for percutaneous endoscopic gastrostomy feeding) after stroke. Two distinct patterns influencing recovery of swallowing were recognized. Firstly, impaired recovery of oral intake after ≥7 days was significantly associated with lesions of the superior corona radiata (65% of statistical map, P < 0.05). The affected fibers were connected with the thalamus, primary motor, and supplemental motor areas and the basal ganglia. Secondly, impaired recovery of oral intake after ≥4 weeks significantly correlated with lesions of the anterior insula (54% of statistical map, P < 0.05), which was connected to adjacent operculo-insular areas of deglutition. These findings indicate that early swallowing recovery is influenced by white matter lesions disrupting thalamic and corticobulbar projection fibers. Late recovery is determined by specific cortical lesions affecting association fibers. This knowledge may help clinicians to identify patients at risk of prolonged swallowing problems that would benefit from enteral tube feeding. Hum Brain Mapp 38:2165-2176, 2017. © 2017 Wiley Periodicals, Inc.

Joint awareness in posttraumatic osteoarthritis of the knee: validation of the forgotten joint score in long term condition after tibial plateau fracture.

BACKGROUND: Evaluating patient-reported outcomes (PRO) in early osteoarthritis (OA) of the knee is difficult. Established measurement tools are focused on one of the two major patient groups in knee surgery: young, highly active patients, or older patients with advanced degenerative OA of the knee. Joint awareness in everyday life is a crucial criterion in measuring PRO. The purpose of this study was to validate a German version of the "Forgotten Joint Score" (FJS) in patients after surgical treatment of tibial plateau fractures. METHODS: In this prospective cohort study, clinical and radiological outcomes data were collected from patients after surgical treatment of tibial plateau fractures following a skiing accident. Functional outcome questionnaires were administered including the FJS, the Lysholm-Score, the Tegner-Activity Scale (TAS), the EuroQol-5D (EQ 5-D), and a subjective rating of change. The validation study was carried out according to the COSMIN checklist protocol. The KLS was used to measure the presence and severity of OA on knee radiographs, and correlation with the FJS was measured. RESULTS: Cronbach's alpha was .96 (95%-CI .92, .99) confirming good internal consistency. Test-retest reliability of the FJS was high with an ICC(67) = .91 (95%-CI .85,.95). Furthermore, no relevant floor or ceiling effects were observed. FJS significantly differed in patients with different OA degrees (p = .041). Symptomatic patients had significant lower FJS than asymptomatic patients (p < .001). CONCLUSIONS: This is the first study validating a disease-specific PRO, the FJS, in long-term outcomes after joint fracture. We demonstrated good psychometric properties and a significant correlation between the FJS and the radiologic degree of OA in patients with a history of tibial plateau fracture. TRIAL REGISTRATION: Clinical Trial Registry University of Regensburg Z-2015-0872-2 . Registered 01. October 2015.