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Purpose: The purpose of this study was to prospectively evaluate the clinical and radiological results of double level osteotomy (distal femoral lateral closed wedge and proximal tibial medial open wedge) in medial osteoarthritis and varus malalignment due to bifocal deformity of femur and tibia. Methods: From 2017 to 2019 all cases of DLO in osteoarthritic varus malaligned knees with bifocal deformity (femoral and tibial deformity) were prospectively enrolled into this observational therapeutic study. Evaluation was performed preoperatively, at six, twelve, 18 and 24 months with regard to survival (not requiring arthroplasty), functional outcome [subjective International Knee Documentation Committee score (IKDC), Oxford Knee Score (OKS), Knee Injury and Osteoarthritis Outcome score (KOOS) and Tegner Activity Scale], pain level (numeric rating scale), subjective satisfaction (rating 1–5), radiographic parameters on a pre-and postoperative full leg x-rays (mechanical axis, mechanical proximal tibial and distal femoral angles) and complications. For statistical evaluation student's t test, Mann–Whitney U test and Wilcoxon-signed-rank test were used. Results: Fifty-two consecutive cases in 48 patients were enrolled in the study. Three cases were excluded, resulting in a follow-up rate of 94%. No arthroplasties were performed within follow-up. All functional outcome scores substantially and significantly increased as early as six months after the index procedure and further increased until final follow-up (p < 0.001). Pain level significantly decreased (p < 0.001). At final follow-up all patients stated that they would retrospectively undergo the operation again, and rated the result with 4.5 ± 0.6 out of 5 (3–5). Radiographic parameters were within physiological limits postoperatively. No severe complications occurred. Conclusions: Double level osteotomy has excellent short-term results while maintaining physiological radiographic parameters. Therefore, it should be an integral part and standard procedure in realignment surgery for monocompartimental osteoarthritis. Level of evidence: IV (prospective observational therapeutic study). [ABSTRACT FROM AUTHOR]

Background: The posterior tibial slope has been identified as an anatomic risk factor for anterior cruciate ligament insufficiency and reruptures after anterior cruciate ligament reconstruction. Anterior tibial closing wedge osteotomy for correction of sagittal plane deformities has the potential to cause an unintended change in coronal plane alignment. Purpose: To evaluate the effects of anterior tibial closing wedge osteotomies for correction of posterior tibial slope on coronal plane alignment using an infratuberosity surgical approach and to identify predictive factors for a change in medial proximal tibial angle (MPTA). Study Design: Case series; Level of evidence, 4. Methods: This study reports on retrospectively obtained data from radiographic measurements of 38 anterior tibial closing wedge osteotomies. All patients underwent revision anterior cruciate ligament reconstruction and had undergone ≥1 previous anterior cruciate ligament reconstruction. In all patients, an infratuberosity approach was used with angular stable plate fixation. Pre- and postoperative radiographs were examined retrospectively to detect changes in the sagittal and coronal plane alignment (posterior tibial slope and MPTA). A multivariate regression analysis was used to identify predictors for a change in MPTA. Results: The study group consisted of 14 women and 24 men whose mean ± SD age at the index procedure was 31.6 ± 8.7 years (range, 17-51 years). Posterior tibial slope decreased significantly (by 7.2° ± 2.3°; P <.001) from 14.6° ± 2.0° preoperatively to 7.4° ± 2.1° postoperatively. MPTA decreased significantly by 1.3° ± 1.5° (P =.005) from pre- to postoperative measurement. Mean wedge height was 9.3 ± 1.1 mm. A lower preoperative MPTA (coefficient = 0.32; P =.017; 95% CI, 0.06-0.59) and larger wedge height (coefficient = 0.48; P =.029; 95% CI, 0.05-0.9) were significant predictive factors for a decrease in MPTA. Conclusion: Anterior tibial closing wedge osteotomy for posterior tibial slope reduction resulted in a slight but significant decrease of the MPTA in the coronal plane. These changes were dependent on the preoperative MPTA and the wedge height. [ABSTRACT FROM AUTHOR]

Purpose: To determine the prevalence of an "increased posterior tibial slope (PTS)" (PTS ≥ 12°) in a population with one, two or ≥ three anterior cruciate ligament (ACL) graft insufficiencies. Furthermore, to investigate whether the prevalence of an increased PTS and the absolute PTS increases with an increasing number of ACL graft insufficiencies, as well as to determine the survival time of the first ACL graft. Methods: Patients diagnosed with an ACL graft insufficiency between January 2021 and March 2022 were included. The PTS was measured using the proximal anatomical tibial axis on long lateral knee radiographs. Patients were divided into 3 groups depending on the number of ACL graft insufficiencies: group A (1 graft insufficiency), group B (2 graft insufficiencies) and group C (≥ 3 graft insufficiencies). The prevalence of increased PTS and absolute PTS between groups was compared alongside the survival of the first ACL graft between patients with or without increased PTS. Results: Two-hundred and six patients (147 males/59 females) met the inclusion criteria. 73 patients showed an increased PTS [prevalence 35% [95% confidence interval (CI) (29%; 42%)]. 155 patients were found in category A, 42 patients in B and 9 patients in C. The prevalence of increased PTS for group A, B and C was, 32% [95% CI (25%; 40%)], 38% [95% CI (23%; 53%)] and 78% [95% CI (51%; 100%)], respectively. The prevalence of increased PTS and mean PTS did not increase significantly between group A and B. However, both parameters increased significantly between group A and C, and group B and C (p < 0.05). The survival time of the first ACL graft in patients with or without an increased PTS was 3 (interquartile range (IQR) 5) and 6 years (IQR 9), respectively (p < 0.05). Conclusion: There is a 35% prevalence of increased PTS in the studied ACL graft insufficient patient cohort. The survival of the first ACL graft is shorter in patients with an increased PTS. Surgeons should be aware of the high prevalence of increased PTS when consulting patients for revision ACL reconstruction as it is an important risk factor for recurrent instability. Level of evidence: 3. [ABSTRACT FROM AUTHOR]

Background: Medial patellofemoral ligament reconstruction in skeletally immature patients who experience lateral patellar dislocation has been reported to yield good results. Whether bony abnormalities such as patellar height and trochlear dysplasia should be addressed additionally is a topic of discussion. Purpose: To evaluate patient-reported outcomes and redislocation rates after isolated medial patellofemoral ligament reconstruction as first-line surgical treatment for lateral patellar dislocation in skeletally immature patients. Further, to analyze epidemiological, intraoperative, and radiographical factors influencing redislocation and clinical outcome. Study Design: Case series; Level of evidence, 4. Methods: Prospectively collected data were retrospectively analyzed for adolescent patients younger than 16 years who underwent medial patellofemoral ligament reconstruction between 2014 and 2018. Inclusion criteria were isolated medial patellofemoral ligament reconstruction with gracilis tendon and availability of accurate pre- and postoperative radiographs with the presence of open physes. The patients were questioned regarding further surgery, redislocation, and clinical outcomes using the Tegner Activity Scale, International Knee Documentation Committee (IKDC) Subjective Knee Form, Lysholm score, and Kujala score. The influence of diverse epidemiological, intraoperative, and radiographical parameters on the redislocation rates and clinical outcome was analyzed. Results: A total of 54 medial patellofemoral ligament reconstructions (49 patients) met the inclusion criteria. After 4.3 ± 1.7 years (range, 2.0-7.3 years), 45 reconstructions (83.3%) in 41 patients were available for follow-up. The distribution of trochlear dysplasia was as follows: type A and B, 19 cases (42.2%) each; type C, 6 cases (13.3%); and type D, 1 case (2.2%). Patellar redislocation occurred in 3 patients (6.7%). The mean Tegner, subjective IKDC, Lysholm, and Kujala scores at follow-up were 6.3 ± 1.6 (range, 3-9), 93.6 ± 8.8, 95.9 ± 7.4, and 97.9 ± 7.1, respectively. Patellar height and trochlear dysplasia had no influence on redislocation or clinical scores. The Lysholm score was lower in knees with intraoperative retropatellar chondral lesion grade ≥III versus grade

Introduction: Influenza is a major concern in hospitals, including the emergency department (ED), mainly because of a high risk for ED personnel to acquire and transmit the disease. Although influenza vaccination is recommended for health care workers, vaccination coverage is low. Methods: This survey was conducted in the 2016/2017 and 2020/2021 influenza seasons. Questionnaires were sent to ED personnel in 12 hospitals in Bavaria, South-Eastern Germany. The response rates were 62% and 38% in 2016/2017 and 2020/2021, respectively. Data were compared between the two seasons as well as between vaccinated and not vaccinated respondents in 2020/2021. Results: Significantly more ED personnel reported having been vaccinated in the 2020/2021 season. Factors associated with vaccination coverage (or the intention to get vaccinated) were profession (physician / medical student), having been vaccinated at least twice, the availability of an influenza vaccination on site (in the ED) as well as the COVID-19 pandemic. Additionally, significant differences in the assessment and evaluation of influenza, its vaccination side effects and ethical aspects were found between vaccinated and not vaccinated ED personnel in 2020/2021. Unvaccinated respondents estimated higher frequencies of almost all potential vaccination side effects, were less likely to accept lay-offs if employees would not come to work during an influenza pandemic and more likely to agree that work attendance should be an employee´s decision. Vaccinated participants instead, rather agreed that vaccination should be mandatory and were less likely to consider job changes in case of a mandatory vaccination policy. Conclusion: The COVID-19 pandemic might have contributed to a higher influenza vaccination rate among ED workers. Vaccination on site and interventions targeting the perception of influenza vaccination and its side effects may be most promising to increase the vaccination coverage among ED personnel. [ABSTRACT FROM AUTHOR]

Purpose: To determine and compare the incidence of post-operative septic arthritis following revision anterior cruciate ligament reconstruction (R-ACLR) with autologous quadriceps tendon (with patellar bone block) compared to autologous hamstring tendons (semitendinosus and gracilis). Methods: A total of 1638 isolated R-ACLR with either autologous hamstring tendons (n = 1004, 61.3%) or quadriceps tendon (n = 634; 38.7%) were performed between 2004 and 2017 and were retrospectively analysed with regard to the occurrence of post-operative septic arthritis. The technique of R-ACLR did not significantly change during the years of the study. All patients received pre-op i.v.antibiotics, but no presoaking of the grafts in vancomycin was performed in the years of the study. The individual decision of graft choice was based on graft availability, tunnel position and the presence of tunnel widening. Generally, hamstring tendons were preferred. There were no clinically relevant differences between the groups regarding gender or age. Routine follow-up examination was performed 6 weeks after the index operation (follow-up rate 96.5%), and patients unsuspicious for septic arthritis at that time were classified as non-infected. Results: Fourteen patients with septic arthritis were identified, resulting in an overall incidence of 0.85%. There was one patient with septic arthritis in the quadriceps tendon group (incidence: 0.16%) and 13 patients in the hamstring tendons group (incidence: 1.29%), respectively. The difference was significant (p = 0.013). Conclusion: In this series, the incidence of post-operative septic arthritis after R-ACLR was lower when quadriceps tendon graft was used compared to hamstring tendon grafts. Level of evidence: III. [ABSTRACT FROM AUTHOR]

Purpose: To analyse 1000 consecutive patients, treated with isolated or combined posterior cruciate ligament (PCL) reconstruction in a single centre according to the epidemiological factors and differences in injury patterns depending on the activity during trauma. Methods: Between 2004 and 2019, one thousand isolated and combined PCL reconstructions were performed. The medical charts and surgical reports of all patients were analysed regarding epidemiological factors. The PCL lesions were divided into isolated and combined lesions with at least one additional ligamentous injury. The influence of activity during accident and additional injury on the presence of isolated or combined lesions and injury patterns was calculated. Results: In 388 patients (38.8%), sporting activity was the main activity in PCL lesions, followed by traffic accidents in 350 patients (35.0%). Combined injuries were present in 227 patients (58.5%) with sports injuries and 251 patients (71.7%) with traffic accidents. Only during handball, an isolated PCL lesion (69.1%) was more common than a combined lesion. Highest rate of combined lesions was present in car accidents (91.7%). In all activities except skiing and biking, the most common additional peripheral injury was a tear of the posterolateral corner. In skiing and biking accidents, the most common additional peripheral lesion was a lesion of the medial collateral ligament. In patients with PCL lesion and additional fracture of the same lower extremity, a combined lesion was more common than an isolated lesion (p = 0.001). Conclusion: Combined PCL lesions are more common than isolated lesions, even in sports injuries (except handball). Incidence and injury pattern vary depending on activity during trauma. Main additional peripheral lesion is a lesion of the posterolateral corner, except biking and skiing accidents where a medial lesion is more common. Level of evidence: Level III. [ABSTRACT FROM AUTHOR]

Purpose: To determine and compare the incidence of postoperative septic arthritis following revision anterior cruciate ligament reconstruction (R-ACLR) with and without soaking of the graft in vancomycin solution prior to implantation in a large single-centre series.Methods: A total of 2155 isolated R-ACLR with autologous tendons were performed from 2004 to 2019 and were reviewed with regard to the occurrence of postoperative septic arthritis. From February 2017 onwards, all grafts were wrapped in a vancomycin-soaked (5 mg/ml) gauze swab between harvest and implantation (517 patients, treatment group (2), prospectively followed). These were compared to 1638 patients before that date (control group (1), retrospectively evaluated). The technique of R-ACLR did not significantly change during the years of the study. Hamstring tendons were used in 1310 patients (60.8%) and quadriceps tendons with patellar bone block were used in 845 patients (39.2%), respectively, with no difference between the groups (n.s.). Routine follow-up examination was performed 6 weeks postoperatively (follow-up rate 96.5%), and patients with no treatment for septic arthritis until that time were classified as non-infected.Results: There were 14 cases of postoperative septic arthritis in group 1 (incidence 0.9%), and none in group 2 (incidence 0.0%), respectively. The difference was significant (p = 0.029).Conclusion: Soaking of the graft in vancomycin solution prior to implantation dramatically reduces the incidence of postoperative septic arthritis in R-ACLR.Level Of Evidence: III. [ABSTRACT FROM AUTHOR]

Purpose: To determine survivorship and functional results of medial open-wedge high tibial osteotomy (HTO) combined with anterior cruciate ligament reconstruction (ACLR) and a chondral resurfacing (CR) procedure (abrasion/microfracture) in patients with Kellgren-Lawrence grade 3 and 4 osteoarthritis with full thickness-cartilage defects, ACL-insufficiency and varus alignment.Methods: A cohort of 23 patients undergoing a combined procedure of HTO (fixation with angular stable internal fixator, Tomofix®), ACLR and CR for the treatment of severe symptomatic medial osteoarthritis, ACL insufficiency and varus alignment (> 4°) between 2005 and 2009 was prospectively surveyed with a minimum follow-up of 10 years with regard to survival (not requiring arthroplasty), functional outcome (subjective IKDC score), pain level (numeric rating scale), Oxford Knee Score (OKS) and subjective satisfaction. The Wilcoxon signed-rank-test was used for statistical evaluation of non-parametric data in these related samples.Results: Twenty-one cases were included, one case with incomplete follow-up data and another case excluded. The follow-up rate was 91% at 12.0 ± 1.0 years (10.0-13.4). Mean age at time of surgery was 47.3 ± 5.9 years (37.8-57.7). At final follow-up, no arthroplasty was performed in any of the cases (survival: 100%). Subjective IKDC score improved from 47 ± 11 to 75 ± 15 at 1, 72 ± 15 at 3, 73 ± 17 at 6 years and 70 ± 16 at final follow-up (p < 0.001), respectively. At final follow-up the OKS was 40 ± 7 (17-48) and pain-level significantly decreased from 7.5 ± 1.0 preoperatively to 2.9 ± 2.3 (p < 0.001) at final follow-up. All patients were satisfied with the result and stated that they would retrospectively undergo the procedure again.Conclusion: A combined approach of HTO, ACLR and a CR shows excellent results in a long-term follow-up in selected young patients even in severe osteoarthritis. However, the role and potential benefit of the ACLR and CR compared to HTO alone remains unclear.Level Of Evidence: Therapeutic case series, Level IV. [ABSTRACT FROM AUTHOR]

Effect handlers are a promising way to structure effectful programs in a modular way. We present the Scala library Effekt, which is centered around capability passing and implemented in terms of a monad for multi-prompt delimited continuations. Effekt is the first library implementation of effect handlers that supports effect safety and effect polymorphism without resorting to type-level programming. We describe a novel way of achieving effect safety using intersection types and path-dependent types. The effect system of our library design fits well into the programming paradigm of capability passing and is inspired by the effect system of Zhang & Myers (2019, Proc. ACM Program. Lang.3(POPL), 5:1-5:29). Capabilities carry an abstract type member, which represents an individual effect type and reflects the use of the capability on the type level. We represent effect rows as the contravariant intersection of effect types. Handlers introduce capabilities and remove components of the intersection type. Reusing the existing type system of Scala, we get effect subtyping and effect polymorphism for free. [ABSTRACT FROM AUTHOR]

Purpose: To clinically evaluate an arthroscopic autologous chondrocyte implantation (ACI) technique with an in situ crosslinking matrix for the treatment of full thickness cartilage defects of the knee and to present histological results of a graft cartilage biopsy obtained after 1.5 years.Methods: Fifteen cases of arthroscopic autologous chondrocyte implantation in the knee performed between November 2011 and October 2012 were included in the study. Medical charts and operational reports were screened and the patients were contacted after 0.8 ± 0.3 years (0.4-1.3) and 4.3 ± 0.3 years (4.0-4.8) to asses subjective IKDC and re-operation. The Tegner activity scale was collected at the second follow-up time point. Subjective IKDC response rates were assessed at both follow-up time points.Results: The first and second follow-up was completed by all 15 patients (100%). The subjective IKDC scores showed a significant improvement (pre-operative 44.5 ± 15.9, first follow-up 71.1 ± 15.9, p < 0.001, second follow-up 72.6 ± 17.3, p < 0.001). The overall response rate was 66.7% (n = 10) at follow-up one and two. There were no significant differences in pre-injury (4, range 1-9) and follow-up two (4, range 2-7) Tegner activity scales (p = n.s.). Two patients required re-operation in the index knee, not related to the ACI procedure. No complication related to the ACI or the implantation technique occurred. The histological results showed excellent cartilage regeneration.Conclusion: Arthroscopic ACI using an in situ crosslinking matrix is a safe and reliable treatment option for full-thickness cartilage defects of the knee. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions Level of Evidence Most studies about medial open‐wedge high tibial osteotomy (HTO) reported outcomes without focusing on gender differences. Therefore, the study compared the long‐term survival rate and postoperative subjective knee function after HTO in female versus male patients with symptomatic medial compartment knee osteoarthritis.The data of three cohorts with long‐term outcomes were analysed (n = 245; 32% females; age: 49 ± 7 years; Kellgren Lawrence Grade I 6.1%, II 32.7%, III 42.4%; IV 18.8%). The minimum follow‐up was at least 6 years or an earlier conversion to total knee arthroplasty (TKA). The gender‐specific survival rate after HTO was calculated after 5 and 10 years and compared using Kaplan–Meier analysis and the logrank test. Baseline characteristics and subjective knee function (International Knee Documentation Committee [IKDC]/Lysholm) were analysed between both genders.Forty of 78 (51.3%) women and 41 of 167 men (24.5%) underwent TKA. HTO survival in females was significantly lower (p = 0.0010). The 5‐ and 10‐year survival rates were 85.9% and 62.6% for females and 93.4% and 77.7% for males. In females and males, from preoperative to the last follow‐up, the IKDC (43 ± 15 to 58 ± 17; 47 ± 14 to 67 ± 18) and the Lysholm (42 ± 18 to 72 ± 18; 55 ± 22 to 77 ± 23) improved significantly (all p < 0.0001). Females had significantly lower preoperative and postoperative IKDC (p = 0.0438; p = 0.0035) and Lysholm scores (p = 0.0002; p = 0.0323). But the absolute improvements of the IKDC and Lysholm were not significantly different between genders.Females had higher conversion rates to TKA and lower knee function at the last follow‐up. However, preoperative knee function was lower in females and the absolute improvement following HTO was similar for both genders. In general, females benefit from HTO to treat medial knee arthritis, and TKA could be postponed for half of female patients for more than 10 years. However, surgeons must be aware of the described inferior outcomes in females for realistic patient expectation management.Level II. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine the incidence of septic arthritis following arthroscopic posterior cruciate ligament (PCL) and multi-ligament reconstructions, and to evaluate a treatment regime with sequential arthroscopic irrigation and debridement procedures combined with antibiotic therapy that is focused on retention of the graft.Methods: Between 2004 and 2016 a total of 866 PCL reconstructions and multi-ligament reconstructions were performed at our institution (408 isolated PCL reconstructions, 458 combined reconstructions). Medical charts of all cases were retrospectively reviewed with regard to the occurrence of septic complications. These cases were analysed with special focus on clinical management, number of reoperations and if the grafts were retained. Further, microbiological findings, postoperative clinical course and available clinical outcome data were evaluated.Results: Four cases of septic arthritis (0.5%) were identified (follow-up rate 96.5%): two following isolated PCL reconstruction (0.5%), and two following multi-ligament reconstruction (0.4%), respectively. Septic arthritis was successfully treated in all cases with a mean of 2.5 ± 2.4 irrigation and debridement procedures (1-6). In one case of isolated PCL reconstruction, the graft was resected within the fifth irrigation and debridement due to septic loosing of the femoral fixation. All other grafts were retained. With regard to the outcome, all patients were subjectively satisfied with good stability (stress radiographs) in cases of retained grafts.Conclusion: Postoperative septic arthritis after arthroscopic PCL and complex knee ligament reconstructions is a rare but serious complication. Arthroscopic graft-retaining treatment is recommended, as it is established in ACL surgery. Graft retention can be expected in the majority of the cases.Level Of Evidence: Case series, Level 4. [ABSTRACT FROM AUTHOR]

Purpose: No systematic studies on optimal treatment of postoperative septic arthritis following arthroscopic meniscus repair are available. The purpose of this study was to retrospectively evaluate the fate of repaired menisci in cases of postoperative septic arthritis, with treatment for infection focused on arthroscopic irrigation and debridement (I&D) and intention to maintain the meniscus.Methods: Data of two sports orthopedics centers of the last 10 years were pooled (approximately 25,000 arthroscopic procedures of the knee). All cases of septic arthritis following arthroscopic meniscus repair were identified. These cases were retrospectively evaluated with regard to clinical course and management, especially the number of necessary I&Ds, if eradication was achieved, and if the repaired meniscus was retained or a partial resection was necessary ('early failure'). Patients with initially maintained meniscus repairs were contacted if further meniscus surgery was performed in further follow-up ('late failure').Results: 20 patients with 23 repaired menisci were included. In 65% (13 cases), a concomitant anterior cruciate ligament reconstruction was performed. A mean of 2.0 ± 1.0 (1-4) arthroscopic I&Ds were performed in the treatment of septic arthritis. In two cases, additional open surgery was performed (after outside-in sutures). Eradication was achieved in all cases. Four repaired menisci (17.4%) showed loosened fixation or substantial degradation and were consequently partially resected within treatment for septic arthritis (early failures). The follow-up rate for the 19 initially maintained menisci was 94.7% after 3.0 ± 2.2 years (median 2.8, 0.4-7.8). Three of these underwent further partial resection (13.0%). Cumulative 3-year survival rate (Kaplan-Meier method) of all repairs was 70.7% (95% CI 50.3-91.1%), and for the subgroup of initially maintained menisci 85.6% (95% CI 67.0-100.0%), respectively.Conclusion: Septic arthritis following meniscus repair can be successfully treated with (sequential) arthroscopic I&Ds. There is a considerable rate of early failures, however, in a mid-term follow-up the failure rate of initially retained menisci is low and comparable to what we know from the literature for cases without infection. Therefore, it is generally recommended to try to save the repaired menisci in these cases.Level Of Evidence: IV, therapeutic case series. [ABSTRACT FROM AUTHOR]

Background: High tibial osteotomy (HTO) is a widely used treatment option for medial osteoarthritis and varus malalignment, especially in young patients with early osteoarthritis. Limited outcome data are available for this procedure in severe osteoarthritis, and no long-term data are available using newer implants. Purpose: To determine survivorship and functional results of medial open-wedge HTO combined with a chondral resurfacing (CR) procedure (abrasion plus microfracture) in severe medial osteoarthritis (Kellgren-Lawrence grade 3 and 4) and varus malalignment. Furthermore, factors that potentially influence the outcome were analyzed. Study Design: Case series; Level of evidence, 4. Methods: From September 2005 to December 2008, all cases of HTO (fixation with an angular-stable internal fixator) combined with CR were prospectively surveyed with regard to survival (Kaplan-Meier-method, not requiring arthroplasty) and functional outcome (subjective International Knee Documentation Committee [IKDC] score). Cartilage regeneration at the time of hardware removal, tibial bone varus angle (TBVA), pre- and postoperative mechanical medial proximal tibial angle (MPTA), and postoperative alignment were analyzed with regard to the result. Results: Seventy-nine knees were included (73 patients; mean age 50.9 ± 7.6 years). The follow-up rate was 90% at 10.0 ± 1.2 years (range, 8.3-12.1 years). Pre- and postoperative mechanical tibiofemoral axis were 9.6° ± 3.0° of varus and 0.6° ± 2.7° of valgus, respectively. Survival rate was 81.7% (95% CI, 72.5%-90.9%) at 10 years. Subjective IKDC score significantly improved from 44 ± 11 preoperatively to 70 ± 13 at one, 66 ± 15 at three, 66 ± 15 at five, and 65 ± 17 at ten years (P< .001 at any point of followup). Poor cartilage regeneration and low preoperative IKDC score (< 40) were associated with decreased survival. High preoperative TBVA was associated with better and an overcorrected MPTA (>95°) with inferior functional outcome at final follow-up, respectively. Conclusion: Even in cases of severe medial osteoarthritis and varus malalignment, HTO in combination with a CR procedure is a good to excellent treatment option. The role of the CR procedure remains unclear. Although good results are obtained with overcorrected MPTA, long-term functional outcome is inferior. [ABSTRACT FROM AUTHOR]

Introduction: Patients who have undergone hip or knee replacement surgery are exposed to a high risk of developing a post-operative venous thromboembolus and so have a need for an effective, medication-based, thrombosis prophylaxis. New orally active anticoagulants have been available for a few years now. These specific substances directly block either thrombin (e.g., dabigatran etexilate) or Factor Xa (e.g., apixaban). It is not clear whether there are any efficacy differences between these two substances because there have never been any head-to-head studies carried out.Materials and Methods: We have carried out a study comparing two new orally active anticoagulants dabigatran etexilate (Pradaxa®) and apixaban (Eliquis®) that were each given to two groups of 200 patients respectively, who had undergone elective hip or knee arthroplasty (100 each). Each patient was assessed for pre- and post-operative hemoglobin concentrations, post-operative blood loss, the number of transfused erythrocyte concentrates, the duration of wound secretion, clinical thromboembolic complications (deep vein thrombosis, pulmonary embolism, myocardial infarct), as well as gastrointestinal, intracranial or wound-related bleeding complications.Results: Dabigatran etexilate treatment led to a significant increase in the duration of wound secretion in both arthroplasty groups when compared to apixaban: wound secretion lasted 1.2 days longer on average in the dabigatran etexilate group than in the apixaban group (4.1 ± 2.1 vs. 2.9 ± 1.8 days). There were no significant differences observed between the two anticoagulant groups when comparing pre- and post-operative Hb values, post-operative blood loss and the other clinical parameters.Conclusions: Thus, it appears that the direct thrombin inhibitor, dabigatran etexilate, is associated with a longer period of wound secretion following the implantation of hip and knee endoprostheses than that associated with the Factor Xa inhibitor, apixaban. [ABSTRACT FROM AUTHOR]

Purpose: To determine incidence and risk factors for traumatic graft rupture following primary and revision anterior cruciate ligament (ACL) reconstruction.Methods: All cases of isolated ACL reconstructions (primary or revision) performed at our institution between January 2007 and December 2010 were included. From this group of 2467 primary reconstructions (32.4 ± 12.2 years) and 448 revision reconstructions (33.0 ± 10.4 years), we identified all patients who underwent revision ACL reconstruction following traumatic graft rupture in further course and all patients who underwent contralateral primary ACL reconstruction until January 2014. Age, gender, time from index procedure and graft diameter (for hamstring autografts) were analysed in terms of being a potential risk factor for graft rupture.Results: Within a follow-up period of 5.0 ± 1.1 years (3.0-7.0), a total of 82 traumatic graft ruptures were identified, resulting in an incidence of 2.8 %. Seventy-three cases were seen following primary reconstructions (3.0 %), and nine cases following revision reconstructions (2.0 %), respectively (n.s.). Age younger than 25 years was identified as a risk factor for both groups (p = 0.001 and p = 0.008; odds ratio 6.0 and 6.4, respectively). In primary reconstruction, male patients had a higher risk of graft rupture compared with females (3.7 vs. 1.6 %; p = 0.005), and the first year after index procedure was associated with a higher risk of graft rupture compared with the following (p < 0.001). Graft diameter did not influence the risk of graft rupture. Incidence of contralateral ACL rupture was 3.1 %, which was not different to the incidence of graft rupture ipsilaterally (n.s.).Conclusion: No statistically significant differences were seen between graft rupture incidence of primary and revision ACL reconstructions. Young age (<25 years) and short time to the index procedure (especially within the first year) were confirmed as risk factors for graft rupture in both groups. Male gender was a risk factor for primary reconstructions. Graft diameter had no influence on graft rupture rates. No difference in incidence of graft rupture compared to ACL rupture on the contralateral side was apparent.Level Of Evidence: Retrospective case series, Level IV. [ABSTRACT FROM AUTHOR]

Background: Septic arthritis after anterior cruciate ligament (ACL) reconstruction is a rare but severe complication. Treatment regimens differ, and optimal management has not been established. Purpose: To determine the incidence of postoperative infections after ACL reconstruction, to identify the microbiological spectrum, and to evaluate a standardized graft-retaining treatment protocol consisting of sequential arthroscopic irrigation and debridement (I&D) procedures and antibiotic therapy until C-reactive protein levels are within normal range. Study Design: Case series; Level of evidence, 4. Methods: From January 2004 to June 2014, a total of 7096 consecutive arthroscopic ACL reconstructions were performed at a single institution (5907 primary and 1189 revision reconstructions). Thirty-six cases with postoperative septic arthritis were identified and retrospectively analyzed with regard to incidence, clinical presentation, time to and number of arthroscopic reoperations, and microbiological findings. The follow-up examination consisted of a clinical examination, instrumeted measurement of laxity (KT-1000 arthrometer), classification according to objective and subjective International Knee Documentation Committee (IKDC) scores, and radiological evaluation. Results: The incidence of septic arthritis was 0.51% (n = 36), with 0.41% (n = 24) in primary and 1.01% (n = 12) in revision reconstructions (odds ratio, 2.5; P = .008). The first I&D was performed a mean (±SD) of 19.6 ± 10.6 days after the index procedure. Eradication was achieved in all patients after a mean of 2.25 ± 1.22 procedures, with graft retention in all but 1 patient (97.2%). The mean duration of antibiotic treatment was 5.4 ± 2.3 weeks (range, 2.1-12.9 weeks) and ≤4 weeks in 13 patients (36%). No recurrence of infections was seen. Coagulase-negative staphylococci (62.5%) and Staphylococcus aureus (21.9%) were the most frequent pathogens. Twenty-nine patients were available for follow-up (80.6%) after a mean 4.7 ± 3.2 years (range, 0.7-11.2 years). Two patients suffered recurrent nontraumatic ACL insufficiency (6.9%), and all others (93.1%) had an intact graft, with a mean KT-1000 arthrometer side-to-side difference of 1.4 ± 0.9 mm. The mean subjective IKDC score was 80.4 ± 11.2. No emergence or deterioration of osteoarthritis related to infections was seen. Conclusion: Postoperative septic arthritis is rare but serious after arthroscopic ACL reconstruction. Graft retention and good to excellent clinical results can be obtained with an arthroscopic treatment protocol. The duration of antibiotic therapy should be based on the individual course. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we measure the extent and dissemination of the retreat of the state from entrepreneurial activities in 20 OECD countries during the 1980–2007 period using a three-dimensional concept and a new dataset, the REST database. We consider privatization, deregulation in network-based services, and the cutback of subsidies. Though the empirical analysis confirms a clear trend towards diminishing state influence in all three dimensions, the analysis of both sigma and conditional beta convergence indicates convergence only for privatization (measured by public employment) and for subsidization, indicating that OECD countries have become similar and have converged to a common equilibrium with respect to these dimensions. [Copyright &y& Elsevier]

For sustainable energy storage, all‐organic batteries based on redox‐active polymers promise to become an alternative to lithium ion batteries. Yet, polymers contribute to the goal of an all‐organic cell as electrodes or as solid electrolytes. Here, we replace the electrolyte with a deep eutectic solvent (DES) composed of sodium bis(trifluoromethanesulfonyl)imide (NaTFSI) and N‐methylacetamide (NMA), while using poly(2,2,6,6‐tetramethylpiperidin‐1‐yl‐oxyl methacrylate) (PTMA) as cathode. The successful combination of a DES with a polymer electrode is reported here for the first time. The electrochemical stability of PTMA electrodes in the DES at the eutectic molar ratio of 1 : 6 is comparable to conventional battery electrolytes. More viscous electrolytes with higher salt concentration can hinder cycling at high rates. Lower salt concentration leads to decreasing capacities and faster decomposition. The eutectic mixture of 1 : 6 is best suited uniting high stability and moderate viscosity. [ABSTRACT FROM AUTHOR]

Vollorganische Batterien auf Grundlage redoxaktiver Polymere versprechen eine Alternative zu Lithium‐Ionen‐Batterien für die nachhaltige Energiespeicherung zu werden. Polymere tragen bisher als Elektroden oder als feste Elektrolyte zum Ziel einer rein organischen Zelle bei. Hier ersetzen wir den Elektrolyten durch ein Deep Eutectic Solvent (DES), das aus Natriumbis(trifluormethansulfonyl)imid (NaTFSI) und N‐Methylacetamid (NMA) besteht, und verwenden Poly(2,2,6,6‐tetramethylpiperidin‐1‐yl‐oxylmethacrylat) (PTMA) als Kathode. Von der erfolgreichen Kombination eines DES mit einer Polymerelektrode wird hier zum ersten Mal berichtet. Die elektrochemische Stabilität von PTMA‐Elektroden im DES ist beim eutektischen Stoffmengenverhältnis von 1 : 6 mit herkömmlichen Batterieelektrolyten vergleichbar. Viskosere Elektrolyte mit höherer Salzkonzentration können das Zykeln bei hohen Raten behindern. Eine niedrigere Salzkonzentration führt zu sinkenden Kapazitäten und schnellerer Zersetzung. Die eutektische Mischung von 1 : 6 ist am besten geeignet, um hohe Stabilität und moderate Viskosität zu vereinen. [ABSTRACT FROM AUTHOR]

In 1999, two independent groups identified plasmacytoid dendritic cells (PDC) as major type I interferon- (IFN-) producing cells in the blood. Since then, evidence is accumulating that PDC are a multifunctional cell population effectively coordinating innate and adaptive immune responses. This paper focuses on the role of different immune cells and their interactions in the surveillance of alpha herpes virus infections, summarizes current knowledge on PDC surface receptors and their role in direct cell-cell contacts, and develops a risk factor model for the clinical implications of herpes simplex and varicella zoster virus reactivation. Data from studies involving knockout mice and cell-depletion experiments as well as human studies converge into a "spider web", in which the direct and indirect crosstalk between many cell populations tightly controls acute, latent, and recurrent alpha herpes virus infections. Notably, cells involved in innate immune regulations appear to shape adaptive immune responses more extensively than previously thought. [ABSTRACT FROM AUTHOR]

Human plasmacytoid dendritic cells (PDC) are crucial for innate and adaptive immune responses against viral infections, mainly through production of type I interferons. Evidence is accumulating that PDC surface receptors play an important role in this process. To investigate the PDC phenotype in more detail, a chip-based expression analysis of surface receptors was combined with respective flow cytometry data obtained from fresh PDC, PDC exposed to interleukin-3 (IL-3) and/or herpes simplex virus type 1 (HSV-1). CD156b, CD229, CD305 and CD319 were newly identified on the surface of PDC, and CD180 was identified as a new intracellular antigen. After correction for multiple comparisons, a total of 33 receptors were found to be significantly regulated upon exposure to IL-3, HSV-1 or IL-3 and HSV-1. These were receptors involved in chemotaxis, antigen uptake, activation and maturation, migration, apoptosis, cytotoxicity and costimulation. Infectious and ultraviolet-inactivated HSV-1 did not differentially affect surface receptor regulation, consistent with the lack of productive virus infection in PDC, which was confirmed by HSV-1 real-time polymerase chain reaction and experiments involving autofluorescing HSV-1 particles. Viral entry was mediated at least in part by endocytosis. Time–course experiments provided evidence of a co-ordinated regulation of PDC surface markers, which play a specific role in different aspects of PDC function such as attraction to inflamed tissue, antigen recognition and subsequent migration to secondary lymphatic tissue. This knowledge can be used to investigate PDC surface receptor functions in interactions with other cells of the innate and adaptive immune system, particularly natural killer cells and cytotoxic T lymphocytes. [ABSTRACT FROM AUTHOR]

Background: The reconstruction of the individual anatomy is important in total hip replacement. The aim of the study was to compare two different kinds of stems with respect to the reconstruction of the individual anatomy of the hip.Methods: We compared the restoration of the anatomical parameters (horizontal and vertical offset, femoral neck-shaft angle (NSA) and leg length) of 100 unilateral CoreHip (CH) implantations with 100 unilateral implantations of a standard anatomical stem (Exception (E)). The CoreHip has three different NSAs and exhibits a constant femoral neck length for the different sizes. The Exception stem has a standard and lateralized version with two different NSAs and, in both versions, the femoral neck length increases proportionately with size. The anatomical parameters of the operated and healthy sides were measured and the differences between the two stems compared.Results: The horizontal (2.5 ± 2.8 mm (mean ± SD) for CH vs. 5.4 ± 4.1 mm for E, p < 0.001) and vertical offset (4.1 ± 3.5 mm for CH vs. 5.0 ± 3.8 mm, p = 0.024) and femoral neck-shaft-angle (1.7 ± 1.6 degrees for CH vs. 5.6 ± 3.4 degrees for E, p < 0.001) could be reconstructed significantly better with the CoreHip system. There was a tendency for the leg length (4.0 ± 3.9 mm for CH vs. 4.5 ± 3.8 mm; p = 0.11) to be better restored with the CoreHip.Conclusion: The reconstruction of the individual anatomy of the hip with an endoprosthesis could be realized significantly better with the stem that was designed with three different femoral neck-shaft angles and a constant femoral neck length over different sizes. [ABSTRACT FROM AUTHOR]

Purpose: To determine and compare the incidence of postoperative septic arthritis following anterior cruciate ligament reconstruction (ACLR) with and without soaking of the graft in vancomycin solution prior to implantation in a large single-centre case series.Methods: From 2004 to 2019, a total of 10,516 primary ACLR were performed and reviewed with regard to the occurrence of postoperative septic arthritis. From February 2017 onwards, all grafts were wrapped in a vancomycin-soaked (5 mg/ml) gauze swab between harvest and implantation (2294 patients, treatment group (2), prospectively followed). These were compared to 8222 patients before that date (control group (1), retrospectively evaluated). The technique of ACLR did not significantly change during the years of the study. There was no difference between the groups with regard to graft choice: Hamstring tendons were used in 99% and quadriceps tendons were used in 1% in both groups, respectively (n.s.). Routine follow-up examination was performed at 6 weeks (follow-up rate 97.1%) postoperatively. Patients with no treatment for septic arthritis at that time were classified as non-infected.Results: There were 35 cases of postoperative septic arthritis in group 1 (incidence: 0.4%), and none in group 2 (incidence 0.0%), respectively. The difference was significant (p < 0.001).Conclusions: Soaking of the graft in vancomycin solution prior to implantation dramatically reduces the incidence of postoperative septic arthritis in primary ACLR and should, therefore, be used in prevention of this major complication.Level Of Evidence: III. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the present study was to evaluate midterm outcomes 5–7 years after matrix-associated autologous chondrocyte implantation (MACI) in the patellofemoral joint. Materials and methods: Twenty-six patients who had undergone MACI using the Novocart® 3D scaffold were prospectively evaluated. Clinical outcomes were determined by measuring the 36-Item Short-Form Health Survey (SF-36) and International Knee Documentation Committee (IKDC) scores and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) values preoperatively and 3, 6, and 12 months, and a mean of 6 years postoperatively. At the final follow-up, the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score was evaluated. Results: Twenty-two patients with 23 focal cartilage defects (19 patella and four trochlea) were available for the final follow-up. The mean defect size was 4.0 ± 1.9 cm2 (range 2.4–9.4 cm2). All clinical outcome scores improved significantly until 5–7 years after MACI (SF-36 score, 61.2 ± 19.6 to 83.2 ± 11.6; P = 0.001; IKDC score, 47.5 ± 20.6 to 74.7 ± 15.5; P < 0.001; and WOMAC, 29.8 ± 15.7 to 8.2 ± 10.3; P < 0.001). The mean MOCART score was 76.0 ± 11.0 at the final follow-up. Nineteen of the 22 patients (86.4%) were satisfied with the outcomes after 5–7 years and responded that they would undergo the procedure again. Conclusion: MACI in the patellofemoral joint demonstrated good midterm clinical results with a significant reduction in pain, improvement in function, and high patient satisfaction. These clinical findings are supported by radiological evidence from MOCART scores. Level of evidence: IV–case series. [ABSTRACT FROM AUTHOR]

The major type I interferon-producing plasmacytoid dendritic cells (pDC) surround and infiltrate certain tumors like malignant melanoma, head and neck cancer, and ovarian and breast cancer. The presence of pDC in these tumors is associated with an unfavorable prognosis for the patients as long as these cells are unstimulated. Upon activation by synthetic Toll-like receptor agonists or viruses, however, pDC develop cytotoxic activities. Viruses have the additional advantage to augment cytotoxic activities of pDC via lytic replication in malignant lesions. These effects turn cold tumors into hotspots, recruiting further immune cells to the site of inflammation. Activated pDC contribute to cross-presentation of tumor-associated antigens by classical dendritic cells, which induce cytotoxic T-cells in particular in the presence of checkpoint inhibitors. The modification of oncolytic herpes viruses via genetic engineering favorably affects this process through the enhanced production of pro-inflammatory cytokines, curbing of tumor blood supply, and removal of extracellular barriers for efficient viral spread. Importantly, viral vectors may contribute to stimulation of memory-type adaptive immune responses through presentation of tumor-related neo- and/or self-antigens. Eventually, both replication-competent and replication-deficient herpes simplex virus 1 (HSV-1) may serve as vaccine vectors, which contribute to tumor regression by the stimulation of pDC and other dendritic cells in adjuvant and neo-adjuvant situations. [ABSTRACT FROM AUTHOR]

(1) Background: Patellar tendinopathy (PT) is an overuse condition of the knee extensor mechanism characterized by ventral knee pain at the lower pole of the patella and limited functionality. (2) Methods: In this retrospective study, a group of patients with PT (n = 41) was compared with a control group (n = 50) in terms of patient-related data and magnetic resonance imaging (MRI) characteristics. (3) Results: Patellar height was higher in the PT patient group and there was a significant difference in Caton–Deschamps index (CD) compared to the control group (p = 0.021). Patients with PT showed a lower patella–patellar tendon angle (PPTA) (p = 0.011). The patellar tendon thickness (PTT) in the proximal (PTTprox), middle (PTTmid) and distal (PTTdistal) part of the tendon was significantly thickened (p < 0.001). Increased signal intensity in MRI was detected in symptomatic tendons over 6 months compared to a duration of less than 6 months (p = 0.025). A significant relationship between the PTTprox and an increased signal intensity was observed (p < 0.001). (4) Conclusions: Patients with PT showed a significant difference in the patellar height and PPTA. With persistence of symptoms over 6 months, MRI seems suitable to detect the morphologic tendon changes and further identify patients suitable for surgical procedures. [ABSTRACT FROM AUTHOR]

(1) Quadriceps tendon rupture (QTR) is a rare pathology, usually occurring in elderly patients with comorbidities, requiring surgical therapy. The aim of this study was to analyze rupture patterns and concomitant injuries using preoperative magnetic resonance imaging (MRI) and to evaluate patient-reported outcome measures. (2) In this retrospective cross-sectional study, 113 patients with QTR were screened and rupture patterns/concomitant injuries (n = 33) were analyzed via MRI. Clinical outcome was assessed in 45 patients using the International Knee Documentation (IKDC) and Lysholm score with a mean follow-up of 7.2 (±5.0) years. (3) The evaluation of preoperative MRIs showed multiple ruptures of subtendons in 67% with concomitant knee injuries in 45%. The most common associated pathology detected using MRI was pre-existing tendinosis (31.2%). Surgical refixation demonstrated good results with a mean post-operative IKDC score of 73.1 (±14.1) and mean Lysholm score of 84.2 (±16.1). Patient characteristics and individual radiologic rupture patterns did not significantly affect the clinical outcome of patients. (4) Acute QTRs are complex injuries with common involvement of multiple subtendons. MRI imaging can be useful for achieving an accurate diagnosis as pre-existing tendinosis as well as concomitant injuries are common, and might be useful for providing an individual surgical strategy and improving outcomes. [ABSTRACT FROM AUTHOR]

Non-invasive imaging might assist in the clinical translation of tissue-engineered vascular grafts (TEVG). It can e.g. be used to facilitate the implantation of TEVG, to longitudinally monitor their localization and function, and to provide non-invasive and quantitative feedback on their remodeling and resorption. We here incorporated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles into polyvinylidene fluoride (PVDF)-based textile fibers, and used them to prepare imageable tissue-engineered vascular grafts (iTEVG). The USPIO-labeled scaffold materials were molded with a mixture of fibrin, fibroblasts and smooth muscle cells, and then endothelialized in a bioreactor under physiological flow conditions. The resulting grafts could be sensitively detected using T1-, T2- and T2*-weighted MRI, both during bioreactor cultivation and upon surgical implantation into sheep, in which they were used as an arteriovenous shunt between the carotid artery and the jugular vein. In vivo, the iTEVG were shown to be biocompatible and functional. Post-mortem ex vivo analyses provided evidence for efficient endothelialization and for endogenous neo-vascularization within the biohybrid vessel wall. These findings show that labeling polymer-based textile materials with MR contrast agents is straightforward and safe, and they indicate that such theranostic tissue engineering approaches might be highly useful for improving the production, performance, personalization and translation of biohybrid vascular grafts. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to compare the maximum load to failure and stiffness of three medial patella-femoral ligament (MPFL) reconstruction techniques: (i) suture anchor fixation (SA), (ii) interference screw fixation (SF), and (iii) suture knot (SK) patellar fixation. The null hypothesis was that the comparison between these three different patella fixation techniques would show no difference in the ultimate failure load and stiffness. Methods: Reconstruction of the MPFL with gracilis tendon autograft was performed in 12 pairs of fresh-frozen cadaveric knees (24 knees total; mean age, 63.6 ± 8.0 years). The specimens were randomly distributed into 3 groups of 8 specimens; SA reconstruction was completed with two 3.0-mm metal suture anchors; (SF) fixation was accomplished by two 6-mm bio-composite interference screws; SK fixation at the lateral side of the patella was accomplished after drilling two semi-patellar tunnels with a diameter of 4.5 mm. The reconstructions were subjected to cyclic loading for 10 cycles to 30 N and tested to failure at a constant displacement rate of 15 mm/min using a materials-testing machine (MTS 810 Universal Testing System). The final load of failure (N), stiffness (N / mm) and failure mode was recorded in each specimen and followed by statistical analysis. Results: There was no significant difference in mean ultimate failure load among the three groups. The SK group failed at a mean (± SD) ultimate load of 253.5 ± 38.2 N, the SA group failed at 243 ± 41.9 N and the SF group at 263.2 ± 9.06 N. The SF group had a mean stiffness of 37.8 ± 5.7 N/mm. This was significantly higher (p < 0.05) than the mean stiffness value achieved for the SK group 21.4 ± 9.5 N/mm and the SA group 18.7 ± 3.4 N/mm. The most common mode of failure in the SA group was anchor pullout, and in the SK group was failure at the graft–suture interface. All the reconstructions in the SF group failed due to tendon graft slippage from the tunnel. Conclusion: Load to failure was not significantly different between the 3 techniques. However, screw fixation was found to be significantly stronger than the anchor and the suture knot fixation in terms of rigidity of the reconstruction. From a clinical point of view, all methods of fixation can be used reliably for MPFL reconstruction, since they were found to be stronger than the native MPFL. [ABSTRACT FROM AUTHOR]

Abstract: Chronic immune activation, triggered by plasmacytoid dendritic cell (PDC) interferon (IFN)-alpha production, plays an important role in HIV-1 pathogenesis. As the entry of HIV-1 seems to be important for the activation of PDC, we directly characterized the viral entry into these cells using immuno-electron microscopy, cellular fractionation, confocal imaging, and functional experiments. After attachment to PDC, viruses were taken up in an energy-dependent manner. The virions were located in compartments positive for caveolin; early endosomal antigen 1; Rab GTPases 5, 7 and 9; lysosomal-associated membrane protein 1. PDC harbored more virus in endocytic vesicles than CD4+ T cells (p<0.05). Blocking CD4 inhibited the uptake of virions into cytosolic and endosomal compartments. Dynasore, an inhibitor of dynamin-dependent endocytosis, not the fusion inhibitor T-20, reduced the HIV-1 induced IFN-alpha production. Altogether, our morphological and functional data support the role of endocytosis for the entry and IFN-alpha induction of HIV-1 in PDC. [Copyright &y& Elsevier]

Purpose: To report on the outcome and complications of minimal invasive medial unicondylar knee arthroplasty (UKA) after failed prior high tibial osteotomy (HTO) as treatment for medial osteoarthritis in the knee. The hypothesis was that good results can be achieved, if no excessive postoperative valgus alignment and abnormal proximal tibial geometry is present. Methods: All medial UKAs after failed prior HTO (n = 30), performed between 2010 and 2018 were retrospectively reviewed. The patients were followed for revision surgery and survival of the UKA (defined as revision to TKA). Clinical examination using the Knee Society Score (KSS), Oxford Knee Score (OKS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), as well as radiological examination was performed. Radiographs were studied and the influence of the demographic factors and the radiographic measurements on the survival and the clinical outcome was analysed. Results: After a follow-up of 4.3 ± 2.6 years (2.1–9.9) 27 UKAs were available. The survival rate was 93.0%. Two UKAs were revised to TKA (excessive valgus alignment and tibial loosening with femoropatellar degeneration). Two further patients had revision surgery (hematoma and lateral meniscus tear). Follow-up clinical and radiological examination was performed in 21 cases: KSS 82.9 ± 10.1 (54.0–100.0), KSS (function) 93.3 ± 9.7 (70.0–100.0); OKS 42.7 ± 6.0 (25.0–48.0); WOMAC 7.9 ± 15.6 (0.0–67.1). No significant influence of demographic factors or radiological measurements on the clinical outcome was present. Conclusion: Prior HTO is not a contraindication for medial UKA, because good-to-excellent results can be achieved in selected patients with medial osteoarthritis and previous HTO, treated with medial UKA, in a midterm follow-up. Excessive mechanical valgus axis should be avoided; therefore, patient selection and accurate evaluation of medial laxity, preoperative mechanical axis, joint line convergence and proximal tibial geometry are important. Level of evidence: III. [ABSTRACT FROM AUTHOR]

• We present an unusual case of a young COVID-19 patient presenting with hyperinflammation and severe liver injury. • The underlying causative events were sHLH, hepatic SARS-CoV-2 infection induced by immunosuppression and Wilson's disease. • SARS-CoV-2 was detected in hepatocytes by EM as well as virus isolation from a diagnostic liver biopsy. • When immunosuppression is applied, (systemic) virus replication has to be closely monitored. A 21-year-old woman was hospitalized due to coronavirus disease 2019 (COVID-19)-associated respiratory and hepatic impairment concomitant with severe hemolytic anemia. Upon diagnosis of secondary hemophagocytic lymphohistiocytosis, immunosuppression with anakinra and steroids was started, leading to a hepatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and viremia. Subsequent liver biopsy revealed virus particles in hepatocytes by electron microscopy and SARS-CoV-2 virus could be isolated and cultured. Immunosuppression was stopped and convalescent donor plasma given. In the differential diagnosis, an acute crisis of Wilson's disease was raised by laboratory and genetic testing. This case highlights the complexity of balancing immunosuppression to control hyperinflammation versus systemic SARS-CoV-2 dissemination. [ABSTRACT FROM AUTHOR]

Background: Preoperative diagnosis of periprosthetic joint infection (PJI) is important because of the therapeutic consequences. The aim of the present study is to investigate whether the serum C-reactive protein (CRP) level can be used as a screening tool for late PJI.Materials and Methods: A cohort of 390 patients with revision surgery of total hip prostheses (200) or total knee prostheses (190) was assessed for late PJI by determining CRP serum level and performing preoperative aspiration with cultivation and intraoperative tissue analyses with cultivation and histologic examination, using the Musculoskeletal Infection Society (MSIS) and International Consensus Meeting (ICM) criteria.Results: A total of 180 joints were rated as PJI (prevalence 46%). Of these, 42.8% (77) showed a CRP level below 10 mg/L and 28.3% (51) showed a normal CRP level of less than 5 mg/L. The 76.9% of the cases with slow-growing bacteria showed a CRP level below 10 mg/L, and 61.5% showed a normal CRP level.Conclusions: Serum CRP level should not be used as a screening tool to rule out late PJI.Level Of Evidence: Level 2 (diagnostic study). [ABSTRACT FROM AUTHOR]

This study aimed to investigate exposure adjusted injury incidence rates and profiles associated with training and competition in an elite taekwondo athlete population. 82 athletes were investigated for injuries over a period of 5 years. Individual fight time exposure for training and competition was recorded. The type and location of the injuries were classified and exposure-adjusted injury incidence rates (IIR) were calculated per 1000 h for training and competition. 66 athletes with a mean age of 19.3±4.2 years and 172 injuries were included in the final data assessment. The exposure adjusted IIR was significantly higher during competition (p<0.001) with a rate ratio of 6.33 (95% CI 4.58–8.69). Ankle and foot region as well as hand and wrist were most affected with significant higher IIR in competition (p<0.001). Joint injuries, fractures, and bruising occurred the most. Fractures occurred mainly to the hand and wrist region. Future investigations should focus on exposure adjusted injury data including analyses of the detailed mechanism leading to especially severe injuries to improve specific injury prevention in competition and promote evolution of protective gear. [ABSTRACT FROM AUTHOR]

Preoperative diagnosis of periprosthetic joint infection (PJI) is important because of the therapeutic consequences. This prospective study was designed to answer the question, if preoperative PCR analysis of the synovial fluid in addition to the culture and the CRP analysis of the blood are helpful for the diagnosis of PJI in knee arthroplasties. Before revision CRP analysis of the blood, cultivation and PCR analysis of synovial fluid of 116 knee endoprostheses were performed. During revision surgery, five tissue samples of the periprosthetic tissue were cultured and five further samples subjected to histological analysis. These analyses of the periprosthetic tissue were used to verify the results of the preoperative diagnostic methods. Twenty-seven prostheses were identified as infected (prevalence 23.3%). The combined analyses of the joint fluid cultivation and the CRP blood level resulted in a sensitivity of 77.8%, a specificity of 95.5%, a positive-predictive value of 84.0%, a negative-predictive value of 93.4% and an accuracy of 91.4%. The PCR analysis of the synovial fluid resulted in a sensitivity of 55.6%, a specificity of 82.0%, a positive-predictive value of 48.4%, a negative-predictive value of 85.9% and an accuracy of 75.9%. The sensitivity for culture of the aspirate and PCR analysis in combination with an elevated CRP level was 85.2%, the specificity 82.0%, the positive-predictive value 58.9%, the negative-predictive value 94.8% and the accuracy 82.7%. The preoperative PCR analysis of synovial fluid has only limited value in addition to the standard culture analysis. [ABSTRACT FROM AUTHOR]

Malignant melanoma is an aggressive tumour of the skin with increasing incidence, frequent metastasis and poor prognosis. At the same time, it is an immunogenic type of cancer with spontaneous regressions. Most recently, the tumoricidal effect of plasmacytoid dendritic cells (pDC) and their capacity to overcome the immunosuppressive tumour microenvironment are being investigated. In this respect, we studied the effect of the infectious, but replication-deficient, herpes simplex virus 1 (HSV-1) d106S vaccine strain, which lacks essential immediate early genes, in pDC co-cultures with 11 melanoma cell lines. We observed a strong cytotoxic activity, inducing apoptotic and necrotic cell death in most melanoma cell lines. The cytotoxic activity of HSV-1 d106S plus pDC was comparable to the levels of cytotoxicity induced by natural killer cells, but required only a fraction of cells with effector : target ratios of 1 : 20 ( P < 0·05). The suppressive activity of cell-free supernatants derived from virus-stimulated pDC was significantly neutralized using antibodies against the interferon- α receptor ( P < 0·05). In addition to type I interferons, TRAIL and granzyme B contributed to the inhibitory effect of HSV-1 d106S plus pDC to a minor extent. UV-irradiated viral stocks were significantly less active than infectious particles, both in the absence and presence of pDC ( P < 0·05), indicating that residual activity of HSV-1 d106S is a major component and sensitizes the tumour cells to interferon-producing pDC. Three leukaemic cell lines were also susceptible to this treatment, suggesting a general anti-tumour effect. In conclusion, the potential of HSV-1 d106S for therapeutic vaccination should be further evaluated in patients suffering from different malignancies. [ABSTRACT FROM AUTHOR]

Herpes simplex virus type 1 ( HSV-1), a member of the herpes virus family, is characterized by a short replication cycle, high cytopathogenicity and distinct neurotropism. Primary infection and reactivation may cause severe diseases in immunocompetent and immunosuppressed individuals. This study investigated the role of human plasmacytoid dendritic cells (p DC) in the activation of natural killer ( NK) cells for the control of herpesviral infections. Within peripheral blood mononuclear cells, UV-inactivated HSV-1 and Cp G- A induced CD69 up-regulation on NK cells, whereas infectious HSV-1 was particularly active in inducing NK cell effector functions interferon- γ ( IFN- γ) secretion and degranulation. The p DC-derived IFN- α significantly contributed to NK cell activation, as evident from neutralization and cell depletion experiments. In addition, monocyte-derived tumour necrosis factor- α ( TNF- α) induced after exposure to infectious HSV-1 was found to stimulate IFN- γ secretion. A minority of monocytes was shown to be non-productively infected in experiments using fluorescently labelled viruses and quantitative PCR analyses. HSV-1-exposed monocytes up-regulated classical HLA- ABC and non-classical HLA- E molecules at the cell surface in an IFN- α-dependent manner, whereas stress molecules MICA/ B were not induced. Notably, depletion of monocytes reduced NK cell effector functions induced by infectious HSV-1 ( P < 0·05). Altogether, our data suggest a model in which HSV-1-stimulated p DC and monocytes activate NK cells via secretion of IFN- α and TNF- α. In addition, infection of monocytes induces NK cell effector functions via TNF- α-dependent and TNF- α-independent mechanisms. Hence, p DC and monocytes, which are among the first cells infiltrating herpetic lesions, appear to have important bystander functions for NK cells to control these viral infections. [ABSTRACT FROM AUTHOR]

Several applications in tissue engineering require transplantation of cells embedded in appropriate biomaterial scaffolds. Such structures may consist of 3D non-woven fibrous materials whereas little is known about the impact of mesh size, pore architecture and fibre morphology on cellular behavior. In this study, we have developed polyvinylidene fluoride (PVDF) non-woven scaffolds with round, trilobal, or snowflake fibre cross section and different fibre crimp patterns (10, 16, or 28 needles per inch). Human mesenchymal stromal cells (MSCs) from adipose tissue were seeded in parallel on these scaffolds and their growth was compared. Initial cell adhesion during the seeding procedure was higher on non-wovens with round fibres than on those with snowflake or trilobal cross sections. All PVDF non-woven fabrics facilitated cell growth over a time course of 15 days. Interestingly, proliferation was significantly higher on non-wovens with round or trilobal fibres as compared to those with snowflake profile. Furthermore, proliferation increased in a wider, less dense network. Scanning electron microscopy (SEM) revealed that the MSCs aligned along the fibres and formed cellular layers spanning over the pores. 3D PVDF non-woven scaffolds support growth of MSCs, however fibre morphology and mesh size are relevant: proliferation is enhanced by round fibre cross sections and in rather wide-meshed scaffolds. [ABSTRACT FROM AUTHOR]

Although a signature of increased interferon (IFN-)alpha production is observed in HIV-1 infection, the response of circulating plasmacytoid dendritic cells (PDC) to Toll-like receptor ligand stimulation is substantially impaired. This functional PDC deficit, which we specifically observed in HIV-1 infected individuals with less than 500 CD4+ T cells/ml, is not well understood. We provide evidence that the peripheral IFN-alpha production in HIV-1 infection is actively suppressed by the enhanced interaction of CD40 ligand (CD40L), a member of the tumor necrosis factor family, and its receptor CD40, which are both upregulated upon immune activation. Plasma levels of soluble CD40L were significantly higher in untreated HIV-1 infected individuals (n = 52) than in subjects on long-term antiretroviral therapy (n = 62, p<0.03) and in uninfected control donors (n = 16, p<0.001). Concomitantly, cell-associated CD40L and the expression of the receptor CD40 on the PDC were significantly upregulated in HIV-1 infection (p<0.05). Soluble and cell-associated CD40L inhibited the PDC-derived IFNalpha production by CpG oligodeoxynucleotides dose-dependently. This suppressive effect was observed at much lower, physiological CD40L concentrations in peripheral blood mononuclear cells (PBMC) of HIV-1 infected individuals compared to controls (p<0.05). The CpG-induced IFN-alpha production in PBMC of HIV-1 infected donors was directly correlated with PDC and CD4+ T cell counts, and inversely correlated with the viral loads (p<0.001). In HIV-1 infected donors with less than 500 CD4+ T cells/ml, the CpG-induced IFN-alpha production was significantly correlated with the percentage of CD40- expressing PDC and the level of CD40 expression on these cells (p<0.05), whereas CD40L plasma levels played a minor role. In addition, low-dose CD40L contributed to the enhanced production of interleukin 6 and 8 in PBMC of HIV-1 infected donors compared to controls. Our data support the conclusion that the chronic immune activation in HIV-1 infection impairs peripheral PDC innate immune responses at least in part via enhanced CD40:CD40L interactions. [ABSTRACT FROM AUTHOR]

Simple Summary: Talimogene laherparepvec (T-VEC), a first-in-class oncolytic herpes simplex virus, improves the outcome of patients suffering from unresectable melanoma, in particular in combination with checkpoint inhibitors. However, a certain percentage of patients does not profit from this treatment, which raises the question of potential biomarkers to predict success or failure of oncolytic herpes viruses. For these purposes, we studied the oncolytic activity of T-VEC in a panel of 20 melanoma cell lines and evaluated the clinical response of 35 melanoma metastases to intralesional T-VEC application. Through these studies, we characterized Nectin-1 as a suitable biomarker predicting 86% and 78% of melanoma regression in vitro and in vivo, respectively. In contrast, other molecules involved in the entry (HVEM) and signal transduction (cGAS, STING) of herpes simplex viruses were not predictive. Altogether, our data support the role of Nectin-1 in pretreatment biopsies to guide clinical decision-making in malignant melanoma and supposedly other tumor entities. Talimogene laherparepvec (T-VEC), an oncolytic herpes simplex virus, is approved for intralesional injection of unresectable stage IIIB/IVM1a melanoma. However, it is still unclear which parameter(s) predict treatment response or failure. Our study aimed at characterizing surface receptors Nectin-1 and the herpes virus entry mediator (HVEM) in addition to intracellular molecules cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) as potential bio-markers for oncolytic virus treatment. In 20 melanoma cell lines, oncolytic activity of T-VEC was correlated with the expression of Nectin-1 but not HVEM, as evaluated via flow cytometry and immunohistochemistry. Knockout using CRISPR/Cas9 technology confirmed the superior role of Nectin-1 over HVEM for entry and oncolytic activity of T-VEC. Neither cGAS nor STING as evaluated by Western Blot and immunohistochemistry correlated with T-VEC induced oncolysis. The role of these biomarkers was retrospectively analyzed for the response of 35 cutaneous melanoma metastases of 21 patients to intralesional T-VEC injection, with 21 (60.0%) of these lesions responding with complete (n = 16) or partial regression (n = 5). Nectin-1 expression in pretreatment biopsies significantly predicted treatment outcome, while the expression of HVEM, cGAS, and STING was not prognostic. Altogether, Nectin-1 served as biomarker for T-VEC-induced melanoma regression in vitro and in vivo. [ABSTRACT FROM AUTHOR]

• Does prior infection with seasonal human coronavirus OC43 protect against critical COVID-19? • Findings: In an international multi-center study inpatients without anti-HCoV OC43 NP antibodies had an increased risk of critical disease. • Meaning: Prior infections with seasonal HCoV OC43 have a protective effect against critical COVID-19. The vast majority of COVID-19 patients experience a mild disease. However, a minority suffers from critical disease with substantial morbidity and mortality. To identify individuals at risk of critical COVID-19, the relevance of a seroreactivity against seasonal human coronaviruses was analyzed. We conducted a multi-center non-interventional study comprising 296 patients with confirmed SARS-CoV-2 infections from four tertiary care referral centers in Germany and France. The ICU group comprised more males, whereas the outpatient group contained a higher percentage of females. For each patient, the serum or plasma sample obtained closest after symptom onset was examined by immunoblot regarding IgG antibodies against the nucleocapsid protein (NP) of HCoV 229E, NL63, OC43 and HKU1. Median age was 60 years (range 18-96). Patients with critical disease (n =106) had significantly lower levels of anti-HCoV OC43 nucleocapsid protein (NP)-specific antibodies compared to other COVID-19 inpatients (p =0.007). In multivariate analysis (adjusted for age, sex and BMI), OC43 negative inpatients had an increased risk of critical disease (adjusted odds ratio (AOR) 2.68 [95% CI 1.09 - 7.05]), higher than the risk by increased age or BMI, and lower than the risk by male sex. A risk stratification based on sex and OC43 serostatus was derived from this analysis. Our results suggest that prior infections with seasonal human coronaviruses can protect against a severe course of COVID-19. Therefore, anti-OC43 antibodies should be measured for COVID-19 inpatients and considered as part of the risk assessment for each patient. Hence, we expect individuals tested negative for anti-OC43 antibodies to particularly benefit from vaccination against SARS-CoV-2, especially with other risk factors prevailing. [ABSTRACT FROM AUTHOR]

As most chemotherapeutic drugs are ineffective in the treatment of chondrosarcoma, we studied the expression pattern and function of SOX9, the master transcription factor for chondrogenesis, in chondrosarcoma, to understand the basic molecular principles needed for engineering new targeted therapies. Our study shows an increase in SOX9 expression in chondrosarcoma compared to normal cartilage, but a decrease when the tumors are finally defined as dedifferentiated chondrosarcoma (DDCS). In DDCS, SOX9 is almost completely absent in the non-chondroid, dedifferentiated compartments. CRISPR/Cas9-mediated knockout of SOX9 in a human chondrosarcoma cell line (HTB94) results in reduced proliferation, clonogenicity and migration, accompanied by an inability to activate MMP13. In contrast, adhesion, apoptosis and polyploidy formation are favored after SOX9 deletion, probably involving BCL2 and survivin. The siRNA-mediated SOX9 knockdown partially confirmed these results, suggesting the need for a certain SOX9 threshold for particular cancer-related events. To increase the efficacy of chondrosarcoma therapies, potential therapeutic approaches were analyzed in SOX9 knockout cells. Here, we found an increased impact of doxorubicin, but a reduced sensitivity for oncolytic virus treatment. Our observations present novel insight into the role of SOX9 in chondrosarcoma biology and could thereby help to overcome the obstacle of drug resistance and limited therapy options. [ABSTRACT FROM AUTHOR]

Plasmacytoid dendritic cells (PDC) are major producers of type I interferons (IFN) in response to human immunodeficiency virus type 1 (HIV-1) infection. To better define the underlying mechanisms, we studied the magnitude of alpha IFN (IFN-α) induction by recombinant viruses containing changes in the Env protein that impair or disrupt CD4 binding or expressing primary env alleles with differential coreceptor tropism. We found that the CD4 binding affinity but not the viral coreceptor usage is critical for the attachment of autofluorescing HIV-1 to PDC and for subsequent IFN-α induction. Our results illustrate the importance of the gp120-CD4 interaction in determining HIV-1-induced immune stimulation via IFN-α production. [ABSTRACT FROM AUTHOR]