Quiescence of Memory CD8(+) T Cells Is Mediated by Regulatory T Cells through Inhibitory Receptor CTLA-4.

Immune memory cells are poised to rapidly expand and elaborate effector functions upon reinfection yet exist in a functionally quiescent state. The paradigm is that memory T cells remain inactive due to lack of T cell receptor (TCR) stimuli. Here, we report that regulatory T (Treg) cells orchestrate memory T cell quiescence by suppressing effector and proliferation programs through inhibitory receptor, cytotoxic-T-lymphocyte-associated protein-4 (CTLA-4). Loss of Treg cells resulted in activation of genome-wide transcriptional programs characteristic of effector T cells and drove transitioning as well as established memory CD8(+) T cells toward terminally differentiated KLRG-1(hi)IL-7Rα(lo)GzmB(hi) phenotype, with compromised metabolic fitness, longevity, polyfunctionality, and protective efficacy. CTLA-4 functionally replaced Treg cells in trans to rescue memory T cell defects and restore homeostasis. These studies present the CTLA-4-CD28-CD80/CD86 axis as a potential target to accelerate vaccine-induced immunity and improve T cell memory quality in current cancer immunotherapies proposing transient Treg cell ablation.

[Comparison of DRG revenues between fast and slow-track procedures for a two-stage replacement of prostheses for periprosthetic hip infections in the aG-DRG system 2020]. / Vergleich der DRG-Erlöse zwischen Fast- und Slow-Track-Verfahren beim zweizeitigen Prothesenwechsel bei periprothetischen Hüftinfektionen im aG-DRG-System 2020.

BACKGROUND: The treatment of periprosthetic hip infections is usually cost intensive, so it is generally not cost effective for hospitals. In chronic infections, a two-stage procedure is often indicated, which can be done as a fast-track procedure with a short prosthetic-free interim interval (2-4 weeks) or as a slow-track procedure with a long prosthetic-free interim interval (over 4 weeks). AIM: The aim of this study was to elucidate the revenue situation of both forms of treatment in the aG-DRG-System 2020, taking into account revenue-relevant influencing factors. METHODS: For fast-track and slow-track procedures with two-stage revision and detection of a staphylococcus aureus (MSSA), treatment cases were simulated using a grouper software (3M KODIP Suite) based on the diagnoses (ICD-10-GM) and procedures (OPS) and then grouped into DRGs. Revenue-relevant parameters, such as length of stay and secondary diagnoses (SD), were taken into account. In addition, two real treatment cases with fast-track and slow-track procedures were compared to each other. RESULTS: The total revenues for the slow-track procedure with a length of stay of 25 days (without SD) were 27,551 € and for a length of stay of 42 days (with SD) even 40,699 €, compared to 23,965 € with the fast-track procedure with a length of stay of 25 days (without SD) and 27,283 € for a length of stay of 42 days (with SD). The real treatment cases also showed a big difference in the total revenues of 12,244 € in favor of the slow-track procedure. DISCUSSION: Even in the aG-DRG-System 2020, the two-stage revision procedure with a long interim interval seems to be more interesting from a financial point of view and the hospital perspective compared to the fast-track procedure, especially with multimorbid patients. This creates a financial barrier to the treatment of such patients with a short interim interval.

[PJI-TNM as new classification system for periprosthetic joint infections : An evaluation of 20 cases]. / PJI-TNM als neues Klassifikationssystem für Endoprotheseninfektionen : Eine Evaluation von 20 Fällen.

BACKGROUND: Current classifications for periprosthetic joint infections (PJIs) often lack a detailed description of the overall underlying situation of a patient. The PJI-TNM classification uses the principles of the TNM classification from oncology for the description of critical parameters in PJIs: affected joint, type of implant and implant stability, soft tissue conditions, maturity of biofilm formation, causative microorganism, comorbidities of the patient and recurrence of infection. The aim of the current work is to evaluate the feasibility of this new PJI-TNM classification in clinical practice. METHODS: The PJI-TNM classification was used in 20 patients with hip, knee and shoulder PJIs. Based on a retrospective chart review, the respective parameters T (tissue and implants), N (non-eukaryotic cells and fungi), M (morbidity) and r (reinfection) were classified for each case. RESULTS: All 20 cases (12 male, 8 female, average age 72.2 (40-88 years)) with 13 hip, 6 knee and 1 shoulder PJIs were to be classified with the new TNM-PJI classification system. There was a considerable heterogeneity among the cases: 12 protheses were fixed (T0), 6 were loosened (T1) and 2 were associated with a soft tissue defect (T2). Biofilm formation was considered immature in 7 cases (N0). Out of the PJIs, 13 were considered to be associated with mature biofilm formation. Out of the patients, 9 were systemically not or only mildly compromised (M0), 7 patients moderately (M1) and 3 patients (M2) severely compromised. One patient refused surgical treatment (M3a). Recurrent infections (r) were diagnosed in three cases. CONCLUSIONS: The principles of the TNM classification from oncology can also be used for the classification of PJIs. Despite the limited number of cases in this study, a considerable heterogeneity of the evaluated PJIs is shown, which is a phenomenon that is also known from clinical practice. This heterogeneity can be adequately addressed by this new classification, which might be beneficial in decision-making in the future.

Programming of CD8 T Cell Quantity and Polyfunctionality by Direct IL-1 Signals.

IL-1, generally considered an amplifier of adaptive immune responses, has been proposed for use as adjuvant during immunization with weak immunogens. However, its effects on memory T cell function remain largely undefined. Using the murine model of acute viral infection, in this paper, we show that in addition to augmenting the size of the Ag-specific pool, IL-1 signals act directly on CD8 T cells to promote the quality of effector and memory responses. Ablation of IL-1R1 or MyD88 signaling in T cells led to functional impairment; both the ability to produce multiple cytokines on a per cell basis (polyfunctionality) and the potential for recall proliferation in response to antigenic restimulation were compromised. IL-1 supplementation during priming augmented the expansion of Ag-specific CD8 T cells through the MyD88-IRAK1/4 axis, resulting in a larger memory pool capable of robust secondary expansion in response to rechallange. Together, these findings demonstrate a critical role of the IL-1-MyD88 axis in programming the quantity and quality of memory CD8 T cell responses and support the notion that IL-1 supplementation may be exploited to enhance adoptive T cell therapies against cancers and chronic infections.

Patient-reported outcome after patient-specific unicondylar knee arthroplasty for unicompartmental knee osteoarthritis.

BACKGROUND: Unicondylar knee arthroplasty was introduced in the late 1960s and remains a topic of controversial discussion. Patient-specific instruments and patient-specific implants are not yet the standard of care. The question remains whether this time-consuming and costly technique can be beneficial for the patient. The aim of this study was to evaluate whether a custom-made unicondylar knee arthroplasty leads to improved patient-reported outcome. METHODS: This retrospective study evaluates the patient-reported outcome after custom-made unicondylar knee arthroplasty (CM-UKA, ConforMIS™ iUni® G2, ConforMIS Inc., Billerica, MA, USA). We evaluated 29 patients (31 knees) at an average of 2.4 years (range 1.2-3.6 years) after operation for unicondylar osteoarthritis of the knee. The target zone for the postoperative leg axis was a slight under-correction of 0-2° varus. Follow-up evaluation included the Forgotten Joint Score (FJS), the Knee Society Score (KSS), a Visual Analogue Scale (VAS) and a radiographic evaluation including a long-leg radiograph. Primary outcome measure was patient satisfaction based on the Forgotten Joint Score. RESULTS: We found an excellent postoperative health-related quality of life with a mean FJS of 76.8 (SD 17.9) indicating a low level of joint awareness after CM-UKA. The mean preoperative KSS was 66.0 (SD 13.71) and 59.4 (17.9) for the KSS function score. The increase was 22.8 points for the KSS knee score (p < 0.0001) and 34.8 points for the KSS function score (p < 0.0001). The VAS for pain decreased from a mean of 5.4 (SD 1.8) to 1.1 (SD 1.2) (p < 0.0001). The malalignment rate with a postoperative deviation of more than 2° in the leg axis was 29%. There was no evidence of component loosening after a mean follow-up of 2.4 years. CONCLUSIONS: Custom-made unicondylar knee arthroplasty (CM-UKA) can provide improved clinical and functional outcomes for patients with isolated knee osteoarthritis of the medial compartment. We found excellent results regarding patient satisfaction and a low malalignment rate for CM-UKA. Further studies are needed to investigate long-term survivorship of the implant. LEVEL OF EVIDENCE: Level IV. TRIAL REGISTRATION: Trial Registration number: Z-2014-0389-10 Regensburg Clinical Studies Center (REGCSC) 09/07/2014.

Attenuation of Hypertrophy in Human MSCs via Treatment with a Retinoic Acid Receptor Inverse Agonist.

In vitro chondrogenically differentiated mesenchymal stem cells (MSCs) have a tendency to undergo hypertrophy, mirroring the fate of transient "chondrocytes" in the growth plate. As hypertrophy would result in ossification, this fact limits their use in cartilage tissue engineering applications. During limb development, retinoic acid receptor (RAR) signaling exerts an important influence on cell fate of mesenchymal progenitors. While retinoids foster hypertrophy, suppression of RAR signaling seems to be required for chondrogenic differentiation. Therefore, we hypothesized that treatment of chondrogenically differentiating hMSCs with the RAR inverse agonist, BMS204,493 (further named BMS), would attenuate hypertrophy. We induced hypertrophy in chondrogenic precultured MSC pellets by the addition of bone morphogenetic protein 4. Direct activation of the RAR pathway by application of the physiological RAR agonist retinoic acid (RA) further enhanced the hypertrophic phenotype. However, BMS treatment reduced hypertrophic conversion in hMSCs, shown by decreased cell size, number of hypertrophic cells, and collagen type X deposition in histological analyses. BMS effects were dependent on the time point of application and strongest after early treatment during chondrogenic precultivation. The possibility of modifing hypertrophic cartilage via attenuation of RAR signaling by BMS could be helpful in producing stable engineered tissue for cartilage regeneration.

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.

Patient-related quality of life after pelvic ring fractures in elderly.

PURPOSE: Pelvic ring fractures, occurring in elderly patients are a challenging problem. Little known is about the patient-related outcome after these injuries. The primary objective of this study is to evaluate the quality of life after pelvic ring injuries in patients aged over 60 years. METHODS: Patients (≥ 60 years) with pelvic ring fractures treated in our trauma department between 2004 and 2014 were included. Next to patient data, injury-related details as well as treatment details were assessed. After a follow-up of at least two years, the survival rate and the patient-related outcome were evaluated using the SF-36 and the EQ-5D score. RESULTS: One hundred ninety-six patients (138 women; 58 men; mean age 75.3 ± 7.8 years) were identified. Ninety-six patients were treated operatively, 100 patients conservatively. The overall complication rate was significantly lower for conservatively compared to operatively treated patients (conservatively 18% vs. operatively 33%; p = 0.014). The total mortality rate over 2 years is 29% with no significant difference of the two-year survival rate (2-year survival rate: operatively 77% vs. non-operatively 65%; p = 0.126). Fifty-five patients completed the SF-36 and EQ-5D score after a mean follow-up of 4.2 ± 2.9 years. The mean physical component score of the SF-36 is 33.6 ± 8.3, and the mean mental component score is 45.3 ± 8.4. The mean EQ-5D VAS reached 62.5 ± 27.9. CONCLUSION: Elderly patients with pelvic ring fractures show a high mortality rate and a limited patient-related outcome. While the complication rate of conservatively treated patients is lower compared to operated patients, the two year survival rate is steady.

Clinical application of a minimally invasive cement-augmentable Schanz screw rod system to treat pelvic ring fractures.

PURPOSE: The purpose of this study is to analyze the results using the USS fracture MIS system (DePuy Synthes) to treat instable pelvic ring fractures. As its outstanding feature, it is the only Schanz screw and rod system at present that combines angular stability, perforation/fenestration of the screws for cement-augmentation, a variable screw length, and a large screw diameter. MATERIALS AND METHODS: Retrospective investigation of 134 pelvic ring fractures treated in 2012-2013. Twenty-five patients obtained the abovementioned implant. Besides baseline characteristics of the included patients and the surgical procedure, a clinical/radiological follow-up of six months was analyzed. RESULTS: Dividing the collective into two groups, I high-energy trauma and II fragility fracture of the pelvis, the following results were recorded: group I: ten patients, six male, age 48.4 ± 19.7 years. Mean ISS 41 ± 22.5, fracture classification: AO/OTA type 61 B1/C1/C3 = 1/5/4. Operative treatment: three transiliac internal fixator, seven iliolumbar fixation, one implant was cement-augmented. Group II: 15 patients, 14 female, age 77.5 ± 10.1 years. Fracture classification according to Rommens: FFPII/III/IV = 6/1/8. Operative treatment: eight transiliac internal fixator, seven iliolumbar fixation, 14 implants were cement-augmented. Overall surgical side complications: 16%. Radiological examination: correct positioning of all ilium screws. Follow-up after six month (16 patients): all showed fracture consolidation. One ilium screw was broken close to the connecting clamp. CONCLUSION: The investigated Schanz screw rod system is a suitable implant to broaden the established procedures to stabilize dorsal pelvic ring fractures. TRIAL REGISTRATION: The study is registered at the Clinical Trial Registry University of Regensburg (Number Z-2017-0878-3).

Reduced joint-awareness in bicruciate-retaining total knee arthroplasty compared to cruciate-sacrificing total knee arthroplasty.

PURPOSE: There is rising impact of patient-reported outcome (PRO) measurement in joint arthroplasty over the past years. Bicruciate-retaining implants have shown more physiologic knee kinematics and provide superior proprioceptive capacities. The aim of this study was to evaluate if the functional properties of this new implant design lead to improved PRO results after total knee arthroplasty (TKA). METHODS: This prospective, controlled trial compares PRO of bicruciate-retaining total knee arthroplasty (BCR-TKA) to unicondylar knee arthroplasty (UKA) and standard posterior-stabilized total knee arthroplasty (PS-TKA). We evaluated 102 patients (34 patients in each group) 18 months postoperatively after knee arthroplasty. Primary outcome measure was the Forgotten Joint Score (FJS). RESULTS: The BCR-group showed the same level of joint awareness as the UKA-group (p = 0.999). The second control group of PS-TKA patients had a lower mean score value in the FJS compared to the BCR-group (p = 0.035) and UKA-group (p = 0.031). There was no correlation of age, gender, body mass index (BMI) and the FJS. No relevant floor- or ceiling effects occurred. CONCLUSIONS: This study found reduced joint awareness for BCR-TKA compared to a standard total knee arthroplasty. The score values of the BCR-group were equal to the UKA-group. Further prospective, randomized studies to investigate long-term survivorship of bicruciate-retaining implants are needed. LEVEL OF EVIDENCE: Level II.

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.

Proprioception after bicruciate-retaining total knee arthroplasty is comparable to unicompartmental knee arthroplasty.

PURPOSE: Rising expectations in functional performance of total knee joints are inciting further improvement of knee arthroplasty implants. From a patient-centred view, bicruciate-retaining models provide a more natural feeling knee. However, there is no evidence of functional advantage for these implants. The aim of this study was to evaluate balance ability as a measure of proprioception in patients with a bicruciate-retaining total knee arthroplasty. METHODS: A prospective, controlled trial was conducted to compare balance ability in 60 patients after arthroplasty of the knee for osteoarthritis. We compared patients with a bicruciate-retaining knee arthroplasty (BCR group) to a control group of patients with a medial unicompartmental knee arthroplasty (UKA group) and another control group of patients with a posterior stabilized total knee arthroplasty (PS group). The patient population comprised 30 women (50.0 %) and 30 men in three cohorts of 20 each. The mean age was 62.1 ± 8.0 years (range 43-78). Patients were evaluated preoperatively and 9 months post-operatively. The evaluation included clinical, radiological, and balance testing-a single-leg stance with eyes closed compared to eyes open. The difference in area of sway between eyes closed and eyes open represents static balance ability after knee arthroplasty. RESULTS: Perioperative data showed that there was no intra-operative fracture of the intercondylar eminence. There was a decreased post-operative knee extension 9 months post-operative in the BCR group, which was not clinically relevant in any case. We recorded a lower difference in the area of sway between eyes closed and eyes open (ΔA (ec-eo)) for the BCR group (p = 0.01) and the UKA group (p = 0.04) compared to the PS group. CONCLUSIONS: This study found superior static balance ability after preservation of both cruciate ligaments in arthroplasty of the knee, indicating superior proprioceptive function. Hence, BCR implants could provide improved functional properties. Superior proprioceptive function of bicruciate-retaining implants can be an important factor in implant selection. Further prospective, randomized studies to investigate kinematics and long-term survivorship of bicruciate-retaining implants are needed. LEVEL OF EVIDENCE: II.

Validation of a German version of the International Hip Outcome Tool 12 (iHOT12) according to the COSMIN checklist.

BACKGROUND: Patient Reported Outcome (PRO) measurements have become an important tool to evaluate disease-related quality of life. The "International Hip Outcome Tool" (iHOT12) is a self-administered patient-reported outcome tool, which includes questions on the patient's symptoms, functional and sports limitations as well as social, emotional, and occupational limitations. The purpose of this study was to adapt and validate a German version of the iHOT12 according to the COSMIN checklist. METHODS: In order to validate the German translation of the iHOT12, we conducted a prospective multicenter cohort study on patients with hip disorders and a score ≥4 on the modified Tegner Activity Scale (mTAS). The patients completed the German iHOT12 questionnaire and other functional scores (Hip Outcome Score, modified Tegner Activity Scale, EuroQol-5D) twice at intervals of at least two weeks. Evaluation of psychometric properties was conducted following the COSMIN checklist for validation of health status measurement instruments. The methodical testing for reliability included internal consistency, test-retest reliability, and measurement error. For testing of validity, we analyzed construct validity, hypotheses testing, interpretability and responsiveness. RESULTS: Between December 2013 and December 2014, eighty-three consecutive patients completed both questionnaires and were available for data analysis. Cronbach's alpha was 0.94 (95 %-CI: 0.91, 0.95) confirming internal consistency and test-retest reliability of the iHOT-12 was high with an ICC = 0.94 (95 %-CI: 0.89, 0.97). All a priori hypotheses were confirmed. Further, no relevant floor- or ceiling effects occurred. The iHOT12 showed good responsiveness with a minimal important change (MIC) under 14 points. CONCLUSIONS: The German translation of the iHOT-12 is a reliable, valid, and responsive tool for the evaluation of disease-related quality of life in active patients with a hip disorder. We could show that the minimal important change, a change of health condition the patient discerns, is less than 14 points in the iHOT12 scale.

Validation of the German Forgotten Joint Score (G-FJS) according to the COSMIN checklist: does a reduction in joint awareness indicate clinical improvement after arthroplasty of the knee?

PURPOSE: Evaluation of further improvement in treatment of patients with osteoarthritis of the knee requires measurement tools with a high discriminatory power. In this context, joint awareness in everyday life is seen as crucial criterion. Purpose of this study was to adapt and validate a German version of the "Forgotten Joint Score" (FJS) according to the COSMIN checklist. METHODS: We evaluated a German translation of the FJS for reliability, validity and responsiveness according to the COSMIN checklist. Therefore, patients with an artificial knee joint completed the G-FJS questionnaire twice at intervals of at least 2 weeks. In addition, the Knee Society Score, the Oxford Knee Score, the Tegner Activity Scale, a Visual Analogue Scale, the EuroQol-5D (EQ 5-D), and a subjective assessment of the limitations were recorded. RESULTS: Between June and December 2014, one hundred and five patients (average age 65.2 years) completed both questionnaires and were available for data analysis. Test-retest reliability of the FJS was high with an ICC = 0.80 (95 % CI 0.69, 0.90) and with a Cronbach's alpha of 0.95 (95 % CI 0.92, 0.99). CONCLUSIONS: The German translation of the FJS is a viable tool for the postoperative monitoring after arthroplasty of the knee. This is the first study providing data on test-retest reliability of the FJS. The FJS is a reliable and valid measurement tool for evaluation of patient rated outcome in patients with an artificial knee joint. LEVEL OF EVIDENCE: Validating cohort study, Level 1b.

Validation of a German version of the International Hip Outcome Tool (G-iHOT33) according to the COSMIN checklist: how much improvement is clinically relevant?

PURPOSE: The evaluation of the subjective health-related quality of life is especially for young, active patients with hip joint disorders important. The MAHORN study group has recently developed the "International Hip Outcome Tool" (iHOT33), a self-administered patient-reported outcome tool, which includes questions on the patient's symptoms, functional and sports limitations as well as social, emotional, and occupational limitations. The purpose of this study was to adapt and validate a German version of the iHOT33 according to the COSMIN checklist. METHODS: To validate the G-iHOT33, we conducted a prospective multicenter cohort study on patients with hip disorders and a score ≥4 on the modified Tegner Activity Scale. The patients completed the G-iHOT33 questionnaire twice at intervals of at least 2 weeks. In addition, we recorded the Hip Outcome Score (HOS), a modified Tegner Activity Scale (TAS), the EuroQol-5D (EQ5-D), and a subjective assessment of the limitations. Evaluation of psychometric properties was conducted following the COSMIN checklist for validation of health status measurement instruments. The methodical testing for reliability included internal consistency, test-retest reliability, and measurement error. For testing of validity, we analyzed construct validity, hypotheses testing, interpretability, and responsiveness. RESULTS: Between December 2013 and December 2014, eighty-three consecutive patients completed both questionnaires and were available for data analysis. Cronbach's α was 0.97 (95% CI 0.96, 0.99) confirming internal consistency and test-retest reliability of the G-iHOT-33 was high with an ICC = 0.88 (95% CI 0.80, 0.99). All a priori hypotheses were confirmed, further, no floor- or ceiling-effects occurred. The G-iHOT33 showed good responsiveness with a minimal important change (MIC) of 10 points. CONCLUSIONS: The German translation of the iHOT-33 (G-iHOT-33) is a viable tool for the evaluation of active patients with a hip disorder. Following the complete COSMIN checklist, we could prove that G-iHOT33 is a reliable, valid, and responsive PRO measurement tool. We could show that the minimal important change, a change of health condition the patient discerns is 10 points in the G-iHOT33 scale. This is the first study providing results on psychometric properties of the iHOT33 subscales. Level of evidence 1b validating cohort study.

Pediatric Cervical Spine Injuries: A Rare But Challenging Entity.

BACKGROUND: Injuries to the cervical spine in pediatric patients are uncommon. A missed injury can have devastating consequences in this age group. Because of the lack of routine in diagnosis and management of pediatric cervical spine injuries (PCSI), each of these cases represents a logistic and personal challenge. METHODS: By means of clinical cases, we demonstrate key points in diagnostics and treatment of pediatric spine injuries. We highlight typical pediatric injury patterns and more adult-like injuries. RESULTS: The most common cause of injury is blunt trauma. There is an age-related pattern of injuries in pediatric patients. Children under the age of 8 frequently sustain ligamentous injuries in the upper cervical spine. After the age of 8, the biomechanics of the cervical spine are similar to adults, and therefore, bony injuries of the subaxial cervical spine are most likely to occur. Clinical presentation of PCSI is heterogeneous. Younger children can neither interpret nor communicate neurological abnormalities, which make timely and accurate diagnosis difficult. Plain radiographs are often misinterpreted. We find different types of injuries at different locations, because of different biomechanical properties of the immature spine. We outline that initial management is crucial for long-term outcome. CONCLUSIONS: Knowledge of biomechanical properties and radiographic presentation of the immature spine can improve the awareness for PCSI. Diagnosis and management of pediatric patients after neck trauma can be demanding. LEVEL OF EVIDENCE: Level IV.

Vitamin D receptor signals regulate effector and memory CD8 T cell responses to infections in mice.

BACKGROUND: Vitamin D insufficiency is associated with broad-ranging human disease sequelae such as bone disease, cancer, cardiovascular disease, allergy, autoimmune disorders, diabetes, and infectious diseases. Disease risk and severity of a large proportion of the nonskeletal disorders heavily involve the cytotoxic cluster of differentiation (CD) 8 T lymphocyte (CTL) arm of cellular adaptive immunity. Considering the importance of vitamin D in CTL-dependent diseases, there is a critical need for systematic in-depth explorations into the role of vitamin D deficiency in generation and maintenance of CTL immunity during infections and vaccinations. OBJECTIVE: With the use of wild-type (WT) vitamin D-sufficient mice and the vitamin D receptor knockout (Vdr(-/-)) mouse model of in vivo deficiency of vitamin D signaling, we systematically analyzed the impact of vitamin D deficiency on antigen-specific effector and memory CD8 T cell responses to acute viral and bacterial infections. METHODS: WT and Vdr(-/-) mice were infected with lymphocytic choriomeningitis virus, a natural mouse pathogen, and antigen-specific CTL responses were analyzed during priming, expansion, contraction, and memory phases. Magnitude, breadth, cytokine production, and localization of antiviral effector and memory CTLs to lymphoid and nonlymphoid tissues were specifically assessed. RESULTS: The absence of vitamin D signals led to 1) aberrant CD8 T cell effector differentiation (∼2-fold lower granzyme B and reduced B cell lymphoma 2; P ≤ 0.05) and enhanced contraction (∼15% increase; P ≤ 0.05) in antigen-specific CTLs; 2) a significantly restricted (P ≤ 0.05) breadth of the antigen-specific CD8 T cell effector and memory repertoire; and 3) preferential localization of effector (∼2.5-fold increase; P ≤ 0.01) and memory (∼5-fold increase; P ≤ 0.001) CD8 T cells to the lymph nodes compared to nonlymphoid tissues. CONCLUSION: Our data show a previously unrecognized impact of vitamin D deficiency on the quantity, quality, breadth, and location of CD8 T cell immunity to acute viral and bacterial infections.

[Navigated or conventional acetabular surgery : Comparison of positional accuracy exemplified by the infra-acetabular screw]. / Navigiert oder konventionell in der Acetabulumchirurgie : Vergleich der Positionsgenauigkeit am Beispiel der infraazetabulären Schraube.

BACKGROUND: The principle of joint-preserving treatment of acetabular fractures is the anatomic reduction of joint-bearing elements and internal osteosynthesis. For stabilization of the anterior and posterior columns against each other, the infra-acetabular screw (IAS) is regularly used in the clinical routine. OBJECTIVE: The aim of this study was to compare the position of the IAS in the infra-acetabular corridor after navigated placement and after freehand placement. MATERIAL AND METHOD: The position of the screw was evaluated in 42 patients using multiplanar reconstructions. The screw was placed freehand in 30 patients and using image-guided navigation in 12 patients. In addition to measurement of the position of the screw, demographic data, operating time, radiation exposure and blood loss were recorded. RESULTS: The vast majority of the patients were male (86%), the median age was 67 years and the median body mass index (BMI) was 25 kg/m2. The median operating time was 166 min and the median blood loss was 900 ml. The adjusted values in the whole sample considering the position of the screw were: distance of screw to cartilage mean value (m) = 3.8 mm, distance of screw to corridor center m = 3.5 mm and angle of screw to corridor m = 1.4°. There were no differences between the groups in the demographic parameters and the accuracy of positioning of the screw (p-value > 0.05). There was a longer irradiation time and a higher radiation dose in the navigated group compared to the group without navigation (p-value < 0.001). CONCLUSION: With appropriate experience both procedures are comparable taking into account the accuracy. Taking into consideration other perioperative parameters, such as radiation exposure and planned operating time, patient-related factors should be taken into consideration.

The PJI-TNM classification for periprosthetic joint infections.

Aims: This study aimed to evaluate the clinical application of the PJI-TNM classification for periprosthetic joint infection (PJI) by determining intraobserver and interobserver reliability. To facilitate its use in clinical practice, an educational app was subsequently developed and evaluated. Methods: A total of ten orthopaedic surgeons classified 20 cases of PJI based on the PJI-TNM classification. Subsequently, the classification was re-evaluated using the PJI-TNM app. Classification accuracy was calculated separately for each subcategory (reinfection, tissue and implant condition, non-human cells, and morbidity of the patient). Fleiss' kappa and Cohen's kappa were calculated for interobserver and intraobserver reliability, respectively. Results: Overall, interobserver and intraobserver agreements were substantial across the 20 classified cases. Analyses for the variable 'reinfection' revealed an almost perfect interobserver and intraobserver agreement with a classification accuracy of 94.8%. The category 'tissue and implant conditions' showed moderate interobserver and substantial intraobserver reliability, while the classification accuracy was 70.8%. For 'non-human cells,' accuracy was 81.0% and interobserver agreement was moderate with an almost perfect intraobserver reliability. The classification accuracy of the variable 'morbidity of the patient' reached 73.5% with a moderate interobserver agreement, whereas the intraobserver agreement was substantial. The application of the app yielded comparable results across all subgroups. Conclusion: The PJI-TNM classification system captures the heterogeneity of PJI and can be applied with substantial inter- and intraobserver reliability. The PJI-TNM educational app aims to facilitate application in clinical practice. A major limitation was the correct assessment of the implant situation. To eliminate this, a re-evaluation according to intraoperative findings is strongly recommended.