Phagocytic cell death leads to enhanced release of pro-inflammatory S100A12 in familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever (FMF) is a prototypical autoinflammatory syndrome associated with phagocytic cell activation. Pyrin mutations are the genetic basis of this disease, and its expression has been shown in monocytes, granulocytes, dendritic cells, and synovial fibroblasts. Pyrin functions as a cytosolic pattern recognition receptor and forms a distinct pyrin inflammasome. The phagocyte-specific protein S100A12 is predominantly expressed in granulocytes and belongs to the group of damage associated molecular patterns (DAMP). S100A12 can be detected at massively elevated levels in the serum of FMF patients, even in clinically inactive disease. Whether this is crucial for FMF pathogenesis is as yet unknown, and we therefore investigated the mechanisms of S100A12 release from granulocytes of FMF patients presenting clinically inactive. RESULTS: We demonstrate that FMF neutrophils from patients in clinical inactive disease possess an intrinsic activity leading to cell death even in exogenously unstimulated neutrophils. Cell death resembles NETosis and is dependent on ROS and pore forming protein gasdermin D (GSDMD), as inhibitors for both are capable of completely block cell death and S100A12 release. When pyrin-activator TcdA (Clostridium difficile toxin A) is used to stimulate, neutrophilic cell death and S100A12 release are significantly enhanced in neutrophils from FMF patients compared to neutrophils from HC. CONCLUSIONS: We are able to demonstrate that activation threshold of neutrophils from inactive FMF patients is decreased, most likely by pre-activated pyrin. FMF neutrophils present with intrinsically higher ROS production, when cultured ex vivo. This higher baseline ROS activity leads to increased GSDMD cleavage and subsequent release of, e.g., S100A12, and to increased cell death with features of NETosis and pyroptosis. We show for the first time that cell death pathways in neutrophils of inactive FMF patients are easily triggered and lead to ROS- and GSDMD-dependent activation mechanisms and possibly pathology. This could be therapeutically addressed by blocking ROS or GSDMD cleavage to decrease inflammatory outbreaks when becoming highly active.

The effects of force application on the compressive properties of femoral spongious bone.

BACKGROUND: End artefacts play a major role in uniaxial compression tests with cancellous bone specimens. They lead to misinterpretation of mechanical parameters of bones due to uncontrolled introduction of bending moments into the free ends of trabeculae. This work aims to simplify current methods preventing end-artefacts and furthermore to investigate the influence of end artefacts on plateau stress. METHODS: 176 cylindrical cancellous bone specimens were taken from human femoral condyles and tested in uniaxial compression. The specimens were divided into 2 groups (direct, end-cap) and compressive modulus, maximum stress, plateau stress, energy absorbtion as well as apparent density were evaluated. Density values are from separate specimens which are immediately adjacent to the mechanical specimen. FINDINGS: All mechanical parameters were significantly higher in the end-cap specimens than in the direct ones by about 30 - 40 %, thus reaching similar differences as the previous studies. Greatest differences between groups were determined for compressive modulus (45 %) and plateau stress (35 %). Energy absorbtion can be explained with great accuracy by plateau stress (P < 0.001; R2 = 0.95). Among all parameters plateau stress can be best explained by apparent density using an exponential function (P < 0.001; R2 = 0.38). INTERPRETATION: The end-cap method used here to prevent end artefacts showed variations consistent with the literature when compared to the direct method. Additionally it was shown that the way in which the force is applied to the specimen has a major influence on the failure progression behavior, which was characterized using the plateau stress.

Risk factors for revision surgery in operative treatment of traumatic injuries of the olecranon and prepatellar bursa.

INTRODUCTION: Traumatic lacerations of the prepatellar (PB) and olecranon bursa (OB) are common injuries. The aim of this study was to gain descriptive data and to identify risk factors associated with complications that made revision surgery after primary bursectomy necessary. MATERIAL AND METHODS: In this retrospective monocentric study at a level I trauma center, all patients with traumatic lacerations of the PB or OB who were treated with primary surgical bursectomy from 2015 to 2020 were analyzed. RESULTS: 150 consecutive patients were included. In 44% of cases, the PB was affected (n = 66), in 56% the OB (n = 84). The reoperation rate after surgical bursectomy was 10.7% (n = 16). The main cause of reoperation was wound infection (50%; n = 8). The most common pathogen of postoperative infections was Staphylococcus aureus (87.5%). Several comorbidities have been identified as risk factors for reoperation after primary surgical bursectomy, such as heart diseases, arterial hypertension, the use of antihypertensives and anticoagulation. In contrast, surgical expertise, use of drains, postoperative immobilization, and postoperative antibiotics had no statistically significant effect. A significantly higher postoperative infection rate (17.6%) was observed in patients who were operated more than 48 h after initial trauma. CONCLUSIONS: Given the limited recommendations for therapy of these common injuries, further investigations should focus on standardized therapeutic options for lacerations of the PB or OB. Delayed surgical interventions after trauma were associated with higher complication rates. Therefore, urgent surgery within 48 h after trauma may help to prevent revisions. LEVEL OF EVIDENCE: Level of evidence IV.

Influence of osteoporosis on the compressive properties of femoral cancellous bone and its dependence on various density parameters.

Data collection of mechanical parameters from compressive tests play a fundamental role in FE modelling of bone tissues or the developing and designing of bone implants, especially referring to osteoporosis or other forms of bone loss. A total of 43 cylindrical samples (Ø8 × 16 mm) were taken from 43 freshly frozen proximal femora using a tenon cutter. All femora underwent BMD measurement and additionally apparent- and relative- and bulk density (ρapp, ρr, ρb) were determined using samples bordering the compressive specimen on the proximal and distal regions. All samples were classified as "normal", "osteopenia" and "osteoporosis" based on the DEXA measurements. Distal apparent density was most suitable for predicting bone strength and BMD. One novel aspect is the examination of the plateau stress as it describes the stress at which the failure of spongious bone progresses. No significant differences in mechanical properties (compressive modulus E; compressive stress σmax and plateau stress σp) were found between osteopenic and osteoporotic bone. The results suggest that already in the case of a known osteopenia, actions should be taken as they are applied in the case of osteoporosis A review of the literature regarding extraction and testing methods illustrates the urgent need for standardized biomechanical compressive material testing.

Comparison of three different screw trajectories in osteoporotic vertebrae: a biomechanical investigation.

BACKGROUND: Pedicle screw insertion in osteoporotic patients is challenging. Achieving more screw-cortical bone purchase and invasiveness minimization, the cortical bone trajectory and the midline cortical techniques represent alternatives to traditional pedicle screws. This study compares the fatigue behavior and fixation strength of the cement-augmented traditional trajectory (TT), the cortical bone trajectory (CBT), and the midline cortical (MC). METHODS: Ten human cadaveric spine specimens (L1 - L5) were examined. The average age was 86.3 ± 7.2 years. CT scans were provided for preoperative planning. CBT and MC were implanted by using the patient-specific 3D-printed placement guide (MySpine®, Medacta International), TT were implanted freehand. All ten cadaveric specimens were randomized to group A (CBT vs. MC) or group B (MC vs. TT). Each screw was loaded for 10,000 cycles. The failure criterion was doubling of the initial screw displacement resulting from the compressive force (60 N) at the first cycle, the stop criterion was a doubling of the initial screw displacement. After dynamic testing, screws were pulled out axially at 5 mm/min to determine their remaining fixation strength. RESULTS: The mean pull-out forces did not differ significantly. Concerning the fatigue performance, only one out of ten MC of group A failed prematurely due to loosening after 1500 cycles (L3). Five CBT already loosened during the first 500 cycles. The mean displacement was always lower in the MC. In group B, all TT showed no signs of failure or loosening. Three MC failed already after 26 cycles, 1510 cycles or 2144 cycles. The TT showed always a lower mean displacement. In the subsequent pull-out tests, the remaining mean fixation strength of the MC (449.6 ± 298.9 N) was slightly higher compared to the mean pull-out force of the CBT (401.2 ± 261.4 N). However, MC (714.5 ± 488.0 N) were inferior to TT (990.2 ± 451.9 N). CONCLUSION: The current study demonstrated that cement-augmented TT have the best fatigue and pull-out characteristics in osteoporotic lumbar vertebrae, followed by the MC and CBT. MC represent a promising alternative in osteoporotic bone if cement augmentation should be avoided. Using the patient-specific placement guide contributes to the improvement of screws' biomechanical properties.

[Are Higher Prices for Larger Femoral Heads in Total Hip Arthroplasty Justified from the Perspective of Health Care Economics? An Analysis of Costs and Effects in Germany]. / Sind höhere Preise für größere Kopfdurchmesser in der Hüftendoprothetik medizinökonomisch vertretbar? Eine Analyse der Kosten und Effekte in Deutschland.

Background: In total hip arthroplasty (THA), femoral head diameter has not been regarded as a key parameter which should be restored when reconstructing joint biomechanics and geometry. Apart from the controversial discussion on the advantages and disadvantages of using larger diameter heads, their higher cost is another important reason that they have only been used to a limited extent. The goal of this study was to analyse the price structure of prosthetic heads in comparison to other components used in THA. A large group of patients with hip endoprostheses were evaluated with respect to the implanted socket diameter and thus the theoretically attainable head diameter. Materials and Methods: The relative prices of various THA components (cups, inserts, stems and ball heads) distributed by two leading German manufacturers were determined and analysed. Special attention was paid to different sizes and varieties in a series of components. A large patient population treated with THA was evaluated with respect to the implanted cup diameter and therefore the theoretically attainable head diameter. Results: The pricing analysis of the THA components of two manufacturers showed identical prices for cups, inserts and stems in a series. In contrast to this, the prices for prosthetic heads with a diameter of 36-44 mm were 11-50 % higher than for 28 mm heads. Identical prices for larger heads were the exception. The distribution of the head diameter in 2719 THA cases showed significant differences between the actually implanted and the theoretically attainable heads. Conclusion: There are proven advantages in using larger diameter ball heads in THA and the remaining problems can be solved. It is therefore desirable to correct the current pricing practice of charging higher prices for larger components. Instead, identical prices should be charged for all head diameters in a series, as is currently established practice for all other THA components. Thus when reconstructing biomechanics and joint geometry in THA, it should be possible to recover not only leg length, femoral offset and antetorsion of the femoral neck, but also to approximately restore the diameter of the femoral head and thereby optimise the functional outcome.

A pilot trial comparing the tear-out behavior in screw-sockets and cemented polyethylene acetabular components - a cadaveric study.

BACKGROUND: The removal of well-fixed acetabular components following THA (total hip arthroplasty) is a difficult operation and could be accompanied by the loss of acetabular bone stock. The optimal method for fixation is still under debate. The aim of this pilot study was to compare the tear-out resistance and failure behavior between osseo-integrated and non-integrated screw cups. Furthermore, we examined whether there are differences in the properties mentioned between screw sockets and cemented polyethylene cups. HYPOTHESIS: Tear-out resistance and related mechanical work required for the tear-out of osseo-integrated screw sockets are higher than in non-integrated screw sockets. PATIENTS AND METHODS: Ten human coxal bones from six cadavers with osseo-integrated screw sockets (n=4), non-integrated (implanted post-mortem, n=3) screw sockets and cemented polyethylene cups (n=3) were used for tear-out testing. The parameters axial failure load and mechanical work for tear-out were introduced as measures for determining the stability of acetabular components following THA. RESULTS: The osseo-integrated screw sockets yielded slightly higher tear-out resistance (1.61±0.26kN) and related mechanical work compared to the non-integrated screw sockets (1.23±0.39kN, P=0.4). The cemented polyethylene cups yielded the lowest tear-out resistance with a failure load of 1.18±0.24kN. Compared to the screw cups implanted while alive, they also differ on a non-significant level (P=0.1). Osseous failure patterns differed especially for the screw sockets compared to the cemented polyethylene cups. DISCUSSION: Osseo-integration did not greatly influence the tear-out stability in cementless screw sockets following axial loading. Furthermore, the strength of the bone-implant-interface of cementless screw sockets appears to be similar to cemented polyethylene cups. However, given the high failure load, high mechanical load and because of the related bone failure patterns, removal should not be performed by means of tear-out but rather by osteotomes or other curved cutting devices to preserve the acetabular bone stock. LEVEL OF EVIDENCE: Level III, case-control-study.

[Larger heads compensate for an increased risk of THA dislocation in high-risk patients]. / Größere Köpfe kompensieren erhöhte Hüft-TEP-Luxationsgefahr bei Hochrisikopatienten.

BACKGROUND: Dislocation is a devastating complication after total hip arthroplasty (THA) and occurs in 2-5% of primary THA cases and 5-10% of revision THA cases. Assuming correct implantation, dislocation risk can be reduced primarily by capsular repair and the use of larger prosthetic heads. However, larger heads are also associated with risks like accelerated wear or implant loosening, which is why heads with a maximum diameter of 36 mm are currently standard in primary THA. In cases with high dislocation risk, the use of 40 mm and 44 mm heads should be considered. OBJECTIVES: This study aimed to quantify THA dislocation risk and retrospectively analyze the course of disease in high-risk patients treated with 40 mm or 44 mm femoral heads after primary or revision THA, concerning dislocation and other complications suffered. MATERIALS AND METHODS: All patients with increased THA dislocation risk, treated from 2009-2014, were evaluated regarding dislocations. The cases with installation of 40 mm or 44 mm prosthetic heads were classified using a self-developed 5-level risk score and retrospectively analyzed. RESULTS: During the observation period, 288 THA interventions with increased dislocation risk were performed. In 278 cases with ball diameters ≤ 36 mm the dislocation rate was 15.1% (n=42). In 10 high dislocation-risk cases (3A to 4B according to recommended scoring system), 40 mm and 44 mm heads were used. After a 22.8 month mean follow-up, no THA dislocations were reported. CONCLUSION: Our results with 40 and 44 mm heads and the existing literature confirm much higher joint stability and, thus, significantly reduced dislocation risk with larger prosthetic heads in THA. Their use is, therefore, justified in high-risk patients and should be considered in future THA.

[The impact of capsular repair on the dislocation rate after primary total hip arthroplasty: a retrospective analysis of 1972 cases]. / Der Einfluss der Kapselrekonstruktion auf die Luxationsrate nach primärer Hüftendoprothetik: eine retrospektive Analyse von 1972 Fällen.

BACKGROUND: Dislocation is the second most frequently encountered complication in primary total hip arthroplasty (THA) and occurs more commonly in the early postoperative rehabilitation phase. Sir Charnley recommended the "avoidance of resection of the capsule" and emphasised its contribution to hip joint stability in THA. Several authors, however, doubted its significance and considered resection of the capsule to be essential. Since 2002, some surgeons increasingly adopted a modified, less invasive technique of THA via Bauer approach, including the preservation and repair of the hip joint capsule with focus on maintaining its acetabular origin. Another group of surgeons applied the traditional technique including the resection of the joint capsule via an anterolateral approach. In this case-control study we investigated whether the dislocation rate can be reduced through joint capsule reconstruction and whether any negative impact on patient satisfaction, functional results or revision rate is observed. MATERIAL AND METHODS: All cases of primary THA performed in our institution in a timeframe between 2002 and 2009 were included with the only exceptions of resurfacing arthroplasty, dual mobility and tumour hip replacements. Joint capsule repair cases were gathered in the study group (SG), capsule resection cases in the control group (CG). Additional patient-related data were taken from the anaesthesia records. The WOMAC score and a questionnaire focusing on detection of dislocations and revision surgeries was sent out for each case. Further targeted research was conducted that included requesting records and reports from external hospitals. In the case of non-responding patients, all available data (operating room documentation, electronic files, archive, X-rays) were reviewed for incidents of dislocation and revision surgery. Groupings and classifications were exclusively performed by senior surgeons. SG and CG were compared regarding epidemiologic, implant-associated and surgery-specific data. Statistical evaluations were performed using the Chi-squared test and the Mann-Whitney U test. RESULTS: 1972 cases of primary THA were included: 992 in the SG and 980 in the CG. The follow-up rates were 92.7 % in the SG and 76.4 % in the CG, the mean follow-up times 33.5 months and 73.4 months, respectively, with a follow-up of at least 12 months in all cases. In the SG, the dislocation rate was 0.3 % (n = 3) and thus significantly lower than the 2.55 % in the CG (n = 25, p < 0.001). Both the WOMAC score (SG: 1.46 ± 1.73; CG: 1.53 ± 1.80; p > 0.05) and the revision rate (SG: 5.24 %; CG: 6.84 %; p = 0.139) showed no significant differences. CONCLUSION: Preservation and repair of the hip joint capsule causes an 88-%-reduction of the dislocation rate in primary THA in this large series including 1972 cases, operated via the Bauer or the anterolateral approach. Several authors reported comparable results after THA using similar techniques of soft tissue and capsular repair through the posterior or posterolateral approach. Sparing and reconstructing the hip joint capsule therefore seems to reduce the dislocation rate after primary THA by one order of magnitude regardless of the surgical approach and, especially, if the acetabular origin is preserved. Capsule-related specific complications such as an increased revision rate, malfunction or pain were neither recorded in our study nor by others. Thus, careful preservation and reconstruction of the hip joint capsule may be expressly recommended in primary THA.