In December 2000, the Inter-Op acetabular component (Sulzer Orthopedics Inc., TX) was recalled. Contamination by an oil-based residue that was inadvertently left in the porous coating following a change in manufacturing processes was suspected to have resulted in lack of fixation. The aim of this study was to characterize the histopathology of the these failures for consistency with this hypothesis. Materials and methods: Four hundred and fifty cups were submitted for gross and histopathological examination. H& E stained paraffin sections of tissue taken from the socket, membranes and/or capsules from the first 100 cases were reviewed histologically using a new rating scheme which accounts for the presence and extent of inflammatory cells, wear particles, and uncharacteristic tissue features. Immunohistochemical staining was performed on paraffin sections for IL1b, IL6 and TNFa (N=10) and for lymphocytes (CD3, CD4, CD20; N=8), and lipid stains were applied to selected frozen sections. Results: Cases were revised after ave. 6 months for pain and lack of fixation. Grossly the components had minimal attached tissue, if any. Histologically, the most common finding was extensive chronic inflammation (mostly lymphocytic), although many also had abundant acute inflammation (neutrophils and early granulation tissue). Lymphocytes were mostly common T and helper T cells. Eosinophils (cells associated with intense allergic reactions) were rare. Other uncharacteristic findings included histiocyte-rich granulomas, peculiar metal-like dust associated with silicate-like structures, vacuolated cells and unusual tissue spaces (20 – 50 mm in diameter) some of which were positive with lipid stains. Tissues stained strongly positive for IL-1b and IL-6 but only weakly for TNFa. A similar inflammatory response was noted to have spread into the capsular tissues. Conclusion: Given the absence of conclusive bacterial cultures in the majority of cases, the histopathology seems consistent with an oil-based contaminant mixed with debris generated from the machines used at the manufacturing plant

Objective. To determine the reliability, reproducibility, variability and validity of the Osteoarthritis Research Society International (OARSI) Osteoarthritis Cartilage Histopathology (OACH) system and Mankin Histopathology – Histochemical Grading System (HHGS) when applied to the characterisation of the osteoarthritic human knee. Method. Kellgren-Lawrence and Line Drawing Atlas (LDA) radiology scores clinically graded the knees of ten patients undergoing total knee arthroplasty due to osteoarthritis. The tibial plateaux were scored using the Modified Collins (MC) and Société Française d'Arthroscopie (SFA). Three observers, twice scored, using both the OACH and HHGS systems across a single complete medial and lateral tibial plateau transect taken to include the region with the most severe OA lesion. Intra and inter-observer reliability, reproducibility, variability and validity were quantified, and the correlation between the two histopathology scoring systems was calculated. Results. We identified that both histopathology scoring systems are reliable and reproducible exhibiting similar variability, when applied to characterise OA specimens sampled from a well defined patient group with knee osteoarthritis. A strong correlation between the mean OACH and HHGS scores was identified (Spearman'sρ 0.973). Conclusion. Both scoring systems provide useful measures in the characterisation of knee osteoarthritis. It is of note that an additional parameter within the OACH score over the HHGS that defines the extent of the disease, where the HHGS is a grade attributed to the most representative level of the biological aggression within the OA lesions. This study has confirmed the OACH system's utility in human knee OA and is supported by good correlation with the established Mankin HHGS

The management of bony lesions associated with glenohumeral instability has been open to debate. Invariably a significant period of time elapses between injury and surgery during which the bony fragment may atrophy and reduce both in size and in quality. Histomorphometric bone analyses were prospectively performed on the glenoid bone fragments harvested during the modified Latarjet operation. The main purpose of the study was to assess the viability of the bone. Biopsies were obtained from 21 patients that had given informed consent. Median age was 21 years (range 16–50). All were male patients. The most important sports identified were rugby (64%) and water sports (surfing, water polo, water skiing, surfing (21%)). Mean glenoid bone loss on CT scan was 17% (range 10–50%). Thirty-three percent had bone loss greater than 20%. Gross morphology of glenolabral fragments identified a single large fragment (11/21); dominant large fragment plus smaller fragments (7/21); multiple fragments (4/21). Single large fragments comprised 52% of the study. Mean volume and mass of bony fragments were 2.18 ml (range 1–3 ml) and 1.64 gms (range 0.43–2.8 g), respectively. Histology of the specimens revealed no bone in three of the 21 specimens. Bony necrosis was present in 8/18 (44%) of the specimens. From a histopathological point of view, reattachment of these devitalized bone fragments by screws or anchors may result in predictable operative failure and recurrent instability. We can therefore not support the practice of “repair” of bony Bankart lesions based on the above findings.

The management of bony lesions associated with glenohumeral instability is the subject of debate. Invariably some time elapses between injury and surgery, during which atrophy may reduce both size and quality of the bone.

The main purpose of our study was to assess the viability of the bone. Histomorphometric bone analyses were prospectively performed on glenoid fragments harvested from 21 male patients during modified Latarjet operations. Their median age was 21 years (16 to 50). Rugby was the main sport of 64% and water sports (surfing, water polo, water skiing) of 21%.

The mean glenoid bone loss on CT scan was 17% (10% to 50%). In 33% of patients, bone loss exceeded 20%. Gross morphology of glenolabral fragments identified a single large fragment in 11 patients, a dominant large fragment with smaller fragments in seven, and multiple fragments in the remaining patients. The mean volume of bony fragments was 2.18 ml (1 to 3) and the mean mass was 1.64 gm (0.43 to 2.8). Histological examination revealed that there was no bone in three of the 21 specimens. Bony necrosis was present in eight of the 18 specimens that contained bone (44%).

Given the histopathological findings, attempts to reattach these devitalised bone fragments by screws or anchors may fail and lead to recurrent instability.

To investigate the histological findings for a herniated cervical intervertebral disc that produces a high intensity signal on MR images.

Fifty-five herniated cervical intervertebral discs harvested from 49 patients were histologically and immunohistochemically examined. Herniated cervical intervertebral discs with a high intensity signal on axial T2 MR images were classified as a globular, linear, or mosaic type. The specimens were embedded with paraffin using standard procedures. Serial 4 μm thick cryostat sagittal sections were prepared for HE, toluidine blue, PAS, and Elastica van Gieson staining as well as immunohistochemical study. The monoclonal antibodies used were specific for human CD68, IL-1β, and TNF-α.

Preoperative axial T2 MR images indicated that 3 discs had no high intensity signal and 52 discs had a high intensity signal; 22 discs were globular, 20 were linear, and 10 were mosaic. Histopathologically, high intensity signal areas in globular discs consisted of nucleus pulposus surrounded by macrophages. These macrophages and the chondrocytes around them expressed IL-1β and TNF-α. Almost all of the patients with a globular disc, had had severe radicular pain. For the linear disc patients, the fissure was observed consistent with the high intensity signal. A substance that would produce positive results for PAS staining was rarely observed.

The current histological study suggests that a globular type of disc with a high intensity signal on an axial T2 MR image consisted of a nucleus pulposus. Results demonstrated that, in these herniated discs, infiltrated macrophages and chondrocytes expressed inflammatory cytokines, and these reactions were associated with radicular pain. In contrast, linear and mosaic discs showed no obvious substance corresponding with the high-intensity zone, but the fissure was observed. It appears that a high-intensity zone for a linear or mosaic type of disc suggested of a fluid-filled area and/or mucoid fluid.

Cutaneous nerve injury occurs commonly with knee arthroplasty, causing altered skin sensation and, infrequently, the formation of painful neuromas. The infrapatellar branch of the saphenous nerve is the structure most commonly damaged.

The aim of this study was to establish the frequency of cutaneous nerve injury with three incisions commonly used in knee arthroplasty.

Ten knees from five cadavers were studied. Skin strips representing three different incisions, were excised and examined for number and thickness of nerves.

There were more nerve endings found in the dermis layer than the subcutaneous fatty layer. There was no significant difference in the total number of nerves when the 3 studied incisions were compared. The lower part of all incisions was found to have more thick and a higher number of nerves than the upper part (P=0.005).

Careful incision placement is required to avoid damage to cutaneous nerves during knee arthroplasty. This may be of long-term advantage to patients especially those for whom kneeling is important.

Purpose: During surgery for repair of rotator cuff tears, some authors always associate tenotomy-tenodesis of the long head of the brachial biceps. Others decide as a function of the gross aspect of the tendon and its position in relation to the bicipital groove. It is a classical notion the preservation of the long head of the brachial biceps is a cuase of persistent pain in operated shoulders. This study was conducted to search for a histological validation of the decision to perform tenotomy.

Material and methods: Fifty tendons of the long head of the brachial biceps presented a thick and inflammatory aspect with or without subluxation during 68 procedures to repair recent rotator cuff tears (23 men, 27 women, mean age 53.5 years). Tenodesis of the long head of the brachial biceps was associated with proximal tenotomy. The histological examination concerned the most proximal centimeter of the tendon. Four parameters were studied: two concerned the tendon (organisation of the collagen network and aspect of the interstitial connective tissue), two concerned the synovial border (sub-synoviocytic layer and synovial mesothelium). Sixteen tendons which appeared perfectly healthy were harvested from cadaver shoulders to determine the normal aspect of histological parameters (parallel and cohesive orientation of the collagen network, absence of hypertrophic interstitial connective tissue, thin subsynovio-cytic layer and pluristratified synovial mesothelium).

Results: The tendon. The collagen bundles were oriented in 32 cases but thick in 40 and dissociated in 47. Microscopic signs of fissuration or intratendinous tears were present in 17 cases. The tendinous connective tissue was oedematous in 49 cases, presenting fibroblastic hyper-cellularity in 37 and hypervascularity in 43. Scar-like fibrosis was observed in 28 cases. The synovial layer was regular in 11 tendons and clearly thickened in 26 with a mixed irregular aspect in the others. The subsynoviocytic layer was thick in 33 tendons with signs of hypervascularity or hypercellularity in 12. The synovial mesothelium was paucistratifed in 23 cases, thick in 12, and regular in 15. Lesions had an inflammatory aspect and were intense in 26 cases. Degenerative lesions were observed in 21 tendons. These four histological parameters demonstrated that the lesions were advanced and associated with degenerative sclerosis with reactional synovitis in 30 cases, moderate combined lesions in 13, tendon and synovial inflammation alone in four, and advanced degenerative lesions of the tendon and the synovial in six.

Discussion: Histological lesions of the long head of the brachial biceps tendon are generally degenerative and irreversible while most synovial lesions are reversible inflammatory reactions. The zones of intratendinous fibrosis, vascularity and weak or absent cellularity constitute the anatomic conditions before tendon tears in chronic tendinopathy. This histological study confirmed the validity of the intra-operative decision for tenodesistenotomy of the long head of the brachial biceps in 46 (92%) of the cases. The oedematous and fissu-rated aspect of the tendon appeared to be a reliable criteria while inflammatory synovitis, which surrounds the tendon, does not constitute in itself a formal argument in favour of tendon sacrifice.

Aims. Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI). Methods. A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR. Results. The group with LIPUS and 0.35% PI exhibited decreased levels of serum biochemical markers, improved weightbearing scores, reduced reactive bone changes, absence of viable bacteria, and decreased inflammation compared to the Control group. Despite the greater antibiofilm activity observed in the PI group compared to the LIPUS and saline group, none of the monotherapies were successful in preventing reactive bone changes or eliminating the infection. Conclusion. In the rat model of PJI treated with DAIR, LIPUS combined with 0.35% PI demonstrated stronger antibiofilm potential than monotherapy, without impairing any local soft-tissue. Cite this article: Bone Joint Res 2024;13(7):332–341

Aims. Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium. Methods. Periprosthetic metal concentrations in the synovia and histopathological samples were analyzed from 230 patients from our institution from October 2016 to December 2019. An ordinal regression model was calculated to investigate the effect of the accumulated metals on the histopathological reaction of the synovia. Results. Median metal concentrations were as follows: cobalt: 0.69 μg/g (interquartile range (IQR) 0.10 to 6.10); chromium: 1.1 μg/g (IQR 0.27 to 4.10); and titanium: 1.6 μg/g (IQR 0.90 to 4.07). Moderate ALVAL scores were found in 30% (n = 39) of the revised knees. There were ten patients with an ALVAL score of 6 or more who were revised for suspected periprosthetic joint infection (PJI), aseptic loosening, or osteolysis. R2 varied between 0.269 and 0.369 for the ordinal regression models. The most important variables were model type, indication for revision, and cobalt and chromium in the ordinal regression models. Conclusion. We found that metal particles released from the knee prosthesis can accumulate in the periprosthetic tissues. Several patients revised for suspected culture-negative PJI had features of an ALVAL reaction, which is a novel finding. Therefore, ALVAL-type reactions can also be found around knee prostheses, but they are mostly mild and less common than those found around metal-on-metal prostheses. Cite this article: Bone Joint Res 2024;13(4):149–156

Aims. This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated. Methods. Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA). Results. Cartilage degeneration of the humeral head was associated with the histological presentation of: 1) pannus overgrowing the cartilage surface; 2) pores in the subchondral bone plate; and 3) chondrocyte clusters in OmA patients. In contrast, hyperplasia of the synovial lining layer was revealed as a significant indicator of inflammatory processes predominantly in CTA. The abundancy of collagen I, collagen II, and the C1,2C neoepitope correlated significantly with the histopathological degeneration of humeral head cartilage. No evidence for differences in MMP levels between OmA and CTA patients was found. Conclusion. This study provides a comprehensive histological characterization of humeral cartilage and synovial tissue within the glenohumeral joint, both in normal and diseased states. It highlights synovitis and pannus formation as histopathological hallmarks of OmA and CTA, indicating their roles as drivers of joint inflammation and cartilage degradation, and as targets for therapeutic strategies such as rotator cuff reconstruction and synovectomy. Cite this article: Bone Joint Res 2024;13(10):596–610

Aims. Adenosine, lidocaine, and Mg. 2+. (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Methods. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed. Results. Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased. Conclusion. At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials. Cite this article: Bone Joint Res 2024;13(6):279–293

Introduction. The intra-operative diagnosis of Prosthetic Joint Infection (PJI) is a dilemma requiring intra-operative sampling of suspicious tissues for frozen section, deep tissue culture and histopathology to secure a diagnosis. Alfa defensin-1 testing has been introduced as a quick and reliable test for confirming or ruling out PJI. This study aims to assess its intra-operative reliability compared to the standard tests. Methods. Twenty patients who underwent revision hip and knee arthroplasty surgery were included. Patients joint aspirate was tested intra-operatively with the Synovasure kit, which takes approximately ten minutes for a result. Our standard protocol of collecting 5 deep tissue samples for culture and one sample for histopathology was followed. Results for Alfa defensin-1 test were then compared with final culture and histopathology results in all these patients. Results. Our results show an excellent correlation with the final deep tissue cultures and histopathology outcomes. Literature reports frozen section to have low (58–73%) sensitivity but high (96%) specificity. Conclusions. Alfa defensin-1 test is easy, quick and efficient; results were available immediately intra-operatively. Cryosection is time consuming with samples shipped to the reference laboratory at times resulting in intra-operative delays. In our practice Alfa defensin-1 test certainly will replace frozen section for intra-operative testing

The use of routine sampling for histological analysis during revision hip replacement has been standard practice in our unit for many years. It is used to identify the presence of inflammatory processes that may represent peri-prosthetic infection. This study follows up on a smaller study in the same unit in 2019 where an initial 152 cases were scrutinised. In this follow up study we examined 1,361 consecutive patients over a 16-year period whom had undergone revision hip replacement in a tertiary orthopaedic centre for any reason excluding primary bone tumour or malignant metastasis. All patients had tissue sampling for histopathological analysis performed by consultant histopathologists with a specialist interest in musculoskeletal pathology. The presence of bacteria in greater than 50% of samples sent for microbiological analysis in each patient was used as the gold standard diagnostic comparator for infection. This was then compared with the histology report for each patient. After excluding 219 patients with incomplete data and 1 sample rejection, 1,141 cases were examined. Microbiology confirmed infection in 132 cases (prevalence of infection 11.04%) and histopathology analysis suggested infection in 171 cases. Only 64 cases with confirmed infection in more than 50% of microbiology samples had concurrent diagnosis of infection on histological analysis (5.60% of total; PPV 51.20%). Furthermore, microbiology analysis confirmed infection in 62 cases where histological analysis failed to identify infection (5.43% of total; False negative rate 49.21%). Overall, histopathology analysis was seen to have a good specificity of 93.99% but poor sensitivity of 50.79%. We believe that this is the largest series in the literature and is somewhat unique in that all histology analysis was performed by consultant histopathologists with specialist interest in musculoskeletal pathology. Based on the costs incurred by this additional investigation our experience does not support routine sampling for histological analysis in revision hip arthroplasty. This is a substantial paradigm shift from current practice among revision arthroplasty surgeons in the United Kingdom but would equate to a substantial cost saving

Aim. The localization of sequestrum in chronic osteomyelitis (COM) is crucial in preoperative planning. The identification of sequestrum on plain X-ray could be difficult. CT and MRI were reported to show the sequestrum. We aimed to analyze the sequestrum characteristics on 18F-FDG-PET-CT images. Methods. A prospective study included all patients diagnosed with long-bone chronic osteomyelitis. All patients had preoperative 18F-FDG-PET-CT. Images were analyzed using RadiAnt DICOM Viewer. Axial cuts were used to measure the Standard Uptake Ratio (SUV)max in the Region of Interest (ROI) in the sequestrum, the surrounding area, and the normal bone in the same cut. Surgical debridement was done as standard; samples were taken for microbiology and histopathology, and the intraoperative finding was documented. Results. Nineteen patients (17 males/2 females) were operated on in one center between October/2021 and Jan/2023 at a mean age of 32±18. There were 10 tibias, 7 femurs, one ulna, and one fibula. Ten had postoperative COM, six open fractures, and three hematogenous OM. They all showed sequestrum on PET-CT; the dead bone appeared void, surrounded by a halo of increased uptake. There was a trend of lower uptake in the sequestrum compared to the halo around. The mean SUVmax at the sequestrum was 4.18±3.16, compared to the surrounding halo, 7.08±5.81. The normal bone has a mean SUVmax of 1.61±1.42. Sequestrum was removed successfully in all cases. Conclusion. 18F-FDG-PET-CT can precisely localize the sequestrum preoperatively, it has a lower uptake than tissues around it. This would facilitate planning and improve the quality of debridement

Although autografts represent the gold standard for anterior cruciate ligament (ACL) reconstruction, tissue-engineered ACLs provide a prospect to minimize donor site morbidity and limited graft availability. This given study characterizes the ligamentogenesis in embroidered poly(L-lactide-co-ε-caprolactone) (P(LA-CL)) / polylactic acid (PLA) constructs using a dynamic nude mice xenograft model. (P(LA-CL))/PLA scaffolds remained either untreated (co) or were functionalized by gas fluorination (F), collagen foam cross-linked with hexamethylene diisocyanate (HMDI) (coll), or gas fluorination combined with the foam (F+coll). Cell free constructs or those seeded for 1 week with lapine ACL ligamentocytes were implanted into nude mice for 12 weeks. Following explantation, biomechanical properties, cell vitality and content, histopathology of scaffolds (including organs: liver, kidney, spleen), sulphated glycosaminoglycan (sGAG) contents and biomechanical properties were assessed. Implantation of the scaffolds did not negatively affect mice weight development and organs, indicating biocompatibility. All scaffolds maintained their size and shape for the duration of the implantation. A high cell viability was detected in the scaffolds prior to and following implantation. Coll or F+coll scaffolds seeded with cells yielded superior macroscopic properties when compared to the controls. Mild signs of inflammation (foreign-body giant cells, hyperemia) were limited to scaffolds without collagen. Microscopical score values and sGAG content did not differ significantly. Although remaining stable in vivo, elastic modulus, maximum force, tensile strength and strain at Fmax were significantly lower in the in vivo compared to the samples cultured 1 week in vitro, but did not differ between scaffold subtypes, except for a higher maximum force in F+coll compared with F samples (in vivo). Scaffold functionalization with fluorinated collagen foam provides a promising approach for ACL tissue engineering. (shared first authorship). Acknowledgement: The study was supported by DFG grants SCHU1979/9-1 and SCHU1979/14-1

TGF-β/Smad2 signaling is considered to be one of the important pathways involved in osteoarthritis (OA) and protein phosphatase magnesium-dependent 1A (PPM1A) functions as an exclusive phosphatase of Smad2 and regulates TGF-β signaling, here, we investigated the functional role of PPM1A in OA pathogenesis. PPM1A expressions in both human OA cartilage and experimental OA mice chondrocytes were analyzed immunohistochemically. Besides, the mRNA and protein expression of PPM1A induced by IL-1β treatment were also detected by q-PCR and immunofluorescence in vitro. OA was induced in PPM1A knockout (KO) mice by destabilization of the medial meniscus (DMM), and histopathological examination was performed. OA was also induced in wild-type (WT) mice, which were then treated with an intra-articular injection of a selective PPM1A inhibitor for 8 weeks. PPM1A protein expressions were increased in both human OA cartilage and experimental OA mice chondrocytes. We also found that treatment with IL-1β in mouse primary chondrocytes significantly increased both mRNA and protein expression of PPM1A in vitro. Importantly, our data showed that PPM1A deletion could substantially protect against surgically induced OA. Concretely, the average OARSI score and quantification of BV/TV of subchondral bone in KO mice were significantly lower than that in WT mice 8 weeks after DMM surgery. Besides, TUNEL staining revealed a significant decrease in apoptotic chondrocytes in PPM1A-KO mice with DMM operation. With OA induction, the rates of chondrocytes positive for Mmp-13 and Adamts-5 in KO mice were also significantly lower than those in WT mice. Moreover, compared with WT mice, the phosphorylation of Smad2 in chondrocytes was increased in KO mice underwent DMM surgery. However, articular-injection with SD-208, a selective inhibitor of TGF-β/Smad2 signaling could significantly abolish the chondroprotective phenotypes in PPM1A-KO mice. Additionally, both cartilage degeneration and subchondral bone subchondral bone sclerosis in DMM model were blunted following intra-articular injection with BC-21, a small-molecule inhibitor for PPM1A. Our study demonstrated that PPM1A inhibition attenuates OA by regulating TGF-β/Smad2 signaling. Furthermore, PPM1A is a potential target for OA treatment and BC-21 may be employed as alternative therapeutic agents for the management of OA

INTRODUCTION. Tuberculosis (TB) is a public health challenge. However, musculoskeletal involvement represents 10–15% of all extrapulmonary cases. Upper extremity involvement is extremely rare. The slow progressive course of clinical symptoms and lack of radiological signs lead to difficulties in establishing early diagnosis. Hence, the patients who have tuberculosis of the wrist are usually misdiagnosed. We report 5 cases of tuberculosis of the wrist seen in our unit from the year 2012 to 2021. METHODS. Cases were retrospectively evaluated on demographics, nature of history, clinical presentation, culture finding, and histopathological findings from 2012 to 2021 at our unit. RESULTS. A total of 5 cases were evaluated retrospectively. Three patients were more than 60 years old and two were less than 30 years old. Four of the patients presented with wrist swelling 2 of them had wrist pain and only 1 patient had discharge from the wound. The duration of the symptoms ranges from 2 months to 3 years. Only one of the patients had a history of pulmonary TB contact whereas the others didn't. All patients underwent surgery. All of the patients had positive cultures for Mycobacterium tuberculosis complex and histopathological examination showed necrotizing granulomatous inflammation from specimens taken intraoperatively, which confirmed the diagnosis of tuberculosis of the wrist. DISCUSSIONS. Our cases show that the common presentation of tuberculosis of the wrist was comparable to other literature. Most of the patients presented with chronic wrist swelling with or without wrist pain. The diagnosis of the disease was delayed an average of 10 - 12 months from symptoms onset to diagnosis. S. Bayram et al reported a case where the diagnosis was made 45 months later. Due to its rarity, it often is misdiagnosed, resulting in delays in the proper treatment. CONCLUSION. The diagnosis of the TB wrist remains difficult because of insidious and non-specific. presentation. However, early diagnosis is essential to avoid delays in treatment and complications. Hence, chronic wrist pain, and swelling with or without unexplained bone erosion around the wrist area must be highly suspected of being osteoarticular tuberculosis

Background and aim. In 2019, specific diagnostic and antibiotic treatment recommendations for diabetic foot infection (DFI) and osteomyelitis (DFO) were introduced in our institution. They include principles on numbers of biopsies to obtain for microbiological/histopathological examinations, labeling anatomic localization, and antibiotic treatment (ABT) duration based on the aforementioned findings. ABT should be stopped after complete resection of infected bone. In case of incomplete resection, treatment is continued for 4–6 weeks. Two years after the introduction of these recommendations, we investigated the degree of implementation for hospitalized patients. Method. Adult patients with DFI/DFO undergoing surgical intervention from 01/2019–12/2021 were reviewed retrospectively. Diagnostic procedures were assigned to each episode when performed ≤30 days before surgical invention. Chi-square and Mann-Whitney-U tests were performed where appropriate. Results. We included 80 patients with 117 hospital episodes and 163 surgical interventions (mean 1.5 episodes and 2 interventions per patient). The mean age was 69.6 (SD 11.5) years, 75% were male. Vascular examination and MRI were performed in 70.9% and 74.4% of episodes, respectively. Impaired perfusion and DFO were confirmed in 34.9% and 56.3%, respectively. Blood cultures were sampled in 34.2%, bacteremia detected in 7.7% with S. aureus being the most common microorganism. Biopsies were obtained in 71.8% of operations, in 90.5% of those 3–5 samples. These were sent for histological examination in 63.2% of the interventions. In 43.6% the anatomic location was labeled ‘proximal to the resection margin’. Preoperative antibiotics were administered in 41.9% of the episodes because of concomitant soft-tissue infections. The most commonly used compound was amoxicillin/clavulanate (74.4%). ABT duration varied significantly when there were signs of DFO in preoperative MRI (p=0.015). The mean duration of antibiotic therapy was 9 (IQR 5–15) days in surgically cured episodes and 40.5 (IQR 15–42) days in cases with resection margins in non-healthy bone (p<0.0001). The results were similar when analyzing treatment duration with respect to osteomyelitis in histology: 13 (IQR 8–42) versus 29 (IQR 13–42) days, respectively (p=0.026). Conclusions. The adherence to recommendations in terms of biopsy sampling was excellent, moderate for sending samples to histology and poor for labeling the anatomic location. The adherence to ABT duration was good but can be improved by shortening treatment duration for surgically cured cases. Results of preoperative MRI appear to be influential on the decision-making for treatment duration

Aim. Treatment algorithms for fracture-related nonunion depend on the presence or absence of bacterial infection. However, the manifestation of septic nonunion varies. Low-grade infections, unlike manifest infections, lack clinical signs of infection and present similarly to aseptic nonunion. The clinical importance of low-grade infection in nonunion is not entirely clear. Therefore, the aim of this study was to evaluate the clinical relevance of low-grade infection in the development and management of femoral or tibial nonunion. Method. A prospective, multicenter clinical study enrolled patients with nonunion and regular healed fractures. Preoperatively, complete blood count without differential, C-reactive protein (CRP), and procalcitonin were obtained, clinical signs of infection were recorded, and a suspected septic or aseptic diagnosis was made based on history and clinical examination. During surgical nonunion revision or routine implant removal, tissue samples were collected for microbiology and histopathology, and osteosynthesis material for sonication. Nonunion patients were followed for 12 months. Definitive diagnosis of “septic” or “aseptic” nonunion was made according to diagnostic criteria for fracture-related infection, considering the results of any further revision surgery during follow-up. Results. 34 patients with regular healed fractures were included. 62 nonunion patients were diagnosed as aseptic, 22 with manifest, and 23 with low-grade infection. The positive predictive value was 88% and the negative predictive value 72% for the suspected diagnosis. The nonunion groups had significantly higher CRP levels than the regular healer group. Differentiation between septic and aseptic nonunion based on blood values was not possible. Low-grade infection demonstrated less frequently histopathologic signs of infection than manifest infection (22% vs. 50%, p=0.048), with 15% of regular healers having histopathologic signs of infection. Cutibacterium acnes was less present in manifest compared to low-grade infection (p=0.042). Healing rates for septic nonunion involving C. acnes were significantly lower for manifest infection (20%) than for low-grade infection (100%, p=0.002). Patients with low-grade infection were treated with systemic antibiotics less frequently than patients with manifest infection (p=0.026), with no significant difference in healing rate (83% vs. 64%), which was slightly lower for low-grade infection than for aseptic nonunion (90%). Conclusions. Low-grade infections play a significant role in nonunion development and are difficult to diagnose preoperatively due to the lack of clinical signs of infection and unremarkable blood counts. However, our results imply that for low-grade infections, antibiotic therapy may not always be mandatory to heal the nonunion. This study was supported by the German Social Accident Insurance (FF-FR0276)

Aim. To make an inoculum for induction of Implant-Associated Osteomyelitis (IAO) in pigs based on bacterial aggregates resembling those found on the human skin, i.e. aggregates of 5–15 µm with low metabolic activity. The aggregates were evaluated and compared to a standard planktonic bacterial inoculum. Method. The porcine Staphylococcus aureus strain S54F9 was cultured in Tryptone Soya Broth for seven days. Subsequently, the culture was filtered through cell strainers with pore sizes of 15 µm and 5 µm, respectively. The fraction of 5–15 µm aggregates in the top of the 5 µm filter was collected as the aggregate-inoculum. The separation of aggregates into different size fractions was evaluated by light microscopy. The metabolism of the aggregate-inoculum and a standard overnight planktonic inoculum was evaluated with isothermal microcalorimetry. In total, six female minipigs were allocated into three groups (n=2), receiving different inoculums. Group A: overnight planktonic inoculum; 10. 4. CFU S. aureus (S54F9), Group B: seven days old 5–15 µm aggregate-inoculum; 10. 4. CFU S. aureus (S54F9), Group C: saline. All inoculums were placed in a pre-drilled implant cavity in the right tibia of the pig and a sterile stainless-steel implant was inserted. The pigs were euthanized seven days after surgery. Postmortem macroscopic pathology, microbiology, computed tomography and histopathology were performed. Results. The separation of aggregates into different size fractions was done successfully by the filtering method. Isothermal microcalorimetry showed, a delayed Time-to-peak metabolic activity of the aggregate-inoculum compared to the planktonic inoculum. S. aureus was isolated from subcutis, bone and implants from all animals in groups A and B. Both group A animals showed osteomyelitis at gross inspection with suppuration and sequestration, while groups B and C animals had no macroscopic lesions. From CT scans, both group A animals also showed positive signs of osteomyelitis, i.e., osteolysis, while only one animal in group B did, and none in group C. Histopathological examination of the bones showed more extensive inflammation in group A animals compared to those in group B, which showed more osteoid formation. Conclusions. Formation and separation of low metabolism bacterial aggregates into different size fractions was possible. The aggregates can be used as inoculum in the porcine IAO model, with microbiological re-isolation from both implants and tissue. Furthermore, the aggregates caused a less aggressive IAO, than the planktonic counterparts. Using aggregated bacteria as inoculum appears to be more relevant to the clinical situation of infecting bacteria