Aims. The aim of this study was to determine the diagnostic utility of histological analysis in spinal biopsies for spondylodiscitis (SD). Patients and Methods. Clinical features, radiology, results of microbiology, histology, and laboratory investigations in 50 suspected SD patients were evaluated. In 29 patients, the final (i.e. treatment-based) diagnosis was pyogenic SD; in seven patients, the final diagnosis was mycobacterial SD. In pyogenic SD, the neutrophil polymorph (NP) infiltrate was scored semi-quantitatively by determining the mean number of NPs per (×400) high-power field (HPF). Results. Of the 29 pyogenic SD patients, 17 had positive microbiology and 21 positive histology (i.e. one or more NPs per HPF on average). All non-SD patients showed less than one NP per HPF. The presence of one or more NPs per HPF had a diagnostic sensitivity of 72.4%, specificity 100%, accuracy 100%, positive predictive value (PPV) 81.0%, and negative predictive value (NPV) 61.9%. Sensitivity, specificity, and accuracy were greater using the criterion of positive histology and/or microbiology than positive histology or microbiology alone. Granulomas were identified histologically in seven mycobacterial SD patients, and positive microbiology was detected in four. Conclusion. The diagnosis of pyogenic SD was more often confirmed by positive histology (one or more NPs per HPF on average) than by microbiology, although diagnostic sensitivity was greater when both histology and microbiology were positive. Cite this article: Bone Joint J 2019;101-B:246–252

Aims. Histology is widely used for diagnosis of persistent infection during reimplantation in two-stage revision hip and knee arthroplasty, although data on its utility remain scarce. Therefore, this study aims to assess the predictive value of permanent sections at reimplantation in relation to reinfection risk, and to compare results of permanent and frozen sections. Methods. We retrospectively collected data from 226 patients (90 hips, 136 knees) with periprosthetic joint infection who underwent two-stage revision between August 2011 and September 2021, with a minimum follow-up of one year. Histology was assessed via the SLIM classification. First, we analyzed whether patients with positive permanent sections at reimplantation had higher reinfection rates than patients with negative histology. Further, we compared permanent and frozen section results, and assessed the influence of anatomical regions (knee versus hip), low- versus high-grade infections, as well as first revision versus multiple prior revisions on the histological result at reimplantation. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), chi-squared tests, and Kaplan-Meier estimates were calculated. Results. Overall, the reinfection rate was 18%. A total of 14 out of 82 patients (17%) with positive permanent sections at reimplantation experienced reinfection, compared to 26 of 144 patients (18%) with negative results (p = 0.996). Neither permanent sections nor fresh frozen sections were significantly associated with reinfection, with a sensitivity of 0.35, specificity of 0.63, PPV of 0.17, NPV of 0.81, and accuracy of 58%. Histology was not significantly associated with reinfection or survival time for any of the analyzed sub-groups. Permanent and frozen section results were in agreement for 91% of cases. Conclusion. Permanent and fresh frozen sections at reimplantation in two-stage revision do not serve as a reliable predictor for reinfection. Cite this article: Bone Joint J 2024;106-B(4):372–379

The aim of this study was to obtain detailed long-term data on the cement-bone interface in patients with cemented stems, implanted using the constrained fixation technique. A total of eight stems were removed together with adjacent bone during post-mortem examinations of patients with well-functioning prostheses. Specimens were cut at four defined levels, contact radiographs were obtained for each level, and slices were prepared for histological analysis. Clinical data, clinical radiographs, contact radiographs and histological samples were examined for signs of loosening and remodelling. The mean radiological follow-up was 9.6 years and all stems were well-fixed, based on clinical and radiological criteria. Contact radiographs revealed an incomplete cement mantle but a complete filling of the medullary canal for all implants. Various amounts of polyethylene particles were evident at the cement-bone interface of seven stems, with no accompanying inflammatory reaction. Cortical atrophy and the formation of an ‘inner cortex’ were confirmed in six of eight stems by contact radiographs and histology, but were only visible on two clinical radiographs. Our results confirm that a complete cement mantle is not essential for the survival of Müller straight stems into the mid term, and support our hypothesis that no benefit to long-term survival can be expected from modern cementing techniques

Autologous chondrocyte implantation is an option in the treatment of full-thickness chondral or osteochondral injuries which are symptomatic. The goal of surgery and rehabilitation is the replacement of damaged cartilage with hyaline or hyaline-like cartilage, producing improved levels of function and preventing early osteoarthritis. The intermediate results have been promising in terms of functional and clinical improvement. Our aim was to explore the hypothesis that the histological quality of the repair tissue formed after autologous chondrocyte implantation improved with increasing time after implantation. In all, 248 patients who had undergone autologous chondrocyte implantation had biopsies taken of the repair tissue which then underwent histological grading. Statistical analysis suggested that with doubling of the time after implantation the likelihood of a favourable histological outcome was increased by more than fourfold (p < 0.001)

The radiographic and histological features of radiolucent areas at the cement-bone interface were correlated in 15 specimens retrieved at post-mortem from patients who had undergone cemented total hip arthroplasty, two weeks to 15 years prior to death. All but one of the components were securely fixed, as demonstrated by direct measurements of micromotion. Extensive radiolucencies were present in all but one case. In 11 of the 14 specimens with radiolucencies, histological examination showed that the radiolucent areas represented regions of osteoporosis and bone remodelling. The remodelling changes were characterised by osteoporosis, cancellisation and thinning of the endosteal cortex, and osteopenia of the trabecular bone. In two specimens the appearance of radiolucency was found to be due to fibrous tissue at the cement-bone interface and in one specimen there was a mixed picture of osteolysis and fibrosis. The study demonstrates that radiolucent lines can occur with well-fixed components and that they may commonly represent osteoporosis rather than the presence of a fibrous membrane at the cement-bone interface

Aims. The aim of this study was to evaluate the optimal deep tissue specimen sample number for histopathological analysis in the diagnosis of periprosthetic joint infection (PJI). Methods. In this retrospective diagnostic study, patients undergoing revision surgery after total hip or knee arthroplasty (n = 119) between January 2015 and July 2018 were included. Multiple specimens of the periprosthetic membrane and pseudocapsule were obtained for histopathological analysis at revision arthroplasty. Based on the Infectious Diseases Society of America (IDSA) 2013 criteria, the International Consensus Meeting (ICM) 2018 criteria, and the European Bone and Joint Infection Society (EBJIS) 2021 criteria, PJI was defined. Using a mixed effects logistic regression model, the sensitivity and specificity of the histological diagnosis were calculated. The optimal number of periprosthetic tissue specimens for histopathological analysis was determined by applying the Youden index. Results. Based on the EBJIS criteria (excluding histology), 46 (39%) patients were classified as infected. Four to six specimens showed the highest Youden index (four specimens: 0.631; five: 0.634; six: 0.632). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of five tissue specimens were 76.5% (95% confidence interval (CI) 67.6 to 81.4), 86.8% (95% CI 81.3 to 93.5), 66.0% (95% CI 53.2 to 78.7), and 84.3% (95% CI 79.4 to 89.3), respectively. The area under the curve (AUC) was calculated with 0.81 (as a function of the number of tissue specimens). Applying the ICM and IDSA criteria (excluding histology), 40 (34%) and 32 (27%) patients were categorized as septic. Three to five specimens had the highest Youden index (ICM 3: 0.648; 4: 0.651; 5: 0.649) (IDSA 3: 0.627; 4: 0.629; 5: 0.625). Conclusion. Three to six tissue specimens of the periprosthetic membrane and pseudocapsule should be collected at revision arthroplasty and analyzed by a pathologist experienced and skilled in interpreting periprosthetic tissue. Cite this article: Bone Joint J 2023;105-B(2):158–165

Aims. Leucocyte esterase (LE) has been shown to be an accurate marker of prosthetic joint infection (PJI), and has been proposed as an alternative to frozen section (FS) histology for intraoperative diagnosis. In this study, the intraoperative assessment of LE was compared with FS histology for the diagnosis of prosthetic hip infection. Patients and Methods. A total of 119 patients undergoing revision total hip arthroplasty (THA) between June 2015 and December 2017 were included in the study. There were 56 men and 63 women with a mean age of 66.2 years (27 to 88). Synovial fluid was collected before arthrotomy for the assessment of LE using enzymatic colourimetric strips. Between five and six samples were stained with haematoxylin and eosin for FS histology, and considered suggestive of infection when at least five polymorphonuclear leucocytes were found in five high-power fields. Results. The sensitivity and specificity of the LE assay were 100% and 93.8%, respectively; the positive (PPV) and the negative (NPV) predictive values were 79.3% and 100%, respectively. The mean time between the collection of the sample and the result being known was 20.1 minutes (. sd. 4.4). The sensitivity and specificity of FS histology were 78.3% and 96.9%, respectively; the PPV and the NPV were 85.7% and 94.9%, respectively. The mean time between the collection of the sample and the result being known was 27.2 minutes (. sd. 6.9). Conclusion. The sensitivity of LE assay was higher, with similar specificity and diagnostic accuracy, compared with FS histology. The faster turnaround time, its ease of use, and low costs make LE assay a valuable alternative to FS histology. We now use it routinely for the intraoperative diagnosis of PJI. Cite this article: Bone Joint J 2019;101-B:372–377

In a prospective study of the measurement of osteoporosis in patients with fracture of the femoral neck, we compared a histological with a radiological method. We found no significant correlation between histological planimetry and the radiological six metacarpal hand index in patients with either cervical or trochanteric fractures. This demonstrates that metacarpal morphometry cannot predict histological osteoporosis of the iliac crest

Vancomycin-supplemented allografts provide biological restoration of bone stock and sound fixation with a low incidence of re-infection. Experimental incorporation of these grafts is similar to allografts without vancomycin. However, the underlying biology remains unknown. We report the first histological observations of vancomycin-supplemented impacted bone allografts in two reconstructions performed 14 and 20 months after revision surgery because of a periprosthetic fracture. Areas of active bone remodelling (creeping substitution), as well as calcified bone trabeculae and graft particles embedded in dense fibrous tissue, were observed with osteoid and fibroconnective tissue surrounding polymethylmethacrylate particles. These pathological findings are similar to those reported in allografts without vancomycin and support the hypothesis that high levels of vancomycin do not affect the incorporation of bone graft

Acetabular dysplasia was produced in 24 immature white rabbits. A rotational acetabular osteotomy was then carried out and radiological and histological studies of the articular cartilage were made. In the hips which did not undergo osteotomy, radiographs at 26 weeks showed that residual subluxation remained and arthritic changes such as narrowing of the joint space or dislocation were still seen. However, in the operated group there was a remarkable increase in cover, but arthritic changes were not observed. After 24 weeks, the Mankin grading score in the operated group was significantly lower than that in the non-operated group. The latter hips showed an irregular surface of the cartilage, exfoliation and proliferation of synovial tissue. In those undergoing osteotomy, primary cloning of chondrocytes or hypercellularity was seen and at 24 weeks after operation and metaplasia of the cartilage in the fibrous tissue was observed in the boundary between the medial area of the acetabulum and the acetabular fossa

We describe the histology of a specimen taken from an amputated leg seven months after a 15 cm bone gap in the tibia had been closed by bone transport. Lengthening appeared to have occurred by repeated minor trauma to the bone, with the fractured trabeculae in sufficiently close contact for the repair process to proceed. Osteogenesis did not occur through a cartilage phase, but the fracture gaps were bridged by collagen fibres, around which new bone formed. Microfractures had repaired by primary healing with woven bone and with no microcallus. Small regions of bone were necrotic. Resorption of the necrotic bone and remodelling of the immature bundle and woven bone were still at an early stage, suggesting that complete remodelling in man may take years rather than months

This paper describes a study in the human femur of the relationship between cell division in growth cartilage and overall bone growth. Growth rates for the distal femur from birth to eighteen years were determined from serial radiographs available from the Harpenden Growth Study; An average of 1-4 cm/year was found for the ages of five to eight years. The development of the growth plate is illustrated in a series of photomicrographs of femur sections. These sections were also used for quantitative histology; The length of the proliferation zone was estimated from cell counts to be twenty-four cells per column. On the basis of this value and the measured growth rate, an approximate mean cycle time of twenty days was found for the proliferating cells of the human growth plate. Since the corresponding cycle time is two days for rodent growth plates, which also have a different structure, it is unwise to extrapolate the findings in this tissue from mouse to man

We have studied the histological appearances of forty femoral heads with idiopathic avascular necrosis. The characteristic histopathological changes of recurrent necrosis were present in 83 per cent. Recurrent necrosis occurred widely after revascularisation had progressed as far as the subchondral zone. The aetiology of idiopathic avascular necrosis of the femoral head may be a chronic condition which produces repeated infarction. The deformation and incomplete revascularisation of the femoral head may be due to repeated episodes of infarction as well as to mechanical factors related to weight-bearing

A 65-year-old man presented with a painful hip five years after a cemented replacement. Histological examination of a biopsy taken from tissue surrounding the femoral implant showed infiltration of a squamous-cell carcinoma. Further investigation revealed a primary growth in the left lung. This rare example of a metastasis in relation to a joint replacement illustrates the necessity for histological examination of the tissue adjacent to a loose prosthesis

We report the histology of a femur retrieved 3.5 years after a cemented revision of a hip replacement in which impaction allografting had been used to fill two large cortical defects. The allograft chips had largely been replaced by viable cortical bone, and the interface between cement and tissue resembled that seen after primary cemented arthroplasty

In an attempt to improve the accuracy of diagnosis, 16 patients suffering from Morton's metatarsalgia were investigated clinically and electrophysiologically. The histological findings were related to these observations. The precise aetiology of Morton's metatarsalgia remains obscure, but the findings are compatible with an entrapment syndrome. Nerve conduction studies have a place in the investigation of patients with atypical presentation of pain in the foot. Further refinement of the electrophysiological technique should be possible

Previous perfusion studies of the rotator cuff have demonstrated an area of hypovascularity in the distal part of the supraspinatus tendon. This has been implicated in the pathogenesis of its rupture. We performed a quantitative histological analysis of the vascularity of the tendons of supraspinatus and infraspinatus. Vessel number, size and the percentage of the tendon occupied by vessels were measured at 5 mm intervals from the humeral insertions to the muscle bellies. Both tendons were hypovascular in their distal 15 mm. No significant difference was demonstrated between the vascularity of supraspinatus and infraspinatus. We conclude that factors other than vascularity are important in the pathogenesis of supraspinatus rupture

We have performed an arthroscopic and histological study of the remodelling process of allogeneic tendons transplanted into the human knee as anterior cruciate ligament substitutes. Arthroscopic observations from six weeks to 55 months after operation showed that the grafts were viable, and that early surface hypervascularity subsided with time; moreover, these appearances remained unchanged from 11 months postoperatively onwards. Histological studies from three to 55 months after operation showed that all the grafts were infiltrated with fibroblasts, and that cellularity in their substance reduced with time, remaining unchanged from 18 months onwards; the collagen bundles were aligned as in a normal ligament from six months onwards. These findings suggest that the grafts reach maturity within the first 18 months and remain unchanged as viable ligaments thereafter

Aims. This study aimed to investigate the role of quantitative histological analysis in the diagnosis of fracture-related infection (FRI). Patients and Methods. The clinical features, microbiology culture results, and histological analysis in 156 surgically treated nonunions were used to stratify the likelihood of associated infection. There were 64 confirmed infected nonunions (one or more confirmatory criteria: pus, sinus, and bacterial growth in two or more samples), 66 aseptic nonunions (no confirmatory criteria), and 26 possibly infected nonunions (pathogen identified from a single specimen and no confirmatory criteria). The histological inflammatory response was assessed by average neutrophil polymorph (NPs) counts per high-power field (HPF) and compared with the established diagnosis. Results. Assuming a cut-off of over five neutrophils per high-power field to diagnose septic nonunion, there was 80% sensitivity and 100% specificity (accuracy 90%). Using a cut-off of no neutrophils seen in any high-power field to diagnose aseptic nonunion, there was a sensitivity of 85% and a specificity of 98% (accuracy 92%). Conclusion. Histology can be used in a bimodal fashion as a diagnostic test for FRI. The presence of more than five NPs/HPF had a positive predictive value for infected nonunion of 100%, while the complete absence of any NPs is almost always indicative of an aseptic nonunion (positive predictive value of 98%). Cite this article: Bone Joint J 2018;100-B:966–72

In an experimental clinical study, 25 implants of pure titanium were inserted into the proximal tibia of 11 volunteer patients, four with rheumatoid arthritis and seven with osteoarthritis. The implants were removed from five weeks to 24 months later and detailed histological analysis was performed. The implants generally healed with direct bone-metal contact, showing so-called osseointegration. Only one of the 21 implants which had been in place for over five months did not show osseointegration, probably because of inadequate primary contact with bone. The presence of rheumatoid disease did not prevent osseointegration, but accompanying osteoporosis seemed to be a risk factor