Allograft Versus Bioactive Glass (BG-S53P4) in Pediatric Benign Bone Lesions: A Randomized Clinical Trial.

BACKGROUND: Benign bone cysts in children have a high risk of recurrence after bone grafting. The optimal treatment and filling material for these lesions are currently unknown. METHODS: We compared cyst recurrence after intralesional curettage and filling with allograft versus bioactive glass (BG-S53P4; Bonalive) in a randomized clinical trial. The volume of recurrent cyst at 2-year follow-up was the primary outcome. RESULTS: Of 64 eligible children, 51 (mean age, 11.1 years) were randomized to undergo filling of the cyst using morselized allograft (26) or bioactive glass (25). Twelve (46%) of the children in the allograft group and 10 (40%) in the bioactive glass group developed a recurrence (odds ratio [OR] for bioactive glass = 0.79, 95% confidence interval [CI] = 0.25 to 2.56, p = 0.77). The size of the recurrent cyst did not differ between the allograft group (mean, 3.3 mL; range, 0 to 13.2 mL) and the bioactive glass group (mean, 2.2 mL; range, 0 to 16.6 mL, p = 0.43). After adjusting for the type of lesion (aneurysmal bone cyst versus other), bioactive glass also did not prevent larger (>1 mL) recurrent cysts (adjusted OR = 0.42, 95% CI = 0.13 to 1.40, p = 0.16). The Musculoskeletal Tumor Society score improved significantly (p ≤ 0.013) from preoperatively to the 2-year follow-up in both groups (to 28.7 for bioactive glass and 29.1 for bone graft). Four (15%) of the children in the allograft group and 6 (24%) in the bioactive glass group required a reoperation during the follow-up (OR for bioactive glass = 1.74, 95% CI = 0.43 to 7.09, p = 0.50). CONCLUSIONS: Filling with bioactive glass and with allograft in the treatment of benign bone lesions provided comparable results in terms of recurrence and complications. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Increased lesion depth, higher body mass index and older age are risk factors for osteoarthritis during long-term follow-up in patients with osteochondritis dissecans of the knee.

INTRODUCTION: To report on the long-term prognosis of osteochondritis dissecans (OCD) patients regarding radiological and patient-reported outcomes and to analyze possible risk factors. MATERIALS AND METHODS: All patients diagnosed with knee OCD between 2004 and 2014 with radiographic Kellgren-Lawrence (K-L) grades 0-2 at the time of diagnoses, ability to understand the language of the interview, and willingness to participate in the study were retrospectively reviewed. Current knee radiographs and the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire were prospectively collected between May 2020 and March 2021. The extent of osteoarthritis (OA) and KOOS questionnaire results were evaluated. RESULTS: 90 patients (103 knees) with a mean age of 21 years (range 6-60) were included. The mean follow-up time was 12 years (range 7-20). 24 knees (23%) were treated conservatively, and 79 knees (77%) operatively. At the time of diagnoses, 90% of the patients had K-L grades of 0-1; during the follow-up period, 45% of the patients showed radiological progression of OA. Patient body mass index (BMI) (p = 0.004; 95% CI 0.25-0.29), age (p = 0.003; 95% CI 0.18-0.30), operative treatment (p = 0.0075; 95% CI 0.41-0.65) and lesion depth (p = 0.0007) were statistically significantly connected to K-L grade change. Patients with no progression in joint space narrowing had statistically significantly better overall KOOS scores (p = 0.03; 95% CI 0.77-0.88) than patients whose K-L grades worsened. CONCLUSIONS: During the long-term follow-up of 12 years, patients with knee OCD had good clinical results. Lac of radiological progression of cartilage degeneration was noted in 55% of the patients, regardless of treatment method. Lesion depth, higher BMI and older age were associated with the progression of OA. The progression of OA was related to a worsening of functional scores. LEVEL OF EVIDENCE: IV.

The long-term prognostic value of serum 25(OH)D, albumin, and LL-37 levels in acute respiratory diseases among older adults.

BACKGROUND: Older adults are more susceptible to respiratory tract infection than healthy working age adults. The increased susceptibility of older adults is thought to be interlinked with vitamin D status, nourishment, and immunological state in general. Data are scarce whether these parameters could serve as prognostic markers. AIM: To study whether serum 25(OH)D, albumin, and LL-37 level could give prognostic value of long-term survival in the older adults with multimorbidity and acute respiratory infection. METHODS: Consecutive episodes of hospital care of patients 65 years and older with respiratory symptoms were prospectively studied as a cohort. Standard clinical questionnaire was filled by the study physician. Laboratory markers included serum levels of 25(OH)D, albumin and LL-37, C-reactive protein (CRP), white blood cell count (WBC) and polymerase chain reaction diagnostics for 14 respiratory viruses. Pneumonia was confirmed by chest radiographs. Respiratory illness severity, death at ward, length of hospital stays, and 5-year survival were used as outcomes. RESULTS: In total, 289 older adult patients with mean age of 83 years were included in the study. Serum 25(OH)D deficiency (< 50 nmol/liter) was present in 59% and hypoalbuminemia (< 3.5 g/dL) in 55% of the study patients. Low serum albumin level was associated to one, two- and five-year mortality after hospital stay (all P < .05). In addition, it was associated with pneumonia, dyspnea, over 13-night long stay at ward and death at ward (all P < .05). No associations were seen between serum 25(OH)D and LL-37 levels and disease severity, short-term clinical outcome, or long-term survival. Associations between serum 25(OH)D, albumin, and LL-37 levels and respiratory virus presence were not seen. CONCLUSIONS: Serum albumin level on admission seems to give valuable information about the patients' general health and recovery potential in treating older adults with respiratory symptoms. Serum 25(OH)D and LL-37 had no associations with disease severity or long- and short-term prognosis among older adults hospitalized with respiratory symptoms.

The motion between components in a mobile-bearing total ankle replacement measured by cone-beam CT scanning.

BACKGROUND: To measure the motion of polyethylene insert and implant components of mobile-bearing total ankle replacement (TAR) by cone-beam CT scanning. METHODS: 10 TAR patients with high amount of clinical motion after the CCI implant (Ceramic Coated Implant; Wright Medical Technology, Arlington, TN, USA) with average age at operation 64,3 years (range 47-84) and average clinical total range of motion 42 degrees (range 35-55) were included. RESULTS: The average total range of motion between the insert and the tibial component was 0.8mm (range 0-2) in the coronal plane, and 2.9mm (range 1-6) in the sagittal plane. There was wide variation in the axial rotation measurements between the components. CONCLUSION: We found measurable motion between the mobile-bearing insert and the tibial component in all planes. The relevance of this motion to the function and long-term survival of the TAR remains to be determined.

Low Rate of Peri-implant Osteolysis in Trabecular Metal Total Ankle Replacement on Short- to Midterm Follow-up.

BACKGROUND: Peri-implant osteolysis is one of the major complications related to total ankle replacement. The aim of this study was to investigate the short- to midterm incidence of peri-implant osteolysis using computed tomography (CT) as imaging method for the Trabecular Metal Total Ankle (TMTA) implant representing a novel total ankle replacement (TAR) implant design regarding material and surgical technique. METHODS: In total, 104 consecutive patients who had a primary TMTA replacement between March 2013 and October 2017 were included in the study. The radiographic evaluation included weightbearing anteroposterior and lateral views at baseline and after 3, 6, and every 12 months postoperatively. A helical CT was undertaken preoperatively and of the 80 patients available to follow up at least 12 months postoperatively, with average time interval between the TAR operation and the latest CT of 39 (range, 12-85) months. RESULTS: Eight of 80 patients had altogether 11 osteolytic lesions around the components on CT images. Seven lesions were found in tibia, 3 in talus, and 1 in distal fibula. Four of the tibial lesions were situated in the medial malleolus and were not in contact with the prosthesis component. The sizes of the osteolytic lesions ranged between 7 and 20 mm, and the average volume of the lesions was 689 mm3. CONCLUSION: We conclude that the risk of peri-implant osteolysis with the TMTA implant is minimal in short to midterm. The anatomic configuration, unique material, and surgical technique may all contribute to the TMTA implant having a low rate of peri-implant osteolysis. LEVEL OF EVIDENCE: Level IV, case series.

First-in-Humans Study of 68Ga-DOTA-Siglec-9, a PET Ligand Targeting Vascular Adhesion Protein 1.

Sialic acid-binding immunoglubulinlike lectin 9 (Siglec-9) is a ligand of vascular adhesion protein 1. A 68Ga-labeled peptide of Siglec-9, 68Ga-DOTA-Siglec-9, holds promise as a novel PET tracer for imaging of inflammation. This first-in-humans study investigated the safety, tolerability, biodistribution, and radiation dosimetry of this radiopharmaceutical. Methods: Six healthy men underwent dynamic whole-body PET/CT. Serial venous blood samples were drawn from 1 to 240 min after intravenous injection of 162 ± 4 MBq of 68Ga-DOTA-Siglec-9. In addition to γ-counting, the plasma samples were analyzed by high-performance liquid chromatography to detect intact tracer and radioactive metabolites. Radiation doses were calculated using the OLINDA/EXM software, version 2.2. In addition, a patient with early rheumatoid arthritis was studied with both 68Ga-DOTA-Siglec-9 and 18F-FDG PET/CT to determine the ability of the new tracer to detect arthritis. Results:68Ga-DOTA-Siglec-9 was well tolerated by all subjects. 68Ga-DOTA-Siglec-9 was rapidly cleared from the blood circulation, and several radioactive metabolites were detected. The organs with the highest absorbed doses were the urinary bladder wall (0.38 mSv/MBq) and kidneys (0.054 mSv/MBq). The mean effective dose was 0.022 mSv/MBq (range, 0.020-0.024 mSv/MBq). Most importantly, however, 68Ga-DOTA-Siglec-9 was comparable to 18F-FDG in detecting arthritis. Conclusion: Intravenous injection of 68Ga-DOTA-Siglec-9 was safe and biodistribution was favorable for testing of the tracer in larger group of patients with rheumatoid arthritis, as is planned for the next phase of clinical trials. The effective radiation dose of 68Ga-DOTA-Siglec-9 was within the same range as the effective radiation doses of other 68Ga-labeled tracers. Injection of 150 MBq of 68Ga-DOTA-Siglec-9 would expose a subject to 3.3 mSv. These findings support the possible repeated clinical use of 68Ga-DOTA-Siglec-9, such as in trials to elucidate the treatment efficacy of novel drug candidates.

Granulocyte colony-stimulating factor- and chemotherapy-induced large-vessel vasculitis: six patient cases and a systematic literature review.

OBJECTIVE: Patients receiving chemotherapy are prone to neutropoenic infections, presenting with non-specific symptoms such as a high fever and elevated inflammatory parameters. Large-vessel vasculitis (LVV) may have a similar clinical presentation and should be included in differential diagnostics. A few published case reports and adverse event reports suggest a causal association between LVV and the use of granulocyte colony-stimulating factor (G-CSF) and chemotherapy. Our objective was to evaluate the relationship between LVV, G-CSF and chemotherapy. METHODS: Between 2016 and 2018, we identified six patients in Finland with probable drug-induced LVV associated with G-CSF and chemotherapy. All six patients had breast cancer. A systematic literature review was performed according to PRISMA guidelines using comprehensive search terms for cancer, chemotherapy, G-CSF and LVV. RESULTS: The literature search identified 18 similar published case reports, of which most were published after 2014. In all patients combined (n = 24), the time delay from the last drug administration to the LVV symptoms was on average 5 days with G-CSF (range = 1-8 days) and 9 days with chemotherapy (range = 1-21 days). Common symptoms were fever (88%), neck pain (50%) and chest pain (42%). Based on imaging, 17/24 (71%) had vascular inflammation in the thoracic aorta and supra-aortic vessels, but 5/24 (21%) reportedly had inflammation limited to the carotid area. CONCLUSION: This review suggests that LVV may be a possible serious adverse event associated with G-CSF and chemotherapy. Successful management of drug-induced LVV requires early identification, through diagnostic imaging, and discontinuation of the drug.

Results of Trabecular-Metal Total Ankle Arthroplasties With Transfibular Approach.

BACKGROUND: Total ankle arthroplasty is an alternative for arthrodesis. The objective of this study was to investigate the safety of trabecular-metal ankle prosthetic system with transfibular approach and external frame and its association with changes in clinical and functional scores. METHODS: Between May 2013 and June 2017, a total of 104 consecutive patients underwent primary total ankle arthroplasty with a trabecular metal implant. The prospective clinical and radiographic data were collected. The mean follow-up time was 43.6 (14.6) months. RESULTS: Of 104 patients, 88 (89%) reported improved functioning and 65 (66%) were very satisfied with the surgery. Of the patients, 51 (50%) did not report any pain at the end of follow-up at all. The average Kofoed score was 37.6 (SD 17.4) points at baseline and 74.8 (SD 20.6) points at the end of follow-up. There were 37 additional procedures, and the complication rate was nearly 20%. CONCLUSION: Trabecular-metal total ankle prosthesis showed promising clinical results concerning pain and function. At 5-year follow-up, osteolysis and component loosening were rare. LEVEL OF EVIDENCE: Level IV, case series.

Respiratory tract virus infections in the elderly with pneumonia.

BACKGROUND: In children suffering from severe lower airway illnesses, respiratory virus detection has given good prognostic information, but such reports in the elderly are scarce. Therefore, our aim was to study whether the detection of nasopharyngeal viral pathogens and conventional inflammatory markers in the frail elderly correlate to the presence, signs and symptoms or prognosis of radiographically-verified pneumonia. METHODS: Consecutive episodes of hospital care of patients 65 years and older with respiratory symptoms (N = 382) were prospectively studied as a cohort. Standard clinical questionnaire was filled by the study physician. Laboratory analyses included PCR diagnostics of nasopharyngeal swab samples for 14 respiratory viruses, C-reactive protein (CRP) and white blood cell count (WBC). Chest radiographs were systematically analysed by a study radiologist. The length of hospital stay, hospital revisit and death at ward were used as clinical endpoints. RESULTS: Median age of the patients was 83 years (range 76-90). Pneumonia was diagnosed in 112/382 (29%) of the studied episodes. One or more respiratory viruses were detected in 141/382 (37%) episodes and in 34/112 (30%) episodes also diagnosed with pneumonia. Pneumonia was associated with a WBC over 15 × 109/L (P = .006) and a CRP value over 80 mg/l (P < .05). A virus was detected in 30% of pneumonia episodes and in 40% of non-pneumonia episodes, but this difference was not significant (P = 0.09). The presence of a respiratory virus was associated with fewer revisits to the hospital (P < .05), whereas a CRP value over 100 mg/l was associated with death during hospital stay (P < .05). Respiratory virus detections did not correlate to WBC or CRP values, signs and symptoms or prognosis of radiographically-verified pneumonia episodes. CONCLUSION: Among the elderly with respiratory symptoms, respiratory virus detection was not associated with an increased risk of pneumonia or with a more severe clinical course of the illness. CRP and WBC remain important indicators of pneumonia, and according to our findings, pneumonia should be treated as a bacterial disease regardless of the virus findings. Our data does not support routine virus diagnostics for the elderly patients with pneumonia outside the epidemic seasons.

Favourable long-term functional and radiographical outcome after osteoautograft transplantation surgery of the knee: a minimum 10-year follow-up.

PURPOSE: The aim of this study was to assess the progression of radiological cartilage changes and to document the functional, long-term results during a follow-up of 10 years after osteoautograft transplantation (OAT) knee surgery. METHODS: The study was a retrospective analysis of all patients who underwent OAT at Turku University Hospital from 1999 to 2007. Pre- and postoperative cartilage changes were estimated based on standardised radiographs. The extent of osteoarthritis (OA) was graded according to the Kellgren-Lawrence scale. Clinical outcomes were evaluated with the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. RESULTS: A total of 60 patients (64 knees) with a median age of 30 years (range 14-62) were included. The median follow-up was 140 months (range 47-205). Of the 64 knees examined, 14 (22%) had a traumatic chondral lesion and 50 (78%) had osteochondritis dissecans (OCD). Preoperatively, 71% of the patients had Kellgren-Lawrence grades of 0-1; during the follow-up period, 50% of the patients showed radiographical progression of OA. OA progressed most significantly in patients with normal preoperative Kellgren-Lawrence grades (p = 0.0003). Patients with no progression in joint space narrowing had statistically significantly better overall KOOS (p = 0.02) than patients whose Kellgren-Lawrence grades worsened. Patients with defect sizes > 3.0 cm2 scored statistically significantly better in all subscales than patients with smaller defect sizes (p = 0.02). Patients with OCD had statistically significantly better KOOS than patients with chondral defects (p = 0.008). CONCLUSIONS: OAT surgery for treating patients with cartilage defects of the knee had good clinical results after a mean follow-up of 11 years. Radiological analyses revealed a progression of cartilage degeneration in 50% of the operated knees. Patients with no progression of the degenerative changes scored statistically significantly better on the KOOS self-assessment test. These results indicate that OAT surgery appears to be a reasonable therapeutic option to restore knee function in patients with cartilage lesions. LEVEL OF EVIDENCE: IV.

Medium to long-term results of 130 Ankle Evolutive System total ankle replacements-Inferior survival due to peri-implant osteolysis.

BACKGROUND: The study reports the medium to long-term results of 130 Ankle Evolutive System total ankle replacements operated at a single-centre. Previously high amount of peri-implant osteolysis was reported from the same material. METHODS: Between 2002 and 2008 one hundred and thirty consecutive ankles replaced with AES ankle prosthesis were followed both radiologically and clinically. RESULTS: The five-year survival was 87.3% (95% confidence interval (CI) 80.0-92.0%), and ten-year survival 74.9% (95% confidence interval (CI) 65.4-82.2%) at a median follow-up time of 96 months (range 2-161; 8 years). Peri-implant osteolysis was found in 91 (70%) ankles, marked in 78 (60%). 44 ankles (34%) have been revised by filling of the cavities, 24 (18%) by fusion, and 6 by further replacement, resulting in the revision rate of 58%. Osteolysis was the main reason for all revisions. The improvement of the Kofoed Score and pain points was significant (all p<0.0001), and the subjective patient satisfaction was good. CONCLUSIONS: Outcome of the current study was seriously affected by osteolysis and is inferior compared to previous reports.

Are periprosthetic osteolytic lesions in ankle worth bone grafting?

BACKGROUND: We retrospectively evaluated the medium-term follow-up of bone grafting due to periprosthetic osteolytic lesions in ankles. METHODS: 34 ankles (32 patients) with total ankle arthroplasty (TAA) underwent re operation. Indications were large periprosthetic osteolytic lesions or continuous growing of the lesions. The osteolytic lesions were imaged by CT before reoperation and once a year after that. The mean CT follow-up after re operation was 3.8 years (range, 2-6.2 years). Patient's clinical outcome was also monitored. RESULTS: Osteolysis continued to progress in 44 bone grafted lesions (68%) in CT follow-up. Pain (p=0.04) and location of the lesion (p=0.03) were associated with progression of osteolysis. In 18 bone grafted osteolytic lesions (28%) the radiological survival remained excellent. 25 out of 34 ankles showed improvement of the function after bone grafting. CONCLUSIONS: There is no established treatment protocol for osteolysis around TAA. Bone grafting is one alternative in the treatment of osteolytic lesions.

Early presentation of osteonecrosis in acute lymphoblastic leukemia: Two children from the Nordic and Baltic cohort.

Osteonecrosis (ON) is usually considered treatment related in patients with acute lymphoblastic leukemia (ALL). We report two patients with presentation of ON at the time of ALL diagnosis. Both were females and diagnosed with ALL at age 8 and 14 years. In the latter, some symptoms and radiologically verified ON in both knees were still present after the end of ALL therapy. No pediatric patients have previously been reported with ON presenting before initiation of ALL therapy.

Long-term Results of Scandinavian Total Ankle Replacement.

BACKGROUND: The purpose of this study was to evaluate the long-term results of the Scandinavian Total Ankle Replacement (STAR) implant in a single center. METHODS: Between 1997 and 2002, 34 consecutive ankles were replaced with the STAR ankle prosthesis and reviewed in 2016. Patients were followed both radiologically and clinically; clinical outcomes were measured with the Kofoed ankle score and subjective measurements. The median follow-up period was 159 months (13.3 years; range, 13-202 months). RESULTS: The implant survival rate was 93.9% (95% confidence interval [CI], 92.2%-86.7%) at 5 years, 86.7% (95% CI, 69.3%-96.2%) at 10 years, and 63.6% (95% CI, 30.8%-89.0%) at 15 years. A total of 15 ankles (44%) had been revised: 2 by fusion, 3 by further replacement, 5 by insert exchange, and 5 by bone grafting for marked osteolysis. The improvements in the Kofoed ankle score and Kofoed ankle score for pain were statistically significant at every postoperative evaluation point compared to the preoperative values (all P < .0001), and subjective patient satisfaction was high. CONCLUSION: Our results were satisfactory and in agreement with previously reported findings of STAR implants. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Total ankle arthroplasty: optimizing computed tomography imaging protocol.

OBJECTIVE: To evaluate parameters and positioning when imaging total ankle prostheses on computed tomography (CT). MATERIALS AND METHODS: An ankle prosthesis implanted into a pig's knee joint underwent 16 different CT imaging protocols. Four defects were drilled around prosthesis components simulating periprosthetic osteolytic lesions. The specimen with the implant was imaged in four different orientations with the tibial stem parallel to the table and at 25, 45, and 90° angles to it. The protocol consisted of scanning at 100, 120, and 140 kVp in every position with a pitch of 1.2. The scanning at 120 kVp in every position was repeated with a pitch of 1.0. RESULTS: CT proved to be a reliable imaging modality when studying periprosthetic lesions adjacent to the ankle prosthesis when the tibial stem alignment was parallel to the table. When imaging at higher angles, metal artifacts distorted the image, making the analysis of periprosthetic bone structure unreliable. There were no statistically significant differences between different tube voltages or pitch in volume measurements of the osteolytic lesions. CONCLUSIONS: CT is a reliable imaging method to evaluate periprosthetic bone structure around ankle prostheses when orientation of the prosthesis and acquisition parameters is optimized.

Does computed tomography add information on radiographic analysis in detecting periprosthetic osteolysis after total ankle arthroplasty?

BACKGROUND: The major longer term complications of ankle arthroplasty are periprosthetic osteolysis and aseptic loosening. Follow-up studies of total hip arthroplasties show that measurements of periprosthetic osteolytic lesions on radiographs underestimate the size compared with those made on computed tomography (CT), and some of the lesions may even remain undetected on radiographs. However, it is unclear whether the same applies to total ankle arthroplasty (TAA). METHODS: We retrospectively reviewed the radiographs of 123 patients who had undergone TAA with the Ankle Evolutive System (AES) implant. Of these, 43 (34.9%) had at least 1 large (greater than 10 mm) osteolytic lesion on radiographs at a minimum follow-up of 14 months (mean, 43.1 months; range, 14-85 months). Forty of the 43 patients underwent helical CT imaging. RESULTS: Computed tomography showed more osteolytic lesions than radiographs around both tibial and talar components. CT also showed larger lesions than radiographs in 9 of 10 zones around prosthetic components. The difference was highly significant in 3 zones around the talar component. CONCLUSION: Computed tomography showed more and larger periprosthetic lesions than radiographs around an ankle prosthesis. Because osteolysis is progressive in nature, it presumably leads to component failure. Considering our results, we recommend adding CT imaging to postoperative follow-up after TAA for patients with suspected or known periprosthetic lucencies on radiographs. LEVEL OF EVIDENCE: Level III, diagnostic study.

Statin-induced myopathy in a patient with previous poliomyelitis.

This report describes a patient with a history of poliomyelitis who developed new, progressive symptoms of muscle fatigue and weakness, suggestive of postpoliomyelitis syndrome. However, comprehensive investigations led to the diagnosis of statin-induced myopathy as the cause of the patient's symptoms. This case highlights the possibility of statin-induced myopathy in patients with a history of poliomyelitis and the differential diagnosis between postpoliomyelitis syndrome and statin-induced myopathy in these patients. The possibility of statin-induced myopathy should be considered when patients with previous poliomyelitis who take statin medication develop symptoms suggestive of postpoliomyelitis syndrome.