The risk of neurological deterioration while using neoadjuvant denosumab on patients with giant cell tumor of the spine presenting with epidural disease: a meta-analysis of the literature.

BACKGROUND CONTEXT: Giant cell tumor (GCT) of bone is most commonly a benign but locally aggressive primary bone tumor. Spinal GCTs account for 2.7% to 6.5% of all GCTs in bone. En bloc resection, which is the preferred treatment for GCT of the spine, may not always be feasible due to the location, extent of the tumor, and/or the patient's comorbidities. Neoadjuvant denosumab has recently been shown to be effective in downstaging GCT, decreasing the size and extent of GCTs. However, the risk of neurologic deterioration is of major concern for patients with epidural spinal cord compression due to spinal GCT. We experienced this concern when a patient presented to our institution with a midthoracic spinal GCT with progressive epidural disease. The patient was not a good surgical candidate due to severe cardiac disease and uncontrolled diabetes. In considering nonoperative management for this patient, we asked ourselves the following question: What is the risk that this patient will develop neurologic deterioration if we do not urgently operate and opt to treat him with denosumab instead? PURPOSE: The purpose of this study was to assess the literature to (1) determine the risk of neurological deterioration in patients receiving neoadjuvant denosumab for the treatment of spinal GCT and (2) to evaluate the secondary outcomes including radiographic features, surgical/technical complexity, and histological features after treatment. STUDY DESIGN/SETTING: Meta-analysis of the literature. PATIENT SAMPLE: Surgical cases of spinal GCT that (1) presented with type III Campanacci lesions, (2) had epidural disease classified as Bilsky type 1B or above and (3) received neoadjuvant denosumab therapy. OUTCOME MEASURES: The primary outcome measure of interest was neurologic status during denosumab treatment. Secondary outcome measures of interest included radiographic features, surgical/technical complexity, histological features, tumor recurrence, and metastasis. METHODS: Using predetermined inclusion and exclusion criteria, PubMed and Embase electronic databases were searched in August 2022 for articles reporting spinal GCTs treated with neoadjuvant denosumab and surgery. Keywords used were "Spine" AND "Giant Cell Tumor" AND "Denosumab." RESULTS: A total of 428 articles were identified and screened. A total of 22 patients from 12 studies were included for review. 17 patients were female (17/22, 77%), mean age was 32 years (18-62 years) and average follow-up was 21 months. Most GCTs occurred in the thoracic and thoracolumbar spine (11 patients, 50%), followed by 36% in the lumbar spine and 14% in the cervical spine. Almost half of the patients had neurological deficits at presentation (10/22 patients, 45%), and more than 60% had Bilsky 2 or 3 epidural spinal cord compression. None of the patients deteriorated neurologically, irrespective of their neurological status at presentation (p-value=.02, CI -2.58 to -0.18). There were no local recurrences reported. One patient was found to have lung nodules postoperatively. More than 90% of cases had decreased overall tumor size and increased bone formation. Surgical dissection was facilitated in more than 85% of those who had documented surgical procedures. Four patients (18%) underwent initial spinal stabilization followed by neoadjuvant denosumab and then surgical excision of the GCT. Regarding the histologic analyses, denosumab eradicated the giant cells in 95% of cases. However, residual Receptor Activator of Nuclear Factor Kappa B Ligand (RANKL)-positive stromal cells were noted, in 27% (6 cases). CONCLUSIONS: Neoadjuvant denosumab was a safe and effective means of treating spinal GCTs prior to surgery. Neurologic status remained stable or improved in all cases included in our review, irrespective of the presenting neurologic status. The most appropriate dosage and duration of denosumab therapy is yet to be determined. We recommend future well-designed studies to further evaluate the use of neoadjuvant denosumab for patients with spinal GCT.

The Effect of Povidone-Iodine Irrigation on the Efficacy of Antibiotic Cement In Vitro.

Povidone-iodine is a common antiseptic demonstrating success in reducing infection rates in primary arthroplasty; however, recent data suggest that its use in revision arthroplasty may increase infection rates. This study evaluated the effect of povidone-iodine solution on antibiotic cement and investigated the connection between povidone-iodine and increased infection rates in revision arthroplasty. Sixty antibiotic cement samples (ACSs) were formed using gentamicin-impregnated cement. The ACSs were divided into three groups: group A (n=20) was subject to a 3-minute povidone-iodine soak followed by a saline rinse; group B (n=20) underwent a 3-minute saline soak; and group C (n=20) underwent only a saline rinse. The antimicrobial activity of the samples was tested using a Kirby-Bauer-like assay using Staphylococcus epidermidis. The zone of inhibition (ZOI) was measured every 24 hours for 7 days. All groups possessed the greatest antimicrobial activity at 24 hours. Group C displayed a mass-corrected ZOI of 395.2 mm/g, which was statistically greater than the group B ZOI (313.2 mm/g, P<.05) but not the group A ZOI (346.5 mm/g, P>.05). All groups demonstrated a decrease in antimicrobial activity at 48 through 96 hours, with no significant difference at any time point. Prolonged soaking of antibiotic cement in a povidone-iodine or saline solution results in elution of the antibiotic into the irrigation solution, blunting initial antibiotic concentration. When using antibiotic cement, antiseptic soaks or irrigation should be focused prior to cementation. [Orthopedics. 2024;47(1):10-14.].

Advances in Virtual Cutting Guide and Stereotactic Navigation for Complex Tumor Resections of the Sacrum and Pelvis: Case Series with Short-Term Follow-Up.

Primary malignancies of the sacrum and pelvis are aggressive in nature, and achieving negative margins is essential for preventing recurrence and improving survival after en bloc resections. However, these are particularly challenging interventions due to the complex anatomy and proximity to vital structures. Using virtual cutting guides to perform navigated osteotomies may be a reliable method for safely obtaining negative margins in complex tumor resections of the sacrum and pelvis. This study details the technique and presents short-term outcomes. Patients who underwent an en bloc tumor resection of the sacrum and/or pelvis using virtual cutting guides with a minimum follow-up of two years were retrospectively analyzed and included in this study. Preoperative computer-assisted design (CAD) was used to design osteotomies in each case. Segmentation, delineating the tumor from normal tissue, was performed by the senior author using preoperative CT scans and MRI. Working with a team of biomedical engineers, virtual surgical planning was performed to create osteotomy lines on the preoperative CT and overlaid onto the intraoperative CT. The pre-planned osteotomy lines were visualized as "virtual cutting guides" providing real-time stereotactic navigation. A precision ultrasound-powered cutting tool was then integrated into the navigation system and used to perform the osteotomies in each case. Six patients (mean age 52.2 ± 17.7 years, 2 males, 4 females) were included in this study. Negative margins were achieved in all patients with no intraoperative complications. Mean follow-up was 38.0 ± 6.5 months (range, 24.8-42.2). Mean operative time was 1229 min (range, 522-2063). Mean length of stay (LOS) was 18.7 ± 14.5 days. There were no cases of 30-day readmissions, 30-day reoperations, or 2-year mortality. One patient was complicated by flap necrosis, which was successfully treated with irrigation and debridement and primary closure. One patient had local tumor recurrence at final follow-up and two patients are currently undergoing treatment for metastatic disease. Using virtual cutting guides to perform navigated osteotomies is a safe technique that can facilitate complex tumor resections of the sacrum and pelvis.

Spontaneous Extensor Pollicis Longus Rupture Associated With an Extensor Digitorum Brevis Manus.

A 64-year-old left-handed man with no history of rheumatoid arthritis or distal radius fracture presented with spontaneous loss of thumb interphalangeal joint extension. Intraoperatively, the patient was found to have a variant extensor indicis proprius with extensor digitorum brevis manus. Prior extensor digitorum communis ruptures have been reported in the literature secondary to the distal extensor digitorum brevis manus muscle belly, but there are no prior reports of extensor pollicis longus rupture. This case demonstrates a unique etiology of extensor pollicis longus rupture and highlights the alteration in the surgical plan required secondary to the absence of an extensor indicis proprius tendon.

Utility of Repeat MRI in Patients With Degenerative Cervical Disease.

Existing guidelines regarding indications for initial cervical spine magnetic resonance imaging (MRI) do not indicate when to perform repeat MRI in patients with previously documented degenerative disease. This study evaluates the efficacy of repeat MRI in patients with previously diagnosed degenerative cervical disease. Between 2013 and 2018, 153 patients (102 women, 51 men; mean age, 55 years; range, 19-81 years) without a history of trauma or surgery underwent cervical spine MRI 2 or more times at our institution indicated for symptoms of neck pain with or without radiculopathy. The MRI reports of repeat studies were reviewed and compared with index studies for notable changes. Notable radiographic changes were defined as any progression of the existing degenerative disease. Fifty-three of 153 (35%) patients demonstrated progression on repeat MRI. Forty-nine of the 53 patients demonstrating progression had new or worsening symptoms prior to their follow-up study (P=.03). Twenty-nine of 35 (83%) patients with new or worsening radiculopathy progressed on MRI (P<.01). Nine of 10 (90%) patients with new upper motor neuron findings demonstrated progression (P=.01). Axial neck pain alone was not statistically linked to MRI progression (P=.1). Twenty-five (16.3%) patients underwent operative management for their disease. Only 12 (48.0%) of the surgical patients presented MRI progression (P=.1). In the absence of new or worsening degenerative cervical symptoms, additional MRI studies are unlikely to reveal any radiographic progression or change clinical management from nonoperative to operative. [Orthopedics. 2023;46(2):98-102.].

Relationship to drill bit diameter and residual fracture resistance of the distal tibia.

BACKGROUND: The etiology of bone refractures after screw removal can be attributed to residual drill hole defects. This biomechanical study compared the torsional strength of bones containing various sized cortical drill defects in a tibia model. METHODS: Bicortical drill hole defects of 3 mm, 4 mm, and 5 mm diameters were tested in 26 composite tibias versus intact controls without a drill defect. Each tibia was secured in alignment with the rotational axis of a materials testing system and the proximal end rotated internally at a rate of 1 deg./s until mechanical failure. FINDINGS: All defect test groups were significantly lower (P < 0.01) in torque-to-failure than the intact group (82.80 ± 3.70 Nm). The 4 mm drill hole group was characterized by a significantly lower (P = 0.021) torque-to-failure (51.00 ± 3.27 Nm) when compared to the 3 mm drill hole (59.00 ± 5.48 Nm) group, but not different than the 5 mm hole group (55.71 ± 5.71 Nm). All bones failed through spiral fractures, bones with defects also exhibited posterior butterfly fragments. INTERPRETATION: All the tested drill hole sizes in this study significantly reduced the torque-to-failure from intact by a range of 28.4% to 38.4%, in agreement with previous similar studies. The 5 mm drill hole represented a 22.7% diameter defect, the 4 mm drill hole a 18.2% diameter defect, and the 3 mm drill hole a 13.6% diameter defect. Clinicians should be cognizant of this diminution of long bone strength after a residual bone defect in their creation and management of patient rehabilitation programs.

How Does Tibial Pin Placement in Navigated Total Knee Arthroplasty Affect the Torsional Strength of the Tibia?

INTRODUCTION: Surgical navigation technology has recently become more prevalent for total knee arthroplasty. Surgical navigation typically requires pin placement in the proximal tibia diaphysis to stabilize the bone-tracking hardware, and there have been several recent reports of fractures through these residual navigation pin holes. The objective of this biomechanical study was to determine whether a difference exists in the torsional bone strength of a 5-mm navigation pin hole drilled at a single location in three different orientations: unicortical, bicortical, and transcortical. METHODS: Biomechanical composite sawbone tibias were used to test four conditions: the intact condition with no holes, a unicortical hole, a bicortical hole, and a transcortical hole through the proximal diaphysis. Seven specimens from each group were tested in external rotation to failure at 1 deg/sec. Torque-to-failure, absorbed energy-to-failure, and rotational angle-to-failure were statistically compared across the four groups. RESULTS: All specimens failed proximally by spiral oblique fractures. No statistical differences were found between unicortical and bicortical groups in torque-to-failure, energy-to-failure, and angle-to-failure. However, both unicortical and bicortical groups were markedly lower in all measures than the intact group. The transcortical group was markedly lower in all measures than the intact group and both unicortical and bicortical groups. DISCUSSION: An appropriately placed navigation residual pin hole, either unicortical or bicortical, markedly decreases the torque-to-failure, energy-to-failure, and angle-to-failure of the tibia compared with the intact condition in a synthetic sawbones model. No notable difference was detected between the unicortical and bicortical holes; however, an errant transcortical residual navigation pin hole markedly decreases all measures compared with an appropriately placed unicortical or bicortical hole.

Extraction of a Bent Tibial Nail After Refracture: A Case Report.

CASE: A 65-year-old man previously treated by intramedullary nailing for a left tibial shaft fracture presented 6 years later with an open refracture of his left tibia after a motorcycle accident. Treatment required extraction of the bent nail before revision nailing. CONCLUSIONS: Extraction of deformed intramedullary devices is a skill that will continue to be demanded of orthopaedic surgeons. In this case, standard extraction though the entry point proved successful. Standard extraction offers the safest form of removal and should be contemplated before considering more morbid methods of extraction while examining the fracture's morphology and the device's deformity.

Early microRNA expression profile as a prognostic biomarker for the development of pelvic inflammatory disease in a mouse model of chlamydial genital infection.

UNLABELLED: It is not currently possible to predict the probability of whether a woman with a chlamydial genital infection will develop pelvic inflammatory disease (PID). To determine if specific biomarkers may be associated with distinct chlamydial pathotypes, we utilized two Chlamydia muridarum variants (C. muridarum Var001 [CmVar001] and CmVar004) that differ in their abilities to elicit upper genital tract pathology in a mouse model. CmVar004 has a lower growth rate in vitro and induces pathology in only 20% of C57BL/6 mouse oviducts versus 83.3% of oviducts in CmVar001-infected mice. To determine if chemokine and cytokine production within 24 h of infection is associated with the outcome of pathology, levels of 15 chemokines and cytokines were measured. CmVar004 infection induced significantly lower levels of CXCL1, CXCL2, tumor necrosis factor alpha (TNF-α), and CCL2 in comparison to CmVar001 infection with similar rRNA (rs16) levels for Chlamydiae. A combination of microRNA (miRNA) sequencing and quantitative real-time PCR (qRT-PCR) analysis of 134 inflammation-related miRNAs was performed 24 h postinfection to determine if the chemokine/cytokine responses would also be reflected in miRNA expression profiles. Interestingly, 12 miRNAs (miR-135a-5p, miR298-5p, miR142-3p, miR223-3p, miR299a-3p, miR147-3p, miR105, miR325-3p, miR132-3p, miR142-5p, miR155-5p, and miR-410-3p) were overexpressed during CmVar004 infection compared to CmVar001 infection, inversely correlating with the respective chemokine/cytokine responses. To our knowledge, this is the first report demonstrating that early biomarkers elicited in the host can differentiate between two pathological variants of chlamydiae and be predictive of upper tract disease. IMPORTANCE: It is apparent that an infecting chlamydial population consists of multiple genetic variants with differing capabilities of eliciting a pathological response; thus, it may be possible to identify biomarkers specific for a given virulence pathotype. miRNAs are known to regulate genes that in turn regulate signaling pathways involved in disease pathogenesis. Importantly, miRNAs are stable and can reflect a tissue response and therefore have the potential to be biomarkers of disease severity. Currently, with respect to chlamydial infections, there is no way to predict whether an infected patient is more or less likely to develop PID. However, data presented in this study indicate that the expression of a specific miRNA profile associated with a virulent variant early in the infection course may be predictive of an increased risk of pelvic inflammatory disease, allowing more aggressive treatment before significant pathology develops.

Aortic arch advancement for aortic coarctation and hypoplastic aortic arch in neonates and infants.

BACKGROUND: The optimal treatment for infants with aortic coarctation and hypoplastic aortic arch is controversial. The goal of this study was to report the short-term and mid-term outcomes of aortic arch advancement (AAA) in infants with hypoplastic aortic arch. METHODS: All infants who underwent AAA at our institution from 1995 to 2012 were included. AAA consisted of coarctectomy and end-to-side anastomosis of the descending aorta to the distal ascending aorta/proximal arch through a median sternotomy. The cohort was divided into four groups: (1) isolated AAA (n=29, 11%), (2) AAA with closure of ventricular septal defect (n=56, 20%), (3) AAA with other biventricular repairs (n=115, 42%), and (4) AAA as part of single-ventricle palliation (n=75, 27%). RESULTS: The cohort included 275 patients: 125 (45%) were female, and the median age was 14 days (interquartile range, 7-34 days). Genetic abnormalities were present in 48 patients (17%). Neurologic adverse events occurred in 3 patients (1%), all in group 4. Left bronchial compression was seen in 2 patients (0.7%); only one required intervention. Vocal cord dysfunction was noted in 36 of 95 patients (38%) on routine laryngoscopy. Only 1 patient had clinical residual dysfunction at the last follow-up visit. Perioperative mortality was 3% (n=8). At a median follow-up time of 6 years, 8 patients (3%) had reinterventions at a median time of 5 months (3-17 months) after repair. CONCLUSIONS: AAA is a safe, effective, and durable operation with low rates of adverse events and mid-term reintervention. The advantages include native tissue-to-tissue reconstruction and preserved potential for growth. As such, it is the ideal technique for the management of hypoplastic aortic arch in neonates and infants.