Can the Cartilaginous Thickness Determine the Risk of Malignancy in Pelvic Cartilaginous Tumors, and How Accurate is the Preoperative Biopsy of These Tumors?

BACKGROUND: Peripheral osteochondral tumors are common, and the management of tumors presenting in the pelvis is challenging and a controversial topic. Some have suggested that cartilage cap thickness may indicate malignant potential, but this supposition is not well validated. QUESTIONS/PURPOSES: (1) How accurate is preoperative biopsy in determining whether a peripheral cartilage tumor of the pelvis is benign or malignant? (2) Is the thickness of the cartilage cap as determined by MRI associated with the likelihood that a given peripheral cartilage tumor is malignant? (3) What is local recurrence-free survival (LRFS), metastasis-free survival (MFS), and disease-specific survival (DSS) in peripheral chondrosarcoma of the pelvis and is it associated with surgical margin? METHODS: Between 2005 and 2022, 289 patients had diagnoses of peripheral cartilage tumors of the pelvis (either pedunculated or sessile) and were treated at one tertiary sarcoma center (the Royal Orthopaedic Hospital, Birmingham, UK). These patients were identified retrospectively from a longitudinally maintained institutional database. Those whose tumors were asymptomatic and discovered incidentally and had cartilage caps ≤ 1.5 cm were discharged (95 patients), leaving 194 patients with tumors that were either symptomatic or had cartilage caps > 1.5 cm. Tumors that were asymptomatic and had a cartilage cap > 1.5 cm were followed with MRIs for 2 years and discharged without biopsy if the tumors did not grow or change in appearance (15 patients). Patients with symptomatic tumors that had cartilage caps ≤ 1.5 cm underwent removal without biopsy (63 patients). A total of 82 patients (63 with caps ≤ 1.5 cm and 19 with caps > 1.5 cm, whose treatment deviated from the routine at the time) had their tumors removed without biopsy. This left 97 patients who underwent biopsy before removal of peripheral cartilage tumors of the pelvis, and this was the group we used to answer research question 1. The thickness of the cartilage cap was recorded from MRI and measuring to the nearest millimeter, with measurements taken perpendicular in the plane that best allowed the greatest measurement. Patient survival rates were assessed using the Kaplan-Meier method with 95% confidence intervals as median observation times to estimate MFS, LRFS, and DSS. RESULTS: Of malignant tumors biopsied, in 49% (40 of 82), the biopsy result was recorded as benign (or was considered uncertain regarding malignancy). A malignant diagnosis was correctly reported in biopsy reports in 51% (42 of 82) of patients, and if biopsy samples with uncertainty regarding malignancy were excluded, the biopsy identified a lesion as being malignant in 84% (42 of 50) of patients. The biopsy results correlated with the final histologic grade as recorded from the resected specimen in only 33% (27 of 82) of patients. Among these 82 patients, 15 biopsies underestimated the final histologic grade. The median cartilage cap thickness for all benign osteochondromas was 0.5 cm (range 0.1 to 4.0 cm), and the median cartilage cap thickness for malignant peripheral chondrosarcomas was 8.0 cm (range 3.0 to 19 cm, difference of medians 7.5 cm; p < 0.01). LRFS was 49% (95% CI 35% to 63%) at 3 years for patients with malignant peripheral tumors with < 1-mm margins, and LRFS was 97% (95% CI 92% to 100%) for patients with malignant peripheral tumors with ≥ 1-mm margins (p < 0.01). DSS was 100% at 3 years for Grade 1 chondrosarcomas, 94% (95% CI 86% to 100%) at 3 years for Grade 2 chondrosarcomas, 73% (95% CI 47% to 99%) at 3 and 5 years for Grade 3 chondrosarcomas, and 20% (95% CI 0% to 55%) at 3 and 5 years for dedifferentiated chondrosarcomas (p < 0.01). DSS was 87% (95% CI 78% to 96%) at 3 years for patients with malignant peripheral tumors with < 1-mm margin, and DSS was 100% at 3 years for patients with malignant peripheral tumors with ≥ 1-mm margins (p = 0.01). CONCLUSION: A thin cartilage cap (< 3 cm) is characteristic of benign osteochondroma. The likelihood of a cartilage tumor being malignant increases after the cartilage cap thickness exceeds 3 cm. In our experience, preoperative biopsy results were not reliably associated with the final histologic grade or malignancy, being accurate in only 33% of patients. We therefore recommend observation for 2 years for patients with pelvic osteochondromas in which the cap thickness is < 1.5 cm and there is no associated pain. For patients with tumors in which the cap thickness is 1.5 to 3 cm, we recommend either close observation for 2 years or resection, depending on the treating physician's decision. We recommend excision in patients whose pelvic osteochondromas show an increase in thickness or pain, preferably before the cartilage cap thickness is 3 cm. We propose that surgical resection of peripheral cartilage tumors in which the cartilage cap exceeds 3 cm (aiming for clear margins) is reasonable without preoperative biopsy; the role of preoperative biopsy is less helpful because radiologic measurement of the cartilage cap thickness appears to be accurately associated with malignancy. Biopsy might be helpful in patients in whom there is diagnostic uncertainty or when confirming the necessity of extensive surgical procedures. Future studies should evaluate other preoperative tumor qualities in differentiating malignant peripheral cartilage tumors from benign tumors. LEVEL OF EVIDENCE: Level III, diagnostic study.

Controversies in orthopaedic oncology.

Chondrosarcoma is the second most common surgically treated primary bone sarcoma. Despite a large number of scientific papers in the literature, there is still significant controversy about diagnostics, treatment of the primary tumour, subtypes, and complications. Therefore, consensus on its day-to-day treatment decisions is needed. In January 2024, the Birmingham Orthopaedic Oncology Meeting (BOOM) attempted to gain global consensus from 300 delegates from over 50 countries. The meeting focused on these critical areas and aimed to generate consensus statements based on evidence amalgamation and expert opinion from diverse geographical regions. In parallel, periprosthetic joint infection (PJI) in oncological reconstructions poses unique challenges due to factors such as adjuvant treatments, large exposures, and the complexity of surgery. The meeting debated two-stage revisions, antibiotic prophylaxis, managing acute PJI in patients undergoing chemotherapy, and defining the best strategies for wound management and allograft reconstruction. The objectives of the meeting extended beyond resolving immediate controversies. It sought to foster global collaboration among specialists attending the meeting, and to encourage future research projects to address unsolved dilemmas. By highlighting areas of disagreement and promoting collaborative research endeavours, this initiative aims to enhance treatment standards and potentially improve outcomes for patients globally. This paper sets out some of the controversies and questions that were debated in the meeting.

Chondrosarcoma of the Femur: Is Local Recurrence Influenced by the Presence of an Extraosseous Component?

BACKGROUND: Chondrosarcoma (CS) is the second most common surgically treated primary malignancy of the bone. The current study explored the effect of the margin and extraosseous tumor component in CS in the femur on local recurrence (LR), LR-free survival (LRFS), and disease-specific survival (DSS). METHODS: Among 202 patients, 115 were in the proximal extremity of the femur, 4 in the corpus of the femur, and 83 in the distal extremity of femur; 105 patients had an extraosseous tumor component. RESULTS: In the Kaplan-Meier analysis, factors significant for decreased LRFS were the extraosseous tumor component (p < 0.001), extraosseous tumor component arising from the superior aspect (p < 0.001), histological grade (p = 0.031), and narrow surgical margin < 3 mm (p < 0.001). Factors significantly affecting DSS were the histological grade (p < 0.001), extraosseous component (p < 0.001), LR (p < 0.001), metastases (p < 0.001), and surgical margin (p < 0.001). CONCLUSIONS: In CS of the femur, the presence of an extraosseous tumor component has a predictive role in LRFS, and extraosseous tumor component arising from the superior aspect was significant for decreased LRFS. Wide margins were more commonly achieved when the tumor had only an intraosseous component, and the rate of LR was significantly higher in cases with an extraosseous tumor component. When the extraosseous component arose from the superior aspect of the femur, LR occurred more frequently despite achieving adequate margins.

Pelvic bone sarcomas, prognostic factors, and treatment: A narrative review of the literature.

Primary sarcomas of bone are rare malignant mesenchymal tumors. The most common bone sarcomas are osteosarcoma, Ewing's sarcoma, and chondrosarcoma. The prognosis has improved over the years, but bone sarcomas are still life-threatening tumors that need a multidisciplinary approach for diagnosis and treatment. Bone sarcomas arising in the pelvis present a unique challenge to orthopedic oncologists due to the absence of natural anatomical barriers, the close proximity of vital neurovascular structures, and the high mechanical demands placed on any pelvic reconstruction following the excision of the tumor. While radiotherapy has an important role especially in Ewing's sarcoma and chemotherapy for both Ewing's sarcoma and osteosarcoma, surgery remains the main choice of treatment for all three entities. While external hemipelvectomy has remained one option, the main aim of surgery is limb salvage. After complete tumor resection, the bone defect needs to be reconstructed. Possibilities to reconstruct the defect include prosthetic or biological reconstruction. The method of reconstruction is dependent on the location of tumor and the surgery required for its removal. The aim of this article is to give an insight into pelvic bone sarcomas, their oncological and surgical outcomes, and the options for treatment based on the authors' experiences.

Novel one-pot synthesis of a library of 2-aryloxy-1,4-naphthoquinone derivatives. Determination of antifungal and antibacterial activity.

The development of new antibiotics and inexpensive antifungals is an important field of research. Based on the privileged pharmacophore of lawsone, a series of phenolic ether derivatives of 1,4-naphthoquinone were synthesized easily in one step in reasonable yields. All the new compounds were characterized and tested as potential antifungal and antibacterial agents against Candida albicans, Escherichia coli and Staphylococcus aureus. Compound 55 has significant antibacterial action (as good as or better than the controls) against E. coli and S. aureus. Against C. albicans, compounds 38, 46, 47 and 60 were the best candidates as antifungals. Using a qualitative structure-activity analysis, a correlation between molar mass and antimicrobial activity was identified, regardless of the substituent group on the phenolic moiety, except for 55 and 63, where electronic effects seem more important. An in silico evaluation of the absorption, distribution, metabolism and excretion (ADME) for 37, 50, 55 and 63 was made, indicating that the classic Lipinski's rule of five applies in all cases.

Meta-regression Analysis of Study Heterogeneity for Systemic Outcomes after Periodontal Therapy.

INTRODUCTION: The contribution of periodontal disease to adverse systemic consequences remains controversial. This analysis examined 2 well-investigated conditions independently and combined-adverse pregnancy outcomes and glycemic control for patients with diabetes-based on shared pathogenic mechanisms of periodontal infection and inflammation. It was proposed that inconsistencies in study design significantly contribute to outcome discrepancies found between periodontal intervention studies undergoing meta-analysis. METHODS: Meta-analyses evaluating periodontal interventions on the rate of preterm birth and changes in glycated hemoglobin A1c in type 2 diabetes populations were conducted based on a systematic review of randomized controlled trials. Meta-regression covariates for exploring heterogeneity included sample size, level of medical management, and bias risk as moderator variables in a random-effects meta-regression. RESULTS: Systematic review identified 17 studies of diabetes and 13 of pregnancy outcomes. Analyses of these studies identified 0.50% reduction in HbA1c and 0.78 odds ratio for preterm births. The heterogeneity associated with the models was high (I2 = 92.4 and I2 = 62.7%, respectively). The adjusted models evaluating each systemic condition separately accounted for 52.2% of the effect for diabetes and 81.4% for pregnancy outcome effects independently, and 63.5% collectively, across interventional studies. CONCLUSION: This systematic review with meta-regression analysis of heterogeneity demonstrates that disparate results seen in randomized controlled trials of periodontal therapy affecting systemic outcomes may be explained in large part by study design, specifically stringency in consideration of medical management and sample size. The potential for confounding factors to influence outcomes remains a concern in understanding the implications of oral health on systemic conditions. KNOWLEDGE TRANSFER STATEMENT: The findings of this study demonstrate that much of the benefits seen from periodontal therapy on adverse systemic outcomes for diabetes and pregnancy are due to limitations in study design.

Multiple sclerosis: review of eye movement disorders and update of disease-modifying therapies.

PURPOSE OF REVIEW: To review important eye movement disorders in multiple sclerosis (MS) and update the ophthalmologist on disease-modifying therapies in MS, from the perspective of expert neurologists. RECENT FINDINGS: A large study confirmed that eye movement abnormalities in MS can be commonly identified by bedside examination. Identifying such ocular motility disturbances can assist in the diagnosis and prognosis for patients with MS. Articles published on such agents as oral teriflunomide and the biologics, natalizumab and alemtuzumab, have defined emerging roles of these treatments in the management of MS. SUMMARY: Many patients with MS suffer from isolated or a combination of eye movement disorders. Understanding their ocular motility disturbance patterns can help diagnose MS and correlate with the progression of MS. Exciting advances in MS disease-modifying treatments have been developed. Patients have more options than ever before of injectable, infusion and oral therapies. The therapeutic efficacy in lowering relapse rates is counterbalanced by these drugs' side-effects.

Synthesis and biological evaluation of novel ferrocene-naphthoquinones as antiplasmodial agents.

This work deals with the synthesis and evaluation of new compounds designed by combination of 1,4-naphthoquinone and ferrocene fragments in a 3-ferrocenylmethyl-2-hydroxy-1,4-naphthoquinone arrangement. A practical coupling reaction between 2-hydroxy-1,4-naphthoquinone and ferrocenemethanol derivatives has been developed. This procedure can be carried out "on-water", at moderate temperatures and without auxiliaries or catalysts, with moderate to high yields. The synthesized derivatives have shown significant in vitro antiplasmodial activity against chloroquine-sensitive and resistant Plasmodium falciparum strains and it has been shown that this activity is not related to the inhibition of biomineralization of ferriprotoporphyrin IX. Binding energy calculations and docking of these compounds to cytochrome b in comparison with atovaquone have been performed.

Accessory nerve palsies.

Accessory nerve palsies may cause considerable functional disability and they unfortunately continue to occur as a complication of surgery in and, around the posterior triangle of the neck. Here the causes of accessory nerve palsies are reviewed and the symptoms and signs arising as a consequence are summarised. In addition, the various treatments and their indications are highlighted and discussed.

Tubulointerstitial nephritis and uveitis syndrome: a case with an autoimmune reactivity against retinal and renal antigens.

Tubulointerstitial nephritis and uveitis (TINU) generally occurs at young age and has a female preponderance. Renal biopsy reveals interstitial infiltration of inflammatory cells and edema, and the associated intraocular inflammation typically consists of an anterior, bilateral uveitis. The pathogenesis of TINU likely involves both humoral and cellular immunity and is mediated by medications, infectious agents, or other unknown causes. A previous report detected a renal antigen recognized by the serum of a TINU patient. In this report the authors extend these observations to document seroreactivity against a retinal antigen of similar size.

Clinical course of retrobulbar hemangioblastomas in von Hippel-Lindau disease.

OBJECTIVE: To report clinical findings of rare retrobulbar optic nerve hemangioblastomas associated with von Hippel-Lindau disease (VHL). DESIGN: Retrospective observational case series. PARTICIPANTS: Nine patients with VHL. METHODS: The clinical course and magnetic resonance imaging findings of patients with VHL and hemangioblastomas affecting the anterior visual pathway from the intraorbital optic nerve to the optic chiasm are reviewed. MAIN OUTCOME MEASURE: Clinical course of retrobulbar optic nerve hemangioblastomas. RESULTS: The mean age of VHL diagnosis was 24+/-14 years, and mean follow-up was 5+/-4 years. All had other CNS lesions and retinal hemangioblastomas. Approximately 50% (5/9) had a previous enucleation or had visual acuity loss (4/9), some due to other VHL ocular complications. Four patients underwent surgical resection of an intracranial hemangioblastoma. Growth patterns and pathology are similar to those of other hemangioblastomas in the CNS. CONCLUSIONS: Although these lesions are rare, patients with VHL who present with signs of optic neuropathy should be evaluated for anterior visual pathway hemangioblastomas impinging on the optic nerve from the orbit to the chiasm. On neuroimaging, the hemangioblastomas may demonstrate chiasmal or optic tract edema, associated cysts, and T(2) flow voids. Lesions may remain radiologically and clinically stable, evolve radiographically with no visual or neurological progression, or progress clinically and radiographically. Patients at risk for visual loss should be considered for surgical resection. Close coordination among neuroradiology, neurosurgery, and ophthalmology patient care teams is advised for optimal management of these patients.

Frequency of anti-retinal antibodies in normal human serum.

BACKGROUND: Anti-retinal antibodies have been described in the context of autoimmune retinopathies and are often presumed to be pathogenic or disease associated. However, full characterization of patterns of anti-retinal antibody reactivity in normal human serum has been limited. The purpose of this work was to identify the profile of anti-retinal IgG antibodies in serum used as controls in laboratory testing. METHODS: Normal human sera used in commercial diagnostic laboratories were tested for the presence of immunoreactivity against soluble human retinal proteins using Western blot analysis of fractionated soluble human retinal proteins. Reactivity was quantified using computerized densitometry, and the level of reactivity was standardized relative to a control positive serum with known reactivity against recoverin. RESULTS: Some anti-retinal reactivity was observed in the majority of all tested normal sera. Reactivity against one to two protein bands was observed in 33%. Reactivity against five or more distinct bands was observed in 22%. There was a tendency for serum from women to react with three or more protein bands compared with serum from men. CONCLUSIONS: The presence of anti-retinal antibodies is observed in a majority of normal control human sera, suggesting that identification of new candidate retinal autoantigens should be cautiously interpreted and subject to rigorous testing for disease association. Additional studies will aid development of a standardized protocol for validation of potential pathogenic seroreactivity.

Choroidal and optic nerve infarction in hepatitis C-associated polyarteritis nodosa.

A 39-year-old man presented with headache, weight loss, bilateral subdural hematomas, pansinusitis, and visual loss. The neuro-ophthalmologic examination disclosed deep choroidal lesions and bilateral optic disc edema. Orchiectomy for testicular torsion showed acute vasculitis consistent with polyarteritis nodosa (PAN). Polymerase chain reaction (PCR) testing revealed hepatitis C. This is the first reported case of PAN due to hepatitis C with early findings of choroidal and optic nerve infarction.

[Relevance of the systematic culture of the intraoperative swab and drain tip of Redon in orthopaedic-traumatology surgery]. / Intérêt de la culture systématique du prélèvement per opératoire et du drain de Redon en chirurgie orthopédique et traumatologique.

BACKGROUND: Post operative infections are more severe complications in bone surgery. The first stage culture on drain tip or intraoperative swab are not well known according to clear, open and aseptic orthopaedic surgery to predict wounds infections. OBJECTIVE: To show the place of the systemic bacteriological culture of an intraoperative swab and the proximal tip of the Redon in bone surgery. METHODS: This was a prospective continuous series of 92 interventions performed in the service of Orthopaedics Traumatology of Treichville University Hospital (Abidjan, Côte d'Ivoire). The lesions included were allocated into three groups based on the National Research Council classification. Group 1 consisted of 50 subjects with clean lesions and hyper clean. Group 2 was made up of 25 subjects with clean lesions contaminated or contamined ab initio while Group 3 consisted of 17 patients with the septic lesions. Fifty six men and 36 women with an average age of 36.9 years had two types of swabs culture. In the first type sample of intra operative haematoma or the pus before using antiseptic products was used; the second type of culture used the proximal tip of Redon at the time of its ablation. These two swabs were put in a sterile vial and sent to the same laboratory for culture. RESULTS: The overall sepsis rate was of 24(26,1%). The microbial population was dominated by the gram negative bacilli, bacilli positive intraoperative cultures were most frequent in the group 3. 15 (88,2%). The positivity of the culture of the Redon was high in the group 2 (32%) and in the group 3 (52.9%). There was a significant difference between these two groups of surgery. The sensitivity, the specificity, and the predictive values were low. For all groups, the reports of likelihood observed didn't permit to establish a relation of cause or effect between a positive culture and the occurrence of post operative infection. CONCLUSION: The gram negative bacilli were mostly observed on the culture of the site of infection. Although there was no significant relationshionship, it appears from the frequency that there may be a clinical link between the positive culture and open fracture.

Acoustic diffraction by deformed edges of finite length: theory and experiment.

The acoustic diffraction by deformed edges of finite length is described analytically and in the frequency domain through use of an approximate line-integral formulation. The formulation is based on the diffraction per unit length of an infinitely long straight edge, which inherently limits the accuracy of the approach. The line integral is written in terms of the diffraction by a generalized edge, in that the "edge" can be a single edge or multiple closely spaced edges. Predictions based on an exact solution to the impenetrable infinite knife edge are used to estimate diffraction by the edge of a thin disk and compared with calculations based on the T-matrix approach. Predictions are then made for the more complex geometry involving an impenetrable thick disk. These latter predictions are based on an approximate formula for double-edge diffraction [Chu et al., J. Acoust. Soc. Am. 122, 3177 (2007)] and are compared with laboratory data involving individual elastic (aluminum) disks spanning a range of diameters and submerged in water. The results of this study show this approximate line-integral approach to be versatile and applicable over a range of conditions.

Spinocerebellar ataxia type 17: extension of phenotype with putaminal rim hyperintensity on magnetic resonance imaging.

We report on a 50-year-old woman who presented with an 8-year history of involuntary movements, unsteadiness, and cognitive decline. Examination revealed multidomain cognitive deficits, jerky ocular pursuit movements, hypometric saccades, gaze impersistence, dysarthria, upper limb dystonia, and widespread chorea. TATA-binding protein gene test revealed trinucleotide expansion allele sizes of 47 and 39 repeats, confirming the diagnosis of spinocerebellar ataxia type 17 (SCA-17). Magnetic resonance imaging (MRI) showed marked cerebellar atrophy and putaminal rim hyperintensity. This is the first case of SCA-17 reported to show MRI signal change in the basal ganglia, and extends the phenotypic manifestation of SCA-17.

Including dispersion and attenuation directly in the time domain for wave propagation in isotropic media.

When sound propagates in a lossy fluid, causality dictates that in most cases the presence of attenuation is accompanied by dispersion. The ability to incorporate attenuation and its causal companion, dispersion, directly in the time domain has received little attention. Szabo [J. Acoust. Soc. Am. 96, 491-500 (1994)] showed that attenuation and dispersion in a linear medium can be accounted for in the linear wave equation by the inclusion of a causal convolutional propagation operator that includes both phenomena. Szabo's work was restricted to media with a power-law attenuation. Waters et al. [J. Acoust. Soc. Am. 108, 2114-2119 (2000)] showed that Szabo's approach could be used in a broader class of media. Direct application of Szabo's formalism is still lacking. To evaluate the concept of the causal convolutional propagation operator as introduced by Szabo, the operator is applied to pulse propagation in an isotropic lossy medium directly in the time domain. The generalized linear wave equation containing the operator is solved via a finite-difference-time-domain scheme. Two functional forms for the attenuation often encountered in acoustics are examined. It is shown that the presence of the operator correctly incorporates both, attenuation and dispersion.

Abnormal cortical sensory activation in dystonia: an fMRI study.

Despite the obvious motor manifestations of focal dystonia, it is recognised that the sensory system plays an important role in this condition. This functional magnetic resonance imaging study examines the sensory representations of individual digits both within the subregions of the primary sensory cortex (SI) and in other nonprimary sensory areas. Patients with focal dystonia and controls were scanned during vibrotactile stimulation of both the index (digit 2) and little (digit 5) fingers of their dominant hand (which was the affected hand in all the dystonic subjects). The activation maps obtained were analysed for location, size, and magnitude of activation and three-dimensional (3-D) orientation of digit representations. Data from both groups were compared. There were significant differences in the average 3-D separation between the two digit representations in area 1 of SI between subject groups (9.6 +/- 1.2 mm for controls and 4.1 +/- 0.2 mm for dystonic subjects). There were also strong trends for reversed ordering of the representation of the two digits in both the secondary sensory cortex and posterior parietal area between the two groups. In addition, in dystonic subjects, there was significant under activation in the secondary somatosensory cortex (SII/area 40) for both digits and in the posterior parietal area for digit 5. These results indicate the presence of widespread activation abnormalities in the cortical sensory system in dystonia.