Prior Bone Research Articles

Clinical characteristics and prognostic analysis of prolonged cytopenia after CAR-T cell therapy in LBCL patients

Objective: To investigate the clinical features and prognosis of prolonged cytopenia (PC) in patients with large B-cell lymphoma (LBCL) undergoing anti-CD19 chimeric antigen receptor T (CAR-T) cell therapy. Methods: A retrospective case series study was conducted on LBCL patients who received CAR-T cell therapy with a survival time of over one month at the Hematology Department of Peking Union Medical College Hospital from March 2019 to December 2023. Statistical analyses were performed on hematologic changes at 1, 3, 6, and 12 months post-CAR-T infusion, as well as on the progression-free survival (PFS) and post-treatment adverse events, including infections. Patients were categorized into the PC and non-PC groups based on the occurrence of cytopenia at 90 days post-infusion. Differences between groups were compared, and univariate logistic regression analysis was used to identify risk factors. Results: The median age of 27 LBCL patients receiving CAR-T cell therapy was 58 years (range 27-69 years), with 18 males. Among the 27 LBCL patients who received CAR-T cell therapy, PC was observed in 19 patients (70.4%), with instances of neutropenia (48.1%, 13 cases), anemia (37.0%, 10 cases), and thrombocytopenia (22.2%, 6 cases). Univariate logistic regression analysis revealed that prior chemotherapy sensitivity (OR=18.00, 95%CI 1.56-207.45, P=0.020) and bone marrow suppression (OR=18.00, 95%CI 1.38-235.69, P=0.028) were associated with PC. The median follow-up time was 13.5 months. The PC group exhibited a higher risk of infection within 3 months (9/19 vs. 1/8) and a shorter mean PFS (19.3 months vs. 24.4 months), although the difference was not statistically significant (both P>0.05). Conclusions: PC is common following CAR-T cell therapy and is associated with an increased risk of infection and poorer prognosis. Prior treatment sensitivity and bone marrow suppression may serve as indicators of PC.

Outcomes Following Autologous Osteochondral Transplantation for Osteochondral Lesions of the Talus at 10-Year Follow-Up: A Retrospective Review.

The purpose of this study was to evaluate outcomes following autologous osteochondral transplantation (AOT) for the treatment of osteochondral lesions of the talus (OLT) at a minimum of 10-year follow-up. Retrospective chart review identified patients who underwent AOT for the treatment of OLT. Pre-operative magnetic resonance imaging (MRI) scans were obtained in all patients. Clinical outcomes assessed included: pre- and post-operative foot and ankle outcome score (FAOS), visual analog scale (VAS), patient satisfaction, complications, failures and secondary surgical procedures. Thirty-nine patients with a mean lesion size was 122.3 ± 64.1 mm2 and mean follow-up time of 138.9 ± 16.9 months were included. The mean FAOS scores improved from a preoperative score of 51.9 ± 16.0 to 75.3 ± 21.9 (P < 0.001). Increasing lesion size was variable associated with inferior FAOS scores (R2 = 0.2228). There was statistically significant higher mean T2 relaxation values at the superficial layer at the site of the AOT graft (42.9 ± 5.2 ms) compared to the superficial layer of the adjacent native cartilage (35.8 ± 3.8 ms) (P < 0.001). Seventeen complications (43.6%) were observed, the most common of which was anterior ankle impingement (25.6%). There were 2 failures (5.1%), both of which had a history of prior bone marrow stimulation via microfracture and post-operative cysts identified on MRI. This retrospective review found that AOT for the treatment of large OLTs produced a 94.9% survival rate at a minimum of 10-year follow-up. Increasing lesion size was associated with inferior clinical outcomes. The findings of this study indicates that AOT is a viable long-term surgical strategy for the treatment of large OLTs.

Case report: hypertrophic osteoarthropathy improves with immune checkpoint inhibitor therapy.

We report a case of a 66 year-old male with recurrent stage IIIA non-small cell lung cancer (NSCLC) and no prior arthritis or bone disease who developed hypertrophic osteoarthropathy (HOA) prior to immunotherapy treatment. Approximately one month after the first durvalumab infusion and without other interventions for symptom management, the patient reported improvements to his hand pain, with complete resolution of symptoms after five durvalumab treatments. Repeat x-ray after nine cycles of durvalumab showed decreased periosteal thickening of the phalanges bilaterally. He had no evidence of recurrent NSCLC based on serial computed tomography one year after durvalumab initiation. To our knowledge, there are no documented reports on the isolated effect of immune-checkpoint inhibitor (ICI) therapy on HOA. This case suggests that durvalumab may have a positive role in the management of HOA in NSCLC patients. Further research is needed to better understand the interaction of ICIs, HOA and other paraneoplastic syndromes.

Myeloid neoplasm with concurrent BCR::ABL1 translocation, and JAK2 and SF3B1 co-mutations with severe fibrosis: a case report

Abstract Introduction/Objective Myeloproliferative neoplasms (MPNs) arise from hematopoietic stem cells with somatically altered tyrosine kinase signaling. Classification of MPNs is based on hematologic, histopathologic and molecular characteristics including the presence of BCR::ABL1 and JAK2 V617F. Methods/Case Report We present a 72-year-old male with a myeloid neoplasm and severe fibrosis, with concurrent BCR::ABL1 translocation, and co-mutations in JAK2 and SF3B1. Initially, the patient was diagnosed with anemia, thrombocytosis and folic acid deficiency and was prescribed supplemental folic acid. At follow up, normocytic anemia and thrombocytosis were seen. Bone marrow biopsy showed overtly fibrotic marrow with maturing trilineage hematopoiesis, markedly increased megakaryopoiesis and ring sideroblasts. Chromosome analysis and sequential GTG-fluorescence in situ hybridization (FISH) of metaphases using the dual-fusion three color probe BCR/ABL1- ASS1 revealed abnormal results. A t(9;22)(q34;q11.2) was detected along with an atypical FISH signal pattern with a single BCR::ABL1 fusion on the derivative chromosome 22 instead of the typical two fusions, resulting in loss of one BCR::ABL1 fusion signal including loss of the ASS1 on the derivative chromosome 9. Next-generation sequencing (NGS) analysis detected double driver mutations, JAK2 p. Val617Phe and SF3B1 p. Lys700Glu in the patient. JAK2 V617F mutation was further confirmed by real-time quantitative PCR (qPCR) with variant allele frequencies of 39.7%. Additionally, the patient was positive for BCR::ABL1 p190 fusion transcript (10%). The presence of JAK2 and SF3B1 co-mutations along with ring sideroblasts and the patient’s clinical presentation suggests the diagnosis of myelodysplastic/myeloproliferative neoplasm with thrombocytosis and SF3B1 mutation. Results (if a Case Study enter NA) NA Conclusion Although, the detection of t(9;22) by chromosome analysis is a diagnostic feature of chronic myeloid leukemia (CML), our case adds to the limited information on co-existence of BCR::ABL1 and JAK2 V617F with SF3B1 mutations in severe fibrosis. The frequency of co-occurrence, the temporal order of acquisition and clonal relationship of these alterations is poorly understood, and it is also unclear for this case since there is no prior bone marrow biopsy or diagnostic work up. Literature search of these rare cases show that some patients with similar findings progress to myelofibrosis as in this patient. It is possible that the presence of two mutated tyrosine kinase genes accelerates disease progression.

Assessing guideline adherence and child abuse evaluation in infants with fractures: a retrospective quality control study

AIMS OF THE STUDY: To standardise the assessment of infants with fractures at University Children’s Hospital Zurich, a guideline was implemented in February 2021. The aim of this study was to assess adherence to this guideline and to assess changes in management before and after guideline implementation. The primary outcome was the overall adherence rate to the guideline. Additionally, we evaluated specific omissions of guideline steps by clinicians and investigated differences in adherence for infants younger vs older than six months, as well as variations between in- and outpatient care. Secondary outcomes focused on changes in the frequency of involvement of the child protection team, skeletal survey rates and child abuse detection, comparing these rates before and after guideline implementation. METHODS: We conducted a retrospective single-centre quality control study. We included infants younger than 12 months diagnosed with fractures at the emergency department between 1 February 2021 and 31 August 2022. We excluded children with prior bone disease diagnoses and those whose parents did not consent to their children’s data being used for research. RESULTS: A total of 61 emergency department visits of infants with fractures were included in the study. The overall adherence rate to the guideline was 39%. Notably, in 68% of cases where clinicians deviated from the guideline, the primary reason was a missing consultation of the paediatrician or family doctor. Adherence levels were consistent across age groups (under and over six months), but there was a notable discrepancy between inpatient (53%) and outpatient (26%) care settings. Child protection team involvement increased to 54%, twice the rate observed before guideline implementation. CONCLUSIONS: Overall adherence to the guideline was poor, emphasising the necessity for continuous training of clinicians to raise awareness regarding the differential diagnosis of child abuse. Despite the guideline’s implementation leading to a doubled rate of child protection team involvement, there remains a need for improvement. Notably, outpatient care exhibited lower guideline adherence, signalling an area requiring focused attention.

The relationship between serum monoterpene levels and bone health: a retrospective cross-sectional analysis from the National Health and Nutrition Examination Survey (NHANES) data.

Monoterpenes, a subset of the terpene family composed of two isoprene units, have garnered significant attention in research circles owing to their potential medicinal benefits. Recent experimental studies indicate that they might exert positive effects on bone health. Nevertheless, the impact of monoterpenes exposure on bone health remains unexplored in humans. We examined 748 adults (age ≥ 40 years) from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 to explore the correlation between three monoterpenes (α-pinene, β-pinene, and limonene), bone mineral density (BMD) in the total lumbar spine and proximal femur, FRAX® scores, and prior bone fracture history. Our analysis unveiled a significant inverse association between a one-unit increase in the natural logarithm (ln) of α-pinene and limonene and total proximal femur BMD (ß = -0.027, S.E. = 0.008, P = 0.004 and ß = -0.019, S.E. = 0.007, P = 0.016, respectively). As serum α-pinene levels ascended across quintiles, there was a notable decrease in total proximal femur BMD (P for trend = 0.025). The inverse relationship between ln α-pinene levels and total proximal femur BMD was more pronounced in women, especially pre-menopausal women. Compared to subjects with α-pinene and limonene levels at or below the 50th percentiles, those exceeding this threshold exhibited the lowest mean value of total proximal femur BMD (0.8628 g/cm2, S.E. = 0.026, P = 0.009). However, the trend was not statistically significant (P = 0.070). Additionally, all three monoterpenes were linked to a higher prevalence of previous spine fractures, whereas β-pinene showed a reduced incidence of other types of fractures. In this comprehensive survey of American adults aged 40 and above, higher serum levels of α-pinene and limonene correlated with decreased total proximal femur BMD. Furthermore, our findings suggest a potential combined effect of α-pinene and limonene on total proximal femur BMD. Further investigation is essential to elucidate the clinical relevance and causative nature of our findings.

Case Report: The Sausage Technique using Anorganic Bovine Bone Mineral for Horizontal Bone Augmentation at the Crestal Part of a Posterior Mandibular Ridge: A Case Report.

Following tooth extraction, the alveolar bone goes through a natural remodeling process resulting in a significant bone resorption which may complicate dental implant placement without prior bone augmentation treatment. The sausage technique is a modified guided bone regeneration (GBR) method that has been successfully used for horizontal bone augmentation. This technique was developed to increase the bone growth at the alveolar crest. Although the sausage technique uses a combination of autograft chips and xenograft particles with a native collagen membrane, several studies have questioned whether adding autograft chips is essential for bone formation with guided bone regeneration. Moreover, harvesting the bone graft may increase the donor site morbidity and patient discomfort. This case report aimed to investigate the bone gain radiologically when the sausage technique was applied to treat a healthy, thirty-year-old patient with a horizontal defect in the posterior mandibular region using anorganic bovine bone mineral (ABBM) particles with Jason membrane, assess the implant primary stability in the augmented ridge, and present the surgical procedure steps in details. After nine months of healing, the cone-beam computed tomography (CBCT) revealed approximately 4.32 mm of bone gain at the alveolar crest in the buccal-lingual direction. The graft particles were well integrated into the newly formed bone. Two implants were inserted with an insertion torque of 35 N/cm. The ISQ values were 76 for the most anterior implant and 78 for the posterior implant. Within the limitations of this case report, the sausage technique using ABBM particles without autograft chips was an effective approach in achieving the prerequisite bone width at the crest in cases with horizontal bone defects.

Conversion Total Hip Arthroplasty After Pedicled Peri-Hip Bone Flap Grafting: The Chinese Experience

BackgroundThis study investigated the perioperative outcomes of patients undergoing conversion total hip arthroplasty (THA) after failed peri-hip bone flap grafting (PBFG) and compared them with those patients undergoing primary THA for osteonecrosis of the femoral head (ONFH). MethodsFrom January 2010 to December 2021, 163 Chinese patients (163 hips) were treated by conversion THA after failed PBFG (containing 94 patients who had pedicled vascularized iliac bone flap grafting and 69 patients who had pedicled vascularized greater trochanter bone flap grafting), and 178 Chinese patients were treated by primary THA. The preoperative baseline data and perioperative indicators in both groups were compared. ResultsIn the conversion group, patients had significantly greater blood loss, a longer length of stay, and greater changes in serum hemoglobin than those in the primary THA group (P < 0.05). The operative room time, transfusion volume, calculated blood loss, changes in serum hematocrit, and increased superficial infection (P > 0.05) in the conversion group were greater compared with the primary cohort; however, the difference was not statistically significant. The mean postoperative Harris Hip Scoring system (HHS) of the PBFG group at the 1-month follow-up was 81, and the control group had a score of 82. Importantly, subgroup analysis of the PBFG group indicated that there was no significant difference between patients who had prior pedicled vascularized iliac bone flap grafting and pedicled vascularized greater trochanter bone flap grafting (P > 0.05), except for the operative room time (P = 0.032). ConclusionsHip-sparing surgery of ONFH did not make THA more difficult or lead to more perioperative complications, but increased blood loss and extended hospital stay from a prior PBFG are still notable problems in clinical practice. Thus, it is necessary for surgeons to focus attention on the improvement of the preoperative condition and prepare for any specific intraoperative challenges.

Prior Nonmelanoma Skin Cancer is Associated with Fewer Fractures, More Vitamin D Sufficiency, Greater Bone Mineral Density, and Improved Bone Microarchitecture in Older Adults

BackgroundPrior nonmelanoma skin cancer (NMSC), a biomarker of cumulative lifetime sun exposure, is associated with reduced fracture risk later in life. The mechanism is unknown. MethodsProspective cohort analysis of 1099 community-dwelling adults aged 50-80 years with baseline and 10-year follow-up assessments. Histopathologically-confirmed NMSC diagnosis was established by linkage with the Tasmanian Cancer Registry. Bone mineral density (BMD) and vertebral deformity were quantified by DXA, 25-hydroxyvitamin D (25(OH)D) by radioimmunoassay, bone microarchitecture by high-resolution peripheral quantitative CT, melanin density by spectrophotometry, and skin photosensitivity and clinical fracture by questionnaire. 25(OH)D <50 nmol/L was considered deficient. ResultsParticipants with an NMSC reported prior to baseline were less likely to sustain an incident vertebral deformity over 10 years (RR = 0.74, P = .036). There were similar reductions for other fracture types but these did not reach significance. Prior NMSC was associated with baseline (RR = 1.23, P = .005) and 10-year longitudinal (RR = 5.9, P = .014) vitamin D sufficiency and greater total body BMD (β = 0.021g/cm2, P = .034), but not falls risk or muscle strength. The relationship between prior NMSC and bone microarchitecture was age-dependent (pinteraction < 0.05). In the oldest age tertile, prior NMSC was associated with greater volumetric BMD (β = 57.8-62.6, P = .002-0.01) and less porosity (β = −4.6 to −5.2, P = .002-0.009) at cortical, compact cortical and outer transitional zones. ConclusionsPrior NMSC was associated with fewer incident fractures in community-dwelling older adults. This protective association is most likely mediated by modifiable fracture risk factors associated with an outdoor lifestyle, including 25(OH)D, BMD, and bone microarchitecture.

Ambulatory teclistamab administration in patients with relapsed/refractory multiple myeloma.

11146 Background: Teclistamab (Tec) is the first B-Cell Maturation antigen (BCMA)xCD3 bispecific antibody FDA approved for the treatment of relapsed or refractory multiple myeloma (RRMM) in patients who have received ≥4 prior lines of therapy. The phase 1-2 MajesTec-1 study raised concerns for cytokine release syndrome (CRS)/immune effector cell-associated neurotoxicity syndrome (ICANS). 48-hour inpatient observation is recommended for step-up dosing, which imposes financial and logistical burdens. We report our institutional experience with ambulatory Tec administration. Methods: Our inpatient/outpatient (IPOP) hybrid nursing unit is staffed with specialized nurses, advanced practice providers, and attending physicians. Our patients treated in IPOP must live within 1 hour of the hospital and have a 24-hour caregiver. Patients were treated with the recommended step-up dosing schedule. CRS grading and ICE scoring were performed daily. Both CRS and ICANS were graded according to the ASTCT grading systems. We collected toxicities until the second full treatment dose, at which point hospitalization is no longer recommended. Results: In total, 25 patients were treated with Tec between January 2023 to December 2023. The median age was 70 years old (range 59-89), with a median of 6 prior lines of therapy. One patient was dialysis dependent prior to starting Tec. All patients were triple class refractory. Thirteen patients (52%) received prior bone marrow transplant. One (4%) patient received prior anti-BCMA CAR-T therapy. Seventeen patients (68%) required admission during the Tec ramp-up period. CRS was observed in 15 (60 %) patients, all of which were grade I/II events. Fourteen of these patients were hospitalized for CRS. They were admitted for median number of 2 hospital days (range 1-6). Tocilizumab was administered for Grade 2 CRS in 3 patients (12%). ICANS was reported in 4 (16%) patients. Two of those patients developed Grade 2 ICANS which completely resolved with dexamethasone. The median number of admitted hospital days for these patients was 3 days (range 2-49). Neutropenia with ANC &lt; 500 was seen in only 1 (4%) patient. Grade 3/4 infections were seen in 3 (12%) patients during the ramp-up period. Conclusions: Tec administration through an inpatient/outpatient hybrid model is safe and feasible. CRS was common but low grade and short lived. ICANS was observed, but remained low grade and may be attributable to our older patient population. As our center gained experience with the Tec management, we noticed lower rates of admission for low grade CRS. Lower incidences of infections and neutropenia demonstrate that these complications emerge in the months after starting therapy. Future studies will help identify patients who are higher risk for CRS and ICANS during ramp-up treatment and may pave the way for prophylactic interventions and outpatient administration.

Radiological Heatmap of Tarsometatarsal Capsule Locations: A Cadaveric Study

Introduction/Purpose: Minimal invasive proximal metatarsal osteotomy (PMO) offers a successful approach for addressing metatarsus adductus while avoiding exposure of all metatarsals, thereby reducing the risk of complications such as wound infections and non-unions. An important hurdle is the absence of direct visualization for precise osteotomy placement. Staying within the tarsometatarsal (TMT) capsule enhances the chances of better union due to improved blood supply, although operating outside the capsule can aid in correcting more significant deformities. Despite having a macroscopic understanding of anatomical locations through specimens, there has been a lack of prior reports on their mapping in fluoroscopic images. Developing such maps could significantly improve the navigational skills of surgeons. This study aims to present heatmaps that illustrate the positions of distal attachments of TMT capsules. Methods: A total of nine specimens below the knee, devoid of any prior bone or joint abnormalities, were thawed a day prior to the experiments. After dissecting the dorsal skin, neurovascular structures, and tendons, only the bones and capsules remained. Flexible wires were placed alongside the distal edges of TMT capsules, encompassing the 1st, 2nd, 3rd, and 4th tarsometatarsal joints. This arrangement aimed to make the paths of these capsules visible when observed through X-ray imaging. The wires were then securely attached to the structures using a soft tissue adhesive. Fluoroscopy images were captured, including a calibration marker of a known diameter, in addition to taking macroscopic photographs. The specific coordinates of these structures were marked in a three-dimensional space within specialized 3D software. Subsequently, these coordinates were imported into a custom-designed Python script crafted for the purpose of generating heatmaps. Results: The heatmaps were successfully produced encompassing all TMT capsules spanning from the 1st to the 4th, and these were overlaid onto an anteroposterior fluoroscopy image of the foot (refer to Figure 1). This gradient of colors serves as a visual representation of differing magnitudes, with red denoting the most prevalent areas of the distal attachment of the TMT capsule, while blue corresponds to lower occurrences. Conclusion: These heatmaps not only showcase the predominantly observed sites of distal TMT attachments, depicted in red, but also signify diverse deviations, identifiable by the presence of less frequent zones indicated in blue. Consequently, surgeons are advised to consider these findings while planning their osteotomies based on their preferred positions. By furnishing surgeons with an extensive heatmap that outlines potential tarsometatarsal capsule insertions, this research not only furnishes them with a dependable guiding resource but also establishes a foundation for more assured and prosperous minimally invasive midfoot fusion procedures. Figure 1: The heatmap of 1st to 4th tarsometatarsal capsules on AP fluoroscopy.

Survivorship Struggles: Navigating Etiologies and Clinical Parameters of Febrile Neutropenia During Induction Chemotherapy in Acute Leukemia Patients.

Background Acute leukemia, characterized by the uncontrolled proliferation of immature white blood cell precursors, poses significant challenges during induction chemotherapy, including the elevated risk of febrile neutropenia and its associated complications. Our study aims to explain the clinical and etiological parameters of these patients in a resource-limited setting. Methods This retrospective study focused on a total of 102 adult patients with acute leukemia who developed febrile neutropenia during the induction chemotherapy phase. Patients with disease relapse, prior bone marrow transplantation, and cases of acute promyelocytic leukemia were excluded from the study. Demographical characteristics, symptoms at presentation, diagnoses, infectious causes, and outcomes were systematically reported. Infectious etiologies and detailed culture reports were meticulously tabulated, and subsequent data were analyzed. Results Of the 102 patients, 43 (42.2%) were males, with a mean age of 31.9 ± 6.5 years. During the induction chemotherapy, a total of 31 patients died of complicated febrile neutropenia. Severe vomiting was the most common symptom present in 37 (36.2%), followed by cough in 35 (34.3%) and loose stools in 28 (27.5%). Community-acquired pneumonia, neutropenic sepsis, and neutropenic colitis were among the most common etiologies of febrile neutropenia. A total of 72 (70.6%) patients had culture-proven multidrug-resistant Gram-negative bacteremia that contributed to poor outcomes. Conclusions Acute leukemia patients undergoing induction chemotherapy face high infection-associated mortality due to their immunocompromised state. Inadequate infection control measures and antimicrobial resistancecontribute to the emergence of multidrug-resistant organisms. Enhanced infection prevention strategies and evidence-based antibiotic prescription guidelines are need of time in resource-limited settings such as Pakistan to address febrile neutropenia complications and bridge the existing care gap in its management.

Temporal bone histopathology in revision cochlear implantation

An increasing number of young infants, as early as six months of age with congenital hearing loss receive cochlear implantation, and it is probable that many of these patients will require revision surgery later in life. The possibility of explantation of the cochlear electrode and reimplantation may cause damage to the cochlea, compromising the speech perception outcome in revision implant is of concern. There is only one prior temporal bone histopathology study to look at the outcome of revision surgery and no prior study evaluating revision cochlear implantation that used the round window approach. We conducted a histopathological study of four temporal bone specimens from four patients who underwent revision cochlear implantation and when available post-operative speech perception tests were evaluated. In all cases, the reimplanted electrode followed into the same fibrous sheath without evidence of additional intracochlear damage due to revision surgery. The intracochlear damage from the initial cochlear implantation appears to be a more important factor in outcomes rather than changes associated with explantation and reimplantation.

Case of Metastatic Atypical Meningioma to Lung: Utility of Cytological Preparations for Intraoperative Diagnosis

Abstract Introduction/Objective Meningiomas are the most common primary intracranial and intraspinal tumors. They are typically benign with an indolent behavior but can metastasize extracranially to the skin, bone, lymph node and liver. Lung metastasis is exceptionally rare, and the diagnosis can be challenging, especially during intraoperative diagnosis without ancillary studies. We describe a metastatic atypical meningioma to the lung for which intraoperative cytology facilitated the diagnosis and guided management. Methods/Case Report A 53-year-old woman with a history of left frontal atypical meningioma and multiple surgical resections for recurrences at outside hospitals, presented with an incidental left lung nodule. A lung wedge resection was performed and submitted for intraoperative diagnosis. Gross examination revealed a well-circumscribed, tan- white, and rubbery subpleural nodule. Cytological preparations— Diff-Quik and H&amp;E stains—and frozen section were prepared. Cytologically, the nodule displayed cohesive distinctive papillary whorls of uniform eosinophilic cells with indistinct cell membranes, round to oval nuclei with central nucleoli and intranuclear pseudoinclusions. The frozen section exhibited similar cytological features, few identifiable whorls and predominantly solid sheets of tumor cells typical of non-small cell carcinoma. Based primarily on the cytological findings, the intraoperative diagnosis was a neoplasm with papillary growth pattern, and a metastasis was favored based on the whorled pattern and clinical history; no further resection was performed. Permanent sections displayed mitoses and no necrosis. Immunohistochemical analysis revealed positivity for somatostatin receptor 2a, progesterone receptor, and EMA (focal); no staining was seen with pancytokeratin, TTF-1, or p40. A diagnosis of atypical meningioma, WHO grade 2, was rendered. Subsequently, an atypical cranial and temporalis muscle meningioma at the site of the prior craniotomy bone flap was resected and had an identical molecular profile (1p36 deletion) to that in the lung, further supporting metastasis to the lung. Results (if a Case Study enter NA) NA Conclusion This case illustrates a rare presentation of metastatic atypical meningioma and highlights the distinctive intraoperative utility of cytology preparations—architectural and cytological details—for diagnosis and appropriate management. Cytology preparations can be a valuable tool and complement frozen sections, in which certain morphological features may be less obvious or confounded by freezing artifact.

Bone mineral density and the risk of incident dementia: A meta-analysis.

It is not known whether bone mineral density (BMD) measured at baseline or as the rate of decline prior to baseline (prior bone loss) is a stronger predictor of incident dementia or Alzheimer's disease (AD). We performed a meta-analysis of three longitudinal studies, the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the Rush Memory and Aging Project (MAP), modeling the time to diagnosis of dementia as a function of BMD measures accounting for covariates. We included individuals with one or two BMD assessments, aged ≥60 years, and free of dementia at baseline with follow-up available. BMD was measured at the hip femoral neck using dual-energy X-ray absorptiometry (DXA), or at the heel calcaneus using quantitative ultrasound to calculate estimated BMD (eBMD). BMD at study baseline ("baseline BMD") and annualized percentage change in BMD prior to baseline ("prior bone loss") were included as continuous measures. The primary outcome was incident dementia diagnosis within 10 years of baseline, and incident AD was a secondary outcome. Baseline covariates included age, sex, body mass index, ApoE4 genotype, and education. The combined sample size across all three studies was 4431 with 606 incident dementia diagnoses, 498 of which were AD. A meta-analysis of baseline BMD across three studies showed higher BMD to have a significant protective association with incident dementia with a hazard ratio of 0.47 (95% CI: 0.23-0.96; p = 0.038) per increase in g/cm2 , or 0.91 (95% CI: 0.84-0.995) per standard deviation increase. We observed a significant association between prior bone loss and incident dementia with a hazard ratio of 1.30 (95% CI: 1.12-1.51; p < 0.001) per percent increase in prior bone loss only in the FHS cohort. Baseline BMD but not prior bone loss was associated with incident dementia in a meta-analysis across three studies.

SAT262 Bilateral Stress Fractures Of The Femur In A Patient With HIV On Long-term Tenofovir Disoproxil Fumarate And Short-term Alendronate

Abstract Disclosure: R.J. Mahatme: None. A.D. Lindsay: None. F.S. Mirza: None. Background: Tenofovir disoproxil fumarate (TDF) is a reverse transcriptase inhibitor used for HIV treatment, which has been documented to reduce bone mineral density through enhanced osteoclastic activity, reduced osteoblastic activity, disrupted calcium absorption and renal phosphate wasting. Prolonged use of TDF increases the risk of osteoporosis and fractures. Bisphosphonates (BP) are typically used to prevent osteoporotic fractures by inhibiting bone resorption. However, BP use for more than five years, and concomitant suppression of bone remodeling may be associated with an increased risk of subtrochanteric fractures. We report a case of unusual bilateral subtrochanteric stress fractures of the femur in a patient on long term TDF for HIV, who had taken alendronate for a very short duration. Clinical Case: A 56-year-old woman presented to orthopedics in 2017 with complaint of bilateral leg/hip pain associated with weight bearing. Past medical history was significant for HIV diagnosed in 1995, osteopenia diagnosed in 2015 and fibromyalgia. The patient had been taking TDF as part of HIV therapy since 1995 and had been started on alendronate 15 months prior for osteopenia. X-ray of the hips revealed diffuse osteopenia with areas of possible stress reaction/stress fracture at the proximal third of the right femur and in the subtrochanteric left femur. Nuclear medicine bone scan showed faint foci of increased uptake in the lateral subtrochanteric regions of both proximal femora and midshaft of the right femur suggesting insufficiency fractures. The report noted that these areas were present and unchanged compared to a prior bone scan from 2011. In view of significant discomfort and risk of progression to full fracture, she underwent prophylactic intramedullary nailing of the right femur and was referred to endocrine for bone health evaluation. Endocrine evaluation showed vitamin D insufficiency and suboptimal calcium intake which were both corrected. A call to the pharmacy revealed that she had only filled 3 prescriptions of alendronate even though she was initially prescribed alendronate a year and a half prior to her presentation. Alendronate and TDF were discontinued and tenofovir alafenamide (TAF) was added to her HIV regimen due to its less deleterious effects on the skeletal system. Patient did not report significant improvement in her leg pain after the intramedullary nailing and decided to maintain a conservative approach without intervention for the left femur stress fractures. Conclusion: This is an unusual presentation of bilateral stress fractures of the femur likely related to long term TDF therapy in a relatively young postmenopausal female who had taken alendronate for less than a year of cumulative dose. This case highlights the need to use medications that have less harmful effects on the bone in adults with HIV who are also at an increased risk for low bone density and fractures. Presentation: Saturday, June 17, 2023

Artificial intelligence analysis of the sterilization effects on the mechanical properties of human cranial bones

According to the literature, the patient’s own (autologous) bone remains the optimal graft material for cranioplasty. Autografts have an undoubted advantage over competing plastic materials of complete biological compatibility, as well as the absence of interstitial conflict and accessibility. Presently there is still not a single synthetic material that meets all the complex requirements for skull reconstruction in children due to the special complication of accommodating the skull structure that continues to grow. At the same time, the use of autograft is accompanied by the highest percentage of complications in the form of resorption and infection. The purpose of the present study was to evaluate the large volume of measurements (“big data”) obtained after nano-hardness testing of an autograft bone after various preliminary treatments. The latter included the currently optimal method of bone sterilization (boiling peroxide treatment). The measurements performed on different patient allografts were compared and the effects of bone treatment on the mechanical properties were evaluated and compared. Due to the complex hierarchical structural organisation of the bone, the correspondence between the composition, processing, structure, and properties of natural human bone materials were not obvious. Machine Learning, part of the Artificial Intelligence (AI) tool set, was applied to reveal the differences between scull bones of different types, treatment history and patients. It was found that after obtaining the principal mechanical properties of the chosen human skull bone sample it was possible to identify algorithmically the nature of prior bone sterilization and the patient’s sex.

Advantages of Dynamic Navigation in Prosthetic Implant Treatment in Terms of the Clinical Evaluation and Salivary Pro-Inflammatory Biomarkers: A Clinical Study

Successful implantation in augmented areas relies on adequate bone density and quality, along with thorough planning. The minimisation of the risks involved in the surgery and recovery phases is also of tremendous relevance. The aims of the present research were to clinically and biochemically evaluate the healing process after implant surgery (dental implants) using dynamic surgical navigation following prior bone augmentation. Thirty healthy patients who had implant treatment were analysed. The study participants (30 patients) were randomised between two groups. The 15 patients in the study group were treated with Navident dynamic navigation by using a flapless technique. The control group included 15 subjects in whom the implantation procedure was performed classically using the elevation flap full-thickness method. In all cases, the patient’s clinical condition, the patient’s subjective visual assessment of post-operative pain using the Visual Analogue Scale (VAS), and the levels of the salivary biomarkers interleukin 6 (IL 6) and C-reactive protein (CRP) immediately before surgery on the first post-operative day and on the seventh post-operative day were assessed. The healing process was shown to be faster in patients in the study group due to the low invasiveness of the treatment, which was confirmed by lower levels of pro-inflammatory cytokines in the study group versus the control group. The statistical analysis used Student’s t-test and Mann–Whitney test. The implementation of dynamic navigation and the application of the flapless technique reduced post-operative trauma, leading to a reduced risk of infection, reduced patient discomfort, and faster recovery.

Women's perspectives regarding osteoporosis, fracture risk, and pharmacologic treatment: a cross-sectional study.

Bisphosphonate medications can prevent the substantial bone loss that occurs during early menopause, but little is known about whether women would accept bisphosphonate treatment at this time in their life, when imminent fracture risk is low. We assessed women's perspectives regarding bone loss, fracture risk, and preventative pharmacotherapy in early menopause. In this cross-sectional study, Canadian women aged ≥ 45years were recruited via Facebook advertisement to complete an electronic survey. Primary outcome was the proportion of early menopausal respondents (≤ 5years since final menstrual period) who were worried about bone loss and fractures. Secondary outcomes were the proportionof early menopausal women willing to accept pharmacologic intervention aimed at preventingeither bone loss or future fractures. We compared responses between early menopausal women and older women (> 5years since final menstrual period). 2033 women responded to the Facebook advertisement, 1195 eligible women (aged: 45 to 89years) started the survey, and 966 completed it. Among early menopausal respondents (N = 98), 38 (42%) were worried about future fractures and 9 of 25 (36%) who had a prior bone mineral density scan were worried about their results. A total of 42 (47%) were willing to start medication to prevent fractures, and 48 (54%) would start medication to prevent bone loss. Responses were comparable between early menopausal women and older women. Menopausal women are concerned about bone loss and fractures. Many women would consider early menopausal pharmacotherapy, with the goals of preserving bone health and lowering their risk of fractures.

Evaluation of Bone Mineral Density in Children with Celiac Disease

Background: Osteoporosis is a known entity in individuals with celiac disease (CD). Objectives: The aim of this study was to evaluate bone mineral density (BMD) measurements in children with CD. Methods: This was a retrospective design study in a tertiary hospital in Turkey. Results: Totally 106 patients were included, and the mean age was 10.2 ± 3.9 years. The mean L1-L4 Z score was 0.730 ± 0.197 (based on sex and height in Turkish children). About 20.7% (n = 22) had a history of at least one fracture and/or bone pain. Bone mineral density values obtained from lumbar (L1-L4) vertebrae were significantly lower in patients with a prior fracture and/or bone pain compared to the patient group without a fracture (0.822 ± 0.242 g/cm2 vs 0.706 ± 0.178 g/cm2, respectively; P = 0.047). L1-L4 Z score (based on sex and height in Turkish children) was lower in patients with a body mass index (BMI) SDS value below -2 (moderately or severely malnourished) than those with a BMI SDS above -2 (0.02 ± 1.19 vs 1.4 ± 1.82, respectively; P = 0.014). A moderate positive correlation (r = 0.547; P &lt; 0.01) was found between somatomedin-C (IGF-1) level and L1-L4 BMD (g/cm2) measurement. It was remarkable that low BMD was not identified in any patients using L1-L4 Z-score by height and L1-L4 Z-score by age of Turkish children. Nine (8.5%) patients were found to have low BMD using the United States (US) age- and sex-specific L1-L4 Z-score from the GE Healthcare Lunar iDXA system. Conclusions: Bone mineral density should be screened considering risk factors for suboptimal bone health in children with celiac disease. False "normal" BMD interpretations can be avoided by taking into account the model of the BMD measuring device and by using the device's normal ranges in case of inconsistency with the Turkish reference values.