Biomedical knowledge graph-optimized prompt generation for large language models.

MOTIVATION: Large Language Models (LLMs) are being adopted at an unprecedented rate, yet still face challenges in knowledge-intensive domains like biomedicine. Solutions such as pre-training and domain-specific fine-tuning add substantial computational overhead, requiring further domain-expertise. Here, we introduce a token-optimized and robust Knowledge Graph-based Retrieval Augmented Generation (KG-RAG) framework by leveraging a massive biomedical KG (SPOKE) with LLMs such as Llama-2-13b, GPT-3.5-Turbo and GPT-4, to generate meaningful biomedical text rooted in established knowledge. RESULTS: Compared to the existing RAG technique for Knowledge Graphs, the proposed method utilizes minimal graph schema for context extraction and uses embedding methods for context pruning. This optimization in context extraction results in more than 50% reduction in token consumption without compromising the accuracy, making a cost-effective and robust RAG implementation on proprietary LLMs. KG-RAG consistently enhanced the performance of LLMs across diverse biomedical prompts by generating responses rooted in established knowledge, accompanied by accurate provenance and statistical evidence (if available) to substantiate the claims. Further benchmarking on human curated datasets, such as biomedical true/false and multiple-choice questions (MCQ), showed a remarkable 71% boost in the performance of the Llama-2 model on the challenging MCQ dataset, demonstrating the framework's capacity to empower open-source models with fewer parameters for domain-specific questions. Furthermore, KG-RAG enhanced the performance of proprietary GPT models, such as GPT-3.5 and GPT-4. In summary, the proposed framework combines explicit and implicit knowledge of KG and LLM in a token optimized fashion, thus enhancing the adaptability of general-purpose LLMs to tackle domain-specific questions in a cost-effective fashion. AVAILABILITY AND IMPLEMENTATION: SPOKE KG can be accessed at https://spoke.rbvi.ucsf.edu/neighborhood.html. It can also be accessed using REST-API (https://spoke.rbvi.ucsf.edu/swagger/). KG-RAG code is made available at https://github.com/BaranziniLab/KG_RAG. Biomedical benchmark datasets used in this study are made available to the research community in the same GitHub repository. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A novel small molecule ZYZ384 targeting SMYD3 for hepatocellular carcinoma via reducing H3K4 trimethylation of the Rac1 promoter.

SMYD3 (SET and MYND domain-containing 3) is a histone lysine methyltransferase highly expressed in different types of cancer(s) and is a promising epigenetic target for developing novel antitumor therapeutics. No selective inhibitors for this protein have been developed for cancer treatment. Therefore, the current study describes developing and characterizing a novel small molecule ZYZ384 screened and synthesized based on SMYD3 structure. Virtual screening was initially used to identify a lead compound and followed up by modification to get the novel molecules. Several technologies were used to facilitate compound screening about these novel molecules' binding affinities and inhibition activities with SMYD3 protein; the antitumor activity has been assessed in vitro using various cancer cell lines. In addition, a tumor-bearing nude mice model was established, and the activity of the selected molecule was determined in vivo. Both RNA-seq and chip-seq were performed to explore the antitumor mechanism. This work identified a novel small molecule ZYZ384 targeting SMYD3 with antitumor activity and impaired hepatocellular carcinoma tumor growth by reducing H3K4 trimethylation of the Rac1 promoter triggering the tumor cell cycle arrest through the AKT pathway.

Utility of 3D-Printed Models in the Surgical Planning for Primary Spine Tumors: A Survey of International Spinal Oncology Experts.

STUDY DESIGN: Survey study. OBJECTIVES: The purpose of this study was to characterize the utility of 3D printed patient specific anatomic models for the planning of complex primary spine tumor surgeries. METHODS: A survey of individual members of an international study group of spinal oncology surgeons was performed. Participants were provided a clinical vignette, pathologic diagnosis, and pre-operative imaging for three primary spinal oncology cases. Study participants provided a free text surgical plan for resection and were then presented an associated 3D printed model for each case and asked to re-evaluate their surgical plan. RESULTS: Ten spinal oncology surgeons participated in the study, representing nine institutions across five countries. Four of the surgeons (40%) made significant changes to their surgical plan after reviewing the 3D models, including sacrifice of an additional nerve root to obtain negative margins, sparing an SI joint that was originally planned for inclusion in the en bloc resection, adjusting the location of osteotomy cuts, changes to the number of surgical stages and/or staging order, and preservation of neurology that was originally planned for sacrifice. The overall impression of the 3D models was positive, with 90% of the participants stating they found the 3D model useful in developing a surgical plan. CONCLUSIONS: Surgical planning for resection of primary spinal column tumors is challenging and time intensive. 3D printed patient specific surgical models may be an additional tool that can augment surgical planning and execution by improving the chance of accomplishing surgical resection goals and minimizing morbidity.

Soft tissue aneurysmal bone cyst presenting as an enlarging neck mass: Case report and review of the head and neck literature.

Soft tissue aneurysmal bone cysts (STABCs) are rare neoplasms histopathologically identical to aneurysmal bone cysts. These benign lesions are characterized by thin, peripheral ossification and no skeletal continuity. STABC may be difficult to distinguish from myositis ossificans (MO) and malignant entities from imaging and fine needle aspiration, due to rarity and overlapping features. We present a case of a STABC occurring in the paraspinal cervical muscles. The imaging, histopathology, molecular analysis, and treatment are discussed. Four other published cases of STABC of the head and neck are reviewed.

Adjacent venous tumour thrombus in primary osteosarcoma of the pelvis and limbs.

Aims: Venous tumour thrombus (VTT) is a rare finding in osteosarcoma. Despite the high rate of VTT in osteosarcoma of the pelvis, there are very few descriptions of VTT associated with extrapelvic primary osteosarcoma. We therefore sought to describe the prevalence and presenting features of VTT in osteosarcoma of both the pelvis and the limbs. Methods: Records from a single institution were retrospectively reviewed for 308 patients with osteosarcoma of the pelvis or limb treated between January 2000 and December 2022. Primary lesions were located in an upper limb (n = 40), lower limb (n = 198), or pelvis (n = 70). Preoperative imaging and operative reports were reviewed to identify patients with thrombi in proximity to their primary lesion. Imaging and histopathology were used to determine presence of tumour within the thrombus. Results: Tumours abutted the blood vessels in 131 patients (43%) and encased the vessels in 30 (10%). Any form of venous thrombus was identified in 31 patients (10%). Overall, 21 of these thrombi were determined to be involved with the tumour based on imaging (n = 9) or histopathology (n = 12). The rate of VTT was 25% for pelvic osteosarcoma and 1.7% for limb osteosarcoma. The most common imaging features associated with histopathologically proven VTT were enhancement with contrast (n = 12; 100%), venous enlargement (n = 10; 83%), vessel encasement (n = 8; 66%), and visible intraluminal osteoid matrix (n = 6; 50%). Disease-specific survival (DSS) for patients with VTT was 95% at 12 months (95% CI 0.87 to 1.00), 50% at three years (95% CI 0.31 to 0.80), and 31% at five years (95% CI 0.14 to 0.71). VTT was associated with worse DSS (hazard ratio 2.3 (95% CI 1.11 to 4.84). Conclusion: VTT is rare with osteosarcoma and occurs more commonly in the pelvis than the limbs. Imaging features suggestive of VTT include enhancement with contrast, venous dilation, and vessel encasement. VTT portends a worse prognosis for patients with osteosarcoma, with a similar survivability to metastatic disease.

Prolonged treatment of neuroendocrine carcinoma of the cervix with a PARP inhibitor based on next generation sequencing.

•Next generation sequencing identified a BRCA 2 mutation in a patient with stage IVB neuroendocrine cancer of the cervix.•Treatment with rucaparib resulted in disease stabilization for 74 months.•The patient remains fully active working full time as a nurse and pursing a nurse practitioner degree.

Niraparib Population Pharmacokinetics and Exposure-Response Relationships in Patients With Newly Diagnosed Advanced Ovarian Cancer.

PURPOSE: Niraparib is a poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor approved for the maintenance treatment of advanced ovarian cancer (OC). Niraparib was originally approved in recurrent OC at a fixed starting dose (FSD) of 300 mg once daily (QD). This analysis characterized the population pharmacokinetics (PK) of niraparib and evaluated the relationships between exposure, efficacy, and safety to support clinical use of an individualized dosing strategy, in which the starting dose of niraparib was adjusted based on patient characteristics to improve the benefit-risk profile. METHODS: A population PK model was developed by pooling data from four niraparib clinical trials (PN001 [n = 104], QUADRA [n = 455], NOVA [n = 403], and PRIMA [n = 480]) in patients with solid tumors, including OC. Exposure-response analyses were conducted to explore the relationships of niraparib exposure with progression-free survival (PFS) and adverse events in the PRIMA study. A multivariate logistic regression model was also developed to estimate the probability of grade ≥3 thrombocytopenia, using data from patients enrolled in PRIMA and NOVA. The impact of an individualized starting dose (ISD) regimen (200 mg QD in patients with body weight [BW] <77 kg or platelet count [PLT] <150,000/µL, or 300 mg QD in patients with BW ≥77 kg and PLT ≥150,000/µL) on systemic exposure, efficacy, and safety was assessed. FINDINGS: Niraparib disposition was best described by a 3-compartment model with linear elimination. Key covariates included baseline creatinine clearance, BW, albumin, and age, all of which had minor effects on niraparib exposure. Comparable model-predicted exposure up to the time of disease progression/death or censoring in the 300-mg FSD and 200-/300-mg ISD groups was consistent with the lower rate of dose reduction in the ISD groups. No consistent niraparib exposure-response relationship was observed for efficacy in all PRIMA patients (first-line OC), and no statistically significant difference was seen in PFS curves for patients receiving a niraparib dose of 200 mg versus 300 mg. In the multivariate regression model, performed using combined data from PRIMA and NOVA, higher niraparib exposure (area under the concentration-time curve at steady-state [AUCss]), lower BW, and lower PLT were associated with an increased risk of grade ≥3 thrombocytopenia. IMPLICATIONS: Population PK and exposure-response analyses support use of an ISD to improve the safety profile of niraparib, including reducing the rate of grade ≥3 thrombocytopenia, without compromising efficacy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01847274 (NOVA), NCT00749502 (PN001), NCT02655016 (PRIMA), NCT02354586 (QUADRA), www. CLINICALTRIALS: gov.

Comparison of reconstructive techniques for nonprimary malignancies in the proximal humerus.

BACKGROUND: Endoprostheses (EPC) are often utilized for reconstruction of the proximal humerus with either hemiarthroplasty (HA) or reverse arthroplasty (RA) constructs. RA constructs have improved outcomes in patients with primary lesions, but no studies have compared techniques in metastatic disease. The aim of this study is to compare functional outcomes and complications between HA and RA constructs in patients undergoing endoprosthetic reconstruction for proximal humerus metastases. METHODS: We retrospectively reviewed our institutional arthroplasty database to identify 66 (56% male; 38 HA and 28 RA) patients with a proximal humerus reconstruction for a non-primary malignancy. The majority (88%) presented with pathologic fracture, and the most common diagnosis was renal cell carcinoma (48%). RESULTSS: Patients with RA reconstructions had better postoperative forward elevation (74° vs. 32°, p < 0.01) and higher functional outcome scores. HA patients had more complications (odds ratio 13, p < 0.01), with instability being the most common complication. CONCLUSIONS: Patients with nonprimary malignancies of the proximal humerus had improved functional outcomes and fewer complications after undergoing reconstruction with a reverse EPC compared to a HA EPC. Preference for reverse EPC should be given in patients with good prognosis and ability to complete postoperative rehabilitation.

Outcomes of non-angiosarcoma radiation-associated soft tissue sarcomas of the chest.

BACKGROUND: Radiation-associated soft tissue sarcomas (RA-STS) are rare complications of patients receiving radiation therapy (RT) and are generally associated with a poor prognosis. Most of the literature surrounding RA-STS of the chest is centered on angiosarcoma. Therefore, we aim to document the management and outcome of patients with non-angiosarcoma RA-STS of the chest. METHODS: We reviewed 17 patients (all female, median age 65 years) diagnosed with RA-STS. The most common primary malignancy was breast carcinoma (n = 15), with a median RT dose of 57.9 Gy. All patients underwent surgical resection; five patients (29%) received radiotherapy; and five patients (29%) received peri-operative chemotherapy. RESULTS: The 5-year local recurrence and metastatic-free survival were 61% and 60%, while the 5-year disease-specific survival was 53%. Local recurrence was associated with death due to disease (HR 9.06, p = 0.01). Complications occurred in nine of patients, most commonly due to a wound complication (n = 7). At the most recent follow-up, the median Musculoskeletal Tumor Society Score was 63%. CONCLUSION: RA-STS involving the chest wall are aggressive tumors with a high risk of local relapse and death due to disease. Local recurrence was associated with death due to disease; as such, we recommend aggressive surgical management with evaluation for adjuvant therapies.

Chest trauma clinical practice guideline protects against delirium in patients with rib fractures.

Introduction: Traumatic rib fractures present a considerable risk to patient well-being, contributing to morbidity and mortality in trauma patients. To address the risks associated with rib fractures, evidence-based interventions have been implemented, including effective pain management, pulmonary hygiene, and early walking. Vancouver General Hospital, a level 1 trauma center in British Columbia, Canada, developed a comprehensive multidisciplinary chest trauma clinical practice guideline (CTCPG) to optimize the management of patients with rib fractures. This prospective cohort study aimed to assess the impact of the CTCPG on pain management interventions and patient outcomes. Methods: The study involved patients admitted between January 1, 2021 and December 31, 2021 (post-CTCPG cohort) and a historical control group admitted between November 1, 2018 and December 31, 2019 (pre-CTCPG cohort). Patient data were collected from patient charts and the British Columbia Trauma Registry, including demographics, injury characteristics, pain management interventions, and relevant outcomes. Results: Implementation of the CTCPG resulted in an increased use of multimodal pain therapy (99.4% vs 96.1%; p=0.03) and a significant reduction in the incidence of delirium in the post-CTCPG cohort (OR 0.43, 95% CI 0.21 to 0.80, p=0.0099). There were no significant differences in hospital length of stay, ICU (intensive care unit) days, non-invasive positive pressure ventilation requirement, ventilator days, pneumonia incidence, or mortality between the two cohorts. Discussion: Adoption of a CTCPG improved chest trauma management by enhancing pain management and reducing the incidence of delirium. Further research, including multicenter studies, is warranted to validate these findings and explore additional potential benefits of the CTCPG in the management of chest trauma patients. Level of evidence: IIb.

Extended-duration antibiotics are not associated with a reduction in surgical site infection in patients with ovarian cancer undergoing cytoreductive surgery with large bowel resection.

OBJECTIVE(S): To evaluate whether extended dosing of antibiotics (ABX) after cytoreductive surgery (CRS) with large bowel resection for advanced ovarian cancer is associated with reduced incidence of surgical site infection (SSI) compared to standard intra-operative dosing and evaluate predictors of SSI. METHODS: A retrospective single-institution cohort study was performed in patients with stage III/IV ovarian cancer who underwent CRS from 2009 to 2017. Patients were divided into two cohorts: 1) standard intra-operative dosing ABX and 2) extended post-operative ABX. All ABX dosing was at the surgeon's discretion. The impact of antibiotic duration on SSI and other postoperative outcomes was assessed using univariate and multivariable Cox regression models. RESULTS: In total, 277 patients underwent cytoreductive surgery (CRS) with large bowel resection between 2009 and 2017. Forty-nine percent (n = 137) received standard intra-operative ABX and 50.5% (n = 140) received extended post-operative ABX. Rectosigmoid resection was the most common large bowel resection in the standard ABX (89.9%, n = 124) and extended ABX groups (90.0%, n = 126), respectively. No significant differences existed between age, BMI, hereditary predisposition, or medical comorbidities (p > 0.05). No difference was appreciated in the development of superficial incisional SSI between the standard ABX and extended ABX cohorts (10.9% vs. 12.9%, p = 0.62). Of patients who underwent a transverse colectomy, a larger percentage of patients developed a superficial SSI versus no SSI (21% vs. 6%, p = 0.004). CONCLUSION(S): In this retrospective study of patients with advanced ovarian cancer undergoing CRS with LBR, extended post-operative ABX was not associated with reduced SSI, and prolonged administration of antibiotics should be avoided unless clinically indicated.

Proton versus photon adjuvant radiotherapy: a multicenter comparative evaluation of recurrence following spinal chordoma resection.

OBJECTIVE: Chordomas are rare tumors of the skull base and spine believed to arise from the vestiges of the embryonic notochord. These tumors are locally aggressive and frequently recur following resection and adjuvant radiotherapy. Proton therapy has been introduced as a tissue-sparing option because of the higher level of precision that proton-beam techniques offer compared with traditional photon radiotherapy. This study aimed to compare recurrence in patients with chordomas receiving proton versus photon radiotherapy following resection by applying tree-based machine learning models. METHODS: The clinical records of all patients treated with resection followed by adjuvant proton or photon radiotherapy for chordoma at Mayo Clinic were reviewed. Patient demographics, type of surgery and radiotherapy, tumor recurrence, and other variables were extracted. Decision tree classifiers were trained and tested to predict long-term recurrence based on unseen data using an 80/20 split. RESULTS: Fifty-three patients with a mean ± SD age of 55.2 ± 13.4 years receiving surgery and adjuvant proton or photon therapy to treat chordoma were identified; most patients were male. Gross-total resection was achieved in 54.7% of cases. Proton therapy was the most common adjuvant radiotherapy (84.9%), followed by conventional or external-beam radiation therapy (9.4%) and stereotactic radiosurgery (5.7%). Patients receiving proton therapy exhibited a 40% likelihood of having recurrence, significantly lower than the 88% likelihood observed in those treated with nonproton therapy. This was confirmed on logistic regression analysis adjusted for extent of tumor resection and tumor location, which revealed that proton adjuvant radiotherapy was associated with a decreased risk of recurrence (OR 0.1, 95% CI 0.01-0.71; p = 0.047) compared with photon therapy. The decision tree algorithm predicted recurrence with an accuracy of 90% (95% CI 55.5%-99.8%), with the lowest risk of recurrence observed in patients receiving gross-total resection with adjuvant proton therapy (23%). CONCLUSIONS: Following resection, adjuvant proton therapy was associated with a lower risk of chordoma recurrence compared with photon therapy. The described machine learning models were able to predict tumor progression based on the extent of tumor resection and adjuvant radiotherapy modality used.

Assessment of minimum target dose as a predictor of local failure after spine SBRT.

OBJECTIVES: Metastasis-directed stereotactic body radiation therapy (SBRT) has demonstrated robust clinical benefits in carefully selected patients, improving local control and even overall survival (OS). We assess a large database to determine clinical and dosimetric predictors of local failure after spine SBRT. METHODS: Spine SBRT treatments with imaging follow-up were identified. Patients were treated with a simultaneous integrated boost technique using 1 or 3 fractions, delivering 20-24 Gy in 1 fraction to the gross tumor volume (GTV) and 16 Gy to the low dose volume (or 27-36 Gy and 21-24 Gy for 3 fraction treatments). Exclusions included: lack of imaging follow-up, proton therapy, and benign primary histologies. RESULTS: 522 eligible spine SBRT treatments (68 % single fraction) were identified in 377 unique patients. Patients had a median OS of 43.7 months (95 % confidence interval: 34.3-54.4). The cumulative incidence of local failure was 10.5 % (7.4-13.4) at 1 year and 16.3 % (12.6-19.9) at 2 years. Local control was maximized at 15.3 Gy minimum dose for single-fraction treatment (HR = 0.31, 95 % CI: 0.17 - 0.56, p < 0.0001) and confirmed via multivariable analyses. Cumulative incidence of local failure was 6.1 % (2.6-9.4) vs. 14.2 % (8.3-19.8) at 1 year using this cut-off, with comparable findings for minimum 14 Gy. Additionally, epidural and soft tissue involvement were predictive of local failure (HR = 1.77 and 2.30). CONCLUSIONS: Spine SBRT offers favorable local control; however, minimum dose to the GTV has a strong association with local control. Achieving GTV minimum dose of 14-15.3 Gy with single fraction SBRT is recommended whenever possible.

Laparoscopic predictability of minimally invasive interval debulking in advanced ovarian cancer: The MIID-SOC trial.

BACKGROUND: We sought to create a laparoscopic-based model to predict the ability to perform a minimally invasive (MIS) cytoreductive surgery in advanced epithelial ovarian cancer patients who have received neoadjuvant chemotherapy (NACT). METHODS: Fifty women were enrolled in a multi-institutional prospective pilot study (NCT03378128). Each patient underwent laparoscopic evaluation of 43 abdominopelvic sites followed by surgeon dictated surgical approach, either continue MIS or laparotomically. However, if the procedure continued MIS, the placement of a hand-assist port for manual palpation was mandated to emulate a laparotomic approach and all 43 sites were re-evaluated. Sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were calculated for each site to predict MIS resectability. Each parameter was assigned a numeric value based on the strength of statistical association and a total predictive index score (PIV) was assigned for each patient. Receiver operating characteristic curve analysis was used to assess the ability of the model to predict the MIS approach. RESULTS: Twenty-seven patients (61%) underwent MIS surgery. The following abdominopelvic sites were selected for inclusion in the model: gastrosplenic ligament, rectum, left mesocolon, transverse colon, right colon, cecum, appendix, liver capsule, intrahepatic fossa/gallbladder, ileum/jejunum. Using the PIV, a ROC was generated with an AUC = 0.695. In the final model, a PIV <2 identified patients able to undergo an optimal MIS cytoreductive surgery with an accuracy of 68.2%. The specificity, or the ability to identify patients who would not be able to undergo an optimal MIS interval cytoreductive surgery, was 66.7%. CONCLUSION: This predictive index model may help to guide future inclusion criteria in randomized studies evaluating the MIS approach in advanced epithelial ovarian cancer.

Carboplatin, paclitaxel, and pembrolizumab followed by pembrolizumab maintenance for primary treatment of incompletely resected epithelial ovarian cancer.

Objective: Incompletely resected epithelial ovarian cancer represents a poor prognostic subset of patients. Novel treatment strategies are needed to improve outcomes for this population. We evaluated a treatment strategy combining platinum-based chemotherapy with pembrolizumab followed by pembrolizumab maintenance therapy in the first-line treatment after incomplete resection of epithelial ovarian cancer patients. Methods: This was a single-arm, non-randomized pilot study of carboplatin, taxane, and immune checkpoint inhibitor, pembrolizumab, followed by 12 months of maintenance pembrolizumab in patients with incompletely resected epithelial ovarian cancer (EOC). Results: A total of 29 patients were enrolled and evaluated for efficacy and safety. The best response to therapy was complete response in 16 (55%) patients, partial response in 9 (31%) patients, and 3 (10%) patients with progression of disease. The median progression-free survival (PFS) was 13.2 months. Grade 3 and 4 toxicities occurred in 20% of patients. In all, 7 patients discontinued therapy due to adverse events. Quality-of-life scores remained high during therapy. Response to therapy did not correlate with PD-L1 tumor expression. Conclusions: Combination platinum-taxane therapy with pembrolizumab did not increase median progression-free survival in this cohort of patients. Key message: EOC is an immunogenic disease, but immune checkpoint inhibitor therapy has yet to impact outcomes. The current study utilized pembrolizumab in combination with standard chemotherapy followed by a maintenance treatment strategy in incompletely resected EOC. Progression-free survival was not extended in this poor prognostic group with combined chemotherapy and immunotherapy. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT 027766582.

Salivary iodide status as a measure of whole body iodine homoeostasis?

Iodine is a trace element required to produce the thyroid hormones, which are critical for development, growth and metabolism. To ensure appropriate population iodine nutrition, convenient and accurate methods of monitoring are necessary. Current methods for determining iodine status either involve a significant participant burden or are subject to considerable intra-individual variation. The continuous secretion of iodide in saliva potentially permits its use as a convenient, non-invasive assessment of status in populations. To assess its likely effectiveness, we reviewed studies analysing the association between salivary iodide concentration (SIC) and dietary iodine intake, urinary iodide concentration (UIC) and/or 24-h urinary iodide excretion (UIE). Eight studies conducted in different countries met the inclusion criteria, including data for 921 subjects: 702 healthy participants and 219 with health conditions. SIC correlated positively with UIC and/or UIE in four studies, with the strength of relationship ranging from r = 0·19 to r = 0·90 depending on sampling protocol, age, and if salivary values were corrected for protein concentration. Additionally, SIC positively correlated with dietary intake, being strongest when saliva was collected after dinner. SIC varied with external factors, including thyroid function, use of some medications, smoking and overall health status. Evidence provided here supports the use of SIC as a viable, low-burden method for determining iodine status in populations. However, small sample sizes and high variability indicates the need for more extensive analyses across age groups, ethnicities, disease states and dietary groups to clarify the relative accuracy and reliability in each case and standardise procedure.

Durability of intercalary endoprosthesis for humeral reconstruction.

INTRODUCTION: The humerus is a common site of metastases and primary tumors. For some patients with a segmental defect and/or diaphyseal cortical destruction a cemented intercalary device may provide a more reliable construct, however data on their use is limited. METHODS: We reviewed 43 (28 male and 15 female) patients treated with an intercalary humeral spacer at a single tertiary referral center between 1989 and 2022. Humeral lesions were most commonly secondary to metastatic disease (n = 29, 68%), with 25 (58%) patients presenting with a pathologic fracture. Mean age and body mass index were 66 years and 27.9 kg/m2 . First generation taper joint device were used in 22 patients and second-generation lap device in 21 patients. RESULTS: Following reconstruction the 2-year overall survival was 30%. Mechanical complications occurred in 11 patients, most commonly aseptic loosening (n = 6, 14%). With death as a competing risk, the cumulative incidence of mechanical failure was 28% at 2-years postoperative. Following the procedure, mean Musculoskeletal Tumor Society scores was 70% and mean shoulder elevation was 87°. CONCLUSION: Reconstruction of the humeral diaphysis with an intercalary endoprosthesis provides restoration of function of the upper extremity, however, is associated with one in four patients having mechanical failure.

Comparison of Hounsfield units and vertebral bone quality score for the prediction of time to pathologic fracture in mobile spine metastases treated with radiotherapy.

OBJECTIVE: Spine metastases are commonly treated with radiotherapy for local tumor control; pathologic fracture is a potential complication of spinal radiotherapy. Both Hounsfield units (HUs) on CT and vertebral bone quality (VBQ) on MRI have been argued to predict stability as measured by odds of pathologic fracture, although it is unclear if there is a difference in the predictive power between the two methodologies. The objective of the present study was to examine whether one methodology is a better predictor of pathologic fracture following radiotherapy for mobile spine metastases. METHODS: Patients who underwent radiotherapy (conventional external-beam radiation therapy, stereotactic body radiation therapy, or intensity-modulated radiation therapy) for mobile spine (C1-L5) metastases at a tertiary care center were retrospectively identified. Details regarding underlying pathology, patient demographics, and tumor morphology were collected. Vertebral involvement was assessed using the Weinstein-Boriani-Biagini (WBB) system. Bone quality of the non-tumor-involved bone was assessed on both pretreatment CT and MRI. Univariable analyses were conducted to identify independent predictors of fracture, and Kaplan-Meier analyses were used to identify significant predictors of time to pathologic fracture. Stepwise Cox regression analysis was used to determine independent predictors of time to fracture. RESULTS: One hundred patients were included (mean age 62.7 ± 11.9 years; 61% male), of whom 35 experienced postradiotherapy pathologic fractures. The most common histologies were lung (22%), prostate (21%), breast (14%), and renal cell (13%). On univariable analysis, the mean HUs of the vertebrae adjacent to the fractured vertebra were significantly lower among those experiencing fracture; VBQ was not significantly associated with fracture odds. Survival analysis showed that average HUs ≤ 132, nonprostate pathology, involvement of ≥ 3 vertebral body segments on the WBB system, Spine Instability Neoplastic Score (SINS) ≥ 7, and the presence of axial pain all predicted increased odds of fracture (all p < 0.001). Cox regression found that HUs ≤ 132 (OR 2.533, 95% CI 1.257-5.103; p = 0.009), ≥ 3 WBB vertebral body segments involved (OR 2.376, 95% CI 1.132-4.987; p = 0.022), and axial pain (OR 2.036, 95% CI 0.916-4.526; p = 0.081) predicted increased fracture odds, while prostate pathology predicted decreased odds (OR 0.076, 95% CI 0.009-0.613; p = 0.016). Sensitivity analysis suggested that an HU threshold of ≤ 132 and a SINS of ≥ 7 identified patients at increased risk of fracture. CONCLUSIONS: The present results suggest that bone density surrogates as measured on CT, but not MRI, can be used to predict the risk of pathologic fracture following radiotherapy for mobile spine metastases. More extensive vertebral body involvement and the presence of mechanical axial pain additionally predict increased fracture odds.

Whole Blood Metal Levels in the Setting of an Oncologic Endoprosthesis: Is There Cause for Concern?

BACKGROUND: Massive modular endoprostheses have become a primary means of reconstruction after oncologic resection of a lower extremity tumor. These implants are commonly made with cobalt-chromium alloys that can undergo wear and corrosion, releasing cobalt and chromium ions into the surrounding tissue and blood. However, there are few studies about the blood metal levels in these patients. QUESTION/PURPOSE: What is the whole blood cobalt and chromium ion level in patients with massive modular endoprostheses? METHODS: We performed a cross-sectional study of our total joints registry to identify patients with a history of an endoprosthetic reconstruction performed at our institution. Patients who were alive at the time of our review in addition to those undergoing an endoprosthetic reconstruction after an oncologic resection were included. Whole blood samples were obtained from 27 (14 male and 13 female) patients with a history of a lower extremity oncologic endoprosthesis. The median time from surgery to blood collection was 8 years (range 6 months to 32 years). Blood samples were collected and stored in metal-free ethylenediaminetetraacetic acid tubes. Samples were analyzed on an inductively coupled plasma mass spectrometer in an International Organization for Standardization seven-class clean room using polytetrafluoroethylene-coated instruments to reduce the risk of metal contamination. The analytical measuring range was 1 to 200 ng/mL for chromium and cobalt. Cobalt and chromium levels were considered elevated when the blood level was ≥ 1 ppb. RESULTS: Cobalt levels were elevated in 59% (16 of 27) of patients, and chromium levels were elevated in 26% (seven of 27). In patients with elevated metal ion values, 15 of 17 patients had a reconstruction using a Stryker/Howmedica Global Modular Replacement System implant. CONCLUSION: Blood metal levels were elevated in patients who received reconstructions using modular oncology endoprostheses Future work is needed to establish appropriate follow-up routines and determine whether and when systemic complications occur because of elevated metal levels and how to potentially address these elevated levels when complications occur. Prospective and retrospective collaboration between multiple centers and specialty societies will be necessary to address these unknown questions in this potentially vulnerable patient group. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Midterm outcomes of total hip arthroplasty after internal hemipelvectomy and iliofemoral arthrodesis.

BACKGROUND AND OBJECTIVES: Recent studies have reported acceptable outcomes after arthrodesis takedown and conversion to total hip arthroplasty (THA); however, there are no reports on outcomes after oncologic resection, which are inherently complex and may portend poorer outcomes. The purpose of this study was to examine the surgical and functional outcomes of patients who underwent prior hemipelvectomy for tumor resection and were later converted to THA. METHODS: All patients who had prior iliofemoral arthrodesis after oncologic resection that were later converted to THA at a single institution were examined. Charts were reviewed for demographic information, operative information, functional outcomes, and complications/reoperations. RESULTS: All three patients in this study were males who underwent internal hemipelvectomies for chondrosarcoma. Patients were converted to THA at a mean of 26 years after arthrodesis. Mean follow-up after conversion to THA was 7.4 years. During this follow-up period, two of the three patients required revision surgery. At last follow-up, the mean Harris Hip Score was 81 and the mean Mayo Hip Score was 67, and all patients were ambulatory without significant pain. CONCLUSIONS: Overall, patients who undergo iliofemoral arthrodesis after oncologic hemipelvectomy and are later converted to THA can expect to have a reasonable outcome, despite a high rate of complications and revision surgery.