Emergency Patient Triage Improvement through a Retrieval-Augmented Generation Enhanced Large-Scale Language Model.

Objectives: Emergency medical triage is crucial for prioritizing patient care in emergency situations, yet its effectiveness can vary significantly based on the experience and training of the personnel involved. This study aims to evaluate the efficacy of integrating Retrieval Augmented Generation (RAG) with Large Language Models (LLMs), specifically OpenAI's GPT models, to standardize triage procedures and reduce variability in emergency care.Methods: We created 100 simulated triage scenarios based on modified cases from the Japanese National Examination for Emergency Medical Technicians. These scenarios were processed by the RAG-enhanced LLMs, and the models were given patient vital signs, symptoms, and observations from emergency medical services (EMS) teams as inputs. The primary outcome was the accuracy of triage classifications, which was used to compare the performance of the RAG-enhanced LLMs to that of emergency medical technicians and emergency physicians. Secondary outcomes included the rates of under-triage and over-triage.Results: The Generative Pre-trained Transformer 3.5 (GPT-3.5) with RAG model achieved a correct triage rate of 70%, significantly outperforming Emergency Medical Technicians (EMTs) with 35% and 38% correct rates, and emergency physicians with 50% and 47% correct rates (p < 0.05). Additionally, this model demonstrated a substantial reduction in under-triage rates to 8%, compared to 33% for GPT-3.5 without RAG, and 39% for GPT-4 without RAG.Conclusions: The integration of RAG with LLMs shows promise in improving the accuracy and consistency of medical assessments in emergency settings. Further validation in diverse medical settings with broader datasets is necessary to confirm the effectiveness and adaptability of these technologies in live environments.

A novel simultaneous three-dimensional volumetric morphological imaging and T2-mapping method, multi-interleaved X-prepared turbo-spin echo with intuitive relaxometry provides more accurate quantification of cervical spinal nerves.

PURPOSE: MIXTURE is a simultaneous morphological and quantitative imaging sequence developed by Philips that provides high-resolution T2 maps from the imaged series. We aimed to compare the T2 maps of MIXTURE and SHINKEI-Quant (S-Q) in the cervical spine and to examine their usefulness in the functional diagnosis of cervical radiculopathy. METHODS: Seven healthy male volunteers (mean age: 31 ± 8.0 years) and one patient with cervical disc herniation (44 years old, male) underwent cervical spine magnetic resonance imaging (MRI), and T2-mapping of each was performed simultaneously using MIXTURE and S-Q in consecutive sequences in one imaging session. The standard deviation (SD) of the T2 relaxation times and T2 relaxation times of the bilateral C6 and C7 dorsal root ganglia (DRG) and C5/6 level cervical cord on the same slice in the 3D T2-map of the cervical spine coronal section were measured and compared between MIXTURE and S-Q. RESULTS: T2 relaxation times were significantly shorter in MIXTURE than in S-Q for all C6, C7 DRG, and C5/6 spinal cord measurements. The SD values of the T2 relaxation times were significantly lower for MIXTURE in the C5/6 spinal cord and C7 DRG. In cervical disc herniation, MRI showed multiple intervertebral compression lesions with spinal canal stenosis at C5/6 and disc herniation at C6/7. CONCLUSION: MIXTURE is useful for preoperative functional diagnosis. T2-mapping using MIXTURE can quantify cervical nerve roots more accurately than the S-Q method and is expected to be clinically applicable to cervical radiculopathy.

Minimum 10-Year Survivorship of Uncemented Acetabular Reconstruction With Bulk Femoral Head Autografting in Crowe Type IV Developmental Hip Dysplasia.

BACKGROUND: In total hip arthroplasty (THA) for severe dislocations such as Crowe type IV developmental dysplasia of the hip (DDH), sufficient bone volume for stable fixation of the acetabular component can be achieved by placing a reinforcing bone graft prepared from the resected femoral head into the deficient acetabulum. The purpose of the current study was to examine the long-term survivorship of uncemented THA in conjunction with a bulk femoral head autograft in patients who have Crowe type IV DDH. METHODS: A total of 35 patients (42 hips) who have Crowe type IV DDH and underwent THA using uncemented cup fixation with bulk femoral head autografting were followed up for a mean period of 15.0 years (range, 10.0 to 20.0) postoperatively. Anteroposterior pelvic radiographs were used for measurements such as the horizontal coverage of the grafted bone and the center-edge angle. Kaplan-Meier survivorship analyses were performed with revision of the acetabular component as the endpoint. RESULTS: The Kaplan-Meier analysis indicated 15-year survival rates of 90.4%. The mean horizontal coverage of grafted bone was 46.1% (range, 23.7 to 66.0), and there were 16 cases with horizontal coverage of ≥ 50%. There was no difference in the appearance of a thin (< 1 mm) radiolucency line around the cup between cases with < 50% versus ≥ 50% of the horizontal coverage of grafted bone (4 versus 2 hips; P = .446). Trabecular bridging and remodeling were seen in all cases after mean periods of 4.1 and 9.0 months postoperatively, respectively. Trabecular reorientation was seen in 41 of 42 hips (97.6%) at a mean follow-up of 19.9 months. CONCLUSIONS: Acetabular reconstruction with femoral bulk bone grafting for Crowe type IV DDH resulted in high survival rates and was a good method to restore bone stock and obtain long-term fixation.

Bone union-promoting effect of romosozumab in an ovariectomized rat posterolateral lumbar fusion model.

Spinal fixation surgery has been increasingly performed in patients with osteoporosis. Romosozumab, a drug that was introduced in Japan recently, is known to possibly promote bone healing. However, few studies have reported the therapeutic effects of romosozumab in clinical practice in Japan. Therefore, here, we investigated the effects of romosozumab dosage on bone fusion promotion using an ovariectomized rat spinal fusion model. Eight-week-old female Sprague-Dawley rats were matched by body weight and divided into three groups: 1.0 romosozumab (R) group (Evenity®, 25 mg/kg), 1/10R group (Evenity®, 2.5 mg/kg), and control (C) group (saline). Subcutaneous injections were administered twice a week for 8 weeks postoperatively. Computed tomography scans were performed every 2 weeks from the time of surgery till 8 weeks postoperatively. The mean fusion rates in terms of volume were significantly higher in the R groups [1/10R, 1.0R] than in the C group from 4 weeks postoperatively. The rate of increase was significantly higher in the 1.0R group from 4 weeks postoperatively and in the 1/10R group from 6 weeks postoperatively, than in the C group. The proportion of trabecular bone area was approximately 1.5 times higher in the R groups than in the C group. No significant differences were observed between the R groups. Our results suggest that romosozumab stimulates bone growth at the graft site, and similar effects were achieved at 1/10 of the standard dosage.

The γ-glutamyl cycle serves as an amino acids supply system in colorectal cancer organoids under chronic hypoxia.

Malignant tumors are characterized by a hypoxic microenvironment, and metabolic reprogramming is necessary to ensure energy production and oxidative stress resistance. Although the microenvironmental properties of tumors vary under acute and chronic hypoxia, studies on chronic hypoxia-induced metabolic changes are limited. In the present study, we performed a comprehensive metabolic analysis in a chronic hypoxia model using colorectal cancer (CRC) organoids, and identified an amino acid supply system through the γ-glutamyl cycle, a glutathione recycling pathway. We analyzed the metabolic changes caused by hypoxia over time and observed that chronic hypoxia resulted in an increase in 5-oxoproline and a decrease in oxidized glutathione (GSSG) compared to acute hypoxia. These findings suggest that chronic hypoxia induces metabolic changes in the γ-glutamyl cycle. Moreover, inhibition of the γ-glutamyl cycle via γ-glutamyl cyclotransferase (GGCT) and γ-glutamyl transferase 1 (GGT1) knockdown significantly reversed chronic hypoxia-induced upregulation of 5-oxoproline and several amino acids. Notably, GGT1 knockdown downregulated the intracellular levels of γ-glutamyl amino acids. Conclusively, these results indicate that the γ-glutamyl cycle serves as an amino acid supply system in CRC under chronic hypoxia, which provides fresh insight into cancer metabolism under chronic hypoxia.

A Novel Evaluation for Vertebral Artery Course Using 3D Magnetic Resonance Imaging with Computed Tomography -like Bone Contrast and Magnetic Resonance Angiography: A Proof of Concept Study.

OBJECTIVE: Vertebral artery (VA) injury poses a significant risk in cervical spine surgery, necessitating accurate preoperative assessment. This study aims to introduce and validate a novel approach that combines the Fast field echo that resembles a computed tomography using restricted echo spacing (FRACTURE) sequence with Time of Flight (TOF) Magnetic Resonance Angiography (MRA) for comprehensive evaluation of VA courses in the cervical spine. MATERIALS AND METHODS: A total of eight healthy volunteers and two patients participated in this study. The FRACTURE sequence provided high-resolution bone images of the cervical spine, while TOF MRA offered non-invasive vascular imaging. Fusion images were created by merging FRACTURE and MRA modalities to simultaneously visualize cervical spine structures and VA courses. Board-certified orthopedic spine surgeons independently evaluated images to assess the visibility of anatomical characteristics of the VA course by Likert-scale. RESULTS: The FRACTURE-MRA fusion images effectively depicted the extraosseous course of the VA at the craniovertebral junction, the intraosseous course of the VA at the craniovertebral junction, the VA entrance level to the transverse foramen, and the side-to-side asymmetry of bilateral VAs. Additionally, clinical cases demonstrated the utility of the proposed technique in identifying anomalies and guiding surgical interventions. CONCLUSIONS: The integration of the FRACTURE sequence and TOF MRA presents a promising methodology for the precise evaluation of VA courses in the cervical spine. This approach improves preoperative planning for cervical spine surgery with detailed anatomy and is a valuable alternative to conventional methods without contrast agents.

Short-Term Clinical and Radiographic Evaluation of Patients Treated With Expandable and Static Interbody Spacers Following Lumbar Lateral Interbody Fusion.

OBJECTIVE: The goal of this study was to evaluate, using computed tomography (CT) and magnetic resonance imaging (MRI), patients who underwent oblique lateral interbody fusion (OLIF) using either expandable or static interbody spacers. METHODS: Thirty-five patients with degenerative disc disease were surgically treated with one-level OLIF and were followed up for more than 6 months. The Static group consisted of 22 patients, and 13 patients were in the Expandable group. Intraoperative findings included operative time (min), blood loss (ml), and cage size. Low back pain, leg pain, and leg numbness were measured using the Japanese Orthopedic Association score, visual analogue score, and the Roland-Morris Disability Questionnaire. Radiologic evaluation using computed tomography (CT) and magnetic resonance imaging (MRI) allowed measurement of cage subsidence, cross-sectional area (CSA) of the dural sac, disc height, segmental lordosis, foraminal height, and foraminal CSA preoperatively and 6 months postoperatively. RESULTS: The Expandable group had significantly larger cage height and lordosis than the Static group (P < 0.05). The Expandable group also had greater dural sac area expansion and enlargement of the intervertebral foramen, as well as better correction of vertebral body slip (P < 0.05). Cage subsidence was significantly lower in the Expandable group (P < 0.05). JOA and VAS scores for leg numbness were significantly better in the Expandable group (P < 0.05). CONCLUSIONS: Compared with static spacers, expandable spacers significantly enlarged the dural sac area, corrected vertebral body slippage, expanded the intervertebral foramen, and achieved good indirect decompression while reducing cage subsidence, resulting in improvement in clinical symptoms.

Machine learning algorithms for predicting Cobb angle beyond 25 degrees in female adolescent idiopathic scoliosis patients.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To develop a machine learning (ML) model that predicts the progression of AIS using minimal radiographs and simple questionnaires during the first visit. SUMMARY OF BACKGROUND DATA: Several factors are associated with angle progression in patients with AIS. However, it is challenging to predict angular progression at the first visit. METHODS: Among female patients with AIS treated at a single institution from July 2011 to February 2023, 1119 cases were studied. Patient data, including demographic and radiographic data based on anterior-posterior and lateral whole-spine radiographs, were collected at the first and last visits. The last visit was defined differently based on treatment plans. For patients slated for surgery or bracing, the last visit occurred just before these interventions. For others, it was their final visit before turning 18 years. Angular progression was defined as a Cobb angle greater than 25 degrees for each of the proximal thoracic (PT), main thoracic (MT), and thoracolumbar/lumbar (TLL) curves at the last visit. ML algorithms were employed to develop individual binary classification models for each type of curve (PT, MT, and TLL) using PyCaret in Python. Multiple models were explored and analyzed, with the selection of optimal models based on the area under the curve (AUC) and Recall scores. Feature importance was evaluated to understand the contribution of each feature to the model predictions. RESULTS: For PT, MT, and TLL progression, the top-performing models exhibit AUC values of 0.94, 0.89, and 0.84, and achieve recall rates of 0.90, 0.85, and 0.81. The most significant factors predicting progression varied for each curve: initial Cobb angle for PT, presence of menarche for MT, and Risser grade for TLL. CONCLUSIONS: This study introduces an ML-based model using simple data at the first visit to precisely predict angle progression in female patients with AIS.

[A Case of Testicular Torsion of Retractile Testis Requiring Orchidectomy].

We report a case of testicular torsion in an 8-year-old who was referred to our hospital for right groin pain. He was diagnosed with right retractile testis during a 12-month check-up. However, instead of performing orchiopexy, he was placed under observation until the age of 5, after which he did not seek medical attention. Physical examination revealed swelling and tenderness in the right inguinal region and no palpable testis in the right scrotum. Ultrasound and computed tomography revealed right testicular torsion, and emergency surgery was performed. Intraoperative findings revealed a dark and ischemic testis that was twisted at 180°in the right inguinal region. There was no improvement in blood flow even after the testicular torsion was released; therefore, right orchidectomy with left orchiopexy was performed. Although the incidence of testicular torsion is higher in patients with an undescended testis than in those with a normally positioned scrotal position testis, reports of testicular torsion associated with a retractile testis are rare.

Machine Learning and Deep Learning in Spinal Injury: A Narrative Review of Algorithms in Diagnosis and Prognosis.

Spinal injuries, including cervical and thoracolumbar fractures, continue to be a major public health concern. Recent advancements in machine learning and deep learning technologies offer exciting prospects for improving both diagnostic and prognostic approaches in spinal injury care. This narrative review systematically explores the practical utility of these computational methods, with a focus on their application in imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI), as well as in structured clinical data. Of the 39 studies included, 34 were focused on diagnostic applications, chiefly using deep learning to carry out tasks like vertebral fracture identification, differentiation between benign and malignant fractures, and AO fracture classification. The remaining five were prognostic, using machine learning to analyze parameters for predicting outcomes such as vertebral collapse and future fracture risk. This review highlights the potential benefit of machine learning and deep learning in spinal injury care, especially their roles in enhancing diagnostic capabilities, detailed fracture characterization, risk assessments, and individualized treatment planning.

Association between Osteoporosis and Skeletal Muscle Mass in Men.

STUDY DESIGN: Cross-sectional study. PURPOSE: This cross-sectional study aimed to investigate the risk factors for osteoporosis in men by assessing bone mineral density (BMD), skeletal muscle mass, body fat mass, grip strength, and advanced glycation end products (AGEs). OVERVIEW OF LITERATURE: Fewer studies have reported the correlation between BMD and skeletal muscle mass in women. Moreover, a few studies have examined the relationship between osteoporosis and skeletal muscle mass. METHODS: This study included 99 men (mean age, 74.9 years; range, 28-93 years) who visited Qiball Clinic for BMD and body composition examinations. The osteoporosis group consisted of 24 patients (mean age, 72.5 years; range, 44-92 years), and the control group consisted of 75 individuals (mean age, 74.9 years; range, 28-93 years). Whole-body skeletal muscle mass was measured using a bioelectrical impedance analyzer. BMD was measured by dual X-ray absorptiometry. Skin autofluorescence (SAF), a marker of dermal AGE accumulation, was measured using a spectroscope. Osteoporosis was defined as a bone density T score of -2.5 or less. Physical findings, skeletal muscle mass, BMD, grip strength, and SAF were compared between the osteoporosis and control groups. RESULTS: The osteoporosis group had significantly lower trunk muscle mass (23.1 kg vs. 24.9 kg), lower leg muscle mass (14.4 kg vs. 13.0 kg), and skeletal mass index (7.1 kg/m2 vs. 6.7 kg/m2) than the control group (all p<0.05). Lower limb muscle mass was identified as a risk factor for osteoporosis in men (odds ratio, 0.64; p=0.03). CONCLUSIONS: Conservative treatment of osteoporosis in men will require an effective approach that facilitates the maintenance or strengthening of skeletal muscle mass, including exercise therapy with a focus on lower extremities and nutritional supplementation.

Quantitative evaluation of the lumbar ligamentum flavum using MRI T2-mapping: Efficacy of its clinical application in patients with lumbar spinal stenosis.

OBEJECTIVE: To perform a magnetic resonance imaging T2-mapping of the ligamentum flavum in healthy individuals and patients with lumbar spinal stenosis scheduled for surgery and compare the T2 relaxation times. SUBJECTS AND METHODS: The T2 relaxation time of the ligamentum flavum was compared among 3 groups, healthy young individuals (H group (age< 50)), healthy middle-aged and older individuals (H group (age≥50)), and patients with lumbar spinal stenosis (L group). Additionally, the thickness of the ligament was measured in the axial image plane, and the occupied area ratio of each fiber was measured by staining the surgically obtained ligament, and each was correlated with the T2 relaxation time. We also evaluated the adhesion of the ligamentum flavum with the dura mater during the surgery. RESULTS: The T2 relaxation times were significantly prolonged in H group (age ≥50) and L group (P < 0.001) compared to H group (age<50). The relationship between collagen fiber and T2 relaxation times was significantly positive (r = 0.720, P < 0.001). Moreover, the relaxation times were significantly prolonged in those with adhesion of the ligamentum flavum with the dura mater (P < 0.05). The cut-off for the relaxation time was 50 ms (sensitivity: 62.50%, false positive rate: 10.8%). CONCLUSION: Healthy middle-aged and older individuals and patients with lumbar spinal stenosis and adhesion of the ligamentum flavum with the dura mater have prolonged T2 relaxation times. Hence, the adhesion between the ligamentum flavum and dura mater should be considered in cases with a relaxation time ≥50 ms.

Does vacuum phenomenon at non-fused discs affect the postoperative course after transforaminal lumbar interbody fusion in patients showing a positive value of difference in lumbar lordosis?

INTRODUCTION: Preoperative difference in lumbar lordosis (DiLL) was associated with surgical outcomes after single-level transforaminal lumbar interbody fusion (TLIF). Patients with DiLL>0 (DiLL (+)) tended to show worse clinical outcomes and postoperative greater restoration of lumbar lordosis (LL). However, some patients with DiLL (+) showed relatively good outcomes and no postoperative LL restration. This study aimed to elucidate whether the lumbar intervertebral disc vacuum phenomenon (VP) influences clinical course after single-level TLIF in patients with DiLL (+) and DiLL (-). METHODS: Patients with lumbar spinal stenosis and degenerative spondylolisthesis treated with single-level TLIF were included. Pre- and postoperative LL were measured, and postoperative LL improvement was calculated. Preoperative DiLL was calculated as preoperative supine LL minus standing LL. Severity of VP at the non-fused discs (SVP (non-FS)) was evaluated using preoperative reconstructed computed tomography imaging. Clinical outcomes were assessed using the Oswestry disability index, visual analogue scale (VAS; low back pain (LBP), lower-extremity pain, numbness, and the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire. Patients were stratified by the median preoperative SVP (non-FS) score into severe and mild VP groups in patients with DiLL (+) or DiLL (-), and their surgical outcomes were compared. RESULTS: Overall, 89 patients were included. In patients with DiLL (+) (n = 37), patients with severe VP showed worse clinical outcomes, particulary for LBP and DiLL (+) patients with mild VP showed greater LL improvement (6.5° ± 10.0°). In patients with DiLL(-) (n = 52), patients with severe VP showed worse clinical outcomes, particularly for LBP and no differences in preoperative, postoperative, and improvement of LL were observed between two groups. CONCLUSION: Patients with DiLL (+) and DiLL (-) showed different clinical courses depending on VP severity at the non-fused discs after single-level TLIF.

Clonal Origin and Lineage Ambiguity in Mixed Neuroendocrine Carcinoma of the Uterine Cervix.

Small-cell neuroendocrine carcinoma (SCNEC) of the cervix is a rare disease characterized by a high incidence of mixed tumors with other types of cancer. The mechanism underlying this mixed phenotype is not well understood. This study established a panel of organoid lines from patients with SCNEC of the cervix and ultimately focused on one line, which retained a mixed tumor phenotype, both in vitro and in vivo. Histologically, both organoids and xenograft tumors showed distinct differentiation into either SCNEC or adenocarcinoma in some regions and ambiguous differentiation in others. Tracking single cells indicated the existence of cells with bipotential differentiation toward SCNEC and adenocarcinomas. Single-cell transcriptional analysis identified three distinct clusters: SCNEC-like, adenocarcinoma-like, and a cluster lacking specific differentiation markers. The expression of neuroendocrine markers was enriched in the SCNEC-like cluster but not exclusively. Human papillomavirus 18 E6 was enriched in the SCNEC-like cluster, which showed higher proliferation and lower levels of the p53 pathway. After treatment with anticancer drugs, the expression of adenocarcinoma markers increased, whereas that of SCNEC decreased. Using a reporter system for keratin 19 expression, changes in the differentiation of each cell were shown to be associated with the shift in differentiation induced by drug treatment. These data suggest that mixed SCNEC/cervical tumors have a clonal origin and are characterized by an ambiguous and flexible differentiation state.

Objective Assessment of Sleep Disorders in Patients with Lumbar Spinal Stenosis Using Wearable Trackers.

Introduction: Low-back pain causes sleep disorders, which impairs the quality of life (QOL) of patients. Sleep disorders are associated with lumbar spinal stenosis (LSS); however, the postoperative effects of LSS surgery on sleep disorders are unknown. This study aimed to assess sleep disorders in patients with LSS using wearable activity trackers and determine whether surgery improves sleep quality. Methods: A total of 39 patients scheduled for LSS surgery (mean age 71.1±8.7 years; 22 men and 17 women) were studied. Sleep disorders in the participants were objectively evaluated using a wearable Motionlogger Micro system. Sleep efficiency (SEf), mean active count (MAC), and wake after sleep onset (WASO) were measured before and 6 months following surgery. Furthermore, the patient-based outcomes of pain and QOL-related scores were measured and compared with those of healthy participants. The group with improved SEf following surgery was designated as "nonpoor sleepers," whereas the group that did not exhibit improvements was designated as "poor sleepers." The two groups were compared based on patient factors, patient-based questionnaires, and sleep disorder measurements. Results: The SEf and WASO were significantly worse in patients with LSS compared with healthy participants (P<0.05). Furthermore, the SEf in patients with LSS was associated with the Oswestry Disability Index scores. No improvement was observed in the SEf, MAC, and WASO before and after surgery. Evaluation of each case revealed 21 and 12 cases of nonpoor and poor sleepers, respectively. Preoperative low-back pain was significantly associated with improvement in postoperative sleep quality. Conclusions: Sleep disorders in patients with LSS were evaluated, and improvement in sleep disorders following surgery was associated with the intensity of preoperative low-back pain. Sleep disorders are associated with QOL disorders, suggesting that focusing on the treatment of sleep disorders is important in the management of patients with LSS.

Ultra-Rapid and Specific Gelation of Collagen Molecules for Transparent and Tough Gels by Transition Metal Complexation.

Collagen is the most abundant protein in the human body and one of the main components of stromal tissues in tumors which have a high elastic modulus of over 50 kPa. Although collagen has been widely used as a cell culture scaffold for cancer cells, there have been limitations when attempting to fabricate a tough collagen gel with cells like a cancer stroma. Here, rapid gelation of a collagen solution within a few minutes by transition metal complexation is demonstrated. Type I collagen solution at neutral pH shows rapid gelation with a transparency of 81% and a high modulus of 1,781 kPa by mixing with K2 PtCl4 solution within 3 min. Other transition metal ions also show the same rapid gelation, but not basic metal ions. Interestingly, although type I to IV collagen molecules show rapid gelation, other extracellular matrices  do not exhibit this phenomenon. Live imaging of colon cancer organoids in 3D culture indicates a collective migration property with modulating high elastic modulus, suggesting activation for metastasis progress. This technology will be useful as a new class of 3D culture for cells and organoids due to its facility for deep-live observation and mechanical stiffness adjustment.

Denosumab-associated Periprosthetic Atypical Femur Fracture: A Case Report.

Introduction: Denosumab is generally used for 5-10 years to treat postmenopausal osteoporosis. Although atypical fractures caused by bisphosphonate use are well known, reports of denosumab-associated femur fractures are rare. Case Report: Herein, a 75-year-old woman suffered an atypical periprosthetic femoral fracture 31 months after receiving denosumab. The fracture occurred transverse to the stem tip with lateral cortical thickening. The patient underwent revision surgery for conversion to a longer cemented stem. The fracture site healed 10 months after revision surgery. Conclusion: As far as we know, there have been no reports of a case on periprosthetic atypical femur fracture associated with denosumab. Our study shows the potential of periprosthetic atypical femoral fractures in patients using denosumab for a long time.

Risk Factors for Cage Subsidence in Minimally Invasive Lateral Corpectomy for Osteoporotic Vertebral Fractures.

Introduction: This study aims to investigate risk factors for cage subsidence following minimally invasive lateral corpectomy for osteoporotic vertebral fractures. Methods: Eight males and 13 females (77.2±6.0 years old) with osteoporotic vertebral fractures who underwent single corpectomy using a wide-footprint expandable cage with at least a 1-year follow-up were retrospectively included. The endplate cage (EC) angle was defined as the angle between the vertebral body's endplate and the cage's base on the cranial and caudal sides. A sagittal computed tomography scan was performed immediately after surgery and at the final follow-up, with cage subsidence defined as subsidence of ≥2 mm on the cranial or caudal side. Risk factors were analyzed by dividing cases into groups with (n=6) and without (n=15) cage subsidence. Results: No significant differences were noted in age, bone mineral density, number of fixed vertebrae, sagittal parameters, preoperative and final kyphosis angle, amount of kyphosis angle correction, bone union, screw loosening, and number of other vertebral fractures preoperatively and 1-year postoperatively between the two groups. No difference was noted in cranial EC angle, but a significant difference was noted in caudal EC angle in the group with (10.7±4.1°) and without (4.7±4.2°) subsidence (P=0.008). Logistic regression analysis with the dependent variable as presence or absence of subsidence showed that caudal EC angle (>7.5°) was a significant factor (odds ratio: 20, 95% confidence interval: 1.655-241.7, P=0.018). Conclusions: In minimally invasive lateral corpectomy for osteoporotic vertebral fractures, a cage tilted more than 7.5° to the caudal vertebral endplate is a risk factor for cage subsidence. The cage should be placed as perpendicular to the endplate as possible, especially to the caudal vertebral body, to avoid cage subsidence.

De-differentiation in cultures of organoids from luminal-type breast cancer is restored by inhibition of NOTCH signaling.

Estrogen receptor (ER) expression in breast cancer can change during progression and the treatment, but the mechanism has not been well studied. In this study, we successfully prepared organoids from samples obtained from 33 luminal-type breast cancer patients and studied their ER expression. The expression status was well maintained in primary organoids, whereas it decreased after passaging in most of the cases. In fact, the studied organoid lines were classified into those that retained a high level of ER expression (9%), those that completely lost it (9%), and those that repressed it to varying degrees (82%). In some cases, the ER expression was suddenly and drastically decreased after passaging. Marker protein immunohistochemistry revealed that after passaging, the differentiation status shifted from a luminal- to a basal-like status. Differentially expressed genes suggested the activation of NOTCH signaling in the passaged organoids, wherein a NOTCH inhibitor was able to substantially rescue the decreased ER expression and alter the differentiation status. Our findings suggest that the differentiation status of luminal-type cancer cells is quite flexible, and that by inhibiting the NOTCH signaling we can preserve the differentiation status of luminal-type breast cancer organoids.