Extracellular cold-inducible RNA-binding protein mediated neuroinflammation and neuronal apoptosis after traumatic brain injury.

Background: Extracellular cold-inducible RNA-binding protein (eCIRP) plays a vital role in the inflammatory response during cerebral ischaemia. However, the potential role and regulatory mechanism of eCIRP in traumatic brain injury (TBI) remain unclear. Here, we explored the effect of eCIRP on the development of TBI using a neural-specific CIRP knockout (KO) mouse model to determine the contribution of eCIRP to TBI-induced neuronal injury and to discover novel therapeutic targets for TBI. Methods: TBI animal models were generated in mice using the fluid percussion injury method. Microglia or neuron lines were subjected to different drug interventions. Histological and functional changes were observed by immunofluorescence and neurobehavioural testing. Apoptosis was examined by a TdT-mediated dUTP nick end labelling assay in vivo or by an annexin-V assay in vitro. Ultrastructural alterations in the cells were examined via electron microscopy. Tissue acetylation alterations were identified by non-labelled quantitative acetylation via proteomics. Protein or mRNA expression in cells and tissues was determined by western blot analysis or real-time quantitative polymerase chain reaction. The levels of inflammatory cytokines and mediators in the serum and supernatants were measured via enzyme-linked immunoassay. Results: There were closely positive correlations between eCIRP and inflammatory mediators, and between eCIRP and TBI markers in human and mouse serum. Neural-specific eCIRP KO decreased hemispheric volume loss and neuronal apoptosis and alleviated glial cell activation and neurological function damage after TBI. In contrast, eCIRP treatment resulted in endoplasmic reticulum disruption and ER stress (ERS)-related death of neurons and enhanced inflammatory mediators by glial cells. Mechanistically, we noted that eCIRP-induced neural apoptosis was associated with the activation of the protein kinase RNA-like ER kinase-activating transcription factor 4 (ATF4)-C/EBP homologous protein signalling pathway, and that eCIRP-induced microglial inflammation was associated with histone H3 acetylation and the α7 nicotinic acetylcholine receptor. Conclusions: These results suggest that TBI obviously enhances the secretion of eCIRP, thereby resulting in neural damage and inflammation in TBI. eCIRP may be a biomarker of TBI that can mediate the apoptosis of neuronal cells through the ERS apoptotic pathway and regulate the inflammatory response of microglia via histone modification.

The clinical effectiveness and safety of Zone III REBOA for resection of sacropelvic tumors in patients older than 70 years.

BACKGROUND: REBOA is a method used to manage bleeding during surgery involving sacropelvic tumors. Nevertheless, studies on the use of REBOA among elderly people are lacking. The aim of this research was to investigate the efficacy and safety of Zone III REBOA in patients aged more than 70 years. METHODS: A comparative study was conducted using case-control methods. A group of patients, referred to as Group A, who were younger than 70 years was identified and paired with a comparable group of patients, known as Group B, who were older than 70 years. Continuous monitoring of physiological parameters was conducted, and blood samples were collected at consistent intervals. RESULTS: Totally, 188 participants were enrolled and received REBOA. Among the 188 patients, seventeen were aged more than 70 years. By implementing REBOA, the average amount of blood loss was only 1427 ml. Experiments were also conducted to compare Group A and Group B. No notable differences were observed in terms of demographic variables, systolic blood pressure (SBP), arterial pH, lactate levels, blood creatinine levels, potassium levels, or calcium levels at baseline. Additionally, after the deflation of the REBOA, laboratory test results, which included arterial pH, lactate, potassium concentration, calcium concentration, and blood creatinine concentration, were not significantly different (P > 0.05). CONCLUSION: This study indicated that in selected patients aged more than 70 years can achieve satisfactory hemodynamic and metabolic stability with Zone III REBOA. LEVEL OF EVIDENCE: Therapeutic study, Level III.

The efficacy and safety of vincristine, irinotecan and anlotinib in Epithelioid Sarcoma.

BACKGROUND: Epithelioid sarcoma is a rare soft tissue sarcoma characterized by SMARCB1/INI1 deficiency. Much attention has been paid to the selective EZH2 inhibitor tazemetostat, where other systemic treatments are generally ignored. To explore alternative treatment options, we studied the effects of irinotecan-based chemotherapy in a series of epithelioid sarcoma patients. METHODS: We retrospectively reviewed data from patients with metastatic or unresectable epithelioid sarcoma at the Peking University People's Hospital treated with irinotecan (50 mg/m2/d d1-5 Q3W) in combination with Anlotinib (12 mg Qd, 2 weeks on and 1 week off) from July 2015 to November 2021. RESULTS: A total of 54 courses were administered. With a median follow up of 21.2 months (95% CI, 12.2, 68.1), the 5-year overall survival rate was 83.3%. Five of eight (62.5%) patients presented with unresectable localized lesions, including local tumor thrombosis and lymphatic metastasis. The other patients had unresectable pulmonary metastases. Six of eight (75%) patients had progressed following two lines of systemic therapy. The objective response rate reached 37.5% (three of eight patients) while stabilized disease was observed in 62.5% (five of eight) of patients. No patient had progressed at initial evaluation. At the last follow up, two patients were still using the combination and three patients had ceased the therapy due to toxicities such as diarrhea, nausea, and emesis. One patient changed to tazemetostat for maintenance and one patient stopped treatment due to coronavirus disease 2019 (COVID-19). Another patient stopped therapy as residual lesions had been radiated. CONCLUSIONS: The combination of irinotecan and Anlotinib as a salvage regimen may be considered another effective treatment option for refractory epithelioid sarcoma. TRIAL REGISTRATION: This study was approved in the Medical Ethics Committee of Peking University People's Hospital on October 28, 2022 (No.: 2022PHD015-002). The study was registered in Clinicaltrials.gov with identifier no. NCT05656222.

Renal hemodynamic evaluation protocol based on the pathophysiological mechanism of acute kidney injury: Critical Care UltraSound Guided-A(KI)BCDE.

The multiple etiological characteristics of acute kidney injury (AKI) have brought great challenges to its clinical diagnosis and treatment. Renal injury in critically ill patients always indicates hemodynamic injury. The Critical Care UltraSound Guided (CCUSG)-A(KI)BCDE protocol developed by the Chinese Critical Ultrasound Study Group (CCUSG), respectively, includes A(KI) diagnosis and risk assessment and uses B-mode ultrasound, Color doppler ultrasound, spectral Doppler ultrasound, and contrast Enhanced ultrasound to obtain the hemodynamic characteristics of the kidney so that the pathophysiological mechanism of the occurrence and progression of AKI can be captured and the prognosis of AKI can be predicted combined with other clinical information; therefore, the corresponding intervention and treatment strategies can be formulated to achieve targeted, protocolized, and individualized therapy.

The outcomes of proximal femur replacement with hemiarthroplasty after tumor resection in individuals with Parkinson's disease.

Background: Patients with neurological disorders often experience a high incidence of postoperative complications following proximal femur replacement (PFR) surgery. The orthopaedist faces a significant difficulty in treating Parkinson's disease (PD) because of the weakened bone condition, excessive muscle tension, and increased risk of fractures. The objective of this research is to assess the impact of PD on PFR following tumor removal. Methods: A retrospective study was conducted from 2010 to 2020, focusing on a solitary institution, analyzing 9 patients diagnosed with PD who underwent PFR with hemiarthroplasty as a result of tumor removal. The study consists of 2 men and 7 women, with an average age of 71 (SD, 12) years. We assessed the outcomes after surgery in terms of pain management, quality of life, functional ability, occurrence of complications, and survival durations. Results: All nine patients underwent planned surgeries. Intraoperative complications was not observed. The average length of the follow-up period was 24 (SD, 20) months, ranging from 8 to 72 months. Despite the fact that 8 patients passed away due to tumor progression, the endoprostheses were still well at that point. The preoperative VAS score of 7 (SD, 1.87) decreased to a postoperative score of 2 (SD, 1.32). The KPS was improved to73 (SD, 7) from 52 (SD, 14), postoperatively. Post-surgery, there were notable enhancements in both pain levels and the overall quality of life scores. Following the surgical procedure, individuals are able to ambulate steadily, resuming their regular daily routines. Living patients had an average MSTS score of 21 (SD, 2.5), ranging from 17 to 25. In total, there were four (44.4%) patients suffered complications after surgery, comprising of one wound dehiscence, one prosthetic fracture, one hip dislocation, and one local recurrence. Conclusions: Significant improvements in function and pain relief can be achieved through PFR with hemiarthroplasty following tumor removal in patients with PD. The implementation of thorough preparation and carefull nursing results in reduced complications and improved outcomes in PD patients.

Study on the Characteristics of Early Cytokine Storm Response to Cardiac Surgery.

Cardiac surgery can provoke an acute cytokine storm that may contribute to the development of postoperative multiple organ dysfunction syndrome. We prospectively observed patients undergoing cardiac surgery and divided them into two groups: the severe group and the mild group. Healthy individuals were enrolled acting as the control group for comparison. Plasma samples and clinical data were recorded at the initiation of cardiac-pulmonary bypass (CPB) and 3, 6, 12, 24, and 48 h after initiation of CPB. Cytokine levels were detected using the Luminex® technique. Thirty-nine adults were enrolled in this study (14 in the severe group, 15 in the mild group, and 10 in the control group). Cytokine concentrations were significantly higher in the severe group. Principal component analysis was used to establish a cytokine storm intensity curve, which represented the overall trend of 10 cytokines. The peak concentrations of interleukin (IL)-6, IL-10, and IL-16 were 425.1, 198.5, and 623.0 pg/mL, which were more than 1,200, 1,800, and 240 times the normal level, respectively. The maximum cytokine storm intensity predated the maximum Vasoactive-Inotropic Score (VIS) and Sequential Organ Failure Assessment (SOFA) score in the severe group. Cytokine storm response to cardiac surgery occurred early and was associated with disease severity. Interventions to cytokine storm should be initiated early as guided by cytokine storm biomarkers such as IL-6, IL-10, and IL-16 in severe patients undergoing cardiac surgery. Clinical Trial Registration: ChiCTR1900021351.

Surgical results and quality of life after single-stage posterior transpedicular approach for circumferential epidural decompression in patients with thoracolumbar spine metastasis.

Objective: The primary aim of this study was to evaluate the effect of palliative surgery using posterior transpedicular approach (PTA) with posterior instrumentation on pain response and quality of life (QoL) in patients with metastatic thoracic and lumbar tumors. Methods: From 2018 to 2019, 39 patients with metastatic thoracic and/or lumbar tumors were prospectively enrolled to measure the reduction in pain and the changes in QoL after surgical decompression with posterior instrumentation via PTA. The patient group was composed of 27 men and 12 women with a mean age of 60 years (range, 28 to 92 years). Pain response was measured using the visual analog scale (VAS) and neurologic status was evaluated using Frankel grades. QoL was assessed with use of the EORCT QLQ-BM22 questionnaire before surgery (baseline) and at 1-, 3-, 6-, and 12-month after surgery. The survival times of all the patients were also collected. Results: All patients showed either an improvement or a similar pain level after surgery, which the VAS score decreased from 7.10 ± 2.22 preoperatively to 3.10 ± 2.15 one month postoperatively (P<0.05). 19 patients (48.7%, 19/39) showed neurological function improvement postoperatively. Among the 19 patients, 7 cases improved from Frankel grade C to D, 5 cases from grade C to E, and 7 cases from grade D to E. Another 20 patients still have the same Frankel grade postoperatively, however, most of them improved clinically. The QoL improvement of the patients was also evident after treatment. Paired-samples T-test examination of the postoperative scores showed a significant improvement in terms of pain location, pain severity and performance status (P<0.01). Compared with the preoperative score, the 1-month postoperative score of functional interference was significantly improved (63.6 vs. 34.5, P<0.01). There were no significant changes in social or psychological functioning. Three patients experienced cerebrospinal fluid leakage postoperatively, and they were all successfully managed by lying flat without a pillow. One patient experienced rod breakage, at 10 months after surgery. All the patients were alive at 3 months; however, 7 patients died within 3 to 6 months, and another 9 patients died from the disease within 6 to 12 months. Conclusions: The present feasibility study found that the application of the PTA for decompression and fusion in patients with spinal metastases is beneficial for achieving prompt and sustained pain relief, reducing neurologic deficits and improving functional outcomes, health utilities, and HRQoL.

Single-cell transcriptome profiling of sepsis identifies HLA-DRlowS100Ahigh monocytes with immunosuppressive function.

BACKGROUND: Sustained yet intractable immunosuppression is commonly observed in septic patients, resulting in aggravated clinical outcomes. However, due to the substantial heterogeneity within septic patients, precise indicators in deciphering clinical trajectories and immunological alterations for septic patients remain largely lacking. METHODS: We adopted cross-species, single-cell RNA sequencing (scRNA-seq) analysis based on two published datasets containing circulating immune cell profile of septic patients as well as immune cell atlas of murine model of sepsis. Flow cytometry, laser scanning confocal microscopy (LSCM) imaging and Western blotting were applied to identify the presence of S100A9+ monocytes at protein level. To interrogate the immunosuppressive function of this subset, splenic monocytes isolated from septic wild-type or S100a9-/- mice were co-cultured with naïve CD4+ T cells, followed by proliferative assay. Pharmacological inhibition of S100A9 was implemented using Paquinimod via oral gavage. RESULTS: ScRNA-seq analysis of human sepsis revealed substantial heterogeneity in monocyte compartments following the onset of sepsis, for which distinct monocyte subsets were enriched in disparate subclusters of septic patients. We identified a unique monocyte subset characterized by high expression of S100A family genes and low expression of human leukocyte antigen DR (HLA-DR), which were prominently enriched in septic patients and might exert immunosuppressive function. By combining single-cell transcriptomics of murine model of sepsis with in vivo experiments, we uncovered a similar subtype of monocyte significantly associated with late sepsis and immunocompromised status of septic mice, corresponding to HLA-DRlowS100Ahigh monocytes in human sepsis. Moreover, we found that S100A9+ monocytes exhibited profound immunosuppressive function on CD4+ T cell immune response and blockade of S100A9 using Paquinimod could partially reverse sepsis-induced immunosuppression. CONCLUSIONS: This study identifies HLA-DRlowS100Ahigh monocytes correlated with immunosuppressive state upon septic challenge, inhibition of which can markedly mitigate sepsis-induced immune depression, thereby providing a novel therapeutic strategy for the management of sepsis.

Indocyanine green fluorescence imaging may detect tumour residuals during surgery for bone and soft-tissue tumours.

The aim of this study was to determine the rate of indocyanine green (ICG) staining of bone and soft-tissue tumours, as well as the stability and accuracy of ICG fluorescence imaging in detecting tumour residuals during surgery for bone and soft-tissue tumours. ICG fluorescence imaging was performed during surgery in 34 patients with bone and soft-tissue tumours. ICG was administered intravenously at a dose of 2 mg/kg over a period of 60 minutes on the day prior to surgery. The tumour stain rate and signal-to-background ratio of each tumour were post hoc analyzed. After tumour resection, the tumour bed was scanned to locate sites with fluorescence residuals, which were subsequently inspected and biopsied. The overall tumour stain rate was 88% (30/34 patients), and specific stain rates included 90% for osteosarcomas and 92% for giant cell tumours. For malignant tumours, the overall stain rate was 94%, while it was 82% for benign tumours. The ICG tumour stain was not influenced by different pathologies, such as malignant versus benign pathology, the reception (or lack thereof) of neoadjuvant chemotherapies, the length of time between drug administration and surgery, the number of doses of denosumab for patients with giant cell tumours, or the tumour response to neoadjuvant chemotherapy. The overall accuracy rate of successfully predicting tumour residuals using fluorescence was 49% (23/47 pieces of tissue). The accuracy rate after en bloc resection was significantly lower than that after piecemeal resection (16% vs 71%; p < 0.001). A high percentage of bone and soft-tissue tumours can be stained by ICG and the tumour staining with ICG was stable. This approach can be used in both benign and malignant tumours, regardless of whether neoadjuvant chemotherapy is adopted. The technique is also useful to detect tumour residuals in the wound, especially in patients undergoing piecemeal resection.

Outcomes of Fixed-Hinged Knee Prosthesis for Distal Femoral Osteosarcoma in Skeletally Immature Patients: First Results.

The best surgical choice for distal femur osteosarcoma in skeletally immature patients remains controversial. A fixed hinged knee prosthesis has been designed to preserve the growth plates in the adjacent tibia, expecting tibial growth to be continued. This study aims to report the (1) clinical outcomes after prosthetic replacement, (2) postoperative complications, and (3) length of discrepancy of the operative tibia with the unaffected tibia. Thirty-four skeletally immature patients (averaged 9 years at surgery; range, 5-12 years) with distal femoral osteosarcoma underwent placement of this hinged knee prosthesis between January 2015 and August 2018. Postoperative function and complications were assessed. Length discrepancy was measured using a series of full-length standing anteroposterior radiographs of the bilateral lower extremity. The average follow-up duration was 34 months (2.8 years). In the last follow-up, four patients expired because of pulmonary metastasis. Two patients presented with local recurrence of the soft tissue. Postoperatively, the flexion range of the knee joint range was between 100 and 130 degrees, with an average of 115.2 degrees. The mean functional score of living patients evaluated using the Musculoskeletal Tumor Society scoring system was 89.2% (range, 76.7-100%). Types 1 (three patients), 2 (one patient), 3 (two patients), and 5 (two patients) complications exist. Among them, three patients received revision surgery. The proximal tibial physis still grew after surgery, with an average of 74.3% (range, 30-100%) growth potential compared with the unaffected proximal tibial physis. Moreover, 27 children exhibited tibial length discrepancy compared with the contralateral tibia, and the mean discrepancy in tibial length was 1.1 cm (range, 0.2-3.1 cm). This hinged knee prosthesis can keep the growth potential in the adjacent tibia, provides satisfying functional outcomes, and has a lower postoperative complication rate. Thus, it could serve as an alternative intervention for distal femoral osteosarcoma in skeletally immature patients.

Outcomes of Semiknee Replacement in Skeletally Immature Bone Sarcoma Patients.

INTRODUCTION: A semiknee mega endoprosthesis (SKMEP) was used to replace the resected distal femur or proximal tibia in skeletally immature bone sarcoma patients. This study investigated the surgical technique, endoprosthesis survival rate, functional outcome, complications, and approaches to resolve limb-length discrepancy (LLD) following this procedure. PATIENTS AND METHODS: In total, 15 girls and 16 boys with a mean age of 9.1 years (range, 4-12) and 8.9 years (range, 5-13), respectively, were included in this study. The mean length of the resected distal femur (15 cases) and proximal tibia (16) was 145.0 and 122.8 mm, respectively. Altogether, 19 custom-made SKMEPs and 12 modular units were used to reconstruct the bone and joint defects. RESULTS: The average follow-up was 82.8 months (range, 4-225 months). Five patients died of disease. Seven SKMEPs were revised to total knee endoprosthesis after a mean of 40.3 months. Nineteen patients retained the original SKMEP, and the mean LLD was 4.3 cm (range, 0-10 cm). One case each of Henderson type 1B, type 2A, type 2B, and type 5B failures was observed. Knee subluxation occurred in two cases. Although a slight laxity of the knee was identified on physical examination, the average Musculoskeletal Tumor Society 93(MSTS93) functional score was 84.5% (range, 57-97%). The estimated implant survival was 70.5% at 5 years. CONCLUSION: This was the largest retrospective study reporting the application of SKMEP in bone sarcoma patients. For selected skeletally immature bone sarcoma patients, SKMEP is an option with satisfactory functional outcomes and survival rates. However, heightening pads or shoes to compensate the LLD were indispensable before subsequent LLD was adjusted by further operation(s).

Expression and Clinical Significance of Various Checkpoint Molecules in Advanced Osteosarcoma: Possibilities for Novel Immunotherapy.

OBJECTIVES: The fact that studies on anti-programmed cell death 1 (PD-1) or its relevant ligand 1 (PD-L1) have yielded such few responses greatly decreases the confidence in immunotherapy with checkpoint inhibitors for advanced osteosarcoma. We intended to characterize the expression of various checkpoint molecules with immunohistochemistry in osteosarcoma specimens and analyzed the relationship of the expression of these checkpoint molecules with patients' clinical courses. METHODS: This study was a retrospective non-intervention study from August 1st 2017 to March 1st 2020. Immunohistochemistry for B7-H3 (CD276, Cluster of Differentiation 276), CD47 (Cluster of Differentiation 47), PD-L1 (programmed cell death ligand 1), TIM3 (mucin-domain containing-3), TGF-ß (TransformingGrowth Factor ß), CXCR 4 (Chemokine Receptor 4), CD27 (Cluster of Differentiation 27), IDO1 (Indoleamine 2,3-dioxygenase 1), KIRs (Killer cell Immunoglobulin-like Receptors), and SDF-1 (Stromal cell-Derived Factor-1) was performed on 35 resected osteosarcoma specimens. Patients progressed upon first-line chemotherapy with evaluable lesions were qualified for this study, and their specimens previously stored in the pathological department repository would be retrieved for analysis. Associations between the immunohischemistry markers and clinicopathological variables and survival were evaluated by the χ2 displayed by cross-table, Cox proportional hazards regression model, and Kaplan-Meier plots. RESULTS: The positive rates of B7-H3, CD47, PD-L1, TIM3, and TGF-ß expression in this sample of 35 heavily treated osteosarcomas were 29% (10/35), 15% (5/35), 9% (3/35), 6% (2/35), and 6% (2/35), respectively, and diverse staining intensities were observed. Among these advanced patients, 15/35 (43%) had positive checkpoint expression, of which 33% (5/15) showed evidence of the co-expression of more than one checkpoint molecule. We did not find any obvious correlation with clinicopathological characteristics and the positive expression of these molecules. CONCLUSIONS: The present study highlights that only a small subset of progressive osteosarcomas, which had been heavily-treated, expressed tumor immune-associated checkpoint molecules, of which B7-H3 was the most positively expressed checkpoint and might be a promising target for further osteosarcoma investigation.

Botulinum Toxin A Alleviates Persistent Erythema and Flushing in Patients with Erythema Telangiectasia Rosacea.

INTRODUCTION: The persistent erythema and flushing seen in some cases of rosacea do not respond effectively to, or may easily relapse after, oral medication or light-based therapies (laser or intense pulsed light). Intradermal botulinum toxin A (BTX-A) injection can be used to treat intractable erythema and flushing, but studies with large samples and long-term observation have not been conducted to determine its effectiveness and safety. The aim of this study is thus to investigate the effective duration and safety of intradermal BTX-A injection for intractable erythema and flushing. METHODS: Sixteen patients with rosacea with erythema telangiectasia were injected with BTX-A at 1-cm intervals between each point. Clinician Erythema Assessment (CEA) scores were obtained at baseline and 1 month after injection. Flushing assessment and survey using the Dermatological Quality of Life Index (DLQI) questionnaire were conducted at baseline and at 1, 3, and 6 months after injection. RESULTS: At 1 month after injection, CEA scores revealed significant improvements in erythema and flushing; the results of the questionnaire on flushing and DLQI indicated that the improvement of flushing usually lasted for 3-6 months, but the effect decreased significantly at 6 months, and individual patients needed another treatment. CONCLUSIONS: BTX-A significantly improves the symptoms and quality of life of patients with refractory rosacea with few adverse effects.

How to confront the high prevalence of pulmonary micro nodules (PMNs) in osteosarcoma patients?

PURPOSE: Pulmonary metastasis was a negative factor of osteosarcoma prognosis. However, there is no universal criteria to confirm pulmonary metastasis at pulmonary micro nodule (PMN, Dmax ≤ 5 mm) stage other than pathology. We aimed to identify prevalence of PMNs, determine prognosis of osteosarcoma with PMNs, and analyze risk factors related to PMN progression. METHODS: We retrospectively reviewed 425 consecutive osteosarcoma patients. According to dynamic change in size and number of PMNs, patients were divided into PMN progression and non-progression group. Demographic data, initial laboratory data, radiological features, and oncological evaluations were analyzed. Cox regression was used to identify risk factors for PMN progression. Overall survival rate was measured and analyzed with Kaplan-Meier method. Differences with p < 0.05 were considered significant. RESULTS: PMNs were found in 74% (315/425) osteosarcoma patients, half of whom (157/315) suffering PMN progression. Overall survival rate was 70.2%, while survival rates for PMN progression group and non-progression group were 53.40% and 87.40%, respectively. Clinical risk factors for PMN progression in certain patients included blood vessel invasion, extrapulmonary metastases, low tumour cell necrosis rate, and large tumour size. Radiologic risk factors included greatest diameter, distance to pleura, CT value, solid components, and smooth border. CONCLUSION: PMN is quite common in osteosarcoma patients. PMN progression is related to both certain clinical and radiological factors, which could assist surgeons to determine its possibility to progress at an early stage.

Efficacy and safety of a 3D-printed arthrodesis prosthesis for reconstruction after resection of the proximal humerus: preliminary outcomes with a minimum 2-year follow-up.

BACKGROUND: The purpose of this study was to investigate the feasibility of using a three-dimensional (3D)-printed arthrodesis prosthesis for reconstruction of the proximal humeral defect after tumor resection. METHODS: A novel proximal humeral prosthesis was designed to restore bone continuity and shoulder arthrodesis and was fabricated via 3D printing technology. Ten patients with primary malignancies in the proximal humerus underwent intra-articular resection and replacement with this prosthesis from 2017 to 2019. Baseline and operative data, oncological and prosthetic survival, and functional status were summarized. RESULTS: This cohort consisted of 9 males and 1 female with a mean age of 32.1 ± 16.1 years. Diagnoses included 5 cases of osteosarcoma, 3 cases of chondrosarcoma and 1 each case of undifferentiated pleomorphic sarcoma and malignant myoepithelioma. The mean operative duration, intraoperative hemorrhage and postoperative length of hospitalization were 151.5 ± 61.0 min, 410.0 ± 353.4 ml and 5.3 ± 1.9 d, respectively. The mean follow-up duration was 29.3 ± 6.4 months, with a minimum of 24 months for the surviving patients. Two patients experienced local recurrence, and four patients developed distant metastases. Detachment of the taper occurred in two patients. One was managed conservatively, and the other received amputation due to concurrent tumor recurrence. The mean MSTS-93 and ASES scores and ranges of forwards flexion and abduction were 24.9 ± 3.1, 79.4 ± 8.3, 71.3 ± 19.4°, and 61.3 ± 16.4°, respectively. The functional outcomes were independent of the preservation of the axillary nerve. Histological study of the glenoid component showed evidence of bone ingrowth at the bone-prosthesis porous interface. CONCLUSION: Application of the 3D-printed arthrodesis prosthesis might be a safe and efficacious method for functional reconstruction in patients who underwent resection of the proximal humerus, especially for those without preservation of the axillary nerve.

Plate configuration for biological reconstructions of femoral intercalary defect - a finite element evaluation.

BACKGROUND AND OBJECTIVE: Biological reconstruction was commonly used for femoral intercalary defect. The initial stability by plate fixation was believed to have an effect on bone union and implant failure. Our study was proposed to explore relationship of plate configuration and initial stability for femoral intercalary reconstruction using allo-/autograft. METHODS: Femoral intercalary defect models were established with four different plate configurations: (1) Single lateral bridging plate, SLP (2) Lateral bridging plate + Orthogonal adjuvant plate, LP+OAP (3) Lateral bridging plate + Medial adjuvant plate, LP+MAP (4) Lateral bridging plate + Medial bridging plate, LP+MP. A diaphysis defect of 12 cm was simulated, and the removed native femoral bone was used as a structural allograft with the osteotomy gap of 2 mm. Models were analyzed by finite element simulations under an axial compression of 2000N and an axial moment of 10 Nm, respectively. RESULTS: Axial load: (1) The peak von Mises stress of SLP, LP+OAP, LP+MAP, LP+MP were 993.50 MPa, 335.63 MPa, 240.03 MPa, 281.73 MPa, respectively and LP+MAP was the lowest (p < 0.01); (2) The mean displacement of SLP, LP+OAP, LP+MAP, LP+MP was 0.765, 0.130, 0.121, 0.235 mm, respectively. LP+MAP showed the best stability while SLP had a crash in the medial proximal gap; (3) The LP+MAP configuration had the most uniform stress distribution and the lowest maximum von Mises stress of 79.7 MPa within plates. Axial torsional load: (1) The peak von Mises stress of SLP, LP+OAP, LP+MAP, LP+MP were 431.66Mpa, 120.73 MPa, 72.31 MPa, 109.86 MPa, respectively; (2) The rotation angle of SLP, LP+OAP, LP+MAP, LP+MP was 4.30°, 1.35°, 1.20°, 1.57°, respectively. All of LP+OAP, LP+MAP and LP+MP showed an optimal torsional stability. CONCLUSIONS: For femoral intercalary reconstruction using allo-/autograft fixed by plates, LP+MAP and LP+MP configurations showed superior stability in terms of axial compression and torsion load by FE simulation. A better stability was believed to be associated with higher union rate and lower hardware failure rate.

A clinical study of the hemodynamic and metabolic effects of Zone 3 REBOA for sacral and pelvic tumor resections.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a key procedure in sacral and pelvic tumor resection that provides hemorrhage control. However, few studies have been performed to capture the effects of REBOA in a nonshock condition and provide a detailed description of the changes occurring with prolonged occlusion time. This study aimed to examine the hemodynamic and metabolic effects of Zone 3 REBOA for sacral and pelvic tumor resections following different periods of REBOA. METHODS: In total, 121 patients who underwent surgical tumor resections of the pelvis and/or the sacrum with the use of aortic balloon occlusion were prospectively enrolled from October 2020 to December 2021. All cases were divided into Group A (occlusion time ≤ 60 min, n = 57) and Group B (occlusion time ≥ 90 min, n = 64). Physiologic parameters were continuously recorded, and laboratory specimens were obtained at regular intervals. RESULTS: Balloon inflation resulted in a significant increase in SBP from 106 to 120 mmHg and decreased to 96 mmHg immediately following balloon deflation. With the application of REBOA, the median blood loss was only 1200 ml (range, 400-7900). When deflating the REBOA, the arterial pH was lower than baseline (7.36 vs. 7.41, p < 0.01), the arterial lactate concentration increased from 0.9 to 1.4 mmol/L (p < 0.01), serum potassium measurements increased from 3.99 to 4.12 mmol/L, serum calcium measurements decreased from 2.31 to 2.04 mmol/L, and blood creatinine decreased from 64 to 60 µmol/L. The operating time of Group B was longer than that of patients in Group A, and the patients in Group B needed more blood units to be transfused. Although laboratory measurements, including pH, potassium, calcium, and blood creatinine, were at the same level in two groups comparison, the lactate was significantly higher in Group B after deflation (p = 0.01). CONCLUSIONS: The results of this study showed that acceptable hemodynamic and metabolic stability can be attained when the occlusion time of REBOA is more than 90 min, although the long duration of occlusion caused relatively higher lactate levels.

Factors associated with spinal fixation mechanical failure after tumor resection: a systematic review and meta-analysis.

BACKGROUND: No available meta-analysis has been published that systematically assessed spinal fixation mechanical failure after tumor resection based on largely pooled data. This systematic review and meta-analysis aimed to investigate the spinal fixation failure rate and potential risk factors for hardware failure. METHODS: Electronic articles published between January 1, 1979, and January 30, 2021, were searched and critically evaluated. The authors independently reviewed the abstracts and extracted data on the spinal fixation failure rate and potential risk factors. RESULTS: Thirty-eight studies were finally included in the meta-analysis. The pooled spinal fixation mechanical failure rate was 10%. The significant risk factors for hardware failure included tumor level and cage subsidence. Radiotherapy was a potential risk factor. CONCLUSION: The spinal fixation mechanical failure rate was 10%. Spinal fixation failure is mainly associated with tumor level, cage subsidence and radiotherapy. Durable reconstruction is needed for patients with these risk factors.

Ultra-Short Course of Neo-Adjuvant Denosumab for Nerve-Sparing Surgery for Giant Cell Tumor of Bone in Sacrum.

STUDY DEIGN: This was a retrospective study about sacral giant cell tumor of bone (GCTB). OBJECTIVE: This study aimed to investigate whether ultra-short course of neo-adjuvant denosumab treatment for sacral GCTB could (1) induce radiological and histological response? (2) Facilitate nerve-sparing surgery? (3) Achieve satisfactory oncological and functional outcomes? SUMMARY OF BACKGROUND DATA: Previous reports on long course of neo-adjuvant denosumab treatment for GCTB showed significant tumor response and a relatively high recurrent rate after curettage. METHODS: Sixty-six patients with sacral GCTB treated with neoadjuvant denosumab and nerve-sparing surgery were categorized into ultra-short course group (≤3 doses and operation within D21 since 1st dose, 41 patients) or conventional group (>3 doses or operation after D21 since 1st dose, 25 patients). The radiological and histological response, operative data, oncological and functional outcomes were compared. RESULTS: The ultra-short course group demonstrated fewer doses of neo-adjuvant denosumab (mean: 2.1 vs. 4.8, P  < 0.001) and shorter time to surgery (12.2 days vs. 72.3 days, P < 0.001). Similar patterns of radiological and histological response were observed in the two groups with less fibrosis and ossification in the ultra-short course group. The operative duration (199.9 min vs. 187.8 min, P = 0.364) and estimated blood loss (1552.4 mL vs. 1474.0 mL, P = 0.740) were comparable. Most (94.8%) of the patients received adjuvant denosumab. After a mean follow-up of 29.4 months, three cases (8.8%) and five cases (20.8%) showed local recurrence in each group (P = 0.255). The estimated recurrence-free survival (56.2 vs. 51.2 months, P = 0.210) and the functional status [Motor-Urination-Defecation scores: 25.9 vs. 25.7, P = 0.762] did not differ between the two groups. CONCLUSION: Ultra-short course of neo-adjuvant denosumab for sacral GCTB could elicit radiological and histological responses as conventional course did. The less degree of fibrosis and ossification might facilitate nerve-sparing surgery and help to achieve satisfactory local control and functional status.Level of Evidence: 4.