Copper-Mediated Decarboxylative Coupling of 3-Indoleacetic Acids with Sulfoxonium Ylides for the Synthesis of α-Acetoxyl Ketones.

The most convenient and direct method of synthesizing an α-acyloxy ketone is the reaction of a diazo compound with a carboxylic acid via O-H insertion. However, due to the limitations in preparing and storing diazo compounds, the application of this method is restricted. In this study, Cu(OAc)2-mediated (OAc = acetate) decarboxylative coupling reactions of 3-indoleacetic acids with sulfoxonium ylides were developed for use in rapidly synthesizing α-acetoxyl ketones. In this reaction, Cu(OAc)2 was not only used as an oxidant, but also as acetate ion source. Notably, when 5-methoxy-2-methyl-3-indoleacetic acid reacted with different sulfoxonium ylides, the corresponding products exhibited fluorescence, and furthermore, several products displayed antiproliferative activities against various human cancer cell lines.

Intentional Dural Resection during en bloc Spinal Resection Could Provide a Secure Surgical Margin for Patients with Recurrent Spinal Tumors.

OBJECTIVE: It is always difficult to obtain a comfortable surgical margin for patients with recurrent malignant or invasive benign spinal tumors. Tumor intraspinal invasion and dural adhesion are the essential reasons. There are always residual tumor cells maintained at the edge of dura. Dural resection is a key point to obtain a comfortable surgical margin for such cases. Whether such patients benefit from this risky surgical procedure is unknown. This study aims to understand better the oncological results, associated risks, and neurological function of this risky surgical procedure. METHODS: We retrospectively reviewed clinical data from six consecutive patients who registered spinal tumors in our institute and underwent dural resection during en bloc spinal resection from June 2013 to May 2020. The demographic and perioperative data, oncological outcomes, complications, and neurological status were collected and analyzed. RESULTS: All six patients were followed up for 24 to 46 months (mean follow-up time: 32.8 months). Local recurrence was detected in one patient (1/6, 16.7%) at 36 months postoperatively and in five patients with no evidence of disease at the last follow up (survival rate 83.3%). Eleven complications occurred in four patients (66.7%), and the dural resection-related complications included only four cases of cerebrospinal fluid leakage (CSFL), which accounted for 36.4% (4/11) of all complications. Neurologic status evaluated by the Frankel grade showed improvement of one grade in one case and deterioration of one to two grades in five patients immediately after surgery. All deterioration cases recovered to the preoperative level 6 months after the operation. CONCLUSION: Dural resection is significant for patients with dura matter invaded by recurrent primary malignant or invasive benign spinal tumors with the purpose of clinical cure. This study demonstrated that in strictly selected cases, intentional dural resection could provide satisfying local control and long-term disease-free survival with acceptable complications and satisfying neurological function.

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.

Assessing the influence of gastrocnemius reconstruction on stress distribution of femoral tumor rotating hinge knee prosthesis via finite element analysis.

Background: After femoral oncological knee arthroplasty, some patients suffer from rotating axis fracture, which significantly impacts the life span of the rotating hinge knee (RHK) prosthesis. This research aimed to analyze the biomechanical response of anatomical gastrocnemius reconstruction and assess whether it could reduce the risk of rotating axis breakage by finite element (FE) analysis. Methods: A femur-prosthesis-tibia FE model was established using the data from CT scans. The mechanical properties of the RHK implant were quantitatively compared before and after gastrocnemius reconstruction at 6 angles: 10°, 20°, 30°, 40°, 50°, and 60°. Results: Our results showed that gastrocnemius reconstruction effectively altered the stress distribution around the rotating axis, considerably relieving the stress in the fracture-prone region. In addition, the peak stress in the rotating axis, bending axis, prosthesis stem, and femoral condyles decreased variably. Conclusion: In distal femoral resection knee arthroplasty, the rebuilding of gastrocnemius substantially improved the stress distribution within the prosthesis, thereby having the potential to reduce the risk of prosthetic fracture and prolong the overall durability of the prosthesis.

Lumbar functional evaluation of pelvic bone sarcomas after surgical resection and spinal pelvic fixation: A clinical study of 304 cases.

AIMS: We endeavored to introduce a novel scoring system (Lumbar Functional Index, LFI) capable of evaluating lumbar function in pelvic bone sarcoma patients who underwent surgical resection and spinal pelvic fixation, while simultaneously identifying the incidence, outcomes, and risk factors of lumbar function impairment among these populations. PATIENTS AND METHODS: A cohort of 304 primary bone sarcoma patients were recruited. The LFI was created based on the Oswestry Dysfunction Index (ODI) and Japanese Orthopaedic Association (JOA) scores. Lumbar function impairment was defined as LFI score ≥ 18 points, which was identified as high LFI. Demographic data, clinical characteristics, and oncological outcomes were analyzed. RESULTS: The cohort included chondrosarcoma (39.8%), osteosarcoma (29.9%), Ewing sarcoma (8.6%), bone-derived undifferentiated pleomorphic sarcoma (7.2%), giant cell tumor of bone (7.2%), chordoma (2.3%), and other bone sarcomas (5.0%). The LFI score exhibited significant negative correlation with common scoring systems of bone sarcoma. The incidence of high LFI was 23.0%. Patients with high LFI demonstrated a higher prevalence of type I + II + III + IV pelvic tumor, more sacrificed nerve roots and bilateral lumbar spine fixation during surgery, while lower percentage of R0 resection and local control of pelvic tumor. Decreased median overall survival (30 vs. 52 months, p < 0.001) and recurrence-free survival (14 vs. 24 months, p < 0.001) time were observed in these patients. Type I + II + III + IV pelvic tumor and sacrificed nerve roots≥2 were identified as risk factors for high LFI, while R0 resection and local control were identified as protective factors. CONCLUSION: The LFI scoring system exhibited a significant negative correlation to current scoring systems. High LFI patients had worse prognosis and distinct characteristics. The risk factors of high LFI included type I + II + III + IV pelvic tumor and sacrificed nerve roots≥2, and the protective factors included R0 resection and local control.

Exploiting biochemical data to improve osteosarcoma diagnosis with deep learning.

Early and accurate diagnosis of osteosarcomas (OS) is of great clinical significance, and machine learning (ML) based methods are increasingly adopted. However, current ML-based methods for osteosarcoma diagnosis consider only X-ray images, usually fail to generalize to new cases, and lack explainability. In this paper, we seek to explore the capability of deep learning models in diagnosing primary OS, with higher accuracy, explainability, and generality. Concretely, we analyze the added value of integrating the biochemical data, i.e., alkaline phosphatase (ALP) and lactate dehydrogenase (LDH), and design a model that incorporates the numerical features of ALP and LDH and the visual features of X-ray imaging through a late fusion approach in the feature space. We evaluate this model on real-world clinic data with 848 patients aged from 4 to 81. The experimental results reveal the effectiveness of incorporating ALP and LDH simultaneously in a late fusion approach, with the accuracy of the considered 2608 cases increased to 97.17%, compared to 94.35% in the baseline. Grad-CAM visualizations consistent with orthopedic specialists further justified the model's explainability.

Fluoroscopically calibrated 3D-printed patient-specific instruments improve the accuracy of osteotomy during bone tumor resection adjacent to joints.

BACKGROUND: Inadequate surface matching, variation in the guide design, and soft tissue on the skeletal surface may make it difficult to accurately place the 3D-printed patient-specific instrument (PSI) exactly to the designated site, leading to decreased accuracy, or even errors. Consequently, we developed a novel 3D-printed PSI with fluoroscopy-guided positioning markers to enhance the accuracy of osteotomies in joint-preserving surgery. The current study was to compare whether the fluoroscopically calibrated PSI (FCPSI) can achieve better accuracy compared with freehand resection and conventional PSI (CPSI) resection. METHODS: Simulated joint-preserving surgery was conducted using nine synthetic left knee bone models. Osteotomies adjacent to the knee joint were designed to evaluate the accuracy at the epiphysis side. The experiment was divided into three groups: free-hand, conventional PSI (CPSI), and fluoroscopically Calibrated PSI (FCPSI). Post-resection CT scans were quantitatively analyzed. Analysis of variance (ANOVA) was used. RESULT: FCPSI improved the resection accuracy significantly. The mean location accuracy is 2.66 mm for FCPSI compared to 6.36 mm (P < 0.001) for freehand resection and 4.58 mm (P = 0.012) for CPSI. The mean average distance is 1.27 mm compared to 2.99 mm (p < 0.001) and 2.11 mm (p = 0.049). The mean absolute angle is 2.16° compared to 8.50° (p < 0.001) and 5.54° (p = 0.021). The mean depth angle is 1.41° compared to 8.10° (p < 0.001) and 5.32° (p = 0.012). However, there were no significant differences in the front angle compared to the freehand resection group (P = 0.055) and CPSI (P = 0.599) group. The location accuracy observed with FCPSI was maintained at 4 mm, while CPSI and freehand resection exhibited a maximum deviation of 8 mm. CONCLUSION: The fluoroscopically calibrated 3D-printed patient-specific instruments improve the accuracy of osteotomy during bone tumor resection adjacent to joint joints compared to conventional PSI and freehand resection. In conclusion, this novel 3D-printed PSI offers significant accuracy improvement in joint preserving surgery with a minimal increase in time and design costs.

Direct contact between tumor cells and platelets initiates a FAK-dependent F3/TGF-ß positive feedback loop that promotes tumor progression and EMT in osteosarcoma.

Platelets have received growing attention for their roles in hematogenous tumor metastasis. However, the tumor-platelet interaction in osteosarcoma (OS) remains poorly understood. Here, using platelet-specific focal adhesion kinase (FAK)-deficient mice, we uncover a FAK-dependent F3/TGF-ß positive feedback loop in OS. Disruption of the feedback loop by inhibition of F3, TGF-ß, or FAK significantly suppresses OS progression. We demonstrate that OS F3 initiated the feedback loop by increasing platelet TGF-ß secretion, and platelet-derived TGF-ß promoted OS F3 expression in turn and modulated OS EMT process. Immunofluorescence results indicate platelet infiltration in OS niche and we verified it was mediated by platelet FAK. In addition, platelet FAK was proved to mediate platelet adhesion to OS cells, which was vital for the initiation of F3/TGF-ß feedback loop. Collectively, these findings provide a rationale for novel therapeutic strategies targeting tumor-platelet interplay in metastatic OS.

Intraoperative Resection Guidance and Rapid Pathological Diagnosis of Osteosarcoma using B7H3 Targeted Probe under NIR-II Fluorescence Imaging.

Complete removal of all tumor tissue with a wide surgical margin is essential for the treatment of osteosarcoma (OS). However, it's difficult, sometimes impossible, to achieve due to the invisible small satellite lesions and blurry tumor boundaries. Besides, intraoperative frozen-section analysis of resection margins of OS is often restricted by the hard tissues around OS, which makes it impossible to know whether a negative margin is achieved. Any unresected small tumor residuals will lead to local recurrence and worse prognosis. Herein, based on the high expression of B7H3 in OS, a targeted probe B7H3-IRDye800CW is synthesized by conjugating anti-B7H3 antibody and IRDye800CW. B7H3-IRDye800CW can accurately label OS areas after intravenous administration, thereby helping surgeons identify and resect residual OS lesions (<2 mm) and lung metastatic lesions. The tumor-background ratio reaches 4.42 ± 1.77 at day 3. After incubating fresh human OS specimen with B7H3-IRDye800CW, it can specifically label the OS area and even the microinvasion area (confirmed by hematoxylin-eosin [HE] staining). The probe labeled area is consistent with the tumor area shown by magnetic resonance imaging and complete HE staining of the specimen. In summary, B7H3-IRDye800CW has translational potential in intraoperative resection guidance and rapid pathological diagnosis of OS.

Clinical outcomes in patients with neurological disorders following periacetabular tumor removal and endoprosthetic reconstruction of the hemipelvis.

Background: Surgical treatment of musculoskeletal tumors in the periacetabular region present extremely difficult due to the complex anatomy and need for reconstruction. Orthopedic surgeons face more difficulties in patients with neurological conditions, which can cause increased muscle tone, an elevated risk of fractures, and compromised bone quality. There is limited evidence regarding endoprosthetic reconstruction for periacetabular tumors in individuals with neurological disorders. Methods: We conducted a single-center retrospective study to examine the outcomes of patients with preexisting neurological conditions who underwent surgery to remove periacetabular tumors and who underwent endoprosthesis reconstruction. Clinical presentation, detailed neurological conditions, complications, and functional outcomes were studied. Results: Sixteen out of the 838 patients were identified (1.91%), with a mean follow-up time of 33 months. The primary neurological conditions encompassed Parkinson's disease, Alzheimer's disease, dementia, and cerebral ischemic stroke. Every patient was diagnosed with periacetabular lesions that were either primary or oligometastatic. They underwent tumor resection and subsequently received endoprosthetic reconstruction of the hemipelvis. Three patients developed metastasis lesions later, and two patients experienced tumor recurrence. Five cases experienced hip dislocation-one with periprosthetic fracture and one with surgical site infection. The position of the prosthetic rotating center was not correlated with dislocation. The reoperation rate was 31.25%. The cohort of patients all presented with more extended hospital stays and rehabilitation. In 3 patients, the general functional score was good, while in 6 patients, it was fair; in 7 patients, it was regarded as poor. The average MSTS93 score was 49.71%. Conclusion: Endoprosthetic reconstruction after periacetabular tumor resection is an effective way to eliminate tumors and salvage limbs. However, this group of patients has an increased likelihood of secondary surgery, complications, extended hospital stay, and no significant improvement in functional outcomes. Despite the diverse nature of the cohort, it is recommended to consider enhanced soft tissue reconstruction, supervised functional recovery and rehabilitation training.

Two-step osteotomy/discectomy through cannulated screw (TOCS) technique for en bloc resection of spine tumor: surgical technique and preliminary results.

PURPOSE: We have developed a novel technique for osteotomy/discectomy during en bloc resection of spine tumors named two-step osteotomy/discectomy through cannulated screw (TOCS). This study aims at describing the procedure of TOCS technique and assessing its efficiency and safety. METHODS: We retrospectively reviewed fourteen patients who underwent en bloc resection for spine tumors using TOCS technique in our center between August 2018 and September 2022. The technique was based on a specially designed "slotted" cannulated screw which was a cannulated screw with a longitudinal slot to provide the accessibility of T-saw. During osteotomy/discectomy, the "slotted" cannulated screw was inserted obliquely along the plane between the dura and the posterior wall of spine in light of the planned osteotomy/discectomy plane under routine fluoroscopic imaging guidance. The T-saw was introduced through the screw, and the osteotomy/discectomy was performed sequentially in two steps under the guidance of the screw by turning the slot away and toward the dura. The intra-/perioperative complication, neurological function (determined by Frankel grading), surgical margin (determined by a pathologist using AJCC R system), follow-up details were documented. RESULTS: The mean duration of surgery was 599.3 (360-890) min with a mean volume of intra-operative hemorrhage of 2021.4 (800-5000) mL. The intra-/perioperative complications were found in four patients (28.6%). R0 and R1 resections were achieved in nine and five patients, respectively. There was no R2 resection. After a mean follow-up period of 30.6 (10-67) months, all patients were alive except one patient died ten months after surgery due to unrelated cause. No recurrence and implant failure were found. Thirteen patients (92.9%) exhibited completely normal neurological function same as their preoperative neurological status. CONCLUSION: Using TOCS technique can facilitate a precise, complete and safe osteotomy/discectomy procedure during en bloc resection for spine tumor without the aid of intra-operative navigation.

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.

Controlled siRNA Release of Nanopolyplex for Effective Targeted Anticancer Therapy in Animal Model.

Introduction: Spatiotemporally controlled release of siRNA for anti-tumor therapy poses significant challenges. Near-infrared (NIR) light, known for its exceptional tissue penetration and minimal tissue invasiveness, holds promise as a viable exogenous stimulus for inducing controlled siRNA release in vivo. However, the majority of light-responsive chemical bonds exhibit absorption wavelengths in the ultraviolet (UV) or short-wavelength visible light range. Methods: To achieve NIR-controlled siRNA release, the study synthesized a UV-sensitive triblock copolymer cRGD-poly(ethylene glycol)-b-poly(aspartic acid ester-5-(2'-(dimethylamino)ethoxy)-2-nitrobenzyl alcohol)-b-polyphenylalanine, abbreviated as cRGD-PEG-PAsp(EDONB)-PPHE. This copolymer is composed of a cRGD-capped PEG block (cRGD-PEG), a poly(aspartate) block modified with cationic moieties through UV-cleavable 2-nitrobenzyl ester bonds [PAsp(EDONB)], and a hydrophobic polyphenylalanine block (PPHE). The cationic amphiphilic polymer cRGD-PEG-PAsp(EDONB)-PPHE can assemble with hydrophobic upconversion nanoparticles (UCNPs) to form a cationic micelle designated as T-UCNP, which subsequently complexes with siRNA to create the final nanopolyplex T-si/UCNP. siRNA-PLK1 was employed to prepare T-PLK1/UCNP nanopolyplex for anti-tumor therapy. Results: T-PLK1/UCNP not only exhibited outstanding tumor cell targeting through cRGD modification but also achieved 980 nm NIR-controlled PLK1 gene silencing. This was achieved by utilizing the encapsulated UCNPs to convert NIR into UV light, facilitating the cleavage of 2-nitrobenzyl ester bonds. As a result, there was a significant suppression of tumor growth. Conclusion: The UCNPs-encapsulated nanopolyplex T-si/UCNP, capable of co-delivering siRNA and UCNPs, enables precise NIR-controlled release of siRNA at the tumor site for cancer RNAi therapy. This nanopolyplex can enhance the controllability and safety of RNAi therapy for tumors, and it also holds the potential to serve as a platform for achieving controlled release and activation of other drugs, such as mRNA and DNA.

The application of extended reality technology-assisted intraoperative navigation in orthopedic surgery.

Extended reality (XR) technology refers to any situation where real-world objects are enhanced with computer technology, including virtual reality, augmented reality, and mixed reality. Augmented reality and mixed reality technologies have been widely applied in orthopedic clinical practice, including in teaching, preoperative planning, intraoperative navigation, and surgical outcome evaluation. The primary goal of this narrative review is to summarize the effectiveness and superiority of XR-technology-assisted intraoperative navigation in the fields of trauma, joint, spine, and bone tumor surgery, as well as to discuss the current shortcomings in intraoperative navigation applications. We reviewed titles of more than 200 studies obtained from PubMed with the following search terms: extended reality, mixed reality, augmented reality, virtual reality, intraoperative navigation, and orthopedic surgery; of those 200 studies, 69 related papers were selected for abstract review. Finally, the full text of 55 studies was analyzed and reviewed. They were classified into four groups-trauma, joint, spine, and bone tumor surgery-according to their content. Most of studies that we reviewed showed that XR-technology-assisted intraoperative navigation can effectively improve the accuracy of implant placement, such as that of screws and prostheses, reduce postoperative complications caused by inaccurate implantation, facilitate the achievement of tumor-free surgical margins, shorten the surgical duration, reduce radiation exposure for patients and surgeons, minimize further damage caused by the need for visual exposure during surgery, and provide richer and more efficient intraoperative communication, thereby facilitating academic exchange, medical assistance, and the implementation of remote healthcare.

Enhanced recovery after surgery (ERAS) in sacral tumour surgery and comprehensive description of a multidisciplinary program: a prospective study in a specialized hospital in China.

PURPOSE: There were fewer data to guide the application of enhanced recovery after surgery (ERAS) theory into sacral tumour surgery. In the present study, we were aiming to describe a multidisciplinary program of ERAS and evaluate the availability in sacral tumour surgery. METHODS: This was a prospective study of patients with sacral tumour between March 2021 and September 2021 at a single centre. We proposed a multidisciplinary program of ERAS for pre-admission, preoperative, intraoperative, postoperative, and post-discharge clinical care which positively influenced outcomes of patients with sacral tumour. All patients were prospectively assigned into two groups, ERAS group in which patients received ERAS protocols (n = 63), No-ERAS group in which patients had conventional clinical pathways (n = 62). Patient data were collected which included demographics, preoperative preparation, detailed information of surgical procedure, 60-day reoperation rate, 60-day readmission, postoperative length of stay (PLOS), time to first ambulation and flatus after surgery, time to removal of last drainage tube, and visual analogue scale (VAS) score at first ambulation and discharge. Complications referred to ones that occurred within 60 days after surgery. The above parameters were compared between ERAS group and No-ERAS group. RESULTS: Time to first ambulation after surgery in ERAS group (mean 20.9 h) was significantly shorter than that in No-ERAS group (mean 104.3 ho). Meanwhile, time to first flatus after surgery in ERAS group (mean 26.7 h) was also significantly shorter than that in No-ERAS group (mean 37.3 h). Patients in ERAS group had statistically shorter PLOS (10.7 days) as compared to that in No-ERAS group (13.8 days). In ERAS group, 19 of 63 patients (30.2%) were discharged within seven days after surgery as compared to seven of 62 patients (11.3%) in No-ERAS group. VAS score at first ambulation in ERAS group was not obviously higher than that in No-ERAS group though the time of first ambulation in ERAS group was statistically earlier than one in No-ERAS group. Furthermore, VAS score at discharge in ERAS group was significantly lower than that in No-ERAS group. The rate of postoperative incision necrosis was 6.3% (4/63) in ERAS group and 8.1% (5/62) in No-ERAS group and all of these nine patients underwent reoperation before discharge. The difference was not statistically significant in the wound complication of incision necrosis and 60-day reoperation rate. Only one readmission occurred in No-ERAS group due to the surgical site infection and also there was no significant difference of 60-day readmission rate between these two groups. Furthermore, there was no statistical difference of complications of femoral artery thrombosis and rectal rupture between ERAS group and No-ERAS group. CONCLUSIONS: Our proposed ERAS pathway for sacral tumour surgery and early walking facilitate safe and prompt discharge. ERAS protocols of sacral tumour surgery could decrease PLOS without significantly increasing postoperative complications, 60-day readmission rate and 60-day reoperation rate. The application of ERAS pathway in the field of sacral tumour surgery should have personalized feature with regard to resection type.

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.

Transition-Metal-Free Base-Promoted Deaminative Coupling of Gramines with Aminomaleimides.

The direct utilization of amines for C-C bond formation without prefunctionalization remains a significant challenge. Herein, we report the base-promoted deaminative coupling of gramines with aminomalaimides under redox-neutral conditions. In this operationally simple reaction, a series of indolmethyl-substituted aminomaleimides that emitted fluorescence were synthesized in good-to-excellent yields. Biological evaluation revealed that some products exhibited antiproliferative activity against human cancer cell lines.

Exploratory study of an anti-PD-L1/TGF-ß antibody, TQB2858, in patients with refractory or recurrent osteosarcoma and alveolar soft part sarcoma: a report from Chinese sarcoma study group (TQB2858-Ib-02).

BACKGROUND: Novel and effective immunotherapies are required for refractory or recurrent sarcomas. Transforming growth factor-beta (TGF-ß) is a diverse regulatory and fibrogenic protein expressed in multiple sarcoma tumors that promotes epithelial-mesenchymal transition and excessive deposition of extracellular matrix. This study evaluated the efficacy and safety of the anti-PD-L1/TGF-ß antibody TQB2858 in patients with refractory osteosarcoma and alveolar soft part sarcoma (ASPS). METHODS: This single-arm phase 1b exploratory study included patients with refractory osteosarcoma or ASPS who had previously undergone at least two lines of systemic therapy. Patients were administered 1200 mg of TQB2858 once every 3 weeks. The primary endpoint was objective response rate (ORR), with null and alternative hypotheses of ORR ≤5% and ≥20%, respectively. Exploratory biomarker analyses using immunohistochemistry (IHC) staining (for PD-L1 and TGF-ß) were performed on pre-treatment tumor samples. RESULTS: Eleven eligible patients were included in this study. TQB2858 did not demonstrate evidence of efficacy as 0/5 osteosarcomas had any objective response, while 2/6 ASPS showed a partial response. The median progression-free survivals were 1.51 (1.38, Not Evaluable) and 2.86 (1.38, Not Evaluable) months for the osteosarcoma and ASPS groups, respectively. None of the administered cycles met the criteria for unacceptable toxicity. Other Grade 3 toxicities included abnormal liver function and elevation of γ-glutamyl transferase. IHC analysis revealed that functional enrichment in the TGF-ß pathway or PD-L1 was not associated with treatment outcomes. CONCLUSIONS: The combination of PD-L1 and TQB2858 did not significantly improve the ORR in patients with recurrent osteosarcoma. However, it improved immunogenic responses in ASPS, even after progression upon anti-PD-1/PD-L1 therapy, with an acceptable safety profile. IHC profiling with pathway enrichment analysis may not have any predictive value for survival outcomes. TRIAL REGISTRATION: Prospectively registered in the Ethical Review Committee of Peking University People's Hospital. The trial registration number is 2021PHA105-001 and 2021PHA140-001 and the registration date was March 2, 2022. CLINICALTRIALS: gov Identifier CTR20213001 and CTR20220390.

The role of tumor immune microenvironment in chordoma: promising immunotherapy strategies.

Chordoma is a rare malignant bone tumor with limited therapeutic options, which is resistant to conventional chemotherapy and radiotherapy, and targeted therapy is also shown with little efficacy. The long-standing delay in researching its mechanisms of occurrence and development has resulted in the dilemma of no effective treatment targets and no available drugs in clinical practice. In recent years, the role of the tumor immune microenvironment in driving tumor growth has become a hot and challenging topic in the field of cancer research. Immunotherapy has shown promising results in the treatment of various tumors. However, the study of the immune microenvironment of chordoma is still in its infancy. In this review, we aim to present a comprehensive reveal of previous exploration on the chordoma immune microenvironment and propose promising immunotherapy strategies for chordoma based on these characteristics.

Dielectric phenomena of multiferroic oxides at acoustic- and radio-frequency.

In this review, an overview of acoustic- and radio-frequency frequency dielectric properties of multiferroic oxides, the significant dynamic response of electrical polarization to small external ac electrical fields, are present based on the reports in literatures and our recent experimental progresses. The review is begun with some basic terms, concepts and mechanisms associated with dielectric response and dielectric anomalies, namely dielectric peak and plateau upon varying temperatures and dielectric relaxations upon varying frequencies. Subsequently, a variety of quantitative analyses and descriptions of various dielectric effects, including dielectric relaxation, relaxational and transport dynamics, ac conductivity, equivalent circuit models and impedance spectroscopy, are summarized in details. Next is the kernel section. We thoroughly outline various physical mechanisms behind acoustic-/radio-frequency dielectric responses and anomalies of multiferroic oxides. Spin order transition/spin rotation, charge disorder-order transition, exchange striction of the spin interactions, spin-dependentp-dhybridization mechanism, quantum electric-dipole liquids, the interaction of spin order and quantum paraelectric, the motions of charged defects and carriers, quasi-intrinsic and extrinsic heterogeneous interfaces, polar relaxor and multiglass, ferroic domain wall/boundary motions, etc, are involved in these mechanisms. Meanwhile, particular emphasis is placed on intrinsic or extrinsic magnetodielectric effects and related mechanisms in multiferroic oxides. Finally, the review ends with a short perspective of future dielectric research in multiferroic oxides. This review is able to provide the detailed and unique insights into abundant underlying fundamental physics in multiferroic oxides as well as the potential multiferroics-based technological applications.