4539 Background: Previous studies have demonstrated the benefit of combining immunotherapy with antiangiogenic agents in patients with advanced renal cell carcinoma (aRCC). The efficacy of apatinib, a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor (TKI), has been documented in aRCC. In contrast, the efficacy of camrelizumab, a PD-1 inhibitor, has not been reported in RCC, although its efficacy and safety have been established in various cancer types. This study aims to evaluate the efficacy and safety of camrelizumab plus apatinib in aRCC following the failure of first-line TKI therapy. Methods: This multicenter, single-arm, phase II trial enrolled patients with aRCC who had failed first-line TKI treatment. Patients received 200 mg of camrelizumab intravenously every two weeks and 250 mg of apatinib orally once daily until disease progression or unacceptable toxicity occurred, with camrelizumab treatment lasting up to two years. The primary endpoint was progression-free survival (PFS) according to the Response Evaluation Criteria in Solid Tumors version 1.1. Results: Between August 2020 and January 2024, 35 patients were enrolled in the study and received treatment. The median age was 57 years (range: 39-81), with 31 (88.6%) being male. A total of 27 (77.1%) patients presented with lung metastases. As of the cut-off date, January 8, 2024, the median follow-up duration was 16.5 months (range: 0-33). Of these patients, 12 (34.3%) achieved a partial response, and 17 (48.6%) maintained stable disease, resulting in an objective response rate of 34.3% (95% confidence interval [CI], 19.1-52.2) and a disease control rate of 82.9% (95% CI, 66.4-93.4). Two out of five patients with progressive disease (PD) benefited from continued treatment with camrelizumab plus apatinib for more than 4 months after the first PD. The median PFS was 10.0 months (95% CI, 6.1-14.9), and the median overall survival was 28.4 months (95% CI, 19.7-not reached). Of all patients, 27 (77.1%) experienced treatment-related adverse events of grade 3 or higher, with the most common being proteinuria (25.7%), hypertension (20.0%), and alanine aminotransferase increased (14.3%) and aspartate aminotransferase increased (14.3%). Conclusions: The combination of camrelizumab and apatinib demonstrates encouraging antitumor activity and a favorable safety profile as a second-line treatment option for patients with aRCC. Clinical trial information: ChiCTR2000034384. [Table: see text]
Background: The ipsilateral renal parenchymal volume (RPV) experiences a sharp decrease shortly after partial nephrectomy (PN), mainly due to surgical remove or devascularization of kidney tissue. However, the subsequent change of RPV and its association with glomerular filtration rate (GFR) fast decline remains unknown. Our objective was to investigate the change of ipsilateral RPV and renal function status from new baseline (1–12 months after PN) to latest follow-up (≥1 year) after PN, and to explore factors associated with ipsilateral RPV decrease rate and correlation between RPV decrease and GFR fast decline. Materials and methods: A retrospective review of 367 patients with PN was conducted. Three-dimensional reconstruction of computed tomography (CT)/MRI images was performed for RPV calculation. Spectrum score was used to assess the degree of acute kidney injury (AKI) in the operated kidney after PN. GFR decline greater than 3 ml/min/1.73 m 2 /year was defined as GFR fast decline. One hundred fourteen patients underwent abdominal surgery was used as control. Predictive factors for subsequent decrease of RPV rate and GFR fast decline were evaluated by linear and logistic regression, respectively. Results: With a median interval time of 21.1 (interquartile range:13.8–35.5) months, median ipsilateral RPV significantly decreased from 118.7 (interquartile range:100.7–137.1) ml at new baseline to 111.8 (IQR: 92.3–131.3) ml at latest follow-up. The interval time [β: 1.36(0.71–2.01), P <0.001] and spectrum score [β: 5.83 (2.92–8.74), P <0.001] were identified as independent predictors of ipsilateral RPV decrease rate. GFR fast decline was observed in 101 (27.5%) patients. Annual ipsilateral RPV decrease rate [odds ratio:1.67 (1.05–2.67), P =0.03] and overweight [odds ratio:1.63 (1.02–2.60), P =0.04] were independent predictors of GFR fast decline. Conclusions: Ipsilateral RPV experienced a moderate but significant decrease during follow-up after PN, especially in those with severer acute kidney injury. The presence of GFR fast decline was found to be associated with reduction of ipsilateral RPV, particularly in overweight individuals.
Objective
To investigate the early outcomes of revision hip arthroplasty using restoration modular (RM) stem.
Methods
Fifty-nine patients underwent revision hip arthroplasty with RM stem from April 2012 to June 2015 in our center with a minimal of two years follow-up. The patients including 24 male and 35 female had a median age of 61.0 (56, 66) years. The median BMI was 24.0 (22.5, 26.0) kg/m2, while the median interval from the primary surgery was 10.5 (6.0, 14.5) years. The reasons for revision inculded infection in 8 patients, aseptic loosening in 45, recurrent dislocation in 1, and periprosthetic fracture in 5. There were 3 cases of type B2 and 2 cases of B3 periprosthetic fracture according to Vancouver classification. The bone defects severity was conducted according to Paprosky classification that 14 patients in type II, 31 in type IIIA, 8 in type IIIB, and 1 in type IV. Acetabular component were revised in 56 cases. Patients were followed up at 3 months, 6 months, 1 year and annually thereafter for clinical and radiological evaluation.
Results
All the patients were followed up with a median duration of 30.4 (27.3, 37.9) months, the median Harris score significantly improved from 37 (31, 53) points preoperatively to 84 (80, 95) points at the last follow up (Z=-6.681, P=0.000). There were 3 patients had perforation or fracture intra-operatively, two of them were fixed by strut allograft. The other one who did not compromise the implant stability was not fixed. Extended trochanteric osteotomy was applied in 14 cases and they healed well at 3-6 months during follow-up. There was one case of early dislocation at 6 days postoperatively, which was treated with close reduction and immobilization without recurrence. No infection, stem fracture, hematoma formation and sciatic nerve injury were reported. No femoral component loosening was identified at the latest follow-up. Median subsidence was 1.0 (0, 2.0) mm with the maximum case 6.0 mm and 3 cases 3.5 mm. All of subsidence developed within the first year postoperatively but without further aggravation. The affected leg lengthened 17.5±10.1 mm (range 2-40 mm) after operation. The affected leg was shorter 17.5±12.6 mm (shorter 44.4 mm to longer 3.0 mm) than that in the normal side pre-operatively. However, the distinction decreased to 0.1±9.6 mm postoperatively (shorter 24.8 mm to longer 22.4 mm, t=-10.538, P=0.000).
Conclusion
Early satisfactory results are achieved in hip revision using RM modular stem at the femoral side. The modular design could simplify the surgical procedure with better control of leg length and joint stability. Long-term follow-up is still required for further evaluation.
Key words:
Arthroplasty, replacement, hip; Femur; Reoperation; Prosthesis design; Osteolysis; Periprosthetic fractures; Prosthesis failure
Periodontitis is an oral infectious disease that occurs in the tooth supporting tissues, which damages the soft and hard tissues of the periodontium and eventually results in tooth mobility and loss. Traditional clinical treatment can effectively control the periodontal infection and inflammation. However, as the therapeutic effect depending on the local condition of periodontal defect and the systemic factors of patients, it's hard to achieve satisfactory and stable periodontal tissue regeneration for damaged periodontal tissues. Recently, as a promising therapeutic strategy in periodontal regeneration, mesenchymal stem cells (MSC) play an important role in modern regenerative medicine. Combined with the clinical translational researches of MSC in periodontal tissue engineering and the research results of our group in the past decade, it is summarized and explained the mechanism of MSC promoting periodontal regeneration, the preclinical and the clinical transformation researches as well as the future application prospects of MSC in periodontal regeneration therapy in this paper.牙周炎是发生于牙周支持组织的口腔感染性疾病，其破坏牙齿周围软硬组织，最终引发牙齿松动脱落。目前的临床治疗手段可有效控制牙周感染及炎症，但对已遭到破坏的牙周组织，由于受到牙周缺损局部状况和患者全身因素的影响，传统牙周治疗方式尚不能达到满意且稳定的牙周组织再生。近年基于间充质干细胞（mesenchymal stem cells，MSC）的牙周组织再生治疗代表了一种很有前景的治疗策略，在现代再生医学中发挥了不可忽略的作用。本文结合近10年MSC在牙周组织工程中的临床转化应用研究及本课题组前期研究成果，对MSC促进牙周组织再生的机制、MSC在牙周组织再生治疗中的临床前研究、临床转化研究及MSC未来的应用前景进行总结和阐述，以期为后续开展MSC相关研究及临床试验提供参考。.
There are limited therapeutic options for patients with advanced penile squamous cell carcinoma (PSCC) after chemotherapy failure. Thus, we evaluated the feasibility of salvage treatment using the epidermal growth factor receptor (EGFR) mono-antibody nimotuzumab in chemotherapy-failed PSCC patients and explored potential response or resistance biomarkers. Six chemotherapy-failed PSCC patients with locally advanced disease or distant metastasis were enrolled consecutively to nimotuzumab treatment. Clinical responses and side effects were evaluated, and genetic characteristics of cancer specimens were analyzed through the next-generation sequencing of hotspot regions in cancer-related genes. Two of 6 patients showed partial responses, one was identified as having stable disease, while the other 3 had disease progression after nimotuzumab therapy. Side effects were all welltolerated. Genetic analysis revealed that TP53, CDKN2A, RB1, SMAD4, FLT3, and PIK3CA were the most frequently mutated genes in PSCC specimens, while altered KRAS, HRAS, EGFR, ERBB2, and FLT3 may be correlated with nimotuzumab resistance. Furthermore, 3 patients that were human papillomavirus-positive each showed clinical response or stable disease. EGFR mono-antibody may be a potential modality for locally advanced PSCC patients after chemotherapy failure. Further large-scale clinical studies are needed to elucidate the role of human papillomavirus status and critical gene mutations in the clinical response to EGFR-targeted therapy.
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