Anti-PD-L1 antibody retains antitumour effects while mitigating immunotherapy-related colitis in bladder cancer-bearing mice after CT-mediated intratumoral delivery.

Drug local delivery system that directly supply anti-cancer drugs to the tumor microenvironment (TME) results in excellent tumor control and minimizes side effects associated with the anti-cancer drugs. Immune checkpoint inhibitors (ICIs) have been the mainstay of cancer immunotherapy. However, the systemic administration of ICIs is accompanied by considerable immunotherapy-related toxicity. To explore whether an anti-PD-L1 antibody administered locally via a sustained-release gel-forming carrier retains its effective anticancer function while causing fewer colitis-like side effects, CT, a previously reported depot system, was used to locally deliver an anti-PD-L1 antibody together with curcumin to the TME in bladder cancer-bearing ulcerative colitis model mice. We showed that CT-mediated intratumoral coinjection of an anti-PD-L1 antibody and curcumin enabled sustained release of both the loaded anti-PD-L1 antibody and curcumin, which contributed to substantial anticancer effects with negligible side effects on the colons of the UC model mice. However, although the anti-PD-L1 antibody administered systemically synergized with the CT-mediated intratumoral delivery of curcumin in inhibiting tumour growth, colitis was significantly worsened by intraperitoneal administration of anti-PD-L1 antibody. These findings suggested that CT is a promising agent for the local delivery of anticancer drugs, as it can allow effective anticancer functions to be retained while sharply reducing the adverse side effects associated with the systemic administration of these drugs.

A real-world study of recombinant human endostatin combined with PD-1/PD-L1 blockade and chemotherapy for patients with advanced non-small cell lung cancer negative for actionable molecular biomarkers.

The ongoing ENPOWER study exploring the efficacy and safety of the recombinant human endostatin (endostar) combined with programmed cell death 1 antibody sintilimab and chemotherapy showed encouraging efficacy and safety in advanced non-squamous non-small cell lung cancer. To evaluate the real-world efficacy and safety of endostar combined with immune checkpoint inhibitor and chemotherapy (EIC) for advanced non-squamous non-small cell lung cancer patients negative for actionable molecular biomarkers (NSCLCnm), patients with advanced NSCLCnm hospitalized to Zhejiang Provincial People's Hospital from January 2020 to December 2022 were screened for eligibility. The included patients were analyzed for the objective response rate (ORR) and disease control rate (DCR). The pre- and posttreatment expression levels of serum tumor associated biomarkers, chemokines and subpopulations of immune cells in peripheral blood were compared. For the 31 patients with advanced NSCLCnm treated with EIC, the median follow-up and treatment cycles were 18.0 months and 4, respectively. The ORR and DCR were 38.7% and 90.3%, respectively. For those who received EIC as first-line treatment, the ORR and DCR were 63.2% and 94.7%, respectively. EIC significantly decreased expression levels of carcinoma antigen 125, carcinoma embryonic antigen and cytokeratin 19 (P<0.05) in patients who were partial remission or stable disease. Among the 31 patients, 27 (87.1%) experienced at least 1 treatment-related adverse events, and 13 (41.9%) had the treatment-related adverse events of grade 3 or higher. No antiangiogenesis-related adverse events were observed. The current study showed that EIC was potentially effective for patients with NSCLCnm, especially when used as first-line therapy, and well tolerated.

Case Report: Life-threatening pancytopenia with tislelizumab followed by cerebral infarction in a patient with lung adenocarcinoma.

Immune checkpoint inhibitors (ICIs) are an integral antitumor therapy for many malignancies. Most patients show very good tolerability to ICIs; however, serious immune-related adverse events (irAEs) with ICIs have been well documented and prevent some patients from continuing ICIs or even become the direct cause of patient death. Cytopenia is a rare irAE but can be life-threatening. Here, we present the case of a 66-year-old male patient with metastatic lung adenocarcinoma who received two doses of chemotherapy + PD-1 antibody tislelizumab and developed pancytopenia after each dose. Although the first episode of pancytopenia resolved with a treatment regimen of granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), and red blood cell and platelet transfusion, the second episode showed extreme resistance to these treatments and improved only after the administration of steroids. His second pancytopenia episode resolved after a long course of treatment with methylprednisolone, G-CSF, TPO, hetrombopag and multiple red blood cell and platelet transfusions. However, he suffered a cerebral infarction when his platelet count was in the normal range and gradually recovered 1 week later. This case highlights the importance of the early recognition and management of hematological irAEs.

Perioperative Protocol of Ankle Fracture and Distal Radius Fracture Based on Enhanced Recovery after Surgery Program: A Multicenter Prospective Clinical Controlled study.

Background: The enhanced recovery after surgery (ERAS) program is aimed to shorten patients' recovery process and improve clinical outcomes. This study aimed to compare the outcomes between the ERAS program and the traditional pathway among patients with ankle fracture and distal radius fracture. Methods: This is a multicenter prospective clinical controlled study consisting of 323 consecutive adults with ankle fracture from 12 centers and 323 consecutive adults with distal radial fracture from 13 centers scheduled for open reduction and internal fixation between January 2017 and December 2018. According to the perioperative protocol, patients were divided into two groups: the ERAS group and the traditional group. The primary outcome was the patients' satisfaction of the whole treatment on discharge and at 6 months postoperatively. The secondary outcomes include delapsed time between admission and surgery, length of hospital stay, postoperative complications, functional score, and the MOS item short form health survey-36. Results: Data describing 772 patients with ankle fracture and 658 patients with distal radius fracture were collected, of which 323 patients with ankle fracture and 323 patients with distal radial fracture were included for analysis. The patients in the ERAS group showed higher satisfaction levels on discharge and at 6 months postoperatively than in the traditional group (P < 0.001). In the subgroup analysis, patients with distal radial fracture in the ERAS group were more satisfied with the treatment (P=0.001). Furthermore, patients with ankle fracture had less time in bed (P < 0.001) and shorter hospital stay (P < 0.001) and patients with distal radial fracture received surgery quickly after being admitted into the ward in the ERAS group than in the traditional group (P=0.001). Conclusions: Perioperative protocol based on the ERAS program was associated with high satisfaction levels, less time in bed, and short hospital stay without increased complication rate and decreased functional outcomes.

[Establishment and evaluation of animal model for studying the effect of traumatic brain injury on bone fracture healing].

OBJECTIVE: To establish a stable animal model for studying the effect of traumatic brain injury on bone fracture healing. METHODS: Eighty adult male Sprague-Dawley rats were randomly divided into fracture combined brain injury group (A) and simple fracture group (B). Animals of the two groups were killed 6 hours, 1 week, 2 weeks, 1 month and 2 months after trauma, respectively. Their brain histopathology changes were observed and neurological severity scores (NSS, 0 through 25 from no injury to severe injury) determined to measure the brain injury after head trauma, and fracture-healing was assessed by measuring callus volume and X ray examination at the scheduled time points after trauma. The callus volumes were compared between the groups using independent-samples t test 1 week, 2 weeks, 1 month and 2 months after trauma respectively. A value of P<0.05 was considered statistically significant. RESULTS: Ninety percent of the rats of group A presented with hemiplegia and the mortality rate was 10% (4/40) . The survived rats developed decorticated flexion deformity of the forelimbs, with behavioral depression, and lost some reflexes and muscle tone. The NSS were 10.83±1.94, 9.33±0.82, 8.17±1.17, 7.83±0.75 and 8.07±0.82 with 6 hours, 1 week, 2 weeks, 1 month and 2 months after trauma, respectively. It showed that the animals received moderate head injury, which tended to be stable from 2 weeks after trauma. Brain pathology showed that blood brain barrier was destroyed, and neurons were degenerative and necrotic at and around the trauma sites. The callus volumes(unit: mm(3)) of the two groups 1 week, 2 weeks, 1 month and 2 months after trauma were 60.03±28.05 and 32.80±11.04, 78.54±15.16 and 51.36±23.02, 93.01±10.65 and 72.38±20.38, 115.26±40.00 and 60.30±13.34, respectively. The callus volumes of the two groups 2 weeks, 1 month and 2 months after trauma were statistically and significantly different (P values were 0.036, 0.006 and 0.01 respectively), and there was no difference 1 week after trauma (P=0.065). CONCLUSION: This model is capable of producing accurately quantified brain injury. The animal model is credible, stable and reproducible, so it is an effective platform for studying the effect of traumatic brain injury on fracture.

[Clinical analysis of obvious and hidden blood loss in inter-trochanter fracture patients treated with proximal femoral nail anti-rotation and dynamic hip screw].

OBJECTIVE: To analyze the obvious and hidden blood loss before and after operations in the inter-trochanter fracture patients treated with proximal femoral nail anti-rotation (PFNA) and dynamic hip screw (DHS) to provide the data support for clinical perioperative period treatment. METHODS: The clinical data of 216 cases of inter-trochanter fracture patients treated with PFNA and 168 cases of inter-trochanter fracture patients treated with DHS from Dec. 30, 2001 to Sep. 30, 2010, and the obvious, hidden blood loss and blood transfusion before and after operations were retrospectively analyzed, using SPSS 13.0 statistical package. RESULTS: The PFNA group: The mean blood loss of (48.9±2.8) mL was found in 216 cases of inter-trochanter fracture patients during operation. The mean obvious blood loss was (62.3±3.8) mL while the hidden blood loss was (385.0±6.2) mL. The DHS group: The mean blood loss of (124.9±7.8) mL was found in 168 cases during operation. The mean obvious blood loss was (73.9±4.7) mL and the hidden blood loss was (243.4±6.3) mL after operation. The blood loss during operation and obvious blood loss after operation of DHS was larger than that of PFNA, while the hidden blood loss of DHS was smaller than that of PFNA. The gross total blood loss and the hidden blood loss of group PFNA was bigger than that of DHS group. CONCLUSION: There were much hidden blood loss in both PFNA and DHS group for inter-trochanter fracture internal fixation after operation. This reminds surgeons to monitor the life vital signs after PFNA or DHS internal fixation operation in order to decrease the complication.