Implantation and Control of Wireless, Battery-free Systems for Peripheral Nerve Interfacing.

Peripheral nerve interfaces are frequently used in experimental neuroscience and regenerative medicine for a wide variety of applications. Such interfaces can be sensors, actuators, or both. Traditional methods of peripheral nerve interfacing must either tether to an external system or rely on battery power that limits the time frame for operation. With recent developments of wireless, battery-free, and fully implantable peripheral nerve interfaces, a new class of devices can offer capabilities that match or exceed those of their wired or battery-powered precursors. This paper describes methods to (i) surgically implant and (ii) wirelessly power and control this system in adult rats. The sciatic and phrenic nerve models were selected as examples to highlight the versatility of this approach. The paper shows how the peripheral nerve interface can evoke compound muscle action potentials (CMAPs), deliver a therapeutic electrical stimulation protocol, and incorporate a conduit for the repair of peripheral nerve injury. Such devices offer expanded treatment options for single-dose or repeated dose therapeutic stimulation and can be adapted to a variety of nerve locations.

Tumor growth velocity: A modified tumor growth rate defining tumor progression during sorafenib treatment in patients with metastatic renal cell carcinoma.

OBJECTIVES: To investigate the role of tumor growth velocity in defining tumor progression in metastatic renal cell carcinoma patients treated with the vascular endothelial growth factor tyrosine kinase inhibitor, sorafenib. METHODS: A modified calculation for tumor growth velocity was introduced to evaluate the tumor growth velocity, before and after sorafenib withdrawal. Known prognostic factors together with tumor growth velocity before drug withdrawal and tumor growth velocity after drug withdrawal were compared using a χ2 -test from a contingency table, and partial likelihood test from a Cox regression model for overall survival. RESULTS: A total of 114 patients who reached progressive disease and withdrew from sorafenib were enrolled after a median follow-up period of 107.8 months. Tumor growth velocity before drug withdrawal was 7.347 ± 4.040, and tumor growth velocity after drug withdrawal was 11.647 ± 5.937 (P < 0.001). Higher tumor growth velocity before drug withdrawal was correlated with a higher risk Memorial Sloan Kettering Cancer Center score (P = 0.022), Karnofsky Performance Status <80 (P = 0.028), non-clear cell carcinoma (P = 0.037), higher tumor nucleus grade (P < 0.001) and best treatment response (P < 0.001). Patients with tumor growth velocity before drug withdrawal >5.0 had shorter overall survival (P < 0.001). On multivariate analysis, factors associated with overall survival were high/intermediate Memorial Sloan Kettering Cancer Center risk score (hazard ratio 2.119, P = 0.006), non-clear histological subtype (hazard ratio 1.900, P = 0.031), tumor growth velocity before drug withdrawal ≥5.0 (hazard ratio 2.758, P < 0.001) and progressive disease as best response (hazard ratio 2.069, P = 0.001). CONCLUSIONS: Significantly faster tumor growth can be observed if sorafenib is discontinued in the case of disease progression. Thus, we suggest not to withdraw targeted agents until tumor growth velocity is >5.0.

Sorafenib versus sunitinib as first-line treatment agents in Chinese patients with metastatic renal cell carcinoma: the largest multicenter retrospective analysis of survival and prognostic factors.

BACKGROUND: To compare the efficacy of sorafenib and sunitinib with regard to overall survival (OS) and progression free survival (PFS) in Chinese patients with metastatic renal cell carcinoma (mRCC). METHODS: A multicenter, retrospective study was performed to elucidate the relationship between clinical variables and prognosis comparing sorafenib and sunitinib as first-line treatment agents in Chinese patients with mRCC. Between September 2006 and December 2014, 845 patients received either sorafenib (400 mg bid; n = 483) or sunitinib (50 mg q.d; n = 362). The primary end point was OS and PFS. RESULTS: The percentage of patients with low and moderate risk according to Memorial Sloan-Kettering Cancer Centre (MSKCC) score was significantly higher in sunitinib group, and that with high risk was significantly higher in sorafenib group (15.1 vs. 5.2%; p < 0.001). Median OS was similar in sorafenib and sunitinib group (24 vs. 24 months; p = 0.298). Sorafenib group exhibited higher mPFS compared to sunitinib group (11.1 vs. 10.0 months; p = 0.028). Treatment (sorafenib vs sunitinib), pathology, Eastern Cooperative Oncology Group (ECOG) performance status, MSKCC scores, Heng's criteria of risk, and number of metastases were identified as significant predictors for OS and along with liver metastasis for PFS. Clinical outcomes in terms of mOS was significantly better with sorafenib in patients ≥65 years of age (p = .041), ECOG 0 (p = 0.0001), and median MSKCC risk score (p = 0.008). CONCLUSIONS: Sorafenib and sunitinib are both effective in treating mRCC. However, sorafenib might be more effective in elderly patients (≥65 years) and in patients with an ECOG status of 0, classified under MSKCC moderate risk.

Eosinophil percentage elevation as a prognostic factor for overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitor.

BACKGROUND: We tried to investigate the prognostic significance of post-treatment eosinophil percentage(Eo %) in metastatic renal cell carcinoma(mRCC) patients undertaking sorafenib. RESULTS: The median OS for the entire sorafenib treatment period was 21.9 months (95% CI: 17.2-25.9 months). Of the 282 mRCC patients, 101 patients experienced an elevated post-treatment Eo % within two months. Median OS of post-treatment Eo % elevated group and non-elevated group were 42.9 months and 16.8 months(p=0.000). After adding post-treatment Eo % into a modified MSKCC model or Heng's model, 43 and 41 patients were reclassified into favorable group, 5 and 9 patients were reclassified to intermediate group respectively. METHODS: mRCC patients treated with sorafenib from 2006 to 2015 in were evaluated. Pre- and post-treatment Eo % were assessed. Oncologic outcomes were analyzed by overall survival and tumor response rate. Predictive parameters were assessed in a Cox proportional hazard model. CONCLUSIONS: Our study demonstrates that an early elevation of Eo % after sorafenib treatment is a strong predictor of good prognosis. Eo % can be a good supplementary for prognostic models using pre-treatment parameters.

Prognostic value of pathological features of primary lesion in metastatic renal cell carcinoma treated with sorafenib.

AIM: This study aimed to investigate whether the pathological features of primary lesions show additional prognostic value in patients with metastatic renal cell carcinoma who are treated with sorafenib. PATIENTS & METHODS: A consecutive cohort of 284 patients was included from Fudan University Shanghai Cancer Center between 2007 and 2013. The association between survival and pathological features of primary tumors was assessed using the Cox proportional hazards model. The incremental value of prognostication was evaluated. RESULTS: We found that the pathological features of primary lesions provided added prognostic value over the Memorial Sloan-Kettering Cancer Center model in patients with metastatic renal cell carcinoma who were treated with sorafenib. CONCLUSION: Addition of a pathological score in the clinical setting could better identify patients at risk of poor survival.