Case Report: Successful immune checkpoint inhibitor-based rechallenge in a patient with advanced renal clear cell cancer.

With the rapidly evolving of immune checkpoint inhibitors (ICIs), it has shown remarkable clinical benefits in treating various cancers. However, immune-related adverse events (irAEs) remain a significant challenge in the management of patients undergoing immunotherapy. There are limited data about immunotherapy re-challenge in patients with renal clear cell cancer who had irAE in the initial ICI therapy. In this study, we reported the case of a patient with advanced renal clear cell cancer who developed serious irAEs but also achieved a partial remission of tumor after ICI combined with pazopanib in the first-line treatment. After intravenous methylprednisolone therapy for two weeks, the patient fully recovered from treatment-related toxicities. After a multidisciplinary treatment (MDT) discussion and a communication with the patient, the decision was made to undergo a new fully humanized programmed death 1 (PD-1) agent, zimberelimab, combined with pazopanib for immune restart therapy. After two cycles of treatment, the patient demonstrated a partial response (PR), and the disease remained in continuous remission without any irAE at our last follow-up after 14 months' treatment. Re-challenging with immunotherapy after irAEs is an emerging strategy that offers the potential for additional clinical benefits to previously responding patients. However, careful patient selection and monitoring are essential to maximize the safety and efficacy of this approach.

Bait-trap chip for accurate and ultrasensitive capture of living circulating tumor cells.

Accurate analysis of living circulating tumor cells (CTCs) plays a crucial role in cancer diagnosis and prognosis evaluation. However, it is still challenging to develop a facile method for accurate, sensitive, and broad-spectrum isolation of living CTCs. Herein, inspired by the filopodia-extending behavior and clustered surface-biomarker of living CTCs, we present a unique bait-trap chip to achieve accurate and ultrasensitive capture of living CTCs from peripheral blood. The bait-trap chip is designed with the integration of nanocage (NCage) structure and branched aptamers. The NCage structure could "trap" the extended filopodia of living CTCs and resist the adhesion of filopodia-inhibited apoptotic cells, thus realizing the accurate capture (∼95% accuracy) of living CTCs independent of complex instruments. Using an in-situ rolling circle amplification (RCA) method, branched aptamers were easily modified onto the NCage structure, and served as "baits" to enhance the multi-interactions between CTC biomarker and chips, leading to ultrasensitive (99%) and reversible cell capture performance. The bait-trap chip successfully detects living CTCs in broad-spectrum cancer patients and achieves high diagnostic sensitivity (100%) and specificity (86%) of early prostate cancer. Therefore, our bait-trap chip provides a facile, accurate, and ultrasensitive strategy for living CTC isolation in clinical. STATEMENT OF SIGNIFICANCE: A unique bait-trap chip integrated with precise nanocage structure and branched aptamers was developed for the accurate and ultrasensitive capture of living CTCs. Compared with the current CTC isolation methods that are unable to distinguish CTC viability, the nanocage structure could not only "trap" the extended-filopodia of living CTCs, but also resist the adhesion of filopodia-inhibited apoptotic cells, thus realizing the accurate capture of living CTCs. Additionally, benefiting from the "bait-trap" synergistic effects generated by aptamer modification and nanocage structure, our chip achieved ultrasensitive, reversible capture of living CTCs. Moreover, this work provided a facile strategy for living CTC isolation from the blood of patients with early-stage and advanced cancer, exhibiting high consistency with the pathological diagnosis.

Angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) may be safe for COVID-19 patients.

BACKGROUND: To investigate the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARBs) administration to hypertension patients with the coronavirus disease 2019 (COVID-19) induced pneumonia. METHODS: We recorded the recovery status of 67 inpatients with hypertension and COVID-19 induced pneumonia in the Raytheon Mountain Hospital in Wuhan during February 12, 2020 and March 30, 2020. Patients treated with ACEI or ARBs were categorized in group A (n = 22), while patients who were not administered either ACEI or ARBs were categorized into group B (n = 45). We did a comparative analysis of various parameters such as the pneumonia progression, length-of-stay in the hospital, and the level of alanine aminotransferase (ALT), serum creatinine (Cr), and creatine kinase (CK) between the day when these patients were admitted to the hospital and the day when the treatment ended. RESULTS: These 67 hypertension cases counted for 33.17% of the total COVID-19 patients. There was no significant difference in the usage of drug treatment of COVID-19 between groups A and B (p > 0.05). During the treatment, 1 case in group A and 3 cases in group B progressed from mild pneumonia into severe pneumonia. Eventually, all patients were cured and discharged after treatment, and no recurrence of COVID-2019 induced pneumonia occurred after the discharge. The length of stays was shorter in group A as compared with group B, but there was no significant difference (p > 0.05). There was also no significant difference in other general parameters between the patients of the groups A and B on the day of admission to the hospital (p > 0.05). The ALT, CK, and Cr levels did not significantly differ between groups A and B on the day of admission and the day of discharge (p > 0.05). CONCLUSIONS: To treat the hypertension patients with COVID-19 caused pneumonia, anti-hypertensive drugs (ACEs and ARBs) may be used according to the relative guidelines. The treatment regimen with these drugs does not need to be altered for the COVID-19 patients.