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IntroductionThe coronavirus disease 2019 (COVID-19) pandemic was expected to have a negative impact on organ donation. With the differences in health care systems and lockdown policies in various regions, the pandemic's effect on organ donation and transplant service may vary. Most of the deceased donor organ referrals in our hospital came from non–intensive care units (ICUs). The objective of this study is to report our experience and quantify the effects of the COVID-19 pandemic on deceased donor organ donation in our center.MethodsThis was a retrospective observational study comparing the deceased donor organ donation activity during the period January 23 to November 30, 2020 with the same period in 2018 in Queen Elizabeth Hospital, Hong Kong.ResultsThere was a 26.9% reduction in deceased donor organ donor referral in 2020 compared with 2018. No significant difference in the proportion of referrals from ICU or non-ICU areas between the 2 time periods was observed. The brain death confirmation rate was significantly higher in 2020 (40.8% vs 20.2%, P = .003). Nine patients had family consent for organ donation in 2020 (vs 7 patients in the same period in 2018). There were no significant differences in consent rate and number of recovered organs between the 2 periods.ConclusionsWith effective measures to limit the spread of COVID-19 in a community, it is possible to support the needs of both patients with COVID-19 and deceased donor organ donation services.  相似文献   
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(R)-[18F]MH.MZ ([18F]MH.MZ) is a promising positron emission tomography (PET) radiotracer for in vivo study of the 5-HT2A receptor. To facilitate clinical trials, a fully automated radiosynthesis procedure for [18F]MH.MZ was developed using commercially available materials on the iPhase Flexlab module. The overall synthesis time was 100 min with a radiochemical yield of 7 ± 0.9% (n = 3). The radiochemical purity was greater than 99% for [18F]MH.MZ with a molar activity of 361 ± 57 GBq/μmol (n = 3). The protocol described herein reliably provides [18F]MH.MZ that meets all relevant release criteria for a GMP radiopharmaceutical.  相似文献   
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Background

The response to first-line, platinum-based treatment of muscle-invasive bladder cancer has not improved in 3 decades.

Objective

To identify genes that influence cisplatin resistance in bladder cancer.

Design, setting, and participants

We performed a whole-genome CRISPR screen in a bladder cancer cell line to identify genes that mediate resistance to cisplatin.

Outcome measurements and statistical analysis

Targeted validation was performed in two bladder cancer cell lines. The top gene candidate was validated in a publicly available bladder cancer dataset.

Results and limitations

From the CRISPR screen, we identified MSH2 as the most significantly enriched gene and mismatch repair as the most significantly enriched pathway that promoted resistance to cisplatin. Bladder cancer cells with knockdown of MSH2 showed a reduction in cisplatin-mediated apoptosis. MSH2 loss did not impact the sensitivity to other chemotherapies, including the cisplatin analog oxaliplatin. Bladder tumors with low MSH2 protein levels, quantified using reverse-phase protein array, showed poorer survival when treated with cisplatin- or carboplatin-based therapy; these results require future validation using immunohistochemistry. Additionally, results are retrospective from patients with primarily high-grade tumors; thus, validation in a controlled clinical trial is needed.

Conclusions

We generated in vitro evidence that bladder cancer cell lines depleted of MSH2 are more resistant to cisplatin. We additionally found an association between low MSH2 in bladder tumors and poorer patient survival when treated with platinum-based chemotherapy. If successfully validated prospectively, MSH2 protein level could assist in the selection of patients for chemotherapy.

Patient summary

We report the first evidence that MSH2 protein level may contribute to chemotherapy resistance observed in muscle-invasive bladder cancer. MSH2 has potential as a biomarker predictive of response to platinum-based therapy.  相似文献   
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