Clinical Impact of Switching to Ceritinib After Severe AEs Related to Crizotinib/Alectinib in a Novel PTH2R-ALK Fusion Lung Adenocarcinoma: A Case Report.

Lung cancer is still the leading cause of morbidity and mortality by cancer among men, according to the latest epidemiological data in China. Anaplastic lymphoma kinase (ALK) rearrangements act as key oncogenic drivers of non-small cell lung cancer (NSCLC) and have been identified in 5-6% of NSCLC. Although ALK inhibitors (ALK-TKIs) were proven to be more effective than chemotherapy in ALK-positive NSCLC patients and the safety profile of these drugs was favorable, novel ALK fusions NSCLC might discontinue or switch treatment because of adverse events (AEs) have rarely previously been reported. Here, we describe a male patient with stage IV lung adenocarcinoma who carried a novel PTH2R-ALK fusion identified by next-generation sequencing (NGS). The patient first took crizotinib but switched to alectinib due to gastrointestinal AEs. Although alectinib remained effective on tumors, ceritinib (450 mg) was replaced after the AEs of hyperbilirubinemia occurred. After reducing the dose to 300mg, the diarrhea AEs caused by ceritinib were effectively relieved, and the patient obtained sustained clinical benefit with progression-free survival nearly 12 months. Our findings offer valuable information for the safety management of NSCLC patients with a novel PTH2R-ALK fusion treated by ALK-TKIs.

[Clinical experience of high-flow nasal cannula oxygen therapy in severe COVID-19 patients].

Acute respiratory failure due to acute hypoxemia is the major manifestation in severe coronavirus disease 2019 (COVID-19). Rational and effective respiratory support is crucial in the management of COVID-19 patients. High-flow nasal cannula (HFNC) has been utilized widely due to its superiority over other non-invasive respiratory support techniques. To avoid HFNC failure and intubation delay, the key issues are proper patients, timely application and improving compliance. It should be noted that elder patients are vulnerable for failed HFNC. We applied HFNC for oxygen therapy in severe and critical ill COVID-19 patients and summarized the following experiences. Firstly, to select the proper size of nasal catheter, to locate it at suitable place, and to confirm the nose and the upper respiratory airway unobstructed. Secondly, an initial ow of 60 L/min and 37℃ should be given immediately for patients with obvious respiratory distress or weak cough ability; otherwise, low-level support should be given first and the level gradually increased. Thirdly, to avoid hypoxia or hypoxemia, the treatment goal of HFNC should be maintained the oxygen saturation (SpO2) above 95% for patients without chronic pulmonary disease. Finally, patients should wear a surgical mask during HFNC treatment to reduce the risk of virus transmission through droplets or aerosols.

Diagnostic delay and mortality of active tuberculosis in patients after kidney transplantation in a tertiary care hospital in China.

TB infection in patients after kidney transplantation remains a concern in a successful long-term outcome. This retrospective, descriptive study was performed on tuberculosis infection after kidney transplantation in the Department of Infectious Disease of the First Affiliated Hospital of Zhejiang University, a tertiary care hospital in China, from January 2011 to April 2017, with the aim to explain the clinical features of active tuberculosis after kidney transplantation and explore the correlated factors for diagnostic delay and mortality. It included 48 cases. All these cases were followed up for at least 12 months after anti-tuberculosis therapy, except the ones who died during this period. The median time of transplantation to active tuberculosis of these 48 patients was about 5.4 years. The time from a first hospital visit to the diagnosis (diagnostic delay) of 12 (25%) cases was more than 30 days. The correlated factors for the diagnostic delay more than 30 days were a fever for more than 2 weeks and antibiotic use for more than 2 weeks. Nine (18.8%) cases died during the anti-tuberculosis therapy or following-up period due to TB relapse. The risk factors for mortality were severe complications, such as encephaledema, severe pneumonia, intestinal perforation, liver function failure, and the following multiple-organ failure. In conclusion, the possibility of tuberculosis infection should be carefully assessed and sometimes diagnostic anti-tuberculosis therapy may be required for patients who had a fever for more than 2 weeks or used antibiotics for more than 2 weeks after kidney transplantation. Severe complications and the following multiple-organ failure might increase the mortality among these patients.