The FDA-approved anti-androgen Enzalutamide (Enz) has been used successfully as the last line therapy to extend castration-resistant prostate cancer (CRPC) patients’ survival by an extra 4.8 months. However, CRPC patients eventually develop Enz-resistance that may involve the induction of the androgen receptor (AR) splicing variant ARv7. Here we found that Cisplatin (Cis) or Carboplatin, currently used in chemotherapy/radiation therapy to suppress tumor progression, could restore the Enz sensitivity in multiple Enz-resistant (EnzR) CRPC cells via directly degrading/suppressing the ARv7. Combining Cis or Carboplatin with Enz therapy can also delay the development of Enz-resistance in CRPC C4-2 cells. Mechanism dissection found that Cis or Carboplatin might decrease the ARv7 expression via multiple mechanisms including targeting the lncRNA-Malat1/SF2 RNA splicing complex and increasing ARv7 degradation via altering ubiquitination. Preclinical studies using in vivo mouse model with implanted EnzR1-C4-2 cells also demonstrated that Cis plus Enz therapy resulted in better suppression of EnzR CRPC progression than Enz treatment alone. These results not only unveil the previously unrecognized Cis mechanism to degrade ARv7 via targeting the Malat1/SF2 complex and ubiquitination signals, it may also provide a novel and ready therapy to further suppress the EnzR CRPC progression in the near future.

The revised post-Cardiac Arrest Syndrome for Therapeutic hypothermia (rCAST) score was proposed to predict neurologic outcomes and mortality among out-of-hospital cardiac arrest (OHCA) patients. However, it has rarely been validated outside Japan. Therefore, this study aimed to investigate this issue. All adult patients admitted to our medical intensive care unit for targeted temperature management (TTM) between July 2015 and July 2021 were enrolled. Their medical records were retrieved, and rCAST scores were calculated. A total of 108 post-cardiac arrest syndrome (PCAS) patients who received TTM were analyzed. According to the rCAST score, 49.1%, 50.0%, and 0.9% of the patients were classified as low, moderate, and high severity, respectively. The areas under the curves for the rCAST score were 0.806 (95% confidence interval [CI]: 0.719–0.876) and 0.794 (95% CI: 0.706–0.866) to predict poor neurologic outcomes and mortality at day 28, respectively. In contrast to the original report, only low-severity patients had favorable neurologic outcomes. The rCAST score showed moderate accuracy in our OHCA patients with PCAS who received TTM to predict poor neurologic outcomes and mortality at day 28.

SummaryBackgroundThe study investigated the effectiveness of dexamethasone injections for reducing the occurrence of postextubation airway obstruction (PEAO).MethodsOne hundred and thirty-eight patients who were intubated for ≥ 48 hours with a cuff-leak volume (CLV) < 110 mL were treated with low-dose dexamethasone (5 mg; n = 41), high-dose dexamethasone (10 mg; n = 42), or placebo (normal saline; n = 43) injection every 6 hours for a total of four doses on the day preceding extubation. CLV was measured before the first injection, 1 hour after each injection, and 24 hours after the fourth injection. Extubation was performed 24 hours after the last injection. PEAO was recorded within 48 hours postextubation.ResultsAdministration of dexamethasone resulted in a significant increase in absolute CLV and change of CLV relative to baseline tidal volume occurred (p < 0.05). However, there was no significant difference between the low- and high-dose dexamethasone groups. The incidence of PEAO was 7.1% in the high-dose group, 9.8% in the low-dose group, and 30.2% in the placebo group. The incidence of PEAO differed significantly between the dexamethasone groups and the placebo group (p = 0.001). There was no significant difference in the reintubation rates among the high-dose group (2.1%, 1/42), the low-dose group (2.4%, 1/41), and the placebo group (4.7%, 2/43; p = 0.79).ConclusionProphylactic administration of multiple low-dose dexamethasone is sufficient for reducing the incidence of PEAO in high-risk patients

Background: This study aimed to evaluate outcomes of patients and the difference between geriatric and young patients readmitted to the medical intensive care unit. Methods: From January 1, 2011 to December 31, 2013, 117 medical ICU readmissions were included. Results: The study population had a mean Charlson comorbidity score of 7.2 and stayed 12.3 days in the ward before ICU readmission. The most common cause for readmission was respiratory disease in 49 (41.9%) patients, and the average readmission duration was 10.1 days. There were 74 patients (63.2%) who survived. Among the survivors, only 50 were discharged from the hospital. The overall mean duration of hospital stay was 51.5 days. Those who survived the hospital course were younger (64.1 vs. 75.6 years) and had a higher coma score (10.2 vs. 7.5), lower Charlson score (6.4 vs. 8.6), and lower APACHE II score (24.4 vs. 31.3) (p < 0.05). Compared with older patients, younger patients had lower scores on readmission (APACHE II: 24.9 vs. 31.2 and Charlson score: 5.4 vs. 8.3) and had less probabilities of receiving mechanical ventilation (p < 0.05). Although there was no difference between the groups in the durations of ward stay and ICU readmission as well as in the outcome, the younger patients had a better chance of hospital survival (p < 0.05). Conclusion: Readmitted ICU patients, especially the geriatric group, had a very poor prognosis. The worsened APACHE score might be a good predictor for readmission survival. The Charlson score was an important hospital survival predictor

Targeted temperature management (TTM) is often considered to improve post-cardiac arrest patients’ outcomes. However, the optimal timing to initiate cooling remained uncertain. This retrospective analysis enrolled all non-traumatic post-cardiac arrest adult patients with either out-of-hospital cardiac arrest (OHCA) or in-hospital cardiac arrest (IHCA) who received TTM from July 2015 to July 2021 at our hospital. The values of time delay before TTM and time to target temperature were divided into three periods according to optimal cut-off values identified using receiver operating characteristic curve analysis. A total of 177 patients were enrolled. A shorter time delay before TTM (pre-induction time) was associated with a lower survival chance at 28 days (32.00% vs. 54.00%, p = 0.0279). Patients with a longer cooling induction time (>440 minis) had better neurological outcomes (1.58% vs. 1.05%; p = 0.001) and survival at 28 days (58.06% vs. 29.25%; p = 0.006). After COX regression analysis, the influence of pre-induction time on survival became insignificant, but patients who cooled slowest still had a better chance of survival at 28 days. In conclusion, a shorter delay before TTM was not associated with better clinical outcomes. However, patients who took longer to reach the target temperature had better hospital survival and neurological outcomes than those who were cooled more rapidly. A further prospective study was warranted to evaluate the appropriate time window of TTM.

Background: The optimal timing of high-flow nasal cannula (HFNC) application in acute respiratory failure patients remains uncertain. This study aimed to investigate the impact of HFNC on the outcomes of patients with acute respiratory failure, focusing on its use after extubation. Methods: This multicenter retrospective study enrolled adult acute respiratory failure patients requiring invasive mechanical ventilation during the first major outbreak of the COVID-19 pandemic in Taiwan from April to July 2021. Endpoints included prognosis after extubation as 28-day post-extubation mortality. Results: Among the patients, 107 received HFNC before intubation and 461 received conventional oxygen therapy (COT). Pre-intubation HFNC failure did not significantly affect hospital mortality but was associated with prolonged durations of mechanical ventilation and intensive care unit stay. Among 375 patients who underwent planned extubation, 158 received post-extubation HFNC and 217 received COT. HFNC application after extubation was associated with significantly reduced post-extubation 28-day mortality compared with COT. Conclusions: HFNC application after extubation is associated with reduced post-extubation 28-day mortality risks in acute respiratory failure patients who received planned extubation.