Comparison of the 12-month impact of COVID-19 and SARS on physiological capacity and health-related quality of life.

BACKGROUND: Little is known about the differences in medium to long-term recovery on spirometry, 6-minute walking distance (6MWD) and health-related quality of life (HRQoL) between COVID-19 and SARS. METHODS: We performed a 12-month prospective study on COVID-19 survivors. The changes in dynamic lung volumes at spirometry (%predicted FEV1, %predicted FVC), 6MWD and HRQoL at 1-3, 6 to 12 months were compared against a historical cohort of SARS survivors using the same study protocol. The residual radiological changes in HRCT in COVID-19 survivors were correlated with their functional capacity. RESULTS: 108 COVID-19 survivors of various disease severity (asymptomatic 2.9%, mild 33.3%, moderate 47.2%, severe 8.3%, critical 8.3%) were recruited. When compared with 97 SARS survivors, 108 COVID-19 survivors were older (48.1 ± 16.4 vs. 36.1 ± 9.5 years, p < 0.001) and required less additional support during hospitalization; with lower dynamic lung volumes, shorter 6MWD and better physical component score. Both groups of survivors had comparable changes in these parameters at subsequent follow-ups. Both COVID-19 and SARS survivors had similar mental component score (MCS) at 6 and 12 months. COVID-19 survivors initially experienced less (between-group difference, -3.1, 95% confidence interval [CI] -5.5 to -0.7, p = 0.012) and then more improvement (between-group difference 2.9, 95%, CI 0.8 to 5.1, p = 0.007) than SARS survivors in the MCS at 1-3 to 6 months and 6 to 12 months respectively. Forty (44.0%) out of 91 COVID-19 survivors had residual abnormalities on HRCT at 12 months, with a negative correlation between the severity scores of parenchymal changes and 6MWD (r=-0.239, p < 0.05). CONCLUSIONS: COVID-19 survivors demonstrated a similar recovery speed in dynamic lung volumes and exercise capacity, but different paces of psychological recovery as SARS survivors in the convalescent phase. The severity of parenchymal changes in HRCT is negatively correlated with the 6MWD of COVID-19 survivors. TRIAL REGISTRATION: This prospective study was registered at ClinicalTrials.gov on 2 November 2020 (Identifier: NCT04611243).

The Associations Between Loneliness, Hopelessness, and Self-control and Internet Gaming Disorder Among University Students Who Were Men Who Have Sex With Men: Cross-sectional Mediation Study.

BACKGROUND: The minority stress model postulates that men who have sex with men (MSM) often encounter multiple stressors because of their sexual minority status, which may lead to psychological problems and maladaptive coping such as addictive behaviors (eg, internet gaming disorder [IGD]). It was hypothesized that hopelessness and loneliness would be associated with IGD via self-control among MSM. OBJECTIVE: This study investigated the prevalence of IGD and its associations with variables related to minority stress (loneliness and hopelessness) among MSM who were university students. Mediation involving such associations via self-control was also explored. METHODS: With informed consent, 305 MSM attending universities in Sichuan, China participated in the study. The validated Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) checklist was used to assess IGD. Multivariable logistic regression adjusted for background factors and structural equation modeling were conducted. RESULTS: The prevalence of IGD was 12.8% (n=39). Logistic regression found that IGD was positively associated with hopelessness and loneliness, and negatively associated with self-control. The structural equation modeling identified three significant paths between hopelessness/loneliness and IGD: (1) hopelessness → lower self-control → higher IGD (full mediation), (2) loneliness → lower self-control → higher IGD (partial mediation: effect size of 28%), and (3) a direct effect from loneliness to IGD. CONCLUSIONS: IGD was prevalent among young MSM and warrants interventions that may try to reduce the level of psychosocial problems such as loneliness and hopelessness and improve self-control. According to the socioecological model, the promotion of social acceptance and reduction in stigma toward MSM are important in reducing loneliness and hopefulness among MSM. Self-control links up the relationships between psychosocial problems and IGD and should be given special attention. Longitudinal studies are warranted to confirm the findings and test new mediations between loneliness/hopelessness and MSM with IGD.

Delays in Door-to-Diuretic Time and 1-Year Mortality Among Patients With Heart Failure.

BACKGROUND: Achieving prompt euvolemic state in heart failure (HF) is associated with reduced mortality. Time-sensitive metrics such as door-to-diuretic time , or the time between presentation and administration of intravenous diuretics, may be an important facilitator of achieving a faster euvolemic state and reducing mortality. OBJECTIVE: The aim of this study was to investigate whether reduced door-to-diuretic time was associated with lower odds of death among hospitalized patients with HF. METHODS: A retrospective chart review of patients with HF admitted to a medical center was performed between 2020 and 2021. Inclusion criteria were an International Classification of Diseases, 10th Revision code for HF with positive Framingham Criteria and the use of intravenous bolus furosemide. Exclusion criteria included ventricular assist devices, dialysis, and ultrafiltration therapy. Data collected from the medical records included demographics, echocardiography, staff notes, and medications. The end point was 1-year all-cause mortality. Descriptive statistics, t tests or median test, and multivariate logistic regression were used to describe the sample, evaluate group differences, and determine odds of mortality, respectively. RESULTS: Among 160 charts from patients with HF (age, 70 ± 14.4 years; 52%, n = 83, male; 53%, n = 85, ischemic cardiomyopathy; 83%, n = 134, New York Heart Association classes III-IV), 30% (n = 48) died within 1 year. The median diuretic dose was 40 mg (interquartile range, 20 mg), with a median time of administration of 247 minutes (4.12 hours) (interquartile range, 294 minutes to 4.9 hours). After covariate adjustment, prolonged door-to-diuretic time more than doubled (2.22; 95% confidence interval, 1.03-4.8; P = .04) the odds of 1-year mortality. CONCLUSIONS: On the basis of this sample of charts from older highly symptomatic patients with HF, delayed door-to-diuretic time was associated with significantly greater odds of 1-year all-cause mortality.

Level and factors of support for the Living with the Virus policy in a Chinese adult general population: a mediation analysis via positive and negative attitudes toward the policy.

Background: This study investigated the public's support for the Living with the Virus (LWV) policy, its associated factors, and related mediations at a time when more countries were considering adopting the LWV policy amid the COVID-19 pandemic. Methods: A random, population-based telephone survey was conducted among 500 Chinese adults in Hong Kong during March/April 2022. Results: 39.6% of the participants were supportive/strongly supportive of the LWV policy. Perceived efficacy of the control measures was negatively associated with the support and was partially mediated via the perception that the policy would greatly improve the economy/daily life of the policy. Perceived physical harms of the Omicron variant was negatively associated with the support and was fully mediated via perceived negative impacts of the policy. 26.2%/54.6% believed that the policy would improve the economy/daily life greatly; about 40% perceived negative impacts on deaths and the medical system due to the policy. COVID-19 ever infection did not significantly moderate the studied associations. Conclusion: The public was split regarding the support for the LWV policy and whether it would cause better economy/daily life, unnecessary deaths, and the collapse of the medical system. Health communication is needed in shifting toward the LWV policy.

Digital Image Comparison of Cellular Yield in Bronchial Brushing: Pre- and Post-Biopsy Lavage Cytology.

INTRODUCTION: Bronchoscopy is a useful diagnostic tool capable of performing core biopsy, forceps biopsy, bronchoalveolar lavage, and bronchial brushing. This study compares the cellularity of bronchial cytology including pre- and post-biopsy lavage by digital image analysis, aiming to increase diagnostic and tumor yield by optimizing the sequence and combination of bronchial biopsy and cytology. METHODS: Alveolar macrophage, bronchial epithelium, and tumor cell cellularity from liquid-based cytology preparations of bronchial brushing and pre-biopsy and post-biopsy bronchoalveolar lavage were annotated on digitized whole-slide images and compared. Secondary analysis on the relationship of tumor cell and non-lesional cell yield was performed. RESULTS: Overall, 118 cytology specimens from 43 patients were retrieved in total. Bronchial epithelium count was higher in pre-biopsy than post-biopsy lavage (p < 0.01) but not for alveolar macrophages nor tumor cell (p > 0.05). Tumor cell count was higher for bronchial brushing cytology samples than lavage (p = 0.018). The alveolar macrophage count was higher in post-biopsy lavage than bronchial brushing (p = 0.033); otherwise, brushing showed consistently higher bronchial epithelium and tumor cell counts. There were 33 false negative (tumor cell absent) specimens, and the combination of bronchial brushing and pre-biopsy lavage yielded the lowest false negative cases. Correlation between bronchial epithelium and alveolar macrophage counts with tumor cell count was weak (correlation coefficient = -0.168-0.203) except for post-biopsy lavage (correlation coefficient = 0.412-0.479, p < 0.05). CONCLUSION: Bronchial brushing yields a greater amount of tumor cell than lavage, and timing lavage before or after core biopsy does not affect tumor cell yield. Combining bronchial brushing and pre-biopsy lavage results in the lowest false negative rate.

Brief Report: Risk of Recurrent Interstitial Lung Disease From Osimertinib Versus Erlotinib Rechallenge After Symptomatic Osimertinib-Induced Interstitial Lung Disease.

Introduction: Interstitial lung disease (ILD) is the most frequent cause of drug-related mortality from EGFR tyrosine kinase inhibitors (TKIs). Yet, for patients with symptomatic osimertinib-induced ILD, the risk of recurrent ILD associated with EGFR TKI rechallenge, either with osimertinib or another TKI, such as erlotinib, is unclear. Methods: Retrospective study of 913 patients who received osimertinib treatment for EGFR mutation-positive NSCLC. Clinical characteristics, ILD treatment history, and subsequent anticancer therapy of patients with symptomatic osimertinib-induced ILD were collated. The primary end point was to compare the incidence of recurrent ILD with osimertinib versus erlotinib rechallenge. Results: Of 913 patients, 35 (3.8%) had symptomatic osimertinib-induced ILD, of which 12 (34%), 15 (43%), and eight (23%) had grade 2, 3 to 4, and 5 ILD, respectively. On ILD recovery, 17 patients had EGFR TKI rechallenge with eight received osimertinib and nine received erlotinib. The risk of recurrent ILD was higher with osimertinib rechallenge than erlotinib (p = 0.0498). Of eight, five (63%) developed recurrent ILD on osimertinib rechallenge, including three patients with fatal outcomes. In contrast, only one of nine patients (11%) treated with erlotinib had recurrent ILD. Median time to second ILD occurrence was 4.7 (range 0.7-12) weeks. Median time-to-treatment failure of patients with erlotinib rechallenge was 13.2 months (95% confidence interval: 8.6-15.0). Conclusions: The risk of recurrent ILD was considerably higher with osimertinib rechallenge than erlotinib. Osimertinib rechallenge should be avoided, whereas erlotinib may be considered in patients with symptomatic osimertinib-induced ILD.

Risk factors associated with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmission, outbreak duration, and mortality in acute-care settings.

BACKGROUND: Transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in acute-care settings affects patients, healthcare workers, and the healthcare system. We conducted an analysis of risk factors associated with outbreak severity to inform prevention strategies. METHODS: This cross-sectional analysis of COVID-19 outbreaks was conducted at Fraser Health acute-care sites between March 2020 and March 2021. Outbreak severity measures included COVID-19 attack rate, outbreak duration, and 30-day case mortality. Generalized linear models with generalized estimating equations were used for all outcome measures. A P value of 0.05 indicated statistical significance. Analyses were performed using SAS version 3.8 software, R version 4.1.0 software, and Stata version 16.0 software. RESULTS: Between March 2020 and March 2021, 54 COVID-19 outbreaks were declared in Fraser Health acute-care sites. Overall, a 10% increase in the hand hygiene rate during the outbreak resulted in an 18% decrease in the attack rate (P < .01), 1 fewer death (P = .03), and shorter outbreaks (P < .01). A 10-year increase in unit age was associated with 2.2 additional days of outbreak (P < 0.01) and increases in the attack rate (P < .05) and the number of deaths (P < .01). DISCUSSION: We observed an inverse relationship between increased hand hygiene compliance during outbreaks and all 3 severity measures. Increased unit age was also associated with increases in each of the severity measures. CONCLUSION: This study highlights the importance of hand hygiene practices during an outbreak and the difficulties faced by older facilities, many of which have infrastructural challenges. The latter reinforces the need to incorporate infection control standards into healthcare planning and construction.

Pneumomediastinum and subcutaneous emphysema complicating a patient with a lung abscess.

Pneumomediastinum and subcutaneous emphysema are conditions that carry significant morbidity. They are uncommonly seen as complications of lung abscess formation and prompt recognition and treatment is necessary. We present a 59-year-old male patient who complained of shortness of breath and chest pain for 2 weeks. Computed tomography (CT) of the thorax showed a left lower lobe lung abscess. This was associated with leucocytosis and raised C-reactive protein. Ultrasound-guided drainage revealed viscous pus requiring manual aspiration for adequate drainage. The patient later developed extensive pneumomediastinum and subcutaneous emphysema involving the pretracheal space, without evidence of pneumothorax. Left lower lobectomy was performed to control sepsis. The patient achieved a complete recovery following his surgery and antibiotic treatment, with interval resolution of pneumomediastinum and subcutaneous emphysema. We present the radiological and clinical features leading to the diagnosis of pneumomediastinum and subcutaneous emphysema.

Illness representation of COVID-19 affected public's support and anticipated panic regarding the living with the virus policy: a cross-sectional study in a Chinese general population.

Background: There is a global trend for countries to adopt the Living with the Virus (LWV) policy regarding COVID-19. Little is known about the public's supportiveness and emotional responses (e.g., anticipated panic) related to this policy. Such responses may be associated with illness representations of COVID-19 (i.e., how people think and feel about COVID-19). This novel topic was investigated in this study to facilitate policy-making and health communication. Methods: A random, population-based telephone survey interviewed 500 adults aged ≥18 of the Hong Kong general adult population from March to April 2022. Results: The prevalence of the public's support and anticipated panic regarding the LWV policy, which were negatively correlated with each other, was 39.6 and 24.2%, respectively. The illness representation constructs of consequences, timeline, identity, illness concern, and emotional representations were negatively associated with supportiveness and positively associated with anticipated panic regarding the LWV policy. Illness coherence was significantly associated with policy support but not with anticipated panic. The associations between personal control/treatment control and supportiveness/anticipated panic were statistically non-significant. Moderation analyses showed that the above significant associations were invariant between those with and without previous COVID-19 infection. Conclusion: Policymakers need to be sensitized about the public's supportive/unsupportive attitude and potential worry (panic) when adopting the LWV policy. Such attitudes/emotional responses may be affected by people's illness representations of COVID-19. In general, those who found COVID-19 involving a milder nature and less negative emotions would be more supportive and anticipated less panic under the LWV policy.

1-Year Prospective Study of the Relationship of Serial Exhaled Nitric Oxide Level and Asthma Control.

Background and Objective: Previous studies found that the fractional nitric oxide concentration in exhaled breath (FeNO) levels in healthy Chinese adults was higher than in White adults. More understanding of serial changes of FeNO levels with asthma control in a real-life clinical setting would be important to explore the utility of this biomarker in routine asthma management. This study assessed the FeNO levels of Chinese asthma subjects with different levels of asthma control and the serial changes with respect to the changes in asthma control over 1 year. Methods: A 12-month prospective study (subjects recruited between November 2019 and January 2021) with serial measurement of FeNO levels at baseline, 4, 8 and 12 months. Asthma control was assessed by the Global Initiative for Asthma classification, Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ). Results: Altogether, 136 subjects (mean age 51.51±15.09 years, 46[33.8%] male) had successful baseline FeNO measurements. At baseline, the FeNO levels did not show a statistically significant difference for controlled, partly controlled and uncontrolled asthma according to GINA classification, ACT and ACQ. FeNO levels decreased with improving asthma control and stayed at similar levels with unchanged or worsening asthma control for all subjects. For subjects with baseline blood eosinophil levels ≥300 cells/µL(n=59), FeNO levels decreased with improving asthma control, stayed similar without change for asthma control and increased with worsening asthma control. Receiver operating characteristic (ROC) analysis with the highest area under curve (AUC) for changes in FeNO levels for improving asthma control was between ≤ -10 to -25 ppb at various time points in the 12-month study. Conclusion: Changes in FeNO levels over time were associated with changes in clinical asthma control, particularly in those with higher blood eosinophil count and are likely more useful than a single time point measurement in managing asthma.

Psychometric Properties of the Abbreviated Version of the Dual School Climate and School Identification Measure-Student (SCASIM-St15) among Adolescents in China.

School climate and school identification are two distinct yet closely interrelated components of school environment; both are associated with adolescents' multiple health behavioral changes. The 15-item Abbreviated version of the Dual School Climate and School Identification Measure-Student (SCASIM-St15) and its 5-factor model simultaneously and separately assess these two constructs. This study validated the Chinese version of SCASIM-St15 among 1108 students from junior middle schools, senior middle schools, and vocational high schools in Taizhou city, Zhejiang, China, via an anonymous, self-administered cross-sectional survey. Confirmatory factor analysis supports the 5-factor model of the original SCASIM-St15 with a satisfactory model fit. Its four factors (i.e., student-student relations, staff-student relations, academic emphasis, and shared values and approach) assess school climate; its fifth factor assesses school identification. The subscales of the SCASIM-St15 demonstrate good psychometric properties, including measurement invariance (across sex and school type), good internal consistency, an absence of floor effect, and good external validity with four external variables (depression, peer victimization, classmate support, and teacher-student relationship). However, some substantial ceiling effects were observed. The five subscales differ significantly across the school types but not between males and females. The validated SCASIM-St15 can be applied to simultaneously understand school climate/school identification among Chinese adolescents, which may greatly facilitate future related observational and intervention research.

Prevention of docetaxel-associated febrile neutropenia with primary granulocyte colony-stimulating factor in Chinese metastatic hormone-sensitive and castration-resistant prostate cancer patients.

INTRODUCTION: Asian prostate cancer (PC) patients are particularly susceptible to docetaxel-related febrile neutropenia (FN). We evaluated primary granulocyte colony-stimulating factor (GCSF) for preventing FN in Chinese patients with metastatic hormone-sensitive PC (mHSPC) and castration-resistant PC (mCRPC). PATIENTS AND METHODS: Data from two cohorts of 377 Chinese patients with mHSPC (100; 26.5%) and mCRPC (277; 73.5%) treated with docetaxel at six public oncology centres were analysed with multivariate regression. Primary GCSF prophylaxis was defined as administration within 5 days of starting docetaxel. The primary outcome was FN within 21 days of the first docetaxel cycle (1st FN). RESULTS: Primary GCSF was given to 71 (18.8%) patients. FN occurred in 61 patients (16.2%) including 37 (9.8%) during the first cycle. Among patients who developed 1st cycle FN (n = 37) or not (n = 340), 2 and 69 received primary GCSF (5.4 vs. 20.3%, P = .03). Primary GCSF was associated with an overall reduced risk of 1st cycle FN (odds ratio [OR] = 0.22; 95% confidence interval [CI]: 0.05-0.96, P = .04), and similar trends were observed in the mHSPC (OR = 0.36, P = .35) and mCRPC (OR = 0.16, P = .08) subgroups. Poor Eastern Cooperative Oncology Group performance status (>1) was associated with an increased risk of 1st FN (OR = 3.90; 95% CI: 1.66-9.13, P = .002). CONCLUSIONS: To alleviate the risk of docetaxel-related FN, primary GCSF prophylaxis is suggested for Asian mCRPC and mHSPC patients, particularly those with poor performance status.

Collection of lower respiratory specimen by bronchoscopy for the diagnosis of COVID-19.

Bronchoscopy, as an aerosol-generating procedure, is not routinely performed in patients with high-risk of coronavirus disease-2019 (COVID-19) owing to potential transmission to healthcare workers. However, to obtain lower respiratory specimens from bronchoscopy with bronchoalveolar lavage (BAL) is necessary to confirm COVID-19 or other diagnosis that will change clinical management. We report a case of diagnostic difficulty with five negative SARS-CoV-2 RT-PCR testing in four upper respiratory tract and one stool samples following presentation with fever during the quarantine period and a strong epidemiological linkage to an index patient with COVID-19. The final diagnosis was confirmed by BAL. Special precautions to be taken when performing bronchoscopy in high-risk non-intubated patients were discussed.

Efficacy of endoscopy in assessing the local disease response in nasopharyngeal carcinoma patients after treated with intensity-modulated radiotherapy.

AIM: The optimal local disease assessment after intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) patients remains unclear. Our aim was to investigate the efficacy of post-IMRT endoscopies. METHODS: The medical record of NPC patients with IMRT treatments during 2013 to 2015 was reviewed. Endoscopies and nasopharyngeal biopsies were performed at 6 weeks post-IMRT. Second biopsies were performed 4 weeks later for patients with abnormal first biopsies. Results of endoscopic assessments were correlated with histology using standard descriptive statistics. RESULTS: A total of 262 patients were reviewed. Endoscopy showed a sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of 71%, 90%, 41% and 97%, respectively. Disease remission at 6 weeks was observed in 234 patients (89.3%). Sixteen patients (6.1%) had ultimate disease remission (late responders) and 12 (4.6%) had persistent local disease. CONCLUSION: Endoscopy had high specificity and NPV; therefore, invasive biopsy could be exempted in case of normal endoscopy.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy.

Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.

Importance of cycles of chemotherapy and postdocetaxel novel therapies in metastatic castration-resistant prostate cancer.

PURPOSE: With the emergence of various novel therapies including new generation taxane and androgen-targeted therapies, the optimal sequence of systemic treatment in metastatic castration-resistant prostate cancer (mCRPC) patients remains to be defined. Our aim is to investigate the impact of duration of docetaxel-based chemotherapy and postdocetaxel treatment in mCRPC patients. METHODS: The medical data of 57 Chinese mCRPC patients who received docetaxel-based chemotherapy in two oncology centers between 2003 and 2012 were reviewed. The treatment efficacy and toxicity were determined. The potential determinants of efficacy were also determined. RESULTS: Fifty-seven patients (median age 66 years, range 51-82 years) were given docetaxel-based chemotherapy, of whom 48 (84.2%) received 3-weekly docetaxel (52.5-75 mg/m(2)) and nine (15.8%) received weekly docetaxel (35 mg/m(2)). Postdocetaxel treatments were received by 31 (57.4%) patients, including abiraterone in 13 patients and cabazitaxel in one patient. The median follow-up time was 14.3 months. The median overall survival (OS) and progression-free survival were 20.8 months and 5.8 months, respectively. In multivariate analysis, eight cycles or more of chemotherapy [hazard ratio (HR) = 0.151, P < 0.0358], use of postdocetaxel treatment (HR = 0.346, P = 0.0005), and hemoglobin level of <10 (HR = 5.224, P < 0.0001) were independent determinants of OS. Patients who had received abiraterone and cabazitaxel as postdocetaxel treatment had significantly longer OS compared with those who received other postdocetaxel treatments (including rechallenge of docetaxel) and those who did not receive any postdocetaxel treatment (35.3 months vs. 20.8 months vs. 15.3 months, P = 0.00057). CONCLUSIONS: The results suggest that maximizing exposure to docetaxel-based chemotherapy followed by novel therapies would have a favorable survival impact on mCRPC patients.

Attenuation of hind-limb ischemia in mice with endothelial-like cells derived from different sources of human stem cells.

Functional endothelial-like cells (EC) have been successfully derived from different cell sources and potentially used for treatment of cardiovascular diseases; however, their relative therapeutic efficacy remains unclear. We differentiated functional EC from human bone marrow mononuclear cells (BM-EC), human embryonic stem cells (hESC-EC) and human induced pluripotent stem cells (hiPSC-EC), and compared their in-vitro tube formation, migration and cytokine expression profiles, and in-vivo capacity to attenuate hind-limb ischemia in mice. Successful differentiation of BM-EC was only achieved in 1/6 patient with severe coronary artery disease. Nevertheless, BM-EC, hESC-EC and hiPSC-EC exhibited typical cobblestone morphology, had the ability of uptaking DiI-labeled acetylated low-density-lipoprotein, and binding of Ulex europaeus lectin. In-vitro functional assay demonstrated that hiPSC-EC and hESC-EC had similar capacity for tube formation and migration as human umbilical cord endothelial cells (HUVEC) and BM-EC (P>0.05). While increased expression of major angiogenic factors including epidermal growth factor, hepatocyte growth factor, vascular endothelial growth factor, placental growth factor and stromal derived factor-1 were observed in all EC cultures during hypoxia compared with normoxia (P<0.05), the magnitudes of cytokine up-regulation upon hypoxic were more dramatic in hiPSC-EC and hESC-EC (P<0.05). Compared with medium, transplanting BM-EC (n = 6), HUVEC (n = 6), hESC-EC (n = 8) or hiPSC-EC (n = 8) significantly attenuated severe hind-limb ischemia in mice via enhancement of neovascularization. In conclusion, functional EC can be generated from hECS and hiPSC with similar therapeutic efficacy for attenuation of severe hind-limb ischemia. Differentiation of functional BM-EC was more difficult to achieve in patients with cardiovascular diseases, and hESC-EC or iPSC-EC are readily available as "off-the-shelf" format for the treatment of tissue ischemia.