OBJECTIVES: To determine the association between obstructive sleep apnea and 30-day risk of cardiovascular complications after major noncardiac surgery.
DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study involving adult at-risk patients without prior diagnosis of sleep apnea and undergoing major noncardiac surgery from 8 hospitals in 5 countries between January 2012 and July 2017, with follow-up until August 2017. Postoperative monitoring included nocturnal pulse oximetry and measurement of cardiac troponin concentrations.
EXPOSURES: Obstructive sleep apnea was classified as mild (respiratory event index [REI] 5-14.9 events/h), moderate (REI 15-30), and severe (REI >30), based on preoperative portable sleep monitoring.
MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of myocardial injury, cardiac death, heart failure, thromboembolism, atrial fibrillation, and stroke within 30 days of surgery. Proportional-hazards analysis was used to determine the association between obstructive sleep apnea and postoperative cardiovascular complications.
RESULTS: Among a total of 1364 patients recruited for the study, 1218 patients (mean age, 67 [SD, 9] years; 40.2% women) were included in the analyses. At 30 days after surgery, rates of the primary outcome were 30.1% (41/136) for patients with severe OSA, 22.1% (52/235) for patients with moderate OSA, 19.0% (86/452) for patients with mild OSA, and 14.2% (56/395) for patients with no OSA. OSA was associated with higher risk for the primary outcome (adjusted hazard ratio [HR], 1.49 [95% CI, 1.19-2.01]; P = .01); however, the association was significant only among patients with severe OSA (adjusted HR, 2.23 [95% CI, 1.49-3.34]; P = .001) and not among those with moderate OSA (adjusted HR, 1.47 [95% CI, 0.98-2.09]; P = .07) or mild OSA (adjusted HR, 1.36 [95% CI, 0.97-1.91]; P = .08) (P = .01 for interaction). The mean cumulative duration of oxyhemoglobin desaturation less than 80% during the first 3 postoperative nights in patients with cardiovascular complications (23.1 [95% CI, 15.5-27.7] minutes) was longer than in those without (10.2 [95% CI, 7.8-10.9] minutes) (P
Methods: We conducted a retrospective review of 70 patients with LPD (35 with lymphoma and 35 with multiple myeloma) who had undergone APBSCT between January 2008 and December 2016. Data obtained included disease type, treatment, and stem cell characteristics. Kaplan-Meier analysis was performed for probabilities of neutrophil and platelet engraftment occurred and was compared by the log-rank test. The multivariate Cox proportional hazards regression model was used for the analysis of potential independent factors influencing engraftment. A p-value < 0.050 was considered statistically significant.
Results: Most patients were ethnic Malay, the median age at transplantation was 49.5 years. Neutrophil and platelet engraftment occurred in a median time of 18 (range 4-65) and 17 (range 6-66) days, respectively. The majority of patients showed engraftment with 65 (92.9%) and 63 (90.0%) showing neutrophil and platelet engraftment, respectively. We observed significant differences between neutrophil engraftment and patient's weight (< 60/≥ 60 kg), stage of disease at diagnosis, number of previous chemotherapy cycles (< 8/≥ 8), and pre-transplant radiotherapy. While for platelet engraftment, we found significant differences with gender, patient's weight (< 60/≥ 60 kg), pre-transplant radiotherapy, and CD34+ dosage (< 5.0/≥ 5.0 × 106/kg and < 7.0/≥ 7.0 × 106/kg). The stage of disease at diagnosis (p = 0.012) and pre-transplant radiotherapy (p = 0.025) were found to be independent factors for neutrophil engraftment whereas patient's weight (< 60/≥ 60 kg, p = 0.017), age at transplantation (< 50/≥ 50 years, p = 0.038), and CD34+ dosage (< 7.0/≥ 7.0 × 106/kg, p = 0.002) were found to be independent factors for platelet engraftment.
Conclusions: Patients with LPD who presented at an early stage and with no history of radiotherapy had faster neutrophil engraftment after APBSCT, while a younger age at transplantation with a higher dose of CD34+ cells may predict faster platelet engraftment. However, additional studies are necessary for better understanding of engraftment kinetics to improve the success of APBSCT.
METHODS: This was a two-centre randomised controlled trial of CI versus IB dosing of beta-lactam antibiotics, which enrolled critically ill participants with severe sepsis who were not on renal replacement therapy (RRT). The primary outcome was clinical cure at 14 days after antibiotic cessation. Secondary outcomes were PK/PD target attainment, ICU-free days and ventilator-free days at day 28 post-randomisation, 14- and 30-day survival, and time to white cell count normalisation.
RESULTS: A total of 140 participants were enrolled with 70 participants each allocated to CI and IB dosing. CI participants had higher clinical cure rates (56 versus 34 %, p = 0.011) and higher median ventilator-free days (22 versus 14 days, p MIC than the IB arm on day 1 (97 versus 70 %, p
METHODS: In this population-based case series, we evaluated breast cancer risk factors in relation to 10-year all-cause mortality (ACM) and 5-year recurrence by molecular subtype among 3012 women with invasive breast cancer in Sarawak, Malaysia. A total of 579 deaths and 314 recurrence events occurred during a median follow-up period of ~ 24 months. Subtypes (luminal A-like, luminal B-like, HER2-enriched, triple-negative) were defined using immunohistochemical markers for hormone receptors and human epidermal growth factor receptor 2 (HER2) in conjunction with histologic grade. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between risk factors and ACM/recurrence were estimated in subtype-specific Cox regression models.
RESULTS: We observed heterogeneity in the relationships between parity/breastfeeding, age at first full-term pregnancy (FFP), family history, body mass index (BMI), and tumor subtype (p value 30 vs
METHODS: Venous blood samples from 46 pathologically confirmed PDAC patients were collected prospectively before surgery and immunoassayed using a specially designed TU-chip™. Captured CTCs were differentiated into epithelial (E), mesenchymal and hybrid (H) phenotypes. A further 45 non-neoplastic healthy donors provided blood for cell line validation study and CTC false positive quantification.
FINDINGS: A validated multivariable model consisting of disjunctively combined CTC phenotypes: "H-CTC≥15.0 CTCs/2ml OR E-CTC≥11.0 CTCs/2ml" generated an optimal prediction of metastasis with a sensitivity of 1.000 (95% CI 0.889-1.000) and specificity of 0.886 (95% CI 0.765-0.972). The adjusted Kaplan-Meier median OS constructed using Cox proportional-hazard models and stratified for E-CTC
MATERIALS AND METHODS: Two EGFR mutation tests, a tissue-based assay (cobas® v1) and a tissue- and blood-based assay (cobas® v2) were used to analyze matched biopsy and blood samples (897 paired samples) from three Asian studies of first-line erlotinib with similar intent-to-treat populations. ENSURE was a phase III comparison of erlotinib and gemcitabine/platinum, FASTACT-2 was a phase III study of gemcitabine/platinum plus erlotinib or placebo, and ASPIRATION was a single-arm phase II study of erlotinib. Agreement statistics were evaluated, based on sensitivity and specificity between the two assays in subgroups of patients with increasing tumor burden.
RESULTS: Patients with discordant EGFR (tissue+/plasma-) mutation status achieved longer progression-free and overall survival than those with concordant (tissue+/plasma+) mutation status. Tumor burden was significantly greater in patients with concordant versus discordant mutations. Pooled analyses of data from the three studies showed a sensitivity of 72.1% (95% confidence interval [CI] 67.8-76.1) and a specificity of 97.9% (95% CI 96.0-99.0) for blood-based testing; sensitivity was greatest in patients with larger baseline tumors.
CONCLUSIONS: Blood-based EGFR mutation testing demonstrated high specificity and good sensitivity, and offers a convenient and easily accessible diagnostic method to complement tissue-based tests. Patients with a discordant mutation status in plasma and tissue, had improved survival outcomes compared with those with a concordant mutation status, which may be due to their lower tumor burden. These data help to inform the clinical utility of this blood-based assay for the detection of EGFR mutations.