Summary Background Trastuzumab resistance is a key therapeutic challenge in metastatic breast cancer. We postulated that broader inhibition of ErbB receptors with afatinib would improve clinical ...outcomes compared with HER2 inhibition alone in patients who had progressed on previous trastuzumab treatment. LUX-Breast 1 compared afatinib plus vinorelbine with trastuzumab plus vinorelbine for such patients with HER2-positive metastatic breast cancer. Methods We did this open-label trial at 350 hospitals in 41 countries worldwide. We enrolled female patients with HER2-overexpressing metastatic breast cancer who had progressed on or following adjuvant trastuzumab or first-line treatment of metastatic disease with trastuzumab. Participants were randomly assigned (2:1) to receive oral afatinib (40 mg/day) plus intravenous vinorelbine (25 mg/m2 per week) or intravenous trastuzumab (2 mg/kg per week after 4 mg/kg loading dose) plus vinorelbine. Randomisation was done centrally and stratified by previous trastuzumab treatment (adjuvant vs first-line treatment), hormone receptor status (oestrogen receptor and progesterone receptor positive vs others), and region. The primary endpoint was progression-free survival, assessed in the intention-to-treat population. This trial is closed to enrolment and is registered with ClinicalTrials.gov , NCT01125566. Findings Between Aug 26, 2010, and April 26, 2013, we enrolled 508 patients: 339 assigned to the afatinib group and 169 assigned to the trastuzumab group. Recruitment was stopped on April 26, 2013, after a benefit–risk assessment by the independent data monitoring committee was unfavourable for the afatinib group. Patients on afatinib plus vinorelbine had to switch to trastuzumab plus vinorelbine, afatinib monotherapy, vinorelbine monotherapy, or receive treatment outside of the trial. Median follow-up was 9·3 months (IQR 3·7–16·0). Median progression-free survival was 5·5 months (95% CI 5·4–5·6) in the afatinib group and 5·6 months (5·3–7·3) in the trastuzumab group (hazard ratio 1·10 95% CI 0·86–1·41; p=0·43). The most common drug-related adverse events of grade 3 or higher were neutropenia (190 56% of 337 patients in the afatinib group vs 102 60% of 169 patients in the trastuzumab group), leucopenia (64 19% vs 34 20%), and diarrhoea (60 18% vs none). Interpretation Trastuzumab-based therapy remains the treatment of choice for patients with HER2-positive metastatic breast cancer who had progressed on trastuzumab. Funding Boehringer Ingelheim.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract Purpose The aim of this study is to examine the relationship between physician case volume and the outcomes of critically ill children with pneumonia. Materials and methods This is a ...population-based cohort study analyzed data provided from by the National Health Insurance Research Database of Taiwan, 2006-2009. Children (aged 3 months to 17 years) having records of intensive care unit (ICU) admission and a diagnosis of pneumonia were included. A total of 9754 critically ill children and 1042 attending physicians were enrolled. The children were assigned to 1 of 4 groups based on the physician's pneumonia case volume. Results The patients in the very high case volume group had a significantly lower length of hospital stay, in-hospital mortality rate, and hospitalization expenses, and a significantly higher ratio of ICU to hospital stays than the other 3 groups ( P < .001). The probability of death tended to be lower when the physician's case volume was higher. The risk-adjusted odds ratio for in-hospital mortality of very-high case volume group was 0.48 (95% confidence interval, 0.35-0.65; P < .001) compared to low case volume group. Conclusions A higher physician's pneumonia case volume is associated with a lower length of hospital stay, lower in-hospital mortality rate, and lower hospitalization expenses among critically ill children with pneumonia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective Our objective was to evaluate the early and midterm outcomes of palliative arterial switch operation in which a ventricular septal defect was not closed or repaired with a fenestrated patch ...in patients with transposition of the great arteries, ventricular septal defect, and severe pulmonary vascular obstructive disease. Methods Between March 2000 and September 2009, the palliative arterial switch operation was performed in 21 patients with a mean age of 3.7 years (range, 0.5–15). Mean preoperative values for systolic pulmonary arterial pressure and systemic arterial oxygen saturation were 91 mm Hg and 69%, respectively. Eighty-one percent of the patients were in New York Heart Association functional class III or IV preoperatively. Results Early mortality was 14.3%. Mean follow-up was 4.0 years (maximum 9.5 years). Regression of pulmonary arterial pressure occurred in 8 patients (44% of the early survivors). Three of the 8 fenestrations were closed interventionally. Mean postoperative systemic arterial oxygen saturation increased significantly to 93% ( P < .001). One late death occurred 3 months after surgery. All the long-term survivors (n =17) were in New York Heart Association functional class I or II ( P < .001). Conclusions The palliative arterial switch operation significantly improved the quality of life and possibly life expectancy in patients with transposition of the great arteries, ventricular septal defect, and severe pulmonary vascular obstructive disease. Postoperative pulmonary vascular resistance might be reversible in some patients. Closing the ventricular septal defect with a fenestrated patch, which can be easily closed nonsurgically later on, might contribute to a safer postoperative recovery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hepatitis C virus (HCV) infection is a serious disease worldwide and it leads to several serious hepatic sequels. Some studies find possible correlation between HCV and ischemic heart disease in ...retrospective observations. Based on lacked community-based evidence, the study aims to assess correlation between ischemic heart disease and chronic HCV infection via electrocardiogram (ECG) because its abnormalities is strongly associating with cardiovascular disease mortality.
The population was from one community health examination in December 2010 in a southern village of Taiwan. A total of 9856 participants were evaluated and finally 5015 eligible residents with age older than 40 years were included. The baseline characteristics and laboratory data in nonischemic ECG and ischemic ECG groups were compared, and multivariate-adjusted analysis was used to evaluate the risks to ischemic ECG.
The higher prevalence of hypertension, metabolic syndrome and even HCV infection (25.3% versus 11.6%; P < 0.001) in ischemic ECG group than those in nonischemic ECG group. In the multivariate adjusted analysis, HCV infection would lead to a 1.759-fold risk to ischemic ECG when compared with non-HCV subjects.
HCV was strongly associated with ischemic ECG findings in this community study, and it could be a nonconventional risk factor for coronary artery disease.
Abstract Mild head trauma can cause cerebral infarction in children younger than 18 months of age, yet the pathogenesis, clinical characteristics, and risk factors are not fully understood. Data of ...16 cases between August 2008 and September 2011, including clinical manifestations and imaging and laboratory findings were collected and analyzed. All patients had the history of mild head trauma. The median age of the cohort was 13.5 months (range 6 months to 18 months). All children developed neurologic symptoms and signs within 72 hours after trauma, 62.5% (10/16) within 30 minutes. The first symptoms included hemiparesis (9/16), facial paresis (4/16), and convulsion (6/16). Overall, 93.75% (15/16) of the lesions were in the basal ganglia region. Two risk factors were identified, basal ganglia calcification in 10 and cytomegalovirus infection in eight. After conservative therapy, the neurologic deficits recovered to some extent. Cerebral infarction after mild head trauma in children younger than 18 months of age may take place, especially under the circumstances of basal ganglia calcification or cytomegalovirus infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background:. Patient-reported outcome measures (PROMs) and, specifically, the Patient-Reported Outcomes Measurement Information System (PROMIS), are increasingly utilized for clinical research, ...clinical care, and health-care policy. However, completion of these outcome measures can be inconsistent and challenging. We hypothesized that sociodemographic variables are associated with the completion of PROM questionnaires. The purposes of the present study were to calculate the completion rate of assigned PROM forms and to identify sociodemographic and other variables associated with completion to help guide improved collection efforts. Methods:. All new orthopaedic patients at a single academic medical center were identified from 2016 to 2020. On the basis of subspecialty and presenting condition, patients were assigned certain PROMIS forms and legacy PROMs. Demographic and clinical information was abstracted from the electronic medical record. Bivariate analyses were performed to compare characteristics among those who completed assigned PROMs and those who did not. A multivariable logistic regression model was created to determine which variables were associated with successful completion of assigned PROMs. Results:. Of the 219,891 new patients, 88,052 (40%) completed all assigned PROMs. Patients who did not activate their internet-based patient portal had a 62% increased likelihood of not completing assigned PROMs (odds ratio OR, 1.62; 95% confidence interval CI, 1.58 to 1.66; p < 0.001). Non-English-speaking patients had a 90% (OR, 1.90; 95% CI, 1.82 to 2.00; p < 0.001) increased likelihood of not completing assigned PROMs at presentation. Older patients (≥65 years of age) and patients of Black race had a 23% (OR, 1.23; 95% CI, 1.19 to 1.27; p < 0.001) and 24% (OR, 1.24; 95% CI, 1.19 to 1.30; p < 0.001) increased likelihood of not completing assigned PROMs, respectively. Conclusions:. The rate of completion of PROMs varies according to sociodemographic variables. This variability could bias clinical outcomes research in orthopaedic surgery. The present study highlights the need to uniformly increase completion rates so that outcomes research incorporates truly representative cohorts of patients treated. Furthermore, the use of these PROMs to guide health-care policy decisions necessitates a representative patient distribution to avoid bias in the health-care system. Level of Evidence:. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Between 1 July and 30 September 2018, small unmanned aircraft
systems (sUAS), tethered balloon systems (TBSs), and additional radiosondes
were deployed at Oliktok Point, Alaska, to measure the ...atmosphere in support
of the second special observing period for the Year of Polar Prediction
(YOPP). These measurements, collected as part of the Profiling at Oliktok
Point to Enhance YOPP Experiments (POPEYE) campaign, targeted quantities
related to enhancing our understanding of boundary layer structure, cloud
and aerosol properties and surface–atmosphere exchange and providing extra
information for model evaluation and improvement work. Over the 3-month
campaign, a total of 59 DataHawk2 sUAS flights, 52 TBS flights, and 238
radiosonde launches were completed as part of POPEYE. The data from
these coordinated activities provide a comprehensive three-dimensional data
set of the atmospheric state (air temperature, humidity, pressure, and
wind), surface skin temperature, aerosol properties, and cloud microphysical
information over Oliktok Point. These data sets have been checked for
quality and submitted to the US Department of Energy (DOE) Atmospheric
Radiation Measurement (ARM) program data archive
(http://www.archive.arm.gov/discovery/, last access: July 2019) and are accessible at no cost by all
registered users. The primary dataset DOIs are https://doi.org/10.5439/1418259 (DataHawk2
measurements; Atmospheric Radiation Measurement Program, 2016),
https://doi.org/10.5439/1426242 (TBS measurements; Atmospheric Radiation Measurement
Program, 2017) and https://doi.org/10.5439/1021460 (radiosonde measurements; Atmospheric
Radiation Measurement Program, 2013a).
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Miniature chromosome maintenance (MCM) proteins play critical roles in DNA replication licensing, initiation and elongation. MCM8, one of the MCM proteins playing a critical role in DNA repairing and ...recombination, was found to have overexpression and increased DNA copy number in a variety of human malignancies. The gain of MCM8 is associated with aggressive clinical features of several human cancers. Increased expression of MCM8 in prostate cancer is associated with cancer recurrence. Forced expression of MCM8 in RWPE1 cells, the immortalized but non-transformed prostate epithelial cell line, exhibited fast cell growth and transformation, while knock down of MCM8 in PC3, DU145 and LNCaP cells induced cell growth arrest, and decreased tumour volumes and mortality of severe combined immunodeficiency mice xenografted with PC3 and DU145 cells. MCM8 bound cyclin D1 and activated Rb protein phosphorylation by cyclin-dependent kinase 4 in vitro and in vivo. The cyclin D1/MCM8 interaction is required for Rb phosphorylation and S-phase entry in cancer cells. As a result, our study showed that copy number increase and overexpression of MCM8 may play critical roles in human cancer development.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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