Neurological Response to cART vs. cART plus Integrase Inhibitor and CCR5 Antagonist Initiated during Acute HIV

Objective

To compare central nervous system (CNS) outcomes in participants treated during acute HIV infection with standard combination antiretroviral therapy (cART) vs. cART plus integrase inhibitor and CCR5 antagonist (cART+).

Design

24-week randomized open-label prospective evaluation.

Method

Participants were evaluated then randomized to initiate cART (efavirenz, tenofovir, and either emtricitabine or lamivudine) vs. cART+ (cART plus raltegravir and maraviroc) during acute HIV and re-evaluated at 4, 12 and 24 weeks. We examined plasma and CSF cytokines, HIV RNA levels, neurological and neuropsychological findings, and brain MRS across groups and compared to healthy controls.

Results

At baseline, 62 participants were in Fiebig stages I-V. Randomized groups were similar for mean age (27 vs. 25, p = 0.137), gender (each 94% male), plasma log₁₀ HIV RNA (5.4 vs. 5.6, p = 0.382), CSF log₁₀ HIV RNA (2.35 vs. 3.31, p = 0.561), and estimated duration of HIV (18 vs. 17 days, p = 0.546). Randomized arms did not differ at 24 weeks by any CNS outcome. Combining arms, all measures concurrent with antiretroviral treatment improved, for example, neuropsychological testing (mean NPZ-4 of -0.408 vs. 0.245, p<0.001) and inflammatory markers by MRS (e.g. mean frontal white matter (FWM) choline of 2.92 vs. 2.84, p = 0.045) at baseline and week 24, respectively. Plasma neopterin (p<0.001) and interferon gamma-induced protein 10 (IP-10) (p = 0.007) remained elevated in participants compared to controls but no statistically significant differences were seen in CSF cytokines compared to controls, despite individual variability among the HIV-infected group.

Conclusions

A 24-week course of cART+ improved CNS related outcomes, but was not associated with measurable differences compared to standard cART.     

Dysphagia in Acute Stroke: Incidence,Burden and Impact on Clinical Outcome

Background

Reported frequency of post-stroke dysphagia in the literature is highly variable. In view of progress in stroke management, we aimed to assess the current burden of dysphagia in acute ischemic stroke.

Methods

We studied 570 consecutive patients treated in a tertiary stroke center. Dysphagia was evaluated by using the Gugging Swallowing Screen (GUSS). We investigated the relationship of dysphagia with pneumonia, length of hospital stay and discharge destination and compared rates of favourable clinical outcome and mortality at 3 months between dysphagic patients and those without dysphagia.

Results

Dysphagia was diagnosed in 118 of 570 (20.7%) patients and persisted in 60 (50.9%) at hospital discharge. Thirty-six (30.5%) patients needed nasogastric tube because of severe dysphagia. Stroke severity rather than infarct location was associated with dysphagia. Dysphagic patients suffered more frequently from pneumonia (23.1% vs. 1.1%, p<0.001), stayed longer at monitored stroke unit beds (4.4±2.8 vs. 2.7±2.4 days; p<0.001) and were less often discharged to home (19.5% vs. 63.7%, p = 0.001) as compared to those without dysphagia. At 3 months, dysphagic patients less often had a favourable outcome (35.7% vs. 69.7%; p<0.001), less often lived at home (38.8% vs. 76.5%; p<0.001), and more often had died (13.6% vs. 1.6%; p<0.001). Multivariate analyses identified dysphagia to be an independent predictor of discharge destination and institutionalization at 3 months, while severe dysphagia requiring tube placement was strongly associated with mortality.

Conclusion

Dysphagia still affects a substantial portion of stroke patients and may have a large impact on clinical outcome, mortality and institutionalization.     

Effects of Statin Therapy on Clinical Outcomes of Survivors of Acute Myocardial Infarction with Severe Systolic Heart Failure

Objective

Large randomized trials have failed to show a beneficial effect of statin treatment in chronic HF. The investigators tried to evaluate the long-term effects of statin therapy in patients with new onset heart failure (HF) following acute myocardial infarction (AMI).

Methods

Between January 2008 and December 2011, a total of 13,616 AMI patients were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR) which was a prospective, multi-center, nationwide, web-based database of AMI in Korea. From this database, we studied 1,055 patients with AMI who had newly developed severe acute HF [left ventricular ejection fraction ≤ 40%] and were discharged alive. The patients were divided into two groups, a statin group (n = 756) and a no-statin group (n = 299). We investigated the one-year major adverse cardiovascular events (MACEs), including all-cause mortality, MI, and any revascularization of each group. We then performed a propensity-score matched analysis.

Results

In the original cohort, one-year MACEs were similar between the two groups (16.5% vs. 14.7% in the statin or no-statin groups; p = 0.47). Propensity-score matching yielded 256 pairs, and in that population we observed comparable results in terms of MACEs (18.0% vs. 12.5% in the statin or no-statin groups, p = 0.11) and mortality (5.1% vs. 3.5% in the statin or no-statin groups, p = 0.51). Cox-regression analysis revealed that statin therapy was not an independent predictor for occurrence of a MACE [Hazard ratio (HR) 1.11, 95% CI 0.79–1.57, p = 0.54] or all-cause mortality (HR 1.42, 95% CI 0.75–2.70, p = 0.28).

Conclusion

Statin therapy was not associated with a reduction in the long-term occurrence of MACEs or mortality in survivors of AMI with severe acute HF in this retrospective cohort study.     

The Humanistic and Economic Burden of Restless Legs Syndrome

Objectives

To evaluate the humanistic and economic burden of a restless legs syndrome (RLS) diagnosis with regard to health-related quality of life, work productivity loss, healthcare resource use, and direct and indirect costs.

Study Design

Self-reported data came from the 2012 National Health and Wellness Survey (NHWS), a large, annual, nationally representative cross-sectional general health survey of US adults.

Methods

RLS patients (n = 2,392) were matched on demographic and health characteristics to Non-RLS respondents via propensity score matching differences between groups were tested with Bivariate and multivariable analyses.

Results

RLS patients had significantly lower health-related quality of life scores: Mental Component Summary (44.60 vs. 48.92, p<.001), Physical Component Summary (40.57 vs. 46.78, p<.001), Health Utilities (.63 vs. .71, p<.001) and higher levels of work productivity loss in the past seven days including absenteeism (8.1% vs. 9.3%, p<.001), presenteeism (26.5% vs. 15.8%, p<.001), and overall productivity loss (30.1% vs. 18.1%, p<.001) as well as general activity impairment (46.1% vs. 29.7%, p<.001). RLS patients had significantly higher healthcare resource use in the past 6 months than non-RLS patients: healthcare provider visits (7.46 vs. 4.42%, p<.001), ER visits (0.45 vs. 0.24, p<.001), and hospitalizations (0.24 vs. 0.15, p<.001). RLS patients also had higher estimated direct and indirect costs than non-RLS patients. Finally, it was found that across outcomes increasing severity is associated with increased economic and humanistic burden for RLS patients.

Conclusions

RLS patients suffer a greater humanistic and economic burden than those without RLS. Moreover as severity increases so does the burden of RLS.     

Time Interval from Symptom Onset to Hospital Care in Patients with Acute Heart Failure: A Report from the Tokyo Cardiac Care Unit Network Emergency Medical Service Database

Aims

There seems to be two distinct patterns in the presentation of acute heart failure (AHF) patients; early- vs. gradual-onset. However, whether time-dependent relationship exists in outcomes of patients with AHF remains unclear.

Methods

The Tokyo Cardiac Care Unit Network Database prospectively collects information of emergency admissions via EMS service to acute cardiac care facilities from 67 participating hospitals in the Tokyo metropolitan area. Between 2009 and 2011, a total of 3811 AHF patients were registered. The documentation of symptom onset time was mandated by the on-site ambulance team. We divided the patients into two groups according to the median onset-to-hospitalization (OH) time for those patients (2h); early- (presenting ≤2h after symptom onset) vs. gradual-onset (late) group (>2h). The primary outcome was in-hospital mortality.

Results

The early OH group had more urgent presentation, as demonstrated by a higher systolic blood pressure (SBP), respiratory rate, and higher incidence of pulmonary congestion (48.6% vs. 41.6%; P<0.001); whereas medical comorbidities such as stroke (10.8% vs. 7.9%; P<0.001) and atrial fibrillation (30.0% vs. 26.0%; P<0.001) were more frequently seen in the late OH group. Overall, 242 (6.5%) patients died during hospitalization. Notably, a shorter OH time was associated with a better in-hospital mortality rate (odds ratio, 0.71; 95% confidence interval, 0.51−0.99; P = 0.043).

Conclusions

Early-onset patients had rather typical AHF presentations (e.g., higher SBP or pulmonary congestion) but had a better in-hospital outcome compared to gradual-onset patients.     

The Changes of Lipid Metabolism in Advanced Renal Cell Carcinoma Patients Treated with Everolimus: A New Pharmacodynamic Marker?

Background

Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between the baseline values and treatmentrelated modifications of total serum cholesterol (C), triglycerides (T), body mass index (BMI), fasting blood glucose level (FBG) and blood pressure (BP) levels and the outcome of patients treated with everolimus for mRCC.

Methods

177 patients were included in this retrospective analysis. Time to progression (TTP), clinical benefit (CB) and overall survival (OS) were evaluated.

Results

Basal BMI was significantly higher in patients who experienced a CB (p=0,0145). C,T and C+T raises were significantly associated with baseline BMI (p=0.0412, 0.0283 and 0.0001). Median TTP was significantly longer in patients with T raise compared to patients without T (10 vs 6, p=0.030), C (8 vs 5, p=0.042) and C+T raise (10.9 vs 5.0, p=0.003). At the multivariate analysis, only C+T increase was associated with improved TTP (p=0.005). T raise (21.0 vs 14.0, p=0.002) and C+T increase (21.0 vs 14.0, p=0.006) were correlated with improved OS but were not significant at multivariate analysis.

Conclusion

C+T raise is an early predictor for everolimus efficacy for patients with mRCC.     

One-Year Effects of Project EX in Spain: A Classroom-Based Smoking Prevention and Cessation Intervention Program

Background

Tobacco use prevalence rates are high among Spanish adolescents. Programming to counteract tobacco use is needed.

Methods and Findings

The current study provides a one-year follow-up outcome evaluation of Project EX, an eight-session classroom-based curriculum. The intervention was tested using a randomized controlled trial with 1,546 Spanish students, involving three program and three control schools. Compared to the control condition, the program condition revealed a greater reduction in nicotine dependence (p < .05) and CO ppm levels (p < .001), and lower consumption of cigarettes at last month (p = .03).

Conclusions

Long-term outcomes of the Project EX classroom-based program are promising for adolescent prevention and possibly cessation in Spain.     

Healthcare Service Utilization for Practicing Physicians: A Population-Based Study

Background

Physicians are considered to be the most informed consumers in the use of medical services since they have more information about diseases or medical technology. However, although plenty of researchers have suggested that different medical seeking behavior exists among physicians, very few empirical studies have been conducted to investigate differences in medical utilization between physicians and the general population.

Objective

We explored differences in the utilization of healthcare services between physicians and the general population using a population-based dataset.

Design

A cross-sectional study.

Participants

Data for this study were sourced from the Taiwan Longitudinal Health Insurance Database 2000. We included 1426 physicians and 1426 sex- and age-matched comparison subjects.

Methods

We used Wilcoxon-Mann-Whitney tests to explore differences in variables of healthcare resource utilization between physicians and comparison subjects. We further used Kruskal-Wallis tests to examine differences in variables of healthcare resource utilization between physician practice location and comparison subjects.

Results

We found that physicians had significantly fewer outpatient visits (13.2 vs. 15.7, p<0.001) and significantly lower outpatient costs (US$477 vs. US$680, p<0.001) than comparison subjects. Furthermore, physicians had lower total health service costs than comparison subjects (US$643 vs. US$1066, p<0.001). This indicates that the mean total health service costs in the year 2010 was 1.66-fold greater for comparison subjects than for physicians. We also found that there were significant differences in the mean number of outpatient services (p<0.001), outpatient costs (p = 0.001), inpatients costs (p = 0.018), and total costs (p = 0.001) among office-based physicians, hospital-based physicians, and comparison subjects. Specifically, Scheffe contrast tests showed that office-based physicians had significantly more outpatient visits (19.3 vs.10.7, p<0.001) and significantly higher outpatient costs (US$656 vs. US$402, p<0.001) than hospital-based physicians.

Conclusions

Physicians had less healthcare utilization than comparison subjects. Furthermore, hospital-based physicians had higher inpatient costs and less outpatient services and costs than office-based physicians.     

Quantitative Comparison of the Walk and Trot of Border Collies and Labrador Retrievers,Breeds with Different Performance Requirements

Introduction

We hypothesized that breed differences of Border Collies and Labrador Retrievers would be reflected in the temporospatial characteristics of the walk and trot.

Materials and Methods

Twenty healthy Border Collies and 20 healthy Labrador Retrievers made three passes across a pressure sensing walkway system that recorded quantitative temporospatial information at a walk and a trot. The following variables were measured for each dog: velocity, total pressure index percentage (TPI%), ratio of weight borne on the thoracic vs. pelvic limbs (T/P TPI%), stance time percentage (ST%), and thoracic limb stride length (TSrL).

Results

The mean T/P TPI% for Border Collies at a walk and at a trot were significantly lower than for Labrador Retrievers (p = 0.0007 and p = 0.0003). Border Collies had a significantly lower ST% than Labrador Retrievers for the thoracic limbs and pelvic limbs at a walk (p = 0.0058 and 0.0003) and the trot (p = 0.0280 and 0.0448). There was no relationship between ST% and TSrL in Border Collies and an inverse correlation between ST% and TSrL in Labrador Retrievers (p = 0.0002).

Discussion

Key quantitative gait differences were identified in Border Collies and Labrador Retrievers, which could potentially provide each breed with an advantage for their working function.     

Combining Amplitude Spectrum Area with Previous Shock Information Using Neural Networks Improves Prediction Performance of Defibrillation Outcome for Subsequent Shocks in Out-Of-Hospital Cardiac Arrest Patients

Objective

Quantitative ventricular fibrillation (VF) waveform analysis is a potentially powerful tool to optimize defibrillation. However, whether combining VF features with additional attributes that related to the previous shock could enhance the prediction performance for subsequent shocks is still uncertain.

Methods

A total of 528 defibrillation shocks from 199 patients experienced out-of-hospital cardiac arrest were analyzed in this study. VF waveform was quantified using amplitude spectrum area (AMSA) from defibrillator''s ECG recordings prior to each shock. Combinations of AMSA with previous shock index (PSI) or/and change of AMSA (ΔAMSA) between successive shocks were exercised through a training dataset including 255shocks from 99patientswith neural networks. Performance of the combination methods were compared with AMSA based single feature prediction by area under receiver operating characteristic curve(AUC), sensitivity, positive predictive value (PPV), negative predictive value (NPV) and prediction accuracy (PA) through a validation dataset that was consisted of 273 shocks from 100patients.

Results

A total of61 (61.0%) patients required subsequent shocks (N = 173) in the validation dataset. Combining AMSA with PSI and ΔAMSA obtained highest AUC (0.904 vs. 0.819, p<0.001) among different combination approaches for subsequent shocks. Sensitivity (76.5% vs. 35.3%, p<0.001), NPV (90.2% vs. 76.9%, p = 0.007) and PA (86.1% vs. 74.0%, p = 0.005)were greatly improved compared with AMSA based single feature prediction with a threshold of 90% specificity.

Conclusion

In this retrospective study, combining AMSA with previous shock information using neural networks greatly improves prediction performance of defibrillation outcome for subsequent shocks.     

The Prevalence and Characteristics of Primary Headache and Dream-Enacting Behaviour in Japanese Patients with Narcolepsy or Idiopathic Hypersomnia: A Multi-Centre Cross-Sectional Study

Background

Because the prevalence and characteristics of primary headache have yet to be thoroughly studied in patients with hypersomnia disorders, including narcolepsy and idiopathic hypersomnia, we examined these parameters in the Japanese population.

Methods

In a multicentre cross-sectional survey, among 576 consecutive outpatients with sleep disorders, 68 narcolepsy patients and 35 idiopathic hypersomnia patients were included. Additionally, 61 healthy control subjects participated. Semi-structured headache questionnaires were administered to all participants.

Results

The patients with narcolepsy (52.9%) and idiopathic hypersomnia (77.1%) more frequently experienced headache than the healthy controls (24.6%; p<0.0001). The prevalence rates were 23.5%, 41.2% and 4.9% for migraine (p<0.0001) and 16.2%, 23.5% and 14.8% (p = 0.58) for tension-type headache among the narcolepsy patients, the idiopathic hypersomnia patients and the control subjects, respectively. Those who experienced migraine more frequently experienced excessive daytime sleepiness, defined as an Epworth Sleepiness Scale score of ≥10, than those who did not experience headache among the patients with narcolepsy (93.8% vs. 65.6%, p = 0.040) and idiopathic hypersomnia (86.7% vs. 37.5%, p = 0.026). Dream-enacting behaviour (DEB), as evaluated by the rapid eye movement sleep disorders questionnaire, was more frequently observed in the narcolepsy patients than in the idiopathic hypersomnia patients and the control subjects. An increased DEB frequency was observed in the narcolepsy patients with migraines compared to those without headache.

Conclusions

Migraines were frequently observed in patients with narcolepsy and idiopathic hypersomnia. DEB is a characteristic of narcolepsy patients. Further studies are required to assess the factors that contribute to migraines in narcolepsy and idiopathic hypersomnia patients.     

Gender Differences in Patients with Takotsubo Cardiomyopathy: Multi-Center Registry from Tokyo CCU Network

Background

The clinical features of gender differences in takotsubo cardiomyopathy (TC) remain to be determined. The aim of this study was to evaluate the differences in clinical characteristics of male and female patients with TC.

Methods

We obtained the clinical information of 368 patients diagnosed with TC (84 male, 284 female) from the Tokyo CCU Network database collected from 1 January 2010 to 31 December 2012; the Network is comprised of 71 cardiovascular centers in the Tokyo (Japan) metropolitan area. We attempted to characterize clinical differences during hospitalization, comparing male and female patients with TC.

Results

There were no significant differences in apical ballooning type, median echocardiography ejection fraction, serious ventricular arrhythmias (such as ventricular tachycardia or fibrillation), or cardiovascular death between male and female patients. Male patients were younger than female patients (median age at hospitalization for male patients was 72 years vs. 76 years for female patients; p = 0.040). Prior physical stress was more common in male than female patients (50.0% vs.31.3%; p = 0.002), while emotional stress was more common in female patients (19.0% vs. 31.0%; p = 0.039). Severe pump failure (defined as Killip Class > III) (20.2% vs. 10.6%; p = 0.020) and cardiopulmonary supportive therapies (28.6% vs. 12.7%, p < 0.001) were more common in male than female patients. Multivariate analysis revealed that male gender (odds ratio = 4.32, 95% CI = 1.41–13.6, p = 0.011) was an independent predictor of adverse composite cardiac events, including cardiovascular death, severe pump failure, and serious ventricular arrhythmia.

Conclusions

Cardiac complications in our dataset appeared to be more common in male than female patients with TC during their hospitalization. Further investigation is required to clarify the underlying mechanisms responsible for the observed gender differences.     

Response to Therapeutic Plasma Exchange as a Rescue Treatment in Clinically Isolated Syndromes and Acute Worsening of Multiple Sclerosis: A Retrospective Analysis of 90 Patients

Objectives

Experience with therapeutic plasma exchange (TPE) for acute relapses in clinically isolated syndrome (CIS) or multiple sclerosis (MS) patients has been derived from small and inhomogeneous patient populations so far. In the present study, we retrospectively evaluated features associated with TPE response in a larger cohort of CIS and MS patients with acute worsening of disease.

Participants

Ninety CIS and MS patients with acute relapses or acute worsening of symptoms were firstly treated with TPE. The population consisted of 62 women and 28 men with a median age of 38 years (range 18–69 years).

Outcome Measures

Primary endpoint was the clinical response to TPE, focused on the functional improvement of the target neurologic deficit. Secondary endpoint was an improvement in expanded disability status scale (EDSS) scoring.

Results

A clinical response to TPE was observed in 65 out of 90 patients (72.2%), with marked improvement in 18 (20.0%) and moderate improvement in 47 out of 90 patients (52.2%). The median EDSS was reduced from 3.75 before to 3.0 after TPE (p = 0.001). Response to TPE was significantly more frequent in patients with relapsing courses of disease (CIS, RR-MS, p = 0.001), no disease modifying drugs (p = 0.017), gadolinium-positive (Gd⁺) MRI lesions (p = 0.001) and EDSS ≤ 5.0 before TPE (p = 0.014). In the multiple logistic regression analysis only the detection of Gd⁺ MRI lesions was significantly altered (p = 0.004).

Conclusion

Clinical response to TPE was achieved in the majority of our patients. We identified clinical and diagnostic features in CIS and MS relapses that might be helpful to identify patients responding to TPE. Gd⁺ MRI lesions before treatment were the best predictor of the response to TPE in our cohort.     

The Diagnostic Accuracy of Urine Lipoarabinomannan Test for Tuberculosis Screening in a South African Correctional Facility

Background

We evaluated the diagnostic accuracy of the urine lipoarabinomannan (LAM) antigen detection assay (Clearview TB-ELISA) to screen for tuberculosis in a South African correctional facility.

Methods

Between September 2009 and October 2010, male offenders were screened for tuberculosis (symptoms, chest radiograph, two spot sputum specimens for microscopy and culture), and urine tested for LAM. Sensitivity, specificity and predictive values of LAM were calculated using definite and probable tuberculosis combined as our gold standard.

Findings

33/871 (3.8%) participants (26% HIV-positive) had tuberculosis. Amongst HIV-positive vs. HIV-negative offenders the sensitivity and specificity of LAM was 7.1% vs. 0% and 98.5% vs. 99.8% respectively.

Conclusion

Urine LAM ELISA has inadequate sensitivity for TB screening in this population.     

Workplace Health Promotion: Assessing the Cardiopulmonary Risks of the Construction Workforce in Hong Kong

Objective

Health needs of different employee subgroups within an industry can differ. We report the results of a workplace cardiopulmonary risk assessment targeting workers and support staff in the construction industry.

Methods

A free worksite-based cardiopulmonary risk assessment for 1,903 workers on infrastructural contracts across Hong Kong was initiated in May 2014. Cardiopulmonary risk screening was performed in 60-minute blocks for approximately 30 workers/block with individualized feedback and lifestyle counseling. Risk profiles stratified by occupational roles are differentiated using the χ²-test for categorical and Student’s t-test for continuous variables.

Results

Most construction workers and clerks/professionals were male (83.2% and 71.2%, respectively) and Chinese (78.7% and 90.9%, respectively). Construction workers were older (mean: 44.9 years, SD 11.5) and less well-educated (6.1% received tertiary education) than clerks/professionals (35.0 years, 10.7; 72.6% received tertiary education), but more likely to be hypertensive (22.6% vs. 15.4%, p<0.001), overweight/obese (71.7% vs. 56.6%, p<0.001), centrally obese (53.1% vs. 35.5%, p<0.001), and have undesirable levels of high-density lipoprotein (41.6% vs. 35.8%, p<0.05) and diabetic levels of non-fasting blood glucose (4.3% vs. 1.6%, p<0.05). Up to 12.6% of construction workers and 9.7% of office clerks/professions had three or more metabolic syndrome risk factors. While construction workers were more likely than clerks/professionals to be daily smokers, they reported better work-related physical activity and diet.

Conclusions

Simple worksite health risk screening can identify potentially high-cardiopulmonary-risk construction industry employee subgroups for onward confirmatory referral. Separate cardiopulmonary health promotion strategies that account for the varying lifestyle profiles of the two employee subgroups in the industry appear justified.     

Anaplastic Lymphoma Kinase Gene Copy Number Gain in Inflammatory Breast Cancer (IBC): Prevalence,Clinicopathologic Features and Prognostic Implication

Background

Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer, and its molecular pathogenesis still remains to be elucidated. This study aimed to evaluate the prevalence and implication of anaplastic lymphoma kinase (ALK) copy number change in IBC patients.

Methods

We retrospectively collected formalin-fixed, paraffin-embedded tumor tissues and medical records of IBC patients from several institutes in Korea. ALK gene copy number change and rearrangement were assessed by fluorescence in situ hybridization (FISH) assay, and ALK expression status was evaluated by immunohistochemical (IHC) staining.

Results

Thirty-six IBC patients including those with HER2 (+) breast cancer (16/36, 44.4%) and triple-negative breast cancer (13/36, 36.1%) were enrolled in this study. ALK copy number gain (CNG) was observed in 47.2% (17/36) of patients, including one patient who harbored ALK gene amplification. ALK CNG (+) patients showed significantly worse overall survival compared to ALK CNG (-) patients in univariate analysis (24.9 months vs. 38.1 months, p = 0.033). Recurrence free survival (RFS) after curative mastectomy was also significantly shorter in ALK CNG (+) patients than in ALK CNG (-) patients (n = 22, 12.7 months vs. 43.3 months, p = 0.016). Multivariate Cox regression analysis with adjustment for HER2 and ER statuses showed significantly poorer RFS for ALK CNG (+) patients (HR 5.63, 95% CI 1.11–28.44, p = 0.037).

Conclusion

This study shows a significant presence of ALK CNG in IBC patients, and ALK CNG was associated with significantly poorer RFS.     

Circadian Dependence of Infarct Size and Acute Heart Failure in ST Elevation Myocardial Infarction

Objectives

There are conflicting data on the relationship between the time of symptom onset during the 24-hour cycle (circadian dependence) and infarct size in ST-elevation myocardial infarction (STEMI). Moreover, the impact of this circadian pattern of infarct size on clinical outcomes is unknown. We sought to study the circadian dependence of infarct size and its impact on clinical outcomes in STEMI.

Methods

We studied 6,710 consecutive patients hospitalized for STEMI from 2006 to 2009 in a tropical climate with non-varying day-night cycles. We categorized the time of symptom onset into four 6-hour intervals: midnight–6:00 A.M., 6:00 A.M.–noon, noon–6:00 P.M. and 6:00 P.M.–midnight. We used peak creatine kinase as a surrogate marker of infarct size.

Results

Midnight–6:00 A.M patients had the highest prevalence of diabetes mellitus (P = 0.03), more commonly presented with anterior MI (P = 0.03) and received percutaneous coronary intervention less frequently, as compared with other time intervals (P = 0.03). Adjusted mean peak creatine kinase was highest among midnight–6:00 A.M. patients and lowest among 6:00 A.M.–noon patients (2,590.8±2,839.1 IU/L and 2,336.3±2,386.6 IU/L, respectively, P = 0.04). Midnight–6:00 A.M patients were at greatest risk of acute heart failure (P<0.001), 30-day mortality (P = 0.03) and 1-year mortality (P = 0.03), while the converse was observed in 6:00 A.M.–noon patients. After adjusting for diabetes, infarct location and performance of percutaneous coronary intervention, circadian variations in acute heart failure incidence remained strongly significant (P = 0.001).

Conclusion

We observed a circadian peak and nadir in infarct size during STEMI onset from midnight–6:00A.M and 6:00A.M.–noon respectively. The peak and nadir incidence of acute heart failure paralleled this circadian pattern. Differences in diabetes prevalence, infarct location and mechanical reperfusion may account partly for the observed circadian pattern of infarct size and acute heart failure.     

BTNL2 Gene Polymorphism and Sarcoidosis Susceptibility: A Meta-Analysis

Background

Butyrophilin-like 2 (BTNL2) rs2076530 gene polymorphism has been implicated in susceptibility to sarcoidosis. However, results from previous studies are not consistent. To assess the association of BTNL2 polymorphism and sarcoidosis susceptibility, a meta-analysis was performed.

Methods

PubMed, Embase were searched for eligible case-control studies. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.

Results

Ten studies involving a total of 3303 cases and 2514 controls were included in this meta-analysis. Combined data indicated that BTNL2 rs2076530 polymorphism was associated with sarcoidosis susceptibility in allelic model (A vs. G, OR = 1.59, 95%CI: 1.47–1.72), dominant model (AA + AG vs. GG, OR = 2.10, 95%CI: 1.67–2.65), and recessive model (AA vs. AG + GG, OR = 1.93, 95%CI: 1.49–2.50).

Conclusions

This meta-analysis indicates that BTNL2 rs2076530 polymorphism contributes to the risk of sarcoidosis.     

Impact of Postoperative Chemoradiotherapy versus Chemotherapy Alone on Recurrence and Survival in Patients with Stage II and III Upper Rectal Cancer: A Propensity Score-Matched Analysis

Purpose

To compare the impact of postoperative chemoradiotherapy (CRT) versus adjuvant chemotherapy alone on recurrence and survival in patients with stage II and III upper rectal cancer undergoing curative resection.

Materials and Methods

From our institutional database, 190 patients who underwent primary curative resection between 2003 and 2010 for stage II or III upper rectal cancer were identified. None of the patients received preoperative CRT. Of these, 136 patients received postoperative chemotherapy alone (the CTx group) and 54 patients received postoperative CRT (the CRT group). The CRT group had poorer prognostic features (pT4, pN2, poor differentiation, or involved resection margin) compared with the CTx group. To reduce the impact of treatment selection bias on treatment outcomes, propensity score-matching analysis was used.

Results

The matched cohort consisted of 50 CRT and 50 CTx patients with a median follow-up period of 76 and 63 months, respectively. In the matched cohort, CRT resulted in an improved 5-year local control (98.0% vs. 85.2%, p = 0.024) and overall survival rate (89.9% vs. 69.8%, p = 0.021) compared with CTx. In the subgroup analysis to identify subpopulations of patients that benefit most from receiving CRT, local recurrence did not occur in patients who did not have poor prognostic features regardless of the receipt of CRT. For patients with any poor prognostic features, CRT resulted in an improved 5-year local control compared with CTx (96.4% vs. 70.7%, p = 0.013).

Conclusions

After adjusting for clinicopathologic factors by propensity score-matching, postoperative CRT was associated with improved local control and overall survival in stage II and III upper rectal cancer. Our results suggest that surgery followed by chemotherapy alone is acceptable for patients who did not have poor prognostic features, while additional radiotherapy should be given for patients who have any poor prognostic features.