Purpose: Factors associated with invasive recurrence (REC) of ductal carcinoma in situ (DCIS) are less known. This study was aimed at identifying better biomarkers to predict the prognosis of DCIS. Methods: RNA extracted from formalin-fixed paraffin-embedded blocks of twenty-four pure DCIS cases was subjected to differential gene expression analysis. The DCIS cases were selected by matching age and estrogen receptor status. Sixteen REC-free and 8 invasive-REC cases with disease-free interval of > 5 years were analyzed. Immunohistochemistry (IHC) staining was used to validate sixty-one independent pure DCIS cases, including invasive-REC (n = 16) and REC-free (n = 45) cases. Results: Eight differentially expressed genes (DEGs) were statistically significant (log 2-fold change [FC] < –1 or > 1 and p < 0.001). Less than ½ fold expression of CUL1, androgen receptor (AR), RPS27A, CTNNB1, MAP3K1, PRKACA, GNG12, MGMT genes was observed in the REC group compared to the no evidence of disease group. AR and histone deacetylase 1 (HDAC1) genes were selected for external validation (AR: log 2-FC − 1.35, p < 0.001, and HDAC1: log 2-FC − 0.774, p < 0.001). External validation showed that the absence of AR and high HDAC1 expression were independent risk factors for invasive REC (hazard ratio [HR], 5.04; 95% confidence interval [CI], 1.24–20.4; p = 0.023 and HR, 3.07; 95% CI, 1.04–9.04; p = 0.042). High nuclear grade 3 was also associated with long-term invasive REC. Conclusion Comparative gene expression analysis of pure DCIS revealed 8 DEGs among recurring cases. External validation with IHC suggested that the absence of AR and overexpression of HDAC1 are associated with a greater risk of long-term invasive REC of pure DCIS.

BACKGROUND: AND PURPOSE: The aim of this study was to determine the diagnostic performance and safety of a new ¹⁸F-labeled amyloid tracer, ¹⁸F-FC119S. METHODS: This study prospectively recruited 105 participants, comprising 53 with Alzheimer's disease (AD) patients, 16 patients with dementia other than AD (non-AD), and 36 healthy controls (HCs). In the first screening visit, the Seoul Neuropsychological Screening Battery cognitive function test was given to the dementia group, while HC subjects completed the Korean version of the Mini Mental State Examination. Individuals underwent ¹⁸F-FC119S PET, ¹⁸F-fluorodeoxyglucose (FDG) PET, and brain MRI. The diagnostic performance of ¹⁸F-FC119S PET for AD was compared to a historical control (comprising previously reported and currently used amyloid-beta PET agents), ¹⁸F-FDG PET, and MRI. The standardized uptake value (SUV) ratio (ratio of the cerebral cortical SUV to the cerebellar SUV) was measured for each PET data set to provide semiquantitative analysis. All adverse effects during the clinical trial periods were monitored. RESULTS: Visual assessments of the ¹⁸F-FC119S PET data revealed a sensitivity of 92% and a specificity of 84% in detecting AD. ¹⁸F-FC119S PET demonstrated equivalent or better diagnostic performance for AD detection than the historical control, ¹⁸F-FDG PET (sensitivity of 80.0% and specificity of 76.0%), and MRI (sensitivity of 98.0% and specificity of 50.0%). The SUV ratios differed significantly between AD patients and the other groups, at 1.44±0.17 (mean±SD) for AD, 1.24±0.09 for non-AD, and 1.21±0.08 for HC. No clinically significant adverse effects occurred during the trial periods. CONCLUSIONS ¹⁸F-FC119S PET provides high sensitivity and specificity in detecting AD and therefore may be considered a useful diagnostic tool for AD.

PURPOSE: Ductal carcinoma in situ (DCIS) is a high-risk disease for the development of invasive tumors. Although it is associated with excellent prognosis, many patients undergo extensive treatment with surgery, radiation, and endocrine therapy. This study evaluated the clinical and pathologic factors associated with invasive recurrence, particularly locoregional, distant disease after breast-conserving surgery (BCS). METHODS: This study included 431 patients diagnosed with pure DCIS after BCS between January 2000 and December 2008. The clinicopathological characteristics, margin status, adjuvant therapy, and duration of endocrine therapy were evaluated in hormone receptor-positive DCIS patients. RESULTS: The median duration of follow-up was 115 months. During this period, 37 cases (8.5%) of recurrence were observed (12 in situ and 23 invasive recurrence and 2 unknown cases). There was no distant metastasis as first event. Similarly, none of the initial in situ recurrence cases developed distant metastasis while eight (32%, 8/23) developed distant metastasis after invasive recurrence. Overall recurrence was associated with young age (≤40 years) (HR: 3.60, 95% confidence interval [CI]: 1.77–7.32) and hormone receptor negativity (HR: 3.33, 95% CI: 1.52–7.29). Invasive local recurrence was independently associated with young age (≤40 years) (HR: 3.86, 95% CI: 1.50–9.96), high nuclear grade (HR: 4.46, 95% CI: 1.62–12.27) and omission of adjuvant radiotherapy (HR: 6.45, 95% CI: 1.82–22.82). Notably, duration of endocrine treatment among the hormone receptor positive patient group, was numerically shorter for recurred patients, though not statistically significant. CONCLUSION Young age, high nuclear grade and absence of adjuvant radiotherapy were independently associated with an increased risk of invasive recurrence. Moreover, invasive locoregional recurrence as a first event was associated with worse outcomes, yet in situ recurrence didn't affect overall survival. Further studies with larger sample sizes are warranted to confirm the prognostic indicators of recurrence and the optimal strategy for adjuvant therapy in this setting.

INTRODUCTIONRemote monitoring of cardiac implantable electronic devices (CIED) has been shown to improve patient safety and reduce in-office visits. We report our experience with remote monitoring via the Medtronic CareLink(®) network.

METHODSPatients were followed up for six months with scheduled monthly remote monitoring transmissions in addition to routine in-office checks. The efficacy of remote monitoring was evaluated by recording compliance to transmissions, number of device alerts requiring intervention and time from transmission to review. Questionnaires were administered to evaluate the experiences of patients, physicians and medical technicians.

RESULTSA total of 57 patients were enrolled; 16 (28.1%) had permanent pacemakers, 34 (59.6%) had implantable cardioverter defibrillators and 7 (12.3%) had cardiac resynchronisation therapy defibrillators. Overall, of 334 remote transmissions scheduled, 73.7% were on time, 14.5% were overdue and 11.8% were missed. 84.6% of wireless transmissions were on time, compared to 53.8% of non-wireless transmissions. Among all transmissions, 4.4% contained alerts for which physicians were informed and only 1.8% required intervention. 98.6% of remote transmissions were reviewed by the second working day. 73.2% of patients preferred remote monitoring. Physicians agreed that remote transmissions provided information equivalent to in-office checks 97.1% of the time. 77.8% of medical technicians felt that remote monitoring would help the hospital improve patient management. No adverse events were reported.

CONCLUSIONRemote monitoring of CIED is safe and feasible. It has possible benefits to patient safety through earlier detection of arrhythmias or device malfunction, permitting earlier intervention. Wireless remote monitoring, in particular, may improve compliance to device monitoring. Patients may prefer remote monitoring due to possible improvements in quality of life.

Aged ; Arrhythmias, Cardiac ; diagnosis ; Defibrillators, Implantable ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Monitoring, Physiologic ; methods ; Pacemaker, Artificial ; Patient Safety ; Pilot Projects ; Prospective Studies ; Quality of Life ; Remote Consultation ; methods ; Singapore ; Surveys and Questionnaires

INTRODUCTIONThe use of non-fluoroscopic systems (NFS) to guide radiofrequency catheter ablation (RFCA) for the treatment of supraventricular tachycardia (SVT) is associated with lower radiation exposure. This study aimed to determine if NFS reduces fluoroscopy time, radiation dose and procedure time.

METHODSWe prospectively enrolled patients undergoing RFCA for SVT. NFS included EnSiteTM NavXTM or CARTO® mapping. We compared procedure and fluoroscopy times, and radiation exposure between NFS and conventional fluoroscopy (CF) cohorts. Procedural success, complications and one-year success rates were reported.

RESULTSA total of 200 patients over 27 months were included and RFCA was guided by NFS for 79 patients; those with atrioventricular nodal reentrant tachycardia (AVNRT), left-sided atrioventricular reentrant tachycardia (AVRT) and right-sided AVRT were included (n = 101, 63 and 36, respectively). Fluoroscopy times were significantly lower with NFS than with CF (10.8 ± 11.1 minutes vs. 32.0 ± 27.5 minutes; p < 0.001). The mean fluoroscopic dose area product was also significantly reduced with NFS (NSF: 5,382 ± 5,768 mGy*cm2 vs. CF: 21,070 ± 23,311 mGy*cm2; p < 0.001); for all SVT subtypes. There was no significant reduction in procedure time, except for left-sided AVRT ablation (NFS: 79.2 minutes vs. CF: 116.4 minutes; p = 0.001). Procedural success rates were comparable (NFS: 97.5% vs. CF: 98.3%) and at one-year follow-up, there was no significant difference in the recurrence rates (NFS: 5.2% vs. CF: 4.2%). No clinically significant complications were observed in both groups.

CONCLUSIONThe use of NFS for RFCA for SVT is safe, with significantly reduced radiation dose and fluoroscopy time.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Catheter Ablation ; methods ; Child ; Female ; Fluoroscopy ; Humans ; Male ; Middle Aged ; Prospective Studies ; Radiation Dosage ; Radiation, Ionizing ; Tachycardia, Atrioventricular Nodal Reentry ; therapy ; Tachycardia, Supraventricular ; therapy ; Treatment Outcome ; Young Adult

BACKGROUND: Stainless steel wiring remains the most popular technique for primary sternal closure. Recently, a multifilament cable wiring system (Pioneer Surgical Technology Inc., Marquette, MI, USA) was introduced for sternal closure and has gained wide acceptance due to its superior resistance to tension. We aimed to compare conventional steel wiring to multifilament cable fixation for sternal closure in patients undergoing major cardiac surgery. METHODS: Data were collected retrospectively on 1,354 patients who underwent sternal closure after major cardiac surgery, using either the multifilament cable wiring system or conventional steel wires between January 2009 and October 2010. The surgical outcomes of these two groups of patients were compared using propensity score matching based on 18 baseline patient characteristics. RESULTS: Propensity score matching yielded 392 pairs of patients in the two groups whose baseline profiles showed no significant differences. No significant differences between the two groups were observed in the rates of early mortality (2.0% vs. 1.3%, p=0.578), major wound complications requiring reconstruction (1.3% vs. 1.3%, p>0.99), minor wound complications (3.6% vs. 2.0%, p=0.279), or mediastinitis (0.8% vs. 1.0%, p=1.00). Patients in the multifilament cable group had fewer sternal bleeding events than those in the conventional wire group, but this tendency was not statistically significant (4.3% vs. 7.4%, p=0.068). CONCLUSION: The surgical outcomes of sternal closure using multifilament cable wires were comparable to those observed when conventional steel wires were used. Therefore, the multifilament cable wiring system may be considered a viable option for sternal closure in patients undergoing major cardiac surgery.
Hemorrhage ; Humans ; Mediastinitis ; Mortality ; Propensity Score ; Retrospective Studies ; Stainless Steel ; Steel ; Thoracic Surgery* ; Wounds and Injuries

OBJECTIVE: To investigate the predictive index of functional recovery after primary pontine hemorrhage (PPH) using the combined motor evoked potential (MEP) and somatosensory evoked potential (SEP) in comparison to the hematoma volume and transverse diameter measured with computerized tomography. METHODS: Patients (n=14) with PPH were divided into good- and poor-outcome groups according to the modified Rankin Score (mRS). We evaluated clinical manifestations, radiological characteristics, and the combined MEP and SEP responses. The summed MEP and SEP (EP sum) was compared to the hematoma volume and transverse diameter predictive index of global disability, gait ability, and trunk stability in sitting posture. RESULTS: All measures of functional status and radiological parameters of the good-outcome group were significantly better than those of the poor-outcome group. The EP sum showed the highest value for the mRS and functional ambulatory category, and transverse diameter showed the highest value for "sitting-unsupported" of Berg Balance Scale. CONCLUSION: The combined MEP and SEP is a reliable and useful tool for functional recovery after PPH.
Evoked Potentials, Motor ; Evoked Potentials, Somatosensory* ; Gait ; Hematoma ; Hemorrhage* ; Humans ; Posture

OBJECTIVES: This study explored the relationship between alcohol consumption and exposure to traumatic events in male firefighters. METHODS: Data was collected from a sample of 584 firefighters at urban fire stations. We surveyed the firefighters using self-administered questionnaires including sociodemographic and job-related characteristics such as the Alcohol Use Disorders Identification Test (AUDIT), Life Event Checklist (LEC), Perceived Stress Scale (PSS), Korean Occupational Stress Scale-Short Form (KOSS-SF), Impacted Event Scale-Revised (IES-R), Stait Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI). RESULTS: There were significant differences in smoking, traumatic events (LEC), post-traumatic stress disorder symptoms (IES-R), and anxiety (STAI-T) between the two drinking groups (p<0.05). In multivariate logistic regression, smoking (OR=2.084, 95% CI=1.172-3.705), LEC (OR=1.163, 95% CI=1.010-1.339) and IES-R (OR=1.024, 95% CI=1.002-1.046) were significant predictors for AUDIT (p<0.05). CONCLUSION: These results indicate that an appropriate intervention about the exposure to traumatic events should play a useful role in preventing firefighter alcohol problems.
Alcohol Drinking ; Anxiety ; Checklist ; Depression ; Drinking ; Firefighters ; Fires ; Humans ; Logistic Models ; Male ; Surveys and Questionnaires ; Smoke ; Smoking ; Stress Disorders, Post-Traumatic

BACKGROUND: The highly developed endoplasmic reticulum (ER) structure in pancreatic beta cells is heavily involved in insulin biosynthesis. Thus, any perturbation in ER function inevitably impacts insulin biosynthesis. Recent studies showed that the expression of tribbles-related protein 3 (TRB3), a mammalian homolog of Drosophilia tribbles, in various cell types is induced by ER stress. Here, we examined whether ER stress induces TRB3 expression in INS-1 cells and found that TRB3 mediates ER stress-induced suppression of insulin gene expression. METHODS: The effects of tunicamycin and thapsigargin on insulin and TRB3 expression in INS-1 cells were measured by Northern and Western blot analysis, respectively. The effects of adenovirus-mediated overexpression of TRB3 on insulin, PDX-1 and MafA gene expression in INS-1 cells were measured by Northern blot analysis. The effect of TRB3 on insulin promoter was measured by transient transfection study with constructs of human insulin promoter. RESULTS: The treatment of INS-1 cells with tunicamycin and thapsigargin decreased insulin mRNA expression, but increased TRB3 protein expression. Adenovirus-mediated overexpression of TRB3 decreased insulin gene expression in a dose-dependent manner. A transient transfection study showed that TRB3 inhibited insulin promoter activity, suggesting that TRB3 inhibited insulin gene expression at transcriptional level. Adenovirus-mediated overexpression of TRB3 also decreased PDX-1 mRNA expression, but did not influence MafA mRNA expression. CONCLUSIONS: This study showed that ER stress induced TRB3 expression, but decreased both insulin and PDX-1 gene expression in INS-1 cells. Our data suggest that TRB3 plays an important role in ER stress-induced beta cell dysfunction.
Blotting, Northern ; Blotting, Western ; Endoplasmic Reticulum ; Endoplasmic Reticulum Stress ; Gene Expression ; Humans ; Insulin ; Insulin-Secreting Cells ; RNA, Messenger ; Thapsigargin ; Transfection ; Tunicamycin

Sunitinib is a tyrosine-kinase inhibitor used to treat metastatic renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumors. Hypothyroidism is a common side effect of sunitinib therapy. Nevertheless, overt thyrotoxicosis induced by destructive thyroiditis after sunitinib treatment is very rare. Here, we report a patient with overt thyrotoxicosis related to sunitinib therapy.
Carcinoma, Renal Cell ; Humans ; Hypothyroidism ; Indoles ; Pyrroles ; Thyrotoxicosis