Real-world outcome of patients with extensively pretreated multiple myeloma who were treated with selinexor and dexamethasone: a Korean multicenter retrospective analysis.

The outcomes of patients with myeloma after exposed to penta-classes are extremely poor. Selinexor is the first approved exportin inhibitor for those patients, but intractable toxicities may limit its use. This retrospective study evaluated the real-world efficacy and safety of selinexor plus dexamethasone (XD) and involved 48 patients with multiple myeloma, who were treated from November 2020 to October 2022. Their median age was 64 years, and the median number of prior lines of therapy was 6. The overall response rate was 25%, and the median progression-free survival (PFS) was 2.1 months (95% confidence interval (CI), 1.7-2.5). Patients on a reduced initial dose, delayed treatment, and dose reduction had better PFS. After XD treatment failure, 17 patients received subsequent therapy and had a median PFS of 2.4 months. The median overall survival was 4.6 months (95% CI, 2.3-6.9). Among the patients, 12 (25%) and 17 (35%) experienced dose reduction and delayed treatment, respectively. Our data show that the real-world efficacy of XD treatment in heavily pretreated patients was modest and that improving treatment adherence through reducing initial doses or delaying treatments may improve patient outcomes.

Long-term effects of local radiotherapy on growth and vertebral features in children with high-risk neuroblastoma.

BACKGROUND: To evaluate the effects of local radiotherapy (RT) on growth, we evaluated the chronological growth profiles and vertebral features of children with high-risk neuroblastoma. METHODS: Thirty-eight children who received local photon or proton beam therapy to the abdomen or retroperitoneum between January 2014 and September 2019 were included. Simple radiography of the thoracolumbar spine was performed before and every year after RT. The height and vertical length of the irradiated vertebral bodies (VBs) compared with the unirradiated VBs (vertebral body ratio, VBR) were analyzed using the linear mixed model. Shape feature analysis was performed to compare the irradiated and unirradiated vertebrae. RESULTS: The follow-up was a median of 53.5 months (range, 21-81 months) after RT. A decline in height z-scores was mainly found in the early phase after treatment. In the linear mixed model with height, the initial height (fixed, p < 0.001), sex (time interaction, p = 0.008), endocrine dysfunction (time interaction, 0.019), and age at diagnosis (fixed and time interaction, both p = 0.002) were significant. Unlike the trend in height, the change in VBR (ΔVBR) decreased gradually (p < 0.001). The ΔVBR in the group that received more than 30 Gy decreased more than in the group that received smaller doses. In the shape feature analysis, the irradiated VBs changed to a more irregular surface that were neither round nor rectangular. CONCLUSION: The irradiated VBs in children were gradually restricted compared to the unirradiated VBs in long-term follow-up, and higher RT doses were significantly affected. Radiation-induced irregular features of VBs were observed.

Suicide Screening Questionnaire-Self-Rating (SSQ-SR): Development, reliability, and validity in a clinical sample of Korean adults.

The goal of the present study was to evaluate the psychometric properties of the Suicide Screening Questionnaire-Self-Rating (SSQ-SR). A 25-item SSQ-SR is a newly developed suicide screening tool that measures suicide risk factors, including a history of suicidal thoughts and behaviors (STBs), life stress, and mental health problems. To investigate the reliability and validity of the SSQ-SR, we conducted a longitudinal case-control study with adults with and without STBs in the past six months. A total of 176 participants were recruited through 12 hospital-based Crisis Response Centers across South Korea. At the baseline, we administered the SSQ-SR, the Beck Scale for Suicide Ideation (BSSI), and the Patient Health Questionnaire-9 (PHQ-9). In a 6-months follow-up, we investigated whether the participants engaged in suicidal ideation, plan, or attempt since the baseline assessment. As a result, the SSQ-SR demonstrated a strong internal consistency (Cronbach's alpha coefficient = 0.96). In addition, the total score of SSQ-SR had concurrent validity compared to the total scores of the BSSI and the PHQ-9. In comparing the suicidal groups with the control group, the ROC analysis indicated the optimal cut point at 31 with a sensitivity rate of 0.97 and a specificity rate of 0.98. Through explanatory factor analysis, two factors were identified: Mental Health and Environmental Factors and Active Suicidal Thoughts and Behaviors. The SSQ-SR total and sub-factor scores were prospectively associated with subsequent suicidal ideation, plan, and attempt. These findings support that the SSQ-SR is a promising tool in prospectively screening those who are at risk of suicidal thoughts, plans, and nonfatal attempts.

Trimodality therapy for locally advanced esophageal squamous cell carcinoma: the role of volume-based PET/CT in patient management and prognostication.

PURPOSE: To evaluate the role of positron emission tomography/computed tomography (PET/CT) in predicting pathologic complete response (pCR) and identify relevant prognostic factors from clinico-imaging-pathologic features of locally advanced esophageal squamous cell carcinoma (eSCC) patients undergoing trimodality therapy. METHODS: We evaluated 275 patients with eSCCs of T3-T4aN0M0 and T1-T4aN1-N3M0 who received trimodality therapy. We correlated volume-based PET/CT parameters before and after concurrent chemoradiation therapy with pCR after surgery, clinico-imaging-pathologic features, and patient survival. RESULTS: pCR occurred in 75 (27.3%) of 275 patients, of whom 61 (80.9%) showed 5-year survival. Pre-total lesion glycolysis (pre-TLG, OR = 0.318, 95% CI 0.169 to 0.600), post-metabolic tumor volume (post-MTV, OR = 0.572, 95% CI 0.327 to 0.999), and % decrease of average standardized uptake value (% SUVavg decrease, OR = 2.976, 95% CI = 1.608 to 5.507) were significant predictors for pCR. Among them, best predictor for pCR was pre-TLG with best cutoff value of 205.67 and with AUC value of 0.591. Performance status (HR = 5.171, 95% CI 1.737 to 15.397), pathologic tumor size (HR = 1.645, 95% CI 1.351 to 2.002), pathologic N status (N1, HR = 1.572, 95% CI 1.010 to 2.446; N2, HR = 3.088, 95% CI 1.845 to 5.166), and post-metabolic tumor volume (HR = 1.506, 95% CI 1.033 to 2.195) were significant predictors of overall survival. CONCLUSION: Pre-TLG, post-MTV, and % SUVavg decrease are predictive of pCR. Additionally, several clinico-imaging-pathologic factors are significant survival predictors in locally advanced eSCC patients undergoing trimodality therapy.

Independent effects of amyloid and vascular markers on long-term functional outcomes: An 8-year longitudinal study of subcortical vascular cognitive impairment.

BACKGROUND AND PURPOSE: Subcortical vascular cognitive impairment (SVCI) is characterized by the presence of cerebral small vessel disease (CSVD) markers. Some SVCI patients also show Alzheimer's disease and cerebral amyloid angiopathy markers. However, the effects of these imaging markers on long-term clinical outcomes have not yet been established. The present study, therefore, aimed to determine how these imaging markers influence functional disability and/or mortality. METHODS: We recruited 194 participants with SVCI from the memory clinic and followed them up. All participants underwent brain magnetic resonance imaging at baseline, and 177 (91.2%) participants underwent beta-amyloid (Aß) positron emission tomography. We examined the occurrence of ischemic or hemorrhagic strokes. We also evaluated functional disability and mortality using the modified Rankin scale. To determine the effects of imaging markers on functional disability or mortality, we used Fine and Gray competing regression or Cox regression analysis. RESULTS: During a 8.6-year follow-up period, 46 of 194 patients (23.7%) experienced a stroke, 110 patients (56.7%) developed functional disabilities and 75 (38.6%) died. Aß positivity (subdistribution hazard ratio [SHR] = 2.73), greater white matter hyperintensity (WMH) volume (SHR = 3.11) and ≥3 microbleeds (SHR = 2.29) at baseline were independent predictors of functional disability regardless of the occurrence of stroke. Greater WMH volume (hazard ratio = 2.07) was an independent predictor of mortality. CONCLUSIONS: Our findings suggest that diverse imaging markers may predict long-term functional disability and mortality in patients with SVCI, which in turn may provide clinicians with a more insightful understanding of the long-term outcomes of SVCI.

Pharmacokinetic/pharmacodynamic parameters of vancomycin for predicting clinical outcome of enterococcal bacteremia.

PURPOSE: To find pharmacokinetic/pharmacodynamic parameters of vancomycin associated with the optimal outcome of severe infection due to Enterococcus species. METHODS: We retrospectively reviewed enterococcal bacteremia cases treated with vancomycin from January 2015 to December 2020. The primary outcome was 30-day mortality. We calculated cutoff values of the ratio of vancomycin area under the concentration-time curve over 24 h to the minimum inhibitory concentration (AUC24/MIC) and trough concentration (Ctrough) during the initial 72 h of treatment. The optimal cutoff value was determined using the Youden index. Binary variables created based on these cutoffs were further assessed using multivariable analysis. RESULTS: A total of 65 patients were included. The majority (87.7%) had solid or hematologic malignancies. Thirty-day mortality and nephrotoxicity occurred in nine (13.4%) and 14 (21.5%) patients, respectively. Both vancomycin AUC24/MIC and Ctrough showed fair performance in predicting 30-day mortality (AUC of receiver-operator curve for AUC24/MIC, 0.712; 95% confidence interval [CI] 0.539-0.886; AUC for Ctrough, 0.760; 95% CI 0.627-0.892; pairwise AUC comparison: p = 0.570). Ctrough ≥ 13.94 µg/mL, but not AUC24/MIC ≥ 504, had a significant association with 30-day mortality after adjusting for confounders (odds ratio, 8.40; 95% CI 1.60-86.62; p = 0.010). CONCLUSION: Mean Ctrough ≥ 13.94 µg/mL during the initial 72 h was associated with higher 30-day mortality in enterococcal bacteremia. Further studies are warranted to elucidate optimal pharmacokinetic targets for enterococcal bacteremia.

Preoperative Helical Dynamic Enhanced Multidetector Row Computed Tomography: Can It Be a Prognostic Indicator in Early-Stage Non-small Cell Lung Cancer?

OBJECTIVE: This study aimed to investigate the prognostic significance of dynamic contrast-enhanced computed tomography in patients with stage IA non-small cell lung cancer (NSCLC). METHODS: We retrospectively enrolled 139 patients (77 men, 62 women; mean age, 59 years) with stage IA NSCLC who underwent dynamic contrast-enhanced computed tomography. Data on age, pathologic subtype, peak enhancement, and net enhancement of primary lung cancer were collected and correlated with 5-year survival. RESULTS: Peak enhancement had a significant correlation with overall survival in the univariable analysis (hazard ratio [HR], 1.18, confidence interval [CI], 1.01-1.38; P = 0.04) and in the multivariable analysis (HR, 1.19; CI, 1.01-1.39; P = 0.04). Patients with peak enhancement of 90 Hounsfield unit or higher had a significantly increased risk of death compared with patients with less enhancement after curative surgery (HR, 4.15; CI, 1.23-13.95; P = 0.02). CONCLUSIONS: Our study confirmed the prognostic significance of peak enhancement as an indicator for the overall survival of stage IA NSCLC.

Statin Use and the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B.

BACKGROUND AND AIMS: Statins have pleiotropic effects that may include chemoprevention. Several observational studies have suggested that statins may prevent hepatocellular carcinoma (HCC), but they have not yet been fully studied in patients with chronic hepatitis B virus (HBV) infections. APPROACH AND RESULTS: A hospital-based retrospective cohort of 7,713 chronic HBV-infected individuals between January 2008 and December 2012 were analyzed. The primary outcome was the development of HCC. Patients who used statins for at least 28 cumulative defined daily doses during the follow-up period were defined as statin users (n = 713). The association between the use of statin and the incidence of HCC was analyzed using the multivariable Cox regression model with time-dependent covariates. During a median follow-up of 7.2 years (min-max: 0.5-9.9), HCC newly developed in 702 patients (9.1%). Statin use was associated with a lower risk of HCC (adjusted hazard ratio = 0.36, 95% confidence interval: 0.19-0.68, adjusted for age, sex, cirrhosis, diabetes, hypertension, serum alanine aminotransferase, cholesterol, HBV DNA level, antiviral treatment, and antiplatelet therapy). The observed benefit of the statin use was dose-dependent (adjusted hazard ratio [95% confidence interval], 0.63 [0.31-1.29]; 0.51 [0.21-1.25]; 0.32 [0.07,1.36]; and 0.17 [0.06, 0.48] for patients with statin use of 28-365, 366-730, 731-1095, and more than 1,095 cumulative defined daily doses, respectively). In subgroup analysis, the association between statin use and reduced risk of HCC was observed in all prespecified subgroups analyzed. CONCLUSION: Statin use was associated with a reduced risk of HCC development in chronic HBV-infected patients, suggesting that statins may have a chemopreventive role in this population. These findings warrant a prospective evaluation.

Surgeon Volume and Long-Term Oncologic Outcomes in Patients with Medullary Thyroid Carcinoma.

BACKGROUND: Surgery is the most important curative treatment for medullary thyroid carcinoma (MTC). The relationship between surgeon volume (the number of surgeries performed) and short-term surgical outcomes, such as increased postoperative complication or costs, is well established. This study evaluated whether surgeon volume influenced long-term oncologic outcomes. METHODS: We retrospectively reviewed 246 patients diagnosed with MTC after initial thyroid surgery from 1995 to 2019. After exclusion, 194 patients were eligible for inclusion in the study. Surgeons were categorized as low/intermediate volume (fewer than 100 operations per year) or high volume (at least 100 operations per year). RESULTS: Of the 194 included patients, 60 (30.9%) developed disease recurrence, and 9 (4.6%) died of MTC during the median follow-up of 92.5 months. Having a low/intermediate-volume surgeon was associated with high disease recurrence (log-rank test, p < 0.001). After adjustment for age, sex, tumor type (sporadic versus hereditary), primary tumor size, presence of central lymph node metastasis (LNM), presence of lateral LNM, extrathyroidal extension, and positive resection margin, surgeon volume was a significant factor for disease recurrence (hazard ratio 2.28, p = 0.004); however, cancer-specific survival was not affected by surgeon volume (hazard ratio 4.16, p = 0.115). CONCLUSIONS: Surgeon volume is associated with long-term oncologic outcome. MTC patients will be able to make the best decisions for their treatment based on the results of this study.

Prognostication of a 13-immune-related-gene signature in patients with early triple-negative breast cancer.

PURPOSE: We investigated the expression profiles of immune genes in patients with triple-negative breast cancer (TNBC) to identify the prognostic value of immune genes and their clinical implications. METHODS: NanoString nCounter Analysis of 770 immune-related genes was used to measure immune gene expression in patients with TNBC who underwent curative surgery followed by adjuvant chemotherapy at Samsung Medical Center between 2000 and 2004. Statistical analyses were conducted to identify the associations between gene expression and distant recurrence-free survival (DRFS). RESULTS: Of 1189 patients who underwent curative BC surgery, 200 TNBC patients were included and stage was the only clinical factor predictive of DRFS. In terms of immune genes, 155 of 770 genes were associated with DRFS (p < 0.01). Further multivariate analysis revealed that 13 genes, CD1B, CD53, CT45A1, GTF3C1, IL11RA, IL1RN, LRRN3, MAPK1, NEFL, PRKCE, PTPRC, SPACA3 and TNFSF11, were associated with patient prognosis (p < 0.05). The prognostic value of stage and expression levels of 13 immune genes was analyzed and the area under the receiver operating characteristic curve (AUC) was 0.923. Based on the AUC, we divided patients into three genetic risk groups and DRFS rate was significantly different according to genetic risk groups, even in the same stage (p < 0.001). CONCLUSIONS: In this study, a 13-gene expression profile in combination with stage precisely predicted distant recurrence of early TNBC. Therefore, this 13-immune-gene signature could help predict TNBC prognosis and provide guidance for treatment as well as the opportunity to develop new targets for immunotherapy in TNBC patients.

Temporal changes of circadian rhythmicity in cluster headache.

OBJECTIVE: To investigate the temporal changes of circadian rhythmicity in relation to the disease course in patients with cluster headache. METHODS: In this multicenter study, patients with cluster headache were recruited between September 2016 and July 2018. We evaluated the patients for circadian rhythmicity and time of cluster headache attacks in the current bout and any experience of bout-to-bout change in circadian rhythmicity. We analyzed the patterns of circadian rhythmicity in relation to the disease progression (the number of total lifetime bouts, grouped into deciles). RESULTS: Of the 175 patients in their active, within-bout period, 86 (49.1%) had circadian rhythmicity in the current bout. The prevalence of circadian rhythmicity in the active period was overall similar regardless of disease progression. Sixty-three (46.3%) out of 136 patients with ≥2 bouts reported bout-to-bout changes in circadian rhythmicity. The most frequent time of cluster headache attacks was distributed evenly throughout the day earlier in the disease course and dichotomized into hypnic and midday as the number of lifetime bouts increased (p = 0.037 for the homogeneity of variance). When grouped into nighttime and daytime, nighttime attacks were predominant early in the disease course, while daytime attacks increased with disease progression (up to 7th deciles of total lifetime bouts, p = 0.001) and decreased in patients with the most advanced disease course (p = 0.013 for the non-linear association). CONCLUSIONS: Circadian rhythmicity is not a fixed factor, and changes according to the disease course. Our findings will be valuable in providing a new insight into the stability of functional involvement of the suprachiasmatic nucleus in the pathophysiology of cluster headache.

Blood-brain barrier breakdown in reversible cerebral vasoconstriction syndrome: Implications for pathophysiology and diagnosis.

OBJECTIVE: Diagnosis of reversible cerebral vasoconstriction syndrome (RCVS) is currently based on luminographic findings of vasoconstriction. In addition to vasoconstriction, the blood-brain barrier (BBB) breakdown has been postulated as a central mechanism of RCVS. Our aim was to document BBB breakdown in patients with RCVS and its role for the pathophysiology-based diagnosis of RCVS. METHODS: We prospectively recruited 72 consecutive patients with thunderclap headache who did not have aneurysmal subarachnoid hemorrhage from April 2015 to July 2016 at the Samsung Medical Center. Based on the International Classification of Headache Disorders-3 beta criteria and neuroimaging, patients were classified as having RCVS (n = 41; "definite" in 29 imaging-proven patients and "probable" in 12 imaging-negative patients), other secondary causes (n = 7), and thunderclap headache of undetermined cause (n = 24). BBB breakdown was evaluated using contrast-enhanced fluid-attenuated inversion recovery magnetic resonance imaging. RESULTS: BBB breakdown was documented in 20 (69.0%) patients with definite RCVS, 3 (25.0%) patients with probable RCVS, and none with other secondary causes. BBB breakdown was present in RCVS patients with (n = 4) and without (n = 19) concomitant posterior reversible encephalopathy syndrome. In patients with RCVS, the extent of BBB breakdown was independently associated with neurological complications (multivariate odds ratio = 1.48 per 1 territorial increase, 95% confidence interval = 1.04-2.12, adjusted p = 0.032). Three (12.5%) patients with thunderclap headache of undetermined cause were newly classified as having RCVS by the presence of BBB breakdown. INTERPRETATION: This is the first study to show BBB breakdown in patients with RCVS. This finding might broaden our understanding of the pathophysiology and clinical spectrum of RCVS. Ann Neurol 2017;81:454-466.

Relative impact of amyloid-ß, lacunes, and downstream imaging markers on cognitive trajectories.

SEE COHEN DOI101093/AWW183 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Amyloid-ß and cerebral small vessel disease are the two major causes of cognitive impairment in the elderly. However, the underlying mechanisms responsible for precisely how amyloid-ß and cerebral small vessel disease affect cognitive impairment remain unclear. We investigated the effects of amyloid-ß and lacunes on downstream imaging markers including structural network and cortical thickness, further analysing their relative impact on cognitive trajectories. We prospectively recruited a pool of 117 mild cognitive impairment patients (45 amnestic type and 72 subcortical vascular type), from which 83 patients received annual follow-up with neuropsychological tests and brain magnetic resonance imaging for 3 years, and 87 patients received a second Pittsburgh compound B positron emission tomography analysis. Structural networks based on diffusion tensor imaging and cortical thickness were analysed. We used linear mixed effect regression models to evaluate the effects of imaging markers on cognitive decline. Time-varying Pittsburgh compound B uptake was associated with temporoparietal thinning, which correlated with memory decline (verbal memory test, unstandardized ß = -0.79, P < 0.001; visual memory test, unstandardized ß = -2.84, P = 0.009). Time-varying lacune number was associated with the degree of frontoparietal network disruption or thinning, which further affected frontal-executive function decline (Digit span backward test, unstandardized ß = -0.05, P = 0.002; Stroop colour test, unstandardized ß = -0.94, P = 0.008). Of the multiple imaging markers analysed, Pittsburgh compound B uptake and the number of lacunes had the greatest association with memory decline and frontal-executive function decline, respectively: Time-varying Pittsburgh compound B uptake (standardized ß = -0.25, P = 0.010) showed the strongest effect on visual memory test, followed by time-varying temporoparietal thickness (standardized ß = 0.21, P = 0.010) and time-varying nodal efficiency (standardized ß = 0.17, P = 0.024). Time-varying lacune number (standardized ß = -0.25, P = 0.014) showed the strongest effect on time-varying digit span backward test followed by time-varying nodal efficiency (standardized ß = 0.17, P = 0.021). Finally, time-varying lacune number (ß = -0.22, P = 0.034) showed the strongest effect on time-varying Stroop colour test followed by time-varying frontal thickness (standardized ß = 0.19, P = 0.026). Our multimodal imaging analyses suggest that cognitive trajectories related to amyloid-ß and lacunes have distinct paths, and that amyloid-ß or lacunes have greatest impact on cognitive decline. Our results provide rationale for the targeting of amyloid-ß and lacunes in therapeutic strategies aimed at ameliorating cognitive decline.

Prevalence of hearing loss and associated factors in subjects with normal otoscopy: a national cross-sectional study.

OBJECTIVE: To report the prevalence of hearing loss (HL) and associated factors in a nationwide study. DESIGN: Cross-sectional study. STUDY SAMPLE: We investigated the prevalence of HL in 10,845 participants ≥12 years of age and analysed the associated factors with HL from 7434 participants ≥40 years of age. RESULTS: The prevalence of worse ear HL was 21.9% (1.2% in youngest and 81.9% in oldest) and that of better ear was 12.5% (none in youngest and 65.3% in oldest). Based on the worse ear HL, the prevalence of HL was more common in men, and related with low education and income. In univariable analysis, hypertension, smoking, diabetes, depressive mood, stroke or cardiac disease, anaemia, hypercholesterolaemia and underweight showed positive associations with HL, and alcohol consumption and regular walking showed negative associations with HL. There were five associated factors in multivariable analysis, including smoking (OR =1.36 for smokers with <20 pack years; OR =1.55 for smokers with ≥20 pack years), noise exposure at workplace (OR = 1.28), stroke (OR = 1.72), anaemia (OR = 1.36) and depressive mood (OR = 1.29). CONCLUSION: Prevention of smoking and reduction of noise, as well as awareness of the association with stroke, anaemia and depression would help to reduce the burden of HL.

Clinical outcome and predictors of treatment response in foam sodium tetradecyl sulfate sclerotherapy of venous malformations.

OBJECTIVES: To evaluate clinical outcomes and their predictors in patients with venous malformation (VM) treated with foam sodium tetradecyl sulfate (STS) sclerotherapy. METHODS: We retrospectively evaluated clinical outcomes of foam STS sclerotherapy in 86 patients with 91 VMs to assess reduction in pain and mass after treatment. Univariate and multivariate analysis was performed to determine possible predictors of clinical outcome with foam STS sclerotherapy. RESULTS: A positive response of 49.5% in pain reduction and 52.7% in mass reduction was observed. The numerical rating scale (NRS) score improved from 4.36 ± 2.64 to 1.74 ± 1.57, and VM mass volume decreased to 41.7 ± 35.52% of the initial size. On multivariate analysis, a high baseline NRS score (odds ratio: 1.12, 95% confidence interval: 1.09-1.15) and VM location in the trunk versus the head and neck (odds ratio: 1.30, 95% confidence interval: 1.00-1.69) were positive predictors of pain improvement. Minor complications occurred in 11 (12.1%) patients and recurrence in 12 (13.2%) patients. CONCLUSIONS: Foam STS sclerotherapy is an effective treatment in venous malformation, with low complication risk. A high baseline NRS score and location in the trunk versus the head and neck were positive predictors in improvement of pain. KEY POINTS: • Foam STS sclerotherapy is effective in VM, with low risk of complications. • Relief of pain tends to be dramatic in patients with severe pain. • Location of VM is a predictor of pain improvement. • The presence of a draining vein does not affect foam sclerotherapy.

Epstein-Barr virus infection serves as an independent predictor of survival in patients with lymphoepithelioma-like gastric carcinoma.

BACKGROUND: The pathogenesis and clinicopathologic characteristics of Epstein-Barr virus (EBV)-negative lymphoepithelioma-like gastric carcinoma (LELC) are still unclear. In addition, it remains controversial whether EBV infection itself affects the prognosis of LELC. METHODS: Between 1995 and 2011, 145 LELC patients (124 patients with EBV infection and 21 patients without EBV infection) underwent radical gastrectomy with D2 lymph node dissection. The clinicopathologic features and prognosis of EBV-negative LELC cases were compared with those of EBV-positive LELC cases. The median duration of follow-up after surgery was 55 months. Microsatellite instability (MSI) analysis was performed on 20 EBV-negative LELC cases. RESULTS: EBV-negative LELC accounted for 14.5 % of the total LELC cases. EBV-negative LELC was significantly associated with older age, female sex, advanced T stage, and advanced American Joint Committee on Cancer (AJCC) tumor stage compared with EBV-positive LELC. In univariate analysis, patients with EBV-negative LELC had significantly shorter overall, disease-specific, and recurrence-free survival than those with EBV-positive LELC. The 5-year overall survival rates were 81.0 % for patients with EBV-negative LELC and 96.2 % for patients with EBV-positive LELC. In a Cox proportional hazards model, EBV infection, age, and AJCC tumor stage were identified as independent predictors of overall survival. MSI-high, MSI-low, and microsatellite-stable tumors accounted for 25, 10, and 65 % of EBV-negative LELC cases, respectively. MSI status did not affect the prognosis of EBV-negative LELC cases. CONCLUSIONS: EBV infection serves as an independent predictor of survival in patients with LELC. EBV-negative LELC exhibited clinicopathologic features and prognosis distinct from those of EBV-positive LELC.

Factors related to prevalence, persistence, and incidence of depressive symptoms in mild cognitive impairment: vascular depression construct.

OBJECTIVE: Depression is prevalent among elders with cognitive impairment. Cerebral white matter hyperintensities (WMH) have consistently been implicated in late-life depression and in cognitive impairment. This study aims to clarify the factors related to prevalence, persistence, and new onset of depressive symptoms in subjects with mild cognitive impairment (MCI). METHODS: As part of a multicenter prospective study, the Clinical Research Center for Dementia of South Korea (CREDOS) Study, we enrolled 590 subjects diagnosed with MCI and with no prior history of depression. Depressive symptoms were assessed by the Korean version of the Geriatric Depression Scale short form (SGDS-K) at baseline and at follow-up visits. Brain magnetic resonance imaging was performed at baseline to quantify WMH using a visual rating scale. RESULTS: The baseline prevalence of clinically significant depressive symptoms (SGDS-K ≥5) was 51.4%, and this feature was associated with younger age, lower educational achievement, and higher Clinical Dementia Rating Sum of Boxes (CDR-SB) scores. Persistence of depressive symptoms across the study period was significantly associated with baseline CDR-SB and depression scores. New onset of depression (SGDS-K ≥8; incidence 15.7%) among subjects free of depressive symptoms (SGDS-K <5) at baseline was associated with severe deep subcortical, but not periventricular, WMH. CONCLUSIONS: In patients with MCI aged 50 years or older, depressive symptoms were highly prevalent. Cognitive status was closely related to both prevalence and persistence of depressive symptoms, while new onset of depression was associated with deep subcortical WMH severity in this MCI cohort. Our findings provide prospective evidence consistent with the vascular depression hypothesis. Copyright © 2015 John Wiley & Sons, Ltd.

Association of carbon monoxide levels with allergic diseases in children.

BACKGROUND: Air pollution is regarded as a potential reason for the development or aggravation of allergic diseases. OBJECTIVE: To investigate the relationship between exposure to outdoor air pollution during the first year of life and the development of allergic diseases, and to determine the association between outdoor air pollution near the residence and recent symptoms of allergic diseases in children. METHODS: A nationwide cross-sectional survey was conducted in 6- to 7-year-old children. Among them, subjects who had been born (n = 1828) or lived (n = 1894) within 2 km of the nearest air quality monitoring sites were selected. The prevalence of allergic diseases was assessed by using questionnaires. Each subject was examined by pediatricians to determine the presence of eczema. Publicly available data were used regarding the daily ambient concentrations of sulfur dioxide, nitrogen dioxide, ozone, carbon monoxide (CO), and particulate matter. RESULTS: For a 100 ppb increase in the mean daily CO level during the first year of life, the adjusted odds ratio for lifetime allergic rhinitis was 1.10 (95% confidence interval, 1.03-1.19). For a 1 ppm increase in the annual average CO level during the past 12 months, the adjusted odds ratio for the presence of atopic dermatitis on the day of the survey was 8.11 (95% confidence interval, 1.06-62.12). However, the other air pollutants showed no statistical significance. CONCLUSIONS: Higher exposure to CO during infancy increased the risk of development of allergic rhinitis. The risk of current atopic dermatitis symptoms increased in children who were exposed to higher CO levels during the past 12 months.