Weight change and the risk of hip fractures in patients with type 2 diabetes: a nationwide cohort study.

Both weight gain and weight loss in type 2 diabetic population were associated with increased risk of hip fracture, while maintaining weight lowered the risk of hip fracture. Regarding the risk of hip fracture, we can propose active monitoring to maintain the weight of type 2 diabetes patients. INTRODUCTION: In type 2 diabetes, patients are often asked to control their weight in order to reduce their diabetic morbidity. The American Diabetes Association recommends that diabetic patients conduct high-intensity interventions for regulating diet, physical activity, and behavior to reduce weight, followed by long-term comprehensive weight maintenance programs. Although such weight control attempts are required in diabetic patients, there are few studies on the effect of weight change on hip fracture in this population. We aim to investigate the association between body weight change and the incidence of hip fracture in subjects with type 2 diabetes using large-scale, nationwide cohort data on the Korean population. MATERIALS AND METHODS: A total of 1,447,579 subjects (894,204 men and 553,375 women) > 40 years of age, who were diagnosed with type 2 diabetes, were enrolled in this study. Weight change within 2 years was divided into five categories: from weight loss ≥ 10% to weight gain ≥ 10%. The hazard ratios (HRs) and 95% confidence intervals for the incidence of hip fracture were analyzed, compared with the reference of the stable weight group (weight change < 5%). RESULTS: Among 5 weight change groups, more than 10% weight loss showed the highest HR (HR, 1.605; 95% CI, 1.493 to 1.725), followed by more than 10% weight gain (HR, 1.457; 95% CI, 1.318 to 1.612). The effect of weight change on hip fracture risk was greater in males than in females, and those under 65 years of age were greater than those over 65 years of age. Baseline BMI did not play a role of weight change affecting the risk of hip fracture. The HR for hip fracture of subjects with regular exercise was lower than those without regular exercise. CONCLUSIONS: In the type 2 diabetes population, both weight gain and weight loss were significantly associated with a higher risk of hip fracture, whereas maintaining body weight reduced the risk of hip fracture the most.

Effect of follow-up raloxifene therapy after denosumab discontinuation in postmenopausal women.

Follow-up raloxifene therapy after denosumab discontinuation resulted in a decrease in bone mass to the pre-denosumab levels and a rebound increase of bone turnover markers. The decrease in lumbar bone mineral density was particularly evident when the body mass index was low, there were previous vertebral fractures, or lumbar bone mineral density before denosumab administration was low. INTRODUCTION: Selective estrogen receptor modulators may be an alternative to bisphosphonates for treating rebound resorption after discontinuing denosumab. This study aimed to investigate the effects of follow-up raloxifene therapy after denosumab discontinuation in postmenopausal women. METHODS: This retrospective observational study included 61 patients who received 12-month follow-up raloxifene therapy after denosumab discontinuation. The primary endpoint was the bone mineral density change. The secondary endpoints were the changes in bone turnover markers and the incidence of new vertebral fractures. RESULTS: Raloxifene administration for 12 months after denosumab discontinuation resulted in a significantly lower bone mineral density at all sites compared to the level at 6 months after the last denosumab treatment (lumbar spine, - 5.48%; femoral neck, - 2.95%; total hip, - 3.52%; all, p < 0.001). The decrease in lumbar bone mineral density was particularly evident when the body mass index was low, there were previous vertebral fractures, or lumbar bone mineral density before denosumab administration was low. Marked increases in the bone turnover markers from baseline were noted after switching to raloxifene. However, no new vertebral fractures occurred during raloxifene treatment. CONCLUSIONS: Follow-up raloxifene therapy after denosumab discontinuation resulted in a decrease in bone mass to the pre-denosumab levels and a rebound increase of bone turnover markers. Therefore, raloxifene administered sequentially after denosumab discontinuation was not effective in preventing rebound phenomenon.

Optically transparent microwave absorber based on water-based moth-eye structures.

We propose an approach to realize an optically transparent microwave absorber based on water-based moth-eye metamaterial structures. The absorber is made of a periodic array of properly shaped glass caps infiltrated with distilled water. Analytical calculations and numerical simulations show that the water-based metamaterial absorbs electromagnetic waves over a wide spectral band ranging from 4GHz to well above 120GHz, showing absorption levels close to 100% for incident radiation that ranges from normal to grazing angles, for both TE and TM polarizations. Yet, the structure is optically transparent, offering exciting opportunities in a variety of civil and military applications, such as for camouflage and shielding systems and in energy harvesting structures.

Comparison of fracture risk between type 1 and type 2 diabetes: a comprehensive real-world data.

Population-based cohort study of 6,548,784 Korean subjects demonstrates that the risk of fracture was higher in patients with diabetes than in nondiabetic subjects. Furthermore, patients with type 1 diabetes were associated with a higher risk of fracture than patients with type 2 diabetes for all measurement sites. INTRODUCTION: Diabetes mellitus is associated with increased fracture risk. Although the pathophysiologic effect on bone metabolism differs according to the type of diabetes, a higher risk of fracture in patients with diabetes than in nondiabetic patients has been consistently demonstrated. Considering the ever-increasing number of patients with diabetes, we aimed to provide updated information on whether this phenomenon remains valid in real-world settings by using large-scale population datasets. METHODS: We conducted a retrospective longitudinal study using data from the Korean National Health Insurance Service dataset of preventive health check-ups between January 2009 and December 2016. The hazard ratios were calculated for any fracture, vertebral fracture, and hip fracture and were analyzed according to the presence and type of diabetes. Among 10,585,818 subjects, 6,548,784 were eligible for the analysis (2418 patients with type 1 diabetes mellitus [T1DM] and 506,208 patients with type 2 diabetes mellitus [T2DM]). RESULTS: The mean follow-up duration (in years) was 7.0 ± 1.3 for subjects without diabetes, 6.4 ± 2.0 for those with T1DM, and 6.7 ± 1.7 for T2DM. Patients with T1DM had a higher incidence rate for all types of fractures per 1000 person-years. The fully adjusted hazard ratios (HRs) for any fracture, vertebral fracture, and hip fracture were higher in T1DM than in T2DM (1.37 [95% confidence interval (CI): 1.23-1.52] for any fracture, 1.33 [95% CI: 1.09-1.63] for vertebral fracture, and 1.99 [95% CI: 1.56-2.53] for hip fracture). CONCLUSIONS: In this large-scale population analysis, diabetes was associated with a higher risk of all types of fractures. Patients with T1DM had a higher risk of fracture than those with T2DM for all measurement sites, and hip fractures had the highest risk. Therefore, fracture prevention training for patients with diabetes is advisable.

Diazepam induced sleep spindle increase correlates with cognitive recovery in a child with epileptic encephalopathy.

BACKGROUND: Continuous spike and wave of sleep with encephalopathy (CSWS) is a rare and severe developmental electroclinical epileptic encephalopathy characterized by seizures, abundant sleep activated interictal epileptiform discharges, and cognitive regression or deceleration of expected cognitive growth. The cause of the cognitive symptoms is unknown, and efforts to link epileptiform activity to cognitive function have been unrevealing. Converging lines of evidence implicate thalamocortical circuits in these disorders. Sleep spindles are generated and propagated by the same thalamocortical circuits that can generate spikes and, in healthy sleep, support memory consolidation. As such, sleep spindle deficits may provide a physiologically relevant mechanistic biomarker for cognitive dysfunction in epileptic encephalopathies. CASE PRESENTATION: We describe the longitudinal course of a child with CSWS with initial cognitive regression followed by dramatic cognitive improvement after treatment. Using validated automated detection algorithms, we analyzed electroencephalograms for epileptiform discharges and sleep spindles alongside contemporaneous neuropsychological evaluations over the course of the patient's disease. We found that sleep spindles increased dramatically with high-dose diazepam treatment, corresponding with marked improvements in cognitive performance. We also found that the sleep spindle rate was anticorrelated to spike rate, consistent with a competitively shared underlying thalamocortical circuitry. CONCLUSIONS: Epileptic encephalopathies are challenging electroclinical syndromes characterized by combined seizures and a deceleration or regression in cognitive skills over childhood. This report identifies thalamocortical circuit dysfunction in a case of epileptic encephalopathy and motivates future investigations of sleep spindles as a biomarker of cognitive function and a potential therapeutic target in this challenging disease.

Role of tumour location and surgical extent on prognosis in T2 gallbladder cancer: an international multicentre study.

BACKGROUND: In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection. METHODS: Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted. RESULTS: Data from 937 patients were available for evaluation. The overall 5-year disease-free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5-year disease-free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5-year disease-free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five-year disease-free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic. CONCLUSION: Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection.

ANTECEDENTES: En el cáncer de vesícula biliar, la ubicación del tumor subdivide el estadio T2 en tumores con invasión del lado peritoneal y del lado del hígado (T2a y T2b). Para los tumores que invaden el lado peritoneal (T2a) se sugiere que se puede obviar la resección hepática sin que ello comprometa el pronóstico. Sin embargo, este argumento no ha sido validado. El estudio tuvo como objetivo investigar el valor pronóstico de la localización del tumor en el cáncer de vesícula biliar T2 y establecer la extensión adecuada de la resección quirúrgica. MÉTODOS: Se recogieron los datos clínicos de pacientes que se sometieron a cirugía por cáncer de vesícula biliar en 14 hospitales de Corea, Japón, Chile y Estados Unidos. Se realizaron análisis de la supervivencia y de los factores de riesgo. RESULTADOS: Se dispuso de datos de 937 pacientes para ser evaluados. La tasa de supervivencia global libre de enfermedad a los 5 años fue del 70,6%, y las de T2a y T2b del 74,5% y 65,5% (P = 0,028). Con respecto a la resección hepática, la colecistectomía extendida presentó una tasa mejor de supervivencia libre de enfermedad a los 5 años que la colecistectomía simple (73,0% versus 61,5%, P = 0,012). La tasa de supervivencia libre de enfermedad a los 5 años fue marginalmente mejor para la colecistectomía extendida que para la colecistectomía simple tanto en T2a (76,5% versus 66,1%, P = 0,094) como en T2b (68,2% versus 56,2%, P = 0,084). Las tasas de supervivencia libre de enfermedad a los 5 años no fueron diferentes entre la resección hepática en cuña y la segmentectomía S4b+S5 (74,1% versus 71,5%, P = 0,720). En el análisis multivariable, los factores de riesgo independientes para la recidiva fueron la presencia de síntomas (cociente de riesgos instantáneos, hazard ratio, HR 1,52, P = 0,002), la resección R1 (HR 1,96, P = 0,004) y el estadio N1/N2 (N1 HR 3,40, P < 0,001; N2 HR 9,56, P < 0,001). El 70,8% de las recidivas eran metastásicas. CONCLUSIÓN: La localización del tumor no fue un factor pronóstico independiente en el cáncer de vesícula biliar T2. La colecistectomía extendida fue marginalmente superior que la colecistectomía simple. La cirugía radical debe incluir una resección hepática y una linfadenectomía adecuada.

Pooled cohort risk equation and subclinical cerebrovascular diseases.

BACKGROUND AND PURPOSE: In 2013, the American College of Cardiology/American Heart Association (ACC/AHA) introduced a novel pooled cohort risk (PCR) model for atherosclerotic cardiovascular disease. In this study, we evaluated the relationship between the PCR score and cerebral large- and small-vessel diseases (cLVD and cSVD) in a healthy population, METHODS: We assessed consecutive health check-up volunteers from 2006 to 2013. We calculated the estimated 10-year atherosclerotic cardiovascular disease risk as the PCR score based on the 2013 ACC/AHA guidelines. We evaluated both cSVD/cLVD, including the prevalence of cLVD, lacunes and cerebral microbleed (CMB), and the volume of white matter hyperintensity (WMH). In addition to PCR score, the risk factors that were associated with outcome variables at P < 0.10 in univariate analysis were included for further multivariable linear or regression analyses. RESULTS: A total of 2720 participants were evaluated (mean age, 57 years, male sex, 54%). In multivariable analysis, PCR score was associated with WMH volume [ß = 0.361; 95% confidence interval (CI), 0.320-0.402, P < 0.001], cLVD [adjusted odds ratio (aOR), 1.66; 95% CI, 1.29-2.16, P < 0.001], lacunes (aOR, 1.80; 95% CI, 1.52-2.14, P < 0.001) and CMBs (aOR, 1.75; 95% CI, 1.40-2.19, P < 0.001). Furthermore, PCR score also showed dose-response tendencies according to the burden of cLVD, WMH, lacunes and CMB. CONCLUSIONS: A higher PCR score based on the ACC/AHA guidelines is closely associated with a higher prevalence and burden of cLVD and cSVD.

Effect of cholinergic pathway disruption on cortical and subcortical volumes in subcortical vascular cognitive impairment.

BACKGROUND AND PURPOSE: The brain's cholinergic network has various interconnections with the cortical and subcortical structures. Disruption of cholinergic pathways by white matter hyperintensities (WMH) may cause pathologic changes within brain regions. Thus, WMH may represent an important pathological contributor to subcortical vascular cognitive impairment (scVCI). We aimed to investigate associations between the magnitude of WMH and volumetric changes in cortical and subcortical regions innervated by cholinergic neurons in patients with scVCI. METHODS: We enrolled patients with scVCI, defined as moderate to severe WMH or multiple (>2) lacunar infarcts outside the brainstem. Cholinergic Pathway HyperIntensities Scale (CHIPS) scores were used to quantify the magnitude of cholinergic pathway disruptions by WMH. We measured cortical thickness and subcortical volumes of 11 brain regions innervated by cholinergic neurons. Partial correlation of brain region volumes with total CHIPS scores was obtained using multiple linear regression. RESULTS: In total, 80 patients were enrolled. The mean age was 78.4 ± 6.5 years, median Mini-Mental State Examination score was 17 (interquartile range, 13-20) and median CHIPS score was 11 (interquartile range, 7-17). CHIPS scores were positively correlated with subcortical volumes of the putamen (r' = 0.46, P = 0.002) and pallidum (r' = 0.45, P = 0.002), and were negatively associated with inferior temporal (r' = -0.35, P = 0.002) and medial orbitofrontal (r' = -0.32, P = 0.002) cortical thickness. CONCLUSION: Our study suggested that WMH in cholinergic pathways may contribute to volumetric structural changes in cortical and subcortical structures innervated by cholinergic neurons.

Transcription Factor NFAT5 Promotes Migration and Invasion of Rheumatoid Synoviocytes via Coagulation Factor III and CCL2.

Fibroblast-like synoviocytes (FLSs) play a key role in the progression of rheumatoid arthritis (RA) as a primary component of invasive hypertrophied pannus. FLSs of RA patients (RA-FLSs) exhibit cancer-like features, including promigratory and proinvasive activities that largely contribute to joint cartilage and bone destruction. In this study, we hypothesized that the NF of activated T cell 5 (NFAT5), a transcription factor involving tumor invasiveness, would control the migration and invasion of RA-FLSs. Analyses of transcriptomes demonstrated the significant involvement of NFAT5 in locomotion of RA-FLSs and that tissue factor (TF; also known as coagulation factor III) and CCL2 were the major downstream target genes of NFAT5 involving FLS migration and invasion. In cultured RA-FLSs, IL-1ß and TGF-ß increased TF and CCL2 expression by upregulating NFAT5 expression via p38 MAPK. Functional assays demonstrated that NFAT5- or TF-deficient RA-FLSs displayed decreased lamellipodia formation, cell migration, and invasion under IL-1ß- or TGF-ß-stimulated conditions. Conversely, factor VIIa, a specific activator of TF, increased migration of RA-FLSs, which was blocked by NFAT5 knockdown. Recombinant CCL2 partially restored the decrease in migration and invasion of NFAT5-deficient RA-FLSs stimulated with IL-1ß. NFAT5-knockout mouse FLSs also showed decreased expressions of TF and CCL2 and reduced cell migration. Moreover, KRN2, a specific inhibitor of NFAT5, suppressed migration of FLSs stimulated with TGF-ß. Conclusively, to our knowledge, this is the first study to provide evidence of a functional link between osmoprotective NFAT5 and TF in the migration and invasion of RA-FLSs and supports a role for NFAT5 blockade in the treatment of RA.

Effects of quorum quenching on temporal succession of activated sludge microbial community in a membrane bioreactor.

AIMS: Quorum quenching (QQ) is an attractive strategy for mitigating biofouling in membrane bioreactors (MBRs). However, the effects of QQ on the activated sludge (AS) process have not been adequately evaluated. This study investigated the long-term effects of QQ on a laboratory-scale anoxic-oxic MBR, focusing on AS performance and microbial community. METHODS AND RESULTS: Anoxic-oxic MBRs with and without QQ were operated for 91 days. QQ did not affect COD and TN removal efficiencies over the experimental period, during which its activity remained >90%. QQ reduced floc size by approximately 8% but had no effect on biomass concentration. AS microbial communities were regularly analysed using massively parallel sequencing. AS bacterial communities were temporally dynamic irrespective of QQ presence, for example, a temporal increase in bacterial diversity and a temporal decay of community similarity. QQ counteracted the temporal change in diversity and the temporal distance-community decay. Community comparison revealed that QQ changed the successional trajectory of the AS community at a late period, because it decelerated temporal changes of specific members, such as Thiothrix and Sphingomonadaceae*. Correlation networks revealed that QQ increased network clustering, complexity and density. The combined results suggest that the tighter microbial association by QQ increased the community resistance. CONCLUSIONS: QQ can enhance the diversity and stability of the AS community in MBR by counteracting the innate temporal change in community structure. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings are useful for the further advancement of QQ-based strategies in engineered microbial environments.

Comparison of a 1064-nm neodymium-doped yttrium aluminum garnet picosecond laser using a diffractive optical element vs. a nonablative 1550-nm erbium-glass laser for the treatment of facial acne scarring in Asian patients: a 17-week prospective, randomized, split-face, controlled trial.

BACKGROUND: Novel picosecond lasers using a diffractive optical element (P-DOE) have been available for skin resurfacing with distinct mechanisms. However, there are limited data directly comparing P-DOE and conventional fractional lasers for the treatment of atrophic acne scarring. OBJECTIVES: We sought to compare the efficacy and safety of a 1064-nm neodymium-doped yttrium aluminium garnet P-DOE and a non-ablative fractional laser (NAFL) in the treatment of acne scarring. METHODS: A prospective, randomized, split-face, controlled trial was performed. One randomly assigned half-side of each patient's face (n = 25) was treated with four consecutive sessions of P-DOE at 3-week intervals and the other side with NAFL, with subsequent follow-up for 8 weeks after the final sessions. The efficacy and safety of the two lasers were determined by the Echelle d'Evaluation Clinique des Cicatrices d'acné (Scale of Clinical Evaluation of Acne Scars; ECCA) grading scale, Investigator's Global Assessment (IGA) score and patients' reports at the final visit. Histologic analysis was also performed. RESULTS: The P-DOE-treated side achieved a significantly better improvement in acne appearance (ECCA per cent reduction: 55% vs. 42%) with less severe pain (4.3 vs. 5.6) (P < 0.05). The IGA score and subjective satisfaction were consistent with ECCA score results. Occurrences of treatment-related side-effects were also lower in the group treated with P-DOE (P < 0.05). Histologic analysis revealed elongation and increased density of neocollagen fibres, elastic fibres and mucin throughout the dermis from both sides. CONCLUSIONS: Compared with NAFL, P-DOE afforded better clinical outcomes and fewer side-effects in the treatment of acne scarring in Asian patients.

Atrophic acne scar: a process from altered metabolism of elastic fibres and collagen fibres based on transforming growth factor-ß1 signalling.

BACKGROUND: Atrophic acne scar, a persistent sequela from acne, is undesirably troubling to many patients due to its cosmetic and psychosocial aspects. Although there have been some reports emphasizing the role of early inflammatory responses in atrophic acne scarring, evolving perspectives on the detailed pathogenic processes are promptly needed. OBJECTIVES: Examining the histological, immunological and molecular changes in early acne lesions susceptible to atrophic scarring can provide new insights to understand the pathophysiology of atrophic acne scar. METHODS: We experimentally validated several early fundamental hallmarks accounting for the transition of early acne lesions to atrophic scars by comparing molecular profiles of skin and acne lesions between patients who were prone to scar (APS) or not (ANS). RESULTS: In APS, compared with ANS, devastating degradation of elastic fibres and collagen fibres occurred in the dermis, followed by their incomplete recovery. Abnormally excessive inflammation mediated by innate immunity with T helper 17 and T helper 1 cells was observed. Epidermal proliferation was significantly diminished. Transforming growth factor (TGF)-ß1 was drastically elevated in APS, suggesting that aberrant TGF-ß1 signalling is an underlying modulator of all of these pathological processes. CONCLUSIONS: These results may provide a basis for understanding the pathogenesis of atrophic acne scarring. Reduction of excessive inflammation and TGF-ß1 signalling in early acne lesions is expected to facilitate the protection of normal extracellular matrix metabolism and ultimately the prevention of atrophic scar formation. What's already known about this topic? The dermis of atrophic acne scars shows alteration of extracellular matrix components such as collagen fibres. Inflammation in acne lesions is associated with the development of acne scars. What does this study add? Abnormalities in the metabolism of collagen fibres and elastic fibres were observed in the early developmental stages of acne lesions that were progressing into atrophic scars. Exacerbated inflammation and aberrant epidermal proliferation by increased transforming growth factor (TGF)-ß1 signalling may affect the abnormal extracellular matrix metabolism. What is the translational message? Abnormal changes in elastic fibres and collagen fibres are found in the early developmental process of acne in patients who are prone to atrophic scarring. An early treatment regimen strongly inhibiting inflammation and TGF-ß1 signalling to help the normal recovery of the extracellular matrix components is required to prevent atrophic scarring.

Favorable impact of non-alcoholic fatty liver disease on the cerebral white matter hyperintensity in a neurologically healthy population.

BACKGROUND AND PURPOSE: Although non-alcoholic fatty liver disease (NAFLD) shares common cardiovascular risk factors with cerebral white matter hyperintensity (WMH), few studies have reported the association between NAFLD and WMH. The association between the presence of NAFLD with its severity and the volume of WMH was investigated. METHODS: This cross-sectional study was conducted for 2460 subjects who voluntarily participated in health screening check-ups including brain magnetic resonance imaging and liver ultrasonography at the Health Promotion Center at Seoul National University Hospital from 2009 to 2013. Ultrasonography was used to detect the presence and severity of NAFLD combined with the NAFLD fibrosis score and the FIB-4 index. The volume of WMH was measured using a semi-automated quantification method by a trained neurologist. RESULTS: The prevalence of NAFLD was 36.5%, and the median volume of WMH in all the subjects was 1.1 ml (interquartile range 0.2-2.7 ml). The presence of NAFLD was associated with a smaller volume of WMH [ß (standard error, SE) -0.051 (0.046); P = 0.012]. Moderate to severe NAFLD was associated with a smaller volume of WMH than was non-NAFLD [ß (SE) -0.067 (0.061); P = 0.002]. The negative correlation observed between NAFLD severity and WMH volume was persistent only in those with low FIB-4 index and low NAFLD fibrosis scores, whereas there was a positive association in those with high FIB-4 index and NAFLD fibrosis scores. CONCLUSIONS: Non-alcoholic fatty liver disease, and its severity, showed a favorable association with WMH volume. However, its causality and mechanism should be evaluated in further relevantly designed studies.

Left ventricular ejection fraction is associated with small vessel disease in ischaemic stroke patients.

BACKGROUND AND PURPOSE: The purpose was to evaluate the association between the left ventricular ejection fraction (LVEF) and cerebral small vessel disease (cSVD) in ischaemic stroke patients. METHODS: Consecutive first-ever ischaemic stroke patients between 2010 and 2013 were included. White matter hyperintensity (WMH) volumes were rated using both the Fazekas score and quantitative methods on fluid-attenuated inversion recovery images. As spectra of cSVD, lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (EPVSs) were also evaluated. To assess the dose-response relationship between LVEF and cSVD, the burdens of each radiological marker and the total cSVD score were rated. RESULTS: A total of 841 patients were included [median WMH volume 2.98 (1.22-10.50) ml; the frequencies of lacunes, CMBs and moderate to severe EPVSs were 38%, 31% and 35%, respectively]. In the multivariate analysis about predictors of WMH volumes, the LVEF (B = -0.052, P < 0.001) remained significant after adjusting for confounders. LVEF was also a predictor of lacunes [adjusted odds ratio (aOR) 0.978, P = 0.012], CMBs (aOR = 0.96, P < 0.001) and moderate to severe EPVSs (aOR = 0.94, P < 0.001) after adjusting for their confounders. The LVEF values were negatively correlated with the burdens of lacunes (P = 0.026), CMBs (P < 0.001) and EPVSs (P = 0.002). The total cSVD score also showed a negative association with LVEF in a dose-response manner (P < 0.001). CONCLUSIONS: The burden of cSVD is negatively correlated with the LVEF in a dose-response manner. Our results suggest clues for further studies about determining the pathophysiology of cSVD.

White matter hyperintensities and recurrent stroke risk in patients with stroke with small-vessel disease.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) are a predictor of stroke among elderly individuals. This study aimed to evaluate the association between WMH severity and the risk of recurrent vascular events among Asian patients with ischaemic stroke with small-vessel disease (SVD) including micro/macrobleeds and lacunes. METHODS: Data from participants (n = 1454) in the PICASSO (PreventIon of CArdiovascular Events in iSchemic Stroke Patients with High Risk of Cerebral HemOrrhage) trial were reviewed. The severity of WMH in baseline brain magnetic resonance imaging scans was assessed using the Fazekas scale. The association between WMH severity and stroke (ischaemic or hemorrhagic) and major vascular events (MVEs) (a composite of stroke/myocardial infarction/vascular death) was assessed. RESULTS: Study patients had a significant burden of SVD: Fazekas score 0 (n = 2), 1 (n = 426), 2 (n = 650) and 3 (n = 376) [median Fazekas score 2 (mean follow-up, 1.9 ± 1.3 years)]. The stroke incidence rate per 100 personyears was 2.6 in the Fazekas 0-1 group, 3.6 in the Fazekas 2 group and 7.0 in the Fazekas 3 group, and the rates for MVEs were 3.3, 4.3 and 7.6, respectively. Compared with the Fazekas 0-1 group, the Fazekas 3 group was associated with a higher risk of stroke [adjusted hazard ratio (HR), 2.15; 95% confidence interval (CI), 1.19-3.88; P = 0.011], ischaemic stroke (adjusted HR, 2.11; 95% CI, 1.07-4.15; P = 0.031), hemorrhagic stroke (adjusted HR, 3.72; 95% CI, 1.09-12.70; P = 0.036) and MVEs (adjusted HR, 2.09; 95% CI, 1.20-3.66; P = 0.010). CONCLUSION: Advanced WMH in Asian patients with ischaemic stroke with SVD burden was associated with an increased risk of recurrent vascular events. It may exert an effect as a prognostic indicator in high risk of recurrent vascular events.

Clinical relevance of amnestic versus non-amnestic mild cognitive impairment subtyping in Parkinson's disease.

BACKGROUND AND PURPOSE: To clarify whether subtyping of amnestic and non-amnestic mild cognitive impairment (MCI) is clinically relevant in Parkinson's disease (PD) by analyzing patterns of neuroimaging and longitudinal cognitive changes. METHODS: We performed comparative analyses of cortical thickness, hippocampal volume, white matter integrity and resting-state functional connectivity between the patients with de-novo PD with amnestic MCI (PD-aMCI) (n = 50) and non-amnestic MCI (PD-naMCI) (n = 50) subtypes. Additionally, we assessed the longitudinal rate of cognitive decline in each cognitive domain over time and the rate of dementia conversion in patients with de-novo PD-aMCI (n = 125) and PD-naMCI (n = 61). RESULTS: The demographic data showed that scores in memory domains were lower in the PD-aMCI group compared with the PD-naMCI group. There were no significant differences in cortical thickness, hippocampal volume and white matter integrity between the two groups, although the PD-aMCI group exhibited more cortical thinning and hippocampal atrophy relative to the control group. The PD-aMCI group exhibited increased functional connectivity in the left posterior parietal region with the salience network relative to the PD-naMCI group. The longitudinal cognitive assessment demonstrated that patients with PD-aMCI exhibited a more rapid cognitive decline in frontal/executive function than those with PD-naMCI (P = 0.022). In addition, the PD-aMCI group had a higher risk of dementia conversion than the PD-naMCI group. CONCLUSIONS: This study suggests that the designation of PD-MCI subtypes based on memory function would highlight the heterogeneity of functional correlates as well as the longitudinal cognitive prognosis.

Procedural and obstetric outcomes after embryo reduction vs fetal reduction in multifetal pregnancy.

OBJECTIVE: To compare the obstetric outcome and incidence of procedure-related adverse events after embryo reduction (ER) vs fetal reduction (FR), in multifetal pregnancies undergoing reduction to twins or singletons. METHODS: We analyzed retrospectively data from multifetal pregnancies that underwent transvaginal ER (n = 181) at a mean gestational age of 7.6 weeks or transabdominal FR (n = 115) at a mean gestational age of 12.9 weeks between December 2006 and January 2017. FR was performed after a detailed fetal anomaly scan. The two groups were compared with respect to obstetric outcomes, such as incidence of miscarriage, early or late preterm delivery, maternal complications and fetal loss, and procedure-related adverse events, including incidence of subchorionic hematoma and procedure-related fetal loss. RESULTS: Compared with pregnancies that underwent ER, the incidence of procedure-related fetal loss was lower in the FR group (7.2% vs 0.9%; P = 0.039; odds ratio (OR), 0.12; 95% CI, 0.02-0.89). Mean gestational age at delivery for twins was 34.2 weeks in the ER group and 35.7 weeks in the FR group (P = 0.014). Compared with the ER group, the FR group had lower miscarriage (8.8% vs 2.6%; P = 0.045; OR, 0.28; 95% CI, 0.08-0.97) and overall fetal loss (13.3% vs 5.2%; P = 0.031; OR, 0.36; 95% CI, 0.14-0.91) rates. CONCLUSIONS: The FR procedure is, overall, a better and safer approach to reducing morbidity and mortality in multifetal pregnancies. Spontaneous demise of one fetus may occur after ER, and FR has the advantage that chorionic villus sampling and ultrasound screening for increased nuchal translucency and anatomical defects can be conducted before the procedure. The ER approach is still reasonable when a patient's religious or other ethical concerns are of primary importance. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Short communication: Chia seed extract enhances physiochemical and antioxidant properties of yogurt.

Yogurt is a healthy dairy food fermented by lactic acid bacteria (LAB). Because consumers demand healthier and more nutritious yogurt, numerous substances have been used to supplement yogurt. Chia seed has been reported to contain abundant phenolic compounds, dietary fiber, and n-3 fatty acids and therefore is a potential functional food additive. The aim of this study was to investigate the influence of chia seed extracts on the physicochemical and bioactive properties of set-type yogurt. Yogurt was fortified with chia seed water extract (CSWE) or chia seed ethanol extract (CSEE) at 0.05 or 0.1% (vol/vol). Results showed that supplementation with CSWE or CSEE significantly accelerated the fermentation rate and growth of LAB. Both CSWE and CSEE improved the viscosity, syneresis, and water-holding capacity of yogurt. The radical scavenging activity of yogurt was increased with both extracts, and the 0.1% CSEE yogurt exhibited the highest radical scavenging activity. Furthermore, 0.1% CSEE yogurt significantly inhibited lipopolysaccharide-induced production of hydrogen peroxide in human colon cells. Addition of chia seed extract improves the growth of LAB, the physiochemical properties, and the health-beneficial effects of set-type yogurt.

Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus.

Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p < 0.001) remained as significant risk factors for AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p < 0.001). RERI, AP and S, which define the strength of interactions between two risk factors, were 9.01 (95% confidence interval (CI) 1.30-16.73), 0.58 (95% CI 0.36-0.81) and 2.66 (95% CI 1.42-4.99), respectively, supporting the presence of synergistic interactions in the development of symptomatic AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE, especially in patients with high-dose corticosteroid and immunosuppressant use regardless of clinical manifestations and disease activity.

Imaging findings of primary hepatic angiosarcoma on gadoxetate disodium-enhanced liver MRI: comparison with hepatic haemangiomas of similar size.

AIM: To describe imaging characteristics of primary hepatic angiosarcoma on gadoxetate disodium-enhanced dynamic magnetic resonance imaging (MRI) and to determine features that differentiate angiosarcomas from similar-sized haemangiomas. MATERIALS AND METHODS: The study included 15 patients with hepatic angiosarcomas and 35 patients with size-matched hepatic haemangiomas who underwent gadoxetate disodium-enhanced liver MRI. The number, size, growth pattern, signal intensity (SI) characteristics, and SI changes on dynamic scans were evaluated and compared between the two entities. RESULTS: Overall, hepatic angiosarcomas significantly more often showed lesion multiplicity (86.7%), capsular retraction (40%), prominent intratumoural vessels (66.7%), vascular invasion (20%), heterogeneous SI on T2-weighted (100%) and hepatobiliary phase images (80%), and intralesional haemorrhage (60%, all p<0.05). On dynamic scans, angiosarcomas demonstrated enhancing foci of irregular or rim-like nodular/linear or bizarre (86.7%) shapes, with centrifugal or bizarre patterns of progressive enhancement (53.3%). Enhancement of angiosarcomas was less than that of the blood pool on visual grading, but the enhancement curves followed that of the aorta. Regardless of size, angiosarcomas showed heterogeneous T2 SI, intratumoural haemorrhage, and heterogeneity during the hepatobiliary phase, whereas these findings were more common in haemangiomas >6 cm in diameter. CONCLUSION: Gadoxetate disodium-enhanced dynamic liver MRI is capable of depicting vascular hallmarks of hepatic angiosarcomas. Heterogeneous SI on T2-weighted and hepatobiliary phase images, multiplicity, and an enhancement curve following that of the aorta are also distinctive features that differentiate angiosarcomas from haemangiomas.