To evaluate the radiological features of isolated posterior inferior cerebellar artery dissection (PICAD) and the feasibility of using high-resolution vessel-wall imaging (HR-VWI) for diagnosing ...PICAD.
Three hundred and nine patients with arterial dissection involving the posterior cerebral circulation, who underwent HR-VWI between March 2012 and July 2019 were reviewed retrospectively. Among them, 44 patients (14.2%) were diagnosed with isolated PICAD in consensus among a neuroradiologist, a neurointerventionist, and a neurologist. Two neuroradiologists reviewed the vessel wall images independently for evidence of dissection (dissection flap, outer diameter enlargement on T2-weighted imaging WI, mural haematoma). Diagnostic confidence was also scored on a five-point scale. Intra- and interobserver agreement for diagnosing PICAD and detecting evidence of dissection were evaluated.
Dissection flaps were seen on T2WI in all cases (100%) and on contrast-enhanced T1WI in 34 patients (79.1%). Outer diameter enlargement of the steno-occlusive lesions on angiography was detected in most cases (97.7%). A mural haematoma was detected on three-dimensional (3D) contrast-enhanced motion-sensitised driven-equilibrium T1WI in 97.1% of the cases. The mean diagnostic confidence score derived by two neuroradiologists was 4.72. The two reviewers showed substantial to almost perfect agreement (weighted kappa coefficient: 0.62–0.97).
Use of HR-VWI as a diagnostic tool for PICAD is feasible, and a dissection flap with outer wall enlargement on HR-T2WI allows confident dissection diagnosis. The present data suggest that PICAD might be considered as a stroke aetiology in patients with unexplained ischaemic stroke in the PICA territory, and that PICA evaluation with HR-VWI is both necessary and feasible.
•Conventional MRI usually cannot visualize the PICAD.•Use of HR-VWI as a diagnostic tool for PICAD is feasible.•Dissection flap with outer wall enlargement on HR-T2WI allows dissection diagnosis.•HR-VWI might be considered for PICAD evaluation in unexplained stroke.
L-ascorbate (L-ascorbic acid, vitamin C) clearly has an inhibitory effect on cancer cells. However, the mechanism underlying differential sensitivity of cancer cells from same tissue to L-ascorbate ...is yet to be clarified. Here, we demonstrate that L-ascorbate has a selective killing effect, which is influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human breast cancer cells. Treatment of human breast cancer cells with L-ascorbate differentially induced cell death, dependent on the SVCT-2 protein level. Moreover, knockdown of endogenous SVCT-2 via RNA interference in breast cancer cells expressing high levels of the protein induced resistance to L-ascorbate treatment, whereas transfection with SVCT-2 expression plasmids led to enhanced L-ascorbate chemosensitivity. Surprisingly, tumor regression by L-ascorbate administration in mice bearing tumor cell xenograft also corresponded to the SVCT-2 protein level. Interestingly, SVCT-2 expression was absent or weak in normal tissues, but strongly detected in tumor samples obtained from breast cancer patients. In addition, enhanced chemosensitivity to L-ascorbate occurred as a result of caspase-independent autophagy, which was mediated by beclin-1 and LC3 II. In addition, treatment with N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger, suppressed the induction of beclin-1 and LC3 II, implying that the differential SVCT-2 protein-dependent L-ascorbate uptake was attributable to intracellular ROS induced by L-ascorbate, subsequently leading to autophagy. These results suggest that functional SVCT-2 sensitizes breast cancer cells to autophagic damage by increasing the L-ascorbate concentration and intracellular ROS production and furthermore, SVCT-2 in breast cancer may act as an indicator for commencing L-ascorbate treatment.
Coronary artery calcium (CAC) score is a clinically validated marker of cardiovascular disease risk. We developed and validated a novel cardiovascular risk stratification system based on ...deep-learning-predicted CAC from retinal photographs.
We used 216 152 retinal photographs from five datasets from South Korea, Singapore, and the UK to train and validate the algorithms. First, using one dataset from a South Korean health-screening centre, we trained a deep-learning algorithm to predict the probability of the presence of CAC (ie, deep-learning retinal CAC score, RetiCAC). We stratified RetiCAC scores into tertiles and used Cox proportional hazards models to evaluate the ability of RetiCAC to predict cardiovascular events based on external test sets from South Korea, Singapore, and the UK Biobank. We evaluated the incremental values of RetiCAC when added to the Pooled Cohort Equation (PCE) for participants in the UK Biobank.
RetiCAC outperformed all single clinical parameter models in predicting the presence of CAC (area under the receiver operating characteristic curve of 0·742, 95% CI 0·732–0·753). Among the 527 participants in the South Korean clinical cohort, 33 (6·3%) had cardiovascular events during the 5-year follow-up. When compared with the current CAC risk stratification (0, >0–100, and >100), the three-strata RetiCAC showed comparable prognostic performance with a concordance index of 0·71. In the Singapore population-based cohort (n=8551), 310 (3·6%) participants had fatal cardiovascular events over 10 years, and the three-strata RetiCAC was significantly associated with increased risk of fatal cardiovascular events (hazard ratio HR trend 1·33, 95% CI 1·04–1·71). In the UK Biobank (n=47 679), 337 (0·7%) participants had fatal cardiovascular events over 10 years. When added to the PCE, the three-strata RetiCAC improved cardiovascular risk stratification in the intermediate-risk group (HR trend 1·28, 95% CI 1·07–1·54) and borderline-risk group (1·62, 1·04–2·54), and the continuous net reclassification index was 0·261 (95% CI 0·124–0·364).
A deep learning and retinal photograph-derived CAC score is comparable to CT scan-measured CAC in predicting cardiovascular events, and improves on current risk stratification approaches for cardiovascular disease events. These data suggest retinal photograph-based deep learning has the potential to be used as an alternative measure of CAC, especially in low-resource settings.
Yonsei University College of Medicine; Ministry of Health and Welfare, Korea Institute for Advancement of Technology, South Korea; Agency for Science, Technology, and Research; and National Medical Research Council, Singapore.
Objectives
Dietary fiber intake is associated with a lower risk of diabetes, cardiovascular disease, and cancer. However, it is unknown whether dietary fiber has a beneficial effect on preventing the ...development of chronic kidney disease (CKD).
Design, Setting, Participants and Measurements
Using the UK Biobank prospective cohort, 110,412 participants who completed at least one dietary questionnaire and had an estimated glomerular filtration rate ≥60 mL/min/1.73 m
2
, urinary albumin-to-creatinine ratio <30 mg/g, and no history of CKD were included. The primary exposure was total dietary fiber density, calculated by dividing the absolute amount of daily total fiber intake by total energy intake (g/1,000 kcal). We separately examined soluble and insoluble fiber densities as additional predictors. The primary outcome was incident CKD based on diagnosis codes.
Results
A total of 3,507 (3.2%) participants developed incident CKD during a median follow-up of 9.9 years. In a multivariable cause-specific model, the adjusted hazard ratios (aHRs; 95% confidence intervals CIs) for incident CKD were 0.85 (0.77–0.94), 0.78 (0.70–0.86), and 0.76 (0.68–0.86), respectively, for the second, third, and highest quartiles of dietary fiber density (reference: lowest quartile). In a continuous model, the aHR for each +Δ1.0g/1,000 kcal increase in dietary fiber density was 0.97 (95% CI, 0.95–0.99). This pattern of associations was similar for both soluble and insoluble fiber densities and did not differ across subgroups of sex, age, body mass index, hypertension, diabetes, smoking, and inflammation.
Conclusion
Increased fiber intake was associated with a lower risk of CKD in this large well-characterized cohort.
A recent report revealed that phosphoinositide-3-kinase, catalytic, alpha (PIK3CA) gene is somatically mutated in several types of human cancer, suggesting the mutated PIK3CA gene as an oncogene in ...human cancers. However, because the previous report focused the mutational search primarily on colon cancers, the data on PIK3CA mutations in other types of human cancers have been largely unknown. Here, we performed mutational analysis of the PIK3CA gene by polymerase chain reaction-single-strand conformation polymorphism assay in 668 cases of common human cancers, including hepatocellular carcinomas, acute leukemias, gastric carcinomas, breast carcinomas, and non-small-cell lung cancers. We detected PIK3CA somatic mutations in 26 of 73 hepatocellular carcinomas (35.6%), 25 of 93 breast carcinomas (26.9%), 12 of 185 gastric carcinomas (6.5%), one of 88 acute leukemias (1.1%), and three of 229 non-small-cell lung cancers (1.3%). Some of the PIK3CA mutations were detected in the early lesions of breast cancer carcinoma, hepatocellular carcinoma, and gastric carcinomas, suggesting that PIK3CA mutation may occur independent of stage of the tumors. The high incidence and wide distribution of PIK3CA gene mutation in the common human cancers suggest that alterations of lipid kinase pathway by PIK3CA mutations contribute to the development of human cancers.
ICA-ophthalmic artery aneurysms have unique configurations corresponding to relative risks of ophthalmologic morbidities. Presented herein are clinical and radiologic outcomes of coil embolization in ...ophthalmic artery aneurysms.
From January 2003 to September 2013, endovascular coiling was performed in 43 consecutive patients with ophthalmic artery aneurysms, each classified by the degree to which the ophthalmic artery was incorporated by the aneurysm and the contiguity between the ophthalmic artery entry and parent ICA. Clinical and radiologic outcomes of this approach were investigated, including the technical aspects of treatment and the efficacy of balloon test occlusion.
Among 14 patients (32.6%, all ophthalmic artery types) undergoing balloon test occlusion before endovascular coiling, patent collaterals between the external carotid artery and ophthalmic artery were demonstrated in 12 (85.7%) and complete compromise of the ophthalmic artery (without affecting vision) occurred in 4 patients during coiling. Steam-shaped S-configured (67.9%) or straight microcatheters (17.8%) facilitated aneurysm selection in most of the superiorly directed ophthalmic artery aneurysms (n = 28), and steam-shaped pigtail microcatheters (85.7%) were useful in medially directed aneurysms (n = 14). Balloon protection (n = 22) was generally used to facilitate coiling, or a stent (n = 9) was alternatively deployed. Satisfactory aneurysmal occlusion was achieved through coil embolization in 37 lesions (86.1%). During follow-up of 35 patients (mean interval, 12.9 ± 9.4 months), only 1 instance (2.9%) of major recanalization was observed.
If one tailors technical strategies, ophthalmic artery aneurysms are amenable to safe and effective endovascular coil embolization, which tends to be stable in follow-up. Balloon test occlusion may be helpful in devising treatment strategies to preserve vision when coiling ophthalmic artery aneurysms (especially those incorporating an ophthalmic artery origin) is done.
Background
Intraductal papillary mucinous neoplasm (IPMN) is premalignant pancreatic lesion. International guidelines offer limited predictors of individual risk. A nomogram to predict individual ...IPMN malignancy risk was released, with good diagnostic performance based on a large cohort of Asian patients with IPMN. The present study validated a nomogram to predict malignancy risk and invasiveness of IPMN using both Eastern and Western cohorts.
Methods
Clinicopathological and radiological data from patients who underwent pancreatic resection for IPMN at four centres each in Eastern and Western countries were collected. After excluding patients with missing data for at least one malignancy predictor in the nomogram (main pancreatic duct diameter, cyst size, presence of mural nodule, serum carcinoembryonic antigen and carbohydrate antigen (CA) 19‐9 levels, and age).
Results
In total, data from 393 patients who fit the criteria were analysed, of whom 265 were from Eastern and 128 from Western institutions. Although mean age, sex, log value of serum CA19‐9 level, tumour location, main duct diameter, cyst size and presence of mural nodule differed between the Korean/Japanese, Eastern and Western cohorts, rates of malignancy and invasive cancer did not differ significantly. Areas under the receiver operating characteristic (ROC) curve values for the nomogram predicting malignancy were 0·745 for Eastern, 0·856 for Western and 0·776 for combined cohorts; respective values for the nomogram predicting invasiveness were 0·736, 0·891 and 0·788.
Conclusions
External validation of the nomogram showed good performance in predicting cancer in both Eastern and Western patients with IPMN lesions.
Antecedentes
La neoplasia mucinosa papilar intraductal (intraductal papillary mucinous neoplasm, IPMN) es una lesión pancreática premaligna. Las guías internacionales incluyen un número limitado de factores predictivos de riesgo individual. Para predecir el riesgo individual de malignidad del IPMN se ha propuesto un nomograma con un buen rendimiento diagnóstico, basado en una gran cohorte de pacientes asiáticos con IPMN. Este estudio validó el nomograma para predecir el riesgo de cáncer y de invasión de la IPMN utilizando cohortes tanto orientales como occidentales.
Métodos
Se recogieron datos clínico‐patológicos y radiológicos de pacientes en los que se realizó una resección de páncreas por IPMN en 4 centros en países orientales y en 4 centros de países occidentales. Se excluyeron los pacientes en los que en el nomograma faltaba ≥ 1 factor(es) predictivo(s) de malignidad (diámetro del conducto pancreático principal, tamaño del quiste, presencia de nódulo mural, niveles séricos de CEA y CA19‐9, y edad).
Resultados
En total, se analizaron datos de 393 pacientes que cumplían con los criterios de inclusión, de los cuales 265 eran de centros orientales y 128 de centros occidentales. Aunque la edad media, el sexo, el valor logarítmico del nivel sérico de CA19‐9, la localización del tumor, el diámetro del conducto principal, el tamaño del quiste y la presencia de un nódulo mural difirieron entre las cohortes de Corea/Japón y las cohortes oriental y occidental, las tasas de malignidad y de cáncer invasivo no fueron significativamente diferentes. Las áreas bajo la curva operativa del receptor (area under the receiver operating curve, AUC) que mostró el nomograma para predecir la malignidad fueron: cohorte oriental: 0,745; cohorte occidental: 0,856 y cohortes combinadas: 0,776; y para predecir la invasión tumoral fueron: cohorte oriental: 0,736; cohorte occidental: 0,891, y cohortes combinadas: 0,788.
Conclusión
La validación externa del nomograma mostró un buen rendimiento en la predicción de cáncer, tanto en pacientes orientales como occidentales con lesiones IPMN.
A nomogram to predict individual intraductal papillary mucinous neoplasm (IPMN) malignancy risk was released, with good diagnostic performance based on a cohort of 2258 Korean or Japanese patients with IPMN. This study validated a nomogram to predict malignancy risk and invasiveness of IPMN, using Eastern and Western cohorts. External validation of the nomogram showed good performance in predicting malignancy and invasive cancer in both Eastern and Western patients with IPMN. The nomogram could be applicable globally to decide customized treatment options for patients with IPMN.
Useful for patients with IPMN
Background
Recently, aging has been shown to be associated with sarcopenic obesity (SO), of which decreased muscle mass and increased fat mass are features. Sarcopenia and obesity alone are known to ...be associated with abnormal lipid metabolism. However, it remains unclear whether SO has greater adverse effects on dyslipidemia than on sarcopenia or obesity alone.
Aim
We aimed to investigate the association between SO and dyslipidemia in elderly Koreans.
Subjects and methods
This study was based on data collected during the 2008–2010 Korea National Health and Nutrition Examination Survey. We included 1,466 men and 2,017 women aged 65 years and over. Sarcopenia was indicated in participants with height- or weight-adjusted appendicular skeletal muscle that was 1 standard deviation below the sex-specific mean for the young reference group, and obesity was defined as a body mass index ≥25 kg/m
2
. Dyslipidemia was defined according to the National Cholesterol Education Program-Adult Treatment Panel III.
Results
After adjusting for confounding factors, the SO group had a higher risk for dyslipidemia odds ratio (OR) 2.82 (95 % confidence interval 1.76–4.51) than the obese group 2.12 (1.11–4.07) and sarcopenic group 1.46 (1.01–2.11) (
p
< 0.001) only in men. Furthermore, the SO group in men had the highest OR for hypercholesterolemia, hypertriglyceridemia, hypo-high-density lipoprotein cholesterolemia, hyper-low-density lipoprotein cholesterolemia, and a high ratio of triglyceride to high-density lipoprotein cholesterol even after further adjustments.
Conclusions
In Korean elderly men, SO was associated with an increased risk for dyslipidemia compared with sarcopenia or obesity alone.
Summary
Patients with pyogenic vertebral osteomyelitis (PVO) are at greater risk of bone loss. However, treatment guidelines for bone loss have been lacking. Early bisphosphonate treatment within ...6 weeks after PVO diagnosis was significantly associated with superior outcome in femoral BMD at 2-year follow-up, compared to that with late treatment.
Introduction
Due to absence of concern and proper guidelines, management of bone loss or osteoporosis in PVO is often neglected or delayed. A retrospective cohort study was planned to investigate differences in bone mineral density (BMD) in PVO patients with osteoporosis according to the timing of osteoporosis treatment.
Methods
The PVO cohort consisted of 192 patients with osteoporosis who visited our institution between January 2003 and March 2015 and received bisphosphonate treatment for osteoporosis. According to the interval between PVO diagnosis and initiation of bisphosphonate, the patients were divided into three groups: group A (within 6 weeks after PVO diagnosis), group B (between 6 weeks and 3 months after diagnosis), and group C (more than 3 months after PVO diagnosis).
Results
The percent increase in total femoral BMD in group A was significantly larger than that in group B at 2-year follow-up (
p
= 0.036). Similarly, the percent increase in trochanteric (
p
= 0.008) and total femoral (
p
= 0009) BMD in group A was significantly larger than that in group C at 2-year follow-up. Even after multivariate adjustment, total femoral BMD changes were significantly associated with the treatment group. Group B (odds ratio = 2.824,
p
= 0.013) and group C (odds ratio = 3.591,
p
= 0.001) were more significantly associated with total femoral BMD decreases at 2-year follow-up compared with group A.
Conclusions
Early bisphosphonate treatment within 6 weeks after PVO diagnosis (group A) was significantly associated with superior outcome in femoral BMD at 2-year follow-up, compared to that with late treatment (groups B and C).
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