Sagittal computed tomography of lumbal spine showing dural ectasia and Tarlow Cyst (red arrows) (A). Magnetic resonance imaging (MRI) axial slice, susceptibility-weighted imaging (SWI) sequences showing siderosis in cerebellar sulci (red arrows) and in the inset uncharacteristic iron deposition in dental nuclei, more pronounced on the left side (red arrows) (B, inset). MRI, SWI, axial slice, showing numerous foci of superficial siderosis (C).
In recent years, emphasis has shifted from preventing and treating chronic obstructive pulmonary disease (COPD) to early prevention, early treatment, and disease stabilization, with the main goal of improving patients’ quality of life and reducing the frequency of acute exacerbations. This review summarizes pharmacological therapies for stable COPD.
The amyloid hypothesis states that the buildup of ß-amyloid in the brain is the main factor for Alzheimer's disease (AD) pathogenesis. An imbalance between ß-amyloid production and ß-amyloid clearance causes the advanced stages of the disease, including the development of neurofibrillary tangles containing tau protein.1
Many medications that aim to reduce ß-amyloid in AD are not clinically effective. FDA has approved aducanumab, one of four anti-ß-amyloid antibodies that have been demonstrated to mediate the removal of amyloid plaque from the brains of AD patients. FDA accepted the decrease of amyloid plaque as a surrogate endpoint for aducanumab. But there is intense disagreement over the justification for approval and the scope of the clinical benefit provided by antiamyloid antibodies.2
One side effect of the antibodies is brain edema, effusion, and hemorrhages, so called amyloid-related imaging abnormalities (ARIA). ARIA occurs in aged squirrel monkeys as well as in humans.3
Lecanemab, an antiamyloid monoclonal antibody, was associated with edema or effusions in 12.4% of subjects, including three fatal brain hemorrhages; the placebo group had 1.7% brain edema.4-9 In the case of donanemab, another anti-amyloid monoclonal antibody, if edema or effusion occurred with the first three doses of the drug, the dosage was not increased.10
A serious clinical condition, brain edema is defined by a pathological swelling of the brain tissue brought on by an increase in the water content of the brain. In humans11 and in a mouse model, APOE isoform affects neurological prognosis following intracerebral hemorrhage. Poor functional outcome and more cerebral edema are linked to APOE4.12 Three SNPs of the ABCC8 gene, rs2283261, rs3819521, and rs2283258, are significantly associated with brain edema, measured by increased intracranial pressure and CT imaging. Haptoglobin type, Hp2 versus Hp1, may also influence brain edema.13
Aquaporins, a family of water channel proteins that have been found in animals, may provide an explanation for AD brain edema. Aquaporin-4 (AQP4), the most significant form of aquaporin in the central nervous system, mediates water homeostasis in healthy and pathological settings, such as severe brain injury.13, 14
Because brain edema has occurred during clinical trials of most anti-amyloid antibodies, we hypothesize that ß-amyloid might be an important element in brain water homeostasis. Removing ß-amyloid could cause brain edema and bleeding in some AD patients. To investigate this idea, we analyzed structures of aquaporin-4 and ß-amyloid from the RCSB protein data bank.
To help identify the brain regions where anti-amyloid antibodies may act, we used the Allen Brain Atlas and the H
Environmental factors, including chemical/physical pollutants, as well as lifestyle and psychological factors, contribute greatly to the pathways leading to cardiometabolic diseases with a heavy disease burden and economic loss. The concept of exposomes provides a novel paradigm for combining all exposure characteristics to evaluate disease risk. A solution-like exposome requires technological support to provide continuous data to monitor vital signs and detect abnormal fluctuations. Wearable devices allow people to conveniently monitor signals during their daily routines. These new technologies empower users to more actively prevent and manage cardiometabolic disease by reviewing risk factors of the disease, especially lifestyle factors, such as sleeping time, screen time, and mental health condition. Devices with multiple sensors can monitor electrocardiography data, oxygen saturation, intraocular pressure, respiratory rate, and heart rate to enhance the exposome study and provide precise suggestions for disease prevention and management.
Afghanistan is suffering from 40-year chronic conflicts, displacement, and demolition of its infrastructure. Afghanistan mortality survey 2010 shows nearly 46% of all deaths in the country were attributed to noncommunicable diseases (NCDs). In this study, we aimed to understand the differences in mortality and premature death due to NCDs by sex and the trend for the next 8 years.
We applied trend analysis using the secondary data from the Institute for Health Metrics and Evaluation, Global Burden of Diseases 2019. The information on NCD mortality, NCD deaths attributed to its risk factors, NCD percent of total years lived with disability (YLDs) attribution to each risk factor extracted from this database from 2008 to 2019. We investigated the trend from 2008 to 2019 for the mentioned factors and then forecast their trends until 2030.
Our study shows that Afghanistan has had an increasing death number due to NCDs from 2008 to 2019 (50% for both sexes) and this will reach nearly 54% by 2030. Currently, half of NCDs deaths are premature in Afghanistan. The mortality rate and prevalence of risk factors are higher among women. More than 70% of YLDs will be due to NCDs in Afghanistan till 2030. Five risk factors including high systolic blood pressure (28.3%), high body mass index (23.4%), high blood glucose (20.6%), high low-density lipoprotein cholesterol (16.3%), and smoking (12.3%) will have the highest contribution to NCDs death in 2030, respectively.
In general, our study indicates that without any specific intervention to address NCDs in Afghanistan, not only the Sustainable Development Goal target for NCDs will not be met, but an increase in almost all risk factors prevalence, as well as NCD mortality, will be seen in Afghanistan.
Childhood obesity is one of the biggest public health challenges globally. It is associated with various adverse health consequences throughout life. Prevention and early intervention represent the most reasonable and cost-effective approaches. Considerable progress has been achieved in the management of obesity in children and adolescents; yet, implementation in the real world remains a challenge. This article aimed to present an overview of the diagnosis and management of obesity in children and adolescents.
This study aimed to assess the prescribing patterns of evidence-based pharmacotherapy and their association with clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF) in Thailand.
A retrospective cohort study of patients with HFrEF was conducted. Treatment with a β-blocker and renin–angiotensin system inhibitors (RASIs) with or without mineralocorticoid receptor antagonists (MRAs) at discharge was regarded as guideline-directed medical therapy (GDMT). All others were considered non-GDMT. The primary endpoint was the composite of all-cause mortality or heart failure (HF) rehospitalization. Inverse-probability-treatment-weighted adjusted Cox proportional hazard models were used to examine the treatment effects.
In total, 653 patients with HFrEF (mean age 64.1 ± 14.3 years; 55.9% male) were included. GDMT with β-blockers and RASIs with or without MRAs was prescribed at a rate of 35.4%. During a median of 1-year follow-up, 167 patients (27.5%) had a composite event, 81 patients (13.3%) had all-cause mortality, and 109 patients (18.0%) had HF rehospitalization. Patients treated with GDMT at discharge showed significantly lower rates of the primary endpoint (adjusted hazard ratio [HR] 0.63; 95% CI 0.44–0.89; p = 0.009) compared with patients who did not receive GDMT. The use of GDMT was also associated with a significantly lower risk of all-cause mortality (adjusted HR 0.59; 95% CI 0.36–0.98; p = 0.045) and HF rehospitalization (adjusted HR 0.65; 95% CI 0.43–0.96; p = 0.031).
For HFrEF treatment, GDMT initiation at hospital discharge was associated with a significantly reduced risk of all-cause mortality and HF rehospitalization. Nevertheless, prescribing GDMT remains underused, and it could be encouraged to improve HF outcomes in real-world settings.
The epidemic of overweight and obesity has become a worldwide public health problem. Cardiometabolic diseases may originate in childhood. We investigated the association between percent body fat (PBF) measured by the bioelectrical impedance assay and cardiometabolic risk (CMR) in pediatrics.
This cross-sectional study involved 3819 subjects (6–17 years old) in Shanghai. We assessed the association between PBF and body mass index (BMI) with multiple CMR factors. We examined the risk for cardiometabolic abnormalities attributable to overweight and obesity based on age- and sex-specific PBF Z-scores and BMI Z-scores, respectively.
PBF, but not BMI, was positively associated with multiple CMR factors in males and females except for total cholesterol in females (all p < 0.05). Compared with the non-overweight group based on PBF, overweight and obese subjects had increasingly higher odds ratio of dyslipidemia (2.90 (1.99–4.23), 4.59 (2.88–7.32) for males and 1.82 (1.20–2.75), 2.46 (1.47–4.11) for females) and elevated blood pressure (BP) (3.26 (2.35–4.51), 4.55 (2.92–7.09) for males and 1.59 (1.07–2.34), 3.98 (2.27–6.17) for females). Obesity females showed a higher likelihood for hyperglycemia (2.19 (1.24–3.84)) than non-overweight females. In both sexes, the predictive effect of PBF on dyslipidemia and elevated BP in adolescents was better than that in children. For hyperglycemia, the predictive effect of PBF was better in male adolescents and female children. There was no risk difference for cardiometabolic abnormalities attributable to BMI-based obesity categories.
PBF but not BMI was associated with CMR. Overweight and obesity categories based on PBF had an increased risk for cardiometabolic abnormalities in children and adolescents.
The differential diagnosis of mucoepidermoid carcinoma (MEC) from neoplasm undergoing mucinous features brings more pitfalls to pathologists. Combining specific MAML2 gene rearrangement and histological characteristics may be the solution.
Twenty-five tumors with mucinous components were selected for differential diagnosis of MEC. All the cases were detected for MAML2 gene rearrangement. The cases diagnosed as MEC were classified into four variants: classic, oncocytic, Warthin-like, and nonclassified, and they were graded using the Brandwein system. The histological characteristics of non-MECs were summarized for differential diagnosis. Univariate survival analysis was performed on MECs.
There were 16 MECs; 62.5% were MAML2 rearranged. For the low-, intermediate-, and high-grade MECs, the rate of rearrangement was 83.3%, 100%, and 28.6%, respectively. Both the oncocytic and Warthin-like MECs were MAML2 rearranged. For the classic and nonclassified MECs without MAML2 rearrangement, non-keratinized squamoid cells and distinctive mucinous cells were essential diagnostic criteria. On survival analysis, all the disease progression occurred in high-grade MECs (p = 0.038). Nine cases were diagnosed as non-MECs: pleomorphic adenoma with mucinous metaplasia showed no ex-capsular involvement; metaplastic Warthin tumor appeared with overt keratinization and residual oncocytic bilayered epithelium; mix squamous cell and glandular papilloma showed an endobronchial papillary growing pattern; adenosquamous carcinoma was accompanied by squamous carcinoma in situ of the overlying mucosa. All the non-MECs were negative for MAML2 rearrangement.
The application of combining MAML2 rearrangement and histological characteristics is helpful in the differential diagnosis between MEC and other tumors with mucinous components.
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