Lumbar spinal stenosis: an update on the epidemiology, diagnosis and treatment

Lumbar spinal stenosis (LSS) is a common spinal disorder in the older population, and the clinical syndrome consisting of pain in the buttock or lower extremity, with or without low back pain and corresponding imaging findings of narrowing of spaces around neural and vascular elements in the lumbar spine. The diagnosis depends on history, symptoms, physical examination, radiographies. Varieties of non-operative and operative options are available for LSS patients. In this article, an update on the epidemiology, diagnosis and treatment of LSS was reviewed.published_or_final_versio

Relationship between angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and COVID-19 incidence or severe disease

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may be associated with higher susceptibility of COVID-19 infection and adverse outcomes. We compared ACEI/ARB use and COVID-19 positivity in a case-control design, and severity in COVID-19 positive patients. METHODS: Consecutive patients who attended Hong Kong's public hospitals or outpatient clinics between 1 January and 28 July 2020 for COVID-19 real time-PCR (RT-PCR) tests were included. Baseline demographics, past comorbidities, laboratory tests and use of different medications were compared between COVID-19 positive and negative patients. Severe endpoints for COVID-19 positive patients were 28-day mortality, need for intensive care admission or intubation. RESULTS: This study included 213 788 patients (COVID-19 positive: n = 2774 patients; negative: n = 211 014). In total, 162 COVID-19 positive patients (5.83%) met the severity outcome. The use of ACEI/ARB was significantly higher amongst cases than controls (n = 156/2774, 5.62 vs. n = 6708/211014, 3.17%; P 1, P  0.05). CONCLUSION: There was a significant relationship between ACEI/ARB use and COVID-19 positivity and severe disease after adjusting for significant confounders

A Probabilistic Code Balance Constraint with Compactness and Informativeness Enhancement for Deep Supervised Hashing

Building on deep representation learning, deep supervised hashing has achieved promising performance in tasks like similarity retrieval. However, conventional code balance constraints (i.e., bit balance and bit uncorrelation) imposed on avoiding overfitting and improving hash code quality are unsuitable for deep supervised hashing owing to their inefficiency and impracticality of simultaneously learning deep data representations and hash functions. To address this issue, we propose probabilistic code balance constraints on deep supervised hashing to force each hash code to conform to a discrete uniform distribution. Accordingly, a Wasserstein regularizer aligns the distribution of generated hash codes to a uniform distribution. Theoretical analyses reveal that the proposed constraints form a general deep hashing framework for both bit balance and bit uncorrelation and maximizing the mutual information between data input and their corresponding hash codes. Extensive empirical analyses on two benchmark datasets further demonstrate the enhancement of compactness and informativeness of hash codes for deep supervised hash to improve retrieval performance (code available at: https://github.com/mumuxi/dshwr).</jats:p

Development of a multivariable prediction model for severe COVID-19 disease: a population-based study from Hong Kong

Recent studies have reported numerous predictors for adverse outcomes in COVID-19 disease. However, there have been few simple clinical risk scores available for prompt risk stratification. The objective is to develop a simple risk score for predicting severe COVID-19 disease using territory-wide data based on simple clinical and laboratory variables. Consecutive patients admitted to Hong Kong's public hospitals between 1 January and 22 August 2020 and diagnosed with COVID-19, as confirmed by RT-PCR, were included. The primary outcome was composite intensive care unit admission, need for intubation or death with follow-up until 8 September 2020. An external independent cohort from Wuhan was used for model validation. COVID-19 testing was performed in 237,493 patients and 4442 patients (median age 44.8 years old, 95% confidence interval (CI): [28.9, 60.8]); 50% males) were tested positive. Of these, 209 patients (4.8%) met the primary outcome. A risk score including the following components was derived from Cox regression: gender, age, diabetes mellitus, hypertension, atrial fibrillation, heart failure, ischemic heart disease, peripheral vascular disease, stroke, dementia, liver diseases, gastrointestinal bleeding, cancer, increases in neutrophil count, potassium, urea, creatinine, aspartate transaminase, alanine transaminase, bilirubin, D-dimer, high sensitive troponin-I, lactate dehydrogenase, activated partial thromboplastin time, prothrombin time, and C-reactive protein, as well as decreases in lymphocyte count, platelet, hematocrit, albumin, sodium, low-density lipoprotein, high-density lipoprotein, cholesterol, glucose, and base excess. The model based on test results taken on the day of admission demonstrated an excellent predictive value. Incorporation of test results on successive time points did not further improve risk prediction. The derived score system was evaluated with out-of-sample five-cross-validation (AUC: 0.86, 95% CI: 0.82-0.91) and external validation (N = 202, AUC: 0.89, 95% CI: 0.85-0.93). A simple clinical score accurately predicted severe COVID-19 disease, even without including symptoms, blood pressure or oxygen status on presentation, or chest radiograph results

Histone deacetylase adaptation in single ventricle heart disease and a young animal model of right ventricular hypertrophy.

BackgroundHistone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac diseases. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle (SV) heart disease of right ventricular morphology, as well as in a rodent model of right ventricular hypertrophy (RVH).MethodsHomogenates of right ventricle (RV) explants from non-failing controls and children born with a SV were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day-old rat pups were placed in hypoxic conditions, and echocardiographic analysis, gene expression, HDAC catalytic activity, and isoform expression studies of the RV were performed.ResultsClass I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in the hearts of children born with a SV. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression, elevated class I and class IIb HDAC catalytic activity, and protein expression in the RV compared with those in the control.ConclusionsThese data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. Although further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for preclinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies

Acute lyme infection presenting with amyopathic dermatomyositis and rapidly fatal interstitial pulmonary fibrosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Dermatomyositis has been described in the setting of lyme infection in only nine previous case reports. Although lyme disease is known to induce typical clinical findings that are observed in various collagen vascular diseases, to our knowledge, we believe that our case is the first presentation of acute lyme disease associated with amyopathic dermatomyositis, which was then followed by severe and fatal interstitial pulmonary fibrosis only two months later.</p> <p>Case presentation</p> <p>We present a case of a 64-year-old African-American man with multiple medical problems who was diagnosed with acute lyme infection after presenting with the pathognomonic rash and confirmatory serology. In spite of appropriate antimicrobial therapy for lyme infection, he developed unexpected amyopathic dermatomyositis and then interstitial lung disease.</p> <p>Conclusions</p> <p>This case illustrates a potential for lyme disease to produce clinical syndromes that may be indistinguishable from primary connective tissue diseases. An atypical and sequential presentation (dermatomyositis and interstitial lung disease) of a common disease (lyme infection) is discussed. This case illustrates that in patients who are diagnosed with lyme infection who subsequently develop atypical muscular, respiratory or other systemic complaints, the possibility of severe rheumatological and pulmonary complications should be considered.</p

Generic, network schema agnostic sparse tensor factorization for single-pass clustering of heterogeneous information networks

Heterogeneous information networks (e.g. bibliographic networks and social media networks) that consist of multiple interconnected objects are ubiquitous. Clustering analysis is an effective method to understand the semantic information and interpretable structure of the heterogeneous information networks, and it has attracted the attention of many researchers in recent years. However, most studies assume that heterogeneous information networks usually follow some simple schemas, such as bi-typed networks or star network schema, and they can only cluster one type of object in the network each time. In this paper, a novel clustering framework is proposed based on sparse tensor factorization for heterogeneous information networks, which can cluster multiple types of objects simultaneously in a single pass without any network schema information. The types of objects and the relations between them in the heterogeneous information networks are modeled as a sparse tensor. The clustering issue is modeled as an optimization problem, which is similar to the well-known Tucker decomposition. Then, an Alternating Least Squares (ALS) algorithm and a feasible initialization method are proposed to solve the optimization problem. Based on the tensor factorization, we simultaneously partition different types of objects into different clusters. The experimental results on both synthetic and real-world datasets have demonstrated that our proposed clustering framework, STFClus, can model heterogeneous information networks efficiently and can outperform state-of-the-art clustering algorithms as a generally applicable single-pass clustering method for heterogeneous network which is network schema agnostic

Induction of endothelial cell apoptosis by the antivascular agent 5,6-dimethylxanthenone-4-acetic acid

5,6-Dimethylxanthenone-4-acetic acid, synthesised in this laboratory, reduces tumour blood flow, both in mice and in patients on Phase I trial. We used TUNEL (TdT-mediated dUTP nick end labelling) assays to investigate whether apoptosis induction was involved in its antivascular effect. 5,6-Dimethylxanthenone-4-acetic acid induced dose-dependent apoptosis in vitro in HECPP murine endothelial cells in the absence of up-regulation of mRNA for tumour necrosis factor. Selective apoptosis of endothelial cells was detected in vivo in sections of Colon 38 tumours in mice within 30 min of administration of 5,6-Dimethylxanthenone-4-acetic acid (25 mg kg−1). TUNEL staining intensified with time and after 3 h, necrosis of adjacent tumour tissue was observed. Apoptosis of central vessels in splenic white pulp was also detected in tumour-bearing mice but not in mice without tumours. Apoptosis was not observed in liver tissue. No apoptosis was observed with the inactive analogue 8-methylxanthenone-4-acetic acid. Positive TUNEL staining of tumour vascular endothelium was evident in one patient in a Phase I clinical trial, from a breast tumour biopsy taken 3 and 24 h after infusion of 5,6-Dimethylxanthenone-4-acetic acid (3.1 mg m−2). Tumour necrosis and the production of tumour tumour necrosis factor were not observed. No apoptotic staining was seen in tumour biopsies taken from two other patients (doses of 3.7 and 4.9 mg m−2). We conclude that 5,6-Dimethylxanthenone-4-acetic acid can induce vascular endothelial cell apoptosis in some murine and human tumours. The action is rapid and appears to be independent of tumour necrosis factor induction

High Expression Levels of Total IGF-1R and Sensitivity of NSCLC Cells In Vitro to an Anti-IGF-1R Antibody (R1507)

© 2009 Gong et al

Paternal mtDNA and Maleness Are Co-Inherited but Not Causally Linked in Mytilid Mussels

BACKGROUND: In marine mussels of the genus Mytilus there are two mitochondrial genomes. One is transmitted through the female parent, which is the normal transmission route in animals, and the other is transmitted through the male parent which is an unusual phenomenon. In males the germ cell line is dominated by the paternal mitochondrial genome and the somatic cell line by the maternal. Research to date has not allowed a clear answer to the question of whether inheritance of the paternal genome is causally related to maleness. METHODOLOGY/PRINCIPAL FINDINGS: Here we present results from hybrid crosses, from triploid mussels and from observations of sperm mitochondria in fertilized eggs which clearly show that maleness and presence of the paternal mitochondrial genome can be decoupled. These same results show that the female mussel has exclusive control of whether her progeny will inherit the mitochondrial genome of the male parent. CONCLUSIONS/SIGNIFICANCE: These findings are important in our efforts to understand the mechanistic basis of this unusual mode of mitochondrial DNA inheritance that is common among bivalves