Association between dysglycemia and the Charlson Comorbidity Index among hospitalized patients with diabetes

AimInpatient dysglycemia has been linked to short-term mortality, but longer-term mortality data are lacking. Our aim was to evaluate the association between inpatient dysglycemia and one-year mortality risk.MethodsRetrospective chart review of adults with diabetes hospitalized between 2015 and 2019. The Charlson Comorbidity Index (CCI) was used to estimate 1-year mortality risk, stratified into low (CCI ≤ 5) and high risk (CCI ≥6). Simple and multivariable logistic regression was used to evaluate the association between dysglycemic measures and high mortality risk.ResultsAmong 22,639 unique admissions, BG ≥ 180, ≥300, ≤70, <54 and <40 mg/dL were associated with adjusted odds of 1.43 (95 % CI, 1.33, 1.54), 1.58 (95 % CI, 1.48, 1.68), 2.16 (95 % CI, 2.01, 2.32), 2.58 (95 % CI, 2.32, 2.86), and 2.56 (95 % CI, 2.19, 2.99) for high mortality risk, respectively. Older age and Black race were positively associated with hyperglycemia and hypoglycemia. Myocardial infarction, congestive heart failure (CHF), and moderate to severe liver disease were most strongly associated with hyperglycemia, while renal disease, CHF, peripheral vascular disease, and peptic ulcer disease were most strongly associated with hypoglycemia.ConclusionsInpatient hypoglycemia and hyperglycemia were both positively associated with higher one-year mortality risk, with stronger magnitude of association observed for hypoglycemia. The association appears to be mediated mainly by presence of diabetes-related complications.     

Skin3D: Detection and longitudinal tracking of pigmented skin lesions in 3D total-body textured meshes

We present an automated approach to detect and longitudinally track skin lesions on 3D total-body skin surface scans. The acquired 3D mesh of the subject is unwrapped to a 2D texture image, where a trained objected detection model, Faster R-CNN, localizes the lesions within the 2D domain. These detected skin lesions are mapped back to the 3D surface of the subject and, for subjects imaged multiple times, we construct a graph-based matching procedure to longitudinally track lesions that considers the anatomical correspondences among pairs of meshes and the geodesic proximity of corresponding lesions and the inter-lesion geodesic distances.We evaluated the proposed approach using 3DBodyTex, a publicly available dataset composed of 3D scans imaging the coloured skin (textured meshes) of 200 human subjects. We manually annotated locations that appeared to the human eye to contain a pigmented skin lesion as well as tracked a subset of lesions occurring on the same subject imaged in different poses. Our results, when compared to three human annotators, suggest that the trained Faster R-CNN detects lesions at a similar performance level as the human annotators. Our lesion tracking algorithm achieves an average matching accuracy of 88% on a set of detected corresponding pairs of prominent lesions of subjects imaged in different poses, and an average longitudinal accuracy of 71% when encompassing additional errors due to lesion detection. As there currently is no other large-scale publicly available dataset of 3D total-body skin lesions, we publicly release over 25,000 3DBodyTex manual annotations, which we hope will further research on total-body skin lesion analysis.     

Multiscale quantification of morphological heterogeneity with creation of a predictor of longer survival in glioblastoma

Intratumor heterogeneity is a main cause of the dismal prognosis of glioblastoma (GBM). Yet, there remains a lack of a uniform assessment of the degree of heterogeneity. With a multiscale approach, we addressed the hypothesis that intratumor heterogeneity exists on different levels comprising traditional regional analyses, but also innovative methods including computer-assisted analysis of tumor morphology combined with epigenomic data. With this aim, 157 biopsies of 37 patients with therapy-naive IDH-wildtype GBM were analyzed regarding the intratumor variance of protein expression of glial marker GFAP, microglia marker Iba1 and proliferation marker Mib1. Hematoxylin and eosin stained slides were evaluated for tumor vascularization. For the estimation of pixel intensity and nuclear profiling, automated analysis was used. Additionally, DNA methylation profiling was conducted separately for the single biopsies. Scoring systems were established to integrate several parameters into one score for the four examined modalities of heterogeneity (regional, cellular, pixel-level and epigenomic). As a result, we could show that heterogeneity was detected in all four modalities. Furthermore, for the regional, cellular and epigenomic level, we confirmed the results of earlier studies stating that a higher degree of heterogeneity is associated with poorer overall survival. To integrate all modalities into one score, we designed a predictor of longer survival, which showed a highly significant separation regarding the OS. In conclusion, multiscale intratumor heterogeneity exists in glioblastoma and its degree has an impact on overall survival. In future studies, the implementation of a broadly feasible heterogeneity index should be considered.     

Seronegative autoimmune diseases: A challenging diagnosis

Autoimmune diseases (AID) are increasingly prevalent conditions which comprise more than 100 distinct clinical entities that are responsible for a great disease burden worldwide. The early recognition of these diseases is key for preventing their complications and for tailoring proper management. In most cases, autoantibodies, regardless of their potential pathogenetic role, can be detected in the serum of patients with AID, helping clinicians in making a definitive diagnosis and allowing screening strategies for early -and sometimes pre-clinical- diagnosis. Despite their undoubted crucial role, in a minority of cases, patients with AID may not show any autoantibody, a condition that is referred to as seronegative AID. Suboptimal accuracy of the available laboratory tests, antibody absorption, immunosuppressive therapy, immunodeficiencies, antigen exhaustion, and immunosenescence are the main possible determinants of seronegative AID. Indeed, in seronegative AID, the diagnosis is more challenging and must rely on clinical features and on other available tests, often including histopathological evaluation and radiological diagnostic tests. In this review, we critically dissect, in a narrative fashion, the possible causes of seronegativity, as well as the diagnostic and management implications, in several AID including autoimmune gastritis, celiac disease, autoimmune liver disease, rheumatoid arthritis, autoimmune encephalitis, myasthenia gravis, Sjögren’s syndrome, antiphospholipid syndrome, and autoimmune thyroid diseases.     

Rationale for a Clinical Trial That Compares Acute Stroke Rehabilitation at Inpatient Rehabilitation Facilities to Skilled Nursing Facilities: Challenges and Opportunities

In the United States, approximately 400,000 patients with acute stroke are discharged annually to inpatient rehabilitation facilities (IRFs) or skilled nursing facilities (SNFs). Typically, IRFs provide time-intensive therapy for an average of 2-3 weeks, whereas SNFs provide more moderately intensive therapy for 4-5 weeks. The factors that influence discharge to an IRF or SNF are multifactorial and poorly understood. The complexity of these factors in combination with subjective clinical indications contributes to large variations in the use of IRFs and SNFs. This has significant financial implications for health care expenditure, given that stroke rehabilitation at IRFs costs approximately double that at SNFs. To control health care spending without compromising outcomes, the Institute of Medicine has stated that policy reforms that promote more efficient use of IRFs and SNFs are critically needed. A major barrier to the formulation of such policies is the highly variable and low-quality evidence for the comparative effectiveness of IRF- vs SNF-based stroke rehabilitation. The current evidence is limited by the inability of observational data to control for residual confounding, which contributes to substantial uncertainty around any magnitude of benefit for IRF- vs SNF-based care. Furthermore, it is unclear which specific patients would receive the most benefit from each setting. A randomized controlled trial addresses these issues, because random treatment allocation facilitates an equitable distribution of measured and unmeasured confounders. We discuss several measurement, practical, and ethical issues of a trial and provide our rationale for design suggestions that overcome some of these issues.     

Alanine transaminase is predominantly increased in the active phase of anti-HMGCR myopathy

Autoantibodies against 3?hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and the signal recognition particle (SRP) are representative antibodies causing immune-mediated necrotizing myopathies (IMNM), called as anti-HMGCR and anti-SRP myopathies, respectively. Here, we analyzed the differences in routine blood test results between 56 anti-HMGCR and 77 anti-SRP myopathy patients. A higher alanine transaminase (ALT) level and a lower aspartate transaminase (AST)/ALT ratio were observed in anti-HMGCR myopathy patients [ALT, 265.7 ± 213.3 U/L (mean ± standard deviation); AST/ALT ratio, 0.88 ± 0.32] than in anti-SRP-myopathy patients (ALT, 179.3 ± 111.2 U/L, p < 0.05; AST/ALT ratio, 1.28 ± 0.40, p < 0.01). In the active phase, anti-HMGCR myopathy often showed ALT predominance, whereas anti-SRP myopathy often showed AST predominance. In addition, there were differences in erythrocyte sedimentation rate (ESR), total cholesterol (TChol) level, and high-density lipoprotein (HDL) level between anti-HMGCR and anti-SRP myopathies (ESR: HMGCR, 24.4 ± 20.8 mm/1 h; SRP, 35.7 ± 26.7 mm/1 h, p = 0.0334; TChol: HMGCR, 226.7 ± 36.6 mg/dL; SRP, 207.6 ± 40.8 mg/dL, p = 0.0163; HDL: HMGCR, 58.4 ± 13.9 mg/dL; SRP, 46.2 ± 17.3 mg/dL, p < 0.01). Additional studies on the differences in routine blood test results may further reveal the pathomechanisms of IMNM.     

脊髓小脑共济失调2型家系ATXN2基因中间重复病例表型与分子遗传学特征

目的探讨脊髓小脑共济失调2型(SCA2)致病基因ATXN2异常等位基因中间重复个体的表型和分子遗传学特点。方法针对2005—2018年中日友好医院神经科运动障碍与神经遗传病研究中心收集的1383个常染色体显性遗传共济失调家系的先证者和部分家系成员,采用荧光标记毛细管电泳片段分析方法进行动态突变检测,对携带ATXN2基因中间重复的个体进行临床表型和遗传特征分析。结果共检出163个家系(包含先证者和家系成员共203人)携带异常扩展的ATXN2基因CAG重复序列,其中93个家系中有107例的异常扩展等位基因重复次数在29~34次之间。在其中的20个亲子对中,父系遗传16个,异常等位基因的代间扩展增加0~28次,母系遗传4个,异常等位基因的代间扩展增加0~4次。结论对于临床拟诊SCA2家系患者,需对其亲代或成年子代个体进行ATXN2基因检测,以免漏诊。动态突变基因检测有助于识别中间重复的个体,对明确家系致病基因和遗传咨询至关重要。