Effective Therapy of Tocilizumab on Systemic Juvenile Idiopathic Arthritis Associated Refractory Macrophage Activation Syndrome

Objectives To evaluate the safety and efficacy of tocilizumab (TCZ) on refractory macrophage activation syndrome (rMAS) associated with systemic juvenile idiopathic arthritis (sJIA-rMAS). Methods We retrospectively reviewed the charts of 14 patients diagnosed with sJIA-rMAS, who were treated with TCZ after failing conventional therapies at three hospital centers from Jan 2016 to Dec 2020. Demographic, clinical, and laboratory characteristics were recorded at the onset of MAS, before TCZ (pre-TCZ) and 14 days after TCZ (post-TCZ). Results The clinical manifestation of sJIA-rMAS included fever (100%), skin rashes (35.7%), lymphadenomegaly (42.9%), hepatomegaly (57.1%), splenomegaly (7.1%), gastrointestinal symptoms (28.6%), arthritis (14.3%), myalgia (28.6%) and polyserositis (14.3%). After TCZ treatment, fever (100%, 14/14), gastrointestinal symptoms (100%, 4/4) and myalgia (100%, 4/4) were significantly improved after one week (p< 0.05). Skin rashes, lymphadenomegaly and arthritis also improved in many patients but these parameters did not reach statistical significance. In post-TCZ group, decreases in levels of c-reactive protein, erythrocyte sedimentation rate and serum ferritin of sJIA-rMAS were observed compared with pre-TCZ (p< 0.05). Although not statistically significant, post-TCZ group showed normalization of white blood cell, platelet count, alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and triglyceride levels compared with pre-TCZ. No disease relapse or fatality was recorded during the follow-up (25 months, range 3–60 months). Conclusions TCZ is safe and effective for the treatment of sJIA-rMAS after failure of conventional therapies.

Use of Anti-angiogenic Drugs Potentially Associated With an Increase on Serum AST, LDH, CK, and CK-MB Activities in Patients With Cancer: A Retrospective Study

Background: There is a large amount of evidence that anti-angiogenic drugs are effective safe. However, few studies have evaluated the specific effects of anti-angiogenic drugs on myocardial enzyme injury biomarkers: aspartate aminotransferase (AST), lactic dehydrogenase (LDH), creatine kinase (CK) and creatine kinase isoenzyme (CK-MB). The purpose of our study was to determine whether anti-angiogenic drugs serum AST, LDH, CK, and CK-MB activities of cancer patients treated with anti-angiogenic drugs.Methods: This study retrospectively analyzed 81 cancer patients. Patients who had used anti-angiogenic drugs were selected. Serum AST, LDH, CK, and CK-MB activities were measured before and after treatment with anti-angiogenic drugs for 3 weeks.Results: A total of 16 cancer types were analyzed. The distribution of the cancer types in the patients was mainly concentrated in lung, gastric, and colorectal cancers. The anti-angiogenic treatment markedly increased AST, LDH, CK, and CK-MB activities by 32.51, 7.29, 31.25, and 55.56%, respectively in serum.Conclusions: Our findings suggest that patients, who had used anti-angiogenic drugs were likely to have elevated AST, LDH, and CK, indicators of myocardial muscle injury. Use of anti-angiogenic drugs should not be assumed to be completely safe and without any cardiovascular risks.

Jinwujiangu Capsule Treats Fibroblast-Like Synoviocytes of Rheumatoid Arthritis by Inhibiting Pyroptosis via the NLRP3/CAPSES/GSDMD Pathway

Jinwujiangu capsule (JWJGC) is a traditional Chinese medicine formula used to treat rheumatoid arthritis (RA). However, whether its mechanism is associated with pyroptosis remains unclear. In this study, the ability of JWJGC to inhibit the growth of fibroblast-like synoviocytes of RA (RA-FLS) through pyroptosis was evaluated. The cells isolated from patients with RA were identified by hematoxylin and eosin (H&E) staining, immunohistochemistry, and flow cytometry. After RA-FLS were treated with different concentrations of JWJGC-containing serum, the cell proliferation inhibition rate, expression of caspase-1/3/4/5, NOD-like receptor protein 3 (NLRP3), gasdermin-D (GSDMD), and apoptosis-associated speck-like protein containing a CARD (ASC), concentrations of interleukin-1β (IL-1β) and interleukin-18 (IL-18), the activity of lactic dehydrogenase (LDH), and pyroptosis were evaluated. The results showed that JWJGC increased the proliferative inhibition rate, decreased the expression of caspase-1/3/4/5, GSDMD, NLRP3, and ASC, suppressed the expression of IL-1β and IL-18, induced the activity of LDH, and downregulated the number of double-positive FITC anti-caspase-1 and PI. Generally, our findings suggest that JWJGC can regulate NLRP3/CAPSES/GSDMD in treating RA-FLS through pyroptosis.

Association of cardiac injury with hypertension in hospitalized patients with COVID-19 in China

Outbreak of global pandemic Coronavirus disease 2019 (COVID-19) has so far caused countless morbidity and mortality. However, a detailed report on the impact of COVID-19 on hypertension (HTN) and ensuing cardiac injury is unknown. Herein, we have evaluated the association between HTN and cardiac injury in 388 COVID-19 (47.5 ± 15.2 years) including 75 HTN and 313 normotension. Demographic data, cardiac injury markers, other laboratory findings, and comorbidity details were collected and analyzed. Compared to patients without HTN, hypertensive-COVID-19 patients were older, exhibited higher C-reactive protein (CRP), erythrocyte sedimentation rate, and comorbidities such as diabetes, coronary heart disease, cerebrovascular disease and chronic kidney disease. Further, these hypertensive-COVID-19 patients presented more severe disease with longer hospitalization time, and a concomitant higher rate of bilateral pneumonia, electrolyte disorder, hypoproteinemia and acute respiratory distress syndrome. In addition, cardiac injury markers such as creatine kinase (CK), myoglobin, lactic dehydrogenase (LDH), and N-terminal pro brain natriuretic peptide were significantly increased in these patients. Correlation analysis revealed that systolic blood pressure correlated significantly with the levels of CK, and LDH. Further, HTN was associated with increased LDH and CK-MB in COVID- 19 after adjusting essential variables. We also noticed that patients with elevated either high sensitivity-CRP or CRP demonstrated a significant high level of LDH along with a moderate increase in CK (p = 0.07) and CK-MB (p = 0.09). Our investigation suggested that hypertensive patients presented higher risk of cardiac injury and severe disease phenotype in COVID-19, effectively control blood pressure in HTN patients might improve the prognosis of COVID-19 patients.

PSX-A-3 Late-Breaking: Analysis of serum chemistry for metabolic function in GnRH-II receptor knockdown and littermate control boars

Pigs are the only livestock species encoding functional proteins for both the second form of gonadotropin-releasing hormone (GnRH-II) and its receptor (GnRHR-II), which are uniquely expressed in reproductive and non-reproductive tissues. To examine the physiological role of the GnRH-II/GnRHR-II system, we produced a swine line with reduced endogenous levels of GnRHR-II (GnRHR-II KD); males exhibit 70% diminished testicular GnRHR-II mRNA levels and 82% reduced circulating testosterone concentrations. Given that testosterone impacts metabolism, blood was collected from GnRHR-II KD (n = 5) and littermate control (n = 5) boars via indwelling jugular catheters, with serum isolated and subjected to veterinary diagnostic panels for metabolic analyte examination (PhysLab, Lincoln, NE). Statistical analyses utilized the MIXED procedure of SAS; the model included line as fixed and litter as random effects. Creatine kinase and blood urea nitrogen (BUN):creatinine ratios were elevated, creatinine was reduced (P < 0.01), and thyroxine tended to be decreased (P < 0.10) in GnRHR-II KD compared with control boars. Glucose, BUN, amylase, and lipase levels were not different. Liver products differed in transgenic versus control boars; levels of lactic dehydrogenase, aspartate and alanine aminotransferases (AST; ALT), and gamma-glutamyl transpeptidase were higher, whereas AST:ALT ratios, total protein, albumin, and globulin levels were lower (P < 0.05) in GnRHR-II KD boars. Albumin:globulin ratios and bilirubin (total and direct) did not differ. Additionally, serum cholesterol was decreased (P < 0.05), non-high density lipoproteins (HDLs) and low density lipoproteins (LDLs) tended to be decreased (P < 0.10), and triglycerides, HDLs, and cholesterol:HDL ratios did not differ between GnRHR-II KD and control males. These data suggest metabolic disruption in GnRHR-II KD boars, which may be due to suppressed gonadal steroidogenesis or ubiquitous knockdown of GnRHR-II expression. Supported by USDA/NIFA AFRI (2017-67015-26508) and Hatch Multistate (NEB-26–244) funds. USDA is an equal opportunity provider and employer.

Artificial Intelligence Systems for Diagnosis and Clinical Classification of COVID-19

Objectives: COVID-19 is highly infectious and has been widely spread worldwide, with more than 159 million confirmed cases and more than 3 million deaths as of May 11, 2021. It has become a serious public health event threatening people’s lives and safety. Due to the rapid transmission and long incubation period, shortage of medical resources would easily occur in the short term of discovering disease cases. Therefore, we aimed to construct an artificial intelligent framework to rapidly distinguish patients with COVID-19 from common pneumonia and non-pneumonia populations based on computed tomography (CT) images. Furthermore, we explored artificial intelligence (AI) algorithms to integrate CT features and laboratory findings on admission to predict the clinical classification of COVID-19. This will ease the burden of doctors in this emergency period and aid them to perform timely and appropriate treatment on patients.Methods: We collected all CT images and clinical data of novel coronavirus pneumonia cases in Inner Mongolia, including domestic cases and those imported from abroad; then, three models based on transfer learning to distinguish COVID-19 from other pneumonia and non-pneumonia population were developed. In addition, CT features and laboratory findings on admission were combined to predict clinical types of COVID-19 using AI algorithms. Lastly, Spearman’s correlation test was applied to study correlations of CT characteristics and laboratory findings.Results: Among three models to distinguish COVID-19 based on CT, vgg19 showed excellent diagnostic performance, with area under the curve (AUC) of the receiver operating characteristic (ROC) curve at 95%. Together with laboratory findings, we were able to predict clinical types of COVID-19 with AUC of the ROC curve at 90%. Furthermore, biochemical markers, such as C-reactive protein (CRP), LYM, and lactic dehydrogenase (LDH) were identified and correlated with CT features.Conclusion: We developed an AI model to identify patients who were positive for COVID-19 according to the results of the first CT examination after admission and predict the progression combined with laboratory findings. In addition, we obtained important clinical characteristics that correlated with the CT image features. Together, our AI system could rapidly diagnose COVID-19 and predict clinical types to assist clinicians perform appropriate clinical management.

Lactic Dehydrogenase to Albumin Ratio Is Associated With the Risk of Stroke-Associated Pneumonia in Patients With Acute Ischemic Stroke

Background: Stroke-associated pneumonia (SAP) is one of the common complications of stroke patients. Higher lactic dehydrogenase (LDH) and lower albumin levels were associated with SAP, but the contribution of the LDH to albumin ratio (LAR) to the risk of SAP in acute ischemic stroke (AIS) patients remained unclear.Methods: A total of 3173 AIS patients were included in this study, divided into SAP (n = 417) and non-SAP groups (n = 2756). Characteristics were compared between these two groups. The receiver operating characteristic curves (ROC) were used to evaluate the discrimination ability of the LAR, LDH, and albumin levels in predicting SAP. Logistic regression analysis was furtherly adopted to estimate the association between LAR and SAP. We also used the restricted cubic spline (RCS) to clarify the relationship between LAR and the risk of SAP.Results: LAR in the SAP group was significantly higher than that of the non-SAP group (8.75 ± 4.58 vs. 6.10 ± 2.55, P < 0.001). According to the results of ROC, LAR had the highest prognostic accuracy compared to LDH and albumin (P < 0.05). Besides, the logistic regression model showed that higher LAR (LAR > 6.75) were more vulnerable to SAP (OR, 2.80; 95% CI, 2.18–3.59, P < 0.001), controlling the confounders. The RCS model showed that there was a non-linear relationship between LAR and the risk of SAP.Conclusion: High LAR was associated with an increased risk of SAP in patients with AIS. LAR may be a potential predictor for the incidence of SAP. Appropriate prevention measures were needed in patients with high LAR (LAR > 6.75).

Greater Covid-19 Severity and Mortality in Hospitalized Patients in Second (Delta Variant) Wave Compared to the First: Single Centre Prospective Study in India

ABSTRACTBackground & ObjectiveCovid-19 pandemic has led to multiple waves secondary to mutations in SARS-CoV-2 and emergence of variants of concern (VOC). Clinical characteristics of delta (B.1.617.2) VOC are not well reported. To compare demographic, clinical and laboratory features and outcomes in the second Covid-19 wave in India (delta VOC) with the previous wave we performed a registry-based study.MethodsSuccessive SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) confirmed Covid-19 patients presenting to our Advanced Covid Care hospital were prospectively recruited. In the first phase (wave) from March-December 2020, 1395 of 7476 (18.7%) suspected patients tested positive and 863 (61.89%) hospitalized, while in second wave from January-July 2021 out of 1641 confirmed cases out of 8680 (19.4%) suspected 388 (23.6%) were hospitalized. Details of clinical and laboratory features at admission to hospital, management and outcomes in the two waves have been compared.ResultsIn both cohorts, majority were men and 20% less than 40 years. Prevalence of hypertension, diabetes and cardiovascular diseases was more than 20%. Second wave patients had similar pre-hospitalization symptom duration but had significantly greater cough, fever and shortness of breath and lower SpO2 at presentation with greater lymphopenia, C-reactive proteins, interleukin-6, ferritin, lactic dehydrogenase and transaminases. In the second vs first wave patients, requirement of supplementary oxygen (47.9% vs 34.3%), prone positioning (89.2 vs 38.6%), high flow nasal oxygen(15.7 vs 9.1%), non-invasive ventilation (14.4 vs 9.5%), invasive ventilation (16.2 vs 9.5%), steroids (94.1 vs 85.9%), remdesivir (91.2 vs 76.0%) and anticoagulants (94.3 vs 76.0%) was greater (p<0.001). Median (IQR) length of stay [8 (6-10) vs 7 (5-10) days] as well as ICU stay [9 (5-13) vs 6 (2-10) days] was more in second wave (p<0.001). In-hospital deaths occurred in 173 patients (13.9%) and were significantly more in the second wave, 75 (19.3%), compared to the first, 98 (11.5%); unadjusted odds ratio (95% CI) 1.84 (1.32-2.55) which did not change significantly with adjustment for age and sex (2.03, 1.44-2.86), and age, sex and comorbidities (2.09, 1.47-2.95). Greater disease severity at presentation was associated with mortality in both the waves.ConclusionsCovid-19 patients hospitalized during the second wave of the epidemic (delta variant) had more severe disease with greater dyspnea, hypoxia, hematological and biochemical abnormalities compared to first wave patients. They had greater length of stay in intensive care unit, oxygen requirement, non-invasive and invasive ventilatory support. The in-hospital mortality in the second wave was double of the first.

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy in Children: A Retrospective Study

Objective: To describe the clinical features of autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy in children.Method: Data from 11 pediatric patients with autoimmune GFAP astrocytopathywas retrospectively analyzed.Results: All of the patients showed encephalitis and meningoencephalitis or meningoencephalomyelitis with or without myelitis, include fever (45.4%), headaches (27.3%), dizziness (18.2%), drowsiness (18.2%) and mental disorders (18.2%). Cerebrospinal fluid (CSF) were detected in all patients. The white cell counts (WBC) (90.9%), lactic dehydrogenase levels (72.7%), protein level (36.4%), and adenosine deaminase activity (ADA) level (27.3%) were elevated, and the CSF glucose levels (72.7%) were slightly reduced. Nine patients (90%) were found to have brain abnormalities, of which five (50.0%) patients had abnormal symmetrical laminar patterns or line patterns hyperintensity lesions on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images in the basal ganglia, hypothalamus, subcortical white matter and periventricular white matter. The linear radial enhancement pattern of the cerebral white matter was only seen in two patients, the most common being abnormal enhancement of leptomeninges (50%). Five patients had longitudinally extensive spinal cord lesions.Conclusion: The findings of pediatric patients with autoimmune GFAP astrocytopathy is different from the previous reports.