A predictive model for identifying secondary underlying diseases of hemophagocytic lymphohistiocytosis.

Background: Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening disease of immune hyperactivation that arises in the context of infectious, inflammatory, or neoplastic triggers. The aim of this study was to establish a predictive model for the timely differential diagnosis of the original disease resulting in HLH by validating clinical and laboratory findings to further improve the efficacy of therapeutics for HLH. Methods: We retrospectively enrolled 175 secondary HLH patients in this study, including 92 patients with hematologic disease and 83 patients with rheumatic disease. The medical records of all identified patients were retrospectively reviewed and used to generate the predictive model. We also developed an early risk score using multivariate analysis weighted points proportional to the ß regression coefficient values and calculated its sensitivity and specificity for the diagnosis of the original disease resulting in HLH. Results: The multivariate logistic analysis revealed that lower levels of hemoglobin and platelets (PLT), lower levels of ferritin, splenomegaly and Epstein-Barr virus (EBV) positivity were associated with hematologic disease, but young age and female sex were associated with rheumatic disease. The risk factors for HLH secondary to rheumatic diseases were female sex [OR 4.434 (95% CI, 1.889-10.407), P =0.001], younger age [OR 6.773 (95% CI, 2.706-16.952), P<0.001], higher PLT level [OR 6.674 (95% CI, 2.838-15.694), P<0.001], higher ferritin level [OR 5.269 (95% CI, 1.995-13.920), P =0.001], and EBV negativity [OR 27.656 (95% CI, 4.499-169.996), P<0.001]. The risk score included assessments of female sex, age, PLT count, ferritin level and EBV negativity, which can be used to predict HLH secondary to rheumatic diseases with an AUC of 0.844 (95% CI, 0.836~0.932). Conclusion: The established predictive model was designed to help clinicians diagnose the original disease resulting in secondary HLH during routine practice, which might be improve prognosis by enabling the timely treatment of the underlying disease.

Antiphospholipid Syndrome-Related Pulmonary Embolism: Clinical Characteristics and Early Recognition.

Background: Pulmonary thromboembolism is a common disease frequently encountered in the emergency room and has a high mortality rate. Antiphospholipid syndrome (APS) is a high-risk factor for recurrent pulmonary embolism (PE). It is critical to effectively administer anticoagulants to avoid the recurrence of thrombotic events. This study aims to identify the clinical characteristics of APS patients with PE (APS-PE) and to develop a risk score for determining the presence of APS in PE patients in the emergency situations. Methods: We retrospectively enrolled 76 PE patients in this study, with 46 patients in the APS-PE group and 30 patients in the non-APS-PE group. We compared differences in demographics, laboratory parameters, and early mortality risk between the two groups. Risk factors for APS-PE were screened using logistic regression analysis. We also developed an early risk score using multivariate analysis weighted points proportional to the ß- regression coefficient values and calculated the sensitivity and specificity for APS in PE patients. Results: In the APS-PE group, we observed a higher proportion of males (43.6 vs. 20%), a higher proportion of low-risk patients (58.7 vs. 10%), lower levels of white blood cells and platelets (PLT), longer activated partial thromboplastin time (APTT), and a slight increase in D-dimer levels. Patients who were triple positive for antiphospholipid antibodies (aPLs) were younger. The APTT gradually increased as the number of positive aPLs increased. The risk factors for APS included male (OR = 5.565, 95% CI 1.176-26.341), decreased PLT (OR = 0.029, 95% CI 0.003-0.330), slightly increased D-dimer (OR = 0.089, 95% CI 0.019-0.426), and prolonged APTT (OR = 4.870, 95% CI 1.189-19.951). The risk score was named MPDA and included male, PLT, D-dimer and APTT, which can predict APS in PE patients with the AUC at 0.888 (95% CI 0.811-0.965). Conclusion: The risk factors for APS in PE patients are male, low PLT, prolonged APTT and slightly increased D-dimer. The MPDA is a quantitative scoring system which is highly suggestive of APS in PE patients.

Prominent coagulation disorder is closely related to inflammatory response and could be as a prognostic indicator for ICU patients with COVID-19.

The new outbreak of Coronavirus Disease 2019 (COVID-19) has emerged as a serious global public health concern. A more in-depth study of blood coagulation abnormality is needed. We retrospectively analyzed 147 consecutive patients with COVID-19 who were admitted to three ICUs in Wuhan from February 9th, 2020 to March 20th, 2020. The baseline coagulation and other characteristics were studied. Our results showed that the prolonged PT, FDP, DD were positively correlated with the levels of neutrophils, ferritin, LDH, total bilirubin, multi-inflammation cytokines, and negatively correlated with the lymphocytes level (p < 0.01). The level of ATIII was significantly negatively correlated with the levels of neutrophils, ferritin, LDH, total bilirubin, IL2R, IL6 and IL8 (p < 0.05). The patients in the ARDS group had a more prominent abnormality in PT, FDP, DD and ATIII, while the patients in the AKI group had more prolonged PT, more severe FDP and DD level, more inferior ATIII and Fib level than those in the non-AKI group (p < 0.01). The value of PT, DD and FDP were positively correlated with the classical APACHE II, SOFA and qSOFA scores, while the ATIII was negatively correlated with them (p < 0.001). The high levels of PT, FDP and DD were correlated with in-hospital mortality (p < 0.001). In conclusion, blood coagulation disorder was prominent in ICU patients with COVID-19 and was correlated with multi-inflammation factors. The abnormality of blood coagulation parameters could be an adverse prognostic indicator for ICU patients with COVID-19.

Effects of a high-fat diet on intracellular calcium (Ca2+) handling and cardiac remodeling in Wistar rats without hyperlipidemia.

A high-fat diet is often associated with cardiovascular diseases. Research has suggested that consumption of a high-fat diet for 10 weeks is associated with cardiac dysfunction, including arrhythmias, through alterations in cardiac remodeling and myocardial intracellular calcium (Ca2+) handling. In this study, rats were randomly divided into two groups: the standard diet (N = 5) and high-fat diet (N = 5) groups. To evaluate the effects of a high-fat diet on cardiac remodeling, we investigated the myocardium obtained from male Wistar rats fed a high-fat diet or standard diet for ten weeks via scanning electron microscopy, polarization microscopy, and RT-PCR. We found that compared with the standard diet cohort, the high-fat diet cohort exhibited increased levels of SERCA2a and SERCA2b mRNA and a decreased level of PLB mRNA (P < .05). These findings showed that a high-fat diet may lead to cardiac upregulation of Ca2+ transport-related genes in the sarcoplasmic reticulum. Additionally, we observed endocardial injury accompanied by focal dense layered collagen, increased spacing between endocardial cells that was often filled with collagen debris, and increased amounts of collagen fibers among enlarged cardiomyocytes in the high-fat diet cohort. The abnormal intracellular calcium (Ca2+) handling and cardiac remodeling may be contributing factors in arrhythmias and sudden cardiac death in high-fat diet-fed rats.

Effects of artemisinin on ventricular arrhythmias in response to left ventricular afterload increase and microRNA expression profiles in Wistar rats.

BACKGROUND: Patients with dilated cardiomyopathy, increased ventricular volume, pressure overload or dysynergistic ventricular contraction and relaxation are susceptible to develop serious ventricular arrhythmias (VA). These phenomena are primarily based on a theory of mechanoelectric feedback, which reflects mechanical changes that produce alterations in electrical activity. However, very few systematic studies have provided evidence of the preventive effects of artemisinin (ART) on VA in response to left ventricle (LV) afterload increases. MicroRNAs (miRNAs) are endogenous small non-coding RNAs that regulate expression of multiple genes by suppressing mRNAs post-transcriptionally. AIMS: The aims of this study were to investigate preventive effects of ART on mechanical VA and the underling molecular mechanisms of differentially expressed miRNAs (DEMs). METHODS: For the study, 70 male Wistar rats were randomly divided into seven groups: group 1 was a control group (sham surgery); group 2 was a model group that underwent transverse aortic constriction (TAC) surgery; groups 3, 4, 5 and 6 were administered ART 75, 150, 300 and 600 mg/kg before TAC surgery, respectively; and group 7 was administered verapamil (VER) 1 mg/kg before TAC surgery. A ventricular arrhythmia score (VAS) was calculated to evaluate preventive effects of ART and VER on mechanical VA. The high throughput sequencing-based approach provided DEMs that were altered by ART pretreatment between group 2 and group 4. All predicted mRNAs of DEMs were enriched by gene ontology (GO) and Kyoto Encyclopedia annotation of Genes and Genomes (KEGG) databases. These DEMs were validated by a real time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The average VASs of groups 3, 4, 5, 6 and 7 were significantly reduced compared with those of group 2 (2.70 ± 0.48, 1.70 ± 0.95, 2.80 ± 0.79, 2.60 ± 0.97, 1.40 ± 0.52, vs 3.70 ± 0.67, p < 0.01, respectively). The three top GO terms were neuron projection, organ morphogenesis and protein domain specific binding. KEGG enrichment of the 16 DEMs revealed that MAPK, Wnt and Hippo signaling pathways were likely to play a substantial role in the preventive effects of ART on mechanical VA in response to LV afterload increases. All candidate DEMs with the exception of rno-miR-370-3p, rno-miR-6319, rno-miR-21-3p and rno-miR-204-5p showed high expression levels validated by RT-qPCR. CONCLUSIONS: Artemisinin could prevent mechanical VA in response to LV afterload increases. Validated DEMs could be biomarkers and therapeutic targets of ART regarding its prevention of VA induced by pressure overload. The KEGG pathway and GO annotation analyses of the target mRNAs could indicate the potential functions of candidate DEMs. These results will help to elucidate the functional and regulatory roles of candidate DEMs associated with antiarrhythmic effects of ART.