Effect of therapeutic versus prophylactic anticoagulation therapy on clinical outcomes in COVID-19 patients: a systematic review with an updated meta-analysis.

BACKGROUND: Previous studies demonstrate a reduced risk of thrombosis and mortality with anticoagulant treatment in patients with COVID-19 than in those without anticoagulation treatment. However, an open question regarding the efficacy and safety of therapeutic anticoagulation (T-AC) versus a lower dose, prophylaxis anticoagulation (P-AC) in COVID-19 patients is still controversial. METHODS: We systematically reviewed currently available randomized clinical trials (RCTs) and observational studies (OBs) from January 8, 2019, to January 8, 2022, and compared prophylactic and therapeutic anticoagulant treatment in COVID-19 patients. The primary outcomes were risk of mortality, major bleeding, and the secondary outcomes included venous and arterial thromboembolism. Subgroup analysis was also performed between critically ill and non-critically ill patients with COVID-19 and between patients with higher and lower levels of D-dimer. Sensitivity analysis was performed to decrease the bias and the impact of population heterogeneity. RESULTS: We identified 11 RCTs and 17 OBs fulfilling our inclusion criteria. In the RCTs analyses, there was no statistically significant difference in the relative risk of mortality between COVID-19 patients with T-AC treatment and those treated with P-AC (RR 0.95, 95% CI, 0.78-1.15, P = 0.60). Similar results were also found in the OBs analyses (RR 1.21, 95% CI, 0.98-1.49, P = 0.08). The pooling meta-analysis using a random-effects model combined with effect sizes showed that in the RCTs and OBs analyses, patients with COVID-19 who received T-AC treatment had a significantly higher relative risk of the major bleeding event than those with P-AC treatment in COVID-19 patients (RCTs: RR 1.76, 95% CI, 1.19-2.62, P = 0.005; OBs: RR 2.39, 95% CI, 1.56-3.68, P < 0.0001). Compared with P-AC treatment in COVID-19 patients, patients with T-AC treatment significantly reduced the incidence of venous thromboembolism (RR 0.51, 95% CI, 0.39-0.67, P<0.00001), but it is not associated with arterial thrombosis events (RR 0.97, 95% CI, 0.66-1.42, P = 0.87). The subgroup analysis of OBs shows that the mortality risk significantly reduces in critically ill COVID-19 patients treated with T-AC compared with those with P-AC treatment (RR 0.58, 95% CI, 0.39-0.86, P = 0.007), while the mortality risk significantly increases in non-critically ill COVID-19 patients treated with T-AC (RR 1.56, 95% CI, 1.34-1.80, P < 0.00001). In addition, T-AC treatment does not reduce the risk of mortality in COVID-19 patients with high d-dimer levels in RCTs. Finally, the overall sensitivity analysis after excluding two RCTs studies remains consistent with the previous results. CONCLUSIONS: In our integrated analysis of included RCTs and OBs, there is no significant difference between the mortality of T-AC and P-AC treatment in unselected patients with COVID-19. T-AC treatment in COVID-19 patients significantly reduced the incidence of venous thromboembolism but showed a higher risk of bleeding than those with P-AC treatment. In addition, P-AC treatment was superior to T-AC treatment in non-critically ill COVID-19 patients, the evidence supporting the necessity for T-AC treatment in critically ill COVID-19 patients came only from OBs. TRIAL REGISTRATION: Protocol registration: The protocol was registered at PROSPERO (CRD42021293294).

Aberrant cytokine expression in COVID-19 patients: Associations between cytokines and disease severity.

Cytokines play pleiotropic, antagonistic, and collaborative in viral disease. The high morbidity and mortality of coronavirus disease 2019 (COVID-19) make it a significant threat to global public health. Elucidating its pathogenesis is essential to finding effective therapy. A retrospective study was conducted on 71 patients hospitalized with COVID-19. Data on cytokines, T lymphocytes, and other clinical and laboratory characteristics were collected from patients with variable disease severity. The effects of cytokines on the overall survival (OS) and event-free survival (EFS) of patients were analyzed. The critically severe and severe patients had higher infection indexes and significant multiple organ function abnormalities than the mild patients (P < 0.05). IL-6 and IL-10 were significantly higher in the critically severe patients than in the severe and mild patients (P < 0.05). IL-6 and IL-10 were closely associated with white blood cells, neutrophils, T lymphocyte subsets, D-D dimer, blood urea nitrogen, complement C1q, procalcitonin C-reactive protein. Moreover, the IL-6 and IL-10 levels were closely correlated to dyspnea and dizziness (P < 0.05). The patients with higher IL-10 levels had shorter OS than the group with lower levels (P < 0.05). The older patients with higher levels of single IL-6 or IL-10 tended to have shorter EFS (P < 0.05), while the patients who had more elevated IL-6 and IL-10 had shorter OS (P < 0.05). The Cox proportional hazard model revealed that IL-6 was the independent factor affecting EFS. IL-6 and IL-10 play crucial roles in COVID-19 prognosis.

The coronavirus diseases 2019 (COVID-19) pneumonia with spontaneous pneumothorax: a case report.

BACKGROUND: The outbreak of the novel coronavirus (COVID-19) that was firstly reported in Wuhan, China, with cases now confirmed in more than 100 countries. However, COVID-19 pneumonia with spontaneous pneumothorax is unknown. CASE PRESENTATION: We reported a case of 66-year-old man infected with COVID-19, presenting with fever, cough and myalgia; The patient received supportive and empirical treatment including antiviral treatment, anti-inflammatory treatment, oxygen supply and inhalation therapy; The symptoms, CT images, laboratory results got improved after the treatments, and a throat swab was negative for COVID-19 PCR test; However, on the hospital day 30, the patient presented with a sudden chest pain and dyspnea. CT showed a 30-40% left-sided pneumothorax. Immediate thoracic closed drainage was performed and his dyspnea was rapidly improved. With five more times negative PCR tests for SARS-CoV-2 virus, the patient was discharged and home quarantine. CONCLUSION: This case highlights the importance for clinicians to pay attention to the appearance of spontaneous pneumothorax, especially patients with severe pulmonary damage for a long course, as well as the need for early image diagnose CT and effective treatment once pneumothorax occurs.

Inhibition of myeloid differentiation 1 specifically in colon with antisense oligonucleotide exacerbates dextran sodium sulfate-induced colitis.

Myeloid differentiation 1 (MD-1), also known as lymphocyte antigen 86 (Ly86), is a soluble protein homologous to MD-2 and forms a complex with radioprotective 105 (RP105). RP105/MD-1 complex negatively regulates toll-like receptor 4 (TLR4) signaling and is involved in several immune disorders. However, the precise role of MD-1 in inflammatory bowel diseases (IBD) remains poorly understood. To further investigate the involvement of MD-1 in IBD, we inhibited MD-1 in colon with antisense oligonucleotide (AS-ODN) and assessed the effect of MD-1 inhibition on dextran sodium sulfate (DSS)-induced colitis. We discovered that MD-1 protein expression was remarkably decreased in both patients with ulcerative colitis and mice with DSS-induced colitis. For the first time, we showed that oral administration of MD-1 AS-ODN to mice significantly suppressed the MD-1 protein levels in colon rather than systemic tissues. Subsequently, we found that MD-1 AS-ODN treated mice were more susceptible to DSS-induced colitis based on loss of body weight, colon length, histological scores, and disease activity index. MD-1 inhibition also significantly enhanced inflammatory cytokines production such as IL-6 and IL-1ß in colons. Finally, mice treated with MD-1 AS-ODN exhibited increased messenger RNA levels of TLR4 and MyD88 after DSS exposure and showed enhanced nuclear factor (NF)-κB activation compared with the control. Taken together, specifically suppression of MD-1 in colon tissues with AS-ODN exacerbates DSS-induced experimental colitis in mice, which is possibly related to activation of TLR4/NF-κB signaling.

Sulfatide-activated type II NKT cells suppress immunogenic maturation of lung dendritic cells in murine models of asthma.

Our previous study showed that sulfatide-activated type II natural killer T (NKT) cells can prevent allergic airway inflammation in an ovalbumin (OVA)-induced murine model of asthma, but the underlying mechanism is unclear. Recently, sulfatide-activated type II NKT cells were shown to modulate the function of dendritic cells in experimental autoimmune encephalomyelitis and nonobese diabetic mice. Thus, it was hypothesized that sulfatide-activated type II NKT cells may modulate the function of lung dendritic cells (LDCs) in asthmatic mice. Our data showed that, in our mouse models, activation of type II NKT cells by sulfatide administration and adoptive transfer of sulfatide-activated type II NKT cells resulted in reduced expression of surface maturation markers and proinflammatory cytokine production of LDCs. LDCs from sulfatide-treated asthmatic mice, in contrast to LDCs from PBS-treated asthmatic mice, significantly reduced allergic airway inflammation in vivo. However, we found no influence of sulfatide-activated type II NKT cells on the phenotypic and functional maturation of bone marrow-derived dendritic cells in vitro. In addition, adoptive transfer of sulfatide-activated type II NKT cells did not influence the phenotypic and functional maturation of LDCs in CD1d-/- mice, which lack both type I and II NKT cells, immunized and challenged with OVA. Our data reveal that sulfatide-activated type II NKT cells can suppress immunogenic maturation of LDCs to reduce allergic airway inflammation in mouse models of asthma, and it is possible that the immunomodulatory effect needs type I NKT cells.

Disruption of Tumor Necrosis Factor Receptor-Associated Factor 5 Exacerbates Murine Experimental Colitis via Regulating T Helper Cell-Mediated Inflammation.

Tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5) is a key mediator of TNF receptor superfamily members and is important in both T helper (Th) cell immunity and the regulation of multiple signaling pathways. To clarify TRAF5's influence on inflammatory bowel diseases (IBDs), we investigated TRAF5 deficiency's effect on dextran sulfate sodium- (DSS-) induced colitis. Colitis was induced in TRAF5 knockout (KO) mice and their wild-type (WT) littermates by administering 3% DSS orally for 7 days. The mice were then sacrificed, and their colons were removed. Our data suggested that KO mice were more susceptible to DSS-induced colitis. TRAF5 deficiency significantly enhanced IFN-γ, IL-4, and IL-17a mRNA and protein levels in the colons of DSS-fed mice, and the mRNA expression of T-bet and GATA-3 was also markedly elevated. However, ROR-α and ROR-γt mRNA levels did not differ between DSS-induced KO and WT mice. Flow cytometry showed increased frequencies of Th2 and IFN-γ/IL-17a-coproducing CD4(+) T cells in the colons of DSS-induced KO mice. Additionally, TRAF5 deficiency significantly enhanced the activation of NF-κB in CD4(+) T cells after DSS administration. These results indicated that TRAF5 deficiency significantly aggravated DSS-induced colitis, most likely by regulating Th cell-mediated inflammation.

Comparative effectiveness of treatments for recurrent Clostridioides difficile infection: a network meta-analysis of randomized controlled trials.

Background: Clostridioides difficile infection (CDI) is the most common cause of healthcare-associated infectious diarrhea. A major clinical challenge is recurrent CDI (rCDI) without effective standard drug-based therapy. Additionally, a comprehensive comparison of various therapy effectiveness in rCDI patients is still under investigation. Methods: A Bayesian network meta-analysis (NMA) of randomized control trials up to March 2024 was performed to investigate the efficacy of rCDI interventions. Results: Seventeen trials were included, comprising 4,148 CDI patients with ten interventions, including fecal microbiota transplantation (FMT) by lower gastrointestinal (LGI), FMT by upper gastrointestinal (UGI), Autologous FMT (AFMT), vancomycin + FMT, vancomycin, placebo, fidaxomicin, Vowst (SER109), Rebyota (RBX2660), and monoclonal antibody. NMA showed that FMT by LGI had the highest efficacy in treating rCDIs with an odds ratio (95% confidence interval) of 32.33 (4.03, 248.69) compared with placebo. FMT by UGI also showed high efficacy, whereas the efficacy comparison between FMT by LGI and UGI was not statistically significant (ORs) (95% CI), 1.72 (0.65, 5.21). The rankogram and surface under the cumulative ranking curve (SUCRA) also showed FMT by LGI ranked at the top and FMT by UGI ranked second in the curative effect. Conclusion: NMA demonstrates FMT's significant efficacy in rCDI management, regardless of administration route (lower or upper gastrointestinal). Despite its significant benefits, FMT's safety is a concern due to the lack of standardized FDAcompliant manufacturing and oversight. Microbiota-based therapies also exhibit potential. However, limited research mandates further clinical exploration. Antibiotics, in contrast, display comparatively reduced efficacy in rCDI, potentially linked to disruptions in native gut microflora balance. Systematic Review: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=368435, Identifier CRD42022368435.

CureSCi Metadata Catalog-finding and harmonizing studies for secondary analysis of hydroxyurea use for sickle cell disease.

Objectives: Sickle cell disease (SCD) is a rare group of inherited red blood cell disorders that affect hemoglobin, resulting in serious multi-system complications. The limited number of patients available to participate in research studies can inhibit investigating sophisticated relationships. Secondary analysis is a research method that involves using existing data to answer new research questions. Data harmonization enables secondary analysis by combining data across studies, especially helpful for rare disease research where individual studies may be small. The National Heart, Lung, and Blood Institute Cure Sickle Cell Initiative (CureSCi) Metadata Catalog is a web-based tool to identify SCD study datasets for conducting data harmonization and secondary analysis. We present a proof-of-concept secondary analysis to explore factors associated with discontinuation of hydroxyurea, a safe and effective first line SCD therapy, to illustrate the utility of the CureSCi Metadata Catalog to expedite and enable more robust SCD research. Methods: We performed secondary analysis of SCD studies using a multi-step workflow: develop research questions, identify study datasets, identify variables of interest, harmonize variables, and establish an analysis method. A harmonized dataset consisting of eight predictor variables across five studies was created. Secondary analysis involved a generalized linear model was employed to identify factors that significantly impact hydroxyurea discontinuation. Results: The CureSCi Metadata Catalog provided a platform to efficiently find relevant studies and design a harmonization strategy to prepare data for secondary analysis. Multivariate analysis of the harmonized identified that patients who are older, are female, had a history of blood transfusion therapy, had episodes of acute chest syndrome, and had the SC sickle cell genotype are more likely to stop hydroxyurea treatment. Conclusion: This secondary analysis provides a template for how the CureSCi Metadata Catalog expedites dataset discovery of sickle cell studies for identifying relationships between variables or validating existing findings.

Identification of predictive markers of Pneumocystis jirovecii pneumonia in kidney transplant recipients.

BACKGROUND: Kidney transplantation has emerged as the most effective treatment for patients with uremia. Advances in immunosuppressant medications have significantly reduced the risk of rejection. However, a notable increase in opportunistic infections, such as Pneumocystis jirovecii pneumonia (PJP), demands special attention in clinical practice. Our study aims to evaluate risk factors and identify predictive markers associated with PJP in kidney transplantation recipients. METHODS: We conducted a case-control study (1:2 ratio) involving kidney transplant recipients with and without PJP, matched based on the same surgical date. The study was carried out at Zhongnan Hospital of Wuhan University, China. RESULTS: Ninety-three participants were enrolled at Zhongnan Hospital of Wuhan University, comprising 31 with PJP and 62 without PJP. All patients tested negative for HIV. Our findings indicate that PJP patients exhibited lower levels of serum albumin (P = 0.001), reduced counts of total and CD3+ (P < 0.001), CD4+ (P = 0.001), and CD8+ T lymphocytes (P < 0.001), and a lower rate of prophylactic trimethoprim-sulfamethoxazole (TMP-SMZ) usage compared to non-PJP patients (P = 0.02). Conversely, urea levels in PJP patients were significantly higher than in non-PJP controls (P < 0.001). We developed a model combining CD8+ T cell count (< 241.11/µL, P < 0.001) and ALB levels (< 35.2 g/L, P = 0.003), which demonstrated excellent discriminatory power in distinguishing PJP from non-PJP cases, with an area under the curve (AUC) of 0. 920 (95% CI, 0.856-0.989). CONCLUSIONS: Our study suggests that a baseline CD8+ T cell count (< 241.11/µL) and serum ALB levels (< 35.2 g/L) offer robust predictive value for the occurrence of PJP infections in kidney transplant recipients.

Effect of antiplatelet therapy after COVID-19 diagnosis: A systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic disease in the venous and arterial circulations. METHODS: Based on the current debate on antiplatelet therapy in COVID-19 patients, we performed a systematic review and meta-analysis to investigate the effect of antiplatelet treatments. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2023, and only included Randomized clinical trials. The study followed PRISMA guidelines and used Random-effects models to estimate the pooled percentage and its 95% CI. RESULTS: Five unique eligible studies were included, covering 17,950 patients with COVID-19. The result showed no statistically significant difference in the relative risk of all-cause death in antiplatelet therapy versus non-antiplatelet therapy (RR 0.94, 95% CI, 0.83-1.05, P = 0.26, I2 = 32%). Compared to no antiplatelet therapy, patients who received antiplatelet therapy had a significantly increased relative risk of major bleeding (RR 1.81, 95%CI 1.09-3.00, P = 0.02, I2 = 16%). The sequential analysis suggests that more RCTs are needed to draw more accurate conclusions. This systematic review and meta-analysis revealed that the use of antiplatelet agents exhibited no significant benefit on all-cause death, and the upper bound of the confidence interval on all-cause death (RR 95% CI, 0.83-1.05) suggested that it was unlikely to be a substantiated harm risk associated with this treatment. However, evidence from all RCTs suggested a high risk of major bleeding in antiplatelet agent treatments. CONCLUSION: According to the results of our sequential analysis, there is not enough evidence available to support or negate the use of antiplatelet agents in COVID-19 cases. The results of ongoing and future well-designed, large, randomized clinical trials are needed.

Screening of potential key ferroptosis-related genes in Chronic Obstructive Pulmonary Disease.

Purpose: Ferroptosis plays essential roles in the development of COPD. We aim to identify the potential ferroptosis-related genes of COPD through bioinformatics analysis. Methods: The RNA expression profile dataset GSE148004 was obtained from the GEO database. The ferroptosis-related genes were obtained from the FerrDb database. The potential differentially expressed ferroptosis-related genes of COPD were screened by R software. Then, protein-protein interactions (PPI), correlation analysis, gene-ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were applied for the differentially expressed ferroptosis-related genes. Finally, hub gene-microRNA(miRNA), hug gene-transcription factor interaction networks were constructed by miRTarBase v8.0 and JASPAR respectively, and hub gene drugs were predicted by the Enrichr database. Results: A total of 41 differentially expressed ferroptosis-related genes (22 up-regulated genes and 19 down-regulated genes) were identified between 7 COPD patients and 9 healthy controls. The PPI results demonstrated that these ferroptosis-related genes interacted with each other. The GO and KEGG enrichment analyses of differentially expressed ferroptosis-related genes indicated several enriched terms related to ferroptosis, central carbon metabolism in cancer, and the HIF-1 signaling pathway. The crucial miRNAs and drugs associated with the top genes were identified. Conclusion: We identified 41 potential ferroptosis-related genes in COPD through bioinformatics analysis. HIF1A, PPARG, and KRAS may affect the development of COPD by regulating ferroptosis. These results may expand our understanding of COPD and might be useful in the treatment of COPD.

Linking complex disease and exposure data-insights from an environmental and occupational health study.

The disparate measurement protocols used to collect study data are an intrinsic barrier to combining information from environmental health studies. Using standardized measurement protocols and data standards for environmental exposures addresses this gap by improving data collection quality and consistency. To assess the prevalence of environmental exposures in National Institutes of Health (NIH) public data repositories and resources and to assess the commonality of the data elements, we analyzed clinical measures and exposure assays by comparing the Caribbean Consortium for Research in Environmental and Occupational Health study with selected NIH environmental health resources and studies. Our assessment revealed that (1) environmental assessments are widely collected in these resources, (2) biological assessments are less prevalent, and (3) NIH resources can help identify common data for meta-analysis. We highlight resources to help link environmental exposure data across studies to support data sharing. Including NIH data standards in environmental health research facilitates comparing and combining study data, and the use of NIH resources and adoption of standard measures will allow integration of multiple studies and increase the scientific impact of individual studies.

Using PhenX measures to identify opportunities for cross-study analysis.

The PhenX Toolkit provides researchers with recommended, well-established, low-burden measures suitable for human subject research. The database of Genotypes and Phenotypes (dbGaP) is the data repository for a variety of studies funded by the National Institutes of Health, including genome-wide association studies. The dbGaP requires that investigators provide a data dictionary of study variables as part of the data submission process. Thus, dbGaP is a unique resource that can help investigators identify studies that share the same or similar variables. As a proof of concept, variables from 16 studies deposited in dbGaP were mapped to PhenX measures. Soon, investigators will be able to search dbGaP using PhenX variable identifiers and find comparable and related variables in these 16 studies. To enhance effective data exchange, PhenX measures, protocols, and variables were modeled in Logical Observation Identifiers Names and Codes (LOINC® ). PhenX domains and measures are also represented in the Cancer Data Standards Registry and Repository (caDSR). Associating PhenX measures with existing standards (LOINC® and caDSR) and mapping to dbGaP study variables extends the utility of these measures by revealing new opportunities for cross-study analysis.

Identification of quantitative trait loci underlying proteome variation in human lymphoblastoid cells.

Population-based variability in protein expression patterns, especially in humans, is often observed but poorly understood. Moreover, very little is known about how interindividual genetic variation contributes to protein expression patterns. To begin to address this, we describe elements of technical and biological variations contributing to expression of 544 proteins in a population of 24 individual human lymphoblastoid cell lines that have been extensively genotyped as part of the International HapMap Project. We determined that expression levels of 10% of the proteins were tightly correlated to cell doubling rates. Using the publicly available genotypes for these lymphoblastoid cell lines, we applied a genetic association approach to identify quantitative trait loci associated with protein expression variation. Results identified 24 protein forms corresponding to 15 proteins for which genetic elements were responsible for >50% of the expression variation. The genetic variation associated with protein expression levels were located in cis with the gene coding for the transcript of the protein for 19 of these protein forms. Four of the genetic elements identified were coding non-synonymous single nucleotide polymorphisms that resulted in migration pattern changes in the two-dimensional gel. This is the first description of large scale proteomics analysis demonstrating the direct relationship between genome and proteome variations in human cells.

Management of dermatomyositis patients amidst the COVID-19 pandemic: Two case reports.

RATIONALE: In December 2019, a new epidemic of coronavirus disease 2019 (COVID-19) appeared in Wuhan, Hubei Province, and spread rapidly to other parts of China and worldwide. Although established methods exist for the diagnosis and treatment of COVID-19 infection, the management of dermatomyositis (DM) patients with COVID-19 is unknown. PATIENT CONCERNS: In this article, we describe case reports of 2 patients with DM. The first case was a 67-year-old patient with DM and infected with COVID-19 who was admitted to Leishenshan Hospital for a 1-month history of fever, cough, and expectoration. The second case was a 51-year-old male patient who was admitted to Leishenshan Hospital due to fever with cough, expectoration and shortness of breath for 1 month. DIAGNOSES: The first patient was diagnosed with COVID-19 secondary to DM based on repeated SARS-CoV-2 real-time reverse-transcriptase polymerase-chain-reaction (RT-PCR) test, detailed medical history and chest computed tomography; The second patient was diagnosed with interstitial lung disease associated with anti-MDA5 DM based on the results of antirheumatic and anti-inflammatory therapy and the above 3 methods. INTERVENTIONS AND OUTCOMES: The first patient received supportive and empirical treatment, including antiviral treatment, anti-inflammatory treatment, oxygen therapy and prophylactic anticoagulation therapy. The symptoms and laboratory results got improved after the treatments. He was discharged with thrice negative PCR tests for the SARS-CoV-2 virus. The second patient received a comprehensive treatment, including glucocorticoid and plasma exchange; his symptoms were relieved and improved. LESSONS: These cases suggest that repeated new pathogenic test results for the coronavirus and a detailed diagnosis of the medical history are important means to distinguish these diseases. Increased attention to the individual characteristics of different cases may allow for more effective diagnosis and treatment.

Hemophagocytic Lymphohistiocytosis Associated with Synergistic Defects of AP3B1 and ATM Genes: A Case Report and Literature Review.

Hemophagocytic lymphohistiocytosis (HLH) is an overwhelming immune system activation that manifests as hyperinflammation and life-threatening multiple organ failure. However, the clinical manifestations of the systemic inflammatory response in sepsis and fulminant cytokine storm caused by HLH macrophage activation are very similar and difficult to distinguish. HLH triggered by two novel gene defects manifesting with multiorgan dysfunction syndrome (MODS) and distributive shock has not been reported. A 14-year-old male patient was hospitalized with a high fever, his condition deteriorated rapidly, accompanied by cytopenia, shock, and MODS, and he was subsequently transferred to our intensive care unit (ICU) for symptomatic and organ-supportive treatments. Laboratory indicators of cytopenia, hypofibrinogenemia, hypertriglyceridemia, hyperferritinemia, high soluble CD25, low natural killer (NK) cell cytotoxicity, and hemophagocytosis in the bone marrow confirmed the diagnosis of HLH. Molecular genetic analysis revealed that two novel heterozygous gene mutations in AP3B1 (c.3197 C > T) and ATM (c.8077 G > T) might have accounted for the onset. After treatment, the patient's condition successfully improved. This case report demonstrates the timely determination of underlying triggers and critical care supports (supportive and etiological treatment) of HLH related to the improved outcome.

CureSCi Metadata Catalog-Making sickle cell studies findable.

OBJECTIVES: To adopt the FAIR principles (Findable, Accessible, Interoperable, Reusable) to enhance data sharing, the Cure Sickle Cell Initiative (CureSCi) MetaData Catalog (MDC) was developed to make Sickle Cell Disease (SCD) study datasets more Findable by curating study metadata and making them available through an open-access web portal. METHODS: Study metadata, including study protocol, data collection forms, and data dictionaries, describe information about study patient-level data. We curated key metadata of 16 SCD studies in a three-tiered conceptual framework of category, subcategory, and data element using ontologies and controlled vocabularies to organize the study variables. We developed the CureSCi MDC by indexing study metadata to enable effective browse and search capabilities at three levels: study, Patient-Reported Outcome (PRO) Measures, and data element levels. RESULTS: The CureSCi MDC offers several browse and search tools to discover studies by study level, PRO Measures, and data elements. The "Browse Studies," "Browse Studies by PRO Measures," and "Browse Studies by Data Elements" tools allow users to identify studies through pre-defined conceptual categories. "Search by Keyword" and "Search Data Element by Concept Category" can be used separately or in combination to provide more granularity to refine the search results. This resource helps investigators find information about specific data elements across studies using public browsing/search tools, before going through data request procedures to access controlled datasets. The MDC makes SCD studies more Findable through browsing/searching study information, PRO Measures, and data elements, aiding in the reuse of existing SCD data.

Sera Metabolomics Characterization of Patients at Different Stages in Wuhan Identifies Critical Biomarkers of COVID-19.

We have witnessed the 2-year-long global rampage of COVID-19 caused by the wide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, knowledge about biomarkers of the entire COVID-19 process is limited. Identification of the systemic features of COVID-19 will lead to critical biomarkers and therapeutic targets for early intervention and clinical disease course prediction. Here, we performed a comprehensive analysis of clinical measurements and serum metabolomics in 199 patients with different stages of COVID-19. In particular, our study is the first serum metabolomic analysis of critical rehabilitation patients and critical death patients. We found many differential metabolites in the comparison of metabolomic results between ordinary, severe, and critical patients and uninfected patients. Through the metabolomic results of COVID-19 patients in various stages, and critical rehabilitation patients and critical death patients, we identified a series of differential metabolites as biomarkers, a separate queue and precise distinction, and predicted COVID-19 verification. These differentially expressed metabolites, included 1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphate, propylparaben, 20-hydroxyeicosatetraenoic acid, triethanolamine, chavicol, disialosyl galactosyl globoside, 1-arachidonoylglycerophosphoinositol, and alpha-methylstyrene, all of which have been identified for the first time as biomarkers in COVID-19 progression. These biomarkers are involved in many pathological and physiological pathways of COVID-19, for example, immune responses, platelet degranulation, and metabolism which might result in pathogenesis. Our results showed valuable information about metabolites obviously altered in COVID-19 patients with different stages, which could shed light on the pathogenesis as well as serve as potential therapeutic agents of COVID-19.