Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Distress Syndrome Caused by Chlamydia abortus: A Case Report.

Background: Pneumonia infected by Chlamydia abortus (C. abortus) is rare, especially complicated with severe acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). Case Presentation: We presented the clinical details of a 44-year-old male who was diagnosed with C. abortus pneumonia, which rapidly progressed and ultimately led to ARDS, sepsis and MODS. Although he was initially diagnosed with pneumonia upon admission, no pathogenic bacteria were detected in sputum by conventional tests. Empirical intravenous infusion of meropenem and moxifloxacin was administered, but unfortunately, his condition deteriorated rapidly, especially respiratory status. On Day 2 after extracorporeal membrane oxygenation (ECMO) initiation, metagenomic next-generation sequencing (mNGS) was performed on the patient's bronchoalveolar lavage fluid, which indicated an infection with C. abortus. The patient's antimicrobial therapy was adjusted to oral doxycycline (0.1g every 12h), intravenous azithromycin (0.5g every day), and imipenem and cilastatin sodium (1g every 6h). The patient's condition improved clinically and biologically. However, the patient was discharged due to financial reasons and unfortunately passed away eight hours later. Conclusion: Infections with C. abortus can result in severe ARDS and serious visceral complications which necessitate prompt diagnosis and active intervention by clinicians. The case highlights the significance of mNGS as an essential diagnostic tool for uncommon pathogens. Tetracyclines, macrolides or their combinations are effective choices for treatment of C. abortus pneumonia. Further study is needed to explore the transmission routes of C. abortus pneumonia and establish precise guidelines for antibiotic treatment.

Construction of an HLA Classifier for Early Diagnosis, Prognosis, and Recognition of Immunosuppression in Sepsis by Multiple Transcriptome Datasets.

Background: Sepsis is a clinical syndrome, due to a dysregulated inflammatory response to infection. Accumulating evidence shows that human leukocyte antigen (HLA) genes play a key role in the immune responses to sepsis. Nevertheless, the effects of HLA genes in sepsis have still not been comprehensively understood. Methods: A systematical search was performed in the Gene Expression Omnibus (GEO) and ArrayExpress databases from inception to 10 September 2021. Random forest (RF) and modified Lasso penalized regression were conducted to identify hub genes in multi-transcriptome data, thus we constructed a prediction model, namely the HLA classifier. ArrayExpress databases, as external validation, were utilized to evaluate its diagnostic, prognostic, and predictive performance. Immune cell infiltration score was calculated via CIBERSORTx tools and single-sample gene set enrichment analysis (ssGSEA). Gene set variation analysis (GSVA) and ssGSEA were conducted to determine the pathways that are significantly enriched in different subgroups. Next, we systematically correlated the HLA classifier with immunological characteristics from multiple perspectives, such as immune-related cell infiltration, pivotal molecular pathways, and cytokine expression. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to validate the expression level of HLA genes in clinical samples. Results: A total of nine datasets comprising 1,251 patients were included. Based on RF and modified Lasso penalized regression in multi-transcriptome datasets, five HLA genes (B2M, HLA-DQA1, HLA-DPA1, TAP1, and TAP2) were identified as hub genes, which were used to construct an HLA classifier. In the discovery cohort, the HLA classifier exhibited superior diagnostic value (AUC = 0.997) and performed better in predicting mortality (AUC = 0.716) than clinical characteristics or endotypes. Encouragingly, similar results were observed in the ArrayExpress databases. In the E-MTAB-7581 dataset, the use of hydrocortisone in the HLA high-risk subgroup (OR: 2.84, 95% CI 1.07-7.57, p = 0.037) was associated with increased risk of mortality, but not in the HLA low-risk subgroup. Additionally, immune infiltration analysis by CIBERSORTx and ssGSEA revealed that B cells, activated dendritic cells, NK cells, T helper cells, and infiltrating lymphocytes (ILs) were significantly richer in HLA low-risk phenotypes, while Tregs and myeloid-derived suppressor cells (MDSCs) were more abundant in HLA high-risk phenotypes. The HLA classifier was significantly negatively correlated with B cells, activated dendritic cells, NK cells, T helper cells, and ILs, yet was significantly positively correlated with Tregs and MDSCs. Subsequently, molecular pathways analysis uncovered that cytokine-cytokine receptor (CCR) interaction, human leukocyte antigen (HLA), and antigen-presenting cell (APC) co-stimulation were significantly enriched in HLA low-risk endotypes, which was significantly negatively correlated with the HLA classifier in multi-transcriptome data. Finally, the expression levels of several cytokines (IL-10, IFNG, TNF) were significantly different between the HLA subgroups, and the ratio of IL-10/TNF was significantly positively correlated with HLA score in multi-transcriptome data. Results of qRT-PCR validated the higher expression level of B2M as well as lower expression level of HLA-DQA1, HLA-DPA1, TAP1, and TAP2 in sepsis samples compared to control sample. Conclusion: Based on five HLA genes, a diagnostic and prognostic model, namely the HLA classifier, was established, which is closely correlated with responses to hydrocortisone and immunosuppression status and might facilitate personalized counseling for specific therapy.

Characterization of immune-related genes andimmune infiltration features for early diagnosis, prognosis and recognition of immunosuppression in sepsis.

Among the body systems, the immune system plays a fundamental role in the pathophysiology of sepsis. The effects of immunogenomic and immune cell infiltration in sepsis were still not been systematically understood. Based on modified Lasso penalized regression and RF, 8 DEIRGs (ADM, CX3CR1, DEFA4, HLA-DPA1, MAPK14, ORM1, RETN, and SLPI) were combined to construct an IRG classifier. In the discovery cohort, IRG classifier exhibited superior diagnostic efficacy and performed better in predicting mortality than clinical characteristics or MARS/SRS endotypes. Encouragingly, similar results were observed in the ArrayExpress databases. The use of hydrocortisone in IRG high-risk subgroup was associated with increased risk of mortality. In IRG low-risk phenotypes, NK cells, T helper cells, and infiltrating lymphocyte (IL) are significantly richer, while T cells regulatory (Tregs) and myeloid-derived suppressor cells (MDSC) are more abundant in IRG high-risk phenotypes. IRG score were significantly negatively correlated with Cytokine cytokine receptor interaction (CCR) and human leukocyte antigen (HLA). Between the IRG subgroups, the expression levels of several cytokines (IL-10, IFNG, TNF) were significantly different, and IRG score was significantly positively correlated with ratio of IL-10/TNF. Results of qRT-PCR validated that higher expression level of ADM, DEFA4, MAPK14, ORM1, RETN, and SLPI as well as lower expression level of CX3CR1 and HLA-DPA1 in sepsis samples compared to control sample. A diagnostic and prognostic model, namely IRG classifier, was established based on 8 IRGs that is closely correlated with responses to hydrocortisone and immunosuppression status and might facilitate personalized counseling for specific therapy.

Clinical Efficacy of Extracorporeal Cardiopulmonary Resuscitation for Adults with Cardiac Arrest: Meta-Analysis with Trial Sequential Analysis.

OBJECTIVE: This meta-analysis with trial sequential analysis (TSA) compared the clinical efficacy of extracorporeal cardiopulmonary resuscitation (ECPR) with conventional CPR (CCPR) for adult patients who experienced in-hospital cardiac arrest (IHCA) or out-of-hospital CA (OHCA). METHODS: A literature search was used to identify eligible publications (up to 30 July 2018) from PubMed, the Cochrane Library, the ISI Web of Knowledge, and Embase. Two investigators independently conducted the literature search, study selection, data extraction, and quality evaluation. Meta-analysis and TSA were used to analyze each outcome, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the level of evidence. The primary outcome was 30-day survival, and the secondary outcomes were 30-day neurologic outcome, 3-6 months' survival, 3-6 months' neurological outcome, 1-year survival, and 1-year neurological outcome. RESULTS: We identified 13 eligible observational studies for the final analysis. Pooled analyses showed that ECPR was associated with a significantly better 30-day survival (RR = 1.60, 95% CI = 1.25-2.06) and 30-day neurologic outcome (RR = 2.69, 95% CI = 1.63-4.46), and TSA confirmed these results. However, subgroup analysis of patients with OHCA indicated that ECPR and CCPR had similar effects on 30-day survival (RR = 1.18, 95% CI = 0.71-1.97), which was not confirmed by TSA. Analysis of OHCA patients indicated that ECPR provided a better 30-day neurological outcome (RR = 3.93, 95% CI = 1.00-15.50), but TSA did not support these results. Analysis of IHCA patients indicated that ECPR was associated with a better 30-day survival (RR 1.90, 95% CI 1.43-2.52) and 30-day neurologic outcome (RR 2.02, 95% CI 1.21-3.39), and TSA supported these results. Other subgroup analyses showed that the results were generally consistent, regardless of nation, propensity score matching, presumed etiology, whether the CA was witnessed or not, and study quality. CONCLUSIONS: Relative to CCPR, ECPR improved the survival and neurological outcome of patients who had IHCA. Compared to IHCA patients, TSA could not confirm better survival and neurologic outcome of ECPR in OHCA patients, suggesting that further studies are needed. TRIAL REGISTRATION: This trial was registered with PROSPERO (CRD42018100513) on 17 July 2018.

[Sepsis-induced cardiomyopathy complicated with cardiogenic shock patients supported with extracorporeal membrane oxygenation].

OBJECTIVE: Sepsis-induced cardiomyopathy is a reversible myocardial dysfunction due to sepsis, which may be severe enough to complicate cardiogenic shock, and without effective drug and with high mortality during the acute phase. A case of sepsis-induced cardiomyopathy complicated with cardiogenic shock was treated in the intensive care unit (ICU) of Shunde Hospital Southern Medical University. A 37 years old female patient was admitted because she had suffered repeated fever for 5 days, chest tightness and abdominal pain for 3 days. At the same time, there were severe cardiac depression and abdominal infection, which could be explained by the monismtheory of sepsis cardiomyopathy.The cardiogenic shock patient was not improved after antibiotic therapy and hemodynamic support, extracorporeal membrane oxygenation (ECMO) support was prescribed. The circulation failure was smoothly got through with ECMO and was transfer from ICU to ordinary ward. Computed tomographic angiography (CTA) of abdominal aorta and colonoscopy indicated lesions of small intestine. The diagnosis of infection and bleeding in ileum diverticulum was confirmed during the operation and the lesions was removed. She recovered and was discharged 1 week after operation. Through the case review, we aim to improve the awareness of sepsis-induced cardiomyopathy and the value of ECMO support in cardiogenic shock.