Dynamic changes in serum (1-3)-ß-D-glucan caused by intravenous immunoglobulin infusion: A prospective study.

PURPOSE: The purpose of this study was to investigate the dynamic changes in serum (1-3)-ß-D-glucan (BDG) caused by intravenous immunoglobulins (IVIG) infusion in adults. METHODS: This study included patients who received IVIG infusion from October 2021 to October 2022 during hospitalization. We randomly examined two IVIG samples for every patient. Serum samples were collected at nine time points: before (Tpre), immediately (T1-0), 6h (T1-1) and 12h (T1-2) later on the first day; immediately (T2-0) and six hours later (T2-1) on the second day during IVIG infusion, and within three days after IVIG infusion (Ta1, Ta2, and Ta3, respectively). The Friedman test was used for statistical analysis. RESULTS: A total of 159 serum BDG from 19 patients were included in the analysis. The BDG content of IVIG ranged from 249 pg/ml to 4812 pg/ml. Patients had significantly elevated serum BDG on T1-0 (176 (113, 291) pg/ml, p = 0.002) and Ta1 (310 (199, 470) pg/ml, p < 0.001), compared with Tpre (41 (38, 65) pg/ml). The increments of serum BDG (ΔBDG) were associated with BDG concentration of IVIG (Spearman r = 0.59, p = 0.02). Individuals with abnormal renal function indexes showed higher serum ΔBDG values at Ta1 (403 (207, 484) pg/ml) than patients with normal renal function (172 (85, 316) pg/ml, p = 0.036). CONCLUSION: Patients who received IVIG had significantly higher serum BDG values. Elevated BDG levels correlate with BDG content of IVIG and abnormal renal function indexes.

A nationwide study on new onset atrial fibrillation risk factors and its association with hospital mortality in sepsis patients.

Atrial fibrillation (AF) is the most common arrhythmia and its incidence increases with sepsis. However, data on new-onset AF during sepsis hospitalization remain limited in China. We aimed to evaluate the incidence, risk factors, and associated mortality of new-onset AF in sepsis patients in China. We conducted a retrospective study using the National Data Center for Medical Service system, from 1923 tertiary and 2363 secondary hospitals from 31 provinces in China from 2017 to 2019.In total we included 1,425,055 sepsis patients ≥ 18 years without prior AF. The incidence of new-onset AF was 1.49%. Older age, male sex, hypertension, heart failure, coronary disease, valvular disease, and mechanical ventilation were independent risk factor. New-onset AF was associated with a slight increased risk of mortality (adjusted RR 1.03, 95% CI 1.01-1.06). Population attributable fraction suggested AF accounted for 0.2% of sepsis deaths. In this large nationwide cohort, new-onset AF occurred in 1.49% of sepsis admissions and was associated with a small mortality increase. Further research should examine whether optimized AF management can improve sepsis outcomes in China.

Extracorporeal vs. conventional CPR for out-of-hospital cardiac arrest: A systematic review and meta-analysis.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) remains a significant cause of mortality and morbidity worldwide. Extracorporeal cardiopulmonary resuscitation (ECPR) is a potential intervention for OHCA, but its effectiveness compared to conventional cardiopulmonary resuscitation (CCPR) needs further evaluation. METHOD: We systematically searched PubMed, Embase, the Cochrane Library, Web of Science, and ClinicalTrials.gov for relevant studies from January 2010 to March 2023. Pooled meta-analysis was performed to investigate any potential association between ECPR and improved survival and neurological outcomes. RESULTS: This systematic review and meta-analysis included two randomized controlled trials enrolling 162 participants and 10 observational cohort studies enrolling 4507 participants. The pooled meta-analysis demonstrated that compared to CCRP, ECPR did not improve survival and neurological outcomes at 180 days following OHCA (RR: 3.39, 95% CI: 0.79 to 14.64; RR: 2.35, 95% CI: 0.97 to 5.67). While a beneficial effect of ECPR was obtained regarding 30-day survival and neurological outcomes. Furthermore, ECPR was associated with a higher risk of bleeding complications. Subgroup analysis showed that ECPR was prominently beneficial when exclusively initiated in the emergency department. Additional post-resuscitation treatments did not significantly impact the efficacy of ECPR on 180-day survival with favorable neurological outcomes. CONCLUSIONS: There is no high-quality evidence supporting the superiority of ECPR over CCPR in terms of survival and neurological outcomes in OHCA patients. However, due to the potential for bias, heterogeneity among studies, and inconsistency in practice, the non-significant results do not preclude the potential benefits of ECPR. Further high-quality research is warranted to optimize ECPR practice and provide more generalizable evidence. Clinical trial registration PROSPERO, https://www.crd.york.ac.uk/prospero/, registry number: CRD42023402211.

[Clinicians' Practice and Opinions on Sedation Therapy in End-Stage Patients].

Objective To investigate clinicians' practice and opinions on sedation therapy in end-stage patients at Peking Union Medical College Hospital. Methods From August,2022 to April,2023,an online questionnaire survey was conducted among clinicians involved in end-stage patient management. Results A total of 205 questionnaires were distributed,with an effective response rate of 56.1%.Among the clinicians,55.7% of them had experience of applying sedation therapy in end-stage patients;85.2% of clinicians believed that sedation could relieve the suffering of terminal patients from physical refractory symptoms;75.7% of clinicians considered that sedation therapy could be used to relieve agony from psycho-existential distress.Most clinicians had concerns about sedation therapy due to the lack of legal support(86.1%)and the lack of understanding of patients or families(59.1%).The majority (90.4%) of clinicians were willing to receive training on palliative sedation. Conclusions A majority of clinicians agree that sedation therapy could relieve the physical distress and psycho-existential distress in end-stage patients.However,most clinicians have concerns about the application of sedation therapy due to the lack of legal support.It is necessary to enhance the training on palliative sedation.

Cell-free DNA methylation reveals cell-specific tissue injury and correlates with disease severity and patient outcomes in COVID-19.

BACKGROUND: The recently identified methylation patterns specific to cell type allows the tracing of cell death dynamics at the cellular level in health and diseases. This study used COVID-19 as a disease model to investigate the efficacy of cell-specific cell-free DNA (cfDNA) methylation markers in reflecting or predicting disease severity or outcome. METHODS: Whole genome methylation sequencing of cfDNA was performed for 20 healthy individuals, 20 cases with non-hospitalized COVID-19 and 12 cases with severe COVID-19 admitted to intensive care unit (ICU). Differentially methylated regions (DMRs) and gene ontology pathway enrichment analyses were performed to explore the locus-specific methylation difference between cohorts. The proportion of cfDNA derived from lung and immune cells to a given sample (i.e. tissue fraction) at cell-type resolution was estimated using a novel algorithm, which reflects lung injuries and immune response in COVID-19 patients and was further used to evaluate clinical severity and patient outcome. RESULTS: COVID­19 patients had globally reduced cfDNA methylation level compared with healthy controls. Compared with non-hospitalized COVID-19 patients, the cfDNA methylation pattern was significantly altered in severe patients with the identification of 11,156 DMRs, which were mainly enriched in pathways related to immune response. Markedly elevated levels of cfDNA derived from lung and more specifically alveolar epithelial cells, bronchial epithelial cells, and lung endothelial cells were observed in COVID-19 patients compared with healthy controls. Compared with non-hospitalized patients or healthy controls, severe COVID-19 had significantly higher cfDNA derived from B cells, T cells and granulocytes and lower cfDNA from natural killer cells. Moreover, cfDNA derived from alveolar epithelial cells had the optimal performance to differentiate COVID-19 with different severities, lung injury levels, SOFA scores and in-hospital deaths, with the area under the receiver operating characteristic curve of 0.958, 0.941, 0.919 and 0.955, respectively. CONCLUSION: Severe COVID-19 has a distinct cfDNA methylation signature compared with non-hospitalized COVID-19 and healthy controls. Cell type-specific cfDNA methylation signature enables the tracing of COVID-19 related cell deaths in lung and immune cells at cell-type resolution, which is correlated with clinical severities and outcomes, and has extensive application prospects to evaluate tissue injuries in diseases with multi-organ dysfunction.

Impact of Immunosuppressed Status on Prognosis of Carbapenem-Resistant Organisms Bloodstream Infections.

INTRODUCTION: The impact of immunosuppression on prognosis of carbapenem-resistant organism (CRO) bloodstream infection (BSI) remains unclear. The aim of this study was to clarify the relationship between immunosuppression and mortality of CRO-BSI and to identify the risk factors associated with mortality in immunosuppressed patients. METHODS: This retrospective study included 279 patients with CRO-BSI from January 2018 to March 2023. Clinical characteristics and outcomes were compared between the immunosuppressed and immunocompetent patients. The relationship between immunosuppression and 30-day mortality after BSI onset was assessed through logistic-regression analysis, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). Factors associated with mortality in immunosuppressed patients were analyzed using multivariable logistic regression analysis. RESULTS: A total of 88 immunocompetent and 191 immunosuppressed patients were included, with 30-day all-cause mortality of 58.8%. Although the 30-day mortality in immunosuppressed patients was significantly higher than in immunocompetent patients (46.6% vs. 64.4%, P = 0.007), immunosuppression was not an independent risk factor for mortality in multivariate logistic regression analysis (odds ratio [OR] 3.53, 95% confidence interval [CI] 0.74-18.89; P = 0.123), PSM (OR 1.38, 95% CI 0.60-3.18; P = 0.449,) or IPTW (OR 1.40, 95% CI 0.58-3.36; P = 0.447). For patients with CRO-BSI, regardless of immune status, appropriate antibiotic therapy was associated with decreased 30-day mortality, while Charlson comorbidity index (CCI), intensive care unit (ICU)-acquired infection and thrombocytopenia at CRO-BSI onset were associated with increased mortality. CONCLUSION: Despite the high mortality rate of CRO-BSI, immunosuppression did not affect the mortality. Appropriate antibiotic therapy is crucial for improving the prognosis of CRO-BSI, regardless of the immune status.

Comparison of different criteria of metagenomic next-generation sequencing for the diagnosis of invasive pulmonary aspergillosis in critically ill patients.

OBJECTIVE: To compare different criteria of Metagenomic Next-Generation Sequencing (mNGS) in bronchoalveolar lavage fluid (BALF) for diagnosing invasive pulmonary aspergillosis (IPA). METHODS: We compared the diagnostic agreement and performances of six BALF mNGS-derived criteria (SDSMRN>1, SDSMRN≥3, SMRN≥10, SMRN≥50, RPM ratio≥10, and relative abundance of genus>30 %) in pneumonia patients. RESULTS: A total of 115 patients were analyzed, with 28 identified with IPA. Diagnostic agreement among the six mNGS-derived criteria was moderate, with a Cohen's kappa of 0.577(P < 0.001). mNGS-derived criteria had low sensitivity ranging from 21.4 % to 57.1 % and high specificity from 88 % to 92 %. The optimal threshold of SDSMRN, SMRN, RPM ratio, and relative abundance of genus for diagnosing IPA were 5, 0.25, 8, and 20 %, respectively. Although using the optimal threshold, the sensitivity of mNGS is lower than 50 %. CONCLUSIONS: All mNGS-derived criteria had low sensitivity for diagnosing IPA. A combination of mNGS and conventional mycological tests may be the best diagnostic strategy.

Sepsis-induced Coagulopathy: The Different Prognosis in Severe Pneumonia and Bacteremia Infection Patients.

Sepsis-induced coagulopathy (SIC) is a critical condition in sepsis patients, with varying outcomes depending on the type of infection. This study aims to analyze the prognosis of different infections in SIC cohort. A retrospective cohort study was conducted on 525 patients diagnosed with SIC in the intensive care unit from December 2013 to December 2022. These patients were divided into four groups: a non-pneumonia or bacteremia group, a severe pneumonia group, a bacteremia group, and a severe pneumonia concomitant with bacteremia group. The 28-day mortality was 18% (49/271) in the other infections group, 31% (33/106) in the lung infections group, 23% (29/126) in the blood infections group and 36% (8/36) in the lung and blood co-infections group, respectively. Pearson correlation analysis showed that procalcitonin (PCT) correlated strongly with all detected hemostatic markers (p < 0.001). The 28-day mortality rate in Lung infections group was significantly higher (p = 0.019), while Blood infections group had a higher incidence of disseminated intravascular coagulation (p = 0.011). By multivariable model analyses, longer duration of ventilation (p = 0.039) and severe pneumonia (p = 0.040) are risk factors associated with mortality. Different infections, including Lung and Blood infections, indicated different conditions in vivo. Longer duration of ventilation is associated with mortality, while Lung infections indicated higher 28-day mortality rate.

Validation of an ICD-Based Algorithm to Identify Sepsis: A Retrospective Study.

Background: Sepsis surveillance was important for resources allocation, prevention, and development of health policy. Objective: The aim of the study was to validate a modified International Classification of Diseases (ICD)-10 based algorithm for identifying hospitalized patients with sepsis. Methods: We retrospectively analyzed a prospective, single-center cohort of adult patients who were consecutively admitted to one medical ICU ward and ten non-ICU wards with suspected or confirmed infections during a 6-month period. A modified ICD-10 based algorithm was validated against a reference standard of Sequential Organ Failure Assessment (SOFA) score based on Sepsis-3. Sensitivity (SE), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and areas under the receiver operating characteristic curves (AUROCs) were calculated for modified ICD-10 criteria, eSOFA criteria, Martin's criteria, and Angus's criteria. Results: Of the 547 patients in the cohort, 332 (61%) patients met Sepsis-3 criteria and 274 (50%) met modified ICD-10 criteria. In the ICU setting, modified ICD-10 criteria had SE (84.47%), SP (88.57%), PPV (95.60), and NPV (65.96). In non-ICU settings, modified ICD-10 had SE (64.19%), SP (80.00%), PPV (80.33), and NPV (63.72). In the whole cohort, the AUROCs of modified ICD-10 criteria, eSOFA, Angus's criteria, and Martin's criteria were 0.76, 0.75, 0.62, and 0.62, respectively. Conclusion: This study demonstrated that modified ICD-10 criteria had higher validity compared with Angus's criteria and Martin's criteria. Validity of the modified ICD-10 criteria was similar to eSOFA criteria. Modified ICD-10 algorithm can be used to provide an accurate estimate of population-based sepsis burden of China.

Temporal trends of sepsis-related mortality in China, 2006-2020: a population-based study.

BACKGROUND: The scarcity of sepsis epidemiologic data from most low- and middle-income countries (LMICs) hampered estimation of regional and global burden of the disease, and provided limited guidance for policy makers. We aimed to characterize and analyze the temporal trends of sepsis-related mortality in China, by population groups, underlying causes of death, geographic regions, and sociodemographic index (SDI) levels. METHODS: Sepsis-related deaths were identified from the National Mortality Surveillance System (NMSS) of China from 2006 to 2020. Trends of sepsis-related mortality and years of life lost (YLLs), stratified by age, sex, underlying diseases, and regions were analyzed using the Jointpoint regression analysis. We investigated the association of SDI with trends of sepsis-related mortality. RESULTS: In 2020, sepsis was estimated to be responsible for 986,929 deaths and 17.1 million YLLs in China. Age-standardized sepsis-related mortality significantly declined from 130.2 (95%CI, 129.4-131) per 100,000 population in 2006 to 76.6 (76.3-76.9) in 2020. Age-standardized YLLs decreased from 2172.7 (2169.4-2176) per 100,000 population in 2006 to 1271 (1269.8-1272.2) in 2020. Substantial variations of sepsis-related mortality and YLLs were observed between population groups and regions, with higher burden in males, the elderly, and western China. An inverse relation was noted between SDI and sepsis-related mortality or YLLs. CONCLUSIONS: Despite declining trends of age-standardized mortality and YLLs of sepsis in China, significant disparities between population groups and regions highlight a need for targeted policies and measures to close the gaps and improve the outcome of sepsis.

A Comparison of Diagnostic Criteria for Invasive Pulmonary Aspergillosis in Critically Ill Patients.

INTRODUCTION: Invasive pulmonary aspergillosis (IPA) is a common infection in intensive care units (ICUs). There are no consensus criteria for defining IPA in the ICU. We aimed to compare the diagnosis and prognosis performances of three criteria (the 2020 EORTC/MSG criteria, the 2021 EORTC/MSG ICU criteria, the modified AspICU criteria (M-AspICU)) for IPA in the ICU. METHODS: In this retrospective study from our single center, we applied the three different criteria for IPA in patients with suspected pneumonia and undergoing at least one mycological test between November 10, 2016 and November 10, 2021. We compared the diagnosis agreement and prognosis performances of these three criteria in the ICU. RESULTS: Overall, 2403 patients were included. The rates of IPA according to the 2020 EORTC/MSG, 2021 EORTC/MSG ICU, and M-AspICU were 3.37%, 6.53%, and 23.10%, respectively. Diagnostic agreement among these criteria was poor (Cohen's kappa 0.208-0.666). IPA diagnosed by either the 2020 EORTC/MSG (odds ratio = 2.709, P < 0.001) or the 2021 EORTC/MSG ICU (odds ratio = 2.086, P = 0.001) criteria was independently associated with 28-day mortality. IPA diagnosed by M-AspICU is an independent risk factor of 28-day mortality (odds ratio = 1.431, P = 0.031) when excluding patients who fulfilled neither host criteria nor radiological factors of 2021 EORTC/MSG ICU. CONCLUSIONS: Although M-AspICU criteria have the highest "sensitivity", IPA diagnosed by M-AspICU was not an independent risk factor of 28-day mortality. Caution is required when using the M-AspICU criteria in ICU, especially in patients with non-specific infiltration and non-classical host factors.

Tissue oxygen saturation is predictive of lactate clearance in patients with circulatory shock.

BACKGROUND: Tissue oxygen saturation (StO2) decrease could appear earlier than lactate alteration. However, the correlation between StO2 and lactate clearance was unknown. METHODS: This was a prospective observational study. All consecutive patients with circulatory shock and lactate over 3 mmol/L were included. Based on the rule of nines, a BSA (body surface area) weighted StO2 was calculated from four sites of StO2 (masseter, deltoid, thenar and knee). The formulation was as follows: masseter StO2 × 9% + (deltoid StO2 + thenar StO2) × (18% + 27%)/ 2 + knee StO2 × 46%. Vital signs, blood lactate, arterial and central venous blood gas were measured simultaneously within 48 h of ICU admission. The predictive value of BSA-weighted StO2 on 6-hour lactate clearance > 10% since StO2 initially monitored was assessed. RESULTS: A total of 34 patients were included, of whom 19 (55.9%) had a lactate clearance higher than 10%. The mean SOFA score was lower in cLac ≥ 10% group compared with cLac < 10% group (11 ± 3 vs. 15 ± 4, p = 0.007). Other baseline characteristics were comparable between groups. Compared to non-clearance group, StO2 in deltoid, thenar and knee were significantly higher in clearance group. The area under the receiver operating curves (AUROC) of BSA-weighted StO2 for prediction of lactate clearance (0.92, 95% CI [Confidence Interval] 0.82-1.00) was significantly higher than StO2 of masseter (0.65, 95% CI 0.45-0.84; p < 0.01), deltoid (0.77, 95% CI 0.60-0.94; p = 0.04), thenar (0.72, 95% CI 0.55-0.90; p = 0.01), and similar to knee (0.87, 0.73-1.00; p = 0.40), mean StO2 (0.85, 0.73-0.98; p = 0.09). Additionally, BSA-weighted StO2 model had continuous net reclassification improvement (NRI) over the knee StO2 and mean StO2 model (continuous NRI 48.1% and 90.2%, respectively). The AUROC of BSA-weighted StO2 was 0.91(95% CI 0.75-1.0) adjusted by mean arterial pressure and norepinephrine dose. CONCLUSIONS: Our results suggested that BSA-weighted StO2 was a strong predictor of 6-hour lactate clearance in patients with shock.

Impact of intravenous immunoglobulins on serum (1-3)-ß-D-glucan.

BACKGROUND: The purpose of this study was to evaluate the changes in serum (1-3)-ß-D-glucan (BDG) in adults due to intravenous immunoglobulins (IVIG) infusion and the factors that affect these changes. METHODS: Patients who had BDG tests both before and after IVIG infusion during hospitalization were retrospectively included, and trends in BDG values were analyzed before and after IVIG infusion. Factors associated with false-positive BDG were then explored using univariate analysis. RESULTS: A total of 347 serum BDG tests from 131 patients were included in the analysis, and 71.8% (94/131) patients had false positive serum BDG after IVIG infusion. All BDG values on day 7 were negative. Univariate analysis showed that patients with false positive BDG tests had higher daily IVIG doses (P = 0.043) and higher levels of serum IgG increments (P = 0.001). The median peak blood BDG on day 1 after completion of IVIG infusion was 199.6 (154.5-277.7, inter-quartile ranges (IQR)) pg/mL, and both the peak BDG and incremental BDG values (ΔBDG, BDG at the first day after IVIG infusion minus BDG before infusion) were slightly and positively correlated with ΔIgG (BDG vs. ΔIgG, P = 0.0016; ΔBDG vs. ΔIgG, P = 0.0003). CONCLUSION: Most adults showed false positive BDG tests after IVIG infusion and negative BDG tests within 1 week. Daily IVIG dosage may contribute to the evaluation of ΔBDG.

National incidence and mortality of hospitalized sepsis in China.

BACKGROUND: Sepsis is a leading cause of preventable death around the world. Population-based estimation of sepsis incidence is lacking in China. In this study, we aimed to estimate the population-based incidence and geographic variation of hospitalized sepsis in China. METHODS: We retrospectively identified hospitalized sepsis from the nationwide National Data Center for Medical Service (NDCMS) and the National Mortality Surveillance System (NMSS) by ICD-10 codes for the period from 2017 to 2019. In-hospital sepsis case fatality and mortality rate were calculated to extrapolate the national incidence of hospitalized sepsis. The geographic distribution of hospitalized sepsis incidence was examined using Global Moran's Index. RESULTS: We identified 9,455,279 patients with 10,682,625 implicit-coded sepsis admissions in NDCMS and 806,728 sepsis-related deaths in NMSS. We estimated that the annual standardized incidence of hospitalized sepsis was 328.25 (95% CI 315.41-341.09), 359.26 (95% CI 345.4-373.12) and 421.85 (95% CI 406.65-437.05) cases per 100,000 in 2017, 2018 and 2019, respectively. We observed 8.7% of the incidences occurred among neonates less than 1 year old, 11.7% among children aged 1-9 years, and 57.5% among elderly older than 65 years. Significant spatial autocorrelation for incidence of hospitalized sepsis was observed across China (Moran's Index 0.42, p = 0.001; 0.45, p = 0.001; 0.26, p = 0.011 for 2017, 2018, 2019, respectively). Higher number of hospital bed supply and higher disposable income per capita were significantly associated with a higher incidence of hospitalized sepsis. CONCLUSION: Our study showed a greater burden of sepsis hospitalizations than previous estimated. The geographical disparities suggested more efforts were needed in prevention of sepsis.

Mortality and prognostic factors in connective tissue disease-associated pulmonary arterial hypertension patients complicated with right heart failure.

OBJECTIVE: To identify predictive factors associated with mortality in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) patients who were complicated with right heart failure (RHF). METHODS: In this single-center retrospective study, baseline demographics, clinical features, laboratory results, and hemodynamic assessments were collected. Kaplan-Meier analysis was applied to analyze all-cause mortality. Univariate and forward stepwise multivariate Cox proportional regression analyses were performed to identify independent predictors of mortality. RESULTS: A total of 51 right heart catheterization-confirmed CTD-PAH patients complicated with RHF were consecutively enrolled in this study from 2012 to 2022. Forty-eight (94%) enrolled patients were female and the mean age was 36.0 ± 11.8 years. Thirty-two (61.5%) were systemic lupus erythematosus-PAH and 33%/67% showed World Health Organization functional class III/IV, respectively. Twenty-five (49%) of those patients died and Kaplan-Meier analysis showed the overall 1-, 3-, and 5-week survival rates from the time of hospitalization as 86.28%, 60.78%, and 56.86%, respectively. RHF in CTD-PAH patients mainly resulted from progression of PAH (n = 19) and infection (n = 5), which also contributed to the leading causes of death. Statistical analysis between survivors and non-survivors showed that death from RHF was associated with higher levels of urea (9.66 vs 6.34 mmol/L, P = 0.002), lactate (cLac: 2.65 vs 1.9 mmol/L, P = 0.006), total bilirubin (23.1 vs 16.9 µmol/L, P = 0.018) and direct bilirubin (10.5 vs 6.5 µmol/L, P = 0.004), but with lower levels of hematocrit (33.7 vs 39, P = 0.004), cNa+ (131 vs 136 mmol/L, P = 0.003). Univariate and forward stepwise multivariate Cox proportional regression analyses indicated that the level of cLac (hazards ratio:1.297; 95% CI: 1.076-1.564; P = 0.006) was an independent risk factor for mortality. CONCLUSION: The short-term prognosis of CTD-PAH complicated with RHF was very poor, and hyperlactic acidemia (cLac > 2.85 mmoL/L) was an independent predicting factor for mortality of CTD-PAH patients complicated with RHF.

Metagenomic next-generation sequencing for detecting Aspergillosis pneumonia in immunocompromised patients: a retrospective study.

Purpose: The identification of Aspergillus by metagenomic next-generation sequencing (mNGS) remains a challenging task due to the difficulty of nucleic acid extraction. The objective of this study was to determine whether mNGS could provide an accurate and efficient method for detecting invasive pulmonary aspergillosis (IPA) in immunocompromised patients (ICP). Methods: A total of 133 ICP admitted to the ICU between January 2020 and September 2022 were enrolled in the study, of which 46 were diagnosed with IPA and 87 were non-IPA cases. The bronchoalveolar lavage fluid (BALF) was analyzed for the presence of Aspergillosis and other co-pathogens using mNGS, and its diagnostic performance was compared to conventional microbial tests (CMTs) that included smear, cultures, serum and BALF galactomannan (GM) test. Clinical composite diagnosis was used as the reference standard. Results: mNGS had a sensitivity, specificity, and accuracy of 82.6%, 97.7%, and 92.5%, respectively, in diagnosing IPA. These findings were comparable to those of the combination of multiple CMTs. Interestingly, the sensitivity of mNGS was superior to that of any single CMT method, as demonstrated by comparisons with smears (8.7%, P < 0.001), culture (39.1%, P < 0.001), serum GM (23.9%, P < 0.001) and BALF GM (69.6%, P = 0.031). mNGS was capable of accurately distinguish strains of Aspergillus genus, with a consistency of 77.8% with culture. Furthermore, mNGS also identified A. fumigatus, A. flavus, A. terrestris, A. oryzae and Mucor spp. in culture-negative cases. The sequencing reads of Aspergillus by mNGS exhibited extensive variation, ranging from 11 to1702. A positive correlation was observed between the optical density index of BALF GM and unique reads by mNGS (r = 0.607, P = 0.001) in BALF-GM positive patients. Notably, mNGS was able to diagnose 35 out of 37 cases with mixed infection, with P. jirovecii and cytomegalovirus being the most common co-pathogens. Conclusions: mNGS presents a feasible and remarkably sensitive approach for detecting Aspergillus in ICP, thereby serving as a valuable adjunctive tool to CMT. Furthermore, mNGS's ability to accurately identify fungal species and co-pathogens can assist in guiding appropriate antimicrobial therapy.

A case of disseminated Legionnaires' disease: The value of metagenome next-generation sequencing in the diagnosis of Legionnaires.

Background: Legionella rarely causes hospital-acquired pneumonia (HAP), although it is one of the most common pathogens of community-acquired pneumonia. Hospital-acquired Legionnaires' disease, mainly occurring in immunocompromised patients, is often delayed in diagnosis with high mortality. The use of the metagenome Next-Generation Sequencing (mNGS) method, which is fast and unbiased, allows for the early detection and identification of microorganisms using a culture-independent strategy. Case report: A 52-year-old male, with a past medical history of Goods syndrome, was admitted due to nephrotic syndrome. The patient developed severe pneumonia, rhabdomyolysis, and soft tissue infection after receiving immunosuppressive therapy. He did not respond well to empiric antibiotics and was eventually transferred to the medical intensive care unit because of an acute respiratory failure and septic shock. The patient then underwent a comprehensive conventional microbiological screening in bronchoalveolar lavage fluid (BALF) and blood, and the results were all negative. As a last resort, mNGS of blood was performed. Extracellular cell-free and intracellular DNA fragments of Legionella were detected in plasma and blood cell layer by mNGS, respectively. Subsequent positive results of polymerase chain reaction for Legionella in BALF and soft tissue specimens confirmed the diagnosis of disseminated Legionnaires' disease involving the lungs, soft tissue, and blood stream. The patient's condition improved promptly after a combination therapy of azithromycin and moxifloxacin. He was soon extubated and discharged from ICU with good recovery. Conclusion: Early recognition and diagnosis of disseminated Legionnaires' disease is challenging. The emergence and innovation of mNGS of blood has the potential to address this difficult clinical issue.

Metagenomic next-generation sequencing: A promising tool for diagnosis and treatment of suspected pneumonia in rheumatic patients with acute respiratory failure: Retrospective cohort study.

Background: The effectiveness of metagenomic next-generation sequencing (mNGS) in respiratory pathogen detection and clinical decision-making in critically rheumatic patients remains largely unexplored. Methods: A single-center retrospective study of 58 rheumatic patients who were admitted to ICU due to suspected pneumonia with acute respiratory failure if they underwent both bronchoalveolar lavage fluid specimen mNGS and combined microbiological tests (CMTs) was conducted to compare their diagnostic performance, using clinical composite diagnosis as the gold standard. Treatment modifications based on mNGS results were also reviewed. Results: Forty-three patients were diagnosed with microbiologically confirmed pneumonia and 15 were considered as a non-infectious disease. mNGS outperformed CMTs in the accurate diagnosis of infectious and non-infectious lung infiltration (98.1% [57/58] vs. 87.9% [51/58], P = 0.031). A total of 94 causative pathogens were defined by the gold standard and 27 patients had polymicrobial pneumonia. The sensitivity of pathogen detection and complete concordance with the gold standard by mNGS exceeded those by CMTs (92.6% [87/94] vs. 76.6% [72/94], P < 0.001 and 72.1% [31/43] vs. 51.2% [22/43], P = 0.004, respectively). Moreover, 22 pathogens were detected only by mNGS and confirmed by orthogonal test. Accordingly, the etiological diagnosis changed in 19 cases, and the empirical treatment improved in 14 cases, including 8 cases of rescue treatment and 11 of antibiotics de-escalation. At the pathogen-type level, both methods were comparable for bacteria, but mNGS was advantageous to identify viruses (accuracy: 100% vs. 81%, P = 0.004). For Pneumocystis jirovecii detection, mNGS improved the sensitivity compared with Gomori's methenamine silver stain (91.7% vs. 4.2%, P < 0.001) and was higher than polymerase chain reaction (79.2%), but the difference was not significant (P = 0.289). In terms of Aspergillus, the better sensitivity with a combination of culture and galactomannan test than that with mNGS was found (100% vs. 66.7%, P = 0.033). Conclusions: mNGS has an excellent accuracy in etiological diagnosis and pathogen detection of suspected pneumonia in critically rheumatic patients, which has potential significance for clinical decision-making. Its superiority to different types of pathogens depends on the comprehensiveness of CMTs.

Cross-cultural validation of the Chinese version of the EmPHasis-10 questionnaire in connective tissue disease patients with pulmonary arterial hypertension and its relationship with risk stratification.

BACKGROUNDS: The EmPHasis-10 questionnaire is a disease-specific quality of life (QoL) measurement in patients with pulmonary hypertension. We report the results of cross-cultural validation of the Chinese version of the EmPHasis-10 and its relationship with risk stratification in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH). METHODS: The Emphasis-10 was administered to 75 CTD-PAH patients along with the 36-item Medical Outcomes Study Short Form Survey (SF-36) and EuroQol five dimensions questionnaire (EQ-5D). The diagnosis of PAH was confirmed by right heart catheterization. Demographic and clinical data were obtained. Multivariable logistic regression was conducted based on the low risk profile assessed by a 4-strata risk assessment model (COMPERA 2.0) at follow-up. RESULTS: Date from 75 patients with CTD-PAH were analysed. The EmPHasis-10 demonstrated satisfactory reliability (Cronbach α = 0.95) and convergent validity showed by the significant relationship with WHO Functional Class (P = 0.003), SF-36 (P < 0.001) and EQ-5D (P = 0.002). EmPHasis-10 was significantly associated with achieving the low risk profile at 12 months of follow-up (Odds ratio: 0.928, P = 0.029) after adjusting for WHO Functional Class. CONCLUSION: EmPHasis-10 has acceptable reliability and validity in CTD-PAH patients and may serve as an additional parameter in risk stratification.

Diversity of hemodynamic types in connective tissue disease associated pulmonary hypertension: more than a subgroup of pulmonary arterial hypertension.

OBJECTIVE: Connective tissue disease associated pulmonary hypertension (CTD-PH) is classified as a subgroup of WHO group 1 PH, also called pulmonary arterial hypertension (PAH). However, not all CTD-PH fit hemodynamic definition of PAH. This study investigates the diversity of hemodynamic types of CTD-PH, their differences in clinical characteristics and outcomes. METHOD: We performed a retrospective cohort study. CTD-PH patients were enrolled and divided into WHO group1 PH, WHO group 2 PH and hyperdynamic PH (mPAP > 20 mmHg, PVR < 3WU, PAWP < 15 mmHg) according to hemodynamics obtained by right heart catheterization. Patients with severe lung diseases, heart failure with reduced ejection fraction, pulmonary embolism, and hepatic cirrhosis were excluded. Baseline characteristics, autoantibodies, cardiac function, echocardiogram parameters, hemodynamics and survival rates were compared. RESULT: A total of 202 CTD-PH patients were included, 138 in WHO group 1 PH, 33 in WHO group 2 PH and 31 in hyperdynamic PH. We found hyperdynamic PH is less severe, presenting lower NT-proBNP level, better WHO function class, lower mPAP and PVR, higher cardiac output, and less cardiac remodeling. Incidence of anti-RNP was significantly lower in patients with elevated PAWP. Short-term survival was worse in WHO group 2 PH, yet 5-year survival rates didn't differ between groups. CONCLUSION: Considering diversity in hemodynamic types, CTD-PH is more than a subgroup of PAH. Different types of CTD-PH present different clinical phenotypes and outcome. Phenotyping PH in CTD-PH patients is important.