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.

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.

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.

Association of annual hospital septic shock case volume and hospital mortality.

BACKGROUND: The burden of sepsis remains high in China. The relationship between case volume and hospital mortality among patients with septic shock, the most severe complication of sepsis, is unknown in China. METHODS: In this retrospective cohort study, we analyzed surveillance data from a national quality improvement program in intensive care units (ICUs) in China in 2020. Association between septic shock case volume and hospital mortality was analyzed using multivariate linear regression and restricted cubic splines. RESULTS: We enrolled a total of 134,046 septic shock cases in ICUs from 1902 hospitals in China during 2020. In this septic shock cohort, the median septic shock volume per hospital was 33 cases (interquartile range 14-76 cases), 41.4% were female, and more than half of the patients were over 61 years old, with average hospital mortality of 21.2%. An increase in case volume was associated with improved survival among septic shock cases. In the linear regression model, the highest quartile of septic shock volume was associated with lower hospital mortality compared with the lowest quartile (ß - 0.86; 95% CI - 0.98, - 0.74; p < 0.001). Similar differences were found in hospitals of respective geographic locations and hospital levels. With case volume modeled as a continuous variable in a restricted cubic spline, a lower volume threshold of 40 cases before which a substantial reduction of the hospital mortality rate was observed. CONCLUSIONS: The findings suggest that hospitals with higher septic shock case volume have lower hospital mortality in China. Further research is needed to explain the mechanism of this volume-outcome relationship.

Feasibility and efficacy of modified fixed citrate concentration protocol using only commercial preparations in critically ill patients: a prospective cohort study with a historical control group.

BACKGROUND: The cumbersome program and the shortage of commercial solution hindered the regular application of regional citrate anticoagulation (RCA). It is urgent to simplify the protocol using only commercial preparations. The aim of this study was to explore the feasibility and efficacy of the modified protocol for continuous veno-venous hemofiltration (CVVH) in unselected critically ill patients. METHODS: A prospective cohort study was conducted in 66 patients who received a new protocol combining fixed citrate concentration with modified algorithm for supplements (i.e., fixed protocol), and compared the efficacy, safety and convenience for this group to a historical control group with a traditional protocol (n = 64), where citrate was titrated according to the circuit ionized calcium concentration (i.e., titrated protocol). The convenience was defined as the demand for monitoring test and dose adjustment of any supplement. RESULTS: The filter lifespan was 63.2 ± 16.1 h in the fixed group and 51.9 ± 17.7 h in the titrated group, respectively. Kaplan-Meier survival analysis demonstrated longer circuit lifetime for fixed group (log-rank, p = 0.026). The incidence of circuit clotting was lower in the fixed protocol (15.2% vs. 29.7% in the titrated protocol, p = 0.047). Moreover, compared with the titrated group, patients with fixed protocol had less demand for monitoring test and dose adjustment of any supplement (the number of times per person per day) (3.3 [IQR 2.3-4.5] vs. 5.7 [IQR 3.3-6.9], p = 0.001 and 1.9 [IQR 0.5-2.7] vs. 6.3 [IQR 4.2-7.9], p < 0.001; respectively). No new onset bleeding complications occurred in all patients. The overall incidence of suspected citrate accumulation was 4.6% and there was no difference between the two groups (p = 0.969), yet a lower rate of metabolic alkalosis was found in the fixed group (3.0% vs. 14.1%, p = 0.024). CONCLUSIONS: Our modified fixed citrate concentration protocol is feasible, safe and effective to enhance the circuit lifespan and the convenience of implementation while maintaining a similar safety when compared to the traditional protocol. Using only commercial preparations may be helpful for widespread application of RCA. TRIAL REGISTRATION: Clinicaltrials.gov. NCT02663960 . Registered 26 January 2016.

Does training improve diagnostic accuracy and inter-rater agreement in applying the Berlin radiographic definition of acute respiratory distress syndrome? A multicenter prospective study.

BACKGROUND: Poor inter-rater reliability in chest radiograph interpretation has been reported in the context of acute respiratory distress syndrome (ARDS), although not for the Berlin definition of ARDS. We sought to examine the effect of training material on the accuracy and consistency of intensivists' chest radiograph interpretations for ARDS diagnosis. METHODS: We conducted a rater agreement study in which 286 intensivists (residents 41.3%, junior attending physicians 35.3%, and senior attending physician 23.4%) independently reviewed the same 12 chest radiographs developed by the ARDS Definition Task Force ("the panel") before and after training. Radiographic diagnoses by the panel were classified into the consistent (n = 4), equivocal (n = 4), and inconsistent (n = 4) categories and were used as a reference. The 1.5-hour training course attended by all 286 intensivists included introduction of the diagnostic rationale, and a subsequent in-depth discussion to reach consensus for all 12 radiographs. RESULTS: Overall diagnostic accuracy, which was defined as the percentage of chest radiographs that were interpreted correctly, improved but remained poor after training (42.0 ± 14.8% before training vs. 55.3 ± 23.4% after training, p < 0.001). Diagnostic sensitivity and specificity improved after training for all diagnostic categories (p < 0.001), with the exception of specificity for the equivocal category (p = 0.883). Diagnostic accuracy was higher for the consistent category than for the inconsistent and equivocal categories (p < 0.001). Comparisons of pre-training and post-training results revealed that inter-rater agreement was poor and did not improve after training, as assessed by overall agreement (0.450 ± 0.406 vs. 0.461 ± 0.575, p = 0.792), Fleiss's kappa (0.133 ± 0.575 vs. 0.178 ± 0.710, p = 0.405), and intraclass correlation coefficient (ICC; 0.219 vs. 0.276, p = 0.470). CONCLUSIONS: The radiographic diagnostic accuracy and inter-rater agreement were poor when the Berlin radiographic definition was used, and were not significantly improved by the training set of chest radiographs developed by the ARDS Definition Task Force. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (registration number NCT01704066 ) on 6 October 2012.

Prognostic factors for severe Pneumocystis jiroveci pneumonia of non-HIV patients in intensive care unit: a bicentric retrospective study.

BACKGROUND: Pneumocystis jiroveci pneumonia (PJP) in non-HIV patients is still a challenge for intensivists. The aim of our study was to evaluate mortality predictors of PJP patients requiring Intensive care unit (ICU) admission. METHODS: Retrospectively review medical records of patients with diagnosis of PJP admitted to four ICUs of two academic medical centers from October 2012 to October 2015. RESULTS: Eighty-two patients were enrolled in the study. Overall hospital mortality was 75.6 %. Compared with survivors, the non-survivors had older age (55 ± 16 vs. 45 ± 17, p = 0.014), higher APACHE II score (20 ± 5 vs. 17 ± 5, p = 0.01), lower white blood cell count (7.68 ± 3.44 vs. 10.48 ± 4.62, p = 0.005), less fever (80.6%vs. 100 %, p = 0.033), more hypotension (58.1 % vs. 20 %, p = 0.003), more pneumomediastinum (29 % vs. 5 %, p = 0.027). Logistic regression analysis demonstrated that age [odds ratio (OR)1.051; 95 % CI 1.007-1.097; p = 0.022], white blood cell count [OR 0.802; 95 % CI 0.670-0.960; p = 0.016], and pneumomediastinum [OR 16.514; 95 % CI 1.330-205.027; p = 0.029] were independently associated with hospital mortality. CONCLUSIONS: Mortality rate for non-HIV PJP patients requiring ICU admission was still high. Poor prognostic factors included age, white blood cell count and pneumomediastinum.

The utility of initial procalcitonin and procalcitonin clearance for prediction of bacterial infection and outcome in critically ill patients with autoimmune diseases: a prospective observational study.

BACKGROUND: The diagnostic value of procalcitonin (PCT) for patients with autoimmune diseases (AID) remains controversial and few studies focused on ICU patients. We sought to determine its diagnostic and prognostic values in this clowd. METHODS: A prospective observational study was conducted in AID patients admitted to the ICU. Serum PCT levels were measured on ICU admission and subsequently at days 1, 3, 5 and 7, and peak PCT levels within 24 h (PCTpeak) were analyzed the utility for bacterial infection. The relationship of PCTpeak and SOFA score and severity of sepsis was performed correlation analysis. The change of PCT over time reflected as PCT clearance was compared to ICU 28-day mortality. RESULTS: One hundred twelve patients were divided into bacterial infection group (group I, n = 54) and nonbacterial condition group (group II, n = 58). The median PCTpeak (range, µg/L) was higher in the group I than that in the group II (1.95 [0.38-37.56] vs. 0.64 [0.05-7.83], p = 0.002). PCTpeak had the best single predictor of bacterial infection (area under the curve [AUC], 0.902, p < 0.001) with a sensitivity of 79.6 % and a specificity of 89.6 % at the threshold of 0.94 µg/L. PCTpeak was also positive correlation with severity of sepsis (r = 0.731, p = 0.002), but its correlation with SOFA score was only found in subjects with bacterial infection (r = 0.798, p < 0.001). Importantly, the 5-day PCT clearance (PCTc-d5), rather than absolute PCT values, could earlier discriminate survivors (n = 73) from nonsurvivors (n = 39) (68.8 ± 9.8 vs. 21.8 ± 17.5 %, p < 0.001, respectively). PCTc-d5 < 50 % was an independent predictor of mortality (odds ratio 5.1, 95 % confidence interval 3.5 to 7.5; p = 0.001). CONCLUSIONS: In critically ill patients with AID, elevated PCT levels are valuable for bacterial infection and are significantly positive correlation with the septic severity. Five-day PCT clearance may provide independent prognostic information. Larger, prospective trials are warranted to confirm the benefit.

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.

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.

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.

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.

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 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.

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.

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.

The prognostic value of left ventricular systolic function measured by tissue Doppler imaging in septic shock.

INTRODUCTION: Left ventricular (LV) dysfunction is common in septic shock. Its association with the clinical outcome is still controversial. Tissue Doppler imaging (TDI) is a useful tool to quantify LV function; however, little knowledge is available about the prognostic value of these TDI variables in septic shock. Therefore, we performed this prospective study to determine the role of TDI variables in septic shock. METHODS: Patients with septic shock in a medical intensive care unit were studied with transthoracic echocardiography with TDI within 24 hours after the onset of septic shock. Baseline clinical, laboratory, and echocardiographic variables were prospectively collected. Independent predictors of 90-day mortality were analyzed with the Cox regression model. RESULTS: During a 20-month period, 61 patients were enrolled in the study. The 90-day mortality rate was 39%; the mean APACHE IV score was 84 (68 to 97). Compared with survivors, nonsurvivors exhibited significantly higher peak systolic velocity measured at the mitral annulus (Sa) (11.0 (9.1 to 12.5) versus 7.8 (5.5 to 9.0) cm/sec; P < 0.0001), lower PaO2/FiO2 (123 (83 to 187) versus 186 (142 to 269) mm Hg; P = 0.002], higher heart rate (120 (90 to 140) versus 103 (90 to 114) beats/min; P = 0.004], and a higher dose of norepinephrine (0.6 (0.2 to 1.0) versus 0.3 (0.2 to 0.5) µg/kg/min; P = 0.007]. In the multivariate analysis, Sa > 9 cm/sec (hazard ratio (HR), 5.559; 95% confidence interval (CI), 2.160 to 14.305; P < 0.0001), dose of norepinephrine (HR, 1.964; 95% CI, 1.338 to 2.883; P = 0.001), and PaO2/FiO2 (HR, 0.992; 95% CI, 0.984 to 0.999; P = 0.031) remain independent predictors of 90-day mortality in septic-shock patients. CONCLUSIONS: Our study demonstrated that LV systolic function as determined by TDI, in particular, Sa, might be associated with mortality in patients with septic shock.

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.

Efficacy and Safety of Ceftazidime-Avibactam for the Treatment of Carbapenem-Resistant Enterobacterales Bloodstream Infection: a Systematic Review and Meta-Analysis.

Several clinicians use ceftazidime-avibactam (CAZ-AVI) to treat bloodstream infections (BSIs) due to carbapenem-resistant Enterobacterales (CRE), although no conclusive data support this practice. We aimed to assess the efficacy and safety of CAZ-AVI in the treatment of CRE bacteremia. PubMed, Embase, and Cochrane Library were systematically searched until 5 November 2021. Studies comparing the clinical outcome of CAZ-AVI with other regimens in CRE BSI were included if they reported data on mortality. Results were expressed as risk ratios (RRs) or mean differences with accompanying 95% confidence intervals (95% CIs). Eleven articles with 1,205 patients were included. CAZ-AVI groups showed a significantly lower 30-day mortality than control groups of other regimens (RR = 0.55, 95% CI of 0.45 to 0.68, P < 0.00001). The result is robust when a colistin-based regimen serves as the control group (RR = 0.48, 95% CI 0.33 of 0.69, P < 0.0001). In subgroup meta-analyses, the 30-day mortality was significantly lower in patients infected with CRE producing Klebsiella pneumoniae carbapenemase (RR = 0.59, 95% CI of 0.46 to 0.75, P < 0.0001). Additionally, patients in CAZ-AVI groups had a significantly higher clinical cure rate (RR = 1.75, 95% CI of 1.57 to 2.18, P < 0.00001) and lower nephrotoxicity rate (RR = 0.41, 95% CI of 0.20 to 0.84, P = 0.02). No significant differences of relapse rates were demonstrated in 2 groups (RR = 0.69, 95% CI of 0.29 to 1.66, P = 0.41). Although the current study is based on observational studies with a small sample of participants, the findings suggest that CAZ-AVI treatment is effective and safe compared with other antibiotics, including colistin, in CRE BSI. IMPORTANCE Ceftazidime-avibactam (CAZ-AVI) has been used as a frontline agent in the treatment of multidrug-resistant (MDR) Gram-negative bacterial infections. However, the efficacy and safety of CAZ-AVI on carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) remain unclear. Patients with CRE BSIs were often enrolled in small-sized clinical studies, together with other sites of infections, which reported pooled results. In this meta-analysis, the efficacy and safety were compared between CAZ-AVI and any other regimens used against CRE infections. The findings suggest that patients in the CAZ-AVI group had a significantly lower 30-day mortality than any other regimens and than colistin-based regimens. This paper provides a rationale for the use of CAZ-AVI in one of the most urgent antimicrobial-resistant infections of CRE bloodstream infections.