Collective outbreak of severe acute histoplasmosis in immunocompetent Chinese in South America: the clinical characteristics and continuous monitoring of serum cytokines/chemokines.

BACKGROUND: Acute histoplasmosis is a rare fungal disease in China. This study is aimed to summarize the clinical characteristics of the first large-scale outbreak of imported acute histoplasmosis in Chinese, so as to provide suggestions for clinical diagnosis and treatment. METHODS: We collected the symptoms, signs, laboratory examination and imaging data of 10 patients in so far the biggest outbreak of imported acute histoplasmosis in immunocompetent Chinese. Their clinical characteristics and time-varying cytokine/chemokine levels were analyzed, and rank correlation analysis between these markers was utilized to show their condition. RESULTS: The 10 patients of imported acute histoplasmosis were working without any respiratory protection in an abandoned mine tunnel in Guyana. The most common symptoms were fever and cough. Their chest CT imaging showed multiple nodular shadows in lungs. Laboratory examination showed that at admission the CRP, PCT, LDH, CysC, G-test, ß2-MG were all increased in at least 9 patients, and the CD4/CD8 was decreased to < 1 in all patients. Most cytokines/chemokines (other than IL-4, IL-12, INF-α, TNF-α) varied widely with patients and time, but their overall trend is higher at admission and decreasing gradually during hospitalization, especially for the IL-6, IL-8, IL-10 and IFN-γ. The LDH, CysC, G-test, ß2-MG, N/L, IL-6, IL-8, IL-10, IFN-γ, IL-27 are in positive associations to both CRP and PCT. CONCLUSIONS: The diagnosis of acute histoplasmosis needs a comprehensive analysis of epidemiological history, clinical symptoms and signs, and results of imaging, laboratory, microbiological and pathological examinations. Although none of the CRP, PCT, G-test, N/L, LDH, CysC, ß2-MG, IL-6, IL-8, IL-10, IFN-γ shows specificity in the diagnosis of acute histoplasmosis, there is possibility that the above factors might help in the inflammation and prognosis estimation. However, more studies and further investigation are still required for the verification.

An updated HACOR score for predicting the failure of noninvasive ventilation: a multicenter prospective observational study.

BACKGROUND: Heart rate, acidosis, consciousness, oxygenation, and respiratory rate (HACOR) have been used to predict noninvasive ventilation (NIV) failure. However, the HACOR score fails to consider baseline data. Here, we aimed to update the HACOR score to take into account baseline data and test its predictive power for NIV failure primarily after 1-2 h of NIV. METHODS: A multicenter prospective observational study was performed in 18 hospitals in China and Turkey. Patients who received NIV because of hypoxemic respiratory failure were enrolled. In Chongqing, China, 1451 patients were enrolled in the training cohort. Outside of Chongqing, another 728 patients were enrolled in the external validation cohort. RESULTS: Before NIV, the presence of pneumonia, cardiogenic pulmonary edema, pulmonary ARDS, immunosuppression, or septic shock and the SOFA score were strongly associated with NIV failure. These six variables as baseline data were added to the original HACOR score. The AUCs for predicting NIV failure were 0.85 (95% CI 0.84-0.87) and 0.78 (0.75-0.81) tested with the updated HACOR score assessed after 1-2 h of NIV in the training and validation cohorts, respectively. A higher AUC was observed when it was tested with the updated HACOR score compared to the original HACOR score in the training cohort (0.85 vs. 0.80, 0.86 vs. 0.81, and 0.85 vs. 0.82 after 1-2, 12, and 24 h of NIV, respectively; all p values < 0.01). Similar results were found in the validation cohort (0.78 vs. 0.71, 0.79 vs. 0.74, and 0.81 vs. 0.76, respectively; all p values < 0.01). When 7, 10.5, and 14 points of the updated HACOR score were used as cutoff values, the probability of NIV failure was 25%, 50%, and 75%, respectively. Among patients with updated HACOR scores of ≤ 7, 7.5-10.5, 11-14, and > 14 after 1-2 h of NIV, the rate of NIV failure was 12.4%, 38.2%, 67.1%, and 83.7%, respectively. CONCLUSIONS: The updated HACOR score has high predictive power for NIV failure in patients with hypoxemic respiratory failure. It can be used to help in decision-making when NIV is used.

Case Report: The Experience of Managing a Moderate ARDS Caused by SARS-CoV-2 Omicron BA.2 Variant in Chongqing, China: Can We Do Better?

Background: The severe coronavirus disease 2019 (COVID-19) pandemic is still raging worldwide, and the Omicron BA.2 variant has become the new circulating epidemic strain. However, our understanding of the Omicron BA.2 variant is still scarce. This report aims to present a case of a moderate acute respiratory distress syndrome (ARDS) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron BA.2 variant and to discuss some management strategies that may benefit this type of case. Case Presentation: A 78-year-old man, who had four negative nucleic acid tests and a fifth positive, was admitted to our hospital. This patient was generally good upon admission and tested negative for anti-SARS-CoV-2 antibodies even after receiving two doses of the COVID-19 vaccine. On the 7th day of hospitalization, he developed a moderate ARDS. Improved inflammatory index and decreased oxygen index were primarily found in this patient, and a series of treatments, including anti-inflammation and oxygen therapies, were used. Then this patient's condition improved soon and reached two negative results of nucleic acid tests on the 18th day of hospitalization. Conclusion: At-home COVID-19 rapid antigen test could be complementary to existing detection methods, and the third booster dose of COVID-19 vaccine may be advocated in the face of the omicron BA.2 variant. Anti-inflammatory and oxygen therapies are still essential treatments for ARDS patients infected with SARS-CoV-2 Omicron BA.2 variant.

Association between ARDS Etiology and Risk of Noninvasive Ventilation Failure.

Rationale: The etiology of acute respiratory distress syndrome (ARDS) may play an important role in the failure of noninvasive ventilation (NIV). Objectives: To explore the association between ARDS etiology and risk of NIV failure. Methods: A multicenter prospective observational study was performed in 17 intensive care units in China from September 2017 to December 2019. Patients with ARDS who used NIV as a first-line therapy were enrolled. The etiology of ARDS was recorded at study entry. Results: A total of 306 patients were enrolled. Of the patients, 146 were classified as having pulmonary ARDS (ARDSp) and 160 were classified as having extrapulmonary ARDS (ARDSexp). From initiation to 24 hours of NIV, the respiratory rate, heart rate, arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2), and arterial carbon dioxide pressure improved slower in patients with ARDSp than those with ARDSexp. Patients with ARDSp experienced more NIV failure (55% vs. 28%; P < 0.01) and higher 28-day mortality (47% vs. 14%; P < 0.01). The adjusted odds ratios of NIV failure and 28-day mortality were 5.47 (95% confidence interval [CI], 3.04-9.86) and 10.13 (95% CI, 5.01-20.46), respectively. In addition, we combined the presence of ARDSp, presence of septic shock, age, nonpulmonary sequential organ failure assessment score, respiratory rate at 1-2 hours of NIV, and PaO2/FiO2 at 1-2 h of NIV to develop a risk score of NIV failure. With the increase of the risk score, the rate of NIV failure increased. The area under the curve of the receiver operating characteristic was 0.84 (95% CI, 0.79-0.89) and 0.81 (0.69-0.92) in the training and validation cohorts, respectively. Using 5.5 as cutoff value to predict NIV failure, the sensitivity and specificity was good. Conclusions: Among patients with ARDS who used NIV as a first-line therapy, ARDSp was associated with slower improvement, more NIV failure, and higher 28-day mortality than ARDSexp. The risk score combined presence of ARDSp, presence of septic shock, age, nonpulmonary sequential organ failure assessment score, respiratory rate at 1-2 hours of NIV, and PaO2/FiO2 at 1-2 hours of NIV has high accuracy to predict NIV failure among ARDS population.

[Evaluation of clinical value of Xuebijing combined with human immunoglobulin in severe and critically ill patients with coronavirus disease 2019].

OBJECTIVE: To evaluate the clinical efficacy of Xuebijing combined with human immunoglobulin for the treatment of severe and critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: A retrospective study was conducted. The clinical data of 65 patients with severe and critical COVID-19 admitted to Chongqing Public Health Medical Center and Chongqing Three Gorges Central Hospital from January 2020 to March 2020 during the period of supporting to combat COVID-19 by the medical team of the Second Affiliated Hospital of Chongqing Medical University and Chongqing Hospital of Traditional Chinese Medicine were analyzed. According to different treatment regimens, patients were divided into conventional treatment group (conventional antivirus, anti-infection and symptomatic support treatments), Xuebijing group (Xuebijing was applied to patients with elevated inflammatory cytokines) and combination group (Xuebijing combined with human immunoglobulin, human immunoglobulin was applied to patients with low immunity indicated by monitoring results of lymphocytes and their subsets). The improvement of blood routine examination, blood gas analysis, myocardial enzyme spectrum, liver and kidney function, lymphocytes and their subsets and cytokines as well as severity score in three groups before and after treatment were observed. Kaplan-Meier method was used to draw the 28-day survival curve of each group, and the cumulative survival rate among the groups was compared. RESULTS: Among the 65 severe and critically ill COVID-19 patients, only 20 patients received conventional treatment, 22 patients were treated with Xuebijing based on conventional treatment, and 23 patients were treated with Xuebijing combined with human immunoglobulin based on conventional treatment. Before treatment, CD4+ T cell count in combination group was higher than other two groups, and interleukin-6 (IL-6) was lower than other two groups, while other indicators showed no statistically significant differences among the three groups, suggesting that the baseline of the three groups was relatively balanced before treatment. The patients in the conventional treatment group were relieved after treatment, and it was characterized by that the acute physiology and chronic health evaluation II (APACHE II) score and lactate dehydrogenase (LDH) were significantly lower than those before treatment [APACHE II score: 5.20±2.74 vs. 6.20±1.93, LDH (µmol×s-1×L-1): 4.1±1.0 vs. 4.7±0.9, both P < 0.01], but there was still liver damage, which was manifested as higher aspartate aminotransferase (AST) than that before treatment [U/L: 30.5 (23.8, 41.5) vs. 21.0 (17.0, 34.0), P < 0.05]. In Xuebijing group, the respiratory function and immunity of patients were improved after treatment, and the improvement degree of the ratio of CD4+ T cell was more significant than that in the conventional treatment group (4.86±6.31 vs. -0.95±12.38, P < 0.05). However, the patients still lived with an "inflammatory storm" and liver damage after treatment. It was shown that IL-4 was significantly higher than that before treatment (ng/L: 2.57±1.15 vs. 1.92±1.04, P < 0.05), while albumin (ALB) decreased significantly compared with before treatment [g/L: 33.0 (30.5, 35.6) vs. 36.2 (32.1, 41.4), P < 0.01]. While the treatment of Xuebijing combined with human immunoglobulin could improve patients' respiratory function and enhance their immunity more effectively, it was shown that arterial partial pressure of oxygen (PaO2), oxygenation index (PaO2/FiO2), T lymphocyte count, ratio of CD4+ T cell, CD4+ T cell count, CD8+ T cell count and CD4+/CD8+ ratio were significantly higher than those before treatment, while ALB, IL-6, APACHE II score and sequential organ failure assessment (SOFA) score were significantly lower than those before treatment. T lymphocyte count, the ratio of CD4+ T cell and IL-6 in combination group were improved more significantly than those in conventional treatment group and Xuebijing group [T lymphocyte count (×109/L): 310.68±359.28 vs. 46.54±240.01, 81.59±256.76; ratio of CD4+ T cell: 14.53±14.49 vs. -0.95±12.38, 4.86±6.31; IL-6 (ng/L): -25.53±39.05 vs. -1.75±5.45, 12.78±44.81], PaO2/FiO2 was improved more significantly as compared with the Xuebijing group [mmHg (1 mmHg = 0.133 kPa): 146.31±109.73 vs. 59.41±87.70], and the differences were statistically different (all P < 0.05). CONCLUSIONS: The combination of Xuebijing and human immunoglobulin for the treatment of patients with COVID-19 can improve patients' respiratory function, reduce "inflammatory storm", enhance immunity, and alleviate severity of patients' condition.

Diagnostic value of peripheral hematologic markers for coronavirus disease 2019 (COVID-19): A multicenter, cross-sectional study.

BACKGROUND: To determine the diagnostic value of hematologic markers for coronavirus disease 2019 (COVID-19) and explore their relationship with disease severity. METHODS: Subjects included 190 COVID-19 patients, 190 healthy subjects, and 105 influenza pneumonia (IP) patients. COVID-19 patients were divided into the ARDS and non-ARDS groups. Routine blood examination, biochemistry indicator, days in hospital, body temperature, pneumonia severity index (PSI), CURB-65, and MuLBSTA were recorded. Correlations between variables were assessed using Spearman's correlation analysis. Receiver operating characteristic (ROC) curves were used to study the accuracy of the various diagnostic tests. RESULTS: Compared with healthy subjects, COVID-19 patients had lower white blood cell (WBC), lymphocyte, platelet, and hemoglobin levels; higher percentages of neutrophils and monocytes; lower percentages of lymphocytes and higher neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) values (P < .05). COVID-19 patients had higher WBC and neutrophil levels and lower percentages of lymphocytes compared to IP (P < .05). ROC curve analysis revealed that MLR had a high diagnostic value in differentiating COVID-19 patients from healthy subjects, but not from IP patients. NLR showed significant positive correlations with PSI, CURB-65, and MuLBSTA. Lymphocyte count was lower in the ARDS group and yielded a higher diagnostic value than the other variables. CONCLUSIONS: Monocyte-to-lymphocyte ratio showed an acceptable efficiency to separate COVID-19 patients from healthy subjects, but failed to rule out IP patients. NLR may be a reliable marker to evaluate the disease severity of COVID-19. Lymphocyte count may be useful to establish the early diagnosis of ARDS in the COVID-19 patients.

A retrospective study on the epidemiological characteristics and establishment of an early warning system of severe COVID-19 patients.

This paper estimates the magnitude of an informational friction limiting credit reallocation to firms during the 2007-2009 financial crisis. Because lenders rely on private information when deciding which relationship to end, borrowers looking for a new lender are adversely selected. I show how to identify private information separately from information common to all lenders but unobservable to the econometrician by using bank shocks within a discrete choice model of relationships. Quantitatively, these informational frictions seem too small to explain the credit crunch in the U.S. syndicated corporate loan market.