Risk factors for brain injury in patients with exertional heatstroke: A 5-year experience.

PURPOSE: Minimal data exist on brain injury in patients with exertional heatstroke (EHS) in developing country. In this study, we explored the risk factors for brain injury induced by EHS 90-day after onset. METHODS: A retrospective cohort study of patients with EHS was conducted in the intensive care unit of the General Hospital of Southern Theater Command of PLA in China from April 2014 to June 2019. Patients were divided into non-brain injury (fully recovered) and brain injury groups (comprising deceased patients or those with neurological sequelae). The brain injury group was further subdivided into a death group and a sequela group for detailed analysis. General information, neurological performance and information on important organ injuries in the acute stage were recorded and analysed. Multivariable logistic regression was used to identify risk factors for brain injury after EHS and mortality risk factors for brain injury, and Kaplan-Meier survival curve was used to evaluate the effect of the neurological dysfunction on survival. RESULTS: Out of the 147 EHS patients, 117 were enrolled, of which 96 (82.1%) recovered, 13 (11.1%) died, and 8 (6.8%) experienced neurological sequelae. Statistically significant differences were found between non-brain injury and brain injury groups in age, hypotension, duration of consciousness disorders, time to drop core body temperature below 38.5°C, lymphocyte counts, platelet counts, procalcitonin, alanine aminotransferase, aspartate aminotransferase, creatinine, cystatin C, coagulation parameters, international normalized ratio, acute physiology and chronic health evaluation II scores, sequential organ failure assessment (SOFA) scores, and Glasgow coma scale scores (all p < 0.05). Multivariate logistic regression showed that age (OR = 1.090, 95% CI: 1.02 - 1.17, p = 0.008), time to drop core temperature (OR = 8.223, 95% CI: 2.30 - 29.40, p = 0.001), and SOFA scores (OR = 1.676, 95% CI: 1.29 - 2.18, p < 0.001) are independent risk factors for brain injury induced by EHS. The Kaplan-Meier curves suggest significantly prolonged survival (p < 0.001) in patients with early Glasgow coma scale score > 8 and duration of consciousness disorders ≤ 24 h. CONCLUSIONS: Advanced age, delayed cooling, and higher SOFA scores significantly increase the risk of brain injury post-EHS. These findings underscore the importance of rapid cooling and early assessment of organ failure to improve outcomes in EHS patients.

Nature of the work correlated to overweight and obesity for nurses: A 10-year hospital-based cohort study.

BACKGROUND: Nurses are a high-risk group for overweight and obesity due to high stress, low-labor medical work, irregular diet, and lack of exercise. There is scarce information on relationship between job characteristics and overweight and obesity among nurses. This study aimed to answer the question. Does the nature of the work including job position, seniority relate to overweight and obesity among nurses? Their incidence was also investigated. METHODS: We conducted a retrospective cohort study of nurses who underwent annual checkups during 2007 to 2016 in a medical center. Overweight was defined as a body mass index between 24 and 27 kg/m 2 . Obesity was defined as a body mass index higher than 27 kg/m 2 . We calculated the prevalence and incidence of overweight and obesity and estimated relative risks using logistic regression. RESULTS: Overall, 4253 participants were enrolled for the incidence of overweight and obesity. We found that junior staff, administrative directors, working in intensive care units, and old age had a high possibility of overweight. Junior staff, administrative directors, old age, and male sex tend to be obesity. Overweight and obesity occurred rapidly in the first 2 years of their career. CONCLUSION: Our findings suggest that policies should be set up to achieve the goal of workplace health promotion. Health plans focusing on these factors may help nurses avoid obesity and overweight. The director of the hospital should keep track of the health checkup database to confirm the benefits of its long-term implementation.

INSM1 promotes breast carcinogenesis by regulating C-MYC.

Insulinoma-associated protein-1 (INSM1), which is highly expressed in various neuroendocrine tumors, functions as a zinc finger transcription factor capable of regulating the biological behavior of tumor cells. However, its specific role in breast cancer remains unclear. This study aims to investigate the role and mechanism of INSM1 in breast cancer. A total of 158 cohorts were recruited to examine the expression of INSM1 in breast cancer tissues and their corresponding adjacent normal tissues using immunohistochemistry. Follow-up data, along with clinical and pathological information, were collected to analyze the correlation between INSM1 expression and survival outcomes in breast cancer patients. Additionally, we investigated the impact of INSM1 on breast cancer cell proliferation, migration, and aggregation. To further explore the regulatory effect of INSM1 knockdown on breast cancer tumor growth, we utilized a xenograft mouse model. The results revealed that INSM1 was significantly overexpressed in breast cancer patients and correlated with prognosis. Knockdown of INSM1 notably impaired the malignant biological effects of breast cancer cells and inhibited the growth of xenograft tumors in nude mice. Importantly, our data also suggests an interaction between INSM1 and S-phase kinase-associated protein 2 (SKP2), which in turn regulates C-MYC, thereby affecting the p-ERK pathway. Our study provides the first evidence demonstrating the contribution of INSM1 to tumor formation and growth in breast cancer. Furthermore, we found that INSM1 positively regulates C-MYC and the p-ERK pathway by interacting with SKP2 during breast cancer development. Collectively, these findings highlight INSM1 as a promising target for breast cancer treatment.

Effectiveness and Safety of Zercepac and Reference Trastuzumab in the Neoadjuvant Setting for Early-Stage Breast Cancer: A Retrospective Cohort Study.

Aim: Since the high cost of reference trastuzumab limits its clinical application, this study aimed to compare the effectiveness and safety of the Zercepac and reference product trastuzumab in neoadjuvant therapy for HER2-positive breast cancer. Methods: This study retrospectively collected clinical data of patients with early-stageHER2-positive breast cancer, who received trastuzumab, pertuzumab, docetaxel, and platinum as neoadjuvant therapy from November 2020 to July 2021. Patients were divided into the Zercepac and reference trastuzumab groups. Reduction in tumor size, clinical response based on RECIST1.1 criteria, pathological complete response (pCR), and adverse events (AEs) were evaluated. Multivariate logistic regression analyses were used to adjust confounders. Results: A total of 105 patients were included in the study, among them, 65 were in the Zercepac group and 40 were in the reference trastuzumab group. The percentage of tumor shrinkage from baseline was comparable between the Zercepac and reference trastuzumab group (47.6 ± 18.6% vs. 43.0 ± 19.9%, p = 0.235). Clinical partial response rate was similar between the two groups (81.5% vs. 70.0%, p = 0.172). There were 28 cases of pCR (70.0%) in the reference trastuzumab group and 46 cases of pCR (70.8%) in the Zercepac group (p = 0.933). The choice of Zercepac or reference trastuzumab was not significantly associated with pCR (OR = 0.96, 95%CI: 0.41-2.28, p = 0.933). Adverse events (AEs) were observed in all patients, and the incidence of ≥3 grade AEs was comparable between the two groups (81.5% vs. 70.0%, p = 0.172). Conclusion: Zercepac has similar effectiveness and safety profile compared with reference trastuzumab in neoadjuvant therapy, which provides treatment options for patients with HER2-positive breast cancer.

Prevalence, clinical presentation, and associated atopic diseases of pediatric fruit and vegetable allergy: A population-based study.

BACKGROUND: In children, fruit and vegetable allergies are often overlooked compared with well-known allergies such as those to eggs, milk, and shellfish. Therefore, this study aimed to analyze fruit and vegetable allergies in children, including prevalence, types of food allergens, clinical presentation, management, and associated comorbid atopic diseases. METHODS: In 2012, a nationwide, cross-sectional, random sampling questionnaire-based survey for common fruit and vegetable allergies was conducted in Taiwan. Information regarding these plant food allergies was collected. Physicians diagnosed food allergies according to the descriptions of convincing symptoms. Enrolled questionnaires were reviewed by expert pediatricians. RESULTS: A total of 9,982 valid questionnaires were analyzed. The overall prevalence of fruit and vegetable allergies was 5.6% (n = 560) and 3.0% (n = 304), respectively. The most common fruit allergen was mango, followed by kiwifruit, whereas taro and bamboo shoot were the most common vegetable allergens. Meanwhile, most allergic symptoms were of the mucocutaneous tissue, followed by the upper airway and gastrointestinal tract. Most only required avoidance of allergens and not medical treatment. Children with fruit or vegetable allergies had a higher percentage of comorbid atopic dermatitis, allergic rhinitis, and asthma than those without food allergies; additionally, the proportion of comorbid atopic diseases was similar between fruit and vegetable allergies and shellfish allergy. One child developed anaphylaxis due to a corn allergy. CONCLUSIONS: Fruits and vegetables are common food allergens in Taiwanese children who present with diverse and potentially severe symptoms. Children with plant food allergies had a percentage of comorbid atopic diseases similar to that of shellfish allergy, the most common allergen. These findings indicate the importance of considering fruit and vegetable allergies in children.

Immune Cells Characteristics and Their Prognostic Effects in Exertional Heatstroke Patients: A Retrospective Cohort Study.

Background: Exertional heatstroke (EHS) remains a major problem for those who take strenuous physical activity. Inflammation and immune dysfunction were thought to be crucial to the pathophysiological process of heatstroke. The present study was aimed to investigate the dynamic changes of the immune cells in patients with EHS and determine their prognostic effects to provide the clinical evidence of the above process. Methods: This single-center retrospective cohort study collected all patients with EHS admitted to the intensive care unit (ICU) of the General Hospital of Southern Theater Command of PLA from October 2008 to May 2019. The dynamic changes of the main immune cell count and ratio were collected, including white blood cell (WBC), neutrophil, monocyte, and lymphocyte. The neutrophil-to-lymphocyte ratios (NLR) were calculated by the neutrophil count/lymphocyte count × 100%. The main outcome was 90-day mortality. Results: A total of 189 patients were enrolled. For survivors, after 24 h, the WBC and neutrophil counts began to decrease, and they were back to normal in 72 h. In addition, the lymphocyte counts were within normal limits all the time. For non-survivors, the WBC and neutrophil counts were continuous over the normal range, while the lymphocyte count and the ratio began to decrease after 24 h and were continuously low in the following days. Receiver operating characteristic (ROC) curves analysis showed that increased neutrophils and decreased lymphocytes were associated with the poor prognosis of the patients. A prediction model based on immune cell counts and ratios was constructed, and the lymphocyte count was accounted for the maximum weight. Conclusions: In patients with EHS, increased neutrophils and decreased lymphocytes were associated with the poor prognosis. The lymphocyte count at 72 h after admission was the most important prognostic factor.

A High-Sodium Diet Modulates the Immune Response of Food Allergy in a Murine Model.

Mounting evidence demonstrates that a high-salt diet (HSD) not only affects hemodynamic changes but also disrupts immune homeostasis. The T helper 17 (Th17) and regulatory T cells (Tregs) are susceptible to hypersalinity. However, research on the influence of sodium on Th2-mediated food allergies remains scarce. We aimed to investigate the effect of dietary sodium on the immune response to food allergies. Mice maintained on an HSD (4% NaCl), low-salt diet (LSD; 0.4% NaCl), or control diet (CTRL; 1.0% NaCl) were orally sensitized with ovalbumin (OVA) and a cholera toxin (CT) adjuvant, and then subjected to an intragastric OVA challenge. OVA-specific immunoglobulin G (IgG), IgG1, IgG2a, and IgE antibodies were significantly higher in the HSD group than in the CTRL group (p < 0.001, p < 0.05, p < 0.01, and p < 0.05, respectively). Mice on HSD had significantly higher interleukin (IL)-4 levels than the CTRL group (p < 0.01). The IL-10 levels were significantly lower in the HSD group than in the CTRL group (p < 0.05). The serum levels of interferon-γ (IFN-γ), sodium, and chloride did not differ among the three groups. This study indicates that excessive salt intake promotes Th2 responses in a mouse model of food allergy.

Characteristics and Outcome of Exertional Heatstroke Patients Complicated by Acute Hepatic Injury: A Cohort Study.

BACKGROUND AND AIMS: Exertional heatstroke (EHS) is associated with strenuous physical activity in hot environments. The present study aimed to investigate dynamic changes of hepatic function indices in EHS patients and determine risk factors for death. METHODS: This single-center retrospective cohort study considered all patients with EHS admitted to the intensive care unit at the General Hospital of Southern Theater Command of PLA from October 2008 to May 2019. Data on general characteristics, organ function parameters, and the 90-day outcome of enrolled patients were collected. Hepatic indices were collected dynamically, and patients with acute hepatic injury (AHI) were identified by plasma total bilirubin (TBIL) ≥34.2 µmol/L and an international normalized ratio ≥1.5, or with any grade of hepatic encephalopathy. RESULTS: In patients who survived, TBIL, alanine aminotransferase and aspartate aminotransferase were increased at 24 h, peaked at 2-3 days, and began to decrease at 5 days. In non-survivors, TBIL continuously increased post-admission. The area under the receiver operating characteristic curve for the prediction of mortality based on sequential organ failure assessment (SOFA) scores was 89.8%, and the optimal cutoff value was 7.5. Myocardial injury and infection were identified as independent risk factors for death in EHS patients with AHI. CONCLUSIONS: In EHS patients, hepatic dysfunction usually occurred within 24 h. Patients with AHI had more severe clinical conditions, and significantly increased 90-day mortality rates. SOFA scores over 7.5, complicated with myocardial injury or infection, were found to be risk factors for death in EHS patients with AHI.

Sequential Organ Failure Assessment Score for Prediction of Mortality of Patients With Rhabdomyolysis Following Exertional Heatstroke: A Longitudinal Cohort Study in Southern China.

Background: Heatstroke is a medical emergency that causes multi-organ injury and death without intervention, but limited data are available on the illness scores in predicting the outcomes of exertional heat stroke (EHS) with rhabdomyolysis (RM). The aim of our study was to investigate the Sequential Organ Failure Assessment (SOFA) score in predicting mortality of patients with RM after EHS. Methods: A retrospective cohort study was performed, which included all patients with EHS admitted into the intensive care unit (ICU) of General Hospital of Southern Theater Command of Peoples Liberation Army from January 2008 to June 2019. RM was defined as creatine kinase (CK) > 1,000 U/L. Data, including the baseline data at admission, vital organ function indicators, and 90-day mortality, were reviewed. Results: A total of 176 patients were enrolled; among them, 85 (48.3%) had RM. Patients with RM had a significantly higher SOFA score (4.0 vs. 3.0, p = 0.021), higher occurrence rates of disseminated intravascular coagulation (DIC) (53.1 vs. 18.3%, p < 0.001) and acute liver injury (ALI) (21.4 vs. 5.5%, p = 0.002) than patients with non-RM. RM was positively correlated with ALI and DIC, and the correlation coefficients were 0.236 and 0.365, respectively (both p-values <0.01). Multivariate logistics analysis showed that the SOFA score [odds ratio (OR) 1.7, 95% CI 1.1-2.6, p = 0.024] was the risk factor for 90-day mortality in patients with RM after EHS, with the area under the curve (AUC) 0.958 (95% CI 0.908-1.000, p < 0.001) and the optimal cutoff 7.5 points. Conclusions: Patients with RM after EHS have severe clinical conditions, which are often accompanied by DIC or ALI. The SOFA score could predict the prognosis of patients with RM with EHS. Early treatment strategies based on decreasing the SOFA score at admission may be pivotal to reduce the 90-day mortality of patients with EHS.

Disregulations of PURPL and MiR-338-3p Could Serve As Prognosis Biomarkers for Epithelial Ovarian Cancer.

Objective: The present study aimed to explore the expressions of long noncoding RNA (lncRNA) p53 upregulated regulator of p53 levels (PURPL) in different ovarian tissues, and to evaluate the significance of disregulations of PURPL and microRNA-338-3p (miR-338-3p) in epithelial ovarian cancer (EOC). Methods: The expressions of PURPL in ovarian cancer, the relations between PURPL and the prognosis of ovarian cancer, and the relation between PURPL and miR-338-3p were queried in multiple biomedical databases. Real-time PCR was performed to detect the expressions of PURPL in different ovarian tissues. Logistic regression analysis was used to analyze the risk factors of recurrence and death. Kaplan-Meier analysis was implemented to evaluate the relations between PURPL and miR-338-3p expressions and the survival of ovarian cancer. Results: PURPL could target miR-338-3p, PURPL were upregulated in ovarian cancer tissues, upregulation of PURPL in ovarian cancer was negatively related with the recurrence free survival (RFS) and overall survival (OS), which were indicated by biomedical databases query. Our data showed upregulations of PURPL were noted in ovarian cancer tissues. Higher expressions of PURPL were associated with more advanced FIGO stage and developed lymph node metastasis in epithelial ovarian cancer. Upregulation of PURPL was related with the recurrence (P=0.002, OR=21.482, 95%CI: 3.457~94.251) and death (P=0.004, OR=35.643, 95%CI: 2.453~84.359) of ovarian cancer patient. PURPL expressions were negatively correlated to miR-338-3p expressions in different ovarian tissues (r = -0.968, P<0.0001). Poor RFS (χ2=19.410, P=0.0002) and OS (χ2=17.600, P=0.0005) were found in patients with high level PURPL and low level miR-338-3p expressions. Conclusions: Upregulation of PURPL and downregulation of miR-338-3p were related with the poor RFS and OS of ovarian cancer, which indicated disregulations of PURPL and miR-338-3p could serve as prognosis biomarkers for epithelial ovarian cancer.

Effects of hypertension on the outcomes of COVID-19: a multicentre retrospective cohort study.

Objectives: Hypertension is thought to be a contributor to mortality in coronavirus disease 2019 patients; however, limited clinical data on the outcomes of COVID-19 in patients with hypertension are available.Methods: This study was designed to confirm whether hypertension affects the outcomes of COVID-19. Results: A total of 983 patients with COVID-19 (female, 48%; male, 52%) were enrolled. Significantly higher odds of 60-day mortality (p = .017) were observed in the hypertensive group. In the hypertensive group, even after adjustment in multivariate analysis, the subgroup of patients 70 years old and older had higher 28-day mortality and total 60-day mortality rates than the other age subgroups (bothp < .05). A total of 297 (89%) COVID-19 patients with hypertension survived, and 35 (11%) died. In addition, compared with hypertensive patients who survived COVID-19, non-survivors had more pre-existing conditions, including cardiovascular diseases and stroke, higher blood pressure on admission, more severe inflammation, and more liver and kidney damage.Conclusion: Hypertension does not affect the outcome of COVID-19, which is different than the conclusions drawn in other studies. However, the 28-day mortality and total 60-day mortality rates of hypertensive patients (age ≥ 70) with COVID-19 were significantly elevated, and compared with the group of survivors, non-surviving COVID-19 patients with hypertension were older, had more basic diseases and had a more severe clinical condition.

Clinical Characteristics and Risk Factors Associated With Acute Kidney Injury Inpatient With Exertional Heatstroke: An Over 10-Year Intensive Care Survey.

Background: Exertional heat stroke (EHS) is a life-threatening injury that can lead to acute kidney injury (AKI). The clinical characteristics of and risk factors for EHS complicated with AKI have been poorly documented. Methods: A retrospective study with EHS admitted to the intensive care unit (ICU) from January 2008 to June 2019 was performed. Data including baseline clinical information at admission, main organ dysfunction, 90-day mortality and total cost of hospitalization were collected. Results: A total of 187 patients were finally included, of which 82 (43.9%) had AKI. AKI patients had more severe organ injury and higher total hospitalization costs than non-AKI patients. Multivariate logistic analysis showed that lymphocyte, neutrophil, D-dimer and myoglobin (MB) ≥ 1,000 ng/ml were independent risk factors for AKI caused by EHS. In addition, SOFA score [hazard ratio (HR) 4.1, 95% confidence interval (95% CI) 1.6-10.8, P = 0.004] and GCS score (HR 3.2, 95% CI 1.2-8.4 P = 0.017) were the risk factor for 90-day mortality in patients with EHS complicated with AKI, with an area under the curve (AUC) of 0.920 (95% CI 0.842-0.998, P < 0.001) and 0.851 (95% CI 0.739-0.962, P < 0.001), respectively. Survival analysis showed that the 90-day mortality in AKI patients was significantly high (P < 0.0001) and the mortality rate of patients with AKI stage 2 was the highest than other stages. Conclusions: EHS complicated with AKI is associated with higher hospitalization costs and poorly clinical outcomes. MB ≥1,000 ng/ml, Inflammation, coagulation were associated with the occurrence and development of AKI. Early treatment strategies based reducing the SOFA and GCS score may be pivotal for improving the prognosis of EHS.

Risk factors for mortality in critically ill patients with COVID-19: a multicenter retrospective case-control study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread around the world, until now, the number of positive and death cases is still increasing. Therefore, it remains important to identify risk factors for death in critically patients. METHODS: We collected demographic and clinical data on all severe inpatients with COVID-19. We used univariable and multivariable Cox regression methods to determine the independent risk factors related to likelihood of 28-day and 60-day survival, performing survival curve analysis. RESULTS: Of 325 patients enrolled in the study, Multi-factor Cox analysis showed increasing odds of in-hospital death associated with basic illness (hazard ratio [HR] 6.455, 95% Confidence Interval [CI] 1.658-25.139, P = 0.007), lymphopenia (HR 0.373, 95% CI 0.148-0.944, P = 0.037), higher Sequential Organ Failure Assessment (SOFA) score on admission (HR 1.171, 95% CI 1.013-1.354, P = 0.033) and being critically ill (HR 0.191, 95% CI 0.053-0.687, P = 0.011). Increasing 28-day and 60-day mortality, declining survival time and more serious inflammation and organ failure were associated with lymphocyte count < 0.8 × 109/L, SOFA score > 3, Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 7, PaO2/FiO2 < 200 mmHg, IL-6 > 120 pg/ml, and CRP > 52 mg/L. CONCLUSIONS: Being critically ill and lymphocyte count, SOFA score, APACHE II score, PaO2/FiO2, IL-6, and CRP on admission were associated with poor prognosis in COVID-19 patients.

Risk Factors for the 90-Day Prognosis Of Severe Heat Stroke: a Case-Control Study.

BACKGROUND: Severe heat stroke is a clinical syndrome caused by host stress dysfunction due to heat stress and subsequent life-threatening organ dysfunction. We aimed to explore the early risk factors affecting the 90-day prognosis of severe heat stroke patients. METHODS: A case-control study was used to retrospectively analyze the clinical data of 117 severe heat stroke patients admitted to the intensive care unit of the General Hospital of Southern Theater Command from April 2014 to May 2019. The risk factors affecting the 90-day mortality of the patients were analyzed, and subgroup analysis was performed comparing the complete recovery and the sequelae subgroups of survivors. RESULTS: Thirteen patients (11.1%) died within 90 days. The multivariate Cox risk regression model showed that cooling time (HR 4.87; 95% CI: 1.94-12.18; P = 0.001), heart rate (HR 1.04; 95% CI: 1.01-1.09; P = 0.027), and Sequential Organ Failure (SOFA) score (HR 1.41; 95% CI: 1.21-1.65; P < 0.001) were independent risk factors affecting the survival of patients. The area under the Receiver Operating Characteristic (ROC) curve of the combination of cooling time, heart rate, and SOFA score for the prediction of mortality due to severe heat stroke was 98.1% (95% CI 0.957-1.000, P < 0.001), the sensitivity was 96.2%, and the specificity was 92.3%. CONCLUSIONS: The longer the cooling duration, the faster the heart rate at admission, and the higher the SOFA score, the lower the 90-day survival rate was. These three indicators can be used in combination to predict 90-day mortality and poor prognosis in patients with severe heat stroke.

Clinical efficacy of intravenous immunoglobulin therapy in critical ill patients with COVID-19: a multicenter retrospective cohort study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) outbreak is a major challenge all over the world, without acknowledged treatment. Intravenous immunoglobulin (IVIG) has been recommended to treat critical coronavirus disease 2019 (COVID-19) patients in a few reviews, but the clinical study evidence on its efficacy in COVID-19 patients was lacking. METHODS: 325 patients with laboratory-confirmed critical COVID-19 were enrolled from 4 government-designated COVID-19 treatment centres in southern China from December 2019 to March 2020. The primary outcomes were 28- and 60-day mortality, and the secondary outcomes were the total length of in-hospital and the total duration of the disease. Subgroup analysis was carried out according to clinical classification of COVID-19, IVIG dosage and timing. RESULTS: In the enrolled 325 patients, 174 cases used IVIG and 151 cases did not. The 28-day mortality was improved with IVIG after adjusting confounding in overall cohort (P = 0.0014), and the in-hospital and the total duration of disease were longer in the IVIG group (P < 0.001). Subgroup analysis showed that only in patients with critical type, IVIG could significantly reduce the 28-day mortality, decrease the inflammatory response and improve some organ functions (all P < 0.05); the application of IVIG in the early stage (admission ≤ 7 days) with a high dose (> 15 g per day) exhibited significant reduction in 60-day mortality in the critical-type patients. CONCLUSION: Early administration of IVIG with high dose improves the prognosis of critical-type patients with COVID-19. This study provides important information on clinical application of IVIG in the treatment of SARS-CoV-2 infection, including patient selection and administration dosage and timing.

Thymosin α1 therapy in critically ill patients with COVID-19: A multicenter retrospective cohort study.

BACKGROUND: COVID-19 characterized by refractory hypoxemia increases patient mortality because of immunosuppression effects. This study aimed to evaluate the efficacy of immunomodulatory with thymosin α1 for critical COVID-19 patients. METHODS: This multicenter retrospective cohort study was performed in 8 government-designated treatment centers for COVID-19 patients in China from Dec. 2019 to Mar. 2020. Thymosin α1 was administrated with 1.6 mg qd or q12 h for >5 days. The primary outcomes were the 28-day and 60-day mortality, the secondary outcomes were hospital length of stay and the total duration of the disease. Subgroup analysis was carried out according to clinical classification. RESULTS: Of the 334 enrolled COVID-19 patients, 42 (12.6%) died within 28 days, and 55 (16.5%) died within 60 days of hospitalization. There was a significant difference in the 28-day mortality between the thymosin α1 and non-thymosin α1-treated groups in adjusted model (P = 0.016), without obvious differences in the 60-day mortality and survival time in the overall cohort (P > 0.05). In the subgroup analysis, it was found that thymosin α1 therapy significantly reduced 28-day mortality (Hazards Ratios HR, 0.11, 95% confidence interval CI 0.02-0.63, P=0.013) via improvement of Pa02/FiO2 (P = 0.036) and prolonged the hospital length of stay (P = 0.024) as well as the total duration of the disease (P=0.001) in the critical type patients, especially those aged over 64 years, with white blood cell >6.8×109/L, neutrophil >5.3×109/L, lymphocyte < 0.73 × 109/L, PaO2/FiO2 < 196, SOFA > 3, and acute physiology and chronic health evaluation (APACHE) II > 7. CONCLUSION: These results suggest that treatment with thymosin α1 can markedly decrease 28-day mortality and attenuate acute lung injury in critical type COVID-19 patients.