The necessity of a loading dose when prescribing intravenous colistin in critically ill patients with CRGNB-associated pneumonia: a multi-center observational study.

BACKGROUND: The importance or necessity of a loading dose when prescribing intravenous colistin has not been well established in clinical practice, and approximate one-third to half of patients with carbapenem-resistant gram-negative bacteria (CRGNB) infection did not receive the administration of a loading dose. The aim of this study is to investigate the efficacy and risk of acute kidney injury when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB. METHODS: This was a multicenter, retrospective study that recruited ICU-admitted patients who had CRGNB-associated nosocomial pneumonia and were treated with intravenous colistin. Then, we classified the patients into colistin loading dose (N = 85) and nonloading dose groups (N = 127). After propensity-score matching for important covariates, we compared the mortality rate, clinical outcome and microbiological eradication rates between the groups (N = 67). RESULTS: The loading group had higher percentages of patients with favorable clinical outcomes (55.2% and 35.8%, p = 0.037) and microbiological eradication rates (50% and 27.3%, p = 0.042) at day 14 than the nonloading group. The mortality rates at days 7, 14 and 28 and overall in-hospital mortality were not different between the two groups, but the Kaplan-Meier analysis showed that the loading group had a longer survival time than the nonloading group. Furthermore, the loading group had a shorter length of hospital stay than the nonloading group (52 and 60, p = 0.037). Regarding nephrotoxicity, there was no significant difference in the risk of developing acute kidney injury between the groups. CONCLUSIONS: The administration of a loading dose is recommended when prescribing intravenous colistin for critically ill patients with nosocomial pneumonia caused by CRGNB.

Bidirectional association between tuberculosis and sarcoidosis.

BACKGROUND AND OBJECTIVE: Tuberculosis (TB) and sarcoidosis are both granulomatous diseases with potential interassociations. However, much uncertainty remains; thus, the present study aimed to clarify the association between these diseases. METHODS: We established two cohorts in this retrospective longitudinal cohort study using data obtained from the Taiwan National Health Insurance Database from 2000 to 2015. One cohort, which comprised 31 221 patients with TB and 62 442 age-, sex- and index year-matched controls, was used to analyse the risk of sarcoidosis; the other cohort comprised 2442 patients with sarcoidosis and 9688 controls and was used to assess the risk of TB. A Cox proportional hazards model adjusted for potential confounders was used in each cohort. RESULTS: Patients with TB showed an 8.09-fold higher risk of developing sarcoidosis than non-TB subjects (95% CI = 3.66-17.90), whereas patients with sarcoidosis showed a 1.85-fold higher risk of developing TB than non-sarcoidosis subjects (95% CI = 1.36-2.50). The TB subtype analysis revealed the highest risk of developing sarcoidosis in patients with extrapulmonary TB, and the highest risk of developing extrapulmonary TB was observed in patients with sarcoidosis compared with non-sarcoidosis subjects. Patients with TB showed a higher risk of developing sarcoidosis throughout the follow-up period, but patients with sarcoidosis only showed a higher risk of developing TB within the first year. CONCLUSION: TB is a risk factor for developing sarcoidosis. The results of this bidirectional cohort study also highlight the clinical difficulty of diagnosing sarcoidosis and TB.

Tuberculosis increases the risk of peripheral arterial disease: A nationwide population-based study.

BACKGROUND AND OBJECTIVE: According to several studies, tuberculosis (TB) may be involved in the pathogenesis of cardiovascular disease. However, the relationship between TB and peripheral arterial disease (PAD) has not been studied. The aim of this study was to investigate whether patients with TB exhibit an increased risk of developing PAD. METHODS: The data assessed in this national population-based cohort study were obtained from the Taiwan National Health Insurance Database from 2000 to 2010. Patients with newly diagnosed TB were selected using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. The non-TB cohort was randomly frequency-matched to the TB cohort at a ratio of 2:1 according to age, sex and index year. Cox's proportional hazards regression models were used to analyse the risk of PAD. RESULTS: We enrolled 14 350 patients with TB and 28 700 controls in this study. The risk of PAD was 3.93-fold higher in the patients with TB than in the non-TB controls after adjusting for age, sex, co-morbidities and socio-economic status. Based on the subgroup analysis, the TB cohort exhibited an increased risk of developing PAD compared with the non-TB cohort, regardless of age, sex, co-morbidities and socio-economic status. Patients with TB had a higher risk of developing PAD than healthy control subjects after 1 year of follow-up. CONCLUSION: Patients with TB have a significantly higher risk of developing PAD than patients without TB. TB should be considered when evaluating a patient's risk of developing PAD.

Efficacy of combination therapy with standard-dose carbapenem for treating nosocomial pneumonia caused by carbapenem-resistant Acinetobacter baumannii in intensive care units: A multicentre retrospective propensity score-matched study.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infection is common worldwide. Despite carbapenem resistance, standard-dose carbapenems are still used in clinical practice. Hence in this study, we aimed to compare the efficacy and outcomes of a regimen containing standard-dose carbapenems with those of a regimen lacking carbapenems during the treatment of critically ill patients with CRAB nosocomial pneumonia in the intensive care unit (ICU). Initially, 735 patients were recruited for this multicentre retrospective cohort study. After exclusion, time-window bias adjustment, and propensity score matching, multiple clinical outcomes were compared between the carbapenem-containing (CC) (n = 166) and no carbapenem-containing (NCC) (n = 166) groups. The CC group showed a higher risk of clinical failure on day 7 than the NCC group (44.6% vs. 33.1%, P = 0.043). The lengths of ICU stay (21 and 16 days, P = 0.024) and hospital stay (61 and 44 days, P = 0.003) were longer in the CC group than in the NCC group. Multivariate analysis showed that the CC regimen was associated with higher clinical failure (adjusted odds ratio (aOR) = 1.64, 95% CI = 1.05-2.56, P = 0.031) and lower microbiological eradication (aOR = 0.48, 95% CI = 0.23-1.00, P = 0.049) at day 7 than the NCC group. Thus, a regimen containing a standard dose of carbapenem should be prescribed with caution for treating CRAB nosocomial pneumonia in the ICU.

The impact and risk factors for developing pneumogenic bacteremia in carbapenem-resistant Acinetobacter baumannii nosocomial pneumonia in the intensive care unit: a multicenter retrospective study.

OBJECTIVES: This study analyzed the risk and impact of developing pneumogenic bacteremia in patients with CRAB nosocomial pneumonia in ICU. METHODS: This is multicenter retrospective study. Clinical outcomes were compared between bacteremia and non-bacteremia group, and the risk factors for mortality and developing pneumogenic CRAB bacteremia were analyzed. RESULTS: After patient recruitment, 164 cases were in the bacteremia group, and 519 cases were in the non-bacteremia group. The bacteremia group had 22.4 percentage of increase in-hospital mortality than the non-bacteremia group (68.3% vs. 45.9%, p < 0.001). Multivariate analysis showed bacteremia was an independent risk factor for in-hospital mortality (aHR = 2.399, p < 0.001). A long time-interval between ICU admission and pneumonia onset was an independent risk factor for developing bacteremia (aOR = 1.040, p = < 0.001). Spearman's rank correlation analysis indicated a high correlation between the days from ICU admission to pneumonia onset and the days of ventilator use before pneumonia onset (correlation coefficient (ρ) = 0.777). CONCLUSIONS: In patients with CRAB nosocomial pneumonia, bacteremia increased the in-hospital mortality, and a longer interval from ICU admission to pneumonia onset was an independent risk factor for developing bacteremia, which was highly associated with the use of mechanical ventilation.

The prevalence, presentation and outcome of colistin susceptible-only Acinetobacter Baumannii-associated pneumonia in intensive care unit: a multicenter observational study.

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) are both associated with significant morbidity and mortality in daily clinical practice, as well as in a critical care setting. It is unclear whether colistin susceptible-only Acinetobacter baumannii (CSO AB) is a unique phenotype separate from or a subset of CRAB-associated pneumonia. The aim of this study is to investigate the prevalence of CSO AB pneumonia and compare the presentation and outcome between CSO AB and CRAB-associated pneumonia in critically ill patients. This multicenter retrospective cohort study initially recruited 955 patients with CR-GNB pneumonia. After exclusion, 575 patients left who were ICU-admitted and had CRAB nosocomial pneumonia remained. Among them, 79 patients had CSO AB pneumonia, classified as the CSO AB group. The other 496 patients were classified as the CRAB group. We compared demographic characteristics, disease severity, and treatment outcomes between the two groups. The prevalence of CSO AB among all cases of CRAB pneumonia was 13.74% (79/575). The CSO AB and CRAB groups had similar demographic characteristics and disease severities at initial presentation. The in-hospital mortality rate was 45.6% and 46.4% for CSO AB and CRAB groups, respectively (p = 0.991). The CSO AB group had significantly better clinical outcomes at day 7 (65.8% vs 52.4%, p = 0.036) but longer length of ICU stay (27 days vs 19 days, p = 0.043) compared to the CRAB group. However, other treatment outcomes, including clinical outcomes at day 14 and 28, mortality, microbiological eradication, ventilator weaning, and newly onset dialysis, were similar. In conclusion, CSO AB accounted for 13.74% of all cases of CRAB pneumonia, and the clinical presentation and treatment outcomes of CSO AB and CRAB pneumonia were similar.

Clinical effectiveness of tigecycline in combination therapy against nosocomial pneumonia caused by CR-GNB in intensive care units: a retrospective multi-centre observational study.

BACKGROUND: Tigecycline has in vitro bacteriostatic activity against a broad spectrum of bacteria, including carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the role of tigecycline in treatment of nosocomial pneumonia caused by CR-GNB remains controversial and clinical evidences are limited. We aimed to investigate the clinical benefits of tigecycline as part of the combination treatment of nosocomial CR-GNB pneumonia in intensive care unit (ICU). METHODS: This multi-centre cohort study retrospectively enrolled ICU-admitted patients with nosocomial pneumonia caused by CR-GNB. Patients were categorized based on whether add-on tigecycline was used in combination with at least one anti-CR-GNB antibiotic. Clinical outcomes and all-cause mortality between patients with and without tigecycline were compared in the original and propensity score (PS)-matched cohorts. A subgroup analysis was also performed to explore the differences of clinical efficacies of add-on tigecycline treatment when combined with various anti-CR-GNB agents. RESULTS: We analysed 395 patients with CR-GNB nosocomial pneumonia, of whom 148 received tigecycline and 247 did not. More than 80% of the enrolled patients were infected by CR-Acinetobacter baumannii (CRAB). A trend of lower all-cause mortality on day 28 was noted in tigecycline group in the original cohort (27.7% vs. 36.0%, p = 0.088). In PS-matched cohort (102 patient pairs), patients with tigecycline had significantly lower clinical failure (46.1% vs. 62.7%, p = 0.017) and mortality rates (28.4% vs. 52.9%, p < 0.001) on day 28. In multivariate analysis, tigecycline treatment was a protective factor against clinical failure (PS-matched cohort: aOR 0.52, 95% CI 0.28-0.95) and all-cause mortality (original cohort: aHR 0.69, 95% CI 0.47-0.99; PS-matched cohort: aHR 0.47, 95% CI 0.30-0.74) at 28 days. Kaplan-Meier survival analysis in subgroups of patients suggested significant clinical benefits of tigecycline when added to a colistin-included (log rank p value 0.005) and carbapenem-included (log rank p value 0.007) combination regimen. CONCLUSIONS: In this retrospective observational study that included ICU-admitted patients with nosocomial pneumonia caused by tigecycline-susceptible CR-GNB, mostly CRAB, tigecycline as part of a combination treatment regimen was associated with lower clinical failure and all-cause mortality rates.

Mortality and ventilator dependence in critically ill patients with ventilator-associated pneumonia caused by carbapenem-resistant Acinetobacter baumannii.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a key pathogen associated with ventilator-associated pneumonia (VAP). Research on treatment outcomes, especially ventilator dependence, in patients with VAP caused by CRAB remains limited. METHODS: This retrospective multicenter study included ICU-admitted patients with VAP caused by CRAB. The original cohort was included as the mortality evaluation cohort. The ventilator dependence evaluation cohort included cases that survived more than 21 days after VAP and without prolonged ventilation before VAP onset. The mortality rate, ventilator dependence rate, clinical factors associated with treatment outcomes, and treatment outcome differences with various VAP onset times were investigated. RESULTS: In total, 401 patients with VAP caused by CRAB were analyzed. The 21-day all-cause mortality rate was 25.2%, and the 21-day ventilator dependence rate was 48.8%. Clinical factors associated with 21-day mortality included lower body mass index, higher sequential organ failure assessment score, vasopressors usage, CRAB persistence, and VAP onset time > seven days. Clinical factors associated with 21-day ventilator dependence included older age, vasopressors usage, and VAP onset time > seven days. CONCLUSIONS: ICU-admitted patients with CRAB-related VAP had high mortality and ventilator dependence rates. Older age, vasopressor usage, and longer VAP onset time were independent factors associated with ventilator dependence.

Clinical outcome of nosocomial pneumonia caused by Carbapenem-resistant gram-negative bacteria in critically ill patients: a multicenter retrospective observational study.

Nosocomial pneumonia caused by carbapenem-resistant gram-negative bacteria (CRGNB) is a growing threat due to the limited therapeutic choices and high mortality rate. The aim of this study was to evaluate the prognostic factors for mortality in patients with nosocomial pneumonia caused by CRGNB and the impact of colistin-based therapy on the outcomes of intensive care unit (ICU) patients. We conducted a retrospective study of the ICUs in five tertiary teaching hospitals in Taiwan. Patients with nosocomial pneumonia caused by CRGNB from January 2016 to December 2016 were included. Prognostic factors for mortality were analyzed using multivariate logistic regression. The influence of colistin-based therapy on mortality and clinical and microbiological outcomes were evaluated in subgroups using different severity stratification criteria. A total of 690 patients were enrolled in the study, with an in-hospital mortality of 46.1%. The most common CRGNB pathogens were Acinetobacter baumannii (78.7%) and Pseudomonas aeruginosa (13.0%). Significant predictors (odds ratio and 95% confidence interval) of mortality from multivariate analysis were a length of hospital stay (LOS) prior to pneumonia of longer than 9 days (2.18, 1.53-3.10), a sequential organ failure assessment (SOFA) score of more than 7 (2.36, 1.65-3.37), supportive care with vasopressor therapy (3.21, 2.26-4.56), and escalation of antimicrobial therapy (0.71, 0.50-0.99). There were no significant differences between the colistin-based therapy in the deceased and survival groups (42.1% vs. 42.7%, p = 0.873). In the subgroup analysis, patients with multiple organ involvement (> 2 organs) or higher SOFA score (> 7) receiving colistin-based therapy had better survival outcomes. Prolonged LOS prior to pneumonia onset, high SOFA score, vasopressor requirement, and timely escalation of antimicrobial therapy were predictors for mortality in critically ill patients with nosocomial CRGNB pneumonia. Colistin-based therapy was associated with better survival outcomes in subgroups of patients with a SOFA score of more than 7 and multiple organ involvement.

Bidirectional Relationship Between Tuberculosis and Hypothyroidism: An 18-Year Nationwide Population-Based Longitudinal Cohort Study.

Some antituberculosis agents may cause hypothyroidism, and thyroid hormones play a vital role in Mycobacterium tuberculosis infection. However, the relationship between tuberculosis (TB) and hypothyroidism has not been clearly established. Therefore, this retrospective, longitudinal cohort study aimed to investigate the association between these two diseases using the 2000-2017 data from the Taiwan's National Health Insurance Research Database. The hypothyroidism and TB cohorts were matched with the control group in a 1:4 ratio. Adjusted hazard ratios (aHRs) were assessed using Cox proportional hazards regression analysis in each cohort. In total, 3,976 individuals with hypothyroidism and 35 120 individuals with TB were included in this study. The risk of developing TB in patients with hypothyroidism was 2.91 times higher than that in those without hypothyroidism (95% confidence interval [CI], 1.50-3.65). The subgroup of thyroxine replacement therapy (TRT) had a 2.40 times higher risk (95% CI, 1.26-3.01), whereas the subgroup of non-TRT had a 3.62 times higher risk of developing TB than those without hypothyroidism (95% CI, 2.19-4.84). On the other hand, the risk of developing hypothyroidism in patients with TB was 2.01 times higher than that in those without TB (95% CI, 1.41-2.38). Our findings provide evidence that TB and hypothyroidism are interrelated. Thus, clinicians and public health authorities should monitor the association between these two diseases to reduce the relevant disease burden.

Efficacy of adjunctive nebulized colistin in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial pneumonia: a multi-centre observational study.

OBJECTIVES: To investigate the association between adjunctive nebulized colistin and treatment outcomes in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial (CR-GNB) pneumonia. METHODS: This retrospective, multi-centre, cohort study included individuals admitted to the intensive care unit with nosocomial pneumonia caused by colistin-susceptible CR-GNB. Enrolled patients were divided into groups with/without nebulized colistin as adjunct to at least one effective intravenous antibiotic. Propensity score matching was performed in the original cohort (model 1) and a time-window bias-adjusted cohort (model 2). The association between adjunctive nebulized colistin and treatment outcomes was analysed. RESULTS: In total, 181 and 326 patients treated with and without nebulized colistin, respectively, were enrolled for analysis. The day 14 clinical failure rate and mortality rate were 41.4% (75/181) versus 46% (150/326), and 14.9% (27/181) versus 21.8% (71/326), respectively. In the propensity score-matching analysis, patients with nebulized colistin had lower day 14 clinical failure rates (model 1: 41% (68/166) versus 54.2% (90/166), p 0.016; model 2: 35.3% (41/116) versus 56.9% (66/116), p 0.001). On multivariate analysis, nebulized colistin was an independent factor associated with fewer day 14 clinical failures (model 1: adjusted odds ratio (aOR) 0.59, 95% CI 0.37-0.92; model 2: aOR 0.37, 95% CI 0.21-0.65). Nebulized colistin was not associated independently with a lower 14-day mortality rate in the time-dependent analysis in both models 1 and 2. CONCLUSIONS: Adjunctive nebulized colistin was associated with lower day 14 clinical failure rate, but not lower 14-day mortality rate, in critically ill patients with nosocomial pneumonia caused by colistin-susceptible CR-GNB.

Efficacies of Colistin-Carbapenem versus Colistin-Tigecycline in Critically Ill Patients with CR-GNB-Associated Pneumonia: A Multicenter Observational Study.

Background: Evaluating the options for antibiotic treatment for carbapenem-resistant Gram-negative bacteria (CR-GNB)-associated pneumonia remains crucial. We compared the therapeutic efficacy and nephrotoxicity of two combination therapies, namely, colistin + carbapenem (CC) versus colistin + tigecycline (CT), for treating CR-GNB-related nosocomial pneumonia in critically ill patients. Methods: In this multicenter, retrospective, and cohort study, we recruited patients admitted to intensive care units and diagnosed with CR-GNB-associated nosocomial pneumonia. We divided the enrolled patients into CC (n = 62) and CT (n = 59) groups. After propensity score matching (n = 39), we compared the therapeutic efficacy by mortality, favorable outcome, and microbiological eradication and compared nephrotoxicity by acute kidney injury between groups. Results: There was no significant difference between the CC and CT groups regarding demographic characteristics and disease severities as assessed using the Acute Physiology and Chronic Health Evaluation (APACHE) II score, Sequential Organ Failure Assessment (SOFA) score, and other organ dysfunction variables. Therapeutic efficacy was non-significantly different between groups in all-cause mortality, favorable outcomes, and microbiological eradication at days 7, 14, and 28; as was the Kaplan-Meier analysis of 28-day survival. For nephrotoxicity, both groups had similar risks of developing acute kidney injury, evaluated using the Kidney Disease Improving Global Outcomes criteria (p = 1.000). Conclusions: Combination therapy with CC or CT had similar therapeutic efficacy and risk of developing acute kidney injury for treating CR-GNB-associated nosocomial pneumonia in critically ill patients.

Metabolically healthy obesity and physical fitness in military males in the CHIEF study.

The metabolically healthy obese (MHO) characterized by the absence of metabolic syndrome have shown superior cardiorespiratory fitness (CRF) and similar muscular strength as compared with the metabolically unhealthy obese (MUO). However, this finding might be biased by the baseline sedentary behavior in the general population. This study utilized 3669 physically active military males aged 18-50 years in Taiwan. Obesity and metabolically unhealthy were respectively defined as body mass index ≥ 27.5 kg/m2 and presence of at least two major components of the metabolic syndrome, according to the International Diabetes Federation criteria for Asian male adults. Four groups were accordingly classified as the metabolically healthy lean (MHL, n = 2510), metabolically unhealthy lean (MUL, n = 331), MHO (n = 181) and MUO (n = 647). CRF was evaluated by time for a 3-km run, and muscular strengths were separately assessed by numbers of push-up and sit-up within 2 min. Analysis of covariance was utilized to compare the difference in each exercise performance between groups adjusting for age, service specialty, smoking, alcohol intake and physical activity. The metabolic syndrome prevalence in MUL and MUO was 49.8% and 47.6%, respectively. The performance of CRF did not differ between MHO and MUO (892.3 ± 5.4 s and 892.6 ± 3.0 s, p = 0.97) which were both inferior to MUL and MHL (875.2 ± 4.0 s and 848.6 ± 1.3 s, all p values < 0.05). The performance of muscular strengths evaluated by 2-min push-ups did not differ between MUL and MUO (45.3 ± 0.6 and 45.2 ± 0.4, p = 0.78) which were both less than MHO and MHL (48.4 ± 0.8 and 50.6 ± 0.2, all p values < 0.05). However, the performance of 2-min sit-ups were only superior in MHL (48.1 ± 0.1) as compared with MUL, MHO and MUO (45.9 ± 0.4, 46.7 ± 0.5 and 46.1 ± 0.3, respectively, all p values < 0.05). Our findings suggested that in a physically active male cohort, the MHO might have greater muscle strengths, but have similar CRF level compared with the MUO.

Association of Tobacco Smoking with Physical Fitness of Military Males in Taiwan: The CHIEF Study.

Tobacco smoking has been found associated with lower cardiorespiratory fitness in white and black males; however, few studies have not been conducted to clarify such relationship in Asian males. We performed a cross-sectional study to investigate the association between tobacco smoking status and physical fitness in 3,669 military males, averaged 29.4 years of age, from the cardiorespiratory fitness and hospitalization events in armed forces (CHIEF) study in Taiwan during 2014. There were 1,376 current smokers, and the others were noncurrent smokers. The effective sample size estimated was 1,230 participants, as the margin of error was ±3% at the 99% confidence level. Physical fitness was evaluated by time for a 3000-meter run test (aerobic fitness) and repetitive numbers of 2-minute sit-ups and 2-minute push-ups (anaerobic fitness) where all procedures were standardized by using computerized scoring systems. A multiple linear analysis adjusting for age, service specialty, body mass index, heart rate, alcohol intake, and training frequency was used to determine the relationship. As compared with noncurrent smoking, current smoking was inversely correlated with longer time for a 3000-meter run (ß = 15.66 (95% confidence intervals (CI): 10.62, 20.70)) and fewer repetitive numbers of 2-minute sit-ups and 2-minute push-ups (ß = -1.53 (95% CI: -2.08, -0.97) and -1.31 (95% CI: -2.12, -0.50), respectively). Our finding reconfirms the concept that tobacco smoking might reduce both aerobic and anaerobic fitness among young Asian males.

In silico immune infiltration profiling combined with functional enrichment analysis reveals a potential role for naïve B cells as a trigger for severe immune responses in the lungs of COVID-19 patients.

COVID-19, caused by SARS-CoV-2, has rapidly spread to more than 160 countries worldwide since 2020. Despite tremendous efforts and resources spent worldwide trying to explore antiviral drugs, there is still no effective clinical treatment for COVID-19 to date. Approximately 15% of COVID-19 cases progress to pneumonia, and patients with severe pneumonia may die from acute respiratory distress syndrome (ARDS). It is believed that pulmonary fibrosis from SARS-CoV-2 infection further leads to ARDS, often resulting in irreversible impairment of lung function. If the mechanisms by which SARS-CoV-2 infection primarily causes an immune response or immune cell infiltration can be identified, it may be possible to mitigate excessive immune responses by modulating the infiltration and activation of specific targets, thereby reducing or preventing severe lung damage. However, the extent to which immune cell subsets are significantly altered in the lung tissues of COVID-19 patients remains to be elucidated. This study applied the CIBERSORT-X method to comprehensively evaluate the transcriptional estimated immune infiltration landscape in the lung tissues of COVID-19 patients and further compare it with the lung tissues of patients with idiopathic pulmonary fibrosis (IPF). We found a variety of immune cell subtypes in the COVID-19 group, especially naïve B cells were highly infiltrated. Comparison of functional transcriptomic analyses revealed that non-differentiated naïve B cells may be the main cause of the over-active humoral immune response. Using several publicly available single-cell RNA sequencing data to validate the genetic differences in B-cell populations, it was found that the B-cells collected from COVID-19 patients were inclined towards naïve B-cells, whereas those collected from IPF patients were inclined towards memory B-cells. Further differentiation of B cells between COVID-19 mild and severe patients showed that B cells from severe patients tended to be antibody-secreting cells, and gene expression showed that B cells from severe patients were similar to DN2 B cells that trigger extrafollicular response. Moreover, a higher percentage of B-cell infiltration seems associated with poorer clinical outcome. Finally, a comparison of several specific COVID-19 cases treated with targeted B-cell therapy suggests that appropriate suppression of naïve B cells might potentially be a novel strategy to alleviate the severe symptoms of COVID-19.

Benzodiazepines Associated With Acute Respiratory Failure in Patients With Obstructive Sleep Apnea.

Aims: Obstructive sleep apnea (OSA) and insomnia commonly coexist; hypnotics are broadly prescribed for insomnia therapy. However, the safety of hypnotics use in OSA patients is unclear. We conducted a retrospective case-control study to investigate the risk of adverse respiratory events in hypnotics-using OSA patients. Methods: We obtained data from the Taiwan National Health Insurance Database from 1996 to 2013. The case group included 216 OSA patients with newly diagnosed adverse respiratory events, including pneumonia and acute respiratory failure. The control group included OSA patients without adverse respiratory events, which was randomly frequency-matched to the case group at a 1:1 ratio according to age, gender, and index year. Hypnotics exposure included benzodiazepines (BZD) and non-benzodiazepines (non-BZD). A recent user was defined as a patient who had taken hypnotics for 1-30 days, while a long-term user was one who had taken hypnotics for 31-365 days. Results: Multivariable adjusted analysis showed recent BZD use is an independent risk for adverse respiratory events (OR = 2.70; 95% CI = 1.15-6.33; P < 0.001). Subgroup analysis showed both recent and long-term BZD use increased the risk of acute respiratory failure compared to never BZD use (OR = 28.6; 95% CI = 5.24-156; P < 0.001, OR = 10.1; 95% CI = 1.51-67.7; P < 0.05, respectively). Neither BZD nor non-BZD use increased the risk of pneumonia in OSA patients. Conclusion: BZD use might increase the risk of acute respiratory failure in OSA patients.

Pneumocystis jirovecii pneumonia induced by low-dose methotrexate in a patient with chronic urticaria.

Methotrexate has immunosuppressive effects and is administered for refractory chronic urticaria. We present a case of Pneumocystis jirovecii pneumonia in a patient with refractory chronic urticaria managed by low-dose weekly methotrexate treatment (total cumulative dose 195mg). Our study highlights the importance of providing prompt diagnosis and treatment of Pneumocystis jirovecii pneumonia in patients with chronic urticaria under methotrexate therapy.