Changes in respiratory infection trends during the COVID-19 pandemic in patients with haematologic malignancy.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has changed respiratory infection patterns globally. However, its impact on community-acquired pneumonia (CAP) in high-risk patients with haematological malignancies (HM) is uncertain. We aimed to examine how community-acquired pneumonia aetiology in patients with haematological malignancies changed during the COVID-19 pandemic. METHODS: This was a retrospective study that included 524 patients with haematological malignancies hospitalised with community-acquired pneumonia between March 2018 and February 2022. Patients who underwent bronchoscopy within 24 h of admission to identify community-acquired pneumonia aetiology were included. Data on patient characteristics, laboratory findings, and results of bronchioalveolar lavage fluid cultures and polymerase chain reaction tests were analysed and compared to identify changes and in-hospital mortality risk factors. RESULTS: Patients were divided into the 'pre-COVID-19 era' (44.5%) and 'COVID-19 era' (55.5%) groups. The incidence of viral community-acquired pneumonia significantly decreased in the COVID-19 era, particularly for influenza A, parainfluenza, adenovirus, and rhinovirus (pre-COVID-19 era vs. COVID-19 era: 3.0% vs. 0.3%, P = 0.036; 6.5% vs. 0.7%, P = 0.001; 5.6% vs. 1.4%, P = 0.015; and 9.5% vs. 1.7%, P < 0.001, respectively), whereas that of bacterial, fungal, and unknown community-acquired pneumonia aetiologies remain unchanged. Higher Sequential Organ Failure Assessment scores and lower platelet counts correlated with in-hospital mortality after adjusting for potential confounding factors. CONCLUSIONS: In the COVID-19 era, the incidence of community-acquired pneumonia with viral aetiologies markedly decreased among patients with haematological malignancies, with no changes in the incidence of bacterial and fungal pneumonia. Further studies are required to evaluate the impact of COVID-19 on the prognosis of patients with haematological malignancies and community-acquired pneumonia.

Management of Immunosuppressive Therapy in Kidney Transplant Recipients with Sepsis: A Multicenter Retrospective Study.

BACKGROUND: Up to 6% of kidney transplant recipients (KTRs) experience life-threatening complications requiring intensive care unit (ICU) admission, and one of the most common medical complications requiring ICU admission is infection. This study aimed to evaluate the effect of immunosuppressive therapy (IST) modification on prognosis of KTRs with sepsis. METHODS: We conducted a multicenter retrospective study in 4 university-affiliated hospitals to evaluate the effect of adjusting the IST in KTRs with sepsis. Only patients who either maintained IST after ICU admission or those who underwent immediate (within 24 h of ICU admission) reduction or withdrawal of IST following ICU admission were included in this study. "Any reduction" was defined as a dosage reduction of any IST or discontinuation of at least 1 IST. "Complete withdrawal of IST" was defined as concomitant discontinuation of all ISTs, except steroids. RESULTS: During the study period, 1596 of the KTRs were admitted to the ICU, and 112 episodes of sepsis or septic shock were identified. The overall in-hospital mortality rate was 35.7%. In-hospital mortality was associated with higher sequential organ failure assessment score, simplified acute physiology score 3, non-identical human leukocyte antigen relation, presence of septic shock, and complete withdrawal of IST. After adjusting for potential confounding factors, complete withdrawal of IST remained significantly associated with in-hospital mortality (adjusted coefficient, 1.029; 95% confidence interval, 0.024-2.035) and graft failure (adjusted coefficient, 2.001; 95% confidence interval, 0.961-3.058). CONCLUSIONS: Complete IST withdrawal was common and associated with worse outcomes in critically ill KTRs with sepsis.

Clinical relevance of false-negative interferon-gamma release assays in patients with tuberculous pleurisy in an intermediate tuberculosis burden country.

Background: There have been few studies to verify factors associated with a false-negative interferon-gamma release assay (IGRA) in patients with tuberculous pleurisy. We investigated the clinical relevance of false-negative results of the blood QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and its risk factors in patients diagnosed with pleural tuberculosis (TB). Methods: Medical records of 650 pleural TB patients in a tertiary hospital between January 2009 and December 2020 were reviewed retrospectively. Patients who underwent the blood QFT-GIT assay and pleural fluid analysis before starting anti-TB medication were included. Results: Of 199 patients with pleural TB who were performed QFT-GIT assay, 36 (18.1%) were false-negative results. These patients tended to be older than those with a positive result (P=0.060). The QFT-GIT-false-negative group of had significantly more comorbidities such as end-stage renal disease (ESRD), haematological cancer or pneumoconiosis than the QFT-GIT-positive group. Hypoproteinaemia and pH >6 in pleural fluid were associated with a false-negative QFT-GIT. Of the 199 patients, 163 (81.9%) were cured or completed anti-TB treatment; 13 patients (6.5%) died. The QFT-GIT-negative patients had significantly worse outcomes including mortality [unfavourable outcome: 33.3% (12/36 patients) in QFT-GIT-negative groups vs. 14.7% (24/163 patients) in QFT-GIT-positive groups, P<0.017; overall mortality: 16.7% (6/36 patients) vs. 4.3% (7/163 patients), respectively, P<0.015]. Conclusions: In pleural TB, a false-negative QFT-GIT result was 18.1% in a country of intermediate TB incidence. This discordant result in GFT-GIT was associated with ESRD, pneumoconiosis, hypoproteinaemia and a poor outcome. Clinicians should keep in mind the possibility of false-negativity in the blood IGRA test, especially in specific situations and its impact on TB outcome in managing patients with pleural TB.

Prognostic Value of Estimated Plasma Volume Status in Patients With Sepsis.

BACKGROUND: In patients with sepsis, timely risk stratification is important to improve prognosis. Although several clinical scoring systems are currently being used to predict the outcome of sepsis, but they all have certain limitations. The objective of this study was to evaluate the prognostic value of estimated plasma volume status (ePVS) in patients admitted to the intensive care unit (ICU) with sepsis or septic shock. METHODS: This single-center, prospective observational study, included 100 patients admitted to the ICU with sepsis or septic shock. Informed consent, blood samples, and co-morbidity data were obtained from the patients on admission, and the severity of sepsis was recorded. The primary outcome was in-hospital mortality and multivariable logistic regression analysis was used to adjust for confounding factors to determine the significant prognostic factor. RESULTS: The in-hospital mortality was 47%. The ePVS was correlated with the amount of total fluids administered 24 hours before the ICU admission. The mean ePVS in patients who died was higher than in those who survived (7.7 ± 2.1 dL/g vs. 6.6 ± 1.6 dL/g, P = 0.003). To evaluate the utility of ePVS in predicting in-hospital mortality, a receiver operating characteristic curve was produced. Sensitivity and specificity were optimal at a cut-off point of 7.09 dL/g, with an area under the curve of 0.655. In the multivariate analysis, higher ePVS was significantly associated with higher in-hospital mortality (adjusted odds ratio, 1.39; 95% confidence interval, 1.04-1.85, P = 0.028). The Kaplan-Meier curve showed that an ePVS value above 7.09 was associated with an increased risk of in-hospital mortality compared with the rest of the population (P = 0.004). CONCLUSION: The ePVS was correlated with the amount of intravenous fluid resuscitation and may be used as a simple and novel prognostic factor in patients with sepsis or septic shock who are admitted to the ICU.

Case report: atrial septostomy as a bridge to lung transplantation in a patient with venovenous extracorporeal membrane oxygenation.

INTRODUCTION: Advances in critical care management have led to the recent increase in the use of extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation (LT). Patients with respiratory failure requiring venovenous ECMO usually experience progressive right ventricular (RV) failure. Diagnosis and treatment of RV failure during ECMO are essential for improving the prognosis of patients. PATIENT CONCERNS: A 28-year-old female patient underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor for acute myeloid leukemia presenting with progressive dyspnea. DIAGNOSES: Computed tomography revealed multifocal patchy peribronchial and subpleural ground-glass opacities in both lungs, and the patient was clinically diagnosed with cryptogenic organizing pneumonia. INTERVENTIONS AND OUTCOMES: Despite intensifying systemic corticosteroid therapy, her symptoms deteriorated, and mechanical ventilation and ECMO were applied. During treatment, her respiratory failure continued to progress, and systemic hypotension developed. An echocardiogram showed evidence of RV failure, and percutaneous atrial septostomy was performed for RV decompression. After a balloon atrial septostomy was performed, RV failure of the patient improved, and LT was successfully performed. LESSONS: We report the first case of atrial septostomy as a successful bridge to LT in a HSCT recipient with venovenous ECMO. Atrial septostomy could be an option for management of RV failure during ECMO. Further studies need to be conducted to validate the effect of atrial septostomy in patients with RV failure during ECMO.

Retroactive memory interference reduces false positive outcomes of informed innocents in the P300-based concealed information test.

In the Concealed Information Test (CIT), differential responses between crime-relevant and crime-irrelevant items are indicative of concealed knowledge of a crime, and are used to classify an individual as either "guilty" or "innocent". However, when crime-relevant items are leaked before the test, an innocent examinee can exhibit enhanced responses to the crime-relevant items, thus causing such examinee to be wrongly classified as guilty. In an attempt to solve this problem, we examined the role of retroactive memory interference (RI) in differentiating informed innocents from guilty participants, using a P300-based CIT. Participants acquired crime-related knowledge either by committing a mock crime (guilty group) or reading a paper that described a mock crime (informed innocent group). Subsequently, the participants within each condition were randomly assigned to either an RI group, where they were exposed to new crime-related details before the CIT, or a control group. We found an interaction between guilty and RI groups: in the guilty group, there was a significant difference in P300 amplitude between the probe and irrelevant items, regardless of RI manipulation, whereas in the informed innocent group, a difference in P300 amplitude between the probe and irrelevant items was significant only in the control group, but not in the RI group. This led to an improved detection rate of the informed innocents (31% for the control group vs. 77% for the RI group). These results suggest that RI manipulation could be used to reduce the false positive outcomes of informed innocents without affecting the detection rate of guilty participants.

Prevalence and clinical course of upper airway respiratory virus infection in critically ill patients with hematologic malignancies.

BACKGROUND: The clinical significance of upper airway respiratory virus (RV) detection in patients with hematologic malignancies remains unclear. We aimed to investigate the association between upper airway RV detection and prognosis in critically ill patients with hematologic malignancies. METHODS: This retrospective observational study included 331 critically ill patients with hematologic malignancies who presented respiratory symptoms and their nasopharyngeal swab was tested using a multiplex PCR assay between January 2017 and December 2018. A logistic regression model was used to adjust for potential confounding factors in the association between assay positivity and in-hospital mortality. RESULTS: Among the 331 analyzed patients, RVs were detected in 29.0%. The overall mortality rates in the intensive care unit and hospital were 56.8% and 65.9%, respectively. Positive upper airway RV detection was associated with relapsed hematologic malignancies, higher level of C-reactive protein, and prior use of high dose steroids and anti-cancer chemotherapeutic drugs. Furthermore, it was independently associated with in-hospital mortality (adjusted odds ratio, 2.36; 95% confidence interval, 1.23 to 4.54). Among different RVs, parainfluenza virus was more prevalent among patients who died in the hospital than among those who survived (11.5% vs. 3.5%, P = 0.027). CONCLUSIONS: RV detection in the upper respiratory tract was relatively common in our cohort and was significantly associated with a poor prognosis. Thus, it can be used as a predictor of prognosis. Moreover, RV presence in the upper respiratory tract should be examined in patients who have previously been prescribed with high dose corticosteroids and anti-cancer drugs.

Comparison of SARS-CoV-2 Antibody Responses and Seroconversion in COVID-19 Patients Using Twelve Commercial Immunoassays.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays have high clinical utility in managing the pandemic. We compared antibody responses and seroconversion of coronavirus disease 2019 (COVID-19) patients using different immunoassays. METHODS: We evaluated 12 commercial immunoassays, including three automated chemiluminescent immunoassays (Abbott, Roche, and Siemens), three enzyme immunoassays (Bio-Rad, Euroimmun, and Vircell), five lateral flow immunoassays (Boditech Med, SD biosensor, PCL, Sugentech, and Rapigen), and one surrogate neutralizing antibody assay (GenScript) in sequential samples from 49 COVID-19 patients and 10 seroconversion panels. RESULTS: The positive percent agreement (PPA) of assays for a COVID-19 diagnosis ranged from 84.0% to 98.5% for all samples (>14 days after symptom onset), with IgM or IgA assays showing higher PPAs. Seroconversion responses varied across the assay type and disease severity. Assays targeting the spike or receptor-binding domain protein showed a tendency for early seroconversion detection and higher index values in patients with severe disease. Index values from SARS-CoV-2 binding antibody assays (three automated assays, one LFIA, and three EIAs) showed moderate to strong correlations with the neutralizing antibody percentage (r=0.517-0.874), and stronger correlations in patients with severe disease and in assays targeting spike protein. Agreement among the 12 assays was good (74.3%-96.4%) for detecting IgG or total antibodies. CONCLUSIONS: Positivity rates and seroconversion of SARS-CoV-2 antibodies vary depending on the assay kits, disease severity, and antigen target. This study contributes to a better understanding of antibody response in symptomatic COVID-19 patients using currently available assays.

The Association between Dynamic Changes in Serum Presepsin Levels and Mortality in Immunocompromised Patients with Sepsis: A Prospective Cohort Study.

Presepsin is a subtype of soluble CD14 that is increased in the blood of septic patients. We investigated the role of dynamic changes in serum presepsin levels in critically ill, immunocompromised patients with sepsis. This is a prospective cohort study that included 119 adult patients admitted to the intensive care unit (ICU). Presepsin level was measured on day 1 and day 3 after ICU admission. The primary outcome was in-hospital mortality. In immunocompromised patients, presepsin levels on day 1 were higher in patients with sepsis than those in patients without sepsis. The area under the curve (AUC) of presepsin for diagnosing sepsis in immunocompromised patients was 0.87, which was comparable with that of procalcitonin (AUC, 0.892). Presepsin levels on day 3 were higher in patients who died in the hospital than in those who survived. In immunocompromised patients who died in the hospital, presepsin levels on day 3 were significantly higher than those on day 1. In the multivariate analysis, ΔPresepsin+ alone was independently correlated with in-hospital mortality in immunocompromised patients. These findings suggest that dynamic changes in presepsin levels between day 1 and day 3 are associated with in-hospital mortality in patients with sepsis, especially in immunocompromised patients.

Mortality prediction of serum neutrophil gelatinase-associated lipocalin in patients requiring continuous renal replacement therapy.

BACKGROUND/AIMS: We investigated whether serum neutrophil gelatinase-associated lipocalin (NGAL) can predict mortality in patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT). METHODS: This study enrolled 169 patients who underwent serum NGAL testing at CRRT initiation from June 2017 to January 2019. The predictive power of serum NGAL level for 28-day mortality was compared to the Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score and Sequential Organ Failure Assessment (SOFA) score via area under the receiver operating characteristic curve (AuROC) value. RESULTS: There were 55 survivors and 114 non-survivors at 28 days post-CRRT initiation. Median serum NGAL level was significantly higher in the non-survivor group than in the survivor group (743.0 ng/mL vs. 504.0 ng/mL, p = 0.003). The AuROC value of serum NGAL level was 0.640, which was lower than APACHEII score and SOFA score values (0.767 and 0.715, respectively). However, in the low APACHE-II score group (< 27.5), AuROC value of serum NGAL was significantly increased (0.698), and it was an independent risk factor for 28 day-mortality (hazard ratio, 2.405; 95% confidence interval, 1.209 to 4.783; p = 0.012). CONCLUSION: In patients with AKI requiring CRRT, serum NGAL levels may be useful for predicting short-term mortality in those with low APACHE-II scores.

Normothermia in Patients With Sepsis Who Present to Emergency Departments Is Associated With Low Compliance With Sepsis Bundles and Increased In-Hospital Mortality Rate.

OBJECTIVES: To investigate the impact of normothermia on compliance with sepsis bundles and in-hospital mortality in patients with sepsis who present to emergency departments. DESIGN: Retrospective multicenter observational study. PATIENTS: Nineteen university-affiliated hospitals of the Korean Sepsis Alliance participated in this study. Data were collected regarding patients who visited emergency departments for sepsis during the 1-month period. The patients were divided into three groups based on their body temperature at the time of triage in the emergency department (i.e., hypothermia [< 36°C] vs normothermia [36-38°C] vs hyperthermia [> 38°C]). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 64,021 patients who visited emergency departments, 689 with community-acquired sepsis were analyzed (182 hyperthermic, 420 normothermic, and 87 hypothermic patients). The rate of compliance with the total hour-1 bundle was lowest in the normothermia group (6.0% vs 9.3% in hyperthermia vs 13.8% in hypothermia group; p = 0.032), the rate for lactate measurement was lowest in the normothermia group (62.1% vs 73.1% vs 75.9%; p = 0.005), and the blood culture rate was significantly lower in the normothermia than in the hyperthermia group (p < 0.001). The in-hospital mortality rates in the hyperthermia, normothermia, and hypothermia groups were 8.5%, 20.6%, and 30.8%, respectively (p < 0.001), but there was no significant association between compliance with sepsis bundles and in-hospital mortality. However, in a multivariate analysis, compared with hyperthermia, normothermia was significantly associated with an increased in-hospital mortality (odds ratio, 2.472; 95% CI, 1.005-6.080). This association remained significant even after stratifying patients by median lactate level. CONCLUSIONS: Normothermia at emergency department triage was significantly associated with an increased risk of in-hospital mortality and a lower rate of compliance with the sepsis bundle. Despite several limitations, our findings suggest a need for new strategies to improve sepsis outcomes in this group of patients.

Use of intrapulmonary administration of thrombin in hematological malignancy patients with alveolar haemorrhage: A case series.

INTRODUCTION: Alveolar hemorrhage (AH) is characterized by the acute onset of alveolar bleeding and hypoxemia and can be fatal. Thrombin has been widely used to achieve coagulation and hemostasis. However, the efficacy of thrombin in patients with AH is unclear. Thus, this study aimed to evaluate the efficacy of thrombin administration in patients with hematological malignancy and AH. PATIENT CONCERNS AND DIAGNOSES: This retrospective study included 15 hematological malignancy patients (8 men and 7 women; mean age 47.7 ±â€Š17.3 years) with AH who were administered intrapulmonary thrombin between March 2013 and July 2018. INTERVENTIONS AND OUTCOMES: All patients received bovine-origin thrombin (1000 IU/ml, Reyon Pharmaceutical Co., Ltd., Seoul, Korea) via a fiberoptic bronchoscope. A maximum of 15 ml of thrombin was injected via the working channel to control bleeding. The ability of thrombin to control bleeding was assessed. Additionally, the change in the PaO2/FiO2 (PF) ratio after intrapulmonary thrombin administration was evaluated. Intrapulmonary thrombin was administered a minimum of 3 days after starting mechanical ventilation in all patients, and it immediately controlled the active bleeding in 13 of 15 patients (86.7%). However, AH relapse was noted in 3 of the 13 patients (23.1%). The PF ratio improved in 10 of 15 patients (66.6%), and the mean PF ratio was significantly higher after thrombin administration than before administration (P = .03). No adverse thromboembolic complications or systemic adverse events were observed. CONCLUSION: Thrombin administration was effective in controlling bleeding in hematological malignancy patients with AH. Intrapulmonary thrombin administration might be a good therapeutic option for treating AH.

Utilization of a rapid response team and associated outcomes in patients with malignancy.

BACKGROUND: Recent advances in diagnosis and treatment have improved long-term outcomes in cancer patients. As a result, the requirement for a rapid response team (RRT) for cancer patients is also increasing. This study aimed to analyze utilization of an RRT and the associations between related factors and mortality in a population of cancer patients. METHODS: This retrospective cohort study included hospitalized patients at a single academic medical center in Seoul, Korea, who required RRT activation during a 6-year period from June 2013 to December 2018. RESULTS: Overall, 164 of the 457 patients who met the above criteria were cancer patients, and they had a significantly higher Charlson comorbidity score than the non-cancer patients (5.0 vs. 7.0, P<0.001). A significantly larger proportion of cancer patients required intensive care unit transfer (51.8% vs. 41.0%, P=0.032). Cancer patients also had significantly higher in-hospital mortality compared with other patients (39.6% vs. 10.9%, P<0.001). Furthermore, presence of cancer was independently associated with in-hospital mortality (adjusted odds ratio [OR], 2.09; 95% confidence interval [CI], 1.11 to 3.93). Among cancer patients, higher Acute Physiology and Chronic Health Evaluation (APACHE) II at the time of RRT activation was significantly associated with in-hospital mortality regardless of malignancy (adjusted OR, 1.08; 95% CI, 1.01 to 1.15). CONCLUSIONS: Cancer patients requiring RRT activation have significantly higher rates of inhospital mortality than patients not using RRT. Higher severity score at the time of RRT activation in patients with malignancy was significantly associated with in-hospital mortality.

Characteristics, management and clinical outcomes of patients with sepsis: a multicenter cohort study in Korea.

BACKGROUND: Mortality rates associated with sepsis have increased progressively in Korea, but domestic epidemiologic data remain limited. The objective of this study was to investigate the characteristics, management and clinical outcomes of sepsis patients in Korea. METHODS: This study is a multicenter retrospective cohort study. A total of 64,021 adult patients who visited an emergency department (ED) within one of the 19 participating hospitals during a 1-month period were screened for eligibility. Among these, patients diagnosed with sepsis based on the third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) were included in the study. RESULTS: Using the Sepsis-3 criteria, 977 sepsis patients were identified, among which 36.5% presented with septic shock. The respiratory system (61.8%) was the most common site of infection. The pathogen involved was identified in 444 patients (45.5%) and multi-drug resistance (MDR) pathogens were isolated in 171 patients. Empiric antibiotic therapy was appropriate in 68.6% of patients, but the appropriateness was significantly reduced in infections associated with MDR pathogens as compared with non-MDR pathogens (58.8% vs. 76.0%, P<0.001). Hospital mortality was 43.2% and 18.5% in sepsis patients with and without shock, respectively. Of the 703 patients who survived to discharge, 61.5% were discharged to home and 38.6% were transferred to other hospitals or facilities. CONCLUSIONS: This study found the prevalence of sepsis in adult patients visiting an ED in Korea was 1.5% (15.2/1,000 patients). Patients with sepsis, especially septic shock, had a high mortality and were often referred to step-down centers after acute and critical care.

Clinical implications of discrepant results between genotypic MTBDRplus and phenotypic Löwenstein-Jensen method for isoniazid or rifampicin drug susceptibility tests in tuberculosis patients.

BACKGROUND: The widespread use of molecular, genotypic drug susceptibility tests (DSTs) for antituberculosis (anti-TB) drugs has led to the dilemma of interpreting discordant results between genotypic and conventional, phenotypic DSTs. We investigated the clinical characteristics, including treatment patterns and outcomes, of TB patients with a genotype-phenotype discrepancy in susceptibility to isoniazid (INH) or rifampicin (RIF). METHODS: We retrospectively reviewed the medical records of TB patients who had results for 2 DSTs (genotypic method, MTBDRplus test for INH and RIF, and phenotypic method) treated between August 2010 and October 2016 in a tertiary university hospital. RESULTS: Among 1,069 TB patients, 63 (5.9%) had discrepant results for the 2 DSTs. Of the 57 multidrug-resistant (MDR) TB cases diagnosed by either DST, 18 (31.6%) showed discordant results for INH or RIF. The most frequent pattern of discordance was genotypic susceptibility with phenotypic resistance to INH. RIF-discordant subjects with genotypic resistance were more likely to have been exposed previously to anti-TB drugs and to have an MDR TB diagnosis and concurrent INH resistance. Forty-five of the 54 patients managed in our hospital (83.3%) had a favorable outcome with a mean treatment duration of 14.0 months. Ten of the 16 INH-discrepant patients with a genotypic mutation continued taking INH, but more than half patients in the RIF-discrepant group (8/14) with a genotypic mutation discontinued taking RIF. CONCLUSIONS: Despite the low frequency, discordant results were obtained between the genotypic and phenotypic DSTs for INH or RIF, especially for patients with MDR TB or INH resistance. Furthermore, it seemed that RIF discrepancy with a genotypic mutation might have a greater impact on the clinical outcome than INH discrepancy.

Expression of Muscarinic Receptors and the Effect of Tiotropium Bromide in Aged Mouse Model of Chronic Asthma.

BACKGROUND: Efficacy and safety of tiotropium bromide, a muscarinic receptor antagonist, in treatment of asthma have been reported. However, its effect on airway remodeling in chronic asthma of the elderly has not been clearly verified. The objective of this study was to investigate the effect of tiotropium and expression of muscarinic receptors as its related mechanism in an aged mouse model of chronic asthma with airway remodeling. METHODS: BALB/c female mice age 6 weeks, 9 and 15 months were sensitized and challenged with ovalbumin (OVA) for three months. Tiotropium bromide was administered during the challenge period. Airway hyperresponsiveness (AHR) and pulmonary inflammation were measured. Parameters of airway remodeling, and expression levels of M2 and M3 receptors were examined. RESULTS: Total cell with eosinophils, increased in the OVA groups by age, was decreased significantly after treatment with tiotropium bromide, particularly in the age group of 15 months. AHR and levels of interleukin (IL)-4, IL-5, and IL-13 were decreased, after tiotropium administration. In old aged group of 9- and 15-months-treated groups, hydroxyproline contents and levels of α-smooth muscle actin were attenuated. Tiotropium enhanced the expression of M2 but decreased expression of M3 in all aged groups of OVA. CONCLUSION: Tiotropium bromide had anti-inflammatory and anti-remodeling effects in an aged mouse model of chronic asthma. Its effects seemed to be partly mediated by modulating expression M3 and M2 muscarinic receptors. Tiotropium may be a beneficial treatment option for the elderly with airway remodeling of chronic asthma.

Clinical significance of Glasgow Prognostic Score in patients with tuberculous pleurisy.

BACKGROUND: The Glasgow Prognostic Score (GPS) reflects the host systemic inflammatory response and is a validated, independent prognostic factor for various malignancies. We investigated the clinical significance of the GPS in patients with tuberculosis (TB) pleurisy, focusing on treatment outcomes including paradoxical response (PR). METHODS: This was a retrospective study performed between January 2010 and December 2015 in two referral and university hospitals in South Korea, with intermediate incidences of TB. In all, 462 patients with TB pleurisy were registered in the study. The patients were classified into three groups based on GPS score, as follows: (I) GPS of 2, elevated CRP level (>1.0 mg/dL) and hypoalbuminemia (<3.5 g/dL); (II) GPS of 1, elevated CRP level or hypoalbuminemia; and (III) GPS of 0, neither elevated CRP level nor hypoalbuminemia. RESULTS: A total of 367 patients with TB pleurisy were finally included. PR occurred in 102 (27.8%) patients after a mean of 75 days following initiation of anti-TB treatment. The proportion of PR occurrence was significantly lower in the GPS 2 group (P=0.007). Successful treatment outcomes including cure and completion were also significantly lower in the GPS 2 group (P=0.001), while all-cause mortality and TB-specific mortality were higher in the GPS 2 group (P=0.001 and <0.001, respectively). Old age over than 65 years old was an independent predicting factor for high mortality and lower PR occurrence. However, the TB relapse rate was not different among the three GPS groups. CONCLUSIONS: Higher GPS value and elderly age were identified as prognostic factors for poor outcomes in TB pleurisy and as predicting factors for lower PR occurrence. More prospective studies are needed to clarify the utility of GPS in patients with TB pleurisy.

Characteristics and Clinical Outcomes of Critically Ill Cancer Patients Admitted to Korean Intensive Care Units.

BACKGROUND: The objective of this study was to investigate the characteristics and clinical outcomes of critically ill cancer patients admitted to intensive care units (ICUs) in Korea. METHODS: This was a retrospective cohort study that analyzed prospective collected data from the Validation of Simplified Acute Physiology Score 3 (SAPS3) in Korean ICU (VSKI) study, which is a nationwide, multicenter, and prospective study that considered 5,063 patients from 22 ICUs in Korea over a period of 7 months. Among them, patients older than 18 years of age who were diagnosed with solid or hematologic malignancies prior to admission to the ICU were included in the present study. RESULTS: During the study period, a total of 1,762 cancer patients were admitted to the ICUs and 833 of them were deemed eligible for analysis. Six hundred fifty-eight (79%) had solid tumors and 175 (21%) had hematologic malignancies, respectively. Respiratory problems (30.1%) was the most common reason leading to ICU admission. Patients with hematologic malignancies had higher Sequential Organ Failure Assessment (12 vs. 8, P<0.001) and SAPS3 (71 vs. 69, P<0.001) values and were more likely to be associated with chemotherapy, steroid therapy, and immunocompromised status versus patients with solid tumors. The use of inotropes/vasopressors, mechanical ventilation, and/or continuous renal replacement therapy was more frequently required in hematologic malignancy patients. Mortality rates in the ICU (41.7% vs. 24.6%, P<0.001) and hospital (53.1% vs. 38.6%, P=0.002) were higher in hematologic malignancy patients than in solid tumor patients. CONCLUSIONS: Cancer patients accounted for one-third of all patients admitted to the studied ICUs in Korea. Clinical characteristics were different according to the type of malignancy. Patients with hematologic malignancies had a worse prognosis than did patients with solid tumor.

Inhibiting IGF-1R attenuates cell proliferation and VEGF production in IGF-1R over-expressing EGFR mutant non-small cell lung cancer cells.

PURPOSE: The aim of the present study was to demonstrate the role of insulin-like growth factor-1 receptor (IGF-1R) tyrosine kinase inhibitors (TKIs) in IGF-1R expressed epidermal growth factor receptor (EGFR) mutant cells. MATERIALS AND METHODS: Human lung adenocarcinoma PC9, HCC827, and H1975 cells were exposed to a combination of IGF-1, gefitinib, or linsitinib. Cell viability was assessed by the MTT assay. The expression of EGFR, IGF-1R, AKT, extracellular regulated kinases 1 and 2 (ERK1/2), cleaved poly ADP ribose polymerase (PARP), cleaved caspase 3, and hypoxia-inducible factor (HIF)-1α were measured by Western blot. The concentrations of vascular endothelial growth factor (VEGF) were measured using an enzyme-linked immunosorbent assay kit. RESULTS: Cell growth in PC9 and HCC827 cells was synergistically suppressed by co-treatment with gefitinib and linsitinib. Gefitinib did not affect H1975 cell growth; however, linsitinib suppressed cell proliferation. Co-treatment with gefitinib and linsitinib inhibited pAKT and pERK, and linsitinib treatment profoundly reduced IGF-1-induced pIGF-1R expression in PC9 and HCC827 cells. Dual treatment increased the number of Annexin-V-positive HCC827 and H1975 cells, and expression of cleaved caspase 3 and cleaved PARP increased in H1975 cells following linsitinib treatment. Gefitinib inhibited HIF-1α and VEGF expression in HCC827 cells, and linsitinib inhibited VEGF production in H1975 cells. CONCLUSION: IGF-1R TKIs had modest anti-tumor efficacy and their effects were explained by blocking the EGFR and IGF-1R pathway in IGF-1R expressing EGFR-sensitive cells. IGF-1R TKI had pro-apoptotic activity and inhibited cellular growth in EGFR-resistant cells.

Epidemiology and Clinical Characteristics of Rapid Response Team Activations.

BACKGROUND: To ensure patient safety and improvements in the quality of hospital care, rapid response teams (RRTs) have been implemented in many countries, including Korea. The goal of an RRT is early identification and response to clinical deterioration in patients. However, there are differences in RRT systems among hospitals and limited data are available. METHODS: In Seoul St. Mary's Hospital, the St. Mary's Advanced Life Support Team was implemented in June 2013. We retrospectively reviewed the RRT activation records of 287 cases from June 2013 to December 2016. RESULTS: The median response time and median modified early warning score were 8.6 minutes (interquartile range, 5.6 to 11.6 minutes) and 5.0 points (interquartile range, 4.0 to 7.0 points), respectively. Residents (35.8%) and nurses (59.1%) were the main activators of the RRT. Interestingly, postoperative patients account for a large percentage of the RRT activation cases (69.3%). The survival rate was 83.6% and survival was mainly associated with malignancy, Acute Physiology and Chronic Health Evaluation-II score, and the time from admission to RRT activation. RRT activation with screening showed a better outcome compared to activation via a phone call in terms of the intensive care unit admission rate and length of hospital stay after RRT activation. CONCLUSIONS: Malignancy was the most important factor related to survival. In addition, RRT activation with patient screening showed a better outcome compared to activation via a phone call. Further studies are needed to determine the effective screening criteria and improve the quality of the RRT system.