Lung Organoid on a Chip: A New Ensemble Model for Preclinical Studies

The lung is a complex organ comprising a branched airway that connects the large airway and millions of terminal gas-exchange units. Traditional pulmonary biomedical research by using cell line model system have limitations such as lack of cellular heterogeneity, animal models also have limitations including ethical concern, race-to-race variations, and physiological differences found in vivo. Organoids and on-a-chip models offer viable solutions for these issues.Organoids are three-dimensional, self-organized construct composed of numerous cells derived from stem cells cultured with growth factors required for the maintenance of stem cells. On-a-chip models are biomimetic microsystems which are able to customize to use microfluidic systems to simulate blood flow in blood channels or vacuum to simulate human breathing. This review summarizes the key components and previous biomedical studies conducted on lung organoids and lung-on-a-chip models, and introduces potential future applications. Considering the importance and benefits of these model systems, we believe that the system will offer better platform to biomedical researchers on pulmonary diseases, such as emerging viral infection, progressive fibrotic pulmonary diseases, or primary or metastatic lung cancer.

Guidelines for Manufacturing and Application of Organoids: Lung

The objective of standard guideline for utilization of human lung organoids is to provide the basic guidelines required for the manufacture, culture, and quality control of the lung organoids for use in non-clinical efficacy and inhalation toxicity assessments of the respiratory system. As a first step towards the utilization of human lung organoids, the current guideline provides basic, minimal standards that can promote development of alternative testing methods, and can be referenced not only for research, clinical, or commercial uses, but also by experts and researchers at regulatory institutions when assessing safety and efficacy.

The serotype-specific prevalence of pneumococci in hospitalized pneumonia patients with COPD: a prospective, multi-center, cohort study

Background/Aims@#The overall incidence of pneumococcal pneumonia is declining. However, the change in the pathogenic distribution of community-acquired pneumonia (CAP) in chronic obstructive pulmonary disease (COPD) patients and the serotype specificity of Streptococcus pneumoniae have not been evaluated in the post-era of pneumococcal vaccination in Korea. @*Methods@#We conducted a prospective, multi-center, cohort study from seven University-affiliated hospitals. The primary objective was the identification of serotype-specific prevalence of pneumococcal pneumonia in COPD patients hospitalized for CAP. For the purpose, we conducted serotype-specific urine antigen detection (SS-UAD) assays for S. pneumoniae. The secondary objectives were other clinical characteristics of pneumonia including vaccination status. @*Results@#The total number of participants was 349. Most of them were male (95.1%) with old ages (75.55 ± 8.59 y). The positive rate for S. pneumoniae was 9.2% with SS-UAD assay and the common serotypes were 22F, 6A, and 6B. In the sputum, Pseudomonas aeruginosa (5.0%) and Haemophilus influenzae (4.0%) were common pathogens. The vaccination rate was 78.8%, 53.0%, and 25.8% for influenza, pneumococcal polysaccharide vaccine 23 (PPV 23), and pneumococcal protein- conjugated vaccine 13 (PCV 13), respectively. Thirteen patients died during hospitalization (mortality rate; 3.7%). There was no difference in the respective rate of influenza vaccination (79.2% vs. 69.2%, p = 0.288) and PCV 13 vaccination (25.6% vs. 30.8%, p = 0.443) between survivors and the deceased. @*Conclusions@#Serotypes 22F, 6A, and 6B, which are covered either by PPV 23 or by PCV 13, are still common pneumococcal serotypes in COPD pneumonia in the post-vaccination era in Korea.

Subtype-Based Microbial Analysis in Non-small Cell Lung Cancer / 결핵및호흡기질환

Background@#The human lung serves as a niche for a unique and dynamic bacterial community related to the development and aggravation of multiple respiratory diseases. Therefore, identifying the microbiome status is crucial to maintaining the microecological balance and maximizing the therapeutic effect on lung diseases. Therefore, we investigated the histological type-based differences in the lung microbiomes of patients with lung cancer. @*Methods@#We performed 16S rRNA sequencing to evaluate the respiratory tract microbiome present in bronchoalveolar lavage fluid. Patients with non-small cell lung cancer were stratified based on two main subtypes of lung cancer: adenocarcinoma and squamous cell carcinoma (SqCC). @*Results@#Among the 84 patients analyzed, 64 (76.2%) had adenocarcinoma, and 20 (23.8%) had SqCC. The α- and β-diversities showed significant differences between the two groups (p=0.004 for Chao1, p=0.001 for Simpson index, and p=0.011 for PERMANOVA). Actinomyces graevenitzii was dominant in the SqCC group (linear discriminant analysis [LDA] score, 2.46); the populations of Haemophilus parainfluenza (LDA score, 4.08), Neisseria subflava (LDA score, 4.07), Porphyromonas endodontalis (LDA score, 3.88), and Fusobacterium nucleatum (LDA score, 3.72) were significantly higher in the adenocarcinoma group. @*Conclusion@#Microbiome diversity is crucial for maintaining homeostasis in the lung environment, and dysbiosis may be related to the development and prognosis of lung cancer. The mortality rate was high, and the microbiome was not diverse in SqCC. Further large-scale studies are required to investigate the role of the microbiome in the development of different lung cancer types.

Antibiogram of Multidrug-Resistant Bacteria Based on Sepsis Onset Location in Korea: A Multicenter Cohort Study

Background@#Administration of adequate antibiotics is crucial for better outcomes in sepsis. Because no uniform tool can accurately assess the risk of multidrug-resistant (MDR) pathogens, a local antibiogram is necessary. We aimed to describe the antibiogram of MDR bacteria based on locations of sepsis onset in South Korea. @*Methods@#We performed a prospective observational study of adult patients diagnosed with sepsis according to Sepsis-3 from 19 institutions (13 tertiary referral and 6 universityaffiliated general hospitals) in South Korea. Patients were divided into four groups based on the respective location of sepsis onset: community, nursing home, long-term-care hospital, and hospital. Along with the antibiogram, risk factors of MDR bacteria and drug-bug match of empirical antibiotics were analyzed. @*Results@#MDR bacteria were detected in 1,596 (22.7%) of 7,024 patients with gram-negative predominance. MDR gram-negative bacteria were more commonly detected in long-termcare hospital- (30.4%) and nursing home-acquired (26.3%) sepsis, whereas MDR grampositive bacteria were more prevalent in hospital-acquired (10.9%) sepsis. Such findings were consistent regardless of the location and tier of hospitals throughout South Korea. Patients with long-term-care hospital-acquired sepsis had the highest risk of MDR pathogen, which was even higher than those with hospital-acquired sepsis (adjusted odds ratio, 1.42; 95% confidence interval, 1.15–1.75) after adjustment of risk factors. The drug-bug match was lowest in patients with long-term-care hospital-acquired sepsis (66.8%). @*Conclusion@#Gram-negative MDR bacteria were more common in nursing home- and long-term-care hospital-acquired sepsis, whereas gram-positive MDR bacteria were more common in hospital-acquired settings in South Korea. Patients with long-term-care hospitalacquired sepsis had the highest the risk of MDR bacteria but lowest drug-bug match of initial antibiotics. We suggest that initial antibiotics be carefully selected according to the onset location in each patient.

Negative Conversion of Polymerase Chain Reaction and Clinical Outcomes according to the SARS-CoV-2 Variant in Critically Ill Patients with COVID-19 / 결핵및호흡기질환

Background@#Coronavirus disease 2019 (COVID-19) is an ongoing global public health threat and different variants of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been identified. This study aimed to analyse the factors associated with negative conversion of polymerase chain reaction (PCR) and prognosis in critically ill patients according to the SARS-CoV-2 variant. @*Methods@#This study retrospectively analysed 259 critically ill patients with COVID-19 who were admitted to the intensive care unit of a tertiary medical center between January 2020 and May 2022. The Charlson comorbidity index (CCI) was used to evaluate comorbidity, and a negative PCR test result within 2 weeks was used to define negative PCR conversion. The cases were divided into the following three variant groups, according to the documented variant of SARS-CoV-2 at the time of diagnosis: non-Delta (January 20, 2020–July 6, 2021), Delta (July 7, 2021– January 1, 2022), and Omicron (January 30, 2022–April 24, 2022). @*Results@#The mean age of the 259 patients was 67.1 years and 93 (35.9%) patients were female. Fifty (19.3%) patients were smokers, and 50 (19.3%) patients were vaccinated. The CCI (hazard ratio [HR], 1.555; p<0.001), vaccination (HR, 0.492; p=0.033), and Delta variant (HR, 2.469; p=0.002) were significant factors for in-hospital mortality. The Delta variant (odds ratio, 0.288; p=0.003) was associated with fewer negative PCR conversion; however, vaccination (p=0.163) and remdesivir (p=0.124) treatments did not. @*Conclusion@#The Delta variant of SARS-CoV-2 is associated with lower survival and negative PCR conversion. Contrary to expectations, vaccination and remdesivir may not affect negative PCR conversion in critically ill patients with COVID-19.

Anti-cancer effect of fenbendazole-incorporated PLGA nanoparticles in ovarian cancer / 부인종양

Objective@#Fenbendazole (FZ) has potential anti-cancer effects, but its poor water solubility limits its use for cancer therapy. In this study, we investigated the anti-cancer effect of FZ with different drug delivery methods on epithelial ovarian cancer (EOC) in both in vitro and in vivo models. @*Methods@#EOC cell lines were treated with FZ and cell proliferation was assessed. The effect of FZ on tumor growth in cell line xenograft mouse model of EOC was examined according to the delivery route, including oral and intraperitoneal administration. To improve the systemic delivery of FZ by converting fat-soluble drugs to hydrophilic, we prepared FZ-encapsulated poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles (FZ-PLGA-NPs). We investigated the preclinical efficacy of FZ-PLGA-NPs by analyzing cell proliferation, apoptosis, and in vivo models including cell lines and patient-derived xenograft (PDX) of EOC. @*Results@#FZ significantly decreased cell proliferation of both chemosensitive and chemoresistant EOC cells. However, in cell line xenograft mouse models, there was no effect of oral FZ treatment on tumor reduction. When administered intraperitoneally, FZ was not absorbed but aggregated in the intraperitoneal space. We synthesized FZ-PLGA-NPs to obtain water solubility and enhance drug absorption. FZ-PLGA-NPs significantly decreased cell proliferation in EOC cell lines. Intravenous injection of FZ-PLGA-NP in xenograft mouse models with HeyA8 and HeyA8-MDR significantly reduced tumor weight compared to the control group. FZ-PLGA-NPs showed anti-cancer effects in PDX model as well. @*Conclusion@#FZ-incorporated PLGA nanoparticles exerted significant anti-cancer effects in EOC cells and xenograft models including PDX. These results warrant further investigation in clinical trials.

Efficacy of lower dose pirfenidone for idiopathic pulmonary fibrosis in real practice: a retrospective cohort study

Background/Aims@#Pirfenidone slows the progression of idiopathic pulmonary fibrosis (IPF). We investigated its efficacy and safety in terms of dose and disease severity in real-world patients with IPF. @*Methods@#This multicenter retrospective cohort study investigated 338 patients treated with pirfenidone between July 2012 and March 2018. Demographics, pulmonary function, mortality, and pirfenidone-related adverse events were also investigated. Efficacy was analyzed according to pirfenidone dose and disease severity using linear mixed-effects models to assess the annual decline rate of forced vital capacity (FVC) and diffusing capacity of the lungs for carbon monoxide (DLCO). @*Results@#The mean %FVCpredicted and %DLCOpredicted values were 72.6% ± 13.1% and 61.4% ± 17.9%, respectively. The mean duration of pirfenidone treatment was 16.1 ± 9.0 months. In the standard dose (1,800 mg/day) group, the mean %FVCpredicted was −6.56% (95% confidence interval [CI], −9.26 to −3.87) per year before, but −4.43% (95% CI, −5.87 to −3.00) per year after treatment with pirfenidone. In the non-standard lower dose group, the mean %FVCpredicted was −4.96% (95% CI, −6.82 to −3.09) per year before, but −1.79% (95% CI, −2.75 to −0.83) per year after treatment with pirfenidone. The FVC decline rate was significantly reduced, regardless of the Gender-Age-Physiology (GAP) stage. Adverse events and mortality were similar across dose groups; however, they were more frequent in GAP stages II–III than in the stage I group. @*Conclusions@#The effect of pirfenidone on reducing disease progression of IPF persisted even with a consistently lower dose of pirfenidone.

The Distribution of Multidrugresistant Microorganisms and Treatment Status of Hospital-acquired Pneumonia/Ventilator-associated Pneumonia in Adult Intensive Care Units: a Prospective Cohort Observational Study

Background@#It is essential to determine the distribution of the causative microorganisms in the region and the status of local antibiotic resistance for the proper treatment of hospitalacquired pneumonia/ventilator-associated pneumonia (HAP/VAP). This study aimed to investigate the occurrence and causative strains of HAP/VAP, distribution of resistant bacteria, use of antibiotics, and the ensuing outcomes of patients in Korea. @*Methods@#A multicenter prospective observational cohort study was conducted among patients with HAP/VAP admitted to the medical intensive care unit of 5 tertiary referral centers between August 2012 and June 2015. Patients' demographic and clinical data were collected. @*Results@#A total of 381 patients were diagnosed with HAP/VAP. Their median age was 69 (59–76) years and 71% were males. A majority of the patients (88%) had late-onset (> 5 days) HAP/VAP. One-quarter of the patients (n = 99) had at least one risk factor for multidrug-resistant (MDR) pathogens, such as prior intravenous antibiotic use within the last 90 days. Microbiological specimens were mostly obtained noninvasively (87%) using sputum or endotracheal aspirates. Pathogens were identified in 235 (62%) of the 381 patients. The most common bacterial pathogen was Acinetobacter baumannii (n = 89), followed by Staphylococcus aureus (n = 52), Klebsiella pneumoniae (n = 25) and Pseudomonas aeruginosa (n = 22). Most of isolated A. baumannii (97%) and S. aureus (88%) were multidrug resistant. The most commonly used empirical antibiotic regimens were carbapenem-based antibiotics (38%), followed by extended-spectrum penicillin/ β-lactamase inhibitor (34%). Glycopeptide or linezolid were also used in combination in 54% of patients. The 28-day mortality rate of the patients with HAP/VAP was 30% and the 60-day mortality was 46%. Patients who used empirical antibiotics appropriately had significantly lower mortality rates than those who did not (28-day mortality: 25% vs. 40%, P = 0.032; 60-day mortality: 41% vs. 55%, P = 0.032, respectively). Administration of appropriate empirical antibiotics (odds ratio [OR], 0.282; confidence interval [CI], 0.092–0.859; P = 0.026), Day 7 treatment failure (OR, 4.515; CI, 1.545–13.192; P= 0.006), and APACHE II score on day 1 (OR, 1.326; CI, 0.988–1.779; P = 0.012) were the factors that determined the 28-day mortality in patients with HAP who had identified bacteria as pathogens. @*Conclusion@#In HAP/VAP patients, there was a large burden of MDR pathogens, and their associated mortality rate was high. Proper selection of empirical antibiotics was significantly associated with the patient's prognosis; however, there was a discrepancy between major pathogens and empirical antibiotic therapy.

The Impact of Mechanical Ventilation Duration on the Readmission to Intensive Care Unit: A Population-Based Observational Study / 결핵및호흡기질환

Background@#If the duration of mechanical ventilation (MV) is related with the intensive care unit (ICU) readmission must be clarified. The purpose of this study was to elucidate if prolonged MV duration increases ICU readmission rate. @*Methods@#The present observational cohort study analyzed national healthcare claims data from 2006 to 2015. Critically ill patients who received MV in the ICU were classified into five groups according to the MV duration: MV for <7 days, 7–13 days, 14–20 days, 21–27 days, and ≥28 days. The rate and risk of the ICU readmission were estimated according to the MV duration using the unadjusted and adjusted analyses. @*Results@#We found that 12,929 patients had at least one episode of MV in the ICU. There was a significant linear relationship between the MV duration and the ICU readmission (R2=0.85, p=0.025). The total readmission rate was significantly higher as the MV duration is prolonged (MV for <7 days, 13.9%; for 7–13 days, 16.7%; for 14–20 days, 19.4%; for 21–27 days, 20.4%; for ≥28 days, 35.7%; p<0.001). The analyses adjusted by covariables and weighted with the multinomial propensity scores showed similar results. In the adjusted regression analysis with a Cox proportional hazards model, the MV duration was significantly related to the ICU readmission (hazard ratio, 1.058 [95% confidence interval, 1.047–1.069], p<0.001). @*Conclusion@#The rate of readmission to the ICU was significantly higher in patients who received longer durations of the MV in the ICU. In the clinical setting, closer observation of patients discharged from the ICU after prolonged periods of MV is required.

Factors Predicting the Need for Early Surgical Intervention for Small Bowel Obstruction

Purpose@#Small bowel obstruction (SBO) is a common disease that requires hospitalization. The most common cause of SBO is postoperative adhesion. Delayed timing of operations in patients who need surgical intervention results in mortality or morbidity. A number of studies on SBO have established criteria for emergency surgery. However, few objective clinical parameters are available for screening patients who need a delayed operation. Therefore, we analyzed factors that affect the clinical course of SBO to select appropriate therapeutic plans for reducing the risk of complications in these patients. @*Methods@#We investigated the clinical characteristics of patients admitted to the surgery department of our hospital between January 1, 2015, and December 31, 2016, who were diagnosed with SBO. Patients were divided into an operative treatment group (n = 12) and a conservative treatment group (n = 96). We compared clinical characteristics between the 2 groups. @*Results@#The operative treatment group underwent more operations before SBO than the conservative treatment group (P = 0.007). Initial leukocyte counts (P = 0.004) and C-reactive protein (CRP) levels (P = 0.028) were elevated in the operative group. Body mass index (BMI) was lower in the operative group (P = 0.013). @*Conclusion@#The number of operations before SBO, leukocyte counts, CRP levels, and BMI were useful parameters for selecting patients who needed an urgent operation for SBO.

Therapeutic Temperature Modulation for a Critically Ill Patient with COVID-19

We report a rapidly deteriorating coronavirus disease 2019 (COVID-19) patient, a-58-year-old woman, with severe acute respiratory distress syndrome and shock with hyperpyrexia up to 41.8°C, probably due to the cytokine storm syndrome. Considering extracorporeal membrane oxygenation (ECMO) as the last resort, we applied therapeutic temperature modulation for management of hyperpyrexia. The patient demonstrated rapid improvement in oxygenation and shock after achieving normothermia, and fully recovered from COVID-19 three weeks later. Therapeutic temperature modulation may have successfully offloaded the failing cardiorespiratory system from metabolic cost and hyperinflammation induced by hyperpyrexia. The therapeutic temperature modulation can safely be applied in a specific group of patients with cytokine storm syndrome and hyperpyrexia, which may reduce the number of patients requiring ECMO in the global medical resource shortage.

Lung ultrasound for early diagnosis and severity assessment of pneumonia in patients with coronavirus disease 2019

Background/Aims@#Current evidence supports lung ultrasound as a point-ofcare alternative diagnostic tool for various respiratory diseases. We sought to determine the utility of lung ultrasound for early detection of pneumonia and for assessment of respiratory failure among patients with coronavirus disease 2019 (COVID-19). @*Methods@#Six patients with confirmed COVID-19 by reverse transcription-polymerase chain reaction were enrolled. All had undergone chest X-ray and chest computed tomography (CT) on the day of admission and underwent multiple point-of-care lung ultrasound scans over the course of their hospitalization. @*Results@#Lung ultrasound detected early abnormal findings of representative B-lines in a patient with a normal chest X-ray, corresponding to ground-glass opacities on the chest CT scan. The ultrasound findings improved as her clinical condition improved and her viral load decreased. In another minimally symptomatic patient without significant chest X-ray findings, the ultrasound showed B-lines, an early sign of pneumonia before abnormalities were detected on the chest CT scan. In two critically ill patients, ultrasound was performed to assess for evaluation of disease severity. In both patients, the clinicians conducted emergency rapid sequence intubation based on the ultrasound findings without awaiting the laboratory results and radiological reports. In two children, ultrasound was used to assess the improvement in their pneumonia, thus avoiding further imaging tests such as chest CT. @*Conclusions@#Lung ultrasound is feasible and useful as a rapid, sensitive, and affordable point-of-care screening tool to detect pneumonia and assess the severity of respiratory failure in patients hospitalized with COVID-19.

A population-based observational study of patients with pulmonary disorders in intensive care unit

Background/Aims@#Only a few epidemiologic studies on the patients with pulmonary disorders admitted to intensive care unit exist. We investigated the characteristics and clinical outcomes of the patients with severe pulmonary disorders. @*Methods@#The sample cohort database of National Health Insurance Sharing Service from 2006 to 2015 was used. Operational definition of critically ill patients was adults who were either admitted to intensive care unit for at least 3 days or expired within first 2 days in the unit. The pulmonary disorder group comprised of critically ill patients with respiratory disease as the main diagnosis. @*Results@#Among the 997,173 patients, 12,983 (1.3%) in 383 intensive care units were categorized as critically ill. Patients in the pulmonary disorder group tended to have more comorbidities or disabilities. The length of hospital stay and duration of mechanical ventilation were longer in the pulmonary disorder group. Overall mortality and re-admission were higher in the pulmonary disorder group, with adjusted incidence rate ratios of 1.22 (95% confidence interval, 1.18 to 1.27) and 1.26 (95% confidence interval, 1.17 to 1.36), respectively. After adjustment by Cox regression, the pulmonary disorder group was an independent risk factor for in-hospital mortality. @*Conclusions@#In critically ill patients with pulmonary disorder, the use of healthcare resources was higher, and their clinical outcomes were significantly worse than the non-pulmonary disorder group.

Clinical Significance of Pleural Attachment and Indentation of Subsolid Nodule Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Lung cancers presenting as subsolid nodule commonly have peripheral location, making the cancer-pleura relationship noteworthy. We aimed to evaluate the effect of pleural attachment and/or indentation on visceral pleural invasion (VPI) and recurrence-free survival. MATERIALS AND METHODS: Patients who underwent curative resection of lung cancer as subsolid nodules from April 2007 to January 2016 were retrospectively evaluated. They were divided into four groups according to their relationship with the pleura. Clinical, radiographical, and pathological findings were analyzed. RESULTS: Among 404 patients with malignant subsolid nodule, 120 (29.7%) had neither pleural attachment nor indentation, 26 (6.4%) had attachment only, 117 (29.0%) had indentation only, and 141 (34.9%) had both. VPI was observed in nodules of 36 patients (8.9%), but absent in nonsolid nodules and in those without pleural attachment and/or indentation. Compared to subsolid nodules with concurrent pleural attachment and indentation, those with attachment only (odds ratio, 0.12; 95% confidence interval [CI], 0.02 to 0.98) and indentation only (odds ratio, 0.10; 95% CI, 0.03 to 0.31) revealed lower odds of VPI. On subgroup analysis, the size of the solid portion was associated with VPI among those with pleural attachment and indentation (p=0.021). Such high-risk features for VPI were associated with earlier lung cancer recurrence (adjusted hazard ratio, 3.31; 95% CI, 1.58 to 6.91). CONCLUSION: Concurrent pleural attachment and indentation are risk factors for VPI, and the odds increase with larger solid portion in subsolid nodules. Considering the risk of recurrence, early surgical resection could be encouraged in these patients.

Extended Use of Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: A Retrospective Multicenter Study / 결핵

BACKGROUND: Beyond its current function as a rescue therapy in acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) may be applied in ARDS patients with less severe hypoxemia to facilitate lung protective ventilation. The purpose of this study was to evaluate the efficacy of extended ECMO use in ARDS patients. METHODS: This study reviewed 223 adult patients who had been admitted to the intensive care units of 11 hospitals in Korea and subsequently treated using ECMO. Among them, the 62 who required ECMO for ARDS were analyzed. The patients were divided into two groups according to pre-ECMO arterial blood gas: an extended group (n=14) and a conventional group (n=48). RESULTS: Baseline characteristics were not different between the groups. The median arterial carbon dioxide tension/fraction of inspired oxygen (FiO2) ratio was higher (97 vs. 61, p<0.001) while the median FiO2 was lower (0.8 vs. 1.0, p<0.001) in the extended compared to the conventional group. The 60-day mortality was 21% in the extended group and 54% in the conventional group (p=0.03). Multivariate analysis indicated that the extended use of ECMO was independently associated with reduced 60-day mortality (odds ratio, 0.10; 95% confidence interval, 0.02–0.64; p=0.02). Lower median peak inspiratory pressure and median dynamic driving pressure were observed in the extended group 24 hours after ECMO support. CONCLUSION: Extended indications of ECMO implementation coupled with protective ventilator settings may improve the clinical outcome of patients with ARDS.

Extended Use of Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: A Retrospective Multicenter Study / 결핵및호흡기질환

BACKGROUND@#Beyond its current function as a rescue therapy in acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) may be applied in ARDS patients with less severe hypoxemia to facilitate lung protective ventilation. The purpose of this study was to evaluate the efficacy of extended ECMO use in ARDS patients.@*METHODS@#This study reviewed 223 adult patients who had been admitted to the intensive care units of 11 hospitals in Korea and subsequently treated using ECMO. Among them, the 62 who required ECMO for ARDS were analyzed. The patients were divided into two groups according to pre-ECMO arterial blood gas: an extended group (n=14) and a conventional group (n=48).@*RESULTS@#Baseline characteristics were not different between the groups. The median arterial carbon dioxide tension/fraction of inspired oxygen (FiO2) ratio was higher (97 vs. 61, p<0.001) while the median FiO2 was lower (0.8 vs. 1.0, p<0.001) in the extended compared to the conventional group. The 60-day mortality was 21% in the extended group and 54% in the conventional group (p=0.03). Multivariate analysis indicated that the extended use of ECMO was independently associated with reduced 60-day mortality (odds ratio, 0.10; 95% confidence interval, 0.02–0.64; p=0.02). Lower median peak inspiratory pressure and median dynamic driving pressure were observed in the extended group 24 hours after ECMO support.@*CONCLUSION@#Extended indications of ECMO implementation coupled with protective ventilator settings may improve the clinical outcome of patients with ARDS.

Molecular epidemiology of sequence type 33 of Shiga toxin-producing Escherichia coli O91:H14 isolates from human patients and retail meats in Korea

Sequence type (ST) 33 of Shiga toxin-producing Escherichia coli (STEC) strain O91:H14 has been proposed as a potential domestic clone of STEC in Korea because of its high prevalence among human patients with mild diarrhea or asymptomatic carriers. Herein, the clonal diversity of 17 STEC O91:H14 isolates of ST33 during 2003 to 2014 was analyzed by pulsed-field gel electrophoresis, including 14 isolates from human patients and 3 from retail meats. Their virulence characteristics, acid resistance, and antimicrobial susceptibility were also determined. Our results showed that all isolates were clustered mainly into three different pulsotypes and were likely low pathogenic without antimicrobial resistance.

Sepsis / 대한내과학회지

Diagnosis and treatment criteria were recently updated based on the Sepsis-3 guidelines, which recommend the sequential organ failure assessment for accurate characterization of organ dysfunction. Large randomized controlled trials have found neutral results with early goal-directed therapy. To improve outcomes, treatment bundles incorporating standards for early sepsis treatment, including antibiotic and steroid treatment, were developed. Thus, future research should address the effects of steroids and immune-modulating agents on refractory septic shock as well as the development of new coagulopathy therapies and dynamic assessment tools.

Sepsis / 대한내과학회지

Diagnosis and treatment criteria were recently updated based on the Sepsis-3 guidelines, which recommend the sequential organ failure assessment for accurate characterization of organ dysfunction. Large randomized controlled trials have found neutral results with early goal-directed therapy. To improve outcomes, treatment bundles incorporating standards for early sepsis treatment, including antibiotic and steroid treatment, were developed. Thus, future research should address the effects of steroids and immune-modulating agents on refractory septic shock as well as the development of new coagulopathy therapies and dynamic assessment tools.