Evaluation of the Daily Change in PaO2/FiO2 Ratio as a Predictor of Abnormal Chest X-rays in Intensive Care Unit Patients Post Mechanical Ventilation Weaning: A Retrospective Cohort Study.

Background and Objectives: The routine daily chest X-ray (CXR) strategy is no longer recommended in intensive care unit (ICU) patients. However, it is difficult for intensivists to collectively accept the on-demand CXR strategy because of the ambiguous clinical criteria for conducting CXRs. This study evaluated the predictive value of the change in PaO2/FiO2 (PF ratio) for abnormal CXR findings in ICU patients after mechanical ventilation (MV). Materials and Methods: A retrospective cohort study was conducted between January 2016 and March 2021 on ICU patients with MV who had at least 48 h of MV, and stayed at least 72 h in the ICU post-MV. Routine daily CXRs and daily changes in the PF ratios were investigated during the three days post-MV. Results: The 186 patients included in the study had a median age of 77 years (interquartile range: 65-82), and 116 (62.4%) were men. One hundred and eight (58.1%) patients had abnormal CXR findings, defined as one or more abnormal CXRs among the daily CXRs during the three days post-extubation. The reintubation rate was higher in the abnormal CXR group (p = 0.01). Of the 558 CXRs (normal = 418, abnormal = 140) and PF ratios, the daily change in PF ratio had a significant predictive accuracy for abnormal CXR findings (AUROC = 0.741, p < 0.01). Conclusions: The change in PF ratio (the Youden index point: ≤-23) had a sensitivity of 65.7%, and a specificity of 79.9%. Based on these results, the daily change in the PF ratio could be utilized as a predictive indicator of abnormal CXRs in ICU patients after MV treatment.

Tracheitis Caused by Coinfection with Cytomegalovirus and Herpes Simplex Virus.

Clinically significant isolated viral tracheitis is scarce in adults, and upper airway obstruction caused by viral tracheitis is even more infrequent. A 74-year-old woman, who was administered low-dose steroids for two months for chronic obstructive pulmonary disease (COPD), developed dyspnea with stridor and required mechanical ventilation for respiratory failure. Chest computed tomography showed a diffuse tracheal wall thickening with luminal narrowing and peribronchial consolidation in the right upper lobe. Bronchoscopy revealed a proximal tracheal narrowing with multiple ulcerations of the tracheal mucosa surrounded by an erythematous margin. Pathologic examinations of the tracheal mucosal tissue, including immunohistochemistry, revealed a cytomegalovirus (CMV) and herpes simplex virus (HSV) infection. Furthermore, the bronchial alveolar lavage fluid was positive on the CMV real-time polymerase chain reaction. The patient was treated with intravenous ganciclovir for 44 days. The follow-up bronchoscopy 49 days after the initiation of ganciclovir revealed improved multiple ulcerations with scars. We report a rare case of tracheitis caused by coinfection with CMV and HSV in a patient with COPD who had been taking low-dose steroids for months. The case showed that CMV and HSV are potential causes of serious tracheitis and respiratory failure.

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.

Quantitation of plasma and biliary cefpiramide concentrations in human samples using high-performance liquid chromatography.

Cefpiramide is frequently used to treat biliary infections. However, no bioanalytical method has been validated to quantitate cefpiramide in human samples, particularly in bile. Therefore, this study was conducted to develop a simple, selective and validated high-performance liquid chromatographic method to determine cefpiramide in human plasma and bile. A protein precipitation procedure was used to extract cefpiramide and cefoperazone (internal standard, IS) from 200 µl of plasma and bile. Utilizing a Capcell Pak C18 column (4.6 × 250 mm), cefpiramide and IS were separated using the timed-gradient mobile phase consisting of 0.1 m sodium acetate (pH 5.2) and acetonitrile at a flow rate of 1 ml/min with photodiode array detector (wavelength set at 273 nm). The calibration curves showed linearity at concentrations ranging from 1 to 150 µg/ml in both plasma and bile (r2 > 0.999). The within- and between-run coefficients of variation (CVs) for plasma samples were 0.570-4.43 and 1.10-2.76%, respectively; for bile samples, the within- and between-day precision (CV) was 0.814-6.34 and 2.05-4.00%, respectively. Our newly developed bioanalytical method was successfully employed to quantify cefpiramide concentrations in both plasma and bile at multiple time points in patients with acute cholangitis.

Comparison of outcomes between vertical and transverse skin incisions in percutaneous tracheostomy for critically ill patients: a retrospective cohort study.

BACKGROUND: Percutaneous tracheostomy (PT) is a common procedure in critical care medicine. No definite clinical practice guidelines recommended on the choice of the direction of skin incision, vertical or transverse for tracheostomy in critically ill patients. The objective of this retrospective study was to compare the outcomes associated with vertical and transverse skin incisions in patients undergoing PT. METHODS: Patients who underwent PT between March 2011 and December 2015 in the intensive care unit (ICU) of a tertiary hospital were retrospectively included. PTs were performed by pulmonary intensivists at the ICU bedside using the single tapered dilator technique assisted by flexible bronchoscopy. The primary outcome was the incidence of tracheostomy site ulcers at 7 days after PT. RESULTS: Of the 458 patients who underwent PT, a vertical incision was made in 27.1% and a transverse incision was made in 72.9%. There were no tracheostomy-related mortalities, and no significant difference in the incidence of immediate postoperative complications, including bleeding, tracheal ring fracture, and subcutaneous emphysema. Thirty-five patients (7.6%) developed complications within 7 days after PT, in which tracheostomy-related pressure ulcers were the most frequent. Compared with vertical incisions, transverse incisions were associated with significantly lower incidence of complications (14.1% vs. 5.4%, P = 0.001). CONCLUSIONS: This retrospective study showed that transverse skin incisions in PTs for critically ill patients, resulted in a significant decrease in overall complications, particularly ulcers in the tracheostomy site.

Visceral adiposity is associated with an increased risk of functional dyspepsia.

BACKGROUND: The relationship between visceral adiposity and the incidence of functional dyspepsia (FD) has not yet been studied. The purpose of the present study is to evaluate the association between visceral adiposity and the risk of FD. METHODS: This is a case-control study that compares the abdominal adipose tissue area between subjects with FD and control subjects without FD, who underwent abdomen computerized tomography (CT) for health examinations in a tertiary center. Retrospectively, a telephone survey was conducted to diagnose FD using the Rome III criteria. We measured various indices of obesity including body mass index (BMI), waist circumference (WC), visceral adipose tissue (VAT) area, subcutaneous adipose tissue (SAT) area and the VAT/SAT ratio in order to evaluate the association between FD and abdominal adiposity. KEY RESULTS: A total of 363 subjects were included in the present study. FD was diagnosed in 90 subjects (24.8%). In the univariate analysis, WC, VAT area, TAT area, VAT/SAT ratio, and the presence of erosive esophagitis were significantly higher in the FD group than in the non-FD group. In the multivariate analysis, a higher VAT area (odds ratio (OR), 3.76; 95% confidence interval (CI), 1.24-11.40; highest quartile vs lowest quartile, p = 0.019) and VAT/SAT ratio (OR, 2.35; 95% CI, 1.27-4.32; highest quartile vs lowest quartile, p = 0.006) were independently associated with a risk of FD. CONCLUSION AND INFERENCES: Visceral adiposity as measured by the VAT area and VAT/SAT ratio is associated with an increased risk of FD.

Underestimation of smoking hazards and smoking cessation intervention efficiency among healthcare professionals: A cross-sectional study among Korean occupational health nurses.

INTRODUCTION: Occupational health nurses (OHNs) in South Korea who visit the workplace periodically could play a key role in smoking cessation. It would be helpful to assess their understanding of smoking hazards and smoking cessation methods to encourage them to provide smoking intervention services at the workplace. This study aimed to investigate the knowledge of smoking hazards and perceptions of smoking cessation methods among OHNs. METHODS: We conducted an anonymous self-administered cross-sectional questionnaire survey of 108 OHN nurses employed in an occupational health service outsourcing specialized agency with 19 regional branches in Korea from July to August 2019. We assessed the perceptions of the OHNs about smoking interventions, hazards of smoking, and perceived competence to counsel smokers according to training experience, using chi-squared tests and Fisher's exact tests. RESULTS: The majority of the nurses underestimated the smoking-attributable fraction for lung cancer (78.7%), chronic obstructive pulmonary disease (64.8%), and mortality (49.0%), regardless of training experience on smoking cessation, while more than half perceived their skill and knowledge to counsel patients concerning smoking as inadequate (56.5%). However, those trained in smoking cessation interventions felt more competent in smoking cessation counselling, with 52.2% and 29.3% in the trained and non-trained groups, respectively (p=0.019). CONCLUSIONS: The OHNs in this study underestimated smoking hazards and perceived themselves as lacking counselling skills regarding smoking cessation interventions. It is necessary to encourage OHNs to promote smoking cessation by increasing their knowledge, skills and competence in smoking cessation interventions.

Simple and robust LC-MS/MS method for quantification of colistin methanesulfonate and colistin in human plasma for therapeutic drug monitoring.

A rapid, simple, and robust LC-MS/MS method was developed and validated for the quantitation of colistin and colistin methanesulfonate (CMS) in human plasma. The method also prevented overestimation of colistin concentration by establishing the stability of CMS under sample preparation conditions, including blood and plasma storage conditions. Polymyxin B1 was used as an internal standard, and positive-ion electrospray ionization in multiple reaction monitoring mode was used for quantification. Chromatographic separation was achieved using a Zorbax eclipse C18 column (3.5 µm, 2.1 mm i.d. × 100 mm), with a flow rate of 0.5 mL/min, 5 µL injection volume, and gradient elution with a mixture of acetonitrile-water (containing 0.1 % trifluoroacetic acid). The method had a quantifiable range of 0.043-8.61 and 0.057-11.39 µg/mL for colistin A and B in human plasma, respectively, under a total runtime of 6.0 min. Further, it demonstrated appropriate extraction efficiency, no significant interference from co-eluting endogenous compounds, and satisfactory intraday and interday precision and accuracy. The proposed procedure for sample preparation successfully addressed the issue of CMS instability, consequently diminishing the probability of overestimating the concentration of colistin. Therefore, this simple and robust LC-MS/MS method for CMS and colistin quantification in human plasma is a valuable tool for clinicians to accurately monitor colistin treatment in patients with infections caused by multidrug-resistant (MDR) Gram-negative bacteria.

Effects of Early Initiation of High-Dose Dexamethasone Therapy on Pro-Inflammatory Cytokines and Mortality in LPS-Challenged Mice.

This study aims to explore the effects of early dexamethasone therapy at low to high doses on the survival and inflammatory responses in lipopolysaccharide (LPS)-challenged mice. We performed two-series experiments to explore the impact of early dexamethasone therapy at different doses (0.5 mg/kg, 1.5 mg/kg, and 5 mg/kg; PO) on pro-inflammatory cytokine levels, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), as well as survival in LPS-treated mice (10 mg/kg, IP). Dexamethasone was administered daily from 24 h before and 5 days after LPS challenge. Dose-dependent improved survival was demonstrated with dexamethasone (p < 0.05). Body weight was significantly decreased within 24 h of LPS injection, with significantly greater weight loss in the dexamethasone groups (p < 0.05). Weight changes were significantly associated with the days after LPS administration (p < 0.01), but not with the dexamethasone dose (p > 0.05). Mice treated with high-dose dexamethasone (5 mg/kg) had a significantly lowered serum TNF-α (134.41 ± 15.83 vs. 408.83 ± 18.32) and IL-6 (22.08 ± 4.34 vs. 91.27 ± 8.56) compared with those without dexamethasone. This study provides essential insights that the suppression of early-phase hyperactivation of pro-inflammatory activities through the early initiation of high-dose dexamethasone therapy increases sepsis-related prognosis.

Potentially Inappropriate Medication Use in Patients with Dementia.

The objective of this study was to characterize the epidemiology of using potentially inappropriate medications associated with dementia exacerbation (DPIMs) in elderly outpatients with dementia. Electronic medical records were retrospectively reviewed for geriatric patients with dementia who were prescribed at least one medication in 2016 at a tertiary, university-affiliated hospital. The 2015 Beers criteria were used to define DPIMs. Logistic regression was performed to identify factors associated with prescribing DPIMs in patients with dementia. Among 2100 patients included in our study, 987 (47.0%) patients were prescribed at least one DPIM. Benzodiazepines were the most frequently prescribed DPIM followed by anticholinergics, histamine H2-receptor blockers, and zolpidem. The risk of prescribing DPIMs was significantly increased in female patients (odds ratio (OR) 1.355) with polypharmacy (OR 5.146) and multiple comorbidities (OR 1.129) (p < 0.05 for all). Coexistence of Parkinson's disease (OR 1.799), mood disorder (OR 1.373), or schizophrenia (OR 4.116) in patients with dementia further increased the likelihood of receiving DPIMs. In conclusion, DPIMs were commonly used in elderly patients with dementia in Korea with benzodiazepines most frequently prescribed followed by anticholinergics. Female patients using polypharmacy with multiple comorbidities should be closely monitored to minimize unnecessary DPIM use and, ultimately, DPIM-related harms.

Clinical outcomes of esophagogastroduodenoscopy in critically ill patients using high-dose proton pump inhibitor for suspected bleeding: A retrospective cohort study.

ABSTRACT: Esophagogastroduodenoscopy (EGD) is a useful procedure performed for gastrointestinal (GI) bleeding. No definite clinical guidelines recommend EGD implementation in intensive care unit (ICU) patients with suspected GI bleeding. The objective of this study was to compare the clinical effectiveness of EGD in critically ill patients who are using high-dose proton pump inhibitor (PPI) for suspected GI bleeding.We retrospectively analyzed ICU patients using high-dose PPI for suspected GI bleeding from January 2012 to September 2020. Major cases of GI bleeding, such as those with hematemesis and hematochezia, were excluded, and 1:1 propensity score matching was performed. The change in hemoglobin level, requirement of red blood cell transfusion, re-suspected bleeding event, length of ICU stay, and ICU mortality were compared between the EGD and non-EGD groups.Of the 174 subjects included, 52 patients underwent EGD within 24 hours of PPI administration. In the EGD group, 22 (42.3%) patients showed normal findings, while esophagitis and gastritis were most common abnormal finding (n = 11, 21.2%), and 14 patients (26.9%) underwent a hemostatic procedure. While comparing the 2 groups, the EGD group required a higher amount of red blood cell transfusion (packs) than the non-EGD group for a week (3.04 ±â€Š0.44 vs 2.07 ±â€Š0.25, P = .01). There was no significant difference in the change in hemoglobin level after 1 week (P = .15). After propensity score matching, the EGD group showed similar the requirement of red blood cell transfusion and change in hemoglobin level for a week (P = .52, P = .97, respectively). In analyses for all patients and propensity score matched patients, there was no statistically significant difference in term of re-suspected bleeding event rate, duration of ICU stay, and ICU mortality. However, re-suspected bleeding event rate and ICU mortality were lower trend in the EGD group than the non-EGD group.This study showed that EGD had no definite clinical benefit in ICU patients using high-dose PPI for suspected GI bleeding and aggressive EGD is not necessarily recommended. However, it is necessary to consider EGD in patients who are tolerant.

Overexpression of Reactive Oxygen Species Modulator 1 Predicts Unfavorable Clinical Outcome in EGFR-Mutant Lung Adenocarcinomas Treated With Targeted Therapy.

PURPOSE: Reactive oxygen species modulator 1 (Romo1) is a novel protein that regulates the production of intracellular reactive oxygen species. Romo1 has been shown to be associated with poor survival in various clinical settings for the treatment of lung cancer. In this study, we evaluated whether tissue Romo1 expression was associated with clinical outcomes in epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma treated with tyrosine kinase inhibitors (TKIs). METHOD: Romo1 expression in tumor tissues was examined by immunohistochemistry and evaluated by histologic score. Univariate and multivariate analyses were performed to identify the clinicopathologic parameters, including Romo1 expression, which may be associated with progression-free survival (PFS), overall survival (OS), and incidence of secondary T790M mutation. RESULTS: A total of 96 tumor specimens were analyzed. With the cut-off value of 200, 71 (74.0%) and 25 (26.0%) patients were classified into low and high Romo1 groups, respectively. The median PFS of the high Romo1 group was significantly shorter than that of the low Romo1 group (13.1 vs 19.9 months, p = 0.0165). The median OS of the high Romo1 group was also significantly shorter than that of the low Romo1 group (19.8 vs 37.0 months, p = 0.0006). Multivariate analyses showed that high Romo1 expression was independently associated with both poor PFS (hazard ratio [HR] = 2.48, 95% confidence interval [CI]: 1.35-4.56, p = 0.0034) and poor OS (HR = 3.17, 95% CI: 1.57-6.41, p = 0.0013). In addition, the rate of secondary T790M mutation after TKI failure was significantly lower in the high Romo1 group than the low Romo1 group (16.7% vs. 38.3%, p = 0.0369). CONCLUSIONS: Romo1 overexpression was associated with poor response to treatment and short survival in patients treated with EGFR-TKIs, suggesting a distinct subgroup warranting active surveillance and tailored therapeutic approach. In addition, our data highlight that Romo1 could be a potential predictive and prognostic biomarker for this patient population.

Comparative Safety Profiles of Sedatives Commonly Used in Clinical Practice: A 10-Year Nationwide Pharmacovigilance Study in Korea.

This study aims to compare the prevalence and seriousness of adverse events (AEs) among sedatives used in critically ill patients or patients undergoing invasive procedures and to identify factors associated with serious AEs. Retrospective cross-sectional analysis of sedative-related AEs voluntarily reported to the Korea Adverse Event Reporting System from 2008 to 2017 was performed. All AEs were grouped using preferred terms and System Organ Classes per the World Health Organization-Adverse Reaction Terminology. Logistic regression was performed to identify factors associated with serious events. Among 95,188 AEs, including 3132 (3.3%) serious events, the most common etiologic sedative was fentanyl (58.8%), followed by pethidine (25.9%). Gastrointestinal disorders (54.2%) were the most frequent AEs. The most common serious AE was heart rate/rhythm disorders (33.1%). Serious AEs were significantly associated with male sex; pediatrics; etiologic sedative with etomidate at the highest risk, followed by dexmedetomidine, ketamine, and propofol; polypharmacy; combined sedative use; and concurrent use of corticosteroids, aspirin, neuromuscular blockers, and antihistamines (reporting odds ratio > 1, p < 0.001 for all). Sedative-induced AEs are most frequently reported with fentanyl, primarily manifesting as gastrointestinal disorders. Etomidate is associated with the highest risk of serious AEs, with the most common serious events being heart rate/rhythm disorders.

Prospective observational study of the impact of plasma colistin levels in patients with carbapenem-resistant Acinetobacter baumannii pneumonia.

OBJECTIVES: Colistin, an important drug to treat carbapenem-resistant Acinetobacter baumannii (CRAB) infections, has a narrow therapeutic window with nephrotoxicity. This study was conducted to determine the importance of colistin concentrations in predicting nephrotoxicity when treating CRAB pneumonia with colistin. METHODS: A prospective cohort study was performed in one teaching hospital from May 2015 to January 2018. Patients with CRAB pneumonia were treated with intravenous colistin methanesulfonate (CMS) at 2.5-5.0 mg/kg/day. On Days 3 and 4, plasma colistin and CMS concentrations were determined by six serial blood samples (immediately prior to dosing and 1 h and 4 h after the end of infusion). RESULTS: The 25 patients included in the analysis had hospital-acquired pneumonia caused by CRAB. Nephrotoxicity occurred in five patients (20%) on Day 7. There was no difference in clinical characteristics of patients with or without nephrotoxicity. The maximum plasma CMS concentration (mean ± standard deviation) was significantly higher in patients with nephrotoxicity on Day 7 than those without nephrotoxicity (15.3 ± 4.2 mg/L vs. 8.3 ± 3.8 mg/L; P = 0.014). The maximum plasma colistin concentration (Cmax,col) was significantly higher in the nephrotoxicity group on Day 7 (4.8 ± 2.0 mg/L vs. 2.1 ± 1.0 mg/L; P = 0.002). Cmax,col was lower in patients with microbiological failure than those without microbiological failure (1.92 mg/L vs. 3.01 mg/L; P = 0.038). CONCLUSION: This study confirmed that plasma levels of CMS and colistin, especially maximum levels, are important for predicting nephrotoxicity in patients with CRAB pneumonia. [ClinicalTrials.gov ID NCT02482961].

Simultaneous Pretreatment of Aspirin and Omega-3 Fatty Acid Attenuates Nuclear Factor-κB Activation in a Murine Model with Ventilator-Induced Lung Injury.

Ventilator-induced lung injury (VILI) is an important critical care complication. Nuclear factor-κB (NF-κB) activation, a critical signaling event in the inflammatory response, has been implicated in the tracking of the lung injury. The present study aimed to determine the effect of simultaneous pretreatment with enteral aspirin and omega-3 fatty acid on lung injury in a murine VILI model. We compared the lung inflammation after the sequential administration of lipopolysaccharides and mechanical ventilation between the pretreated simultaneous enteral aspirin and omega-3 fatty acid group and the non-pretreatment group, by quantifying NF-κB activation using an in vivo imaging system to detect bioluminescence signals. The pretreated group with enteral aspirin and omega-3 fatty acid exhibited a smaller elevation of bioluminescence signals than the non-pretreated group (p = 0.039). Compared to the non-pretreated group, the pretreatment group with simultaneous enteral aspirin and omega-3 fatty acid showed reduced expression of the pro-inflammatory cytokine, tumor necrosis factor-α, in bronchoalveolar lavage fluid (p = 0.038). Histopathological lung injury scores were also lower in the pretreatment groups compared to the only injury group. Simultaneous pretreatment with enteral administration of aspirin and omega-3 fatty acid could be a prevention method for VILI in patients with impending mechanical ventilation therapy.

Fatal Events Associated with Adverse Drug Reactions in the Korean National Pharmacovigilance Database.

Adverse drug reactions (ADRs) pose a global public health threat, substantially contributing to death. Due to the relative paucity of clinical evidence regarding fatal ADRs, this study was performed to characterize the epidemiology of fatal ADRs in Korea. This was a retrospective, cross-sectional analysis of ADR cases reported to the Korea Adverse Event Reporting System from 2010 to 2019. All ADRs were coded using the World Health Organization-Adverse Reaction Terminology system and classified as either fatal or non-fatal events. Logistic regression was performed to identify factors associated with fatal events. Among 289,756 ADR records, 629 fatal events (0.2%) occurred. The most common causative agent of fatal ADRs was antibacterials (20.3%), followed by antimycobacterials (5.4%), analgesics (4.0%), and contrast media (1.9%). Among antimicrobials, vancomycin was most frequently implicated without significantly increasing the risk of fatal events. The risk for fatal ADRs was significantly increased with male sex; advanced age; polypharmacy; piperacillin/ß-lactamase inhibitor; cefotetan; ceftriaxone; combination antimycobacterial therapy consisting of rifampicin, isoniazid, pyrazinamide, and ethambutol; morphine; and iopromide (reporting odds ratio > 1, p < 0.05 for all). Although fatal ADRs are uncommon (<1%) in Korea, they are primarily caused by commonly used medications including antibiotics, analgesics, and contrast media.

Validation of a Questionnaire for Patient Awareness and the Need for a Community-Based Outpatient Antimicrobial Stewardship Program (O-ASP): A Pilot Study.

An outpatient antimicrobial stewardship program (O-ASP) was developed and implemented to promote appropriate antibiotic therapy in outpatient settings. As active patient involvement is a critical component of an effective O-ASP, this study aimed to develop and validate a questionnaire addressing patient awareness for appropriate antibiotic therapy and the need for pharmaceutical care services (PCS) in the O-ASP in Korea. The questionnaire was drafted based on ASPs and PCS guidelines and validated for content and construct validity using the item-content validity index (I-CVI) and Cronbach's alpha, respectively. The estimated I-CVI and Cronbach's alpha were considered excellent or adequate (≥0.8 and 0.70-0.90, respectively) for most of the survey items (17 out of 23 items). The validated questionnaire was utilized in a pilot survey study, including 112 individuals (37% male) with the mean ± SD age of 37 ± 13 years. Among the survey participants, 68% responded that antibiotics had been prescribed appropriately; however, ≥50% showed a lack of knowledge regarding their antibiotic therapy. The participants expressed the need for PCS as part of an O-ASP in the questionnaire (average Likert score ≥3.4/5). In conclusion, our newly validated questionnaire successfully measured patient awareness and knowledge of antimicrobial use and the need for PCS in the O-ASP.

Clinical impact of early reinsertion of a central venous catheter after catheter removal in patients with catheter-related bloodstream infections.

OBJECTIVE: Early replacement of a new central venous catheter (CVC) may pose a risk of persistent or recurrent infection in patients with a catheter-related bloodstream infection (CRBSI). We evaluated the clinical impact of early CVC reinsertion after catheter removal in patients with CRBSIs. METHODS: We conducted a retrospective chart review of adult patients with confirmed CRBSIs in 2 tertiary-care hospitals over a 7-year period. RESULTS: To treat their infections, 316 patients with CRBSIs underwent CVC removal. Among them, 130 (41.1%) underwent early CVC reinsertion (≤3 days after CVC removal), 39 (12.4%) underwent delayed reinsertion (>3 days), and 147 (46.5%) did not undergo CVC reinsertion. There were no differences in baseline characteristics among the 3 groups, except for nontunneled CVC, presence of septic shock, and reason for CVC reinsertion. The rate of persistent CRBSI in the early CVC reinsertion group (22.3%) was higher than that in the no CVC reinsertion group (7.5%; P = .002) but was similar to that in the delayed CVC reinsertion group (17.9%; P > .99). The other clinical outcomes did not differ among the 3 groups, including rates of 30-day mortality, complicated infection, and recurrence. After controlling for several confounding factors, early CVC reinsertion was not significantly associated with persistent CRBSI (OR, 1.59; P = .35) or 30-day mortality compared with delayed CVC reinsertion (OR, 0.81; P = .68). CONCLUSIONS: Early CVC reinsertion in the setting of CRBSI may be safe. Replacement of a new CVC should not be delayed in patients who still require a CVC for ongoing management.

Primary Resistance to Immune Checkpoint Blockade in an STK11/TP53/KRAS-Mutant Lung Adenocarcinoma with High PD-L1 Expression.

Several studies have shown that STK11 and TP53 mutations have different effects on the susceptibility to immune checkpoint blockade in KRAS-mutant non-small cell lung cancer (NSCLC). However, the impact of STK11/TP53 co-mutations on treatment outcomes in the same clinical setting has never been reported. We recently encountered a case of a 70-year-old man who was diagnosed with advanced lung adenocarcinoma with high-programmed death-ligand 1 (PD-L1) expression. He received pembrolizumab monotherapy as a frontline treatment; however, the tumor did not respond to this therapy and showed deleterious outcome. Next-generation sequencing revealed that the tumor harbored a rare STK11/TP53/KRAS triple mutation. Our case suggests that these compound mutations may constitute a distinct, aggressive subset that is resistant to immunotherapy even when the tumor strongly expresses PD-L1. In addition, this report highlights the importance of using molecular profiling to detect co-mutations that can be associated with primary resistance or disease progression to improve survival even in the immunotherapy setting.

Computed tomographic findings of chest injuries following cardiopulmonary resuscitation: More complications for prolonged chest compressions?

Chest injuries are common and inevitable complications of chest compressions during cardiopulmonary resuscitation (CPR). This study aimed to investigate lung parenchymal and thoracic skeletal injuries after CPR by using computed tomography (CT) and to analyze the correlation between the duration of CPR and related complications.We examined 43 non-traumatic cardiac arrest patients who were successfully resuscitated after CPR and had chest CT scans within 24 hours of CPR. Lung parenchymal injuries were assessed by quantifying the lung contusion score (LCS) on the CT images, and each skeletal injury was investigated by classifying the location and the distribution. Other CPR-related chest injuries were also described, such as pleural effusion/hemothorax, pneumothorax, and retrosternal hematoma. Statistical analysis was conducted to determine whether the duration of CPR was correlated with each complication.Lung contusions were found in all of the patients (mean LCS: 22, range: 5-47). The distribution of lung contusions were predominantly in the bilateral dependent portions of the lungs (41 patients). All of the rib fractures occurred in the anterior arc (43 patients), and the sternal fractures occurred predominantly in the mid-sternal body (31 patients). In patients younger than 70 years old, the number of rib fractures significantly increased among those who underwent CPR for more than 25 minutes compared to those who received CPR for less than 25 minutes (median 4.5 vs 9; mean 8.3 vs 5.6 per person, respectively; P = .035). The risk of sternal fracture tended to be higher for patients who received CPR for more than 10 minutes compared to those who received CPR for less than 10 minutes (odds ratio: 3.60; 95% confidence interval: 0.86-15.06; P = .079). However, there was no statistically significant correlation between the duration of CPR and LCS or other CPR-related chest injuries.The duration of CPR was associated with the number of rib fractures and the occurrence of sternal fractures, but it did not affect the extent of CPR-related lung contusions or other CPR-related chest injuries. All of the rib fractures occurred in the anterior arc, while the sternal fractures occurred predominantly in the mid-sternal body. However, since this study was conducted in a single institution, the number of patients included was relatively small, thus limiting the statistical analysis.