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.

Genetic Alterations in Preinvasive Lung Synchronous Lesions / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Despite advances in treatment, lung cancer remains the leading cause of cancer mortality. This study aimed to characterise genome-wide tumorigenesis events and to understand the hypothesis of the multistep carcinogenesis of lung adenocarcinoma (LUAD) @*Materials and Methods@#We conducted multiregion whole-exome sequencing of LUAD with synchronous atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ, or minimally invasive adenocarcinoma of 19 samples from three patients to characterize genome-wide tumorigenesis events and validate the hypothesis of the multistep carcinogenesis of LUAD. We identified potential pathogenic mutations preserved in preinvasive lesions and supplemented the finding by allelic variant level from RNA sequencing. @*Results@#Overall, independent mutational profiles were observed per patient and between patients. Some shared mutations including epidermal growth factor receptor (EGFR , p.L858R) were present across synchronous lesions. @*Conclusion@#Here, we show that there are driver gene mutations in AAH, and they may exacerbate as a sequence in a histological continuum, supporting the Darwinian evolution model of cancer genome. The intertumoral and intratumoral heterogeneity of synchronous LUAD implies that multi-biomarker strategies might be necessary for appropriate treatment.

Development of Protocol for Korean Lung Cancer Screening Project (K-LUCAS) to Evaluate Effectiveness and Feasibility to Implement National Cancer Screening Program / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To reduce lung cancer mortality, lung cancer screening was recommended using low-dose computed tomography (LDCT) to high-risk population. A protocol for multicenter lung cancer screening pilot project was developed to evaluate the effectiveness and feasibility of lung cancer screening to implement National Cancer Screening Program in Korea. MATERIALS AND METHODS: Multidisciplinary expert committee was comprised to develop a standardized protocol for Korean Lung Cancer Screening Project (K-LUCAS). K-LUCAS is a population-based single arm trial that targets high-risk population aged 55-74 years with at least 30 pack-year smoking history. LDCT results are reported by Lung-RADS suggested by American Radiology Society. Network-based system using computer-aided detection program is prepared to assist reducing diagnostic errors. Smoking cessation counselling is provided to all currently smoking participants. A small pilot test was conducted to check the feasibility and compliance of the protocols for K-LUCAS. RESULTS: In pilot test, 256 were participated. The average age of participants was 63.2 years and only three participants (1.2%) were female. The participants had a smoking history of 40.5 pack-year on average and 53.9% were current smokers. Among them, 86.3% had willing to participate in lung cancer screening again. The average willingness to quit smoking among current smokers was 12.7% higher than before screening. In Lung-RADS reports, 10 (3.9%) were grade 3 and nine (3.5%) were grade 4. One participant was diagnosed as lung cancer. CONCLUSION: The protocol developed by this study is assessed to be feasible to perform K-LUCAS in multicenter nationwide scale.

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.

Successful Rescue Therapy with Pumpless Extracorporeal Carbon Dioxide Removal in a Patient with Persistent Air Leakage Due to Empyema / 대한구급학회지

A young metastatic lung cancer patient developed empyema due to an infection with carbapenem-resistant Acinetobacter baumannii. Hydropneumothorax was detected and managed by a tube thoracotomy. However, persistent air leakage through the chest tube was observed due to the presence of a bronchopleural fistula (BPF). As hypercapnic respiratory failure had progressed and the large air leak did not diminish by conservative management, a pumpless extracorporeal lung assist (pECLA) device was inserted. The pECLA allowed the patient to be weaned from mechanical ventilation and the BPF to heal. The present case shows the effective application of pECLA in a patient with empyema complicated with BPF and severe hypercapnic respiratory failure. pECLA enabled us to minimize airway pressure to aid in the closure of the BPF in the mechanically ventilated patient.

Who Dies after ICU Discharge? Retrospective Analysis of Prognostic Factors for In-Hospital Mortality of ICU Survivors

We investigated the causes of inpatient death after intensive care unit (ICU) discharge and determined predictors of in-hospital mortality in Korea. Using medical ICU registry data of Seoul National University Hospital, we performed a retrospective cohort study involving patients who were discharged alive from their first ICU admission with at least 24 hours of ICU length of stay (LOS). From January 2011 to August 2013, 723 patients were admitted to ICU and 383 patients were included. The estimated in-hospital mortality rate was 11.7% (45/383). The most common cause of death was respiratory failure (n = 25, 56%) followed by sepsis and cancer progression; the causes of hospital death and ICU admission were the same in 64% of all deaths; sudden unexpected deaths comprised about one-fifth of all deaths. In order to predict in-hospital mortality among ICU survivors, multivariate analysis identified presence of solid tumor (odds ratio [OR], 4.06; 95% confidence interval [CI], 2.01–8.2; P < 0.001), hematologic disease (OR, 4.75; 95% CI, 1.51–14.96; P = 0.013), Sequential Organ Failure Assessment (SOFA) score upon ICU admission (OR, 1.08; 95% CI, 0.99–1.17; P = 0.075), and hemoglobin (Hb) level (OR, 0.67; 95% CI, 0.52–0.86; P = 0.001) and platelet count (Plt) (OR, 0.99; 95% CI, 0.99–1.00; P = 0.033) upon ICU discharge as significant factors. In conclusion, a significant proportion of in-hospital mortality is predictable and those who die in hospital after ICU discharge tend to be severely-ill, with comorbidities of hematologic disease and solid tumor, and anemic and thrombocytopenic upon ICU discharge.

Comparing tuberculin skin test and interferon γ release assay (T-SPOT.TB) to diagnose latent tuberculosis infection in household contacts

BACKGROUND/AIMS: The tuberculin skin test (TST) and interferon γ release assay are currently used as diagnostic tools to detect latent tuberculosis (TB) infection; however, there are inconsistencies about the degree of agreement between the tests. We aimed to evaluate the concordance rate between the two tests in household contacts of a country with intermediate TB burden, where most people were vaccinated. METHODS: We recruited household contacts who spent > 8 hours daily with patients with microbiologically confirmed active pulmonary TB, and received both TST and T-SPOT.TB (Oxford Immunotec) simultaneously. The degree of agreement was analysed according to TST cutoff and Bacille Calmette-Guerin (BCG) vaccination status. Relevant factors were analysed to establish the association with TST or T-SPOT.TB. RESULTS: Among 298 household contacts, 122 (40.9%) were spouses, and 250 (83.9%) had received BCG vaccination. In the contact sources, 117 (39.3%) showed a positive result for acid-fast bacillus (AFB) sputum smear and 109 (36.6%) had cavities. The highest agreement rate of 69.5% and κ value of 0.378 were found with a 10 mm cutoff. Spouse, time interval from TB diagnosis to test, and AFB sputum smear positivity were significantly associated with a positive result for T-SPOT.TB. Sex, BCG vaccination, and cavity on chest computed tomography were related to TST positivity. CONCLUSIONS: The present study suggested it was not possible for TST and T-SPOT.TB to replace each other because of considerable discrepancy between the two tests in household contacts in a country with intermediate TB prevalence.

Comparing tuberculin skin test and interferon γ release assay (T-SPOT.TB) to diagnose latent tuberculosis infection in household contacts

BACKGROUND/AIMS: The tuberculin skin test (TST) and interferon γ release assay are currently used as diagnostic tools to detect latent tuberculosis (TB) infection; however, there are inconsistencies about the degree of agreement between the tests. We aimed to evaluate the concordance rate between the two tests in household contacts of a country with intermediate TB burden, where most people were vaccinated. METHODS: We recruited household contacts who spent > 8 hours daily with patients with microbiologically confirmed active pulmonary TB, and received both TST and T-SPOT.TB (Oxford Immunotec) simultaneously. The degree of agreement was analysed according to TST cutoff and Bacille Calmette-Guerin (BCG) vaccination status. Relevant factors were analysed to establish the association with TST or T-SPOT.TB. RESULTS: Among 298 household contacts, 122 (40.9%) were spouses, and 250 (83.9%) had received BCG vaccination. In the contact sources, 117 (39.3%) showed a positive result for acid-fast bacillus (AFB) sputum smear and 109 (36.6%) had cavities. The highest agreement rate of 69.5% and κ value of 0.378 were found with a 10 mm cutoff. Spouse, time interval from TB diagnosis to test, and AFB sputum smear positivity were significantly associated with a positive result for T-SPOT.TB. Sex, BCG vaccination, and cavity on chest computed tomography were related to TST positivity. CONCLUSIONS: The present study suggested it was not possible for TST and T-SPOT.TB to replace each other because of considerable discrepancy between the two tests in household contacts in a country with intermediate TB prevalence.

Successful Rescue Therapy with Pumpless Extracorporeal Carbon Dioxide Removal in a Patient with Persistent Air Leakage Due to Empyema / 대한중환자의학회지

A young metastatic lung cancer patient developed empyema due to an infection with carbapenem-resistant Acinetobacter baumannii. Hydropneumothorax was detected and managed by a tube thoracotomy. However, persistent air leakage through the chest tube was observed due to the presence of a bronchopleural fistula (BPF). As hypercapnic respiratory failure had progressed and the large air leak did not diminish by conservative management, a pumpless extracorporeal lung assist (pECLA) device was inserted. The pECLA allowed the patient to be weaned from mechanical ventilation and the BPF to heal. The present case shows the effective application of pECLA in a patient with empyema complicated with BPF and severe hypercapnic respiratory failure. pECLA enabled us to minimize airway pressure to aid in the closure of the BPF in the mechanically ventilated patient.

Intermediate risk of multidrug-resistant organisms in patients who admitted intensive care unit with healthcare-associated pneumonia

BACKGROUND/AIMS: Healthcare-associated pneumonia (HCAP) was proposed asa new pneumonia category in 2005, and treatment recommendations includebroad-spectrum antibiotics directed at multidrug-resistant (MDR) pathogens.However, this concept continues to be controversial, and microbiological data arelacking for HCAP patients in the intensive care unit (ICU). This study was conductedto determine the rate and type of antibiotic-resistant organisms and theclinical outcomes in patients with HCAP in the ICU, compared to patients withcommunity-acquired pneumonia (CAP) or hospital-acquired pneumonia (HAP). METHODS: We conducted a retrospective cohort analysis of patients with pneumonia(n = 195) who admitted to medical ICU in tertiary teaching hospital fromMarch 2011 to February 2013. Clinical characteristics, microbiological distributions,treatment outcomes, and prognosis of HCAP (n = 74) were compared tothose of CAP (n = 75) and HAP (n = 46). RESULTS: MDR pathogens were significantly higher in HCAP patients (39.1%) thanin CAP (13.5%) and lower than in HAP (79.3%, p < 0.001). The initial use of inappropriateantibiotic treatment occurred more frequently in the HCAP (32.6%) andHAP (51.7%) groups than in the CAP group (11.8%, p = 0.006). There were no differencesin clinical outcomes. The significant prognostic factors were pneumoniaseverity and treatment response. CONCLUSIONS: MDR pathogens were isolated in HCAP patients requiring ICU admissionat intermediate rates between those of CAP and HAP.

The Anti-Inflammatory Effect of Arginine-Vasopressin on Lipopolysaccharide-Induced IkappaBalpha/Nuclear Factor-kappaB Cascade / 대한구급학회지

BACKGROUND: Arginine vasopressin (AVP) is widely used as a vasopressor agent. Some recent studies have suggested that AVP may exert an immunomodulatory effect. However, the mechanism about the anti-inflammatory effect of AVP is not well known. We investigated the effect of AVP on the ihibitor of kappa B (IkappaBalpha)/nuclear factor-kappa B (NF-kappaB) pathway in RAW 264.7 cells. METHODS: Cultured RAW 264.7 cells were pretreated with AVP and stimulated with lipopolysaccharide (LPS). To evaluate the effect of AVP on inflammatory cytokines, the concentration of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assessed by an enzyme-linked immunosorbent assay technique. The expression of IkappaBalpha and nuclear translocation of NF-kappaB p65 were measured by Western blotting, and IkappaB kinase (IKK) activity was analyzed by an in vitro immune complex kinase assay. To confirm the AVP effect on IkappaBalpha/NF-kappaB cascade and via V2 receptor, we added tolvaptan (V2 receptor antagonist) after AVP pretreatment. RESULTS: The increase of IL-6 and TNF-alpha in LPS-stimulated RAW 264.7 cells was suppressed by a treatment with AVP. Pretreatment of AVP inhibited increasing of IKK activity and IkappaBalpha degradation induced by LPS in RAW 264.7 cells. Furthermore, LPS induced and NF-kappaB transcription was inhibited by AVP pretreatment. The observed changes in IKK activity, IkappaBalpha degradation and NF-kappaB transcription by AVP was abolished by tolvaptan treatment. CONCLUSIONS: Our results suggest that AVP showed anti-inflammatory effect on LPS-induced IkappaBalpha/NF-kappaB cascade in mouse macrophages via V2 receptors.

Bone Marrow Recurrence with Microscopic Pulmonary Tumor Embolism after Excision of Extramammary Paget's Disease in Scrotum Three Years Ago

Here we report a case of a 72-year-old male patient recurred in bone marrow alone with pulmonary tumor embolism after an excision of extramammary Paget's disease of scrotum 3 years ago. The patient received paclitaxel/carboplatin chemotherapy with respiratory support in intensive care unit. Four days after chemotherapy, the oxygen demand decreased and the patient was transferred to general ward. The platelet count recovered after 2 weeks. Finally, he died of hepatic failure from Paget's disease hepatic involvement confirmed by liver biopsy at 10 months after recurrence. This is a rare case of recurred extramammary Paget's disease in bone marrow alone with pulmonary tumor embolism, which was properly diagnosed with high suspicion and was successfully treated with immediate chemotherapy.

The Anti-Inflammatory Effect of Arginine-Vasopressin on Lipopolysaccharide-Induced IkappaBalpha/Nuclear Factor-kappaB Cascade / 대한중환자의학회지

BACKGROUND: Arginine vasopressin (AVP) is widely used as a vasopressor agent. Some recent studies have suggested that AVP may exert an immunomodulatory effect. However, the mechanism about the anti-inflammatory effect of AVP is not well known. We investigated the effect of AVP on the ihibitor of kappa B (IkappaBalpha)/nuclear factor-kappa B (NF-kappaB) pathway in RAW 264.7 cells. METHODS: Cultured RAW 264.7 cells were pretreated with AVP and stimulated with lipopolysaccharide (LPS). To evaluate the effect of AVP on inflammatory cytokines, the concentration of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assessed by an enzyme-linked immunosorbent assay technique. The expression of IkappaBalpha and nuclear translocation of NF-kappaB p65 were measured by Western blotting, and IkappaB kinase (IKK) activity was analyzed by an in vitro immune complex kinase assay. To confirm the AVP effect on IkappaBalpha/NF-kappaB cascade and via V2 receptor, we added tolvaptan (V2 receptor antagonist) after AVP pretreatment. RESULTS: The increase of IL-6 and TNF-alpha in LPS-stimulated RAW 264.7 cells was suppressed by a treatment with AVP. Pretreatment of AVP inhibited increasing of IKK activity and IkappaBalpha degradation induced by LPS in RAW 264.7 cells. Furthermore, LPS induced and NF-kappaB transcription was inhibited by AVP pretreatment. The observed changes in IKK activity, IkappaBalpha degradation and NF-kappaB transcription by AVP was abolished by tolvaptan treatment. CONCLUSIONS: Our results suggest that AVP showed anti-inflammatory effect on LPS-induced IkappaBalpha/NF-kappaB cascade in mouse macrophages via V2 receptors.

Readmission to Medical Intensive Care Units: Risk Factors and Prediction

PURPOSE: The objectives of this study were to find factors related to medical intensive care unit (ICU) readmission and to develop a prediction index for determining patients who are likely to be readmitted to medical ICUs. MATERIALS AND METHODS: We performed a retrospective cohort study of 343 consecutive patients who were admitted to the medical ICU of a single medical center from January 1, 2008 to December 31, 2012. We analyzed a broad range of patients' characteristics on the day of admission, extubation, and discharge from the ICU. RESULTS: Of the 343 patients discharged from the ICU alive, 33 (9.6%) were readmitted to the ICU unexpectedly. Using logistic regression analysis, the verified factors associated with increased risk of ICU readmission were male sex [odds ratio (OR) 3.17, 95% confidence interval (CI) 1.29-8.48], history of diabetes mellitus (OR 3.03, 95% CI 1.29-7.09), application of continuous renal replacement therapy during ICU stay (OR 2.78, 95% CI 0.85-9.09), white blood cell count on the day of extubation (OR 1.13, 95% CI 1.07-1.21), and heart rate just before ICU discharge (OR 1.03, 95% CI 1.01-1.06). We established a prediction index for ICU readmission using the five verified risk factors (area under the curve, 0.76, 95% CI 0.66-0.86). CONCLUSION: By using specific risk factors associated with increased readmission to the ICU, a numerical index could be established as an estimation tool to predict the risk of ICU readmission.

Membranous Insulin-like Growth Factor-1 Receptor (IGF1R) Expression Is Predictive of Poor Prognosis in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma

BACKGROUND: Insulin-like growth factor-1 receptor (IGF1R) is a membrane receptor-type tyrosine kinase that has attracted considerable attention as a potential therapeutic target, although its clinical significance in non-small cell lung cancer (NSCLC) is controversial. This study aimed to clarify the clinical significance of IGF1R expression in human NSCLC. METHODS: IGF1R protein expression was evaluated using immunohistochemistry in 372 patients with NSCLC who underwent curative surgical resection (146 squamous cell carcinomas [SqCCs] and 226 adenocarcinomas [ADCs]). We then analyzed correlations between expression of IGF1R and clinicopathological and molecular features and prognostic significance. RESULTS: Membranous and cytoplasmic IGF1R expression were significantly higher in SqCCs than in ADCs. In patients with SqCC, membranous IGF1R expression was associated with absence of vascular, lymphatic, and perineural invasion; lower stage; and better progression-free survival (PFS) (hazard ratio [HR], 0.586; p = .040). In patients with ADC, IGF1R expression did not have a significant prognostic value; however, in the subgroup of epidermal growth factor receptor (EGFR)-mutant ADC, membranous IGF1R expression was associated with lymphatic and perineural invasion, solid predominant histology, and higher cancer stage and was significantly associated with worse PFS (HR, 2.582; p = .009). CONCLUSIONS: Lung ADC and SqCC showed distinct IGF1R expression profiles that demonstrated prognostic significance. High membranous IGF1R expression was predictive of poor PFS in EGFR-mutant lung ADC, while it was predictive of better PFS in SqCC. These findings will help improve study design for subsequent investigations and select patients for future anti-IGF1R therapy.

Successful High Flow Nasal Oxygen Therapy for Excessive Dynamic Airway Collapse: A Case Report / 결핵및호흡기질환

Excessive dynamic airway collapse (EDAC) is a disease entity of excessive reduction of the central airway diameter during exhalation, without cartilage collapse. An 80-year-old female presented with generalized edema and dyspnea at our hospital. The patient was in a state of acute decompensated heart failure due to pneumonia with respiratory failure. We accordingly managed the patient with renal replacement therapy, mechanical ventilation and antibiotics. Bronchoscopy confirmed the diagnosis of EDAC. We scheduled extubation after the improvement of pneumonia and heart condition. However, extubation failure occurred due to hypercapnic respiratory failure with poor expectoration. Her EDAC was improved in response to high flow nasal oxygen therapy (HFNOT). Subsequently, the patient was stabilized and transferred to the general ward. HFNOT, which generates physiologic positive end expiratory pressure (PEEP) effects, could be an alternative and effective management of EDAC. Further research and clinical trials are needed to demonstrate the therapeutic effect of HFNOT on EDAC.

Drug-induced Hepatotoxicity of Anti-tuberculosis Drugs and Their Serum Levels

The correlation between serum anti-tuberculosis (TB) drug levels and the drug-induced hepatotoxicity (DIH) remains unclear. The purpose of this study was to investigate whether anti-TB DIH is associated with basal serum drug levels. Serum peak levels of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) were analyzed in blood samples 2 hr after the administration of anti-TB medication. Anti-TB DIH and mild liver function test abnormality were diagnosed on the basis of laboratory and clinical criteria. Serum anti-TB drug levels and other clinical factors were compared between the hepatotoxicity and non-hepatotoxicity groups. A total of 195 TB patients were included in the study, and the data were analyzed retrospectively. Seventeen (8.7%) of the 195 patients showed hepatotoxicity, and the mean aspartate aminotransferase/alanine aminotransferase levels in the hepatotoxicity group were 249/249 IU/L, respectively. Among the 17 patients with hepatotoxicity, 12 showed anti-TB DIH. Ten patients showed PZA-related hepatotoxicity and 2 showed INH- or RMP-related hepatotoxicity. However, intergroup differences in the serum levels of the 4 anti-TB drugs were not statistically significant. Basal serum drug concentration was not associated with the risk anti-TB DIH in patients being treated with the currently recommended doses of first-line anti-TB treatment drugs.

Drug-induced Hepatotoxicity of Anti-tuberculosis Drugs and Their Serum Levels

The correlation between serum anti-tuberculosis (TB) drug levels and the drug-induced hepatotoxicity (DIH) remains unclear. The purpose of this study was to investigate whether anti-TB DIH is associated with basal serum drug levels. Serum peak levels of isoniazid (INH), rifampicin (RMP), pyrazinamide (PZA), and ethambutol (EMB) were analyzed in blood samples 2 hr after the administration of anti-TB medication. Anti-TB DIH and mild liver function test abnormality were diagnosed on the basis of laboratory and clinical criteria. Serum anti-TB drug levels and other clinical factors were compared between the hepatotoxicity and non-hepatotoxicity groups. A total of 195 TB patients were included in the study, and the data were analyzed retrospectively. Seventeen (8.7%) of the 195 patients showed hepatotoxicity, and the mean aspartate aminotransferase/alanine aminotransferase levels in the hepatotoxicity group were 249/249 IU/L, respectively. Among the 17 patients with hepatotoxicity, 12 showed anti-TB DIH. Ten patients showed PZA-related hepatotoxicity and 2 showed INH- or RMP-related hepatotoxicity. However, intergroup differences in the serum levels of the 4 anti-TB drugs were not statistically significant. Basal serum drug concentration was not associated with the risk anti-TB DIH in patients being treated with the currently recommended doses of first-line anti-TB treatment drugs.

Clinical Application of Bioelectrical Impedance Analysis and its Phase Angle for Nutritional Assessment of Critically Ill Patients

PURPOSE: Phase angle (PA) is objectively determined from resistance and reactance measured by bioelectrical impedance analysis (BIA)-a quick, noninvasive method. The aim of this study was to evaluate the clinical application of PA by BIA for nutritional assessment of critically ill patients. METHODS: Eighty nine adult patients admitted to a medical intensive care unit (ICU) of a tertiary academic hospital from August 2012 to September 2013 were analyzed. PA values were measured by direct segmental multi-frequency BIA. As traditional nutrition assessment tools, body mass index (BMI), serum albumin levels, total lymphocyte counts, and our hospital's nutrition screening index (NSI) were also recorded. Correlations between the results of BIA and other traditional parameters were analyzed. RESULTS: PA showed correlation with traditional nutritional parameters, including BMI (r=0.479), serum albumin (r=0.347), and NSI score (r=0.483). Patients with PA lower than the median value (3.5degrees) had significantly lower nutritional status, increased duration of mechanical ventilation (P=0.039), and increased length of ICU stay (P=0.041). CONCLUSION: PA, as a reflection of body cell mass, measured by BIA could be a potentially useful parameter for nutritional assessment in critically ill patients.

The Optimal Dose of Midazolam for Promoting Sleep in Critically Ill Patients: A Pilot Study / 대한구급학회지

BACKGROUND: Many critically ill patients treated in the intensive care unit (ICU) experience sleep disruption. Midazolam is commonly used for the sedation of critically ill patients. This pilot study is aimed to identify the optimal dose of midazolam for achieving sound sleep in critically ill patients. METHODS: This prospective study was conducted in the medical ICU of a tertiary referral hospital. Polysomnography recording was performed over 24 hours to assess the quantity and quality of sleep in patients sedated with midazolam. RESULTS: A total of five patients were enrolled. Median total sleep time was 494.0 (IQR: 113.5-859.0) min. The majority of sleep was stage 1 (median 82.0 [IQR 60.5-372.5] min) and 2 (median 88.0 [60.5-621.0] min) with scant REM (median 10.0 [6.0-50.5] min) and no stage 3 (0.0 min) sleep. The median number of wakings in 1 hour was 16.1 (IQR: 7.6-28.6). The dose of midazolam showed a positive correlation with total sleep time (r = 0.975, p = 0.005). CONCLUSIONS: The appropriate quantity of sleep in critically ill patients was achieved with a continuous infusion of 0.02-0.03 mg/kg/h midazolam. However, the quality of sleep was poor. Further study is required for the promotion of quality sleep in such patients.