Clinical Prognosis of Lung Cancer in Patients with Moderate Chronic Kidney Disease.

The clinical outcomes of patients with lung cancer coexisting with chronic kidney disease (CKD) are reported to have been conflicting. There is insufficient evidence for treatment and prognosis of lung cancer according to renal function in patients with CKD. We evaluate clinical course and prognostic factors of lung cancer according to the renal function of moderate CKD patients. A retrospective, multicenter study of lung cancer patients with moderate CKD was performed. Moderate CKD was defined as having an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. CKD was classified as stage 3, stage 4, and stage 5 according to eGFR. The cumulative mortality of lung cancer was calculated by competing risks survival analysis, and the risk factors were evaluated by the Cox-proportional hazards model. Among the lung cancer patients with moderate CKD (n = 181), median overall survival (OS) was 11.1 (4.2−31.3) months for stage 3 CKD patients, 6.0 (1.8−16.3) months for stage 4 CKD patients, and 4.7 (2.1−40.1) months for stage 5 CKD patients (p = 0.060), respectively. In a subgroup analysis, CKD stage was associated with an increased mortality in early-stage non-small cell lung cancer (NSCLC). Cox regression analysis revealed that age ≥ 75 years (adjusted hazard ratio (aHR), 1.581; 95% confidence interval (CI), 1.082−2.310), Charlson comorbidity index (aHR, 1.669; 95% CI, 10.69−2.605), and stage IV NSCLC (aHR, 2.395; 95% CI, 1.512−3.796) were associated with increased mortality risk, whereas adenocarcinoma (aHR, 0.580; 95% CI, 0.352−0.956) and stage 3 CKD (aHR, 0.598; 95% CI, 0.399−0.895) were associated with decreased mortality risk. In conclusion, the mortality risk of patients with lung cancer was lower in stage 3 CKD compared with stage 4 or 5 CKD. In addition, in the early stages of NSCLC, the CKD stage affected the prognosis, but not in the advanced stage NSCLC.

Population pharmacokinetics of piperacillin/tazobactam in critically ill Korean patients and the effects of extracorporeal membrane oxygenation.

OBJECTIVES: To explore extracorporeal membrane oxygenation (ECMO)-related alterations of the pharmacokinetics (PK) of piperacillin/tazobactam and determine an optimal dosage regimen for critically ill adult patients. METHODS: Population PK models for piperacillin/tazobactam were developed using a non-linear mixed effect modelling approach. The percentage of time within 24 h for which the free concentration exceeded the MIC at a steady-state (50%fT>MIC, 100%fT>MIC, and 100%fT>4×MIC) for various combinations of dosage regimens and renal function were explored using Monte-Carlo simulation. RESULTS: A total of 226 plasma samples from 38 patients were used to develop a population PK model. Piperacillin/tazobactam PK was best described by two-compartment models, in which estimated glomerular filtration rate (eGFR), calculated using CKD-EPI equation based on cystatin C level, was a significant covariate for total clearance of each piperacillin and tazobactam. ECMO use decreased the central volume of distribution of both piperacillin and tazobactam in critically ill patients. Patients with Escherichia coli or Klebsiella pneumoniae infection, but not those with Pseudomonas aeruginosa infection, exhibited a PK/pharmacodynamic target attainment >90% when the target is 50%fT>MIC, as a result of applying the currently recommended dosage regimen. Prolonged or continuous infusion of 16 g/day was required when the treatment goal was 100%fT>MIC or 100%fT>4×MIC, and patients had an eGFR of 130-170 mL/min/1.73 m2. CONCLUSIONS: ECMO use decreases piperacillin/tazobactam exposure. Prolonged or continuous infusion can achieve the treatment target in critically ill patients, particularly when MIC is above 8 mg/L or when patients have an eGFR of 130-170 mL/min/1.73 m2.

Pretreatment Neutrophil-to-Lymphocyte Ratio and Smoking History as Prognostic Factors in Advanced Non-Small Cell Lung Cancer Patients Treated with Osimertinib.

BACKGROUND: The remarkable efficacy of osimertinib in non‒small cell lung cancer (NSCLC) with acquired T790M mutation has been widely documented in clinical trials and real-world practice. However, some patients show primary resistance to this drug. Even patients who initially show a favorable response have inconsistent clinical outcomes later. Therefore, the aim of this study was to identify additional clinical predictive factors for osimertinib efficacy. METHODS: A prospective cohort of patients with acquired T790M positive stage IV lung adenocarcinoma treated with osimertinib salvage therapy in Hallym University Medical Center were analyzed. RESULTS: Sixty-one eligible patients were analyzed, including 38 (62%) women and 39 (64%) who never smoked. Their mean age was 63.3 years. The median follow-up after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) was 36.0 months (interquartile range, 24.7-50.2 months). The majority (n=45, 74%) of patients were deceased. Based on univariate analysis, low baseline neutrophil-to-lymphocyte ratios (NLR), age ≥50 years, never-smoking history, stage IVA at osimertinib initiation, and prolonged response to previous TKIs (≥10 months) were associated with a significantly longer progression-free survival (PFS). Multivariate analysis showed that never-smoking status (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.30-0.98; p=0.041) and a baseline NLR less than or equal to 3.5 (HR, 0.23; 95% CI, 0.12-0.45; p-lt;0.001) were independently associated with a prolonged PFS with osimertinib. CONCLUSION: Smoking history and high NLR were independent negative predictors of osimertinib PFS in patients with advanced NSCLC developing EGFR T790M resistance after the initial EGFR-TKI treatment.

Impact of the severity of restrictive spirometric pattern on nutrition, physical activity, and quality of life: results from a nationally representative database.

The general disease burden associated with the restrictive spirometric pattern (RSP) is substantial. However, the impact of RSP by its severity on general health problems and quality of life has not been well elucidated. This study aimed to analyse nutrition, physical activity, and quality of life in subjects who participated in the Korea National Health and Nutrition Examination Survey 2007-2016 according to severity of RSP. Participants were classified as subjects with normal spirometry, those with mild-to-moderate RSP, and those with severe RSP. Poor quality of life was defined as 25th percentile value on the EuroQoL five dimensions (Eq5D) questionnaire index, i.e., 0.90. This study included 23,615 subjects composed of 20,742 with normal spirometry, 2758 with mild-to-moderate RSP, and 115 with severe RSP. The subjects with severe RSP were more likely to have attained lower education levels, had a lower total caloric intake, had less physical activity, had experienced a higher prevalence of comorbidities, and poorer quality of life than those with normal spirometry (P < 0.001 for all). In multivariable analysis, subjects with a mild-to-moderate RSP and severe RSP were more likely to show decreased total calories (coefficient for change in calorie = - 56.6 kcal and - 286.7 kcal, respectively) than those with normal spirometry; subjects with mild-to-moderate RSP and those with severe RSP were 1.26 times and 1.96 times more likely, respectively, to have a poorer quality of life than those with normal spirometry. Additionally, subjects with mild-to-moderate RSP and those with severe RSP were 0.84 times and 0.36 times less likely, respectively, to have high-intensity physical activity than those with normal spirometry in univariable analysis. The trends of a poorer quality of life and physical activity were only significant in the male subgroups. In conclusion, our study revealed that the severity of general health problems and quality of life reductions are correlated with the severity of RSP, especially in males.

Collateral effects of the coronavirus disease 2019 pandemic on lung cancer diagnosis in Korea.

BACKGROUND: The COVID-19 pandemic is predicted to significantly affect patients with lung cancer, owing to its rapid progression and high mortality. Studies on lung cancer diagnosis and treatment during an epidemic are lacking. We analyzed the impact of COVID-19 on lung cancer diagnosis in Korea, where lung cancer incidence continues to rise. METHODS: The number of newly diagnosed lung cancer cases in three university-affiliated hospitals during the pandemic and their clinical features were compared with lung cancer cases diagnosed during the same period in the past 3 years. The effectiveness of measures taken by the study hospitals to prevent nosocomial transmission was reviewed. RESULTS: A total of 612 patients were diagnosed with lung cancer from February through June, 2017-2020. During the pandemic, the number of patients who sought consultation at the division of pulmonology of study hospitals dropped by 16% from the previous year. Responding to the pandemic, the involved hospitals created physically isolated triage areas for patients with acute respiratory infection symptoms. Wide-range screening and preventive measures were implemented, thus minimizing the delay in lung cancer diagnosis. No patient acquired COVID-19 due to hospital exposure. The proportion of patients with stage III-IV non-small-cell lung cancer (NSCLC) significantly increased (2020: 74.7% vs. 2017: 57.9%, 2018: 66.7%, 2019: 62.7%, p = 0.011). The number of lung cancers diagnosed during this period and the previous year remained the same. CONCLUSIONS: The proportion of patients with advanced NSCLC increased during the COVID-19 pandemic.

Thyroid transcription factor-1 as a prognostic indicator for stage IV lung adenocarcinoma with and without EGFR-sensitizing mutations.

BACKGROUND: Thyroid transcription factor (TTF)-1 expression is a diagnostic marker and a good prognostic indicator for lung adenocarcinoma. However, its good prognostic ability might be due to epidermal growth factor receptor (EGFR)-sensitizing mutations as shown by the positive correlation between TTF-1 expression and EGFR mutations. We explored the prognostic impact of TTF-1 expression according to EGFR-sensitizing mutation status in lung adenocarcinoma patients. METHODS: We conducted a retrospective cohort study of patients with stage IV lung adenocarcinoma. Data were extracted from the lung cancer registry of Hallym University Medical Centers (three hospitals) in Korea between March 2006 and March 2016. RESULTS: Overall, 173 patients were included. EGFR-sensitizing mutations were detected in 84 (51.4%) patients. TTF-1 expression was positive in 139 (80.3%) patients; it was significantly correlated with EGFR-sensitizing mutations (p < 0.001). TTF-1-positive lung adenocarcinoma patients had longer overall survival (OS) than those who were TTF-1 negative (19.3 vs. 5.8 months, p < 0.001). In a Cox regression analysis, TTF-1 positivity, Stage IV M1a, good performance status, and EGFR-sensitizing mutations were independently associated with prolonged OS. In the subgroup of wild-type EGFR adenocarcinoma patients, TTF-1 positivity was also a good prognostic indicator for OS and progression-free survival (PFS) after first-line cytotoxic chemotherapy. CONCLUSIONS: TTF-1 expression was a good prognostic indicator for OS and PFS in stage IV lung adenocarcinoma patients with and without EGFR-sensitizing mutations.

Endoscopic Treatment of Jejunal Heterotopic Gastric Mucosa that Caused Recurrent Intussusception.

Heterotopic gastric mucosa (HGM) is a rare anomaly in the small bowel and may be the cause of intussusception when it gets a lead point in the jejunum. All cases of intussusception due to intestinal HGM have been treated with surgical resection. A 5-year-old girl presented with chief complaints of vomiting and abdominal pain for 2 weeks. A computed tomography scan of the abdomen showed intussusception at the proximal jejunal loops. Three air reductions and one saline reduction were attempted without success. She continued to be symptomatic, and endoscopic evaluation was performed. Enteroscopy revealed some variable-sized polypoid mucosal lesions with erosions on the proximal jejunum. Endoscopic mucosal resection was performed using a snare. The resected tissues histologically showed a hyperplastic polyp arising from the HGM. Her symptoms did not recur within 1 year after the treatment. Our case showed that enteroscopy could be useful for the diagnosis and management of jejunal intussusception caused by HGM.