The impact of comorbidities, neutrophil-to-lymphocyte ratio, and drug toxicities on quality of life in lung cancer patients receiving EGFR-TKI therapy.

BACKGROUND: Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are used as the standard first-line treatment for patients with advanced EGFR-mutated non-small cell lung cancer (NSCLC). However, the impact of comorbidities and treatment toxicities on quality of life (QoL) was seldom investigated. OBJECTIVE: We aimed to investigate the association of comorbidities, adverse events (AEs), and QoL in treatment-naïve advanced NSCLC patients receiving EGFR-TKI treatments. METHODS: This multi-center prospective observational study was conducted to evaluate QoL and AEs at baseline, the 2nd, 4th, 12th, and 24th week. Clinical characteristics, comorbidities, and pre-treatment laboratory data were recorded. QoL was assessed by using the summary score of the EORTC QLQ-C30 and the dermatology life quality index. The impact of comorbidities, neutrophil-to-lymphocyte ratio (NLR), and AEs on QoL was analyzed by generalized estimating equations. RESULTS: A total of 121 patients were enrolled. Diarrhea (p = 0.033), anorexia (p < 0.001), and NLR ≥4 (p = 0.017) were significantly associated with a QoL impairment. Among skin toxicities, acneiform rash (p = 0.002), pruritus (p = 0.002), visual analogue scale for pruritus (≥3 and < 7, p = 0.006; ≥7, p = 0.001) and pain (1-3, p = 0.041) were associated with a QoL impairment. No significant association was found between comorbidities and QoL changes. CONCLUSION: Diarrhea, anorexia, skin pain, and pruritus may cause a deterioration in QoL in patients receiving EGFR-TKI therapy. NLR may be a potential predictive factor for QoL impairment. Aggressive management and close monitoring for these clinical factors are crucial to improve QoL.

Toll-like receptor and matrix metalloproteinase single-nucleotide polymorphisms, haplotypes, and polygenic risk score differentiated between tuberculosis disease and infection.

OBJECTIVES: The association of toll-like receptors (TLRs) and matrix metalloproteinases (MMPs) single-nucleotide polymorphisms (SNPs) among latent tuberculosis (TB) infection and active TB remained less studied. METHODS: We recruited participants with TB disease (active TB) (n = 400) and TB infection (latent TB infection) (n = 203) in this study. We genotyped SNPs in TLR1, TLR2, TLR4, MMP1, MMP8, MMP9, MMP12, and tissue inhibitor of MMP2. Single-variant analysis and haplotype analysis were performed, and a polygenic risk score (PRS) was created. RESULTS: We found that SNPs in TLR1 (rs5743580, rs5743551), TLR2 (rs3804100), and MMP8 (rs2508383) were associated with different TB disease status risks. TLR1 rs5743580 was associated with a higher risk of TB disease status in genotypic, recessive, and additive models. TLR2 rs3804100 polymorphisms demonstrated significant association with TB disease status in genotypic, dominant, and additive models. In the haplotype analysis, the TLR1 haplotype was associated with a higher risk of TB disease, and the MMP12 haplotype was associated with a lower risk of TB disease. A PRS using 3 SNPs was associated with a higher risk of TB disease. CONCLUSION: This study revealed that SNP variants in TLR1, TLR2, and MMP8 differed among TB infection and disease. Haplotypes and PRS could potentially help predict TB disease status.

Comparison of clinically indicated replacement and routine replacement of peripheral intravenous catheters: A systematic review and meta-analysis of randomized controlled trials.

Background: It is unknown whether clinically indicated replacement of peripheral intravenous catheters (PIVCs) increases the risks of PIVC-associated complications and infections compared to routine replacement of PIVCs. Methods: We searched PubMed, the Web of Science, the Cochrane Library, Ovid MEDLINE, and Clinicaltrials.gov for randomized controlled trials (RCTs) that compare the safety outcomes of routine replacement and clinically indicated replacement of PIVCs were included for meta-analysis. The primary outcome was the incidence of phlebitis, and secondary outcomes included the risks of occlusion, local infection, infiltration, catheter-related bloodstream infection (CRBSI), and accidental removal of the PIVC. Results: A total of 9 RCTs involving 10 973 patients were included in this meta-analysis, of whom 5,546 and 5,527 were assigned to the study group (clinically indicated replacement of PIVCs) and control group (routine replacement of PIVCs every 72-96 h), respectively. The incidence of phlebitis in the study group was significantly higher than that in the control group [risk ratio (RR), 1.20; 95% confidence interval (CI), 1.01-1.44, P = 0.04, I2 = 49%]. In addition, the study group was associated with a higher risk of occlusion (RR, 1.45; 95% CI, 1.08-1.95, P = 0.01, I2 = 82%) and infiltration (fluid leaks) (RR, 1.27; 95% CI, 1.06-1.53, P = 0.01, I2 = 72%) than the control group. However, no significant differences were observed in the risks of local infection (RR, 1.75; 95% CI, 0.38-8.16, P = 0.48, I2 = 0%) and CRBSI (RR, 0.61; 95% CI, 0.08-4.68, P = 0.64, I2 = 0%) between the study and control groups. Conclusion: The clinically indicated replacement of PIVCs may increase the risks of PIVC-associated phlebitis, infiltration, and occlusion compared to the routine replacement of PIVCs, but did not increase the risk of PIVC-associated infections. Based on these findings, routine replacement of PIVCs every 72-96 h maybe a preferred option than clinically indicated replacement of PIVCs. Systematic review registration: [www.crd.york.ac.uk/prospero/], identifier [CRD42022302021].

The impact of driver mutation on the treatment outcome of early-stage lung cancer patients receiving neoadjuvant immunotherapy and chemotherapy.

Neoadjuvant immunotherapy and chemotherapy have improved the major pathological response (MPR) in patients with early-stage operable non-small cell lung cancer (NSCLC). This study aimed to assess whether the presence of targetable driver mutations affects the efficacy of the combination of immunotherapy and chemotherapy. We enrolled patients with early-stage operable NSCLC who received preoperative neoadjuvant therapy between January 1, 2017, and December 30, 2020. Neoadjuvant therapy was delivered with platinum-doublet chemotherapy; moreover, pembrolizumab was added at the attending physician's discretion based on patient's request. Pathological responses were assessed; moreover, disease-free survival was estimated. Next-generation sequencing was performed in case sufficient preoperative biopsy specimens were obtained. We included 23 patients; among them, 11 received a combination of neoadjuvant immunotherapy and chemotherapy while 12 received neoadjuvant chemotherapy alone. The MPR and pathological complete response rates were 54.5% and 27.3%, respectively, in patients who received a combination of neoadjuvant immunotherapy and chemotherapy. These rates were significantly higher than those in patients who only received neoadjuvant chemotherapy. Three patients in the combination group experienced disease recurrence during the follow-up period even though two of them showed an MPR. These three patients had targetable driver mutations, including an EGFR exon 20 insertion, EGFR exon 21 L858R substitution, and MET exon 14 skipping. Only one patient who remained disease-free had a targetable driver mutation. Among patients with early-stage operable NSCLC requiring neoadjuvant therapy, comprehensive genomic profiling is crucial before the administration of the combination of neoadjuvant immunotherapy and chemotherapy.

S-1 plus cisplatin as first-line treatment of patients with advanced non-small cell lung cancer in Taiwan.

AIM: S-1 combined with cisplatin is known to be noninferior to taxanes plus platinum as the first-line treatment for patients with advanced nonsmall cell lung cancer (NSCLC) in the Japanese population. This study aimed to evaluate the efficacy and safety profiles of oral S-1 plus cisplatin (SP) in Taiwanese patients. METHODS: Patients with previously untreated stage IIIB or IV NSCLC were prospectively recruited to receive 40-60 mg of S-1 twice daily on days 1-21 plus 60 mg/m2 of cisplatin on day 8 in a 5-week cycle for up to six cycles. RESULTS: A total of 55 patients from five cancer centers in Taiwan were enrolled. Among the 46 evaluable patients, those administered with SP achieved disease control rate of 69.6% (partial response, 19.6%; stable disease, 50.0%), with median overall survival and progression-free survival (PFS) of 15.1 and 5.7 months, respectively. Moreover, a better survival trend was observed in epidermal growth factor receptor mutation-positive patients versus mutation-negative patients treated with SP (PFS, 8.6 vs 5.6 months). The most commonly observed treatment-related adverse events (AEs) were nausea (41.8%), followed by decreased appetite, anemia, and diarrhea. Grade of ≥3 AEs related to the study treatment occurred in 11 patients (20.0%). No febrile neutropenia or treatment-related death was found in this study. CONCLUSIONS: This study demonstrated that SP is an effective and safe first-line regimen for Taiwanese patients with advanced NSCLC.

Association of chronic kidney disease with mortality risk in patients with lung cancer: a nationwide Taiwan population-based cohort study.

OBJECTIVE: Our population-based research aimed to clarify the association between chronic kidney disease (CKD) and mortality risk in patients with lung cancer. DESIGN: Retrospective cohort study SETTING: National health insurance research database in Taiwan PARTICIPANTS: All (n=1 37 077) Taiwanese residents who were diagnosed with lung cancer between 1997 and 2012 were identified. Eligible patients with baseline CKD (n=2269) were matched with controls (1:4, n=9076) without renal disease according to age, sex and the index day of lung cancer diagnosis. METHODS: The cumulative incidence of death was calculated by the Kaplan-Meier method, and the risk determinants were explored by the Cox proportional hazards model. RESULTS: Mortality occurred in 1866 (82.24%) and 7135 (78.61%) patients with and without CKD, respectively (P=0.0001). The cumulative incidences of mortality in patients with and without chronic renal disease were 72.8% vs 61.6% at 1 year, 82.0% vs 76.6% at 2 years and 88.9% vs 87.2% at 5 years, respectively. After adjusting for multiple confounding factors including age and comorbidities, Cox regression analysis revealed that CKD was associated with an increased risk of mortality (adjusted HR 1.38; 95% CI 1.29 to 1.47). Stratified analysis further showed that the association was consistent across patient subgroups. CONCLUSION: Comorbidity associated with CKD is a risk factor for mortality in patients with lung cancer.

Scabies increased the risk and severity of COPD: a nationwide population-based study.

BACKGROUND: Scabies is a common parasitic infectious disease, and COPD is a major pulmonary disease. However, there have been no previous studies that have investigated the relationship between scabies and COPD. MATERIALS AND METHODS: This nationwide population-based study included a total of 3,568 patients with scabies as the study group and 14,255 patients as a control group. We followed up patients in both groups for a 5-year period to identify any new diagnoses of COPD. We then followed them up for an additional 2-year period to determine the severity of any newly diagnosed cases of COPD as indicated by acute respiratory events. Cox proportional hazard regression analyses were performed to calculate the hazard ratio (HR) of COPD during the 5-year follow-up period and COPD complication during the additional 2-year follow-up period. RESULTS: Of the 17,823 patients in the study, 2,765 (15.5%) were newly diagnosed with COPD during the 5-year follow-up period; 904 (32.7%) were from the scabies group; and 1,861 (67.3%) were from the control group. Compared to the patients without scabies, the adjusted HR (aHR) for COPD for the subjects with scabies was 1.72 (95% CI: 1.59-1.87) during the 5-year follow-up period. For those newly diagnosed with COPD, the aHR for COPD with acute exacerbation was 1.85 (95% CI: 1.67-2.06), the aHR for COPD with pneumonia was 3.29 (95% CI: 2.77-3.92), the aHR for COPD with acute respiratory failure was 4.00 (95% CI: 3.08-5.19), and the aHR for COPD with cardiopulmonary arrest was 3.95 (95% CI: 2.25-6.95) during the additional 2-year follow-up period. CONCLUSION: The results of this study indicate a 72% increased risk for COPD among patients with scabies. The results also reveal an increased risk of severe COPD complications such as acute respiratory failure, cardiopulmonary arrest, pneumonia, and acute exacerbation among patients with scabies. This useful information may help physicians in treating scabies and remaining alert to the potential development of COPD and its severe complications.

Sleep Disordered Breathing Mimicking Myasthenia Crisis in a Patient with Myasthenia Gravis.

ABSTRACT: Myasthenia gravis (MG) can result in weakness of the respiratory muscles in 30% of patients. A life-threatening exacerbation, MG crisis can cause respiratory insufficiency requiring mechanical ventilation. Sleep disordered breathing (SDB) is seen in 40% to 60% of stable MG patients. Factors associated with SDB include age, male sex, obesity, and steroid use. Continuous positive airway pressure (CPAP) can reverse paradoxical weakness in MG patients with obstructive sleep apnea (OSA), but whether SDB can contribute to respiratory failure in MG and whether CPAP works in such patients remain unclear. This report presents a 54-year-old woman with MG with a history of 7 episodes of respiratory failure requiring mechanical ventilation. For each episode, she was treated for MG crisis using plasmapheresis and high-dose steroids. Later, OSA and obesity hypoventilation syndrome were confirmed by polysomnography with transcutaneous CO2 monitoring. Thereafter, the patient had no further recurrence of MG crisis for 5 years, using pyridostigmine and CPAP only.

Clinical characteristics of Q fever and etiology of community-acquired pneumonia in a tropical region of southern Taiwan: a prospective observational study.

BACKGROUND: The clinical characteristics of Q fever are poorly identified in the tropics. Fever with pneumonia or hepatitis are the dominant presentations of acute Q fever, which exhibits geographic variability. In southern Taiwan, which is located in a tropical region, the role of Q fever in community-acquired pneumonia (CAP) has never been investigated. METHODOLOGY/PRINCIPAL FINDINGS: During the study period, May 2012 to April 2013, 166 cases of adult CAP and 15 cases of acute Q fever were prospectively investigated. Cultures of clinical specimens, urine antigen tests for Streptococcus pneumoniae and Legionella pneumophila, and paired serologic assessments for Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Q fever (Coxiella burnetii) were used for identifying pathogens associated with CAP. From April 2004 to April 2013 (the pre-study period), 122 cases of acute Q fever were also included retrospectively for analysis. The geographic distribution of Q fever and CAP cases was similar. Q fever cases were identified in warmer seasons and younger ages than CAP. Based on multivariate analysis, male gender, chills, thrombocytopenia, and elevated liver enzymes were independent characteristics associated with Q fever. In patients with Q fever, 95% and 13.5% of cases presented with hepatitis and pneumonia, respectively. Twelve (7.2%) cases of CAP were seropositive for C. burnetii antibodies, but none of them had acute Q fever. Among CAP cases, 22.9% had a CURB-65 score ≧2, and 45.8% had identifiable pathogens. Haemophilus parainfluenzae (14.5%), S. pneumoniae (6.6%), Pseudomonas aeruginosa (4.8%), and Klebsiella pneumoniae (3.0%) were the most common pathogens identified by cultures or urine antigen tests. Moreover, M. pneumoniae, C. pneumoniae, and co-infection with 2 pathogens accounted for 9.0%, 7.8%, and 1.8%, respectively. CONCLUSIONS: In southern Taiwan, Q fever is an endemic disease with hepatitis as the major presentation and is not a common etiology of CAP.

Trends and predictors of changes in pulmonary function after treatment for pulmonary tuberculosis.

OBJECTIVES: The present study aimed to investigate the trends in changes in pulmonary function and the risk factors for pulmonary function deterioration in patients with pulmonary tuberculosis after completing treatment. INTRODUCTION: Patients usually have pulmonary function abnormalities after completing treatment for pulmonary tuberculosis. The time course for changes in pulmonary function and the risk factors for deterioration have not been well studied. METHODS: A total of 115 patients with 162 pulmonary function results were analyzed. We retrieved demographic and clinical data, radiographic scores, bacteriological data, and pulmonary function data. A generalized additive model with a locally weighted scatterplot smoothing technique was used to evaluate the trends in changes in pulmonary function. A generalized estimating equation model was used to determine the risk factors associated with deterioration of pulmonary function. RESULTS: The median interval between the end of anti-tuberculosis treatment and the pulmonary function test was 16 months (range: 0 to 112 months). The nadir of pulmonary function occurred approximately 18 months after the completion of the treatment. The risk factors associated with pulmonary function deterioration included smear-positive disease, extensive pulmonary involvement prior to anti-tuberculosis treatment, prolonged anti-tuberculosis treatment, and reduced radiographic improvement after treatment. CONCLUSIONS: After the completion of anti-tuberculosis TB treatment, several risk factors predicted pulmonary function deterioration. For patients with significant respiratory symptoms and multiple risk factors, the pulmonary function test should be followed up to monitor the progression of functional impairment, especially within the first 18 months after the completion of anti-tuberculosis treatment.

Trends and predictors of changes in pulmonary function after treatment for pulmonary tuberculosis

OBJECTIVES: The present study aimed to investigate the trends in changes in pulmonary function and the risk factors for pulmonary function deterioration in patients with pulmonary tuberculosis after completing treatment. INTRODUCTION: Patients usually have pulmonary function abnormalities after completing treatment for pulmonary tuberculosis. The time course for changes in pulmonary function and the risk factors for deterioration have not been well studied. METHODS: A total of 115 patients with 162 pulmonary function results were analyzed. We retrieved demographic and clinical data, radiographic scores, bacteriological data, and pulmonary function data. A generalized additive model with a locally weighted scatterplot smoothing technique was used to evaluate the trends in changes in pulmonary function. A generalized estimating equation model was used to determine the risk factors associated with deterioration of pulmonary function. RESULTS: The median interval between the end of anti-tuberculosis treatment and the pulmonary function test was 16 months (range: 0 to 112 months). The nadir of pulmonary function occurred approximately 18 months after the completion of the treatment. The risk factors associated with pulmonary function deterioration included smear-positive disease, extensive pulmonary involvement prior to anti-tuberculosis treatment, prolonged anti-tuberculosis treatment, and reduced radiographic improvement after treatment. CONCLUSIONS: After the completion of anti-tuberculosis TB treatment, several risk factors predicted pulmonary function deterioration. For patients with significant respiratory symptoms and multiple risk factors, the pulmonary function test should be followed up to monitor the progression of functional impairment, especially within the first 18 months after the completion of anti-tuberculosis treatment.