Bronchial washing fluid sequencing is useful in the diagnosis of lung cancer with necrotic tumor.

BACKGROUND: Early-stage lung cancers detected by low-dose computed tomography (CT) often require confirmation through invasive procedures due to the absence of endobronchial lesions. This study assesses the diagnostic utility of bronchial washing fluid (BW) sequencing, a less invasive alternative, aiming to identify patient characteristics most suited for this approach. METHODS: From June 2017 to March 2018, we conducted a prospective cohort study by enrolling patients with incidental lung lesions suspected of early-stage lung cancer at two independent hospitals, and 114 were diagnosed with lung cancer while 50 were diagnosed with benign lesions. BW sequencing was performed using a targeted gene panel, and the clinical characteristics of patients detected with cancer through sequencing were identified. RESULTS: Malignant cells were detected in 33 patients (28.9 %) through BW cytology. By applying specificity-focused mutation criteria, BW sequencing classified 42 patients (36.8 %) as having cancer. Among the cancer patients who were BW sequencing positive and BW cytology negative, 15 patients (75.0 %) showed necrosis on CT. The sensitivity of BW sequencing was particularly enhanced in patients with necrotic tumors, reaching 75 %. CONCLUSIONS: BW sequencing presents a viable, non-invasive diagnostic option for early-stage lung cancer, especially valuable in patients with necrotic lesions. By potentially reducing the reliance on more invasive diagnostic procedures, this method could streamline clinical workflows, decrease patient burden, and improve overall diagnostic efficiency.

Mortality and Discharge Outcome in Acute Myocardial Infarction Patients: A Study Based on Korean National Hospital Discharge In-Depth Injury Survey Data.

Purpose: The aim of this study was to analyze hospital-discharged acute myocardial infarction (AMI) patients in Korea (2006-2020) to understand how pre-existing conditions affect mortality rates. Participants and Methods: This study utilized the 2006-2020 Korean National Hospital Discharge In-depth Injury Survey data. A weighted frequency analysis estimated discharged AMI patients and calculated age-standardized discharge and mortality rates, Charlson Comorbidity Index (CCI) score distribution, and general patient characteristics. Weighted logistic regression analysis examined influencing mortality factors. Results: There were 486,464 AMI patients (143,751 female), with AMI-related mortality rates at 7.5% (36,312): 5.7% for males (19,190) and 11.8% for females (17,122). The highest mortality rate was among individuals aged 70-79 years (25%). Factors influencing mortality included sex, insurance type, admission route, hospital bed count, region, operation status, and CCI score. Mortality risk at discharge was 1.151 times higher in females than males (95% CI: 1.002-1.322), 0.787 times lower among those with national health insurance than Medicaid recipients (95% CI 0.64-0.967), 2.182 times higher among those admitted via the emergency department than the outpatient department (95% CI 1.747-2.725), and 3.402 times higher in patients with a CCI score of 3 points than those with 0 points (95% CI 1.263-9.162). Conclusion: The number of discharged AMI patients and related mortality rates increased, underscoring the need for proactive management of chronic diseases, particularly for those with higher CCI scores.

Toxicological Evaluation of a Polyherbal Formulation (18KHT01) and Validation of UPLC-DAD Method for Quality Control.

Background: 18KHT01 is a novel synergistic composition of Quercus acutissima, Camellia sinensis, Geranium thunbergii, and a small portion of Citrus limon. Our previous report demonstrated that the 18KHT01 exhibits potent antiobesity effects, with synergistic antioxidant, antiadipogenic, and antiobesity activities in diet-induced obese mice. This study explores the toxicity profile and quality control parameters of the 18KHT01 formulation. Methods: Broad-spectrum acute and subacute oral toxicity studies were performed using male and female ICR mice. In order to simultaneous analysis of the 18KHT01 formulation, an ultraperformance liquid chromatography coupled with a diode array detector (UPLC-DAD) method was developed and validated using six marker compounds. Results: Acute oral toxicity evaluation of 18KHT01, administered at single high doses of 2, 2.5, 3, and 5 g/kg, identified 2 g/kg as the no-observed adverse effect level (NOAEL). The LD50 (50% lethal dose) and LD100 (100% lethal dose) of 18KHT01 for male ICR mice were 3.99 and 7.77 g/kg, and those for the female mice were 2.94 and 4.70 g/kg, respectively. In addition, a 30-day repeated dose oral subacute toxicity evaluation indicated that 18KHT01 is safe below 500 mg/kg/day for long-term administration in ICR mice of either sex. UPLC-DAD method validation revealed that each calibration curve for the marker compounds showed good linearity, as well as the validation parameters such as precision, specificity, and accuracy met the acceptance criteria. Conclusion: The present study evidenced the toxicological profile of 18KHT01 polyherbal formulation in mice as well as developed a simple, rapid, and accurate chromatographic method for quality control.

Evaluation of Anti-Obesity and Antidiabetic Activities of Orostachys japonicus in Cell and Animal Models.

Orostachys japonicus is a popular traditional medicinal herb used in Asian countries. This study is focused on evaluating its role in lipid and glucose metabolism in cell and animal models to establish the plant as an anti-obesity and antidiabetic herb. A butanol fraction of O. japonicus was used in the study. The lipid production was evaluated by the Oil Red O technique while the expression of adipogenic markers by Western blotting and RT-PCR using 3T3-L1 preadipocyte. The effect on glucose uptake activity was evaluated in C2C12 myoblast cells. The animal study was carried out in C57BL mice to evaluate anti-obesity activity using the high-fat diet model. The evaluation of serum lipid, blood glucose, adipogenic and fibrosis markers in the liver, and fat deposition in the liver and adipose tissue (by histology) of mice was conducted. Butanol fraction of O. japonicus significantly inhibited the lipid production in the 3T3-L1 cells and reduced the expression of PPARγ, C/EBPα, SREBP-1c and aP2. It enhanced glucose uptake in insulin-resistant C2C12 myoblast cells. It reduced body weight, triglycerides, and blood glucose in the obese mice. It significantly inhibited lipid accumulation in the liver and adipose tissue of obese mice along with suppression of expression of adipogenic and fibrosis markers in the liver. In summary, supporting the previous results, this study helped to establish the potent anti-obesity, antidiabetic, and liver-protecting effect of the butanol fraction of O. japonicus.

Racial Disparity of Mental Health Service Utilization Among Low-Income Head Start Eligible Parents.

Based on the Head Start Impact Study, 1706 parents who had mild, moderate, and severe depressive symptoms were selected to examine the following questions: (1) Are there racial disparities in mental health service utilization among low-income parents? (2) Does Head Start have an impact on mental health service utilization across white, African American, and Hispanic parents? The present research found that, compared to white parents, African American and Hispanic parents are significantly less likely to utilize mental health services. Head Start impact was found for white parents but not for African American and Hispanic parents. Furthermore, parents who spoke a language other than English had higher household risk factors, and reside in rural areas are less likely to utilize mental health services. Mental health providers should deliver patient-centered services that consider cultural and linguistic competency as well as the personal life context of their patients to remove any barriers to accessing mental health services.

Lazertinib versus Gefitinib as First-Line Treatment for EGFR-mutated Locally Advanced or Metastatic NSCLC: LASER301 Korean Subset.

PURPOSE: This subgroup analysis of the Korean subset of patients in the phase 3 LASER301 trial evaluated the efficacy and safety of lazertinib versus gefitinib as first-line therapy for epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with locally advanced or metastatic EGFRm NSCLC were randomized 1:1 to lazertinib (240 mg/day) or gefitinib (250 mg/day). The primary endpoint was investigator-assessed progression-free survival (PFS). RESULTS: In total, 172 Korean patients were enrolled (lazertinib, n=87; gefitinib, n=85). Baseline characteristics were balanced between the treatment groups. One-third of patients had brain metastases (BM) at baseline. Median PFS was 20.8 months (95% confidence interval [CI], 16.7 to 26.1) for lazertinib and 9.6 months (95% CI, 8.2 to 12.3) for gefitinib (hazard ratio [HR], 0.41; 95% CI, 0.28 to 0.60). This was supported by PFS analysis based on blinded independent central review. Significant PFS benefit with lazertinib was consistently observed across predefined subgroups, including patients with BM (HR, 0.28; 95% CI, 0.15 to 0.53) and those with L858R mutations (HR, 0.36; 95% CI, 0.20 to 0.63). Lazertinib safety data were consistent with its previously reported safety profile. Common adverse events (AEs) in both groups included rash, pruritus, and diarrhoea. Numerically fewer severe AEs and severe treatment-related AEs occurred with lazertinib than gefitinib. CONCLUSION: Consistent with results for the overall LASER301 population, this analysis showed significant PFS benefit with lazertinib versus gefitinib with comparable safety in Korean patients with untreated EGFRm NSCLC, supporting lazertinib as a new potential treatment option for this patient population.

The Development and Validation of an AI Diagnostic Model for Sacroiliitis: A Deep-Learning Approach.

PURPOSE: Sacroiliitis refers to the inflammatory condition of the sacroiliac joints, frequently causing lower back pain. It is often associated with systemic conditions. However, its signs on radiographic images can be subtle, which may result in it being overlooked or underdiagnosed. This study aims to utilize artificial intelligence (AI) to create a diagnostic tool for more accurate sacroiliitis detection in radiological images, with the goal of optimizing treatment plans and improving patient outcomes. MATERIALS AND METHOD: The study included 492 patients who visited our hospital. Right sacroiliac joint films were independently evaluated by two musculoskeletal radiologists using the Modified New York criteria (Normal, Grades 1-4). A consensus reading resolved disagreements. The images were preprocessed with Z-score standardization and histogram equalization. The DenseNet121 algorithm, a convolutional neural network with 201 layers, was used for learning and classification. All steps were performed on the DEEP:PHI platform. RESULT: The AI model exhibited high accuracy across different grades: 94.53% (Grade 1), 95.83% (Grade 2), 98.44% (Grade 3), 96.88% (Grade 4), and 96.09% (Normal cases). Sensitivity peaked at Grade 3 and Normal cases (100%), while Grade 4 achieved perfect specificity (100%). PPVs ranged from 82.61% (Grade 1) to 100% (Grade 4), and NPVs peaked at 100% for Grade 3 and Normal cases. The F1 scores ranged from 64.41% (Grade 1) to 95.38% (Grade 3). CONCLUSIONS: The AI diagnostic model showcased a robust performance in detecting and grading sacroiliitis, reflecting its potential to enhance diagnostic accuracy in clinical settings. By facilitating earlier and more accurate diagnoses, this model could substantially impact treatment strategies and patient outcomes.

In vivo study of newly developed albumin-conjugated urate oxidase for gout treatment.

BACKGROUND: Exogenously providing engineered Uox with enhanced half-life is one of the important urate-lowering treatments for gout. The potential of PAT101, a recombinant human albumin (rHA)-conjugated variant, was evaluated and compared as a novel gout treatment through various in vivo studies with PAT101 and competing drugs. METHODS: PAT101 was produced by site-specific conjugation of rHA and Aspergillus flavus Uox (AfUox-rHA) through clickable non-natural amino acid (frTet) and Inverse electron demand Diels-Alder (IEDDA) reaction. In vivo pharmacokinetics, efficacy tests and in vitro immunogenetic assay were performed after single or multiple doses of PAT101 and its competitors in BALB/c mice, transgenic (TG) mice, Sprague-Dawley (SD) rats, and non-human primate (NHP). RESULTS: The half-life of PAT101 in single-dose treated TG mice was more than doubled compared to pegloticase. In SD rats with 4 weeks of repeated administration of rasburicase, only 24% of Uox activity remained, whereas in PAT101, it was maintained by 86%. In the Uox KO model, the survival rate of PAT101 was comparable to that of pegloticase. In addition, human PBMC-based CD4+/CD8+ T-cell activation analysis demonstrated that PAT101 has a lower immune response compared to the original drug, rasburicase. CONCLUSION: All results suggest that this rHA-conjugated AfUox, PAT101, can be provided as a reliable source of Uox for gout treatment.

The Usefulness of Present-on-Admission Data as an Indicator of Healthcare Quality Evaluation Using the Korean National Hospital Discharge in-Depth Injury Survey Data from 2006 to 2019.

Purpose: Comorbidities of a principal diagnosis have varying impacts on disease and require different management depending on the onset timing. This study investigated the usefulness of present-on-admission (POA), specifically focusing on decubitus ulcers, delirium, and hypokalemia, as an indicator of healthcare quality. Patients and Methods: We analyzed patient discharge data for 14 years from 2006 to 2019 using Korean National Hospital Discharge In-Depth Injury Survey (KNHDIS). Results: Out of 3,231,731 discharged patients, 19,871 had secondary diagnosis codes for decubitus ulcers (n=10,390, 52.3%), delirium (n=6103, 30.7%), or hypokalemia (n=3378, 17.0%). Analysis of patients with secondary diagnoses of decubitus ulcers, delirium, or hypokalemia revealed notable differences in demographics, including gender distribution, mean age, admission route, insurance type, surgical intervention rates, mortality rates, and length of stay (LOS). Among patients with one of the top 20 principal diagnoses, those with secondary diagnoses of decubitus ulcers, delirium, or hypokalemia exhibited higher odds of surgery, increased mortality risks, and longer LOS compared to those without these secondary diagnoses. Conclusion: All three of these diseases commonly occur postoperatively or during treatment and thus should be designated as potentially preventable complications that require special attention, and should also be considered as quality-of-care indicators.

Racial Disparities in the Impact of Head Start on Health Outcomes Among Low-Income Head Start-Eligible Children and Parents.

This study examined racial disparities in Head Start's impact on health outcomes for families with young children in poverty. Research questions were as follows: (a) are there racial disparities in health outcomes among low-income families? (b) Does Head Start participation promote better health outcomes? And (c) does Head Start's impact on health outcomes differ by race and ethnicity? Logistic regression analysis found that African American and Hispanic children experience lower health outcomes than their white peers, including lower rates of dental screening, more frequent injury-related care, lower overall health status, and lower rates of health insurance coverage. In comparison to White parents, African American and Hispanic parents reported lower levels of cigarette smoking. Children enrolled in Head Start received significantly more dental screening than their non-Head Start peers, regardless of race and ethnicity. The positive impacts of Head Start were particularly pronounced for African American and Hispanic children when compared to White children. Families that do not speak English as their primary language and those with lower household incomes experienced worse health outcomes. The positive impact of Head Start on the health outcomes of marginalized populations highlights the need for continued expansion of Head Start programs, as they strive to provide equal opportunities for improvements in academic, socio-emotional, and health outcomes for children and their parents in low-income households. The recruitment and enrollment process for Head Start should provide eligibility and application information in multiple languages for families in deep poverty.

Safety and Effectiveness of Trastuzumab Biosimilar SB3 in Korean Patients, a Post-Marketing Surveillance Study.

INTRODUCTION: SB3 is a trastuzumab biosimilar approved in Australia, Brazil, Canada, the European Union, the Republic of Korea, Switzerland, and the United States. This real-world study evaluated safety and effectiveness of SB3 as part of the Korean post approval safety management system. METHODS: This post-marketing surveillance in Korea included patients in line with approved indications, i.e. patients with early or metastatic breast cancer or metastatic gastric cancer. Safety outcomes were adverse events and adverse drug reactions. Effectiveness outcomes were tumor response and event-free survival. RESULTS: 424 patients were evaluated: 366 patients (86%) with early breast cancer, 53 patients (13%) with metastatic breast cancer, and 5 patients (1%) with metastatic gastric cancer. Among patients with breast cancer, adverse events (mostly mild) and adverse drug reactions were reported by 158 (37.7%) and 57 (13.6%) patients, respectively. Most patients with an AE (141, 75.9%) had no change in treatment schedule. Treatment was temporarily suspended in 14 (8.2%) patients with an AE and completely discontinued in 7 (3.7%). Among patients with early and metastatic breast cancer who were evaluated for efficacy, objective response rates were 82.7% and 38.3%, respectively. Pathological complete response was 64.6% in patients with early breast cancer. DISCUSSION/CONCLUSION: Safety and efficacy of SB3 demonstrated in this real-world study were comparable with previous studies of reference trastuzumab.

Central Nervous System Outcomes of Lazertinib Versus Gefitinib in EGFR-Mutated Advanced NSCLC: A LASER301 Subset Analysis.

INTRODUCTION: Lazertinib, a third-generation mutant-selective EGFR tyrosine kinase inhibitor, improved progression-free survival compared with gefitinib in the phase 3 LASER301 study (ClinicalTrials.gov Identifier: NCT04248829). Here, we report the efficacy of lazertinib and gefitinib in patients with baseline central nervous system (CNS) metastases. METHODS: Treatment-naive patients with EGFR-mutated advanced NSCLC were randomized one-to-one to lazertinib (240 mg/d) or gefitinib (250 mg/d). Patients with asymptomatic or stable CNS metastases were included if any planned radiation, surgery, or steroids were completed more than 2 weeks before randomization. For patients with CNS metastases confirmed at screening or subsequently suspected, CNS imaging was performed every 6 weeks for 18 months, then every 12 weeks. End points assessed by blinded independent central review and Response Evaluation Criteria in Solid Tumors version 1.1 included intracranial progression-free survival, intracranial objective response rate, and intracranial duration of response. RESULTS: Of the 393 patients enrolled in LASER301, 86 (lazertinib, n = 45; gefitinib, n = 41) had measurable and or non-measurable baseline CNS metastases. The median intracranial progression-free survival in the lazertinib group was 28.2 months (95% confidence interval [CI]: 14.8-28.2) versus 8.4 months (95% CI: 6.7-not reached [NR]) in the gefitinib group (hazard ratio = 0.42, 95% CI: 0.20-0.89, p = 0.02). Among patients with measurable CNS lesions, the intracranial objective response rate was numerically higher with lazertinib (94%; n = 17) versus gefitinib (73%; n = 11, p = 0.124). The median intracranial duration of response with lazertinib was NR (8.3-NR) versus 6.3 months (2.8-NR) with gefitinib. Tolerability was similar to the overall LASER301 population. CONCLUSIONS: In patients with CNS metastases, lazertinib significantly improved intracranial progression-free survival compared with gefitinib, with more durable responses.

In silico investigation of the structural stability as the origin of the pathogenicity of α-synuclein protofibrils.

α-Synuclein is a presynaptic neuronal protein. The fibril form of α-synuclein is a major constituent of the intraneuronal inclusion called Lewy body, a characteristic hallmark of Parkinson's disease. Recent ssNMR and cryo-EM experiments of wild-type α-synuclein fibrils have shown polymorphism and observed two major polymorphs, rod and twister. To associate the cytotoxicity of α-synuclein fibrils with their structural features, it is essential to understand the origins of their structural stability. In this study, we performed molecular dynamics simulations of the two major polymorphs of wild-type α-synuclein fibrils. The predominance of specific fibril polymorphs was rationalized in terms of relative structural stability in aqueous environments, which was attributed to the cooperative contributions of various stabilizing features. The results of the simulations indicated that highly stable structures in aqueous environments could be maintained by the cooperation of compact sidechain packing in the hydrophobic core, backbone geometry of the maximal ß-sheet content wrapping the hydrophobic core, and solvent-exposed sidechains with large fluctuations maximizing the solvation entropy. The paired structure of the two protofilaments provides additional stability, especially at the interface region, by forming steric zipper interactions and hiding the hydrophobic residues from exposure to water. The sidechain interaction analyses and pulling simulations showed that the rod polymorph has stronger sidechain interactions and exhibits higher dissociation energy than the twister polymorph. It is expected that our study will provide a basis for understanding the pathogenic behaviors of diverse amyloid strains in terms of their structural properties.Communicated by Ramaswamy H. Sarma.

Impacts of Subtype on Clinical Feature and Outcome of Male Breast Cancer: Multicenter Study in Korea (KCSG BR16-09).

PURPOSE: The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea. MATERIALS AND METHODS: We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016. RESULTS: The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003). CONCLUSION: Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.

Effects of formal center-based care and positive parenting practices on children in foster care.

BACKGROUND: The current study examined whether children in foster care have better cognitive and social-emotional outcomes at kindergarten age when they enroll in formal center-based care and when they receive positive parenting practices at home. OBJECTIVE: Two primary questions were addressed: (1) Do children in foster care who attended formal center-based care (including Head Start) have higher cognitive and socio-emotional outcomes than children in foster care who did not attend formal center-based care? (2) Does positive parenting practice promote better cognitive and socio-emotional outcomes? PARTICIPANTS AND SETTING: Based on the Early Childhood Longitudinal Study-K: 2011 data, 299 children in foster care were selected. METHODS: Regression analyses were conducted on children's cognitive and social-emotional scores by types of children's childcare arrangements (formal vs informal care) and positive parenting practices. Active parental involvement was measured based on how frequently parents read books with their children, and authoritarian parenting discipline was measured based on whether parents spanked their children. RESULTS: Children in foster care who enrolled in formal center-based childcare at pre-school age have higher cognitive and socio-emotional scores at kindergarten age. Positive parenting practice also promotes children's outcomes. Children in foster care who are both enrolled in formal center-based care and experience positive parenting practice had the most positive outcomes. CONCLUSIONS: Parents raising children in foster care should be informed about the positive impacts of certain parenting practices on their children. Foster parents should be connected to available community resources, including formal-center-based preschool programs and required to continuously attend parenting classes to sustain positive impact of parenting practice on foster children.

Effects of a Metacognitive Smartphone Intervention With Weekly Mentoring Sessions for Individuals With Schizophrenia: A Quasi-Experimental Study.

Application (app)-based interventions using smartphones could provide effective alternatives to traditional treatment programs during and beyond the coronavirus disease 2019 pandemic. The current quasi-experimental study with a non-equivalent comparison group tested the effects of a smartphone app-based metacognitive intervention program with weekly mentoring sessions on the meta-cognitive beliefs, psychotic symptoms, and social functioning of individuals with schizophrenia from community psychosocial rehabilitation centers. The study was conducted with 20 participants with severe psychotic symptoms and low social functioning and 24 participants with relatively light psychotic symptoms and good social functioning as a comparison group. For the experimental group, the app-based intervention was combined with weekly contact mentoring sessions over 10 weeks. The comparison group received only the app-based intervention over 10 weekly sessions. No differences were observed between groups' total scores; however, the experimental group showed a tendency toward improved psychotic symptoms and social functioning over time, unlike the comparison group. These findings provide an empirical basis for managing schizophrenia symptoms with smartphone apps. [Journal of Psychosocial Nursing and Mental Health Services, 61(2), 27-37.].

Effectiveness of a Metacognitive Intervention for Schizophrenia (MCI-S) Program for Symptom Relief and Improvement in Social Cognitive Functioning in Patients with Schizophrenia.

This study investigated the effectiveness of a metacognitive intervention program for symptom relief and improvement in social cognitive functioning among adults with schizophrenia. The program focused on enhancing metacognition to encourage self-awareness and step-by-step perspective expansion. There were 24 participants in the experimental group and 19 participants in the control group. Delusions decreased, and social cognition and social functioning improved in the experimental group compared to the control group. The program demonstrated utility as a treatment modality, which can be part of an overall program of a mental health promotion institution to improve functioning in patients with schizophrenia.

Efficacy of crizotinib retreatment after crizotinib-related interstitial lung disease in a patient with ROS1-rearranged advanced lung adenocarcinoma: A case report and potential crizotinib retreatment strategy.

Crizotinib is an oral selective small-molecular tyrosine kinase inhibitor (TKI) that suppress the activity of anaplastic lymphoma kinase (ALK) and ROS1 kinases, as well as mesenchymal-epithelial transition. The cumulative clinical trials in patients with advanced ALK- or ROS1-rearrangement NSCLC indicate that crizotinib has significant antitumor activity and a tolerable safety profile, with mild or moderate adverse events of visual disorders, diarrhea, nausea, and vomiting. As with other TKIs, however, the occurrence of crizotinib-related interstitial lung disease (crizotinib-ILD) remains a major clinical dilemma that can lead to the permanent discontinuation of TKI during cancer treatment. When there is no suitable alternative therapy for patients who develop crizotinib-ILD, some clinicians have reported successful crizotinib retreatment in cases of ALK-rearrangement NSCLC. Unfortunately, there are no specific guidelines for the treatment or retreatment of TKI-related ILD. We herein report the first successful crizotinib retreatment after crizotinib-ILD in a patient with ROS1-rearranged NSCLC, and suggest a retreatment strategy after crizotinib-ILD based on a literature review.

Factors influencing patient disclosure of cancer diagnosis to the family dentist: online survey in Japan.

Oral care during cancer treatment constitutes essential supportive care. We aimed to identify factors associated with cancer patients informing their family dentists about their cancer diagnosis. Using the generated original questionnaire, we conducted a cross-sectional questionnaire study in 500 cancer patients (gastric, colorectal, lung, breast, and prostate cancer) through the Internet from September 10 to 13, 2019. The factors influencing patients' disclosure of their cancer diagnosis to their family dentist were identified by multivariable logistic regression analysis. Nearly half of the respondents (42.2%) informed their family dentist that they had cancer. The disclosing behavior of cancer patients was distinctively associated with their physician's advice (odds ratio [OR] 59.3; 95% confidence interval [CI] 7.7-456.3); 8.6% of all respondents were advised to inform their dentist about their cancer diagnosis. In the group without the physician's advice, good relationship with family dentist was associated with disclosing behavior. This study indicates the need for support for cancer patients to receive appropriate oral care; patients' perceptions of the physician's advice and communication with the family dentist should be motivators for disclosing the cancer diagnosis to dentists. Medical workers involved in cancer care should demonstrate the benefit of medical-dental collaboration in cancer care of patients.

Temporal trends in clinical characteristics and in-hospital mortality among patients with COVID-19 in Japan for waves 1, 2, and 3: A retrospective cohort study.

INTRODUCTION: Little information is available on the temporal trends in the clinical epidemiology and in-hospital mortality of patients with coronavirus disease 2019 (COVID-19) in Japan for waves 1, 2, and 3. METHODS: A national claims database was used to analyze the time trends in admission, medical procedure, and in-hospital mortality characteristics among patients with COVID-19. Patients who were ≥18 years and discharged from January 1, 2020 to February 28, 2021 were included. RESULTS: A multilevel logistic regression analysis of 51,252 patients revealed a decline in mortality in waves 2 and 3 (risk-adjusted mortality range = 2.17-4.07%; relative risk reduction = 23-59%; reference month of April 2020 = 5.32%). In the subgroup analysis, a decline in mortality was also observed in patients requiring oxygen support but not mechanical ventilation (risk-adjusted mortality range = 5.98-11.68%; relative risk reduction = 22-60%; reference month of April 2020 = 15.06%). Further adjustments for medical procedure changes in the entire study population revealed a decrease in mortality in waves 2 and 3 (risk-adjusted mortality range = 2.66-4.05%; relative risk reduction = 24-50%). CONCLUSIONS: A decline in in-hospital mortality was observed in waves 2 and 3 after adjusting for patient/hospital-level characteristics and medical treatments. The reasons for this decline warrant further research to improve the outcomes of hospitalized patients.