Artificial intelligence-based analysis of the spatial distribution of abnormal computed tomography patterns in SARS-CoV-2 pneumonia: association with disease severity.

BACKGROUND: The substantial heterogeneity of clinical presentations in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia still requires robust chest computed tomography analysis to identify high-risk patients. While extension of ground-glass opacity and consolidation from peripheral to central lung fields on chest computed tomography (CT) might be associated with severely ill conditions, quantification of the central-peripheral distribution of ground glass opacity and consolidation in assessments of SARS-CoV-2 pneumonia remains unestablished. This study aimed to examine whether the central-peripheral distributions of ground glass opacity and consolidation were associated with severe outcomes in patients with SARS-CoV-2 pneumonia independent of the whole-lung extents of these abnormal shadows. METHODS: This multicenter retrospective cohort included hospitalized patients with SARS-CoV-2 pneumonia between January 2020 and August 2021. An artificial intelligence-based image analysis technology was used to segment abnormal shadows, including ground glass opacity and consolidation. The area ratio of ground glass opacity and consolidation to the whole lung (GGO%, CON%) and the ratio of ground glass opacity and consolidation areas in the central lungs to those in the peripheral lungs (GGO(C/P)) and (CON(C/P)) were automatically calculated. Severe outcome was defined as in-hospital death or requirement for endotracheal intubation. RESULTS: Of 512 enrolled patients, the severe outcome was observed in 77 patients. GGO% and CON% were higher in patients with severe outcomes than in those without. Multivariable logistic models showed that GGO(C/P), but not CON(C/P), was associated with the severe outcome independent of age, sex, comorbidities, GGO%, and CON%. CONCLUSION: In addition to GGO% and CON% in the whole lung, the higher the ratio of ground glass opacity in the central regions to that in the peripheral regions was, the more severe the outcomes in patients with SARS-CoV-2 pneumonia were. The proposed method might be useful to reproducibly quantify the extension of ground glass opacity from peripheral to central lungs and to estimate prognosis.

Serial interferon-gamma release assay in lung cancer patients receiving immune checkpoint inhibitors: a prospective cohort study.

Recent advancements in cancer immunotherapy using immune checkpoint inhibitors (ICIs) have received considerable attention. Although advantageous, ICI therapies cause unique immune-related adverse events (irAEs) in some patients. Moreover, infectious diseases, such as tuberculosis, have been recognized as emerging concerns during immunotherapy. We aimed to evaluate the interferon-gamma release assay (IGRA) conversion rate and active tuberculosis incidence during immunotherapy to elucidate the incidence of tuberculosis reactivation after ICI therapy induction.We prospectively assessed IGRA results in lung cancer patients who received ICI monotherapy before ICI treatment and at 6 and 12 months after ICI treatment. We also assessed computed tomography findings to determine the presence of active tuberculosis when positive IGRA results were obtained. The ICIs used were nivolumab, pembrolizumab, atezolizumab, and durvalumab.In all, 178 patients were prospectively recruited between March 2017 and March 2020. Of these, 123 completed serial IGRAs, of whom 18, 101, and 4, respectively, had positive, negative, and indeterminate IGRAs at baseline. Three and four patients, respectively, showed IGRA reversion and conversion during immunotherapy. One patient with a sustained, stable positive IGRA and one with IGRA conversion developed active pulmonary tuberculosis during immunotherapy.We found that 3.3% and 1.6% of the patients developed IGRA conversion and active tuberculosis, respectively. Of the four patients who developed IGRA conversion, one developed active pulmonary tuberculosis during immunotherapy. Another patient with sustained, stable positive IGRA developed active tuberculosis. Physicians should be alert to tuberculosis development during ICI therapy, and IGRA testing is a useful tool to assess the risk of developing active tuberculosis.

Comparison of frailty in patients with nontuberculous mycobacterial lung disease and bronchiectasis: a prospective cohort study.

BACKGROUND: The incidence of nontuberculous mycobacterial lung disease (NTM-LD) peaks in middle- and old age groups, coinciding with senescence; thus, chronic infectious diseases can accelerate frailty and worsen mental health in the elderly. In this study, we aimed to compare the prevalence of physical and psychiatric frailty between patients with NTM-LD and bronchiectasis (BE). METHODS: The Kihon Checklist Questionnaire (KCQ) was used to assess physical and psychiatric frailties and identify those at risk of requiring care among patients with newly diagnosed NTM-LD and BE. Additionally, the Hospital Anxiety and Depression Scale (HADS) scores and chronic inflammatory biomarkers of the alveolar region (surfactant protein [SP]-A, SP-D, and human cationic antibacterial protein [hCAP]/LL-37) were assessed and compared between NTM-LD and BE patients. RESULTS: There were no significant differences in the background characteristics between the 33 NTM and 36 BE patients recruited. The KCQ revealed that the proportion of frail NTM patients at diagnosis was higher than that of frail BE patients (48.5% vs. 22.2%, p = 0.026). HADS scores were significantly higher in the NTM group than in the BE group (p < 0.01). Bronchoalveolar lavage fluid (BALF) hCAP/LL-37 and SP-D levels were significantly higher (p = 0.001), but serum hCAP/LL-37 levels were significantly lower in the NTM group than in the BE group (p = 0.023). However, there were no significant differences in the BALF and serum SP-D levels between the two groups. CONCLUSIONS: The number of frail NTM patients at diagnosis was significantly higher than that of frail BE patients. Biomarker analysis suggested that the former had more localized lung inflammation than the latter. TRIAL REGISTRATION: This trial was prospectively registered in the Clinical Trials Registry (UMIN 000027652).

Association of heated tobacco product use with tobacco use cessation in a Japanese workplace: a prospective study.

We investigated how use of heated tobacco products (HTPs) affects tobacco cessation in a Japanese workplace. We offered cessation programmes for 158 tobacco users from November 2018 to April 2019 and surveyed the quitting rate in August 2019. Successful quitting was defined as stopping use of all kinds of nicotine-containing tobacco products. A Poisson regression analysis adjusted with inverse probability weighting showed that HTP users (either exclusive HTP users or dual users) were less likely than exclusive cigarette users to quit tobacco (risk ratio, 0.77; 95% CIs 0.61 to 0.97, p=0.024). The use of HTPs should not be recommended to assist in smoking cessation. Trial registration UMIN000034719.

Management and Outcomes of Newly Diagnosed Non-Small Cell Lung Cancer Patients with Brain Metastases: A Real-World Study in Japan.

BACKGROUND: Brain metastases (BM) are one of the strongest negative prognostic factors in patients with non-small cell lung cancer (NSCLC). Molecularly targeted agents are standard of care for NSCLC patients with a driver mutation; however, their efficacy in patients with BM is not fully understood because patients with BM are usually excluded from clinical studies. This study investigated the current management and outcomes of newly diagnosed NSCLC patients with BM in Japanese clinical practice, focusing on their driver mutation status. PATIENTS AND METHODS: We enrolled newly diagnosed, treatment-naïve NSCLC patients with BM between January 2012 and December 2015 from 4 institutions in Japan. The medical records of each patient were retrospectively reviewed, and the treatment details and outcomes were evaluated. RESULTS: In total, 203 patients with BM were enrolled in this study and 73 (36%) were neurologically symptomatic. Regarding initial treatment, 110 patients (54%) received local therapy, including radiotherapy and surgery, whereas 77 (38%) received systemic therapy. The median overall survival (OS) was 14.3 months for all patients, and it was significantly longer among patients with a driver mutation (28.9 months; 95% confidence interval [CI], 20.9-41.0) than among patients without a driver mutation (9.9 months; 95% CI, 7.0-13.4) (hazard ratio [HR] 0.39; 95% CI, 0.27-0.57; p < 0.001). Multivariate analysis identified performance status (HR 1.78; 95% CI, 1.16-2.72; p = 0.009) and driver mutation status (HR 0.27; 95% CI, 0.17-0.44; p < 0.001) as significant prognostic factors. No significant difference in OS was noted according to the type of initial treatment, i.e., local versus systemic. CONCLUSION: The median OS of patients with a driver mutation was longer than 2 years, even of patients with BM, and it was significantly longer than that of patients without a driver mutation. Driver mutation status, in addition to performance status, was a significant prognostic factor in NSCLC patients with BM.

Factors Associated With Efficacy and Nivolumab-Related Interstitial Pneumonia in Non-Small Cell Lung Cancer: A Retrospective Survey.

BACKGROUND AND OBJECTIVES: Immune-checitors have been established as a novel standard treatment for non-small cell lung cancer (NSCLC). The aim of this study was to identify factors associated with efficacy and nivolumab-related interstitial pneumonia in NSCLC by evaluating clinical data at the initiation of and during treatment. METHODS: We retrospectively reviewed the medical records of patients who underwent treatment with nivolumab between October 2015 and December 2017. Using pretreatment patient data, we investigated factors associated with overall survival (OS) and the onset of nivolumab-related pneumonitis. We investigated serum biochemistry during treatment to identify the determinants associated with progressive disease (PD) and the onset of nivolumab-related pneumonitis. RESULTS: A total of 94 patients were included. Eleven patients continued treatment, and 54 patients were diagnosed with progressive disease. Nivolumab-related pneumonitis occurred in 15 patients. A pretreatment Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 0 was linked to significantly longer OS than ECOG PS = 1 (median: 20.1 vs. 6.5 months, respectively; p < 0.001). There was a higher incidence of nivolumab-related pneumonitis in patients with a history of interstitial pneumonia than in those without it (p = 0.008). During treatment, the level of albumin gradually decreased prior to PD and onset of nivolumab-related pneumonitis. CONCLUSION: These results suggest that the pretreatment ECOG PS is the determining factor that is associated with OS, whereas history of interstitial pneumonia is the factor associated with nivolumab-related pneumonitis. A decrease in albumin during treatment may be associated with both PD and nivolumab-related pneumonitis.

Decreased handgrip strength can predict lung function impairment in male workers: a cross sectional study.

BACKGROUND: Spirometry is useful for evaluating respiratory health status and predicting health-related outcomes. As spirometry requires skilled technician and takes time, it is useful to find simple way for predicting lung function impairment. The aim of this study was to investigate which tests could predict lung function impairment among workers. METHODS: This prospective study included workers of manufacturing industry who underwent health check-ups in 2017. Subjects underwent the chronic obstructive pulmonary disease (COPD) assessment test (CAT), spirometry, and physical fitness assessments, including handgrip strength (HGS). Lung function impairment was defined as a decline in any of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), or a FEV1/FVC ratio less than the lower limit of normal (LLN). RESULTS: Complete data on 475 workers (366 men, 50.4% ever smokers) were available. Lung function impairment was observed in 99 subjects (64 men). Men with lung function impairment had significantly higher rate of ever-smoking, passive smoking at home in childhood, high CAT scores, and decreased HGS, compared with those without. On multivariate analyses, ever-smoking (odds ratio [OR], 2.50; 95% confidence intervals [CI], 1.25-4.97), passive smoking at home in childhood (OR, 2.71; 95% CI, 1.16-6.32), CAT scores (OR, 1.06; 95% CI, 1.01-1.12), and HGS (OR, 0.73; 95% CI, 0.57-0.92) were independently associated with lung function impairment in men. CONCLUSIONS: Ever-smoking, passive smoking at home in childhood, high CAT scores, and decreased HGS are significantly associated with lung function impairment in men. TRIAL REGISTRATION: Registration number: UMIN000028011. Date of registration: July 1, 2017.

Osimertinib in Elderly Patients with Epidermal Growth Factor Receptor T790M-Positive Non-Small-Cell Lung Cancer Who Progressed During Prior Treatment: A Phase II Trial.

LESSONS LEARNED: Non-small-cell lung cancer (NSCLC) represents 85% of lung cancer in elderly patients.In the present study performed in the 36 elderly subjects with epidermal growth factor receptor (EGFR) T790M mutation-positive NSCLC, osimertinib 80 mg demonstrated statistically significant improvement in the objective response rate, which was comparable to those in the nonelderly population.Osimertinib appears to be an effective and safe treatment option in elderly patients with advanced NSCLC with EGFR mutation; further research in larger scale is warranted. BACKGROUND: Previous findings suggest the possibility of relatively safe use of osimertinib for patients with T790M-positive non-small-cell lung cancer (NSCLC), with few serious adverse events for the elderly in comparison with conventional endothelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), and with an antitumor effect. METHODS: This phase II study was performed to prospectively investigate the efficacy and safety of osimertinib for elderly patients aged ≥75 years with ineffective prior EGFR TKI treatment or with recurrence in T790M EGFR TKI resistance mutation-positive NSCLC. RESULTS: A total of 36 patients were included in the analyses. Among the 36 subjects, 63.9% were female, with mean age of 79.9 years. The objective response rate (ORR) was 58.3% (95% confidence interval [CI], 42.2%-72.9%), demonstrating statistically significant efficacy of osimertinib (p = .0017). The median duration of response (DOR) was 27.9 weeks (95% CI, 21.1-82.0). Complete response (CR) and partial response (PR) were 2.8% and 55.6%, respectively. Disease control rate (DCR) was 97.2%. A waterfall plot revealed that 33 (91.6%) subjects exhibited tumor shrinkage during treatment, including 12 of 14 subjects who had stable disease (SD). All adverse events were not reason for discontinuation of the study drug. CONCLUSION: Osimertinib may be an effective and safe treatment option in elderly patients with advanced NSCLC with EGFR mutation.

Perspectives on End-of-Life Treatment among Patients with COPD: A Multicenter, Cross-sectional Study in Japan.

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality. Since patients with severe COPD may experience exacerbations and eventually face mortality, advanced care planning (ACP) has been increasingly emphasized in the recent COPD guidelines. We conducted a multicenter, cross-sectional study to survey the current perspectives of Japanese COPD patients toward ACP. "High-risk" COPD patients and their attending physicians were consecutively recruited. The patients' family configurations, understanding of COPD pathophysiology, current end-of-life care communication with physicians and family members, and preferences for invasive life-sustaining treatments including mechanical ventilation (MV) and cardiopulmonary resuscitation (CPR) were evaluated using a custom-made, structured, self-administered questionnaire. Attending physicians were also interviewed, and we evaluated the patient-physician agreement. Among the 224 eligible "high-risk" patients, 162 participated. Half of the physicians (54.4%) thought they had communicated detailed information; however, only 19.4% of the COPD patients thought the physicians did so (κ score = 0.16). Less than 10% of patients wanted to receive invasive treatment (MV, 6.3% and CPR, 9.4%); interestingly, more than half marked their decision as "refer to the physician" (MV 42.5% and CPR 44.4%) or "refer to family" (MV, 13.8% and CPR, 14.4%). Patients with less knowledge of COPD were less likely to indicate that they had already made a decision. Although ACP is necessary to cope with severe COPD, Japanese "high-risk" COPD patients were unable to make a decision on their preferences for invasive treatments. Lack of disease knowledge and communication gaps between patients and physicians should be addressed as part of these patients' care.

Afatinib treatment of severe respiratory failure due to malignant lymphangitis in a dialysis patient with squamous cell carcinoma of the lung.

Patients on dialysis have limited treatment options for advanced lung cancer because some chemotherapeutic agents are unavailable due to renal dysfunction. A man in his 70s on peritoneal dialysis presented with persistent fever refractory to antibiotics for 2 weeks. Subsequent whole-body CT showed a 5 cm diameter mass in the right lower lobe of the lung with right-sided pleural effusion and osteolytic metastasis of the right iliac bone. The patient was diagnosed with squamous cell carcinoma (cT3N2M1b, stage IVB) harbouring the p.Gly719Ala point mutation on exon 18 of the epidermal growth factor receptor. The patient developed severe respiratory failure due to malignant lymphangitis after a bronchoscopy. He received 30 mg/day of afatinib, resulting in tumour shrinkage and recovery from respiratory failure. We advocate for aggressive screening of driver oncogenes in patients with lung cancer on dialysis, including those with squamous cell lung cancer.

Kristen rat sarcoma virus (KRAS) G12F-positive non-small cell lung cancer mimicking KRAS G12C positivity: A case report.

Searching for driver gene alteration is a prerequisite for chemotherapy of non-small cell lung cancer. Due to its high sensitivity and concordance rate, the Amoy Dx Pan Lung Cancer PCR panel has been approved and is widely used in Japan. In this report, we describe a case in which a positive result for Kristen rat sarcoma virus (KRAS) exon2 p.G12F, a rare KRAS mutation, may have led to a false-positive result for KRAS exon2 p.G12C on AMOY. Genetic analysis in this case was performed by LC-SCRUM-Asia.

Safety of flexible bronchoscopy and clinical course for elderly patients with suspected primary lung cancer.

BACKGROUND: There have been several reports demonstrating the safety of flexible bronchoscopy (FB) in the elderly, but none have focused specifically on lung cancer, which is a frequent biopsy procedure. METHODS: In this study, we retrospectively evaluated the safety of FB and subsequent treatment in elderly patients with suspected primary lung cancer. Elderly patients were defined as 75 years of age or older. RESULTS: A total of 141 patients, 77 in the elderly group and 64 in the nonelderly group, were reviewed. The median age of the elderly group was 80 years. Transbronchial lung biopsy was performed in more than 80% of all patients. Primary lung cancer was diagnosed in 42 (54.4%) of the elderly group and 35 (54.7%) of the nonelderly group (p = 0.38). Approximately 70% of the elderly patients with a confirmed diagnosis were treated, while more than half of the undiagnosed elderly patients had best supportive care. Complications such as bleeding, pneumothorax, fever, and pneumonia were similar in the elderly and nonelderly groups. CONCLUSIONS: This study suggests that flexible bronchoscopy can be performed as safely in the elderly as in the nonelderly. Furthermore, even elderly patients may have a greater chance of receiving treatment when a definitive diagnosis is achieved.

Clinical features of pneumothorax associated with COVID-19: A retrospective analysis of two centres.

BACKGROUND: Pneumothorax is a known sequela of coronavirus disease 2019 (COVID-19). However, the clinical features of pneumothorax associated with COVID-19 have not been fully elucidated. METHODS: Patients who developed pneumothorax within 6 months of being diagnosed with COVID-19 were retrospectively analysed at two institutions. We investigated the background factors, COVID-19 severity and treatment, timing of pneumothorax onset, treatment modalities, treatment duration, and prognosis of these patients. RESULTS: A total of 21 patients were diagnosed with pneumothorax within 6 months of COVID-19 diagnosis. The combined incidence rate of pneumothorax at two institutions was 0.89 %. The mean age of these patients was 72.5 years, and they were predominantly male (90.5 %), with a history of smoking (76.1 %). The most frequent comorbidity was hypertension, followed by type 2 diabetes mellitus, COPD, and malignancy. Approximately 76 % of the patients had moderate or severe disease requiring oxygenation. Moreover, 90.5 % of these patients were taking antiviral drugs; 52.4 %, immunosuppressant agents (baricitinib/tocilizumab); and 66.7 % were on dexamethasone. The median time to the onset of pneumothorax was 15.0 days, and 86 % of cases occurred within 1 month of COVID-19 diagnosis. Bilateral pneumothorax and pneumomediastinum were noted in one patient each. Chest drainage was performed in 71.4 % of the patients. The mean treatment duration for pneumothorax was 14.1 days, and the 30-day mortality rate was 28.6 %. CONCLUSION: Pneumothorax associated with COVID-19 was more common in patients with moderate or severe disease requiring oxygenation, and occurred within 1 month of COVID-19 diagnosis. Pneumothorax associated with COVID-19 is a serious complication with a high mortality rate and clinicians should pay attention to it.

Treatment patterns and clinical outcomes of resectable clinical stage III non-small cell lung cancer in a Japanese real-world setting: Surgery cohort analysis of the SOLUTION study.

BACKGROUND: To elucidate the treatment and surgery outcomes with or without perioperative therapies in Japanese patients with clinical stage III non-small cell lung cancer (NSCLC) in real-world settings. METHODS: We performed subset analyses of the SOLUTION study, a multicenter, noninterventional, observational study of Japanese patients diagnosed with clinical stage III NSCLC, for those who started first-line treatment (surgery±perioperative therapy) between January 2013 and December 2014 (study registration: UMIN000031385). Follow-up data were obtained using medical records from diagnosis to March 1, 2018. RESULTS: Of 149 eligible patients, 67 underwent surgery alone (median age 71 years) and 82 underwent surgery+perioperative therapy (median age 63 years). Lung resection was performed in 137 patients and the others underwent exploratory thoracotomy or other procedures. Perioperative therapies included adjuvant therapy only (n = 41), neoadjuvant therapy only (n = 24), and neoadjuvant+adjuvant therapy (n = 17). The median overall survival (OS) and 3-year OS rate were 29.3 months and 44.0%, respectively, in patients who underwent surgery alone, and not reached and 61.1%, respectively, in patients who underwent surgery+perioperative therapy. The 3-year progression-free survival (PFS) and disease-free survival (DFS) rates were 42.4% and 47.1%, respectively, in patients who underwent surgery+perioperative therapy and 28.5% and 28.9%, respectively, in patients who underwent surgery alone. In multivariable Cox regression, perioperative therapy was associated with improved OS (hazard ratio [95% confidence interval] 0.49 [0.29-0.81]), PFS (0.62 [0.39-0.96]), and DFS (0.62 [0.39-0.97]) versus surgery alone. CONCLUSIONS: Our study suggested that perioperative therapy may be associated with better survival among patients undergoing surgical treatment of clinical stage III NSCLC.

[A case of postoperative thymic carcinoma recurrence that was effectively treated with combination chemotherapy of nedaplatin and docetaxel].

We report a case of postoperative recurrence of thymic carcinoma that was effectively treated with combination chemotherapy of nedaplatin(NDP)and docetaxel(DOC). We performed thymectomy for thymoma in a 55-year-old man. The pathological diagnosis was squamous cell thymic carcinoma(pT3N0M0, Stage III). The patient was observed without postoperative radiotherapy being administered. Six months after the operation, the patient was admitted to our department with carcinomatous pericarditis. Whole-body examination revealed multiple lung and liver metastases and a left femoral metastasis. After pericardiocentesis, radiation therapy was administered for the left femoral metastasis. Combination chemotherapy (NDP[60mg/m2]/DOC[70mg/m2])was administered for the multiple lung and liver metastases. After 4 cycles of chemotherapy, the multiple lung metastases were completely resolved and the liver metastases were clearly reduced. Partial response and acceptable toxicity were identified. Thymic carcinoma is a rare epithelial neoplasm for which the optimal chemotherapy regimen has not yet been established. Combination chemotherapy with NDP/DOC was effective in the case of our patient with postoperative thymic squamous cell carcinoma recurrence, and it can be considered as a promising regimen for patients from the standpoint of clinical efficacy.

Pegfilgrastim-Induced Aortitis in a Patient with Small-Cell Lung Cancer Who Received Immunotherapy Combined with Chemotherapy.

Introduction: Granulocyte colony-stimulating factor (G-CSF), including pegfilgrastim, increases the peripheral blood leukocyte count and is widely used in clinical practice in combination with cytotoxic chemotherapy. The most frequent side effects of G-CSF are pain and fever; aortitis, in contrast, is a rare and serious side effect. Case Presentation: A 73-year-old man with small-cell lung cancer was treated with a full dose of a combination of carboplatin/etoposide/durvalumab and pegfilgrastim. The patient developed fever and right ear pain 12 days after pegfilgrastim administration and was diagnosed with aortitis by contrast-enhanced computed tomography 5 days later. Because the patient had already been administered the immune checkpoint inhibitor and had a history of hepatitis B, the patient was followed up without corticosteroid administration, and the patient's symptoms resolved spontaneously. Conclusion: In situations where immunosuppression should be avoided, we believe that follow-up without corticosteroids for G-CSF-induced aortitis is a promising option.

Successful Rechallenge with Osimertinib following Osimertinib-Induced Ventricular Tachycardia: A Case Report.

Osimertinib, a third-generation tyrosine kinase inhibitor, is the first-line treatment for metastatic non-small cell lung cancer (NSCLC) with sensitizing epidermal growth factor receptor (EGFR) mutations. It is known to cause drug-induced cardiotoxicity, including QT prolongation syndrome, heart failure, and ventricular arrhythmias, which can lead to sudden death. Once severe arrhythmias occur, it is difficult to continue osimertinib treatment. We report a case of a 66-year-old woman with recurrent NSCLC after concurrent chemoradiotherapy who experienced osimertinib-induced ventricular arrhythmia-causing syncope. The patient was initially treated with concurrent chemoradiotherapy, and genetic testing revealed EGFR exon 19 deletion. Three years following treatment initiation, the primary tumor progressed, and new bone metastases developed. The patient was diagnosed with recurrent NSCLC and was treated with targeted therapy with osimertinib. On the 10th day of osimertinib administration, syncope occurred. Electrocardiography showed polymorphic non-sustained ventricular tachycardia, which was believed to be the cause of syncope. The patient was switched to erlotinib. Two and a half years later, disease progression in the primary lesion was observed. A liquid biopsy revealed an EGFR T790M resistance mutation. Therefore, osimertinib (40 mg) was administered every alternate day. After confirming the absence of palpitations and arrhythmias on electrocardiogram, the osimertinib dosing was increased to 40 mg daily. Thereafter, no further events occurred, and tumor shrinkage was observed. Low-dose osimertinib rechallenge after induced ventricular arrhythmia may be considered an option under close monitoring; however, osimertinib rechallenge must be carefully selected based on the risk-benefit analysis.

Safety and Efficacy of Flexible Bronchoscopy in Elderly Patients: A Retrospective Comparative Study.

Background: Flexible bronchoscopy (FB) is a common method used for diagnostic sampling of the thorax. Although the safety and efficacy of FB in the general population are well-established, data on the elderly population are limited. This study aimed to determine the safety and efficacy of FB in elderly people aged ≥80 years. Materials and Methods: We retrospectively studied elderly patients aged ≥80 years who underwent FB at our hospital between April 2021 and March 2022. Outcomes, such as indications, sampling methods, diagnostic results, and complications, were compared with those of a control group of patients aged 18-79 years. Results: In total, 247 patients (154 men) were included in the study, with 65 and 182 patients in the elderly and non-elderly groups, respectively. The most frequent indication for FB was the presence of a mass or nodule, with transbronchial lung biopsy, transbronchial biopsy, and endobronchial ultrasound-guided transbronchial needle aspiration performed in 162 (65.6%), 29 (11.7%), and 36 (15.6%) patients, respectively. FB led to a diagnosis in 36 (57.1%) and 103 (56%) patients in the elderly and non-elderly groups, respectively, with no significant difference observed. There were no patient deaths or significant differences in the incidence of hemorrhage, hypoxia, pneumothorax, fever, or pneumonia between the two groups. Conclusions: The findings of this study indicate that FB can be performed effectively and safely in elderly patients aged ≥80 years, similar to non-elderly patients.

Antecedentes: La broncoscopia flexible (FB) es un método común utilizado para el muestreo diagnóstico del tórax. Aunque la seguridad y eficacia de la FB en la población general están bien establecidas, los datos sobre la población anciana son limitados. El objetivo de este estudio es determinar la seguridad y eficacia de la FB en ancianos ≥80 años. Materiales y métodos: Se estudiaron retrospectivamente los pacientes ancianos de ≥80 años sometidos a FB en nuestro hospital entre abril de 2021 y marzo de 2022. Los resultados, como las indicaciones, los métodos de muestreo, los resultados diagnósticos y las complicaciones, se compararon con los de un grupo control de pacientes de 18-79 años. Resultados: En total, 247 pacientes (154 hombres) fueron incluidos en el estudio, con 65 y 182 pacientes en los grupos de ancianos y no ancianos, respectivamente. La indicación más frecuente fue la presencia de una masa o nódulo, realizándose biopsia pulmonar transbronquial, biopsia transbronquial y aspiración transbronquial con aguja guiada por ecografía endobronquial en 162 (65,6%), 29 (11,7%) y 36 (15,6%) pacientes, respectivamente. Conclusiones: Los resultados de este estudio indican que la FB se puede Los resultados de este estudio indican que la FB puede realizarse de forma eficaz y segura en pacientes de edad ≥80 años, de forma similar a los pacientes no ancianos.

Re-immunotherapy with nivolumab plus ipilimumab in advanced non-small cell lung cancer patients previously treated with anti-programmed death-1 and/or anti-programmed death ligand-1 antibodies.

BACKGROUND: The role of re-immunotherapy in advanced non-small cell lung cancer (NSCLC) remains unclear. No studies have evaluated the re-immunotherapy regimen including anti-cytotoxic T-lymphocyte antigen-4 antibody for lung cancer treatment. This study aimed to investigate the efficacy and safety of re-immunotherapy with nivolumab plus ipilimumab in patients with advanced NSCLC previously treated with anti-programmed death-1 (PD-1) and/or anti-programmed death ligand-1 (PD-L1) antibodies. METHODS: We retrospectively reviewed patients with advanced or recurrent NSCLC who received immunotherapy with nivolumab plus ipilimumab (without concomitant cytotoxic chemotherapy) between November 2020 and November 2022 at the National Hospital Organization Kyoto Medical Center, Kyoto, Japan. Data were extracted from patients who had previously received immunotherapies with anti-PD-1 and/or anti-PD-L1 antibodies. Treatment responses and adverse events were evaluated. RESULTS: Of the 67 patients who received immunotherapy with nivolumab plus ipilimumab, 23 were included in final analysis. The objective response rate was 17%, and the disease control rate was 48% for nivolumab plus ipilimumab therapy. The highest grade of immune-related adverse events was grade 3, occurring in 11% of cases. CONCLUSION: Re-immunotherapy with nivolumab plus ipilimumab after anti-PD-1 and/or anti-PD-L1 immunotherapy may be feasible and provide clinical benefit in selected patients. Further prospective studies are warranted to identify the patient population that may benefit from re-immunotherapy.

Impact of the COVID-19 pandemic on the trajectory of the number of bronchoscopies performed in a tertiary hospital in Kyoto city.

The coronavirus disease 2019 (COVID-19) pandemic has restricted many medical practices. We aimed to investigate the impact of the COVID-19 pandemic on the number of bronchoscopies, outpatients, and hospital admissions. We retrospectively analyzed the number of outpatients, admissions, and bronchoscopies performed between March 2020 and May 2022. We defined "Peak month of the pandemic," "Wave of the pandemic," "Month in the wave," and "Period of a state of emergency" for each analysis. In the first year of the COVID-19 pandemic, analysis of variance (ANOVA) in linear mixed models indicated significant effects of "month in each wave" on the number of bronchoscopies (P = .003), outpatients (P = .041), and admissions (P = .017). The number of outpatients, admissions, and bronchoscopies was significantly influenced by the first wave of the COVID-19 pandemic. In contrast, in the second year of the COVID-19 pandemic, a mixed-ANOVA indicated significant effects of "month in each wave" only on the number of outpatients (P = .020) but no significant effects on the number of bronchoscopies (P = .407) and admissions (P = .219). During the second year of the pandemic, the number of bronchoscopies and admissions was not significantly affected by the waves of the pandemic. There were no significant differences in the number of admissions and bronchoscopies between the fourth and sixth waves. Although the number of bronchoscopies was found to be significantly affected in the early stages of the COVID-19 pandemic, the impact of the pandemic was much more limited thereafter.