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).

Efficacy of corticosteroid therapy for oxygen-free coronavirus disease 2019-derived pneumonia.

Corticosteroid therapy for oxygen-free coronavirus disease 2019 (COVID-19) is not recommended due to its negative prognostic impact, but the efficacy of corticosteroids when limited to COVID-19 pneumonia is unclear. We aimed to evaluate the efficacy of corticosteroid monotherapy for patients with COVID-19 pneumonia without supplemental oxygen. We retrospectively reviewed patients with oxygen-free COVID-19 pneumonia at our institute between September 2020 and August 2021 and assessed the use of corticosteroids and the timing of initiation. We classified the patients into the following 2 groups: those who were initiated corticosteroids without developing respiratory failure (early steroid group) and those who were not (standard of care [SOC] group). We used inverse probability of treatment weighting (IPW) to balance between the groups. The primary outcome was the incidence of respiratory failure. A total of 144 patient records were reviewed; 63 patients were in the early steroid group and 81 patients were in the SOC group. Of all patients, 14 (22.2%) and 27 (33.3%) patients in the early steroid and SOC group, respectively, required supplemental oxygen (P = .192). After adjusted by the IPW method, 10 (16.0%) and 32 (40.1%) patients in the early steroid and SOC groups, respectively, required supplemental oxygen (P = .004). The logistic regression analysis indicated that early corticosteroid use was significantly associated with a decreased incidence of respiratory failure (odds ratio; 0.17, 95% confidence intervals; 0.06-0.46, P < .001). Corticosteroid monotherapy may suppress the development of exacerbation requiring oxygen supply in patients with oxygen-free COVID-19 pneumonia.

Organizing pneumonia secondary to pulmonary cryptococcosis in immunocompromised patient.

Pulmonary cryptococcal infections are fungal infections that often occur in immunocompromised patients and present with a variety of radiographic patterns ranging from nodular to infiltrative shadows. In the present case, we experienced a rare case of organizing pneumonia due to cryptococcal infection in a 71-year-old woman with rheumatoid arthritis. Transbronchial lung biopsy showing fibrotic changes in the alveolar walls, small granulation lesions and cryptococcal organisms with positive Grocott staining. Serum cryptococcal antigen was also found to be positive. Based on these findings, we confirmed the diagnosis of secondary organizing pneumonia due to cryptococcal infection. Treatment with corticosteroids and antifungal drugs led to improvement of the cough and reduction of organizing pneumonia. In immunocompetent patients with organizing pneumonia, it is essential to perform bronchoscopic lung biopsies and serum antigen tests to search for the cause, whenever possible, as it may be due to an infection caused by Cryptococcus, as in the present case.

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.

Single-centre observational study of the safety and efficacy of thoracoscopy under local anaesthesia for the management of thoracic infections.

OBJECTIVES: Thoracoscopy under local anaesthesia is widely performed to diagnose malignancies and infectious diseases. However, few reports have described the use of this procedure for diagnosing and treating intrathoracic infections. This study aimed to evaluate the safety and efficacy of thoracoscopy under local anaesthesia for the management of intrathoracic infections. RESULTS: Data from patients who underwent thoracoscopy procedures performed by chest physicians under local anaesthesia at our hospital between January 2018 and December 2023 were retrospectively reviewed. We analysed their demographic factors, reasons for the examinations, diseases targeted, examination lengths, anaesthetic methods used, diagnostic and treatment success rates, as well as any adverse events. Thirty patients were included. Of these, 12 (40%) had thoracoscopies to diagnose infections, and 18 (60%) had them to treat pyothorax. In terms of diagnosing pleurisy, the causative microorganism of origin was identified via thoracoscopy in only three of 12 (25.0%) patients. For diagnosing pyothorax, the causative microorganism was identified in 7 of 18 (38.9%) patients. Methicillin-resistant Staphylococcus aureus was the most common causative microorganism identified. The treatment success rates were very high, ranging between 94.4 and 100%, whereas the identification rate of the causative microorganisms behind infections was low, ranging between 25.0 and 38.9%. The most frequent adverse events included perioperative hypoxaemia and pain. There were two (6.7%) serious adverse events of grade ≥ 3, but none resulted in death. CONCLUSIONS: The efficacy of managing intrathoracic infections through thoracoscopy under local anaesthesia is commendable. Nonetheless, the diagnostic accuracy of the procedure, regarding the precise identification of the causative microorganisms responsible for intrathoracic infections, persists at a notably low level, presenting a substantial clinical hurdle.

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.

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.

A 92-year-old patient with thoracic empyema successfully treated by CT-guided insertion of a pigtail catheter.

We present a case report of a 92-year-old patient with thoracic empyema, who was successfully treated via CT-guided insertion of a pigtail catheter. The advanced age of the patient often poses challenges in managing pyothorax due to limited physical activity and cognitive decline stemming from decreased activities of daily living. In instances where thoracic drainage is not feasible, the course of treatment is protracted and the prognosis is poor. Our case report exemplifies the successful treatment of pyothorax in a geriatric patient via CT-guided insertion of a pigtail catheter. We believe that this educational case serves as a testament to the fact that even the most aged patients can be successfully treated with resourcefulness.

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.

De Novo SCLC Transformation From KRAS G12C-Mutated Lung Adenocarcinoma With Excellent Response to Sotorasib: A Case Report.

The transformation to SCLC is a known mechanism of resistance against molecularly targeted therapies. This study reports a patient with untreated lung adenocarcinoma, characterized by a KRAS G12C mutation, which transformed into SCLC before treatment. Both the adenocarcinoma and SCLC components were responsive to sotorasib.

Simultaneous regression of non-small cell lung cancer and orbital extranodal marginal zone lymphoma with chemoradiotherapy for lung cancer.

This report describes the case of a 79-year-old Japanese man diagnosed with orbital extranodal marginal zone lymphoma (EMZL) and stage IIIA lung cancer. The patient received concurrent chemoradiation for lung cancer with carboplatin/paclitaxel treatment, resulting in regression of both the lymphoma and lung cancer. To our knowledge, this is the first reported case of concurrent orbital EMZL and lung cancer. In this case, a treatment strategy that prioritized lung cancer treatment was deemed appropriate. This case suggests that chemotherapy with carboplatin and paclitaxel may serve as an effective treatment for both lung cancer and lymphoma.

Efficacy and safety of immune checkpoint inhibitors in patients with non-small cell lung cancer aged 80 years or older.

BACKGROUND: In Japan, over 25% of the population is elderly. As the risk of lung cancer increases with age, the number of elderly patients with lung cancer also increases. Given the challenges of an aging society, it is critical that elderly patients receive safe therapies. AIM: We assessed the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer (NSCLC) aged ≥80 years. METHODS: We retrospectively reviewed NSCLC patients aged ≥80 years old who received ICIs in the National Hospital Organization Kyoto Medical Center. We collected data on patient characteristics, prior treatments, number of cycles, response, and immune-related adverse events (irAEs) during ICI monotherapy. RESULTS: A total of 45 patients were reviewed. The patients' median age was 85 years. Twenty-one, 17, and 7 patients received nivolumab, pembrolizumab, and atezolizumab, respectively. The disease control rate (partial response [PR] + stable disease [SD]) was 60.0%, and the progression-free survival was 3.4 months. In patients with nivolumab, seven patients (33.3%) achieved SD, and three patients (14.2%) achieved PR. In patients treated with pembrolizumab, seven patients (41.2%) achieved SD, and six patients (35.3%) achieved PR. In patients with atezolizumab, three patients (42.9%) achieved SD, and one patient (14.2%) achieved PR. Sixteen (36%) patients presented with a poor performance status. Three patients treated with pembrolizumab experienced grade 3 pneumonia, while one patient treated with nivolumab experienced grade 5 pneumonia. CONCLUSION: This study suggested that ICIs are an acceptable treatment option for NSCLC patients aged ≥80 years. Oncologists should pay attention to severe irAEs.

Effect of cyclooxygenase inhibitor use on immunotherapy efficacy in non-small cell lung cancer.

BACKGROUND: A synergistic effect of cyclooxygenase inhibitors (COX-I) and immune checkpoint inhibitors (ICIs) has been suggested. However, the impact of COX-I on the efficacy of ICIs is unclear. Here, we aimed to evaluate the relationship between COX-I use and the efficacy of ICI in patients with non-small cell lung cancer (NSCLC). METHODS: We retrospectively reviewed NSCLC patients who received ICI monotherapy. We defined COX-I use as regular use of COX-I other than low-dose aspirin during the initiation of ICIs to the first evaluation of efficacy. The efficacy of ICIs was evaluated with response rate (RR), disease control rate (DCR), progression free survival (PFS), and overall survival (OS). Differences in baseline characteristics by COX-I use were controlled by using an inverse probability of treatment weighting (IPW) adjusted analysis. RESULTS: A total of 198 patients with NSCLC received ICIs; 128, 50, and 20 patients received nivolumab, pembrolizumab, and atezolizumab, respectively; there were 65 (32.8%) COX-I users. While there was no significant difference in RR (15.4% vs. 13.5%; p = 0.828), DCR (41.5% vs. 49.6%; p = 0.294), PFS (median, 2.69 vs. 3.68 months; 95% confidence intervals [CI], 1.77-5.19 vs. 2.20-4.60 months; p = 0.630), COX-I users had significantly shorter OS than non-COX-I users (median, 6.08 vs. 16.10 months; 95% CI: 3.78-11.66 vs. 9.49-19.68 months; p = 0.003). On IPW adjusted analysis, there was no significant difference in OS (median, 7.85 vs. 15.11 months; 95% CI: 5.03-14.92 vs. 9.49-19.32 months; p = 0.081). CONCLUSIONS: There was no additional or negative impact of COX-I use on the efficacy of ICIs in NSCLC.

Impact of COVID-19 pandemic on lung cancer treatment scheduling.

The current coronavirus disease 2019 (COVID-19) pandemic is associated with a heavy burden on the mental and physical health of patients, regional healthcare resources, and global economic activity. Many patients with lung cancer are thought to be affected by this situation. Therefore, in this study, we aimed to evaluate the impact of COVID-19 pandemic on lung cancer treatment scheduling. We retrospectively reviewed the medical records of lung cancer patients who were undergoing anticancer treatment at the National Hospital Organization Kyoto Medical Center (600 beds) in Kyoto, Japan, between 1 March 2020 and 31 May 2020. After the medical records were reviewed, the patients were assigned to one of two groups, depending on whether their lung cancer treatment schedule was delayed. We assessed the characteristics, types of histopathology and treatment, and the reason for the delay. A total 15 (9.1%) patients experienced a delay in lung cancer treatment during the COVID-19 pandemic. Patients with a treatment delay received significantly more immune checkpoint inhibitor (ICI) monotherapy than patients without a treatment delay (P = 0.0057). On the contrary, no patients receiving molecular targeted agents experienced a treatment delay during the COVID-19 pandemic period (P = 0.0027). The treatments of most of the patients were delayed at their request. We determined that 9.1% lung cancer patients suffered anxiety and requested a treatment delay during the COVID-19 pandemic. Oncologists should bear in mind that patients with cancer have more anxiety than expected under unprecedented circumstances such as the COVID-19 pandemic.

Pleural involvement of diffuse large B-cell lymphoma mimicking malignant pleural mesothelioma.

Diffuse large B-cell lymphoma (DLBCL) is a common cancer in haematology. We report a case of DLBCL mimicking malignant pleural mesothelioma (MPM). A 75-year-old man with a 1-week exacerbation of dyspnoea on exertion and right pleural effusion on chest radiography was admitted to our hospital. Positron emission tomography/computed tomography revealed diffuse pleural thick lesions and massive pleural effusion, and these lesions had accumulation of fluorodeoxyglucose. Because we suspected MPM or lung cancer, we performed a biopsy with thoracoscopy to confirm the diagnosis. A biopsy of the pleural effusion with thoracoscopy revealed DLBCL. Chemotherapy was immediately selected, and the diffuse thickened pleural wall and massive pleural effusion of the right chest were significantly improved after two cycles of chemotherapy.