Association of Novel Antihyperglycemic Drugs Versus Metformin With a Decrease in Asthma Exacerbations.

BACKGROUND: Similar to metformin, dipeptidyl peptidase-4 inhibitors (DPP-4 Is), glucagon-like peptidase 1 receptor agonists (GLP-1 RAs), and sodium glucose co-transporter-2 inhibitors (SGLT-2 Is) may improve control of asthma owing to their multiple potential mechanisms, including differential improvements in glycemic control, direct anti-inflammatory effects, and systemic changes in metabolism. OBJECTIVE: To investigate whether these novel antihyperglycemic drugs were associated with fewer asthma exacerbations compared with metformin in patients with asthma comorbid with type 2 diabetes. METHODS: Using a Japanese national administrative database, we constructed 3 active comparators-new user cohorts of 137,173 patients with a history of asthma starting the novel antihyperglycemic drugs and metformin between 2014 and 2022. Patient characteristics were balanced using overlap propensity score weighting. The primary outcome was the first exacerbation requiring systemic corticosteroids, and the secondary outcomes included the number of exacerbations requiring systemic corticosteroids. RESULTS: DPP-4 Is and GLP-1 RAs were associated with a higher incidence of exacerbations requiring systemic corticosteroids compared with metformin (DPP-4 Is: 18.2 vs 17.4 per 100 person-years, hazard ratio: 1.09, 95% confidence interval [CI]: 1.05-1.14; GLP-1 RAs: 24.9 vs 19.0 per 100 person-years, hazard ratio: 1.14, 95% CI: 1.01-1.28). In contrast, the incidence of exacerbations requiring systemic corticosteroids was similar between the SGLT-2 Is and metformin groups (17.3 vs 18.1 per 100 person-years, hazard ratio: 1.00, 95% CI: 0.97-1.03). While DPP-4 Is and GLP-1 RAs were associated with more exacerbations requiring systemic corticosteroids, SGLT-2 Is were associated with slightly fewer exacerbations requiring systemic corticosteroids (53.7 vs 56.6 per 100 person-years, rate ratio: 0.95, 95% CI: 0.91-0.99). CONCLUSIONS: While DPP-4 Is and GLP-1 RAs were associated with poorer control of asthma compared with metformin, SGLT-2 Is offered asthma control comparable to that of metformin.

Epidemiology of patients with lymphangioleiomyomatosis: A descriptive study using the national database of health insurance claims and specific health checkups of Japan.

BACKGROUND: Using patient registries or limited regional hospitalization data may result in underestimation of the incidence and prevalence of rare diseases. Therefore, we used the national administrative database to estimate the incidence and prevalence of lymphangioleiomyomatosis over six years (2014-2019) and describe changes in clinical practice and mortality. METHODS: We extracted data from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between January 2013 and December 2020. This database covers ≥99% of the population. We used the diagnostic code for lymphangioleiomyomatosis to estimate the incidence and prevalence from 2014 to 2019. Additionally, we examined the demographic characteristics, treatments, comorbidities, and mortality of the patients. RESULTS: In women, the incidence and prevalence of lymphangioleiomyomatosis in 2019 were approximately 3 per 1,000,000 person-years and 28.7 per 1,000,000 persons, respectively. While, in men, the incidence and prevalence of lymphangioleiomyomatosis were <0.2 per 1,000,000 person-years and 0.8 per 1,000,000 persons, respectively. From 2014 to 2019, the proportion of prescriptions of sirolimus and everolimus increased, while the use of home oxygen therapy, chest drainage, comorbid pneumothorax, and bloody phlegm decreased. The mortality rate remained stable at approximately 1%. CONCLUSIONS: The incidence and prevalence of lymphangioleiomyomatosis were higher in women than those reported previously. Although the incidence did not change during the 6-year period, the prevalence gradually increased. Moreover, lymphangioleiomyomatosis was observed to be rare in men. The practice of treating patients with lymphangioleiomyomatosis changed across the six years while mortality remained low, at approximately 1%.

Lung Adenocarcinoma Size Decrease after SARS-CoV-2 Vaccination during Long-Term Pembrolizumab Treatment: A Case Report.

A man in his late 40s was diagnosed with clinical stage 4B lung adenocarcinoma with a PD-L1 tumor proportion score of 100% and high tumor mutational burden. A partial response was achieved after administration of pembrolizumab. The patient received two doses of a SARS-CoV-2 vaccine (BNT162b2) after 59 courses, and a chest computed tomography revealed consolidation in the peri-tumoral area, which subsequently disappeared, and the tumor continued to shrink in the next 4 months. This case provides indirect evidence for the persistence of cancer immunity during long-term treatment with immune checkpoint inhibitors and the potential for further activation.

Effectiveness and safety of the co-administration of Yokukan-San (Japanese herbal medicine) with antipsychotics in hospitalized older patients with pneumonia.

AIM: Behavioral and psychological symptoms and delirium frequently occur in hospitalized older patients with pneumonia and are associated with longer hospital stays. Yokukan-San (YKS, traditional Japanese [Kampo] medicine) and antipsychotics are often used to treat delirium and behavioral and psychological symptoms in Japan. Hence, this study aimed to assess the effectiveness and safety of the co-administration of YKS with atypical antipsychotics in older patients with pneumonia. METHODS: We used the Japanese Diagnosis Procedure Combination inpatient database to retrospectively identify older patients (≥65 years) hospitalized for pneumonia who received antipsychotics within 3 days of hospitalization. The patients were divided into two groups: those who received atypical antipsychotics alone (control group) and those who received both atypical antipsychotics and YKS (YKS group). We compared length of hospital stay, in-hospital mortality, bone fractures, and administration of potassium products between the two groups using propensity score overlap weighting. RESULT: We identified 4789 patients in the YKS group and 61 641 in the control group. After propensity score overlap weighting, length of hospital stay was statistically significantly shorter in the YKS group (percentage difference -3.0%; 95% confidence interval -5.8% to -0.3%). The proportion of patients who received potassium products was higher in the YKS group (odds ratio 1.34; 95% confidence interval 1.15-1.55). In-hospital death and bone fractures were not significantly different. CONCLUSION: Co-administration of YKS with atypical antipsychotics could be a reasonable treatment option for hospitalized older patients with pneumonia and aggressive psychiatric symptoms. Geriatr Gerontol Int 2023; 23: 849-854.

Pulmonary carcinoid tumour with remarkably high levels of pro-gastrin-releasing peptide: A case report.

An 86-year-old woman presented with chronic cough and chest pain. Computed tomography revealed two masses in the right lower lobe of the lung accompanied by multiple lymphadenopathies and metastasis to the rib. The pro-gastrin-releasing peptide (ProGRP) levels were notably elevated (888 pg/mL). Based on these findings, our initial clinical diagnosis was small-cell lung cancer. However, the pathological diagnosis turned out to be an atypical carcinoid. The patient was finally treated with everolimus. Clinicians should be aware that carcinoid tumours are sometimes difficult to distinguish from small-cell lung cancer with respect to high ProGRP levels and multiple metastases.

Association Between Systemic Corticosteroid Use and Mortality in Patients with Epiglottitis.

OBJECTIVES: To clarify whether treatment with systemic corticosteroids at a certain dose was associated with better outcomes in patients with epiglottitis requiring airway management (tracheotomy or airway intubation). METHODS: This was a retrospective cohort study on patients hospitalized for epiglottitis requiring airway management from a nationwide inpatient database (between July 2010 and March 2019). Patients treated with systemic corticosteroids equivalent to methylprednisolone ≥40 mg/d within 2 days of admission and patients who were not treated with corticosteroids within 2 days of admission were compared after inverse probability of treatment weighting using covariate balancing propensity score. The primary outcome was all-cause 30-day in-hospital mortality, and secondary outcomes included all-cause 7-day in-hospital mortality, length of hospital stay, and total medical cost. RESULTS: There were 1986 and 1771 patients in the corticosteroid and control groups, respectively. A total of 72 of 3757 (1.9%) patients died within 30 days of admission, including 17 of 1986 (0.9%) patients in the corticosteroid group and 55 of 1771 (3.1%) in the control group (weighted odds ratio, 0.28 [95% confidence interval, 0.11-0.70]; weighted risk difference, -2.2% [-3.2% to -1.3%]). Treatment with corticosteroids was associated with lower total medical costs (weighted median, $6,187 vs. $6,587; weighted difference, $-1,123 [-2,238 to -8]) but not all-cause 7-day in-hospital mortality (weighted odds ratio, 0.63 [0.22-1.82]; weighted risk difference, -0.3% [-0.9 to 0.2]) and length of hospital stay (weighted median, 13 vs. 13 days; weighted difference, -0.2 days [-2.1 to 1.8]). CONCLUSIONS: Systemic corticosteroids may be beneficial to patients with epiglottitis requiring airway management. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:344-349, 2023.

Association between Inhalation Instruction Method in Community Pharmacies and Inhaler Device Handling Error in Patients with Obstructive Lung Disease: An Evaluation of the Impact of Practical Demonstration by Pharmacists.

Inhaler devices play an important role in the management of obstructive lung diseases including asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap. Some of these patients show suboptimal inhaler techniques; however, time for inhaler instruction by pharmacists is limited in daily clinical practice. Therefore, sufficient education regarding inhaler device handling should be provided within a limited time frame. The current study aimed to investigate the instruction methods provided by community pharmacists and their influence on inhaler device handling techniques in outpatient clinical care settings. We retrospectively collected the data of outpatients with obstructive lung diseases who were referred to our hospital and who underwent inhalation technique assessments conducted by community pharmacists. The prevalence of handling errors, clinical characteristics of patients, and instruction methods were analyzed. In total, 138 patients (170 devices) were included in this study. Approximately 70.0% of patients received verbal explanations combined with leaflets about inhaler instructions. In a device-based analysis, 63 (37.1%) of 170 devices had at least one technical error and 18 (10.6%) of the devices had critical errors. Patients without critical errors received practical demonstration instructions from pharmacists combined with leaflets and verbal explanations more frequently than those with critical errors (22.8 vs. 0%, p < 0.01). This study revealed that patients with obstructive lung diseases commonly present with inhaler device handling errors and critical errors were observed with non-negligible frequency in daily practice in Japan. Combined instruction with leaflet, verbal explanation, and pharmacist demonstration may be effective in improving proper inhaler treatment.

Multiple Brain Metastases in a Patient with ROS1 Fusion-Positive Lung Adenocarcinoma as a Disease Flare due to Crizotinib Cessation Caused by Disseminated Aseptic Inflammation from Crizotinib-Associated Renal Cysts: A Case Report.

Rapid tumor growth after cessation of molecularly targeted drugs, called "disease flare," may occur and affect the prognosis of lung cancer. However, this phenomenon has never been reported in ROS proto-oncogene 1 (ROS1) fusion-positive lung adenocarcinoma. Herein, we report a disease flare in a patient with ROS1 fusion-positive lung adenocarcinoma. A 60-year-old female was diagnosed with stage IVA ROS1 fusion-positive lung adenocarcinoma via bronchoscopy. Although crizotinib, an ROS1 tyrosine kinase inhibitor, achieved a partial response, a mass lesion appeared in the patient's right kidney 12 months after starting crizotinib, which was diagnosed pathologically as crizotinib-associated renal cysts (CARCs). Given that readministration of crizotinib repeatedly induced CARC-like aseptic inflammation that appeared to be disseminated around surgical site, crizotinib treatment had to be abandoned. Around 25 days after crizotinib cessation, she was referred to the emergency department with a convulsive seizure and hemiparesis due to new, rapidly growing brain metastases. Whole-brain irradiation and administration of another ROS1 tyrosine kinase inhibitor, entrectinib, markedly ameliorated the metastases and improved hemiparesis. This has been the first report of a disease flare after crizotinib cessation due to CARCs in a patient with ROS1 fusion-positive lung adenocarcinoma. Attention should be paid to disease flare, especially in the brain, when molecularly targeted medication is stopped due to adverse events in ROS1 fusion-positive lung adenocarcinoma. Switching to drugs that penetrate the blood-brain barrier could overcome disease flare in the brain.

Measurement of chest wall motion using a motion capture system with the one-pitch phase analysis method.

Spirometry is a standard method for assessing lung function. However, its use is challenging in some patients, and it has limitations such as risk of infection and inability to assess regional chest wall motion. A three-dimensional motion capture system using the one-pitch phase analysis (MCO) method can facilitate high precision measurement of moving objects in real-time in a non-contacting manner. In this study, the MCO method was applied to examine thoraco-abdominal (TA) wall motion for assessing pulmonary function. We recruited 48 male participants, and all underwent spirometry and chest wall motion measurement with the MCO method. A significant positive correlation was observed between the vital capacity (Spearman's ρ = 0.68, p < 0.0001), forced vital capacity (Spearman's ρ = 0.62, p < 0.0001), and tidal volume (Spearman's ρ = 0.61, p < 0.0001) of spirometry and the counterpart parameters of MCO method. Moreover, the MCO method could detect regional rib cage and abdomen compartment contributions and could assess TA asynchrony, indicating almost complete synchronous movement (phase angle for each compartment: - 5.05° to 3.86°). These findings suggest that this technique could examine chest wall motion, and may be effective in analyzing chest wall volume changes and pulmonary function.

Pulmonary disease as a risk factor for transfusion-related acute lung injury.

Transfusion-related acute lung injury (TRALI) is a severe condition characterised by noncardiogenic pulmonary oedema that develops within 6 h of blood transfusion. Patient factors and blood products have both been implicated in the development of TRALI; however, the role of pulmonary disease has not been investigated. We aimed to determine whether pulmonary disease is a risk factor for TRALI. We conducted a nested case-control study using data from the Diagnosis Procedure Combination database, a nationwide inpatient database in Japan, between July 2010 and March 2015. Case patients who developed TRALI were 1:4-matched with control patients for sex, age and same hospital for receipt of blood transfusion. We conducted a multivariable conditional logistic regression analysis to evaluate the associations of TRALI with various factors including comorbidities, body mass index (BMI) and plasma-containing blood products. We identified 2 019 501 hospitalised patients who received a blood transfusion. Among these patients, 72 developed TRALI. The 72 case patients had higher proportions of haematological malignancy, trauma and interstitial lung disease (ILD) than the 288 matched control patients. The multivariable conditional logistic regression analysis showed that occurrence of TRALI was associated with ILD (odds ratio, 3.88; 95% confidence interval, 1.11-13.6), BMI ≥25.0 kg·m-2 (2.10; 1.05-4.24) and plasma-containing blood products (1.94; 1.10-3.42), but not with infectious lung disease or obstructive airway disease. In conclusion, ILD was an independent risk factor for the development of TRALI. Physicians should be aware of the increased risk of TRALI in patients with ILD.

Multiple cerebral infarctions in ROS1-rearranged lung adenocarcinoma.

Rearrangements of specific tyrosine kinases are associated with an elevated risk of venous thrombosis in lung adenocarcinoma, although their effects on arterial thrombosis have not been fully elucidated. Here, we report two cases of ROS proto-oncogene 1 (ROS1)-rearranged lung adenocarcinoma with cerebral infarction during the peri-diagnostic period. Two cases took contrasting clinical courses: one patient could not receive targeted therapy because of a significant decline in performance status, whereas in the other patient, the performance status was maintained and targeted therapy drastically reduced the tumour size. Our cases suggest close monitoring could be considered in the selected cohort.

Standardized reporting systems of chest computed tomography in a population with low coronavirus disease 2019 prevalence: A retrospective comparative study.

PURPOSE: To compare the diagnostic performance and interobserver agreement of three reporting systems for computed tomography findings in coronavirus disease 2019 (COVID-19), namely the COVID-19 Reporting and Data System (CO-RADS), COVID-19 Imaging Reporting and Data System (COVID-RADS), and Radiological Society of North America (RSNA) expert consensus statement, in a low COVID-19 prevalence area. METHOD: This institutional review board approval single-institutional retrospective study included 154 hospitalized patients between April 1 and May 21, 2020; 26 (16.9 %; 63.2 ± 14.1 years, 21 men) and 128 (65.7 ± 16.4 years, 87 men) patients were diagnosed with and without COVID-19 according to reverse transcription-polymerase chain reaction results, respectively. Written informed consent was waived due to the retrospective nature of the study. Six radiologists independently classified chest computed tomography images according to each reporting system. The area under receiver operating characteristic curves, sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and interobserver agreements were calculated and compared across the systems using paired t-test and kappa analysis. RESULTS: Mean area under receiver operating characteristic curves were as follows: CO-RADS, 0.89 (95 % confidence interval [CI], 0.87-0.90); COVID-RADS, 0.78 (0.75-0.80); and RSNA expert consensus statement, 0.88 (0.86-0.90). Average kappa values across observers were 0.52 (95 % CI: 0.45-0.60), 0.51 (0.41-0.61), and 0.57 (0.49-0.64) for CO-RADS, COVID-RADS, and RSNA expert consensus statement, respectively. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were the highest at 0.71, 0.53, 0.72, 0.96, and 0.56 in the CO-RADS; 0.56, 0.31, 0.54, 0.95, and 0.35 in the COVID-RADS; 0.83, 0.49, 0.61, 0.96, and 0.55 in the RSNA expert consensus statement, respectively. CONCLUSIONS: The CO-RADS exhibited the highest specificity, positive predictive value, which are especially important in a low-prevalence population, while maintaining high accuracy and negative predictive value, demonstrating the best performance in a low-prevalence population.

Factors affecting in-hospital mortality of non-tuberculous mycobacterial pulmonary disease.

BACKGROUND: The incidence and prevalence of non-tuberculous mycobacterial pulmonary disease (NTM-PD) are reportedly increasing in many parts of the world. However, there are few published data on NTM-PD-related death. Using data from a national inpatient database in Japan, we aimed in this study to identify the characteristics of patients with NTM-PD and clinical deterioration and to identify risk factors for in-hospital mortality. METHODS: We examined data from the Diagnosis Procedure Combination (DPC) database in Japan from July 2010 to March 2014. We extracted data for HIV-negative NTM-PD patients who required unscheduled hospitalization. We evaluated these patients' characteristics and performed multivariable logistic regression analysis to identify risk factors for all-cause in-hospital mortality. RESULTS: A total of 16,192 patients (median age: 78 years; women: 61.2%) were identified. The median body mass index (BMI) was 17.5 kg/m2 (IQR 15.4-20.0). All cause In-hospital death occurred in 3166 patients (19.6%). The median BMI of the patients who had died was 16.0 kg/m2 (IQR 14.2-18.4). Multivariable analysis revealed that increased mortality was associated with male sex, lower BMI, lower activities of daily living scores on the Barthel index, hemoptysis, and comorbidities, including pulmonary infection other than NTM, interstitial lung disease, pneumothorax, and malignant disease. CONCLUSIONS: We found associations between being underweight and having several comorbidities and increased in-hospital mortality in patients with NTM-PD. Preventing weight loss and management of comorbidities may have a crucial role in improving this disease's prognosis.

Diagnostic prediction of COVID-19 based on clinical and radiological findings in a relatively low COVID-19 prevalence area.

BACKGROUND: Distinguishing coronavirus disease 2019 (COVID-19) pneumonia from other lung diseases is often difficult, especially in a highly comorbid patient population in a low prevalence region. We aimed to distinguish clinical data and computed tomography (CT) images between COVID-19 and other lung diseases in an advanced care hospital. METHODS: We assessed clinical characteristics, laboratory data, and chest CT images of patients with COVID-19 and non-COVID-19 patients who were suspected of having COVID-19 between February 20 and May 21, 2020, at the University of Tokyo Hospital. RESULTS: Typical appearance for COVID-19 on CT images were found in 24 of 29 COVID-19 cases and 21 of 168 non-COVID-19 cases, according to the Radiological Society of North America Expert Consensus Statement (for predicting COVID-19, sensitivity 0.828, specificity 0.875, positive predictive value 0.533, negative predictive value 0.967). When we focused on cases with typical CT images, loss of taste or smell, and close contact with COVID-19 patients were exclusive characteristics for the COVID-19 cases. Among laboratory data, high fibrinogen (P < 0.01) and low white blood cell count (P < 0.01) were good predictors for COVID-19 with typical CT images in multivariate analysis. CONCLUSIONS: In a relatively low prevalence region, CT screening has high sensitivity to COVID-19 in patients with suspected symptoms. When chest CT findings are typical for COVID-19, close contact, loss of taste or smell, lower white blood cell count, and higher fibrinogen are good predictors for COVID-19.

Interrupted time-series analyses of routine vaccination program for elderly pneumonia patients in Japan; an ecological study using aggregated nationwide inpatient data.

A national routine pneumococcal pneumonia immunization program started in Japan in 2014. It targeted the population aged ≥65 years and used a 23-valent pneumococcal polysaccharide vaccine; PPSV23. However, its effectiveness was not well defined because of the lack of a comprehensive database on the PPSV23 vaccination status of each subject. We used interrupted time-series analyses to assess the changes in the incidence and prognosis of elderly patients hospitalized for pneumonia before and after initiation of the program. First, we estimated the PPSV23 coverage rates in subjects aged ≥65 years based on the number of shipped PPSV23 syringes and the estimated population in each prefecture. The estimated coverage rates reached around 40% in 2014 for the 3 Tohoku prefectures, while those in the other prefectures remained below 20%. After the national routine immunization program started, the estimated coverage rate increased significantly in every prefecture and exceeded 40% in 2017. Next, we aggregated the data extracted from the Japanese Diagnosis Procedure Combination database from April 2011 through February 2017 for hospitalized pneumonia patients aged ≥65 years. The data included data from 655,746 patients, excluding those in the 3 Tohoku prefectures. Interrupted time-series analyses found no change in the incidence of hospitalized pneumonia patients and in-hospital mortality after the vaccination program, but there was a decrease in the in-hospital mortality of pneumonia patients with severe comorbidities defined by the modified Charlson comorbidity index. These results suggest an association between the vaccination program and an improved outcome in hospitalized elderly pneumonia patients with severe comorbidities in Japan.

Early Arterial Embolization and Mortality in Mechanically Ventilated Patients With Hemoptysis: A Nationwide Retrospective Cohort Study.

OBJECTIVES: Hemoptysis, a symptom common across various respiratory diseases, can cause airway obstruction leading to a life-threatening condition. Arterial embolization has been used to control bleeding from the lower airways. However, limited studies have evaluated its effects on in-hospital mortality in patients with hemoptysis requiring mechanical ventilation. The objective of this study was to clarify whether early intervention by arterial embolization reduced mortality in mechanically ventilated patients with hemoptysis. DESIGN: Retrospective cohort study from July 2010 to March 2017. SETTING: More than 1,200 acute-care hospitals, comprising approximately 90% of all tertiary-care emergency hospitals in Japan. PATIENTS: The study cohort was patients with pulmonary diseases hospitalized for hemoptysis and mechanically ventilated within 2 days of admission. INTERVENTIONS: We compared patients who had undergone arterial embolization within 3 days of endotracheal intubation (early embolization group) with patients who did not (control group). MEASUREMENTS AND MAIN RESULTS: A total of 12,287 patients with hemoptysis requiring mechanical ventilation were analyzed. After 1:4 propensity score matching, there were 226 and 904 patients in the early embolization and control groups, respectively. The early embolization group was associated with lower 7-day and 30-day mortalities (7-d mortality: 1.3% vs 4.0%; odds ratio, 0.39; 95% CI, 0.16-0.97; p = 0.044 and 30-d mortality: 7.5% vs 16.8%; odds ratio, 0.45; 95% CI, 0.28-0.73; p = 0.001) and shorter duration of mechanical ventilation (median 6 d, interquartile range 4-13 d vs 8 d, interquartile range 4-19 d; p = 0.003) compared with the control group. CONCLUSIONS: Our results show that early intervention by arterial embolization may be effective in reducing 7-day and 30-day mortalities in patients with life-threatening hemoptysis requiring mechanical ventilation.

Alpha-Fetoprotein-Producing Lung Hepatoid Adenocarcinoma with Brain Metastasis Treated with S-1.

Lung hepatoid adenocarcinoma (HAC) is a rare primary lung carcinoma pathologically characterized by hepatocellular carcinoma-like tumor cells, the majority of which produce alpha-fetoprotein (AFP). The clinical prognosis of lung HAC is generally poor, and effective therapeutic regimens for inoperable or recurrent cases have not been established. Here, we report a case of AFP-producing lung HAC with brain metastasis with long-term disease control, treated with the 5-fluorouracil-derived regimen S-1. The patient was a 66-year-old male admitted to the hospital with alexia. Chest X-ray revealed a massive tumor in the left upper lobe, and a head CT scan revealed a metastasis in the left parietal lobe. The laboratory data showed a remarkably elevated AFP level (97,561 ng/mL). Pathological assessment of the resected brain tumor revealed HAC, which was compatible with the lung biopsies. Together with the absence of other metastatic lesions, a final diagnosis of primary lung HAC, stage IV T4N3M1b, was given. The patient first underwent non-small cell lung cancer chemotherapy regimens (carboplatin and paclitaxel as the first line, and pemetrexed as the second line), but had clinical progression. After third-line oral S-1 (tegafur/gimeracil/oteracil) administration, the serum AFP level significantly dropped and the patient achieved long-term disease control without relapse, surviving more than 19 months after disease presentation. The autopsy result was consistent with the diagnosis of primary lung HAC, and immunohistochemical staining was AFP+, glypican 3+, and spalt-like transcription factor 4+. Here, we report the case of a rare primary lung HAC with apparent disease control on S-1 therapy, together with a literature review.

Renal Effects after Pembrolizumab Treatment for Non-small Cell Lung Carcinoma.

Immune checkpoint inhibitors (CPIs), including pembrolizumab, are becoming common oncological treatments. CPIs have been associated with a significant risk of developing immune-related adverse events (irAEs), such as nephritis and interstitial nephritis. However, the occurrence of glomerulonephritis has only rarely been reported. We herein present the case of a 75-year-old woman with non-small cell lung carcinoma (NSCLC) who developed proteinuria and microscopic hematuria during treatment with pembrolizumab. Renal biopsy revealed tubulointerstitial nephritis and IgA nephropathy. Considering that a urinalysis showed no abnormality before treatment, the condition might have been induced by pembrolizumab. In this report, we focus on the correct diagnosis and management of renal irAEs, which remain controversial.