Olanzapine Plus Triple Antiemetic Therapy for the Prevention of Carboplatin-Induced Nausea and Vomiting: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial.

PURPOSE: We evaluated the efficacy and safety of antiemetic therapy with olanzapine, a neurokinin-1 receptor antagonist (RA), a 5-hydroxytryptamine-3 (5-HT3) RA, and dexamethasone for preventing chemotherapy-induced nausea and vomiting in patients receiving carboplatin-containing chemotherapy. PATIENTS AND METHODS: Chemotherapy-naïve patients scheduled to receive carboplatin (AUC ≥5) were randomly assigned to receive either olanzapine 5 mg once daily (olanzapine group) or placebo (placebo group) in combination with aprepitant, a 5-HT3 RA, and dexamethasone. The primary end point was the complete response (CR; no vomiting and no rescue therapy) rate in the overall phase (0-120 hours). Secondary end points included the proportion of patients free of nausea and safety. RESULTS: In total, 355 patients (78.6% male, median age 72 years, 100% thoracic cancer), including 175 and 180 patients in the olanzapine and placebo groups, respectively, were evaluated. The overall CR rate was 86.9% in the olanzapine group versus 80.6% in the placebo group. The intergroup difference in the overall CR rate was 6.3% (95% CI, -1.3 to 13.9). The proportions of patients free of chemotherapy-induced nausea in the overall (88.6% in the olanzapine group v 75.0% in the placebo group) and delayed (89.7% v 75.6%, respectively) phases were significantly higher in the olanzapine group than in the placebo group (both P < .001). Somnolence was observed in 43 (24.6%) and 41 (22.9%) patients in the olanzapine and placebo groups, respectively, and no events were grade ≥3 in severity. CONCLUSION: The addition of olanzapine was not associated with a significant increase in the overall CR rate. Regarding the prevention of nausea, adding olanzapine provided better control in patients receiving carboplatin-containing chemotherapy, which needs further exploration.

Particle Size Measurement and Detection of Bound Proteins of Non-Porous/Mesoporous Silica Microspheres by Single-Particle Inductively Coupled Plasma Mass Spectrometry.

Single-particle inductively coupled plasma mass spectrometry (spICP-MS) has been used for particle size measurement of diverse types of individual nanoparticles and micrometer-sized carbon-based particles such as microplastics. However, its applicability to the measurement of micrometer-sized non-carbon-based particles such as silica (SiO2) particles is unclear. In this study, the applicability of spICP-MS to particle size measurement of non-porous/mesoporous SiO2 microspheres with a nominal diameter of 5.0 µm or smaller was investigated. Particle sizes of these microspheres were measured using both spICP-MS based on a conventional calibration approach using an ion standard solution and scanning electron microscopy as a reference technique, and the results were compared. The particle size distributions obtained using both techniques were in agreement within analytical uncertainty. The applicability of this technique to the detection of metal-containing protein-binding mesoporous SiO2 microspheres was also investigated. Bound iron (Fe)-containing proteins (i.e., lactoferrin and transferrin) of mesoporous SiO2 microspheres were detected using Fe as a presence marker for the proteins. Thus, spICP-MS is applicable to the particle size measurement of large-sized and non-porous/mesoporous SiO2 microspheres. It has considerable potential for element-based detection and qualification of bound proteins of mesoporous SiO2 microspheres in a variety of applications.

Discovery of long-chain polyamines embedded in the biosilica on the Bacillus cereus spore coat.

Biosilicification is the process by which organisms incorporate soluble, monomeric silicic acid, Si(OH)4, in the form of polymerized insoluble silica, SiO2. Although the mechanisms underlying eukaryotic biosilicification have been intensively investigated, prokaryotic biosilicification has only recently begun to be studied. We previously reported that biosilicification occurs in the gram-positive, spore-forming bacterium Bacillus cereus, and that silica is intracellularly deposited on the spore coat as a protective coating against acids, although the underlying mechanism is not yet fully understood. In eukaryotic biosilicifying organisms, such as diatoms and siliceous sponges, several relevant biomolecules are embedded in biogenic silica (biosilica). These biomolecules include peptides, proteins, and long-chain polyamines. In this study, we isolated organic compounds embedded in B. cereus biosilica to investigate the biomolecules involved in the prokaryotic biosilicification process and identified long-chain polyamines with a chemical structure of H2N-(CH2)4-[NH-(CH2)3]n-NH2 (n: up to 55). Our results demonstrate the common presence of long-chain polyamines in different evolutionary lineages of biosilicifying organisms, i.e., diatoms, siliceous sponges, and B. cereus, suggesting a common mechanism underlying eukaryotic and prokaryotic biosilicification.

Increased skeletal muscle mass index was involved in glycemic efficacy following diabetes treatment, and changes in fat mass index correlated with the changes in the lipid ratio in type 2 diabetes.

AIM: This study aimed to investigate the association between changes in body composition, glycated hemoglobin, and lipid ratio during the treatment of patients with type 2 diabetes mellitus (T2DM). METHODS: This retrospective analysis used data from outpatients with T2DM who had confirmed body composition and measured laboratories at administration and after treatment. The baseline characteristics and prescribed treatment were collected. The total cholesterol/high-density lipoprotein cholesterol (HDL) ratio, low-density lipoprotein cholesterol (LDL)/HDL ratio, and triglyceride-glucose (TyG) index were also calculated. RESULTS: A total of 207 patients (mean patient age, 62.0 ± 13.7 years; 68.1 % males) were enrolled. Fat mass index (FMI) changes correlated with the changes in the lipid ratio, whereas skeletal muscle mass index (SMI) changes inversely correlated with glycated hemoglobin (HbA1c) changes. Multiple regression analysis showed that changes in LDL/HDL and TyG correlated with FMI changes (t = 2.388, p = 0.017, t = 2.022, p = 0.044). Conversely, HbA1c changes correlated with SMI changes (t = -2.552, p = 0.011). CONCLUSION: In patients with T2DM, increased SMI was involved in glycemic efficacy, and FMI changes were associated with LDL/HDL and TyG.

Six-week oral prednisolone therapy for immune-related pneumonitis: a single-arm phase II study.

BACKGROUND: There has been no prospective trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs). METHODS: In this single-arm phase II study, patients with cancer with grade ≥2 irP received oral prednisolone (1 mg/kg/day), tapered over 6 weeks. The primary endpoint was a pneumonitis control rate at 6 weeks from the start of the study treatment, defined as complete disappearance or partial improvement of irP in high-resolution CT of the chest. RESULTS: Among 57 patients enrolled, 56 were included in the final analysis. The most frequent cause of irP was single ICI therapy (51.8%), followed by combination with chemotherapy plus ICI (39.3%). Thirty-five (62.5%) patients had grade 2 irP and 21 (37.5%) had grade ≥3. Fifty-one (91.1%) patients completed the study treatment while 5 discontinued the study treatment because of relapse of irP (n=1), death from cancer (n=1), occurrence of immune-related hepatitis (n=1), extension of the treatment duration more than 6 weeks (n=1), and attending physician's decision (n=1). Six weeks after the start of the study treatment, 16 (28.5%) patients demonstrated complete recovery from irP, 35 (62.5%) had a partial improvement in irP, 1 (1.8%) had a relapse of irP, and 4 (7.1%) were not evaluable. The pneumonitis control rate at 6 weeks was 91.1% (95% CI, 80.7% to 96.1%). Twelve weeks after the start of the study treatment, 5 (8.9%), 27 (48.2%), and 15 (26.8%) patients demonstrated complete recovery, partial improvement, and relapse, respectively, and 9 (16.1%) were not evaluable. The pneumonitis control rate at 12 weeks was 57.1% (95% CI, 44.1% to 69.2%). During the observation period, 18 (32.1%) patients experienced a relapse of irP, and of those, 17 received re-treatment with corticosteroids. Grade ≥3 adverse events occurred in 10 (17.9%) patients, in which hyperglycemia was most frequent (n=6). There was no treatment-related death. CONCLUSIONS: In this first prospective study for irP, prednisolone at 1 mg/kg/day, tapered over 6 weeks, demonstrated a promising clinical benefit and manageable toxicity, suggesting a potential treatment option for irP. TRIAL REGISTRATION NUMBER: jRCT: 1041190029.

The Prognostic Nutritional Index before durvalumab after chemoradiation predict the overall survival in patients with stage III non-small cell lung cancer.

BACKGROUND: Adjuvant durvalumab after chemoradiation has become the standard of care for patients with stage III NSCLC, according to the PACIFIC trial. Whether biomarkers before durvalumab for patients with stage III NSCLC showed predictive and prognostic effects remains unknown. METHODS: This is a retrospective study in the Fujieda Municipal General Hospital between October 2018 and March 2022. We assessed the predictive value of the Prognostic Nutritional Index (PNI) in stage III non-small cell lung cancer (NSCLC) patients treated with durvalumab after chemoradiation. RESULTS: After applying the inclusion and exclusion criteria, the study included 56 patients for further analysis. The median follow-up period was 17.6 months (range, 3.0-45.4 months). According to receiver operating characteristic curve results, the PNI cutoff value to predict overall survival (OS) was 37.9, with sensitivity and specificity at 67.9% and 67.9%. Accordingly, the patients were divided into low- and high-PNI groups. Patients with the low-PNI group had a significantly shorter progression-free survival compared to the high-PNI group (median, 9.1 vs. 21.3 months, p = 0.032). OS was also shorter in the low-PNI group (median, 19.0 months vs. not reached, p < 0.001). In the multivariate Cox hazards regression analyses, the high-PNI was an independent prognostic factor for OS (hazard ratio, 0.187; 95% confidence interval, 0.046-0.760; p = 0.019).It seems that PNI could be used as a predictor for OS in patients with stage III NSCLC treated with durvalumab after chemoradiation.KEY MESSAGESInadequate immunocompetence and nutritional status after chemoradiation therapy may result in poor antitumor efficacy of ICIs.Pretreatment immune and nutritional assessment using PNI could be considered an independent predictor for the survival of stage III NSCLC patients treated with durvalumab after chemoradiation therapy.

Cytokine profiling identifies circulating IL-6 and IL-15 as prognostic stratifiers in patients with non-small cell lung cancer receiving anti-PD-1/PD-L1 blockade therapy.

Whether circulating levels of specific cytokines at baseline link with treatment efficacy of immune checkpoint blockade (ICB) therapy in patients with non-small cell lung cancer remains unknown. In this study, serum samples were collected in two independent, prospective, multicenter cohorts before the initiation of ICB. Twenty cytokines were quantified, and cutoff values were determined by receiver operating characteristic analyses to predict non-durable benefit. The associations of each dichotomized cytokine status with survival outcomes were assessed. In the discovery cohort (atezolizumab cohort; N = 81), there were significant differences in progression-free survival (PFS) in accordance with the levels of IL-6 (log-rank test, P = 0.0014), IL-15 (P = 0.00011), MCP-1 (P = 0.013), MIP-1ß (P = 0.0035), and PDGF-AB/BB (P = 0.016). Of these, levels of IL-6 and IL-15 were also significantly prognostic in the validation cohort (nivolumab cohort, N = 139) for PFS (log-rank test, P = 0.011 for IL-6 and P = 0.00065 for IL-15) and overall survival (OS; P = 3.3E-6 for IL-6 and P = 0.0022 for IL-15). In the merged cohort, IL-6high and IL-15high were identified as independent unfavorable prognostic factors for PFS and OS. The combined IL-6 and IL-15 status stratified patient survival outcomes into three distinct groups for both PFS and OS. In conclusion, combined assessment of circulating IL-6 and IL-15 levels at baseline provides valuable information to stratify the clinical outcome of patients with non-small cell lung cancer treated with ICB. Further studies are required to decipher the mechanistic basis of this finding.

An autopsy case of disseminated Cunninghamella bertholletiae infection in an immunocompetent patient: a case report.

BACKGROUND: Recently, deaths due to mucormycosis in immunocompromised hosts have increased; however, the clinical and pathological features of mucormycosis are not fully understood, especially in view of the associated high mortality and rare incidence in immunocompetent patients. CASE PRESENTATION: We have described a rare autopsy case of a 67-year-old Japanese man with chronic obstructive pulmonary disease who contracted mucormycosis. He had not been on any immunosuppressants, and his immune functions were intact. Since 3 days prior to admission to our hospital, he had experienced progressive dyspnea, productive cough, and fever. Chest computed tomography revealed pleural effusion in the left lower hemithorax and consolidation in the right lung field. Although he was administered with tazobactam-piperacillin hydrate (13.5 g/day), renal dysfunction occurred on the ninth disease day. Therefore, it was switched to cefepime (2 g/day). However, his general condition and lung-field abnormality worsened gradually. Cytological analysis of the sputum sample at admission mainly revealed sporangiophores and unicellular sporangioles, while repeated sputum culture yielded Cunninghamella species. Therefore, he was diagnosed with pulmonary mucormycosis. Liposomal amphotericin B (5 mg/kg/day) was initiated on the 28th disease day. However, chest radiography and electrocardiography detected cardiomegaly and atrial fibrillation, respectively, and he died on the 37th disease day. A postmortem examination revealed clusters of fungal hyphae within the arteries of the right pulmonary cavity wall, the subpericardial artery, intramyocardial capillary blood vessels, and the esophageal subserosa vein. Direct sequencing revealed that all fungal culture samples were positive for Cunninghamella bertholletiae. CONCLUSIONS: Cunninghamella bertholletiae could rapidly progress from colonizing the bronchi to infecting the surrounding organs via vascular invasion even in immunocompetent patients.

Serum immune modulators associated with immune-related toxicities and efficacy of atezolizumab in patients with non-small cell lung cancer.

PURPOSE: Identifying patients at high risk of immune-related adverse events (irAEs) that impede the achievement of durable efficacy of programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) blockade therapy is important in improving their management. Identification of a novel predictive factor of therapeutic benefit is also important in improving patient selection for treatment with PD-1/PD-L1 inhibitors. Further determinants driving response and linking with irAEs are urgently required. METHODS: To address these unmet needs in the field, we explored whether 27 soluble checkpoint proteins and immunomodulatory proteins in serum at the therapy baseline and after week 3 were associated with irAE onset and therapeutic efficacy using MILLIPLEX Human Immuno-Oncology Checkpoint Protein Panel assays in a prospective, multicenter cohort of 81 patients with non-small cell lung cancer (NSCLC) receiving atezolizumab monotherapy. RESULTS: By competing-risks regression analysis, we identified that high levels of B cell-activating factor (BAFF) at baseline were a significant and strong risk factor of irAEs (hazard ratio, 5.61; 95% confidence interval, 2.43-12.96; P < 0.0001). We also identified that increased inducible T cell co-stimulator (ICOS) during the first therapeutic cycle was an independent factor associated with prolonged progression-free survival and overall survival. CONCLUSION: These findings are in keeping with the reported mechanistic basis of these molecules and may provide potential guidance for clinical decision-making to improve patient care. Further validation studies are warranted. Trial registration UMIN000035616 (January 28, 2019).

Chemotherapy for patients with advanced lung cancer with interstitial lung disease: a prospective observational study.

Introduction: Although recent advances in chemotherapy for lung cancer are remarkable, most clinical trials have excluded patients with interstitial lung disease (ILD) due to the concern of developing acute exacerbation (AE) of ILD. Hence, accumulating original evidence of cancer treatment for this population is important. Methods: Between 2016 and 2020, a prospective observational study was conducted across 11 Japanese hospitals. Patients with chemotherapy-naïve, inoperable, advanced lung cancer with ILD were included. The primary outcome was the frequency of AE-ILD after registration; the secondary outcomes were the risk factor of AE-ILD and the efficacy of chemotherapy. Results: Among 124 patients enrolled, 109 patients who received chemotherapy were analyzed. The median age was 72 years, and the majority showed usual interstitial pneumonia (UIP)/probable UIP pattern upon chest computed tomography. The median percent-predicted forced vital capacity (%FVC) was 81% (interquartile range: 66-95%). After registration, 23 patients (21.1%; 95% confidence interval [CI]: 14.4-29.7%) developed AE-ILD. The logistic analysis revealed that lower %FVC slightly but significantly increased the risk of AE-ILD (odds ratio per 10% decrease: 1.27; 95% CI: > 1.00-1.62). Overall response rates/median overall survival times in non-small-cell lung cancer and small-cell lung cancer for the first-line chemotherapy were 41% (95% CI: 31-53)/8.9 months (95% CI: 7.6-11.8) and 91% (95% CI: 76-98)/12.2 months (95% CI: 9.2-14.5), respectively. Conclusion: AE-ILD during chemotherapy is a frequent complication among patients with lung cancer with ILD, particularly those with lower %FVC. Conversely, even in this population, passable treatment response can be expected.

Highly Precise and Sensitive Polymerase Chain Reaction Using Mesoporous Silica-Immobilized Enzymes.

A highly precise and sensitive technology that enables DNA amplification/detection from minimal amounts of nucleic acid is expected to find applicability in genetic testing involving small amounts of samples. The use of a free enzyme in conventional DNA amplification techniques, such as the polymerase chain reaction (PCR), frequently causes side reactions (i.e., nonspecific DNA amplification) when ≤103 substrate DNA molecules are present, thereby preventing selective amplification of the target DNA. To address this issue, we have developed a novel DNA amplification system, mesoporous silica-enhanced PCR (MSE-PCR), which involves the immobilization of a thermostable DNA polymerase from Thermococcus kodakaraensis (KOD DNA polymerase) into highly ordered nanopores of the mesoporous silica to control the reaction environment around the enzyme. In the MSE-PCR system using immobilized KOD DNA polymerase, such nonspecific DNA amplification was remarkably inhibited under the same conditions. Furthermore, the optimization of mesoporous silica pore sizes enabled selective and efficient DNA amplification from DNA substrates at the single-molecule level, i.e., one ten-thousandth of the amount of substrate DNA required for a DNA amplification reaction using a free enzyme. The results obtained in this study have shown that the nanopores of mesoporous silica can inhibit nonspecific reactions in DNA amplification, thereby considerably improving the specificity and sensitivity of the DNA polymerase reaction.

Sarcopenia is associated with the Geriatric Nutritional Risk Index in elderly patients with poorly controlled type 2 diabetes mellitus.

AIMS/INTRODUCTION: Diabetes and sarcopenia have a two-way relationship with each other with advanced age. Additionally, malnutrition is correlated with a higher risk of sarcopenia in elderly patients. This study evaluated the association between sarcopenia and geriatric nutritional risk index (GNRI) in elderly patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Patients with type 2 diabetes mellitus aged ≥60 years were recruited from June 2018 to August 2020. This study analyzed 234 patients, who completed a physical performance test required for the diagnosis of sarcopenia. To investigate the effect of GNRI on sarcopenia, logistic regression analyses was used. RESULTS: Patients with sarcopenia were significantly older with a lower body mass index (BMI) and GNRI compared with normal patients. The GNRI showed a positive correlation with the skeletal muscle index (SMI) and handgrip strength (SMI: R = 0.486, P < 0.001 for male; R = 0.589, P < 0.001 for female, handgrip strength: R = 0.470, P < 0.001 for male, R = 0.364, P < 0.001 for female). In the multivariate logistic regression model, a higher GNRI was associated with a lower risk of sarcopenia in older men and women with diabetes (adjusted odds ratio [OR], 0.892; 95% confidence interval [CI], 0.839-0.948 for male; adjusted OR, 0.928; 95% CI, 0.876-0.982 for female). One year of diabetes treatment improved the GNRI in the sarcopenia group with type 2 diabetes mellitus. CONCLUSIONS: A low GNRI was associated with an increased risk of sarcopenia in elderly patients with type 2 diabetes mellitus. Treatment with glucose-lowering drugs improved the GNRI in the sarcopenia group.

The Geriatric Nutritional Risk Index and Prognostic Nutritional Index Predict the Overall Survival of Advanced Non-Small Cell Lung Cancer Patients.

We aimed to assess the prognostic and predictive significance of pretreatment Geriatric Nutritional Risk Index (GNRI) and Prognostic Nutritional Index (PNI) measurements on advanced non-small cell lung cancer (NSCLC) patients treated with first-line therapy. Patients with advanced NSCLC treated between February 2014 and August 2020 were retrospectively analyzed. The optimal cutoff points for GNRI and PNI were measured with receiver operating characteristic (ROC) curve analysis according to overall survival (OS). The predictive factors for progression-free survival (PFS) and OS were evaluated with univariate and multivariate analyses via the Cox hazards regression. A total of 160 patients were included in the study. Significant differences between the low and high-GNRI or PNI groups were found regarding ECOG-PS. The low-GNRI and low-PNI groups had significantly shorter PFS and OS than the high-GNRI and high-PNI groups. A multivariate analysis using a Cox regression model revealed that the high-GNRI group was an independent prognostic factor of OS and PFS, and the PNI group was an independent prognostic factor of OS. Pretreatment GNRI and PNI may therefore be a potential effective predictor of the survival of advanced NSCLC patients undergoing first-line treatment.

Increased serum cholesterol and long-chain fatty acid levels are associated with the efficacy of nivolumab in patients with non-small cell lung cancer.

BACKGROUND: Lipids have immunomodulatory functions and the potential to affect cancer immunity. METHODS: The associations of pretreatment serum cholesterol and long-chain fatty acids with the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated in 148 patients with non-small cell lung cancer who received nivolumab. RESULTS: When each lipid was separately evaluated, increased low-density lipoprotein (LDL)-cholesterol (P < 0.001), high-density lipoprotein (HDL)-cholesterol (P = 0.014), total cholesterol (P = 0.007), lauric acid (P = 0.015), myristic acid (P = 0.022), myristoleic acid (P = 0.035), stearic acid (P = 0.028), linoleic acid (P = 0.005), arachidic acid (P = 0.027), eicosadienoic acid (P = 0.017), dihomo-γ-linolenic acid (P = 0.036), and behenic acid levels (P = 0.032) were associated with longer PFS independent of programmed death ligand 1 (PD-L1) expression. Meanwhile, increased LDL-cholesterol (P < 0.001), HDL-cholesterol (P = 0.009), total cholesterol (P = 0.036), linoleic acid (P = 0.014), and lignoceric acid levels (P = 0.028) were associated with longer OS independent of PD-L1 expression. When multiple lipids were evaluated simultaneously, LDL-cholesterol (P = 0.003), HDL-cholesterol (P = 0.036), and lauric acid (P = 0.036) were independently predictive of PFS, and LDL-cholesterol (P = 0.008) and HDL-cholesterol (P = 0.031) were predictive of OS. ORR was not associated with any serum lipid. CONCLUSIONS: Based on the association of prolonged survival in patients with increased serum cholesterol and long-chain fatty acid levels, serum lipid levels may be useful for predicting the efficacy of immune checkpoint inhibitor therapy.

Efficacy of immune checkpoint inhibitors in non-small cell lung cancer with uncommon histology: a propensity-score-matched analysis.

BACKGROUND: Clinical efficacy of immune checkpoint inhibitors (ICIs) for non-small cell lung cancer (NSCLC) with uncommon histology (uNSCLC) is unknown. METHODS: Patients with NSCLC treated with ICI monotherapy between January 2014 and December 2018 in 10 Japanese hospitals were retrospectively evaluated. The patients were divided into: (1) NSCLC with common histology (cNSCLC), defined as adenocarcinoma and squamous cell carcinoma; and (2) uNSCLC, defined as incompatibility with morphological and immunohistochemical criteria for adenocarcinoma or squamous cell carcinoma. Propensity score matching was performed to balance the two groups. RESULTS: Among a total of 175 patients included, 44 with uNSCLC (10 pleomorphic carcinomas, 9 large cell neuroendocrine carcinomas, 2 large cell carcinomas, and 23 not otherwise specified) and 44 with matched cNSCLC (32 adenocarcinomas and 12 squamous cell carcinomas) were selected for analyses. Median progression-free survival (PFS) (4.4 months, 95% confidence interval [CI] 1.8-7.7 months) and overall survival (OS) (11.4 months, 95% CI 7.4-27.4 months) in the uNSCLC patients were not significantly different from those in matched cNSCLC patients (5.4 months, 95% CI 3.1-7.6 months, p = 0.761; and 14.1 months, 95% CI 10.6-29.6 months, p = 0.381). In multivariate analysis, Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-1 and programmed death ligand-1 (PD-L1) expression were predictive for PFS and OS in uNSCLC. CONCLUSIONS: ICIs had similar clinical efficacy for treatment of uNSCLC and cNSCLC. Good ECOG-PS and PD-L1 expression were predictive for efficacy of ICIs in uNSCLC.

Argon plasma coagulation with atezolizumab and chemoradiation in lung pleomorphic cancer showed a remarkable response: Case report.

RATIONALE: Lung pleomorphic carcinoma (LPC) is generally resistant to chemotherapy or radiotherapy. However, a combination of immune checkpoint inhibitors and radiotherapy has a remarkable efficacy against LPC. PATIENT CONCERNS AND DIAGNOSES: Here, we report the case of a 50-year old man diagnosed with progressive LPC. The tumor invaded the carina and predominantly obstructed the right main bronchus; therefore, a combination of palliative chemoradiotherapy and atezolizumab was initiated. However the trachea was gradually obstructed. INTERVENTION AND OUTCOME: Argon plasma coagulation (APC) was performed to prevent tumor invasion. After three APC sessions, the tumor showed a necrotic change and was easily excised using biopsy forceps. LESSONS: A combination of chemoradiotherapy, atezolizumab, and APC showed a good efficacy, and the patient had a good response to atezolizumab maintenance therapy. Multidisciplinary treatments, such as a combination of immune checkpoint inhibitors and APC, could have synergistic efficacy in lung cancer.

Programmed cell death-1 blockade in kidney carcinoma may induce eosinophilic granulomatosis with polyangiitis: a case report.

BACKGROUND: Immune checkpoint inhibitors have potential applications in treating various cancers but are associated with immune-related adverse events, such as inflammation, in a wide range of organs; however, allergic inflammation caused by these agents has not been extensively studied. CASE PRESENTATION: A 65-year-old man was diagnosed with a kidney neuroendocrine carcinoma. Three months after kidney resection surgery, the tumor cells had metastasized to his liver and lymph nodes. Subsequently, the patient started chemotherapy; however, regardless of treatment, the tumor grew, and the patient experienced a series of adverse effects, such as taste disorder, anorexia, and general fatigue. Finally, he was administered a programmed cell death (PD)-1 inhibitor, nivolumab (biweekly, toal 200 mg/body), which was effective against kidney carcinoma. However, the patient had a bronchial asthma attack at 22 cycles of nivolumab treatment and chest computed tomography (CT) revealed an abnormal bilateral shadow after 37 cycles of nivolumab treatment. Bronchoscopy findings revealed eosinophil infiltration in the lungs along with severe alveolar hemorrhage. Paranasal sinus CT scanning indicated sinusitis and nerve conduction analysis indicated a decrease in his right ulnar nerve conduction velocity. Based on these findings, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis; he was treated with prednisolone, which alleviated his bronchial asthma. To restart nivolumab treatment, the dose of prednisolone was gradually tapered, and the patient was administered a monthly dose of mepolizumab and biweekly dose of nivolumab. To date, there have been no bronchial attacks or CT scan abnormalities upon follow up. CONCLUSIONS: We present a rare case in which a patient with cancer was diagnosed with eosinophilic granulomatosis with polyangiitis following treatment with a PD-1 inhibitor. Blockade of PD-1 and the programmed cell death ligand (PD-L) 1/PD-1 and PD-L2/PD-1 signaling cascade may cause allergic inflammation. Further studies are needed to identify the specific mechanisms underlying allergic inflammation after PD-1 blockade.

Efficient production of γ-aminobutyric acid by glutamate decarboxylase immobilized on an amphiphilic organic-inorganic hybrid porous material.

A novel organic-inorganic hybrid porous material (KCS-2), containing both lipophilic and hydrophilic nanospaces to mimic a lipid bilayer, was utilized as an immobilization support and reaction accelerator for glutamate decarboxylase (GADß). Upon evaluation of the adsorption of GADß on KCS-2, the amount of immobilization was found to be approximately four times higher than that on non-porous silica, and a comparable adsorbability to mesoporous silica was observed. Following γ-aminobutyric acid (GABA) production by the decarboxylation of l-glutamic acid using these immobilized enzymes, the enzymatic activity of the GADß-KCS-2 composite was found to be significantly higher than that of the free enzyme. In contrast, the activity of the more common GADß-mesoporous silica composite decreased. Furthermore, the enzymatic activity of the GADß-KCS-2 composite was superior to those of the un-immobilized free enzyme and the amorphous material itself over a wide temperature range. Thereby, these findings suggest that the amphiphilic nanospace of KCS-2 is suitable as a stable enzyme immobilization field and reaction acceleration field under such conditions. In addition, the durability of the immobilized enzyme was examined in terms of GABA production, with approximately 20% activity retention being observed after 10 cycles using KCS-2. Such durability was not observed for the non-porous silica material due to enzyme desorption.

Erlotinib and bevacizumab in elderly patients ≥75 years old with non-small cell lung cancer harboring epidermal growth factor receptor mutations.

The efficacy and safety of combination therapy with erlotinib and bevacizumab in elderly patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) gene mutations are unknown. Elderly patients aged ≥75 years old with advanced or recurrent NSCLC and EGFR mutations (exon 19 deletion or L858R mutation in exon 21) received erlotinib (150 mg, daily) and bevacizumab (15 mg/kg on day 1 of a 21-day cycle) until disease progression or the occurrence of unacceptable toxicities. The primary endpoint was progression-free survival from enrollment. Twenty-five patients were enrolled in this study, and the median age was 80 years. Fifteen (60.0%) and 10 patients (40.0%) had exon 21 L858R mutations and exon 19 deletions, respectively. The median progression-free survival from enrollment was 12.6 months [95% confidence interval (CI): 8.0-33.7 months]. The objective response rate was 88.0% [95% CI: 74.0%-99.0%], and the disease control rate was 100% [95% CI: 88.7%-100%]. Grade 3 or higher adverse events occurred in 12 patients (48.0%), and rash and nausea were the most common. Grade 3 or higher bevacizumab-related toxicities occurred in 4 (16.0%) patients, including proteinuria (n = 2), gastrointestinal perforation (n = 1) and pneumothorax (n = 1). A dose reduction of erlotinib and cessation of bevacizumab was required in 16 (64.0%) and 18 patients (72.0%), respectively. Erlotinib and bevacizumab combination therapy showed a minimal survival benefit with frequent dose reductions and/or treatment discontinuations in elderly patients with EGFR-positive NSCLC.

Difference in Local Lung Movement During Tidal Breathing Between COPD Patients and Asthma Patients Assessed by Four-dimensional Dynamic-ventilation CT Scan.

Background: The validity of four-dimensional dynamic-ventilation CT scan for distinguishing COPD from asthma has not been established. Purpose: To assess whether four-dimensional dynamic-ventilation CT scan can aid in the diagnosis of COPD by comparing local lung movement during tidal breathing between COPD and asthma. Patients and Methods: Thirty-three COPD patients (30 males and three females; median age 74; range 44-89 years) and 11 asthma patients (five males and six females; median age 55; range: 32-75 years) underwent whole-lung dynamic-ventilation CT scan. CT data were reconstructed, one respiratory cycle to 10 phases, and in addtion we reconstructed threefold new phase data sets. We then analyzed local lung movement during tidal breathing using unpaired t-tests and chi-squared tests. Results: The local lung movement in COPD patients was significantly smaller than in asthma patients, especially in the ventral part of the lung. This was so even in patients who had mild emphysema (Goddard score <8). Conclusion: Quantitative evaluation using four-dimensional dynamic-ventilation CT scan demonstrated that local lung movement during tidal breathing, particularly in the ventral lung, was smaller in COPD than in asthma patients, which may help distinguish COPD from asthma.