Late-onset acute type 1 diabetes mellitus 7 months after discontinuation of pembrolizumab against lung cancer

Immune-related adverse events (irAEs) occur in rare cases, even after the completion of immune checkpoint inhibitor (ICI) therapy. We encountered a lung cancer patient diagnosed with acute-onset type 1 diabetes mellitus (DM) 7 months after the cessation of ICI. A 68-year old woman was referred to our hospital for chest abnormalities. She was diagnosed with lung adenocarcinoma cT4N2M1c, stage IVB. Immunostaining showed that the expression of programmed death ligand 1 in tumor cells was negative. A genetic analysis using the Oncomine Dx Target Test Multi-CDx System revealed that the primary tumor was positive for ERBB2. Combined immunotherapy with carboplatin, pemetrexed, and pembrolizumab was performed as first-line therapy, followed by maintenance therapy with pemetrexed plus pembrolizumab, which was successful. After the seventh course, maintenance therapy was stopped because only the primary tumor showed local enlargement. Local chest radiotherapy (66 Gy/33 Fr) was performed, and the patient was followed up. HbA1c was 4.9% 3 months after the completion of pembrolizumab, and dry mouth and polyuria occurred after 5 months. Seven months later, the patient developed diabetic ketoacidosis with a blood glucose of 348 mg/dL and an HbA1c of 11.3%. Antiglutamic acid decarboxylase antibodies were negative and urinary C-peptide was 9.3 μg/day. The patient was diagnosed with acute-onset type 1 diabetes and received insulin therapy. There has been no case report of type 1 diabetes diagnosed 7 months after the last administration of an ICI. These results indicate that irAE needs to be considered even after the cessation of ICI

Non-small cell lung cancer with EGFR (L858R and E709X) and CNNB1 mutations responded to afatinib

Lung cancer with complex epidermal growth factor receptor (EGFR) and CTNNB1 comutations is rare, and the efficacy of tyrosine kinase inhibitors (TKIs) is generally poor. Here, we encountered a lung cancer patient with complex EGFR (L858R and E709X) and CTNNB1 comutations who successfully responded to afatinib. A 78-year-old woman visited our hospital with a cough and bloody sputum that had worsened over the past year. She had multiple mass shadows in both lungs and nodular shadows in the bronchi. The patient was diagnosed with lung adenocarcinoma cT4N3M1c stage IVB. A genetic analysis of the primary tumor using the Oncomine Dx target test multi-CDx system revealed positivity for EGFR (L858R and E709X) and CTNNB1 mutations. The expression of programmed death ligand 1 (22C3 clones) in tumor cells was negative by immunostaining. The patient was treated with afatinib as first-line therapy and achieved clinical improvement and a partial response and is continuing treatment 1 year later. Case reports of lung cancer patients with EGFR/CTNNB1 comutations are rare, and TKIs are not considered to be effective. We herein present the first case report of lung cancer with the co-occurrence of uncommon and complex EGFR (L858R and E709X) and CTNNB1 mutations that was successfully treated with afatinib

Non-small cell lung cancer with EGFR (L858R and E709X) and CNNB1 mutations responded to afatinib

Lung cancer with complex epidermal growth factor receptor (EGFR) and CTNNB1 comutations is rare, and the efficacy of tyrosine kinase inhibitors (TKIs) is generally poor. Here, we encountered a lung cancer patient with complex EGFR (L858R and E709X) and CTNNB1 comutations who successfully responded to afatinib. A 78-year-old woman visited our hospital with a cough and bloody sputum that had worsened over the past year. She had multiple mass shadows in both lungs and nodular shadows in the bronchi. The patient was diagnosed with lung adenocarcinoma cT4N3M1c stage IVB. A genetic analysis of the primary tumor using the Oncomine Dx target test multi-CDx system revealed positivity for EGFR (L858R and E709X) and CTNNB1 mutations. The expression of programmed death ligand 1 (22C3 clones) in tumor cells was negative by immunostaining. The patient was treated with afatinib as first-line therapy and achieved clinical improvement and a partial response and is continuing treatment 1 year later. Case reports of lung cancer patients with EGFR/CTNNB1 comutations are rare, and TKIs are not considered to be effective. We herein present the first case report of lung cancer with the co-occurrence of uncommon and complex EGFR (L858R and E709X) and CTNNB1 mutations that was successfully treated with afatinib

Late-onset acute type 1 diabetes mellitus 7 months after discontinuation of pembrolizumab against lung cancer

Immune-related adverse events (irAEs) occur in rare cases, even after the completion of immune checkpoint inhibitor (ICI) therapy. We encountered a lung cancer patient diagnosed with acute-onset type 1 diabetes mellitus (DM) 7 months after the cessation of ICI. A 68-year old woman was referred to our hospital for chest abnormalities. She was diagnosed with lung adenocarcinoma cT4N2M1c, stage IVB. Immunostaining showed that the expression of programmed death ligand 1 in tumor cells was negative. A genetic analysis using the Oncomine Dx Target Test Multi-CDx System revealed that the primary tumor was positive for ERBB2. Combined immunotherapy with carboplatin, pemetrexed, and pembrolizumab was performed as first-line therapy, followed by maintenance therapy with pemetrexed plus pembrolizumab, which was successful. After the seventh course, maintenance therapy was stopped because only the primary tumor showed local enlargement. Local chest radiotherapy (66 Gy/33 Fr) was performed, and the patient was followed up. HbA1c was 4.9% 3 months after the completion of pembrolizumab, and dry mouth and polyuria occurred after 5 months. Seven months later, the patient developed diabetic ketoacidosis with a blood glucose of 348 mg/dL and an HbA1c of 11.3%. Antiglutamic acid decarboxylase antibodies were negative and urinary C-peptide was 9.3 μg/day. The patient was diagnosed with acute-onset type 1 diabetes and received insulin therapy. There has been no case report of type 1 diabetes diagnosed 7 months after the last administration of an ICI. These results indicate that irAE needs to be considered even after the cessation of ICI

Serum Concentrations of Antigen-Specific IgG4 in Patients with Japanese Cedar Pollinosis

Purpose: To elucidate the usefulness of Japanese cedar pollen (JCP)-specific antigen-specific immunoglobulin (IgG) 4 as a biomarker for predicting the efficacy of sublingual immunotherapy for cedar pollen-induced allergic rhinitis. Methods: We divided a total of 105 cases with Japanese cedar pollinosis into three groups: “SLIT Successful,” SLIT Unsatisfactory,” and “SCIT” groups. The SLIT group patients were treated with JCP Droplet (Torii Pharmaceutical Co. Ltd., Tokyo, Japan) for one year from 2015 and were divided into two groups, the SLIT Successful group or the SLIT Unsatisfactory group. The SLIT Successful group (n = 16) were subjects treated by SLIT only, who were able to experience control of their naso-ocular symptoms without the need for antiallergic rescue agents during the peak season of atmospheric pollen. The SLIT Unsatisfactory group (n = 76) comprised subjects treated with SLIT only, who did not respond successfully, and were administered with rescue agents to control their naso-ocular symptoms. The SCIT group had been treated with standardized JCP extract (Torii Pharmaceutical Co., Ltd., Tokyo, Japan) for three years from 2012, and were also able to experience control of their symptoms during the peak pollen season without the need for antiallergic rescue agents. We determined the serum level of JCP-specific immunoglobulin E (IgE), IgG, and IgG4 used in the 3gAllergy-specific IgE assay (3gAllergy). The serum levels of periostin and SCCA2 were measured using established ELISA procedures (clones SS18A and SS17B; Shino-Test, Japan) following the manufacturer’s instructions. We then made ROC curves for each group and assessed which index was best able to predict the efficacy of sublingual immunotherapy. Results: Serum JCP-specific IgE was significantly lower in the SCIT group than in the SLIT Successful group and the SLIT Unsatisfactory group (p < 0.05). Serum JCP-specific IgG was significantly higher in the SCIT group and the SLIT Successful group than in the SLIT Unsatisfactory group (p < 0.05). Serum JCP-specific IgG4 was also significantly higher in the SCIT group and the SLIT Successful group than in the SLIT Unsatisfactory group (p < 0.05). There was no significant difference among serum levels of periostin in the SCIT group, the SLIT Successful group, or the SLIT Unsatisfactory group. There was also no significant difference in SCCA2 among the three groups. In terms of ROC curves, a serum JCP-specific IgG4 value greater than 989.5 UA/mL showed the best sensitivity (93.3%) and specificity (94.7%) (p < 0.05) among other parameters. Conclusions: The serum JCP-specific IgG4 level is significantly correlated with the clinical efficacy of SLIT. Serum JCP-specific IgG4 cutoff levels greater than 989.5 UA/mL were correlated with an effective clinical response to SLIT, with a sensitivity of 93.3% and a specificity of 94.7%

Similarity in neuronal firing regimes across mammalian species

The architectonic subdivisions of the brain are believed to be functional modules, each processing parts of global functions. Previously, we showed that neurons in different regions operate in different firing regimes in monkeys. It is possible that firing regimes reflect differences in underlying information processing, and consequently the firing regimes in homologous regions across animal species might be similar. We analyzed neuronal spike trains recorded from behaving mice, rats, cats, and monkeys. The firing regularity differed systematically, with differences across regions in one species being greater than the differences in similar areas across species. Neuronal firing was consistently most regular in motor areas, nearly random in visual and prefrontal/medial prefrontal cortical areas, and bursting in the hippocampus in all animals examined. This suggests that firing regularity (or irregularity) plays a key role in neural computation in each functional subdivision, depending on the types of information being carried. © 2016 the authors9911Nsciescopu

Similarity in Neuronal Firing Regimes across Mammalian Species

The architectonic subdivisions of the brain are believed to be functional modules, each processing parts of global functions. Previously, we showed that neurons in different regions operate in different firing regimes in monkeys. It is possible that firing regimes reflect differences in underlying information processing, and consequently the firing regimes in homologous regions across animal species might be similar. We analyzed neuronal spike trains recorded from behaving mice, rats, cats, and monkeys. The firing regularity differed systematically, with differences across regions in one species being greater than the differences in similar areas across species. Neuronal firing was consistently most regular in motor areas, nearly random in visual and prefrontal/medial prefrontal cortical areas, and bursting in the hippocampus in all animals examined. This suggests that firing regularity (or irregularity) plays a key role in neural computation in each functional subdivision, depending on the types of information being carried