Successful continuous nivolumab therapy for metastatic non-small cell lung cancer after local treatment of oligometastatic lesions.

The patient in this report was a 57-year-old man with metastatic non-small cell lung cancer (NSCLC). After no response to two lines of systemic chemotherapy, he was treated with nivolumab as third-line therapy, which resulted in a partial response. After 17 months of nivolumab treatment, he developed bone metastasis in his left femur which was treated with radiation therapy. Nivolumab was restarted after radiation therapy. Four months after radiation therapy, he developed another metastatic lesion in the small intestine which was surgically resected. Because there were no recurrent NSCLC lesions after surgical resection, nivolumab was restarted again. At 18 months after surgery, there were no recurrent NSCLC lesions. Immunohistochemical analysis of peritumoral T lymphocytes showed higher expression of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) and lymphocyte activation gene 3 (LAG-3) in recurrent lesions of bone and small intestine than in primary lesions. Upregulation of TIM-3 and LAG-3 could be associated with mechanisms of adaptive resistance to nivolumab in this case. Here, we report a successful case of continued nivolumab therapy with remission after local treatments consisting of radiation therapy and surgical resection for oligometastases. Continuation of immune checkpoint inhibitor (ICI) treatment may be worth considering if oligometastases can be controlled. KEY POINTS: Significant findings of the study We report a successful case of continued nivolumab treatment with remission after local treatment (radiation therapy and surgical resection) for oligometastases. What this study adds Upregulation of T cell immunoglobulin and mucin domain-containing protein 3 and lymphocyte-activation gene 3 could be associated with mechanisms of adaptive resistance to nivolumab.

Neuropsychiatric Immune-related Adverse Events Induced by Pembrolizumab in a Patient with Lung Adenocarcinoma and Systemic Lupus Erythematosus.

The patient was a 73-year-old woman with lung adenocarcinoma and systemic lupus erythematosus (SLE) who was treated with pembrolizumab. After six cycles of pembrolizumab, she developed symptoms suggestive of neuropsychiatric SLE, such as resting tremor, confusional state, depression, mood disorder, and anxiety disorder. In addition, her cerebrospinal fluid level of interleukin-6 was elevated. Her symptoms resolved one month after the discontinuation of pembrolizumab. This is the first report of neuropsychiatric symptoms in a patient with lung cancer and SLE on immune checkpoint blockade therapy.

Metformin decreases glycated albumin to glycated haemoglobin ratio in patients with newly diagnosed type 2 diabetes.

BACKGROUND: To know whether metformin improves postprandial hyperglycaemia, we examined the effect of metformin on the glycated albumin (GA) to glycated haemoglobin (HbA1c) ratio (GA/HbA1c ratio) in patients with newly diagnosed type 2 diabetes. METHODS: Metformin and lifestyle interventions were initiated in 18 patients with newly diagnosed type 2 diabetes. Metformin was titrated to 1500 mg/day or maximum-tolerated dose. HbA1c and GA were measured every four weeks up to 24 weeks. RESULTS: HbA1c decreased significantly from 9.0 ± 2.1% at baseline to 6.5 ± 0.9% at week 24, and GA decreased significantly from 24.3 ± 8.2% to 16.2 ± 3.1%. The GA/HbA1c ratio decreased significantly from 2.66 ± 0.37 at baseline to 2.47 ± 0.29 at week 24 (P<0.01), despite that the GA/HbA1c ratio reached a plateau value at week 16. The change in the GA/HbA1c ratio during 24 weeks (ΔGA/HbA1c ratio) was significantly correlated with both baseline HbA1c and GA. Moreover, the ΔGA/HbA1c ratio was significantly correlated with the change in GA during 24 weeks but not with the change in HbA1c. CONCLUSIONS: Metformin decreased the GA/HbA1c ratio in patients with newly diagnosed type 2 diabetes. This suggests that metformin improves postprandial hyperglycaemia in patients with newly diagnosed type 2 diabetes.

Low serum level of high-sensitivity C-reactive protein in a Japanese patient with maturity-onset diabetes of the young type 3 (MODY3).

High-sensitivity C-reactive protein (hs-CRP) levels in European populations are lower in patients with maturity-onset diabetes of the young type 3 (MODY3) than in those with type 2 diabetes. hs-CRP levels have been suggested to be useful for discriminating MODY3 from type 2 diabetes. As hs-CRP levels are influenced by various factors including race and body mass index, it is worthwhile to examine whether hs-CRP can serve as a biomarker for MODY3 in Japanese. Here we describe the case of a Japanese MODY3 patient with a nonsense mutation in the HNF1A gene. Two measurements showed consistently lower hs-CRP levels (<0.05 and 0.09 mg/L) than in Japanese patients with type 1 and type 2 diabetes. Hepatic expression of Crp messenger ribonucleic acid was significantly decreased in Hnf1a knockout mice. The hs-CRP level might be a useful biomarker for MODY3 in both Japanese and European populations.

Effectiveness of metformin and lifestyle interventions as an initial treatment in Japanese patients with newly diagnosed type 2 diabetes: a prospective observational study.

Although global guidelines recommend metformin and lifestyle interventions as an initial treatment in patients with newly diagnosed type 2 diabetes (T2DM), few reports exist about its effectiveness in Japanese patients. To examine its effectiveness, we performed a prospective observational study within a routine clinical setting. We provided metformin (≥1,500 mg/day) and lifestyle interventions to 23 patients with newly diagnosed T2DM (20 men and 3 women, mean age 53 years, mean body mass index [BMI] 25.7 kg/m(2)). After 16 weeks, HbA1c levels significantly decreased from 9.1±2.1% (mean±SD) to 6.6±0.8% (p<0.001). Thirteen patients (56.5%) achieved a target HbA1c<6.5%. We did not find a significant correlation between baseline BMI and the changes in HbA1c (ΔHbA1c) (r=-0.165, p=0.451). In contrast, we found a significant correlation between baseline fasting plasma glucose and ΔHbA1c (r=-0.755, p<0.001). Body weight decreased from 73.3±13.3 kg to 69.8±11.6 kg (p<0.001). Total cholesterol, low density lipoprotein - cholesterol, non-high density lipoprotein-cholesterol, and serum vitamin B-12 concentrations also significantly decreased. Adverse events included diarrhea (26.1%) and mild elevation of liver enzymes (8.7%). These results suggest that metformin and lifestyle interventions is effective and safe as an initial treatment in Japanese patients with newly diagnosed T2DM.