RESUMO
An elderly patient with upper back pain and hypertension was diagnosed as having spontaneous spinal epidural hematoma (SSEH) after excluding artery dissection. The initial symptoms of SSEH mimic those of artery dissection, and the symptoms of spinal damage frequently appear later. Physicians should, therefore, be mindful of SSEH.
RESUMO
Immune checkpoint inhibitors (ICIs) are widely used in cancer treatment; however, they can lead to immune-related adverse events, including immune checkpoint inhibitor-induced type 1 diabetes mellitus (ICI-T1DM). While fulminant T1DM is common in East Asia, ICI-T1DM has predominantly been reported in Western countries. In this report, we present the case of a 66-year-old Japanese man with type 2 diabetes mellitus undergoing dialysis for diabetic nephropathy. The patient was diagnosed with left upper lobe lung cancer, and treatment with nivolumab and ipilimumab was initiated. After 48 days, the patient experienced impaired consciousness and difficulty moving. His blood glucose levels were 815 mg/dL, and metabolic acidosis was detected, leading to a diagnosis of diabetic ketoacidosis. The patient was subsequently treated with continuous intravenous insulin. However, his C-peptide levels rapidly depleted, and new-onset ICI-T1DM was diagnosed. Although most Japanese patients with ICI-T1DM test negative for glutamic acid decarboxylase (GAD) antibodies, this case exhibited a strong positivity. Thus, we reviewed the literature on 15 similar Japanese cases, revealing a mean HbA1c level at onset of 8.7% and a mean time from ICI administration to onset of 9.7 weeks, which was shorter than that in GAD-negative cases. Moreover, human leukocyte antigen typing revealed five cases of DRB1*04:05-DQB1*04:01, including the present case, and one case of DRB1*09:01-DQB1*03:03, both of which were susceptible to T1DM haplotypes. These findings suggest that GAD antibody positivity may be associated with acute onset and disease progression in some cases of Japanese patients with ICI-T1DM. Given that the prediction of new-onset ICI-T1DM is challenging, monitoring GAD antibody levels might be useful. However, further studies with large sample sizes and validation across different racial and ethnic populations are warranted.
Assuntos
Diabetes Mellitus Tipo 1 , Glutamato Descarboxilase , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Inibidores de Checkpoint Imunológico , Humanos , Masculino , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/induzido quimicamente , Idoso , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Cadeias HLA-DRB1/genética , Glutamato Descarboxilase/imunologia , Cadeias beta de HLA-DQ/genética , Autoanticorpos/sangue , Autoanticorpos/imunologia , Haplótipos , Japão , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , População do Leste AsiáticoRESUMO
Lung alveolar structure and function are maintained by subsets of alveolar type II stem cells (AT2s), but there is a need for characterization of these subsets and their associated niches. Here, we report a CD44high subpopulation of AT2s characterized by increased expression of genes that regulate immune signaling even during steady-state homeostasis. Disruption of one of these immune regulatory transcription factor STAT1 impaired the stem cell function of AT2s. CD44high cells were preferentially located near macro- blood vessels and a supportive niche constituted by LYVE1+ endothelial cells, adventitial fibroblasts, and accumulated hyaluronan. In this microenvironment, CD44high AT2 cells were more responsive to transformation by KRAS than general AT2 cells. Moreover, after bacterial lung injury, there was a significant increase of CD44high AT2s and niche components distributed throughout the lung parenchyma. Taken together, CD44high AT2 cells and their perivascular niche regulate tissue homeostasis and tumor formation.
Assuntos
Células Epiteliais Alveolares , Homeostase , Receptores de Hialuronatos , Nicho de Células-Tronco , Animais , Receptores de Hialuronatos/metabolismo , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/citologia , Camundongos , Pulmão/metabolismo , Células-Tronco/metabolismo , Células-Tronco/citologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Fator de Transcrição STAT1/metabolismo , Células Endoteliais/metabolismoRESUMO
AIMS/INTRODUCTION: The time course of chronic kidney disease in young-onset type 2 diabetes mellitus remains unclear. We compared the trajectories of proteinuria and estimated glomerular filtration rate (eGFR) decline between young-onset (aged ≤40 years) and late-onset (aged >40 years) type 2 diabetes mellitus in a Japanese multicenter cohort. MATERIALS AND METHODS: Participants without diabetic kidney disease were divided into two groups according to age at diagnosis: young- and late-onset. The primary endpoint was eGFR <60 mL/min/1.73 m2, proteinuria or both. Multivariable Cox proportional hazards were calculated to estimate incidence. RESULTS: Among 626 participants with type 2 diabetes mellitus, 78 (12.4%) had young-onset and 548 (87.6%) had late-onset diabetes. The incidence of eGFR <60 mL/min/1.73 m2 was lower (16.7% vs 33.5%, P = 0.003), but that of proteinuria was higher (46.2% vs 28.9%, P = 0.002) in the young-onset type 2 diabetes mellitus group. The Kaplan-Meyer curve showed that young-onset type 2 diabetes mellitus was associated with a decreased hazard ratio (HR) for eGFR <60 mL/min/1.73 m2 and an increased HR for proteinuria compared with late-onset type 2 diabetes mellitus. In the multivariate Cox analysis, young-onset type 2 diabetes mellitus increased the HR (95% confidence interval) of proteinuria (1.53, 95% confidence interval 1.03-2.26), but did not change the eGFR <60 mL/min/1.73 m2 HR. CONCLUSIONS: Young-onset type 2 diabetes mellitus has a lower HR of eGFR <60 mL/min/1.73 m2 and an increased HR of proteinuria compared with late-onset type 2 diabetes mellitus, indicating that young-onset type 2 diabetes mellitus has a different time course for the development of proteinuria and subsequent eGFR decline.