Management of gingival hyperplasia associated with sore mucositis in an acute leukemia patient

Gingival enlargement is a prominent symptom in patients with myelomonocytic leukemia (AML-M4) and acute monocytic leukemia (AML-M5). Poor oral hygiene may aggravate the condition. However, patients are apt to avoid oral care out of fear of the pain and hemorrhage associated with the myelopoietic disorder. Here we report a case of a patient with AML-M4 in whom oral care intervention from an early stage improved the quality of life by relieving the pain associated with mucositis and gingival overgrowth aggravated by preceding periodontal lesions

Successful outcome of second allogeneic bone marrow transplantation for blastic plasmacytoid dendritic cell neoplasm with MYC locus rearrangement

A 62-year-old male was diagnosed with blastic plasmacytoid dendritic cell neoplasm (BPDCN) with a MYC rearrangement. Four months after the first unrelated bone marrow transplantation (BMT), he developed the relapsed BPDCN. After the achievement of partial remission following re-induction therapy, he underwent a second BMT from another unrelated donor, and experienced complete remission with grade II acute graft-versus-host disease and moderate chronic graft-versus-host disease. He remains alive in complete remission more than 71 months after the second BMT. These results suggested that donor change at the second transplantation may represent a considerable therapeutic option for patients with relapsed BPDCN

Molecular analysis of the BCR-ABL1 kinase domain in chronic-phase chronic myelogenous leukemia treated with tyrosine kinase inhibitors in practice: Study by the Nagasaki CML Study Group

An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment

Automated recognition of glomerular lesions in the kidneys of mice by using deep learning

Background: In recent years, digital pathology has been rapidly developing and applied throughout the world. Especially in clinical settings, it has been utilized in a variety of situations, including automated cancer diagnosis. Conversely, in non-clinical research, it has not yet been utilized as much as in clinical settings. We have been performing automated recognition of various pathological animal tissues and quantitative analysis of pathological findings, including liver and lung. In this study, we attempted to construct an artificial intelligence (AI)-based trained model that can automatedly recognize glomerular lesions in mouse kidneys that are characterized by complex structures. Materials and methods: By using hematoxylin and eosin (HE)-stained whole slide images (WSI) from Col4a3 KO mice as variation data, normal glomeruli and glomerular lesions were annotated, and deep learning (DL) was performed with the use of the neural network classifier DenseNet system in HALO AI. The trained model was refined by correcting the annotation of misrecognized tissue area and reperforming DL. The accuracy of the trained model was confirmed by comparing the AI-obtained results with the pathological grades evaluated by pathologists. The generality of the trained model was also confirmed by analyzing the WSI of adriamycin (ADR)-induced nephropathy mice, which is a different disease model. Results: Glomerular lesions (including mesangial proliferation, crescent formation, and sclerosis) observed in Col4a3 KO mice and ADR mice were detected by our trained model. The number of glomerular lesions detected by our trained model were also highly correlated with that of counted by pathologists. Conclusion: In this study, we constructed a trained model allowing us to automatedly recognize glomerular lesions in the mouse kidney with the use of the HALO AI system. The findings and insights of this study will facilitate the development of digital pathology in non-clinical research and improve the probability of success in drug discovery research

Management of gingival hyperplasia associated with sore mucositis in an acute leukemia patient

Gingival enlargement is a prominent symptom in patients with myelomonocytic leukemia (AML-M4) and acute monocytic leukemia (AML-M5). Poor oral hygiene may aggravate the condition. However, patients are apt to avoid oral care out of fear of the pain and hemorrhage associated with the myelopoietic disorder. Here we report a case of a patient with AML-M4 in whom oral care intervention from an early stage improved the quality of life by relieving the pain associated with mucositis and gingival overgrowth aggravated by preceding periodontal lesions

Clinical features of non-infectious pulmonary complications after donor lymphocyte infusion in post-transplant patients: The Nagasaki Transplant Group Experience

Donor lymphocyte infusion (DLI) is a therapeutic modality for relapsed hematological malignancies after allogeneic hematopoietic stem cell transplantation. We retrospectively analyzed non-infectious pulmonary complications (non-IPCs) following DLI therapy in 41 post-transplant patients with hematological malignancies, and found that 7 developed post-DLI non-IPCs. The 6-year cumulative incidence of non-IPCs was 18.0%. In these patients, non-IPCs were classified into three subtypes: acute respiratory distress syndrome (ARDS), nonspecific interstitial pneumonia (NSIP), and bronchiolitis obliterans syndrome (BOS). The median intervals from the last date of DLI to the development of ARDS and BOS were 12 days (range, 12–14) and 9.4 months (range, 2.6–61.8), respectively; the intervals between DLI and the development of NSIP were 3.5 and 24.7 in 2 patients. Regarding the status of GVHD before the diagnosis with ARDS, 2 out of 3 patients showed the progression of acute GVHD following DLI therapy. One out of 2 patients with NSIP and all 3 patients with BO had chronic GVHD symptoms prior to the development of non-IPCs. In our cohort, 1 patient died of the progression of NSIP. In conclusion, the present study showed the clinical features of non-IPCs following DLI, suggesting the importance of careful followups for non-IPCs in post-DLI patients

Beneficial effects of canagliflozin in combination with pioglitazone on insulin sensitivity in rodent models of obese type 2 diabetes.

BACKGROUND:Despite its insulin sensitizing effects, pioglitazone may induce weight gain leading to an increased risk of development of insulin resistance. A novel sodium glucose co-transporter 2 (SGLT2) inhibitor, canagliflozin, provides not only glycemic control but also body weight reduction through an insulin-independent mechanism. The aim of this study was to investigate the combined effects of these agents on body weight control and insulin sensitivity. METHODS:Effects of combination therapy with canagliflozin and pioglitazone were evaluated in established diabetic KK-Ay mice and prediabetic Zucker diabetic fatty (ZDF) rats. RESULTS:In the KK-Ay mice, the combination therapy further improved glycemic control compared with canagliflozin or pioglitazone monotherapy. Furthermore, the combination significantly attenuated body weight and fat gain induced by pioglitazone and improved hyperinsulinemia. In the ZDF rats, early intervention with pioglitazone monotherapy almost completely prevented the progressive development of hyperglycemia, and no further improvement was observed by add-on treatment with canagliflozin. However, the combination significantly reduced pioglitazone-induced weight gain and adiposity and improved the Matsuda index, suggesting improved whole-body insulin sensitivity. CONCLUSIONS:Our study indicates that combination therapy with canagliflozin and pioglitazone improves insulin sensitivity partly by preventing glucotoxicity and, at least partly, by attenuating pioglitazone-induced body weight gain in two different obese diabetic animal models. This combination therapy may prove to be a valuable option for the treatment and prevention of obese type 2 diabetes