Real-world treatment patterns and clinical outcomes in patients with AML in Japan who were ineligible for first-line intensive chemotherapy.

Acute myeloid leukemia (AML) predominantly affects elderly adults, and its prognosis worsens with age. Treatment options for patients in Japan ineligible for intensive chemotherapy include cytarabine/aclarubicin ± granulocyte colony-stimulating factor (CA ± G), azacitidine (AZA), low-dose cytarabine (LDAC), targeted therapy, and best supportive care (BSC). The country's aging population and the evolving treatment landscape are contributing to a need to understand treatment pathways and associated outcomes. This retrospective chart review evaluated outcomes in patients across Japan with primary/secondary AML who were ineligible for intensive chemotherapy and began first-line treatment or BSC between 01/01/2015 and 12/31/2018. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS) and healthcare resource utilization (HRU). Of 199 patients (58% > 75 years), 121 received systemic therapy (38 CA ± G, 37 AZA, 7 LDAC, 39 other) and 78 received BSC. Median OS was 5.4, 9.2, 2.2, 3.8, and 2.2 months for CA ± G, AZA, LDAC, other systemic therapy, and BSC, respectively; median PFS was 3.4, 7.7, 1.6, 2.3, and 2.1 months, respectively. HRU rates were uniformly high, with > 80% patients hospitalized in each cohort. The poor clinical outcomes and high HRU among Japanese AML patients who are ineligible for intensive chemotherapy highlight an unmet need for novel therapies.

Periodontal wound healing/regeneration of two-wall intrabony defects following reconstructive surgery with cross-linked hyaluronic acid-gel with or without a collagen matrix: a preclinical study in dogs.

OBJECTIVES: In-vitro data have shown that cross-linked hyaluronic acid (HA) enhances the proliferative and migratory properties of cells involved in periodontal wound healing/regeneration, stabilizes the blood clot, reduces the inflammatory response, and facilitates angiogenesis. The aim of this study was to histologically evaluate the effects of cross-linked HA alone or combined with a collagen matrix (CM) on the periodontal wound healing/regeneration in intrabony defects. METHOD AND MATERIALS: Two-wall intrabony defects (5 mm wide, 5 mm deep) were surgically created at the distal and mesial aspects of mandibular premolars in six beagle dogs. The 24 defects were randomly treated as follows: open flap debridement (OFD) + HA, OFD + CM, OFD + HA + CM (HA/CM), and OFD alone (control). At 2 months, the animals were euthanized for histologic evaluation. RESULTS: The HA (2.43 ±â€¯1.25 mm) and HA/CM (2.60 ±â€¯0.99 mm) groups yielded statistically significantly (P < .05) greater formation of new attachment (ie, linear length of new cementum adjacent to newly formed bone, with inserting collagen fibers) compared with the OFD (0.55 ± 0.99 mm) group. Among the four treatment groups, the HA/CM group demonstrated the highest amount of regenerated tissues, although no statistically significant differences in any of the histometric parameters were observed between the HA and HA/CM groups. CONCLUSION: Within their limits, it can be concluded that cross-linked HA alone or combined with CM promotes periodontal wound healing/regeneration in two-wall intrabony defects in dogs.

Healing of buccal gingival recessions following treatment with coronally advanced flap alone or combined with a cross-linked hyaluronic acid gel. An experimental study in dogs.

AIM: To clinically and histologically evaluate in dogs the healing of gingival recessions treated with coronally advanced flap (CAF) with or without cross-linked hyaluronic acid (HA). MATERIALS AND METHODS: Gingival recession defects were surgically created on the vestibular side of both maxillary canines in 8 dogs. After 8 weeks of plaque accumulation, the 16 chronic defects were randomly treated with either CAF alone or CAF and HA-gel (CAF/HA). Clinical and histological outcomes were evaluated at 10 weeks post-surgically. RESULTS: Compared to baseline, the clinical measurements at 10 weeks revealed a statistically significant decrease in gingival recession for both CAF (p < 0.01) and CAF/HA (p < 0.001) groups. Statistically significant differences were found in clinical attachment level (p < 0.05) and width of gingival recession (p < 0.01) favouring the CAF/HA group. Bone formation was statistically significantly greater in the CAF/HA group than in the CAF group (1.84 ± 1.16 mm vs., 0.72 ± 0.62 mm, respectively, p < 0.05). Formation of cementum and connective tissue attachment were statistically significantly higher in the CAF/HA group compared with the CAF group (i.e. 4.31 ± 1.78 mm versus 2.40 ± 1.35 mm and 1.69 ± 0.98 mm versus 0.74 ± 0.68 mm, respectively (p < 0.05)). CONCLUSIONS: The present data have for the first time provided histologic evidence for periodontal regeneration of gingival recession defects following treatment with CAF and HA. CLINICAL RELEVANCE: The use of HA in conjunction with CAF may represent a novel modality for treating gingival recession defects.

A natural therapeutic approach for the treatment of periodontitis by MK615.

Periodontitis is a chronic inflammatory disease that affects the tooth-supporting tissues. Gingival fibroblasts are the most abundant cells in periodontal tissues and they participate actively in the host inflammatory response to periodontal pathogens that is known to mediate local tissue destruction in periodontitis. The Japanese apricot, known as Ume in Japanese, has been a traditional Japanese medicine for centuries and is a familiar and commonly consumed food. The health benefits of Ume are widely recognized and have been confirmed in recent studies showing that MK615, an extract of compounds from Ume, has strong anticancer and anti-inflammatory effects. However, the potential role of MK615 in oral health is unknown. We hypothesized that the anti-inflammatory activities of MK615 could be exploited to inhibit the effects of lipopolysaccharide (LPS) produced by periodontal bacterial pathogens, such as Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis. Here, we show that LPS-induced interleukin (IL)-6 and IL-8 production by gingival fibroblasts was dose-dependently inhibited by MK615. As a potent inhibitor of the inflammatory responses induced by periodontal pathogens, MK615 merits further testing as a therapeutic agent in inflammatory diseases such as periodontitis.

Dentin and pulp sense cold stimulus.

Dentin hypersensitivity is a common symptom, and recent convergent evidences have reported transient receptor potential (TRP) channels in odontoblasts act as mechanical and thermal molecular sensor, which detect stimulation applied on the exposed dentin surface, to drive multiple odontoblastic cellular functions, such as sensory transduction and/or dentin formation. In the present study, we confirmed expression of TRP melastatin subfamily member-8 (TRPM8) channels in primary cultured cells derived from human dental pulp cells (HPCs) and mouse odontoblast-lineage cells (OLCs) as well as in dentin matrix protein-1 (DMP-1) and dentin sialoprotein (DSP) positive acutely isolated rat odontoblasts from dental pulp tissue slice culture by immunohistochemical analyses. In addition, we detected TRPM8 channel expression on HPCs and OLCs by RT-PCR and Western blotting analyses. These results indicated that both odontoblasts and dental pulp cells express TRPM8 channels in rat, mouse and human, and therefore we hypothesize they may contribute as cold sensor in tooth.

Hypohomocysteinemic effect of cysteine is associated with increased plasma cysteine concentration in rats fed diets low in protein and methionine levels.

Rats were fed diets with and without 0.5% L-cysteine supplement for 14 d or shorter periods to clarify the mechanism by which dietary cysteine elicits its hypohomocysteinemic effect. Cysteine supplementation significantly decreased plasma homocysteine concentration with an increase in plasma cysteine concentration in rats fed 10% casein diet (10C) or 15% soybean protein diet (15S) but not in rats fed 25% casein diet (25C) or 25% soybean protein diet. Cysteine supplementation also significantly suppressed hyperhomocysteinemia induced by choline-deprived 10C with an increase in plasma cysteine concentration but not that induced by 25C+0.65% methionine or 25C+0.4% guanidinoacetic acid. Hepatic S-adenosylmethionine (SAM) and homocysteine concentrations were significantly decreased by cysteine supplementation of 15S. These decreases in plasma homocysteine concentration and hepatic SAM and homocysteine concentrations due to cysteine supplementation disappeared when 15S was fortified with 0.3% methionine. The plasma homocysteine concentration significantly decreased with an increase in plasma cysteine concentration only 1 d after diet change from 15S to cysteine-supplemented 15S, while hepatic cystathionine beta-synthase and betaine-homocysteine S-methyltransferase activities were not altered. Unlike cysteine, cysteic acid and 2-mercaptoethylamine did not decrease plasma homocysteine concentration. These results indicate that cysteine markedly decreases plasma homocysteine concentration only when added to diets low in both protein and methionine levels and suggest that increased plasma cysteine concentration and decreased flow of methionine toward homocysteine formation, but not alteration of homocysteine-metabolizing enzyme activities, are associated with the hypohomocysteinemic effect of cysteine.

Fatigue of tooth-colored restoratives in aqueous environment.

The purpose of this study was to investigate the interaction between mechanical and chemical fatigue in resin composites and dental ceramics, and the effects thereof on fatigue resistance of tooth-colored restoratives. To this end, the fatigue fracture resistance of restoratives under dry and aqueous conditions were analyzed by a dynamic fatigue crack propagation test using beam-shaped specimens with a precrack. Fatigue crack propagation characteristics were expressed by the correlation between fatigue crack growth rate (da/dN) and stress intensity factor range (deltaK). In addition, fatigue crack growth threshold (deltaKth) was calculated. Following the fatigue test, a fractographic examination was performed using scanning electron microscopy. Fatigue crack initiation was retarded in resin composites under aqueous condition, but dental ceramics were susceptible to slow crack growth after crack initiation. SEM images of the fatigue facture surfaces reflected inorganic and organic filler particles of different sizes in composites and the bonding at crystal-glass interface in ceramics. It was concluded that water exerted different effects on the fatigue resistance of composites and ceramics.