Protective effect of cryotherapy against oral mucositis among allogeneic hematopoietic stem cell transplant recipients using melphalan-based conditioning.

PURPOSE: Oral cryotherapy is an effective method to prevent oral mucositis (OM) induced by chemotherapeutic agents, such as melphalan (Mel). However, there is limited data about cryotherapy in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients; thus, the current study aimed to examine the efficacy of cryotherapy among allo-HSCT recipients treated with Mel-containing regimens. METHODS: Medical records of 78 consecutive allo-HSCT recipients were retrospectively analyzed. Baseline characteristics and clinical courses between the patients who received cryotherapy (cryotherapy group, n = 42) and those who did not (control group, n = 36) were compared, especially focusing on methotrexate (MTX) use as a part of graft-versus-host disease (GVHD) prophylaxis. RESULTS: Binary logistic regression analysis revealed that a higher dose of Mel (OR, 3.82; 95%CI, 1.085-13.46; P = 0.037) or MTX use (OR, 7.61; 95% CI, 2.41-23.97; P < 0.001) was associated with the incidence of OM. MTX use was also significantly associated with the duration of OM (ß = 0.515; 95% CI, 9.712-21.636; P < 0.001). Among 31 patients without MTX use, cryotherapy was associated with a significant reduction of OM development (0% in the cryotherapy group vs 35% in the control group, P = 0.021). We did not find such an association in 47 patients with MTX use. CONCLUSION: Cryotherapy was useful to prevent the incidence of OM in allo-HSCT recipients in the cases without MTX for GVHD prophylaxis.

Disrupted tongue microbiota and detection of nonindigenous bacteria on the day of allogeneic hematopoietic stem cell transplantation.

Disruption of the intestinal microbiota caused by intensive chemotherapy, irradiation and antibiotics can result in development of severe gut graft-versus-host disease and infectious complications, leading to poorer outcomes among allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Although the oral cavity is also densely colonized by indigenous microorganisms, the bacterial composition in allo-HSCT recipients remains unclear. We determined the tongue microbiota composition of 45 patients with hematological disorders on the day of transplantation and compared them to 164 community-dwelling adults. The V1-V2 regions of the 16S rRNA gene sequences demonstrated that the allo-HSCT recipients had less diverse and distinct microbiota from that of community-dwelling adults. The full-length 16S rRNA gene sequences identified 146 bacterial taxa in the microbiota of allo-HSCT recipients, of which 34 bacterial taxa did not correspond to bacteria primarily inhabiting the oral cavity deposited in the expanded Human Oral Microbiome Database. Notably, the detection of Staphylococcus haemolyticus and/or Ralstonia pickettii was significantly associated with a higher risk of mortality during the follow-up period. These results demonstrate that the oral cavity of allo-HSCT recipients is colonized by a disrupted microbiota on the day of transplantation and suggest that detection of specific nonindigenous taxa could be a predictor of transplant outcome.

A Cross-Sectional Study of Age-Related Changes in Oral Function in Healthy Japanese Individuals.

BACKGROUND: Oral function deterioration is related to a variety of factors, including aging, decline in activities of daily living, malnutrition, and cognitive decline. This cross-sectional study examined the effects of aging on oral function in healthy individuals. METHODS: A retrospective study was conducted on 175 healthy, independent patients aged 40-89 years, without dementia and with ≥20 teeth, who visited a local dental clinic in Japan. Patients were compared with 92 university students aged 20-29 years. The seven criteria proposed by the Japanese Society of Gerodontology to diagnose "oral hypofunction" were observed and statistically analyzed. RESULTS: Compared with those in the control group, the degree of tongue coating was increased in the group aged over 80 years, occlusal force was decreased in the group aged 70-79 years, tongue motor function was decreased in the groups aged 60-69 years and older, and tongue pressure was decreased in the groups aged 70-79 years and older. CONCLUSIONS: Healthy, independent individuals maintained several oral function criteria across aging, including oral mucosal wetness, occlusal force, lip motor function, masticatory function, and swallowing function. Tongue motor function and tongue pressure decreased with aging, indicating that these may be rehabilitation targets.

Tooth extraction in patients taking nonvitamin K antagonist oral anticoagulants.

BACKGROUND/PURPOSE: The nonvitamin K antagonist oral anticoagulants direct-thrombin inhibitor dabigatran and the Xa inhibitors rivaroxaban and apixaban are now being used clinically. The course of the patients on these anticoagulants who underwent tooth extraction was assessed. MATERIALS AND METHODS: The medical charts of these patients were investigated. Tooth extraction was performed while maintaining conventional anticoagulant therapy. RESULTS: Twenty-three teeth were extracted in 19 patients, including two surgical extractions. Among the 19 patients, nine patients ingested rivaroxaban, six apixaban, and four dabigatran. One patient on rivaroxaban showed persistent postoperative bleeding following two surgical extractions. Mild oozing was observed in five patients (two on rivaroxaban and three on apixaban). There was no bleeding episode in the patients on dabigatran. CONCLUSION: The patients on rivaroxaban with a prolonged prothrombin time value have a higher risk of bleeding, especially undergoing surgical extraction. Apixaban correlates to neither activated partial thromboplastin time nor prothrombin time values and the countermeasures should be employed based on the clinical findings.

Dual signaling pathways of arterial constriction by extracellular uridine 5'-triphosphate in the rat.

We investigated actions of uridine 5'-triphosphate (UTP) in rat aorta, cerebral and mesenteric arteries, and their single myocytes. UTP (≥10 µM) elicited an inward-rectifying current strongly reminiscent of activation of P2X(1) receptor, and a similar current was also induced by α,ß-methylene adenosine 5'-triphosphate (ATP) (≥100 nM). UTP desensitized α,ß-methylene ATP-evoked current, and vice versa. The UTP-activated current was insensitive to G-protein modulators, TRPC3 inhibitors, or TRPC3 antibody, but was sensitive to P2-receptor inhibitors or P2X(1)-receptor antibody. Both UTP (1 mM) and α,ß-methylene ATP (10 µM) elicited similar conductance single channel activities. UTP (≥10 µM) provoked a dose-dependent contraction of de-endothelialized aortic ring preparation consisting of phasic and tonic components. Removal of extracellular Ca(2+) or bath-applied 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP) (30 µM) or nifedipine (10 µM) completely inhibited the phasic contraction while only partially reducing the tonic one. The tonic contraction was almost completely abolished by additional application of thapsigargin (2 µM). Similar biphasic rises in [Ca(2+)](i) were also evoked by UTP in rat aortic myocytes. In contrast to the low expression of TRPC3, significant expression of P2X(1) receptor was detected in all arteries by RT-PCR and immunoblotting, and its localization was limited to plasma membrane of myocytes as indicated by immunohistochemistry. These results suggest that UTP dually activates P2X(1)-like and P2Y receptors, but not TRPC3.

[Postoperative bleeding after tooth extractions in patients controlled with warfarin--a clinico-statistical study on the factors influencing postoperative bleeding].

There are many reports about tooth extractions of patients taking warfarin, however PT-INR level is used to examine the postoperative bleeding in patients. To investigate other factors, postoperative bleeding, age, gender, PT-INR level, combined use of anti-platelet drugs, conditions of extracted tooth, a number of tooth extractions at a treatment, methods of management for warfarin therapy, degree of the alveolar bone loss and size of radiolucency of apical region were examined in this study. To apply Mann-Whitney U-test and chi2-test, ninety-three patients (38 male and 55 female) who took warfarin and visited our clinic for tooth extractions from April 1994 to November 2002 were classified into 2 groups: One group showed hemostasis by the next day (77 patients), the other showed the continuous bleeding after the next day (16 patients). These analyses indicated that PT-INR level, a number of tooth extractions at a treatment, methods of management for warfarin therapy, and size of radiolucency of apical region influenced postoperative bleeding. In addition, stepwise logistic regression analysis was applied to all of the factors, obtained from 77 patients out of 93 patients. This data showed that PT-INR level, a number of tooth extractions at a treatment and methods of management for warfarin therapy influenced postoperative bleeding. These results suggest that before the tooth extractions not only PT-INR level but methods of management for warfarin therapy and size of wound could be important to control the postoperative bleeding in warfarin taking patients.