Factors influencing delayed referral of oral cancer patients from family dentists to the core hospital.

Background/purpose: Most oral cancer (OC) cases are identified by family dentists in Japan. However, a significant number of patients with OC in Japan are referred to core hospitals at advanced stages. Therefore, identifying the factors that contribute to delayed referrals from family dentists to core hospitals is crucial for detecting OC in its earlier stages. The aim of this retrospective study was to identify the risk factors for referral delays from family dentists to core hospitals. Materials and methods: The study included 63 patients with OC who were referred by family dentists to the Yamagata University Hospital between 2010 and 2022. The clinical parameters related to referral delays were retrospectively investigated using letters of reference provided by the family dentists and patient charts. Backward multiple regression analysis was performed to identify the relationships between the length of referral delay and potential risk factors. Additionally, backward multivariate logistic regression analysis was performed to examine the independent association between referral delays of >4 weeks and several clinical parameters. Results: Multiple regression analysis revealed that misdiagnosis of malignant lesions by family dentists (P = 0.047) was significantly associated with longer referral delays. Additionally, misdiagnosis of malignant lesions by family dentists was also an independent risk factor for referral delays of >4 weeks (odds ratio, 10.387; P = 0.006). Conclusion: Misdiagnosis of malignant lesions by family dentists was a significant risk factor for referral delays from family dentists to core hospitals. Our results will motivate family dentists to improve their ability to diagnose OC.

Evaluation of radiographic characteristics and surgical removal of 147 mesiodens.

The aim of this study was to evaluate the radiographic characteristics and surgical removal of mesiodens among patients who had attended the Department of Dentistry, Oral and Maxillofacial-Plastic and Reconstructive Surgery of the Faculty of Medicine, Yamagata University. This study included 121 patients in the final analysis. We retrospectively reviewed medical records including patient age, sex, mesiodens number, direction, position, opportunity for detection, surgical approach and operating time. The 121 patients comprised 82 males and 39 females. Mean age was 7.6 ± 3.1 years (range, 4-35 years). The total number of mesiodens among these 121 patients was 147. Ninety-six patients had one mesiodens, 24 patients had two mesiodens and 1 patient had 3 mesiodens. Seventy-nine mesiodens were detected while taking X-rays for routine dental examination and/or orthodontic treatment at their family dental/orthodontic clinic. Mean operating time for removal of the 147 mesiodens was 32.2 ± 18.1 min. Among the 96 patients with one mesiodens, mean operating time for removal of the mesiodens was 30.7 ± 16.5 min. Operating time for removal of a mesiodens tended to be prolonged with increased distance from the alveolar crest. Early detection of mesiodens on routine radiographic check-ups and surgical planning considering patient age, crown direction, position of the mesiodens will contribute to improved treatment of mesiodens.

Effects of shorter activated coagulation time on hemorrhage during venoarterial extracorporeal membrane oxygenation.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used for decades, but optimal anticoagulation control remains unknown. This study aimed to compare shorter target activated coagulation time (ACT) criteria with the usual target ACT criteria in terms of complications. METHODS: We retrospectively identified patients who received ECMO between 1 January 2013 and 31 December 2018 in an acute tertiary care hospital. Patients were divided into two groups: (I) those whose target ACT was 160-180 sec and (II) those whose target ACT was 180-220 sec. Cox proportional hazard models and Fine-Gray models adjusted for propensity score to account for the competing risk of death were used to compare the incidence of hemorrhage during ECMO between the groups. RESULTS: We identified 74 patients, 25 of whom were managed with target ACT 160-180 sec, and 49 of whom were managed with target ACT 180-220 sec. In crude analysis, the proportions of patients with hemorrhage in the under 180-sec group were significantly more than those in the over 180-sec group [60.0% (15/25) vs. 28.6% (14/49), p = 0.009]. Shorter target ACT was not associated with hemorrhage during ECMO in either Cox regression (hazard ratio, 1.67; 95% confidence interval, 0.59-4.80; p = 0.336) or Fine-Gray model (hazard ratio, 1.58; 95% confidence interval, 0.64-3.91; p = 0.324). CONCLUSIONS: The shorter ACT target was not associated with improved hemorrhage and inappropriate coagulation than the usual target ACT criteria. This study is the first to compare the ACT target of patients with ECMO.

Association between the duration of antibiotic prophylaxis and surgical site infection after orthognathic surgery in Japan.

PURPOSE: This study aimed to evaluate the risk factors for surgical site infection (SSI) after orthognathic surgery, focusing on the duration of prophylactic antibiotic administration in Japan. STUDY DESIGN: The study included 181 patients who underwent orthognathic surgery at the Department of Oral and Maxillofacial Surgery of Yamagata University Hospital between 2012 and 2021. The clinical parameters of SSI were retrospectively investigated using patient charts. Logistic regression analysis was used to estimate the odds ratios (ORs) with 95% confidence intervals (CIs) for risk factors for SSI after orthognathic surgery. RESULTS: Nineteen patients (10.5%) were complicated with SSI. Male sex (OR, 3.638; 95% CI, 1.316-10.058) and an antibiotic prophylaxis duration ≤3 days (OR, 12.718; 95% CI, 1.639-98.673) were independent risk factors for SSI after orthognathic surgery. CONCLUSION: Extended-term antibiotic prophylaxis was more effective for prevention of SSI after orthognathic surgery than short-term in this study.

Balancing potency and basicity by incorporating fluoropyridine moieties: Discovery of a 1-amino-3,4-dihydro-2,6-naphthyridine BACE1 inhibitor that affords robust and sustained central Aß reduction.

ß-Site amyloid precursor protein cleaving enzyme 1 (BACE1) has been pursued as a prime target for the treatment of Alzheimer's disease (AD). In this report, we describe the discovery of BACE1 inhibitors with a 1-amino-3,4-dihydro-2,6-naphthyridine scaffold. Leveraging known inhibitors 2a and 2b, we designed the naphthyridine-based compounds by removing a structurally labile moiety and incorporating pyridine rings, which showed increased biochemical and cellular potency, along with reduced basicity on the amidine moiety. Introduction of a fluorine atom on the pyridine culminated in compound 11 which had improved cellular activity as well as further reduced basicity and demonstrated a robust and sustained cerebrospinal fluid (CSF) Aß reduction in dog. The crystal structure of compound 11 bound to BACE1 confirmed van der Waals interactions between the fluorine on the pyridine and Tyr71 in the flap.

Safety and efficacy of cold-water immersion in the treatment of older patients with heat stroke: a case series.

BACKGROUND: Heat stroke treatment focuses on rapid cooling because symptom severity correlates with the duration of hyperthermia (i.e., time during which the core body temperature is sustained above the critical threshold). Several reports have revealed that cold-water immersion is a safe and appropriate therapy for exertional heat stroke in young, otherwise healthy patients. However, few reports have assessed cold-water immersion in older patients. We document three cases of cold-water immersion in older heat stroke patients and evaluate its safety and efficacy. CASE PRESENTATION: Three older patients with severe heat stroke were treated with cold-water immersion. Core body temperatures decreased rapidly, and no complications occurred during the treatment. CONCLUSION: Cold-water immersion can achieve rapid cooling and is effective in treating heat stroke. With special precautions, it can be performed safely for older patients. Further investigation is warranted to establish appropriate cooling methods in older adults.

Rehabilitation after maxillectomy in patients with implant-retained obturator: A preliminary report.

OBJECTIVE: The aim of this study was to evaluate the clinical outcomes of implant-retained obturator rehabilitation after maxillectomy, based on quality of life (QOL) and masticatory function. STUDY DESIGN: The present study included 12 patients who underwent dental implant surgery after maxillectomy. Oral health-related QOL and masticatory function before and after completion of implant-retained obturator rehabilitation were evaluated. RESULTS: Oral Health Impact Profile-Short Form (OHIP-14) scores showed significant differences in the domain for functional limitation (before, 4.08 ± 2.47; after, 1.33 ± 0.98; P < .01); physical pain (before, 2.75 ± 2.05; after, 0.42 ± 0.51; P < .01); physical disability (before, 3.24 ± 2.11; after, 1.33 ± 1.30; P < .01), psychological disability (before, 3.83 ± 2.48; after, 1.67 ± 2.50; P < .01); social disability (before, 2.17 ± 1.75; after, 1.08 ± 1.38; P < .05); handicap (before, 3.17 ± 1.90; after, 1.08 ± 1.00; P < .01); and total score (before, 22.41 ± 10.17; after, 8.83 ± 6.82; P < .01) Furthermore, masticatory function score was significantly higher after completing implant-retained obturator rehabilitation (before, 38.75 ± 22.97; after, 69.17 ± 21.41; P < .01). CONCLUSIONS: Implant-retained obturator rehabilitation contributed to improved masticatory function and oral health-related QOL after maxillectomy.

A convergent total synthesis of ouabagenin.

A convergent total synthesis of ouabagenin, an aglycon of cardenolide glycoside ouabain, was achieved by assembly of the AB-ring, D-ring and butenolide moieties. The multiply oxygenated cis-decalin structure of the AB-ring was constructed from (R)-perillaldehyde through the Diels-Alder reaction and sequential oxidations. The intermolecular acetal formation of the AB-ring and D-ring fragments, and combination of the intramolecular radical and aldol reactions, assembled the requisite steroidal skeleton in a stereoselective fashion. Finally, stereoselective installation of the C17-butenolide via the Stille coupling and hydrogenation led to ouabagenin.

Direct construction of 1,3-diaxial diol derivatives by C-H hydroxylation.

Direct hydroxylation of tertiary C-H bonds for construction of 1,3-diaxial diol derivatives was achieved by devising a new detachable dioxirane precursor containing a trifluoromethyl ketone moiety and ethylene tether. Oxone treatment of the ketones led to the corresponding dioxiranes, enabling hydroxy group installment into cyclohexane and steroid derivatives in a regio- and stereoselective manner through intramolecular oxygen insertion.

Total synthesis and bioactivity of an unnatural enantiomer of merrilactone a: development of an enantioselective desymmetrization strategy.

(-)-Merrilactone A [(-)-1], isolated from Illicium merrillianum in 2000, possesses neurite outgrowth activity in cultures of fetal rat cortical neurons, and, therefore, is expected to show therapeutic potential for the treatment of neurodegeneration associated with Alzheimer's and Parkinson's diseases. Apart from its biological aspects, the caged pentacyclic skeleton of 1 poses interesting synthetic challenges. Here, we report the total synthesis of the unnatural enantiomer of merrilactone A [(+)-1], based on a novel desymmetrization strategy. The chiral lithium amide 16g promoted an enantioselective transannular aldol reaction of eight-membered meso-diketone 3d, establishing the absolute stereochemistries of four chiral centers of the cis-bicyclo[3.3.0]octane framework of 1 in a single step. The obtained compound 4d served as a platform for the subsequent functional group manipulations necessary for the construction of (+)-1. Surprisingly, both the natural and unnatural enantiomers of synthetic merrilactone A equally promoted neurite outgrowth in primary neuronal cultures.