Incidence of antiresorptive agent-related osteonecrosis of the jaw: A multicenter retrospective epidemiological study in Hyogo Prefecture, Japan.

Background/purpose: The incidence of medication-related osteonecrosis of the jaw is increasing worldwide, mostly due to the use of antiresorptive agents (ARAs) such as bisphosphonate (BP) and denosumab (Dmab). However, the proportion of BP-related osteonecrosis of the jaw (BRONJ) and Dmab-related osteonecrosis of the jaw (DRONJ) among all ARA-related osteonecrosis of the jaw (ARONJ) cases is not clear; this hinders appropriate treatment, recurrence-prevention planning, and avoidance of unnecessary Dmab withdrawal. Moreover, the causative drug administered at each disease stage remains unknown. Therefore, we conducted a retrospective study of patients with ARONJ who visited oral and maxillofacial surgery departments at hospitals in Hyogo Prefecture, Japan, over 3 years to classify and compare patient characteristics with those having BRONJ and DRONJ. We sought to identify the proportion of DRONJ in ARONJ. Materials and methods: After excluding stage 0 patients, 1021 patients were included (471 high-dose; 560 low-dose). ARA treatment for bone metastases of malignant tumors and multiple myeloma was considered high dose, while that for cancer treatment-induced bone loss and osteoporosis was low dose. Results: Low doses of BP and Dmab accounted for >50% patients; the results differed from those in other countries. DRONJ accounted for 58% and 35% of high-dose and low-dose cases, respectively. Stage 3 ARONJ cases comprised 92 (19.5%) low-dose BRONJ, 39 (20.1%) high-dose BRONJ, 24 (30%) low-dose DRONJ, and 68 (24.5%) high-dose DRONJ. Eighty-nine patients who received switch therapy were divided into BRONJ or DRONJ, but there was no difference in the ratio of each stage compared to the non-switch therapy. Conclusion: To the best of our knowledge, this is the first study to clarify the proportion of BRONJ and DRONJ cases, causative drug, and its doses by disease stages. DRONJ accounted for approximately 30% of the ARONJ, approximately 60% of which was due to high doses.

Construction of Acyclic All-Carbon Quaternary Stereocenter Based on Asymmetric Michael Addition of Chiral Amine.

Acyclic asymmetric quaternary stereocenters, which are composed of four carbon-carbon bonds, were finely constructed by utilizing a face-selective alkylation of enolate intermediates derived from an asymmetric Michael addition reaction of a chiral lithium amide with trisubstituted (E)-α,ß-unsaturated esters. The present face-selective alkylation was able to employ diverse alkyl halides as an electrophile to afford various Michael adducts having an all-carbon quaternary stereocenter. With regard to the deprotection of the chiral auxiliary, N-iodosuccinimide used in our previous study did not work in the present cases; however, we found that pyridine iodine monochloride in the presence of H2O was effective to remove the bornyl group and the benzyl group on the amino group to provide the ß-amino ester derivative.

A Facile and Convenient Synthesis of Trisubstituted (E)-α,ß-Unsaturated Esters by Tandem Acetylation-E1cB Reaction.

A facile and convenient synthesis of trisubstituted (E)-α,ß-unsaturated esters was developed by improving our previously established method. The new method circumvented the separation of the intermediates, which have an activating group of the hydroxyl group in ß-hydroxy esters, furnishing α,ß-unsaturated esters in shorter steps than the previous method: an acetylation of ß-hydroxy group and subsequent E1cB reaction proceeded in tandem. In addition, the new method can not only employ a diastereomeric mixture of the substrate for the E1cB reaction, it has a wide substrate scope as well, which would enable the synthesis of various trisubstituted (E)-α,ß-unsaturated esters.

A literature review of perioperative antibiotic administration in surgery for medication-related osteonecrosis of the jaw.

PURPOSE: Few studies exist that focus on the details of perioperative antibiotic administration for surgery to treat medication-related osteonecrosis of the jaw (MRONJ). The regime and duration of perioperative antibiotics applied in published studies were reviewed to clarify appropriate perioperative antibiotic use in MRONJ surgery. METHODS: A literature search was conducted using the MEDLINE database via PubMed. RESULTS: The search resulted in 453 hits on PubMed. After reading the downloaded full-text articles, 17 articles met the inclusion and exclusion criteria. The most common perioperative antibiotic used for MRONJ surgery was a combination of penicillin-based antibiotics and ß-lactamase inhibitor (52.9%), and the second most common regime was penicillin-based antibiotics with metronidazole (17.6%). The duration of administration was 2 weeks postoperatively in nine studies, whereas four studies applied long-term administration (2-6 weeks postoperatively). CONCLUSIONS: Oral and maxillofacial surgeons mostly prefer penicillin-based antibiotics plus ß-lactamase inhibitor or metronidazole for MRONJ surgery. The duration of administration of these medications may be based on empirical experience.

Green Synthesis of (R)-Terbutaline for Recyclable Catalytic Asymmetric Transfer Hydrogenation in Ionic Liquids.

We synthesize optically active (R)-terbutaline 2, which is an anti-asthmatic drug, through recyclable catalytic asymmetric transfer hydrogenation (RCATH). Various chloroketones 4 were prepared and RCATH was performed on them. The products exhibit moderate to high enantioselectivity. In particular, the hydrogenation of acyl substituted substrates 4c yields chiral secondary alcohols 5c in good yield and enantioselectivity. Furthermore, (R)-terbutaline 2 can be synthesized in one step from the resulting secondary alcohol 5 without racemization.

Retrospective study of treatment outcomes after postoperative chemoradiotherapy in Japanese oral squamous cell carcinoma patients with risk factors of recurrence.

BACKGROUND: The purpose of this study was to investigate the feasibility of postoperative concomitant chemoradiotherapy (CRT) with cisplatin (CDDP), and compare the prognosis in 3 groups-without postoperative therapy (S-only), with radiotherapy (RT) alone (S+RT), and with CRT (S+CRT)-in oral squamous cell carcinoma (OSCC) patients at high risk of recurrence. METHODS: Clinicopathologic data and treatment modality were investigated. Endpoints evaluated were locoregional control (LRC), relapse-free survival, overall survival (OS), and type of recurrence. RESULTS: The S+CRT group was associated with a better LRC rate than the S-only (P < .001) and S+RT groups (P = .044). However, there was no significant difference in OS rates between the S+RT and S+CRT groups. CONCLUSION: The addition of concomitant CDDP to postoperative RT improved LRC. However, there may be no benefit from the addition of concomitant CDDP to postoperative RT for improvement of distant metastasis and OS rates in OSCC patients.

Palladium-Catalyzed 1,3-Difunctionalization Using Terminal Alkenes with Alkenyl Nonaflates and Aryl Boronic Acids.

A Pd-catalyzed 1,3-difunctionalization of terminal alkenes using 1,1-disubstituted alkenyl nonaflates and arylboronic acid coupling partners is reported. This transformation affords allylic arene products that are difficult to selectively access using traditional Heck cross-coupling methodologies. The evaluation of seldom employed 1,1-disubstituted alkenyl nonaflate coupling partners led to the elucidation of subtle mechanistic features of π-allyl stabilized Pd-intermediates. Good stereo- and regioselectivity for the formation of 1,3-addition products can be accessed through a minimization of steric interactions that emanate from alkenyl nonaflate substitution.

Magnitude-based Asymmetric Fourier Imaging (MagAFI).

PURPOSE: We propose and assess 2 novel asymmetric Fourier imaging (AFI) techniques, magnitude-based AFI (MagAFI) and MagAFI combined with projection on to convex sets (POCS) (MagAFI+POCS). MagAFI does not require phase information because it uses only the magnitude image with zero-filling. MagAFI+POCS requires phase information but further reduces image errors. MATERIALS AND METHODS: We initially compared phase maps obtained using asymmetrically sampled data for the whole of the k-space and symmetrically sampled data for the low frequency part of the k-space. We used one-dimensional simulation data and 3-dimensional gradient echo data for 2 different echo times (TEs) of the brains of volunteers and assessed the differences between the image reconstructed from the full k-space data and AFI images reconstructed from truncated k-space data. We generated AFI images in this study using the zero-filling, Margosian (homodyne), Margosian+POCS (standard POCS), MagAFI, and MagAFI+POCS techniques. RESULTS: We confirmed the assumption of smaller phase errors for the full k-space data than for the symmetric low frequency k-space data. Our proposed MagAFI technique provides images with smaller phase-induced errors than those obtained using conventional methods, including standard POCS methods, which have been regarded as the best methods. MagAFI+POCS improves image quality as well as robustness. CONCLUSION: Our proposed MagAFI technique achieves a practical balance of image quality and simplicity to perform better than conventional methods using only the 0-filled magnitude image. Combined with POCS, this technique can produce images of even better quality.

Multicenter Retrospective Study of Adjuvant Therapy for Patients with Pathologically Lymph Node-Positive Oral Squamous Cell Carcinoma: Analysis of Covariance Using Propensity Score.

BACKGROUND: The presence of pathologically positive lymph nodes (pN+) is a well-known prognostic factor in oral squamous cell carcinoma (OSCC). The aims of this retrospective multicenter study were to assess the prognosis of OSCC patients with pN+ disease; to compare the prognosis of patients with pN+ disease who underwent surgery plus radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) with that of patients who underwent surgery only; and to account for biases associated with treatment selection of adjuvant RT or CCRT. METHODS: The records of 313 OSCC patients with pN+ disease were retrospectively reviewed. The main outcome measures were 5-year disease-specific survival (DSS) and overall survival (OS) rates. To reduce selection biases associated with retrospective data, the treatment groups were evaluated by Cox proportional hazard analysis with propensity score as a covariate. RESULTS: The 5-year OS and DSS survival rates for the entire patient cohort were 51.8 and 59.2 %, respectively. T3-4 stage, closed (<5 mm) margin distance, ≥4 involved nodes, and extracapsular spread were significant poor prognostic factors for OS and DSS. In the propensity score analysis, postoperative RT/CCRT significantly improved OS and DSS compared to surgery only. However, OS and DSS were not significantly different between patients who received postoperative RT and CCRT. CONCLUSION: The addition of cytotoxic chemotherapy to RT does not provide additional survival benefit in OSCC patients with pN+ disease. Alternative strategies, such as molecular targeted therapies, are needed to further improve the survival of high-risk OSCC patients with pN+ disease.

Tunnel Technique for the Closure of an Oroantral Fistula with a Pedicled Palatal Mucoperiosteal Flap.

BACKGROUND: Oroantral fistula may develop as a complication of tooth extraction owing to infection, trauma, or removal of maxillary cyst or tumors. Closure by using a palatal mucoperiosteal flap with the greater palatine vessels is a very traditional and basic technique. The palatal mucosa is thick and is firm. However, deformation can occur with shifting of the mucoperiosteal flap, survival of the flap may be unsuccessful, and patients may have substantial intraoral discomfort felt until healing of the eminence with the arcuation. As a method to relieve these problems, we present a mucoperiosteal tunnel technique for the closure of oroantral fistula by using a palatal mucoperiosteal flap pedicled with the greater palatine vessels. METHOD: A 42-year-old man and a 69-year-old woman each had a palatal fistula after palatal tumor resection and tooth extraction, respectively. We designed a mucoperiosteal flap pedicled with the left greater palatine vessel. We ablated the mucoperiosteum between the fistula and the mucoperiosteal flap, and passed this flap under the ablated mucoperiosteum as a tunnel. RESULT: One year after surgery, the fistula had not reappeared and the mucoperiosteal flap harvest did not generate dyskinesis of the soft palate. CONCLUSION: Tunnel technique for the closure of an oroantral fistula with a pedicled palatal mucoperiosteal flap is obtains good fructification.