Recombinant human bone morphogenetic protein-2 (rhBMP-2) has shown potential in maxillofacial surgery owing to its osteoinductive properties. However, concerns about its safety and high cost have limited its widespread use. This review presents the status of rhBMP-2 use in maxillofacial surgery, focusing on its clinical application, efficacy, safety, and limitations. Studies have demonstrated rhBMP-2’s potential to reduce donor site morbidity and increase bone height in sinus and ridge augmentation; however, it may not outperform autogenous bone grafts. In medication-related osteonecrosis of the jaw treatment, rhBMP-2 has been applied adjunctively with promising results, although its long-term safety requires further investigation. However, in maxillofacial trauma, its application is limited to the restoration of large defects. Safety concerns include postoperative edema and the theoretical risk of carcinogenesis. Although postoperative edema is manageable, the link between rhBMP-2 and cancer remains unclear. The limitations include the lack of an ideal carrier, the high cost of rhBMP-2, and the absence of an optimal dosing regimen. In conclusion, rhBMP-2 is a promising graft material for maxillofacial surgery. However, it has not yet become the gold standard owing to safety and cost concerns. Further research is required to establish long-term safety, optimize dosing, and develop better carriers.
Background: This phase 3 trial (JAVELIN Ovarian 200) compared avelumab alone or avelumab plus pegylated liposomal doxorubicin (PLD) with PLD alone in patients with platinum-resistant or platinum-refractory ovarian cancer.Methods: Eligible women (≤3 prior lines, none for platinum-resistant disease) were randomised 1:1:1 to avelumab (10 mg/kg intravenously every 2 weeks), avelumab plus PLD (40 mg/m2 intravenously every 4 weeks), or PLD. Primary endpoints were progression-free survival by blinded independent central review and overall survival. Findings: Between January 5, 2016 and May 16, 2017, 566 patients were randomised. Improvement in progression-free survival by blinded independent central review or overall survival with avelumab plus PLD vs PLD alone did not reach statistical significance (hazard ratios, 0·78 [repeated CI 0·587–1·244; one-sided nominal P=0·0301] and 0·89 [repeated CI 0·744–1·241; one-sided nominal P=0·2082]). Avelumab alone did not improve progression-free survival by blinded independent central review or overall survival vs PLD (hazard ratios, 1·68 [repeated CI 1·320–2·601; one-sided nominal P>0·999] and 1·14 [repeated CI 0·948–1·580; one-sided nominal P=0·8253]). Progression-free survival rates at 12 months were 18% (95% CI 12–25) in the combination arm, 9% (95% CI 5–16) in the PLD arm, and 6% (95% CI 3–11) in the avelumab arm; 12-month overall survival rates were 60% (95% CI 52–67), 57% (95% CI 49–64), and 50% (95% CI 42–57), respectively. In the combination, PLD, and avelumab arms, grade ≥3 treatment-related adverse events occurred in 43%, 32%, and 16%, respectively. Treatment-related adverse events resulted in death in 2 patients (sepsis [PLD arm] and intestinal obstruction [avelumab arm]).Interpretation: The trial did not meet its primary objectives of significantly improving progression-free survival or overall survival with avelumab plus PLD or avelumab alone vs PLD.Trial Registration: This trial is registered with ClinicalTrials.gov, number NCT02580058.Funding Statement: The trial was sponsored by Pfizer as part of an alliance between Pfizer and Merck KGaA, Darmstadt, Germany.Declaration of Interests: Dr Pujade-Lauraine reports serving as a consultant or advisor for AstraZeneca, Clovis Oncology, Incyte, Merck & Co., Merck KGaA/EMD Serono, Pfizer, Roche, and Tesaro; has received honoraria from AstraZeneca, GSK, and Tesaro; and has received reimbursement for travel and accommodation expenses from AstraZeneca, Roche, and Tesaro. Dr Fujiwara reports serving as a consultant or advisor for Eisai, Merck & Co., and Pfizer; has received research funding from AstraZeneca, Eisai, Immunogen, Kaken Pharmaceutical, Merck & Co., Oncotherapeutics, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, and Zeria Pharmaceutical; has received honoraria from Bayer, Chugai Pharma, Daiichi Sankyo, Kyowa Hakko Kirin, Nippon Kayaku, Ono Pharmaceutical, Taiho Pharmaceutical, and Zeria Pharmaceutical; and has received reimbursement for travel and accommodation expenses from Pfizer. Prof. Ledermann reports serving as a consultant or advisor for Artios Pharma, AstraZeneca, Clovis Oncology, Cristal Therapeutics, Eisai, Merck & Co., Pfizer, Seattle Genetics/Genmab, and Tesaro/GSK; has received research funding from AstraZeneca and Merck & Co./MSD; has received honoraria from AstraZeneca; has received reimbursement for travel and accommodation expenses from Clovis Oncology; is a member of a speakers’ bureau for Clovis Oncology, Pfizer, and Tesaro/GSK; and has other relationships with Regeneron. Dr Oza reports serving as a consultant or advisor for Immunogen and Merck KGaA; has received research funding from AstraZeneca and Immunovaccine; has received honoraria from Intas; has received reimbursement for travel and accommodation expenses from AstraZeneca; and has other relationships with AstraZeneca, Clovis Oncology, Merck KGaA, and Tesaro. Dr Kristeleit reports serving as a consultant or advisor for Basilea, Cerulean Pharma, Clovis Oncology, Roche/Genentech, and Sotio; has received honoraria from AstraZeneca, Clovis Oncology, Merck & Co., Roche/Genentech, and Tesaro; and has received reimbursement for travel and accommodation expenses from Basilea, Clovis Oncology, and Valirx. Dr Ray-Coquard reports serving as a consultant or advisor for Abbvie, AstraZeneca, Bristol- Myers Squibb, Clovis Oncology, Deciphera, Genmab, Merck & Co./MSD, Merck KGaA/EMD Serono, Mersana Therapeutics, Pfizer, PharmaMar, Roche, and GSK/Tesaro; has received honoraria from Abbvie, AstraZeneca, Bristol-Myers Squibb, Clovis Oncology, Genmab, & Co./MSD, Pfizer, PharmaMar, Roche, and Tesaro; has received research funding from Bristol-Myers Squibb and Merck & Co./MSD; and has received reimbursement for travel and accommodation expenses from Advaxis, AstraZeneca, Bristol-Myers Squibb, Clovis, GSK, PharmaMar, Roche, and Tesaro. Dr Richardson has received research funding from Alphamab, AstraZeneca, BeiGene, Bristol-Myers Squibb, CBT Pharmaceuticals, Corvus Pharmaceuticals, Five Prime Therapeutics, Inc., Fosun Pharma, Merck KGaA, Novotech, Pfizer, Roche/Genentech, Shanghai Henlius Biotech, and Takeda. Dr Sessa has no competing interests. Dr Yonemori is a member of a speakers’ bureau for AstraZeneca, Eisai, and Pfizer. Dr Banerjee reports serving as a consultant or advisor for Amgen, AstraZeneca/MedImmune, Carrick Therapeutics, Clovis Oncology, Genmab, Merck & Co., Roche, Seattle Genetics, and Tesaro; has received honoraria from Roche; has received research funding from AstraZeneca, GSK, and Janssen; and has received reimbursement for travel and accommodation expenses from AstraZeneca and NuCana BioMed. Dr Leary reports serving as a consultant or advisor for Ability Pharma, AstraZeneca, BIOCAD, Clovis Oncology, Gritstone Oncology, GSK, Merck KGaA/EMD Serono, Merck & Co., Seattle Genetics, and Tesaro; has received honoraria from AstraZeneca and Clovis Oncology; has received research funding from GamaMabs Pharma, Inivata, and Merus; and has received reimbursement for travel and accommodation expenses from AstraZeneca and Tesaro. Dr Tinker reports serving as a consultant or advisor for and has received research funding from AstraZeneca. Dr Jung reports serving as a consultant or advisor for AstraZeneca Korea, Celgene Korea, Eisai Korea, Roche Korea, and Takeda Pharmaceuticals Korea. Dr Madry reports serving as a consultant or advisor for AstraZeneca and GSK; is a member of a speakers’ bureau for AstraZeneca, GSK, and Roche; and has received reimbursement for travel and accommodation expenses from AstraZeneca and Roche. Dr Park has no competing interests. Dr Anderson has no competing interests. Dr Zohren reports employment at and holds stock in Pfizer. Dr Stewart reports employment at and holds stock in Pfizer. Dr Wei reports employment at Pfizer. Dr Dychter reports employment at Pfizer. Dr Monk reports serving as a consultant or advisor for Abbvie, Advaxis, Amgen, AstraZeneca, Cerulean Pharma, ChemoCare, ChemoID, Clovis Oncology, Eisai, Geistlich Pharma, ImmunoGen, Incyte, Mateon Therapeutics, Merck & Co., Myrexis, NuCana BioMed, OncoMed, OncoSec, Perthera, Pfizer, Precision Oncology, Roche/Genentech, Samumed, Takeda, Tesaro, and VBL Therapeutics; has received honoraria from Abbvie, Advaxis, Agenus, Amgen, AstraZeneca, ChemoCare, ChemoID, Clovis Oncology, Conjupro Biotherapeutics, Eisai, Geistlich Pharma, ImmunoGen, Immunomedics, Incyte, Janssen/Johnson&Johnson, Mateon Therapeutics (formally Oxigene), Merck & Co., Myrexis, NuCana BioMed, OncoQuest, Perthera, Pfizer, Precision Oncology, Puma Biotechnology, Roche/Genentech, Samumed, Seattle Genetics/Genmab, Takeda, Tesaro/GSK, and VBL Therapeutics; is a member of a speakers’ bureau for AstraZeneca, Clovis Oncology, Janssen/Johnson&Johnson, Roche/Genentech, and Tesaro/GSK; and has received research funding from Advaxis, Amgen, Array BioPharma, AstraZeneca, Genentech, Immunogen, Janssen, Lilly, Morphotek, Novartis, NuCana Biomed, Pfizer, Regeneron, and Tesaro.Ethics Approval Statement: The trial was conducted in accordance with the ethics principles of the Declaration of Helsinki and the International Council for Harmonisation guidelines on Good Clinical Practice. The protocol was approved by the institutional review board or independent ethics committee of each centre or country. All patients provided written informed consent before enrolment.
Maxillofacial skeletal surgery often involves the use of patient-specific implants. However, errors in obtaining patient data and designing and manufacturing patient-specific plates and guides can occur even with accurate virtual surgery. To address these errors, bespoke Snowman plates were designed to allow movement of the mandible. This study aimed to compare the stability of bespoke four-hole miniplates with that of a bespoke Snowman plate for bilateral sagittal split ramus osteotomy (SSRO), and to present a method to investigate joint cavity changes, as well as superimpose virtual and actual surgical images of the mandible. This retrospective study included 22 patients who met the inclusion criteria and underwent orthognathic surgery at a university hospital between 2015 and 2018. Two groups were formed on the basis of the plates used: a control group with four-hole bespoke plates and a study group with bespoke Snowman plates. Stability was assessed by measuring the condyle-fossa space and superimposing three-dimensional virtual surgery images on postoperative cone-beam computed tomography (CBCT) scans. No significant differences were observed in the condyle-fossa space preoperatively and 1 year postoperatively between the control and study groups. Superimposing virtual surgery and CBCT scans revealed minimal differences in the landmark points, with no variation between groups or timepoints. The use of bespoke Snowman plates for stabilizing the mandible following SSRO exhibited clinical stability and reliability similar to those with bespoke four-hole plates. Additionally, a novel method was introduced to evaluate skeletal stability by separately analyzing the condyle-fossa gap changes and assessing the mandibular position.
In this paper, we present an algorithm which detects human hand by skin color information in YCbCr and HIS color model. And for confirming special human hand we use circle rate of region to detect hand region because human hand have complex edge than other region, thus circle rate of hand region is usually more greater. For the recognition of detected hand, we use the Hausdorff to tracking the hand region. And we employed a recognition method based on PCA algorithm to recognize the hand gestures. The experimental results show that an algorithm plays an efficient effort for hand gesture recognition.
This study was designed to determine the maximum tolerated dose and toxicity profile of belotecan in combination with oral etoposide in patients with platinum-resistant or heavily treated ovarian cancer, fallopian tubal cancer, and primary peritoneal cancer. Belotecan (0.5 mg/m/day) was administered daily (days 1-5) followed by etoposide (50, 75 mg/day) for up to 5 days (days 6-10) every 3 weeks. Dose-limiting toxicities (DLT) were defined as follows: grade 4 neutropenia less than 1 week; either neutropenic fever less than 24 h or sepsis; grade 4 thrombocytopenia; and grade of at least 3 nonhematologic toxicity except alopecia. At the first dose level (50 mg) of etoposide, none of the three patients developed DLT, whereas DLT was observed in two of three patients at the next dose level. Thus, the dose level was reduced to 50 mg, and another three patients were enrolled. DLT was found in one of six patients who received etoposide at the dose level of 50 mg/m. Thus, the maximum tolerated dose was reached (50 mg of oral etoposide) and the trial was terminated. The response was evaluable in nine patients and an objective response was observed in four patients (44%) including two complete responses. The combined regimen of belotecan followed by oral etoposide showed promising activity in platinum-resistant or heavily pretreated ovarian cancer patients at the dose level of 50 mg of oral etoposide.
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