Reliability of a chairside CAD-CAM surgical guide for dental implant surgery on the anterior maxilla: An in vitro study.

PURPOSE: This study evaluated the reliability of the chair-side CAD-CAM surgical guide (CSG) in the anterior maxilla by comparing its accuracy with the laboratory 3D-printed surgical guide (3DSG) and manual surgical guide (MSG) concerning different levels of dentists' surgical experience. MATERIALS AND METHODS: Ten surgical guides of each type (MSG, 3DSG, and CSG) were fabricated on a control study model with missing right and left central incisors. Sixty implants were placed in 30 study models by two dentists (one inexperienced and one experienced) using three different types of surgical guides. Horizontal deviations at shoulder and at apex, vertical, and angular deviations were measured after superimposing the planned and placed implant positions in the software. Kruskal-Wallis and Mann-Whitney U tests were used to compare the accuracy of three types of surgical guides in each dentist group and the accuracy of each surgical guide between two dentists (α = .05). RESULTS: There were no significant differences in any deviations between CSG and 3DSG, apart from angular deviation, for both dentists' groups. Moreover, both CSG and 3DSG showed no significant differences in accuracy between the two dentists (P > .05). In contrast, MSG demonstrated significant differences from CSG and 3DSG and a significant difference in accuracy between the two dentists (P < .05). CONCLUSION: CSG provides superior accuracy to MSG in implant placement in the maxillary anterior region and is comparable to 3DSG at different levels of surgical experience, while offering the benefits of shorter manufacturing time and reduced patient visits.

Extraction of mandibular third molars: relationship of preoperative anxiety with body mass index, serum high-sensitivity C-reactive protein levels, and visual analog scale scores and predictors of postoperative complications.

Objectives: Patients undergoing oral surgery exhibit high anxiety, which may elevate their cortisol levels and affect postoperative recovery. Overweight patients are often encountered in the dental clinic due to the increasing prevalence of overweight. We aimed to investigate the relationships between preoperatively assessed body mass index (BMI), serum cortisol and high-sensitivity C-reactive protein (hs-CRP) levels, and visual analog scale (VAS) scores and preoperative anxiety in patients undergoing mandibular third molar (MM3) extraction and to identify predictors of postoperative complications. Patients and Methods: We analyzed 43 patients (age, 20-42 years) undergoing MM3 extraction. At the first visit, patients completed the Modified Dental Anxiety Scale (MDAS) and Amsterdam Preoperative Anxiety and Information Scale (APAIS) questionnaires. Their BMI and VAS scores were also calculated. The participants underwent blood tests 1 hour before MM3 extraction. On the first postoperative day, the participants' VAS scores and serum hs-CRP levels were reevaluated. Results: We found that BMI was significantly correlated with preoperative VAS scores. Further, BMI and preoperative hs-CRP levels were significantly correlated among women and patients undergoing extractions of fully impacted MM3s. No correlations were found between serum cortisol and other variables. The preoperative MDAS and VAS scores were significantly positively correlated, especially among patients undergoing extractions of fully impacted MM3s. Multiple linear regression showed that BMI and the eruption status of the MM3 were significant predictors of postoperative hs- CRP levels and VAS scores, respectively. Conclusion: In MM3 removals, patients with higher BMI showed elevated hs-CRP and higher VAS scores before surgery. Patients with higher anxiety among those undergoing extractions of fully impacted MM3s showed higher preoperative VAS scores. The two main predictors of postoperative complications were BMI and MM3 eruption status.

The double-barrier technique using platelet-rich fibrin for closure of oroantral fistulas.

An oroantral fistula (OAF) or oroantral communication (OAC) is an opening between the oral cavity and the maxillary sinus. If left untreated, these openings may cause chronic maxillary sinusitis. Although small defects (diameter <5 mm) may close spontaneously, larger communications require surgical intervention. Various studies have been conducted on OAC closure using a platelet-rich fibrin (PRF) membrane; most of these prior studies have involved simple direct application of PRF clots. This study introduces a new "double-barrier technique" using PRF for closure of an OAF involving sinus mucosal lifting and closure. The PRF material is inserted into the prepared maxillary sinus space, and the buccal advancement flap covers the oral side. This technique was successfully used to treat two patients with chronic OAF in the posterior maxillary region after implant removal or tooth extraction. The use of a PRF membrane in a double-barrier technique may have advantages in soft-tissue healing and could enable easy closure of chronic OAF with minimal trauma.

Altered functional connectivity of the ascending reticular activating system in obstructive sleep apnea.

Repeated arousals during sleep in obstructive sleep apnea (OSA) may lead to altered functional connectivity (FC) of the ascending reticular activating system (ARAS). We evaluated resting-state FC between eight ARAS nuclei and 105 cortical/subcortical regions in OSA patients and healthy controls. Fifty patients with moderate to severe OSA and 20 controls underwent overnight polysomnography and resting-state functional magnetic resonance imaging. Seed-to-voxel analysis of ARAS-cortex FC was compared between OSA patients and controls. The ARAS nuclei included the locus coeruleus (LC), laterodorsal tegmental nucleus (LDTg), and ventral tegmental area (VTA). FC values of three ARAS nuclei (the LC, LDTg, and VTA) significantly differed between the groups. FC of the LC with the precuneus, posterior cingulate gyrus, and right lateral occipital cortex (LOC) was stronger in OSA patients than controls. FC between the LDTg and right LOC was stronger in OSA patients than controls, but FC between the VTA and right LOC was weaker. Average LC-cortex FC values positively correlated with the arousal, apnea, and apnea-hypopnea index in OSA patients. Alterations in ARAS-cortex FC were observed in OSA patients. The strength of LC-cortex noradrenergic FC was related to arousal or OSA severity in patients.

Cosmetic Treatment Using Botulinum Toxin in the Oral and Maxillofacial Area: A Narrative Review of Esthetic Techniques.

Botulinum toxin (BoNT) is an anaerobic rod-shaped-neurotoxin produced by Clostridium botulinum, that has both therapeutic and lethal applications. BoNT injection is the most popular cosmetic procedure worldwide with various applications. Patients with dynamic wrinkles in areas such as the glabella, forehead, peri-orbital lines, nasal rhytides, and perioral rhytides are indicated. Excessive contraction of muscles or hyperactivity of specific muscles such as bulky masseters, cobble stone chins, gummy smiles, asymmetric smiles, and depressed mouth corners can achieve esthetic results by targeting the precise muscles. Patients with hypertrophic submandibular glands and parotid glands can also benefit esthetically. There are several FDA-approved BoNTs (obabotuli-numtoxinA, abobotulinumtoxinA, incobotulinumtoxinA, letibotulinumtoxinA, prabotulinumtox-inA, daxibotulinumtoxinA, rimbotulinumtoxinB) and novel BoNTs on the market. This paper is a narrative review of the consensus statements of expert practitioners and various literature on the injection points and techniques, highlighting both the Asian and Caucasian population separately. This paper can serve as a practical illustrative guide and reference for optimal, safe injection areas and effective doses for application of BoNT in the face and oral and maxillofacial area. The history of BoNT indications, contraindications, and complications, and the merits of ultrasonography (US)-assisted injections are also discussed.

Altered intrinsic brain functional network dynamics in moderate-to-severe obstructive sleep apnea.

OBJECTIVES: Obstructive sleep apnea (OSA) can affect temporal fluctuations in brain activity during rest. Dynamic functional connectivity (dFC) captures the fluctuations in FC during the resting state. This study aimed to investigate differences in dFC between moderate-to-severe OSA patients and healthy controls using resting-state functional magnetic resonance imaging (fMRI) and sliding-window analysis. METHODS: Thirty-seven consecutive patients with moderate-to-severe OSA and 16 age- and sex-matched controls underwent resting-state fMRI in the morning following overnight polysomnography. The dynamics of aberrant FC between the groups and the correlation between the dynamics and clinical variables were evaluated. RESULTS: dFC analysis revealed two distinct connectivity states: hypoconnected (State I) and hyperconnected (State II). In OSA patients, State I occurred 34% more often than in the controls and the occurrence of State II was proportionally reduced. The time in State I positively correlated with the Pittsburg Sleep Quality Index score in the OSA patients. CONCLUSIONS: This study showed dFC alterations in moderate-to-severe OSA patients, which may serve as a novel physiological biomarker for OSA.

Face painting as an anatomical learning tool based on individual ultrasonographic examination.

Considering the shift to online education during the COVID-19 pandemic, new and easily accessible educational videos and content on clinical anatomy are necessary. This study utilized numerous references and data on the anatomy of Asian facial muscles and blood vessels to accurately depict human anatomy through face painting. It aimed to provide clinicians accurate educational video content on anatomy to help prevent possible complications during noninvasive facial and surgical procedures. A 26-year-old Korean-Chinese male volunteer was used as a face painting model. The location of the blood vessels of the face was confirmed through ultrasonography images using a real-time two-dimensional B-mode. The model's face was painted by an artist majoring in anatomy. To reveal most anatomical structures on both sides of the face, the left side showed the structures observed when the skin and superficial fat layer are removed, and the right side revealed the deeper layer structures that can be seen when some muscles are cut. Fifteen superficial and deep muscles important in esthetic procedures were meticulously painted on the face. The face painting took a total of 6 h, and the video was edited to 5 min. This study merged the advantages of 2D and 3D by painting directly on the skin surface of a living model. Thus, it can provide more dynamic surface anatomy data. These contents inform clinicians about 3D anatomic location, which can help avoid complications when performing clinical procedures on the face.

Bicycle Injury Prevention Education Using 360° Virtual Reality Experiences of Accidents and Computer-Based Activity.

Injury prevention programs for children and adolescents need to be immersive and interactive. This study assessed a bicycle injury prevention program using technology-based education based on the Activated Health Education model and evaluated its effect on environmental factor awareness and attitude toward helmet-wearing. Using virtual reality technology, elementary and middle school students could experience simulated bicycle accidents. It was followed by an awareness phase that included a 30-min lecture where students self-learned and discussed risk-preventive factors. Students then developed user-created content and customized helmets they were given. We assessed students before the program, immediately afterward, and one month after the program. The number of respondents who said they were aware of surrounding bicycle lanes increased from 75.3% (pre-program) to 92.5% (one month after). Those who said they wore helmets often or always rose from 14.3% (pre-program) to 32.5% (one month later). The number needed to treat helmet-wearing behavior was approximately four, meaning that four people were required to participate in the program to have an impact on one person's helmet-wearing. We found that virtual reality and computer-based activities can help children and adolescents experience bicycle accidents, be aware of risk factors, and change their behaviors responsibly.

Nanophotosensitizers Composed of Phenyl Boronic Acid Pinacol Ester-Conjugated Chitosan Oligosaccharide via Thioketal Linker for Reactive Oxygen Species-Sensitive Delivery of Chlorin e6 against Oral Cancer Cells.

Chlorin E6 (Ce6)-incorporated nanophotosensitizers were fabricated for application in photodynamic therapy (PDT) of oral cancer cells. For this purpose, chitosan oligosaccharide (COS) was conjugated with hydrophobic and reactive oxygen species (ROS)-sensitive moieties, such as phenyl boronic acid pinacol ester (PBAP) via a thioketal linker (COSthPBAP). ThdCOOH was conjugated with PBAP to produce ThdCOOH-PBAP conjugates and then attached to amine groups of COS to produce a COSthPBAP copolymer. Ce6-incorporated nanophotosensitizers using the COSthPBAP copolymer were fabricated through the nanoprecipitation and dialysis methods. The Ce6-incorporated COSthPBAP nanophotosensitizers had a small diameter of less than 200 nm with a mono-modal distribution pattern. However, it became a multimodal and/or irregular distribution pattern when H2O2 was added. In a morphological observation using TEM, the nanophotosensitizers were disintegrated by the addition of H2O2, indicating that the COSthPBAP nanophotosensitizers had ROS sensitivity. In addition, the Ce6 release rate from the COSthPBAP nanophotosensitizers accelerated in the presence of H2O2. The SO generation was also higher in the nanophotosensitizers than in the free Ce6. Furthermore, the COSthPBAP nanophotosensitizers showed a higher intracellular Ce6 uptake ratio and ROS generation in all types of oral cancer cells. They efficiently inhibited the viability of oral cancer cells under light irradiation, but they did not significantly affect the viability of either normal cells or cancer cells in the absence of light irradiation. The COSthPBAP nanophotosensitizers showed a tumor-specific delivery capacity and fluorescence imaging of KB tumors in an in vivo animal tumor imaging study. We suggest that COSthPBAP nanophotosensitizers are promising candidates for the imaging and treatment of oral cancers.

Strategies for dental aspiration and ingestion accidents that can lead to serious complications: a report of three cases and a review of articles.

Population aging and the usage of small devices in implant prosthetic procedures have led to many incidents of dental aspiration and ingestion. Various preventive measures have been introduced to prevent these accidents. However, accidents can occur at any time. Dental aspiration and ingestion lead to fatal consequences if the issue is not promptly and appropriately dealt with. Preparing a collaborative system for dealing with accidents before they occur can prevent further sequelae. This study involves ingestion and aspiration accidents that occurred during dental treatment: two ingestion cases and one aspiration case. All dental foreign bodies were removed according to the guidelines presented in our review. With the cooperation of other medical departments, the issues were quickly resolved. Simple and accurate protocols should be provided to all dentists and dental staff to respond to such dental emergencies. In addition, collaboration among other medical departments should be established before any accidental ingestion and aspiration events occur.

Positional deformation of the parotid gland: Application to minimally invasive procedures.

Anatomical studies of the parotid gland are important for mid- and lower face filler, botulinum toxin, and thread lifting procedures. The purpose of this study was to observe the topographic anatomy of the parotid gland using cadaveric dissections. The superficial lobe of the parotid gland was studied in 30 hemisected heads. Reference lines were made on the lateral aspect of the face. A reference line (the line connecting the mandibular angle to the upper margin of the zygomatic arch, along the posterior border of the ramus) was divided into four sections (P1, P2, P3, and P4). The superior, inferior, anterior, and posterior borders of the parotid gland were measured using the reference lines and sections. Using these measurements, we categorized the superficial lobe of the parotid gland into two types: type Ia, pistol-shaped; Ib, pistol-shaped with an accessory lobe; and type II, oval-shaped. The superior border of the parotid gland started just below the inferior margin of the zygomatic arch. The parotid gland covered the posterior part of the masseter muscle near P1 and P2, but at P3 and below P3, the tail of the parotid gland was located posterior to the ramus and covered the anterior part of the sternocleidomastoid muscle. The topographic anatomy of the parotid gland serves as a reliable reference for esthetic procedures in the lower face and neck region.

Data resource profile: the Korea National Hospital Discharge In-depth Injury Survey.

The Korea National Hospital Discharge In-depth Injury Survey (KNHDIS), which was started in 2005, is a national probability survey of general hospitals in Korea with 100 or more beds conducted by the Korea Disease Control and Prevention Agency (KDCA). The KNHDIS captures approximately 9% of discharged cases from sampled hospitals using a 2-stage stratified cluster sampling scheme, among which 13% are injury related cases, defined as S00-T98 (injury, poisoning, and certain other consequences of external causes) using International Classification of Diseases, 10th revision codes. The KNHDIS collects information on characteristics of injury-related discharges in order to understand the scale of injuries, identify risk factors, and provide data supporting prevention policies and intervention strategies. The types of data captured include the hospitals' information, detailed clinical information, and injury-related codes such as the mechanism, activities undertaken when injured (sports, leisure activities, work, treatment, and education), external causes of the injury, and location of the occurrence of the injury based on the International Classification of External Causes of Injuries. Furthermore, the means of transportation, risk factors for suicide, and toxic substances are recoreded. Annual reports of the KNHDIS are publicly accessible to browse via the KDCA website (http://www.kdca.go.kr) and microdata are available free of charge upon request via email (kcdcinjury@korea.kr).

A large invasive chondroblastoma on the temporomandibular joint and external auditory canal: a case report and literature review.

BACKGROUND: Chondroblastomas, which account for approximately 1% of all bone tumors, typically occur in long bones, such as the femur, humerus, and tibia. However, in extremely rare cases, they may also occur in the craniofacial region where the tumor is often found in the squamous portion of the temporomandibular joint (TMJ) and in the temporal bone. CASE PRESENTATION: This case report describes a large chondroblastoma (diameter, approximately 37 mm) that occurred in the TMJ. The tumor was sufficiently aggressive to destroy the TMJ, mandibular condyle neck, external auditory canal (EAC), mandibular fossa of the temporal bone, and facial nerve. The tumor was completely excised using a pre-auricular approach. The EAC and surgical defect were successfully reconstructed using a temporoparietal fascia flap (TPFF) and an inguinal free fat graft. There was no local tumor recurrence at the 18-month follow-up visits. However, the patient developed sensory neural hearing loss, and his eyebrow paralysis worsened, eventually requiring plastic surgery. CONCLUSION: Large, invasive chondroblastomas of the TMJ can be completely removed through a pre-auricular approach, and the resulting surgical defect can be reconstructed using TPFF and free fat grafts. However, preoperative evaluation of the facial nerve and auditory function is necessary. Therefore, a multidisciplinary approach is essential.

The use of a pedicled buccal fat pad for reconstruction of posterior mandibular defects.

BACKGROUND: The pedicled buccal fat pad has been used for a long time to reconstruct oral defects due to its ease of flap formation and few complications. Many cases related to reconstruction of defects in the maxilla, such as closing the oroantral fistula, have been reported, but cases related to the reconstruction of defects in the mandible are limited. Under adequate anterior traction, pedicled buccal fat pad can be a reliable and effective method for reconstruction of surgical defects in the posterior mandible. CASE PRESENTATION: This study describes two cases of reconstruction of surgical oral defects in the posterior mandible, all of which were covered by a pedicled buccal fat pad. The size of the flap was sufficient to perfectly close the defect without any tension. Photographic and radiologic imaging showed successful closure of the defects and no problems were noted in the treated area. CONCLUSION: In conclusion, the pedicled buccal fat pad graft is a convenient and reliable method for the reconstruction of surgical defects on the posterior mandible.

Prediction of patients requiring intensive care for COVID-19: development and validation of an integer-based score using data from Centers for Disease Control and Prevention of South Korea.

BACKGROUND: Unavailability or saturation of the intensive care unit may be associated with the fatality of COVID-19. Prioritizing the patients for hospitalization and intensive care may be critical for reducing the fatality of COVID-19. This study aimed to develop and validate a new integer-based scoring system for predicting patients with COVID-19 requiring intensive care, using only the predictors available upon triage. METHODS: This is a retrospective study using cohort data from the Korean Centers for Disease Control and Prevention that included all admitted patients with COVID-19 between January 19 and June 3, 2020, in South Korea. The primary outcome was patients requiring intensive care defined as actual admission to the intensive care unit; at any time use of an extracorporeal life support device, mechanical ventilation, or vasopressors; and death. Patients admitted until March 20 were included for the training dataset to develop the prediction models and externally validated for the patients admitted afterward. Two logistic regression models were developed with different predictors and the predictive performance was compared: one with patient-provided variables and the other with added radiologic and laboratory variables. An integer-based scoring system was developed based on the developed logistic regression model. RESULTS: A total of 5193 patients were considered, with 4663 patients included after excluding patients with age under 18 or insufficient data. For the training dataset, 3238 patients were included. Of the included patients, 444 (9.5%) patients required intensive care. The model developed with only the clinical variables showed an area under the curve of 0.884 for the validation set. The performance did not differ when radiologic and laboratory variables were added. Seven variables were selected for developing an integer-based scoring system: age, sex, initial body temperature, dyspnea, hemoptysis, history of chronic kidney disease, and activities of daily living. The area under the curve of the scoring system was 0.880. CONCLUSIONS: An integer-based scoring system was developed for predicting patients with COVID-19 requiring intensive care, with high performance. This system may aid decision support for prioritizing the patient for hospitalization and intensive care, particularly in a situation with limited medical resources.

An Easy-to-Use Machine Learning Model to Predict the Prognosis of Patients With COVID-19: Retrospective Cohort Study.

BACKGROUND: Prioritizing patients in need of intensive care is necessary to reduce the mortality rate during the COVID-19 pandemic. Although several scoring methods have been introduced, many require laboratory or radiographic findings that are not always easily available. OBJECTIVE: The purpose of this study was to develop a machine learning model that predicts the need for intensive care for patients with COVID-19 using easily obtainable characteristics-baseline demographics, comorbidities, and symptoms. METHODS: A retrospective study was performed using a nationwide cohort in South Korea. Patients admitted to 100 hospitals from January 25, 2020, to June 3, 2020, were included. Patient information was collected retrospectively by the attending physicians in each hospital and uploaded to an online case report form. Variables that could be easily provided were extracted. The variables were age, sex, smoking history, body temperature, comorbidities, activities of daily living, and symptoms. The primary outcome was the need for intensive care, defined as admission to the intensive care unit, use of extracorporeal life support, mechanical ventilation, vasopressors, or death within 30 days of hospitalization. Patients admitted until March 20, 2020, were included in the derivation group to develop prediction models using an automated machine learning technique. The models were externally validated in patients admitted after March 21, 2020. The machine learning model with the best discrimination performance was selected and compared against the CURB-65 (confusion, urea, respiratory rate, blood pressure, and 65 years of age or older) score using the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 4787 patients were included in the analysis, of which 3294 were assigned to the derivation group and 1493 to the validation group. Among the 4787 patients, 460 (9.6%) patients needed intensive care. Of the 55 machine learning models developed, the XGBoost model revealed the highest discrimination performance. The AUC of the XGBoost model was 0.897 (95% CI 0.877-0.917) for the derivation group and 0.885 (95% CI 0.855-0.915) for the validation group. Both the AUCs were superior to those of CURB-65, which were 0.836 (95% CI 0.825-0.847) and 0.843 (95% CI 0.829-0.857), respectively. CONCLUSIONS: We developed a machine learning model comprising simple patient-provided characteristics, which can efficiently predict the need for intensive care among patients with COVID-19.

Main results of the Korea National Hospital Discharge In-depth Injury Survey, 2004-2016.

OBJECTIVES: The purpose of this study was to estimate the incidence of injuries and to identify their causes by classifying injuries according to various categories including age, sex, mechanism of injury, body parts injured, and place of injury. METHODS: This study used data from the Korea National Hospital Discharge In-depth Injury Survey (KNHDIS) from 2004 to 2016. The KNHDIS is conducted annually by the Korea Centers for Disease Control and Prevention, and its survey population includes all hospitalized patients discharged from medical institutions that have 100 or more beds, such as hospitals, general hospitals, and secondary community health centers. The number of injured cases is weighted and estimated using the mid-year estimated population of each year. RESULTS: The injury discharge rate steadily increased since 2004 (1,505 per 100,000 population in 2004, 2,007 per 100,000 population in 2016) and most injuries were unintentional (annual average of 94.7%). On average, during the 13-year study period, the injury rate for males was 1.5 times as high as for females. The 2 main causes of injury were consistently traffic accidents and falls. Notably, the rate of injuries resulting from falls rose by 1.7-fold from 463 to 792 per 100,000 people, and exceeded the rate of traffic accidents in 2016. CONCLUSIONS: The incidence of injuries steadily increased after the survey was first conducted, whereas mortality resulting from injuries mostly remained unchanged. This suggests that effective strategies and interventions should be reinforced to reduce unintentional injuries.

Presenting characteristics and clinical outcome of patients with COVID-19 in South Korea: A nationwide retrospective observational study.

BACKGROUND: More than 13,000 cases were reported to be infected with COVID-19 by RT-PCR in South Korea. Most studies report clinical characteristics of hospitalized patients with COVID-19; the full spectrum of disease severity has thus not yet been well described. METHODS: Using retrospective observational methods, this study analyzed factors affecting early clinical symptoms, clinical progress, and severity of disease for COVID-19 positive patients released from quarantine to provide information on establishing optimized care for new patients. The medical data of 7803 laboratory-confirmed patients who had been discharged or died by April 30, 2020 were analyzed using multivariate logistic regression analysis. FINDINGS: On admission, 7383 (94•5%) patients were asymptomatic or showed mild illness, and 372 (4•8%) patients were severe illness. Also, 48 (0 0•6%) were hospitalized with critically ill when diagnosed. Most patients with asymptomatic or mild illness on admission remained mild until discharge, 253 (3•4%) progressed to severe illness, and 83 (1•1%) died in hospital. However, the case fatality were 29•8% and 62•5% in severe and critically ill patients, respectively. At admission, 73•0% of hospitalized patients had symptoms; most common were cough (42•5%), sputum (28•8%), and fever (20•1%). Only 35•2% of laboratory confirmed patients admitted to the temporary care facility complained of symptoms. Increasing odds of being critically ill was associated with older age (OR 28•93, 95% CI 13•34-62•75 for age >70y, vs. age <50 y; p<0•0001), being male (OR 2•15, 95% CI1•59-2•89; p<0•0001), fever (OR 2•52, 95% CI 1.84-3•45; p<0•0001), and shortness of breath (OR 7•40, 95% CI 5•37-10•19; p<0•0001). Comorbid illness significantly increased risk of critical illness or death. INTERPRETATION: Most cases were discharged as asymptomatic or recovered from mild illness, and only 9•7% developed severe disease requiring oxygen therapy or more. Case fatality rate was 2•9%, and markedly increased in those over age 50. Risk factors such as age, sex, fever, shortness of breath, and underlying disease can be useful in predicting future clinical severity. Additionally, the number of confirmed asymptomatic COVID-19 patients significantly contribute to continued spread. FUNDING: none.

The Effect of Polydeoxyribonucleotide Extracted from Salmon Sperm on the Restoration of Bisphosphonate-Related Osteonecrosis of the Jaw.

Bisphosphonates (BPs) used for treating skeletal diseases can induce bisphosphonate-related osteonecrosis of the jaw (BRONJ). Despite much effort, effective remedies are yet to be established. In the present study, we investigated the feasibility of polydeoxyribonucleotide (PDRN) extracted from salmon sperm for the treatment of BRONJ, in a BRONJ-induced rat model. Compared with BRONJ-induced samples, PDRN-treated samples exhibited lower necrotic bone percentages and increased numbers of blood vessels and attached osteoclast production. Moreover, local administration of PDRN at a high concentration (8 mg/kg) remarkably resolved the osteonecrosis. Findings from this study suggest that local administration of PDRN at a specific concentration may be considered clinically for the management of BRONJ.

The Cocktail Effect of BMP-2 and TGF-ß1 Loaded in Visible Light-Cured Glycol Chitosan Hydrogels for the Enhancement of Bone Formation in a Rat Tibial Defect Model.

Bone tissue engineering scaffolds offer the merits of minimal invasion as well as localized and controlled biomolecule release to targeted sites. In this study, we prepared injectable hydrogel systems based on visible light-cured glycol chitosan (GC) hydrogels containing bone morphogenetic protein-2 (BMP-2) and/or transforming growth factor-beta1 (TGF-ß1) as scaffolds for bone formation in vitro and in vivo. The hydrogels were characterized by storage modulus, scanning electron microscopy (SEM) and swelling ratio analyses. The developed hydrogel systems showed controlled releases of growth factors in a sustained manner for 30 days. In vitro and in vivo studies revealed that growth factor-loaded GC hydrogels have no cytotoxicity against MC3T3-E1 osteoblast cell line, improved mRNA expressions of alkaline phosphatase (ALP), type I collagen (COL 1) and osteocalcin (OCN), and increased bone volume (BV) and bone mineral density (BMD) in tibia defect sites. Moreover, GC hydrogel containing BMP-2 (10 ng) and TGF-ß1 (10 ng) (GC/BMP-2/TGF-ß1-10 ng) showed greater bone formation abilities than that containing BMP-2 (5 ng) and TGF-ß1 (5 ng) (GC/BMP-2/TGF-ß1-5 ng) in vitro and in vivo. Consequently, the injectable GC/BMP-2/TGF-ß1-10 ng hydrogel may have clinical potential for dental or orthopedic applications.