Decellularized allogeneic cartilage paste with human costal cartilage and crosslinked hyaluronic acid-carboxymethyl cellulose carrier augments microfracture for improved articular cartilage repair.

Articular cartilage lacks natural healing abilities and necessitates surgical treatments for injuries. While microfracture (MF) is a primary surgical approach, it often results in the formation of unstable fibrocartilage. Delivering hyaline cartilage directly to defects poses challenges due to the limited availability of autologous cartilage and difficulties associated with allogeneic cartilage delivery. We developed a decellularized allogeneic cartilage paste (DACP) using human costal cartilage mixed with a crosslinked hyaluronic acid (HA)-carboxymethyl cellulose (CMC) carrier. The decellularized allogeneic cartilage preserved the extracellular matrix and the nanostructure of native hyaline cartilage. The crosslinked HA-CMC carrier provided shape retention and moldability. In vitro studies confirmed that DACP did not cause cytotoxicity and promoted migration, proliferation, and chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells. After 6 months of implantation in rabbit knee osteochondral defects, DACP combined with MF outperformed MF alone, demonstrating improved gait performance, defect filling, morphology, extracellular matrix deposition, and biomechanical properties similar to native cartilage. Thus, DACP offers a safe and effective method for articular cartilage repair, representing a promising augmentation to MF. STATEMENT OF SIGNIFICANCE: Directly delivering hyaline cartilage to repair articular cartilage defects is an ideal treatment. However, current allogeneic cartilage products face delivery challenges. In this study, we developed a decellularized allogeneic cartilage paste (DACP) by mixing human costal cartilage with crosslinked hyaluronic acid (HA)-carboxymethyl cellulose (CMC). DACP preserves extracellular matrix components and nanostructures similar to native cartilage, with HA-CMC ensuring shape retention and moldability. Our study demonstrates improved cartilage repair by combining DACP with microfracture, compared to microfracture alone, in rabbit knee defects over 6 months. This is the first report showing better articular cartilage repair using decellularized allogeneic cartilage with microfracture, without the need for exogenous cells or bioactive substances.

High-Intensity Focused Ultrasound Therapy Versus Coblation for the Treatment of Inferior Turbinate Hypertrophy: A Clinical Trial.

OBJECTIVES: To compare the efficacy and safety of high-intensity focused ultrasound (HIFU) therapy with coblation for the treatment of inferior turbinate hypertrophy (ITH). METHODS: In this randomized controlled clinical trial, 20 patients underwent inferior turbinate surgery, which consisted of either HIFU or coblation therapy. Efficacy, safety, and tolerability were evaluated by subjective symptom scores, acoustic rhinometry, and nasal endoscopy. RESULTS: The modified nasal obstruction symptom evaluation (NOSE) score and nasal obstruction visual analog scale (NO-VAS) significantly decreased in both groups 12 weeks postoperatively. The between-group differences in the evaluation scores were not statistically significant. On nasal endoscopy, the HIFU patients showed improvements in mucosal swelling sooner than the patients undergoing coblation therapy. Nasal crusting significantly increased in the patients undergoing coblation compared to the patients undergoing HIFU therapy until postoperative week 4. Mucosal preservation was superior in the HIFU patients. Although HIFU was less painful than coblation therapy during the procedure, the difference was not significant (4.9 vs. 6.3, P=0.143). The difference in global satisfaction between the two groups was not statistically significant, although satisfaction was slightly higher among the HIFU patients than among the coblation patients (4.6 vs. 4.1, P=0.393). CONCLUSION: HIFU provided results similar to those of coblation therapy for patients with nasal obstruction due to ITH, but HIFU therapy caused less discomfort during the procedure. HIFU therapy appears to be a good noninvasive alternative to the current surgical modalities for ITH.

Development of High-Intensity Focused Ultrasound Therapy for Inferior Turbinate Hypertrophy.

OBJECTIVES: Inferior turbinate (IT) hypertrophy is the main cause of chronic nasal obstruction. We developed a high-intensity focused ultrasound (HIFU) ablation device to treat patients with IT hypertrophy. METHODS: First, computed tomography images of patients with no evidence of sinonasal disease were evaluated to measure and compare the IT, medial mucosal thickness (MT), and space between the nasal septum and IT according to clinical characteristics such as septal deviation. A HIFU prototype was developed based on the above human anatomical studies. The experimental study was performed in five pigs; the nasal volume and histological changes at 1 and 4 weeks postoperatively were evaluated to compare the efficacy of HIFU turbinoplasty with that of radiofrequency turbinoplasty and a control group. RESULTS: The mean medial MT of the anterior, middle, and posterior portions of the IT were 4.66±1.14, 4.23±0.97, and 6.17±1.29 mm, respectively. The mean medial space was 2.65±0.79 mm. The diameter and focal depth of the prototype were 4 mm and 3 mm, respectively. HIFU showed no postoperative complications, including bleeding or scar formation. After HIFU treatment, the nasal volume increased by 196.62 mm3 (7.8%) and 193.74 mm3 (8.3%) at 1 week and 4 weeks, compared with the increase of 87.20 mm3 (3.1%) and 213.81 mm3 (9.0%), respectively, after radiofrequency therapy. A qualitative histological analysis after radiofrequency turbinoplasty showed epithelial layer disruption at 1 week and increased fibrosis, along with decreased glandular structure, at 4 weeks. The HIFU group had an intact epithelial layer at 1 week postoperatively. However, significant differences were observed at 4 weeks, including increased fibrosis and decreased glandular structure. CONCLUSION: The efficacy and safety of HIFU turbinoplasty were demonstrated in an animal study. Our. RESULTS: warrant further human clinical trials.

Efficacy and safety of rupatadine fumarate in the treatment of perennial allergic rhinitis: A multicenter, double-blinded, randomized, placebo-controlled, bridging study in Koreans.

BACKGROUND: The efficacy of rupatadine for the treatment of AR has been confirmed in numerous clinical studies, however there are very few studies on asian patients. OBJECTIVE: To assess the safety and efficacy of rupatadine fumarate in the treatment of Korean perennial allergic rhinitis (PAR) patients. METHODS: A multicenter, double-blind, randomized, placebo-controlled, comparative study of rupatadine fumarate and bepotastine besilate was conducted. Each group was administered rupatadine, bepotastine or placebo for 4 weeks. Primary parameters for efficacy included morning and evening symptom reduction from baseline at 4 weeks. Treatment safety and tolerability were evaluated according to a self-reported incidence and type of adverse events at each follow up visit. RESULTS: Rupatadine showed a significant reduction in symptoms at morning and evening evaluations, in both 5TSS (-5.69, P < 0.0006) and 4NTSS (-4.74, P < 0.0015) compared to placebo. There was a significant reduction from baseline for 5TSS (-65.4%, P = 0.002) and 4NTSS (-63.7%, P = 0.003) with rupatadine compared with placebo. At evening evaluations, there were significant reductions of 5TSS (-63.2%, P = 0.009) and 4NTSS (-61.6%, P = 0.013) for the rupatadine group. Compared with bepotastine, rupatadine showed greater reduction in the morning symptoms at 4 weeks. When individual symptoms were assessed with 12-hour reflective mean daily symptom score, rupatadine showed better efficacy than placebo in sneezing (P = 0.016) and rhinorrhea (P = 0.097). The rate of adverse events showed no statistical significance. CONCLUSIONS: Rupatadine is a safe and effective treatment option for Korean PAR patients and possibly a better choice over bepotastine for controlling morning symptom.

Health-related quality of life after transoral robotic thyroidectomy in papillary thyroid carcinoma.

BACKGROUND: Health-related quality of life after transoral robotic thyroidectomy has not been evaluated thoroughly. The purpose of this study was to compare health-related quality of life after transoral robotic thyroidectomy and after conventional thyroidectomy. METHODS: This study is a prospective, cross-sectional, and observational study of 114 patients who underwent transoral robotic thyroidectomy (57 patients) or conventional transcervical thyroidectomy (57 patients) for the treatment of papillary carcinoma. We used 2 questionnaires: the University of Washington Quality of Life questionnaire for head and neck cancer and the thyroid cancer-specific Quality of Life questionnaire (Thyroid Version). The survey was performed preoperatively, and 3 months and 1 year after thyroidectomy. RESULTS: Mean scores for neck appearance were higher after surgery in the transoral robotic thyroidectomy group than the conventional group at both 3 months and 1 year. Anxiety was significantly improved after surgery in both groups. Total scores for health-related quality of life after surgery were similar in both groups. Health-related quality of life and overall quality of life over the previous 7 days as measured by the University of Washington Quality of Life questionnaire were significantly better at 1 year than in the preoperative period in both groups. Before surgery, patients in the both groups regarded anxiety and mood as the most important aspects of health-related quality of life. After surgery, patients in the transoral robotic thyroidectomy group identified anxiety, mood, and speech as the most significant issues, while patients in the conventional group selected anxiety, mood, and neck appearance. CONCLUSION: Quality of life related to neck appearance is higher after transoral robotic thyroidectomy than after transcervical thyroidectomy. However, total scores for health-related quality of life did not differ in the 2 groups after surgery.

A Patient Presentation of Large Septal Perforation Repair Using Inferior Based Contra-Lateral Nasal Floor Flap, a New Surgical Technique for Large Septal Perforation.

ABSTRACT: A nasal septal perforation is a defect of cartilage, bone, or mucosa of nasal septum, which is caused by previous septal surgery, trauma, chemicals, inflammatory disease, or drugs. If conservative managements, such as nasal saline irrigation or ointments, are not effective, surgical treatment can be considered. Various methods for the reconstruction of nasal septal perforation were reported, such as local flaps, free flaps, autografts, allografts, or xenografts. However, there is no standardized method due to low success rate and high recurrence rate, especially in large perforations. The authors report a successful repair case of large anteroinferior nasal septal perforation, using inferior based contralateral nasal floor flap. The authors believe that our method is an effective way to repair large nasal septal perforation and to minimalize donor site morbidity, without using other allografts.

Treatment Strategy for Odontogenic Sinusitis.

BACKGROUND: The treatment options for odontogenic sinusitis (OS) include medical management including antibiotics and saline nasal irrigation, endoscopic sinus surgery (ESS), and dental treatment. OBJECTIVE: The purpose of this study was to evaluate whether OS caused by dental caries and periapical abscess can be cured by dental treatment alone and which patients should consider surgery early. METHODS: A total of 33 patients with OS caused by dental caries and periapical abscess were enrolled. Patients with OS caused by dental implants, trauma, surgery, or tooth extraction were excluded. All patients were initially treated with dental treatment and medical management without ESS. The patients were divided into two groups according to the results of dental treatment and multiple clinical parameters were compared between the two groups. RESULTS: Among the 33 enrolled patients, 22 patients (67%) were cured with dental and medical management, and 11 patients (33%) required ESS after the failure of dental and medical management. Based on the multivariate analysis results, patients who were smokers (OR 33.4) and had a higher Lund-Mackay score on CT (OR 2.0) required ESS after the failure of dental and medical treatment. CONCLUSIONS: Two-thirds of the patients with OS caused by dental caries and periapical abscess were cured with dental treatment and medical management without ESS. We recommend dental treatment and medical management first in OS caused by dental caries and periapical abscess. However, we recommend early ESS in patients with smoking habits and severe CT findings of the sinus.

Impact of Particulate Matter on the Clinical Characteristics of Rhinitis.

OBJECTIVES/HYPOTHESIS: To investigate the association between PM10 concentration and the severity of rhinitis symptoms. STUDY DESIGN: Retrospective cohort study. METHODS: Retrospective analysis of the data of 590 participants prospectively enrolled in a regional population-based cohort study was performed. The ambient PM10 concentrations were measured at 12 different observatories located in three cities. All participants were screened for allergic sensitization by skin prick tests and asked to complete questionnaires regarding their rhinitis symptoms. The severity and duration of rhinitis were analyzed and compared at different levels of PM10 concentration. RESULTS: On multivariate analysis, the PM10 concentration significantly correlated with the severity of symptoms when adjusting for age, sex, presence of sensitized allergen, region, and the time of enrolment (ß = 0.102, P = .021). Positive correlation was found between PM10 concentration and the duration of allergic rhinitis symptoms (ß = 0.082, P = .077). In the stratified analysis on the atopic status, there was a significant correlation between PM10 concentration and the severity and duration of rhinitis symptoms in those without allergic sensitization (ß = 0.104; P = .032 and ß = 0.104; P = .011, respectively). CONCLUSIONS: The significant correlation between the annual PM10 concentration and severity and duration of rhinitis symptoms suggests the necessity of intensive management of rhinitis patients exposed to elevated levels of ambient PM10 concentration. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E1753-E1759, 2021.

The clinical efficacy of relocation pharyngoplasty to improve retropalatal circumferential narrowing in obstructive sleep apnea patients.

Lateral pharyngeal wall appears to be a critical culprit of obstructive sleep apnea (OSA) subjects and relocation pharyngoplasty has been expected to be a promising surgical option to correct retropalatal circumferential narrowing in OSA patients. The purpose of our study is to evaluate the therapeutic outcomes of relocation pharyngoplasty and its clinical effectiveness in OSA patients with retropalatal circumferential narrowing. We performed relocation pharyngoplasty combined with nasal surgery in 133 OSA patients with the following characteristics: apnea-hypopnea index (AHI) over 10, retropalatal circumferential narrowing greater than grade I when awake, and redundant soft tissue around the lateral pharyngeal wall. The analysis of surgical success rate was performed with the data of 68 subjects who underwent pre and postoperative polysomnography. The objective success rate of relocation pharyngoplasty was 52.9%, and significant reduction of mean AHI with improvement of lowest SpO2 was seen in 69% of patients 3 months after the surgery. The median AHI was decreased from preoperative 37.3 to postoperative 21.4. Median lowest SpO2 changed from 78.4 to 84.1%. Total sleep time, daytime sleepiness, and visual analogue scale for snoring showed improvement as well. Postoperative complications including pain or bleeding were minimal in 133 subjects and a few patients complained of subtle taste loss. Our data demonstrate that relocation pharyngoplasty can be a favorable surgical option fighting against retropalatal circumferential narrowing.

Indications for and Outcomes of Expansion Sphincter Pharyngoplasty to Treat Lateral Pharyngeal Collapse in Patients With Obstructive Sleep Apnea.

IMPORTANCE: The lateral pharyngeal wall is recognized as an important site of upper airway collapse during sleep in patients with obstructive sleep apnea (OSA), and expansion sphincter pharyngoplasty (ESP) may have promising clinical utility in patients with OSA and lateral pharyngeal wall collapse. OBJECTIVES: To evaluate the therapeutic outcomes of ESP in conjunction with other surgical procedures and to investigate indications for ESP in patients with OSA. DESIGN, SETTING, AND PARTICIPANTS: Cohort study of 63 patients with OSA diagnosed with lateral pharyngeal collapse under drug-induced sleep endoscopy who underwent ESP combined with tonsillectomy, uvuloplasty, or nasal surgery at Seoul National University Hospital in Seoul, Korea, between March 1, 2015, and December 1, 2016. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the change in the apnea-hypopnea index (AHI) after surgery (AHI represents the number of apnea-hypopnea events per hour). Other outcome measures were differences in the surgical response rates, lowest oxygen saturation, subjective visual analog scale scores for snoring and apnea, and Epworth Sleepiness Scale score. RESULTS: Fifty of the 63 patients (79%) were male; the mean age was 42.1 (range, 20-54) years, and the mean body mass index (calculated as weight in kilograms divided by height in meters squared) was 27.6 (range, 19.0-32.1). Expansion sphincter pharyngoplasty was performed in patients with OSA with an AHI greater than 15 events per hour, more than 75% retropalatal circumferential narrowing when awake, and narrowed oropharynx due to bulky soft tissue around the lateral pharyngeal wall. In 42 of the 63 patients (67%), ESP was objectively successful in correcting lateral pharyngeal collapse; there was a significant reduction in mean AHI from 35.5 to 17.3 (mean difference, 18.1; 95% CI, 16.3-20.0) and improvement of the lowest mean (SD) oxygen saturation measurement from 78.2% (21.3%) to 86.4% (10.6%) (mean difference, 8.60%; 95% CI, 6.60%-10.60%) 6 months after the operation. The rate of postoperative complications, including pain and bleeding, was minimal after ESP, and a few patients reported an abnormal sensation around the soft palate and swallowing difficulty after ESP. CONCLUSIONS AND RELEVANCE: Expansion sphincter pharyngoplasty appears to be a promising surgical technique to reduce lateral pharyngeal collapse in patients with moderate or severe OSA. Clinical data suggest that both severe palatal circumferential narrowing and bulky lateral pharyngeal tissue are favorable surgical indications for ESP in patients with OSA.

Photoconversion Mechanisms and the Origin of Second-Harmonic Generation in Metal Iodates with Wide Transparency, NaLn(IO3)4 (Ln = La, Ce, Sm, and Eu) and NaLa(IO3)4:Ln3+ (Ln = Sm and Eu).

Four new metal iodates, namely, NaLn(IO3)4 (Ln = La, Ce, Sm, and Eu), and a series of NaLa(IO3)4:Ln3+ (Ln = Sm and Eu) solid solutions were synthesized through hydrothermal reactions. The structures of the title compounds are similar to that of NaY(IO3)4 crystallizing in the acentric monoclinic space group Cc. The iodate materials reveal layered structures composed of LnO8 square antiprisms and IO3 polyhedra, in which each layer is connected by the I···O interactions. NaLa(IO3)4 suggests a great potential as a matrix for optical source attributed to its acentricity and broad transparency from visible to mid-IR region. The photoluminescence properties depending on the concentration of Sm3+ reveal that NaLa(IO3)4:Sm3+ undergoes a self-quenching relaxation over 7 mol % of Sm3+ by dipole-quadrupole interactions. Attributable to the asymmetric coordination environment of Ln3+, stronger electric dipole transitions compared to magnetic dipole transitions were observed for both compounds. In addition, the materials exhibit strong second-harmonic generation (SHG) responses and are type I phase-matchable. The structural origin of the SHG properties for the reported iodates is elucidated.

Augmentation Rhinoplasty With Silicone Implant Covered With Acellular Dermal Matrix.

BACKGROUND: Alloplastic materials are a mainstay in Asian rhinoplasty. However, the outline of alloplastic implants can become conspicuous over time in rhinoplasty patients, which is a significant cause for revision. In revision rhinoplasty, alloplastic materials can remain a viable and affordable option in Asian patients. The acellular dermal matrices (ADM) are often used to interface between the silicone material and the skin envelope. This study assesses histologic changes following implantation of ADM-covered silicone material in rats. METHODS: To demonstrate differences at the histologic level, silicone blocks with and without ADM were implanted in the subcutaneous plane of 10 rats. These implants were harvested after 9 weeks and examined histologically for capsule thickness and myofibroblast activity. RESULT: In the in vivo study, the presence of ADM was associated with significantly decreased capsule thickness and myofibroblast activity around the implant and maintained the structure of ADM well. CONCLUSION: The authors suggest that using the ADMs to cover silicone implants can be an alternative method for decreasing the visibility of implant contour, by the prevention of capsular contracture and the addition of a soft tissue layer to the dorsal skin envelope.

Fermented Rhizoma Atractylodis Macrocephalae alleviates high fat diet-induced obesity in association with regulation of intestinal permeability and microbiota in rats.

Accumulating evidence suggests the anti-inflammatory and anti-obesity activities of Rhizoma Atractylodis Macrocephalae (RAM). Here, we evaluated the anti-obesity impact of unfermented (URAM) versus fermented RAM (FRAM) using both in vitro and in vivo models. Both URAM and FRAM exhibited marked anti-inflammatory, anti-adipogenic, and anti-obesity activities, and modulation of the gut microbial distribution. However, FRAM, compared to URAM, resulted in more efficient suppression of NO production and normalization of transepithelial electrical resistance in LPS-treated RAW 264.7 and HCT 116 cells, respectively. Compared to URAM, FRAM more effectively reduced the adipose tissue weight; ameliorated the serum triglyceride and aspartate transaminase levels; restored the serum HDL level and intestinal epithelial barrier function in the LPS control group. The relative abundance of Bifidobacterium and Akkermansia as well as Bacteriodetes/Firmicutes ratio in the gut of the LPS control group was significantly enhanced by both URAM and FRAM. However, FRAM, but not URAM, resulted in a significant increase in the distribution of Bacteriodetes and Lactobacillus in the gut of the HFD + LPS group. Our results suggest that FRAM with probiotics can exert a greater anti-obesity effect than URAM, which is probably mediated at least in part via regulation of the intestinal microbiota and gut permeability.

Small GTPase RhoE/Rnd3 is a critical regulator of Notch1 signaling.

Aberrations of Notch signaling have been implicated in a variety of human cancers. Oncogenic mutations in NOTCH1 are common in human T-cell leukemia and lymphomas. However, loss-of-function somatic mutations in NOTCH1 arising in solid tumors imply a tumor suppressor function, which highlights the need to understand Notch signaling more completely. Here, we describe the small GTPase RhoE/Rnd3 as a downstream mediator of Notch signaling in squamous cell carcinomas (SCC) that arise in skin epithelia. RhoE is a transcriptional target of activated Notch1, which is attenuated broadly in SCC cells. RhoE depletion suppresses Notch1-mediated signaling in vitro, rendering primary keratinocytes resistant to Notch1-mediated differentiation and thereby favoring a proliferative cell fate. Mechanistic investigations indicated that RhoE controls a key step in Notch1 signaling by mediating nuclear translocation of the activated portion of Notch1 (N1IC) through interaction with importins. Our results define RhoE as a Notch1 target that is essential for recruitment of N1IC to the promoters of Notch1 target genes, establishing a regulatory feedback loop in Notch1 signaling. This molecular circuitry may inform distinct cell fate decisions to Notch1 in epithelial tissues, where carcinomas such as SCC arise.

Discovery of a potent and selective DDR1 receptor tyrosine kinase inhibitor.

The DDR1 receptor tyrosine kinase is activated by matrix collagens and has been implicated in numerous cellular functions such as proliferation, differentiation, adhesion, migration, and invasion. Here we report the discovery of a potent and selective DDR1 inhibitor, DDR1-IN-1, and present the 2.2 Å DDR1 co-crystal structure. DDR1-IN-1 binds to DDR1 in the 'DFG-out' conformation and inhibits DDR1 autophosphorylation in cells at submicromolar concentrations with good selectivity as assessed against a panel of 451 kinases measured using the KinomeScan technology. We identified a mutation in the hinge region of DDR1, G707A, that confers >20-fold resistance to the ability of DDR1-IN-1 to inhibit DDR1 autophosphorylation and can be used to establish what pharmacology is DDR1-dependent. A combinatorial screen of DDR1-IN-1 with a library of annotated kinase inhibitors revealed that inhibitors of PI3K and mTOR such as GSK2126458 potentiate the antiproliferative activity of DDR1-IN-1 in colorectal cancer cell lines. DDR1-IN-1 provides a useful pharmacological probe for DDR1-dependent signal transduction.

Expression of the p53 target CDIP correlates with sensitivity to TNFα-induced apoptosis in cancer cells.

TNFα is a pleiotropic cytokine that signals for both survival and apoptotic cell fates. It is still unclear that the dual role of TNFα can be regulated in cancer cells. We previously described an apoptotic pathway involving p53→CDIP→TNFα that was activated in response to genotoxic stress. This pathway operated in the presence of JNK activation; therefore, we postulated that CDIP itself could sensitize cells to a TNFα apoptotic cell fate, survival, or death. We show that CDIP mediates sensitivity to TNFα-induced apoptosis and that cancer cells with endogenous CDIP expression are inherently sensitive to the growth-suppressive effects of TNFα in vitro and in vivo. Thus, CDIP expression correlates with sensitivity of cancer cells with TNFα, and CDIP seems to be a regulator of the p53-mediated death versus survival response of cells to TNFα. This CDIP-mediated sensitivity to TNFα-induced apoptosis favors pro- over antiapoptotic program in cancer cells, and CDIP may serve as a predictive biomarker for such sensitivity.