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A relatively loud sound is audible when a vibrator is attached to the aural cartilage. This form of conduction is referred to as cartilage conduction (CC). In Japan, a new type of hearing aid has been developed using CC and has been available in clinical practice since 2017. A clinical study conducted prior to its launch demonstrated its benefits, particularly in patients with aural atresia who were unable to use air conduction hearing aids. Several studies have been published on the benefits of CC hearing aids since their introduction into clinical practice. Most of the patients included in these studies had canal stenosis or aural atresia, and the purchase rates of CC hearing aids in these patients were relatively high. However, the number of patients with canal-open ears was small, with overall poor results in the trials, with the exception of patients with continuous otorrhea. CC hearing aids are considered a good option for compensating for hearing loss in ears with canal stenosis or atresia in both bilateral and unilateral cases. However, CC hearing aids are not currently considered the first choice for patients with a canal-open ear. [ABSTRACT FROM AUTHOR]

Introduction: In this study, we evaluated the differences and measurement accuracy in the force–displacement relationship of the distal radioulnar joint (DRUJ) between patients with triangular fibrocartilage complex (TFCC) injury and healthy controls using force-monitor ultrasonography. Methods: This study included 11 TFCC injury patients and 22 healthy controls. We evaluated differences in the force–displacement relationship of the DRUJ in these patients using force-monitor ultrasonography. Cyclic compression was applied to the dorsal surface of the ulnar head. Distance between the dorsal surface of the distal radius and ulnar head at the DRUJ level was measured in the initial and pressed-down positions. Changes in radioulnar displacement, applied force, and displacement-to-force ratio were measured. Furthermore, we compared the parameters between the affected and unaffected wrists and between TFCC injury patients and controls. Results: The radioulnar displacement and displacement-to-force ratio were significantly larger in the affected wrists than in the unaffected wrists (P = 0.003 and P = 0.02). The affected/unaffected side ratio of radioulnar displacement and displacement-to-force ratio were significantly larger in the TFCC injury patients than in the controls (P = 0.003 and P = 0.02). The area under the curve was 0.82 for the affected/unaffected ratio of the radioulnar displacement. The optimal cutoff value indicated by the receiver-operating characteristic curve for the affected/unaffected ratio of the radioulnar displacement was 1.71; the sensitivity and specificity were 82% and 86%, respectively. Conclusions: Assessing the DRUJ instability with force-monitor ultrasonography may help identify TFCC-injured wrists. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the incidence of laryngeal penetration and aspiration in elderly patients who underwent supracricoid laryngectomy with cricohyoidoepiglottopexy for laryngeal cancer. Method: A retrospective analysis of dynamic videofluoroscopic swallowing studies was performed in patients who had received supracricoid laryngectomy with cricohyoidoepiglottopexy as a treatment for laryngeal cancers. Digital analysis of videofluoroscopic swallowing studies included measurements of displacement and timing related to swallowing safety. Results: Videofluoroscopic swallowing studies from 52 patients were analysed. All participants were male and over 65 years old. Studies were performed five years after surgery. Among 52 videofluoroscopic swallowing studies, analysis showed that elevated pharyngeal constriction ratio (pharyngeal constriction ratio more than 0.0875, odds ratio = 5.2, p = 0.016), reduced pharyngoesophageal sphincter opening time (pharyngoesophageal sphincter open less than 0.6 seconds, odds ratio = 11.6, p = 0.00018) and reduced airway closure time (airway close less than 0.6 seconds, odds ratio = 10.6, p = 0.00057) were significantly associated with aspiration. Conclusion: Deteriorated pharyngeal constriction, shortened airway closure and reduced pharyngoesophageal sphincter opening time are key factors for predicting laryngeal penetration or aspiration after supracricoid laryngectomy with cricohyoidoepiglottopexy. [ABSTRACT FROM AUTHOR]

Cartilage conduction (CC) is a form of conduction that allows a relatively loud sound to be audible when a transducer is placed on the aural cartilage. The CC transmission mechanism has gradually been elucidated, allowing for the development of CC hearing aids (CC-HAs), which are clinically available in Japan. However, CC is still not fully understood. This review summarizes previous CC reports to facilitate its understanding. Concerning the transmission mechanism, the sound pressure level in the ear canal was found to increase when the transducer was attached to the aural cartilage, compared to an unattached condition. Further, inserting an earplug and injecting water into the ear canal shifted the CC threshold, indicating the considerable influence of cartilage-air conduction on the transmission. In CC, the aural cartilage resembles the movable plate of a vibration speaker. This unique transduction mechanism is responsible for the CC characteristics. In terms of clinical applications, CC-HAs are a good option for patients with aural atresia, despite inferior signal transmission compared to bone conduction in bony atretic ears. The advantages of CC, namely comfort, stable fixation, esthetics, and non-invasiveness, facilitate its clinical use. [ABSTRACT FROM AUTHOR]

Background: Plug protuberance occasionally occurs in osteochondral autologous transplantation (OAT). The incongruity of plugs results in poor clinical outcomes, especially in cases of protuberance. However, a surgical procedure to deal with this problem has not been reported. Purpose/Hypothesis: The purpose was to evaluate the efficacy and safety of cartilage resection of elevated plugs, with the hypothesis that patients whose elevated plugs were resected and leveled would achieve clinical outcomes equivalent to those of patients with flush plugs. Study Design: Cohort study; Level of evidence, 3. Methods: Cases (group P) included 22 patients who underwent OAT of the knee and whose plugs showed protuberance greater than 1 mm that was resected with a scalpel to obtain smooth congruity, while controls (group C) included 22 background-matched patients who did not require plug resection. The International Knee Documentation Committee (IKDC) subjective score, IKDC objective grade, and Japanese Orthopaedic Association score for knee osteoarthritis (JOA knee score) were used preoperatively and at the final follow-up (mean ± SD, 49.3 ± 18.1 months). International Cartilage Repair Society (ICRS) Cartilage Repair Assessment was used to evaluate lesion healing during the second-look arthroscopy. Results: IKDC subjective scores of group C (82.5 ± 11.8) and group P (82.1± 15.1) showed no difference at the final follow-up. On postoperative IKDC objective grading, 86% of group C and 82% of group P patients were graded as “nearly normal” or better (P = .639). The mean JOA knee scores of group C (90.9 ± 8.9) and group P (90.1 ± 9.5) did not differ significantly (P = .647). Nine second-look arthroscopies were performed in group C versus 8 in group P, and all patients had plugs that were graded as “nearly normal” or better by the ICRS Cartilage Repair Assessment. Larger plugs tended to be used in those patients who required resection. Conclusion: Resection of the elevated plug surface did not negatively affect patient outcomes in the midterm follow-up period. [ABSTRACT FROM AUTHOR]

Background: Osteochondral lesions of the talar dome (OLTs) involve the articular cartilage and subchondral bone. The subchondral bone plate (SBP) plays a crucial role in cartilage metabolism, and computed tomography (CT) can provide more precise information on subchondral bone. CT image prediction of the histological findings on OLT will be useful to determine the most appropriate therapeutic strategy. Purpose: To evaluate the unique features of the CT findings that relate to the condition of the articular cartilage in OLT. Study Design: Cohort study; Level of evidence, 3. Methods: Thirty ankles in 29 patients who had OLT with an osteochondral fragment were retrospectively reviewed. At surgery, the osteochondral fragment of 19 ankles could be preserved (preservation group) by fixation or drilling, and in the remaining 11 ankles, the osteochondral fragment was removed (excision group). Preoperative CT findings were compared between the 2 groups. Biopsies of the osteochondral fragment from 13 ankles were performed. The relationship between the CT and histological findings were evaluated. Results: The area of lesion in the preservation group was significantly larger than that in the excision group. The CT images of the lesion showed the rate of absorption of the SBP in the preservation group to be lower than that in the excision group. As for the lesion bed absorption, it was higher in the preservation group than in the excision group. All cases in the excision group showed bed sclerosis, compared with 42.1% in the preservation group. The specimens with disruption of the SBP exhibited cartilage degeneration and abundant chondrocyte cloning. OLT with absorption of the SBP on CT showed severe cartilage degeneration, while the remaining SBP on CT showed low-grade cartilage degeneration. Conclusion: This study shows the features of preoperative CT and histological findings in OLT with osteochondral fragments. The condition of the SBP affects the cartilage degeneration. CT findings provide important information for the determination of surgical treatment. [ABSTRACT FROM AUTHOR]

Background: Although osteochondral autograft transplantation (OAT) provides satisfactory outcomes for osteochondral defects, for large defects OAT is often inadequate because of graft availability. Osteochondral allograft transplantation is an alternative treatment for large defects, but this approach is limited by graft storage constraints and carries disease transmission risks. Platelet-rich fibrin (PRF) is a second-generation platelet concentrate, and its positive effect on articular cartilage has been reported. However, the effect of PRF with OAT of osteochondral defects is unknown. Purpose: To compare the effects of OAT with platelet-rich plasma (PRP) and PRF on osteochondral defects in a rabbit model. Study Design: Controlled laboratory study. Methods: Forty-two juvenile rabbits were divided into control, PRP, and PRF groups. In the control and PRP groups, a cylindrical osteochondral defect (5 mm in diameter and 2 mm in depth) was created on the patellar groove, and an osteochondral graft (3.5 mm in diameter and 5 mm in length) harvested from the contralateral side was inserted into the distal portion of the defect. After wound closure, either normal saline or PRP was injected in the knee. In the PRF group, a PRF clot was placed in the defect before grafting. The surgical site was macroscopically and histologically assessed after 3 and 12 weeks. Results: At 3 weeks, the PRF group (n = 8) was macroscopically healed compared with the other 2 groups (control, n = 7; PRP, n = 6) (P < .005). Histologically, osteochondral graft cartilage of the PRF group had normal cellularity and higher amounts of safranin O staining relative to the other 2 groups (P < .005). At 12 weeks, all 3 groups (n = 8 per group) were macroscopically healed with normal or nearly normal cartilage, and osteochondral graft cartilage was histologically hyaline cartilage. In contrast, the PRF group healed with hyaline-like cartilage at nongrafted defects, whereas the other 2 groups healed with fibrocartilage (P < .001). Conclusion: OAT with PRF maintained hyaline cartilage, and the nongrafted defect healed with hyaline-like cartilage. Clinical Relevance: PRF has the potential to improve clinical outcomes of OAT used to treat osteochondral lesions. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to compare the levels of bone and cartilage metabolism markers in the synovial fluid of the hip joint between patients with secondary OA due to osteonecrosis of the femoral head (ONFH), rapidly destructive arthrosis (RDA) and developmental dysplasia of the hip (DDH).Methods. We studied 70 synovial fluid samples obtained from 57 patients with ONFH (mean age 46 years, 34 males, 23 females), 21 samples obtained from 21 patients with RDA (mean age 70 years, 2 males, 19 females) and 20 samples obtained from 20 patients with DDH (mean age 56 years, 2 males, 18 females). The levels of bone alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase 5b (TRACP-5b), as bone metabolism markers, and matrix metalloproteinase 3 (MMP-3) and keratan sulphate (KS), as cartilage metabolism markers, were analysed.Results. The levels of BAP, MMP-3 and KS were significantly higher in the ONFH group than in the RDA and DDH groups. The levels of TRACP-5b were highest in the RDA group. The levels of BAP in the ONFH group after the development of osteoarthritic changes were significantly lower than those observed in earlier stages. In comparisons between the samples obtained from each group with a terminal condition, the ONFH samples exhibited significantly higher MMP-3 and KS levels, while the TRACP-5 levels were highest in the RDA group.Conclusion. The ONFH patients showed a relatively bone formative condition before the osteoarthritic stage and maintained a higher rate of cartilage turnover throughout several stages compared with the RDA and DDH patients. RDA patients were characterized by a significantly high osteoclast activity. [ABSTRACT FROM PUBLISHER]

Objective. Relapsing polychondritis (RPC) is relatively rare and early diagnosis is difficult. We investigated the utility of fluorodeoxyglucose (FDG)-PET/CT for the diagnosis of RPC and evaluation of disease activity.Methods. Five RPC patients undergoing FDG-PET/CT in our hospital between 2006 and 2012 were studied. Eight RPC cases examined by PET reported in the literature were also assessed. Data from a total of 13 patients were analysed.Results. Typical FDG accumulation was noted in the tracheobronchial trees of nine patients, the costal cartilage of five, joints of five, larynx of four, nasal cavity/paranasal sinuses of three, auricles of three, lymph nodes of three and the aorta of one. One patient showed nasal chondritis on a PET scan despite the absence of nasal changes on physical examination. Of five patients with costochondritis, four remained asymptomatic. Of nine patients with airway FDG accumulation, eight developed respiratory symptoms and all had CT abnormalities. In the other patient, airway FDG accumulation was evident despite the absence of airway symptoms and a lack of abnormalities in the respiratory function test and CT. PET also revealed bronchial chondritis in asymptomatic patients. The mean maximum standardized uptake values (SUVmax) of the upper and lower airways was 5.79 (s.d. 2.87) and 6.47 (s.d. 4.08), respectively. In five patients with a PET after treatment, FDG accumulation had diminished with symptomatic and inflammatory improvement.Conclusion. FDG-PET/CT is a potentially powerful tool for the early diagnosis of RPC, especially in patients without easily biopsied organ involvement. This modality also facilitates evaluation of disease extent and disease activity during treatment. [ABSTRACT FROM PUBLISHER]

Objective Tofacitinib (CP-690,550) is a novel JAK inhibitor that is currently in clinical trials for the treatment of rheumatoid arthritis (RA). The aim of this study was to examine the effects of tofacitinib in vitro and in vivo in RA, in order to elucidate the role of JAK in the disease process. Methods CD4+ T cells, CD14+ monocytes, and synovial fibroblasts (SFs) were purified from the synovium and peripheral blood of patients with RA and were evaluated for the effect of tofacitinib on cytokine production and cell proliferation. For in vivo analysis, synovium and cartilage samples obtained from patients with RA were implanted in immunodeficient mice (SCID-HuRAg mice), and tofacitinib was administered via an osmotic minipump. Results Tofacitinib treatment of CD4+ T cells originating from synovium and peripheral blood inhibited the production of interleukin-17 (IL-17) and interferon-γ (IFNγ) in a dose-dependent manner, affecting both proliferation and transcription, but had no effect on IL-6 and IL-8 production. Tofacitinib did not affect IL-6 and IL-8 production by RASFs and CD14+ monocytes. However, conditioned medium from CD4+ T cells cultured with tofacitinib inhibited IL-6 production by RASFs and IL-8 production by CD14+ monocytes. Treatment of SCID-HuRAg mice with tofacitinib decreased serum levels of human IL-6 and IL-8 and markedly suppressed invasion of synovial tissue into cartilage. Conclusion Tofacitinib directly suppressed the production of IL-17 and IFNγ and the proliferation of CD4+ T cells, resulting in inhibition of IL-6 production by RASFs and IL-8 production by CD14+ cells and decreased cartilage destruction. In CD4+ T cells, presumably Th1 and Th17 cells, JAK plays a crucial role in RA synovitis. [ABSTRACT FROM AUTHOR]

Conclusion: This new regenerative therapy shows great potential for the treatment of stenosis of the trachea and/or cricoids (STC). Objectives: To estimate the potential of tissue-engineered artificial trachea (AT) for treatment of STC in clinical applications. We previously reported that AT was a useful material for implantation into a tracheal defect after resection of cancer. There are many causes of stenosis of the respiratory tract and STC is particularly difficult to treat. Methods: The AT was a spiral stent composed of Marlex mesh made of polypropylene and covered with collagen sponge made from porcine skin. Three patients with STC were treated by this tissue-engineering method. All of them suffered from STC caused by long endotracheal intubations. They underwent a two-stage operation. In the first operation, after resection of the stenotic regions, the edge of the tracheal cartilage was sutured to the edge of the skin. The tracheal lumen was exposed and a T-shaped cannula was inserted into the large tracheostoma. At 3 weeks to 2 months after the first operation, the trachea and skin were separated. The trimmed AT with venous blood and basic fibroblast growth factor (b-FGF) was then implanted into the cartilage defect. Results: Postoperatively, all patients were able to breathe easily and had no discomfort in their daily activities. Six months after the second operation, we observed enough air space in the trachea and cricoid by computed tomography (CT) imaging and fiber endoscopy. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is one of the most common musculoskeletal disorders and is characterized by degeneration of articular cartilage. Sulfation of extracellular ma-trix proteins in articular cartilage is an important step in maintaining normal cartilage metabolism. Two sulfation-related genes have been reported as the causal genes of severe chondrodysplasias: mutations in PAPSS2 (3′-phosphoadenosine 5′-phosphosulfate synthase 2) cause spondylo-epimetaphyseal dysplasia (SEMD), and mutations in SLC26A2 (solute carrier family 26, member 2) cause diastrophic dysplasia. Given their critical roles in cartilage metabolism and the severe phenotypes that result from mutations in these genes, we examined PAPSS2 and SLC26A2 as candidate susceptibility loci for OA. We identified sequence polymorphisms in the coding and core promoter regions of these genes and analyzed their potential association with knee OA within the Japanese population. Ten sequence polymorphisms were detected in PAPSS2 and five in SLC26A2. An association analysis showed suggestive association of one minor polymorphism in the promoter region of SLC26A2. This 4-bp adenine deletion allele, del4A, was over-represented in knee OA (P = 0.043, odds ratio = 3.43) and is thought to confer a minor susceptibility to knee OA within the Japanese population. Haplotype analysis showed no evidence of association with the two genes, however, excluding them as major susceptibility loci for knee OA. [ABSTRACT FROM AUTHOR]

Examines the concepts in tissue engineering technique for repair of cartilage defect in Japan. Preparation of cartilage-like tissue; Procedure for the repair of cartilage defect; Transplantation of cartilage-like tissue.

The authors discuss a case of a 63-year-old woman who presented with chondritis, polyarthritis, and dyspnoea. On examination the patient was diagnosed with relapsing polychondritis; she was given prednisolone (PSL) which improved her condition. However, she developed thrombocytopenia and was diagnosed with immune thrombocytopenic purpura (ITP); this was a unique case of relapsing polychondritis coexisting with ITP; methylprednisolone (mPSL), platelet transfusions and antibiotics improved her.

Recently, regenerative medicine has attracted attention worldwide and also in Japan. Several guidelines on regenerative medicine have been released from the Japanese regulatory agency. Within the guidelines, Japan Tissue Engineering Co., Ltd. has been developing tissue-engineered products of cultured epidermis, cartilage and cornea using autologous cells. In this paper, we describe the industrialization of regenerative medicine as well as regulations based on our experiences of the culture cartilage development.

Mutations in the cartilage oligomeric matrix protein (COMP) gene cause two skeletal dysplasias, pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), which are autosomal dominant disorders characterized by short-limb dwarfism. We report novel mutations of the COMP gene identified in two sporadic Japanese cases of PSACH. One had a novel single base substitution in exon 9, resulting in a missense mutation of Gly309Arg in the second type 3 repeat of COMP protein. The other patient had no mutations in any of the exonic sequences of the gene, but she did have a novel base substitution in intron 13. Although this mutation was not located in the conserved sequences for splicing donor and acceptor sites, it might disturb the precise splicing of the COMP transcripts, resulting in the production of abnormal protein with defective last type 3 repeat and/or C-terminal domain.

Hind III restriction fragment length polymorphism (RFLP) in the cartilage-specific type II collagen gene was studied in a sample of 135 persons randomly selected from the Japanese population. Localization of the Hind III site was determined by the dideoxy method. Based on this sequence, a pair of primers was designed and a polymerase chain reaction (PCR) was carried out. The Hind III allele had a frequency of 0.52 in the Japanese. The genotype digested by Hind III, (++) genotype was present with a frequency of 16.9%, (+-) was present in 70.0% and (--) was present in 13.1%, showing a lower rate of the (--) genotype in the Japanese compared to the Finnish. The difference was statistically significant, tested by chi 2 analysis (p < 0.0001). The present study is the first to report a race-dependent variance in Hind III RFLP on the type II collagen gene.