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Purpose: If the primary suture is difficult due to the large size of a tendon defect, reconstruction of the defective tendon is attempted through tendon transfer or tendon graft. The Pulvertaft technique is most commonly used, but it increases bulk and friction, and it could cause adhesion formation. In order to overcome these problems, we aimed to introduce a new technique.Methods: We retrospectively reviewed 22 patients who underwent tendon reconstruction using the modified Pulvertaft technique due to tendon defects from January 2016 to December 2021. An abbreviated version of the original DASH (Disabilities of Arm, Shoulder and Hand) outcome measure (QuickDASH) was measured 3 months after surgery. Until the final follow-up observation, tendon rerupture, infection, tendon-related complications (quadriga effect, motion limitation due to bulky size of the suture site), and contracture were measured. QuickDASH was compared according to the cause of the tendon defect and the type of operation using the Mann-Whitney test.Results: The mean QuickDASH score measured 3 months after surgery was 10.42±7.83. No statistically significant difference in the QuickDASH score was found between patients who underwent tendon transfer and those who underwent tendon grafts (p=0.988). Rerupture occurred in 1 case, and there were no cases of infection, tendon-related complications (quadriga effect, motion limitation due to bulky size of the suture site), or contracture.Conclusion: The orthogonal passing-through suture technique could be a new alternative to the tendon reconstruction technique.

Among the various intraoperative neurophysiologic monitoring (IONM) techniques, transcranial motor-evoked potential (Tc-MEP) has recently become the most widely used method to monitor motor function. However, we often find that Tc-MEP is not sufficiently detected at the start of surgery. Therefore, we aimed to analyze the reasons and risk factors for not detecting sufficient baseline signal of Tc-MEP from the beginning of spinal surgery.We categorized IONM data from 1058 patients who underwent spine surgeries at a single institution from 2014 to 2020 and categorized them into 2 groups: 1) "poor MEP" if Tc-MEP could not be sufficiently obtained and 2) "normal MEP" if Tc-MEP could be sufficiently obtained from the surgery. We analyzed the patient's age, gender, underlying disease, operation type, level numbers, baseline motor function, existence of pathologic reflex, myelopathy, and duration from the onset and clinical diagnosis.The rate of failure to obtain sufficient baseline Tc-MEP signals in spine surgery was 21.8% (231/1058). Multivariate analysis showed significant associations of existence of diabetes mellitus, myelopathy, thoracic spine surgery, baseline motor deficit and tumor, and trauma disease with loss of meaningful and interpretable signals in baseline Tc-MEP (P0.05). Only 15 of 231 patients (6.4%) showed a trend of signal recovery after decompression procedures.Various factors (myelopathy, diabetes mellitus, thoracic surgery, baseline motor deficit, tumor, and trauma) were closely related to not obtaining sufficient baseline signals for Tc-MEP. When operating on patients with these considerations, we need to consider the efficacy and usefulness of Tc- MEP.

We evaluated the efficacy and safety of postoperative radiotherapy (PORT) for differentiated thyroid cancer (DTC) with high risk features.This retrospective study analyzed 187 patients treated for DTC from 1985 to 2019. DTC referred to nonanaplastic thyroid cancer originating from follicular cells. PORT was defined as the administration of external beam radiation to the thyroid and regional lymph nodes following surgery for initially diagnosed DTC. The patients were included in the analysis if they received PORT or exhibited any of the following features: (a) pT4 or pN1b according to the 8th American Joint Committee on Cancer, (b) poorly differentiated thyroid cancer (PDTC), or (c) unfavourable variants such as anaplastic foci and etc. After 1:1 propensity matching, a total of 108 patients were analyzed according to PORT receipt. The median follow-up duration of the matched group was 10.4 years.After matching, most of the variables became balanced, but the PORT group still had more PDTC and DTC with anaplastic foci. Radioactive iodine (RAI) was less frequently administered in the PORT group. PORT yielded a significantly higher 5-year locoregional recurrence free survival (LRFS) than the No PORT group (5-year LRFS 86.1% vs. 72.7%, p = 0.022), but the 10-year cancer specific survival (CSS) was similar between them (97.8% vs. 85.9%, p = 0.122). The multivariable analysis indicated that PORT was a favourable prognostic factor (Hazard ratio 0.3, 95% Confidence interval 0.1-0.8, p = 0.02) for LRFS, but not for CSS. Among 133 patients without PORT for initial disease, 39 of them received salvage surgery followed by salvage PORT. No severe toxicity after PORT was reported.PORT reduced locoregional recurrence in DTC patients without severe toxicity. PORT can be an effective and safe treatment to improve locoregional control in DTC with high risk features. However, further study is warranted to identify those who can benefit from PORT.

Enthesophyte formation plays a crucial role in the development of spinal ankylosis in ankylosing spondylitis (AS). We aimed to investigate the role of platelet-derived growth factor B (PDGFB) in enthesophyte formation of AS using in vitro and in vivo models, and to determine the association between PDGFB and spinal progression in AS. Serum PDGFB levels were measured in AS patients and healthy controls (HC). Human entheseal tissues attached to facet joints or spinous processes were harvested at the time of surgery and investigated for bone-forming activity. The impact of a pharmacological agonist and antagonist of platelet-derived growth factor B receptor (PDGFRB) were investigated respectively in curdlan-treated SKG mice. PDGFB levels were elevated in AS sera and correlated with radiographic progression of AS in the spine. Mature osteoclasts secreting PDGFB proteins were increased in the AS group compared to HC and were observed in bony ankylosis tissues of AS. Expression of PDGFRB was significantly elevated in the spinous enthesis and facet joints of AS compared to controls. Moreover, recombinant PDGFB treatment accelerated bone mineralization of enthesis cells, which was pronounced in AS, whereas PDGFRB inhibition efficiently reduced the PDGFB-induced bone mineralization. Also, PDGFRB inhibition attenuated the severity of arthritis and enthesophyte formation at the joints of curdlan-treated SKG mice. This study suggests that regulating PDGFB/PDGFRB signaling could be a novel therapeutic strategy to block key pathophysiological processes of AS. This article is protected by copyright. All rights reserved.

Aims To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs). Methods Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 106 ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed. Results In the graft reseeded with ACL-derived cells, a large number of elongated cells that integrated into the matrix were evident at day 3 and day 7. However, in the graft reseeded with ADMSCs, only a small number of elongated cells were found integrated into the matrix. Immunofluorescence for Ki-67 and type I collagen confirmed the pronounced production of type I collagen by Ki-67-positive ACL-derived cells integrated into the ECM. A messenger RNA (mRNA) expression assay demonstrated significantly higher gene expression levels of types I (p = 0.013) and III (p = 0.050) collagen in the composites reseeded with ACL-derived cells than ADMSCs. Conclusion ACL-derived cells, when reseeded to acellularized tendon graft, demonstrated earlier better survival and integration in the tendon ECM and resulted in higher gene expression levels of collagen, which may be essential to the normal ligamentization process compared to ADMSCs. Cite this article: Bone Joint Res 2022;11(11):777–786.

Rhythm control is associated with lower risk for adverse cardiovascular outcomes compared with usual care among patients recently diagnosed with atrial fibrillation (AF) with a CHATo investigate whether the results can be generalized to patients with low stroke risk.Population-based cohort study.Nationwide claims database of the Korean National Health Insurance Service.54 216 patients with AF having early rhythm control (antiarrhythmic drugs or ablation) or rate control therapy that was initiated within 1 year of the AF diagnosis.The effect of early rhythm control on the primary composite outcome of cardiovascular death, ischemic stroke, hospitalization for heart failure, or myocardial infarction was compared between eligible and ineligible patients for EAST-AFNET 4 (CHAIn total, 37 557 study participants (69.3%) were eligible for the trial (median age, 70 years; median CHAResidual confounding.In routine clinical practice, the beneficial association between early rhythm control and cardiovascular complications was consistent among low-risk patients regardless of trial eligibility.The Ministry of Health and Welfare and the Ministry of Food and Drug Safety, Republic of Korea.

Neurovascular compression syndrome is generally caused by vascular compression at the root entry or exit zone of the corresponding cranial nerve. Trigeminal neuralgia is the most frequent syndrome, followed by hemifacial spasm. Despite ongoing debate in the literature, pulsatile tinnitus is also known to be a neurovascular compression syndrome resulting from vascular compression of the vestibulocochlear nerve. Combined manifestations of neurovascular compression symptoms are very rare. We report a case with a simultaneous manifestation of trigeminal neuralgia, hemifacial spasm, and pulsatile tinnitus as neurovascular compression syndrome with separate offending vessels. A 53-year-old female presented with lancinating pain in the left face, left hemifacial spasm, and ipsilateral pulsatile tinnitus for 2 years. Trigeminal neuralgia and hemifacial spasm were diagnosed after a neurological examination, imaging study, and electromyography. Microvascular decompression via a retrosigmoid approach for separate offenders, including the superior cerebellar artery, anterior inferior cerebellar artery, and posterior inferior cerebellar artery was performed using Teflon sponges. The patient’s hemifacial spasm, pulsatile tinnitus, and hemifacial pain improved immediately after microvascular decompression.

The aim of this clinical trial was to assess the efficacy and safety of low-dose triple combinations of amlodipine, telmisartan, and chlorthalidone in patients with essential hypertension. After a 2-week placebo run-in period, 176 patients were randomized to seven treatment groups (placebo, quarter-dose combination, third-dose combination, half-dose combination, amlodipine 5 mg, amlodipine 10 mg, and telmisartan 80 mg) and administered the assigned study drug orally for 8 weeks. The primary efficacy endpoint was the change in the mean sitting systolic blood pressure (BP) (MSSBP) at Week 8. The MSSBP and mean sitting diastolic BP in the quarter-dose and half-dose groups were significantly lower compared to the placebo and amlodipine 5 mg groups, with similar BP-lowering effects observed compared to the amlodipine 10 mg and telmisartan 80 mg groups. However, the third-dose group showed significant BP improvement only compared to the placebo group. A similar pattern was observed for the control rate of hypertension and response rates. Additional analysis was conducted after correcting for gender and age effects, and, as a result, the third-dose group showed similar results with regard to the BP-lowering effect as the quarter-dose and half-dose groups. In terms of safety, no special adverse events and clinically significant results were noted, and all dose groups of the triple combination are considered safe for use in essential hypertension patients. The current findings indicated that low-dose triple combination of amlodipine, telmisartan, and chlorthalidone over 8 weeks effectively improved the BP-lowering effect in patients with essential hypertension without any safety concerns.

Surgical site infection (SSI) is a major complication after the surgical treatment of ankle fractures that can result in catastrophic consequences. This study aimed to determine the incidence of SSI in several cohorts from national insurance databases over the past 12 years and identify its predictors. The claimed data for patients (n = 1,449,692) with ankle fractures between 2007 and 2019 were investigated, and a total of 41,071 patients were included in the final analysis. The covariates included were age, sex, season, fracture type (closed vs. open), type of surgical fixation procedure, and comorbidities of each patient. All subjects were divided into two groups according to the SSI after the surgical fixation of the ankle fracture (no infection group vs. infection group). The number of SSIs after the surgical treatment of ankle fractures was 874 (2.13%). Open fractures [odds ratio, (OR) = 4.220] showed the highest risk for SSI, followed by the male sex (OR = 1.841), an increasing number of comorbidities (3–5, OR = 1.484; ≥6, OR = 1.730), a history of dementia (OR = 1.720) or of myocardial infarction (OR = 1.628), and increasing age (OR = 1.010). The summer season (OR = 1.349) showed the highest risk among the four seasons for SSI after ankle fracture surgery.

Marmosets have emerged as a valuable primate model in ophthalmic research due to their similarity to the human visual system and their potential for generating transgenic models to advance the development of therapies. In this study, we isolated and cultured primary retinal pigment epithelium (RPE) cells from marmosets to investigate the mechanisms underlying RPE dysfunction in aging and age-related macular degeneration (AMD). We confirmed that our culture conditions and materials supported the formation of RPE monolayers with functional tight junctions that closely resembled the in vivo RPE. Since serum has been shown to induce epithelial–mesenchymal transition (EMT) in RPE cells, we compared the effects of fetal bovine serum (FBS) with serum-free supplements B27 on transepithelial electrical resistance (TER), cell proliferation, and morphological characteristics. Additionally, we assessed the age-related morphological changes of in vivo and primary RPE cells. Our results indicate that primary marmoset RPE cells exhibit in vivo-like characteristics, while cells obtained from an older donor show evidence of aging, including a failure to form a polarized monolayer, low TER, and delayed cell cycle. In conclusion, our primary marmoset RPE cells provide a reliable in vitro model for developing novel therapeutics for visual-threatening disorders such as AMD, which can be used before animal experiments using marmosets.

ObjectiveTo investigate the associations between exercise habit changes following an incident cardiovascular event and mortality in older adults.MethodsWe analysed the relationship between exercise habit change and all-cause, cardiovascular and non-cardiovascular deaths in adults aged ≥60 years between 2003 and 2012 who underwent two consecutive health examinations within 2 years before and after diagnosis of cardiovascular disease (CVD). They were categorised into four groups according to exercise habit changes: persistent non-exercisers, exercise dropouts, new exercisers and exercise maintainers. Differences in baseline characteristics were adjusted using inverse probability of treatment weighting.ResultsOf 6076 participants, the median age was 72 (IQR 69–76) years and men accounted for 50.6%. Compared with persistent non-exercisers (incidence rate (IR) 4.8 per 100 person-years), new exercisers (IR 3.5, HR 0.73, 95% CI 0.58 to 0.91) and exercise maintainers (IR 2.9, HR 0.53, 95% CI 0.38 to 0.73) were associated with reduced risk of all-cause death. The rate of non-cardiovascular death was significantly lower in new exercisers (IR 2.3, HR 0.73, 95% CI 0.56 to 0.95) and exercise maintainers (IR 2.3, HR 0.61, 95% CI 0.42 to 0.90) than in persistent non-exercisers (IR 3.2). Also, trends towards reduced cardiovascular death in new exercisers and exercise maintainers were observed (p value for trend ConclusionsMore virtuous exercise trajectories in older adults with CVD are associated with lower mortality rates. Our results support public health recommendations for older adults with CVD to perform physical activity.

Our study's purpose was to determine the most reliable Hounsfield unit (HU) measurement method to reflect bone mineral density (BMD) on cervical spine computed tomography (CT) and to identify any factors that influence these results.We retrospectively analyzed 439 consecutive patients with mild head and neck injuries. Mean HU values of the C2-C7 vertebra were determined on each sagittal, coronal, and axial CT image. Correlation patterns were analyzed between the HU value and corresponding dual-energy X-ray absorptiometry (DXA) in the lumbar vertebra (T-score) and femoral neck (T-score). A sub-group analysis was performed according to patient age, sex, and degree of spinal degeneration.The correlation coefficients for HU and DXA ranged from 0.52 to 0.65 in all cervical segments. A simple linear regression analysis revealed the following formula: T-score = 0.01 × (HU) - 4.55. The mean HU values for osteopenia and osteoporosis were 284.0 ± 63.3 and 231.5 ± 52.8, respectively. The ROC curve indicated that the HU method has a sensitivity of 89.2% and specificity of 88.7% to diagnose osteoporosis. The HU measurement showed a high correlation value (range: r = 0.64-0.70) with spine DXA score regardless of the degree of degeneration or patient age or sex.HU values using the upper two cervical vertebrae (C2 and C3) reflected a more reliable BMD level than other segments. Additionally, the HU of cervical CT provided reliable information regardless of measurement plane, age or sex, and degree of degeneration.

Nanofibrillated cellulose (NFC) has generated significant interest due to growing concerns about low carbon emission, environmental issues, and the guaranteed outstanding performance of applied products. Because of this trend, the importance of NFC production from an industrial angle has also been emphasized. In this study, ground pulps (at -300 μm clearance, 40 passes) were homogenized by using a pilot-scale microfluidizer (at 1,500 bar, up to 5 passes) to produce the NFC, and its characteristics were investigated. Scanning electron microscope (SEM) images showed that the size and distribution of the NFC particles gradually decreased by up to three passes on account of the microfluidizer treatment and remained constant after that mechanical pass number. The viscoelastic properties (dynamic moduli) and viscosity of the NFC suspension steadily increased with three passes of the treatment, and the same trends as in the SEM images were observed after these passes. These results demonstrated that the NFC fluid behavior inside the equipment depends on the morphological properties of the manufactured NFC particles. Additionally, a good agreement between the morphological and rheological results implied that rheological analysis can be a reasonable approach to predicting the quality (size and distribution) of manufactured NFC particles.

To quantify the dose-response relationship between moderate to vigorous physical activity and primary cardiac arrest (PCA).There were 504,840 participants older than 18 years who underwent the Korean National Health Screening Program, including a self-administered questionnaire for physical activity from January 1, 2009, through December 31, 2014. Physical activity levels were converted into metabolic equivalent tasks (METs) per week and categorized to correspond with multiples of public health recommendations. We evaluated the quantitative and categorical dose-response relationship between physical activity and PCA.A curvilinear dose-response relationship between physical activity and PCA was observed; the benefits started at two-thirds (5 MET-hour/week) of the United States and World Health Organization guidelines-recommended minimum (7.5 MET-hour/week) and continued to 5 times (40 MET-hour/week) the recommended minimum (P nonlinearity.001). The largest benefit was noted at a level of 2 to 3 times the recommended minimum (hazard ratio, 0.6; 95% CI, 0.4 to 0.8). In addition, there was no evidence of an increased PCA risk at a level more than 5 times the recommended minimum (hazard ratio, 0.7; 95% CI, 0.5 to 1.1). These associations were consistent regardless of age, sex, body mass index, comorbid conditions, and estimated 10-year risk for cardiovascular disease.The beneficial effect of physical activity on PCA started at two-thirds of the recommended minimum and continued to 5 times the recommended minimum. No excess risk for PCA was present among individuals with activity levels more than 5 times the recommended minimum regardless of cardiovascular disease or lifestyle risk factor presence.

Supplementary Data from The Reversible Fourth-Generation EGFR Tyrosine Kinase Inhibitor OBX02–011 Overcomes C797S-Mediated Resistance in Lung Cancer

Osimertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) that was initially developed to overcome the EGFR T790M mutation and is used as a standard therapy in patients with advanced non–small cell lung cancer (NSCLC) with EGFR-activating mutations. Despite the remarkable initial efficacy, osimertinib, like other EGFR-TKIs, is limited by the emergence of acquired resistance. As the EGFR mutation C797S has been identified as a key driver of acquired resistance to osimertinib, development of a drug that targets this clinically relevant mutation could help improve patient outcomes. Here, we report the discovery and preclinical efficacy of OBX02–011, a reversible fourth-generation EGFR-TKI that overcomes the EGFR C797S mutation. Compared with approved EGFR-TKIs, OBX02–011 showed potent anticancer effects and inhibited EGFR-related signaling in various models, including those harboring the EGFR C797S mutation. In addition, in transgenic mouse models (EGFRL858R/T790M/C797S), OBX02–011 treatment effectively inhibited tumor growth and EGFR activity, leading to enhanced survival. Collectively, these results suggest that OBX02–011 may be a promising new EGFR-TKI to overcome C797S-mediated resistance in NSCLC.Significance:OBX02–011 is designed to target EGFR C797S and can overcome EGFR double and triple mutations to effectively treat lung cancer.