RESUMEN
Objectives Our hospital was newly opened in the spring of 2020 in a rural area of Japan, with a remarkably developing aging society and population decline. This study aimed to clarify and evaluate the practice of osteoporosis care in our hospital for three years since its establishment. We report a retrospective review of therapeutic interventions for osteoporosis for patients who underwent surgical treatment for non-vertebral fragility fractures in our hospital. Methods We evaluated the practice of osteoporosis intervention in patients who underwent surgery for proximal humerus fractures (PHFs), distal radius fractures (DRFs), or proximal femoral fractures (PFFs) from April 2020 to the end of March 2023. Results There were 115 surgical cases with non-vertebral fractures (10 patients with PHF, 41 patients with DRF, and 64 with PFF). Among the patients who had received osteoporosis treatment at other hospitals before the injury, only 15 (13.0%) patients had been administered therapeutic intervention for osteoporosis by other clinics or hospitals. Also, 82 (71.3%) patients were newly diagnosed with osteoporosis in our hospital after surgery according to the Japanese osteoporosis guideline. New postoperative osteoporosis interventions were administered to 39 (47.0%) patients, of which the rate was higher than the previous reports in Japan. While there was no significant difference between upper limb fracture and PFF in the percentage per young adult mean of spine areal bone marrow density (aBMD), the femoral neck aBMDs in the upper limb fracture group were significantly higher than in the PFF group. The serum total P1NP levels were significantly lower and the 25(OH)D levels were also greater in the upper limb fracture group than in the PFF group, whereas the serum TRACP-5b levels were not significantly different between the two groups. Two (1.7%) patients were affected with secondary fractures during the study period. Conclusions The rates of therapeutic intervention for osteoporosis of patients with non-vertebral fractures, especially in those with upper limb fractures, in our hospital were considered to be greater than those in the previous reports. However, the intervention rate for patients with PFFs was not much, and there was still room for improvement in our hospital concerning osteoporosis diagnosis and treatment.
RESUMEN
BACKGROUND: Since lung transplant recipients (LTRs) exhibit low immunogenicity after two doses of SARS-CoV-2 mRNA vaccines, optimal vaccine strategies for SARS-CoV-2 are required in LTRs. This study aimed to investigate the efficacy and safety of the third and fourth doses of the SARS-CoV-2 mRNA vaccines in LTRs. METHODS: We conducted a single-center study of 73 LTRs and 23 healthy controls (HCs). Participants received two-to-four doses of SARS-CoV-2 mRNA vaccines. The LTRs were divided into three groups based on the number of vaccine dose. IgG titers against SARS-CoV-2 spike protein were measured, and adverse events were assessed. Factors associated with humoral response were analyzed using univariate and multivariate analyses. RESULTS: The Dose 4 group (n = 27) had a higher humoral response rate (P = 0.018) and higher levels of anti-SARS-CoV-2 IgG antibody (P = 0.04) than the Dose 2 group (n = 14). The Dose 3 group (n = 32) had lower humoral response rates (P = 0.005) and levels of anti-SARS-CoV-2 IgG antibody (P = 0.0005) than the HCs (n = 23) even after the same dose. Systemic adverse events were milder in the LTRs than in the HCs (P < 0.05). Increased number of vaccine dose was identified as a predictor of positive humoral response (P = 0.021). CONCLUSION: Booster doses of SARS-CoV-2 mRNA vaccines may enhance humoral response with mild adverse events in LTRs. Repeated vaccination might be warranted for LTRs to prevent SARS-CoV-2 infection.
RESUMEN
The global pandemic of coronavirus infection 2019 (COVID-19) was an unprecedented public health emergency. Several clinical studies reported that heart disease, lung disease, diabetes, hypertension, dyslipidemia, and obesity are critical risk factors for increased severity of and hospitalization for COVID-19. This is largely because patients with these underlying medical conditions can show poor immune responses to the COVID-19 vaccinations. Diabetes is one of the underlying conditions most highly associated with COVID-19 susceptibility and is considered a predictor of poor prognosis of COVID-19. We therefore investigated factors that influence the anti-SARS-CoV-2 spike IgG antibody titer after three doses of vaccination in patients with type 2 diabetes. We found that obesity was associated with low anti-SARS-CoV-2 spike IgG antibody titers following three-dose vaccination in type 2 diabetics. Obese patients with type 2 diabetes may have attenuated vaccine efficacy and require additional vaccination; continuous infection control should be considered in such patients.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Diabetes Mellitus Tipo 2 , Obesidad , SARS-CoV-2 , Humanos , Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/complicaciones , Obesidad/inmunología , Obesidad/complicaciones , Vacunas contra la COVID-19/inmunología , Estudios Transversales , COVID-19/inmunología , COVID-19/prevención & control , COVID-19/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Anciano , SARS-CoV-2/inmunología , Anticuerpos Antivirales/sangre , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunogenicidad VacunalRESUMEN
To investigate the prevalence of and factors associated with sarcopenia in Japanese patients with rheumatoid arthritis (RA). We analyzed a cross-section of patients with RA participating in the Institute of Rheumatology Rheumatoid Arthritis cohort survey in 2021. Participants completed self-administered questionnaires, including a 5-item sarcopenia screening index (SARC-F). Patients with a SARC-F score of 4 or higher were categorized as having sarcopenia. Among 2416 Japanese patients with RA (2113 women and 303 men; mean age 63.9 years), 341 (14.1%) patients were categorized as having sarcopenia. In a multivariable analysis of patients of all ages, age, body mass index (BMI), disease duration, history of fracture, patient pain on a visual analog scale (VAS), patient or physician global assessments based on VAS, and use of nonsteroidal anti-inflammatory drugs (NSAIDs), biologic disease-modifying antirheumatic drugs (bDMARDs), and corticosteroids were significantly (P < 0.05) associated with sarcopenia. Disease duration, patient global assessments based on VAS, and use of NSAIDs and bDMARDs were significantly associated with sarcopenia among the patients aged < 65 years, whereas age, female sex, BMI, disease duration, history of fracture, patient pain VAS and global assessments based on VAS, and use of bDMARDs and corticosteroids were significantly associated with sarcopenia in patients aged ≥ 65 years. In Japanese patients with RA, age, BMI, disease duration, history of fracture, patient pain VAS and global assessments based on VAS, and use of NSAIDs, bDMARDs, and corticosteroids were associated with sarcopenia. Among older patients with RA, female sex was additionally associated with sarcopenia. Key Points ⢠To our knowledge, this is the first report showing factors associated with sarcopenia in Japanese patients with rheumatoid arthritis using a large cohort database. ⢠Age, BMI, disease duration, history of fracture, patient pain on a visual analog scale, and use of nonsteroidal anti-inflammatory drugs, biologic disease-modifying antirheumatic drugs, and corticosteroids were associated with sarcopenia in Japanese patients with rheumatoid arthritis. Limited to elderly patients, female sex was also associated with sarcopenia.
Asunto(s)
Antirreumáticos , Artritis Reumatoide , Sarcopenia , Anciano , Masculino , Humanos , Femenino , Persona de Mediana Edad , Estudios de Cohortes , Sarcopenia/complicaciones , Sarcopenia/epidemiología , Japón/epidemiología , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Antirreumáticos/uso terapéutico , Dolor/complicaciones , Antiinflamatorios no Esteroideos/uso terapéutico , Corticoesteroides/uso terapéutico , Antiinflamatorios/uso terapéuticoRESUMEN
Introduction: Lipoma arborescens is a tumor-like lesion that occurs inside joints and synovial bursae, especially in knee joints. It rarely occurs in the shoulder joints and this disease usually causes severe shoulder pain. This study aims to report a rare case of lipoma arborescens occurring in the subdeltoid bursa with severe shoulder pain. Case Report: A 59-year-old woman with severe pain and restriction of range of motion (ROM) for her right shoulder consisting for 2 months was referred to our hospital. Magnetic resonance imaging (MRI) findings revealed that a tumor-like lesion exists in the subdeltoid bursa in her right shoulder and blood examinations revealed no abnormal findings. Surgical resection of the tumor-like lesion was performed and the rotator cuff was repaired because this tumor-like lesion invaded the rotator cuff partially. Pathology examination of the resected tissues was consistent with lipoma arborescens. One year after surgery, the patient's shoulder pain was diminished and its ROM recovered. There was no significant difficulty in activities of daily living. Conclusion: Lipoma arborescens should be considered when patients present with complaints of severe shoulder pain. Even if their physical findings do not suggest rotator cuff injuries, MRI should be performed to rule out lipoma arborescens.
RESUMEN
BACKGROUND: To mitigate the COVID-19 pandemic, many countries have recommended the use of booster vaccinations. The relationship between the degree of adverse vaccine reactions and elevated antibody titers is of interest; however, no studies have investigated the temporal changes in antibody titers based on repeated measurements after a third dose of the BNT162b2 vaccine. METHODS: This prospective longitudinal cohort study was conducted with 62 healthcare workers who received a third dose of the BNT162b2 at Okayama University Hospital, Japan. Venous blood draw and fingertip whole blood test sample collection were conducted at the early (3-13 days) and 1-month time points; only FWT sample collection was conducted at the 2-month time point. Information on adverse reactions within 1 week after vaccination was also obtained. The association between fever of 37.5 °C or higher and antibody titers after the third dose of BNT162b2 was examined using a mixed-effects model and Poisson regression with robust variance. RESULTS: A trend toward higher antibody titers in the early period after vaccination was observed in the febrile individuals, but the differences were not significant at 1 and 2 months post-vaccination (the partial regression coefficient for fever was 8094.3 [-1910.2, 18,098.8] at 1 month after vaccination, and 1764.1 [-4133.9, 7662.1] at 2 months after vaccination in the adjusted models). CONCLUSION: The findings suggest that the presence of fever after the third vaccine does not predict a sustained elevation in serum antibody titers.
Asunto(s)
COVID-19 , Vacunas , Humanos , Vacuna BNT162 , Estudios Prospectivos , Estudios Longitudinales , Pandemias , COVID-19/prevención & control , Anticuerpos AntiviralesRESUMEN
Amid the Coronavirus Disease 2019 pandemic, we aimed to demonstrate the accuracy of the fingertip whole blood sampling test (FWT) in measuring the antibody titer and uncovering its dynamics shortly after booster vaccination. Mokobio SARS-CoV-2 IgM & IgG Quantum Dot immunoassay (Mokobio Biotechnology R&D Center Inc., MD, USA) was used as a point-of-care FWT in 226 health care workers (HCWs) who had received two doses of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) at least 8 months prior. Each participant tested their antibody titers before and after the third-dose booster up to 14-days. The effect of the booster was observed as early as the fourth day after vaccination, which exceeded the detection limit (> 30,000 U/mL) by 2.3% on the fifth day, 12.2% on the sixth day, and 22.5% after the seventh day. Significant positive correlations were observed between the pre- and post-vaccination (the seventh and eighth days) antibody titers (correlation coefficient, 0.405; p < 0.001). FWT is useful for examining antibody titers as a point-of-care test. Rapid response of antibody titer started as early as the fourth day post-vaccination, while the presence of weak responders to BNT162b2 vaccine was indicated.
Asunto(s)
Vacuna BNT162 , COVID-19 , Humanos , Vacunas contra la COVID-19 , ARN Mensajero , Cinética , Sistemas de Atención de Punto , COVID-19/diagnóstico , COVID-19/prevención & control , SARS-CoV-2/genética , Pruebas en el Punto de Atención , Vacunación , Inmunoglobulina G , Anticuerpos Antivirales , Vacunas de ARNmRESUMEN
In this study, we assess the association between the occurrence of new fractures and vitamin D deficiency in Japanese patients with rheumatoid arthritis using our large IORRA cohort. The results suggest that vitamin D deficiency is a significant risk factor for new fractures in Japanese female patients over the age of 50 years with rheumatoid arthritis. PURPOSE: Both rheumatoid arthritis (RA) and menopause are known risk factors for the onset of osteoporosis. The occurrence of new clinical fractures in patients with RA can significantly lower quality of life. The purpose of this study was to investigate whether vitamin D deficiency in Japanese women with RA could be a risk factor for new fractures. METHODS: Between 2011 and 2017, a total of 2567 female patients with RA over the age of 50 years (mean age, 65.9 years) were enrolled in a prospective observational study. Self-reported occurrences of new fractures were verified using patient medical records. Vitamin D deficiency was defined as serum 25(OH)D levels < 20 ng/mL. Cox proportional hazards models were used to analyze the independent contributions of various risk factors to the occurrence of a new fracture. RESULTS: New clinical fractures were sustained by 205 patients in the included cases. Among them, new osteoporotic fractures were sustained by 139 patients (63 vertebral fractures and 76 non-vertebral fractures). Among all patients, the mean (SD) serum 25(OH)D level was 16.9 (5.89) ng/mL and the prevalence of vitamin D deficiency was 72.6%. A Cox proportional hazards model revealed that vitamin D deficiency was significantly associated with all new clinical fractures (hazard ratio, 1.44 [95% confidence interval 1.02â2.05]; p = 0.0365) and all new osteoporotic fractures (hazard ratio, 1.75 [95% confidence interval 1.14â2.69]; p = 0.0109). CONCLUSION: Vitamin D deficiency is a risk factor for new fractures in Japanese female patients over the age of 50 years with RA. Screening these patients for serum 25(OH)D could potentially be seminal to reducing their risk of fractures.
Asunto(s)
Artritis Reumatoide , Fracturas Osteoporóticas , Deficiencia de Vitamina D , Anciano , Artritis Reumatoide/epidemiología , Estudios de Cohortes , Femenino , Humanos , Japón/epidemiología , Persona de Mediana Edad , Fracturas Osteoporóticas/epidemiología , Posmenopausia , Calidad de Vida , Factores de Riesgo , Vitamina D , Deficiencia de Vitamina D/epidemiologíaRESUMEN
Blood flow governs transport of oxygen and nutrients into tissues. Hypoxic tissues secrete VEGFs to promote angiogenesis during development and in tissue homeostasis. In contrast, tumors enhance pathologic angiogenesis during growth and metastasis, suggesting suppression of tumor angiogenesis could limit tumor growth. In line with these observations, various factors have been identified to control vessel formation in the last decades. However, their impacts on the vascular transport properties of oxygen remain elusive. Here, we take a computational approach to examine the effects of vascular branching on blood flow in the growing vasculature. First of all, we reconstruct a 3D vascular model from the 2D confocal images of the growing vasculature at postnatal day 5 (P5) mouse retina, then simulate blood flow in the vasculatures, which are obtained from the gene targeting mouse models causing hypo- or hyper-branching vascular formation. Interestingly, hyper-branching morphology attenuates effective blood flow at the angiogenic front, likely promoting tissue hypoxia. In contrast, vascular hypo-branching enhances blood supply at the angiogenic front of the growing vasculature. Oxygen supply by newly formed blood vessels improves local hypoxia and decreases VEGF expression at the angiogenic front during angiogenesis. Consistent with the simulation results indicating improved blood flow in the hypo-branching vasculature, VEGF expression around the angiogenic front is reduced in those mouse retinas. Conversely, VEGF expression is enhanced in the angiogenic front of hyper-branching vasculature. Our results indicate the importance of detailed flow analysis in evaluating the vascular transport properties of branching morphology of the blood vessels.
Asunto(s)
Neovascularización Patológica , Vasos Retinianos/fisiopatología , Animales , Ratones , Ratones Transgénicos , Vasos Retinianos/anatomía & histología , Vasos Retinianos/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Receptor endocytosis is crucial for integrating extracellular stimuli of pro-angiogenic factors, including vascular endothelial growth factor (VEGF), into the cell via signal transduction. VEGF not only triggers various angiogenic events including endothelial cell (EC) migration, but also induces the expression of negative regulators of angiogenesis, including vasohibin-1 (VASH1). While we have previously reported that VASH1 inhibits angiogenesis in vitro and in vivo, its mode of action on EC behavior remains elusive. Recently VASH1 was shown to have tubulin carboxypeptidase (TCP) activity, mediating the post-translational modification of microtubules (MTs) by detyrosination of α-tubulin within cells. However, the role of VASH1 TCP activity in angiogenesis has not yet been clarified. Here, we showed that VASH1 detyrosinated α-tubulin in ECs and suppressed in vitro and in vivo angiogenesis. In cultured ECs, VASH1 impaired endocytosis and trafficking of VEGF receptor 2 (VEGFR2), which resulted in the decreased signal transduction and EC migration. These effects of VASH1 could be restored by tubulin tyrosine ligase (TTL) in ECs, suggesting that detyrosination of α-tubulin negatively regulates angiogenesis. Furthermore, we found that detyrosinated tubulin-rich MTs were not adequate as trafficking rails for VEGFR2 endocytosis. Consistent with these results, inhibition of TCP activity of VASH1 led to the inhibition of VASH1-mediated suppression of VEGF-induced signals, EC migration, and in vivo angiogenesis. Our results indicate a novel mechanism of VASH1-mediated inhibition of pro-angiogenic factor receptor trafficking via modification of MTs.
Asunto(s)
Inductores de la Angiogénesis/metabolismo , Carboxipeptidasas/metabolismo , Proteínas de Ciclo Celular/metabolismo , Endocitosis , Neovascularización Patológica/patología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Inhibidores de la Angiogénesis/farmacología , Animales , Movimiento Celular/efectos de los fármacos , Endocitosis/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Cinética , Ratones , Microtúbulos/efectos de los fármacos , Microtúbulos/metabolismo , Modelos Biológicos , Proteínas Mutantes/metabolismo , Fosforilación/efectos de los fármacos , Transducción de Señal , Tubulina (Proteína)/metabolismo , Tirosina/metabolismoRESUMEN
STUDY DESIGN: Retrospective cohort study. PURPOSE: This study aimed to evaluate aggravated lateral recess stenosis and clarify the indirect decompression threshold by combined lateral interbody fusion and percutaneous pedicle screw fixation (LIF/PPS). OVERVIEW OF LITERATURE: No previous reports have described an effective radiographic indicator for determining the surgical indication for LIF/PPS. METHODS: A retrospective review of 185 consecutive patients, who underwent 1- or 2-level lumbar fusion surgery for degenerative spondylolisthesis (DS). According to their symptomatic improvement, they were placed into either the "recovery" or "no-recovery" group. Preoperative computed tomography (CT) images were evaluated for the position of the superior articular processes at the slipping level, followed by a graded classification (grades 0-3) using the impingement line (I line), a new radiographic indicator. All 432 superior articular facets in 216 slipped levels were classified, and both groups' characteristics were compared. RESULTS: There were 171 patients (92.4%) in the recovery group and 14 patients in the no-recovery group (7.6%). All patients in the no-recovery group were diagnosed with symptoms associated with deteriorated bony lateral recess stenosis. All superior articular processes of the lower vertebral body in affected levels reached and exceeded the I line (I line-; grade 2 and 3) on preoperative sagittal CT images. In the recovery group, most superior articular processes did not reach the I line (I line+; grade 0 and 1; p=0.0233). CONCLUSIONS: In DS cases that are classified as grade 2 or greater, the risk of aggravated bony lateral recess stenosis due to corrective surgery is high; therefore, indirect decompression by LIF/PPS is, in principle, contraindicated.
RESUMEN
OBJECTIVES: This study aimed to evaluate factors associated with osteoporosis medication use in Japanese patients with rheumatoid arthritis (RA). METHODS: Patients with RA who enrolled in our cohort completed self-administered questionnaires which included questions regarding their osteoporosis medications. Logistic regression was used to determine the association of variables with the use of these medications. RESULTS: Among 5660 Japanese patients with RA who responded to the questionnaires (mean age, 61.8 years; 86.0% female), 1983 patients (35.0%) and 1211 patients (21.4%) reported taking osteoporosis medications and antiresorptive agents, respectively. In multivariate models, age, female sex, lower body mass index (BMI), self-reported fracture history, Japanese Health Assessment Questionnaire-Disability Index (JHAQ-DI), daily dosage of prednisone (PSL), weekly dosage of methotrexate (MTX), and concomitant use of hypertension and hyperlipidemia medications were significantly associated with the use of osteoporosis medications (P < 0.05). Among women with RA, the use of hypertension medications was significantly correlated with the use of both osteoporosis medications and antiresorptive agents (P < 0.05). CONCLUSIONS: Age, female sex, a lower BMI, duration of RA, self-reported fracture history, JHAQ-DI, daily dosage of PSL, weekly dosage of MTX, and the use of medications for hypertension and hyperlipidemia appear to be associated with the use of osteoporosis medications in Japanese patients with RA.
RESUMEN
BACKGROUND: Transmembrane and immunoglobulin domain-containing protein 1 (TMIGD1) is a recently identified cell adhesion molecule which is predominantly expressed by epithelial cells of the intestine and the kidney. Its expression is downregulated in both colon and renal cancer suggesting a tumor suppressive activity. The function of TMIGD1 at the cellular level is largely unclear. Published work suggests a protective role of TMIGD1 during oxidative stress in kidney epithelial cells, but the underlying molecular mechanisms are unknown. RESULTS: In this study, we address the subcellular localization of TMIGD1 in renal epithelial cells and identify a cytoplasmic scaffold protein as interaction partner of TMIGD1. We find that TMIGD1 localizes to different compartments in renal epithelial cells and that this localization is regulated by cell confluency. Whereas it localizes to mitochondria in subconfluent cells it is localized at cell-cell contacts in confluent cells. We find that cell-cell contact localization is regulated by N-glycosylation and that both the extracellular and the cytoplasmic domain contribute to this localization. We identify Synaptojanin 2-binding protein (SYNJ2BP), a PDZ domain-containing cytoplasmic protein, which localizes to both mitochondria and the plasma membrane, as interaction partner of TMIGD1. The interaction of TMIGD1 and SYNJ2BP is mediated by the PDZ domain of SYNJ2BP and the C-terminal PDZ domain-binding motif of TMIGD1. We also find that SYNJ2BP can actively recruit TMIGD1 to mitochondria providing a potential mechanism for the localization of TMIGD1 at mitochondria. CONCLUSIONS: This study describes TMIGD1 as an adhesion receptor that can localize to both mitochondria and cell-cell junctions in renal epithelial cells. It identifies SYNJ2BP as an interaction partner of TMIGD1 providing a potential mechanism underlying the localization of TMIGD1 at mitochondria. The study thus lays the basis for a better understanding of the molecular function of TMIGD1 during oxidative stress regulation.
Asunto(s)
Células Epiteliales/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas de la Membrana/metabolismo , Mitocondrias/metabolismo , Membranas Mitocondriales/metabolismo , Adhesión Celular/genética , Línea Celular Tumoral , Membrana Celular/metabolismo , Citoplasma/metabolismo , Glicosilación , Humanos , Moléculas de Adhesión de Unión/genética , Moléculas de Adhesión de Unión/metabolismo , Glicoproteínas de Membrana/genética , Proteínas de la Membrana/genética , Mitocondrias/genética , Dominios PDZ/genética , Unión ProteicaRESUMEN
INTRODUCTION: A volar dislocation of the metacarpophalangeal (MCP) joint of the thumb is a rare trauma, and in combination with a radial collateral ligament (RCL) injury is much rarer. We present a surgical case with a recurrent volar dislocation of the MCP joint of the thumb with RCL injury. PRESENTATION OF CASE: A 47-year-old man was referred to our hospital in the subacute phase. Open reduction was performed through a dorsal incision and the RCL was repaired. X-rays taken six weeks later revealed a recurrent dislocation of the MCP joint. At the revision surgery, the extensor pollicis brevis (EPB) was detached from the proximal phalanx. As there was volar tightness, the volar plate was incised horizontally and the EPB was attached to the proximal phalanx. The final X-rays six months post-operatively revealed that the MCP joint was slightly subluxated but there was no pain on motion. DISCUSSION: This case revealed that it is not enough only to repair the RCL to reduce a volar dislocation of the MCP joint of the thumb with an RCL injury. It revealed that re-attachment of the extensor tendons and the volar procedure are also important for a perfect reduction of a recurrent volar dislocation of the MCP joint of the thumb. CONCLUSION: For a volar dislocation of the MCP joint of the thumb with RCL injury, it is important not only to repair the RCL, but also to perform arthroplasty with the extensor tendons and a volar procedure to prevent recurrent dislocation after surgery.
RESUMEN
Enlarged vestibular aqueduct (EVA) is one of the most commonly identified inner ear malformations in hearing loss patients including Pendred syndrome. While biallelic mutations of the SLC26A4 gene, encoding pendrin, causes non-syndromic hearing loss with EVA or Pendred syndrome, a considerable number of patients appear to carry mono-allelic mutation. This suggests faulty pendrin regulatory machinery results in hearing loss. Here we identify EPHA2 as another causative gene of Pendred syndrome with SLC26A4. EphA2 forms a protein complex with pendrin controlling pendrin localization, which is disrupted in some pathogenic forms of pendrin. Moreover, point mutations leading to amino acid substitution in the EPHA2 gene are identified from patients bearing mono-allelic mutation of SLC26A4. Ephrin-B2 binds to EphA2 triggering internalization with pendrin inducing EphA2 autophosphorylation weakly. The identified EphA2 mutants attenuate ephrin-B2- but not ephrin-A1-induced EphA2 internalization with pendrin. Our results uncover an unexpected role of the Eph/ephrin system in epithelial function.
Asunto(s)
Efrina-A2/genética , Bocio Nodular/genética , Pérdida Auditiva Sensorineural/genética , Transportadores de Sulfato/genética , Secuencia de Aminoácidos , Animales , Efrina-A1/genética , Efrina-A1/metabolismo , Efrina-A2/química , Efrina-A2/metabolismo , Efrina-B2/genética , Efrina-B2/metabolismo , Bocio Nodular/metabolismo , Pérdida Auditiva Sensorineural/metabolismo , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Mutación Puntual , Unión Proteica , Receptor EphA2 , Transportadores de Sulfato/química , Transportadores de Sulfato/metabolismoRESUMEN
OBJECTIVE: To investigate whether abatacept (ABA) causes more adverse events (AE) than conventional synthetic disease-modifying antirheumatic drugs (csDMARD) after orthopedic surgery in patients with rheumatoid arthritis (RA). METHODS: A retrospective multicenter nested case-control study was performed in 18 institutions. Patients receiving ABA (ABA group) were matched individually with patients receiving csDMARD and/or steroids (control group). Postoperative AE included surgical site infection, delayed wound healing, deep vein thrombosis or pulmonary embolism, flare, and death. The incidence rates of the AE in both groups were compared with the Mantel-Haenszel test. Risk factors for AE were analyzed by logistic regression model. RESULTS: A total of 3358 cases were collected. After inclusion and exclusion, 2651 patients were selected for matching, and 194 patients in 97 pairs were chosen for subsequent comparative analyses between the ABA and control groups. No between-group differences were detected in the incidence rates of each AE or in the incidence rates of total AE (control vs ABA: 15.5% vs 20.7% in total, 5.2% vs 3.1% in death). CONCLUSION: Compared with csDMARD and/or steroids without ABA, adding ABA to the treatment does not appear to increase the incidence rates of postoperative AE in patients with RA undergoing orthopedic surgery. Large cohort studies should be performed to add evidence for the perioperative safety profile of ABA.
Asunto(s)
Antirreumáticos , Artritis Reumatoide , Drogas Sintéticas , Abatacept/efectos adversos , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Estudios de Casos y Controles , Humanos , Estudios Retrospectivos , Drogas Sintéticas/uso terapéutico , Resultado del TratamientoRESUMEN
The expression of immune checkpoint proteins such as programmed cell death protein 1 (PD-1) and its ligand (PD-L1) has been shown to correlate with patient prognosis in many malignant cancers. The expression of PD-L1 is controlled by c-Myc; however, further upstream regulation of PD-L1 expression is largely unknown. We have previously shown that atypical protein kinase C lambda/iota (aPKCλ) phosphorylates the Forkhead box protein O1 (FoxO1) transcription factor at Ser218 to suppress its DNA-binding ability, thereby regulating c-Myc expression and controlling physiologic and pathologic endothelial proliferation. The presence of phosphorylation of FoxO1 at Ser218 (pSer218 FoxO1) in cutaneous angiosarcoma (CAS) strongly correlates with poor patient prognosis. Here, we reported that patients with PD-L1+ cells in CAS lesions showed significantly worse prognosis compared to those that were PD-L1- . Expression of PD-L1 correlated with that of aPKCλ or the presence of pSer218FoxO1. Moreover, suppression of aPKCλ expression or inhibition of its activity in HUVECs or AS-M, an established human angiosarcoma cell line, resulted in decreased PD-L1 expression. Our results suggest that combined treatment with immune checkpoint inhibitors and aPKCλ inhibitors could be a novel treatment strategy for CAS patients.