Gestational Ectopic Hyperparathyroidism: A Case Report of Perioperative and Perinatal Outcomes.

In the realm of obstetric care, discerning the subtle signs of primary hyperparathyroidism (PHPT) amidst common pregnancy symptoms remains a formidable challenge. Our exploration into a case of gestational hypercalcemia peels back the layers of this complexity, revealing the clinical conundrum posed by overlapping gastrointestinal manifestations. The journey from diagnosis through surgical intervention to the resolution of symptoms underscores the importance of vigilance for PHPT in pregnant patients. This case further prompts consideration of gamma-aminobutyric acid (GABA) as a potential piece in the puzzle of persistent symptoms post-calcium normalization, inviting a broader dialogue on the intricacies of parathyroid pathology in pregnancy.

Single-center experience of thoracoscopic sympathectomy for palmar hyperhidrosis with long-term postoperative questionnaire survey.

OBJECTIVES: Thoracoscopic sympathectomy is an effective treatment for palmar hyperhidrosis. However, compensatory hyperhidrosis occurs frequently as a postoperative complication of the procedure. The goal of this study was to elucidate the clinical significance of thoracoscopic sympathectomy using our surgical procedure. METHODS: Consecutive 151 patients who underwent thoracoscopic sympathectomy for palmar hyperhidrosis were studied. In addition, to investigate patients' satisfaction and long-term quality of life, 111 patients were asked to complete a mailing questionnaire survey, and 84 responded (response rate of 75.7%). RESULTS: All of the 151 patients reported a reduction in palmar sweating during the immediate postoperative period. None of the patients had pneumothorax, hemothorax, Horner's syndrome, or worsening of bradycardia. Based on the questionnaire, the surgical success rate was 98.8%. None of the patients had a recurrence of palmar hyperhidrosis during the long-term postoperative period. However, compensatory hyperhidrosis was reported in 82 patients (97.6%). In total, 94.0% of patients had high levels of postoperative satisfaction. CONCLUSIONS: Thoracoscopic sympathectomy is an effective surgical treatment for palmar hyperhidrosis. By contrast, the careful preoperative explanation of compensatory hyperhidrosis is considered to be very important.

Favorable effect of CD26/DPP-4 inhibitors on postoperative outcomes after lung transplantation: A propensity-weighted analysis.

BACKGROUND: We have shown the efficacy of CD26/dipeptidyl peptidase 4 (CD26/DPP-4) inhibitors, antidiabetic agents, in allograft protection after experimental lung transplantation (LTx). We aimed to elucidate whether CD26/DPP-4 inhibitors effectively improve postoperative outcomes after clinical LTx. METHODS: We retrospectively reviewed the records of patients undergoing LTx at our institution between 2010 and 2021 and extracted records of patients with diabetes mellitus (DM) at 6 months post-LTx. The patient characteristics and postoperative outcomes were analyzed. We established 6 months post-LTx as the landmark point for predicting overall survival (OS) and chronic lung allograft dysfunction (CLAD)-free survival. Hazard ratios were estimated by Cox regression after propensity score weighting, using CD26/DPP-4 inhibitor treatment up to 6 months post-LTx as the exposure variable. We evaluated CLAD samples pathologically, including for CD26/DPP-4 immunohistochemistry. RESULTS: Of 102 LTx patients with DM, 29 and 73 were treated with and without CD26/DPP-4 inhibitors, respectively. Based on propensity score adjustment using standardized mortality ratio weighting, the 5-year OS rates were 77.0% and 44.3%, and the 5-year CLAD-free survival rates 77.8% and 49.1%, in patients treated with and without CD26/DPP-4 inhibitors, respectively. The hazard ratio for CD26/DPP-4 inhibitor use was 0.34 (95% confidence interval (CI) 0.14-0.82, p = 0.017) for OS and 0.47 (95% CI 0.22-1.01, p = 0.054) for CLAD-free survival. We detected CD26/DPP-4 expression in the CLAD grafts of patients without CD26/DPP-4 inhibitors. CONCLUSIONS: Analysis using propensity score weighting showed that CD26/DPP-4 inhibitors positively affected the postoperative prognosis of LTx patients with DM.

Impact of perioperative airway pathogens on living-donor lobar lung transplantation outcomes.

PURPOSE: To elucidate the clinical impact of pathogenic organism (PO) positivity early after transplantation, we evaluated the impact of perioperative airway POs on outcomes after living-donor lobar lung transplantation (LDLLT), where the graft airway is supposed to be sterile from a healthy donor. METHOD: A retrospective review of 67 adult LDLLT procedures involving 132 living donors was performed. Presence of POs in the recipients' airways was evaluated preoperatively and postoperatively in intensive-care units. RESULTS: POs were detected preoperatively in 13 (19.4%) recipients. No POs were isolated from the donor airways at transplantation. POs were detected in 39 (58.2%) recipients postoperatively; most were different from the POs isolated preoperatively. Postoperative PO isolation was not associated with short-term outcomes other than prolonged postoperative ventilation. The 5-year overall survival was significantly better in the PO-negative group than in the PO-positive group (89.1% vs. 63.7%, P = 0.014). In the multivariate analysis, advanced age (hazard ratio [HR]: 1.041 per 1-year increase, P = 0.033) and posttransplant PO positivity in the airway (HR: 3.684, P = 0.019) significantly affected the survival. CONCLUSIONS: The airways of the living-donor grafts were microbiologically sterile. PO positivity in the airway early after transplantation negatively impacted long-term outcomes.

Correlation between the preoperative maximum soleal vein diameter and the postoperative bilateral deep venous thrombosis in THA: a case-control study.

Background: Patients with bilateral lower limb deep venous thrombosis (DVT) have a higher risk of pulmonary thromboembolism (PTE) and mortality than patients with unilateral lower limb DVT. Preoperative dilatation of the soleal vein (SV) diameter is a predictor of postoperative DVT. The purpose of this study is to investigate the cutoff value for SV diameter as a risk factor for VTE development. Materials and methods: The authors examined 274 patients with unilateral THA who met the inclusion criteria in a retrospective study. The mean age of the patients was 65.7±11.2 years, with 70 males and 204 females. Bilateral lower limb vein ultrasonography was performed preoperatively and ~1 week after THA. The frequency and localization of DVT were investigated in postoperative ultrasonography. The patients were divided into three groups: no DVT (non-DVT), unilateral lower limb DVT (Uni-DVT), and bilateral lower limb DVT (Bi-DVT). The three groups were compared in terms of preoperative venous vessel maximum diameter. Results: There were 62 patients (22.6%) who had postoperative DVT. There are no symptomatic PTE patients. DVT was found in 44 patients (16.0%) of the Uni-DVT group and 18 patients (6.6%) of the Bi-DVT group. The SV maximum diameter was 6.41±1.79 mm in the non-DVT group, 7.06±2.13 mm in the Uni-DVT group, and 8.06±2.26 mm in the Bi-DVT group, with a significant difference (P=0.001) between the non-DVT and Bi-DVT groups. In the Bi-DVT group, the cutoff value for preoperative SV maximum diameter was 6.75 mm (95% CI: 0.625-0.831; P=0.001; sensitivity, 77.8%; specificity, 60.4%; area under the curve, 0.728). Conclusions: In THA, preoperative ultrasonography with a maximum SV diameter of 6.75 mm or greater was the risk of bilateral DVT leading to fatal PTE is increased.

Wnt7b expressed by hypertrophic chondrocytes is a stimulatory factor for endochondral ossification that is regulated by Smad4 activity.

Endochondral ossification contributes to longitudinal skeletal growth. Osteoblasts, which are bone-forming cells, appear close to terminally differentiated hypertrophic chondrocytes during endochondral ossification. We established mice with conditional knockout (cKO) of Smad4, an essential co-activator for transforming growth factor ß family signaling. The mice showed a marked increase in bone volume in the metaphysis as a result of increased bone formation by osteoblasts, in which ß-catenin, an effector of canonical Wnt signaling, accumulated. We identified Wnt7b as a factor with increased expression in growth plate cartilage in Smad4 cKO mice. Wnt7b mRNA was expressed in differentiated chondrocytes and suppressed by BMP4 stimulation. Ablation of Wnt7b blunted the increase in bone in adult Smad4 cKO mice and reduced skeletal growth in juvenile mice. Overall, we conclude that Wnt7b is a crucial factor secreted from hypertrophic chondrocytes to initiate endochondral ossification. These results suggest that Smad4-dependent BMP signaling regulates the Wnt7b-ß-catenin axis during endochondral ossification.

Reduction of donor mononuclear phagocytes with clodronate-liposome during ex vivo lung perfusion attenuates ischemia-reperfusion injury.

OBJECTIVES: Clodronate-liposome is used for depleting mononuclear phagocytes associated with ischemia-reperfusion injury. We hypothesized that administration of clodronate-liposome into the perfusate during ex vivo lung perfusion could reduce mononuclear phagocytes and attenuate ischemia-reperfusion injury. METHODS: First, the number of mononuclear phagocytes in flushed grafts (minimum cold ischemic time, 6-hour cold ischemic time, 15-hour cold ischemic time, and 18-hour cold ischemic time; n = 6 each) was determined using flow cytometry. Second, grafts (15-hour cold ischemic time) were allocated to control or clodronate (n = 5 each). In the clodronate group, clodronate-liposome is administered into the perfusate. After 4 hours of ex vivo lung perfusion, the number of mononuclear phagocytes in the perfusate and lung tissues was measured. Third, grafts (15-hour cold ischemic time) were allocated to control or clodronate (n = 6 each). After 4 hours of ex vivo lung perfusion, the left lungs were transplanted and reperfused for 2 hours. Lung function was evaluated, and samples were analyzed. RESULTS: First, mononuclear phagocytes remain in flushed grafts after prolonged cold ischemia. Second, the number of mononuclear phagocytes in lung tissues after ex vivo lung perfusion was significantly reduced in the clodronate group (P = .008). Third, lung compliance and vascular resistance during ex vivo lung perfusion were significantly improved in the clodronate group (P < .001 for both). Blood oxygenation and pulmonary edema were significantly improved in the clodronate group after 2 hours of reperfusion (P = .015 and P = .026, respectively). Histological findings showed reduced lung injury in the clodronate group (P = .013). CONCLUSIONS: Administration of clodronate-liposome into the perfusate during ex vivo lung perfusion resulted in a significant reduction of mononuclear phagocytes in donor lungs, leading to attenuation of ischemia-reperfusion injury.

Specialized Proresolving Lipid Meditators Agonistic to Formyl Peptide Receptor Type 2 Attenuate Ischemia-reperfusion Injury in Rat Lung.

BACKGROUND: Lung ischemia-reperfusion injury (IRI) is a form of acute lung injury characterized by nonspecific alveolar damage and lung edema due to robust inflammation. Little is known about the roles of specialized proresolving lipid mediators (SPMs) in lung IRI. Therefore, we aimed to evaluate the dynamic changes in endogenous SPMs during the initiation and resolution of lung IRI and to determine the effects of SPM supplementation on lung IRI. METHODS: We used a rat left hilar clamp model with 90 min of ischemia, followed by reperfusion. Dynamic changes in endogenous SPMs were evaluated using liquid chromatography-tandem mass spectrometry. RESULTS: Endogenous SPMs in the left lung showed a decreasing trend after 1 h of reperfusion. Oxygenation improved between 3 and 7 d following reperfusion; however, the level of endogenous SPMs remained low compared with that in the naïve lung. Among SPM receptors, only formyl peptide receptor type 2 (ALX/FPR2) gene expression in the left lung was increased 3 h after reperfusion, and the inflammatory cells were immunohistochemically positive for ALX/FPR2. Administration of aspirin-triggered (AT) resolvin D1 (AT-RvD1) and AT lipoxin A4 (AT-LXA4), which are agonistic to ALX/FPR2, immediately after reperfusion improved lung function, reduced inflammatory cytokine levels, attenuated lung edema, and decreased neutrophil infiltration 3 h after reperfusion. The effects of AT-RvD1 and AT-LXA4 were not observed after pretreatment with the ALX/FPR2 antagonist. CONCLUSIONS: The level of intrapulmonary endogenous SPMs decreased during lung IRI process and the administration of AT-RvD1 and AT-LXA4 prevented the exacerbation of lung injury via ALX/FPR2.

Development of the Protocol to Deliver Graded Stimulation Intensity on Lower Limbs Using Belt-shaped Electrode Skeletal Muscle Stimulation.

OBJECTIVES: Current advancements in neuromuscular electrical stimulation (NMES) include belt-shaped electrode skeletal muscle electrical stimulation (B-SES), which was developed to induce whole leg muscle contraction in a single session. Delivering the optimal amount of stimulation is critical in NMES; therefore, we set out to establish a method to determine the B-SES stimulation intensity needed to induce muscle contraction sufficient for clinical purposes. METHODS: We used the Auto Tens Pro system (Homer Ion Laboratory), which is a B-SES device. Stimulation at 20 Hz was delivered for 5 s, followed by 2 s rest. Twenty-four patients who were hospitalized for musculoskeletal diseases were enrolled at two hospitals. Patients were randomly assigned to one of three groups of subjectively graded stimulation intensities: moderate, strong, or very strong. To achieve each target intensity, we developed a structured verbal instruction protocol that aimed to help therapists deliver the target level of stimulation. As a physiological assessment of muscle contraction, serum lactate levels were measured before and after a single 20-min B-SES session. RESULTS: The electric current intensity required to achieve a target subjective muscle contraction gradually increase according to the subjective contraction level. The increase in serum lactate level was significantly larger in the very strong group than in the moderate group. CONCLUSIONS: B-SES stimulators have the potential to induce efficient muscle strengthening in patients with musculoskeletal diseases. The structured verbal protocol developed here could help therapists achieve the appropriate stimulation intensity for each patient.

Oncologic emergency in patients with skeletal metastasis of unknown primary.

AIM: Patients with skeletal metastasis from prediagnosed primary malignancy sometimes have concurrent oncologic emergency (OE) during the first visit. This study aims to investigate the types of OEs and treatment outcome in such patients. METHODS: We have experienced 359 patients with skeletal metastasis from unknown primary malignancy. Among them, 130 patients required immediate admission for OE treatment (OE group), 229 patients had no OE and did not required immediate admission (non-OE group). RESULTS: The recognized types of OE were spinal cord compression in 60 patients, cancer pain in 30, hypercalcemia in 19, delirium in 16, deep vein thrombosis in 13, acute renal failure in 6, respiratory failure in 3, gastrointestinal hemorrhage in 3, and disseminated intravascular coagulation in 1. The overall 5-year survival rates were 28% and 37% in the OE and non-OE groups, respectively (P < 0.001). The multivariate analysis revealed that delirium (hazard ratio 4.2; 95% confidence interval, 1.6-12.5; P < 0.005) and respiratory failure (hazard ratio 22.6; 95% confidence interval, 4.5-92.8; P < 0.001) were significant prognostic factors in patients with OEs, whereas other OEs did not confer a significant risk for patient outcomes. CONCLUSION: In this study, OE was observed in as many as 36% of patients with skeletal metastasis from unknown primary malignancy. Delirium and respiratory failure were only two significant prognostic risk factors, which suggest that many of the OEs in untreated advanced cancer patients have probable chance to resolve. Early detection followed by appropriate treatment of such OEs is recommended.

Characterization and Function of Tumor Necrosis Factor and Interleukin-6-Induced Osteoclasts in Rheumatoid Arthritis.

OBJECTIVE: We have previously reported that stimulation of mouse bone marrow-derived macrophages with tumor necrosis factor (TNF) and interleukin-6 (IL-6) induces differentiation of osteoclast-like cells. We undertook this study to clarify the characterization and function of human TNF and IL-6-induced osteoclasts using peripheral blood collected from patients with rheumatoid arthritis (RA) and healthy donors. METHODS: Peripheral blood monocytes were cultured with a combination of TNF and IL-6, TNF alone, IL-6 alone, or with RANKL, and their bone resorption ability was evaluated. Expression levels of NFATc1, proinflammatory cytokines, and matrix metalloproteinase 3 were analyzed. The effects of NFAT inhibitor and JAK inhibitor were examined. Furthermore, the relationship between the number of TNF and IL-6-induced osteoclasts or RANKL-induced osteoclasts differentiated from peripheral blood mononuclear cells (PBMCs) in patients with RA and the modified total Sharp score (mTSS) or whole-body bone mineral density (BMD) was examined. RESULTS: Peripheral blood monocytes stimulated with a TNF and IL-6-induced osteoclasts were shown to demonstrate the ability to absorb bone matrix. Cell differentiation was not inhibited by the addition of osteoprotegerin. Stimulation with a combination of TNF and IL-6 promoted NFATc1 expression, whereas the NFAT and JAK inhibitors prevented TNF and IL-6-induced osteoclast formation. Expression levels of IL1ß, TNF, IL12p40, and MMP3 were significantly increased in TNF and IL-6-induced osteoclasts, but not in RANKL-induced osteoclasts. The number of TNF and IL-6-induced osteoclasts differentiated from PBMCs in patients with RA positively correlated with the mTSS, whereas RANKL-induced osteoclast numbers negatively correlated with the whole-body BMD of the same patients. CONCLUSION: Our results demonstrate that TNF and IL-6-induced osteoclasts may contribute to the pathology of inflammatory arthritis associated with joint destruction, such as RA.

Relationship between the physician-based clinical scale for foot and ankle surgery and patient-reported outcomes in patients with long-standing rheumatoid arthritis: Results from a multicenter prospective observational cohort study.

OBJECTIVES: To validate and establish targets for the physician-based clinical scale for foot surgery in rheumatoid arthritis (RA) patients based on patient-reported outcomes from a multicenter prospective cohort. METHODS: We collected data on demographics, values from the RA foot and ankle scale by the Japanese Society for Surgery of the Foot (JSSF-RA), and patient-reported outcomes (PROs) including the Health Assessment Questionnaire Disability Index (HAQ-DI) before (baseline) and 6 and 12 months after joint surgery. Target values for JSSF-RA were determined according to the lower limit of the 95% CI of JSSF-RA in patients with HAQ-DI ≤0.5 after adjusting for age and sex. We used multiple linear regression analysis to examine potential predictors of JSSF-RA target achievement at baseline. RESULTS: Cross-sectional analysis was conducted on data from 417 cases. The JSSF-RA target for foot and ankle surgery was set at 74 according to the JSSF-RA value corresponding to HAQ-DI ≤0.5 (mean 77.6, 95% CI: 74.3-80.9). Longitudinal analysis of patients who underwent foot surgery (N = 59) determined target cut-off values of 1.188 and 65 for HAQ-DI and JSSF-RA at baseline, respectively, as being predictive for achieving JSSF-RA ≥74 after surgery. CONCLUSIONS: A JSSF-RA value of 74 represents an important target for patients with RA who have undergone foot surgery. In order to achieve this target, the timing of the surgery should be considered in the treatment of established RA patients.

Imaging evaluation of the cartilage in rheumatoid arthritis patients with an x-ray phase imaging apparatus based on Talbot-Lau interferometry.

X-ray Talbot-Lau interferometry is one of the x-ray phase imaging methods that has high sensitivity in depicting soft tissues. Unlike earlier x-ray phase imaging methods that required particular types of x-ray sources, such as a synchrotron or a micro-focus x-ray tube, x-ray Talbot-Lau interferometry enables to perform clinical x-ray phase imaging using a conventional x-ray source with a relatively compact configuration. We developed an apparatus to depict cartilage in the metacarpophalangeal joints of the hands. In addition, we examined the apparatus performance by applying it to healthy volunteers and patients with rheumatoid arthritis (RA). Cartilage deformation, which is thought to be a precursor of destruction of the joints, was successfully depicted by the apparatus, suggesting a potential early diagnosis of RA.

Living-donor single-lobe lung transplantation for pulmonary hypertension due to alveolar capillary dysplasia with misalignment of pulmonary veins.

This is a case report of a successful single-lobe lung transplantation for pulmonary hypertension secondary to alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV). A 6-year-old boy underwent living-donor single-lobe transplantation with the right lower lobe from his 31-year-old mother. The pretransplantation graft size matching was acceptable: the estimated graft forced vital capacity (FVC) was 96.5% of the recipient's predicted FVC, and the graft size measured by computed tomography (CT) volumetry was 166% of the recipient's chest cavity volume. Right pneumonectomy followed by implantation was performed under cardiopulmonary bypass (CPB). The pulmonary arterial pressure was significantly decreased to 31/12 mm Hg immediately after transplantation, and the first PaO2 /FiO2 in the intensive-care unit (ICU) was 422 mm Hg. Lung perfusion scintigraphy showed 97.5% perfusion to the right implanted lung 3 months after transplantation. Chest CT showed a mass rapidly growing in the native left upper lobe 6 months after transplantation, which was diagnosed as posttransplant lymphoproliferative disorder (PTLD) by a CT-guided biopsy. After immunosuppressant reduction and six courses of chemotherapy with rituximab, he underwent native left upper lobectomy for salvage lung resection 13 months after transplantation. Seven months after lobectomy, he has returned to normal school life without any sign of tumor recurrence.

Use of a Three-Dimensional Model in Lung Transplantation for a Patient With Giant Pulmonary Aneurysm.

Management of a giant pulmonary trunk aneurysm in lung transplantation is a challenge. Herein, we present a patient undergoing replacement of the giant pulmonary artery aneurysm with a donor's aorta in bilateral lung transplantation for idiopathic pulmonary arterial hypertension. A plastic three-dimensional model of the pulmonary artery aneurysm created accurately based on computed tomography data allowed us to simulate the procedure on the back table. Our intraoperative findings and management are discussed in this article.

Emergent surgical treatment for acute thrombosis caused by pulmonary artery kinking after left upper sleeve lobectomy.

This is a report on the pulmonary arterioplasty for mechanical stenosis post-left upper sleeve lobectomy. A 64-year-old man had a tumour protruding into the left upper bronchus with a diagnosis of squamous cell carcinoma (cT1cN1M0). Left upper bronchial sleeve lobectomy was performed through posterolateral thoracotomy. On postoperative day 1, he received veno-arterial extracorporeal membrane oxygen support due to sudden pulseless electrical activity. We detected left pulmonary artery (PA) kinking with an impaired blood flow by using pulmonary angiography and immediately performed PA thrombectomy and arterioplasty using rethoracotomy. Following the en bloc removal of a thrombus that had completely occluded the left PA, the redundant PA was resected, and PA reconstruction was performed by direct end-to-end anastomosis. A postoperative contrast-enhanced computed tomography scan showed no signs of PA kinking and no residual thrombus formation. When PA bending and mechanical stenosis are detected after bronchial sleeve lobectomy, resection of the redundant PA is also required to prevent PA thrombosis.

The impact of antecedent primary malignancy in soft tissue sarcoma patients.

BACKGROUND: It is unclear whether antecedent primary malignancies (APMs) have any negative impact on the prognosis of soft tissue sarcoma (STS). We retrospectively reviewed STS patients with APMs (STS-APM) and compared their survival to those of STS only (STS-O). METHODS: Twenty-one cases of STS-APM from 2008 to 2017 in our institution were analyzed. One hundred and seventy cases of STS-O at the same period were compared as a control group. Overall survival was estimated using Kaplan-Meier survival curves and prognostic factors were analyzed using logistic regression analyses and contingency table analyses. RESULTS: As the final status of STS-APM patients, 12 patients were in disease-free survival, 5 were alive with disease, 3 have died of disease, and 1 has died of another disease. There was no case that died of APM. The 5-year overall survival rates were 88% in STS-APM and 78% in STS-O, showing no statistical significant ( p = 0.65). The 5-year overall survival rates in each stage of STS-APM and STS-O were 100/100% in stage I, 100/85% in stage II, 86/72% in stage III, and the 3-year overall survival rates were 67/51% in stage IV, with no statistical significance. With regard to prognostic factor, histological grade of STS was the only significant factor. Although antecedent radiotherapy tended to show a high odds ratio, the association was not statistically significant. Antecedent chemotherapy did not show any estimated prognostic risk. CONCLUSIONS: Our study suggested that APM in STS patient would not be a negative prognostic factor.

Target setting for lower limb joint surgery using the Timed Up and Go test in patients with rheumatoid arthritis: A prospective cohort study.

OBJECTIVE: This prospective observational cohort study aimed to set targets for lower limb joint surgery based on the Timed Up and Go test (TUG), an objective functional outcome measure, in patients with established rheumatoid arthritis (RA). METHODS: We validated TUG as an outcome measure of lower limb joint surgery and compared it with changes in patient-reported outcomes, including the Health Assessment Questionnaire Disability Index (HAQ-DI) and European Quality of life scale with five dimensions (EQ-5D). Changes in these outcomes were compared by performed surgery and by achievement of the minimal clinically important difference (MCID) for EQ-5D using univariate analysis of variance. Associations between TUG and HAQ remission (HAQ-DI ≤0.5) were determined using logistic regression analysis. Cut-off values of TUG at baseline and 6 months after surgery for HAQ remission were determined using receiver operating characteristic curves. RESULTS: A total of 126 patients were analyzed. Mean age, HAQ-DI, and TUG were 65.4 years, 1.036, and 12.8 seconds, respectively. After surgery, patients showed improvements in TUG as well as HAQ-DI. TUG at 6 months after surgery was significantly associated with HAQ remission (adjusted OR: 0.78; 95% CI: 0.65-0.93). TUG cut-off values at baseline and 6 months after surgery for achieving HAQ remission were 12.1 and 8.8 seconds, respectively. Significant improvements in TUG (∆TUG, 3.7 seconds) were associated with achievement of the MCID for EQ-5D (≥0.05) at 6 months after surgery. CONCLUSION: Timed Up and Go test is a useful tool for assessing the outcome of lower limb joint surgery in RA patients. We propose that TUG ≤9 seconds could be an objective target for achieving good physical function after lower limb joint surgery.

Altered gene expression profiles of histone lysine methyltransferases and demethylases in rheumatoid arthritis synovial fibroblasts.

OBJECTIVES: Aberrant histone lysine methylation (HKM) has been reported in rheumatoid arthritis (RA) synovial fibroblasts (SFs). As histone lysine methyltransferases (HKMTs) and demethylases (HKDMs) regulate HKM, these enzymes are believed to be dysregulated in RASFs. The aim of this study is to clarify whether gene expressions of HKMTs and HKDMs are altered in RASFs. METHODS: SFs were isolated from synovial tissues obtained from RA or osteoarthritis (OA) patients during total knee joint replacement. The mRNA levels of 34 HKMTs and 22 HKDMs were examined after stimulation with tumour necrosis factor α (TNF-α) in RASFs and OASFs. RESULTS: The gene expression of the 12 HKMTs, including MLL1, MLL3, SUV39H1, SUV39H2, PRDM2, EZH2, SETD2, NSD2, NSD3, SMYD4, DOT1, and PR-set7, that catalyse the methylation of H3K4, H3K9, H3K27, H3K36, H3K79, or H4K20 was higher after TNFα stimulation in RASFs vs. OASFs. The gene expression of the 4 HKDMs, including FBXL10, NO66, JMJD2D, and FBXL11, that catalyse the methylation of H3K4, H3K9, or H3K36 was higher after TNFα stimulation in RASFs vs. OASFs. CONCLUSIONS: The study findings suggest that the HKM-modifying enzymes are involved in the alteration of HKM, which results in changes in the gene expression of RASFs.

Validation and reliability of the Timed Up and Go test for measuring objective functional impairment in patients with long-standing rheumatoid arthritis: a cross-sectional study.

AIM: This study aimed to validate the Timed Up and Go test (TUG) for measuring objective functional impairment in patients with established rheumatoid arthritis (RA) based on a prospective observational cohort of RA patients undergoing joint surgery. METHODS: We collected data on demographics, Health Assessment Questionnaire Disability Index (HAQ-DI), and associations between TUG and HAQ-DI and other patient-reported outcomes, including European Quality of life scale (EQ-5D) were determined. Cut-off values of TUG for HAQ remission (HAQ-DI ≤0.5), normal HAQ (HAQ-DI ≤0.25), and the absence of disability in each HAQ-DI category were also determined by age. RESULTS: A total of 435 patients were enrolled and analyzed. Mean age was 64.2 years, mean disease duration was 17.1 years, mean HAQ-DI was 1.14, and mean TUG was 11.1 sec. TUG was significantly correlated with aging, EQ-5D, and HAQ-DI categories related to lower limb function (arising, walking, reach and activity). After adjusting for age and sex, mean TUG values were 9.0 sec (95% CI, 7.7-10.3) in patients with HAQ remission and 8.7 sec (7.4-10.4) in those with normal HAQ. By age, mean TUG values for HAQ remission were 7.2 sec (5.9-8.5) in young patients (≤61 years), 9.1 sec (7.6-10.5) in middle-aged patients (62-70 years) and 10.0 sec (5.7-14.2) in old patients (≥71 years). CONCLUSION: TUG was significantly associated with functional impairment and aging in patients with long-standing RA. Thus, TUG could be useful in setting treatment goals for joint surgery and rehabilitation in established RA patients.