Miliary tuberculosis-associated hemophagocytic lymphohistiocytosis with a high level of soluble interleukin-2 receptor successfully treated with concomitant recombinant thrombomodulin: A case report.

Hemophagocytic lymphohistiocytosis (HLH) is a fatal disease characterized by a highly inflammatory state due to the abnormal activation of T lymphocytes and macrophages. Miliary tuberculosis (MTB) is a rare cause of HLH and its clinical appearances occasionally resembles that of intravascular lymphoma (IVL). A 76-year-old woman presented with persistent fever and fatigue. Abnormal laboratory findings showing thrombocytopenia (13,000/µL), hypofibrinogenemia (101 mg/dL), hyperferritinemia (2,312 ng/mL), and markedly elevated soluble interleukin-2 receptor (sIL-2R) level (32,200 U/mL), in addition, hemophagocytosis in the bone marrow (BM) smear, were suggestive of IVL-associated HLH. The pathology of the BM biopsy specimen showed granuloma with non-caseous necrosis, and culture tests using sputum, gastric fluid, urine, and peripheral and bone marrow blood revealed the presence of Mycobacterium tuberculosis, leading to the final diagnosis of MTB-associated HLH. Anti-TB medications and corticosteroids were administered, but thrombocytopenia, hypofibrinogenemia, and hyperferritinemia persisted. Concomitant use of recombinant thrombomodulin (rTM) enabled regression of clinical status. In this case, BM biopsy served as the diagnosis of MTB-associated HLH, although IVL-associated HLH is initially suspected by an extremely high level of sIL-2R. Furthermore, this case report informs that using rTM could improve the outcomes of MTB-associated HLH.

Effects of dimension reduction of hyperspectral images in skin gross pathology.

BACKGROUND: Hyperspectral imaging (HSI) is an emerging modality for the gross pathology of the skin. Spectral signatures of HSI could discriminate malignant from benign tissue. Because of inherent redundancies in HSI and in order to facilitate the use of deep-learning models, dimension reduction is a common preprocessing step. The effects of dimension reduction choice, training scope, and number of retained dimensions have not been evaluated on skin HSI for segmentation tasks. MATERIALS AND METHODS: An in-house dataset of HSI signatures from pigmented skin lesions was prepared and labeled with histology. Eleven different dimension reduction methods were used as preprocessing for tumor margin detection with support vector machines. Cluster-wise principal component analysis (ClusterPCA), a new variant of PCA, was proposed. The scope of application for dimension reduction was also investigated. RESULTS: The components produced by ClusterPCA show good agreement with the expected optical properties of skin chromophores. Random forest importance performed best during classification. However, all methods suffered from low sensitivity and generalization. CONCLUSION: Investigation of more complex reduction and segmentation schemes with emphasis on the nature of HSI and optical properties of the skin is necessary. Insights on dimension reduction for skin tissue could facilitate the development of HSI-based systems for cancer margin detection at gross level.

Effects of Unrestricted Kinematically Aligned Total Knee Arthroplasty with a Modified Soft-Tissue Respecting Technique on the Deformity of Limb Alignment in Japanese Patients.

Background and Objectives: Unrestricted kinematic alignment total knee arthroplasty (KA-TKA) with a soft-tissue respecting technique (STRT) is a soft-tissue-dependent tibial resection entailing the restoration of the original soft-tissue tension using ligamentotaxis after resurfacing the femur, based on the concept of restoring the native or pre-osteoarthritis alignment in each patient. However, there is no consensus on the indications of unrestricted KA-TKA with the STRT. We modified the STRT, followed by an investigation of the effects of surgery on the postoperative hip-knee-ankle angle (HKAA). Materials and Methods: We retrospectively analyzed the clinical background data, including the preoperative and postoperative HKAA, of 87 patients who underwent unrestricted KA-TKA with the modified STRT. Univariate and multivariate analyses were performed to determine the factors affecting the postoperative HKAA. A receiver operating characteristic (ROC) curve was plotted to investigate the change in the cut-off values of preoperative HKAA with respect to the safe zone of the postoperative HKAA. We generated two regression models, the linear regression model and generalized additive model (GAM) using machine learning, to predict the postoperative HKAA. Results: Univariate and multivariate analyses revealed the preoperative HKAA as the factor most relevant to the postoperative HKAA. ROC analysis revealed that the preoperative HKAA exhibited a high predictive utility, with a cut-off value of -10°, when the safe range of postoperative HKAA was set at ±5°. The GAM was the superior machine learning model, indicating a non-linear association between the preoperative and postoperative HKAA. Patients with preoperative HKAAs ranging from -18° to 4° were more likely to fall within the ±5° safe range of the postoperative HKAA. Conclusions: The preoperative HKAA influences the postoperative HKAA in unrestricted KA-TKA with the modified STRT. Machine learning using the GAM may contribute to the selection of patients eligible for the surgical approach.

Effects of empagliflozin versus placebo on cardiac sympathetic activity in acute myocardial infarction patients with type 2 diabetes mellitus: the EMBODY trial.

BACKGROUND: Protection from lethal ventricular arrhythmias leading to sudden cardiac death (SCD) is a crucial challenge after acute myocardial infarction (AMI). Cardiac sympathetic and parasympathetic activity can be noninvasively assessed using heart rate variability (HRV) and heart rate turbulence (HRT). The EMBODY trial was designed to determine whether the Sodium-glucose cotransporter 2 (SGLT2) inhibitor improves cardiac nerve activity. METHODS: This prospective, multicenter, randomized, double-blind, placebo-controlled trial included patients with AMI and type 2 diabetes mellitus (T2DM) in Japan; 105 patients were randomized (1:1) to receive once-daily 10-mg empagliflozin or placebo. The primary endpoints were changes in HRV, e.g., the standard deviation of all 5-min mean normal RR intervals (SDANN) and the low-frequency-to-high-frequency (LF/HF) ratio from baseline to 24 weeks. Secondary endpoints were changes in other sudden cardiac death (SCD) surrogate markers such as HRT. RESULTS: Overall, 96 patients were included (46, empagliflozin group; 50, placebo group). The changes in SDANN were + 11.6 and + 9.1 ms in the empagliflozin (P = 0.02) and placebo groups (P = 0.06), respectively. Change in LF/HF ratio was - 0.57 and - 0.17 in the empagliflozin (P = 0.01) and placebo groups (P = 0.43), respectively. Significant improvement was noted in HRT only in the empagliflozin group (P = 0.01). Whereas intergroup comparison on HRV and HRT showed no significant difference between the empagliflozin and placebo groups. Compared with the placebo group, the empagliflozin group showed significant decreases in body weight, systolic blood pressure, and uric acid. In the empagliflozin group, no adverse events were observed. CONCLUSIONS: This is the first randomized clinical data to evaluate the effect of empagliflozin on cardiac sympathetic and parasympathetic activity in patients with T2DM and AMI. Early SGLT2 inhibitor administration in AMI patients with T2DM might be effective in improving cardiac nerve activity without any adverse events. TRIAL REGISTRATION: The EMBODY trial was registered by the UMIN in November 2017 (ID: 000030158). UMIN000030158; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000034442 .

Reduced oxygenation but not fibrosis defined by functional magnetic resonance imaging predicts the long-term progression of chronic kidney disease.

BACKGROUND: Although chronic hypoxia and fibrosis may be a key to the progression of chronic kidney disease (CKD), a noninvasive means of measuring these variables is not yet available. Here, using blood oxygen level-dependent (BOLD) and diffusion-weighted (DW) magnetic resonance imaging (MRI), we assessed changes in renal tissue oxygenation and fibrosis, respectively, and evaluated their correlation with prognosis for renal function. METHODS: The study was conducted under a single-center, longitudinal, retrospective observational design. We examined the prognostic significance of T2* values of BOLD-MRI and apparent diffusion coefficient (ADC) values on DW-MRI and other clinical parameters. The rate of decline in estimated glomerular filtration rate (eGFR) was calculated by linear regression analysis using changes in eGFR during the observation period. RESULTS: A total of 91 patients were enrolled, with a mean age of 55.8 ± 15.6 years. Among patients, 51 (56.0%) were males and 38 (41.8%) had diabetes mellitus. The mean eGFR was 49.2 ± 28.9 mL/min/1.73 m2 and the mean observation period was 5.13 years. ADC values of DW-MRI but not T2* values of BOLD-MRI were well correlated with eGFR at the initial time point. The mean annual rate of decline in eGFR during the 5-year observation period was -1.92 ± 3.00 mL/min/1.73 m2. On multiple linear regression analysis, the rate of decline in eGFR was significantly correlated with eGFR at the start point, period average amount of proteinuria and T2* values, but not with ADC values (t = 2.980, P = 0.004). CONCLUSIONS: Reduced oxygenation as determined by low T2* values on BOLD-MRI is a clinically useful marker of CKD progression.

Soluble Lectin-like Oxidized Low-Density Lipoprotein Receptor 1 Predicts the Changes of Rheumatoid Factor Titers in Rheumatoid Arthritis.

OBJECTIVE: The aim of this longitudinal study was to examine the clinical significance of soluble lectin-like oxidized low-density lipoprotein receptor 1 (sLOX-1) in patients with rheumatoid arthritis. METHODS: We gathered demographic and clinical data for a large rheumatoid arthritis cohort at 3 time points. Blood samples were collected at each time point; the number of samples was 282 cases in 2012, 431 cases in 2013, and 500 cases in 2014. Plasma sLOX-1 was measured by enzyme-linked immunosorbent assay. Correlations between sLOX-1 and clinical data were analyzed. Predictive factors associated with changes in sLOX-1 and rheumatoid factor (RF) were analyzed by multivariate linear regression. RESULTS: Plasma sLOX-1 level was significantly correlated with RF titer and other clinical parameters. The longitudinal analyses showed that changes in sLOX-1 were significantly correlated with changes in RF titers and with those at baseline. Multivariate linear regression analysis revealed that changes in RF and baseline RF were predictive factors for changes in sLOX-1. Conversely, the changes in RF were significantly correlated with the changes in sLOX-1 in all years. A stepwise regression analysis showed that the change in sLOX-1 was a predictive factor for the change in RF. CONCLUSIONS: The change in sLOX-1 has predictive value for assessing the change in RF, indicating the usefulness of sLOX-1 in clinical practice.

Semi-Automatic Calibration Method for a Bed-Monitoring System Using Infrared Image Depth Sensors.

With the aging of society, the number of fall accidents has increased in hospitals and care facilities, and some accidents have happened around beds. To help prevent accidents, mats and clip sensors have been used in these facilities but they can be invasive, and their purpose may be misinterpreted. In recent years, research has been conducted using an infrared-image depth sensor as a bed-monitoring system for detecting a patient getting up, exiting the bed, and/or falling; however, some manual calibration was required initially to set up the sensor in each instance. We propose a bed-monitoring system that retains the infrared-image depth sensors but uses semi-automatic rather than manual calibration in each situation where it is applied. Our automated methods robustly calculate the bed region, surrounding floor, sensor location, and attitude, and can recognize the spatial position of the patient even when the sensor is attached but unconstrained. Also, we propose a means to reconfigure the spatial position considering occlusion by parts of the bed and also accounting for the gravity center of the patient's body. Experimental results of multi-view calibration and motion simulation showed that our methods were effective for recognition of the spatial position of the patient.

A case of infection-related glomerulonephritis with massive eosinophilic infiltration
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Infection-related glomerulonephritis (IRGN) is rarely complicated with eosinophil infiltration into the glomerulus. Here we report a case of eosinophilic proliferative glomerulonephritis related with infection. A 70-year-old man with respiratory symptoms displayed hypereosinophilia, hypocomplementemia, impaired renal function, and nephrotic syndrome. Renal biopsy revealed endocapillary proliferative glomerulonephritis with immunostaining for immunoglobulin G and complement 3, and subepithelial hump-like electron-dense deposits, thus fulfilling the criteria for IRGN. Immunostaining for the nephritis-associated plasmin receptor (NAPlr) in the glomerulus confirmed the diagnosis of IRGN. Of note, eosinophils infiltrated into the glomerular subendothelial spaces, renal tubules, peritubular capillaries, and the interstitium in the kidney as well as in the alveolar walls and pulmonary arteries in the lung. Corticosteroid therapy rapidly improved hypereosinophilia as well as respiratory symptoms and renal function. Urinary protein exertion was decreased, and serum level of complement and albumin was increased. These findings suggest that eosinophil infiltration might play a prominent role in respiratory and renal disorders. Severe endothelial damage of glomeruli and tubulointerstitial nephritis, caused by eosinophil-rich inflammation, might significantly contribute to exacerbation of renal insufficiency.
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Effects of tolvaptan on urine output in hospitalized heart failure patients with hypoalbuminemia or proteinuria.

Hypoalbuminemia is an independent prognostic factor in hospitalization for heart failure (HHF). Hypoalbuminemia or proteinuria is related to resistance to loop diuretics. Tolvaptan is an oral non-peptide, competitive antagonist of vasopressin receptor-2. It has been used for the treatment of volume overload in HHF patients in several Asian countries. Several studies have demonstrated marked improvement in congestion in HHF patients. However, whether tolvaptan is useful for HHF patients with hypoalbuminemia or proteinuria (both of which are related to resistance to loop diuretics) has not been clarified. We examined the diuretic response to tolvaptan in HHF patients with hypoalbuminemia or proteinuria. We defined hypoalbuminemia as a serum level of albumin < 2.6 g/dl. Fifty-one HHF patients who received additional tolvaptan upon therapies with loop diuretics were divided into the hypoalbuminemia group (n = 24) or control group (n = 27). The changes in urine output per day were not different between the two groups [610 (range 100-1032); 742 (505-1247) ml, P = 0.313]. There was no difference in diuretic responses between patients with and without proteinuria. The serum level of albumin did not correlate with changes in urine output per day after tolvaptan treatment (P = 0.276, r = 0.156). Thus, additional administration of tolvaptan elicited a good diuretic response in HHF patients with hypoalbuminemia or proteinuria. These data suggest that tolvaptan might be beneficial for such HHF patients.

Noise Generation With Good Range of Motion but Without Femorotibial Instability Has Small Effect on Patient Satisfaction After Total Knee Arthroplasty.

BACKGROUND: There are several causes of patient dissatisfaction after total knee arthroplasty (TKA). This study hypothesized that noise occurring in the knee would worsen patient satisfaction after TKA. METHODS: We mailed a newly developed questionnaire to 103 consecutive participants who were followed for one year, resulting in data from 61 knees in 60 patients (47 women and 13 men, mean age 73 years) who underwent cruciate-substituting TKA. We evaluated postoperative range of motion, knee instability, and the 2011 Knee Society Score in terms of noise generation after TKA. RESULTS: Over half of the patients noticed postoperative noise that occurred during the mid range of knee motion, but noise was not associated with feelings of instability. Postoperative range of motion differed significantly between the group with noise (122.8 ± 12.0°) and that without noise (106.3 ± 23.3°). The patellar tilt angle was also significantly larger in the group with noise (7.4 ± 5.5°) than that without noise (3.3 ± 2.6°). However, collateral ligament laxity had no significant effect on noise, and the 2011 Knee Society Score did not differ significantly different between the noise and no-noise groups. CONCLUSION: Our hypothesis was refuted, and these findings suggest patient satisfaction after TKA is influenced more by good knee function than by noise generation.

Subsidence of total ankle component associated with deterioration of an ankle scale in non-inflammatory arthritis but not in rheumatoid arthritis.

OBJECTIVES: Modern three-component total ankle arthroplasty (TAA) has favorable clinical results and survival rates. However, radiographic deterioration and worsening of clinical symptoms may occur in patients with rheumatoid arthritis (RA) or non-inflammatory arthritis (NA). The associations between outcomes and clinical and radiological factors are not clear. We compared midterm clinical and radiographic outcomes after TAA between patients with RA and those with NA. METHODS: Twenty-six TAAs were performed using a three-component prosthesis, the FINE Total Ankle System during the study period. Fourteen TAAs with 11 RA patients undergoing primary TAA were compared with twelve TAAs with 12 NA patients. Clinical and radiographic outcomes were evaluated before and after operation, and at the final follow-up. RESULTS: The Japanese Society for Surgery of the Foot (JSSF) scale improved significantly following TAA in both groups (p = 0.0039 and 0.0156, respectively). Tibial subsidence, talar subsidence and age were significantly associated with postoperative JSSF score only in the NA group (p = 0.0027, 0.0017 and p < 0.0001, respectively). Stepwise regression analysis showed that talar subsidence was an independent predictor of a worse JSSF score in the NA group (F = 10.3). CONCLUSIONS: The final clinical outcome was negatively influenced by talar subsidence in patients with NA, but not in those with RA.

No condylar lift-off occurs because of excessive lateral soft tissue laxity in neutrally aligned total knee arthroplasty: a computer simulation study.

PURPOSE: Condylar lift-off can induce excessive polyethylene wear after total knee arthroplasty (TKA). A computer simulation was used to evaluate the influence of femoral varus alignment and lateral collateral ligament (LCL) laxity on lift-off after single-design TKA. It was hypothesised that proper ligament balancing and coronal alignment would prevent lift-off. METHODS: The computer model in this study is a dynamic musculoskeletal program that simulates gait up to 60° of knee flexion. The lift-off phenomenon was defined as positive with an intercomponent distance of >2 mm. In neutrally aligned components in the coronal plane, the femoral and tibial components were set perpendicular to the femoral and tibial mechanical axis, respectively. The femoral coronal alignment was changed from neutral to 5° varus in 1° increments. Simultaneously, the LCL length was elongated from 0 to 5 mm in 1-mm increments to provide a model of pathological slack. RESULTS: Within 2° of femoral varus alignment, lift-off did not occur even if the LCL was elongated by up to 5 mm. However, lift-off occurred easily in the stance phase in femoral varus alignments of >3° with slight LCL slack. The contact forces of the tibiofemoral joint were influenced more by femoral varus alignment than by LCL laxity. CONCLUSIONS: Aiming for neutral alignment in severely varus knees makes it difficult to achieve appropriate ligament balance. Our study suggests that no lift-off occurs with excessive LCL laxity alone in a neutrally aligned TKA and therefore that varus alignment should be avoided to decrease lift-off after TKA. LEVEL OF EVIDENCE: Case series, Level IV.

Quadriceps strength affects patient satisfaction after total knee arthroplasty.

BACKGROUND: Total knee arthroplasty is one of the most successful surgeries with respect to relieving pain and restoring function of the knee. However, some studies have reported that patients are not always satisfied with their results after total knee arthroplasty. The aim of this study was to determine whether the muscle strength around the knee joint and the walking status influence patients' expectations and satisfaction before and after total knee arthroplasty. METHODS: We evaluated 28 patients who underwent 30 primary total knee arthroplasties from March 2012 to June 2013. We assessed patient-reported scores using the 2011 Knee Society Scoring System, knee extensor and flexor strength, the 10-m walking test, and the timed up-and-go test. All assessments were performed preoperatively and 1 year after total knee arthroplasty. We determined the correlation between the patient-reported scores and each variable. RESULTS: Preoperative patient satisfaction was significantly correlated with knee symptoms and functional activities, but not with muscle strength or walking status. Postoperative patient satisfaction was significantly correlated with knee symptoms, functional activities, knee extensor strength, and walking status, including the 10-m walking test and timed up-and-go test, after total knee arthroplasty. In stepwise regression analysis, predictors of patient satisfaction with total knee arthroplasty were knee symptoms, functional ability, and knee extensor strength. CONCLUSIONS: Our study demonstrates that pain relief and restoration of functional activity are highly correlated with increasing patient satisfaction after total knee arthroplasty. The results also indicate that the quadriceps is important for patient satisfaction and restoration of functional activity following total knee arthroplasty.

Limited extension after linked total elbow arthroplasty in patients with rheumatoid arthritis.

OBJECTIVE: Total elbow arthroplasty (TEA) has become an established procedure to relieve pain and to increase the range of motion of the destructed elbow in patients with rheumatoid arthritis (RA). However, some patients still have limited extension after TEA, and the causes of limited extension after TEA have yet to be elucidated. METHODS: To examine whether widening of the joint space can cause such limited extension, we retrospectively analyzed 55 cases of linked TEA in patients with RA. There were seven male and 40 female with a mean age of 63.8 years (range, 30-80 years) and a mean follow-up of 7.5 ± 4.2 years (range, 2.5-15.6 years). The Mayo Elbow Performance Score (MEPS) and radiological measurements were recorded. Widening of the joint space was calculated by subtracting the length measured on postoperative radiograph from preoperative radiograph. RESULTS: MEPS and range of motion were significantly improved after surgery except for extension. The degree of extension was significantly correlated with radiological widening of the joint space in the limited extension group. Correlation analyses showed that postoperative limited extension was correlated with lower MEPS daily function. CONCLUSIONS: Limited extension after linked TEA is partly derived from perioperative widening of the joint space and potentially limits daily function in patients with RA.

Plasma sLOX-1 is a potent biomarker of clinical remission and disease activity in patients with seropositive RA.

OBJECTIVES: Soluble lectin-like oxidized low-density lipoprotein receptor 1 (sLOX-1) is present in the circulation and synovial fluid in patients with rheumatoid arthritis (RA). The aim of this study was to assess whether sLOX-1 level is associated with clinical remission and disease activity in patients with RA. METHODS: Clinical and laboratory data were analyzed for 282 patients with RA. Plasma sLOX-1 level was measured by enzyme-linked immunosorbent assay (ELISA). The remission status and sLOX-1 levels were compared between four groups of patients based on the positivity of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs). Relationships between sLOX-1 level and the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) were analyzed by multivariate logistic regression. RESULTS: The patients in the RF + ACPA + group tended to exhibit higher sLOX-1 levels when compared to the other three groups. In the RF + ACPA + group, the sLOX-1 level was significantly higher in the non-remission group than in the remission group, irrespective of treatment. Multivariate logistic regression showed significant correlations between sLOX-1 level and DAS28-ESR. CONCLUSIONS: sLOX-1 level might be a useful biomarker for assessing clinical remission and disease activity in double-positive RA patients.

Cross-cultural adaptation and validation of the Japanese version of the new Knee Society Scoring System for osteoarthritic knee with total knee arthroplasty.

BACKGROUND: The purposes of this study were to translate the new Knee Society Score (KSS) into Japanese and to evaluate the construct and content validity, test-retest reliability, and internal consistency of the Japanese version of the new KSS. METHODS: The Japanese version of the KSS was developed according to cross-cultural guidelines by using the "translation-back translation" method to ensure content validity. KSS data were then obtained from patients who had undergone total knee arthroplasty (TKA). The psychometric properties evaluated were as follows: for feasibility, response rate, and floor and ceiling effects; for construct validity, internal consistency using Cronbach's alpha, and correlations with quality of life. Construct validity was evaluated by using Spearman's correlation coefficient to quantify the correlation between the KSS and the Japanese version of the Oxford 12-item Knee Score or Short Form 36 Health Survey (SF-36) questionnaires. RESULTS: The Japanese version of the KSS was sent to 93 consecutive osteoarthritic patients who underwent primary TKA in our institution. Fifty-five patients completed the questionnaires and were included in this study. Neither a floor nor ceiling effect was observed. The reliability proved excellent in the majority of domains, with intraclass correlation coefficients of 0.65-0.88. Internal consistency, assessed by Cronbach's alpha, was good to excellent for all domains (0.78-0.94). All of the four domains of the KSS correlated significantly with the Oxford 12-item Knee Score. The activity and satisfaction domains of the KSS correlated significantly with all and the majority of subscales of the SF-36, respectively, whereas symptoms and expectation domains showed significant correlations only with bodily pain and vitality subscales and with the physical function, bodily pain, and vitality subscales, respectively. CONCLUSIONS: The Japanese version of the new KSS is a valid, reliable, and responsive instrument to capture subjective aspects of the functional symptoms and abilities of patients who undergo TKA.

Outcome of shortened extra-small ulnar component in linked total elbow arthroplasty for patients with rheumatoid arthritis.

OBJECTIVE: We compared the clinical and radiological results of the 3-inch shortened ulnar stem of the extra-small component of Coonrad-Morrey prosthesis with those of the other ulnar components for patients with rheumatoid arthritis (RA). METHODS: A total of 33 Coonrad-Morrey total elbow arthroplasty (TEA) procedures were performed. Of these, 27 elbows of 25 patients with RA underwent primary TEA. The results of the clinical and radiological findings were compared between groups of patients receiving the shortened ulnar stem of extra-small components (shortened group) and of those receiving the components of the other sizes (control group). RESULTS: The mean follow-up was 6.2 ± 2.8 years in the shortened group and 7.2 ± 2.5 years in the control group. The Mayo elbow performance score and range of motion results were substantially improved after the operation for both groups. We encountered several peri- and postoperative complications, but no significant differences in clinical results were found between the groups. The control group had three cases of osteolysis around the implant, while the shortened group did not. CONCLUSIONS: TEA with a shortened ulnar implant of the extra-small size of the Coonrad-Morrey prosthesis gave satisfactory mid-term results among patients with RA.

Delayed wound healing after forefoot surgery in patients with rheumatoid arthritis.

OBJECTIVE: To elucidate the systemic and local risk factors and the effect of surgical procedures for delayed wound healing after forefoot surgery in patients with rheumatoid arthritis (RA). METHODS: Fifty forefoot surgeries were performed in 39 patients using resection arthroplasty or a joint-preserving procedure (25 feet for each procedure). The associations between the occurrence of delayed wound healing and clinical variables, radiological assessment, or surgical procedures were analyzed. RESULTS: Delayed wound healing was recorded in nine feet of eight patients. The duration of RA was significantly longer in the delayed healing group than that in the healed group. Age, sex, smoking history, concomitant diabetes, and RA medication did not differ between the groups. Radiological evaluation showed significant differences between groups in metatarsophalangeal dorsal flexion angle. The shortened length of the fourth and the fifth metatarsal bones affected the occurrence of the complication. The joint-preserving procedure had significantly less delayed wound healing compared with resection arthroplasty. CONCLUSIONS: Preoperative dorsoplantar deformity and perioperative tissue damage can cause delayed wound healing after forefoot surgery in RA patients.

TNFα, PDGF, and TGFß synergistically induce synovial lining hyperplasia via inducible PI3Kδ.

OBJECTIVES: To determine the mechanism underlying hypertrophic synovium in rheumatoid arthritis (RA). METHODS: We examined micromass cultures of fibroblast-like synoviocytes (FLSs) stimulated with tumor necrosis factor α (TNFα), platelet-derived growth factor (PDGF), and/or transforming growth factor ß (TGFß). The hypertrophic architecture of the micromasses, expression of phosphoinositide 3 kinase (PI3K) isoforms, and persistent activation of PI3K-Akt pathways were investigated. FLSs transfected with siRNA were also examined in the micromass cultures. RESULTS: The combination of TNFα, PDGF, and TGFß (TPT condition) induced obvious hypertrophic architecture of the intimal lining layer in FLSs in micromass cultures, and was accompanied by upregulated expression of matrix metalloproteinase-3 (MMP3), Cadherin-11, and PI3Kδ. In monolayer FLSs, the TPT condition enhanced the expression of PI3Kδ and persistent activation of the PI3K-Akt pathway. Knockdown of PI3Kδ significantly inhibited the formation of the hypertrophic synovial lining in the TPT condition. CONCLUSIONS: These results collectively indicate that inducible PI3Kδ plays a crucial role in persistent activation of PI3K-Akt in FLSs, and in the formation of a hypertrophic synovial lining. PI3Kδ may be an alternative treatment target for the regulation of proliferative synovium in RA.