Fractional Flow Reserve Cardio-Oncology Effects on Inpatient Mortality, Length of Stay, and Cost Based on Malignancy Type: Machine Learning Supported Nationally Representative Case-Control Study of 30 Million Hospitalizations.

Background and Objectives: There are no nationally representative studies of mortality and cost effectiveness for fractional flow reserve (FFR) guided percutaneous coronary interventions (PCI) in patients with cancer. Our study aims to show how this patient population may benefit from FFR-guided PCI. Materials and Methods: Propensity score matched analysis and backward propagation neural network machine learning supported multivariable regression was performed for inpatient mortality in this case-control study of the 2016 National Inpatient Sample (NIS). Regression results were adjusted for age, race, income, geographic region, metastases, mortality risk, and the likelihood of undergoing FFR versus non-FFR PCI. All analyses were adjusted for the complex survey design to produce nationally representative estimates. Results: Of the 30,195,722 hospitalized patients meeting criteria, 3.37% of the PCIs performed included FFR. In propensity score adjusted multivariable regression, FFR versus non-FFR PCI significantly reduced inpatient mortality (OR 0.47, 95%CI 0.35−0.63; p < 0.001) and length of stay (LOS) (in days; beta −0.23, 95%CI −0.37−−0.09; p = 0.001) while increasing cost (in USD; beta $5708.63, 95%CI, 3042.70−8374.57; p < 0.001), without significantly increasing complications overall. FFR versus non-FFR PCI did not specifically change cancer patients' inpatient mortality, LOS, or cost. However, FFR versus non-FFR PCI significantly increased inpatient mortality for Hodgkin's lymphoma (OR 52.48, 95%CI 7.16−384.53; p < 0.001) and rectal cancer (OR 24.38, 95%CI 2.24−265.73; p = 0.009). Conclusions: FFR-guided PCI may be safely utilized in patients with cancer as it does not significantly increase inpatient mortality, complications, and LOS. These findings support the need for an increased utilization of FFR-guided PCI and further studies to evaluate its long-term impact.

Reclassification of Treatment Strategy with Fractional Flow Reserve in Cancer Patients with Coronary Artery Disease.

Background and Objectives: Cancer and coronary artery disease (CAD) often coexist. Compared to quantitative coronary angiography (QCA), fractional flow reserve (FFR) has emerged as a more reliable method of identifying significant coronary stenoses. We aimed to assess the specific management, safety and outcomes of FFR-guided percutaneous coronary intervention (PCI) in cancer patients with stable CAD. Materials and Methods: FFR was used to assess cancer patients that underwent coronary angiography for stable CAD between September 2008 and May 2016, and were found to have ≥50% stenosis by QCA. Patients with lesions with an FFR > 0.75 received medical therapy alone, while those with FFR ≤ 0.75 were revascularized. Procedure-related complications, all-cause mortality, nonfatal myocardial infarction, or urgent revascularizations were analyzed. Results: Fifty-seven patients with stable CAD underwent FFR on 57 lesions. Out of 31 patients with ≥70% stenosis as measured by QCA, 14 (45.1%) had an FFR ≥ 0.75 and lesions were reclassified as moderate and did not receive PCI nor DAPT. Out of 26 patients with <70% stenosis as measured by QCA, 6 (23%) had an FFR < 0.75 and were reclassified as severe and were treated with PCI and associated DAPT. No periprocedural complications, urgent revascularization, acute coronary syndromes, or cardiovascular deaths were noted. There was a 22.8% mortality at 1 year, all cancer related. Patients who received a stent by FFR assessment showed a significant association with decreased risk of all-cause death (HR: 0.37, 95% CI 0.15−0.90, p = 0.03). Conclusions: Further studies are needed to define the optimal therapeutic approach for cancer patients with CAD. Using an FFR cut-off point of 0.75 to guide PCI translates into fewer interventions and can facilitate cancer care. There was an overall reduction in mortality in patients that received a stent, suggesting increased resilience to cancer therapy and progression.

Connective Tissue Graft with or without Enamel Matrix Derivative for Treating Gingival Recession Defects: A Systematic Review and Meta-Analysis.

OBJECTIVES: The aim of this systematic review is to compare the root coverage outcomes of using a connective tissue graft (CTG) with and without the application of enamel matrix derivative (EMD). METHODOLOGY: An electronic search was performed up to July 2020 in 4 databases, including Ovid MEDLINE, EMBASE, Web of Science and Cochrane Central. Human clinical studies with data on comparing outcomes of root coverage using CTG with and without the application of EMD were included. Meta-analyses for the recorded parameters were performed and the weighted mean difference (WMD) between the 2 groups and 95% confidence interval (CI) were reported. RESULTS: Nine clinical studies were selected for inclusion in this review. The WMD of clinical attachment level gain was 0.78 mm (95% CI of 0.23-1.34 mm, P = .005) and the WMD of recession depth reduction was 0.28 mm (95% CI of 0.06-0.51 mm, P = .01), favoring the CTG + EMD approach. However, the comparisons for the percentage of complete root coverage and mean root coverage between the 2 approaches were not statistically significant. CONCLUSION: Although the use of a CTG with and without the application of EMD in root coverage procedures achieved a similar percentage of complete root coverage and mean root coverage, the addition of EMD to CTG may improve the outcome of recession depth reduction and clinical attachment level gain.

Post-cardiac arrest PCI is underutilized among cancer patients: Machine learning augmented nationally representative case-control study of 30 million hospitalizations.

BACKGROUND: Cancer patients are less likely to undergo percutaneous coronary intervention (PCI) after cardiac arrest, although they demonstrate improved mortality benefit from the procedure. We produced the largest nationally representative analysis of mortality of cardiac arrest and PCI for patients with cancer versus non-cancer. METHODS: Propensity score adjusted multivariable regression for mortality was performed in this case-control study of the United States' largest all-payer hospitalized dataset, the 2016 National Inpatient Sample. Regression models of mortality and PCI weighted by the complex survey design were fully adjusted for age, race, income, cancer metastases, NIS-calculated mortality risk by Diagnosis Related Group (DRG), acute coronary syndrome, and likelihood of undergoing PCI. RESULTS: Of the 30,195,722 hospitalized adult patients, 15.43% had cancer, and 0.79% of the whole sample presented with cardiac arrest (of whom 20.57% underwent PCI). In fully adjusted regression analysis among patients with cardiac arrest, PCI significantly reduced mortality (OR 0.15, 95 %CI 0.13-0.19; p < 0.001) among patients with cancer greater than those without it (OR 0.21, 95 %CI 0.20-0.23; p < 0.001). CONCLUSIONS: This nationally representative study suggests that post-cardiac arrest PCI is underutilized among patients with cancer despite its significant mortality reduction for such patients (independent of clinical acuity).

Artificial intelligence-augmented analysis of contemporary procedural, mortality, and cost trends in carcinoid heart disease in a large national cohort with a focus on the "forgotten pulmonic valve".

Background: Carcinoid heart disease is increasingly recognized and challenging to manage due to limited outcomes data. This is the largest known cohort study of valvular pathology, treatment (including pulmonary and tricuspid valve replacements [PVR and TVR]), dispairties, mortality, and cost in patients with malignant carcinoid tumor (MCT). Methods: Machine learning-augmented propensity score-adjusted multivariable regression was conducted for clincal outcomes in the 2016-2018 U.S. National Inpatient Sample (NIS). Regression models were weighted by the complex survey design and adjusted for known confounders and the likelihood of undergoing valvular procedures. Results: Among 101,521,656 hospitalizations, 55,910 (0.06%) had MCT. Patients with MCT vs. those without had significantly higher inpatient mortality (2.93 vs. 2.04%, p = 0.002), longer mean length of stay (12.20 vs. 4.62, p < 0.001), and increased mean total cost of stay ($70,252.18 vs. 51,092.01, p < 0.001). There was a step-wise increased rate of TVR and PVR with each subsequent year, with significantly more TV (0.16% vs. 0.01, p < 0.001) and PV (0.03 vs. 0.00, p = 0.040) diagnosed with vs. without MCT for 2016, with comparable trends in 2017 and 2018. There were no significant procedural disparities among patients with MCT for sex, race, income, urban density, or geographic region, except in 2017, when the highest prevalence of PV procedures were performed in the Western North at 50.00% (p = 0.034). In machine learning and propensity score augmented multivariable regression, MCT did not significantly increase the likelihood of TVR or PVR. In sub-group analysis restricted to MCT, neither TVR nor PVR significantly increased mortality, though it did increase cost (respectively, $141,082.30, p = 0.015; $355,356.40, p = 0.012). Conclusion: This analysis reflects a favorable trend in recognizing the need for TVR and PVR in patients with MCT, with associated increased cost but not mortality. Our study also suggests that pulmonic valve pathology is increasingly recognized in MCT as reflected by the upward trend in PVRs. Further research and updated societal guidelines may need to focus on the "forgotten pulmonic valve" to improve outcomes and disparities in this understudied patient population.

Effect of whole-body vibration therapy on lower extremity function in subacute stroke patients.

This study aimed to investigate the effect of whole-body vibration therapy on lower extremity function in subacute stroke patients. Subacute stroke patients who were able to undergo gait training were randomly divided into a vibration therapy group and a control group. All patients attended 20-min training sessions twice daily, 5 times a week for 2 weeks. Each session included 45 squats. The vibration group trained on a vibration platform and the control group trained on the ground. The degree of maximal isokinetic voluntary contraction torque was evaluated, and manual muscle tests of hip and knee flexion and extension were performed. The Berg Balance Scale, 10-m walk test, Timed Up and Go Test, and Functional Ambulation Category were used. A total of 38 patients, 20 in the vibration group and 18 in the control group, were included in the analysis. After the 2-week therapy, the vibration group showed significant improvements in lower extremity strength, balance, and gait performance. The vibration group showed significantly better performance on the Berg Balance Scale, 10-m walk test, and Functional Ambulation Category than the control group. There were no significant differences in maximal isokinetic voluntary contraction torque or manual muscle tests between the groups. Our results suggest that additional training with whole-body vibration may effectively improve the balance and gait performance of subacute stroke patients. Further studies on large populations are required to determine the therapy's clinical efficacy.

Evaluation of Clinical Accuracy of Implant Abutment-Level Impression Technique Using Digital Superimposition of Customized Abutment.

Taking a conventional implant abutment-level impression with the gingival retraction technique can cause side effects such as gingival recession and bleeding. In order to overcome these problems, an impression technique using digital superimposition of the customized abutment is newly introduced. In this technique, digital impression data and pre-scanned abutment data are superimposed to reproduce the abutment's location and shape on computer-aided design software. The present investigation was conducted to evaluate the clinical accuracy of the newly adapted digital superimposition impression technique by assessing the fit of fabricated prostheses. The results showed clinical efficacy of this technique, satisfying both convenience and clinically acceptable marginal and internal fit.

Cardiac Toxicities Associated with Immune Checkpoints Inhibitors: Mechanisms, Manifestations and Management.

Immune checkpoint inhibitor (ICI) associated cardiovascular adverse events (CVAE) have become more frequent with the growing use of cancer immunotherapy. CVAEs include a wide spectrum of diseases such as myocarditis, pericarditis, heart failure, arrhythmias, coronary artery disease, and hypertension. The induction of cardiovascular side effects by ICI use is hypothesized to occur due to inflammation and immune dysregulation of normal tissue in response to immunotherapy. Management of ICI-associated CVAEs mitigates an overactive immune response by utilizing steroids, immunomodulatory drugs and hemodynamic stabilization. However, few controlled studies on the cardiovascular safety of ICIs exist and treatment of their side effects are mostly from limited case series. Our review seeks to provide the most recent understanding of ICI-associated CVAEs and their management.

Anti-wrinkle activity of Platycarya strobilacea extract and its application as a cosmeceutical ingredient.

In order to investigate the potential of Platycarya strobilacea fruit extract as an active ingredient for cosmetics, we measured their free-radical scavenging activity, elastase inhibitory activity, the expression of MMP-1 (matrix metalloproteinase-1), and type I collagen synthesis in normal human fibroblast cells. To isolate the main component compounds from P. strobilacea fruit extract, we purified the extract through solvent fractionation, column chromatography, and recrystallization. The component compounds were identified as ellagic acid and 4-O-xyloside of ellagic acid (ellagic acid 4-O-xylopyranoside). P. strobilacea fruit extract and ellagic acid increased the expression of type I collagen mRNA in a dose-dependent manner (up to 37% and 41% at 20 microg/ml and 1.0 microg/ml, respectively), comparable to that of ascorbic acid (up to 39% at 500 muM). A clinical study of measurements using visual evaluation and image analysis showed a statistically significant difference (p < 0.05) between the effects of the test and placebo products. This result suggests that P. strobilacea fruit extract could be used as an active ingredient for antiaging cosmetics.

AMPA Receptor Surface Expression Is Regulated by S-Nitrosylation of Thorase and Transnitrosylation of NSF.

The regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking affects multiple brain functions, such as learning and memory. We have previously shown that Thorase plays an important role in the internalization of AMPARs from the synaptic membrane. Here, we show that N-methyl-d-aspartate receptor (NMDAR) activation leads to increased S-nitrosylation of Thorase and N-ethylmaleimide-sensitive factor (NSF). S-nitrosylation of Thorase stabilizes Thorase-AMPAR complexes and enhances the internalization of AMPAR and interaction with protein-interacting C kinase 1 (PICK1). S-nitrosylated NSF is dependent on the S-nitrosylation of Thorase via trans-nitrosylation, which modulates the surface insertion of AMPARs. In the presence of the S-nitrosylation-deficient C137L Thorase mutant, AMPAR trafficking, long-term potentiation, and long-term depression are impaired. Overall, our data suggest that both S-nitrosylation and interactions of Thorase and NSF/PICK1 are required to modulate AMPAR-mediated synaptic plasticity. This study provides critical information that elucidates the mechanism underlying Thorase and NSF-mediated trafficking of AMPAR complexes.

Pharmacokinetic interaction between oltipraz and silymarin in rats.

PURPOSE: To evaluate the pharmacokinetic interaction between oltipraz and silymarin after intravenous and oral administration of both drugs to male Sprague-Dawley rats. METHODS: Oltipraz (single doses of 10 and 30 mg/kg for intravenous and oral administration, respectively), silymarin (single doses of 50 and 100 mg/kg for intravenous and oral administration, respectively, and 14 days oral administration of 100 mg/kg), alone and together were administered to control rats. RESULTS: The pharmacokinetic parameters of oltipraz did not significantly altered by silymarin. However, after intravenous administration of the drugs together, the AUCs of unconjugated, conjugated, and total (unconjugated plus conjugated) silibinin were significantly different (32.7% decrease, and 32.1% and 27.2% increase, respectively), and total and (CL) and non-renal (CL NR ) clearance of unconjugated silibinin were significantly faster (49.4% and 61.1% increase, respectively) than those of silymarin alone (without oltipraz). After oral administration of silymarin with or without oltipraz, however, the pharmacokinetic parameters of unconjugated, conjugated, and total silibinin were comparable. CONCLUSIONS: After single intravenous administration of the drugs together, the AUC of unconjugated silibinin was significantly smaller, but that of both conjugated and total silibinin was significantly greater. This could have been due to an increase in the formation of conjugates (glucuronidation and sulfation) of silibinin as induced by oltipraz. After simultaneous oral administration of the drugs, however, the AUCs (or AUC 0-12 h) of unconjugated, conjugated, and total silibinin were comparable.

Late Mobile-Bearing Dislocation in Unicompartmental Knee Arthroplasty.

The authors present 2 cases of late mobile-bearing dislocation after unicompartmental knee arthroplasty with long-term follow-up. Patients had anterior bearing dislocation more than 10 years after primary unicompartmental knee arthroplasty. Retrieved mobile bearings showed severe erosion on the posterior lip, suggesting frequent deep knee flexion as the cause of wear. Bearing dislocation is known to occur in the early postoperative phase. However, for Asians with a lifestyle that requires high knee flexion, dislocation might occur in the late postoperative phase. Such late bearing dislocation has a mechanism different from those reported in previous studies. Loss of bump in the posterior lip was found to be the cause. After late bearing dislocation, conversion to total knee arthroplasty is unnecessary because a simple bearing exchange will suffice. [Orthopedics. 2019; 42(1):e124-e127.].

Hemodynamic effects of different types of pneumatic compression of the lower extremities during anesthesia induction: a prospective randomized controlled trial.

BACKGROUND: The current study evaluated the hemodynamic effects of different types of pneumatic compressions of the lower extremities during anesthesia induction. In addition, the hemodynamic effects were compared between patients older than 65 age years and those aged 65 years or younger. METHODS: One hundred and eighty patients (90: > 65 years and 90: ≤ 65 years) were enrolled. Each age group of patients was randomly assigned to one of three groups; Group 1 (no compression), Group 2 (sequential pneumatic compression), and Group 3 (sustained pneumatic compression without decompression). Invasive blood pressure, cardiac index (CI), and stroke volume variation (SVV) were measured. RESULTS: In patients aged ≤ 65 years, mean arterial pressure (MAP) and CI were significantly higher and SVV was lower in Group 3 compared to Group 1 before tracheal intubation, but there were no differences between Groups 1 and 2. However, there were no differences in MAP, CI, and SVV among the three groups in patients aged > 65 years. The number of patients who showed a MAP < 60 mmHg was less in Group 3 than Group 1 in patients aged ≤ 65 years, but not in patients aged > 65 years. CONCLUSIONS: Sustained pneumatic compression of the lower extremities has more hemodynamic stabilizing effects compared to sequential compression during anesthesia induction in patients aged 65 years or younger. However, no difference between methods of compression was observed in patients older than 65 years.

Influence of a pulsed CO2 laser operating at 9.4 µm on the surface morphology, reflectivity, and acid resistance of dental enamel below the threshold for melting.

Below the threshold for laser ablation, the mineral phase of enamel is converted into a purer phase hydroxyapatite with increased acid resistance. Studies suggest the possibility of achieving the conversion without visible surface alteration. In this study, changes in the surface morphology, reflectivity, and acid resistance were monitored with varying irradiation intensity. Bovine enamel specimens were irradiated using a CO 2 laser operating at 9.4 ?? ? m with a Gaussian spatial beam profile­1.6 to 3.1 mm in diameter. After laser treatment, samples were subjected to demineralization to simulate the acidic intraoral conditions of dental decay. The resulting demineralization and erosion were assessed using polarization-sensitive optical coherence tomography, three-dimensional digital microscopy, and polarized light microscopy. Distinct changes in the surface morphology and the degree of inhibition were found within the laser-treated area in accordance with the laser intensity profile. Subtle visual changes were noted below the melting point for enamel that appear to correspond to thresholds for denaturation of the organic phase and thermal decomposition of the mineral phase. There was significant protection from laser irradiation in areas in which the reflectivity was not increased significantly, suggesting that aesthetically sensitive areas of the tooth can be treated for caries prevention.

Effect of Robot-Assisted Game Training on Upper Extremity Function in Stroke Patients.

OBJECTIVE: To determine the effects of combining robot-assisted game training with conventional upper extremity rehabilitation training (RCT) on motor and daily functions in comparison with conventional upper extremity rehabilitation training (OCT) in stroke patients. METHODS: Subjects were eligible if they were able to perform the robot-assisted game training and were divided randomly into a RCT and an OCT group. The RCT group performed one daily session of 30 minutes of robot-assisted game training with a rehabilitation robot, plus one daily session of 30 minutes of conventional rehabilitation training, 5 days a week for 2 weeks. The OCT group performed two daily sessions of 30 minutes of conventional rehabilitation training. The effects of training were measured by a Manual Function Test (MFT), Manual Muscle Test (MMT), Korean version of the Modified Barthel Index (K-MBI) and a questionnaire about satisfaction with training. These measurements were taken before and after the 2-week training. RESULTS: Both groups contained 25 subjects. After training, both groups showed significant improvements in motor and daily functions measured by MFT, MMT, and K-MBI compared to the baseline. Both groups demonstrated similar training effects, except motor power of wrist flexion. Patients in the RCT group were more satisfied than those in the OCT group. CONCLUSION: There were no significant differences in changes in most of the motor and daily functions between the two types of training. However, patients in the RCT group were more satisfied than those in the OCT group. Therefore, RCT could be a useful upper extremity rehabilitation training method.

Thorase variants are associated with defects in glutamatergic neurotransmission that can be rescued by Perampanel.

The AAA+ adenosine triphosphatase (ATPase) Thorase plays a critical role in controlling synaptic plasticity by regulating the expression of surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Bidirectional sequencing of exons of ATAD1, the gene encoding Thorase, in a cohort of patients with schizophrenia and healthy controls revealed rare Thorase variants. These variants caused defects in glutamatergic signaling by impairing AMPAR internalization and recycling in mouse primary cortical neurons. This contributed to increased surface expression of the AMPAR subunit GluA2 and enhanced synaptic transmission. Heterozygous Thorase-deficient mice engineered to express these Thorase variants showed altered synaptic transmission and several behavioral deficits compared to heterozygous Thorase-deficient mice expressing wild-type Thorase. These behavioral impairments were rescued by the competitive AMPAR antagonist Perampanel, a U.S. Food and Drug Administration-approved drug. These findings suggest that Perampanel may be useful for treating disorders involving compromised AMPAR-mediated glutamatergic neurotransmission.

Pharmacokinetics of oltipraz in rat models of diabetes mellitus induced by alloxan or streptozotocin.

Pharmacokinetic parameters of oltipraz were compared after intravenous (10 mg/kg) and oral (30 mg/kg) administration in rat model of diabetes mellitus induced by alloxan (rat model of DMIA) or streptozotocin (rat model of DMIS) and their respective control male Sprague-Dawley rats. In rat models of DMIA and DMIS, the expressions and mRNA levels of CYP1A2, 2B1/2, and 3A1(23) increased, and oltipraz was metabolized mainly via CYP1A1/2, 2B1/2, 2C11, 2D1, and 3A1/2 in male Sprague-Dawley rats. Hence, it would be expected that the AUC and CL values of oltipraz would be significantly smaller and faster, respectively, in rat models of diabetes. This was proven by the following results. After intravenous administration, the AUC values were significantly smaller in rat models of DMIA (40.1% decrease) and DMIS (26.0% decrease) than those in respective control rats, and this could be due to significantly faster CL values in rat models of DMIA (40.1% increase) and DMIS (26.0% increase). The faster CL could be due to increase in hepatic blood flow rate and significantly faster CL(int) in rat models of diabetes, since oltipraz is an intermediate hepatic extraction ratio drug in male Sprague-Dawley rats. After oral administration, the AUC values of oltipraz were also significantly smaller in rat models of DMIA (54.0% decrease) and DMIS (63.2% decrease). This could be due to increase in hepatic blood flow rate, significantly faster CL(int), and changes in the intestinal first-pass effect in rat models of diabetes. However, this was not due to decrease in absorption in rat models of diabetes.

Evaluation of enamel surface modification using PS-OCT after laser treatment to increase resistance to demineralization.

At laser intensities below ablation, carbonated hydroxyapatite in enamel is converted into a purer phase hydroxyapatite with increased acid resistance. Previous studies suggested the possibility of achieving the conversion without surface modification. This study attempts to evaluate the thresholds for the modification without additional changes in physical and optical properties of the enamel. Bovine specimens were irradiated using an RF-excited CO2 laser operating at 9.4-µm with a pulse duration of 26-µs, pulse repetition rates of 100-1000 Hz, with a Gaussian spatial beam profile - 1.4 mm in diameter. After laser treatment, the samples were subjected to acid demineralization for 48 hours to simulate acidic intraoral conditions of a caries attack. The resulting demineralization and erosion were assessed using polarization sensitive OCT (PS-OCT) and 3D digital microscopy. The images from digital microscopy demonstrated a clear delineation between laser protected zones without visual changes and zones with higher levels of demineralization and erosion. Distinct changes in the surface morphology were found within the laser treated area in accordance with the Gaussian spatial beam profile. There was significant protection from the laser in areas that were not visually altered.

Total Knee Arthroplasty for Severe Flexion Contracture in Rheumatoid Arthritis Knees.

Flexion contracture deformities, as well as severe varus and valgus deformities of the knee joint, accompany osteoarthritis or rheumatoid arthritis (RA). In particular, severe flexion contracture deformity of the knee joint is often found in patients with RA, which renders them nonambulatory. This report describes a 26-year-old female patient diagnosed with RA 10 years ago. She had chronic joint pain, severe flexion contracture, valgus deformity in both knees, and limited range of motion in both knees and became nonambulatory. She underwent a total knee arthroplasty (TKA) and serial casting and physical therapy to restore stable joint movement and correct knee joint deformity. Her pain was successfully relieved, and she was able to walk after surgery. Here, we report the excellent results of TKA in this RA patient with severe flexion contracture of both knees.