Temporary balloon occlusion test can overestimate the risk of acute pulmonary edema after transcatheter atrial septal defect closure.

BACKGROUND: Atrial septal defect (ASD) closure can cause acute pulmonary edema. Before transcatheter closure is performed, temporary balloon occlusion test (BOT) is recommended in patients with left ventricular dysfunction to predict the risk of pulmonary edema. However, the accuracy of BOT has not been verified. This study aimed to compare hemodynamic differences between BOT and transcatheter closure. METHODS: A total of 42 patients with a single ASD over age 18 years who underwent BOT before transcatheter ASD closure between October 2010 and May 2020 were analyzed. Pulmonary capillary wedge pressure (PCWP) was measured using a Swan-Ganz catheter placed in the pulmonary artery at baseline, after 10 min of BOT, and after transcatheter closure. Amplatzer septal occluder was used for all transcatheter closures. RESULTS: Mean patient age was 64 ± 18 years (range, 18-78). Mean ASD diameter and pulmonary to systemic flow ratio were 18 ± 5 and 2.8 ± 1.0 mm, respectively. Mean PCWP at baseline, during BOT, and after transcatheter closure was 8.9 ± 2.9, 13.5 ± 4.2, and 9.5 ± 2.6 mmHg, respectively. The difference between BOT and after transcatheter closure values was significant (p < 0.001). During BOT, PCWP increased ≥18 mmHg in 7 patients, whereas after ASD closure, PCWP was <18 mmHg in all 7 and none developed acute pulmonary edema. CONCLUSION: Temporary balloon occlusion of an ASD and transcatheter ASD closure result in different hemodynamic change. BOT overestimates increase of PCWP after transcatheter ASD closure and requires careful interpretation. Well-designed, larger studies in higher-risk patients are warranted to verify the clinical implications of BOT in more detail.

Acute heart failure associated with toxic shock syndrome due to methicillin-susceptible Staphylococcus aureus during the postpartum period: case report and systematic literature review.

BACKGROUND: Toxic shock syndrome (TSS) caused by Staphylococcus aureus in the postpartum period is a rare but life-threatening disease. We present a case of acute heart failure as the initial presentation of TSS due to methicillin-susceptible Staphylococcus aureus (MSSA) and describe its clinical characteristics with a systematic literature review. CASE PRESENTATION: A 34-year-old woman, 8 days after a normal vaginal delivery presented to our hospital with dyspnea and fever. She had jugular venous distension, bilateral leg edema, and erythema. Laboratory examinations revealed elevated NT-pro-BNP level of 3,233 pg/mL. Transthoracic echocardiography showed elevated tricuspid regurgitation peak gradient, with decreased respiratory variability of the inferior vena cava diameter and bilateral pleural effusions. The patient was hospitalized with suspicion of congestive heart failure. MSSA positive for toxic shock syndrome exotoxin-1 was detected in the culture of the perineal incision wound, and we diagnosed TSS caused by MSSA. Intravenous diuretics were administered, along with eventual cefazolin plus clindamycin. After 2 weeks of antimicrobial therapy, the patient showed improvement and was discharged. No recurrence was observed at the 24-month follow-up. CONCLUSION: This is a rare case report of acute heart failure being the initial manifestation of TSS due to MSSA in the postpartum period. Clinicians should consider TSS as a possibility in postpartum patients with acute heart failure. This systematic review provides insights into its clinical features, treatment regimens, and prognosis of TSS by S. aureus in the postpartum period. TSS requires an appropriate, prompt diagnosis, because delayed treatment can be fatal.

Bone Histomorphometry of Femoral Head Cancellous Bone in Patients Who Underwent Total Hip Arthroplasties due to Destructive Hip in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) affects the hip joints. The microarchitecture of the cancellous bone in RA-affected hip joints has been unclear. Here we investigated the bone metabolism changes in the subcapital cancellous bone of destructive hips of RA patients (n=26 patients; 28 hip joints) which were classified by Larsen grade on X-ray into the groups: destructive hip (Des) (Larsen grade IV, n=18) and neck fracture (Fx) (Larsen grade 0 or 1, n=10). The femoral heads of the Des-group showed significantly higher trabecular thickness versus those of the Fx-group (179±30.8 vs. 151±23.5 µm, p=0.02). The Des-group had significantly higher osteoid volume/tissue volume (OV/TV) and osteoid volume/bone volume (OV/BV) ratios than the Fx-group (OV/TV: 0.72±0.70% vs. 0.27±0.32%, p=0.028; OV/BV: 2.96±2.85% vs. 1.24±1.31%, p=0.039). The osteoblast and osteoclast surface areas of the Des-group were remarkably higher than those of the Fx-group (9.80±10.9 vs. 0.15±0.15%, p=0.0005; 0.34±0.48 vs. 0.06±0.06%, p=0.0285, respectively). The T-scores of hip (femoral neck) bone mineral density (BMD) of the Fx-group were significantly lower versus those of the Des-group (-3.1±0.76 vs. -1.6±1.17, p<0.01). Increased osteoid and resorption parameters and higher femoral neck BMD demonstrate a high bone-turnover state in response to destructive changes in the hips of RA patients.

Pacemaker infection and endocarditis due to Parvimonas micra: A case report and systematic review.

Infective endocarditis caused by Parvimonas micra is rare. Its clinical features are presented in this systematic review. We also describe the case of an 82-year-old man with infective endocarditis and pacemaker infection due to P. micra. There are some reports of recurrence during antimicrobial therapy; hence, careful follow-up is necessary.

Efficacy of catheter ablation for paroxysmal atrial fibrillation in patients with atrial septal defect: a comparison with transcatheter closure alone.

AIMS: There is no valid treatment strategy for addressing paroxysmal atrial fibrillation (AF) in patients with unclosed atrial septal defect (ASD). We aimed to assess the efficacy of catheter ablation (CA) compared with transcatheter ASD closure alone for treating pre-existing paroxysmal AF in patients with ASD. METHODS AND RESULTS: Among 908 patients who underwent transcatheter ASD closure, we evaluated 50 consecutive patients (63 ± 12 years) with paroxysmal AF. We compared the AF outcomes of these patients after transcatheter ASD closure between those with and without CA prior to ASD closure. Thirty (60%) patients underwent CA. During the follow-up period after ASD closure (mean: 49 ± 23 months), recurrence of AF was observed in 6/30 (20%) patients with upfront CA and 12/20 (60%) patients with ASD closure alone. Kaplan-Meier analysis showed that the AF-free survival rate was significantly higher for patients with CA than for those with ASD closure alone (79% vs. 37% at 5 years, P = 0.002). Upfront CA and previous heart failure hospitalization were associated with recurrence of AF after ASD closure [hazard ratio (HR) 0.18, 95% confidence interval (CI) 0.06-0.53; P = 0.002 and HR 4.64, 95% CI 1.60-13.49; P = 0.005, respectively]. CONCLUSION: In ASD patient with paroxysmal AF, transcatheter ASD closure alone demonstrated high AF recurrence rate after ASD closure. On the other hand, upfront CA prior to ASD closure substantially suppressed AF recurrence over the long term. A combination of CA and transcatheter ASD closure may be a feasible treatment strategy for paroxysmal AF in patients with ASD.

Patent foramen ovale with right atrial septal pouch.

A patent foramen ovale (PFO) is a communication across the inter-atrial septum and a right atrial septal pouch (RASP) is an indentation of the atrial septum caused by an incomplete fusion of the septum primum and septum secundum with its base opening into the right atrium. A 63-year-old male who had a history of two strokes and episodes of transient neurological deficit was diagnosed to have a small right-to-left shunt. At the time of PFO closure, an angiogram of the atrial septum revealed a small PFO associated with a RASP. The small PFO was crossed with a straight-tipped guide wire and was closed using a 25-mm GORE CARDIOFORM Septal Occluder (W.L. Gore and Associates, AZ). It is hypothesized that stagnant blood in the RASP may generate a clot that can cross the PFO and cause an infarct. © 2015 Wiley Periodicals, Inc.

Echocardiographic Estimates of Left Ventricular Diastolic Dysfunction Do Not Predict the Clinical Course in Elderly Patients Undergoing Transcatheter Atrial Septal Defect Closure: Impact of Early Diastolic Mitral Annular Velocity.

OBJECTIVE: This study evaluated the effect of echocardiographic left ventricular (LV) diastolic dysfunction on acute congestive heart failure after transcatheter atrial septal defect (ASD) closure in elderly patients. BACKGROUND: Although there is concern that LV diastolic dysfunction develops acute congestive heart failure after ASD closure, limited information is available regarding the influence, especially in elderly patients with severe LV diastolic dysfunction. METHODS: Two hundred consecutive patients older than 60 years were divided into 3 groups according to echocardiographic LV diastolic dysfunction: severe (early diastolic mitral annular velocity [e'] <5.0 cm/s), mild (5.0≤ e' <8.0 cm/s), and normal (e' ≥ 8.0 cm/s). Changes in plasma B-type natriuretic peptide (BNP) levels were evaluated. RESULTS: No patients with severe LV diastolic dysfunction developed acute congestive heart failure immediately after the procedure. BNP levels unchanged after the procedure in patients with severe LV diastolic dysfunction (126 ± 181 to 131 ± 148 pg/ml, P = 0.885), and this increase in BNP levels was not different from that between the diagnosis of ASD and the procedure. The change in BNP levels in patients with severe LV diastolic dysfunction, who were frequently treated with diuretics before the procedure, was equivalent to that in patients with mild LV diastolic dysfunction and normal LV diastolic function (5 ± 119 vs. 16 ± 101 vs. 9 ± 131 pg/ml, P = 0.724). CONCLUSIONS: Our findings suggest that transcatheter ASD closure under volume management is safe and valuable in elderly patients with echocardiographic severe LV diastolic dysfunction.

Treat and Repair Strategy in Patients With Atrial Septal Defect and Significant Pulmonary Arterial Hypertension.

BACKGROUND: A therapeutic strategy in patients with atrial septal defect (ASD) and significant pulmonary arterial hypertension (PAH) remains controversial. This study aimed to assess the effect of PAH-specific medications and subsequent transcatheter shunt closure (ie, a treat and repair strategy) in these patients. METHODS AND RESULTS: Among 646 patients with ASD, 22 patients (mean age of 56±20 years) who had PAH [mean pulmonary artery pressure ≥25 mmHg and pulmonary vascular resistance (PVR) ≥3 Wood units] underwent successful transcatheter ASD closure. Prior to the procedure, 8 patients received PAH-specific medications (PHM group) and 14 patients did not (non-PHM group). Initially, the PHM group had higher PVR compared with non-PHM group (9.6±3.8 vs. 4.2±1.0 Wood units, P<0.01). After treatment with PAH-specific medications, PVR in this group decreased to 4.0±0.8 Wood units (P<0.01). No adverse events were observed in either the PHM or non-PHM group during or after the transcatheter procedure. In the PHM group, during a treatment period of 52±48 months, the World Health Organization Functional Classification significantly improved (3.0±0.5 to 2.0±0.0, P<0.01), as well as in the non-PHM group (2.1±0.6 to 1.5±0.5, P<0.01). CONCLUSIONS: Treat and repair strategy provided substantial improvement and no worsening of the WHO-FC, even in patients with ASD and significant PAH. Long-term hemodynamic follow-up is mandatory to evaluate the ultimate efficacy and safety of this new strategy.

Three-dimensional echocardiography guided closure of complex multiple atrial septal defects.

Transcatheter closure of complex multiple atrial septal defects (ASDs) remains a challenge. We describe our clinical experience with staged device deployment in a patient with multiple ASDs using four Amplatzer septal occluder devices. Three-dimensional transesophageal echocardiography imaging contributed not only to the therapeutic guidance of successful device deployment but also to the decision making for the staged device delivery approach in a case of morphologically complex multiple ASDs.

A case of juvenile-onset ankylosing spondylitis effectively treated with tumour necrosis factor-alpha inhibitor agents.

A 15-year-old girl had experienced hip pain at 11 years of age. At 15 years of age, the patient complained of persistent generalised pain. Her rheumatoid factor and serum matrix metalloproteinase-3 levels were below standard values; there were no inflammatory responses, and the human leukocyte antigen test was negative for B27 and positive for B52 and B62. The bath ankylosing spondylitis disease activity index (BASDAI) value was 8.0 at the time of induction and 3.1 at 6 months after the introduction of adalimumab (at a dose of 40 mg). The BASDAI value improved with an increase in the dose of adalimumab to 80 mg at 8 months after the initial introduction of adalimumab (at 40 mg), although it remained at 4.8 at 16 months after the dose increase. The BASDAI value was 2.6 at 6 months, 2.7 at 1 year, and 1.8 at 1.5 years after the introduction of infliximab, indicating that the patient had progressed well without any adverse events. Based on this case, juvenile ankylosing spondylitis is a differential diagnosis for low back pain and generalised pain since childhood. Tumour necrosis factor (TNF) inhibitors were promptly introduced in this case, although it took 4 years from the initial presentation. TNF inhibitors were effective in treating juvenile ankylosing spondylitis in the present case without any adverse events. This case is notable because juvenile onset ankylosing spondylitis is one of the reasons for severe lumbago since childhood and because TNF inhibitors were administered promptly after diagnosis.

Modified Boyes' procedure for the multiple finger extensor tendon ruptures in patients with rheumatoid arthritis: A report of two cases.

Multiple subcutaneous extensor tendon ruptures in more than the ulnar three fingers sometimes occur in patients with rheumatoid arthritis accompanied by wrist deformity. In these situations, the flexor digitorum superficialis tendon of the middle finger (the FDS3 tendon) and that of the ring finger (the FDS4 tendon) are used for the transferred tendon (modified Boyes' procedure). Here, we treated two patients with rheumatoid arthritis, whose extensor tendons of more than three fingers were ruptured, using the modified Boyes' procedure. Case 1 had ruptures in four fingers (index through little), and Case 2 had ruptures in three fingers (middle through little). The FDS3 and FDS4 tendons were passed subcutaneously around the radial side of the wrist to the extensor sides and interlaced with the distal stump of the ruptured tendons. Switching of the finger movement was achieved smoothly in both cases. The post-operative evaluation showed an extension lag of -15° for the index finger 0° for the middle through the little fingers in Case 1, and 0° for the middle finger and -5° for the ring and little fingers in Case 2. The average post-operative extension lag was -3.5°. However, median nerve palsy occurred in both cases, and it gradually recovered. Stretching of the nerve by the correction of the wrist deformity and increased pressure in the carpal tunnel were supposed to be causes of this palsy. Modified Boyes' procedure is a useful method for more than three ulnar finger extensor tendon ruptures; however, post-operative median nerve palsy should be considered.

Transcatheter closure of atrial septal defect in a geriatric population.

OBJECTIVES: To evaluate the efficacy and safety of transcatheter closure of atrial septal defects (ASD) in patients over 70 years of age. BACKGROUND: Transcatheter closure of ASD is an established procedure in children and young adults, but the benefits of this procedure in geriatric patients are still unclear. METHODS: Between 2005 and 2010, 430 patients with ASD underwent transcatheter closure in our hospital. Among those patients, 30 consecutive patients older than 70 years of age were prospectively evaluated. RESULTS: Mean age at procedure was 75.8 ± 3.8 years (range: 70-85 years). Mean Qp/Qs was 2.4 ± 0.7 and mean ASD diameter was 20.3 ± 6.4 mm. Nine patients (30%) had a history of hospitalization due to heart failure. ASD closure was successfully performed in 28 patients (93%) without significant complications. During the follow-up period (mean period of 19.1 ± 11.3 months), New York Heart Association (NYHA) functional class was significantly improved in 20 patients (74%). Significant improvements of plasma BNP level, resting heart rate, and systolic pulmonary artery pressure were also observed. Improvement of tricuspid regurgitation was observed in 11 of 17 patients with moderate or severe regurgitation during the follow-up period. Conversely, worsening of mitral regurgitation was observed in 10 of the 27 patients. CONCLUSION: Transcatheter closure of ASD in geriatric patients can be performed safely. This procedure contributes to significant improvement of symptoms and positive cardiac remodeling. Long-term follow-up is mandatory, especially for patients with mitral regurgitation.

Transcatheter closure of a large atrial septal defect under microprobe transesophageal echocardiographic guidance.

We present a case of an atrial septal defect (ASD) in a 59-year-old man with an indication for ASD closure who also had a history of chronic obstructive pulmonary disease. Because of his decreased respiratory function with multiple bullae in his lungs, the procedure was performed without general anesthesia under the guidance of fluoroscopy and two-dimensional (2D) transesophageal echocardiography (TEE) using a transesophageal echocardiographic microprobe (micro-TEE) (S8-3t; Philips Medical Systems, Andover, MA, USA). The micro-TEE probe was inserted into the esophagus smoothly and easily in the supine position without sedation. It revealed a deficient superior-anterior rim and adequate rims elsewhere, and the maximal diameter of ASD was measured to be 25 mm. Balloon sizing resulted in a stretched defect diameter of 29 mm using the stop-flow technique. A 30-mm AMPLATZER Septal Occluder (AGA Medical, Plymouth, MN, USA) was deployed. The micro-TEE demonstrated that both disks were on the appropriate sides of the interatrial septum and the device was not interfering with surround cardiac structures. Residual shunt flow was not detected with color Doppler. The device was released successfully without any complications. Recently introduced multiplane micro-TEE can provide adequate information about a large ASD with a less invasive procedure in adult patients. Micro-TEE has a potential to become a novel imaging option for interventions of the interatrial septum.

Catheter closure of coronary sinus atrial septal defect using Amplatzer Septal Occluder.

Coronary sinus defect is a rare type of atrial septal defect. We report two patients who had a coronary sinus atrial septal defect without persistent left superior caval vein, where the orifice of the coronary sinus was closed using the Amplatzer Septal Occluder. The procedure was successful, without any complications including conduction disturbance.

Percutaneous aspiration embolectomy is beneficial for pulmonary thromboembolism in adult patients with Fontan circulation.

In patients with acute pulmonary thromboembolism (PTE), increased pulmonary vascular resistance (PVR) due to thrombus sometimes causes hemodynamic instability, requiring reperfusion therapy with drugs, surgery, or catheterization. In particular, patients with Fontan circulation, which is strongly affected by PVR, are prone to hemodynamic instability. Moreover, these patients sometimes have bleeding complications such as hemoptysis and intrathoracic adhesions, following multiple prior thoracotomies, making it difficult to choose pharmacotherapy. Percutaneous aspiration embolectomy (PAE) is a useful treatment option because it minimizes bleeding complications, is less invasive, and more rapid than surgery, and is easy to perform. Herein, we report two cases of Fontan patients having PTE treated with PAE. In Case 1, a 21-year-old man with a history of a Fontan procedure suddenly developed acute PTE, for which anticoagulants were administered immediately. However, his condition was refractory to treatment and he underwent PAE on the third day of illness. In Case 2, a 28-year-old woman with a history of Fontan procedure who had been on anticoagulants, developed acute PTE on the ninth postpartum day, and underwent PAE on the day of onset. In both cases, the respiratory condition improved, and re-treatment for PTE was not required. Learning objective: Fontan patients with acute pulmonary thromboembolism often require reperfusion therapy because they can easily become hemodynamically unstable due to increased pulmonary vascular resistance. For them, who often have adhesions following multiple prior thoracotomies and bleeding complications, percutaneous aspiration embolectomy may be effective as it has minimal bleeding risk and is minimally invasive, rapid, and straightforward.

Ankle arthrodesis using a retrograde intramedullary rod with fins for highly destructive joints in elderly patients with rheumatoid arthritis: A report of two cases.

Herein, we present two cases of older adult patients with highly destructive changes in ankle joints (Larsen grade IV) who underwent retrograde intramedullary ankle nail fixation with fins. In both patients, bony union was achieved, and full weight-bearing was attained at 3 months after surgery.

Characteristics of the aortic root morphology in conotruncal anomaly of the congenital heart disease.

BACKGROUND: Aortopathy is a well-known feature of conotruncal anomalies, but it remains unknown whether valve-sparing aortic root replacement, such as the David procedure, is feasible in young patients with severe aortic regurgitation. We assessed the aortic valve complex and aortic root morphology in patients with conotruncal anomalies using echocardiography. Furthermore, we evaluated the relevant factors associated with aortopathy in this population. METHODS: A total of 172 adult patients with conotruncal anomalies were enrolled in this study. Dimensions of the aortic valve complex were measured at the level of the sinus of Valsalva (SV) and sinotubular junction (STJ). The geometric height (GH), effective height (EH), and coaptation length (CL) were also assessed to analyze the aortic valve complex in detail. RESULTS: Sixteen of 172 patients were excluded due to poor imaging; 105 patients with tetralogy of Fallot, 24 with double outlet right ventricle, and 27 with transposition of the great arteries totaling 156 patients (32+/-11 years old) were included in the analysis. The patients were divided into four groups: Group 1 (98 patients) had no dilatation of SV or STJ; Group 2 (32 patients) had dilated SV and STJ; Group 3 (14 patients) had dilated SV; and Group 4 (12 patients) had dilated STJ. GH and EH in Group 2 were also highest among the four, whereas CL was not significantly shortened. Multivariate analysis revealed that male sex, age, and conduit repair were risk factors for aortopathy in this population. CONCLUSIONS: Patients with dilated SV and STJ (Group 2) were the most common among the patients with aortopathy (Groups 2, 3, and 4). The aortic valve leaflets themselves were enlarged, and the poor coaptation of the valve tips was compensated in spite of aortic root dilatation, which plays an important role in preventing severe aortic regurgitation in this population. Overall, valve-sparing aortic valve replacement is more feasible in the young populations than we expected.

Clinical characteristics and treatment status of pustulotic arthro-osteitis: A single-center study involving 51 cases.

Pustulotic arthro-osteitis (PAO) is a major complication of palmoplantar pustulosis (PPP). In orthopedic surgery outpatient clinics, PPP patients with osteoarticular symptoms are seen frequently, but PAO's clinical features remain not well known. To determine Japanese patients' clinical features and treatment status with PAO, we conducted a single-center retrospective epidemiologic survey. Clinical features, including gender, age, smoking habit, the onset pattern, interval between skin manifestation and osteoarticular symptoms, and the incidence of sternoclavicular joint lesions, axial and peripheral joint lesions, were examined. The association between physical status and image findings by X-ray, computed tomography, bone scintigraphy with Technetium99 , or magnetic resonance imaging was evaluated. The distribution pattern of peripheral joint lesions and the treatment status were evaluated. We identified 51 patients, 10 men and 41 women, with PAO. The average age was 48 years and 59% were smokers. The frequency of onset patterns was skin-leading type (63%), simultaneous onset (18%), and osteoarticular leading type (16%). The average interval between skin involvement and osteoarticular involvement in skin-leading type was significantly longer than that in osteoarticular leading type (7.1 years vs. 2.0 years). A sternoclavicular joint (SCJ) lesion was detected in 65% cases, and the physical findings of SCJ were significantly related to the image findings. Axial and peripheral joint lesions were detected in the same ratio (23 cases, 45%). In the peripheral joints, the finger joint was the most common (26%), followed by the shoulder joint (21%). Patients were treated with nonsteroidal anti-inflammatory drugs (76%), followed by conventional synthetic disease-modifying antirheumatic drugs (DMARDs) (29%) and biological DMARDs (9.8%). Tonsillectomy was performed in 11 cases. In conclusion, PAO more frequently involves SCJ in middle-aged women who smoke. Given that osteoarticular leading type was detected in 16% cases, seronegative oligoarthritis patients should be monitored for PPP, leading to a diagnosis of PAO.

Direct oral anticoagulant use and outcomes in adult patients with Fontan circulation: A multicenter retrospective cohort study.

BACKGROUND: Many adult patients with Fontan circulation are treated with antithrombotic agents, including direct oral anticoagulants (DOACs). However, few studies have investigated the efficacy, feasibility, and safety of DOACs in adult patients with Fontan circulation. METHODS AND RESULTS: In this retrospective cohort study, clinical records of 139 adult patients with Fontan circulation (70 females, 50.4%) from April 2015 to March 2018 were reviewed and classified into five groups according to the therapeutic agents used: DOAC (n = 36), vitamin K antagonist (VKA; n = 41), antiplatelet drug (n = 43), combination of an antiplatelet and anticoagulant (n = 14), and no-antithrombotic prophylaxis (n = 5). In a 1114-patient-year follow-up, 28 major events occurred, including 10 thrombotic and 18 bleeding events; 11 of 18 (61%) female patients had severe menorrhagia. The incidence (% patient-years) of major events was 0.6, 1.42, 3.74, and 5.13 in the DOAC, antiplatelet, VKA, combination, and no-antithrombotic groups, respectively. The Cox proportional hazards analysis revealed that the DOAC group had a lower rate of primary endpoints than the VKA group in males. CONCLUSIONS: DOAC may be a safe antithrombotic agent for use in adult patients with Fontan circulation, particularly in males. However, these findings should be confirmed in multi-institutional prospective studies.

The JNK pathway represents a novel target in the treatment of rheumatoid arthritis through the suppression of MMP-3.

BACKGROUND AND AIM: The pathophysiology of rheumatoid arthritis (RA) is characterized by excess production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) by neutrophils and macrophages in synovium. Additionally, these cytokines promote the production of reactive oxygen species (ROS), and increased production of matrix metalloproteinases (MMPs), including MMP-3, in synoviocytes that result in joint destruction. There is limited information on how proteolytic enzymes such as MMP-3 can be regulated. We evaluated the effect of the antioxidant N-acetylcysteine (NAC) on RA and identified the relationship between the c-Jun N terminal kinase (JNK) pathway and MMP-3. We hypothesized that elucidating this relationship would lead to novel therapeutic approaches to RA treatment and management. METHODS: We investigated the effect of administering a low dose (1000 µM or less) of an antioxidant (NAC) to human rheumatoid fibroblast-like synoviocytes (MH7A cells). We also investigated the response of antioxidant genes such as nuclear factor erythroid -derived 2-related factor 2 (Nrf2) and Sequestosome 1 (p62). The influence of MMP-3 expression on the JNK pathway leading to joint destruction and the mechanisms underlying this relationship were investigated through primary dispersion culture cells collected from the synovial membranes of RA patients, consisting of rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS). RESULTS: Low-dose NAC (1000 µM) increased the expression of Nrf2 and phospho-p62 in MH7A cells, activating antioxidant genes, suppressing the expression of MMP-3, and inhibiting the phosphorylation of JNK. ROS, MMP-3 expression, and IL-6 was suppressed by administering 30 µM of SP600125 (a JNK inhibitor) in MH7A cells. Furthermore, the administration of SP600125 (30 µM) to RA-FLS suppressed MMP-3. CONCLUSIONS: We demonstrated the existence of an MMP-3 suppression mechanism that utilizes the JNK pathway in RA-FLS. We consider that the JNK pathway could be a target for future RA therapies.