Objective-Capsaicin (CAP) and Resiniferatoxin (RTX) are vanilloid receptor agonists that can normalize Evoked Pain Scores (EPS) and Automated Dynamic Weight Bearing (ADWB) measures in murine acute inflammatory arthritis when given by intra-articular (IA) injection. To determine whether these vanilloid receptor agonists have benefit in Complete Freund's Adjuvant (CFA) induced chronic inflammatory arthritis pain, we measured changes in ADWB and EPS in arthritic mice with and without treatment with IA CAP and RTX.Methods and materials-Chronic inflammatory arthritis was produced by IA injection of 30 µl of Complete Freund's Adjuvant (CFA) into the left knee of C57BL6 male mice 3 weeks prior to pain behavior testing. Mice were injected with either low or high dose IA RTX (10µl of 0.001 or 0.003%), or IA CAP (10 µL of 0.01%) 7 days prior to pain behavior testing.Results-Chronic Inflammatory arthritis pain produced increased EPS and reduced ADWB measures for weight bearing in the affected limb of arthritic mice compared to naïve mice. ADWB measurements for time in CFA when compared with Naive were not significantly different, but suggested off-loading the arthritic limb to the normal limb. Treatment with IA CAP or RTX 7 days prior to pain behavior testing produced significant improvement in EPS but no improvement in ADWB measures. Neither IA CAP nor IA RTX had any impact on EPS or ADWB measurements in non-arthritic mice when given 7 days prior to pain behavioral testing.Conclusion-Using ADWB and EPS, we quantified pain in a murine chronic inflammatory arthritis model. IA CFA caused a significant increase in EPS and decreased ADWB measures in the affected limb. Treatment with IA RTX and CAP produced significant improvement in EPS in mice with mono-articular inflammatory arthritis. IA vanilloid treatment produced no improvement in ADWB measurements for weight and for time.

Valvular heart disease is a relatively common finding in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), sometimes necessitating valve surgery. Valve replacement may result in significant early and late morbidity and mortality. Surgical risks are even greater when co-morbid conditions including active SLE and renal involvement are present. This is the first report of the successful use of transcatheter aortic valve replacement (TAVR) for severe critical aortic stenosis in a patient with active SLE, renal failure and APS. TAVR may represent an additional, safer, approach to cardiac valve replacement in appropriately selected patients particularly where surgical risk is high and active disease present.

Gastrointestinal symptoms are very common in systemic lupus erythematosus (SLE). Lupus “enteritis” is very responsive to treatment but can have devastating consequences if not detected. Most descriptions of enteritis involve the small and large bowel. This is the first report of lupus “enteritis” involving the entire gastrointestinal tract from the esophagus and stomach to the rectum. Lupus “enteritis” is another cause of upper gastrointestinal involvement in SLE (involving even the esophagus and stomach) in addition to involvement of the lower intestinal tract.

Purpose: Joint pain is the earliest symptom of osteoarthritis (OA) although clinical data suggest that it poorly correlates with OA radiological features. Interestingly, recent studies show that OA pain is driven by both nociceptive and neuropathic mechanisms. CR4056 is a promising analgesic drug that binds to imidazoline-2 receptors and that was previously reported to be effective in several animal models of inflammatory, neuropathic, and postoperative pain. The aim of this study was to evaluate the effect of CR4056 in a well-established model of OA pain mimicking the painful components of human OA. The model consisted in the injection of monosodium iodoacetate (MIA) into the knee joint of rats, which produces cartilage degeneration and pain. Methods: Unilateral pain was induced by a single intra-articular injection of 1mg/50ml MIA in the infrapatellar area of the right knee of male Wistar rats (6 animals/group). Pain thresholds were determined as mechanical allodynia (Dynamic Plantar Aesthesiometer -electronic Von Frey test) and mechanical hyperalgesia (Pressure Application Measurement -PAM device) on day 1 before MIA injection, and on day 7, 14 and 21 after MIA injection. CR4056 (2, 6 mg/kg) or 10 mg/kg naproxen were administered orally, as single treatment on day 7 post injury and from day 14 to day 21, once daily, as sub-chronic treatments. Statistical analysis was performed by Two-way RM ANOVA, followed by Dunnett's multiple comparisons test. Results: Intra-articular injection of MIA induced both mechanical allodynia of the ipsilateral paw and mechanical hyperalgesia of the ipsilateral knee, either compared with the contralateral paw and knee or the saline control. Since 7 days after the induction with MIA the difference of pain behaviour between sham and arthritic rats was highly statistically significant both for allodynia (mean ± sem, 36.4 ± 0.82 g vs. 26.5 ± 0.98 g, respectively) and for hyperalgesia (1086 ±13.3 g vs. 692 ± 26.6 g, respectively). The difference between sham and MIA rats remained constant throughout the study. Acute oral administration of CR4056, 7 days after MIA, induced a dose-dependent reversal of MIA induced pain behaviours evaluated 90 minutes after treatment, that attained statistical significance (p<0.05) for the 6 mg/kg dose (40% and 33% reversal for allodynia and hyperalgesia, respectively). Naproxen at 10 mg/kg produced a lower and non-significant analgesia. Even more interestingly, as illustrated in the Figure, subacute treatment from days 14 to 21 after MIA with CR4056 (both doses) and naproxen, showed statistically significant anti-hyperalgesic effects (90' after treatment). Subacute 10 mg/kg Naproxen and 6 mg/kg CR4056 were also significantly effective against allodynia. Moreover, the rats treated for 7 days with 6 mg/kg CR4056 showed a significant reduction of both basal pain behaviours (allodynia and hyperalgesia), demonstrating either a long lasting effect or, even, a true symptom modifying effect. A similar effect was observed after naproxen, but this was only limited t...

Objective: Consideration for placement of an inferior cava filter arises in patients with APS where cessation of anticoagulation is necessary or thrombotic complications continue despite maximal anticoagulation. Permanent IVC filters are recommended to be avoided. We evaluated the safety of placement and removal of retrievable inferior vena cava filters in patients with APS. Methods: Case series of 5 patients with APS and aPL antibodies who had placement and removal of retrievable IVC filter (because of contraindication to anticoagulation or ongoing thrombosis despite full anticoagulation) to assess for safety, presence of clots in the vena cava or on the filter while in the body, evidence of PE, or clot on the explanted filter. Results: Insertion and removal, even while on anticoagulation, was safe. There was no evidence of clot in the vena cava, on the filter or pulmonary embolism in all cases. Conclusion: Where necessary, retrievable IVC filters may be safer in APS patients but should not be left in for long periods of time.