Objective.Evidence from animal studies, case reports, and phase I studies suggests that hemopoietic stem cell transplantation (HSCT) can be effective in the treatment of rheumatoid arthritis (RA). It is unclear, however, if depletion of T cells in the stem cell product infused after high-dose chemotherapy is beneficial in prolonging responses by reducing the number of infused autoreactive T cells. This pilot multicenter, randomized trial was undertaken to obtain feasibility data on whether CD34 selection (as a form of T cell depletion) of an autologous stem cell graft is of benefit in the HSCT procedure in patients with severe, refractory RA.Methods. Thirty-three patients with severe RA who had been treated unsuccessfully with methotrexate and at least 1 other disease-modifying agent were enrolled in the trial. The patients received high-dose immunosuppressive treatment with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected or unmanipulated. Safety, efficacy (based on American College of Rheumatology [ACR] response criteria), and time to recurrence of disease were assessed on a monthly basis for up to 12 months.Results. All patients were living at the end of the study, with no major unexpected toxicities. Overall, on an intent-to-treat basis, ACR 20% response (ACR20) was achieved in 70% of the patients. An ACR70 response was attained in 27.7% of the 18 patients who had received CD34-selected cells and 53.3% of the 15 who had received unmanipulated cells (P ‫؍‬ 0.20). The median time to disease recurrence was 147 days in the CD34-selected cell group and 201 days in the unmanipulated cell group (P ‫؍‬ 0.28). There was no relationship between CD4 lymphopenia and response, but 72% of rheumatoid factor (RF)-positive patients had an increase in RF titer prior to recurrence of disease.Conclusion. HSCT can be performed safely in patients with RA, and initial results indicate significant responses in patients with severe, treatment-resistant disease. Similar outcomes were observed in patients undergoing HSCT with unmanipulated cells and those receiving CD34-selected cells. Larger studies are needed to confirm these findings.

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Objectives:PainDETECT is a self-report questionnaire that can be used to identify features of neuropathic pain. A proportion of patients with knee osteoarthritis (OA) score highly on the PainDETECT questionnaire. This study aimed to determine whether those with a higher “positive neuropathic” score on the PainDETECT questionnaire also had greater pain, hypersensitivity, and reduced function compared with individuals with knee OA with lower PainDETECT scores.Materials and Methods:In total, 130 participants with knee OA completed the PainDETECT, Western Ontario and McMaster Universities Arthritis Index (WOMAC), and Pain Quality Assessment Scale questionnaires. Quantitative sensory testing was carried out at 3 sites (both knees and elbow) using standard methods. Cold and heat pain thresholds were tested using a Peltier thermode and pressure pain thresholds using a digital algometer. Physical function was assessed using 3 timed locomotor function tests.Results:In total, 22.3% of participants scored in the “positive neuropathic” category with a further 35.4% in the unclear category. Participants in the “positive neuropathic” category reported higher levels of pain and more impaired function based on the WOMAC questionnaire (P<0.0001). They also exhibited increased levels of hyperalgesia at the knee and upper limb sites for all stimulation modalities except heat pain thresholds at the OA knee. They were also slower to complete 2 of the locomotion tasks.Discussion:This study identified a specific subgroup of people with knee OA who exhibited PainDETECT scores in the “positive neuropathic” category. These individuals experienced increased levels of pain, widespread, multimodality hyperalgesia, and greater functional impairment than the remaining cohort. Identification of OA patients with this pain phenotype may permit more targeted and effective pain management.

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Twenty-five years after the first paper on etidronate in Paget's disease, there are few published papers that address bisphosphonate resistance as a specific clinical phenomenon. We report our data from two studies. Study 1 is a retrospective study of 20 patients with moderate to severe disease who were treated with intravenous (iv) However the minimum duration of biochemical remission was significantly shorter after the second course-10.9 i 1.7 months (first) and 5.6 f 0.9 months (second) (p c 0.03; Friedman's ANOVA n = 17). A subgroup of 10 patients who were followed for three courses showed a significantly higher PAP nadir in the third 'course. Study 2 is a prospective study of 40 patients, 23 previously untreated (NILPREV) and 17 previously treated with iv pamidronate (PAMPREV) and in biochemical relapse, who were randomly allocated to either oral alendronate 40 mg daily in 3 month units, or iv pamidronate 60 mg every 3 months. Treatment was continued until PAP and fasting urinary deoxypyridinolindcreatinine @py/Cr) ratios (RR 5-27 pmoYmo1) were both in the reference range, or a dear plateau in each marker developed. At baseline, there were no significant differences in either marker between the two NILPREV groups and between the two PAMPREV groups. Using log-transformed data, in NILPREV the PAP reductions were significant and similar over the first 6 months. However, although each Dpy/Cr reduction was also significant, the difference in responses favored alendronate (p c 0.015). In PAMPREV both markers showed no significant response to pamidronate; comparison showed a significantly greater response to alendronate (PAP p < 0.02; Dpy/Cr p c 0.002). Using two-way ANOVA, the PAP responses to alendronate in NILPREV and PAMPREV were similar and thaw to pamidronate were different (p = 0.034). The percentage of patients with both markers in the RR at 6 months or earlier were identical in NILPREV patients: alendronate 87% and pamidronate 87%. However in PAMPREV they were different: alendronate 83% and pamidronate 0% (p = 0.003). These data indicate: 1) patients treated with the same aminobisphosphonates for two courses show similar nadir values of bone turnover markers but a shorter remission time after the second course. In a third course the nadirs are significantly higher; and 2) in the alendronabdpamidronate comparison, NILPREV and PAMPREV