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ID PMID Title PublicationDate abstract
19706352 Older adults' pain communication: the effect of interruption. 2009 Sep The effect of interrupting older adults as they talk about their osteoarthritis pain was examined in a secondary analysis using a nonrandomized two-group design. Participants were part of a study in which older adults orally responded to a series of three pain questions asked by a videotaped practitioner presented on a computer screen. The initial 96 participants were given visual and auditory cues to touch the computer screen to continue to the next question. The remaining 216 participants received only the visual cue after the auditory cue was noted to interrupt participant responses. Older adults' pain communication was audiotaped, transcribed, and content analyzed using 16 a priori criteria from the American Pain Society's (2002)Guidelines for the Management of Pain in Osteoarthritis, Rheumatoid Arthritis, and Juvenile Chronic Arthritis. Older adults in the uninterrupted group responded with significantly more pain information, M=6.3 (SD=3.69), than the interrupted group, M=5.3 (SD=3.22); F(1,300)=4.49, p=.04, chi(2)=0.004. Adjusting for sample size differences, older adults in the interrupted group described 56% less information about the source of their pain, 41% less about the quality of their pain, 29% less about their pain treatments, 24% less about the timing of their pain, and 15% less about their pain intensity. The brief, innocuous interruption diminished the amount of important pain information communicated by the older adults. Deliberate interruptions by practitioners might further reduce communication of important pain information.
20684148 Use of biologic agents in pediatric psoriasis. 2010 Aug Psoriasis affects approximately 2 percent of the population. Approximately 30-45 percent of those affected first experience symptoms during childhood or adolescence. Although biologics have proven to be a relatively safe and effective treatment option for adults with psoriasis, limited information is available regarding the use of biologic agents in pediatric patients with psoriasis. The authors attempt to assess and summarize the available data on the use of biologic agents in patients under the age of 18, regardless of the indication, as well as to examine the limited available data on the use of biologics for psoriasis in the pediatric population. In doing so, the authors aim to provide guidance on the safety and efficacy of biologic therapies in pediatric patients with psoriasis. The authors' findings suggest that biologic agents should be considered for use solely in children with psoriasis that is refractory to conventional therapies, including children currently with severe, widespread, refractory pustular, plaque or psoriatic arthritis. Of all the currently available biologics, etanercept appears to have resulted in fewer and less severe side effects compared to infliximab in the juvenile rheumatoid arthritis population. In addition, while biologics are generally safe and effective in the pediatric population, serious adverse events (including infection), have been reported in the literature and should be taken into account before beginning treatment with any biologic agent. The physician and parents of the patient must carefully consider the risk-benefit ratio when deciding whether to use these medications. Additional randomized, controlled trials are needed to adequately assess the safety and efficacy of biologic medications for childhood psoriasis.
19891048 Hip arthroplasty up to the age of 30 and considerations in relation to subsequent revision 2009 Jul We reviewed a series of 17 hip arthroplasties in 16 patients performed when the patients were 30 years old or younger who presented to us for consideration of revision. The mean age was 23.1 years (14 to 30) at the initial arthroplasty. At the time of the original procedure there were 4 sequelae of septic arthritis, 7 old traumatic hip injures, 3 cases of developmental dysplasia (DDH), 1 case of rheumatoid arthritis (RA), 1 steroid-induced avascular necrosis, and 1 old slipped upper femoral epiphysis (SUFE) The implants inculded 11 total hip arthroplasties (THA), 3 double cup arthroplasties,1 bipolar arthroplasty,1 monopolar arthroplasty and 1 cup arthroplasty. The cause for revision lay on the acetabular side in 16 cases and on the femoral side in 6 cases (some had failure on both sides of the joint). There was one revision for recurrent dislocation. The patients had undergone a mean of 1.1 procedures (range 0-3) before the primary arthroplasty. There was a mean interval of 10.6 years (2-33)between the arthroplasty and the revision and the patients had a mean of 1.9 further revision procedures(0 to 4). Complications of revision surgery inculded 1 case of sepsis, 2 recurrent dislocations and 8 re-revisions. Postel and Merle d'Aubigne (PMA) score increased from 10.1 to 14.6 at an mean follow-up of 5.4 years (1 to 20). The typical patient was male (11/17) having had the first arthroplasty at age 23 for trauma sequelae (7/17), a revision at 34 (acetabular failure (16/17). At age 46.4, and after 1.9 secondary procedures hip scores were not exceptional. Such generally disappointing results arose from errors in implant selection or technical mistakes. Careful surgery is critical, and the way of life of the patient may need to be modified.
19426920 Expression of interferon regulatory factor 1, 3, and 7 in primary Sjögren syndrome. 2009 May OBJECTIVE: The aim was to investigate the level of interferon regulatory factor (IRF) 1, 3, and 7 in peripheral blood cells from patients with primary Sjogren syndrome (pSS) and to determine whether and where IRF1 exists in the parotid glands of pSS. METHODS: Peripheral blood cells and parotid gland biopsy specimens from patients with pSS were studied. The IRF1, IRF3, and IRF7 gene mRNA levels in peripheral blood cells were calculated by using real-time PCR. The IRF1-positive cells in the parotid glands with pSS were observed by using immunohistochemistry and immunofluorescence. Statistical analysis was performed by Student t test. RESULTS: Compared with 24 control samples, the IRF1 mRNA levels in peripheral blood cells of 37 cases with pSS were up-regulated (P < .05), but the IRF3 and IRF7 mRNA levels of pSS were not up-regulated (P > .05). Relative quantitative levels of IRF1 mRNA were 2.17-fold higher in pSS patients than control subjects. The IRF1-positive cells of the pSS group were localized in the epithelial islands, lymphocytes, and ductal epithelial cells of the parotid glands. In all control subjects, the IRF1-positive cells were localized only to the ductal epithelial cells of parotid glands as determined by immunohistochemical staining or immunofluorescence. The scores of IRF1-positive cells of pSS were significantly higher than that of control samples (P < .05). CONCLUSION: These findings indicate that IRF1 mRNA levels are up-regulated in the peripheral blood cells of pSS patients. Also, IRF1-positive cells exist in the epithelial islands, lymphocytes, and ductal epithelial cells of the parotid glands of individuals affected by pSS, but are limited to the ductal epithelial cells of healthy control subjects.
20012975 [Pathogenesis and diagnosis of Sjögren's syndrome]. 2010 Feb Sjögren's syndrome is a common autoimmune disorder. Several genetic risk factors such as STAT-4, ILT6 and the haplotype HLA-B8/DR3 have been identified. In addition, there are environmental risk factors, possibly chronic viral infections. In the pathophysiology of Sjögren's syndrome T and B cells infiltrate the salivary and lacrimal glands. As a consequence of the destruction of glandular cells by cytotoxic T cells, production of cytokines and autoantibodies inhibiting glandular function, the production of saliva and tears is decreased. The feeling of dry eyes and mouth is frequently not noticed by the patients. Therefore, Sjögren's syndrome should also be considered when extraglandular manifestations such as vasculitis, polyneuropathy or arthritis occur, even when the patients do not complain of dry eyes and mouth. Establishing the diagnosis of Sjögren's syndrome requires verification of reduced glandular function, for example using Schirmer's test and the Saxon test. The confirmation of Sjögren's syndrome as a cause of sicca syndrome is subsequently performed by the detection of autoantibodies against Ro (SS-A) and La (SS-B) and/or by a salivary gland biopsy.
19265132 Ectopic germinal centers are rare in Sjogren's syndrome salivary glands and do not exclude 2009 Mar 15 This study reports on the characterization of B cells of germinal center (GC)-like structures infiltrating the salivary glands (SGs) of patients with Sjögren's syndrome. Eight two-color combinations were devised to characterize the phenotype of these B cells in 11 SG specimens selected from biopsies obtained from 40 Sjögren's syndrome patients and three normal tonsils. The 9G4 mAb, which recognizes V4.34-encoded autoAbs, enabled us to identify autoreactive B cells. Quantitative RT-PCR was used to determine the level of mRNAs for activation-induced cytidine deaminase (AICDA), repressors and transcription factors. CD20(+)IgD(-)CD38(+)CD21(+)CD24(-) B cells, similar to those identified in tonsil GCs, were seen in the SGs of four patients and, and since they expressed AICDA, they were termed "real GCs". CD20(+)IgD(+)CD38(-)CD21(+)CD24(+) B cells, seen in aggregates from the remaining seven samples, were characteristically type 2 transitional B cells and marginal zone-type B cells. They lacked AICDA mRNAs and were termed "aggregates". Real GCs from SGs contained mRNAs for Pax-5 and Bcl-6, like tonsil GC cells, whereas aggregates contained mRNAs for Notch-2, Blimp-1, IRF-4, and BR3, similar to marginal zone B cells. Further experimental data in support of this dichotomy included the restriction of CXCR5 expression to real GC cells, while sphingosine 1-phosphate receptor 1 was expressed only in aggregates. In contrast, both types of B cell clusters expressed the idiotype recognized by the 9G4 mAb. Our data indicate that, in SGs, a minority of B cell clusters represent genuine GC cells, while the majority manifest features of being type 2 transitional B cells and marginal zone cells. Interestingly, both types of B cell aggregates include autoreactive B cells.
21172862 Peripheral neuropathies in Sjogren syndrome: a new reappraisal. 2011 Jul BACKGROUND: The prevalence of peripheral neuropathy in patients with Sjögren syndrome remains unclear owing to conflicting results in the published series, with numbers ranging from 2% to over 60% of Sjögren syndrome patients. Whether peripheral neuropathy is a feature of the systemic or glandular disease or whether it is related to a circulating antineuronal antibody remains also uncertain. METHODS: The authors reviewed the records of patients with primary Sjögren syndrome (pSS), fulfilling the Revised European-American Classification Criteria, seen in their department from 1992 to 2009. The patients with previously recorded neuropathic features were re-examined clinically and electrophysiologically. Other causes of polyneuropathy were excluded. The authors also searched for circulating antineural antibodies using immunofluorescence and western blot and for antibodies against muscarinic and nicotinic acetylcholine receptors as potential biomarkers. RESULTS: 509 cases met the diagnostic criteria for pSS. Among these, 44 patients were recorded as having neuropathic symptoms. After completing the evaluation, however, only nine (1.8%) had polyneuropathy with objective clinical signs and abnormal electrophysiological findings. The neuropathy was axonal in all, in five pure sensory and in four sensorimotor. The patients with peripheral neuropathy had extraglandular manifestations such as palpable purpura and vasculitis. No evidence of antineural autoimmunity was found, and no candidate biomarkers were identified. CONCLUSION: Polyneuropathy is a rare manifestation of pSS occurring in 1.8% of patients. In the majority of patients, it is a late event and frequently associated with systemic disease or risk factors for lymphoma development.
19679669 Renal involvement in primary Sjögren's syndrome: a clinicopathologic study. 2009 Sep BACKGROUND & OBJECTIVES: Renal pathology and clinical outcomes in patients with primary Sjögren's syndrome (pSS) who underwent kidney biopsy (KB) because of renal impairment are reported. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Twenty-four of 7276 patients with pSS underwent KB over 40 years. Patient cases were reviewed by a renal pathologist, nephrologist, and rheumatologist. Presentation, laboratory findings, renal pathology, initial treatment, and therapeutic response were noted. RESULTS: Seventeen patients (17 of 24; 71%) had acute or chronic tubulointerstitial nephritis (TIN) as the primary lesion, with chronic TIN (11 of 17; 65%) the most common presentation. Two had cryoglobulinemic GN. Two had focal segmental glomerulosclerosis. Twenty patients (83%) were initially treated with corticosteroids. In addition, three received rituximab during follow-up. Sixteen were followed after biopsy for more than 12 mo (median 76 mo; range 17 to 192), and 14 of 16 maintained or improved renal function through follow-up. Of the seven patients presenting in stage IV chronic kidney disease, none progressed to stage V with treatment. CONCLUSIONS: This case series supports chronic TIN as the predominant KB finding in patients with renal involvement from pSS and illustrates diverse glomerular lesions. KB should be considered in the clinical evaluation of kidney dysfunction in pSS. Treatment with glucocorticoids or other immunosuppressive agents appears to slow progression of renal disease. Screening for renal involvement in pSS should include urinalysis, serum creatinine, and KB where indicated. KB with characteristic findings (TIN) should be considered as an additional supportive criterion to the classification criteria for pSS because it may affect management and renal outcome.
20498206 Excess risk of hospital admission for cardiovascular disease within the first 7 years from 2010 Sep SUBJECTS: with rheumatoid factor positive inflammatory polyarthritis (IP) are known to have increased mortality from cardiovascular disease (CVD). A study was undertaken to examine the risk and baseline predictors of admission with CVD in patients with recent-onset IP. METHODS: Subjects are recruited by the Norfolk Arthritis Register if they present to primary or secondary care with > or =2 swollen joints lasting > or =4 weeks. This analysis includes subjects recruited between 1995 and 1999. Baseline data on lifestyle, demographic characteristics, disease and treatment characteristics were collected. CVD admissions were identified through record linkage with the only acute care hospital in the study region. First-episode hospitalisation rates were compared with those of the general population. Poisson regression was used to calculate the relative risk (RR) of admission for patients with IP (overall and for each risk factor). Death certificates were obtained from the national death register. RESULTS: 800 patients with recent-onset IP were followed for a median of 7.0 years. 64 CVD-related hospitalisations were observed (11.7 per 1000 person-years). Patients with IP were twice as likely (RR=2.0; 95% CI 1.5 to 2.5) to be hospitalised for CVD as the general population. Difficulty walking at baseline was a significant predictor of CVD admission and baseline non-steroidal anti-inflammatory drug use was associated with a reduced risk of CVD admission. CONCLUSIONS: Patients with IP are at increased risk of CVD-related hospitalisation, within 7 years of symptom onset. Informing patients about lifestyle modification may reduce the risk of CVD.
21145154 Endoscopic treatment of salivary glands affected by autoimmune diseases. 2011 Feb PURPOSE: To asses the possibility of an endoscopic technique to diagnose, treat, and maintain the salivary glands in patients with Sjögren syndrome and systemic lupus erythematosus. PATIENTS AND METHODS: A total of 8 patients with Sjögren syndrome and 2 with systemic lupus erythematosus with affected salivary glands were included in the present study. The treatment approach included parotid sialoendoscopy with thorough rinsing, and Stenson's duct dilation using hydrostatic pressure and a high-pressure balloon. Hydrocortisone 100 mg was injected through direct vision into the duct. The study was exempt by the Barzilai Medical Center review board. RESULTS: The main diagnosis of the patients was chronic recurrent parotitis, with the exception of 1 patient, who presented with salivary stones. CONCLUSIONS: The pathologic features of the salivary glands resulting from Sjögren syndrome and systemic lupus erythematosus can be managed successfully using an endoscopic approach.
20806091 MUC1 expression in Sjogren's syndrome, KCS, and control subjects. 2010 Aug 24 PURPOSE: To quantify and compare human mucin 1 (MUC1) protein and mRNA expression in tears and conjunctival epithelial cells collected from Sjogren's syndrome (SS), non-Sjogren's keratoconjunctivitus sicca (KCS) and non-dry eyed (NDE) control subjects. METHODS: Seventy-six subjects were recruited for this study: 25 SS (confirmed via American-European Consensus Criteria 2002), 25 KCS (confirmed by symptoms and Schirmer scores < or = 10 mm) and 26 NDE. Tears were collected using an eye-wash technique. Impression cytology was used to gather protein and mRNA from conjunctival epithelial cells. Soluble and membrane bound MUC1 were quantified via western blotting and MUC1 mRNA was quantified by real time qPCR. RESULTS: The SS group demonstrated significantly higher concentrations of soluble MUC1 (0.12 +/- 0.11 [SS]; 0.013 +/- 0.02 [KCS; p=0.001]; 0.0023 +/- 0.0024 [NDE; p<0.001]) and MUC1 mRNA (3.18 +/- 1.44 [SS]; 1.79 +/- 1.18 [KCS; p<0.05]; 1.60 +/- 0.74 [NDE; p<0.05]) compared to both KCS and NDE groups. Soluble MUC1 expression was also higher in the KCS group compared to the NDE group (p=0.02), where as MUC1 mRNA expression was similar in both KCS and NDE groups. Membrane bound MUC1 expression differed only between the SS and NDE groups (0.005 +/- -0.003 [SS]; 0.003 +/- 0.002 [NDE; p=0.002]). CONCLUSIONS: These results demonstrate that SS subjects express greater quantities of MUC1 protein and mRNA compared to both KCS and control subjects. Increased soluble MUC1 expression was also found in KCS subjects compared to controls. Membrane bound MUC1 was present in higher concentration in SS versus NDE only. These significant changes in MUC1 expression may represent compensatory or protective responses to chronic insult to the ocular surface.
20674271 Activation of the type I interferon pathway in primary Sjogren's syndrome. 2010 Nov Sjogren's syndrome (SS), a chronic autoimmune systemic disease affecting middle aged women, is characterized by lymphocytic infiltration of the salivary and lachrymal glands resulting in dry eyes and dry mouth. Recent advances have revealed a major role for activation of the type I interferon (IFN) pathway in the pathogenesis of the syndrome, as evidenced by the increased circulating type I IFN activity and an IFN "signature" in peripheral blood mononuclear cells (PBMC) and minor salivary gland (MSG) biopsies from these patients. Polymorphisms in genes involved in the IFNα pathway, such as IRF5 and STAT4, have been found to be associated with disease susceptibility. While the initial triggers of the innate immune response in SS remain elusive, preliminary evidence supports the role of inappropriately expressed endogenous LINE-1 (L1) retroelements as potential triggers of type I IFN activation in SS, possibly through Toll-like receptor (TLR) dependent or independent pathways. Proteins of the methylation machinery and the APOBEC family of cytidine deaminases are coordinately overexpressed, suggesting that those proteins might contribute to regulation of the inappropriately expressed L1 endogenous retroelements in SS. Given the apparent central role of IFNα in the pathogenesis of SS, blockade of this cytokine may be a rational therapeutic approach. In the current review we summarize the current evidence regarding the potential triggers of type I IFN activation as well as the data supporting genetic and epigenetic regulation of the type I IFN system in SS.
19487226 Vasculopathy and pulmonary arterial hypertension. 2009 Jun Vasculitis can occur either as a primary condition or secondary to CTDs, infection, medication or malignancy. This article reviews the clinical presentation and management of vascular disease associated with SLE and SS, as well as the primary necrotizing vasculitides. Although pulmonary arterial hypertension (PAH) has traditionally been considered a rare complication of SLE, estimates of its prevalence range from 0.5% to 14% and it has a significant impact on prognosis. In contrast to PAH associated with other CTDs, patients with SLE respond well to immunosuppressive agents (cyclophosphamide in conjunction with corticosteroids). Improvements or stabilization of PAH symptoms and quality of life have also been observed with the oral, dual endothelin receptor antagonist, bosentan. SS is associated with a range of cutaneous and systemic signs of vasculitis. Immunosuppressive agents are effective, but are associated with an increased risk of lymphoma. The necrotizing vasculitides include WG, Churg-Strauss syndrome and microscopic polyangiitis, and are characterized by autoantibodies to neutrophil cytoplasmic constituents. WG is one of the most common forms of vasculitis; patients usually present with signs of respiratory disease. All three necrotizing vasculitides respond to cyclophosphamide and corticosteroids, while the less toxic AZA and MTX are effective for maintenance therapy. Future therapeutic approaches may include rituximab, plasma exchanges, the TNF antagonist infliximab and haematopoietic stem cell transplantation.
19264855 Heterogeneous nuclear ribonucleoprotein h1, a novel nuclear autoantigen. 2009 May BACKGROUND: Serum samples from patients with autoimmune connective tissue diseases that show a finely speckled antinuclear antibody (ANA) on indirect immune-fluorescence often have antibodies against unknown nuclear target antigens. To search for such autoantigens we applied a proteomic approach using sera from patients with a high ANA titer (>or=640) and finely speckled fluorescence but in whom no antibodies to extractable nuclear antigens (ENA) could be identified. METHODS: Using an immunoproteomics approach we identified heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) as a novel nuclear target of autoantibody response. RESULTS: Recombinant rat hnRNP H1 reacted in Western blot analyses with 48% of 93 sera from patients with primary Sjögren syndrome and with 5.2% of 153 sera from patients with other connective tissue diseases (diseased controls). For comparison, the diagnostic sensitivity and specificity of anti-Sjögren syndrome A (SSA) antibodies for primary Sjögren syndrome in the same patient cohort were 88.2% and 76.3%, respectively. Interestingly, 5 of 11 primary Sjögren syndrome patients with no anti-SSA or anti-SSB antibodies had anti-hnRNP H1 antibodies. Anti-hnRNP H1 antibodies were preabsorbed by hnRNP H1, as demonstrated by indirect immunofluorescence. In an evaluation of the presence of anti-hnRNP H1 antibodies in 188 consecutive samples submitted to the clinical laboratory with positive ANA (titer >or=160), anti-hnRNP H1 antibodies were found in 3 of 7 (2 primary and 5 secondary) Sjögren syndrome patients and in 8.3% of the diseased controls. CONCLUSIONS: HnRNP H1 is a newly discovered autoantigen that could become an additional diagnostic marker.
19561618 Targeted depletion of lymphotoxin-alpha-expressing TH1 and TH17 cells inhibits autoimmune 2009 Jul Uncontrolled T helper type 1 (T(H)1) and T(H)17 cells are associated with autoimmune responses. We identify surface lymphotoxin-alpha (LT-alpha) as common to T(H)0, T(H)1 and T(H)17 cells and employ a unique strategy to target these subsets using a depleting monoclonal antibody (mAb) directed to surface LT-alpha. Depleting LT-alpha-specific mAb inhibited T cell-mediated models of delayed-type hypersensitivity and experimental autoimmune encephalomyelitis. In collagen-induced arthritis (CIA), preventive and therapeutic administration of LT-alpha-specific mAb inhibited disease, and immunoablated T cells expressing interleukin-17 (IL-17), interferon-gamma and tumor necrosis factor-alpha (TNF-alpha), whereas decoy lymphotoxin-beta receptor (LT-betaR) fusion protein had no effect. A mutation in the Fc tail, rendering the antibody incapable of Fcgamma receptor binding and antibody-dependent cellular cytotoxicity activity, abolished all in vivo effects. Efficacy in CIA was preceded by a loss of rheumatoid-associated cytokines IL-6, IL-1beta and TNF-alpha within joints. These data indicate that depleting LT-alpha-expressing lymphocytes with LT-alpha-specific mAb may be beneficial in the treatment of autoimmune disease.
19701715 Hereditary gelsolin amyloidosis mimicking Sjögren's syndrome. 2009 Nov Hereditary gelsolin amyloidosis (AGel amyloidosis) belongs to the wide group of amyloidotic diseases, which comprise various hereditary but also sporadic forms, such as inflammation-associated AA amyloidosis, primary or myeloma-associated AL amyloidosis and common Alzheimer's disease and type II diabetes-associated local amyloidoses. AGel amyloidosis caused by a gelsolin G654A gene mutation is autosomally dominantly inherited and presents typically in the 30s with progressive corneal lattice dystrophy, followed by cutis laxa and cranial polyneuropathy. Here, we present a case of sicca syndrome, originally diagnosed as primary Sjögren's syndrome (SS) but later found to represent an initial disease manifestation of AGel amyloidosis, not recognised earlier. This case emphasises both the importance of specific amyloid stainings and comprehensive salivary gland histopathology as well as family history in SS differential diagnostics.
19433433 Treatment of sicca symptoms with hydroxychloroquine in patients with Sjogren's syndrome. 2009 Jul OBJECTIVE: There is no established disease-modifying treatment of xerostomia and xerophthalmia in SS. This retrospective study was performed in order to evaluate the efficacy of HCQ for glandular function, i.e. saliva and tear production. METHODS: Fourteen patients with primary SS (pSS) were included (Group A). All patients were anti-Ro and/or -La antibody positive except one. Patients were treated with HCQ for a period of up to 6 months. Glandular function was determined by Saxon's and Schirmer's tests for the dominant eye at baseline and at the end of the treatment. We included a control group of 21 patients with objective sicca symptoms and positive alpha-fodrin antibodies (Group B). RESULTS: In patients with pSS (Group A), a significant increase in saliva production after HCQ treatment (P = 0.022) was observed. A subanalysis revealed that particularly the alpha-fodrin-positive patients responded to HCQ (P = 0.017 alpha-fodrin positive vs P = 0.4 alpha-fodrin negative). Interestingly, patients with sicca symptoms and alpha-fodrin antibodies (Group B) showed a significant increase in tear production (P = 0.001). In addition, there was a positive correlation between the alpha-fodrin IgA antibody concentration and the Schirmer's test at baseline (r = 0.66; P = 0.001) and after treatment (r = 0.6; P = 0.004) in this group. CONCLUSIONS: HCQ treatment led to a beneficial effect on xerostomia in patients with pSS who lack severe organ manifestations. The response was greater in alpha-fodrin-positive patients.
24281168 YKL-40-A Protein in the Field of Translational Medicine: A Role as a Biomarker in Cancer P 2010 Jul 12 YKL-40 is a 40 kDa glycoprotein produced by cancer cells, inflammatory cells and stem cells. It probably has a role in cell proliferation and differentiation, inflammation, protection against apoptosis, stimulation of angiogenesis, and regulation of extracellular tissue remodelling. Plasma levels of YKL-40 are often elevated in patients with localized or advanced cancer compared to age-matched healthy subjects. Several studies have demonstrated that high plasma YKL-40 is an independent prognostic biomarker of short survival in patients with different types of cancer. However, there is not yet sufficient data to support determination of plasma YKL-40 outside research projects as a biomarker for screening of gastrointestinal cancer and determination of treatment response and poor prognosis before or during treatment and follow-up. Plasma YKL-40 is also elevated in patients with other diseases than cancer, e.g., severe infections, cardiovascular disease, diabetes, chronic obstructive lung disease, asthma, liver fibrosis and rheumatoid arthritis. Co-morbidity should therefore always be considered in patients with cancer, since other sources than cancer cells can increase plasma YKL-40 levels. Future focused translational research projects combining basic and clinical research are needed in a joint effort to answer questions of the complex function and regulation of YKL-40 and the question if plasma YKL-40 is a clinical useful biomarker in patients with cancer.
17987290 First hip arthroplasty register in Italy: 55,000 cases and 7 year follow-up. 2009 Apr The Register for Orthopaedic Prosthetic Implantation (RIPO) has been prospectively collecting data on hip prostheses performed in all the orthopaedic units in the region Emilia-Romagna since January 2000. The register aims to determine the characteristics of patients, evaluate the effectiveness of prostheses, and allow internal audit. Adherence to the register is compulsory (93% capture). By 31 December 2006 the register contained data on 35,041 primary total hip arthroplasty (THA), 14,613 hemiarthoplasties, and 5,878 revisions. All prosthetic components are registered on an individual basis. Survival analysis is done following the Kaplan Meier method. Cumulative survival rate at 7 years is 96.8% (95% CI: 96.4-97.1%) for THA and 97.6% (97.0-98.3%) for hemiarthroplasties. Multivariate analysis verified that survival of the THA is affected by pathology, where the worst conditions are rheumatoid arthritis, femoral neck fracture, and sequelae of coxitis or Paget's disease. Results are comparable to other major registers of Northern Europe and Australia.
21184867 Methodological issues in comparative effectiveness research: clinical trials. 2010 Dec The US Department of Veterans Affairs (VA) Cooperative Studies Program has been conducting comparative effectiveness clinical trials for nearly 4 decades in many disease areas, including cardiovascular disease/surgery, diabetes mellitus, mental health, neurologic disorders, cancer, infectious diseases, and rheumatoid arthritis. The features that have made this program advantageous for conducting comparative effectiveness clinical trials are described along with methodological considerations for future trials based on lessons learned from its experience conducting these types of studies. Some of the lessons learned involve managing risk factors, clinical equipoise, patient preferences, evolving technology, the use of usual care as a comparator and pharmaceutical issues related to study drug blinding. These issues are not unique to the VA but can play an important role in enabling valid comparisons between treatments that may have differences in delivery or mechanisms of action and could affect the execution and feasibility of conducting a clinical trial with a comparative effectiveness aim. We also outline some future directions for comparative effectiveness clinical trials.