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ID PMID Title PublicationDate abstract
28799485 Monoclonal Antibodies: A Review. 2018 BACKGROUND: Over the last three decades, monoclonal antibodies (MAbs) have made a striking transformation from scientific tools to powerful human therapeutics. Muromonab CD3 a murine MAb was the first FDA approved therapeutic MAb for the prevention of kidney transplant rejection. Since its approval in 1986, there has been a decline in further application and approvals until the late 1990s when the first chimeric Mab, Rituximab was approved for the treatment of lowgrade B cell lymphoma in 1997. With the approval by licensing authorities of chimeric, followed by humanized and then fully human monoclonal antibodies, the rate of approval and monoclonal antibodies available in the market for the treatment of various diseases has increased dramatically. As of March 2017, FDA has approved approximately 60 therapeutic MAbs which are currently under evaluation in various phases of clinical trials. OBJECTIVE: MAbs are approved for the treatment of diseases belonging to various systems like cardiovascular, respiratory, hematology, kidney, immunology and oncology. MAbs are approved for the treatment of orphan diseases or indications such as paroxysmal nocturnal hemoglobinuria as well as cancers and multiple sclerosis where hundreds of patients are treated and even diseases such as breast cancer, asthma and rheumatoid arthritis where millions are being treated. This review focuses briefly on types, molecular targets, mechanism of actions and therapeutic indications of FDA approved MAb products that are currently available in the market. CONCLUSION: With the advent of fully human MAbs, the efficacy and safety have improved in the treatment of various cardiovascular, cancer, respiratory, hematology, autoimmune diseases and infections. The introduction of biosimilars will increase the affordability and utilization of MAbs in the treatment of various diseases.
30092305 Clinical outcome and risk factors for failure in late acute prosthetic joint infections tr 2019 Jan OBJECTIVES: Debridement, antibiotics and implant retention (DAIR) is the recommended treatment for all acute prosthetic joint infections (PJI), but its efficacy in patients with late acute (LA) PJI is not well described. METHODS: Patients diagnosed with LA PJI between 2005 and 2015 were retrospectively evaluated. LA PJI was defined as the development of acute symptoms (≤ 3 weeks) occurring ≥ 3 months after arthroplasty. Failure was defined as: (i) the need for implant removal, (ii) infection related death, (iii) the need for suppressive antibiotic therapy and/or (iv) relapse or reinfection during follow-up. RESULTS: 340 patients from 27 centers were included. The overall failure rate was 45.0% (153/340). Failure was dominated by Staphylococcus aureus PJI (54.7%, 76/139). Significant independent preoperative risk factors for failure according to the multivariate analysis were: fracture as indication for the prosthesis (odds ratio (OR) 5.4), rheumatoid arthritis (OR 5.1), age above 80 years (OR 2.6), male gender (OR 2.0) and C-reactive protein > 150 mg/L (OR 2.0). Exchanging the mobile components during DAIR was the strongest predictor for treatment success (OR 0.35). CONCLUSION: LA PJIs have a high failure rate. Treatment strategies should be individualized according to patients' age, comorbidity, clinical presentation and microorganism causing the infection.
30347820 Type I Interferon Signaling Is Required for Dacryoadenitis in the Nonobese Diabetic Mouse 2018 Oct 20 Nonobese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity similar to human Sjögren syndrome. In both humans and NOD mice, the early immune response that drives T-cell infiltration into lacrimal and salivary glands is poorly understood. In NOD mice, lacrimal gland autoimmunity spontaneously occurs only in males with testosterone playing a role in promoting lacrimal gland inflammation, while female lacrimal glands are protected by regulatory T cells (Tregs). The mechanisms of this male-specific lacrimal gland autoimmunity are not known. Here, we studied the effects of Treg depletion in hormone-manipulated NOD mice and lacrimal gland gene expression to determine early signals required for lacrimal gland inflammation. While Treg-depletion was not sufficient to drive dacryoadenitis in castrated male NOD mice, chemokines (Cxcl9, Ccl19) and other potentially disease-relevant genes (Epsti1, Ubd) were upregulated in male lacrimal glands. Expression of Cxcl9 and Ccl19, in particular, remained significantly upregulated in the lacrimal glands of lymphocyte-deficient NOD-severe combined immunodeficiency (SCID) mice and their expression was modulated by type I interferon signaling. Notably, Ifnar1-deficient NOD mice did not develop dacryoadenitis. Together these data identify disease-relevant genes upregulated in the context of male-specific dacryoadenitis and demonstrate a requisite role for type I interferon signaling in lacrimal gland autoimmunity in NOD mice.
29504954 Utility of Novel Autoantibodies in the Diagnosis of Sjögren's Syndrome Among Patients Wit 2018 Apr PURPOSE: To investigate the value of 3 novel autoantibodies [salivary protein 1 (SP1), carbonic anhydrase 6 (CA6), and parotid secretory protein (PSP)] in differentiating Sjögren's syndrome (SS)-related dry eye from non-SS dry eye. METHODS: Forty-six dry eye patients with SS (SS dry eye), 14 dry eye patients without SS (non-SS dry eye), and 25 controls were included. The 2012 American College of Rheumatology classification criteria were used for the diagnosis of SS. After a detailed review of systems, the Ocular Surface Disease Index questionnaire, Schirmer test without anesthesia, tear film breakup time, and ocular surface staining were performed to assess dry eye. All participants underwent serological testing using a commercially available finger prick kit. RESULTS: Thirty-seven patients with SS (80.4%) had a positive traditional autoantibody and 28 (60.9%) had a positive novel autoantibody. Traditional autoantibodies were absent in all non-SS dry eye patients and controls. Novel autoantibodies were present in 7/14 (50%) non-SS dry eye patients and 4/25 (16%) controls. Among 3 novel autoantibodies, anti-CA6 was significantly more prevalent in the SS and non-SS dry eye groups than in controls (52.2% vs. 42.9% vs. 8.0%, P = 0.001). Dry eye patients with positive anti-CA6 alone were significantly younger than patients with only traditional autoantibodies. Anti-CA6 was associated with worse dry eye signs and symptoms. CONCLUSIONS: Anti-CA6 was the most prevalent novel autoantibody in patients with dry eye, and was associated with younger age and more severe disease. Longitudinal studies are needed to determine whether anti-CA6 is a marker for early SS or perhaps another form of an autoimmune dry eye disease.
30334118 Evaluation of subclinical atherosclerosis by ultrasound radiofrequency data technology in 2019 Mar Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease, and inflammation is highly associated with atherosclerosis and increased cardiovascular risk. Carotid intima-media thickness (CIMT) and arterial stiffness measurements are commonly used to detect subclinical atherosclerosis. The aim of this study was to non-invasively demonstrate the presence of subclinical atherosclerosis in patients with pSS through these measurements, using ultrasound (US) radiofrequency (RF) data technology. 30 pSS patients as the study group and 30 age-and sex-matched healthy volunteers as the control group were included in this study. The age of the participants in the entire sample ranged from 18 to 60 years, and no primary cardiovascular risk factors were present, such as diabetes mellitus, hypertension, hyperlipidemia, or obesity. The participants in the study and control groups were evaluated with doppler ultrasonography. Arterial stiffness and CIMT measurements were made from the bilateral common carotid arteries (CCA) using US RF data technology. No statistically significant difference was identified between the patients with pSS and the controls in terms of the right, left, and mean CCA IMT; the right side distensibility coefficient (DC) and compliance coefficient (CC); or the right- and left-side α and β stiffness indices values (p > 0.05). Compared to the control subjects, the pSS patients had higher right and left side pulsed wave velocity (PWV), the mean value of the right and the left sides α stiffness index, β stiffness index, and PWV (p < 0.05). The pSS patients' left DC, left CC, and the mean value of the right and left sides DC and CC were lower than controls (p < 0,05). It was found that patients with pSS show evidence of subclinical atherosclerosis. To determine this situation in patients with pSS, CIMT and PWV measurements may serve as a guide. Radiofrequency data technology represents a non-invasive approach to the accurate and quantitative measurement of CIMT elevation and decreases in vascular elasticity.
28249724 Time-course of ultrasound abnormalities of major salivary glands in suspected Sjögren's s 2018 Mar OBJECTIVE: To evaluate whether major salivary-gland ultrasonography (SGUS) abnormalities change over time in patients with suspected primary Sjögren's syndrome (pSS) during the natural course of the disease. METHODS: We studied patients with suspected pSS who were included in the Brittany cohort of suspected pSS and underwent SGUS at least twice, as part of the routine diagnostic workup done at baseline then at least 1 year later as an additional investigation deemed appropriate by the physician. The evaluation criteria were the semi-quantitative SGUS score (0-4) for each parotid and submandibular gland, the highest SGUS score among the four glands, and the sum of SGUS scores for the four glands. These scores were compared in patients with and without pSS according to the workup at baseline, and their changes over time were assessed. RESULTS: Of 49 included patients, 29 received a diagnosis of pSS at baseline; none of the remaining 20 patients was diagnosed with pSS at either evaluation. The mean (SD) sum of SGUS scores at baseline was 8.9 (5.6) in patients with and 2.1 (2.9) in those without pSS (P<0.01). Mean time between SGUSs was 1.9 (1.6) years. None of the evaluation criteria changed between the two SGUSs in the overall population, pSS group, or group without pSS. Similar results were found in the subgroup with recent-onset symptoms. CONCLUSION: SGUS abnormalities assessed using a semi-quantitative score did not change significantly during a follow-up of nearly 2 years after an initial evaluation for suspected pSS.
30335268 Acute motor and sensory axonal neuropathy associated with Sjögren's syndrome. 2018 Sep 30 Sjögren's syndrome (SS) is an autoimmune disease with mononuclear cell infiltration and destruction of the lacrimal gland and salivary glands, which cause dryness of the eyes and mouth. The most common neurological condition seen in SS is peripheral neuropathy. Initial manifestation of SS as an acute fulminant peripheral neuropathy is extremely rare. We report a 42-year-old patient presenting with acute motor sensory-axonal neuropathy in the presence of SS. She showed partial response to intravenous immunoglobulin but favourable clinical improvement was seen after initiation of corticosteroid treatment.
29463848 Autoantibodies against the Immunoglobulin-Binding Region of Ro52 Link its Autoantigenicity 2018 Feb 20 Ro52/TRIM21 plays a key role in antibody-dependent pathogen neutralization and is a major autoantigen in systemic lupus erythematosus, Sjögren's syndrome (SS), and other autoimmune diseases. Here we evaluated immunoreactivity against Ro52-related molecules in SS and healthy volunteers. Although most proteins examined were not antigenic, several TRIM paralogs, including TRIM22, and TRIM38, showed sporadic immunoreactivity in SS. In contrast, the murine Ro52 ortholog with limited linear homology demonstrated high levels of autoantibodies implicating the importance of shared conformational epitopes. To further explore the autoantigencity of Ro52, deletion and point mutant analyses were employed revealing previously hidden, robust autoantibodies directed against its C-terminal immunoglobulin-binding domain. Another autoantibody, rheumatoid factor, targeting the Fc region of IgG, strongly overlapped with Ro52 seropositivity (odds ratio 14; P < 0.0001). These convergent mechanistic findings support a model whereby intracellular Ro52-bound antibody-coated pathogen complexes, released or misprocessed from infected cells, drive autoantigenicity against Ro52 and the Fc region of IgG.
30264875 Exposure measurement error when assessing current glucocorticoid use using UK primary care 2019 Feb PURPOSE: To quantify misclassification in glucocorticoid (GC) exposure defined using UK primary care prescription data. METHODS: A cross-sectional study including patients with rheumatoid arthritis prescribed oral GCs in the past 2 years. Glucocorticoid exposure based on electronic prescription records was compared with participant-reported GC use captured using a paper diary. Prescription data (containing information about prescriptions issued but no dispensing information) was provided by the Clinical Practice Research Datalink. The following variables were defined: current use and dose of oral GCs and if (and when) participants had received a GC injection. For oral GCs, self-reported use was taken to represent "true" exposure. A dataset representing a hypothetical population was generated to assess the impact of the misclassification found for current use. RESULTS: A total of 67 of 78 study participants (86%) were correctly classified as currently on/off oral GCs; 32/38 (84.2%) participants reporting current GC use and 35/40 (87.5%) participants not reporting current use were correctly classified. Estimated values of current dose were imprecise (correlation coefficient 0.46). Concordance between reported and prescribed GC injections was poor (kappa statistic 0.14). Misclassification bias was demonstrated in the hypothetical population: For "true" relative risks of 1.5, 4, and 9, the "observed" relative risks were 1.33, 2.48, and 3.58, respectively. CONCLUSIONS: Misclassification of current use of oral GCs was low but sufficient to lead to significant bias. Researchers should take care to assess the likely impact of exposure misclassification on their analyses.
29717032 Responsiveness of Single versus Composite Measures of Pain in Knee Osteoarthritis. 2018 Aug OBJECTIVE: In rheumatoid arthritis, composite outcomes constructed from a combination of outcome measures are widely used to enhance responsiveness (sensitivity to change) and comprehensively summarize response. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain is the primary outcome measure in many osteoarthritis (OA) trials. Information from other outcomes, such as rescue medication use and other WOMAC subscales, could be added to create composite outcomes, but the sensitivity of such a composite has not been tested. METHODS: We used data from a completed trial of tanezumab for knee OA (NCT00733902). The WOMAC questionnaire and rescue medication use were measured at several timepoints, up to 16 weeks. Pain and rescue medication outcomes were standardized and combined into 3 composite outcomes through principal components analysis to produce 1 score (composite outcome) and their responsiveness was compared to WOMAC pain, the standard. We pooled all treatment doses of tanezumab into 1 treatment group, for simplicity, and compared this to the control group (placebo). RESULTS: The composite outcomes showed modestly, but not statistically significantly greater responsiveness when compared to WOMAC pain alone. Adding information on rescue medication to the composite improved responsiveness. While improvements in sensitivity were modest, the required sample sizes for trials using composites was 20-40% less than trials using WOMAC pain alone. CONCLUSION: Combining information from related but distinct outcomes considered relevant to a particular treatment improved responsiveness, could reduce sample size requirements in OA trials, and might offer a way to better detect treatment efficacy in OA trials.
30096386 Co-administration with simvastatin or lovastatin alters the pharmacokinetic profile of sin 2018 Sep 15 AIMS: Sinomenine, an anti-rheumatoid arthritis drug used in China for decades, is usually co-administered with cardiovascular (CV) drugs to reduce arthritis-related risk of cardiovascular diseases. This study was to investigate whether and how CV drugs affect the pharmacokinetic profile of sinomenine. MAIN METHODS: In rat liver microsomes (RLMs), the key metabolic enzymes of sinomenine were identified by using specific inhibitors. The influences of CV drugs, including propranolol, verapamil, warfarin, atorvastatin, simvastatin, and lovastatin, on the metabolism of sinomenine were examined. Cocktail probe, RT-qPCR, and western blotting were performed to unveil the underlying mechanism of the drug-drug interaction. KEY FINDINGS: The key metabolic enzymes of sinomenine were identified to be CYP3A1/2 and CYP2D1 in RLMs. Among the CV drugs screened, simvastatin and lovastatin were shown to inhibit the liver metabolism of sinomenine with Ki values of 13.00 and 25.83 μM, respectively. Single administration of simvastatin or lovastatin in rats increased the AUC value of sinomenine to 1.40- or 1.50-fold, and decreased the CLz/F value to 68.19% or 65.44%, respectively. In contrast, multiple administrations of simvastatin, but not lovastatin, increased the CLz/F value of sinomenine to 1.38-fold and decreased the AUC value to 71.59%. Further studies showed that the long-term administration of simvastatin could up-regulate the expression of CYP3A1/2 to account for the effect. SIGNIFICANCE: This study demonstrated the potential effect of simvastatin and lovastatin on the metabolism of sinomenine for the first time. The findings provide guidelines for the co-administration of sinomenine with simvastatin or lovastatin in clinic.
29850873 Herpes Zoster Infection in Patients With Ulcerative Colitis Receiving Tofacitinib. 2018 Sep 15 BACKGROUND: Tofacitinib is an oral, small molecule Janus kinase inhibitor that is being investigated for ulcerative colitis (UC). Tofacitinib is approved for rheumatoid arthritis and psoriatic arthritis, where it has been shown to increase herpes zoster (HZ) risk. We evaluated HZ risk among UC patients using tofacitinib. METHODS: HZ cases were identified in tofacitinib phase II/III/ongoing, open-label, long-term extension (OLE) UC trials. We calculated HZ incidence rates (IRs) per 100 patient-years of tofacitinib exposure within phase III maintenance (Maintenance Cohort) and phase II/III/OLE (Overall Cohort) studies, stratified by baseline demographics and other factors. HZ risk factors were evaluated in the Overall Cohort using Cox proportional hazard models. RESULTS: Overall, 65 (5.6%) patients developed HZ. Eleven patients had multidermatomal involvement (2 nonadjacent or 3-6 adjacent dermatomes), and 1 developed encephalitis (resolved upon standard treatment). Five (7.7%) events led to treatment discontinuation. HZ IR (95% confidence interval [CI]) in the Overall Cohort was 4.07 (3.14-5.19) over a mean (range) of 509.1 (1-1606) days, with no increased risk observed with increasing tofacitinib exposure. IRs (95% CI) were highest in patients age ≥65 years, 9.55 (4.77-17.08); Asian patients, 6.49 (3.55-10.89); patients with prior tumor necrosis factor inhibitor (TNFi) failure, 5.38 (3.86-7.29); and patients using tofacitinib 10 mg twice daily, 4.25 (3.18-5.56). Multivariate analysis identified older age and prior TNFi failure as independent risk factors. CONCLUSIONS: In tofacitinib-treated UC patients, there was an elevated risk of HZ, although complicated HZ was infrequent. Increased HZ rates occurred in patients who were older, Asian, or had prior TNFi failure (NCT00787202, NCT01465763, NCT01458951, NCT01458574, NCT01470612).
29791754 ATP triggers a robust intracellular [Ca(2+) ]-mediated signalling pathway in human synovia 2018 Aug NEW FINDINGS: What is the central question of this study? What are the main [Ca(2+) ](i) signalling pathways activated by ATP in human synovial fibroblasts? What is the main finding and its importance? In human synovial fibroblasts ATP acts through a linked G-protein (G(q) ) and phospholipase C signalling mechanism to produce IP(3) , which then markedly enhances release of Ca(2+) from the endoplasmic reticulum. These results provide new information for the detection of early pathophysiology of arthritis. ABSTRACT: In human articular joints, synovial fibroblasts (HSFs) have essential physiological functions that include synthesis and secretion of components of the extracellular matrix and essential articular joint lubricants, as well as release of paracrine substances such as ATP. Although the molecular and cellular processes that lead to a rheumatoid arthritis (RA) phenotype are not fully understood, HSF cells exhibit significant changes during this disease progression. The effects of ATP on HSFs were studied by monitoring changes in intracellular Ca(2+) ([Ca(2+) ](i) ), and measuring electrophysiological properties. ATP application to HSF cell populations that had been enzymatically released from 2-D cell culture revealed that ATP (10-100 μm), or its analogues UTP or ADP, consistently produced a large transient increase in [Ca(2+) ](i) . These changes (i) were initiated by activation of the P(2) Y purinergic receptor family, (ii) required G(q) -mediated signal transduction, (iii) did not involve a transmembrane Ca(2+) influx, but instead (iv) arose almost entirely from activation of endoplasmic reticulum (ER)-localized inositol 1,4,5-trisphosphate (IP(3) ) receptors that triggered Ca(2+) release from the ER. Corresponding single cell electrophysiological studies revealed that these ATP effects (i) were insensitive to [Ca(2+) ](o) removal, (ii) involved an IP(3) -mediated intracellular Ca(2+) release process, and (iii) strongly turned on Ca(2+) -activated K(+) current(s) that significantly hyperpolarized these cells. Application of histamine produced very similar effects in these HSF cells. Since ATP is a known paracrine agonist and histamine is released early in the inflammatory response, these findings may contribute to identification of early steps/defects in the initiation and progression of RA.
29661192 Policosanol composition, antioxidant and anti-arthritic activities of milk thistle (Silybi 2018 Apr 16 BACKGROUND: Several anti-arthritic drugs and synthetic antioxidants have wide pharmaceutical uses and are often associated with various side effects on the human health. Dietary seed oils and their minor components like policosanol may offer an effective alternative treatment for arthritic and oxidative-stress related diseases. The biological effects of seed oils were affected by different parameters such as the stage of seed maturity. Hence, this study seeks to determine the policosanol content, antioxidant and anti-arthritic activities of milk thistle (Silybium marianum L.) oil extracted at various stages of seed maturation. METHODS: Milk thistle oil samples were extracted from seeds collected at three maturation stages (immature, intermediate, and mature). The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethyl-benzthiazoline-6-sulfonic acid) (ABTS) radical scavenging assays were used to determine the antioxidant activity of the extracted oils. The anti-arthritic activity of oil samples was evaluated with bovine serum protein denaturation and egg albumin denaturation methods. Gas chromatography coupled to mass spectrometry (GC-MS) was employed to determine the policosanol profile. RESULTS: Policosanol profile, antioxidant and anti-arthritic activities of milk thistle oil were influenced by the seed maturity stages. The oil extracted from the immature seeds had the highest total policosanol content (987.68 mg/kg of oil) and displayed the maximum antiradical activity (96.42% and 90.35% for DPPH test and ABTS assay, respectively). Nine aliphatic alcohols were identified in the milk thistle oil. The dominant poliosanol in the mature seed oil was octacosanol (75.44%), while triacontanol was the major compound (40.25%) in the immature seed oil. Additionally, the maximum inhibition of bovine serum protein denaturation (92.53%) and egg albumin denaturation (86.36%) were observed in immature seed oil as compared to mature seed oil. A high correlation was found between the total policosanol content, anti-arthritic activity and antioxidant capacity of oil. CONCLUSIONS: The milk thistle oil exhibited a potential anti-arthritic and antioxidant activities and that it might contribute to the protection of humans from a variety of diseases like rheumatoid arthritis. Also, it could serve as natural antioxidant and anti-arthritic agents for application in the food industries and pharmaceutic. Policosanol level in the seed oils might contribute to their anti-arthritic and antioxidant activities.
29596085 The Influence of Connective Tissue Disease in Breast Reconstruction: A National Database A 2018 Apr BACKGROUND: Patients with connective tissue diseases (CTD), or collagen vascular diseases, are at risk of potentially higher morbidity after surgical procedures. We aimed to investigate the complication profile in CTD versus non-CTD patients who underwent breast reconstruction on a national scale. METHODS: A retrospective analysis of the Healthcare Cost and Utilization Project NIS Database between 2010 and 2014 was conducted for patients 18 years or older admitted for immediate autologous or implant breast reconstruction. Connective tissue disease was defined as systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, scleroderma, Raynaud phenomenon, psoriatic arthritis, or sarcoidosis. Independent t test/Wilcoxon-Mann-Whitney was used to compare continuous variables and Pearson χ/Fischer exact test was used for categorical variables. Outcomes of interest were assessed using multivariable linear regressions for continuous variables and multivariable logistic regressions for categorical variables. RESULTS: There were 19,496 immediate autologous breast reconstruction patients, with 357 CTD and 19,139 non-CTD patients (2010-2014). The CTD patients had higher postoperative complication rates for infection (2.8% vs 0.8%, P < 0.001), wound dehiscence (1.4% vs 0.4%, P = 0.019), and bleeding (hemorrhage and hematoma) (6.7% vs 3.5%, P < 0.001). After multivariable analysis, CTD remained an independent risk factor for bleeding (odds ratio [OR], 1.568; 95% confidence interval [CI], 1.019-2.412). There were a total of 23,048 immediate implant breast reconstruction patients, with 431 CTD and 22,617 non-CTD patients (2010-2014). The CTD patients had a higher postoperative complication rate for wound dehiscence/complication (2.3% vs 0.6%, P < 0.001). They also experienced a longer length of stay (2.31 days vs 2.07 days, P < 0.001). After multivariable analysis, CTD remained an independent risk factor for wound dehiscence (OR, 4.084; 95% CI, 2.101-7.939) and increased length of stay by 0.050 days (95% CI, -0.081 to 0.181). CONCLUSIONS: Connective tissue disease patients who underwent autologous breast reconstruction had significantly higher infection, wound dehiscence, and bleeding rates, and those who underwent implant breast reconstruction had significantly higher wound dehiscence rates. Connective tissue diseases appear to be an independent risk factor for bleeding and wound dehiscence in autologous and implant breast reconstruction, respectively. This information may help clinicians be aware of this increased risk when determining patients for reconstruction.
30215500 [Effectiveness of tibio-talo-calcaneal arthrodesis with full thread headless compression s 2018 Oct 15 OBJECTIVE: To investigate the effectiveness of tibio-talo-calcaneal arthrodesis with full thread headless compression screws via combined minimal incisions. METHODS: Between January 2012 and December 2016, 36 patients (36 feet) with ankle diseases underwent tibio-talo-calcaneal arthrodesis with parallel double thread headless compression screws via minimal anterior and lateral oblique incisions. There were 14 males and 22 females with an average age of 53.8 years (range, 18-76 years). There were 19 cases of left feet and 17 cases of right feet. There were 21 cases of talar necrosis, 7 cases of post-traumatic arthritis, 3 cases of rheumatoid arthritis, 2 cases of tuberculosis infection (inactive), 1 case of talar absence, 1 case of Charcot’s disease, and 1 case of pigmented villonodular synovitis of ankle and subtalar joints. Preoperative American Orthopaedic Foot and Ankle Society (AOFAS) score and visual analogue scale (VAS) score were 53.7±2.5 and 5.9±0.2, respectively. The operation time was recorded and the wound healing and complications were observed. The bone healing was assessed by X-ray film and CT scanning. The function and pain of joint were evaluated by AOFAS and VAS scores. RESULTS: The mean operation time was 49.8 minutes (range, 33-82 minutes). Incision infection occurred in 1 patient (2.8%) at 3 weeks after operation, and recovered after debridement. The other incisions healed by first intention without complications. Thirty-five patients were followed up with an average of 18.5 months (range, 12-29 months). Imaging examination showed fusion of the ankle and subtalar joints with an average fusion time of 10.9 weeks (range, 8-15 weeks). After 1 year, the AOFAS score (84.7±0.6) and VAS score (0.3±0.1) were significantly higher than preoperative scores ( t=12.596, P=0.000; t=30.393, P=0.000). CONCLUSION: It is an effective surgical method of tibio-talo-calcaneal arthrodesis with full thread headless compression screws via combined minimal incisions for end-stage ankle disease because of the less complications incidence and the higher postoperative fusion rate.
29793311 The protective effects of alpha lipoic acid on methotrexate induced testis injury in rats. 2018 Jan Methotrexate (MTX) is frequently used in the treatment of several diseases including cancers, rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, and dermatomyositis. Previously, chemotherapeutic agents have been reported to cause permanent azoospermia and infertility in men. Methotrexate has been also shown to damage the seminiferous tubules of the testicles, lower the sperm count, and cause genetic mutations (in DNA) in sperm. In this study, we aimed to investigate the protective effects of alpha lipoic acid (ALA) on MTX-induced testicle damage in a rat model. A total of 40 male Wistar Albino rats were used in this study. The rats were divided into four groups including 10 rats in each. The first group (control group) received only saline intraperitoneal (i.p.); the second group (ALA group) was given ALA 100 mg/kg i.p.; the third group (MTX group) received single dose MTX 20 mg/kg i.p.; and the fourth group (MTX + ALA group) received single dose MTX 20 mg/kg i.p. and ALA 100 mg/kg i.p. Malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), myeloperoxidase (MPO) levels in the testicular tissue and serum testosterone, serum total antioxidant status (TAS) and total oxidant status (TOS) levels were biochemically evaluated. Testicular tissues histopathologically evaluated. In the MTX group, the MDA, TAS and TOS levels were higher, while the SOD, CAT, GPx, MPO and serum testosterone levels decreased. Compared to the MTX group, the MDA, TAS and TOS levels were lower and the SOD, CAT, GPx, MPO and serum testosterone levels increased in the MTX + ALA group. In the histopathological examination, the mean seminiferous tubule length (MSTD), germinal epithelial cell thickness (GECT), and mean testicular biopsy score (MTBS) were found to significantly decrease in the MTX group, compared to the control group. These values were significantly higher in the MTX + ALA group, compared to the MTX group (p < 0.05). In our experimental study, MTX caused severe tissue destruction in testicles by increasing the formation of free oxygen radicals. Based on our study results, we suggest that, as a potent free radical scavenger, ALA can reduce MTX-induced testicular tissue damage thanks to its antioxidant and anti-inflammatory properties.
29872620 Biomimetic nanoparticles for inflammation targeting. 2018 Jan There have been many recent exciting developments in biomimetic nanoparticles for biomedical applications. Inflammation, a protective response involving immune cells, blood vessels, and molecular mediators directed against harmful stimuli, is closely associated with many human diseases. As a result, biomimetic nanoparticles mimicking immune cells can help achieve molecular imaging and precise drug delivery to these inflammatory sites. This review is focused on inflammation-targeting biomimetic nanoparticles and will provide an in-depth look at the design of these nanoparticles to maximize their benefits for disease diagnosis and treatment.
30086735 Transcriptomic signatures reveal immune dysregulation in human diabetic and idiopathic gas 2018 Aug 7 BACKGROUND: Cellular changes described in human gastroparesis have revealed a role for immune dysregulation, however, a mechanistic understanding of human gastroparesis and the signaling pathways involved are still unclear. METHODS: Diabetic gastroparetics, diabetic non-gastroparetic controls, idiopathic gastroparetics and non-diabetic non-gastroparetic controls underwent full-thickness gastric body biopsies. Deep RNA sequencing was performed and pathway analysis of differentially expressed transcripts was done using Ingenuity®. A subset of differentially expressed genes in diabetic gastroparesis was validated in a separate cohort using QT-PCR. RESULTS: 111 genes were differentially expressed in diabetic gastroparesis and 181 in idiopathic gastroparesis with a log(2)fold difference of | ≥ 2| and false detection rate (FDR) < 5%. Top canonical pathways in diabetic gastroparesis included genes involved with macrophages, fibroblasts and endothelial cells in rheumatoid arthritis, osteoarthritis pathway and differential regulation of cytokine production in macrophages and T helper cells by IL-17A and IL-17F. Top canonical pathways in idiopathic gastroparesis included genes involved in granulocyte adhesion and diapedesis, agranulocyte adhesion and diapedesis, and role of macrophages, fibroblasts and endothelial cells in rheumatoid arthritis. Sixty-five differentially expressed genes (log(2)fold difference | ≥ 2|, FDR < 5%) were common in both diabetic and idiopathic gastroparesis with genes in the top 5 canonical pathways associated with immune signaling. 4/5 highly differentially expressed genes (SGK1, APOLD1, CXCR4, CXCL2, and FOS) in diabetic gastroparesis were validated in a separate cohort of patients using RT-PCR. Immune profile analysis revealed that genes associated with M1 (pro inflammatory) macrophages were enriched in tissues from idiopathic gastroparesis tissues compared to controls (p < 0.05). CONCLUSIONS: Diabetic and idiopathic gastroparesis have both unique and overlapping transcriptomic signatures. Innate immune signaling likely plays a central role in pathogenesis of human gastroparesis.
30572134 Disease activity assessment of rheumatic diseases during pregnancy: a comprehensive review 2019 Feb Pregnancy requires a special management in women with inflammatory rheumatic diseases (RDs), with the aim of controlling maternal disease activity and avoiding fetal complications. Despite the heterogeneous course of RDs during pregnancy, their impact on pregnancy largely relates to the extent of active inflammation at the time of conception. Therefore, accurate evaluation of disease activity is crucial for the best management of pregnant patients. Nevertheless, there are limitations in using conventional measures of disease activity in pregnancy, as some items included in these instruments can be biased by symptoms or by physiological changes related to pregnancy and the pregnancy itself may influence laboratory parameters used to assess disease activity. This article aims to summarize the current literature about the available instruments to measure disease activity during pregnancy in RDs. Systemic lupus erythematosus is the only disease with instruments that have been modified to account for several adaptations which might interfere with the attribution of signs or symptoms to disease activity during pregnancy. No modified-pregnancy indices exist for women affected by other RDs, but standard indices have been applied to pregnant patients. The current body of knowledge shows that the physiologic changes that occur during pregnancy need to be either adapted from existing instruments or developed to improve the management of pregnant women with RDs. Standardized instruments to assess disease activity during pregnancy would be helpful not only for clinical practice but also for research purposes.