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ID PMID Title PublicationDate abstract
32311836 Experiences of Patients With Rheumatic Diseases in the United States During Early Days of 2020 Jun OBJECTIVE: Patients with rheumatic diseases such as rheumatoid arthritis (RA) and lupus have increased risk of infection and are treated with medications that may increase this risk yet are also hypothesized to help treat COVID-19. We set out to understand how the COVID-19 pandemic has impacted the lives of these patients in the United States. METHODS: Participants in a US-wide longitudinal observational registry responded to a supplemental COVID-19 questionnaire by e-mail on March 25, 2020, about their symptoms, COVID-19 testing, health care changes, and related experiences during the prior 2 weeks. Analysis compared responses by diagnosis, disease activity, and new onset of symptoms. Qualitative analysis was conducted on optional free-text comment fields. RESULTS: Of the 7061 participants invited to participate, 530 responded, with RA as the most frequent diagnosis (61%). Eleven participants met COVID-19 screening criteria, of whom two sought testing unsuccessfully. Six others sought testing, three of whom were successful, and all test results were negative. Not quite half of participants (42%) reported a change to their care in the prior 2 weeks. Qualitative analysis revealed four key themes: emotions in response to the pandemic, perceptions of risks from immunosuppressive medications, protective measures to reduce risk of COVID-19 infection, and disruptions in accessing rheumatic disease medications, including hydroxychloroquine. CONCLUSION: After 2 weeks, many participants with rheumatic diseases already had important changes to their health care, with many altering medications without professional consultation or because of hydroxychloroquine shortage. As evidence accumulates on the effectiveness of potential COVID-19 treatments, effort is needed to safeguard access to established treatments for rheumatic diseases.
32249160 A rare case of Trichosporon mycotoxinivorans and Cryptococcus neoformans co-infection in l 2020 Aug A 70-year-old woman with liver cirrhosis caused by primary biliary cirrhosis and rheumatoid arthritis was found to have multiple pulmonary nodular shadows in the right middle and lower lung fields on chest radiography. The multiple pulmonary nodules and masses rapidly increased over 2 months. Trichosporon mycotoxinivorans and Cryptococcus neoformans were identified in brushing specimens, bronchial lavage, and transbronchial lung biopsy specimens. The patient was diagnosed as having a co-infection of the lung with T. mycotoxinivorans and C. neoformans, and was treated with fluconazole. Although the pulmonary shadows were under control with treatment, she died 5 months later due to liver failure. We report herein a rare case of co-infection of the lung with T. mycotoxinivorans and C. neoformans.
32131001 Screw Internal Fixation and Ilizarov External Fixation: A Comparison of Outcomes in Ankle 2020 Mar The purpose of this study was to compare the mid-term clinical outcomes between screw internal fixation and Ilizarov external fixation in patients who underwent ankle arthrodesis and to elucidate the differences between the 2 fixation methods. This study investigated 43 ankles in 41 patients who underwent ankle arthrodesis at 1 of the 2 study institutions. There were 15 men and 26 women, and their mean age was 66.2 (range 49 to 87) years. The primary disease included osteoarthritis (OA) (79%), rheumatoid arthritis (RA) (16.3%), and Charcot joint (4.7%). Patients were divided into 2 groups depending on the surgical approach: the screw group (S) and the Ilizarov group (I). The following items were evaluated and compared between the 2 groups: patient characteristics, Tanaka-Takakura classification based on preoperative plain X-ray images, duration of surgery, blood loss, surgical complications, time to start weightbearing, and the Japanese Society of Surgery of the Foot (JSSF) standard rating system for the ankle-hindfoot. Duration of surgery was significantly shorter in the S group (162.3 versus 194.9 min), and the amount of blood loss was also significantly lower in the S group (29.2 versus 97.5 ml). Preoperative JSSF scale was significantly lower in the I group (44.8 versus 33), but postoperative JSSF scale was not significantly different between the 2 groups (82.1 versus 77.9). The S group had satisfactory clinical outcomes with a shorter duration of surgery and smaller amount of blood loss than the I group. However, severe patients in the I group achieved similar treatment outcomes.
32093030 Structure-Based Design, Synthesis and Bioactivity of a New Anti-TNFα Cyclopeptide. 2020 Feb 19 As opposed to small molecules, macrocyclic peptides possess a large surface area and are recognised as promising candidates to selectively treat diseases by disrupting specific protein-protein interactions (PPIs). Due to the difficulty in predicting cyclopeptide conformations in solution, the de novo design of bioactive cyclopeptides remains significantly challenging. In this study, we used the combination of conformational analyses and molecular docking studies to design a new cyclopeptide inhibitor of the interaction between the human tumour necrosis factor alpha (TNFα) and its receptor TNFR-1. This interaction is a key in mediating the inflammatory response to tissue injury and infection in humans, and it is also an important causative factor of rheumatoid arthritis, psoriasis and inflammatory bowel disease. The solution state NMR structure of the cyclopeptide was determined, which helped to deduce its mode of interaction with TNFα. TNFα sensor cells were used to evaluate the biological activity of the peptide.
32088810 Craniocervical junction involvement in musculoskeletal diseases: an area of close collabor 2020 Jul The involvement of the cervical spine in musculoskeletal diseases can be crucial in terms of prognosis and morbidity. Early diagnosis of possible involvement of the craniocervical junction is essential to avoid the onset of neurological complications with poor prognosis. Among inflammatory diseases, rheumatoid arthritis affects the cervical spine frequently (in about 25% of patients). Atlantoaxial inflammatory changes are also detectable in spondyloarthritis. The involvement of the cervical spine in diffuse idiopathic skeletal hyperostosis is recognized as the cause of various clinical manifestations that may involve the pharynx, larynx and esophagus. The cervical spine may be specifically frequently implicated in crystal-associated arthropathies. Spinal cord infections are infrequent diseases that account for 3-4% of all spine infections. This pictorial review attempts to provide insights to interpret the radiological appearances of the craniocervical junction on conventional radiography, computed tomography and magnetic resonance imaging in relation to various musculoskeletal disease processes.
32066498 The paradox of cancer genes in non-malignant conditions: implications for precision medici 2020 Feb 17 Next-generation sequencing has enabled patient selection for targeted drugs, some of which have shown remarkable efficacy in cancers that have the cognate molecular signatures. Intriguingly, rapidly emerging data indicate that altered genes representing oncogenic drivers can also be found in sporadic non-malignant conditions, some of which have negligible and/or low potential for transformation to cancer. For instance, activating KRAS mutations are discerned in endometriosis and in brain arteriovenous malformations, inactivating TP53 tumor suppressor mutations in rheumatoid arthritis synovium, and AKT, MAPK, and AMPK pathway gene alterations in the brains of Alzheimer's disease patients. Furthermore, these types of alterations may also characterize hereditary conditions that result in diverse disabilities and that are associated with a range of lifetime susceptibility to the development of cancer, varying from near universal to no elevated risk. Very recently, the repurposing of targeted cancer drugs for non-malignant conditions that are associated with these genomic alterations has yielded therapeutic successes. For instance, the phenotypic manifestations of CLOVES syndrome, which is characterized by tissue overgrowth and complex vascular anomalies that result from the activation of PIK3CA mutations, can be ameliorated by the PIK3CA inhibitor alpelisib, which was developed and approved for breast cancer. In this review, we discuss the profound implications of finding molecular alterations in non-malignant conditions that are indistinguishable from those driving cancers, with respect to our understanding of the genomic basis of medicine, the potential confounding effects in early cancer detection that relies on sensitive blood tests for oncogenic mutations, and the possibility of reverse repurposing drugs that are used in oncology in order to ameliorate non-malignant illnesses and/or to prevent the emergence of cancer.
32004939 Total glucosides of paeony decreases apoptosis of hepatocytes and inhibits maturation of d 2020 Apr Total glucosides of paeony (TGP), an active mixture extracted from paeony root, has anti-inflammatory and immunoregulatory effects and is widely used for the treatment of autoimmune diseases such as rheumatoid arthritis. However, the role of TGP in autoimmune hepatitis (AIH) is still unknown. In this study, we aimed to investigate the effect of TGP in autoimmune liver disease (AILD) patients and in concanavalin A (Con A)-induced experimental autoimmune hepatitis (EAH). Changes in biochemical parameters of AILD patients showed that treatment with TGP exerts significant protective effects on liver function, as reflected by decreased levels of serum alanine transaminase, aspartate transaminase, γ-glutamyl transpeptidase and total bilirubin. In EAH mice, we found that pretreatment with TGP reduced the levels of serum liver enzyme levels, histopathological damage and hepatocyte apoptosis. Importantly, flow cytometry analysis showed that pretreatment with TGP reduced the infiltration of mature dendritic cells in the liver. In vitro, TGP pretreatment ameliorated the Con A-induced mitochondrial membrane potential decline, reactive oxygen species increase, and apoptosis increase in hepatocytes. In addition, the levels of Bax, Cleaved Caspase-3 and cytoplasmic Cytochrome C decreased during this process, whereas those of Bcl-2 and mitochondrial Cytochrome C increased. Therefore, TGP might decrease hepatocyte apoptosis through the mitochondrial apoptotic pathway. Moreover, the maturation of bone marrow dendritic cells was also inhibited by TGP treatment. In conclusion, TGP treatment ameliorates AIH by regulating hepatocyte apoptosis and DC maturation. TGP is a potential compound for AIH treatment.
31960514 Conformational states of TNFR1 as a molecular switch for receptor function. 2020 Jun Tumor necrosis factor receptor 1 (TNFR1) is a transmembrane receptor that plays a key role in the regulation of the inflammatory pathway. While inhibition of TNFR1 has been the focus of many studies for the treatment of autoimmune diseases such as rheumatoid arthritis, activation of the receptor is important for the treatment of immunodeficiency diseases such as HIV and neurodegenerative diseases such as Alzheimer's disease where a boost in immune signaling is required. In addition, activation of other TNF receptors such as death receptor 5 or FAS receptor is important for cancer therapy. Here, we used a previously established TNFR1 fluorescence resonance energy transfer (FRET) biosensor together with a fluorescence lifetime technology as a high-throughput screening platform to identify a novel small molecule that activates TNFR1 by increasing inter-monomeric spacing in a ligand-independent manner. This shows that the conformational rearrangement of pre-ligand assembled receptor dimers can determine the activity of the receptor. By probing the interaction between the receptor and its downstream signaling molecule (TRADD) our findings support a new model of TNFR1 activation in which varying conformational states of the receptor act as a molecular switch in determining receptor function.
31780370 Butyrate alleviates inflammatory response and NF-κB activation in human degenerated inter 2020 Jan Butyrate has multiple protective effects in inflammation-related intestinal diseases. Previous studies have found that butyrate could inhibit inflammation in rheumatoid arthritis. Inflammation is a pivotal inducement in the degeneration progress of the intervertebral disc. The anti-inflammatory treatment has an apparent curative effect in the symptomatic treatment of spine-related disease. Herein we investigated whether butyrate plays a protective role in degenerated intervertebral disc model. To mimic the lumbar disc local inflammatory environment, human primary nucleus pulposus cells were cultured with interleukin-1β (IL-1β, 10 ng/ml) to build a nucleus pulposus cell inflammation model. Butyrate was added to the cell culture medium to test the effect of butyrate on disc inflammation. Furthermore, a cultured nucleus pulposus tissue model was treated with butyrate (1 mM) to simulate the local treatment of intervertebral disc disease. Herein, we found that butyrate could downregulate the production of the inflammatory mediator caused by IL-1β stimulation in the cell culture model. Additionally, butyrate inhibits the secretion of pro-inflammatory cytokines or graded enzymes in disc tissues from lumbar disc herniation patients. Furthermore, the anti-inflammatory function of butyrate in lumbar disc degenerated model may be caused by inhibiting the activation of the nuclear factor kappa B (NF-κB) signal pathway. This study presents butyrate as a candidate therapeutic method to treat lumbar disc degenerative disease.
31762221 Identifying damage clusters in patients with systemic lupus erythematosus. 2020 Jan AIM: Systemic lupus erythematosus (SLE) causes irreversible damage to organ systems. Recently, evidence has been obtained for subphenotypes of SLE. This study aimed to identify damage clusters and compare the associated clinical manifestations, SLE disease activity, mortality, and genetic risk scores (GRS). METHODS: The study was conducted on the Hanyang BAE lupus cohort. Patients with disease duration <5 years were excluded to minimize confounding effects of disease duration. They were grouped into 3 clusters based on the Systemic Lupus International Collaborating Clinics Damage Index using k-means cluster analysis. RESULTS: Among the 1130 analyzed patients, musculoskeletal damage was most prevalent (20.2%), followed by ocular (11.4%), renal (10.5%), and neuropsychiatric damage (10.2%). Three significantly different damage clusters were identified. Patients in cluster 1 (n = 824) showed the least damage. Cluster 2 (n = 195) was characterized by frequent renal (55.4%) and ocular (58.0%) damage, and cluster 3 (n = 111) was dominated by neuropsychiatric (100%) and musculoskeletal damage (35.1%). Cluster 2 had the highest adjusted mean AMS (adjusted mean SLE Disease Activity Index score; mean ± SD: 5.4 ± 2.9), while cluster 3 had the highest mortality (14.4%). Weighted GRS did not differ significantly between the clusters. CONCLUSION: Patients in prevalent renal and ocular damage cluster had the highest AMS scores, while the cluster with frequent neuropsychiatric damage had the highest mortality.
31730889 Physicochemical characterization of Suvarna Bhasma, its toxicity profiling in rat and beha 2020 Mar 1 ETHNOPHARMACOLOGICAL RELEVANCE: Suvarna Bhasma is a gold-based Ayurved medicine that has a wide range of therapeutic indications like tuberculosis, diabetes mellitus, rheumatoid arthritis and nervous diseases. Suvarna Bhasma is also used in Suvarnaprashana, an Ayurved advocated therapy being practised to improve immunity in children. AIM OF THE STUDY: To augment traditional understanding, here we present an evidence-based study on Suvarna Bhasma regarding its physicochemical properties, toxicity and efficacy. MATERIALS AND METHODS: Suvarna Bhasma was characterised by physicochemical characterization techniques such as scanning electron microscope (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and atomic emission spectroscopy (ICP-AES). Toxicity of Suvarna Bhasma was studied in Holtzman rats with daily oral dose from 3 mg/kg (therapeutic dose, TD) up to 30 mg/kg (10 TD) body weight for 90 days. Behavioural study, such as motor and geotactic behaviour were examined in zebrafish model to find out any sign of neurotoxicity or behavioural changes due to Suvarna Bhasma administration. RESULTS: Suvarna Bhasma has two types of gold particles, large ones (~60 μm) having irregular shapes, and nano-sized spherical particles (starting from ~10 nm), the latter coated with Fe, Si, O, P and Na. XRD study revealed that all the peaks of Suvarna Bhasma match well with pure gold (face centred cube) with crystallites size 45 ± 2.8 nm. In rat studies, some change in biochemical parameters such as urea, creatinine and alanine aminotransferase (ALT) was observed mainly at the higher therapeutic dose; however, those parameters were within the normal range. There were no significant macroscopic as well as microscopic treatment-related alteration observed, in any of the organs and tissues evaluated. In zebrafish behavioural study, the motor parameters of Suvarna Bhasma treated fish showed normal behaviour analogous to the vehicle control group. Interestingly, the geotactic behaviour showed anxiolytic effects of Suvarna Bhasma as evidenced by the time spent in the upper zone, and average swimming height. The anxiolytic effects persisted for more than 30 days after withdrawing the Suvarna Bhasma treatment. CONCLUSIONS: Suvarna Bhasma contained spherical gold nanoparticles. It was nontoxic in rat model at the does tested. Suvarna Bhasma has anxiolytic effects in zebrafish behavioural model.
33396220 Bee Venom in Wound Healing. 2020 Dec 31 Bee venom (BV), also known as api-toxin, is widely used in the treatment of different inflammatory diseases such as rheumatoid arthritis or multiple sclerosis. It is also known that BV can improve the wound healing process. BV plays a crucial role in the modulation of the different phases of wound repair. It possesses anti-inflammatory, antioxidant, antifungal, antiviral, antimicrobial and analgesic properties, all of which have a positive impact on the wound healing process. The mentioned process consists of four phases, i.e., hemostasis, inflammation, proliferation and remodeling. The impaired wound healing process constitutes a significant problem especially in diabetic patients, due to hypoxia state. It had been found that BV accelerated the wound healing in diabetic patients as well as in laboratory animals by impairing the caspase-3, caspase-8 and caspase-9 activity. Moreover, the activity of BV in wound healing is associated with regulating the expression of transforming growth factor (TGF-β1), vascular endothelial growth factor and increased collagen type I. BV stimulates the proliferation and migration of human epidermal keratinocytes and fibroblasts. In combination with polyvinyl alcohol and chitosan, BV significantly accelerates the wound healing process, increasing the hydroxyproline and glutathione and lowering the IL-6 level in wound tissues. The effect of BV on the wounds has been proved by numerous studies, which revealed that BV in the wound healing process brings about a curative effect and could be applied as a new potential treatment for wound repair. However, therapy with bee venom may induce allergic reactions, so it is necessary to assess the existence of the patient's hypersensitivity to apitoxin before treatment.
33321727 Primary Breast Extranodal Marginal Zone Lymphoma in Primary Sjögren Syndrome: Case Presen 2020 Dec 10 The association between autoimmune diseases, mostly rheumatoid arthritis, systemic lupus erythematosus, celiac disease and Sjögren syndrome, and lymphoma, has been widely demonstrated by several epidemiologic studies. By a mechanism which has not yet been entirely elucidated, chronic activation/stimulation of the immune system, along with the administration of specific treatments, may lead to the onset of different types of lymphoma in such patients. Specifically, patients affected by Sjögren syndrome may develop lymphomas many years after the original diagnosis. Several epidemiologic, hematologic, and histological features may anticipate the progression from Sjögren syndrome into lymphoma but, to the best of our knowledge, a definite pathogenetic mechanism for such progression is still missing. In fact, while the association between Sjögren syndrome and non-Hodgkin lymphoma, mostly extranodal marginal zone lymphomas and, less often, diffuse large B-cell, is well established, many other variables, such as time of onset, gender predilection, sites of occurrence, subtype of lymphoma, and predictive factors, still remain unclear. We report on a rare case of primary breast lymphoma occurring three years after the diagnosis of Sjögren syndrome in a 57-year-old patient. The diagnostic work-up, including radiograms, core needle biopsy, and histological examination, is discussed, along with emerging data from the recent literature, thus highlighting the usefulness of breast surveillance in Sjögren syndrome patients.
33123598 Association of Glycemic Indices (Hyperglycemia, Glucose Variability, and Hypoglycemia) wit 2020 Oxidative stress (OS) is defined as a disturbance in the prooxidant-antioxidant balance of the cell, in favor of the former, which results in the antioxidant capacity of the cell to be overpowered. Excess reactive oxygen species (ROS) production is very harmful to cell constituents, especially proteins, lipids, and DNA, thus causing damage to the cell. Oxidative stress has been associated with a variety of pathologic conditions, including diabetes mellitus (DM), cancer, atherosclerosis, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, obstructive sleep apnea, and accelerated aging. Regarding DM specifically, previous experimental and clinical studies have pointed to the fact that oxidative stress probably plays a major role in the pathogenesis and development of diabetic complications. It is postulated that hyperglycemia induces free radicals and impairs endogenous antioxidant defense systems through several different mechanisms. In particular, hyperglycemia promotes the creation of advanced glycation end-products (AGEs), the activation of protein kinase C (PKC), and the hyperactivity of hexosamine and sorbitol pathways, leading to the development of insulin resistance, impaired insulin secretion, and endothelial dysfunction, by inducing excessive ROS production and OS. Furthermore, glucose variability has been associated with OS as well, and recent evidence suggests that also hypoglycemia may be playing an important role in favoring diabetic vascular complications through OS, inflammation, prothrombotic events, and endothelial dysfunction. The association of these diabetic parameters (i.e., hyperglycemia, glucose variability, and hypoglycemia) with oxidative stress will be reviewed here.
33082070 Conversion of Fused Hip to Total Hip Arthroplasty: Long-Term Clinical and Radiological Out 2021 Mar BACKGROUND: Despite promising results at the mid-term followup, several aspects of conversion of the fused hip to total hip arthroplasty (THA) remain controversial. The aim of this study was to evaluate clinical and radiological outcomes with a minimum 5-year followup in patients who underwent conversion of the fused hip to THA. METHODS: Fifty-seven patients (59 hips) were evaluated. The Harris Hip Score (HHS), range of motion (ROM), and the Visual Analogue Scale (VAS) were used to assess hip function and low back pain. Subjective satisfaction with surgery and the presence of the Trendelenburg sign was also evaluated. Radiological assessment was performed pre- and postoperatively to evaluate loosening and heterotopic ossification (HO). RESULTS: After a mean followup of 13.0 ± 6.2 years, HHS and VAS significantly improved from 46.0 ± 16.7 to 80.8 ± 18.8 and from 4.4 ± 1.5 to 2.1 ± 1.4 (both P < .001), respectively. Twenty-three patients (40.4%) had a positive Trendelenburg sign, and HOs were found in 29 cases (49.1%). An overall 29.8% complication rate was noted. Smoking habits and rheumatoid arthritis were predictive of Trendelenburg sign (P = .046 and P = .038, respectively). Implant survival rate as the end point was 98.7 ± 1.3% at 5 years, 92.4 ± 3.3% at 10 years, 82.1 ± 5.7% at 15 years, and 73.4 ± 8.0% at 20 and 25 years. A worse cumulative implant survival rate was noted in patients who underwent previous hip surgery, defined as any hip operation before fusion (P = .005). CONCLUSION: Conversion of the fused hip to hip arthroplasty provides high levels of hip functionality and satisfaction with surgery at long-term followup. An implant survival rate higher than 70% can be expected 25 years postoperatively.
33022649 Contemporary Population-Based Analysis of Bone Mineral Density Testing in Men Initiating A 2020 Oct BACKGROUND: Androgen deprivation therapy (ADT) is a cornerstone of treatment for advanced prostate cancer (PCa); however, it accelerates the loss of bone mineral density (BMD), which increases fracture risk. Guidelines recommend BMD testing when initiating ADT to assess baseline fracture risk properly. The objective of this study was to examine the proportion of BMD testing in men initiating ADT in Quebec and to identify factors associated with receipt of this testing. METHODS: The study cohort consisted of men extracted from Quebec public healthcare insurance administrative databases who initiated continuous ADT from 2000 to 2015 for >12 months. The primary study outcome was receipt of BMD testing in the period from 6 months before through 12 months after ADT initiation. Multivariable generalized linear mixed regression modeling with a logit link was performed to identify variables associated with BMD testing. RESULTS: We identified 22,033 patients, of whom 3,910 (17.8%) underwent BMD testing. Rates of BMD testing increased from 4.1% in 2000 to 23.4% in 2015. After multivariable analyses, prior history of osteoporosis (odds ratio [OR], 1.84; 95% CI, 1.32-2.57; P<.001), rheumatoid arthritis (OR, 1.64; 95% CI, 1.15-2.34; P=.006), use of bisphosphonates (OR, 1.47; 95% CI, 1.25-1.73; P<.001), and long-term corticosteroid use (OR, 1.63; 95% CI, 1.15-2.31; P=.006) were associated with higher odds of BMD testing. Patient age >80 years (OR, 0.67; 95% CI, 0.59-0.76; P<.001), metastases (OR, 0.79; 95% CI, 0.70-0.89; P<.001), higher Charlson comorbidity score (OR, 0.65; 95% CI, 0.51-0.81; P<.001), and rural residence (OR, 0.77; 95% CI, 0.68-0.87; P<.001) were associated with lower odds of BMD testing. CONCLUSIONS: In our study population, BMD testing rates in men initiating ADT were low, although they increased over the years especially in the years after the publication of recommendations for BMD testing in these patients. Potential gaps identified include being older, more comorbid, and rural areas. Overall, additional efforts emphasizing the importance of BMD testing in PCa guidelines may be needed.
32809146 Urinary soluble CD163 is a good biomarker for renal disease activity in lupus nephritis. 2021 Mar OBJECTIVES: Activated macrophages expressing CD163 (M2) are the most abundant macrophage subtype in renal biopsies from lupus nephritis (LN) patients. We studied the role of proteolytically cleaved soluble CD163 (sCD163) as a biomarker of LN disease activity. METHODS: SLE patients were classified as active LN (AN), inactive disease (ID), and active non-renal disease (ANR). Urine and plasma samples were collected at baseline from all patients and at 3 monthly follow-up from AN patients. sCD163 was measured by ELISA. Urine values were normalized to urinary creatinine excretion and expressed as pg/mg. Urine samples from 25 healthy controls (HC) and 20 rheumatoid arthritis patients served as disease controls (DC). RESULTS: Among the 122 patients studied (114 females, 57 AN, 42 ID, 23 ANR), baseline median urinary sCD163 in the AN group (114.01 pg/mg) was significantly higher (p < 0.001) as compared with ID (10.34 pg/mg), ANR (3.82 pg/mg), HC (0 pg/mg), and DC (7.56 pg/mg) groups and showed modest correlation with renal SLEDAI (r = 0.47; p < 0.001). Urinary sCD163 performed the best on receiver operating characteristics (ROC) analysis (AUC = 0.76) at baseline to differentiate between AN and ANR as compared with plasma sCD163, anti-ds DNA antibodies, and C3 and C4. In follow-up study, urinary sCD163 decreased significantly (p < 0.001) in AN patients at 3 (22.07 pg/mg), 6 (12.7 pg/mg), 9 (11.09 pg/mg), and 12 months (7.2 pg/mg). In 4 patients who had either relapse or developed CKD, urinary sCD163 levels correlated with the changing disease activity. CONCLUSIONS: Urinary sCD163 is a good biomarker of LN disease activity. Key Points • Urinary sCD163 levels are raised in patients with active lupus nephritis and correlate with renal SLEDAI. • Urinary sCD163 levels fall after treatment and may be helpful in monitoring response to therapy in lupus nephritis.
32728591 High-Grade Patellar Chondral Defects: Promising Results From Management With Osteochondral 2020 Jul BACKGROUND: Patellar chondral defects represent up to 34.6% of defects found during routine arthroscopy. Surgical management has evolved during the past 20 years in an effort to develop techniques to replace hyaline cartilage. Currently, the only technique that achieves this is osteochondral autologous transfer (OAT). Although good and excellent results have often been reported at midterm and long-term follow-up for femoral lesions, little is known about isolated patellar defects. PURPOSE: To assess clinical and imaging results of patients treated with OAT for high-grade patellar defects. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: This was a retrospective study on all patients who received OAT for high-grade symptomatic patellar chondral defects between 2010 and 2018 at our institution. The study included patients younger than 40 years of age with anterior knee pain and a grade 4 International Cartilage Repair Society patellar chondral defect between 1 and 2.5 cm(2). Patients with surgery in other knee compartments, concomitant anterior cruciate ligament ruptures, infection, rheumatoid arthritis, and degenerative lesions were excluded. Six months postoperatively, all patients underwent magnetic resonance imaging (MRI) to allow assessment of graft integrity via the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) score to evaluate morphologic features and integration. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Kujala scores were used to assess functional outcomes at final follow-up. RESULTS: A total of 26 patients who received a patellar OAT were included. Most patients were male (88.4%), and the mean ± SD age was 28.5 ± 9.7 years. Patellar chondral defects had a median size of 180 mm(2) (range, 64-250 mm(2)), and patients received a median of 1 autograft (range, 1-3). Functional outcomes assessed at a minimum of 1 year after surgery showed a mean Kujala score of 90.42 ± 6.7 and a mean WOMAC score of 95 ± 3.6. MRI revealed a median MOCART score of 75 points (range, 20-90 points). CONCLUSION: To our knowledge, this is the largest series to date regarding isolated patellar OAT. At midterm follow-up, most patients reported good and excellent results regarding symptoms and activity levels. Most autografts showed good osseous integration and excellent filling of the chondral surface, as evidenced on MRI. OAT is a good alternative to treat high-grade patellar chondral defects, especially among young patients.
32720978 The Thrilling Journey of SARS-CoV-2 into the Intestine: From Pathogenesis to Future Clinic 2020 Aug 20 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a direct impact on the gastrointestinal system, as up to 50% of fecal samples from coronavirus disease 2019 (COVID-19) patients contain detectable viral RNA despite a negative rhino-pharyngeal swab. This finding, together with an intestinal expression of angiotensin conversion enzyme 2 protein, suggests a possible fecal-oral transmission for SARS-CoV-2. Furthermore, gastrointestinal (GI) symptoms are common in COVID-19 patients including watery diarrhea, vomiting-particularly in children-nausea, and abdominal pain. Pathogenesis of SARS-CoV-2 infection presents significant similarities to those of some immune-mediated diseases, such as inflammatory bowel diseases or rheumatoid arthritis, leading to the hypothesis that targeted therapies used for the treatment of immune-mediated disease could be effective to treat (and possibly prevent) the main complications of COVID-19. In this review, we synthesize the present and future impact of SARS-CoV-2 infection on the gastrointestinal system and on gastroenterology practice, hypothesizing a potential role of the "gut-lung axis" and perhaps of the gut and lung microbiota into the interindividual differential susceptibility to COVID-19 19 disease. Finally, we speculate on the reorganization of outpatient gastroenterology services, which need to consider, among other factors, the major psychological impact of strict lockdown measures on the whole population.
32710852 Interaction of the small-molecule kinase inhibitors tofacitinib and lapatinib with membran 2020 Nov 1 Lapatinib and tofacitinib are small-molecule kinase inhibitors approved for the treatment of advanced or metastatic breast cancer and rheumatoid arthritis, respectively. So far, the mechanisms which are responsible for their activities are not entirely understood. Here, we focus on the interaction of these drug molecules with phospholipid membranes, which has not yet been investigated before in molecular detail. Owing to their lipophilic characteristics, quantitatively reflected by large differences of the partition equilibrium between water and octanol phases (expressed by logP values), rather drastic differences in the membrane interaction of both molecules have to be expected. Applying experimental (nuclear magnetic resonance, fluorescence and ESR spectroscopy) and theoretical (molecular dynamics simulations) approaches, we found that lapatinib and tofacitinib bind to lipid membranes and insert into the lipid-water interface of the bilayer. For lapatinib, a deeper embedding into the membrane bilayer was observed than for tofacitinib implying different impacts of the molecules on the bilayer structure. While for tofacitinib, no influence to the membrane structure was found, lapatinib causes a membrane disturbance, as concluded from an increased permeability of the membrane for polar molecules. These data may contribute to a better understanding of the cellular uptake mechanism(s) and the side effects of the drugs.