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ID PMID Title PublicationDate abstract
33162485 Triglyceride Deposit Cardiomyovasculopathy with Massive Myocardial Triglyceride which Was 2021 Apr 15 The patient was a 73-year-old man with a history of hypertension, diabetes mellitus, dyslipidemia, rheumatoid arthritis, repeated percutaneous coronary intervention and percutaneous peripheral intervention procedures. He was frequently admitted to our hospital for congestive heart failure with orthopnea. The myocardial washout rate of iodine-123-β-methyl iodophenyl-pentadecanoic acid was defective on scintigraphy. He was diagnosed with triglyceride deposit cardiomyovasculopathy (TGCV). Proton magnetic resonance spectroscopy ((1)H-MRS) indicated the level of myocardial triglyceride (TG) content to be extremely high (4.92%). This is the first report to confirm a massive accumulation of TG in the myocardium of a patient with TGCV using (1)H-MRS noninvasively.
33115800 Implementation of a novel home delivery service during pandemic. 2021 Nov INTRODUCTION: During the COVID-19 pandemic, measures have been put in place to adapt to patients' needs during home quarantine, such as "telehealthcare". With this service, hospital pharmacists develop a distinct role via the implementation of pharmacovigilance services and pharmaceutical care plans for patients with comorbidities, and for special populations as immunosuppressed patients.MethodsCross-sectional study involving hospital and community pharmacists actively practising during the COVID-19 pandemic. Patients who could not come to the hospital pharmacy department were provided with a delivery service to the community pharmacy of their choice. RESULTS: A total of 1186 patients requested this service. Erythropoiesis-stimulating agents were the most in-demand medication, followed by rheumatoid arthritis and antiretroviral drugs. 125 patients responded to the telephone survey, most of whom stated that they would use the delivery service again, and expressed their desire to continue doing so. DISCUSSION: Without a doubt, telepharmacy and medication delivery services have provided multiple benefits during home quarantine. The delivery service enabled us to provide drugs to patients in their immediate environment through a service that was free for both the patient and the hospital pharmacy service. However, at present, the available evidence of the impact of telepharmacy models is sparse. CONCLUSIONS: This medication delivery service has provided multiple benefits to patients during home quarantine. Although the users of this service seem to be satisfied with the current model, in the future, we should consider which patients would benefit most from this service and shape it to individual needs.
32964653 Insights on the Evidence of Cardiotoxicity of Hydroxychloroquine Prior and During COVID-19 2021 Jan The recent empirical use of hydroxychloroquine (HCQ) in coronavirus disease 2019 (COVID-19) revived the interest in its cardiac toxicity, increasingly sidelined over time. We aimed to assess and compare the profile of cardiac adverse drug reactions (CADRs) associated with HCQ before and during COVID-19. We performed a retrospective comparative observational study using the French Pharmacovigilance network database between 1985 and May 2020 to assess all postmarketing CADRs associated with HCQ notified before COVID-19 in its approved indications for lupus and rheumatoid arthritis (preCOV), and those concerning its empirical use in COVID-19 (COV). Eighty-five CADR in preCOV were compared with 141 CADRs in COV. The most common CADR of preCOV were cardiomyopathies (42.4%) and conduction disorders (28.2%), both statistically more frequent than in COV (P < 0.001). COV notifications significantly highlighted repolarization and ventricular rhythm disorders (78.0%, P < 0.001) as well as sinus bradycardias (14.9%, P = 0.01) as compared with preCOV. Estimated incidence of CADR was significantly higher among patients exposed to off-label use of HCQ in COVID-19 (2.9%) than before COVID-19 in its approved indications (0.01%, P < 0.001). The use of HCQ in COVID-19 sheds a new light on the spectrum of its cardiac toxicity. This fosters the value of a closer monitoring of all patients treated with HCQ, regardless of its indication, and the importance of an update of its summary of product characteristics.
28722873 C Reactive Protein. 2022 Jan C-reactive protein (CRP) was discovered by Tillett and Francis in 1930. The name CRP arose because it was first identified as a substance in the serum of patients with acute inflammation that reacted with the "c" carbohydrate antibody of the capsule of pneumococcus. CRP is a pentameric protein synthesized by the liver, whose level rises in response to inflammation. CRP is an acute-phase reactant protein that is primarily induced by the IL-6 action on the gene responsible for the transcription of CRP during the acute phase of an inflammatory/infectious process. There is some question of whether dysregulation of the role of CRP in the clearance of apoptotic cells and cellular debris plays a role in the pathogenesis of systemic lupus erythematosus (SLE), but this has not been definitively demonstrated. It has been demonstrated to have some protective properties in animal studies on lung tissue in alveolitis by reducing neutrophil-mediated damage to the alveoli and protein leakage into the lung. CRP has both proinflammatory and anti-inflammatory properties. It plays a role in the recognition and clearance of foreign pathogens and damaged cells by binding to phosphocholine, phospholipids, histone, chromatin, and fibronectin. It can activate the classic complement pathway and also activate phagocytic cells via Fc receptors to expedite the removal of cellular debris and damaged or apoptotic cells and foreign pathogens. This can become pathologic, however, when it is activated by autoantibodies displaying the phosphocholine arm in auto-immune processes, such as idiopathic thrombocytopenic purpura (ITP). It can also worsen tissue damage in certain cases by activation of the complement system and thus inflammatory cytokines. As compared to the erythrocyte sedimentation rate, which is an indirect test for inflammation, the levels of CRP rise and fall rapidly with the onset and removal of the inflammatory stimulus respectively. Persistently elevated CRP levels can be seen in chronic inflammatory conditions such as chronic infections or inflammatory arthritides such as rheumatoid arthritis. There are numerous causes of an elevated C-reactive protein.  These include acute and chronic conditions, and these can be infectious or non-infectious in etiology. However, markedly elevated levels of CRP are most often associated with an infectious cause (an example of pathogen-associated molecular pattern recognition).  Trauma can also cause elevations in CRP (alarmin response). More modest elevations tend to be associated with a broader spectrum of etiologies, ranging from sleep disturbances to periodontal disease.
34324435 Intra-Articular Injection of BPC 157 for Multiple Types of Knee Pain. 2021 Jul INTRODUCTION: Knee pain, a common complaint in primary care, has many causes, the most common of which is osteoarthritis (OA). Other common causes are meniscus tears, tendinosis, ligament tears or sprains, rheumatoid arthritis, lupus and septic arthritis. Also, referred pain from hip joint pathology like slipped capital femoral epiphysis can result in knee pain.1 The use of peptides BPC157 and thymosin-beta-4 (TB4) has not been studied in the treatment of knee pain. METHODS: A retrospective study was done at the Institute for Hormonal Balance in Orlando, Florida, USA to see whether intra-articular injection of the peptide BPC 157, alone or combined with TB4, helped relieve knee pain. A 1-year chart review from 2019 to 2020 was performed. Since this was a retrospective study, patient follow-up varied, with most patients having had an injection of peptide into their knee 6 months to 1 year prior to the study. Of the 17 patients in the study, 16 were contacted by phone to follow up on the status of their knee pain. Only 1 patient could not be reached for the survey. Patients were asked to rate their pain prior to injection, the length of time the peptides helped ease the pain and the degree to which the injection helped them. No specific tools were used to measure their improvement in function, quality of life, stiffness or activities of daily living. The survey's main goal was to determine whether BPC157 helped with multiple types of knee pain in a primary care setting. RESULTS: Of the 16 patients, 12 had received only BPC 157 as an intra-articular injection. In this group, 11 of the 12 patients (91.6%) had significant improvement in knee pain, whereas 1 patient (8.3 %) had no improvement. The other 4 patients received a combination of 2 peptide injections of BPC 157 and TB4. Of the patients who received both peptides, 75% showed significant improvement, but 25% had no relief of their knee pain. Overall, 14 of 16 patients (87.5%) had relief of their knee pain when BPC 157 or a combination of BPC 157 and TB4 was used. CONCLUSION: This small study suggests that intra-articular injection of BPC-157 helps with multiple types of knee pain. CLINICAL IMPLICATIONS: BPC157 is a peptide with regenerative properties that can be used to relieve multiple types of knee pain.2,3 Future studies are needed to look at the different causes of knee pain with follow-up magnetic resonance imaging scans (MRIs) to document the peptide's benefits. BPC157 has the potential to repair tears, build cartilage and reduce the number of knee surgeries. Because of its reparative properties, treatment with BPC157 offers advantages over the use of steroids. RESULTS: BPC157 is a peptide with regenerative properties that can be used to relieve multiple types of knee pain.2,3 Future studies are needed to look at the different causes of knee pain with follow-up MRIs to document the peptide's benefits. BPC157 has the potential to repair tears, build cartilage and reduce the number of knee surgeries. Because of its reparative properties, treatment with BPC157 offers advantages over the use of steroids.
34266484 Immune-mediated inflammatory diseases and nutrition: results from an online survey on pati 2021 Jul 16 BACKGROUND: The central role of microbiota and the contribution of diet in immune-mediated inflammatory diseases (IMID) are increasingly examined. However, patients' perspectives on nutrition and its impact on their disease has not received a lot of attention. We aimed to directly collect information from patients with IMID about their dietary behaviors and their perceptions of the influence of nutrition on their disease. METHODS: Adult patients with rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn's disease, ulcerative colitis or psoriasis registered in an online patient community were invited to participate in the study and complete an online self-administered questionnaire. We assessed patients' dietary knowledge and choices by collecting information on the diet regimens they were following or recommended and their perceptions of the diet and its consequences on their disease. RESULTS: Fifty patients per target disease were included with a mean age of 48.1 years (95%CI 46.7-49.6). Other sociodemographic and clinical characteristics varied across the diseases. Since diagnosis, 44% of the patients changed their eating habits, mainly patients with inflammatory bowel disease with 69% of these making the change on their own initiative. Patients who did not change their diet habits reported not having received nutritional advice from their healthcare professionals (HCP) in 69% of the cases. The perceived impact of nutrition on their symptoms was mixed (overall 74% of the patients reported positive consequences and 60% negative ones) and varied across the diseases. Patients with psoriasis only experienced positive consequences from changing their diet, such as reduction of stress and improved mental health, while patients with Crohn's disease reported more negative effects such as increased fatigue and disturbed sleep. Patients with rheumatic diseases and ulcerative colitis reported weight loss and better physical fitness, but also increased fatigue. CONCLUSIONS: Even if differences exist across diseases, the importance of nutrition and its potential positive role in symptom management is acknowledged by the majority of the patients. However, there is a need and a demand from patients to receive more dietary advice. Developing therapeutic education tools on nutrition for people with IMID and involving patients' organizations would provide useful information and encourage communication between HCP and patients.
32828145 Utilisation patterns and clinical impact of the introduction of infliximab-biosimilar in T 2021 Jul OBJECTIVES: This study was aimed at assessing the impact of a non-medical recommendation on drug-utilisation patterns and clinical outcomes in a central Region of Italy (Tuscany). METHODS: We performed a pre-post study on data collected in Tuscan healthcare administrative databases. We included patients with diagnosis of rheumatoid arthritis, or psoriatic arthritis, or ankylosing spondylitis, or ulcerative colitis, or Crohn's disease, or psoriasis. The first analysis compared patients treated with infliximab on January 1st, 2013 (originator only available) to those on January 1st, 2016 (both originator and biosimilar available). The second analysis compared infliximab-originator users with infliximab-biosimilar ones. Adjusted odds ratios (OR) of persistence on treatment, Emergency Department (ED) admissions, hospitalisations and specialist visits were calculated. RESULTS: The first analysis included 606 patients and the second 434. In both analyses, we did not observe any significant difference in persistence. In the first analysis, the 2016 infliximab-originator cohort showed a significant association with the risk of having at least one ED admission (OR 1.54, 95% CI 1.02 to 2.31). A significant difference of accessing a specialist visit (more frequently rheumatologic) was observed in the 2016 cohort (OR 1.52, 95% CI 1.05 to 2.20). In the second analysis, the risk of having at least one hospitalisation decreased significantly in switchers to infliximab-biosimilar (OR 0.49, 95% CI 0.26 to 0.96). CONCLUSIONS: Our study showed no relevant changes in the clinical outcomes following the introduction of infliximab-biosimilar. The few observed differences observed can be explained mainly by a selective switching to infliximab-biosimilar in patients with lower burden of disease.
32766762 Tofacitinib, an Oral Janus Kinase Inhibitor: Analysis of Malignancy (Excluding Nonmelanoma 2021 May 17 BACKGROUND: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). Here, we performed an integrated analysis of malignancy events from the tofacitinib phase 3 UC clinical development program (excluding nonmelanoma skin cancer [NMSC]). METHODS: Data (up to May 2019) were pooled from two phase 3 induction studies, a phase 3 maintenance study, and an ongoing, open-label, long-term extension (OLE) study, and analyzed as 3 cohorts: induction (N = 1139), maintenance (N = 592), and overall (induction, maintenance, and ongoing OLE study; N = 1124). Proportions and incidence rates (IRs; unique patients with events per 100 patient-years [PY] of exposure) for malignancies confirmed by adjudication were calculated. RESULTS: The overall cohort consisted of patients who received at least 1 dose of tofacitinib at 5 or 10 mg twice daily, for up to 6.8 years, with an exposure of 2576.4 PY. Of the 1124 overall cohort tofacitinib-treated patients, 20 developed a malignancy (excluding NMSC; IR, 0.75; 95% confidence interval, 0.46-1.16), of which 17 occurred in patients treated with tofacitinib 10 mg twice daily; importantly, more than 80% of patients predominantly received this dose. Furthermore, there was no apparent clustering of malignancy types, and IRs were stable over time. CONCLUSIONS: In the tofacitinib UC clinical development program, malignancy events were infrequent, and rates were comparable with those in the tofacitinib rheumatoid arthritis and psoriatic arthritis clinical development programs, and for biologic UC treatments. ClinicalTrials.gov: NCT01465763, NCT01458951, NCT01458574, and NCT01470612.
34699634 Apremilast effectively inhibits TNFα-induced vascular inflammation in human endothelial c 2022 Feb BACKGROUND: Patients with chronic inflammatory diseases (e.g. psoriasis and rheumatoid arthritis) are at increased risk for the development of atherosclerosis and cardiovascular diseases (CVD). Previous studies have suggested that phosphodiesterase 4 (PDE4) inhibitors possess anti-inflammatory properties. OBJECTIVES: Here we examined the effect of the PDE4 inhibitor apremilast, a well-established anti-psoriatic drug, on pro-inflammatory responses in TNFα-activated endothelial cells. METHODS: Human umbilical vein endothelial cells (HUVEC) were treated with tumour necrosis factor-α (TNFα) in the presence or absence of apremilast. Expression levels of pro-inflammatory cytokines, chemokines and adhesion molecules were assessed by ELISA, western blot and RT-PCR. Effects of apremilast on adhesion and transendothelial migration (TEM) of THP-1 monocytic cells were analysed in transwell assays. RESULTS: Apremilast suppressed TNFα-induced expression and secretion of important endothelial and monocytic pro-inflammatory factors, including granulocyte-macrophage colony-stimulating factor (GM-CSF), C-X-C motif chemokine ligand 10 (CXCL10), chemokine (C-C motif) ligand 2 (CCL2), vascular cell adhesion molecule 1 (VCAM-1), E-selectin and matrix metalloproteinase-9 (MMP9). Functionally, apremilast reduced adhesion of THP-1 cells to activated HUVECs and TEM in response to TNFα. Mechanistically, apremilast suppressed activation of nuclear factor κB (NFκB) and mitogen-activated protein kinases (MAPK) signalling in activated HUVECs. Furthermore, inhibition of p38, C-Jun-N-terminale Kinase (JNK) and NFκB in activated HUVECs decreased expression of GM-CSF, VCAM-1 and E-selectin. Additionally, apremilast decreased IL-17A-induced secretion of IL-6 and CCL2. CONCLUSIONS: We demonstrate that apremilast has distinct anti-inflammatory effects in activated HUVECs, indicating that apremilast could have the therapeutic potential to prevent higher risk for CVD in patients with chronic inflammatory diseases.
32776178 The impact of pharmaceutical care on the efficacy and safety of transdermal glucosamine su 2021 Feb Background Arthritis is a common chronic joint disease. It progressively causes joint pain, stiffness, and disability. Glucosamine sulfate has been shown to be an effective symptom-relieving biological agent. Pharmaceutical care, including patient counseling, is very important to overcome inconsistencies in compliance and adherence. Objective The aim of this study is to evaluate the impact of pharmaceutical care on the efficacy and safety of transdermal glucosamine sulfate and capsaicin (TGC-Plus cream) in the management of chronic joint pain. Settings A rheumatology outpatient clinic, Jordan University Hospital, Amman, Jordan. Methods A cross sectional study with a single treatment group was conducted. One hundred (100) patients diagnosed with either osteoarthritis, rheumatoid arthritis or chronic joint pains were recruited. Patients started on TGC-Plus cream applied twice daily for duration of 12 weeks. Patients received pharmaceutical care services during the study duration. Main outcome measure Efficacy and safety of TGC-Plus cream in pain relief and joint function improvement (alleviating joint stiffness) the need of alternative analgesics and number of doctor's visits. Results There was a significant reduction of numerical pain score (7 ± 1.40 vs. 3.53 ± 2.13, p < 0.05), with significant reduction in the limitation of joint movement (6.18 ± 2.14 vs. 3.47 ± 2.23, p < 0.05) after 12 weeks. In addition, the need for analgesics and the number of doctor's visits were significantly reduced (1.99 ± 2.77 vs. 0.71 ± 1.90, p < 0.05), (1.11 ± 1.28 vs. 0.06 ± 0.293, p < 0.05) respectively. Conclusion Pharmacist supervised treatment with the TGC-Plus cream significantly reduces pain and enhances locomotor function in patients with chronic pain who failed to achieve adequate prior pain relief.
33268075 Risk factors for atypical forearm fractures associated with bisphosphonate usage. 2021 Jun BACKGROUND: The purpose of this study was to find the diagnostic factors for atypical forearm fractures additional to atypical femur fractures, via a retrospective case-control study. Thus, our authors performed a complete enumeration survey for patients under the treatment of bisphosphonate (BP). METHODS: We identified 53 patients that met the following inclusion criteria between March 2009 and February 2019: a BP therapy history or ongoing administration of at least 1 year, presence of simple radiographs of bilateral femurs and forearms, and availability of complete medical records and radiological data. The patients were divided into two groups: those with any lesion of atypical fractures of ulna or radius, regardless of the displacement of at least one side extremity in simple radiographs (group 1, 20 patients); and those without any lesions of pathognomonic finding or fractures in either forearm in simple radiographs (group 2, 33 patients). RESULTS: Univariate analyses of basic demographic characteristic such as age, smoking, comorbidity of diabetes mellitus or any connective tissue disease needing steroid treatment, and BMD showed no significant differences between the groups (P > 0.05). The co-morbidity of malignant cancer inevitably needing BP usage was not different between the two groups. Multivariate analyses of the several variables that differed significantly between the two groups in univariate analyses demonstrated that total period and single prescribing physician/surgeon were significantly associated with forearm fractures. A cut-off value of 65 months for the total period predicted the presence atypical forearm fractures. CONCLUSIONS: Atypical forearm fractures are probably more common than reported in the literature to date, and all forearm lesions were accompanied by preceding atypical femur fractures. The period of BP administration had the main effect on the occurrence of atypical forearm fractures, particularly if more than 65 months. Also, the prescription by multiple physician was predicting factor for forearms lesion additionally to AFFs, however, more evidence-based study is needed to understand the effects of cancer-related BP usage on the forearm. LEVEL OF EVIDENCE: Level III, retrospective case-control study.
33934576 Social Distancing, Health Care Disruptions, Telemedicine Use, and Treatment Interruption D 2021 Jun BACKGROUND: We aimed to compare concerns, social distancing, health care disruptions, and telemedicine use in patients with autoimmune rheumatic disease (ARD) and non-ARD and to evaluate factors associated with immunomodulatory medication interruptions. METHODS: Patients in a multistate community rheumatology practice network completed surveys from April 2020 to May 2020. Adults with common ARD (rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus) or non-ARD (gout, osteoarthritis, osteoporosis) were evaluated. Concerns about coronavirus disease 2019 (COVID-19), social distancing, health care disruptions, and telemedicine use were compared in patients with ARD versus non-ARD, adjusting for demographics, rural residence, and zipcode-based measures of socioeconomic status and COVID-19 activity. Factors associated with medication interruptions were assessed in patients with ARD. RESULTS: Surveys were completed by 2319/36 193 (6.4%) patients with non-ARD and 6885/64 303 (10.7%) with ARD. Concerns about COVID-19 and social distancing behaviors were similar in both groups, although patients receiving a biologic or Janus kinase (JAK) inhibitor reported greater concerns and were more likely to avoid friends/family, stores, or leaving the house. Patients with ARD were less likely to avoid office visits (45.2% vs. 51.0%, odds ratio [OR] 0.79 [0.70-0.89]) with similar telemedicine use. Immunomodulatory medications were stopped in 9.7% of patients with ARD, usually (86.9%) without a physician recommendation. Compared with patients with an office visit, the likelihood of stopping medication was higher for patients with a telemedicine visit (OR 1.54 [1.19-1.99]) but highest for patients with no visits (OR 2.26 [1.79-2.86]). CONCLUSION: Patients with ARD and non-ARD reported similar concerns about COVID-19 and similar social distancing behaviors. Missed office visits were strongly associated with interruptions in immunomodulatory medication.
33582239 Identification of a distinct lipidomic profile in the osteoarthritic synovial membrane by 2021 May OBJECTIVE: Synovial inflammation is one of the most characteristic events in different types of arthritis, including Osteoarthritis (OA). Emerging evidence also suggests the involvement of lipids in the regulation of inflammatory processes. The aim of this study was to elucidate the heterogeneity and spatial distribution of lipids in the OA synovial membrane and explore their putative involvement in inflammation. METHOD: The abundance and distribution of lipids were examined in human synovial membranes. To this end, histological cuts from this tissue were analysed by matrix-assisted laser desorption ionization - mass spectrometry imaging (MALDI-MSI). The lipidomic profile of OA synovium was characterized and compared with healthy and other forms of inflammatory arthropathies as Rheumatoid Arthritis (RA) and Psoriatic Arthritis (PsA) using principal component analysis and discriminant analysis methods. Lipid identification was undertaken by tandem MS analyses and database queries. RESULTS: Our results reveal differential and characteristic lipidomic profiles between OA and control samples. Specifically, we unveiled that OA synovium presents elevated levels of phosphatidylcholines, fatty acids and lysophosphatidic acids and lower levels of lysophosphatidylcholines compared to control tissues. The spatial distribution of particular glycerophospholipids was also correlated with hypertrophic, inflamed or vascularized synovial areas. Compared with other inflammatory arthritis, the OA tissue showed lower amounts of phosphatidylethanolamine-based plasmalogens. CONCLUSIONS: This study provides a novel insight into the lipid profiles of synovial membrane and differences in abundance between OA and control tissues. The lipidomic alterations improves understanding of the pathogenic mechanisms of OA and may be important for its diagnosis.
33488861 Urate crystal deposition in hyperuricemic children: a dual energy computed tomography stud 2021 INTRODUCTION: The incidence of hyperuricemia (HUA) at younger ages is increasing along the coastal regions of China. This study aimed to compare the frequency of dual energy CT (DECT) urate crystal deposition between symptomatic hyperuricemic children and asymptomatic hyperuricemic children. MATERIAL AND METHODS: Fifty-six hyperuricemic children were divided into a Joint Group (n = 33) and an Asymptomatic Group (n = 23) according to whether they had a history of arthritis symptoms, which includes rapid onset monoarthritis with intense pain and swelling. We analyzed DECT scans of their feet from the Joint Group and the Asymptomatic Group and compared their clinical features. RESULTS: DECT urate deposits were observed in 28/33 (84.8%) children with symptomatic HUA and 14/23 (60.9%) with asymptomatic HUA. We found 60 areas of urate deposition in the Joint Group; DECT urate crystal deposition was most frequently observed in the first metatarsophalangeal (MTP) joint (30.0%), ankle joint (15.0%), and calcaneus (13.3%). 39 urate deposits were found in the Asymptomatic Group; DECT urate crystal deposition was most frequently observed in the calcaneus (25.6%), the first MTP joint (17.9%), and the first phalanx (15.4%). CONCLUSIONS: Urate deposition can occur in children with HUA, and these deposits occur more frequently in hyperuricemic children with a history of arthritis symptoms. Also, the urate deposition in the first MTP joint and calcaneus was more prevalent than in other joints. It is important to give more attention to hyperuricemic children.
34652339 Cytokine Drizzle-The Rationale for Abandoning "Cytokine Storm". 2021 Nov 1 BACKGROUND: "Cytokine storm" has been used to implicate increased cytokine levels in the pathogenesis of serious clinical conditions. Similarities with Severe Acute Respiratory Syndrome Coronoavirus-2 (SARS CoV-2) and the 2012 Middle Eastern Respiratory Syndrome led early investigators to suspect a "cytokine storm" resulting in an unregulated inflammatory response associated with the significant morbidity and mortality induced by SARS CoV-2. The threshold of blood cytokines necessary to qualify as a "cytokine storm" has yet to be defined. METHODS: A literature review was conducted to identify cytokine levels released during 11 assorted clinical conditions or diseases. Weighted averages for various cytokines were calculated by multiplying the number of patients in the paper by the average concentration of each cytokine. Correlation between cytokine levels for individual conditions or diseases were assessed using Pearson correlation coefficient. RESULTS: The literature was reviewed to determine blood levels of cytokines in a wide variety of clinical conditions. These conditions ranged from exercise and autoimmune disease to septic shock and therapy with chimeric antigen receptor T cells. The most frequently measured cytokine was IL-6 which ranged from 24,123 pg/mL in septic shock to 11 pg/mL after exercise. In patients with severe SARS CoV-2 infections, blood levels of IL-6 were only 43 pg/mL, nearly three magnitudes lower than IL-6 levels in patients with septic shock. The clinical presentations of these different diseases do not correlate with blood levels of cytokines. Additionally, there is poor correlation between the concentrations of different cytokines among the different diseases. Specifically, blood levels of IL-6 did not correlate with levels of IL-8, IL-10, or TNF. Septic shock had the highest concentrations of cytokines, yet multiple cytokine inhibitors have failed to demonstrate improved outcomes in multiple clinical trials. Patients with autoimmune diseases have very low blood levels of cytokines (rheumatoid arthritis, IL-6 = 34 pg/mL; Crohn's disease, IL-6 = 5 pg/mL), yet respond dramatically to cytokine inhibitors. CONCLUSION: The misleading term "cytokine storm" implies increased blood levels of cytokines are responsible for a grave clinical condition. Not all inflammatory conditions resulting in worsened disease states are correlated with significantly elevated cytokine levels, despite an association with the term "cytokine storm". "Cytokine storm" should be removed from the medical lexicon since it does not reflect the mediators driving the disease nor does it predict which diseases will respond to cytokine inhibitors.
34314075 Cf-02, a novel benzamide-linked small molecule, blunts NF-κB activation and NLRP3 inflamm 2021 Aug In the present study, acute onset of severe lupus nephritis was successfully treated in mice using a new, benzamide-linked, small molecule that targets immune modulation and the NLRP3 inflammasome. Specifically, 6-(2,4-difluorophenyl)-3-(3-(trifluoromethyl)phenyl)-2H-benzo[e][1,3]oxazine-2,4(3H)-dione (Cf-02) (a) reduced serum levels of IgG anti-dsDNA, IL-1β, IL-6, and TNF-α, (b) inhibited activation of dendritic cells and differentially regulated T cell functions, and (c) suppressed the NF-κB/NLRP3 inflammasome axis, targeting priming and activating signals of the inflammasome. Moreover, treatment with Cf-02 significantly inhibited secretion of IL-1β in lipopolysaccharide-stimulated macrophages, but this effect was abolished by autophagy induction. These results recommend Cf-02 as a promising drug candidate for the serious renal conditions associated with systemic lupus erythematosus. Future investigations should examine whether Cf-02 may also be therapeutic in other types of chronic kidney disease involving NLRP3 inflammasome-driven signaling.
33931020 Hypokalaemic paralysis and metabolic alkalosis in a patient with Sjögren syndrome: a case 2021 Apr 30 BACKGROUND: Acquired Gitelman syndrome is a very rare disorder reported in association with autoimmune disorders, mostly Sjögren syndrome. It is characterized by the presence of hypokalaemic metabolic alkalosis, hypocalciuria, hypomagnesaemia and hyper-reninaemia, in the absence of typical genetic mutations associated with inherited Gitelman syndrome. CASE PRESENTATION: A 20 year old woman who was previously diagnosed with primary Sjögren syndrome and autoimmune thyroiditis presented with two week history of lower limb weakness and salt craving. Examination revealed upper limb and lower limb muscle weakness with muscle power of 3/5 on MRC scale and diminished deep tendon reflexes. On evaluation, she had hypokalaemia with high trans-tubular potassium gradient, metabolic alkalosis and hypocalciuria, features suggestive of Gitelman syndrome. New onset hypokalaemic alkalosis in a previously normokalaemic patient with Sjögren syndrome strongly favored a diagnosis of acquired Gitelman syndrome. Daily potassium supplementation and spironolactone resulted in complete clinical recovery. CONCLUSIONS: Acquired Gitelman syndrome associated with Sjögren syndrome is rare. It should be considered as a differential diagnosis during evaluation of acute paralysis and hypokalaemic metabolic alkalosis in patients with autoimmune disorders, especially Sjögren syndrome.
32390096 Immunobiology of T Cells in Sjögren's Syndrome. 2021 Feb Sjögren's syndrome (SjS) is a systemic autoimmune disease marked by xerostomia (dry mouth), keratoconjunctivitis sicca (eye dryness), and other systematic disorders. Its pathogenesis involves an inflammatory process that is characterized by lymphocytic infiltration into exocrine glands and other tissues. Although the development of ectopic lymphoid tissue and overproduction of autoantibodies by hyperactive B cells suggest that they may promote SjS development, treatment directed towards them fails to induce significant laboratory or clinical improvement. T cells are overwhelming infiltrators in most phases of the disease, and the involvement of multiple T cell subsets of suggests the extraordinary complexity of SjS pathogenesis. The factors, including various cellular subtypes and molecules, regulate the activation and suppression of T cells. T cell activation induces inflammatory cell infiltration, B cell activation, tissue damage, and metabolic changes in SjS. Knowledge of the pathways that link these T cell subtypes and regulation of their activities are not completely understood. This review comprehensively summarizes the research progress and our understanding of T cells in SjS, including CD4(+) T cells, CD8(+) T(RM) cells, and innate T cells, to provide insights into for clinical treatment.
34146129 Qualitative validation of audiovisual educational material for use on rheumatoid arthritis 2021 Jun 19 Medication compliance is critical to achieve therapeutic efficacy in patients with rheumatoid arthritis; however, among other factors, low patient-health literacy plays a negative role. Therefore, the development and validation of audiovisual educational material with the participation of health specialists and patients could lead to an improved level of compliance with treatment, while favoring its acceptance. To design and validate audiovisual educational material generated by a multidisciplinary and participative group of patients and health specialists. This study was carried out using a sequential methodology, including qualitative and quantitative techniques: (1) a non-participative observational study with patients and a non-systematic literature search were performed to identify conceptual topics. (2) Pilot videos were qualitatively assessed by patients and health specialists (focus groups and expert committees). (3) Improved versions of seven videos were quantitatively evaluated by patients and specialists following qualitative criteria of attraction, understanding, involvement, acceptance and induction of action. 74 patients with RA, 10 rheumatologists, 4 pharmacists and 2 medical anthropologists participated in the different phases of validation. A total of seven videos lasting 3 min each were generated, incorporating the most relevant suggestions by patients and healthcare professionals. The final version of the videos led to a mean compliance of 96.04 ± 5.2%, according to a representative group of patients and a mean 89.6 ± 9.4%, according to health professionals. With the participation of both patients and health specialists, seven audiovisual educational video recordings were developed and validated, reaching high levels of compliance in accordance with international criteria.
34334359 Screening for Hepatitis B Virus Prior to Initiating Tocilizumab and Tofacitinib in Patient 2022 Jan OBJECTIVE: Hepatitis B virus (HBV) can reactivate among rheumatology patients initiating tocilizumab (TCZ) or tofacitinib (TOF). HBV screening is recommended by the Centers for Disease Control and Prevention (CDC), the American Association for the Study of Liver Diseases (AASLD), and the Canadian Rheumatology Association, but it is not explicitly recommended by the American College of Rheumatology. METHODS: We conducted a cross-sectional study to characterize HBV screening practices for adult rheumatology patients initiating TCZ or TOF before December 31, 2018, in the Greater Boston area. We classified appropriate HBV screening patterns prior to TCZ or TOF (i.e., HBV surface antigen [HBsAg], total core antibody [anti-HBcAb], and surface antibody [HBsAb]) as follows: complete (all 3 tested), partial (any 1 or 2 tests), or none. We determined the frequency of inappropriate HBV testing (HBV e-antigen, anti-HBcAb IgM, or HBV DNA without a positive HBsAg or total anti-HBcAb) and used multivariable regression to assess factors associated with complete HBV screening. RESULTS: Among 678 subjects initiating TCZ, 194 (29%) completed appropriate HBV screening, 307 (45%) had partial screening, and 177 (26%) had none. Among 391 subjects initiating TOF, 94 (24%) completed appropriate HBV screening, 195 (50%) had partial screening, and 102 (26%) had none. Inappropriate testing was performed in 22% of subjects. Race was associated with complete HBV screening (White vs non-White: OR 0.74, 95% CI 0.57-0.95), whereas prior immunosuppression was not (conventional synthetic disease-modifying antirheumatic drugs [DMARDs]: OR 1.05, 95% CI 0.72-1.55; biologic DMARDs: OR 0.73, 95% CI 0.48-1.12). CONCLUSION: Patients initiating TCZ or TOF are infrequently screened for HBV despite recommendations from the AASLD and CDC.