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ID PMID Title PublicationDate abstract
30337056 Tumor necrosis factor inhibitors and risk of peripheral neuropathy in patients with rheuma 2019 Jun IMPORTANCE: Tumor necrosis factor inhibitors (TNFi) are widely used in the treatment of a variety of autoimmune diseases. A number of case reports have linked TNFi to neurologic adverse events including peripheral neuropathy (PN) in patients with rheumatic diseases. OBJECTIVES: To quantify the risk of peripheral neuropathy with TNFi in patients with rheumatic diseases. DESIGN: Nested-Case Control study within a cohort of patients with rheumatic diseases. SETTING: PharMetrics Plus™ health claims database from the United States. PARTICIPANTS: From a random sample of 9,053,240 subjects from the PharMetrics Plus™ database a cohort of patients with rheumatic diseases who had two physician visit codes for rheumatoid arthritis, ankylosing spondylitis and psoriasis in addition to a medication used in the treatment of each condition from 2006 to 2016 was created. EXPOSURE: We created different risk periods of current use (day 0-60), recent use (day 61-180) and past use (day 180-365) from the index date. MAIN OUTCOME MEASURES: New cases of PN were identified from the rheumatic disease cohort. Each case was matched to 10 controls by calendar time and age using density based sampling. Rate ratios (RRs) for new users of TNFi were computed using conditional logistic regression adjusting for gender, vitamin B(12) deficiency, fluoroquinolone use, HIV, viral hepatitis, chronic renal failure and diabetes. RESULTS: Among a cohort of 61,570 patients with rheumatic diseases 1358 cases of PN and 13,580 corresponding controls were identified. The adjusted rate ratio (RR) of PN among recent users of TNFi was 1.14 (95% CI:0.90-1.43). The RR for past use of TNFi was 2.77 (95% CI:1.67-4.58). Past users who used three or more prescriptions had a higher risk of PN 3.49 (1.63-7.49). The RRs did not change when the risk of PN with TNFi was compared to those taking methotrexate and one additional disease modifying anti rheumatic drug (DMARD) for recent and past use (RR = 0.95 [95% CI:0.72-1.24] and RR = 2.30 (1.37-3.87), respectively). CONCLUSIONS: Patients with rheumatic diseases who are past users of TNFi are at higher risk of developing PN compared to those taking methotrexate and one additional DMARD.
31806421 The pathogenesis of systemic lupus erythematosus: Harnessing big data to understand the mo 2020 Jun Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease that causes damage to multiple organ systems. Despite decades of research and available murine models that capture some aspects of the human disease, new treatments for SLE lag behind other autoimmune diseases such as Rheumatoid Arthritis and Crohn's disease. Big data genomic assays have transformed our understanding of SLE by providing important insights into the molecular heterogeneity of this multigenic disease. Gene wide association studies have demonstrated more than 100 risk loci, supporting a model of multiple genetic hits increasing SLE risk in a non-linear fashion, and providing evidence of ancestral diversity in susceptibility loci. Epigenetic studies to determine the role of methylation, acetylation and non-coding RNAs have provided new understanding of the modulation of gene expression in SLE patients and identified new drug targets and biomarkers for SLE. Gene expression profiling has led to a greater understanding of the role of myeloid cells in the pathogenesis of SLE, confirmed roles for T and B cells in SLE, promoted clinical trials based on the prominent interferon signature found in SLE patients, and identified candidate biomarkers and cellular signatures to further drug development and drug repurposing. Gene expression studies are advancing our understanding of the underlying molecular heterogeneity in SLE and providing hope that patient stratification will expedite new therapies based on personal molecular signatures. Although big data analyses present unique interpretation challenges, both computationally and biologically, advances in machine learning applications may facilitate the ability to predict changes in SLE disease activity and optimize therapeutic strategies.
31777841 HLA-C: An Accomplice in Rheumatic Diseases. 2019 Nov Human leukocyte antigen c (HLA-C) is a polymorphic membrane protein encoded by the HLA-C gene in the class I major histocompatibility complex. HLA-C plays an essential role in protection against cancer and viruses but has also been implicated in allograft rejection, preeclampsia, and autoimmune disease. This review summarizes reports and proposed mechanisms for the accessory role of HLA-C in rheumatic diseases. Historically, contributions of HLA-C to rheumatic diseases were eclipsed by the stronger association with HLA-DRB1 alleles containing the "shared epitope" with rheumatoid arthritis. Larger genetic association studies and more powerful analytical approaches have revealed independent associations of HLA-C with rheumatic disease-associated phenotypes, including development of anticitrullinated peptide antibodies. HLA-C functions by presenting antigens to T cells and by binding activatory and inhibitory receptors on natural killer (NK) cells, but the exact mechanisms by which the HLA-C locus contributes to autoimmunity are largely undefined. Studies have suggested that HLA-C and NK cell receptor polymorphisms may predict responsiveness to pharmacotherapy. Understanding the mechanisms of the role of HLA-C in rheumatic disease could uncover therapeutic targets or guide precision pharmacologic treatments.
31747802 Therapeutic potential of enhancer of zeste homolog 2 in autoimmune diseases. 2019 Dec Introduction: Autoimmune diseases (ADs) are idiopathic and heterogeneous disorders with contentious pathophysiology. Great strides have been made in epigenetics and its involvement in ADs. Zeste homolog 2 (EZH2) has sparked extensive interest because of its pleiotropic roles in distinct pathologic contexts.Areas covered: This review summarizes the epigenetic functions and the biological significance of EZH2 in the etiology of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), inflammatory bowel disease (IBD), multiple sclerosis (MS), and systemic sclerosis (SSc). A brief recapitulation of the therapeutic potential of EZH2 targeting is provided.Expert opinion: There are questions marks and controversies surrounding the feasibility and safety of EZH2 targeting; it is recommended in RA and SLE, but queried in T1D, IBD, MS, and SSc. Future work should focus on contrast studies, systematic analyses and preclinical studies with optimizing methodologies. Selective research studies conducted in a stage-dependent manner are necessary because of the relapsing-remitting clinical paradigms.
31708915 Blue and Long-Wave Ultraviolet Light Induce in vitro Neutrophil Extracellular Trap (NET) F 2019 Neutrophil Extracellular Traps (NETs) are produced by neutrophilic granulocytes and consist of decondensed chromatin decorated with antimicrobial peptides. They defend the organism against intruders and are released upon various stimuli including pathogens, mediators of inflammation, or chemical triggers. NET formation is also involved in inflammatory, cardiovascular, malignant diseases, and autoimmune disorders like rheumatoid arthritis, psoriasis, or systemic lupus erythematosus (SLE). In many autoimmune diseases like SLE or dermatomyositis, light of the ultraviolet-visible (UV-VIS) spectrum is well-known to trigger and aggravate disease severity. However, the underlying connection between NET formation, light exposure, and disease exacerbation remains elusive. We studied the effect of UVA (375 nm), blue (470 nm) and green (565 nm) light on NETosis in human neutrophils ex vivo. Our results show a dose- and wavelength-dependent induction of NETosis. Light-induced NETosis depended on the generation of extracellular reactive oxygen species (ROS) induced by riboflavin excitation and its subsequent reaction with tryptophan. The light-induced NETosis required both neutrophil elastase (NE) as well as myeloperoxidase (MPO) activation and induced histone citrullination. These findings suggest that NET formation as a response to light could be the hitherto missing link between elevated susceptibility to NET formation in autoimmune patients and photosensitivity for example in SLE and dermatomyositis patients. This novel connection could provide a clue for a deeper understanding of light-sensitive diseases in general and for the development of new pharmacological strategies to avoid disease exacerbation upon light exposure.
31368705 Discovery of Evobrutinib: An Oral, Potent, and Highly Selective, Covalent Bruton's Tyrosin 2019 Sep 12 Bruton's tyrosine kinase (BTK) inhibitors such as ibrutinib hold a prominent role in the treatment of B cell malignancies. However, further refinement is needed to this class of agents, particularly in terms of adverse events (potentially driven by kinase promiscuity), which preclude their evaluation in nononcology indications. Here, we report the discovery and preclinical characterization of evobrutinib, a potent, obligate covalent inhibitor with high kinase selectivity. Evobrutinib displayed sufficient preclinical pharmacokinetic and pharmacodynamic characteristics which allowed for in vivo evaluation in efficacy models. Moreover, the high selectivity of evobrutinib for BTK over epidermal growth factor receptor and other Tec family kinases suggested a low potential for off-target related adverse effects. Clinical investigation of evobrutinib is ongoing in several autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus.
31322087 [Clinical Features of Comorbid Cluster and Premorbidly Manifestations in Patients with Hig 2019 Jul 19 OBJECTIVE: to study clinical and cluster features of cardiovascular burdening taking into account the comorbid polymorbid background in patients of middle age (45-60 years) with the presence of multifocal atherosclerosis (MFA). MATERIALS AND METHODS: Patients were examined in the Regional Vascular Center of Ufa (RVCU). Depending on the predominant localization of lesions in the vascular bed patients were divided into 3 clusters by the method of hierarchical analysis of categorical variables according to the clinical manifestation of atherosclerotic lesions of the heart, brain and lower limb arteries confirmed by coronary angiography, ultrasound Doppleroscopy of main arteries of the head and lower extremities. Ninety-six patients had predominant lesions in the heart (1st cluster), 96 - in carotid arteries (2nd cluster), and 96 patients had ischemia of lower extremities (3rd cluster). Examination during hospitalization in RVCU included when indicated echocardiography, magnetic resonance imaging of the chest and abdomen, ultrasound studies of abdomen, kidney, and pelvis. RESULTS: According to data obtained the following conditions were most often observed in different combinations and with varying degrees of severity of clinical manifestation.Claster 1. Clinical manifestation of atherosclerotic heart disease mainly due to stage III hypertension, history of myocardial infarction were combined with pneumonia, chronic obstructive pulmonary disease with the outcome in pneumosclerosis and emphysema, as well as the presence of cholecysto-cardial syndrome, chronic gastritis, chronic cholecysto-pancreatitis, abdominal ischemic syndrome, rheumatoid arthritis, diabetes mellitus, and chronic pyelonephritis.Claster 2. Hemodynamically significant lesions of brachiocephalic arteries mainly with acute ischemic disturbance of cerebral circulation were combined with bronchial asthma, (the development of which was associated with prolonged persistent eosinophilic inflammation), worsening of chronic kidney disease with urolithiasis, angionephropathy and iron deficiency anemia, as well as the presence of dorsopathy associated with stenotic atherosclerosis of brain vessels.Claster 3.Hemodynamic ischemia with clinical manifestation of vascular lesions of lower extremities was accompanied by type 2 diabetes, chronic cholecysto-pancreatitis, erosive and ulcerative lesions in the stomach and duodenum, polyosteoarthrosis, abdominal-ischemic syndrome. Type 2 diabetes prevailed in patients with occlusion of right posterior tibial artery and trophic ulcer of the right foot. CONCLUSION: Interdependence of comorbid and polymorbid background and cardiovascular burdening changes their clinical picture and course, increases number of complications and their severity.
31223608 Extracts of Flavoparmelia sp. Inhibit Receptor Activator of Nuclear Factor-κB Ligand-Medi 2019 May BACKGROUND: Osteoporosis is a geriatric disease with diminished bone density. The increase in the number of patients and medical expenses due to a global aging society are recognized as problems. Bone loss is the most common symptom of bone disease, not only osteoporosis but Paget's disease, rheumatoid arthritis, multiple myeloma, and other diseases. The main cause of this symptoms is excessive increase in the number and activity of osteoclasts. Osteoclasts are multinucleated giant cells that can resorb bone. They are differentiated and activation from monocytes/macrophages in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand (RANKL). METHODS: The effect of extract of Flavoparmelia sp. (EFV), a genus of lichenized fungi within the Parmeliaceae, on the differentiation of bone marrow-derived macrophages (BMMs) into osteoclasts was examined by phenotype assay and the cell cytotoxicity was evaluated by cell counting kit-8. The osteoclast differentiation-related genes and proteins were investigated by real-time polymerase chain reaction and immunoblotting. The functional activity of osteoclast in response to EFV treatment was evaluated by an Osteo Assay plate. RESULTS: In this study, we found that EFV, a genus of lichenized fungi within the Parmeliaceae, inhibited osteoclast formation. And we investigated its inhibitory mechanism. EFV reduced RANKL-mediated osteoclast formation and activation by inhibiting expression of nuclear factor of activated T cells 1, a key factor of osteoclastogenesis. CONCLUSIONS: Taken together, our results show that EFV is a promising candidate for health functional foods or therapeutic agents that can help treat bone diseases such as osteoporosis.
31143695 Effects of Boswellia serrata resin extract on motor dysfunction and brain oxidative stress 2019 May OBJECTIVE: Boswellia serrata oleo-gum resin (frankincense) exerted antioxidant and anti-inflammatory effects against several diseases, such as; asthma, rheumatoid arthritis and irritable bowel syndrome. In the current study, the influences of B. serrata resin extract on motor dysfunction and oxidative stress markers were investigated in the intrastriatal 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD). MATERIALS AND METHODS: The animals were randomly assigned to sham, lesion (6-OHDA), and three lesion groups treated with ethyl alcoholic extract of B. serrata at doses of 125, 250 and 500 mg/kg for 3 weeks. The neurotoxin 6-OHDA (12.5 µg) was microinjected into the left striatum to induce PD in male rats. Motor behavior was assessed by rotational and elevated narrow beam tests. Oxidative stress markers were measured in striatal and midbrain homogenates. RESULTS: There was a significant increase in contralateral rotations in 6-OHDA group versus sham group (p<0.001), and treatment with B. serrata resin extract at doses of 125 and 250 mg/kg significantly decreased the rotations in comparison to 6-OHDA group (p<0.001 and p<0.001, respectively). The 6-OHDA group also showed considerable elevation in the latency to initiate crossing (p<0.001) and the total time (p<0.001) on narrow beam test. Moreover, treatment with B. serrata extract at doses of 125, 250 and 500 mg/kg caused a significant reduction in the latency and total time (p<0.001, p<0.001, and p<0.01, respectively). Biochemical analysis showed no significant difference in oxidative stress markers levels among the groups. CONCLUSION: Our findings suggest that B. serrata resin extract acts as an anti-inflammatory and antioxidant agent that protects nigrostriatal dopaminergic neurons and improve motor impairments in PD.
31064684 Intraoperative neuromonitoring during reverse shoulder arthroplasty. 2019 Aug BACKGROUND: The aim of this study was to evaluate the risk of nerve injury with neuromonitoring during reverse total shoulder arthroplasty. MATERIALS: This study included 15 shoulders of 15 patients (11 females and 4 males) who underwent reverse total shoulder arthroplasty. The mean age was 74.8 ± 4.4 years. Nine shoulders had cuff tear arthropathy, 4 had massive rotator cuff tears, 2 had osteoarthritis, and 1 had rheumatoid arthritis. The somatosensory evoked potentials of the median nerve, transcranial motor evoked potentials, and free-electromyograms from 6 upper-extremity muscles were measured intraoperatively. We defined a nerve alert as 50% amplitude attenuation or 10% latency prolongation of the somatosensory evoked potentials and transcranial motor evoked potentials and sustained neurotonic discharge on free-electromyogram. RESULTS: Thirty-one alerts were recorded in 11 patients. The axillary nerve was associated with 17 alerts. Eleven alerts occurred during the glenoid procedure and 5 alerts occurred during the humeral procedure. One patient who did not recover from the alert of the axillary nerve had clinically incomplete paralysis of the deltoid muscle. CONCLUSION: The present findings suggest that the axillary nerve was the nerve most frequently exposed to the risk of injury, especially during glenoid and humeral implantation.
30941138 What Are the Peripheral Blood Determinants for Increased Osteoclast Formation in the Vario 2019 Local priming of osteoclast precursors (OCp) has long been considered the main and obvious pathway that takes place in the human body, where local bone lining cells and RANKL-expressing osteocytes may facilitate the differentiation of OCp. However, priming of OCp away from bone, such as in inflammatory tissues, as revealed in peripheral blood, may represent a second pathway, particularly relevant in individuals who suffer from systemic bone loss such as prevalent in inflammatory diseases. In this review, we used a systematic approach to review the literature on osteoclast formation in peripheral blood in patients with inflammatory diseases associated with bone loss. Only studies that compared inflammatory (bone) disease with healthy controls in the same study were included. Using this core collection, it becomes clear that experimental osteoclastogenesis using peripheral blood from patients with bone loss diseases in prevalent diseases such as rheumatoid arthritis, osteoporosis, periodontitis, and cancer-related osteopenia unequivocally point toward an intrinsically increased osteoclast formation and activation. In particular, such increased osteoclastogenesis already takes place without the addition of the classical osteoclastogenesis cytokines M-CSF and RANKL in vitro. We show that T-cells and monocytes as OCp are the minimal demands for such unstimulated osteoclast formation. In search for common and disease-specific denominators of the diseases with inflammation-driven bone loss, we demonstrate that altered T-cell activity and a different composition-such as the CD14+CD16+ vs. CD14+CD16- monocytes-and priming of OCp with increased M-CSF, RANKL, and TNF- α levels in peripheral blood play a role in increased osteoclast formation and activity. Future research will likely uncover the barcodes of the OCp in the various inflammatory diseases associated with bone loss.
30897044 Case 268. 2019 Apr History A 65-year-old man presented to the emergency department with a 1-week history of constipation, which was associated with increasing abdominal distention and not passing flatus. Four weeks prior to the current admission he had been diagnosed with metastatic primary adenocarcinoma of the appendix. One week ago, he had been hospitalized with small-bowel obstruction, for which he required laparotomy and loop ileostomy. His medical history included basal cell carcinoma, rheumatoid arthritis, and Barrett esophagus. Physical examination revealed a distended abdomen with tenderness at palpation within the right upper quadrant and lower abdomen and reduced bowel sounds at auscultation. Initial plain-film radiography of the abdomen at admission revealed dilated gas-filled small-bowel loops, suggestive of obstruction. His small-bowel obstruction was managed conservatively on this occasion. Nine days after his admission, the patient became unwell and reported a productive cough. He became tachycardic, tachypneic, and hypotensive. Relevant blood tests at this stage revealed a C-reactive protein level of 206 mg/L (normal range, 0-10 mg/L), a white blood cell count of 24.5 × 10(9)/L (normal range, [4.0-11.0] × 10(9)/L), a red blood cell count of 3.39 × 10(12)/L (normal range, [4.5-5.5] × 10(12)/L), a hemoglobin level of 93 g/L (normal range, 130-170 g/L), and a hematocrit level of 0.27 (normal range, 0.4-0.5). CT of the abdomen and pelvis with intravenous contrast material (100 mL Omnipaque 350; GE Healthcare, Oslo, Norway) was performed ( Figs 1 , 2 ). Figure 1a: (a) Axial and (b) curved reformatted contrast-enhanced CT images of the upper abdomen. Figure 1b: (a) Axial and (b) curved reformatted contrast-enhanced CT images of the upper abdomen. Figure 2a: (a) Axial and (b) coronal contrast-enhanced CT images of the upper abdomen obtained 12 days before the CT images shown in Figures 1a and 1b , respectively. Figure 2b: (a) Axial and (b) coronal contrast-enhanced CT images of the upper abdomen obtained 12 days before the CT images shown in Figures 1a and 1b , respectively.
30815921 Alcohol use and periodontal pocket development: findings from a 4-yr longitudinal study. 2019 Jun This study investigated whether alcohol use influences periodontal pocket development during a 4-yr follow-up period. The study included those participants who took part in both the Health 2000 Survey and the Follow-up Study on Finnish Adults' Oral Health. The participants at baseline were aged ≥30 yr, periodontally healthy, and did not have diabetes or rheumatoid arthritis. The development of periodontal pockets at follow-up was measured as the number of teeth with periodontal pockets and the presence of periodontal pockets. Alcohol use at baseline was measured as g/wk, frequency, and use over the risk limit. Incidence rate ratios with 95% CI were estimated using negative binomial regression models and Poisson regression models with a robust variance estimator. No consistent association was found between any of the alcohol variables and periodontal pocket development in the total population or among non-smokers. Among smokers, a positive association was found with the frequency of alcohol use. In general, risk estimates were slightly higher for women than for men. In summary, light-to-moderate alcohol use appears not to be consistently associated with the development of periodontal pockets. The adverse effects on the periodontium seem, to some extent, to be dependent on gender and smoking.
30773373 Clinical significance and immunobiology of IL-21 in autoimmunity. 2019 May Interleukin-21 (IL-21), an autocrine cytokine predominantly produced by follicular helper T (Tfh) and T helper 17 (Th17) cells, has been proven to play an important role in the immune system, for example, by promoting proliferation and the development of Tfh and Th17 cells, balancing helper T cell subsets, inducing B cell generation and differentiation into plasma cells, and enhancing the production of immunoglobulin. These effects are mainly mediated by activation of the JAK/STAT, MAPK and PI3K pathways. Some IL-21 target genes, such as B lymphocyte induced maturation protein-1 (Blimp-1), suppressor of cytokine signaling (SOCS), CXCR5 and Bcl-6, play important roles in the immune response. Therefore, IL-21 has been linked to autoimmune diseases. Indeed, IL-21 levels are increased in the peripheral blood and tissues of patients with systematic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D), immune thrombocytopenia (ITP), primary Sjogren's syndrome (pSS), autoimmune thyroid disease (AITD) and psoriasis. This increased IL-21 even positively associates with Tfh cells, plasma cells, autoantibodies and disease activity in SLE and RA. Additionally, IL-21 has been utilized as a therapeutic target in SLE, RA, T1D and psoriatic mouse models. Profoundly, clinical trials have shown safety and improvement in RA patients. However, tolerance and long-term pharmacodynamics effects with low bioavailability have been found in SLE patients. Therefore, this review aims to summarize the latest progress on IL-21 function and its signaling pathway and discuss the role of IL-21 in the pathogenesis of and therapy for autoimmune diseases, with the hope of providing potential therapeutic and diagnostic strategies for clinical use.
30507725 Does the clinical phenotype of mucolipidosis-IIIγ differ from its αβ counterpart?: supp 2019 Jan Mucolipidosis-IIIγ (ML-IIIγ) is a recessively inherited slowly progressive skeletal dysplasia caused by mutations in GNPTG. We report the genetic and clinical findings in the largest cohort with ML-IIIγ so far: 18 affected individuals from 12 families including 12 patients from India, five from Turkey, and one from the USA. With consanguinity confirmed in eight of 12 families, molecular characterization showed that all affected patients had homozygous pathogenic GNPTG genotypes, underscoring the rarity of the disorder. Unlike ML-IIIαβ, which present with a broader spectrum of severity, the ML-III γ phenotype is milder, with onset in early school age, but nonetheless thus far considered phenotypically not differentiable from ML-IIIαβ. Evaluation of this cohort has yielded phenotypic findings including hypertrophy of the forearms and restricted supination as clues for ML-IIIγ, facilitating an earlier correct choice of genotype screening. Early identification of this disorder may help in offering a timely intervention for the relief of carpal tunnel syndrome, monitoring and surgery for cardiac valve involvement, and evaluation of the need for joint replacement. As this condition may be confused with rheumatoid arthritis, confirmation of diagnosis will prevent inappropriate use of immunosuppressants and disease-modifying agents.
30359170 The Oral Microbiota Is Modified by Systemic Diseases. 2019 Feb Periodontal diseases are initiated by bacteria that accumulate in a biofilm on the tooth surface and affect the adjacent periodontal tissue. Systemic diseases such as diabetes, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) increase susceptibility to destructive periodontal diseases. In human studies and in animal models, these diseases have been shown to enhance inflammation in the periodontium and increase the risk or severity of periodontitis. All 3 systemic diseases are linked to a decrease in bacterial taxa associated with health and an increase in taxa associated with disease. Although there is controversy regarding the specific oral bacterial changes associated with each disease, it has been reported that diabetes increases the levels of Capnocytophaga, Porphyromonas, and Pseudomonas, while Prevotella and Selenomonas are increased in RA and Selenomonas, Leptotrichia, and Prevotella in SLE. In an animal model, diabetes increased the pathogenicity of the oral microbiome, as shown by increased inflammation, osteoclastogenesis, and periodontal bone loss when transferred to normal germ-free hosts. Moreover, in diabetic animals, the increased pathogenicity could be substantially reversed by inhibition of IL-17, indicating that host inflammation altered the microbial pathogenicity. Increased IL-17 has also been shown in SLE, RA, and leukocyte adhesion deficiency and may contribute to oral microbial changes in these diseases. Successful RA treatment with anti-inflammatory drugs partially reverses the oral microbial dysbiosis. Together, these data demonstrate that systemic diseases characterized by enhanced inflammation disturb the oral microbiota and point to IL-17 as key mediator in this process.
30222598 US FDA Breast Implant Postapproval Studies: Long-term Outcomes in 99,993 Patients. 2019 Jan OBJECTIVE: To analyze the long-term safety and efficacy outcomes of patients with breast implants. SUMMARY BACKGROUND DATA: Research is ongoing regarding the safety of silicone breast implants. Despite the number of patients with breast implants followed by United States Food and Drug Administration large postapproval studies (LPAS), this database has not been thoroughly analyzed or reported. METHODS: This is a multicentered, cohort study. LPAS prospectively monitor long-term implant-related outcomes and systemic harms for silicone/saline implants from 2 manufacturers (Allergan and Mentor) placed for primary/revision augmentation/reconstruction. Systemic harms, self-harm, and reproductive outcomes are compared with normative data. Implant-related complications are analyzed by implant composition and operative indication in the short and long terms. RESULTS: LPAS data includes 99,993 patients, 56% of implants were silicone for primary augmentation. Long-term magnetic resonance imaging surveillance is under 5%. Compared with normative data, silicone implants are associated with higher rates of Sjogren syndrome (Standardized incidence ratio [SIR]8.14), scleroderma (SIR 7.00), rheumatoid arthritis (SIR5.96), stillbirth (SIR4.50), and melanoma (SIR3.71). One case of BI-ALCL is reported. There is no association with suicide. In the short term, rupture is higher for saline (2.5% vs. 0.5%, P < 0.001), and capsular contracture higher for silicone (5.0% vs. 2.8%, P < 0.001). At 7 years, reoperation rate is 11.7% for primary augmentation, and 25% for primary/revision reconstruction. Capsular contracture (III/IV) occurs in 7.2% of primary augmentations, 12.7% primary reconstructions, and is the most common reason for reoperation among augmentations. CONCLUSIONS: This is the largest study of breast implant outcomes. Silicone implants are associated with an increased risk of certain rare harms; associations need to be further analyzed with patient-level data to provide conclusive evidence. Long-term safety and implant-related outcomes should inform patient and surgeon decision-making when selecting implants.
30098424 Sarcopenia. 2019 May Sarcopenia is defined as a combination of low muscle mass with low muscle function. The term was first used to designate the loss of muscle mass and performance associated with aging. Now, recognized causes of sarcopenia also include chronic disease, a physically inactive lifestyle, loss of mobility, and malnutrition. Sarcopenia should be differentiated from cachexia, which is characterized not only by low muscle mass but also by weight loss and anorexia. Sarcopenia results from complex and interdependent pathophysiological mechanisms that include aging, physical inactivity, neuromuscular compromise, resistance to postprandial anabolism, insulin resistance, lipotoxicity, endocrine factors, oxidative stress, mitochondrial dysfunction, and inflammation. The prevalence of sarcopenia ranges from 3% to 24% depending on the diagnostic criteria used and increases with age. Among patients with rheumatoid arthritis 20% to 30% have sarcopenia, which correlates with disease severity. Sarcopenia exacts a heavy toll of functional impairment, metabolic disorders, morbidity, mortality, and healthcare costs. Thus, the consequences of sarcopenia include disability, quality of life impairments, falls, osteoporosis, dyslipidemia, an increased cardiovascular risk, metabolic syndrome, and immunosuppression. The adverse effects of sarcopenia are particularly great in patients with a high fat mass, a condition known as sarcopenic obesity. The diagnosis of sarcopenia rests on muscle mass measurements and on functional tests that evaluate either muscle strength or physical performance (walking, balance). No specific biomarkers have been identified to date. The management of sarcopenia requires a multimodal approach combining a sufficient intake of high-quality protein and fatty acids, physical exercise, and antiinflammatory medications. Selective androgen receptor modulators and anti-myostatin antibodies are being evaluated as potential stimulators of muscle anabolism.
29251559 Structural refinement and prediction of potential CCR2 antagonists through validated multi 2019 Jan Chemokines trigger numerous inflammatory responses and modulate the immune system. The interaction between monocyte chemoattractant protein-1 and chemokine receptor 2 (CCR2) may be the cause of atherosclerosis, obesity, and insulin resistance. However, CCR2 is also implicated in other inflammatory diseases such as rheumatoid arthritis, multiple sclerosis, asthma, and neuropathic pain. Therefore, there is a paramount importance of designing potent and selective CCR2 antagonists despite a number of drug candidates failed in clinical trials. In this article, 83 CCR2 antagonists by Jhonson and Jhonson Pharmaceuticals have been considered for robust validated multi-QSAR modeling studies to get an idea about the structural and pharmacophoric requirements for designing more potent CCR2 antagonists. All these QSAR models were validated and statistically reliable. Observations resulted from different modeling studies correlated and validated results of other ones. Finally, depending on these QSAR observations, some new molecules were proposed that may exhibit higher activity against CCR2.
31497760 The Prevalence of Systemic Rheumatic Diseases Among Breast Cancer Patients and Its Relatio 2019 Jun OBJECTIVES: This study aims to investigate the prevalence of systemic rheumatic diseases (SRDs) among patients with breast cancer (BC) and to identify the clinicopathological characteristics of these patients. PATIENTS AND METHODS: A total of 3,744 female patients with BC (mean age 49±11.7 years; range, 18 to 92 years) followed in Hacettepe University Faculty of Medicine, Medical Oncology Department between January 2006 and December 2015 were retrospectively assessed. Patients with or without SRD were compared in terms of clinicopathological features including age, menopausal state, smoking status, Body Mass Index (BMI), age of menarche, age at first labor, and number of children. The groups were also evaluated regarding tumor grade, stage, estrogen receptor and progesterone receptor expression, human epidermal growth factor receptor 2 overexpression, and survival. RESULTS: Of the patients analyzed, 68 (1.81%) had concomitant SRD. Among these patients, 33 (48.6%) had rheumatoid arthritis, eight (11.8%) had familial Mediterranean fever, eight (11.8%) had Behçet's disease, four (5.8%) had Sjögren's syndrome, four (5.8%) had systemic lupus erythematosus, six (8.8%) had ankylosing spondylitis, three (4.4%) had systemic sclerosis, one (1.4%) had polymyositis, and one (1.4%) had temporal arteritis. The groups with or without SRDs were similar in terms of age, smoking status, BMI, menopausal state, breast feeding duration, age at menarche and first birth. Stage 1 and 2 BC was more prevalent in SRD patients (74.6% vs. 64.5%, p=0.018). The rate to receive chemotherapy was significantly lower in patients with SRD. However, there was no significant difference in five-year overall survival rates between patients with or without SRD. CONCLUSION: Among patients with BC, 1.81% had concomitant SRD. These patients were diagnosed at early stages and given chemotherapy less frequently. However, they had similar survival rates compared to those without SRDs.