Special Issue:
Challenges and Opportunities in Sepsis
Kristen Anne Salava, MD
Geisinger Medical Center 100 N. Academy Avenue M.C. 21-52 Rheumatology, Danville, PA 17822
Ruchi Patel, DO
Geisinger Medical Center 100 N. Academy Avenue M.C. 21-52 Rheumatology, Danville, PA 17822
Eric Newman, MD
Geisinger Medical Center 100 N. Academy Avenue M.C. 21-52 Rheumatology, Danville, PA 17822
P. Daniel Nicoholas, DO
Geisinger Medical Center 100 N. Academy Avenue M.C. 21-52 Rheumatology, Danville, PA 17822
Dante M. Grassi, PharmD, BCPS
Geisinger Medical Center 100 N. Academy Avenue M.C. 21-52 Rheumatology, Danville, PA 17822
Swana Thomas, PharmD, MPH
Pennsylvania Presbyterian Medical Center 3737 Market Street 11th Fl, Philadelphia, PA 19115
Joseph Chronowski, MBA
Geisinger Medical Center 100 N. Academy Avenue M.C. 21-52 Rheumatology, Danville, PA 17822
David Pugliese, DO
Geisinger Medical Center 100 N. Academy Avenue M.C. 21-52 Rheumatology, Danville, PA 17822
Jonida Cote, DO
Geisinger Medical Center 100 N. Academy Avenue M.C. 21-52 Rheumatology, Danville, PA 17822
Abstract
Objective: To close laboratory screening care gaps via rheumatology-pharmacy co-management in patients starting disease-modifying antirheumatic drugs.
Methods: Laboratory data were obtained from patients who started disease-modifying antirheumatic drugs (DMARDs) during the pre-and post-intervention periods. The intervention consisted of a rheumatology-pharmacy collaborative screening with guideline-driven DMARD protocol for hepatitis B, hepatitis C, and tuberculosis. The care gap closure for patients starting any type of DMARDs such as a conventional synthetic disease-modifying antirheumatic drug (csDMARD), a biologic disease-modifying antirheumatic drug (bDMARD), or a targeted synthetic disease-modifying antirheumatic drug (tsDMARD), was defined as meeting hepatitis screening completion. The care gap closure for patients starting a bDMARD or tsDMARD alone was defined as meeting both the hepatitis and tuberculosis screening completion. The Chi square method was used for the statistical analysis of the data comparing laboratory screening rates of rheumatologists’ pre-intervention versus rheumatologist-pharmacist co-management post-intervention. Post-intervention, subgroup analysis of laboratory screening rates among rheumatologists alone versus rheumatologist-pharmacist co-management was also performed.
Results: During the 30-month period 6/1/2019 to 11/30/2021, hepatitis screening for patients on DMARDs improved from 77% with rheumatologists alone to 82% with co-management post-intervention (P=0.005), whereas hepatitis/tuberculosis screening for patients on bDMARDs/tsDMARDs improved from 75% to 85% respectively (P=0.005). In post-intervention subgroup analysis, hepatitis screening for patients on DMARDs improved from 80% with rheumatologists alone to 95% with co-management(P=0.00), whereas hepatitis/tuberculosis screening for patients on bDMARDs/tsDMARDs improved from 83% to 94% respectively (P=0.033).
Conclusion: By integrating clinical pharmacists into our rheumatology clinic, we significantly improved hepatitis and tuberculosis laboratory screening in our immunosuppressed rheumatic population.
Implications: Rheumatologists can consider integrating clinical pharmacists into their practices to improve patient safety by closing laboratory screening care gaps in the immunosuppressed rheumatic population.
Niclas Stefan Rasmussen
Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.; Copenhagen Research Center for Autoimmune Connective Tissue Diseases – COPEACT, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.; Department of Clinical Biochemistry, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Søren Jacobsen
Copenhagen Research Center for Autoimmune Connective Tissue Diseases – COPEACT, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Claus Henrik Nielsen
Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Christoffer Tandrup Nielsen
Copenhagen Research Center for Autoimmune Connective Tissue Diseases – COPEACT, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
Abstract
Background: Generation of galectin-3 binding protein (G3BP)-expressing microvesicles can be induced in-vitro by Toll-like receptor 9 ligation in mononuclear cells. Microvesicles co-expressing G3BP and double-stranded DNA are associated with active lupus nephritis. However, whether the microvesicular G3BP mainly deposits from circulation or is endogenously derived is unknown. In this study, we aim to delineate the origin of G3BP on in-vitro generated microvesicles by using serum as a source of native G3BP.
Methods: G3BP-expressing microvesicles, generated by stimulation of systemic lupus erythematosus patient-derived mononuclear cells with the Toll-like receptor 9-agonist ODN2395, were incubated with normal human serum, heat-inactivated human serum, recombinant human C1q or human albumin. The expression of G3BP by microvesicles was examined by flow cytometry, and the binding of soluble recombinant human C1q to recombinant human G3BP was investigated by ELISA.
Results: Approximately half of the microvesicles released from mononuclear cells expressed G3BP. Surprisingly, the staining was abrogated by incubation of the microvesicles with normal human serum, while incubation with heat-inactivated human serum did not have a similar effect. Reasoning that C1q might be the heat-labile factor blocking access of our G3BP antibody detection system, we incubated microvesicles with recombinant human C1q, which on average inhibited the detectable proportion of G3BP-bearing microvesicles by 87%. Soluble recombinant human C1q bound to immobilized recombinant human G3BP in a dose-dependent manner.
Conclusion: Our data suggest that soluble C1q binds to G3BP on Toll-like receptor 9-induced microvesicles released from systemic lupus erythematosus patient-derived mononuclear cells. This interaction may exarcerbate inflammation in systemic lupus erythematosus but may also serve as a general mechanism for the appropriate clearance of these potentially pathogenic factors.
Thomas F Lansdale III, MD
Deceased, Department of Medicine, Greater Baltimore Medical Center, Johns Hopkins University School of Medicine, Baltimore MD
Geoffrey M. Gratwick, MD
Block and Gratwick PA, Bangor, ME
Samar X. Gupta, MD
Section of Rheumatology, Ann Arbor VA Healthcare System, University of Michigan, Ann Arbor, Michigan,
Stanford M. Shoor
Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, CA
Cindy Flower, MBBS, DM, FACP
Faculty of Medical Sciences, University of the West Indies, Cave Hill campus
Matthew H. Liang, MD, MPH
Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital and Section of Rheumatology, Boston VA Healthcare Services, Harvard Medical School, Boston, MA.
Abstract
Mentor has roots in Greek mythology. Its current practitioners have lent their own interpretation and meaning by their actions. We offer the case studies and lived experience of a select group who have never met all the others. Each asked the same questions, they tell the story of how each found their mentor(s), try to be mentors themselves, and what they try to impart to their mentees through the vicissitudes of their professional responsibilities and personal lives over a career.
Céu Tristão Martins Conceição
Psychologist and Psychoanalyst, PhD – Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
Ivone Minhoto Meinão
Rheumatologist, MD, PhD- Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
Sérgio Luís Blay
Professor of Psychiatry and Psychoanalysis, MD, PhD – Department of Psychiatry, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
Emília Inoue Sato
Professor of Rheumatology MD, PhD – Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
Abstract
Objective: To evaluate the effectiveness in the long-term follow-up of brief group psychoanalytic psychotherapy in improving quality of life, symptoms, coping strategies, anxiety, and depression levels in systemic lupus erythematosus (SLE) patients.
Methods: Prospective, randomized clinical trial including 80 SLE patients divided into two groups: therapy (n=37) and control (n=43), with standard clinical care. Therapy group received weekly therapy for 20 weeks. The assessments were at baseline, after 20 weeks and after 24 months from the end of intervention. Damage and disease activity were assessed by rheumatologists. Self-administered questionnaires were supervised by blind evaluators: quality of life, symptoms, coping strategies, anxiety, and depression. Intent to treat statistical analysis. Comparisons of variance between groups over time (ANOVA repeated measures). P <0.05 significant.
Results: At baseline, both groups were homogeneous. After intervention, therapy group showed significant improvement in most domains of quality of life, symptoms, all domains of anxiety, and depression and several domains of coping strategies. Benefits in quality of life and coping remained at 24 months follow-up. However, the improvement in anxiety, and depression was not maintained. Medications and clinical variables did not change.
Conclusion: This study showed the effectiveness of brief group psychoanalytic psychotherapy in improving quality of life, symptoms and coping strategies in SLE patients even in the long-term follow-up. Depression and anxiety levels reduced at the end of therapy, although, the improvement did not last 24 months.
Nicola Volpi
Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy
Abstract
The various Rheumatology/Osteoarthritis Societies (the American College of Rheumatology, the Arthritis Foundation, the European League Against Rheumatism, the National Institute for Health and Care Excellence, the European society for clinical and economic aspects of osteoporosis and osteoarthritis, and the Italian consensus on appropriateness of osteoarthrosis therapies) published specific recommendations for the management of osteoarthrosis affecting hand, hip and knee. These evidence-based guidelines take into account safety and tolerability of pharmacological and non-pharmacological interventions available from the scientific literature as well as the opinions of the clinical specialists to provide complete, clear and transparent recommendations for the management of osteoarthrosis. This article provides an update of the scientific literature for selected treatments of osteoarthrosis focusing on the therapy with symptomatic slow-acting drugs (SYSADOAs) and disease modifying anti-osteoarthrosis drugs (DMOADs) (chondroitin sulfate, glucosamine, diacerein, unsaponifiable soy and avocado extracts). Moreover, the management of osteoarthrosis pain and function, avoidance of adverse events and long-term outcomes by SYSADOAs/DMOADs molecules is considered. Finally, based on the real-world data, the opinion of the various Rheumatology/Osteoarthritis Societies of all over the word is illustrated and discussed also by considering the structure, quality and properties of the SYSADOAs/DMOADs agents used in the treatment of osteoarthrosis. In particular, the results reported in numerous studies are contradictory and not always convincing about the efficacy of chondroitin sulfate and glucosamine as SYSADOAs and DMOADs. The cause of these non-homogeneous results could be due to the use in different studies of chondroitin sulfate and glucosamine preparations of varying quality. It is therefore mandatory to carry out new clinical studies using chondroitin sulfate and glucosamine of pharmaceutical grade or of the best possible quality to ascertain their usefulness as biomolecules in the treatment of osteoarthrosis.
George A Karpouzas, MD
Division of Rheumatology, Harbor-UCLA Medical Center and Lundquist Institute for Biomedical Innovation, Torrance, CA, USA
Elizabeth Hernandez, MA
Division of Rheumatology, Harbor-UCLA Medical Center and Lundquist Institute for Biomedical Innovation, Torrance, CA, USA
Matthew J Budoff, MD
Division of Cardiology, Harbor-UCLA Medical Center and Lundquist Institute for Biomedical Innovation, Torrance, CA, USA
Sarah R Ormseth, PhD
Division of Rheumatology, Harbor-UCLA Medical Center and Lundquist Institute for Biomedical Innovation, Torrance, CA, USA
Abstract
Objectives. Underweight patients with rheumatoid arthritis incur greater total and cardiovascular mortality compared to overweight or obese. We explored whether obesity confounded cardiovascular risk estimates and the potential utility of noninvasive coronary atherosclerosis assessment and cardiac damage biomarkers in optimizing risk prediction in obese patients with rheumatoid arthritis.
Methods. We evaluated 150 participants undergoing screening atherosclerosis evaluation with coronary computed tomography angiography and follow-up over 6.0±2.4 years. Framingham 2008 modified general cardiovascular risk score was computed at baseline. Obesity was defined as waist circumference >88 cm in females and >102 cm in males. Serum highly-sensitive cardiac troponin I (hs-cTnI) and leptin were measured at baseline.
Results. An interaction between the Framingham risk score and obesity on cardiovascular risk was observed (p=0.032); lower estimates were seen in obese (area under the curve-AUC 0.660, 95% CI 0.487-0.832) vs. non-obese patients (AUC 0.952, 95% CI 0.897-1.007, p=0.002). Likewise, risk estimates were inferior in patients with high (>22.1 ng/ml) vs. low leptin (AUC 0.618, 95% CI 0.393-0.842 vs. 0.874, 95% CI 0.772-0.976, p=0.042). In obese patients, sequential addition of the top highly-sensitive cardiac troponin I tertile values and extensive atherosclerotic plaque (>5 segments) information to a base model including the Framingham risk score alone significantly improved risk estimates, based on changes in net reclassification index (1.093 95% CI 0.517-1.574), integrated discrimination improvement (0.188, 95% CI 0.060-0.526), and AUC (0.179, 95% CI 0.058-0.378, p=0.02). The final, combined model accurately predicted 83.9% of incident cardiovascular events.
Conclusion. Obesity attenuated cardiovascular risk estimate accuracy in patients with rheumatoid arthritis. Risk optimization employing non-invasive assessment of coronary atherosclerosis burden and serum cardiac damage biomarkers may warrant further study.
Amorn Sankhaanuruk, M.D.
Division of Rheumatology, Department of Internal Medicine 1 , Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Nuntana Kasitanon, M.D.
Division of Rheumatology, Department of Internal Medicine 1 , Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Worawit Louthrenoo, M.D.
Division of Rheumatology, Department of Internal Medicine 1 , Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Abstract
Background: Nowadays, we have standard treatment guidelines for lupus nephritis (LN), a substantial proportion of patients have LN flare. The aims here to determine the incidence of LN flare in patients who had renal complete remission (CR) after receiving induction therapy (IT) and to identify factors associated with renal flare after CR in clinical practice.
Methods: Retrospective analysis in a tertiary-level center for the clinical outcomes of patients who had first LN episode, achieved CR (24hr urine protein <0.5 gm/day with normal renal function) within 12 months after received IT and received the maintenance therapy (MT).
Results: Eighty-seven out of 548 patients (96.6% female with mean age 29.5±10.8 years) met the inclusion criteria. During 6.1±3.4 years of observation after CR, 42 (48.3%) patients had LN flare. The incidence ratio of LN flare was 10.9/100 patient-years. The mean time from CR to flare was 3.1 years. Using Cox-regression analysis, induction to remission therapy ≥6 months (OR=0.33, p=0.006), and using statins ≥9 months after reached CR (OR=0.44, p=0.032) had a lower incidence of LN flare, while age at onset of disease ≤20 years had a higher incidence of LN flare.
Conclusion: Despite achieving CR with standard treatment, almost half of the patients had an LN flare within a few years. Young SLE patients had an increased incidence of LN flare, the long period of induction therapy and using statins may retard a flare of the disease.
George A Karpouzas, MD
Division of Rheumatology, Harbor-UCLA Medical Center and Lundquist Institute for Biomedical Innovation, Torrance, CA, USA
Sarah R Ormseth, PhD
Division of Rheumatology, Harbor-UCLA Medical Center and Lundquist Institute for Biomedical Innovation, Torrance, CA, USA
Elizabeth R Hernandez
Division of Rheumatology, Harbor-UCLA Medical Center and Lundquist Institute for Biomedical Innovation, Torrance, CA, USA
Matthew J Budoff, MD
Division of Cardiology, Harbor-UCLA Medical Center and Lundquist Institute for Biomedical Innovation, Torrance, CA, USA
Abstract
Methods. The sample included 144 patients with complete biomarker data who underwent plaque evaluation with coronary computed tomography angiography; 95 were re-imaged within 6.9±0.3 years. Presence of >5 segments with plaque or coronary artery calcium >100 constituted extensive disease; lesions rendering >50% stenosis were considered obstructive. The Framingham 2008 cardiovascular risk score was included in all models.
Results. Hs-cTnI added to the cardiovascular risk score increased area-under-the curve (AUC) from 0.710 to 0.729 and improved prediction accuracy for baseline plaque presence [Net Reclassification Improvement =0.538 (95% confidence interval 0.143-0.895)] and Integrated Discrimination Improvement (IDI) =0.035 (0.001-0.128). In contrast, a-b2GPI-IgA did not, and the combination offered no added benefit over hs-cTnI alone. While hs-cTnI alone did not predict plaque progression, a-b2GPI-IgA presence did (p=0.005), especially in patients with >median hs-cTnI (p=0.015). In patients with >median hs-cTnI, adding a-b2GPI-IgA to a cardiovascular risk score model predicting progression from non-extensive/non-obstructive to extensive/obstructive plaque increased AUC from 0.796 to 0.878 and improved model precision [IDI=0.277 (0.011-0.946)].
Conclusion. High hs-cTnI significantly improved prediction of baseline plaque presence and may trigger an initial non-invasive coronary atherosclerosis evaluation. A-b2GPI-IgA presence may justify a follow-up interrogation in patients with non-extensive, non-obstructive plaque at baseline.
Wen Liu
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Neuroscience, Uppsala University, Uppsala, Sweden
Mark Gonn
Unit of Internal Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
Susanna von Holst
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Jessada Thutkawkorapin
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Xiang Jiao
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Jan Björk2
Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Gastroenterology section, medical unit Gastroenterology, Rheumatology and Dermatology, Karolinska University hospital, Stockholm, Sweden
Ann-Sofie Backman
Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden: Gastroenterology section, medical unit Gastroenterology, Rheumatology and Dermatology, Karolinska University hospital, Stockholm, Sweden
Kristina Lagerstedt-Robinson
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
Annika Lindblom
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
Abstract
Colorectal cancer (CRC) is a multifactorial disease, where both the environment and genetics play a role. It is estimated that approximately 35% of CRCs have a potentially identifiable genetic cause. Well-known and highly penetrant genetic causes make up less than 5% of all CRC, and leave many families not explained by known predisposing genes/mutations. Low penetrant alleles have also been thought to modify the risk of CRC. Linkage studies have been successful in discovering and localizing highly penetrant genes in CRC and risk loci has become possible to discover performing genome wide association studies (GWAS).
In this study we have analyzed families with CRC where individuals with CRC as well as individuals with premalignant lesions, adenomas, were codes as affected. In total 600 individuals in 121 families were included in the study.
In total three genomic regions were found with suggestive linkage located at 4p16.3, 6p24.3 and 10p14. These regions were further studied using sequencing analysis and association studies using haplotypes.
Anokhi Saklecha, BS
Division of Rheumatology, Allergy and Immunology University of California, San Diego, USA
Chelsey J. F. Smith, MD
Division of Rheumatology, Allergy and Immunology University of California, San Diego, USA
Abstract
Active lupus nephritis poses severe maternal and fetal risks in pregnant patients. Management in pregnancy is challenging and limited by lack of pregnancy-safe medication options. Preeclampsia is an associated maternal risk that shares many clinical features with lupus nephritis, often making it difficult to identify the primary disease process. In this report, we present a case of severe preeclampsia superimposed on active lupus nephritis in a 25-year-old pregnant female. We highlight the risks and management options for lupus nephritis in pregnancy, the overlaps in presentation between lupus nephritis and preeclampsia, and techniques to clinically distinguish between the two.
Thomas P. Olenginski, MD
Geisinger Department of Rheumatology, Danville, PA, USA
Abstract
Background: In 2008, Geisinger Rheumatology established a Fracture Liaison Service (FLS) termed HiROC (High-Risk Osteoporosis Clinic). Inpatient HiROC teams integrated with outpatient HiROC clinics.
Aim: We review the history of Geisinger HiROC, performance and lessons learned. We examine this: In a high-risk, post-fracture, drug-indicated patient without treatment contraindications, was patient treated? If a patient chose followup with Geisinger primary care physician (PCP), was that patient treated?
Results: Four Geisinger HiROC analyses are presented: 2008-2011; 2013-2015;2016; and 2017-2018. HiROC treatment rates are 80 %, 75.4 %, 74 %, and 72 %, respectively. Geisinger PCP treatment rates are 32.2 %, 13.8 %, and 14 %. (PCP data from 2017-2018 not included) 2008-2011 analysis included 888 patients, mean age 76.1, 77.6 % women and 22.4 % men. Mean 25-OH Vit. D was 25.6. Hip fractures represented 58.2 % of cohort and vertebral fractures (VF) 11.6 %. At discharge, 44.3 % went to Rehab, 31.5 % to Nursing Home (NH) and 24 % home. Six- month mortality was 14.7 % and HiROC followup 51.5 %.
2013-2015 analysis included 1279 patients with mean age of 77.8 and 74 % women, 26 % men. Hip fractures were seen in 67.6 % and VF in 6.6 % and mean 25-OH Vit. D was 25.8. Patients chose HiROC 42.6 %, 37 % HiROC patients were lost to followup, and 6 month mortality was 16 %. GHP insured 27.4 % and within GHP-insured patients, HiROC treated 74.7 % versus 19.7 % by Geisinger PCP. In 2016, we reported 380 patients, mean age 78, 69 % women, 31 % men. Hip fractures accounted for 74.5 %, VF 6.6 %, with mean 25-OH Vit.D 25.8 and 17 % six month mortality. Patients chose HiROC 46 % of time.
2017-2018 analysis included 740 patients, mean age 78, with 89 % women and 11 % men. Hip fractures accounted for 78 % and VF 6.6 %. HiROC was chosen by 45 % patients and 6-month mortality was 14 %.
Conclusions: Geisinger HiROC treated high-risk, post-fractured, drug indicated patients 72 – 80 % of time, far superior to Geisinger PCP rates of 13.8 – 32.2 %.
George A Karpouzas
Division of Rheumatology, Harbor-UCLA Medical Center and The Lundquist Institute, Torrance, CA, USA
Nicoletta Ronda
Department of Food and Drug, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy
Matthew J Budoff
Division of Cardiology, Harbor-UCLA Medical Center and The Lundquist Institute, Torrance, CA, USA
Sarah R Ormseth
Division of Rheumatology, Harbor-UCLA Medical Center and The Lundquist Institute, Torrance, CA, USA
Abstract
Methods. Coronary artery calcium, number of coronary plaques, and extensive ( 5 plaques) or obstructive (>50% stenosis) disease was evaluated with computed tomography angiography in 150 patients at baseline and 101 patients 6.9±0.4 years later. Cardiovascular events were recorded. Oxidized LDL was measured with monoclonal antibody E06. Serum cholesterol loading capacity on macrophages was measured as intracellular cholesterol content with a fluorometric assay.
Results. Abdominal obesity was not associated with per-patient number of coronary plaques or coronary artery calcium score at baseline. Low LDLc positively associated with number of plaques (b 2.13 [95% confidence interval 1.03 to 3.22]), likelihood of extensive or obstructive plaque (odds ratio 6.58, 95% confidence interval [1.63 to 26.46]), and log-transformed CAC (b 1.90 [0.89 to 2.91]) exclusively in nonobese patients (p-for-interaction <0.001, 0.061, and 0.001 respectively). Low LDLc associated with increased likelihood of >median oxidized LDL and higher ratio of cholesterol loading capacity to LDLc in nonobese patients (p-for-interaction 0.041 and 0.001 respectively). Abdominal obesity negatively associated with likelihood of plaque stenosis progression (odds ratio 0.19 [0.07 to 0.54]). Low LDLc associated with greater likelihood of per-segment plaque formation (OR 4.68 [2.26 to 9.66]) and increased stenotic severity (odds ratio 5.35 [1.62 to 17.67]) only in nonobese patients (p-for-interaction 0.002 and 0.040 respectively). Abdominal obesity was not linked to cardiovascular risk (Hazard Ratio 1.57, 95% confidence interval [0.66-3.73]). Low LDLc associated with higher cardiovascular risk in nonobese (Hazard Ratio 7.94 [1.52 to 41.36]) but not obese patients (p-for-interaction=0.017).
Conclusion. Abdominal obesity was not linked to plaque progression or cardiovascular risk in RA. Only in nonobese patients, low LDLc associated with higher atherosclerosis burden, plaque progression and cardiovascular risk. This may reflect higher oxidation and macrophage cholesterol loading capacity of LDL when LDLc is <70mg/dl.
Iman Kandil
Abstract
Background: Systemic lupus Erthymatosus (SLE) affects predominantly women of reproductive age, and can lead to both negative effect on their fertility and adverse pregnancy outcomes. Antimullerian hormone (AMH) serum levels have been found to be a reliable marker of ovarian reserve.
Objectives: This research aimed to assess ovarian reserve by measuring AMH level in premenopausal SLE patients and to study different factors that can have an effect on it, and also to evaluate pregnancy outcomes in SLE patients.
Methods: The study was performed on 60 subjects divided into 2 groups; (I): 30 SLE female patients and (II): control group which includes 30 healthy female subjects. Full history taking and examination were carried out including assessment of disease activity by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-2K) score and damage index by Systemic Lupus International Collaborating Clinics American College of Rheumatology Damage index (SLICC/ACR) on SLE patients, pregnancy questionnaire were used for taking history of the pregnancy outcomes. AMH levels were measured in both groups using AMH Gen II ELISA kits.
Results: There was no statistically significant difference between both groups as regard to median AMH levels and there was no statistically significant correlation between AMH and disease duration, BMI, SLEDAI-2K activity score, damage index and the immunosuppressive drugs such as cyclophosphamide, mycophenolate mofetil and azathioprine. There was statistically significant difference between both groups as regards to occurrence of miscarriage (P<0.0166) and hypertension in pregnancy (P<0.04).
Conclusion: From these results we can conclude that AMH values did not differ between SLE patients and healthy subjects, and the disease duration and/or activity did not affect its level. Moreover, the study reflected that immunosuppressive agents such as cyclophosphamide, azathioprine and mycophenolate mofetil did not affect the fertility in SLE patients. However, it was noted that adverse pregnancy outcomes were relatively more common in SLE patients, namely hypertension in pregnancy and miscarriages.
Wen Liu
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Neuroscience, Uppsala University, Uppsala, Sweden
Mark Gonn
Unit of Internal Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
Susanna von Holst
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Jessada Thutkawkorapin
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Xiang Jiao
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
Jan Björk2
Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Gastroenterology section, medical unit Gastroenterology, Rheumatology and Dermatology, Karolinska University hospital, Stockholm, Sweden
Ann-Sofie Backman
Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden: Gastroenterology section, medical unit Gastroenterology, Rheumatology and Dermatology, Karolinska University hospital, Stockholm, Sweden
Kristina Lagerstedt-Robinson
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
Annika Lindblom
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
Abstract
Colorectal cancer (CRC) is a multifactorial disease, where both the environment and genetics play a role. It is estimated that approximately 35% of CRCs have a potentially identifiable genetic cause. Well-known and highly penetrant genetic causes make up less than 5% of all CRC, and leave many families not explained by known predisposing genes/mutations. Low penetrant alleles have also been thought to modify the risk of CRC. Linkage studies have been successful in discovering and localizing highly penetrant genes in CRC and risk loci has become possible to discover performing genome wide association studies (GWAS).
In this study we have analyzed families with CRC where individuals with CRC as well as individuals with premalignant lesions, adenomas, were codes as affected. In total 600 individuals in 121 families were included in the study.
In total three genomic regions were found with suggestive linkage located at 4p16.3, 6p24.3 and 10p14. These regions were further studied using sequencing analysis and association studies using haplotypes.
Heberth Moran, MD
Ochsner Medical Center, Department of Endocrinology, Diabetes and Metabolism, 1514 Jefferson Highway, New Orleans, LA 70121, USA
Alfredo O. Labrada, MD
Department of Rheumatology, Nicklaus Children’s Hospital, 3100 SW 62nd Ave, Miami, FL 33155, USA
Bryan Grissett, MD
Ochsner Medical Center, Department of Endocrinology, Diabetes and Metabolism, 1514 Jefferson Highway, New Orleans, LA 70121, USA
Monica C. Chiang, MD
Southeast Louisiana Veteran Health Care System (SLVHCS) Section of Endocrinology, Diabetes and Metabolism, 2400 Canal Street, New Orleans, LA, 70119, USA
Gabriel I. Uwaifo, MD
Ochsner Medical Center, Department of Endocrinology, Diabetes and Metabolism, 1514 Jefferson Highway, New Orleans, LA 70121, USA
Abstract
Energy drinks (EDs) are a brand of non-alcoholic beverages that are typically distinguished from regular sweetened caloric beverages (SCBs) by their augmented carbohydrate and purine alkaloids/methylxanthines (usually either caffeine; 1,3,7 trimethylxanthine and/or theobromine; 3,7 dimethylxanthine) content touted as being able to boost energy levels. At initial inception they were dominantly consumed by young adults (with an initial strong male preponderance) but in the last few decades as their variety, main-stream acceptance and widespread marketing has increased their appeal and consumption has become widespread and virtually universal to the general population including virtually all age, gender and ethno-racial demographics. With increased widespread consumption concerns regarding their safety and potential impact on long term health have started being raised. This is particularly pertinent as their regulatory oversight and monitoring is often presently minimal.
Diabetes and Obesity represent two dominant halves of the global diabesity epidemic that afflicts over 650 million adults worldwide with over 40% of the adult population in the United States affected. The well documented cardiometabolic spectrum (CMS) of diseases that are associated comorbidities of diabesity are well documented and it is inevitable that the increasing consumption of EDs would involve these group of persons in adult, geriatric, adolescent and even pediatric populations.
This review summarizes and synthesizes the limited published data on the described and potential health impact of EDs use particularly in persons with and/or at risk for diabetes, obesity and other CMS diseases to make the case for need of more careful study, monitoring and scrutiny of the use of these beverages in these group of persons. After providing an overview of the history, epidemiology and major components of EDs we detail the major potential and reported systemic complications of their long-term intake especially in at risk populations discussing the modulating effects of genetics, present comorbidities and alcohol co-intake. The prominent roles of caffeine and carbohydrates in the potential poly-systemic effects of EDs and their reported toxidromes is also highlighted while acknowledging the limitations in the present body of published data in this area.
Oliver Gross, Prof, Dr
Clinic for Nephrology and Rheumatology, University Medical Center Goettingen, 37075 Goettingen, Germany
Abstract
This article reviews the circumstances why and how the pharmaceutical industry is avoiding the pediatric investigation plans for their block-buster drugs in chronic kidney diseases. The “why” is easy to answer because it is just about economic reasons. This is much to the disadvantage of sick children, who are thus deprived of the opportunity for evidence-based therapy. Just as in the time prior to the pediatric trial regulation, pediatricians remain in a legal gray zone of off-label use and expose themselves to the risk of lawsuits. The article is intended to start a discussion on how regulatory authorities could support the development of better treatment recommendations for children with kidney disease for drugs that are not promoted by the industry. This could be by working more closely with patient representatives and academia, by supporting the planning phase of investigator-initiated trials, or by scientific advice on cumulative real world and randomized controlled trial data on specific medications or substance groups.
Teresa V. Gouveia
Department of Internal Medicine, Centro Hospitalar Lisboa-Norte, Lisboa, Portugal.
Lucía B. Molinero
Department of Internal Medicine, Hospital Provincial del Centenario, Rosario, Argentina.
David A. Isenberg
Centre for Rheumatology, Department of Medicine, University College London, London, United Kingdom
Abstract
Systemic lupus erythematosus (SLE) is a life-threatening autoimmune disease, which involves the production of class-switched autoantibodies against intracellular antigens, particularly nuclear antigens, leading to tissue damage and immune complex deposition in multiple organs. Strategies for B cell modulation include direct depletion using monoclonal antibodies, such as rituximab, or indirect impairment of survival via targeting B cell activating factors, notably belimumab. While the pursuit of autoreactive B cell modulation has yielded progress, challenges persist, including modest therapeutic responses, allergic reactions and infections. Thus, to overcome these challenges and focus on achieving a more effective B cell depletion, new strategies may involve fully humanized monoclonal antibodies, such as obinutuzumab, which demonstrated promising results in the NOBILITY study, involving patients with lupus nephritis, Another approach is the use of chimeric antigen receptor T cells therapy, a strategy that has been approved for the treatment of patients with relapsed or refractory B-cell malignancies and has been shown in lupus patients to lead to a rapid and sustained breakdown of the B cell-mediated autoimmune response, reported to lead to drug-free remission of refractory SLE. In addition, combinations of existing therapies and innovative cellular approaches, such rituximab plus belimumab, have been studied. There have now been four studies describing the use of a rituximab plus belimumab in lupus nephritis and non-renal lupus. In the BEAT-LUPUS, the primary endpoint (reduction in anti-double strand DNA) was achieved, however, in BLISS-BELIEVE study the primary endpoint (Systemic Lupus Erythematosus Disease Activity Index 2000) was not met. The CALIBRATE trial was a safety study. The SynBioSe 1 study demonstrated clinical improvement, as indicated by the Systemic Lupus Erythematosus Disease Activity Index and Lupus Low Disease Activity State indices.
This review will provide a brief review of the established conventional approaches to B cell depletion and then discuss the trends towards innovative concepts aimed at achieving this goal.
W. Benjamin Nowell, PhD, MSW
Global Healthy Living Foundation, Upper Nyack, NY, USA
Jeffrey R. Curtis, MD, MS, MPH
Illumination Health, Hoover, AL, USA; University of Alabama at Birmingham, Birmingham, AL, USA
Abstract
Therapeutic Monitoring (RTM) is a new program in the United States that began in 2022 allowing electronic patient-reported outcomes (ePRO) and other patient-generated data to be reviewed by clinical staff between visits so that patients can receive clinical attention as needed. Remote Therapeutic Monitoring simultaneously enhances the capacity to generate prospective longitudinal data that may be useful for secondary research purposes. As many governmental and private insurance programs in the United States now provide reimbursement for Remote Therapeutic Monitoring, increasing numbers of rheumatologists may be incentivized to provide this service for their patient populations. Launched in 2015, the ArthritisPower® Research Registry and associated mobile and desktop application, registered with the Food & Drug Administration (FDA) as a Class I medical device, enables patients to track their disease across dozens of domains and to securely participate in voluntary research studies. ArthritisPower, in partnership with Illumination Health, has developed infrastructure and a clinical workflow for Remote Therapeutic Monitoring that will help rheumatologists more closely track their patients’ disease activity and flares, identify primary non-adherence, record changes in key health domains (e.g. fatigue, pain, physical function, mental health) and meet the needs for other data elements important for clinical care identified by individual providers. Ultimately, the approach to use digital health tools between visits seeks to improve clinical outcomes for patients with rheumatic and musculoskeletal diseases. This editorial review discusses the evolution of remote monitoring in rheumatologic care, describes the opportunities for physician reimbursement as of 2023, and provides a suggested workflow in order to establish Remote Therapeutic Monitoring within rheumatology practices.
Veronica Mezhov, Emma Guymer, Sudha Raghunath, Rangi Kandane-Rathnayake, Michelle Leech Eric, Morand Geoffrey Littlejohn
Abstract
Objective: To assess the impact of central sensitization as measured by the ‘Central Sensitivity Score’ on rheumatoid arthritis disease activity change.
Methods: This was a prospective cohort study of rheumatoid arthritis patients receiving routine clinical care. At baseline, participants had assessment of rheumatoid arthritis disease activity from a 3-variable Disease Activity Score with 28 Joint Count Erythrocyte Sedimentation Rate, symptoms of central sensitization (from central sensitivity score, the numerical score derived from the 2016 American College of Rheumatology Fibromyalgia diagnostic criteria), demographic and clinical variables. A follow-up 3-variable Disease Activity Score with 28 Joint Count Erythrocyte Sedimentation Rate was collected on the next routine clinic appointment (median 3 months). The association of central sensitivity score and change in rheumatoid arthritis disease activity was assessed using a multivariate linear regression analysis.
Results: Data were obtained from 82 participants. The median baseline 3-variable Disease Activity Score with 28 Joint Count Erythrocyte Sedimentation Rate across the cohort was 2.44. On multivariate linear regression a higher baseline central sensitivity score independently predicted improvement in 3-variable Disease Activity Score with 28 Joint Count Erythrocyte Sedimentation Rate (regression coefficient=-0.02, 95% CI [-0.08 to -0.01]). A higher C-Reactive Protein was also an independent predictor of improvement in the 3-variable Disease Activity Score with 28 Joint Count Erythrocyte Sedimentation Rate (regression coefficient -0.02, 95% CI [-0.04 to 0.01]). Exposure to a higher number of biologics predicted worsening in 3-variable Disease Activity Score with 28 Joint Count Erythrocyte Sedimentation Rate (regression coefficient=0.28, 95% CI [0.08 to 0.48]).
Conclusion: In this closely monitored cohort with relatively well-controlled disease, a higher baseline central sensitivity score was predictive of a small but not clinically meaningful change in objective rheumatoid arthritis disease activity.
Youssef Abdullah
Department of Internal Medicine, Dell Medical School. The University of Texas, 1601 Trinity St., Austin, TX 78712, USA
Rija Aziz
Department of Internal Medicine, Dell Medical School. The University of Texas, 1601 Trinity St., Austin, TX 78712, USA
Michelle M Osuna Diaz
Department of Internal Medicine, Dell Medical School. The University of Texas, 1601 Trinity St., Austin, TX 78712, USA
Lianbo Yu
Center of Biostatistics and Bioinformatics, The Ohio State University, Columbus, OH 43210
Katherine R. Sebastian
Department of Internal Medicine, Dell Medical School. The University of Texas, 1601 Trinity St., Austin, TX 78712, USA
M. Monica Giusti
Department of Food Science and Technology, The Ohio State University, Columbus, Ohio 43210
Luis Rodriguez-Saona
Department of Food Science and Technology, The Ohio State University, Columbus, Ohio 43210
Kevin V. Hackshaw
Department of Internal Medicine, Division of Rheumatology, Dell Medical School, The University of Texas, 1601 Trinity St, Austin, TX 78712, USA
Abstract
Fibromyalgia (FM) is a common, complex, and chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, and tenderness in localized areas. A multitude of other central sensitization related symptoms contribute to a profound medication burden and diminished quality of life for affected individuals. We evaluated the impacts of gender, chronicity of headache, migraine, obesity and medication burden on overall FM impact. We used the following validated questionnaires: Fibromyalgia Impact Questionnaire (FIQR), Beck Depression Inventory (BDI), Central Sensitization Inventory (CSI) and measured weight and body mass index (BMI) on a large university cohort of FM subjects. We found that female subjects with FM showed a significant increase in FIQR compared to males with FM. Additionally, we noted positive correlations between weight (Wt) and FIQR, BDI and CSI; BMI and FIQR, and BMI and CSI. Fibromyalgia subjects with a history of migraines (FM-migraine) showed statistically significant increases in FIQR, BDI and CSI compared to FM subjects with no reported history of migraines (FM-non-migraine). There was a steady increase in FIQR, BDI and CSI values with an increase in the frequency of headaches in both the FM -migraine and FM -non-migraine groups. When evaluating BMI, when comparing survey responses of overweight and obese patients to normal weight patients, all FIQR, BDI and CSI values were significantly increased in the various classes of overweight except CSI for the overweight category which appeared to approach significance (p=0.057). There were no statistically significant differences in questionnaire responses for individuals with FM on medications relative to those on no medications. Taken together, a history of migraines and headaches, frequency of headaches and obesity may impact survey responses significantly, negatively impact quality of life and correlate with higher levels of depression but medication burden did not.
Abdulsatar J Mathkhor
Basrah teaching hospital
Abdulnasser H Abdullah
Alsader Teaching Hospital
Ali H Atwan
Basrah Teaching Hospital
Zahraa Mustafa Kamel
Basrah Teaching Hospital
Abstract
Background: Levels of Vitamin D may impact the development and progression of knee osteoarthritis (OA), a disorder common in elderly people The aim of this study was to investigate the association between serum Vitamin D deficiency and knee OA.
Methods: One hundred twenty (40 male and 80 female) consecutive patients were recruited from the rheumatology outpatient clinic for the study. X-rays in two anterior-posterior and lateral views of the knees were performed for all patients. Staging of knee OA was done according to Kellgren-Lawrence criteria and divided into two groups; group A consisting of grades 1 and 2, and group B, consisting of grades 3 and 4. One hundred (30 male and 70 female) healthy individuals without clinical and radiographic signs of the disease were defined as a control group. Hematological and biochemical investigations, including measurement of 25-hydroxyvitamin D serum level, were performed for all participants. Pain intensity using a visual analog scale (VAS) and disease severity using the Western Ontario and McMaster Universities Arthritis Index was measured for all patients.
Results: The mean age of patients and controls were 60±3.5 and 54±2.6 years, respectively. Vitamin D levels of patients and controls were 13±3.3 and 32±2.5, respectively. More severe disease and diseases with prolonged duration were associated with a lower vitamin D level, and low vitamin D levels were associated with high VAS and WOMAC.
Conclusion: Vitamin D deficiency was associated with the development and the severity of knee OA as well as with the disease duration.
Howard J. M. Warren
Centre for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada
Gabriela Ioachim
Centre for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada
Gabriela Ioachim
Centre for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada
Jocelyn M. Powers
Centre for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada
Roland Staud
Division of Rheumatology, Department of Medicine, University of Florida, Gainesville, Florida, USA
Caroline Pukall
Centre for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada; Department of Psychology, Queen’s University, Kingston, Ontario, Canada
Patrick W. Stroman
Centre for Neuroscience Studies, Queen’s University, Kingston, Ontario, Canada; Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, Ontario, Canada; Department of Physics, Queen’s University, Kingston, Ontario, Canada
Abstract
Participants with fibromyalgia (FM) and healthy controls (HC) experienced an identical ‘threat/safety’ experimental pain paradigm while undergoing functional magnetic resonance imaging (fMRI) to investigate the differences in pain processing between the two groups. In the ‘threat’ (Pain) imaging runs, participants were told that they would receive noxious heat stimuli to their right hands, calibrated to elicit subjectively moderate levels of pain. In the ‘safety’ (No-Pain) imaging runs, no stimulus was given. This design enabled the study of both continuous and reactive components of pain processing, as well as brain activity associated with anticipation and reward. The fMRI data were analyzed with a data-driven structural equation modeling approach, and significant group-level connectivity differences were identified in both study conditions, in both time periods of interest (Expectation, Stimulation). Group-level connectivity differences in the No-Pain condition occurred mainly during the expectation of pain, and involved regions associated with emotion and reward, suggesting FM may involve altered affective/reward processing. Group-level connectivity differences in the Pain condition occurred mainly during stimulation, with the FM group having decreased connectivity between the anterior cingulate cortex (ACC) and the amygdala, and increased connectivity between the posterior cingulate cortex (PCC) and the thalamus. The decreased ACC→Amygdala connectivity supports previous findings, suggesting FM likely involves altered responses in motivational-affective aspects of pain processing. The increased PCC→Thalamus connectivity may suggest the FM group experienced heightened saliency toward the noxious stimuli, which may contribute toward the mechanism which causes hyperalgesia in FM.
Imre Lázár
Semmelweis University, Institute of Behavioral Sciences, Medical Humanities Research Group, Budapest; Károli Gáspár University of Reformed Church, Institute of Social and Communication Sciences, Budapest
Abstract
Psoriasis is a common immune-mediated inflammatory disease that can often be associated with psychiatric problems such as depression and anxiety. Although psychiatric disorders were initially considered secondary, the high prevalence suggests that common pathophysiological mechanisms may be involved in the development of psoriasis and psychiatric disorders. The shared neuroendocrine and immune mediators weave a web of networks with bidirectional pathways. Biopsychosocial patterns of psoriasis include psychological and behavioral consequences influencing personal social networks, psychological dispositions, and brain-skin psychoimmunological network patterns, which sums in a network of networks. The pathodynamics of other organ diseases like diabetes, liver diseases, internal organ tumors, and latent long-term inflammatory processes (chronic tonsillitis, prostatitis, abscesses and inflammations in the gums, chronic sinusitis) influence psoriasis. Vice versa, psoriasis might cause a pathological impact on other organ systems via networked connections, like arthritis or psychological dispositions. Treatment of psoriasis needs networking through the cooperation of dermatology, rheumatology, and psychiatry and by combining different therapies.
