The Incidence and Predictors of Solid- and Hematological Malignancies in Patients with Giant Cell Arteritis: A Large Real-World Database Study

Background: The association between giant cell arteritis (GCA) and malignancies had been widely investigated with studies reporting conflicting results. Therefore, in this study, we aimed to investigate this association using a large nationwide electronic database. Methods: This study was designed as a retrospective cohort study including GCA patients first diagnosed between 2002–2017 and age, sex and enrollment time-matched controls. Follow-up began at the date of first GCA-diagnosis and continued until first diagnosis of malignancy, death or end of study follow-up. Results: The study enrolled 7213 GCA patients and 32,987 age- and sex-matched controls. The mean age of GCA diagnosis was 72.3 (SD 9.9) years and 69.1% were women. During the follow-up period, 659 (9.1%) of GCA patients were diagnosed with solid malignancies and 144 (2.0%) were diagnosed with hematologic malignancies. In cox-multivariate-analysis the risk of solid- malignancies (HR = 1.12 [95%CI: 1.02–1.22]), specifically renal neoplasms (HR = 1.60 [95%CI: 1.15–2.23]) and sarcomas (HR = 2.14 [95%CI: 1.41–3.24]), and the risk of hematologic malignancies (HR = 2.02 [95%CI: 1.66–2.47]), specifically acute leukemias (HR = 1.81 [95%CI: 1.06–3.07]), chronic leukemias (HR = 1.82 [95%CI: 1.19–2.77]), Hodgkin’s lymphomas (HR = 2.42 [95%CI: 1.12–5.20]), non-Hodgkin’s-lymphomas (HR = 1.66: [95%CI 1.21–2.29]) and multiple myeloma(HR = 2.40 [95%CI: 1.63–3.53]) were significantly increased in GCA patients compared to controls. Older age at GCA-diagnosis (HR = 1.36 [95%CI: 1.25–1.47]), male-gender (HR = 1.46 [95%CI: 1.24–1.72]), smoking (HR = 1.25 [95%CI: 1.04–1.51]) and medium-high socioeconomic status (HR = 1.27 [95%CI: 1.07–1.50]) were independently associated with solid malignancy while age (HR = 1.47 [95%CI: 1.22–1.77]) and male-gender (HR = 1.61 [95%CI: 1.14–2.29]) alone were independently associated with hematologic- malignancies. Conclusion: our study demonstrated higher incidence of hematologic and solid malignancies in GCA patients. Specifically, leukemia, lymphoma, multiple myeloma, kidney malignancies, and sarcomas. Age and male gender were independent risk factors for hematological malignancies among GCA patients, while for solid malignancies, smoking and SES were risk factors as well

From Psoriasis to Psoriatic Arthritis: Decoding the Impact of Treatment Modalities on the Prevention of Psoriatic Arthritis

Introduction Biologic therapies are licensed for both psoriasis (PsO) and psoriatic arthritis (PsA) with some electronic medical record data suggest that IL (Interleukin)-23 blockers might be more protective in PsA prevention than TNF blockers; however, the findings have been inconsistent. Higher Psoriasis Area and Severity Index (PASI) scores have also been linked to an increased PsA risk. To clarify these unresolved issues we investigated biologic agents, methotrexate, phototherapy, and topical therapy for PsA prevention in patients with psoriasis. Methods This retrospective cohort study analyzed data from 58,671 patients with psoriasis from the Israeli Meuhedet Health Services Organization database was evaluated for incident PsA. Patients were categorized on the basis of treatment: group 1, topical therapy; group 2, phototherapy; group 3, conventional disease-modifying antirheumatic drugs (cDMARDs; methotrexate); group 4, biologic DMARDs which was also stratified according to biologic class. Results The PsA incidence rate was lower in the biologic agents’ group versus the methotrexate group (HR 0.46 [95% CI 0.35–0.62]). The incidence rates per 100 person-years varied across biologic treatment groups, with the anti‑IL‑12/23 or anti‑IL‑23p19 group at 4.57, the anti-IL-17 group at 4.35, and the TNF inhibitor group at 2.55. No differences were found between various biological agents in terms of preventing PsA. The phototherapy group exhibited a higher PsA development rate than the topical therapy group (HR 1.85 [95% CI 1.65–2.07]). Conclusion Biological agents are more effective than methotrexate in reducing incident PsA in patients with psoriasis. This lower rate of PsA on topical therapy compared to phototherapy supports the importance of psoriasis severity as a risk factor

Increased risk of osteoporosis and femoral neck fractures in patients with familial Mediterranean fever—a large retrospective cohort study

Objectives The direct impact of inflammatory conditions and their therapy with corticosteroids contribute to an increased risk of osteoporosis with associated fractures. Familial Mediterranean fever (FMF) is an autoinflammatory disorder not commonly treated with corticosteroids. Evidence regarding FMF association with osteoporosis and femur fractures is anecdotal. We aimed to evaluate the incidence and risk of osteoporosis and femoral neck fracture in FMF patients compared with the general population. Methods A retrospective cohort study using the electronic database of Clalit Health Services of all FMF patients first diagnosed between 2000 and 2016 and controls was conducted including age- and sex-matched controls in a 1:1 ratio. Follow-up continued until the first diagnosis of osteoporosis or fracture. Risk for these conditions was compared using univariate and multivariate Cox regression models. Results A total of 9769 FMF patients were followed for a median period of 12.5 years. Of these, 304 FMF patients were diagnosed with osteoporosis compared with 191 controls, resulting in an incidence rate (per 10 000 persons-years) of 28.8 and 17.8, respectively, and a crude hazard ratio of 1.62 (95% CI 1.35, 1.93; P < 0.001). Patients were diagnosed with osteoporosis at a considerably younger age than controls [60.1 (s.d. 12.4) vs 62.5 (s.d. 11.0) years; P = 0.028]. A total of 56 FMF patients were diagnosed with femoral neck fracture compared with 35 controls, resulting in an incidence rate of 5.3 and 3.3, respectively, and a crude HR of 1.60 (95% CI 1.05, 2.44; P < 0.05). Conclusion FMF patients are at increased risk for osteoporosis and consequently femur fracture. Our findings emphasize the importance of considering bone health in the management of FMF patients

Temporal stability of the rumen microbiota in beef cattle, and response to diet and supplements

Acknowledgements Sampling of ruminal digesta was carried out at Scotland’s Rural College (SRUC) by Laura Nicoll, Lesley Deans and Claire Broadbent. Sequencing using Illumina MiSeq was carried out by Edinburgh Genomics, The University of Edinburgh. Edinburgh Genomics is partly supported through core grants from NERC (R8/H10/56), MRC (MR/K001744/1) and BBSRC (BB/J004243/1). Data were processed using the Maxwell High Performance Computing Cluster of the University of Aberdeen IT Service (www.abdn.ac.uk/staffnet/research/hpc.php), provided by Dell Inc. and supported by Alces Software. Funding This work was funded by the Rural and Environment Science and Analytical Services Division (RESAS) of the Scottish Government as a collaborative HEI project between The University of Aberdeen, The Roslin Institute, and Scotland’s Rural College (SRUC). The funding body had no role in the design of the study or collection, analysis, or interpretation of data or in writing the manuscript.Peer reviewedPublisher PD

Farming amphetamines: Khat (Catha edulis Forsk) a traditional plant with psychoactive and medicinal properties

Khat (Catha edulis Forsk., Celastraceae) is a flowering perennial shrub with a long history of use and cultivation in East Africa and the Arabian Peninsula. Young khat leaves are traditionally chewed in social gatherings to attain special states of mind, aimed especially at awakeness and enhanced mind focus. Since khat chewing contains amphetamine-like molecules and reponedly causes addiction among users it is banned in most countries, but it is part of social life and legal in some countries. The main phannacoactive compounds present in khat leaves are the phenylpropylamino alkaloids (S) cathinone and (S)-cathine. L-Phenylalan:ine serves as a key biosynthetic precursor of phenylpropylalkaloids. Phenylalanine is converted by a series of not yet fully characterized reactions involving chain-shortening to benzaldehyde, then ligation to decarboxylated pyruvate, oxidation and incorporation of an amino group to yield (S)-cath inone, the most active compound accumulating in young leaves. (S)-Cathinone is subsequently reduced to (S)-cathine, the main compound accumulated in mature leaves, but pharmacologically less active than (S)-cathinone. The pharmacological prospects of khat uses and some personal experiences of one of the authors in khat chewing are described here