Vertebral fractures are increased in rheumatoid arthritis despite recent therapeutic advances: a case-control study.

Prevalence and risk factors of vertebral fractures in postmenopausal RA women were assessed in 323 patients and compared with 660 age-matched women. Of patients, 24.15% had at least one vertebral fracture vs.16.06% of controls. Age, glucocorticoids and falls were the main fracture risks. Vertebral fractures were associated with disease severity. INTRODUCTION: There is little quality data on the updated prevalence of fractures in rheumatoid arthritis (RA) that may have changed due to advances in the therapeutic strategy in recent years. This study was aimed at analysing the prevalence and risk factors of vertebral fractures in postmenopausal women with RA and comparing it with that of the general population. METHODS: We included 323 postmenopausal women diagnosed with RA from 19 Spanish Rheumatology Departments, randomly selected and recruited in 2018. Lateral radiographs of the thoracic and lumbar spine were obtained to evaluate morphometric vertebral fractures and the spinal deformity index. We analysed subject characteristics, factors related to RA, and fracture risk factors. The control group consisted of 660 age-matched Spanish postmenopausal women from the population-based Camargo cohort. RESULTS: Seventy-eight (24.15%) RA patients had at least one vertebral fracture. RA patients had increased fracture risk compared with controls (106 of 660, 16.06%) (p = 0.02). Logistic regression analysis showed that age (OR 2.17; 95% CI 1.27-4.00), glucocorticoids (OR 3.83; 95% CI 1.32-14.09) and falls (OR 3.57; 95% CI 1.91-6.86) were the independent predictors of vertebral fractures in RA patients. The subgroup with vertebral fractures had higher disease activity (DAS28: 3.15 vs. 2.78, p = 0.038) and disability (HAQ: 0.96 vs. 0.63, p = 0.049), as compared with those without vertebral fractures. CONCLUSION: The risk of vertebral fracture in RA is still high in recent years, when compared with the general population. The key determinants of fracture risk are age, glucocorticoids and falls. Patients with vertebral fractures have a more severe RA.

SCRT1 is a novel beta cell transcription factor with insulin regulatory properties.

Here we show that scratch family transcriptional repressor 1 (SCRT1), a zinc finger transcriptional regulator, is a novel regulator of beta cell function. SCRT1 was found to be expressed in beta cells in rodent and human islets. In human islets, expression of SCRT1 correlated with insulin secretion capacity and the expression of the insulin (INS) gene. Furthermore, SCRT1 mRNA expression was lower in beta cells from T2D patients. siRNA-mediated Scrt1 silencing in INS-1832/13 cells, mouse- and human islets resulted in impaired glucose-stimulated insulin secretion and decreased expression of the insulin gene. This is most likely due to binding of SCRT1 to E-boxes of the Ins1 gene as shown with ChIP. Scrt1 silencing also reduced the expression of several key beta cell transcription factors. Moreover, Scrt1 mRNA expression was reduced by glucose and SCRT1 protein was found to translocate between the nucleus and the cytosol in a glucose-dependent fashion in INS-1832/13 cells as well as in a rodent model of T2D. SCRT1 was also regulated by a GSK3ß-dependent SCRT1-serine phosphorylation. Taken together, SCRT1 is a novel beta cell transcription factor that regulates insulin secretion and is affected in T2D.

Management of Psoriasis During Preconception, Pregnancy, Postpartum, and Breastfeeding: A Consensus Statement. / Consenso sobre las actuaciones a seguir durante la edad fértil, el embarazo, el posparto y la lactancia en pacientes con psoriasis.

OBJECTIVE: To develop evidence- and experience-based recommendations for the management of psoriasis during preconception, pregnancy, postpartum, and breastfeeding. METHODS: The nominal group technique and the Delphi method were used. Fifteen experts (12 dermatologists, 2 of whom were appointed coordinators; 1 rheumatologist; and 2 gynecologists) were selected to form an expert panel. Following a systematic review of the literature on fertility, pregnancy, postpartum, and breastfeeding in women with psoriasis, the coordinators drew up a series of preliminary recommendations for discussion by the panel at a nominal group meeting. The experts defined the scope, sections, and intended users of the statement and prepared a final list of recommendations. Consensus was obtained using a Delphi process in which an additional 51 dermatologists rated their level of agreement with each recommendation on a scale of 1 (total disagreement) to 10 (total agreement). Consensus was defined by a score of 7 or higher assigned by at least 70% of participants. Level of evidence and strength of recommendation were reported using the Oxford Center for Evidence-Based Medicine categories. The final statement was approved by the expert panel. RESULTS: The resulting consensus statement includes 23 recommendations on preconception (fertility and contraception), pregnancy (planning, pharmacological management, and follow-up), and breastfeeding (management and follow-up). Consensus was achieved for all recommendations generated except one. CONCLUSIONS: These recommendations for the better management of psoriasis in women of childbearing age could improve outcomes and prognosis.

Ghrelin suppresses insulin secretion in human islets and type 2 diabetes patients have diminished islet ghrelin cell number and lower plasma ghrelin levels.

It is not known how ghrelin affects insulin secretion in human islets from patients with type 2 diabetes (T2D) or whether islet ghrelin expression or circulating ghrelin levels are altered in T2D. Here we sought out to identify the effect of ghrelin on insulin secretion in human islets and the impact of T2D on circulating ghrelin levels and on islet ghrelin cells. The effect of ghrelin on insulin secretion was assessed in human T2D and non-T2D islets. Ghrelin expression was assessed with RNA-sequencing (n = 191) and immunohistochemistry (n = 21). Plasma ghrelin was measured with ELISA in 40 T2D and 40 non-T2D subjects. Ghrelin exerted a glucose-dependent insulin-suppressing effect in islets from both T2D and non-T2D donors. Compared with non-T2D donors, T2D donors had reduced ghrelin mRNA expression and 75% less islet ghrelin cells, and ghrelin mRNA expression correlated negatively with HbA1c. T2D subjects had 25% lower fasting plasma ghrelin levels than matched controls. Thus, ghrelin has direct insulin-suppressing effects in human islets and T2D patients have lower fasting ghrelin levels, likely as a result of reduced number of islet ghrelin cells. These findings support inhibition of ghrelin signaling as a potential therapeutic avenue for stimulation of insulin secretion in T2D patients.

A systematic review on the optimum management of the use of methotrexate in rheumatoid arthritis patients in the perioperative period to minimize perioperative morbidity and maintain disease control.

OBJECTIVE: To examine the use of metho-trexate (MTX) in rheumatoid arthritis (RA) patients during the perioperative period. METHODS: Systematic review of studies retrieved by a sensitive search strategy in Medline (1961-July 2007), Embase (1961-July 2007), Cochrane Library (up to July 2007), and from the abstracts of the ACR (2005, 2006) and EULAR (2005-2007) annual scientific meetings. SELECTION CRITERIA: (population) studies had to include patients with RA undergoing surgery; (intervention and control) studies had to test continuing MTX versus stopping MTX; and (outcomes), studies had to report complications within a year after the surgery including infections, wound morbidity, surgery complications, and RA flares. Only randomized controlled trials (RCT) or high quality cohort studies with a control group were included. RESULTS: Patients from the four included studies were mostly women with mean ages around 60. All of them underwent elective orthopaedic surgery and were taking MTX doses mainly from 5 mg/week to 10 mg/week. By order of level of evidence, we found two RCTs, in which continuing on MTX was not associated with increasing risk of surgery complications, but it was statistically associated with less RA flares. In a prospective cohort study, four infections were observed in the MTX group while none were observed in the control group. No disease flare was reported in any group. A retrospective study showed that patients on MTX reported fewer cases of wound morbitity (p=0.038), RA flares (p=0.050), and no differences related to infections compared to those who stopped MTX. CONCLUSIONS: Continuing with low doses of MTX seems to be a safe option during the perioperative period in RA patients without relevant comorbidities and/or risk factors of infections, undergoing elective orthopaedic surgery, while maintaining disease control.

Systematic review on the safety of methotrexate in rheumatoid arthritis regarding the reproductive system (fertility, pregnancy, and breastfeeding).

OBJECTIVE: To analyze the safety of methotrexate (MTX) in rheumatoid arthritis (RA) regarding the reproductive system (fertility, pregnancy, and breastfeeding). METHODS: Systematic review of studies retrieved by a sensitive search strategy in Medline (1961 - October 2007), Embase (1961 - October 2007), Cochrane Library (up to October 2007), and from the abstracts of the ACR (2005, 2006) and EULAR (2005 - 2007) annual scientific meetings. SELECTION CRITERIA: a) population: studies had to include patients with RA; b) intervention and control: discontinuation of MTX or elective abortion versus continuation of MTX or continuing pregnancy; and c) outcomes: infertility, oligospermia, reversibility, miscarriages, malformations, premature babies, healthy newborn, percent of the dose of MTX that passes to human milk, adverse effects in the lactating child. There was no limitation regarding study design, except for case reports, or language. RESULTS: MTX and pregnancy: we selected 6 articles for detailed evaluation from 847 initial ones from the literature search. They were descriptions of cases obtained from searching retrospectively clinical databases of individual centers or from surveys. Patients had been exposed to MTX at doses used in rheumatology (5-25 mg/w), from conception to first trimester of pregnancy. Total number of MTX exposed pregnancies is 101, and the pooled outcomes (elective abortion not included): 19 miscarriages (23% of pregnancies); 55 live births (66% of pregnancies); and 5 of them had minor neonatal malformations (5% of pregnancies). The rate of induced abortions is 18%. MTX and lactation and fertility: no articles fulfilled the selection criteria. There is indirect evidence on the excretion of MTX in human milk and probably of reversible infertility from case reports. CONCLUSIONS: This review exposes the shortage of data on the safety and risks of MTX during conception, pregnancy and lactation at the doses commonly used in rheumatology. MTX and pregnancy: there is not sufficient evidence to support whether it is MTX or the disease what underlies miscarriage in these patients. Pooling the data from the studies included, the rates of miscarriages and of birth defects are similar to the rates observed in healthy population. MTX and lactation and fertility: there is absence of confirming evidence.

Multinational evidence-based recommendations for the use of methotrexate in rheumatic disorders with a focus on rheumatoid arthritis: integrating systematic literature research and expert opinion of a broad international panel of rheumatologists in the 3E Initiative.

OBJECTIVES: To develop evidence-based recommendations for the use of methotrexate in daily clinical practice in rheumatic disorders. METHODS: 751 rheumatologists from 17 countries participated in the 3E (Evidence, Expertise, Exchange) Initiative of 2007-8 consisting of three separate rounds of discussions and Delphi votes. Ten clinical questions concerning the use of methotrexate in rheumatic disorders were formulated. A systematic literature search in Medline, Embase, Cochrane Library and 2005-7 American College of Rheumatology/European League Against Rheumatism meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford levels of evidence. Each country elaborated a set of national recommendations. Finally, multinational recommendations were formulated and agreement among the participants and the potential impact on their clinical practice was assessed. RESULTS: A total of 16 979 references was identified, of which 304 articles were included in the systematic reviews. Ten multinational key recommendations on the use of methotrexate were formulated. Nine recommendations were specific for rheumatoid arthritis (RA), including the work-up before initiating methotrexate, optimal dosage and route, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy and management in the perioperative period and before/during pregnancy. One recommendation concerned methotrexate as a steroid-sparing agent in other rheumatic diseases. CONCLUSIONS: Ten recommendations for the use of methotrexate in daily clinical practice focussed on RA were developed, which are evidence based and supported by a large panel of rheumatologists, enhancing their validity and practical use.

Fístula arteriovenosa radial oscilante / An oscillating radial arteriovenous fistula

Introducción. Las fístulas arteriovenosas de aparición espontánea constituyen una patología vascular poco frecuente. Caso clínico. Varón de 44 años, trabajador de la construcción sin antecedentes traumáticos, que presentó una tumoración pulsátil en la muñeca izquierda. Un estudio con eco-Doppler evidencia la existencia de una fístula arteriovenosa en la arteria radial. Posteriormente se realiza una arteriografía que fue normal, y tras ella desaparece la clínica del paciente. Al cabo de tres semanas reaparece y un nuevo eco-Doppler informa de la existencia de una fístula arteriovenosa. Se realiza otra arteriografía y también una flebografia; ambas son normales, y también desaparece la clínica tras los procedimientos. Se realiza un eco-Doppler, y es normal. Al cabo de tres semanas reaparece nuevamente la tumoración y un eco-Doppler confirma los diagnósticos anteriores. También se realiza una angiotomografía computarizada que sugiere la existencia de una fístula arteriovenosa. El paciente fue intervenido quirúrgicamente, y se pudo ver un plexo venoso alrededor de la arteria radial muy dilatado y con paredes arterializadas, que se le extirpó. El estudio anatomopatológico informó de la existencia de estructuras vasculares de pequeño y mediano calibre con morfología de arteria (AU)