Antirheumatic drugs and reproduction in women and men with chronic arthritis.

The impact of rheumatic disease on fertility and reproduction can be remarkable. Many disease-related factors can influence patients' sexual functioning, perturb fertility and limit family planning. Antirheumatic pharmacological treatment can also have a crucial role in this field. Proper counselling, preferably provided by a multidisciplinary team of rheumatologists, obstetricians, gynaecologists and neonatologists, is recommended for patients taking antirheumatic drugs, not only at the beginning, but also during the course of treatment. Paternal exposure to antirheumatic drugs was not found to be specifically associated with congenital malformation and adverse pregnancy outcome, therefore discontinuation of these drugs while planning for conception should be weighed against the risk of disease flare. Drugs in Food and Drug Administration (FDA) category 'X' should be withdrawn in a timely manner in women who desire a pregnancy. Meanwhile, disease control can be achieved with anti-tumour necrosis factor (TNF)-α agents, which are not teratogenic drugs. If maternal disease control is permissive, they can be stopped as soon as the pregnancy test turns positive and be resumed during pregnancy in case of a flare

Update on safety during pregnancy of biological agents and some immunosuppressive anti-rheumatic drugs

A consensus paper concerning the interaction of anti-rheumatic drugs and reproduction was published in 2006, representing data collected during the year 2004 and 2005. Because of an increasing use of biological agents in women of fertile age, the information was updated for the years 2006 and 2007. Experts disagree whether TNF-inhibitors should be stopped as soon as pregnancy is recognized or may be continued throughout pregnancy. Pregnancy experience with abatacept and rituximab is still too limited to prove their safety for the developing fetus. They must be withdrawn before a planned pregnancy. LEF has not been proven to be a human teratogen. Registries of transplant recipients have shown that cyclosporin (CsA) and tacrolimus do not increase the rate of congenital anomalies, whereas mycophenolate mofetil (MMF) clearly carries a risk for congenital anomalies. Prophylactic withdrawal of drugs before pregnancy is mandatory for abatacept, rituximab, LEF and MMF. Data remain insufficient for gonadal toxicity of immunosuppressive drugs in men and for excretion of these drugs in human breast mil

Update on safety during pregnancy of biological agents and some immunosuppressive anti-rheumatic drugs

A consensus paper concerning the interaction of anti-rheumatic drugs and reproduction was published in 2006, representing data collected during the year 2004 and 2005. Because of an increasing use of biological agents in women of fertile age, the information was updated for the years 2006 and 2007. Experts disagree whether TNF-inhibitors should be stopped as soon as pregnancy is recognized or may be continued throughout pregnancy. Pregnancy experience with abatacept and rituximab is still too limited to prove their safety for the developing fetus. They must be withdrawn before a planned pregnancy. LEF has not been proven to be a human teratogen. Registries of transplant recipients have shown that cyclosporin (CsA) and tacrolimus do not increase the rate of congenital anomalies, whereas mycophenolate mofetil (MMF) clearly carries a risk for congenital anomalies. Prophylactic withdrawal of drugs before pregnancy is mandatory for abatacept, rituximab, LEF and MMF. Data remain insufficient for gonadal toxicity of immunosuppressive drugs in men and for excretion of these drugs in human breast mil

Combined Effects of Age and Comorbidities on Electrocardiographic Parameters in a Large Non-Selected Population

Background: Previous studies have evaluated average electrocardiographic (ECG) values in healthy subjects or specific subpopulations. However, none have evaluated ECG average values in not selected populations, so we examined ECG changes with respect to age and sex in a large primary population. Methods: From digitized ECG stored from 2008 to 2021 in the Modena province, 130,471 patients were enrolled. Heart rate, P, QRS and T wave axis, P, QRS and T wave duration, PR interval, QTc, and frontal QRS-T angle were evaluated. Results: All ECG parameters showed a dependence on age, but only some of them with a straight-line correlation: QRS axis (p < 0.001, R2 = 0.991, r = 0.996), PR interval (p < 0.001, R2 = 0.978, r = 0.989), QTc (p < 0.001, R2 = 0.935, r = 0.967), and, in over 51.5 years old, QRS-T angle (p < 0.001, R2 = 0.979, r = 0.956). Differences between females and males and in different clinical settings were observed. Conclusions: ECG changes with ageing are explainable by intrinsic modifications of the heart and thorax and with the appearance of cardiovascular diseases and comorbidities. Age-related reference values were computed and applicable in clinical practice. Significant deviations from mean values and from Z-scores should be investigated

Polarization of TH2 response is decreased during pregnancy in systemic lupus erythematosus

This study evaluated some cytokines involved in the Th1-Th2 shift during pregnancy in patients with systemic lupus erythematosus (SLE) and healthy women. Twenty-seven consecutive successful pregnancies in 26 SLE patients and 28 pregnancies in 28 matched healthy subjects, as controls, were enrolled and prospectively studied. Sera obtained at first and third trimesters of pregnancy were tested for IL-1α, IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12p70, INF-γ, and TNF-α with a highly sensitive, multiplexed sandwich ELISA (SearchLight Human Inflammatory Cytokine Array). Statistics were performed by SPSS package. IL-8 serum levels were higher in the first (P<0.0001) and third (P=0.003) trimesters of pregnancy in SLE patients compared with controls, INF-γ serum levels in the third trimester (P=0.009), and IL-10 serum levels in the first and third trimesters (P=0.055 and P<0.0001, respectively). IL-2 (r=0.524 P=0.010), IL-12 (r=0.549 P=0.007), IFN-γ (r=0.492 P=0.017), and IL-6 (r=0.515 P=0.020) serum levels correlated with disease activity in SLE patients in the first trimester of pregnancy. Cytokine profile was similar in patients with and without lupus nephritis both in the first and in the third trimesters of pregnancy. IL-8 serum levels were lower in patients with a previous diagnosis of antiphospholipid antibody syndrome compared with those without, both in the first and in the third trimesters of pregnancy. In SLE patients, a lower than expected decrease in Th1 cytokine serum levels was observed in the third trimester of gestation which could contribute to a lower Th2 cytokine polarization during pregnancy

Design and proof of concept for multi degree of freedom hydrostatically coupled dielectric elastomer actuators with roto-translational kinematics for object handling

In this article we present an upgraded design of the existing push-pull hydrostatically coupled dielectric elastomer actuator (HC-DEA) for use in the field of soft manipulators. The new design has segmented electrodes, which stand as four independent elements on the active membrane of the actuator. When properly operated, the actuator can generate both out of plane and in-plane motions resulting in a multi-degrees of freedom soft actuator able to exert both normal pushes (like a traditional HC-DEA) and tangential thrusts. This novel design makes the actuator suitable for delicate flat object transportation. In order to use the actuator in soft systems, we experimentally characterized its electromechanical transduction and modeled its contact mechanics. Finally, we show that the proposed actuator can be employed as a modular unit to develop active surfaces for flat object roto-translation. © 2018 IOP Publishing Ltd

Reduced T-cell repertoire restrictions in abatacept-treated rheumatoid arthritis patients.

BACKGROUND: CD28(neg) T cells, which display functional characteristic of oligoclonally expanded cytotoxic memory T lymphocytes, are believed to be pathologically relevant in rheumatoid arthritis manifestation. The CD28 co-stimulation blockade by abatacept can prevent the generation of CD28(neg) T-cell populations in these patients. METHODS: Samples were obtained before and after 12 months of abatacept therapy. T-cell phenotype and T-cell receptor diversity were evaluated by flow cytometry and complementarity-determining region-3 spectratyping, respectively, while telomerase reverse-transcriptase gene level was measured by real-time PCR. RESULTS: Abatacept induces a decrease of the percentage and number of CD4(+)CD28(neg) T cells and a reduction of T-cell repertoire restrictions; these features are directly correlated. Thymic output and telomerase activity are not modified by the therapy. CONCLUSIONS: Abatacept-induced decrease of peripheral T-cell repertoire restrictions can due to a reduced generation of senescent, chronically stimulated CD4(+)CD28(neg) T cells