2019 update of the EULAR recommendations for the management of systemic lupus erythematosus.

Our objective was to update the EULAR recommendations for the management of systemic lupus erythematosus (SLE), based on emerging new evidence. We performed a systematic literature review (01/2007-12/2017), followed by modified Delphi method, to form questions, elicit expert opinions and reach consensus. Treatment in SLE aims at remission or low disease activity and prevention of flares. Hydroxychloroquine is recommended in all patients with lupus, at a dose not exceeding 5 mg/kg real body weight. During chronic maintenance treatment, glucocorticoids (GC) should be minimised to less than 7.5 mg/day (prednisone equivalent) and, when possible, withdrawn. Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of GC. In persistently active or flaring extrarenal disease, add-on belimumab should be considered; rituximab (RTX) may be considered in organ-threatening, refractory disease. Updated specific recommendations are also provided for cutaneous, neuropsychiatric, haematological and renal disease. Patients with SLE should be assessed for their antiphospholipid antibody status, infectious and cardiovascular diseases risk profile and preventative strategies be tailored accordingly. The updated recommendations provide physicians and patients with updated consensus guidance on the management of SLE, combining evidence-base and expert-opinion.

Brain ventricular dimensions and relationship to outcome in adult patients with bacterial meningitis.

BACKGROUND: Experimental studies suggest that changes in brain ventricle size are key events in bacterial meningitis. This study investigated the relationship between ventricle size, clinical condition and risk of poor outcome in patients with bacterial meningitis. METHODS: Adult patients diagnosed with bacterial meningitis admitted to two departments of infectious diseases from 2003 through 2010 were identified. Clinical and biochemical data as well as cerebral computed tomographic images were collected. The size of the brain ventricles were presented as a Ventricle to Brain Ratio (VBR). Normal range of VBR was defined from an age matched control group. A multivariate analysis was performed to identify predictors of 30-day mortality. RESULTS: One hundred and seven patients were included. Eighty-one patients had a CT scan at the time of diagnosis. VBR was identified as an independent risk factor of 30-day mortality, Mortality Rate Ratio: 6.03 (95 % confidence interval: 1.61-22.64, p = 0.008) for highest versus lowest tertile. A VBR deviating more than 2 standard deviations from the normal range was associated with increased mortality. CONCLUSIONS: Brain ventricles are commonly subject to marked changes in size as a consequence of meningitis. Increased brain ventricle size in the acute phase of bacterial meningitis was associated with increased mortality.

Effects of acute clonidine administration on power spectral analysis of heart rate variability in healthy humans.

1. To investigate the relationship between the autonomic drive to the heart and heart rate variability, as evaluated by power spectral analysis, we studied the effect of clonidine (300 microg), a central sympatholytic agent, on heart rate variability. 2. Six healthy subjects (mean age 31 +/- 3 years) were studied in the supine and the sitting position (15 min each) on two different occasions, respectively, before and after clonidine administration. Using an autoregressive approach, the low frequency (LF) and the high frequency (HF) components of power spectral analysis were measured, and their ratio was calculated. Blood pressure was monitored throughout the study and plasma catecholamines were measured at the end of each period. 3. Before clonidine, assumption of the sitting position induced increases in LF, LF/HF ratio, blood pressure and plasma noradrenaline. Clonidine induced remarkable reductions in the normalized values of the LF component and the LF/HF ratio in both the resting and the sitting position (supine: LF = -68%, LF/HF ratio = -80%; sitting: LF = -23%, LF/HF ratio = -55%) without affecting the central frequencies of LF and HF components. Blood pressure and plasma catecholamines also significantly decreased after clonidine. 4. These results support the hypothesis that the LF component of HRV, expressed in normalized units, is an indicator of the sympathetic control of the heart. In addition, this component seems to be largely of central origin, because it is markedly reduced by the central sympatholytic action of clonidine.

Urinary mutagenicity on TA98 and YG1024 Salmonella typhimurium strains after a hamburger meal: influence of GSTM1 and NAT2 genotypes.

Mutagenicity on TA98 and YG1024 Salmonella typhimurium strains of pan-fried hamburger extracts and of 24 h post-meal urine from 32 non-smoking volunteers was evaluated. Each participant in the study was GSTM1 and NAT2 genotyped. After cooking the meat showed mutagenic activity (mean +/- SD) on strains TA98 and YG1024 of 114 +/- 129 and 1437 +/- 1536 net revertants/g respectively. Twenty three of 32 urine samples showed clear mutagenic activity (i.e. caused at least a doubling of the number of spontaneous revertants) on the O-acetyltransferase over-producing strain YG1024, while none of the post-meal 24 h urine samples was clearly mutagenic on strain TA98. Total 24 h post-meal YG1024-active urinary mutagens were well correlated with the levels of mutagen intake with the meal (r2 = 0.5977, F = 44.58, P < 0.01). In the group under study GSTM1 genotypes did not influence urinary mutagenicity. Highly exposed subjects (n = 15) with the NAT2-ss genotype showed significantly increased levels of urinary mutagenicity on strain YG1024 in comparison with NAT2-R subjects (mutagen intake-adjusted total 24 h mutagen excretion = 1.00 +/- 0.29 versus 0.66 +/- 0.32, Mann-Whitney U test, U = 12.5, P < 0.05). Our results suggest that the levels of urinary mutagens derived from diets rich in heterocyclic aromatic amines, which are specifically detected by the YG1024 Salmonella strain, are modulated by NAT2-dependent enzyme activity, slow acetylators having higher levels of mutagens in their urine. Subjects with the rapid acetylator genotype, who are known to be at risk for colon cancer, seem to be partially protected with respect to the risk of bladder cancer.

Effects of clonidine on power spectral analysis of heart rate variability in mild essential hypertension.

Patients with essential hypertension often show alterations of the autonomic nervous system. We evaluated the sympathetic and parasympathetic drive to the heart in 12 mildly hypertensive patients and 9 healthy subjects by power spectral analysis of heart rate variability. All subjects underwent measurements of RR interval, low (LF) and high frequency (HF) components of heart rate variability, LF/HF ratio and blood pressure in the resting and sitting positions, both before and after oral clonidine (300 microg), a central sympatholytic agent. In the supine position before clonidine, hypertensive patients had higher blood pressure and lower HF values than healthy subjects. Clonidine induced increases in RR interval and HF in both groups, while LF and LF/HF ratio decreased in healthy subjects, but not in hypertensive patients. On assuming the sitting position, both groups showed reductions in RR and HF and increments in LF and LF/HF. In healthy subjects, the response to the postural challenge was unaffected by clonidine. In contrast, hypertensive patients showed no changes in LF and LF/HF ratio, and a significantly lower decrease in HF. These differences were probably due to the existence of two subsets of patients, one exhibiting similar responses to clonidine as healthy subjects, and the other showing no appreciable response to the drug. These results suggest that hypertensive patients have an altered sympatho-vagal balance to the heart, which can be unmasked by clonidine. This phenomenon should be taken into account to achieve a better control of the overall cardiovascular risk of hypertensive patients.

[Epidemiological analysis of nosocomial infections at the "Arcispedale St. Anna" in Ferrara between 1989 and 1991]. / Analisi epidemiologica delle infezioni nosocomiali verificatesi presso l'"Arcispedale S. Anna" di Ferrara tra il 1989 ed il 1991.

The Authors describe the results of an epidemiology project on nosocomial infection performed from 1989 through 1991 at the "Arcispedale S. Anna", Ferrara, Italy. Data are considered from 4.183 patients who were hospitalized for surgical treatment and intensive care: 301 patients (7.2%) developed 402 episodes of infection, namely 1.34 infections per patient. 8.2% of the patients who underwent surgery had at least one infection, while 3.9% of the those who did not have surgery showed at least one infection. The majority of infections came out higher among those submitted (11.4%) than among those not submitted (4.4%) to antibiotic prophylaxis. Infections were caused by both Gram+ and Gram- bacteria, and often the infections were polimicrobial.