Impaired virus-specific T cell responses in patients with myeloproliferative neoplasms treated with ruxolitinib

Ruxolitinib is effective in myeloproliferative neoplasms (MPN) but can cause reactivation of silent infections. We aimed at evaluating viral load and T-cell responses to human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) in a cohort of 25 MPN patients treated with ruxolitinib. EBV-DNA and HCMV-DNA were quantified monthly using real-time polimerase chain reaction (PCR) on peripheral blood samples, and T-cell subsets were analyzed by flowcytometry. HCMV and EBV-directed T-cell responses were evaluated using the IFN-γ ELISPOT assay. Most patients had CD4+ and/or CD8+ T-cells below the normal range; these reductions were related to the duration of ruxolitinib treatment. In fact, reduced T-lymphocytes' subsets were found in 93% of patients treated for ≥5 years and in 45% of those treated for <5 years (P = .021). The former also had lower median numbers of CD4+ and CD8+ cells. Subclinical reactivation of EBV and HCMV occurred in 76% and 8% of patients. We observed a trend to an inverse relationship between EBV and CMV-specific CD4+ and CD8+ T-cell responses and viral load, and a trend to an inverse correlation with ruxolitinib dose. Therefore, our data suggest that the ruxolitinib treatment may interfere with immunosurveillance against EBV and HCMV.     

Guidelines on clinical presentation and management of nondystrophic myotonias

The nondystrophic myotonias are rare muscle hyperexcitability disorders caused by gain-of-function mutations in the SCN4A gene or loss-of-function mutations in the CLCN1 gene. Clinically, they are characterized by myotonia, defined as delayed muscle relaxation after voluntary contraction, which leads to symptoms of muscle stiffness, pain, fatigue, and weakness. Diagnosis is based on history and examination findings, the presence of electrical myotonia on electromyography, and genetic confirmation. In the absence of genetic confirmation, the diagnosis is supported by detailed electrophysiological testing, exclusion of other related disorders, and analysis of a variant of uncertain significance if present. Symptomatic treatment with a sodium channel blocker, such as mexiletine, is usually the first step in management, as well as educating patients about potential anesthetic complications.     

Apremilast efficacy and safety in a psoriatic arthritis patient affected by HIV and HBV virus infections

Treatment of psoriasis and psoriatic arthritis in patients with concomitant chronic, severe viral infections, particularly HIV or HBV, represents a challenge, due to contraindication to conventional immunomodulating systemic drugs and biologics, including anti-TNF alpha, anti-IL12/23, and anti-IL17 agents. Recently, apremilast, a selective inhibitor of phosphodiesterase E4 has been suggested to be a safe and effective therapeutic option in HIV-infected population with psoriatic arthritis. We report the case of a patient with psoriatic arthritis and concomitant HIV and HBV infection successfully treated with apremilast.     

Equity in Access to Health Care Services in Italy

ObjectiveTo provide new evidence on whether and how patterns of health care utilization deviate from horizontal equity in a country with a universal and egalitarian public health care system: Italy.ConclusionsDespite its universal and egalitarian public health care system, Italy exhibits a significant degree of SES-related horizontal inequity in health services utilization.     

Early presentation of urinary retention in multiple system atrophy: can the disease begin in the sacral spinal cord?

Journal of Neurology - Lower urinary tract (LUT) dysfunction presents early in multiple system atrophy (MSA), usually initially as urinary urgency, frequency and incontinence, and voiding...     

A novel approach to infertility treatment of advance-age patient with prominent intramural fibroid

We report for the first time on a case of infertile advance-age patient with large intramural fibroid, who conceived following a course of Ulipristal. The patient underwent two fresh fertility preserving IVF cycles, with cryopreservation of 9?day-3 embryos, followed by a 12?weeks course of Ulipristal (5?mg per day) and a subsequent frozen-thawed embryo transfer with her own previously cryopreserved embryos. We, therefore, believe that Ulipristal is a valuable addition to treatment armamentarium of advance-age infertile patient with prominent intramural fibroid.     

Acute Reduction of Anandamide‐Hydrolase (FAAH) Activity is Coupled With a Reduction of Nociceptive Pathways Facilitation in Medication‐Overuse Headache Subjects After Withdrawal Treatment

Objectives.— We investigated (1) a possible relationship between the functional activity of the endocannabinoid system and the facilitation of pain processing in migraineurs with medication‐overuse headache, and (2) the effect of withdrawal treatment on both. Background.— The endocannabinoid system antinociception effect includes prevention of nociceptive pathways sensitization. The sensitization of the pain pathways has been demonstrated to be pivotal in the development and maintenance of chronic form of migraine, including medication‐overuse headache. Methods.— We used the temporal summation threshold of the nociceptive withdrawal reflex to explore the spinal cord pain processing, and the platelet activity of the enzyme fatty acid amide hydrolase to detect the functional state of the endocannabinoid system in 27 medication‐overuse headache subjects before and 10 and 60 days after a standard withdrawal treatment and compared results with those of 14 controls. Results.— A significantly reduced temporal summation threshold and increased related pain sensation was found in subjects before withdrawal treatment when compared with controls. A significant fatty acid amide hydrolase activity reduction coupled with a significant improvement (reduction) in facilitation of spinal cord pain processing (increase in temporal summation threshold and reduction in related pain sensation) was found in medication‐overuse headache subjects at both 10 and 60 days after withdrawal treatment when compared with medication‐overuse headache subjects before withdrawal treatment. Conclusions.— We demonstrated a marked facilitation in spinal cord pain processing in medication‐overuse headache before withdrawal treatment when compared with controls. Furthermore, the acute reduction of the fatty acid amide hydrolase activity coupled with a reduction of the facilitation in pain processing immediately (10 days) after withdrawal treatment and its persistence 60 days after withdrawal treatment could represent the consequence of a mechanism devoted to acutely reduce the degradation of endocannabinoids and aimed to increase the activity of the endocannabinoid system that results in an antinociceptive effect.     

A relaxometric method for the assessment of intestinal permeability based on the oral administration of gadolinium‐based MRI contrast agents

Herein, a new relaxometric method for the assessment of intestinal permeability based on the oral administration of clinically approved gadolinium (Gd)‐based MRI contrast agents (CAs) is proposed. The fast, easily performed and cheap measurement of the longitudinal water proton relaxation rate (R₁) in urine reports the amount of paramagnetic probe that has escaped the gastrointestinal tract. The proposed method appears to be a compelling alternative to the available methods for the assessment of intestinal permeability. The method was tested on the murine model of dextran sulfate sodium (DSS)‐induced colitis in comparison with healthy mice. Three CAs were tested, namely ProHance®, MultiHance® and Magnevist®. Urine was collected for 24 h after the oral ingestion of the Gd‐containing CA at day 3–4 (severe damage stage) and day 8–9 (recovery stage) after treatment with DSS. The Gd content in urine measured by ¹H relaxometry was confirmed by inductively coupled plasma‐mass spectrometry (ICP‐MS). The extent of urinary excretion was given as a percentage of excreted Gd over the total ingested dose. The method was validated by comparing the results obtained with the established methodology based on the lactulose/mannitol and sucralose tests. For ProHance and Magnevist, the excreted amounts in the severe stage of damage were 2.5–3 times higher than in control mice. At the recovery stage, no significant differences were observed with respect to healthy mice. Overall, a very good correlation with the lactulose/mannitol and sucralose results was obtained. In the case of MultiHance, the percentage of excreted Gd complex was not significantly different from that of control mice in either the severe or recovery stages. The difference from ProHance and Magnevist was explained on the basis of the (known) partial biliary excretion of MultiHance in mice. Copyright © 2016 John Wiley & Sons, Ltd.