Treatment of lymphocyte-variant hypereosinophilic syndrome (L-HES): what to consider after confirming the elusive diagnosis.

Lymphocyte-variant hypereosinophilic syndrome (L-HES) is a rare disease driven by immunophenotypically aberrant T cells producing eosinophilopoetic cytokines such as interleukin-5 (IL-5). Treatment is challenging because L-HES is relatively steroid resistant and not amenable to tyrosine kinase inhibitors. We searched the literature for clinical trials and observational studies, including case reports, of patients treated for L-HES. In all, 25 studies were selected; two were randomised controlled trials of IL-5 blockade, which included some patients with L-HES, and the rest were observational studies. Corticosteroids are often used as first-line therapy, but patients with L-HES have lower response rates than other types of HES. Treatments that reduce symptoms and steroid dependence in some patients include interferon-alpha (IFN-α), anti-IL-5 monoclonal antibodies, cyclosporine and mycophenolate. These drugs target T-cell activation and proliferation, or IL-5 directly. Although effective, IFN-α and cyclosporine were commonly reported to cause side-effects resulting in discontinuation. Alemtuzumab can induce remissions, but these are generally short lived. The anti-IL-5 monoclonal antibodies mepolizumab and benralizumab are effective and well tolerated, but with a high rate of relapse once withdrawn. Hydroxyurea, methotrexate, imatinib were unsuccessful in most patients studied. More prospective clinical trials are needed for patients with L-HES.

Interventions to improve benzodiazepine tapering success in the elderly: a systematic review.

BACKGROUND: Long-term benzodiazepine use in the elderly population is a significant public health problem that leads to impaired cognitive functioning, medication dependence and increased risks for adverse drug reactions. The aim of this review was to examine randomized controlled trials (RCTs) on the efficacy of different methods for tapering and discontinuing benzodiazepines. METHOD: We used four databases (Ovid, PubMed, Academic Search Complete, Web of Science) to retrieve randomized controlled trials published in peer-reviewed journals that explored different methods for tapering benzodiazepine use in a primarily geriatric population. RESULTS: Eleven papers met the inclusion criteria. Methods to assist in benzodiazepine tapering included patient education, cognitive behavioural therapy (CBT), and pharmaceutical adjuvants (SSRIs, melatonin, progesterone). Patient education was consistently effective in increasing benzodiazepine discontinuation success while CBT had mixed but promising results. The use of medications to help improve tapering success was inconclusive. CONCLUSIONS: Patient education is a successful, time- and cost-effective intervention that can significantly help with benzodiazepine discontinuation success. CBT may also be an effective approach. However, cost can be an issue since public healthcare coverage in Canada does not cover psychotherapy. More research is needed in looking at pharmaceutical adjuvants and their role in assisting with benzodiazepine discontinuation.

Chemical exchange saturation transfer magnetic resonance imaging and its main and potential applications in pre-clinical and clinical studies.

Chemical exchange saturation transfer (CEST) imaging is a novel contrast mechanism, relying on the exchange between mobile protons in amide (-NH), amine (-NH2) and hydroxyl (-OH) groups and bulk water. Due to the targeted protons present in endogenous molecules or exogenous compounds applied externally, CEST imaging can respectively, generate endogenous or exogenous contrast. Nowadays, CEST imaging for endogenous contrast has been explored in pre-clinical and clinical studies. Amide CEST, also called amide proton transfer weighted (APT) imaging, generates CEST effect at 3.5 ppm away from the water signal and has been widely investigated. Given the sensitivity to amide proton concentration and pH level, APT imaging has shown robust performance in the assessment of ischemia, brain tumors, breast and prostate cancer as well as neurodegenerative diseases. With advanced methods proposed, pure APT and Nuclear Overhauser Effect (NOE) mediated CEST effects were separately fitted from original APT signal. Using both effects, early but promising results were obtained for glioma patients in the evaluation of tumor response to therapy and patient survival. Compared to amide CEST, amine CEST is also mobile proton concentration and pH dependent, but has a faster exchange rate between amine protons and water. The resultant CEST effect is usually introduced at 1.8-3 ppm. Glutamate and creatine, as two main metabolites with amine groups for CEST imaging, have been applied to quantitatively assess diseases in the central nervous system and muscle system, respectively. Glycosaminoglycan (Gag) as a representative metabolite with hydroxyl groups has also been measured to evaluate the cartilage of knee or intervertebral discs in CEST MRI. Due to limited frequency difference between hydroxyl protons and water, 7T for better spectral separation is preferred over 3T for GagCEST measurement. The applications of CEST MRI with exogenous contrast agents are still quite limited in clinic. While certain diamagnetic CEST agents, such as dynamic-glucose, have been tried in human for brain tumor or neck cancer assessment, most exogenous agents, i.e., paramagnetic CEST agents, are still tested in the pre-clinical stage, mainly due to potential toxicity. Engineered tissues for tissue regeneration and drug delivery have also shown a great potential in CEST imaging, as many of them, such as hydrogel and polyamide materials, contain mobile protons or can be incorporated with CEST specific chemical compounds. These engineered tissues can thus generate CEST effect in vivo, allowing a possibility to understand the fate of them in vivo longitudinally. Although the CEST MRI with engineered tissues has only been established in early stage, the obtained first evidence is crucial for further optimizing these biomaterials and finally accomplishing the translation into clinical use.