Can clinical staging of primary amoebic meningoencephalitis be of any therapeutic benefit

Naegleria fowleri, is a free-living amoeba (FLA) known to infect humans and cause a fatal disease called primary amoebic meningoencephalitis (PAM). All of the patients are commonly admitted to the emergency room (ER). Often, treatment in the ER is delayed due to the rarity of disease leading to a delay in the diagnosis and late arrival of patients to the ER. The attempts to reduce raised intracranial pressure and subsequent herniation of the brain stem are challenging and become the cause of death in the affected patients during their stay in ER. Use of drugs like mannitol to reduce raised intra-cerebral pressure (ICP) could prove dangerous in the presence of cerebral haemorrhage and this fact could be overlooked during the management of patients with PAM. No precise therapy is followed for PAM, and most often a course of broad spectrum anti-protozoal drugs is employed. A CDC recommended drug miltefosine has show success in early diagnosed cases. So far, there is no clinical staging of PAM, and patients are managed for the complications that develop while their stay in the ER. Given the health scare associated with N. fowleri in countries with tropical climates, and its potential ability to cause severe meningoencephalitis that often progresses to lethal outcomes, we believe it is imperative to stage PAM into clear progressive stages to help its management in the ER and debate its therapeutic gains. Such a clinical staging could aid in efforts to diagnose and treat PAM. Furthermore, it will help in raising public awareness, in educating healthcare and allied personne

Herpes Zoster During Immunosuppressive Therapy For Autoimmune Diseases

Background: Patients on immunosuppressive therapy are at a greater risk for herpes zoster reactivation and are more likely to have adverse outcomes. Propylactic antivrials and vaccinations may potentially prevent these complications.Methods: Medical literature addressing the clinical course and therapy of herpes zoster in patients receiving immunosuppressive therapy for autoimmune disorders, and the roles of anti-viral prophylaxis and vaccination was reviewed. Research databases including PubMed, Ovid, Medline, Google Scholar and Cochrane were utilized.Results: Acyclovir and its derivatives are most commonly used in this setting for treatment and reduction of post-zoster complications. Foscarnet may be used for acyclovir-resistant strains. At both conventional and ultralow doses, acyclovir has proven effective when used as prophylaxis, reducing the incidence of zoster and its complications in immunosuppressed patients. Additionally, ultra-low doses are associated with significantly reduced side effects. The zoster vaccine, Zostavax, a live-attenuated vaccine has shown promising results in several clinical trials. However, live-attenuated vaccines should be cautiously used in immunosuppressed patients. For patients who require immunosuppressive therapy, vaccination 2-3 months prior to therapy may be appropriate.CONCLUSIONS: Prophylactic antiviral therapy and vaccination help significantly reduce morbidity and mortality from zoster reactivation in patients receiving immunosuppressive therapy

Overview of the mutational landscape in primary myelofibrosis and advances in novel therapeutics

Primary Myelofibrosis is a BCR-ABL negative myeloproliferative neoplasm with a variety of hematological presentations, including thrombosis, bleeding diathesis and marrow fibrosis. It is estimated to have an incidence of 1.5 per 100,000 people each year. Although JAK2 or MPL mutations are seen in PMF, several other mutations have recently been documented, including mutations in CALR, epigenetic regulators like TET, ASXL1, and 13q deletions. The identification of these mutations has improved the ability to develop novel treatment options. These include JAK inhibitors like ruxolitinib, heat shock protein-90 inhibitors like ganetespib, histone deacetylase inhibitors including panobinostat, pracinostat, vorinostat and givinostat, hypomethylating agents like decitabine, hedgehog inhibitors like glasdegib, PI3K, AKT and mTOR inhibitors like everolimus as well as telomerase inhibitors like imtelstat. Research on novel therapeutic options is being actively pursued in order to expand treatment options for primary myelofibrosis however currently, there is no curative therapy other than allogenic hematopoietic stem cell transplantation (ASCT) which is possible in select patients