- JAK-inhibitors in dermatology. Current evidence and future applications. [Journal Article]
- JDJ Dermatolog Treat 2018 Nov 15; :1-22
- The Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway is a ubiquitous intracellular signaling network. Selective JAK-inhibitors have anti-inflammatory properties ...
The Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway is a ubiquitous intracellular signaling network. Selective JAK-inhibitors have anti-inflammatory properties and have been approved in many countries for the treatment of rheumatoid arthritis (tofacitinib, baricitinib) and myelofibrosis or polycythemia vera (ruxolitinib). The aim of the publication was to summarize and critically analyze the efficacy and safety of JAK-inhibitors in skin diseases, such as psoriasis, alopecia areata, atopic dermatitis and vitiligo. Databases PubMed, Scopus and EBSCO were searched. After exclusions, 17 articles were analyzed (11 randomized clinical trials, 4 case reports, 1 retrospective study of a case series and 1 nonrandomized pilot study). The strongest evidence of JAK-inhibitor efficacy was established for treatment of psoriasis. Additionally, data are available on the potential efficacy of JAK-inhibitors in alopecia areata, atopic dermatitis and vitiligo. Mostly, JAK-inhibitors are used orally. However, there are studies showing efficacy of topical administration of this group of drugs in psoriasis and vitiligo. Further research is needed, especially the head-to-head comparison studies with JAK-inhibitors and current therapeutic methods to verify the superiority of this new group of drugs in these dermatological diseases.
- A guideline for the management of specific situations in polycythaemia vera and secondary erythrocytosis: A British Society for Haematology Guideline. [Journal Article]
- BJBr J Haematol 2018 Nov 13
- Expression of CD markers in JAK2V617F positive myeloproliferative neoplasms: Prognostic significance. [Journal Article]
- OROncol Rev 2018 Jul 04; 12(2):373
- Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders characterized by the presence of JAK2V617F mutation. Thrombohemorrhagic as well as autoimmune or inflammatory phenomena are common c...
Myeloproliferative neoplasms (MPNs) are clonal stem cell disorders characterized by the presence of JAK2V617F mutation. Thrombohemorrhagic as well as autoimmune or inflammatory phenomena are common clinical outcomes of these disorders. Recent studies have shown that abnormality in frequency and function of blood cells manifested by an alteration in CD markers' expression patterns play a key role in these complications. So, there may be a relationship between CD markers' expressions and prognosis of JAK2V617F positive MPNs. Therefore, in this review, we have focused on these abnormalities from the perspective of changing expressions of CD markers and assessment of the relationship between these changes with prognosis of JAK2V617F positive MPNs. It can be stated that the abnormal expression of a large number of CD markers can be used as a prognostic biomarker for clinical outcomes including thrombohememorrhagic events, as well as autoimmune and leukemic transformation in JAK2V617F positive MPNs. Considering the possible role of CD markers' expressions in JAK2V617F MPNs prognosis, further studies are needed to confirm the relationship between the expression of CD markers with prognosis to be able to find an appropriate therapeutic approach via targeting CD markers.
- Safety of Therapeutic Plasma Exchange for the Treatment of Guillain-Barré Syndrome in Polycythemia Vera. [Journal Article]
- NNeurologist 2018; 23(6):185-187
- Polycythemia vera (PV) is a risk factor for systemic thromboses and ischemic stroke. This has been attributed to blood hyperviscosity, the result of increased blood cell production. Intravenous immun...
Polycythemia vera (PV) is a risk factor for systemic thromboses and ischemic stroke. This has been attributed to blood hyperviscosity, the result of increased blood cell production. Intravenous immunoglobulin, which is indicated for the treatment of numerous hematologic and neurological conditions also causes increased serum viscosity and has been associated with ischemic strokes in the setting of PV. Here we report a case of a 70-year-old man with prior stroke and PV who developed Guillain-Barré syndrome, an acute inflammatory demyelinating disorder of peripheral nerves causing ascending paresis, numbness, and paresthesia, who was treated safely with therapeutic plasma exchange. Plasma exchange may be preferable to administration of intravenous immunoglobulin for treatment of various medical conditions in patients with comorbid PV.
- Macular perfusion velocities in the ocular ischaemic syndrome. [Case Reports]
- AOActa Ophthalmol 2018 Oct 27
- CONCLUSIONS: Motion-contrast imaging revealed markedly reduced macular perfusion velocities in OIS eyes compared with unaffected fellow eyes and healthy control eyes. The method appears to provide a clinically meaningful quantitative measure of macular hypoperfusion.
- Jak2V617F and Dnmt3a loss cooperate to induce myelofibrosis through activated enhancer-driven inflammation. [Journal Article]
- BloodBlood 2018 Oct 26
- Myeloproliferative neoplasms (MPN) are a group of blood cancers that arise following the sequential acquisition of genetic lesions in hematopoietic stem and progenitor cells (HSPC). We identify mutat...
Myeloproliferative neoplasms (MPN) are a group of blood cancers that arise following the sequential acquisition of genetic lesions in hematopoietic stem and progenitor cells (HSPC). We identify mutational cooperation between Jak2V617F expression and Dnmt3a loss that drives progression from early stage polycythemia vera to advanced myelofibrosis. Using in vivo CRISPR-Cas9 disruption of Dnmt3a in Jak2V617F knockin HSPCs, we show that Dnmt3a loss blocks the accumulation of erythroid elements and causes fibrotic infiltration within the bone marrow and spleen. Transcriptional analysis and integration with human datasets identified a core DNMT3A-driven gene expression program shared across multiple models and contexts of Dnmt3a loss. Aberrant self-renewal and inflammatory signaling, was seen in Dnmt3a-/- Jak2V617F HSPC and was driven by increased chromatin accessibility at enhancer elements. These findings identify oncogenic cooperativity between Jak2V617F-driven MPN and Dnmt3a loss, leading to activation of HSPC enhancer driven inflammatory signaling.
- Risk Factors for Adverse Cardiac Events After Lumbar Spine Fusion. [Journal Article]
- IJInt J Spine Surg 2018; 12(5):638-643
- CONCLUSIONS: Cardiac events after lumbar fusion are a rare but devastating series of complications. Several risk factors were identified, including insulin-dependent diabetes mellitus, smoking, advanced age, male sex, ASA score of >3, and anemia/polycythemia. Considering the severity of these consequences, appropriate risk stratification is imperative, and optimization of modifiable risk factors may mitigate this risk.
- Dramatic response of refractory sarcoidosis under ruxolitinib in a patient with associated JAK2-mutated polycythemia. [Letter]
- EREur Respir J 2018 Oct 25
- Effect of a functional food (vegetable soup) on blood rheology in patients with polycythemia. [Journal Article]
- AJAvicenna J Phytomed 2018 Sep-Oct; 8(5):389-398
- CONCLUSIONS: This trial showed that the plant-based food used in this study could improve blood rheology.
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- The impact of phlebotomy and hydroxyurea on survival and risk of thrombosis among older patients with polycythemia vera. [Journal Article]
- BABlood Adv 2018 Oct 23; 2(20):2681-2690
- Current guidelines recommend therapeutic phlebotomy for all polycythemia vera (PV) patients and additional cytoreductive therapy (eg, hydroxyurea [HU]) for high-risk PV patients. Little is known abou...
Current guidelines recommend therapeutic phlebotomy for all polycythemia vera (PV) patients and additional cytoreductive therapy (eg, hydroxyurea [HU]) for high-risk PV patients. Little is known about the impact of these therapies in the real-world setting. We conducted a retrospective cohort study of older adults diagnosed with PV from 2007 to 2013 using the linked Surveillance, Epidemiology, and End Results-Medicare database. Multivariable Cox proportional hazards models were used to assess the effect of phlebotomy and HU on overall survival (OS) and the occurrence of thrombotic events. Of 820 PV patients (median age = 77 years), 16.3% received neither phlebotomy nor HU, 23.0% were managed with phlebotomy only, 19.6% with HU only, and 41.1% with both treatments. After a median follow-up of 2.83 years, 37.2% (n = 305) of the patients died. Phlebotomy (yes/no; hazard ratio [HR] = 0.65; 95% confidence interval [CI], 0.51-0.81; P < .01), increasing phlebotomy intensity (HR = 0.71; 95% CI, 0.65-0.79; P < .01), and a higher proportion of days covered (PDC) by HU were all significantly associated with lower mortality. When thrombosis was the outcome of interest, phlebotomy (yes/no; HR = 0.52; 95% CI, 0.42-0.66; P < .01) and increasing phlebotomy intensity (HR = 0.46; 95% CI, 0.29-0.74; P < .01) were significantly associated with a lower risk of thrombotic events, so was a higher HU PDC. In this population-based study of older adults with PV reflecting contemporary clinical practice, phlebotomy and HU were associated with improved OS and decreased risk of thrombosis. However, both treatment modalities were underused in this cohort of older PV patients.