Use of a Mobile Intermittent Pneumatic Compression Device (Vekroosan) in Mobile Patients With Chronic Venous Disease.

BACKGROUND: Compression therapy is an essential part of chronic venous disorder (CVD) treatment in reducing associated complications. This observational study aimed to note the use, effects and tolerance of a mobile intermittent pneumatic calf compression (IPC) device, Vekroosan® (DVT Solution P/L). METHODS: In 56 patients, Doppler ultrasonography was used to measure venous blood peak flow velocity (PFV) at external iliac, common femoral, distal superficial femoral and popliteal vein levels both before and after application of Vekroosan calf compressor for comparison. RESULTS: Vekroosan was able to show significant clinical benefit in 45 patients (80%). There was a significant increase in femoral PFV pressure in post-compression measurement when compared to the pre-compression measurement (43.1 vs. 32.4 cm/s, P < 0.001), even when patients mobilize. On average, the PFV pressure increased by 10.7 cm/s when compared to baseline. A significant decrease was seen in calf swelling after calf compression (31.3 vs. 21.9 cm, P < 0.01), also with mobilization. Eighty-seven percent of patients tolerated the device well. CONCLUSIONS: Our study shows that use of mobile IPC devices, such as Vekroosan, is safe and effective in the treatment of CVD, can be used while mobilizing and can achieve results comparable to non-mobile devices.

Is 6-Shogaol an Effective Phytochemical for Patients With Lower-risk Myelodysplastic Syndrome? A Narrative Review.

Myelodysplastic syndrome (MDS) evolves due to genomic instability, dysregulated signaling pathways, and overproduction of inflammatory markers. Reactive oxygen species contribute to the inflammatory response, which causes gene damage, cellular remodeling, and fibrosis. MDS can be a debilitating condition, and management options in patients with MDS aim to improve cytopenias, delay disease progression, and enhance quality of life. High serum ferritin levels, a source of iron for reactive oxygen species production, correlate with a higher risk of progression to acute myeloid leukemia, and iron overload is compounded by blood transfusions given to improve anemia. 6-shogaol is a natural phenolic compound formed when ginger is exposed to heat and/or acidic conditions, and it has been shown to possess anti-tumor activity against leukemia cell lines and antioxidant effects. This narrative review assessed the potential benefits of this phytochemical in lower-risk MDS patients through examining the current evidence on the pharmacological and therapeutic properties of ginger and 6-shogaol.

Outcomes of Reduced Frequency Dosing of Ibrutinib in Chronic Lymphocytic Leukemia Patients Following Complete or Partial Remission: A Pilot Study.

BACKGROUND: Ibrutinib is a Bruton's tyrosine kinase inhibitor that has shown to be a superior choice in the treatment of chronic lymphocytic leukemia (CLL) and a simple, oral alternative to other chemoimmunotherapies. The standard dose is 420 mg daily; however, its irreversible binding mechanism allows adequate target blockade at much lower doses due to prolonged effect. Dose reductions or interruptions are often used in clinical practice to limit its distinct side effects, including diarrhea, bleeding and atrial fibrillation and emerging evidence exists that these do not hinder efficacy. Using a retrospective clinical audit of a single-center outpatient hematology clinic, we aimed to examine outcomes and toxicities of a reduced frequency dose regimen of ibrutinib in patients beyond the confines of a clinical trial. METHODS: A small pilot study was conducted on 16 voluntary CLL patients that had achieved partial or complete remission on standard dose ibrutinib and were considering cessation due to side effects. Patients were consented and prescribed a 420 mg thrice weekly regimen and side effects and outcomes were recorded on routine review. A retrospective clinical audit from 2015 to 2018 was then conducted to compare pilot participants to patients that had remained on standard dosing and results from the extended follow-up of the landmark RESONATE trial. RESULTS: None of the 16 patients in the pilot relapsed or died during the study period equating to a 100% progression free and overall survival. There was resolution or reduction in all side effects reported following switchover; however, the study was too small to establish a statistical relationship. CONCLUSION: This is the first study to demonstrate use of a thrice weekly regimen to reduce ibrutinib-related toxicities whilst preserving safety and efficacy in patients following complete or partial remission on standard dose therapy. Higher powered, prospective studies are required to establish positive health and financial implications in the elderly and vulnerable CLL demographic.

Cardiac and hepatic siderosis in myelodysplastic syndrome, thalassemia and diverse causes of transfusion-dependent anemia: the TIMES study.

The significant morbidity and mortality associated with iron overload can be reduced by effective iron chelation. Magnetic resonance imaging (MRI) provides accurate and reproducible iron load assessment. The aim of this epidemiological study was to assess the prevalence and severity of cardiac and hepatic siderosis by MRI and to evaluate the impact of MRI on clinical management in patients with transfusion-dependent anemia and non-transfusion-dependent thalassemia (NTDT). We enrolled 243 patients with myelodysplastic syndromes (MDS), thalassemia major (TM), NTDT or other chronic anemia. Overall, 10% and 48% had cardiac and hepatic siderosis, respectively. Mean liver iron concentration (LIC) was above target range in all groups; mean myocardial T2∗ was normal. Hepatic siderosis was more prevalent than myocardial siderosis in patients with MDS, occurring in 54.4% and 4.4% of patients, respectively. As also observed in patients with NTDT or other anemia, hepatic siderosis was present in a large proportion of MDS patients who were chelation naïve (57.7%), as well as in patients receiving iron chelation therapy (ICT) (52.4%), despite a lower transfusion load compared with TM. Correlation between LIC and serum ferritin was observed across diseases; however, not all patients requiring ICT could be identified with serum ferritin alone, as serum ferritin underestimated LIC in 4.4% and overestimated LIC in 7.5% of patients. Exploratory analyses showed serum ferritin thresholds for liver siderosis detected by MRI at approximately 300 ng/mL higher in MDS than in TM. Most patients reported low-medium adherence to ICT; MRI assessment led to change in ICT in 46% of evaluable patients, including 52% of MDS patients. Accurate organ iron monitoring by MRI facilitated appropriate initiation of chelation, dose optimization and clinical decision making. Trial registration: ClinicalTrials.gov: NCT01736540.

Integrative Genomics Identifies the Molecular Basis of Resistance to Azacitidine Therapy in Myelodysplastic Syndromes.

Myelodysplastic syndromes and chronic myelomonocytic leukemia are blood disorders characterized by ineffective hematopoiesis and progressive marrow failure that can transform into acute leukemia. The DNA methyltransferase inhibitor 5-azacytidine (AZA) is the most effective pharmacological option, but only ∼50% of patients respond. A response only manifests after many months of treatment and is transient. The reasons underlying AZA resistance are unknown, and few alternatives exist for non-responders. Here, we show that AZA responders have more hematopoietic progenitor cells (HPCs) in the cell cycle. Non-responder HPC quiescence is mediated by integrin α5 (ITGA5) signaling and their hematopoietic potential improved by combining AZA with an ITGA5 inhibitor. AZA response is associated with the induction of an inflammatory response in HPCs in vivo. By molecular bar coding and tracking individual clones, we found that, although AZA alters the sub-clonal contribution to different lineages, founder clones are not eliminated and continue to drive hematopoiesis even in complete responders.

Factor V inhibitors: rare or not so uncommon? A multi-laboratory investigation.

Acquired deficiencies of, or inhibitors to, factor V are considered rare events. We report a series of 14 acquired factor V deficiencies, 10 of which were confirmed to have inhibitors to factor V, as identified within Australia in the past 5 years following a multi-laboratory investigation. The initial index case seen by one laboratory was followed within 4 months by a separate similar case. This prompted local contact with colleagues (n = 20) working in other haemostasis referral laboratories to identify the current case series. In total, nearly one-half of all haemostasis referral laboratories contacted had seen a case within the past 5 years. Clinical features and the apparent associated risk of bleeding complications generally varied, as did laboratory findings and the likely causal event. There were three females and 11 males. Age ranged from 44 to 95 years (median, 81 years). The level of inhibitor ranged from undetectable to over 250 Bethesda units. The probable cause leading to development of the inhibitors ranged from exposure to bovine thrombin, exposure to antibiotics, surgery and malignancy. Of additional interest was the apparent association of anti-phospholipid antibodies in many of the cases. For example, in the two similar index cases, with factor V inhibitor titres > 200 Bethesda units, high levels of anti-cardiolipin antibodies (> 70 GPL units) were also detected. Although less clear because of inhibitor interference, many of the cases also showed evident co-associated lupus anticoagulant activity. In conclusion, we report a series of factor V inhibitors recently identified within our geographic region that would represent an annual incidence of around 0.29 cases per million Australians. Although considered a rare finding, there is a high likelihood that most haemostasis referral laboratories will see a case every five or so years.

Sustained long-term remissions with weekly interferon maintenance therapy in hairy cell leukemia.

AIM: This study evaluates the efficacy of weekly α-interferon (IFN) maintenance therapy in hairy cell leukaemia (HCL), a disease that remains incurable. METHOD: Nine patients (six male, three female, aged 41-69 yrs) with hairy cell leukaemia (HCL) received IFN 3mU s.c. once weekly as long-term maintenance therapy after achieving optimal clinical and hematological response to initial therapy with thrice weekly IFN. RESULTS: Eight of the nine patients are in a state of sustained response at 3-17 years (median 12 years). CONCLUSION: Our results are similar to those from three previous studies using long-term IFN maintenance therapy, bringing the total number of patients in sustained remission to 118. We hope these reports will lead to a multi-centre, phase III study of IFN maintenance therapy (including pegylated IFN, given less frequently) in HCL patients achieving optimal response to initial therapy, be it IFN or a purine analogue.