Optimized flow cytometric detection of transient receptor potential vanilloid-1 (TRPV1) in human hematological malignancies.

The ectopic overexpression of transient receptor potential vanilloid-1 (TRPV1) has been detected in numerous solid cancers, including breast, prostate, pancreatic, and tongue epithelium cancer. However, the expression of TRPV1 in hematological malignancies remains unknown. Here we show through in silico analysis that elevated TRPV1 mRNA expression occurs in a range of hematological malignancies and presents an optimized flow cytometry method to rapidly assess TRPV1 protein expression for both cell lines and primary patient samples. Three anti-TRPV1 antibodies were evaluated for intracellular TRPV1 detection using flow cytometry resulting in an optimized protocol for the evaluation of TRPV1 in hematological malignant cell lines and patients' peripheral blood mononuclear cells (PBMC). Overexpression of TRPV1 was observed in THP-1 (acute monocytic leukemia) and U266B1 (multiple myeloma, MM), but not U937 (histiocytic lymphoma) compared to healthy PBMC. TRPV1 was also detected in all 49 patients including B-cell non-Hodgkin's lymphoma (B-NHL), MM, and others and 20 healthy controls. TRPV1 expression was increased in 8% of patients (MM = 2, B-NHL = 2). In conclusion, we provide an optimized flow cytometry method for routine expression analysis of clinical samples and show that TRPV1 is increased in a subset of patients with hematological malignancies.

Real-World Data on Characteristics and Management of Community Patients Receiving Anticoagulation Therapy Who Presented with Acute Bleeding to the Emergency Department at a Regional Australian Hospital: A Prospective Observational Study.

OBJECTIVE: To study patients receiving anticoagulants with or without antiplatelet therapy presenting at a regional Australian hospital with bleeding. The main aims are to explore: (1) patients' characteristics and management provided; (2) association between the type of anticoagulant and antiplatelet agent used and the requirement of reversal; (3) and the length of hospital stay (LoS) in conjunction with bleeding episode and management. METHODS: A prospective cross-sectional review of medical records of all patients who presented at a tertiary referral centre with bleeding while receiving anticoagulation therapy between January 2016 and June 2018. Data included: patients, demographics, investigations (kidney and liver function tests, coagulation profile, FBC), LoS, bleeding site, type of and reason for anticoagulation therapy, and management provided. Data analysis included descriptive statistics, χ2 association, and regression models. RESULTS: Among the 144 eligible patients, 75 (52.1%) were male, and the mean age was 76 years (SD=11.1). Gastrointestinal tract bleeding was the most common (n=48, 33.3%), followed by epistaxis (n=32, 22.2%). Atrial fibrillation was the commonest reason for anticoagulation therapy (n=65, 45.1%). Warfarin was commonly used (n=74, 51.4%), followed by aspirin (n=29, 20.1%), rivaroxaban (n=26, 18.1%), and apixaban (n=12, 8.3%). The majority had increased blood urea nitrogen (n=67, 46.5%), while 58 (40.3%) had an elevated serum creatinine level, and 59 (41.0%) had a mild reduction in eGFR. Thirty-five of the warfarinised patients (47.3%) had an INR above their condition's target range despite normal liver function. Severe anaemia (Hb<80g/L) was reported in 88 patients (61.1%). DOACs were associated with a reduced likelihood of receiving reversal (B= -1.7, P=<.001), and with a shorter LoS (B= -4.1, P=.046) when compared with warfarin, LMWH, and antiplatelet therapy. CONCLUSION: Warfarin use was common among patients who presented with acute bleeding, and the INR in many warfarinised patients exceeded the target for their condition. DOACs were associated with a reduced likelihood of receiving reversal and a shorter LoS than warfarin, LMWH, which might support a broader application of DOACs into community practice.

Assessment of von Willebrand disease and pregnancy outcomes at regional Australian hospitals.

BACKGROUND: von Willebrand disease (vWD) is a heterogeneous hereditary bleeding disorder and is associated with risk of primary postpartum haemorrhage (PPH). DESIGN AND METHODS: An observational study at a tertiary referral centre in Australia of 16 women with 23 deliveries with a median age of 27.5 years (range, 21-39; IQR = 9). Median gestational age at delivery was 39 weeks (range, 35-41; IQR = 1.1). RESULTS: All cases had type 1 vWD, apart from one case with type 2. Patients were managed in combined obstetrics and haematology clinics. PPH occurred in ten deliveries (44%). Intravenous desmopressin was administered in 6 cases, and IV human vWF was administered in 4 cases. Two cases with mild vWD had received oral tranexamic acid. The median Apgar score at 1 and 5 min was 9 (IQR = 1.0), while the median Apgar score at 10 min was 10.0 (IQR = 0.0). One case required transfusion of blood products postdelivery. There were no other significant complications observed. CONCLUSIONS: vWD was associated with a high incidence of primary PPH. Individualised treatment to restore haemostasis, according to the severity of the disease, could achieve as possible, normal haemostasis with favourable outcomes for both mothers and their infants. Further studies to confirm our findings are warranted.

A Prospective Randomised Controlled Trial of a Single Intravenous Infusion of Ferric Carboxymaltose vs Single Intravenous Iron Polymaltose or Daily Oral Ferrous Sulphate in the Treatment of Iron Deficiency Anaemia in Pregnancy.

Iron deficiency anaemia (IDA) is the most common nutritional deficiency affecting pregnant women worldwide. This study aims to compare the efficacy and safety of a newly available intravenous (IV) iron preparation, ferric carboxymaltose (FCM), against IV iron polymaltose (IPM), and standard oral iron (ferrous sulphate) for the treatment of IDA in pregnancy. This is an open-labelled prospective randomised controlled trial (RCT) with intention-to-treat analysis conducted at a primary health care facility with a single tertiary referral centre in Launceston. Tasmania, Australia. A 3-arm randomised controlled trial was conducted comparing a single IV infusion of 1000mg of FCM (n = 83 patients) over 15 minutes against a single IV infusion of 1000mg of IPM (n = 82) over 2 hours against 325mg daily oral ferrous sulphate (n = 81) until delivery, for the treatment of IDA in pregnancy. A total of 246 consecutive pregnant women were recruited between September 2013 and July 2014. The median age was 28 years, with a median and mean gestation of 27 weeks. The median serum ferritin was 9µg/L, with a mean of 13µg/L. The mean haemoglobin (Hb) was 114g/L. The primary outcome was the change in ferritin and Hb levels at 4 weeks after intervention. Secondary outcomes included ferritin and Hb improvements at predelivery, safety, tolerability, quality of life (QoL), cost utility, and fetal outcomes. The mean Hb level differences between the baseline intervention time point and 4 weeks thereafter were significantly higher in the FCM versus the oral group by 4.35g/L (95% CI: 1.64-7.05; P = 0.0006) and in the IPM vs the oral group by 4.08g/L (95% CI: 1.57-6.60; P = 0.0005), but not different between the FCM and IPM groups (0.26g/L; 95% CI: -2.59 to 3.11; P = 0.9740). The mean ferritin level differences were significantly higher at 4 weeks in the FCM vs oral iron group by 166µg/L (95% CI: 138-194; P < 0.0001) and in the IPM vs oral iron group by 145µg/L (95% CI: 109-1180, P < 0.0001), but not between the 2 IV groups (21.5µg/L; 95% CI: -23.9 to 66.9; P = 0.4989). Administration of IV FCM during pregnancy was safe and better tolerated than IV IPM or oral iron. Compliance to oral iron was the lowest amongst treatment groups with one-third of the patients missing doses of daily iron tablets. Significant improvement in overall QoL scores was observed in both IV iron supplement groups by achieving normal ferritin following effective and prompt repletion of iron stores, compared to the oral iron group (P = 0.04, 95% CI: 21.3, 1.8). The overall cost utility of IV FCM and IV IPM appear to be similar to oral iron. There were no differences in the fetal outcomes between the 3 trial arms. In conclusion, this study demonstrates that a single IV iron infusion is an effective and safe option for treatment of IDA during pregnancy. FCM was more convenient than other treatments. Rapid parenteral iron repletion can improve iron stores, Hb levels and QoL in pregnant women, with ongoing benefits until delivery. Integration of IV iron for IDA in pregnancy can potentially improve pregnancy outcomes for the mother. Update of guidelines to integrate the use of new IV iron preparations in pregnancy is warranted.

Concurrent Hairy Cell Leukemia and Metastatic Merkel Cell Carcinoma.

Hairy cell leukemia (HCL) and Merkel cell carcinoma (MCC) are two rare malignancies with distinct cells of origin. HCL is a lymphoid malignancy of mature B cells, and MCC derives from neuroendocrine cell origin. HCL has a favorable prognosis with most patients achieving long-term remission and potential cure. In contrast, MCC is an aggressive malignancy affecting the skin and can metastasize quickly with a dismal prognosis. Immunocompromised patients, such as those with AIDS, posttransplant, and the elderly, have higher incidences than the general population, suggesting a possible immune mechanism. We report a case where a patient presented with HCL and metastatic MCC synchronously. This is the first reported case of these two rare malignancies occurring concurrently at initial presentation and may represent a role of immunosuppression in the pathogenesis of MCC.

Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials.

Spleen tyrosine kinase (Syk) signaling is central to phagocytosis-based, antibody-mediated platelet destruction in adults with immune thrombocytopenia (ITP). Fostamatinib, an oral Syk inhibitor, produced sustained on-treatment responses in a phase 2 ITP study. In two parallel, phase 3, multicenter, randomized, double-blind, placebo-controlled trials (FIT1 and FIT2), patients with persistent/chronic ITP were randomized 2:1 to fostamatinib (n = 101) or placebo (n = 49) at 100 mg BID for 24 weeks with a dose increase in nonresponders to 150 mg BID after 4 weeks. The primary endpoint was stable response (platelets ≥50 000/µL at ≥4 of 6 biweekly visits, weeks 14-24, without rescue therapy). Baseline median platelet count was 16 000/µL; median duration of ITP was 8.5 years. Stable responses occurred in 18% of patients on fostamatinib vs. 2% on placebo (P = .0003). Overall responses (defined retrospectively as ≥1 platelet count ≥50 000/µL within the first 12 weeks on treatment) occurred in 43% of patients on fostamatinib vs. 14% on placebo (P = .0006). Median time to response was 15 days (on 100 mg bid), and 83% responded within 8 weeks. The most common adverse events were diarrhea (31% on fostamatinib vs. 15% on placebo), hypertension (28% vs. 13%), nausea (19% vs. 8%), dizziness (11% vs. 8%), and ALT increase (11% vs. 0%). Most events were mild or moderate and resolved spontaneously or with medical management (antihypertensive, anti-motility agents). Fostamatinib produced clinically-meaningful responses in ITP patients including those who failed splenectomy, thrombopoietic agents, and/or rituximab. Fostamatinib is a novel ITP treatment option that targets an important mechanism of ITP pathogenesis.

Successful treatment of concomitant metastatic prostate cancer and B-cell non-Hodgkin's lymphoma with R-EPOCH chemotherapy regimen and antiandrogen therapy.

A 70-year-old man presented with left loin pain without urinary symptoms. Initial investigations with CT showed enlarged para-aortic, mediastinal lymph nodes, right-side renal mass and enlarged prostate. A prostatic-specific antigen (PSA) was alarmingly high at 4750 µg/L (normal <4.0 µg/L). Further investigations included positron emission tomography (PET); both prostate-specific membrane antigen and 18-fluorodeoxyglucose as well as bone scan and bone marrow examination confirmed dual malignancies with B-cell non-Hodgkin's lymphoma (B-NHL) and wide spread metastatic prostatic adenocarcinoma (PA) to the skull, spine, pelvis, liver and lungs. The patient was treated with six cycles of rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin(R-EPOCH) containing regimen for B-NHL and goserelin hormonal therapy for PA. Restaging with PET scans thereafter showed complete remission of NHL with disappearance of his metastatic PA and normalisation of PSA levels. R-EPOCH regimen and antiandrogen therapy resulted in a good outcome and remission of both malignancies.

Inherited haemochromatosis with C282Y mutation in a patient with alpha-thalassaemia: a treatment dilemma.

A Caucasian 24-year-old female patient suffers from two hereditary disorders: alpha-thalassaemia, which is prevalent in Asia and rare in Europe, and haemochromatosis, which is prevalent among northern Europe and rare in Asia. The clinical presentation and management of one of these diseases is controversial for the other. She presented 5 years ago with a clinical picture of refractory iron-deficiency anaemia secondary to menorrhagia. On treating her with the standard iron therapy, her anaemia persists although with adquate iron stores. This prompted further investigations that revealed in addition to hereditary haemochromatosis, alpha-thalassaemia because of abnormal blood indices. The treatment of thalassaemia with either iron or blood transfusion is not advisable in haemochromatosis, while standard treatment of haemochromatosis with venesection will worsen the anaemia. As iron chelating agents were not approved in Australia for haemochromatosis, haematinics support was commenced with a satisfactory improvement of anaemia thus allowing for further venesection.

Venous thromboembolism in medical patients during hospitalisation and 3†months after hospitalisation: a prospective observational study.

OBJECTIVES: This study was conducted to assess the incidence and risk factors for venous thromboembolism (VTE) in a cohort of medical patients both during the period of hospitalisation and following discharge. DESIGN: This was a prospective observational study to document the risk profile and incidence of VTE posthospitalisation among all medical patients admitted to our institution during the trial period. SETTINGS: Primary healthcare. Single tertiary referral centre, Tasmania, Australia. PARTICIPANTS: A total of 986 patients admitted to the medical ward between January 2012 and September 2012 were included in the study with male to female ratio of 497:489. The mean age of patients was 68 years (range 17-112, SD 16). RESULTS: Overall, 54/986 patients (5.5%) had a VTE during the study period. Of these, 40/54 (74.1%) occurred during hospitalisation and 14/54 (25.9%) occurred following discharge. VTE risk factors revealed in multivariate analysis to be associated with a previous diagnosis of VTE (p<0.001, OR=6.63, 95% CI 3.3 to 13.36), the occurrence of surgery within the past 30 days (p<0.001, OR=2.52, 95% CI 1.33 to 4.79) and an admission diagnosis of pulmonary disease (p<0.01, OR 3.61, 95% CI 1.49 to 8.76). Mobility within 24 hours of admission was not associated with an increased risk. There was risk of VTE when the length of stay prolonged (p=0.046, OR=1.01, 95% CI 1.00 to 1.03), however it was not sustained with multivariate modelling. VTE-specific prophylaxis was used in 53% of the studied patients. Anticoagulation including antiplatelet agents were administered in 63% of patients who developed VTE. CONCLUSIONS: This prospective observational study found that 5.5% of the studied patients developed VTE. Among those, 25.9% (14/54) of patients had a detected VTE posthospitalisation with this risk being increased if there was a history of VTE, recent surgery and pulmonary conditions. Thromboprophylaxis may be worth considering in these cohorts. Further study to confirm these findings are warranted. TRIAL REGISTRATION NUMBER: ACTRN12611001255976.

Intravenous ferric carboxymaltose versus standard care in the management of postoperative anaemia: a prospective, open-label, randomised controlled trial.

BACKGROUND: Despite increasing efforts in perioperative management, postoperative iron deficiency anaemia persists, and few data are available about the management of this condition. In this study, we aimed to determine whether giving postoperative intravenous iron (in the form of ferric carboxymaltose) improved iron stores, haemoglobin concentrations, and outcomes following surgery. METHODS: We did a prospective, open-label, randomised, controlled study of patients at two centres (a general hospital and a private health-care centre) in Tasmania, Australia, undergoing elective surgery with functional iron deficiency anaemia (haemoglobin 70-120 g/L and ferritin ≤100 µg/L or iron saturation ≤20%), measured at day 1 postoperatively. Consecutive routine elective surgical patients who were having major orthopaedic surgery, abdominal, and genitourinary surgery, and other surgeries were recruited. Via computer-generated randomisation, patients were randomly assigned (1:1) to either a single dose of intravenous 1000 mg ferric carboxymaltose (intervention group) or standard care, consisting of observation (control group). The primary endpoints were changes in haemoglobin concentrations and iron stores at 4 weeks postoperatively, and the number of transfused units of blood required postoperatively until discharge. Analyses were done on an intention-to-treat basis. This trial is registered with the Australian New Zealand Clinical Trials Registry and the WHO International Clinical Trials Registry platform (number ACTRN12614001261606). FINDINGS: Between Dec 17, 2014, and May 7, 2015, we recruited 201 eligible patients, assigning 103 to intravenous ferric carboxymaltose and 98 to standard care only. Baseline mean haemoglobin was 105·5 g/L (SD 13·8) in the standard care group versus 106·2 g/L (11·9) in the ferric carboxymaltose group, improving at 4 weeks to 121·5 g/L (SD 14·5) in the standard group and 130·1 g/L (11·3) in the ferric carboxymaltose group (mean difference of 7·84 g/L, 95% CI 3·79-11·9; p<0·0001 in favour of the ferric carboxymaltose group). Significant improvements in serum iron (5·36 µmol/L, 95% CI 3·62-7·09; p<0·0001), iron saturation (11·40%, 95% CI 8·33-14·50; p<0·0001), and serum ferritin concentrations (468 µg/L, 95% CI 355-582; p<0·0001) were also noted in the ferric carboxymaltose group at 4 weeks compared with standard care, although no differences were noted in transferrin concentrations (0·06 g/L, 95% CI -0·97 to 1·09; p=0·62). Fewer transfused blood units were given in the ferric carboxymaltose group (to one of 103 patients [<1%]) than in the standard care group (to five of 98 patients [5%]; incidence rate ratio 0·10; 95% CI 0·01-0·85; p=0·035). No adverse events were observed with ferric carboxymaltose treatment. INTERPRETATION: Postoperative intravenous ferric carboxymaltose is a feasible and pragmatic management approach in surgical patients with functional iron deficiency anaemia. Our study suggests that patient blood management guidelines should be updated, incorporating the use of postoperative intravenous iron infusion to optimise patient outcomes. Further trials to assess our approach are warranted. FUNDING: Launceston General Hospital, Launceston, TAS, Australia, in affiliation with the University of Tasmania, TAS, Australia.

Changes to fibrinolysis in patients with systemic lupus erythematosus are associated with endothelial cell damage and inflammation, but not antiphospholipid antibodies.

We investigated whether changes to fibrinolysis were associated with other manifestations of systemic lupus erythematosus (SLE), including antiphospholipid (APL) antibody status, endothelial damage, and inflammation. Ninety-four patients (36 SLE patients, 58 healthy controls) were recruited from Tasmania, Australia. Circulating levels of plasminogen, α2-antiplasmin, tissue-type plasminogen activator, plasminogen activator inhibitor-1, and thrombin-activatable fibrinolysis inhibitor (TAFI) were measured, as well as APL antibodies (including lupus anticoagulant, anticardiolipin, and antibeta-2 glycoprotein-1 antibodies), soluble E-selectin, and interleukin-6. Whereas there was a significant decrease in plasminogen (patient vs. control; median) (210 vs. 444 ng/ml; P < 0.0001) and increase in α2-antiplasmin (0.53 vs. 0.09 µg/ml; P = 0.0007), there was increased t-PA (0.65 vs. 0.40 ng/ml; P = 0.0001) and decreased TAFI (8.8 vs. 10.0 ng/ml; P = 0.002) in SLE patients compared to healthy controls. Plasminogen was significantly associated with α2-antiplasmin (rho = -0.563, P < 0.001); TAFI (rho = 0.410, P = 0.011); soluble E-selectin (rho = 0.531, P = 0.001); and interleukin-6 (rho = 0.489, P = 0.002) in SLE patients; however, APL antibody status was not associated with any of the markers measured. This study has demonstrated that fibrinolysis is significantly altered in patients with SLE compared to controls, and associated with endothelial cell damage and inflammation, but not APL antibody status.

Review of Management and Outcomes in Women with Thrombophilia Risk during Pregnancy at a Single Institution.

Pregnancy is a hypercoagulable state associated with an increased risk of venous thromboembolic disease (VTE). We retrospectively studied 38 Caucasian pregnant women with thrombophilia risk and compared their obstetric outcomes with a matched cohort without known thrombophilia risk during the period between January 2007 and December 2010. There were (2) cases with factor V Leiden, (6) prothrombin gene mutation, (1) antithrombin III deficiency, (2) protein C deficiency, (3) protein S deficiency, (10) MTHFR mutation, (7) anti-cardiolipin antibodies, and (1) lupus anticoagulant. Patients without thrombophilia who presented with recurrent unprovoked VTE were considered as high risk (6 cases). Most patients received anticoagulation (34/38) with aspirin only (6), enoxaparin (27), and warfarin (1). Twenty-six out of thirty-eight pregnant women (68.4%) with an increased risk of thrombophilia experienced one or more obstetric complications defined as hypertension, preeclampsia, placenta abruptio, VTE, and oligohydramnios, compared with 15 out of 40 (37.5%) pregnant women in the control group (OR 3.6; 95% CI 1.42, 9.21, P < 0.001). The incidence of obstetric complications was significantly higher in the thrombophilia group compared to the controls. However, these complications were the lowest among patients who received full-dose anticoagulation. Our study suggests that strict application of anticoagulation therapy for thrombophilia of pregnancy is associated with an improved pregnancy outcome. The study was registered in the Australian and New Zealand Clinical Trials Registry under ACTRN12612001094864.

Hypereosinophilic syndrome associated with ulcerative colitis presenting with recurrent Loeffler's endocarditis and left ventricular thrombus treated successfully with immune suppressive therapy and anticoagulation.

We reported a case of a 28-year-old Caucasian woman with hypereosinophilic syndrome (HES) associated with ulcerative colitis who presented on separate occasions with Loeffler's endocarditis. She was admitted in 2008 with fever, headache, confusion and visual loss. Diagnostic workup uncovered an eosinophilia of 3.1×109/L and major ECG abnormalities. Subsequent echocardiography revealed left ventricular wall motion abnormalities with mural thrombus. MRI brain scan showed multiple white matter lesions consistent with acute infarcts. She recovered rapidly with corticosteroids and anticoagulation. Four years later she re-presented with headache, fatigue and an eosinophilia of 13.4×109/L. This occurred 3 months after cessation of immunosuppression and within 12 months of total colectomy for fulminant ulcerative colitis. Echocardiography was suggestive of hypereosinophilic endomyocardial fibrosis with left ventricular thrombus. Anticoagulation and corticosteroids were resumed with good effect. This report highlights the findings, treatment and outcome of ulcerative colitis-associated HES manifesting as recurrent Loeffler's endocarditis.

Ophthalmic manifestations of herpes zoster virus in patients with multiple myeloma following bone marrow transplantation.

We report three patients with ophthalmic herpes zoster (HZ) manifestations on the background diagnosis of multiple myeloma (MM). It seems that immunocompromised status has caused reactivation of the varicella zoster virus (VZV) producing a well-characterised neurological syndrome and subsequent postherpetic neuralgia in two patients. One patient experienced lymphocytic leptomeningitis resulting in unilateral optic neuritis. All patients received similar myeloma disease-specific treatment prior to HZ reactivation. All patients were treated with thalidomide and steroids, and they thereafter underwent autologous stem cell transplantation. Prior to HZ reactivation they received new immunomodulatory drugs in the form of thalidomide in addition to bortezomib (2 patients) and lenalidomide (1 patient). Immediate specific antiviral therapy was successfully applied with intravenous acyclovir for 10 days, followed by long-term oral famciclovir maintenance. Two patients progressed to have chronic HZ ophthalmicus and postherpetic neuralgia requiring ongoing antiviral therapy and neuroepileptic medications for the neuropathic pain.

Early Application of High Cut-Off Haemodialysis for de-Novo Myeloma Nephropathy is Associated with Long-Term Dialysis-Independency and Renal Recovery.

BACKGROUND: Multiple myeloma (MM) is a haematological malignancy associated with kidney injury resulting from cast nephropathy, which can be caused by monoclonal free light chains (FLC). It has been demonstrated that early reduction of FLC can lead to a higher proportion of patients recovering renal function with a better outcome, especially if high cut-off haemodialysis (HCO-HD) combined with chemotherapy is used. PATIENTS AND METHODS: In this study, four cases with MM nephropathy were treated with HCO-HD and chemotherapy at a single institution during the period from August 2009 to August 2011. All of the patients presented with acute renal failure and high serum FLC. All patients underwent a bone marrow biopsy to confirm the diagnosis of MM, according to the WHO criteria. Three patients had de novo MM and one patient had relapsed light chain myeloma disease. All patients underwent HCO-HD concomitantly with specific myeloma therapy once the diagnosis or relapse of MM was established. RESULTS: After a medial follow up of 26 months, (range, 13-36) our data showed that all patients had a significant decrease in serum FLC through HCO-HD, proving the effectiveness of HCO-HD in managing MM. De-novo MM patients restored their renal function and achieved low-level FLC early in the treatment and became dialysis-independent. One patient with relapsed myeloma remained dialysis-dependent. CONCLUSION: In summary, our study suggests that in myeloma nephropathy associated with light-chain MM, HCO-HD should be initiated as early as possible. At the same time a specific MM treatment should be initiated to gain control of the disease and salvage the kidneys in order to achieve dialysis-independency. Further randomized trials to confirm our results are warranted.

Assessment of whole body MRI and sestamibi technetium-99m bone marrow scan in prediction of multiple myeloma disease progression and outcome: a prospective comparative study.

OBJECTIVES: This study aims primarily to determine whether whole body MRI (WB-MRI) and Sestamibi Technetium-99m-bone marrow (MIBI) scans in the same patients produce the same estimate of disease load and location, and secondly, to study possible association between the bone disease detected by these scans and the effect on disease outcome and survival. Bone disease occurs in about 90% of multiple myeloma (MM) patients. There are no data comparing the new diagnostic modalities with WB-MRI and MIBI in MM. DESIGN: A prospective comparative study between WB-MRI and MIBI scans in assessing bone disease and outcome of MM. PARTICIPANTS AND METHODS: Sixty-two consecutive patients with confirmed MM underwent simultaneous WB-MRI (both axial T1 and turbo spin echo short tau inversion recovery (STIR)) and MIBI scans at a single institution from January 2010 to January 2011, and their survival status was determined in January 2012. The median age was 62 years (range 37-88) with a male-to-female ratio of 33 : 29. RESULTS: In vertebrae and long bones, MRI scan detected more disease compared with MIBI scan (p<0.001) but there was less difference in the skull (p=0.09). In the ribcage, the MIBI scan detected more lytic lesions of the ribs compared with MRI scan (p<0.001). Thirteen of the 62 patients died during the 24-month follow-up. Increased disease detected in all bones by both scans was associated with increased mortality risk (MIBI p=0.001; MRI-STIR p=0.044; but not MRI-T1 p=0.44). In all combined bone groups, the mean MIBI scan results provided a better prediction of mortality than MRI scan over the follow-up period (MRI-T1 vs MIBI p=0.019; MRI-STIR vs MIBI p=0.047). CONCLUSIONS: Although WB-MRI detected more MM bone disease, MIBI scan predicted overall disease outcome and mortality better than MRI scan. Further studies to define optimum use of these imaging techniques are warranted. TRIAL REGISTRATION NUMBER: The study was registered prospectively in the Australian and New Zealand Clinical Trials Registry at http://www.ANZCTR.org.au under No: ACTRN12609000761268.

Extensive venous thrombosis in a healthy young man with a short inferior vena cava syndrome treated successfully with rivaroxaban.

We report a case of an incidental finding of congenital absence of the intrahepatic segment of the inferior vena cava (IVC) complicated by extensive bilateral deep venous thrombosis (DVT) with significant oedema following a long-distance road trip. Initially the patient failed treatment with standard anticoagulation therapy with enoxaparin and warfarin. However, he has responded to the new oral antifactor-Xa anticoagulant (rivaroxaban). Within a few days, rivaroxaban improved the oedema and DVT. The significant features of this case are the unusual presentation, the poor response to initial standard anticoagulation therapy and the beneficial outcomes when managed with the novel new anticoagulant. The patient has continued the new treatment regularly for the last 12 months with good toleration and without side effects. This report presents the findings, management and outcomes in a case of extensive bilateral DVT in a previously healthy young man who was found to have a congenital short IVC.

Three-year follow-up of a randomised clinical trial of intravenous versus oral iron for anaemia in pregnancy.

BACKGROUND: To date, there are no data available concerning the impact of iron therapy on the long-term well-being and health-related quality of life (HRQoL) in pregnancy. OBJECTIVE: To assess the long-term effect of iron therapy on HRQoL in pregnancy. DESIGN: This is a follow-up study conducted between January 2010 and January 2011 of an earlier randomised open-label clinical trial of intravenous and oral iron versus oral iron for pregnancy-related iron deficiency anaemia. We used a modified version of the SF-36 questionnaire together with the original prospective HRQoL data collected during and after pregnancy. PARTICIPANTS AND INTERVENTIONS: Of the original evaluable 183 pregnant Caucasian women randomised to receive oral iron or a single intravenous iron polymaltose infusion followed by oral iron maintenance, 126 women completed the follow-up HRQoL study. METHODS: The participants were followed up 4 weeks after treatment, predelivery and postdelivery for a median period of 32 months (range, 26-42) with a well-being and HRQoL questionnaire using a modified SF-36 QoL-survey and child growth charts as set by the Australasian Paediatric Endocrine Group (APEG). RESULTS: Patients who received intravenous iron demonstrated significantly higher haemoglobin and serum ferritin levels (p<0.001). There were strong associations between iron status and a number of the HRQoL parameters, with improved general health (p<0.001), improved vitality (physical energy) (p<0.001), less psychological downheartedness (p=0.005), less clinical depression (p=0.003) and overall improved mental health (p<0.001). The duration of breastfeeding was longer (p=0.046) in the intravenous iron group. The babies born in both groups recorded similarly on APEG growth chart assessments. CONCLUSIONS: Our data suggest that HRQoL is improved until after pregnancy in anaemic pregnant women by repletion of their iron stores during pregnancy. About 80% of the intravenous iron group showed a maintained normal ferritin until delivery with long-term benefits. Further studies to confirm these findings are warranted.

Iron deficiency anaemia in pregnancy and postpartum: pathophysiology and effect of oral versus intravenous iron therapy.

Nutritional iron-deficiency anaemia (IDA) is the most common disorder in the world, affecting more than two billion people. The World Health Organization's global database on anaemia has estimated a prevalence of 14% based on a regression-based analysis. Recent data show that the prevalence of IDA in pregnant women in industrialized countries is 17.4% while the incidence of IDA in developing countries increases significantly up to 56%. Although oral iron supplementation is widely used for the treatment of IDA, not all patients respond adequately to oral iron therapy. This is due to several factors including the side effects of oral iron which lead to poor compliance and lack of efficacy. The side effects, predominantly gastrointestinal discomfort, occur in a large cohort of patients taking oral iron preparations. Previously, the use of intravenous iron had been associated with undesirable and sometimes serious side effects and therefore was underutilised. However, in recent years, new type II and III iron complexes have been developed, which offer better compliance and toleration as well as high efficacy with a good safety profile. In summary, intravenous iron can be used safely for a rapid repletion of iron stores and correction of anaemia during and after pregnancy.