ALBERT

Description: We quantify the timing, intensity, and distribution of bird migration through one of the largest migration corridors in the Western Hemisphere, the Gulf of Mexico, by integrating citizen science (eBird) observations with weather surveillance radar data. We estimate that an average of 2.1 billion birds pass through this region each spring, with half of these individuals pass through the region in just 18 days, between April 19 and May 7. We did not detect an overall change in the annual numbers of migrants (2007–2015) or the annual timing of peak migration (1995–2015). Abstract Quantifying the timing and intensity of migratory movements is imperative for understanding impacts of changing landscapes and climates on migratory bird populations. Billions of birds migrate in the Western Hemisphere, but accurately estimating the population size of one migratory species, let alone hundreds, presents numerous obstacles. Here, we quantify the timing, intensity, and distribution of bird migration through one of the largest migration corridors in the Western Hemisphere, the Gulf of Mexico (the Gulf). We further assess whether there have been changes in migration timing or intensity through the Gulf. To achieve this, we integrate citizen science (eBird) observations with 21 years of weather surveillance radar data (1995–2015). We predicted no change in migration timing and a decline in migration intensity across the time series. We estimate that an average of 2.1 billion birds pass through this region each spring en route to Nearctic breeding grounds. Annually, half of these individuals pass through the region in just 18 days, between April 19 and May 7. The western region of the Gulf showed a mean rate of passage 5.4 times higher than the central and eastern regions. We did not detect an overall change in the annual numbers of migrants (2007–2015) or the annual timing of peak migration (1995–2015). However, we found that the earliest seasonal movements through the region occurred significantly earlier over time (1.6 days decade−1). Additionally, body mass and migration distance explained the magnitude of phenological changes, with the most rapid advances occurring with an assemblage of larger‐bodied shorter‐distance migrants. Our results provide baseline information that can be used to advance our understanding of the developing implications of climate change, urbanization, and energy development for migratory bird populations in North America.

Description: The safety and efficacy of weekly rituximab 375 mg/m2 (×4), given within 3 days of acute TTP admission, with standard therapy (PEX and steroids) was evaluated. Clinical outcomes were compared to historical controls (n = 40) who had not received rituximab. Within the trial group, 15 of 40 required ICU admission and 15% of all cases with the highest troponin T levels on admission were ventilated. Before the second rituximab infusion, 68% of cases had a platelet count 〉 50 × 109/L and 38% 〉 150 × 109/L. Fewer PEX were required in whites compared to nonwhite in the rituximab group (mean 14 vs 21, P = .0095). Inpatient stay was reduced by 7 days in the non-ICU trial cases compared to historical controls (P = .04), especially in whites, with a mean reduction of 7 days (P = .05). Ten percent of trial cases relapsed, median, 27 months (17-31 months), compared to 57% in historical controls, median 18 months (3-60 months; P = .0011). There were no excess infections or serious adverse events with rituximab. In conclusion, rituximab appears a safe and effective therapy. Inpatient stay and relapse are significantly reduced in the rituximab cohort. Rituximab should be considered in conjunction with standard therapy on acute presentation of TTP. This study was registered at www.clinicaltrials.gov as NCT009-3713.

Description: Thrombotic thrombocytopenic purpura (TTP) is a life threatening disorder characterised by thrombocytopenia and microangiopathic haemolytic anaemia associated with a deficiency in ADAMTS 13. Human Immunodeficiency Virus (HIV) remains an important infectious cause of TTP. We report the characteristics and treatment of patients presenting over a 6.5 year period to a tertiary referral centre. Cases: 9 patients, 8 female, 1 male, all heterosexual Africans. In 5 of the patients, TTP presentation was associated with the initial diagnosis of HIV. Only 1 patient was on highly active anti-retroviral therapy (HAART) at diagnosis. Median haemoglobin on admission was 6.4 (range 4.6–7.2) g/dl, platelet count-12 (range 5–53) X 109/L, lactate dehydrogenase (LDH) 1401 (range 914-2532) IU/L. In 6 patients there were neurological features at presentation, from headache, to transient ischaemic attacks and coma;6 patients had renal impairment, median creatinine 127 (range 63–418) μmol/L. Notably, HIV associated TTP was not a late onset disorder associated with poor CD 4 counts and poor prognosis. Median CD 4 counts were 170 (range 70–400) cells/μl, with a median viral load 74,400 copies/ml. ADAMTS 13 activity ranged from

Description: Pregnancy is an initiating event for acute thrombotic thrombocytopenic purpura (TTP). Patients with a history of TTP have a high risk of relapse during pregnancy with associated maternal and fetal morbidity/mortality. We report 5 TTP patients who underwent serial clinical and laboratory monitoring (haemoglobin, platelets, blood film, reticulocytes, lactate dehydrogenase (LDH), ADAMTS-13 activity and IgG antibodies) and treatment within a specialist obstetric/haematology clinic, resulting in successful pregnancy outcomes. Patients: Cases 1 and 2 presented with TTP in their first pregnancy and had second trimester fetal losses. Case 3 had four TTP relapses and soon after achievement of clinical remission became pregnant. Case 4 had a single acute episode of TTP 6 years prior to pregnancy and normal ADAMTS 13 activity at the onset of pregnancy. Case 5 presented with acute TTP and a left sided stroke at 16 weeks gestation. ADAMTS-13 activity was 15% during pregnancy (range 15–78%, normal range 66–126%) by collagen binding assay. Case 4 had normal laboratory parameters, including serial ADAMTS 13 activity levels, throughout pregnancy, requiring no specific therapy for TTP. Case 5 received intensive PEX (84 procedures) and pulsed methylprednisolone during pregnancy. Rituximab (375mg/m2, weekly for 4 weeks) was given at 28 weeks gestation with no observed toxicity except asymptomatic transient neonatal neutropenia. All 5 cases continued low dose aspirin (75 mg daily) throughout pregnancy. Case 1 and 2 received prophylactic low molecular weight heparin (LMWH) and cases 3 and 5 received treatment doses of LMWH for pulmunory emboli and TTP associated stroke at presentation. Live healthy infants were delivered in all 5 cases in the third trimester (31–41 weeks). These data suggest successful pregnancy outcome is achievable in patients with a history of TTP/acute TTP with therapy based on close clinical and laboratory monitoring. Regular PEX in patients with a history of TTP and severely reduced ADAMTS 13 activity/IgG antibodies to ADAMTS 13 at the onset of pregnancy was associated with successful pregnancy outcome. Serial ADAMTS 13 activity and antibody levels during pregnancy and post-partum provided a useful adjunct to decision making on intensity of treatment.

Description: This multi-centre, phase II non-randomised trial, using Rituximab, in conjunction with standard therapy, plasma exchange (PEX) and pulsed methylprednisolone (MP), to include 40 adult patients with acute idiopathic thrombotic thrombocytopenic purpura (TTP). Rituximab 375mg/m2 was given once a week for 4 weeks, following plasma exchange, started within 3 days of admission, having excluded secondary TTP causes such as pregnancy/retroviral infection. ADAMTS 13 activity/IgG antibody levels guided further therapy to a maximum of 8 treatments. Historical cases were used as comparisons to determine if Rituximab therapy on admission was associated with improved time to remission, defined by platelet count and number of PEX. Secondary outcomes were relapse rate, mortality at 3 months, safety/toxicity of Rituximab, effect on B-lymphocytes, ADAMTS 13 activity and IgG antibodies to ADAMTS 13. Results from the first 20 patients (15 females and 5 males), median age 43 years with 5 females presenting with an acute relapse TTP, none previously receiving Rituximab. All received 4 weekly Rituximab treatments and 2 continued to 8. Eight were afro-Caribbean (A/C), 9 Caucasian and 3 SE Asian. Historical controls: 17 females and 3 males, 5 with relapsed acute TTP, median age 42 years. 14 were Caucasian, 5 A/C and 1 Asian. There were comparable presenting features in both groups. The median number of PEX to remission in the trial group was 13.5 and 19 in the historical group. Platelet counts on admission were 12 (8–31) x109/L for trial cases and 14 (4–78) x109/L in historical controls. Pre 1st Rituximab therapy, median platelet count was 23x 109/L. By day 7 platelet counts were 211 x109/L for the historic controls but 9/20 had platelets〈 150 x109/L. Pre 2nd Rituximab (day 8) for trial cases, median platelet counts were 91 x109/L and 10/20 had platelets

Description: The standard treatment of thrombotic antiphospholipid syndrome (APS) is lifelong oral anticoagulation with a vitamin K antagonist (VKA), generally warfarin. A minority of APS patients re-thrombose despite seemingly adequate anticoagulation. These patients are deemed anticoagulant-refractory. The management of anticoagulant-refractory APS is largely empirical and extrapolated from other clinically similar situations. Further options include increased VKA anticoagulation intensity or alternative antithrombotic strategies, including low-molecular-weight heparin, fondaparinux, the addition of antiplatelet therapy and consideration of vascular options. Anticoagulant-refractory thrombotic APS patients may have APS-associated thrombocytopenia, which necessitates balancing the risk of recurrent thrombosis versus bleeding, to achieve adequate anticoagulation. The multiple mechanisms involved in the generation of the thrombotic phenotype in APS suggest that anticoagulation alone may not control thrombosis. Thus, other modalities, including adjunctive treatment (hydroxychloroquine, statins and vitamin D) for APS-related thrombosis merit consideration, as well as immunomodulatory therapy and complement inhibition. APS patients may have coexistent systemic lupus erythematosus, which adds to the complexity of managing their thromboembolic disease. However, with attention to detail and judicious application of the limited data, it is possible to minimise the morbidity resulting from anticoagulant-refractory thrombotic APS. Multicentre studies are required to guide the sequence of interventions and their comparative efficacy in patients with anticoagulant-refractory thrombotic APS.

Description: Background Complement activation may play a role in the pathogenesis of thrombosis and other pathological processes in the antiphospholipid syndrome (APS). Since coagulation proteases, such as factor Xa, can cleave complement proteins, we investigated complement activation in thrombotic APS patients receiving rivaroxaban, a direct factor Xa inhibitor. Aims To assess markers of complement activation (C3a, C5a, terminal complement complex (SC5b-9) and Bb fragment) in patients with thrombotic APS treated with rivaroxaban or warfarin in a prospective randomised controlled trial. Methods 116 APS patients with previous venous thromboembolism, including 22 with systemic lupus erythematosus (SLE), on long-term warfarin (target INR 2.5) were studied. 59 patients remained on warfarin and 57 (11 with SLE in each group) switched to rivaroxaban (20mg daily). EDTA samples were collected at baseline (all patients on warfarin) and on day 42 (2-4 hours after the last dose of rivaroxaban in patients on rivaroxaban). 5/116 patients were excluded (samples from four patients were haemolysed and one patient withdrew from the trial after randomisation), leaving 111 (55 rivaroxaban and 56 warfarin) patients for analysis at both baseline and day 42. Samples were also collected from 55 normal controls (NC). C3a, C5a SC5b-9 and Bb fragment were assessed using ELISA assay kits (QUIDEL Corp). Results Median (95% CI) C3a, C5a, SC5b-9 and Bb fragment were 48.9 (30.1-100.2) ng/mL, 6.8 (2.2-11.8 ng/mL, 113.9 (50.5-170) ng/mL and 1.1 (0.64-1.86) µg/mL in NC, respectively. APS patients had significantly higher complement activation markers compared to NC at both time points irrespective of the anticoagulant (p

Description: Thrombotic thrombocytopenic purpura (TTP) presents in childhood or adult life and is caused by a deficiency of von Willebrand factor-cleaving protease (ADAMTS13) activity. Several mutations and polymorphisms have been reported in ADAMTS13 in congenital TTP. The study aim was to elucidate whether a mutation(s) may be linked to adult onset TTP, which may be precipitated by infection, pregnancy or oestrogen-containing preparations and is associated with antibodies to ADAMTS13. We investigated 58 adult onset TTP patients (median age 39 (range 16–74) years) with ADAMTS13 activity levels