Immunosuppressive treatment is reported to improve cytopenia in some patients with myelodysplastic syndrome (MDS). Combined antithymocyte globulin (ATG) and cyclosporine (CSA) is most effective in ...patients with immune-mediated marrow failure.
This trial was designed to assess the impact of immunosuppression on hematopoiesis, transfusion requirements, transformation, and survival in patients with MDS randomly assigned to 15 mg/kg of horse ATG for 5 days and oral CSA for 180 days (ATG+CSA) or best supportive care (BSC), stratified by treatment center and International Prognostic Scoring System (IPSS) risk score. Primary end point was best hematologic response at 6 months. Eligible patients had an Eastern Cooperative Oncology Group performance status of ≤ 2 and transfusion dependency of less than 2 years in duration.
Between 2000 and 2006, 45 patients received ATG+CSA (median age, 62 years; range, 23 to 75 years; 56% men) and 43 patients received BSC (median age, 65 years; range, 24 to 76 years; 81% men). IPSS score was low, intermediate-1, intermediate-2, high, and not evaluable in eight, 24, seven, one, and five patients on ATG+CSA, respectively, and eight, 25, five, zero, and five patients on BSC, respectively. Refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess of blasts (RAEB) -I, RAEB-II, and hypoplastic disease were present in 21, six, nine, zero, and nine patients on ATG+CSA, respectively, and 18, eight, 11, two, and four patients on BSC, respectively. By month 6, 13 of 45 patients on ATG+CSA had a hematologic response compared with four of 43 patients on BSC (P = .0156). Two-year transformation-free survival (TFS) rates were 46% (95% CI, 28% to 62%) and 55% (95% CI, 34% to 70%) for ATG+CSA and BSC patients, respectively (P = .730), whereas overall survival (OS) estimates were 49% (95% CI, 31% to 66%) and 63% (95% CI, 42% to 78%), respectively (P = .828).
This open-label randomized phase III trial demonstrates that ATG+CSA treatment seems to be associated with hematologic response in a subset of patients without apparent impact on TFS and OS.
Lower risk myelodysplastic syndromes (MDS), defined as MDS with a Revised International Prognostic Scoring System score ≤3.5 points, will remain a challenging entity in 2018. Supportive care ...continues to be the linchpin of treatment, although the options to reduce transfusion needs are broadening. To achieve red blood cell transfusion independence in non-del(5q) patients, erythropoiesis-stimulating agents remain a mainstay of therapy as long as endogenous erythropoietin levels are <500 U/L (and preferably <200 U/L). Experimental strategies for patients ineligible for erythropoiesis-stimulating agents or relapsing after gaining transfusion independence include immunosuppressive agents, transforming growth factor β inhibitors, and lenalidomide. All these alternatives have shown reasonable response rates in selected patient populations with lower risk MDS. Patients with del(5q) disease can derive long-term benefit from lenalidomide, and some patients remain transfusion free for extended periods even after discontinuation of the drug. In rare cases in which thrombocytopenia is the main clinical problem leading to clinically significant bleeding events, thrombopoietin receptor analogues may alleviate bleeding, increase platelet counts, and rarely lead to trilineage responses. It seems prudent to use these drugs only in patients with confirmed bone marrow blast counts <5%. Allogeneic stem cell transplantation is reasonable for patients with high molecular risk of progression and those failing several lines of treatment with signs of progression toward higher-risk MDS.
Background. Despite increasing evidence of the development of Plasmodium vivax chloroquine (CQ) resistance, there have been no trials comparing its efficacy with that of artemisinin-based combination ...therapies (ACTs) in Latin America. Methods. This randomized controlled trial compared the antischizontocidal efficacy and safety of a 3-day supervised treatment of the fixed-dose combination artesunate-amodiaquine Winthrop® (ASAQ) versus CQ for treatment of uncomplicated P. vivax infection in Manaus, Brazil. Patients were followed for 42 days. Primary endpoints were adequate clinical and parasitological responses (ACPR) rates at day 28. Genotype-adjustment was performed. Results. From 2012 to 2013, 380 patients were enrolled. In the per-protocol (PP) analysis, adjusted-ACPR was achieved in 100% (165/165) and 93.6% (161/172) of patients in the ASAQ and CQ arm (difference 6.4%, 95% CI 2.7%; 10.1%) at day 28 and in 97.4% (151/155) and 77.7% (129/166), respectively (difference 19.7%, 95% CI 12.9%; 26.5%), at day 42. Apart from ITT D28 assessment, superiority of ASAQ on ACPR was demonstrated. ASAQ presented faster clearance of parasitaemia and fever. Based on CQ blood level measurements, CQ resistance prevalence was estimated at 11.5% (95% CI: 7.5-17.3) up to day 42. At least one emergent adverse event (AE) was recorded for 79/190 (41×6%) in the ASAQ group and for 85/190 (44×7%) in the CQ group. Both treatments had similar safety profiles. Conclusions. ASAQ exhibited high efficacy against CQ resistant P. vivax and is an adequate alternative in the study area. Studies with an efficacious comparator, longer follow-up and genotype-adjustment can improve CQR characterization. Clinical Trials Registration. NCT01378286.
ABSTRAK
Pendahuluan : Eritrosit merupakan salah satu komponen darah yang jumlahnya paling banyak dalam susunan komponen darah manusia eritrosit normal selalu berbentuk bikonkaf, tidak memiliki inti, ...dan mengandung hemoglobin yang merupakan representasi warna merah dalam darah. Pemeriksaan hitung jumlah eritrosit adalah pemeriksaan yang bertujuan untuk menentukan jumlah eritrosit dalam 1 µL darah dan digunakan sebagai tes skrining anemia dan polistemia,Menghitung jumlah eritrosit dapat dilakukan dengan dua metode, yaitu manual dan otomatis larutan isotonic yang kemudian dihitung didalam kamar hitung. Pemeriksaan hitung jumlah eritrosit metode manual menggunakan reagen hayen. Tujuan: untuk mengetahui perbandingan hasil pemeriksaan eritrosit menggunakan garam dapur dan reagen hayem. Metode: Jenis penelitian ini adalah cross sectional komperatif . penelitian ini dilakukan dilaboratorium hematologi IkesT Muhammadiyah palembang pada tanggal 5 januari 2022 dengan jumlah sempel sebanyak 32 sempel. Hasil : hasil penelitian memiliki nilai Rata-rata hitung erirosit dengan garam dapur sebesar 422.812 sel/mm3 dan Rata-rata hitung eritrosit dengan reagen hayem sebesar 2.263.750 sel/mm3. Hasil uji T berpasangan didapatkan nilai p = 0.000 Kesimpulan dari hasil penelitian adalah terdapat bebedaan hasil hitung eritrosit menggunakan garam dapur dan reagen hayem
We have generated a large, unique database that includes morphologic, clinical, cytogenetic, and follow-up data from 2124 patients with myelodysplastic syndromes (MDSs) at 4 institutions in Austria ...and 4 in Germany. Cytogenetic analyses were successfully performed in 2072 (97.6%) patients, revealing clonal abnormalities in 1084 (52.3%) patients. Numeric and structural chromosomal abnormalities were documented for each patient and subdivided further according to the number of additional abnormalities. Thus, 684 different cytogenetic categories were identified. The impact of the karyotype on the natural course of the disease was studied in 1286 patients treated with supportive care only. Median survival was 53.4 months for patients with normal karyotypes (n = 612) and 8.7 months for those with complex anomalies (n = 166). A total of 13 rare abnormalities were identified with good (+1/+1q, t(1q), t(7q), del(9q), del(12p), chromosome 15 anomalies, t(17q), monosomy 21, trisomy 21, and −X), intermediate (del(11q), chromosome 19 anomalies), or poor (t(5q)) prognostic impact, respectively. The prognostic relevance of additional abnormalities varied considerably depending on the chromosomes affected. For all World Health Organization (WHO) and French-American-British (FAB) classification system subtypes, the karyotype provided additional prognostic information. Our analyses offer new insights into the prognostic significance of rare chromosomal abnormalities and specific karyotypic combinations in MDS.
•Novel fragility models for scoured-critical bridges exposed to multiple hazards were generated•Rigorous FEM included the water-soil-bridge interaction under flooding and earthquakes•Failure modes ...for bridge components exposed to floods were described•Insights on the flood vulnerability of integral and bridges with bearings are provided•Consideration of uncertainties in scour formation enhance the reliability of risk assessment
Building resilient bridges, that are able to withstand multiple natural stressors with minimal damage and quickly restore their functionality is paramount to delivering climate-resilient transport infrastructure. Nevertheless, bridges are proven to be vulnerable to natural hazards, with floods and earthquakes being the main causes of failure. The available research and practice for assessing the vulnerability of river-crossing bridges is predominantly qualitative and therefore relies heavily on visual inspections, while ignoring important characteristics of the complex water-soil-bridge interaction. This is a knowledge gap that this paper aims to fill. This work provides novel fragility models for hydraulically induced stressors and/or combinations of hydraulic and seismic hazards. To achieve this, unique detailed two- and three- dimensional numerical models are employed, for a typical three-span prestressed box-girder river-crossing bridge. This paper is a primer on the vulnerability of flood-critical bridges as it models the entire water-soil-bridge system, taking into account critical hydraulic stressors (scour, debris accumulation, hydraulic forces), the uncertainty in scour hole formation, and all components of integral and isolated bridges: deck, bearings, piers and abutments, backfill, and the foundation soil. A detailed description of the damage modes for each component is given and sets of fragility curves for floods and combinations of hydraulic stressors and earthquakes are developed. The study concludes that integral bridges are in most cases more vulnerable to local scour than bridges with bearings, since the latter are more flexible and can therefore adapt to changes in their geometry. The opposite is true for global scour and/or seismic earthquake excitations. The generated fragility models are useful tools for quantitative risk assessment of transport systems and provide practical means in resilience-based asset management by owners and operators of transport infrastructure.
Display omitted
•Description of cocoa production chain and residual biomass generation.•Cocoa by-products as a source of high-value-added molecules.•Biotechnology as an alternative for the ...biotransformation of cocoa by-products.•Relevance of sustainability, innovation and technology in cocoa industry.
Cocoa beans provide raw materials for global food industries valued in excess of $47 billion in world exportations. Through on-farm processing, about 80% of cocoa fruit is discarded as residual biomass, including cocoa pod husks, cocoa bean shells and cocoa sweatings. Farmers routinely discard these residues/by-products during the initial cocoa bean processing steps, occupying vast areas and raising social and environmental concerns. Alternatively, this residual biomass is used as cocoa tree fertilizer. However, its disposal is performed without proper treatment, resulting in putrid odors and plant diseases. Recently, some studies have reported the use of cocoa by-products in the production of high-value-adding molecules with potential applications in the food, pharmaceutical and cosmetic industries. In this aspect, biotechnological approaches have been shown to be a viable alternative for the transformation of this residual biomass into fine products. This article reviews the biotechnological approaches implemented for the management and exploitation of cocoa by-product. Related topics on cocoa production and residual biomass generation, sustainability and valorization of cocoa chain are addressed and discussed.
The importance of evapotranspiration is well-established in different disciplines such as hydrology, agronomy, climatology, and other geosciences. Reliable estimates of evapotranspiration are also ...vital to develop criteria for in-season irrigation management, water resource allocation, long-term estimates of water supply, demand and use, design and management of water resources infrastructure, and evaluation of the effect of land use and management changes on the water balance. The objective of this Special Issue is to define and discuss several ET terms, including potential, reference, and actual (crop) ET, and present a wide spectrum of innovative research papers and case studies.
PDF
