Abstract Introduction Hemophagocytic lymphohistiocytosis (HLH) is a rare clinical laboratory condition with high mortality rates, resulting from ineffective overactivation of the immune system. Data in the Brazilian literature is scarce, contributing to the challenge in standardizing conducts and performing an early diagnosis of HLH. Objective To describe the clinical, laboratory, and evolutionary findings on HLH patients treated at a pediatric hospital. Methods This is an observational, cross-sectional and retrospective study on children diagnosed with HLH, hospitalized between 2009 and 2019. The diagnostic criteria were those described in the Histiocyte Society protocol. The authors evaluated HLH patient laboratory tests, myelograms and bone marrow biopsies, clinical characteristics and therapy. Results Twenty-three patients were included, 52.2% of whom were males. The age at diagnosis ranged from one to one hundred and eighty months. Four cases were classified as Primary HLH and nineteen, as Secondary HLH. The main triggers were infections and rheumatological diseases. All children had bicytopenia, and 95.4% had hyperferritinemia. Nineteen patients had liver dysfunction, sixteen had neurological disorders and fourteen had kidney injury. Pulmonary involvement was seen in 61.9%, acting as a worse prognosis for death (p= 0.01). Nine patients underwent the immuno-chemotherapy protocol proposed in the HLH 2004. The time to confirm the diagnosis varied from five to eighty days. The lethality found was 56.3%. Conclusions The present study is the most extensive retrospective exclusively pediatric study published in Brazil to date. Despite the limitations, it was possible to demonstrate the importance of discussing HLH as a pediatric emergency. (HLH rates system scarce hospital observational crosssectional cross sectional 200 2019 tests biopsies therapy Twentythree Twenty three included 522 52 2 52.2 males months nineteen diseases bicytopenia 954 95 4 95.4 hyperferritinemia dysfunction injury 619 61 9 61.9% p= p (p 0.01. 001 0.01 . 0 01 0.01) immunochemotherapy immuno chemotherapy 2004 days 563 56 3 56.3% date limitations emergency 20 201 5 52. 95. 6 61.9 00 0.0 56.3 61. 0. 56.

Abstract Objective To understand the impact of the coronavirus disease 2019 pandemic on in vitro fertilization (IVF) clinical pregnancy rates and analyze factors that may have influenced their outcome. Methods This was a retrospective observational study conducted at a tertiary-care Brazilian fertility center. All fresh IVF and embryo warming cycles performed from March 11 to December 31, 2018–2021 were analyzed, and their data were used to calculate fertilization, embryo cleavage, cycle cancellation, embryo transfer (ET), and clinical pregnancy rates. Statistical tests were used to evaluate the alterations found. Logistic regression models were used to explore the association of the categorical variables with the observed clinical pregnancy rates. Data from 2018 and 2019 (prepandemic) and 2020 and 2021 (pandemic) were grouped. Results A total of 756 cycles were analyzed (n = 360 prepandemic and n = 396 pandemic). The age group of the patients, fertilization rates, and cleavage rates did not have significant differences (p > 0.05). There was a reduction in the percentage of fresh IVF and an increase in embryo warming cycles (p = 0.005) during the pandemic. There was also an increase in fresh cycle cancellations (p < 0.001) and a reduction in ET rates (p < 0.001). The pandemic had a negative impact on clinical pregnancy rates (p < 0.001) especially due to the increase in fresh cycle cancellations (p < 0.001). Conclusion Embryo warming cycles with subsequent frozen-thawed ET were presented as a viable alternative to continue assisted reproductive treatments against pandemic restrictions on fresh cycles, ensuring clinical pregnancy, albeit at a lower rate than that of the prepandemic period. 201 (IVF outcome tertiarycare tertiary care center 1 31 20182021 2018–202 cancellation ET, , (ET) found (prepandemic 202 (pandemic grouped 75 36 39 . pandemic) patients p 0.05. 005 0.05 0 05 0.05) 0.005 0005 0.001 0001 001 0.001. frozenthawed frozen thawed period 20 3 2018202 2018–20 (ET 7 00 0.0 0.00 000 2 201820 2018–2 0. 20182 2018–

Resumo Objetivo Compreender os impactos da pandemia de COVID-19 nas taxas de gravidez clínica em fertilização in vitro (FIV) e analisar fatores que possam ter influenciado seu resultado. Métodos Foi realizado um estudo observacional retrospectivo em um centro brasileiro de reprodução assistida. Todos os ciclos de FIV com embriões frescos e descongelados realizados entre 11 de março e 31 de dezembro, 2018-2021 foram analisados, e seus dados utilizados para cálculo das taxas de fertilização, clivagem embrionária, cancelamento de ciclos, transferência de embriões (TE) e gravidez clínica. Testes estatísticos avaliaram significância das alterações encontradas e modelos de regressão logística exploraram associação das variáveis categóricas estudadas com as taxas de gravidez clínica observadas. Os dados de 2018 e 2019 (pré-pandemia) e 2020 e 2021 (pandemia) foram agrupados. Resultados Foram analisados um total de 756 ciclos (n = 360 na pré-pandemia e n = 396 na pandemia). A faixa etária das pacientes e as taxas de fertilização e de clivagem não tiveram alterações significativas (p > 0,05). Na pandemia, houve redução da porcentagem de ciclos de FIV com embriões frescos e aumento dos com descongelamento (p = 0,005). Também foi notado aumento das taxas de cancelamentos de ciclos com embriões frescos (p < 0,001) e redução do número de TEs (p < 0,001). A pandemia exerceu impacto negativo na taxa de gravidez clínica (p < 0,001), especialmente devido ao aumento de cancelamentos dos ciclos a fresco (p < 0,001). Conclusão Frente às limitações pandêmicas impostas aos ciclos com embriões frescos, os ciclos de descongelamento de embriões se apresentaram como alternativa viável à continuidade dos ciclos de FIV, garantindo gravidez clínica ainda que em taxas inferiores às do período pré-pandêmico. COVID19 COVID 19 COVID-1 (FIV resultado assistida 1 3 dezembro 20182021 2018-202 embrionária TE (TE observadas 201 prépandemia pré (pré-pandemia 202 (pandemia agrupados 75 36 39 pandemia. . pandemia) p 0,05. 005 0,05 0 05 0,05) 0,005. 0005 0,005 0,005) 0,001 0001 001 0,001. 0,001, , prépandêmico. prépandêmico pandêmico. pandêmico pré-pandêmico COVID1 COVID- 2018202 2018-20 20 7 00 0,0 000 0,00 201820 2018-2 2 0, 20182 2018-

ABSTRACT Objective: To evaluate the early postoperative complications associated with the surgical approach of the cervical spine of patients with cervical spondylotic myelopathy (CSM), comparing the anterior surgical, the posterior surgical, and the combined approaches. Methods: This is a retrospective study based on a database with 169 patients. Demographic data, such as gender and age, and surgical data, such as surgical approach, number of segments with arthrodesis, surgical time, and complications, were evaluated. Complications were divided into major (deep surgical wound infection, intercurrence with the implant, early new compression, and heart failure) and minor (dysphagia, superficial infection, pain, urinary intercurrence, neuropraxia of the C5 root, acute confusional state, and surgical wound hematoma). Results: This included 169 patients, 57 women (33.7%) and 112 men (66.2%). Age ranged from 21 to 87 years, with a mean of 56.48 (± 11) years. Of these, 52 (30.8%) underwent the anterior approach; 111 (65.7%), the posterior approach; and 6 (3.5%), the combined approach. Conclusion: As in the literature, we evinced dysphagia, pain, and superficial infection of the surgical wound as the most frequent postoperative complications. However, it was impossible to establish a statistical relationship between the incidence of complications and surgical time, access route, and number of fixed segments. Level of Evidence III, Retrospective Comparative Study. Objective CSM, CSM , (CSM) approaches Methods 16 data age arthrodesis time evaluated deep implant compression failure dysphagia (dysphagia pain C root state hematoma. hematoma . hematoma) Results 5 33.7% 337 33 7 (33.7% 11 66.2%. 662 66.2% 66 2 (66.2%) 8 years 5648 56 48 56.4 ± ( these 30.8% 308 30 (30.8% 65.7%, 657 65.7% 65 (65.7%) 3.5%, 35 3.5% 3 (3.5%) Conclusion literature However route III Study (CSM 1 33.7 (33.7 66.2 (66.2% 564 4 56. 30.8 (30.8 65.7 (65.7% 3.5 (3.5% 33. (33. 66. (66.2 30. (30. 65. (65.7 3. (3.5 (33 (66. (30 (65. (3. (3 (66 (65 (6

RESUMO Objetivo: Avaliar as complicações pós-operatórias precoces associadas à abordagem cirúrgica da coluna cervical de pacientes portadores de mielopatia cervical espondilótica (MCE), comparando a abordagem cirúrgica anterior, a abordagem cirúrgica posterior e a abordagem combinada. Métodos: Estudo retrospectivo baseado em um banco de dados com 169 pacientes. Foram avaliados dados demográficos, como gênero e idade, e dados cirúrgicos, como abordagem cirúrgica realizada, número de segmentos artrodesados, tempo cirúrgico e complicações. As complicações foram divididas em maiores (infecção profunda da ferida operatória, intercorrência com o implante, nova compressão precoce, insuficiência cardíaca) e menores (disfagia, infecção superficial, dor, intercorrência urinária, neuropraxia da raiz de C5, estado confusional agudo, hematoma de ferida operatória). Resultados: Foram incluídos 169 pacientes, sendo 57 do sexo feminino (33,7%) e 112 do masculino (66,2%). A idade variou de 21 a 87 anos, com média de 56,48 anos (± 11). Destes, 52 (30,8%) foram submetidos à abordagem anterior, 111 (65,7%) à abordagem posterior e 6 (3,5%) à abordagem combinada. Conclusão: Assim como na literatura, evidenciamos a disfagia, a dor e a infecção superficial da ferida operatória como as complicações pós-operatórias mais frequentes. No entanto, não foi possível estabelecer uma relação estatística da incidência de complicações com o tempo cirúrgico, a via de acesso e o número de segmentos fixados. Nível de Evidência III, Estudo Retrospectivo Comparativo. Objetivo pósoperatórias pós operatórias MCE, MCE , (MCE) anterior combinada Métodos 16 demográficos cirúrgicos realizada artrodesados implante precoce cardíaca disfagia (disfagia urinária C5 C agudo operatória. . operatória) Resultados 5 33,7% 337 33 7 (33,7% 11 66,2%. 662 66,2% 66 2 (66,2%) 8 5648 56 48 56,4 ± ( 11. 11) Destes 30,8% 308 30 (30,8% 65,7% 657 65 (65,7% 3,5% 35 3 (3,5% Conclusão literatura frequentes entanto fixados III Comparativo (MCE 1 33,7 (33,7 66,2 (66,2% 564 4 56, 30,8 (30,8 65,7 (65,7 3,5 (3,5 33, (33, 66, (66,2 30, (30, 65, (65, 3, (3, (33 (66, (30 (65 (3 (66 (6

RESUMO O presente estudo contempla a aplicação de nanopartículas magnéticas de ferrita de manganês MnFe2O4 (NPM) modificadas com poliestireno sulfonado (PSS) na adsorção de íons de Pb (II) para fins de tratamento de água contaminada. A funcionalização da nanopartícula com o polímero objetivou aumentar a capacidade de adsorção e incluir a utilização de material reciclável em função da importância ambiental. Os adsorventes foram caracterizados por espectroscopia no infravermelho por transformada de Fourier, espectroscopia de energia dispersiva por raio X, difração de raios X, microscopia eletrônica de varredura, microscopia de força atômica, análise elementar, análise termogravimétrica, ponto de carga zero, área superficial e porosidade. O PSS representou 14% da massa das nanopartículas magnéticas de MnFe2O4 funcionalizadas com o poliestireno sulfonado (NPM-PSS) e o teor de grupos sulfônicos foi de 17,18%. Os modelos de isoterma de Freundlich e cinético de pseudossegunda ordem apresentaram maior acurácia pelos dados experimentais de adsorção dos íons Pb (II) pela NPM-PSS, cuja capacidade de adsorção das nanopartículas variou de 6,254 a 7,535 mg g−1.

ABSTRACT The present study contemplates the application of magnetic nanoparticles of manganese ferrite MnFe2O4 (NPM) modified with sulfonated polystyrene (PSS) in the adsorption of Pb(II) ions for the purpose of treating wastewater. The functionalization of the nanoparticle with the polymer aimed to increase the adsorption capacity and include the use of recyclable material due to its environmental importance. Adsorbents were characterized by Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, scanning electron microscopy, atomic force microscopy, elemental analysis, thermogravimetric analysis, point of zero charge, surface area, and porosity. PSS represented around 14% of the mass of magnetic nanoparticles of MnFe2O4 functionalized with sulfonated polystyrene (NPM-PSS) and the content of sulfonic groups was 17.18%. The Freundlich isotherm and pseudo second order kinetic models showed greater accuracy by the experimental data of adsorption of Pb (II) ions by NPM-PSS, whose adsorption capacity of nanoparticles ranged from 6.254 to 7.535 mg g−1.

RESUMO Introdução Comparação de diferentes técnicas cirúrgicas em pacientes com rizartrose ou osteoartrite carpometacárpica do polegar. Materiais e Métodos A revisão sistemática foi conduzida em três bancos de dados eletrônicos. Foram incluídos estudos clínicos randomizados e controlados com pacientes submetidos ao tratamento cirúrgico para tratamento de rizartrose. A revisão da literatura seguiu o protocolo PRISMA. Resultados Foram selecionados 15 artigos, envolvendo uma população total de 958 pacientes. Foram comparadas sete técnicas cirúrgicas distintas. Conclusões Concluímos que nenhum procedimento é superior a outro em termos de dor, função física, avaliação geral do paciente, amplitude de movimento ou força. A mensuração dos desfechos obtidos devem ser padronizadas a fim de possibilitar melhor comparação entre as técnicas cirúrgicas assim como, permitir uma análise estatística fidedigna. Nível de Evidência II; Revisão Sistemática.

ABSTRACT Introduction Comparison of different surgical techniques to treat patients with rhizarthrosis or carpometacarpal osteoarthritis of the thumb. Materials and Methods A systematic review was conducted using three electronic databases. Randomized, controlled trials in patients who underwent surgery for the treatment of rhizarthrosis were included. The literature review followed the PRISMA protocol. Results A total of 15 articles involving a total population of 958 patients were selected. Seven different surgical techniques were compared. Conclusions We conclude that no procedure is superior to another in terms of pain, physical function, overall patient assessment, range of motion, or strength. Outcome measurements should be standardized to enable better comparison between surgical techniques. Level of evidence II, Systematic Review.

RESUMO Objetivo: Avaliar as manifestações cutâneas da Doença de Coronavírus 2019 (COVID-19) descritas em pacientes pediátricos e discutir sua relevância para o diagnóstico precoce. Fontes de dados: O estudo consistiu em uma revisão sistemática de artigos originais indexados nas bases de dados PubMed e Embase, assim como na literatura cinzenta localizados via Google Scholar. Uma estratégia de busca, baseada na PICO (Patient, Intervention, Comparison, Outcome) Tool, com os termos “child”, “infant”, “childhood”, “adolescents”, “teenagers”, “COVID-19”, “SARS-CoV-2” e “skin manifestations” foi conduzida para otimizar os achados. Não houve restrições de idiomas. Síntese de dados: 35 dos 310 artigos que inicialmente cumpriram os critérios de inclusão foram selecionados para revisão, totalizando 369 pacientes. As manifestações cutâneas mais comuns de COVID-19 em crianças e adolescentes foram as lesões Chilblain-Like presentes em 67,5% dos casos, seguidas pelas lesões Eritema Multiforme-Like (31,7%) e Varicella-Like (0,8%). As lesões Chilblain-Like surgiram 7,6 dias (IC95% 7,4–7,8) após a infecção viral e tiveram duração de 17,5 dias (IC95% 16,5–18,5); as lesões Eritema Multiforme-Like surgiram em 9,5 dias (IC95% 9–10) e duraram 10,3 dias (IC95% 9,1–11,5) e as lesões Varicella-Like apareceram em 12,3 dias (IC95% 4–20,6) e duraram 7 dias. Conclusões: O conhecimento das diferentes manifestações cutâneas em crianças e adolescentes com COVID-19 é essencial para o diagnóstico precoce da doença, assim como possibilitar adoção de prontos cuidados e interromper cadeias de transmissão do novo coronavírus.

ABSTRACT Objective: The aim of this study was to evaluate the coronavirus disease 2019 (COVID-19) cutaneous manifestations described in pediatric patients and discuss their relevance for early diagnosis. Data source: The study consisted of a systematic review of original articles indexed in PubMed and Embase databases, as well as gray literature articles found through Google Scholar. A search strategy, based on PICO (Patient, Intervention, Comparison, Outcome) Tool, with the terms “child,” “infant,” “childhood,” “adolescents,” “teenagers,” “COVID-19,” “SARS-CoV-2,” and “skin manifestations,” was performed to optimize the findings. The study did not restrict any article regarding language. Data synthesis: Out of the 310 articles that initially met the inclusion criteria, 35 were selected for review, totalizing 369 patients. The most common COVID-19 cutaneous manifestations in children and adolescents were Chilblain-like lesions, presented in 67.5% of the cases, followed by erythema multiforme-like (31.7%) and varicella-like lesions (0.8%). The Chilblain-like lesions appeared 7.6 days (95%CI 7.4–7.8) after the viral infection and lasted for 17.5 days (95%CI 16.5–18.5), erythema multiforme-like lesions appeared in 9.5 days (95%CI 9–10) and lasted for 10.3 days (95%CI 9.1–11.5), and varicella-like lesions appeared in 12.3 days (95%CI 4–20.6) and lasted for 7 days. Conclusions: Knowledge of the different skin manifestations in children and adolescents with COVID-19 is essential for an early diagnosis and, consequently, the possibility of promptly care adoption as well as to interrupt the new coronavirus transmission chains in the current pandemic context.

ABSTRACT Background: Immunological life-threatening complications frequently occur in post-hematopoietic stem cell transplantation (HSCT), despite matching recipient and donor (R/D) pairs for classical human leukocyte antigens (HLA). Studies have shown that R/D non-HLA disparities within the major histocompatibility complex (MHC) are associated with adverse effects post-HSCT. Methods: We investigated the impact of mismatches of single-nucleotide polymorphisms (SNPs) in C4A/C4B genes, for showing the highest diversity in the MHC gamma block, on 238 patients who underwent HLA 10/10 unrelated donor (URD) HSCT. The endpoints were acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD) and mortality. One hundred and twenty-nine R/D pairs had 23 C4-SNPs typed by PCR-SSP (Gamma-Type™v.1.0), and 109 R/D pairs had these 23 SNPs identified by next-generation sequencing (NGS) using the Illumina platform. Results: The percentage of patients who received HSC from HLA 10/10 donors with 1-7 mismatches was 42.9%. The R/D pairs were considered C4 mismatched when bearing at least one disparity. These mismatches were not found to be risk factors for aGVHD, cGVHD or mortality after unrelated HSCT when SNPs were analyzed together (matched or mm ≥ 1), independently or according to the percentage of incompatibilities (full match for 23 SNPs; 1-3 mm and >3 mm). An exception was the association between 1-3 mismatches at the composite of SNPs C13193/T14952/T19588 with the development of aGVHD (P = 0.012) and with grades III-IV of this disease (P = 0.004). Conclusion: Our data are not consistent with the hypothesis that disparities in C4A/C4B SNPs increase the risks of post-HSCT adverse effects for the endpoints investigated in this study.

Abstract Introduction Ruxolitinib has been approved for the treatment of myelofibrosis (MF). In this study, we present safety and efficacy findings from an analysis of 104 patients with intermediate- and high-risk MF in a Brazilian cohort of the JUMP study who received treatment with ruxolitinib. Methods JUMP is a single-arm, open-label, phase IIIb, expanded-access study. The primary endpoint was to evaluate the safety and tolerability (frequency, duration, and severity of adverse events [AEs]) of ruxolitinib. Results All of the 104 patients received the treatment. Median duration of exposure was 35.8 months. The most common hematologic AEs were anemia (57.7), thrombocytopenia (38.5%), neutropenia (11.5%), and leukopenia (9.6%). Second malignancies (all grades) occurred in 19.2% of patients (n = 20). Serious AEs were reported in 62.5% of patients (n = 65). The proportions of patients with ≥50% reduction from baseline in palpable spleen length at weeks 24 and 48 were 62.7% and 69.2%, respectively. The mean change from the baseline in the Functional Assessment of Cancer Therapy (FACT)-Lymphoma total score was 10.8 [15.6%] at week 4, 12.6 [14.1%] at week 24, and 12.2 [14.3%] at week 48. The mean change from the baseline for the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale was 3.9 [42.8%] at week 4, 4.9 [29.9%] at week 24, and 4.7 [28%] at week 48. At week 48, the estimated progression-free survival, leukemia-free survival, and overall survival probabilities were 91%, 91% and 93%, respectively Overall, 21 deaths were observed in the present study. Conclusion Findings from this study suggest that ruxolitinib could be evaluated as a standard-of-care treatment for the MF population in need of a viable treatment option. NCT01493414

Objective to identify the knowledge of nurses of a teaching hospital about multidrug resistant bacteria. Methods cross-sectional and prospective study with the participation of 109 nurses. Data collection used a questionnaire with open and objective questions. Statistical analysis used the Statistical Package for the Social Sciences software. Results 67.0% of the participants considered the knowledge acquired in the graduation regarding multi-resistant bacteria insufficient to deal with them, with a predominance of professionals graduated before the year 2005; in the transmission process, younger professionals predominated. Conclusion knowledge about multidrug-resistant bacteria was higher among younger, more recently graduated professionals, with proactive enough to expand knowledge about the subject and to participate in in-service training. The Hospital Infection Control Service was the main source of knowledge for nurses participating in the study.

Objetivo identificar o conhecimento de enfermeiros de hospital de ensino universitário sobre bactérias multirresistentes. Métodos estudo transversal e prospectivo, com participação de 109 enfermeiros. Coleta de dados por meio de questionário com questões abertas e fechadas. A análise estatística, seu deu por meio do programa Statistical Package for the Social Sciences. Resultados 67,0% dos participantes consideraram o conhecimento adquirido na graduação relativo a bactérias multirresistentes insuficiente para o enfrentamento destas, com predomínio dos formados anterior ao ano de 2005; do processo de transmissão, predominaram os profissionais mais jovens. Conclusão o conhecimento sobre bactérias multirresistentes foi maior entre profissionais mais jovens, de formação mais recente, com iniciativa individual para expandir o conhecimento sobre o tema e participação em treinamentos em serviço. O Serviço de Controle de Infecção Hospitalar foi a principal fonte provedora de conhecimentos para os enfermeiros participantes do estudo.

ABSTRACT Introduction: Mutations in the breakpoint cluster region-Abelson murine leukemia 1 gene are the leading cause of resistance to treatment with tyrosine kinase inhibitors in chronic myeloid leukemia patients. Mutations have been detected throughout the extension of the kinase domain of this gene and it is important to investigate their positions because there may be a difference in clinical relevance. Objective: To evaluate mutations in the transcripts of the BCR-ABL1 gene in Brazilian patients with chronic myeloid leukemia under tyrosine kinase inhibitor treatment in the Hospital de Clínicas of the Universidade Federal do Paraná. Methods: This retrospective observational cross-sectional study analyzed mutation data of BCR-ABL1 gene transcripts. Three hundred and thirty peripheral blood samples from 193 patients were evaluated with the search for mutations being achieved by Sanger sequencing. Results: Sixteen mutation types were identified in 48/193 (24.87%) patients with T315I (20.83%) being the most common. Furthermore, four polymorphisms (T240T, K247R, E275E and Y275Y) were identified. The highest incidence of mutations (19/53: 35.85%) occurred in the P-loop of the tyrosine kinase domain, whereas no mutation was found in the A-loop. In 43/48 (89.58%) patients only one mutation was found and more than one mutation was found in 5/48 (10.42%). The simultaneous presence of two mutations (E189G/V299L and E255K/T315I) was observed in 2/5 patients while the different mutations were seen in sequential samples of the other three patients (Y253Y/T315I, T315I/E255K and E255K/T315I). Conclusions: This molecular characterization contributed to the identification of the resistance profile to tyrosine kinase inhibitors in Brazilian patients, thus enabling the use of adequate therapeutic strategies in a timely manner.

ABSTRACT Background: Human aplastic anemia is a hematologic disease characterized by low peripheral blood cell counts associated with reduced numbers of hematopoietic stem and progenitor cells and a hypocellular bone marrow. Thrombopoietin (THPO) regulates megakaryocytes, but it also stimulates hematopoietic stem and progenitor cells. Biallelic mutations in the THPO gene have been reported in a family with recessive inherited aplastic anemia. Methods: This study screened 83 patients diagnosed with acquired aplastic anemia and 92 paired healthy controls for germline variants in the THPO gene using Sanger sequencing. Results: Three common single nucleotide polymorphisms were identified in patients and controls at comparable allele frequencies. There was no correlation between the single nucleotide polymorphism carrier status and platelet counts at diagnosis. Conclusion: The presence of THPO polymorphisms is comparable between patients with acquired aplastic anemia and healthy individuals.

ABSTRACT Background: This study investigated the influence of two conditioning regimens on the chimerical status of 104 patients with acquired severe aplastic anemia. Methods: Patients were monitored for at least 18 months after related bone marrow transplantation and reaching partial or complete hematologic recovery. Group I patients (n = 55) received 200 mg/kg cyclophosphamide alone and Group II (n = 49) received 120 mg/kg cyclophosphamide associated with 12 mg/kg busulfan. Patients were classified in three chimerism levels according to the percentage of donor cells in the peripheral blood. Results: Chimerism ≤50% occurred in 36.4% of Group I and none of Group II; chimerism 51–90% was found in 20.0% of Group I and 10.2% of Group II; and chimerism >90% was found in 43.6% of Group I versus 89.8% of Group II. A significant association (p-value < 0.001) was found between conditioning type and chimerism levels. A higher number of infused cells was associated with higher levels of chimerism only in Group I (p-value = 0.013). Multivariate analysis showed that chimerism >90% is associated with the cyclophosphamide plus busulfan conditioning (p-value < 0.001) and higher number of infused cells (p-value = 0.009), suggesting that these factors are predictive of graft outcome. Regarding hematological recovery, higher chimerism levels were associated with higher neutrophil (p-value = 0.003) and platelet counts (p-value < 0.001) in Group I only. These results show that myeloablative conditioning favors full donor chimerism and non-myeloablative conditioning predisposes to mixed chimerism or autologous recovery of hematopoiesis. Conclusion: These data show that autologous recovery depends on the intensity of immunosuppression and that the immunosuppressive function of cyclophosphamide alone can induce this type of hematopoietic recovery.

Abstract Background: There is great interest in reducing the number of automated complete blood counts requiring manual blood smear reviews without sacrificing the quality of patient care. This study was aimed at evaluating and establishing appropriate screening criteria for manual blood smear reviews to improve the performance in a hematology laboratory. Method: A total of 1977 consecutive samples from the daily workload were used to evaluate four sets of screening criteria for manual blood smear reviews to identify samples with positive smear findings. Three sets of screening criteria were arbitrarily proposed in this study: Group 1 (narrow ranges), Group 2 (intermediate ranges), and Group 3 (wide limits) and one set (Group 4) was adapted from the International Society for Laboratory Hematology. All samples were run on Sysmex hematology analyzers and were investigated using manual blood smear reviews. Diagnostic accuracy and agreement were performed for each set of screening criteria, including an investigation of microscopic review rate and efficiency. Results: The microscopic review rates for Groups 1, 2, 3 and 4 were 73.85%, 54.52%, 46.33% and 46.38%, respectively; the false-negative rates were 0.50%, 1.97%, 2.73% and 3.95%, respectively. The efficiency and negative predictive values of Group 3 were 73.04% and 4.91%, respectively. Conclusions: Group 3 had the best relationship between safety (false-negative rate: ≤3%) and efficiency to estimate the limits of automation in performing complete blood counts. This study strengthens the importance of establishing screening criteria for manual blood smear reviews, which account for the different contexts in which hematological determinations are performed. Each laboratory should optimize the screening criteria for manual blood smear reviews in order to maximize their efficiency and safety.

Abstract Background Imatinib mesylate has revolutionized the treatment of chronic myeloid leukemia leading to significant reductions of BCR-ABL1 transcript levels in peripheral blood. Objective To evaluate the response to imatinib mesylate treatment (400 mg/day) in Brazilian patients in the chronic phase of chronic myeloid leukemia monitored by quantitative real time polymerase chain reaction. Methods Between October 2002 and October 2010, 3169 peripheral blood samples were collected from 1403 patients from 3 to 5 months, 6 to 11 months, 12 to 17 months, 18 to 23 months and ≥24 months after beginning imatinib treatment. Eighty-two patients had samples available and analyzed for all time intervals. BCR-ABL1 quantification was performed by quantitative real time polymerase chain reaction using the ABL1 gene as the control. Results of the BCR-ABL1 ratio as a percentage were reported by the international scale (IS) using the laboratory conversion factor (0.51). Results In the first interval, 80.8% of patients achieved the optimal response (BCR-ABL1 IS ≤ 10%). In the second period, 69.1% achieved optimal response (BCR-ABL1 IS ≤ 1%) and, between 12 and 17 months, 47.3% achieved major molecular response (BCR-ABL1 IS ≤ 0.1%). Conclusions The results of this retrospective study show that the response to imatinib treatment (400 mg/day) of Brazilian patients in the chronic phase of chronic myeloid leukemia is within the expected profile when compared to patients reported in international prospective randomized studies.