Posttransplant cyclophosphamide beyond haploidentical transplantation.

Posttransplant cyclophosphamide (PTCy) has practically revolutionized haploidentical (Haplo) hematopoietic cell transplantation (HCT). Comparisons between Haplo with PTCy and unrelated donor (URD) with conventional graft-versus-host disease (GVHD) prophylaxis have shown comparable overall survival with lower incidences of GVHD with Haplo/PTCy and led to the following question: is it PTCy so good that can be successfully incorporated into matched related donor (MRD) and URD HCT? In this review, we discuss other ways of doing PTCy, PTCy in peripheral blood haploidentical transplants, PTCy in the context of matched related and matched unrelated donors, PTCy with mismatched unrelated donors, and PTCy following checkpoint inhibitor treatment. PTCy is emerging as a new standard GVHD prophylaxis in haploidentical, HLA-matched, and -mismatched HCT.

Total marrow irradiation in hematopoietic stem cell transplantation for hematologic malignancies.

Total body irradiation (TBI) has been an essential component of the conditioning regimen in hematopoietic cell transplantation for many years. However, higher doses of TBI reduce disease relapse at the expense of more significant toxicities. Therefore, total marrow irradiation and total marrow and lymphoid irradiation have been developed to deliver organ-sparing targeted radiotherapy. Data from different studies show that TMI and TMLI can be safely administered in escalating doses in association with different chemotherapy conditioning regimen protocols, in situations with unmet needs, such as multiple myeloma, high-risk hematologic malignancies, relapsed or refractory leukemias, and elderly or frail patients, with low rates of transplant-related mortality. We reviewed the literature on applying TMI and TMLI techniques in autologous and allogeneic hematopoietic stem cell transplantation in different clinical situations.

Molecular profile of patients with myelofibrosis: a 10-year experience.

OBJECTIVE: To analyze the karyotype test and myeloid panel with next-generation sequencing findings in patients with myelofibrosis, and to compare transplant characteristics in patients referred for bone marrow transplantation. METHODS: Retrospective, single-center study with patients diagnosed with myelofibrosis treated at Hospital Israelita Albert Einstein between 2010 and 2020. RESULTS: A total of 104 patients with myelofibrosis were examined. Patients who had not been submitted to tests in our service were excluded. The final sample comprised 69 patients. Of these 69, 56 were submitted to karyotyping and 22 to myeloid panel with next-generation sequencing. Karyotype was normal in 60% of the patients and altered in 40%. The prevalence of high-risk molecular mutations was higher in patients referred for bone marrow transplantation (100% versus 50%). The median follow-up of transplant patients was 2.4 years and the overall survival at 2 years was 80% (95%CI: 62-100%). CONCLUSION: The molecular analysis enables estimating the patient's risk and thus instituting more aggressive treatment such as bone marrow transplant for patients at higher risk, being a relevant tool to guide therapy. Given the significance of molecular analysis for therapeutic decision-making in myelofibrosis, collection and disclosure of data on the prevalence of cytogenetic changes and findings of next-generation sequencing in affected patients is important.

ATG in HLA-Matched, Peripheral Blood, Hematopoietic Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Secondary Analysis of a CIBMTR Database.

w?>Peripheral blood stem cells (PBSC) are the preferred grafts for hematopoietic cell transplantation (HCT), according to the CIBMTR. Donor recovery is faster with PBSC harvest, but PBSC is associated with higher chronic graft-versus-host disease (GVHD) and poorer quality of life. Anti-T-cell globulin (ATG) is polyclonal IgG from rabbits or horses immunized with human thymocytes or a human T-cell line, which may reduce GVHD in HCT and improve outcomes. The objective of this study was to analyze the impact of ATG in HLA-matched related (MRD) and matched (HLA 8/8) unrelated donor (MUD) HCT. We used a freely available CIBMTR database published online for secondary analyses. The database included patients ≥ 40 years old who have undergone their first PBSC MRD or MUD HCT for acute myeloid leukemia or myelodysplastic syndrome with or without ATG between 2008 and 2017. Patients who received posttransplant cyclophosphamide or alemtuzumab were excluded. Overall survival was not different with ATG (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 1.00-1.19; P = .06) compared with no ATG. Relapse rate was higher with ATG (HR = 1.29; 95% CI, 1.17-1.43; P < .001) and non-relapse mortality was lower with ATG (HR = 0.84; 95% CI, 0.72-0.98; P = .03). Grades II-IV acute GVHD was significantly lower with ATG (HR = 0.77; 95% CI, 0.69-0.87; P < .001) but not grades III-IV acute GVHD (HR = 0.85; 95% CI, 0.69-1.04; P = .11). Both chronic GVHD (HR = 0.54; 95% CI, 0.48-0.60; P < .001) and moderate/severe chronic GVHD (HR = 0.45; 95% CI, 0.38-0.52; P < .001) were lower with ATG. There was an interaction between ATG and conditioning regimen for relapse rate and overall survival. Relapse rate was higher in those who received reduced-intensity (RIC) or non-myeloablative (NMA) conditioning regimens and ATG, compared with MAC ± ATG or RIC without ATG (interaction test, P = .003). Overall survival was also poorer with ATG and RIC or NMA conditioning regimens (interaction test, P = .03). Our results show that ATG can mitigate the more severe forms of chronic GVHD without impairing overall survival in HLA-matched HCT with PBSC grafts and myeloablative conditioning regimen. ATG should be standard in this population. © 2023 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Molecular profile of patients with myelofibrosis: a 10-year experience

ABSTRACT Objective To analyze the karyotype test and myeloid panel with next-generation sequencing findings in patients with myelofibrosis, and to compare transplant characteristics in patients referred for bone marrow transplantation. Methods Retrospective, single-center study with patients diagnosed with myelofibrosis treated at Hospital Israelita Albert Einstein between 2010 and 2020. Results A total of 104 patients with myelofibrosis were examined. Patients who had not been submitted to tests in our service were excluded. The final sample comprised 69 patients. Of these 69, 56 were submitted to karyotyping and 22 to myeloid panel with next-generation sequencing. Karyotype was normal in 60% of the patients and altered in 40%. The prevalence of high-risk molecular mutations was higher in patients referred for bone marrow transplantation (100% versus 50%). The median follow-up of transplant patients was 2.4 years and the overall survival at 2 years was 80% (95%CI: 62-100%). Conclusion The molecular analysis enables estimating the patient's risk and thus instituting more aggressive treatment such as bone marrow transplant for patients at higher risk, being a relevant tool to guide therapy. Given the significance of molecular analysis for therapeutic decision-making in myelofibrosis, collection and disclosure of data on the prevalence of cytogenetic changes and findings of next-generation sequencing in affected patients is important.

Risk factors for adverse outcomes following haploidentical hematopoietic cell transplantation with posttransplant cyclophosphamide: a two-center analysis.

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative therapy for several malignant hematologic diseases and alternative donors, including haploidentical, play a significant role in HCT. Despite the increasing use of haplo-HCT with PTCy, some questions remain open. The objective of the present study was to investigate risk factors for adverse outcomes after haplo-HCT with PTCy. This is a retrospective study conducted at two Brazilian centers. A total of 103 patients with hematologic malignancies who underwent first allogeneic, haploidentical HCT with PTCy were included. Risk factors for death were age at transplant (HR = 1.03 for each year; p = 0.002) and high/very high disease risk index (DRI; HR = 2.77; p = 0.0007) and mother as the donor compared with other donors (HR = 3.53; p = 0.005). In multivariate analysis, PFS was significantly poorer for older patients (HR = 1.02; p = 0.006), high/very high DRI (HR = 2.39; p = 0.003), and mother as the donor compared with other donors (HR = 3.18; p = 0.006). Relapse rate was higher for high/very high DRI (HR = 4.01; p = 0.002) and mother as the donor compared with other donors (HR = 2.52; p = 0.05). NRM was higher for older patients (HR = 1.03 for each year; p = 0.03). Tacrolimus was a protective factor for grades II-IV aGVHD (HR = 0.46; p = 0.04) compared with cyclosporine. Peripheral blood (PBSC) was a risk factor for cGVHD (HR = 3.48; p = 0.006), while tacrolimus was protective (HR = 0.30; p = 0.009). Mother as the donor compared with other donors was also a risk factor for poorer OS, PFS, and relapse, suggesting that this combination should be avoided. Tacrolimus was protective for both grades II-IV aGVHD and cGVHD, suggesting that tacrolimus may be more effective than cyclosporine in preventing GVHD. PBSC was a risk factor for cGVHD without any impact on relapse. Prospective studies comparing tacrolimus with cyclosporine are awaited.

Targeted Marrow Irradiation Intensification of Reduced-Intensity Fludarabine/Busulfan Conditioning for Allogeneic Hematopoietic Stem Cell Transplantation.

Reduced-intensity conditioning (RIC) regimens frequently provide insufficient disease control in patients with high-risk hematologic malignancies undergoing allogeneic hematopoietic stem cell transplantation (HSCT). We evaluated intensification of fludarabine/busulfan (Flu/Bu) RIC with targeted marrow irradiation (TMI) in a dose escalation with expansion phase I clinical trial. TMI doses were delivered at 1.5 Gy in twice daily fractions on days -10 through -7 (dose levels: 3 Gy, 4.5 Gy, and 6 Gy), Flu (30 mg/m2 for 5 days) and Bu (area under the curve, 4800 µM*minute for 2 days). Eligible patients were age ≥18 years with high-risk hematologic malignancy and compromised organ function ineligible for myeloablative transplantation (n = 26). The median patient age was 64 years (range, 25 to 76 years). Nineteen patients (73%) had active or measurable residual disease at transplantation. One-year disease-free survival and overall survival were 55% (95% confidence interval [CI], 34% to 76%) and 65% (95% CI, 46% to 85%), respectively. Day +100 and 1 year transplantation-related mortality were 4% (95% CI, 0.6% to 27%) and 8.5% (95% CI, 2% to 32%), respectively. The 1-year cumulative incidence of relapse was 43% (95% CI, 27% to 69%). Rates of grade II-IV and III-IV acute GVHD rates were 57% (95% CI, 39% to 84%) and 22% (95% CI, 9% to 53%), respectively. Whole blood immune profiling demonstrated enrichment of central/transitional memory-like T cells with higher TMI doses, which correlated with improved survival compared with control samples from patients undergoing allogeneic HSCT. Intensification of a Flu/Bu RIC regimen with TMI is feasible with a low incidence of transplantation-related mortality in medically frail patients with advanced malignancies. The recommended phase 2 TMI dose is 6 Gy.

COVID-19 in HSCT recipients: a collaborative study of the Brazilian Society of Marrow Transplantation (SBTMO).

In the COVID-19 scenario, patients undergoing hematopoietic stem cell transplantation (HSCT) infected with SARS-CoV-2 may have an increased risk of death. Through a national multicenter study, we aimed to describe the impact of COVID-19 on the survival of HSCT recipients in Brazil. Eighty-six patients with a confirmed diagnosis of SARS-CoV-2 (92% by RT-PCR) were included. There were 24 children and 62 adults receiving an autologous (n = 25) and allogeneic (n = 61) HSCT for malignant (n = 72) and non-malignant (n = 14) disorders. Twenty-six patients died, (10 on autologous (38%) and 16 patients (62%) on allogeneic group). The estimated overall survival (OS) at day 40 was 69%. Adults had decreased OS compared to children (66% vs 79%, p = 0.03). The severity of symptoms at the time of diagnosis, ECOG score, laboratory tests (C-reactive protein, urea values) were higher in patients who died (p < 0.05). In conclusion, HSCT recipients infected with SARS-CoV-2 have a high mortality rate mainly in adults and patients with critical initial COVID-19 presentation. These findings show the fragility of HSCT recipients with SARS-CoV-2 infection. Therefore, the importance of adherence to preventive measures is evident, in addition to prioritizing the vaccination of family members and the HSCT team.

Outcomes after Haploidentical Hematopoietic Cell Transplantation with Post-Transplantation Cyclophosphamide: A Systematic Review and Meta-Analysis Comparing Myeloablative with Reduced-Intensity Conditioning Regimens and Bone Marrow with Peripheral Blood Stem Cell Grafts.

Haploidentical hematopoietic cell transplantation (haplo-HCT) with post-transplantation cyclophosphamide (PTCy) may be the sole available curative option for several hematologic malignancies. However, the best choice of conditioning regimen and graft source has not been established. This study was conducted to compare myeloablative conditioning (MAC) regimens with reduced-intensity conditioning (RIC) regimens and peripheral blood stem cell (PBSC) grafts with bone marrow (BM) grafts in the haplo-HCT setting with PTCy. We performed a systematic review and meta-analysis of studies comparing MAC with RIC and PBSC with BM in the haplo-HCT. The search was conducted in PubMed and TRIALS on February 2, 2021, without a date limit. We excluded studies with >30% non-PTCy graft-versus-host disease (GVHD) prophylaxis and >30% nonmalignant diseases. We screened 570 abstracts from PubMed and TRIALS and selected 20 for full-text review and 17 for inclusion in the qualitative and quantitative analyses. For PBSC versus BM grafts, we found no difference in overall survival (OS; hazard ratio [HR], 1.05; P = .61; nPBSC = 1983; nBM = 2124), progression-free survival (PFS; HR, 0.95; P = .52; nPBSC = 2663, nBM = 2769), graft-versus-host disease (GVHD)-free relapse-free survival (GRFS; HR, 1.16; P = .07; nPBSC = 1454; pBM = 1647), or nonrelapse mortality (HR, 1.14; P = .13; nPBSC = 1664; nBM = 1862). Relapse was lower with the use of PBSC grafts (HR, 0.84; P = .001; nPBSC = 2663; nBM = 2769). The rates of acute GVHD (aGVHD) and chronic GVHD (cGVHD) were higher with PBSC grafts (aGVHD grade II-IV: HR, 1.67; P < .001; nPBSC = 2663; nBM = 2802; aGVHD grade III-IV: HR, 1.82; P < .001; nPBSC = 1826; nBM = 2000; cGVHD: HR, 1.46; P = .002; nPBSC = 2686; nBM = 2815). Engraftment was higher with PBSC grafts (HR, 1.27; P < .001; nPBSC = 1461; nBM = 1717). Comparing MAC and RIC, the use of MAC was associated with less relapse (HR, 0.70; P < .001; nMAC = 1929; nRIC = 2662), higher nonrelapse mortality (HR, 1.24; P = .002; nMAC = 2016; nRIC = 2790), but better PFS (HR, 0.86; P = .002; nMAC = 1929; nRIC = 2662). There were no differences between the 2 conditioning regimens in OS (HR, .95; P = .32; nMAC = 2123; nRIC = 3155), GRFS (HR, 0.97; P = .67; nMAC = 1182; nRIC = 1330), grade II-IV aGVHD (HR, 1.01; P = .81; nMAC = 2099; nRIC = 3090), or cGVHD (HR, 1.05; P = .44; nMAC=1929; nRIC = 2662). This analysis shows that the use of BM grafts is associated with comparable outcomes as seen with PBSC grafts despite a lower incidence of GVHD and a higher relapse rate. The use of MAC regimens is associated with improved PFS. These results suggest that for fit patients, MAC remains the optimal conditioning regimen in terms of mortality, and that the use of PBSC grafts may further decrease relapse risk and hasten engraftment, provided that further strategies can be incorporated to decrease GVHD. Prospective comparisons are awaited.

Severe hemorrhagic cystitis caused by the BK polyomavirus is associated with decreased survival post-allogeneic hematopoietic stem cell transplantation.

BACKGROUND: BK polyomavirus reactivation can occur following allogeneic hematopoietic stem cell transplantation (allo-HSCT) and may lead to hemorrhagic cystitis (BKPyV-HC). We hypothesized that development of BKPyV-HC is associated with increased mortality post allo-HSCT. METHODS: We retrospectively reviewed data on 133 adult patients (≥18 years old) who underwent allo-HSCT from 2007 until 2014 at Hospital Israelita Albert Einstein in São Paulo, Brazil. RESULTS: Thirty-six patients presented with BKPyV-HC after a median time of 42 days, with a 1-year cumulative incidence probability of 28.9% (95% CI 21.5%-36.7%). In a multivariate Cox model, risk factors for development of BKPyV-HC included younger age, male sex, development of grade 2-4 acute graft-versus-host disease and recipients of umbilical cord blood grafts. Development of grade 3-4 BKPyV-HC (but not grade 1-2) was associated with a decreased overall survival (OS) in a multivariate Cox model (hazard ratio [HR] 7.51, P < 0.0001) and an increased risk of TRM (HR 3.66, P < 0.0001). Grade 3-4 BKPyV-HC was also associated with an increased risk of relapse that did not reach statistical significance (HR 3.01, P = 0.07). Median overall survival (OS) post-BKPyV-HC was 4.7 months, and cidofovir had no impact on survival. CONCLUSION: Development of BKPyV-HC appears to be associated with decreased survival following allo-HSCT.

Diffuse large B-cell lymphoma of the central nervous system presenting as "lymphomatosis cerebri" and dementia in elderly man: Case report and review of the literature.

RATIONALE: Lymphomatosis cerebri is a rare form of PCNSL, characterized by diffuse infiltration of lymphoma cells in cerebral parenchyma, without mass-formation and mild or no contrast enhancement on magnetic resonance (MR) imaging. There are less than 50 cases described in the literature under the term Lymphomatosis cerebri. PATIENT CONCERNS: A 74-year-old man presented to our service with progressive dementia for 12 months and accelerated cognitive decline within the last two months. Brain magnetic resonance imaging showed areas of hyperintensity involving predominantly the white matter of frontal lobes and knee of the corpus callosum, along with areas of blood-brain barrier disruption and areas of restricted diffusion. Stereotaxy brain surgery was indicated into contrasting areas and histologically there was heterogeneous foci of discreet infiltration of rare medium-large lymphoid cells intermingled with inflammatory cells and these atypical lymphoid cells were placed on breakdown neuropil and did not form tumor mass or sheets of cells, but occasionally displayed perivascular distribution. Immunohistochemically, these atypical lymphoid cells expressed CD20, Bcl2, Bcl6 and, heterogeneously, IRF4/MUM1. DIAGNOSIS: The diagnosis of a primary CNS diffuse large B-cell lymphoma manifested as lymphomatosis cerebri was performed. INTERVENTIONS: The treatment of choice was: temozolomide 100 mg/m (D1 to D5), methotrexate 3 g/m (D1, D10, and D20) and rituximab 375 mg/m. OUTCOMES: The patient evolved with progressive neurological deterioration, regardless of the improvement on neuroimaging. LESSONS: We described the diagnostic dilemma we faced with an elderly man with rapid cognitive impairment and a myriad of differential diagnoses, diagnosed with primary CNS diffuse large B-cell lymphoma with a lymphomatosis cerebri-like pattern.

Splenic diffuse red-pulp small B-cell lymphoma associated with hepatitis B virus: a report of two cases.

CONTEXT: Splenic diffuse red-pulp small B-cell lymphoma is a rare disease, representing less than 1% of all non-Hodgkin lymphomas (NHL). This entity is characterized by involvement of bone marrow sinusoids and peripheral blood. The majority of cases are at an advanced stage when diagnosed. Its pathogenesis is still poorly understood. CASE REPORTS: We report on two patients with chronic non-replicating hepatitis B virus (HBV) who developed splenic diffuse red-pulp small B-cell lymphoma. Both of them were in stage IV at diagnosis and evolved with aggressive disease. Both of them achieved a complete response through chemotherapy, but one of them died due to infectious complications during bone marrow transplantation. The other decided not to undergo transplantation and continues not to show any evidence of disease today (three years after treatment). Some studies have shown a possible association between B-cell NHL and HBV. Nonetheless, the mechanism through which this oncogenic virus interacts with B-cell NHL is still poorly understood. HBV is lymphotropic and may insert into the host's genome, thus causing overexpression of oncogenes and downregulation of tumor suppressor genes. Therefore, chronic stimulation by HBV can increase B-cell proliferation, which promotes monoclonal expansion of these cells and results in malignancy. CONCLUSION: HBV may be implicated in the pathogenesis of this lymphoma, although no direct association between these two entities could be proved in the present study. Further investigations are necessary.

Splenic diffuse red-pulp small B-cell lymphoma associated with hepatitis B virus: a report of two cases / Linfoma esplênico difuso da polpa vermelha, de linfócitos B pequenos, associado ao vírus da hepatite B: relato de dois casos

ABSTRACT CONTEXT: Splenic diffuse red-pulp small B-cell lymphoma is a rare disease, representing less than 1% of all non-Hodgkin lymphomas (NHL). This entity is characterized by involvement of bone marrow sinusoids and peripheral blood. The majority of cases are at an advanced stage when diagnosed. Its pathogenesis is still poorly understood. CASE REPORTS: We report on two patients with chronic non-replicating hepatitis B virus (HBV) who developed splenic diffuse red-pulp small B-cell lymphoma. Both of them were in stage IV at diagnosis and evolved with aggressive disease. Both of them achieved a complete response through chemotherapy, but one of them died due to infectious complications during bone marrow transplantation. The other decided not to undergo transplantation and continues not to show any evidence of disease today (three years after treatment). Some studies have shown a possible association between B-cell NHL and HBV. Nonetheless, the mechanism through which this oncogenic virus interacts with B-cell NHL is still poorly understood. HBV is lymphotropic and may insert into the host's genome, thus causing overexpression of oncogenes and downregulation of tumor suppressor genes. Therefore, chronic stimulation by HBV can increase B-cell proliferation, which promotes monoclonal expansion of these cells and results in malignancy. CONCLUSION: HBV may be implicated in the pathogenesis of this lymphoma, although no direct association between these two entities could be proved in the present study. Further investigations are necessary.

RESUMO CONTEXTO: Linfoma esplênico difuso da polpa vermelha, de linfócitos B pequenos, é uma doença rara, representando menos do que 1% de todos os linfomas não Hodgkin. Essa entidade é caracterizada por envolvimento de sinusoides da medula óssea e sangue periférico. A maioria dos casos está em estádio avançado ao diagnóstico. Sua patogênese ainda é pouco compreendida. RELATOS DE CASOS: Reportamos dois pacientes com vírus da hepatite B (HBV) crônica não replicante que desenvolveram linfoma esplênico difuso da polpa vermelha, de linfócitos B pequenos. Ambos estavam em estádio IV ao diagnóstico e evoluíram com doença agressiva. Ambos alcançaram resposta completa com a quimioterapia, porém um deles evoluiu a óbito por intercorrências infecciosas durante o transplante de medula óssea e o outro optou por não realizar o transplante e encontra-se sem evidência de doença até os dias atuais (três anos após tratamento). Alguns estudos demonstraram a possível associação entre linfomas não Hodgkin B e HBV. Entretanto, o mecanismo pelo qual esse vírus oncogênico interage com linfoma não Hodgkin B ainda é pouco compreendido. HBV é linfotrópico e pode se inserir no genoma do receptor, causando superexpressão de oncogenes e downregulation de genes supressores tumorais. Portanto, o estímulo crônico pelo HBV pode aumentar a proliferação de células B, promovendo expansão monoclonal dessas células, resultando em malignidade. CONCLUSÃO: HBV pode estar implicado na patogênese desse linfoma, entretanto, uma associação direta entre essas duas entidades não pôde ser provada no presente estudo e investigações adicionais são necessárias.

Tromboprofilaxia venosa em pacientes clínicos: análise de sua aplicação / Venous thromboprophylaxis in medical patients: an application review

OBJETIVO: A tromboprofilaxia de rotina, a despeito de sua efetividade estar bem estabelecida e o tromboembolismo venoso ser uma condição potencialmente evitável, não se apresenta completamente consolidada na prática clínica. Os objetivos do presente estudo são: 1. Determinar a frequência da utilização da tromboprofilaxia e presença dos fatores de risco para tromboembolismo; 2. Verificar a adequação de sua utilização em pacientes clínicos internados, assumindo como parâmetro uma diretriz nacional estabelecida. MÉTODOS: Estudo retrospectivo transversal envolvendo pacientes internados por doenças clínicas em uma enfermaria geral de adultos de um hospital universitário. A análise foi baseada em diretriz definida. RESULTADOS: Foram incluídos 146 pacientes para análise. Destes, 94,5% possuíam pelo menos um fator de risco para tromboembolismo venoso. Em 130 (89%) pacientes havia indicação para uso de heparina profilática, sendo que em 73,3% dos casos estava prescrito algum tipo de heparina. Quanto à adequação da profilaxia, 53,4% das prescrições estavam corretas em relação à indicação e à dose da profilaxia; 24% apresentavam dose ou frequência incorretas; 19,2% não tinham prescrição de profilaxia, apesar de ela ser indicada; e em cinco casos (3,4%) o fármaco foi prescrito, apesar de não haver indicação. CONCLUSÃO: Existe subutilização da tromboprofilaxia nesta população, com inadequada dose prescrita em 50% dos casos. Portanto, estudos e intervenções futuros devem incluir um programa educacional que se inicie desde o atendimento em pronto-socorro, sendo essencial para aproximar a evidência à prática clínica.

OBJECTIVE: Routine thromboprophylaxis, despite its well-known effectiveness and the fact that venous thromboembolism is a potentially avoidable condition, is not fully established in clinical practice. The objectives of the present study were to determine how often thromboprophylaxis is used and the presence of thromboembolism risk factors, and to verify the appropriateness of its use in medical inpatients, assuming a long-standing national guideline as a parameter. METHODS: This was a retrospective cross-sectional study, involving inpatients with medical conditions in the adult general ward of a university hospital. The review was based on a defined guideline. RESULTS: 146 patients were included in the review. At least one risk factor for venous thromboembolism was found in 94.5%. In 130 (89%) patients, prophylactic heparin was indicated, and some kind of heparin was prescribed in 73.3%. Regarding the adequacy of prophylaxis, 53.4% of prescriptions were correct regarding prophylaxis indication and dose; 24% had incorrect dose or frequency of use; 19.2% had no prophylaxis prescription, although it was indicated; and in five cases (3.4%), the drugwas prescribed, even though itwas not indicated. CONCLUSION: Thromboprophylaxis is underused in this population, and an inappropriate dose was prescribed in 50% of cases. Therefore, future studies and interventions should include an educational program started from the emergency department care, an essential step to bring evidence closer to clinical practice.

[Venous thromboprophylaxis in medical patients: an application review]. / Tromboprofilaxia venosa em pacientes clínicos: análise de sua aplicação.

OBJECTIVE: Routine thromboprophylaxis, despite its well-known effectiveness and the fact that venous thromboembolism is a potentially avoidable condition, is not fully established in clinical practice. The objectives of the present study were to determine how often thromboprophylaxis is used and the presence of thromboembolism risk factors, and to verify the appropriateness of its use in medical inpatients, assuming a long-standing national guideline as a parameter. METHODS: This was a retrospective cross-sectional study, involving inpatients with medical conditions in the adult general ward of a university hospital. The review was based on a defined guideline. RESULTS: 146 patients were included in the review. At least one risk factor for venous thromboembolism was found in 94.5%. In 130 (89%) patients, prophylactic heparin was indicated, and some kind of heparin was prescribed in 73.3%. Regarding the adequacy of prophylaxis, 53.4% of prescriptions were correct regarding prophylaxis indication and dose; 24% had incorrect dose or frequency of use; 19.2% had no prophylaxis prescription, although it was indicated; and in five cases (3.4%), the drug was prescribed, even though it was not indicated. CONCLUSION: Thromboprophylaxis is underused in this population, and an inappropriate dose was prescribed in 50% of cases. Therefore, future studies and interventions should include an educational program started from the emergency department care, an essential step to bring evidence closer to clinical practice.

Uso de material didático sobre embriologia do sistema nervoso: avaliação dos estudantes / Use of teaching material about nervous system embryology: a students' evaluation

A Embriologia Humana é de extrema importância na formação de profissionais de saúde, porém seu estudo, muitas vezes, é considerado desestimulante, decorativo e sem significado prático para muitos estudantes, tornando-se pouco efetivo. Este trabalho objetivou produzir material didático interativo com modelos embrionários representativos do desenvolvimento embrionário do sistema nervoso. Para avaliar de forma qualitativa a real efetividade e capacidade de facilitar o processo de ensino-aprendizagem no contexto da Aprendizagem Baseada em Problemas, o material foi aplicado aos estudantes da primeira série de Medicina e Enfermagem da Faculdade de Medicina de Marília. Os estudantes consideraram que o material contribuiu para o entendimento do tema e facilitou a visualização dos eventos embrionários, além de despertar o interesse pelo estudo da disciplina. O material serviu como recurso para sedimentar o conhecimento e suscitou nos estudantes a integração dos conhecimentos com outras disciplinas. Em termos qualitativos, a análise dos questionários dos estudantes indicou que o material didático produzido foi efetivo na aprendizagem e funcionou como recurso na aprendizagem autodirigida, favorecendo a diversificação de fontes de busca e sendo complementar a livros-texto e outros materiais teóricos.

Human embryology is an extremely important part of training health professionals, but its study is often considered boring, decorative and without practical significance for many students, making it ineffective. This study aimed to produce interactive teaching material with embryonic models representing the embryonic development of the nervous system. To qualitatively evaluate the real effectiveness and ability to facilitate the teaching-learning process in the context of problem-based learning, the material was applied to first-year medicine and nursing students. The students felt that the material contributed to a better understanding of the topic and enabled visualization of embryonic events, as well as arousing interest in studying the subject. The material served to establish understanding and inspire the students to integrate the knowledge with other disciplines. Thus, in qualitative terms, analysis of the student questionnaires indicated that the material produced was effective for learning and worked as a resource in self-directed learning, promoting the diversification of search sources and being complementary to textbooks and other theoretical materials.