Acute myeloid leukemia with paraneoplastic pemphigus successfully treated with a personalized antileukemic and immunosuppressive strategy.

Bullous pemphigoid (BP) is a rare blistering disease often considered a primary sign of a paraneoplastic syndrome. Retrospective studies have established its link with hematological malignancies, particularly lymphoproliferative disorders. Here, we present what we believe to be the inaugural case of successful simultaneous management of BP and de novo acute myeloid leukemia (AML) in a 28-year-old male patient. Given the rarity and severity of both conditions, our treatment strategy aimed to maximize efficacy by combining immunosuppressive therapy (initially plasmapheresis with high-dose corticosteroids, followed by anti-CD20 monoclonal antibody and intravenous immunoglobulins 2 g/m2) with lymphodepleting antileukemic chemotherapy utilizing Fludarabine (FLAG-IDA induction regimen). Following diagnosis, considering the patient's youth and the concurrent presence of two rare and potentially life-threatening diseases, we opted for an aggressive treatment. Upon achieving complete morphological remission of AML with measurable residual disease (MRD) negativity, despite incomplete resolution of BP, we proceeded with high-dose cytarabine consolidation followed by peripheral stem cell harvest and autologous stem cell transplantation (ASCT). Our conditioning regimen for ASCT involved Bu-Cy with the addition of anti-thymocyte globulins. At day + 100 post-ASCT, bone marrow evaluation confirmed morphological remission and MRD negativity. Meanwhile, BP had completely resolved with normalization of BP180 antibody levels.

Reliability of flow-cytometry in diagnosis and prognostic stratification of myelodysplastic syndromes: correlations with morphology and mutational profile.

Diagnosis and prognostic stratification of myelodysplastic syndromes (MDS) have been complemented by new techniques, including flow cytometry and NGS. To analyze the relationship between molecular and cytofluorimetric data, we enrolled in this retrospective study, 145 patients, including 106 diagnosed with MDS and 39 controls. At disease onset, immunophenotypic (IF), cytogenetic tests, and cytomorphological (CM) examination on bone marrow were carried out in all patients, while NGS was performed in 58 cases. Ogata score presented a specificity of 100% and a sensitivity of 59%. The detection of at least two phenotypic aberrancies in Ogata negative patients increased the sensitivity to 83% and specificity to 87%. Correlations were identified between IF aberrancies and mutations, including positive Ogata>2 and mutations in SRSF2 (p=0.035), CD15 and U2AF1 (0.032), CD56 and DNMT3A (p=0.042), and CD38 and TP53 (p=0.026). In multivariate analysis, U2AF1 mutations, associated with del(20q) and/or abnormalities of chromosome 7 (group 4 as defined by the EuroMDS score), significantly correlated with an inferior overall survival (p=0.019). These parameters and Ogata score>2 also showed a significant correlation with inferior event-free survival (p=0.023 and p=0.041, respectively). Both CM and FC features correlated with prognosis and mutational patterns. In an integrated MDS work-up, these tools may guide indications for mutational screening for optimal risk stratification.

Correlation analysis between auto-immunological and mutational profiles in myelodysplastic syndromes.

OBJECTIVE AND DESIGN: Systemic-Inflammatory-Autoimmune-Diseases (SIAD) is increasingly considered in Myelodysplastic-Syndromes (MDS). In this line, we evaluated the MDS auto-immunological profile, correlating it to the mutational landscape, trying to identify a molecular-genetic trigger agent related to SIAD. METHODS AND MATERIALS: Eighty-one MDS were enrolled and t-NGS was performed. Anti-Nuclear-Antibodies (ANA) were tested, and ANA-antigenic-specificity was characterized by ANA-profile, ENA-screen, anti-dsDNA. Non-Hematological-Patients (NHP) and Healthy-Donors (HD) were used as controls. RESULTS: At clinically relevant cut-off (≥ 1:160), ANA was significantly more frequent in MDS, while ANA-antigenic-specificity showed a low association rate. ANA ≥ 1:160-positive MDS showed a mutational landscape similar to ANA-negative/ANA < 1:160 MDS. No significant correlations between mutational and immunological profiles were found and UBA1 mutations, related to VEXAS, were absent. CONCLUSIONS: Although ANA-positivity was found to be increased in MDS, the low ANA-antigenic-specificity suggests that autoantibodies didn't recognize autoimmune-pathognomonic antigens. The lack of relationship between genetic profile and ANA-positivity, suggests that MDS genetic variants may not be the direct cause of SIAD.

Evaluation of serological anti-SARS-CoV-2 chemiluminescent immunoassays correlated to live virus neutralization test, for the detection of anti-RBD antibodies as a relevant alternative in COVID-19 large-scale neutralizing activity monitoring.

The Spike-Receptor Binding Domain (S-RBD) is considered the most antigenic protein in SARS-CoV-2 and probably the key player in SARS-CoV-2 immune response. Quantitative immunoassays may help establish an anti-RBD Abs threshold as an indication of protective immunity. Since different immunoassays are commercial, the standard reference method for the neutralizing activity is the live Virus Neutralization Test (VNT). In this study, anti-RBD IgG levels were detected with two chemiluminescent immunoassays in paucisymptomatic, symptomatic and vaccinated subjects, and their neutralizing activity was correlated to VNT titer, using SARS-CoV-2 original and British variant strains. Both immunoassays confirmed higher anti-RBD Abs levels in vaccinated subjects. Furthermore, despite different anti-RBD Abs median concentrations between the immunoassays, a strong positive correlation with VNT was observed. In conclusion, although the SARS-CoV-2 immune response heterogeneity, the use of immunoassays can help in large-scale monitoring of COVID-19 samples, becoming a valid alternative to VNT test for diagnostic routine laboratories.

Clonal haematopoiesis as a risk factor for therapy-related myeloid neoplasms in patients with chronic lymphocytic leukaemia treated with chemo-(immuno)therapy.

Clonal haematopoiesis of indeterminate potential (CHIP) may predispose for the development of therapy-related myeloid neoplasms (t-MN). Using target next-generation sequencing (t-NGS) panels and digital droplet polymerase chain reactions (ddPCR), we studied the myeloid gene mutation profiles of patients with chronic lymphocytic leukaemia (CLL) who developed a t-MN after treatment with chemo-(immuno)therapy. Using NGS, we detected a total of 30 pathogenic/likely pathogenic (P/LP) variants in 10 of 13 patients with a t-MN (77%, median number of variants for patient: 2, range 0-6). The prevalence of CHIP was then backtracked in paired samples taken at CLL diagnosis in eight of these patients. Six of them carried at least one CHIP-variant at the time of t-MN (median: 2, range: 1-5), and the same variants were present in the CLL sample in five cases. CHIP variants were present in 34 of 285 patients from a population-based CLL cohort, which translates into a significantly higher prevalence of CHIP in patients with a CLL who developed a t-MN, compared to the population-based cohort (5/8, 62.5% vs. 34/285, 12%, p = 0.0001). Our data show that CHIP may be considered as a novel parameter affecting treatment algorithms in patients with CLL, and highlight the potential of using chemo-free therapies in CHIP-positive cases.

Circulating calprotectin as a supporting inflammatory marker in discriminating SARS-CoV-2 infection: an observational study.

OBJECTIVE AND DESIGN: Fecal calprotectin (CLP) is widely known for its detection in stools of patients with inflammatory bowel diseases (IBDs), to investigate the intestinal inflammatory status. Current research is promoting the circulating protein role as a systemic inflammatory marker. However, most studies report serum calprotectin analysis although plasma assay prevents its massive release by granulocytes. In this perspective, the ongoing SARS-CoV-2 pandemic deserves deployment of convenient and easy-to-dose markers that could reliably address the state of infection. METHODS: We analyzed serum circulating calprotectin (cCLP) levels in hospitalized COVID-19 patients and plasma cCLP levels from patients with suspected SARS-CoV-2 infection, then assessed negative or positive on molecular tests. RESULTS: Our results confirm a significant circulating calprotectin increase in infected subjects respect to controls, in serum and plasma. Moreover, plasma calprotectin has higher levels in suspected patients with positive SARS-CoV-2-RT-PCR, compared to suspected patients with negative SARS-CoV-2-RT-PCR. Furthermore, ROC curves results showed the circulating plasma calprotectin discriminatory ability to differentiate infected SARS-CoV-2 patients at a cutoff value greater than 131.3 ng/ml. CONCLUSIONS: Our data propose circulating calprotectin as a new, quantitative and predictive marker, which in addition to being an interesting generic inflammatory marker may provide important indications in SARS-CoV-2 infection.

Microenvironment in acute myeloid leukemia: focus on senescence mechanisms, therapeutic interactions, and future directions.

Acute myeloid leukemia (AML) is a disease with a dismal prognosis, mainly affecting the elderly. In recent years, new drugs have improved life expectancy and quality of life, and a better understanding of the genetic-molecular nature of the disease has shed light on previously unknown aspects of leukemogenesis. In parallel, increasing attention has been attracted to the complex interactions between cells and soluble factors in the bone marrow (BM) environment, collectively known as the microenvironment. In this review, we discuss the central role of the microenvironment in physiologic and pathologic hematopoiesis and the mechanisms of senescence, considered a fundamental protective mechanism against the proliferation of damaged and pretumoral cells. The microenvironment also represents a fertile ground for the development of myeloid malignancies, and the leukemic niche significantly interacts with drugs commonly used in AML treatment. Finally, we focus on the role of the microenvironment in the engraftment and complications of allogeneic hematopoietic stem cell transplantation, the only curative option in a conspicuous proportion of patients.

Evaluation of a robotic system for the recovery of peripheral blood mononuclear cells.

Investigations into immune responses are often based upon recovery of peripheral blood mononuclear cells (PBMC). To this purpose, the recovery of PBMC by gradient centrifugation is labour-intensive and requires a reasonable level of skill by the laboratory technician. Thus, we set out to determine whether laboratory automation equipment could be used for the recovery of PBMC from blood samples of horses, pigs and cattle, based on the Ficoll-Paque gradient centrifugation technique. Mixing of blood samples with PBS, layering of diluted blood onto Ficoll-Paque gradients, recovery of separated PBMC in RPMI 1640 medium were performed using an automated robotic system, the SBF200 (AM Robotic Systems, Warrington, UK) under laminar air flow conditions. Tubes were tagged with bar codes and manually placed after gradient centrifugation into a tube reader to measure the volume and position of the PBMC layer. The results of the automated procedure compared very well to those of the manual one in terms of percent cell recovery, sterility and cell viability. Also, a high throughput of samples could be implemented: with the integration of cell counting it should be possible for 96 blood samples to be processed, including the production of aliquots, by one person in a day.

The Venetoclax/Azacitidine Combination Targets the Disease Clone in Acute Myeloid Leukemia, Being Effective and Safe in a Patient with COVID-19.

The addition of Venetoclax (VEN) to Hypomethylating agents (HMAs) significantly improves the probability of complete remission and prolongs survival in patients with Acute Myeloid Leukemia (AML) when compared to HMA alone. However, the mutated clone composition may impact the probability of response and its duration. Here, we describe the molecular profile of a patient with AML rapidly evolved from a previous therapy-related-Chronic MyeloMonocytic Leukemia, who achieved safely complete remission after treatment with the VEN/Azacitidine combination, even in the presence of SARS-COVID-2 infection. The targeted NGS analysis showed that the VEN/AZA combination led to the eradication of the FLT3-ITD and RUNX1 mutated clone/s primarily associated with AML evolution, and subsequently, the SRSF2, NRAS, and ASXL1 mutated clone/s. This case also underlines the importance of the sequential use of targeted NGS for disease monitoring: the deep molecular remission achieved by this patient allowed to safely guide adjustments of drug dosage and treatment intervals in the presence of neutropenia, helping to rule out disease progression.

An Polycythemia Vera Evolve from Acute Myeloid Leukemia? Report of a Case Showing a Simultaneous Minor JAK2 V617F Mutated Clone.

The evolution of myeloproliferative neoplasms (MPN) to acute myeloid leukemia (AML) occurs in 2-10% of patients, depending on the MPN subtype, treatment, and follow-up length. The reverse-path from AML to MPN has been rarely reported. We herein present a 75 years old woman with AML, in whom a JAK2-V617F positive polycythemia vera (PV) emerged during follow-up, 19 months from the end of consolidation treatment. JAK2-V617F mutation screening retrospectively performed by Next Generation Sequencing (NGS) and JAK2 MutaScreen was negative on the bone marrow sample collected at AML diagnosis. However, using digital droplet PCR (ddPCR), we detected a minor JAK2 V617F mutated clone at AML onset. In addition, a TET2 R550 mutated clone persisted at stable levels throughout the disease course. This case shows that a very small MPN clone masked at AML diagnosis may expand after treatment end and be erroneously interpreted as MPN evolving from AML. Very sensitive techniques such as ddPCR may help to unravel the true disease history in these cases.

Anti-phospholipids antibodies and immune complexes in COVID-19 patients: a putative role in disease course for anti-annexin-V antibodies.

INTRODUCTION: Besides distinctive respiratory and digestive hallmarks, COVID-19 has been recently associated with a high prevalence of pro-inflammatory and hypercoagulable states known as "COVID-19 Associated Coagulopathy" (CAC), corresponding to a worsening in patients' conditions, whose causes are still to be elucidated. A link between anti-phospholipid antibodies (aPLs) and viral infections has long been suggested. APLs are assessed for anti-phospholipid syndrome (APS) diagnosis, characterized by thrombocytopenia, thrombosis, and coagulopathy. Furthermore, circulating immune complexes (CICs), arisen upon inflammatory responses and related immune dysregulation, can lead to endothelial cell damage and thrombotic complications. METHOD: We performed an extended panel including IgG/IgM anti-cardiolipin, IgG/IgM anti-ß2-glycoprotein-1, coupled with IgG/IgM anti-prothrombin, IgG/IgM anti-annexin-V on two COVID-19 patient groups (early and late infection time), and a negative control group. IgG CIC analysis followed to evaluate inflammatory status, through a possible complement system activation. RESULTS: Our results showed low positive case percentage in IgG/IgM anti-cardiolipin and IgG/IgM anti-ß2-glycoprotein-1 assays (4.54%, 6.25%, and 4.55%; in early infection group, late infection group, and control group, respectively); few positive cases in IgG/IgM anti-prothrombin and IgG/IgM anti-annexin-V immunoassays; and no IgG CIC positivity in any patient. CONCLUSIONS: In conclusion, our data show a low aPL prevalence, likely excluding an involvement in the pathogenesis of CAC. Interestingly, IgG/IgM anti-prothrombin and anti-annexin-V positive cases, detected in late infection group, suggest that aPLs could temporarily increase or could trigger a "COVID-19-induced-APS-like-syndrome" in predisposed patients. Key Points • To our knowledge, anti-prothrombin (aPT) antibodies, anti-annexin-V antibodies and CICs in COVID-19 patients have not been reported in the scientific literature. • Lack of uniformity and the low percentage of aCL/aß2GP1 positivity preclude a putative role in CAC pathogenesis. • IgG/IgM anti-prothrombin and IgG/IgM anti-annexin-V data show that distribution of positive case number increases in late infection patients, significantly in anti-annexin-V results, suggesting a possible role for these anti-phospholipid antibodies in disease course. • aPLs can arise transiently in some patients with critical illness and SARS-CoV-2 infection (disappearing in a few weeks), as well as in other genetically predisposed patients; they could trigger a "COVID-19-induced-APS-like-syndrome".

From Clonal Hematopoiesis to Therapy-Related Myeloid Neoplasms: The Silent Way of Cancer Progression.

Clonal hematopoiesis (CH) has been recognized as a predisposing factor for the development of myeloid malignancies. Its detection has been reported at different frequencies across studies, based on the type of genome scanning approach used and the population studied, but the latest insights recognize its virtual ubiquitous presence in older individuals. The discovery of CH in recent years paved the way for a shift in the paradigm of our understanding of the biology of therapy-related myeloid malignancies (t-MNs). Indeed, we moved from the concept of a treatment-induced lesion to a model where CH precedes the commencement of any cancer-related treatment in patients who subsequently develop a t-MN. Invariant patterns of genes seem to contribute to the arising of t-MN cases, with differences regarding the type of treatment received. Here, we review the principal studies concerning CH, the relationship with myeloid progression and the mechanisms of secondary t-MN development.

Serological anti-SARS-CoV-2 neutralizing antibodies association to live virus neutralizing test titers in COVID-19 paucisymptomatic/symptomatic patients and vaccinated subjects.

A large number of immunoassays have been developed to detect specific anti-SARS-CoV-2 antibodies; however, not always they are functional to neutralize the virus. The reference test for the anti-spike neutralizing antibodies (nAbs) ability to counteract the viral infection is the virus neutralization test (VNT). Great interest is developing on reliable serological assays allowing antibodies concentration and antibody protective titer correlation. The aim of our study was to detect nAbs serum levels in paucisymptomatic, symptomatic and vaccinated subjects, to find a cut-off value able to protect from virus infection. nAbs serum levels were detected by a competitive automated immunoassay, in association to VNT with the SARS-CoV-2 original and British variant strains. The median nAbs concentrations were: 281.3 BAU/ml for paucisymptomatics; 769.4 BAU/ml for symptomatics; 351.65 BAU/ml for the vaccinated cohort; 983 BAU/ml considering only the second dose vaccinated individuals. The original strain VNT analysis showed 1:80 median neutralization titers in paucisymptomatic and vaccinated subjects; 1:160 in symptomatic patients; 1:160 in the second dose groups. The British variant VNT analysis showed lower neutralization titers in paucisymptomatic and vaccinated groups (1:40); the same titer in symptomatic patients (1:160); the second dose group confirmed the original strain titer (1:160). In conclusion, our data showed optimal correlations with a proportional increase between neutralizing activity and antibody concentration, making nAbs detection a good alternative to virus neutralization assays, difficult to carry out in routine laboratories. Finally, ROC curve analysis established a cut-off of 408.6 BAU/ml to identify subjects with a low risk of infection.

Mutational profile of ZBTB16-RARA-positive acute myeloid leukemia.

BACKGROUND: The ZBTB16-RARA fusion gene, resulting from the reciprocal translocation between ZBTB16 on chromosome 11 and RARA genes on chromosome 17 [t(11;17)(q23;q21)], is rarely observed in acute myeloid leukemia (AML), and accounts for about 1% of retinoic acid receptor-α (RARA) rearrangements. AML with this rare translocation shows unusual bone marrow (BM) morphology, with intermediate aspects between acute promyelocytic leukemia (APL) and AML with maturation. Patients may have a high incidence of disseminated intravascular coagulation at diagnosis, are poorly responsive to all-trans retinoic acid (ATRA) and arsenic tryoxyde, and are reported to have an overall poor prognosis. AIMS: The mutational profile of ZBTB16-RARA rearranged AML has not been described so far. MATERIALS AND METHODS: We performed targeted next-generation sequencing of 24 myeloid genes in BM diagnostic samples from seven ZBTB16-RARA+AML, 103 non-RARA rearranged AML, and 46 APL. The seven ZBTB16-RARA-positive patients were then screened for additional mutations using whole exome sequencing (n = 3) or an extended cancer panel including 409 genes (n = 4). RESULTS: ZBTB16-RARA+AML showed an intermediate number of mutations per patient and involvement of different genes, as compared to APL and other AMLs. In particular, we found a high incidence of ARID1A mutations in ZBTB16-RARA+AML (five of seven cases, 71%). Mutations in ARID2 and SMARCA4, other tumor suppressor genes also belonging to SWI/SNF chromatin remodeling complexes, were also identified in one case (14%). DISCUSSION AND CONCLUSION: Our data suggest the association of mutations of the ARID1A gene and of the other members of the SWI/SNF chromatin remodeling complexes with ZBTB16-RARA+AMLs, where they may support the peculiar disease phenotype.

Evaluation of the surgical treatment of humeral shaft fractures and comparison between surgical fixation methods.

OBJECTIVE: The objective of this study is to analyze the surgical results of humeral shaft fracture treatment and describe its epidemiology. METHODS: Retrospective study that identified all patients treated with surgical fixation of humeral shaft fractures between December of 2014 and June of 2016 in a trauma reference center. All medical records were reviewed in search of epidemiological data referent to the trauma and post-operative results, including radiographic healing of the fracture and related complications. RESULTS: Fifty-one patients were included, mostly male (78.4%), with an average age of 35.02 years. The most common trauma mechanism was a traffic accident (56.9%) followed by same-level falls (17.6%). No statistically significant difference was found between healing time comparing surgical fixation techniques, including open reduction and internal fixation, minimally invasive technique, intramedullary nailing, and external fixation. CONCLUSION: Although each technique has inherent advantages and disadvantages, all fixation methods proved to be adequate options for the surgical treatment of humeral shaft fractures with high rates of healing and low rates of post-operative complications.

OBJETIVO: Descrever o perfil dos pacientes com fraturas diafisárias do úmero, bem como analisar os resultados das diferentes modalidades cirúrgicas. MÉTODO: Estudo retrospectivo baseado na identificação de todos os casos de fraturas diafisárias de úmero submetidas a tratamento cirúrgico entre dezembro de 2014 e junho de 2016 em um serviço de referência em trauma, bem como na análise dos respectivos prontuários, e que buscou dados epidemiológicos referentes ao trauma e resultados pós-operatórios, inclusive tempo de consolidação e complicações relacionadas. RESULTADOS: Foram incluídos 51 pacientes, dos quais a maioria do sexo masculino (78,4%), com média de 35,02 anos. O mecanismo de trauma mais prevalente foram acidentes de trânsito (56,9%), seguidos de quedas de mesmo nível (17,6%). Não foi encontrada diferença significante entre o tempo de consolidação dos diferentes métodos, inclusive redução aberta e fixação interna com placa e parafusos, técnica minimamente invasiva com placa em ponte, haste intramedular e fixação externa. CONCLUSÕES: Todos os métodos cirúrgicos avaliados mostraram-se adequadas opções para o tratamento cirúrgico das fraturas da diáfise do úmero, ainda que tenham vantagens e desvantagens inerentes a cada técnica, com altas taxas de consolidação e poucas complicações relatadas.

Effect of aging on liver regeneration in rats.

PURPOSE: Regeneration and/or healing of tissues is believed to be more difficult in elderly people. The liver is one of the most complex organs in the human body, and is involved in a variety of functions. Liver regeneration is the body's protection mechanism against loss of functional liver tissue. The aim of this study is to identify the regenerative capacity of the liver in older animals and to compare it with that of young adult animals. METHODS: Thirty-four Wistar rats were used, of which 17 were 90 days old (young animals) and 17 were 460 days old (old animals). Approximately 70% of the liver was surgically removed. Examinations were carried out after 24 hours and on day 7, using 3 methods: KWON et al.'s formula to identify increase in volume; mitotic figure count in 5 fields; and the percentage of PCNA-positive nuclei in 5 fields. RESULTS: The increase in volume of the remaining liver was greater in the young animals after both 24 hours (p=0.0006) and on day 7 (p=0.0000). Histological cuts showed a greater mitotic figure count in young animals evaluated after 24 hours (p=0.0000). Upon evaluation on day 7, recovery was observed in the old animals. This recovery was similar to that of the young ones (p=0.2851). The PCNA-positive nucleus count was greater in the young animals' liver cuts after 24 hours (p=0.0310), and, while it had decreased in young animals by day 7, recovery was observed in the older animals (p=0.0298). CONCLUSION: The data confirm that age is related to delay in liver regeneration in rats.

Evaluation of the surgical treatment of humeral shaft fractures and comparison between surgical fixation methods / Avaliação das fraturas diafisárias do úmero tratadas cirurgicamente e comparação entre os métodos de fixação cirúrgica

ABSTRACT Objective: The objective of this study is to analyze the surgical results of humeral shaft fracture treatment and describe its epidemiology. Methods: Retrospective study that identified all patients treated with surgical fixation of humeral shaft fractures between December of 2014 and June of 2016 in a trauma reference center. All medical records were reviewed in search of epidemiological data referent to the trauma and post-operative results, including radiographic healing of the fracture and related complications. Results: Fifty-one patients were included, mostly male (78.4%), with an average age of 35.02 years. The most common trauma mechanism was a traffic accident (56.9%) followed by same-level falls (17.6%). No statistically significant difference was found between healing time comparing surgical fixation techniques, including open reduction and internal fixation, minimally invasive technique, intramedullary nailing, and external fixation. Conclusion: Although each technique has inherent advantages and disadvantages, all fixation methods proved to be adequate options for the surgical treatment of humeral shaft fractures with high rates of healing and low rates of post-operative complications.

RESUMO Objetivo: Descrever o perfil dos pacientes com fraturas diafisárias do úmero, bem como analisar os resultados das diferentes modalidades cirúrgicas. Método: Estudo retrospectivo baseado na identificação de todos os casos de fraturas diafisárias de úmero submetidas a tratamento cirúrgico entre dezembro de 2014 e junho de 2016 em um serviço de referência em trauma, bem como na análise dos respectivos prontuários, e que buscou dados epidemiológicos referentes ao trauma e resultados pós-operatórios, inclusive tempo de consolidação e complicações relacionadas. Resultados: Foram incluídos 51 pacientes, dos quais a maioria do sexo masculino (78,4%), com média de 35,02 anos. O mecanismo de trauma mais prevalente foram acidentes de trânsito (56,9%), seguidos de quedas de mesmo nível (17,6%). Não foi encontrada diferença significante entre o tempo de consolidação dos diferentes métodos, inclusive redução aberta e fixação interna com placa e parafusos, técnica minimamente invasiva com placa em ponte, haste intramedular e fixação externa. Conclusões: Todos os métodos cirúrgicos avaliados mostraram-se adequadas opções para o tratamento cirúrgico das fraturas da diáfise do úmero, ainda que tenham vantagens e desvantagens inerentes a cada técnica, com altas taxas de consolidação e poucas complicações relatadas.

Italian cardiological guidelines for sports eligibility in athletes with heart disease: part 1.

In Italy the existence of a law on health protection of competitive sports since 1982 has favored the creation and the revision of these cardiological guidelines (called COCIS), which have reached their fourth edition (1989-2009). The present article is the second English version, which has summarized the larger version in Italian. The experience of the experts consulted in the course of these past 20 years has facilitated the application and the compatibility of issues related to clinical cardiology to the sports medicine field. Such prolonged experience has allowed the clinical cardiologist to acquire knowledge of the applied physiology of exercise and, on the other hand, has improved the ability of sports physicians in cardiological diagnostics. All this work has produced these guidelines related to the judgment of eligibility for competitive sports in the individual clinical situations and in the different cardiovascular abnormalities and/or heart disease. Numerous arguments are debated, such as interpretation of the athlete's ECG, the utility of a preparticipation screening, arrhythmias, congenital heart disease, cardiomyopathies, arterial hypertension, ischemic heart disease and other particular issues.