Checkpoint Inhibitors in Dogs: Are We There Yet?

Immune checkpoint inhibitors (ICI) have revolutionised cancer treatment in people. Immune checkpoints are important regulators of the body's reaction to immunological stimuli. The most studied immune checkpoint molecules are programmed death (PD-1) with its ligand (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) with its ligands CD80 (B7-1) and CD86 (B7-2). Certain tumours can evade immunosurveillance by activating these immunological checkpoint targets. These proteins are often upregulated in cancer cells and tumour-infiltrating lymphocytes, allowing cancer cells to evade immune surveillance and promote tumour growth. By blocking inhibitory checkpoints, ICI can help restore the immune system to effectively fight cancer. Several studies have investigated the expression of these and other immune checkpoints in human cancers and have shown their potential as therapeutic targets. In recent years, there has been growing interest in studying the expression of immune checkpoints in dogs with cancer, and a few small clinical trials with ICI have already been performed on these species. Emerging studies in veterinary oncology are centred around developing and validating canine-targeted antibodies. Among ICIs, anti-PD-1 and anti-PD-L1 treatments stand out as the most promising, mirroring the success in human medicine over the past decade. Nevertheless, the efficacy of caninized antibodies remains suboptimal, especially for canine oral melanoma. To enhance the utilisation of ICIs, the identification of predictive biomarkers for treatment response and the thorough screening of individual tumours are crucial. Such endeavours hold promise for advancing personalised medicine within veterinary practice, thereby improving treatment outcomes. This article aims to review the current research literature about the expression of immune checkpoints in canine cancer and the current results of ICI treatment in dogs.

The role of lymph nodes and their drainage in canine mammary gland tumours: Systematic review.

Mammary gland tumours are the most common neoplasms in intact bitches. Over the last decades, veterinary oncology has evolved in detecting and determining the lymph nodes to be removed in these patients for an accurate staging and prognosis, as well as to achieve better disease control and higher overall survival time. Our objective was to describe recent advances related to lymphatic drainage in bitches with mammary gland tumours, focusing on surgery, diagnosis, and prognosis. Through a systematic review using PubMed as the database, a thorough multi-step search reduced 316 studies to 30 for analysis. Vital dyes appear to be crucial in reducing the overall surgery time through transoperative staining of the lymph nodes. Imaging contrasts provide information regarding specific tumour drainage; however, there is still little evidence for their use. The axillary and superficial inguinal lymph nodes are well-established as regional lymph nodes of the cranial and caudal mammary glands. In sequence, accessory axillary, medial iliac, popliteal, and sternal lymph nodes should receive attention if they demonstrate contrast drainage, even considering that the literature has not shown a relationship between drainage and metastasis in these cases. In conclusion, recent studies have provided us with more support in regional lymph node excision regarding the TNM staging system. Studies are highly heterogeneous and method comparisons do not fit due to the non-uniformity of samples, materials, and procedures. We suggest further studies with a larger sample size, complete follow-up of patients, contrast use, and lymph node morphological and immunohistochemical analysis.

Comparison of Different Pneumorrhaphy Methods after Partial Pulmonary Lobectomy in Dogs.

Pulmonary loborraphy can be performed using manual sutures and staples, although other methods, such as tissue adhesives, are also cited in the veterinary literature. Although the surgery is well tolerated in the canine species, failure in pulmonary aerostasis is still a reality since all the methods described so far eventually lead to air leakage after the use of the partial lobectomy technique in the lungs. Within this context, the aim of this research was to compare the effectiveness of different hermetic sealing methods after partial lobectomy of the right caudal lung lobe (RCLL) in dogs. 30 cadavers models were divided in 6 groups: G1-cobbler suture associated with simple continuous; G2-overlapping continuous suture associated with simple continuous suture; G3-Ford interlocking suture; G4-Stapling device; G5-Tissue glue (cyanoacrylate). After performing the sealing techniques, the lungs were submerged in water and inflated with oxygen at positive ventilatory pressures at physiological (up to 14.7 mmHg, which is equivalent to up to 20 cmH2O) and supraphysiological levels (above 14.7 mmHg) to evaluate the performance of the sealing methods. At physiological ventilatory pressure levels, there was no difference between groups. Sealing with surgical glue was superior to interlocking sutures and stapling devices at supraphysiological levels of ventilatory pressure.

Molecular Profile of Canine Hemangiosarcoma and Potential Novel Therapeutic Targets.

Canine hemangiosarcoma (HSA) is a relatively common neoplasia, occurring mainly in the skin, spleen, liver and right atrium. Despite the numerous studies investigating the treatment of canine HSA, no significant improvement in survival has been achieved in the last 20 years. Advancements in genetic and molecular profiling presented molecular similarities between canine HSA and human angiosarcoma. It could therefore serve as a valuable model for investigating new and more effective treatments in people and dogs. The most common genetic abnormalities in canine HSA have been found in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and neuroblastoma RAS viral oncogene homolog (NRAS) pathways. Mutations are also found in tumor protein p53 (TP53), phosphatase and tensin homolog (PTEN) and cyclin dependent kinase inhibitor 2A (CDKN2A). Known abnormal protein expression could be exploited to trial new target treatments that could be beneficial for both canine and human patients. Despite the high expression of vascular endothelial growth factor (VEGF) and its receptor (VEGFR), no correlation with overall survival time has ever been found. In this review, we explore the most recent developments in molecular profiling in canine HSA and discuss their possible applications in the prognosis and treatment of this fatal disease.

Epidemiological study of canine transmissible venereal tumor (CTVT) in Brazil, 2000-2020.

Canine transmissible venereal tumor (CTVT) is a contagious neoplasm, mainly transmitted through coitus. This round cell mesenchymal tumor is common in Brazil, often located in the genitalia although extragenital presentations may also occur, such as cutaneous, oral, and nasal forms. The objective of this study was to perform an epidemiological analysis of CTVT from published data in the recent academic literature to systematically demonstrate the distribution of CTVT in Brazil, identify the frequency of this neoplasm and its main diagnostic tests, and characterize its main clinical manifestations in Brazil. For such purpose, it was analyzed the scientific publications with cases of CTVT in Brazil, in English or Portuguese, published between 2000-2020. The CTVT was identified in 19 Brazilian states plus the Federal District, totaling 3,622 cases across the national territory, with the largest number of cases recorded in the Southeast region. The cytological exam was the most used for the diagnosis of CTVT (89.2 %), followed by histopathological (37.8 %) and immunohistochemistry (13.5 %)1 . Predominant epidemiological aspects of CTVT identified in the study were: Mixed breed dogs (75.2 %), females (62.5 %), in adulthood (between 2 and 7 years) and dogs with free extra outdoor access (91.1 %). Genital presentation was the most frequent in the literature (86 %), followed by cutaneous (21.8 %), nasal (10 %), oral and lymph nodes presentations (10-5 %) and less frequent manifestations as ocular and anal/perianal (< 5 %). CTVT is a neoplasm widely distributed in Brazil, highly frequent and with several forms of clinical presentation, which can be underdiagnosed if there is no adequate knowledge of this tumor and its epidemiological characteristics. The extragenital manifestations of the neoplasm need further studies for its better characterization and more precise definition of its frequencies.

AutoImplant 2020-First MICCAI Challenge on Automatic Cranial Implant Design.

The aim of this paper is to provide a comprehensive overview of the MICCAI 2020 AutoImplant Challenge. The approaches and publications submitted and accepted within the challenge will be summarized and reported, highlighting common algorithmic trends and algorithmic diversity. Furthermore, the evaluation results will be presented, compared and discussed in regard to the challenge aim: seeking for low cost, fast and fully automated solutions for cranial implant design. Based on feedback from collaborating neurosurgeons, this paper concludes by stating open issues and post-challenge requirements for intra-operative use. The codes can be found at https://github.com/Jianningli/tmi.

Perfil de susceptibilidade aos carbapenêmicos de bacilos Gram-negativos fermentadores da glicose isolados de hemoculturas / Carbapenem susceptibility profile of Gram-negative glucose fermenting bacilli isolated from hemocultures

As Enterobacteriaceae são bactérias Gram-negativas e frequentes causadoras de infecções hospitalares. Os carbapenêmicos (CROs) são considerados as mais recentes linhas de defesa contra infecções por microrganismos multirresistentes, no entanto o desenvolvimento de bactérias multirresistentes a esta classe medicamentosa tem prejudicado o tratamento farmacológico. Nesse sentido, o presente estudo trata-se de uma análise retrospectiva, tendo como objetivo avaliar o perfil de resistência e susceptibilidade de bacilos Gram-negativos fermentadores da glicose aos carbapenêmicos em isolados de hemoculturas positivas no período de janeiro de 2018 a janeiro 2019. Das 5.733 hemoculturas realizadas nesse período, cerca de 5,4% (311 amostras) foram positivas. Dentre essas, 34,4% (107 amostras) positivas para enterobactérias e 65,6% (204 amostras) positivas para outras espécies. Foi observada uma maior incidência de Klebsiella pneumoniae (34,6% dos casos), seguido pela Klebsiella sp. (28,9%) e a Escherichia coli (26,2%). Contudo, três (03) isolados de hemocultura da espécie Klebsiella pneumoniae se mostraram resistentes aos três antibióticos (ertapenem, meropenem e imipenem). Dois isolados de Enterobacter cloaceae também obtiveram resistência aos antibióticos utilizados e uma espécie de Enterobacter aerogenes mostrou-se resistente apenas ao ertapenem e meropenem e sensibilidade ao imipenem.Enterobacteriaceae are Gram-negative bacteria and frequent causes hospital infections. Carbapenemic (CRO) are considered the latest lines of defense against infections by multidrug-resistant microorganisms, however the development of multidrug-resistant bacteria in this drug class has impaired treatment pharmacological. The present study is a retrospective analysis, with the objective of evaluating the resistance and susceptibility profile from isolates in blood cultures from January 2018 to January 2019, from positive blood cultures with enterobacteria growth and analysis of antibiograms performed from fermenter Gram-negative glucose bacilli to carbapenem antimicrobials. Of the 5,733 blood cultures performed from January 2018 to January 2019, about 5.4% (311 samples) were positive. Among these, 34.4% (107 samples) positive for enterobacteria and 65.6% (204 samples) for other species. A higher incidence of Klebsiella pneumoniae (34.6% of cases) was observed, followed by Klebsiella sp. (28.9%) and Escherichia coli (26.2%), however, three hemoculture isolates of the species Klebsiella pneumoniae, which were resistant to the three antibiotics (ertapenem, meropenem and imipenem). Two (2) isolates of Enterobacter cloaceae also obtained resistance to the antibiotics used and one (1) species of Enterobacter aerogenes proved resistant only to ertapenem and meropenem and sensitivity to imipenem.

As Enterobacteriaceae são bactérias Gram-negativas e frequentes causadoras de infecções hospitalares. Os carbapenêmicos (CROs) são considerados as mais recentes linhas de defesa contra infecções por microrganismos multirresistentes, no entanto o desenvolvimento de bactérias multirresistentes a esta classe medicamentosa tem prejudicado o tratamento farmacológico. Nesse sentido, o presente estudo trata-se de uma análise retrospectiva, tendo como objetivo avaliar o perfil de resistência e susceptibilidade de bacilos Gram-negativos fermentadores da glicose aos carbapenêmicos em isolados de hemoculturas positivas no período de janeiro de 2018 a janeiro 2019. Das 5.733 hemoculturas realizadas nesse período, cerca de 5,4% (311 amostras) foram positivas. Dentre essas, 34,4% (107 amostras) positivas para enterobactérias e 65,6% (204 amostras) positivas para outras espécies. Foi observada uma maior incidência de Klebsiella pneumoniae (34,6% dos casos), seguido pela Klebsiella sp. (28,9%) e a Escherichia coli (26,2%). Contudo, três (03) isolados de hemocultura da espécie Klebsiella pneumoniae se mostraram resistentes aos três antibióticos (ertapenem, meropenem e imipenem). Dois isolados de Enterobacter cloaceae também obtiveram resistência aos antibióticos utilizados e uma espécie de Enterobacter aerogenes mostrou-se resistente apenas ao ertapenem e meropenem e sensibilidade ao imipenem.

Profile of drug-drug interactions and impact on the effectiveness of antiretroviral therapy among patients living with HIV followed at an Infectious Diseases Referral Center in Belo Horizonte, Brazil.

HIV infection may be considered a chronic condition for people living with HIV with access to antiretrovirals and this has effectively increased survival. Moreover, this has also facilitated the emergence of other comorbidities increasing the risk for drug-drug interactions and polypharmacy. The profile of these interactions as well as their consequences for people living with HIV are still not completely elucidated. The objectives of this study were to describe the profile of these interactions, their prevalence and their classification according to the potential for significant or non-significant drug-drug interactions. From June 2015 to July 2016, people living with HIV on follow-up at an Infectious Diseases Referral Center in Belo Horizonte, Brazil have been investigated for the presence of drug-drug interactions. A total of 304 patients were included and the majority (75%) had less than 50 years of age, male (66.4%), and 37.8% self-defined as brown skinned. Approximately 24% were on five or more medications and half of them presented with drug-drug interactions. Patients older than 50 years had a higher frequency of antiretrovirals drug-drug interactions with other drugs compared to younger patients (p=0.002). No relationship was found between the number of drug-drug interactions and the effectiveness of antiretrovirals. As expected, the higher the number of non-HIV medications used (OR=1.129; 95%CI 1.004-1.209; p=0.04) was associated with an increase in drug-drug interactions. The high prevalence of drug-drug interactions found and the data collected should be useful to establish measures of quaternary prevention and to increase the medication security for people living with HIV.

Profile of drug-drug interactions and impact on the effectiveness of antiretroviral therapy among patients living with HIV followed at an Infectious Diseases Referral Center in Belo Horizonte, Brazil

ABSTRACT HIV infection may be considered a chronic condition for people living with HIV with access to antiretrovirals and this has effectively increased survival. Moreover, this has also facilitated the emergence of other comorbidities increasing the risk for drug-drug interactions and polypharmacy. The profile of these interactions as well as their consequences for people living with HIV are still not completely elucidated. The objectives of this study were to describe the profile of these interactions, their prevalence and their classification according to the potential for significant or non-significant drug-drug interactions. From June 2015 to July 2016, people living with HIV on follow-up at an Infectious Diseases Referral Center in Belo Horizonte, Brazil have been investigated for the presence of drug-drug interactions. A total of 304 patients were included and the majority (75%) had less than 50 years of age, male (66.4%), and 37.8% self-defined as brown skinned. Approximately 24% were on five or more medications and half of them presented with drug-drug interactions. Patients older than 50 years had a higher frequency of antiretrovirals drug-drug interactions with other drugs compared to younger patients (p = 0.002). No relationship was found between the number of drug-drug interactions and the effectiveness of antiretrovirals. As expected, the higher the number of non-HIV medications used (OR = 1.129; 95%CI 1.004-1.209; p = 0.04) was associated with an increase in drug-drug interactions. The high prevalence of drug-drug interactions found and the data collected should be useful to establish measures of quaternary prevention and to increase the medication security for people living with HIV.

The bilateral bispectral and the composite variability indexes during anesthesia for unilateral surgical procedure.

BACKGROUND: The composite variability index (CVI), derived from the bispectral analysis (BIS), has been designed to detect nociception; however, there is no evidence that bilateral BIS and CVI show intrapatient reproducibility or variability. METHODS: We conducted an observational study in patients who underwent for total knee arthroplasty. A BIS Bilateral Sensor was applied and continuously recorded at different points of the anesthesia procedure. Bland-Altman limits of agreement and dispersion for BIS and for CVI were applied. RESULTS: Forty-nine right-handed patients were studied. There were differences between the right and left BIS values after tracheal intubation (which was higher on the right side) and at surgical stimulus (higher on the left side). The maximum BIS and minimum, mean, and maximum CVI scores were higher on the left side for left-side procedures, but there were no differences in any indexes for the right-side procedures. Except for the baseline measurements, both CVI and BIS scores presented high interpatient variability. Although the right to left bias was < 3% for the BIS index, dispersion was large at different stages of the anesthesia. The right to left bias for the CVI was 3.8% at tracheal intubation and 5.7% during surgical stimulus. CONCLUSIONS: Our results indicate that the large interindividual variability of BIS and CVI limits their usefulness. We found differences between the left and right measurements in a right-handed series of patients during surgical stimuli though they were not clinically relevant.

Influência da técnica de polimento na lisura superficial de resinas compostas / Influence of the polishing technique on the surface roughness of composite resins

Realizar o polimento das restaurações diretas em resina composta é importante para estabelecer uma superfície lisa e promover a saúde ao periodonto. O objetivo deste estudo é avaliar a influência de diferentes sistemas de polimento sobre a topografia de superfície de cinco resinas compostas: Master Fill, Vênus, Brilliant, Charisma Opal e Fitek Supreme. Confeccionaram-se 100 corpos de prova com uma matriz metálica cilíndrica de 5mm x 2mm (ISO 4872) distribuídos em cinco grupos teste, de acordo com o tipo polimento (n=20): escova de carbeto de silício (ECS), pasta diamantada (PD), pontas de borracha abrasiva (PB) e discos abrasivos (DA). Os valores de rugosidade (Ra) e as imagens obtidas com a Microscopia de Força Atômica (MFA) foram obtidos antes e após os métodos de polimento. Os resultados foram tabulados e analisados estatisticamente pelo teste de Tukey, com 5% de significância. Conclui-se que os procedimentos de polimento utilizados para as resinas testadas mostraram-se eficazes em reduzir a rugosidade da superfície, com valores variando entre 0,03µm e 0,11µm

Performing the polishing of composite resin direct restorations is important to provide a smooth surface and promote periodontal health. The aim of this study was to evaluate the influence of different polishing systems on surface topography of live composite resins: Master Fill, Venus, Brilliant, Charisma Opal and Filtek Z350. One hundred composite resin specimens were fabricated with a cylindrical metal matrix 5 x 2 mm (ISO 4872) distributed in 5 test groups, according to the type polishing (n:20): SCB – silicon carbide brush, DP – Diamond paste, TRA – tips rubber abrasive and AD – abrasive disc. The values of roughness (Ra) and the images taken by Atomic Force Microscopy (AFM) were obtained before and after polishing methods. The results were statistically analyzed by Tukey test at 5% significance level. It was conclude that the polishing procedure used for the resins tested were effective for reducing the surface roughness, with values ranging between 0.03 and 0,011 µm

Minimal change nephrotic syndrome after stem cell transplantation: a case report and literature review.

Graft-versus-host disease is one of the most frequent complications occurring after haematopoietic stem cell transplantation. Recently, renal involvement has been described as a manifestation of chronic graft-versus-host disease. Immunosuppression seems to play a major role: clinical disease is triggered by its tapering and resolution is achieved with the resumption of the immunosuppressive therapy. Prognosis is apparently favourable, but long term follow up data are lacking.We report a case of a 53-year-old man who developed nephrotic syndrome 142 days after allogeneic stem cell transplantation for acute myeloid leukaemia. Onset of nephrotic syndrome occurred after reduction of immunosuppressants and was accompanied by manifestations of chronic graft-versus-host disease. Histological examination of the kidney was consistent with Minimal Change Disease. After treatment with prednisolone and mycophenolate mofetil he had complete remission of proteinuria and improvement of graft-versus-host disease. Eighteen months after transplantation the patient keeps haematological remission and normal renal function, without proteinuria.Since patients with chronic graft-versus-host disease might be considered at risk for development of nephrotic syndrome, careful monitoring of renal parameters, namely proteinuria, is advisable.

Immunophenotypic and functional characterization of cord blood dendritic cells.

Dendritic cells (DCs) play a pivotal role in the activation of T cells, which are effector cells in graft-versus-host disease (GVHD). A low incidence of GVHD following cord blood (CB) transplantation has long been reported; despite this, little information is currently available on the characteristics of CB DCs. The goal of the present study was to investigate the immunophenotypic characteristics and distribution of CB DCs and their subsets. For that purpose we have analyzed 15 CB samples as compared to normal peripheral blood (PB) (n = 7) and blood from patients submitted to an allogeneic PB stem cell transplantation (allo-PBSCT) (n = 6). Our results show an overall decreased frequency of DCs in CB due to the presence of significantly lower numbers of CD123inter./CD33inter./CD16+ DCs. Phenotypically, CB DCs displayed a tendency to express lower levels of the gamma-chain interleukin-2 (IL-2) receptor (CD132) and of the CD86 co-stimulatory molecule, supporting a higher degree of immaturity for CB as compared to PB DCs. After activation of CB DCs with lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) higher frequencies of cytokine-producing cells were found among CD123inter./CD33inter./CD16+ and CD123dim/CD33bright/CD16- DCs; however, when only the cytokine-producing DCs were considered, a significant decrease in the amount of different cytokine (e.g., IL-1beta and IL-6) produced per cell was observed especially for CD16+ CB DCs. These findings support a higher degree of immaturity for CB as compared to PB DCs that might contribute to explain, at least in part, the low incidence and severity of GVHD observed after CB transplantation.

Unrelated cord blood transplantation for childhood acute myeloid leukemia: a Eurocord Group analysis.

Results of unrelated cord blood transplantation (UCBT) in childhood acute myeloid leukemia (AML) have not been previously reported. We analyzed 95 children receiving UCB transplants for AML (20 in first complete remission [CR1], 47 in CR2, and 28 in more advanced stage). Poor prognosis cytogenetic abnormalities were identified in 29 cases. Most patients received a 1 or 2 HLA antigens-mismatched UCB transplants. The median number of collected nucleated cells (NCs) was 5.2 x 107/kg. Cumulative incidence (CI) of neutrophil recovery was 78% +/- 4%, acute graft-versus-host disease (GVHD) was 35% +/- 5%, and 100-day transplantation-related mortality (TRM) was 20% +/- 4%. In multivariable analysis, a collected NC dose higher than 5.2 x 107/kg was associated with a lower 100-day TRM. The 2-year CI of relapse was 29% +/- 5% and was associated with disease status. The 2-year leukemia-free survival (LFS) was 42% +/- 5% (59% +/- 11% in CR1, 50% +/- 8% in CR2, and 21% +/- 9% for children not in CR). Children with poor prognosis cytogenetic features had similar LFS compared with other patients (44% +/- 11% vs 40% +/- 8%). In CR2, LFS was not influenced by the length of CR1 (53% +/- 11% in CR1 < 9.5 months compared with 50% +/- 12% in later relapses). We conclude that UCBT is a therapeutic option for children with very poor-prognosis AML and who lack an HLA-identical sibling.

Positive selection for CD34+ reduces the incidence and severity of veno-occlusive disease of the liver after HLA-identical sibling allogeneic peripheral blood stem cell transplantation.

OBJECTIVE: T-cell depletion (TCD), primarily developed to prevent graft-vs-host disease (GVHD), might reduce early liver dysfunction after allogeneic hematopoietic stem cell transplantation. However, no comparative studies have been performed to investigate this. We analyzed the influence of selection for CD34(+) cells on the incidence and severity of hepatic veno-occlusive disease (VOD). PATIENTS AND METHODS: Five hundred and one patients who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from HLA-identical siblings were included in the present study. Two hundred and ninety patients (59%) were grafted with CD34+ positively selected grafts and 211 (41%) with nonmanipulated grafts. Their mean age was 38 years (range 17-63). All patients had hematological malignancies and 96% were conditioned with combinations either of cyclophosphamide plus total-body irradiation or of cyclophosphamide plus busulphan. Most of the patients received GVHD prophylaxis with methotrexate (MTX) or cyclosporin A. RESULTS: Fifty-two patients (10.4%) developed VOD. VOD was more frequent in patients receiving nonmanipulated grafts (16.1% vs 6.2%; p<0.0009), in those with a Karnofsky score less than 90 (17.5% vs 7.8%; p=0.001), and with the use of MTX for GVHD prophylaxis (14.8% vs 7%; p=0.005). In multivariate analyses, only CD34+ positive selection (p=0.0007) and Karnofsky score (p=0.004) emerged as independent risk factors for VOD. The same effect was observed in the subset of patients with severe VOD. CONCLUSION: These findings show that CD34+ selection not only decreases the incidence of GVHD but also prevents VOD after HLA-identical sibling PBSCT.

Risk factors for acute graft-versus-host disease in patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings.

A study on 315 patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings was performed to determine risk factors for acute GVHD (aGVHD). Recipients of a dose of CD34+ cells (x 10(6)/kg) of 2 or less, more than 2 to 4, and more than 4 had a cumulative incidence of aGVHD grades I-IV of 21%, 35%, and 43%, respectively (log-rank P =.01); similarly, recipients of a dose of CD3+ cells (x 10(6)/kg) of 0.05 or less, more than 0.05 to 0.1, and more than 0.1 had a cumulative incidence of aGVHD grades I-IV of 18%, 35%, and 44%, respectively (log-rank P =.007). Using a Cox regression model, 4 independent factors for aGVHD I-IV were identified: increased CD34+ cell dose (P =.02), increased CD3+ cell dose (P =.02), female patients (P =.01), and higher patient age (> 42 years) (P =.007). This study shows, for the first time in T-cell-depleted transplantations, a positive correlation between the number of CD34+ cells and aGVHD and, also, that the number of CD3+ cells necessary to initiate aGVHD is lower than previously reported.

Trypanosoma cruzi meningoencephalitis in AIDS mimicking cerebral metastases: case report

A case of Chagas' meningoencephalitis in a 47 year-old patient with AIDS is presented. The diagnosis was established by examination of the cerebrospinal fluid which showed the presence of Trypanosoma cruzi. CT-scan revealed multiple cerebral lesions which only became evident by contrast administration. A second CT after 13 days showed a severe evolution with displacement of the midline structures leading to the patient's death. This case, as well as other case reports published, has shown the fulminant evolution of Chagas'meningoencephalitis in AIDS patients and the importance of cerebrospinal fluid examination for the diagnosis.