Advanced renal cell carcinoma management: the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG) consensus update.

PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.

Global real-world experiences with pembrolizumab in advanced urothelial carcinoma after platinum-based chemotherapy: the ARON-2 study.

BACKGROUND: Immune checkpoint inhibitors have changed previous treatment paradigm of advanced urothelial carcinoma (UC). The ARON-2 study (NCT05290038) aimed to assess the real-world effectiveness of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. PATIENTS AND METHODS: Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were retrospectively collected from 88 institutions in 23 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Cox proportional hazards models were adopted to explore the presence of prognostic factors. RESULTS: In total, 836 patients were included: 544 patients (65%) received pembrolizumab after progression to first-line platinum-based chemotherapy in the metastatic setting (cohort A) and 292 (35%) after recurring within < 12 months since the completion of adjuvant or neoadjuvant chemotherapy (cohort B). The median follow-up time was 15.3 months. The median OS and the ORR were 10.5 months and 31% in the overall study population, 9.1 months and 29% in cohort A and 14.6 months and 37% in cohort B. At multivariate analysis, ECOG-PS ≥ 2, bone metastases, liver metastases and pembrolizumab setting (cohort A vs B) proved to be significantly associated with worst OS and PFS. Stratified by the presence of 0, 1-2 or 3-4 prognostic factors, the median OS was 29.4, 12.5 and 4.1 months (p < 0.001), while the median PFS was 12.2, 6.4 and 2.8 months, respectively (p < 0.001). CONCLUSIONS: Our study confirms that pembrolizumab is effective in the advanced UC real-world context, showing outcome differences between patients recurred or progressed after platinum-based chemotherapy.

Factors influencing COVID-19 mortality among cancer patients: A Brazilian multi-institutional study.

PURPOSE: This study aimed to describe the demographic and clinical characteristics of cancer patients with COVID-19, exploring factors associated with adverse outcomes. PATIENTS AND METHODS: This retrospective cohort study methodically extracted and curated data from electronic medical records (EMRs) of numerous healthcare institutions on cancer patients diagnosed with a confirmed SARS-CoV-2 infection between May 2020 and August 2021, to identify risk factors linked to extended hospitalization and mortality. The retrieved information encompassed the patients' demographic and clinical characteristics, including the incidence of prolonged hospitalization, acute complications, and COVID-19-related mortality. RESULTS: A total of 1446 cancer patients with COVID-19 were identified (mean [Standard deviation] age, 59.2 [14.3] years). Most patients were female (913 [63.1%]), non-white (646 [44.7%]), with non-metastatic (818 [56.6%]) solid tumors (1318 [91.1%]), and undergoing chemotherapy (647 [44.7%]). The rate of extended hospitalization due to COVID-19 was 46% (n = 665), which was significantly impacted by age (p = 0.012), sex (p = 0.003), race and ethnicity (p = 0.049), the presence of two or more comorbidities (p = 0.006), hematologic malignancies (p = 0.013), metastatic disease (p = 0.002), and a performance status ≥ 2 (p = 0.001). The COVID-19-related mortality rate was 18.9% (n = 273), and metastatic disease (<0.001), performance status ≥2 (<0.001), extended hospitalization (p = 0.028), renal failure (p = 0.029), respiratory failure (p < 0.001), sepsis (p = 0.004), and shock (p = 0.040) significantly and negatively influenced survival. CONCLUSION: The rate of extended hospitalization and COVID-19-specific death in cancer patients was notably high and could be influenced by comorbidities, cancer treatment status, and clinical fragility. These observations may aid in developing risk counseling strategies regarding COVID-19 in individuals diagnosed with cancer.

Use of concomitant proton pump inhibitors, statins or metformin in patients treated with pembrolizumab for metastatic urothelial carcinoma: data from the ARON-2 retrospective study.

BACKGROUND: Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab. METHODS: We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model. RESULTS: A total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3 months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2 months, p = 0.002) and OS (8.7 vs. 14.1 months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival. CONCLUSIONS: Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.

Patients' Perceptions Regarding the Relevance of Items Contained in the Functional Assessment of Cancer Therapy Kidney Symptom Index-19.

BACKGROUND: There is a lack of consensus regarding the optimal method of assessing health-related quality of life (HR-QOL) among patients with metastatic renal cell carcinoma (mRCC). This study explored the perceived relevance of items that make up the Functional Assessment of Cancer Therapy Kidney Symptom Index-19 (FKSI-19), as judged by patients with mRCC. METHODS: This was a multinational cross-sectional survey. Eligible patients responded to a questionnaire composed of 18 items that assessed the perceived relevance of each item in the FKSI-19 questionnaire. Open-ended questions assessed additional issues deemed relevant by patients. Responses were grouped as relevant (scores 2-5) or nonrelevant (score 1). Descriptive statistics were collated, and open-ended questions were analyzed and categorized into descriptive categories. Spearman correlation statistics were used to test the association between relevance and clinical characteristics. RESULTS: A total of 151 patients were included (gender: 78.1 M, 21.9F; median age: 64; treatment: 38.4 immunotherapy, 29.8 targeted therapy, 13.9 immuno-TKI combination therapy) in the study. The most relevant questions evaluated fatigue (77.5), lack of energy (72.2), and worry that their condition will get worse (71.5). Most patients rated blood in urine (15.2), fevers (16.6), and lack of appetite (23.2) as least relevant. Qualitative analysis of open-ended questions revealed several themes, including emotional and physical symptoms, ability to live independently, effectiveness of treatment, family, spirituality, and financial toxicity. CONCLUSION: There is a need to refine widely used HR-QOL measures that are employed among patients diagnosed with mRCC treated with contemporary therapies. Guidance was provided for the inclusion of more relevant items to patients' cancer journey.

Analysis of false positive PI-RADS 4 lesions: experience from a single nonacademic center using cognitive fusion.

BACKGROUND: We evaluated pathological findings in targeted biopsies of PI-RADS4 and PI-RADS5 lesions, and clinical data that could predict those patients with benign findings. MATERIALS AND METHODS: A retrospective study was conducted to summarize the experience from a single nonacademic center using cognitive fusion and a 1.5 or 3.0 Tesla scanner. RESULTS: We found a false positive rate of 29 and 3.7% for any cancer in PI-RADS 4 and 5 lesions, respectively. Diverse histologic patterns were observed among target biopsies. At multivariate analysis, size ≤ 6 mm and previous negative biopsy were independent predictors of false positive PI-RADS4 lesions. The small number of false PI-RADS5 lesions precluded further analyses. CONCLUSION: Benign findings are common in PI-RADS4 lesions and most of them do not show obvious glandular or stromal hypercellularity as expected in hyperplastic nodules. Size ≤ 6 mm and previous negative biopsy predict a higher probability of false positive results in patients with PI-RADS 4 lesions.

Repositioning of Disulfiram in Association with Vancomycin Against Enterococcus spp. MDR and XDR.

The identification of molecules that exhibit potent antibacterial activity and are capable of circumventing resistance mechanisms is an unmet need. The repositioning of approved drugs is considered an advantageous alternative in this case, and has gained prominence. In addition, drug synergism can reduce morbidity and mortality in the treatment of nosocomial infections caused by multi-drug resistant microorganisms (MDR). Whole cell growth inhibition assays were used to define the in vitro antibacterial activity of disulfiram against two standard American Type Culture Collection (ATCC) strains and 35 clinical isolates of vancomycin-resistant enterococci (VRE). The ability of disulfiram to synergize with vancomycin was determined by fractional inhibitory concentration index, preceded by the checkerboard test. The cytotoxicity of drugs alone and in combination was tested against Raw 264.7 cells. Disulfiram exhibited potent antibacterial activity against VRE (MIC 16-64 µg mL-1). Results: Associated with vancomycin, disulfiram it had a reduction in MIC of up to 64 times, with values of 0.5-4 µg mL-1. Vancomycin had a MIC of 128-1024 µg mL-1; combined, reduced this value by up to 124 times (8 µg mL-1), with synergy occurring against all strains. Disulfiram and vancomycin alone and in combination did not show cytotoxicity against the eukaryotic cell line. Based on these results, we suggest that the redirection of disulfiram may be promising in the treatment of infections caused by VRE, since it was able to potentiate the activity of vancomycin against the strains, being able to act as an adjuvant in cases of serious infections caused by Enterococcus.

Clinical Trials Using Mesenchymal Stem Cells for Spinal Cord Injury: Challenges in Generating Evidence.

Spinal cord injury (SCI) remains an important public health problem which often causes permanent loss of muscle strength, sensation, and function below the site of the injury, generating physical, psychological, and social impacts throughout the lives of the affected individuals, since there are no effective treatments available. The use of stem cells has been investigated as a therapeutic approach for the treatment of SCI. Although a significant number of studies have been conducted in pre-clinical and clinical settings, so far there is no established cell therapy for the treatment of SCI. One aspect that makes it difficult to evaluate the efficacy is the heterogeneity of experimental designs in the clinical trials that have been published. Cell transplantation methods vary widely among the trials, and there are still no standardized protocols or recommendations for the therapeutic use of stem cells in SCI. Among the different cell types, mesenchymal stem/stromal cells (MSCs) are the most frequently tested in clinical trials for SCI treatment. This study reviews the clinical applications of MSCs for SCI, focusing on the critical analysis of 17 clinical trials published thus far, with emphasis on their design and quality. Moreover, it highlights the need for more evidence-based studies designed as randomized controlled trials and potential challenges to be addressed in context of stem cell therapies for SCI.

Coagulase-negative staphylococci isolates from blood cultures of newborns in a tertiary hospital in southern Brazil

Abstract Neonatal sepsis continues to be a major cause of morbidity and mortality worldwide. Coagulase-negative staphylococci (CoNS), commonly found on the skin, being the main agents isolated. The aim of this study was to evaluate CoNS isolated from blood cultures of newborn (NB) infants. The study took place between 2014 and 2016/2017 in a tertiary hospital in southern Brazil. Using the VITEK 2 system (bioMérieux, Marcy l'Etoile, France), the microorganisms were identified and had their sensitivity profiles determined. The minimum inhibitory concentrations of linezolid, tigecycline, and vancomycin were also determined. The clinical parameters and mortality rates of NBs were evaluated. From January to December 2014, 176 CoNS isolates were obtained from 131 patients and from June 2016 to July 2017, 120 CoNS isolates were obtained from 79 patients. Staphylococcus epidermidis was most prevalent in both periods. Resistance rates increased between 2014 and 2016/2017, especially against ciprofloxacin (52.27% and 73.11%, p = 0.0004), erythromycin (51.40% and 68.07%, p = 0.0054), gentamicin (50.59% and 67.23%, p = 0.0052), and penicillin (71.3% and 99.17%, p = 0.0001), respectively. With 100% susceptibility to linezolid, tigecycline, and vancomycin in both periods and methodologies tested. In 2014, 53.44% of the NBs received antibiotic therapy, and of these, 77.14% used a catheter; in 2016/2017, these were 78.48% and 95.16%, respectively. Regarding laboratory tests, a hemogram was ineffective, since patients with sepsis presented normal reference values. In 2014 and 2016/17, 15.71% and 17.74% of the NBs died, respectively. S. epidermidis was the predominant microorganism, related to catheter use in most cases. The resistance rates have increased over time, demonstrating the importance of adopting control and prevention measures in this hospital. CoNS are responsible for a significant neonatal sepsis mortality rate in infants.

Drug Repositioning in Oncology.

BACKGROUND: The worldwide increase in the occurrence of cancer associated with the limitations of immunotherapy and the emergence of resistance have impaired the prognosis of cancer patients, which leads to the search for alternative treatment methods. Drug repositioning, a well-established process approved by regulatory agencies, is considered an alternative strategy for the fast identification of drugs, because it is relatively less costly and represents lower risks for patients. AREAS OF UNCERTAINTY: We report the most relevant studies about drug repositioning in oncology, emphasizing that its implementation faces financial and regulatory obstacles, making the creation of incentives necessary to stimulate the involvement of the pharmaceutical industry. DATA SOURCES: We present 63 studies in which 52 non-anticancer drugs with anticancer activity against a number of malignancies are described. THERAPEUTIC INNOVATIONS: Some have already been the target of phase III studies, such as the Add-Aspirin trial for nonmetastatic solid tumors, as well as 9 other drugs (aprepitant, artesunate, auranofin, captopril, celecoxib, disulfiram, itraconazole, ritonavir, and sertraline) in the CUSP9* clinical trial for the treatment of recurrent glioblastoma. Others have already been successful in repositioning such as thalidomide, zoledronic acid, celecoxib, methotrexate, and gemcitabine. CONCLUSIONS: Therefore, drug repositioning represents a promising alternative for the treatment of oncological disorders; however, the support from funding agencies and from the government is still needed, the latter regarding regulatory issues.

Real life data of MRI-targeted biopsy - experience from a single nonacademic centre using cognitive fusion and 1.5 tesla scanning.

OBJECTIVES: To date, it is unknown whether systematic biopsies can be safely omitted in patients with unsuspicious MRI findings or if systematic biopsies should be required when targeting focal lesions (PI-RADS 3-5). METHODS: A series of 366 patients (249 without a previous biopsy) were examined in a 1.5 Tesla MRI scanner. All patients were submitted to systematic biopsies (12-14 regions) with additional targeted biopsies (by cognitive fusion) of focal PI-RADS lesions (PI-RADS 3-5). RESULTS: In our series, patients with PI-RADS 1/2 findings had rates of adenocarcinoma of any grade, >GG1 and GG4/5 of 34%, 14% and 3%, respectively. The use of MRI prior to biopsy in our series increased the detection of clinically significant prostate cancer (CSPCa) in 28% of patients with focal lesions, and focal lesions were present in 293/366 (80%) of all patients. For CSPCa (>GG1), targeted biopsies improved the diagnosis in 28% of patients, while systematic biopsies resulted in an additional 19% of cancer cases in the series. CONCLUSION: Systematic biopsies should still be considered in patients with PI-RADS 1/2 findings. Our findings also suggest a stronger benefit of the combined strategy of targeted and systematic biopsies than the findings of previous studies concerning the detection of CSPCa in biopsy-naïve patients.

"Burnout in Medical Oncology Fellows: a Prospective Multicenter Cohort Study in Brazilian Institutions".

Burnout syndrome is a common occurrence among oncologists. Doctors enrolled in residency programs in clinical oncology are exposed to similar risk factors; however, few data are available in this population. This study assessed the occurrence of burnout and associated factors among first-year residents at Brazilian institutions. The present prospective, multicenter, cohort study was conducted with doctors enrolled in residency programs in clinical oncology at Brazilian institutions affiliated with the public health system. The participants answered a sociodemographic questionnaire, the Maslach Burnout Inventory (MBI), Lipp's Stress Inventory, and the Beck Depression Inventory (BDI), upon admission to the program and 6 and 12 months later. Of 37 eligible residency programs in 2009, 11 (30.6 %) agreed to participate in the study. Fifty-four residents, representing 100 % of new admissions to the participating institutions, were included. Most of the participants met the criteria for severe burnout upon admission to the residency programs (emotional exhaustion in 49.0 % and depersonalization in 64.7 %). The scores on MBI domains emotional exhaustion and depersonalization increased significantly (p < 0.01) during the first year of residency, and the prevalence of burnout increased to 88 % at the end of that first year. The present study found a high prevalence of burnout among doctors enrolled in residency programs in clinical oncology at Brazilian institutions. A large fraction of the participants met the criteria for burnout syndrome upon admission to the program, which suggests that the problem began during the course of the previous residency program in internal medicine.

Transplante de células da medula óssea na insuficiência cardíaca chagásica: relato da primeira experiência humana / Bone marrow cell transplantation in chagas' disease heart failure: report of the first human experience / Transplante de células de la médula ósea en la insuficiencia cardíaca de la enfermedad de chagas: relato de la Primera Experiencia Humana

FUNDAMENTO: Insuficiência cardíaca (IC) causada por Doença de Chagas (DC) é uma cardiomiopatia inflamatória progressiva que afeta milhões de pessoas na América Latina. Estudos com modelos de camundongo de IC devido à DC indicam que o transplante de células mononucleares derivadas da medula óssea (TCDMO) pode reduzir a inflamação, fibrose e melhorar a função miocárdica. OBJETIVO: O propósito desse estudo foi avaliar, pela primeira vez em seres humanos, a segurança e a eficácia de TCDMO no miocárdio de pacientes com IC devido à DC. MÉTODOS: Um total de 28 pacientes com IC devido à DC (média de idade de 52,2 ± 9,9 anos) com classe funcional NYHA III e IV foram submetidos à TCDMO através de injeção coronariana. Os efeitos na fração de ejeção do ventrículo esquerdo (FEVE), capacidade funcional, qualidade de vida, arritmias e parâmetros bioquímicos, imunológicos e neuro-humorais foram avaliados. RESULTADOS: Não houve complicações diretamente relacionadas ao procedimento. A FEVE foi 20,1 ± 6,8 por cento e 28,3 ± 7,9 por cento, p < 0,03 a nível basal e 180 dias após o procedimento, respectivamente. No mesmo período, melhoras significantes foram observadas na classe funcional NYHA (3,1 ± 0,3 para 1,8 ± 0,5; p < 0,001), qualidade de vida (50,9 ± 11,7 para 25,1 ± 15,9; p < 0,001), e no teste de caminhada de seis minutos (355 ± 136 m para 437 ± 94 m; p < 0,01). Não houve alterações nos marcadores de ativação imune ou neurohormonais. Nenhuma complicação foi registrada. CONCLUSÃO: Nossos dados sugerem que a injeção intracoronariana de células derivadas da medula óssea é segura e potencialmente efetiva em pacientes com IC devido à DC. A extensão do benefício, entretanto, parece ser discreta e precisa ser confirmada em estudos clínicos maiores, randomizados, duplo-cegos, controlados com placebo.

BACKGROUND: Heart failure due to Chagas' disease (HFCD) is a progressive inflammatory cardiomyopathy that affects millions of individuals in Latin America. Studies using mice models of HFCD indicate that bone marrow mononuclear cell transplantation (BMCT) may reduce inflammation, fibrosis, and improve myocardial function. OBJECTIVE: The purpose of this study was to evaluate, for the first time in humans, the safety and efficacy of BMCT to the myocardium of patients with HFCD. METHODS: A total of 28 HFCD patients (mean age 52.2 ± 9.9 years) with NYHA class III and IV were submitted to BMCT through intracoronary injection. Effects on the left ventricle ejection fraction (LVEF), functional capacity, quality-of-life, arrhythmias, biochemical, immunological, and neuro-humoral parameters, were evaluated. RESULTS: There were no complications directly related to the procedure. LVEF was 20.1 ± 6.8 percent and 28.3 ± 7.9 percent, p < 0.03 at baseline and 180 days after the procedure, respectively. In the same period, significant improvements were observed in the NYHA class (3.1 ± 0.3 to 1.8 ± 0.5; p < 0.001), quality-of-life (50.9 ± 11.7 to 25.1 ± 15.9; p < 0.001), and in the six-minute walking test (355 ± 136 m to 437 ± 94 m; p < 0,01). There were no changes in markers of immune or neurohormonal activation. No complications were registered. CONCLUSION: Our data suggest that the intracoronary injection of BMCT is safe and potentially effective in patients with HFCD. The extent of the benefit, however, appears to be small and needs to be confirmed in a larger randomized, double blind, placebo controlled clinical trial.

FUNDAMENTO: La insuficiencia cardíaca (IC), causada por la enfermedad de Chagas (EC), es una cardiomiopatía inflamatoria progresiva que afecta a millones de personas en Latinoamérica. Estudios con modelos experimentales de IC en razón de la EC, nos indican que el transplante de células mononucleares derivadas de la médula ósea (TCMO), puede reducir la inflamación y la fibrosis, mejorando así la función miocárdica. OBJETIVO:El objetivo de este estudio fue evaluar, por primera vez en seres humanos, la seguridad y la eficacia del TCMO en el miocardio de pacientes con IC debido a la EC. MÉTODOS:Fueron estudiados un total de 28 pacientes con IC debido a la EC (con edad promedio 52,2 ± 9,9 años), en clases funcionales III y IV (NYHA), al TCMO por medio de una inyección coronaria. Se evaluaron los efectos en la fracción de eyección del ventrículo izquierdo (FEVI), capacidad funcional, calidad de vida, arritmias y parámetros bioquímicos, inmunológicos y neurohumorales. RESULTADOS:No se registraron complicaciones relacionadas directamente con el procedimiento. La FEVI pasó de 20,1 ± 6,8 por ciento para 28,3 ± 7,9 por ciento, p < 0,03, cuando se comparó con el período basal y 180 días después del procedimiento, respectivamente. En el mismo período, también se observaron mejorías en la clase funcional NYHA promedio (3,1 ± 0,3 para 1,8 ± 0,5; p < 0,001), puntuación de calidad de vida de Minnesota (50,9 ± 11,7 para 25,1 ± 15,9; p < 0,001), y en el test de esfuerzo de seis minutos (355 ± 136 m para 437 ± 94 m; p < 0,01). No hubo alteraciones en los marcadores de activación inflamatoria o neurohormonales. Ninguna complicación fue registrada. CONCLUSIÓN:Nuestros datos sugieren que la inyección intracoronaria de las células derivadas de la médula ósea es segura y potencialmente efectiva en pacientes con IC debido a la EC. La extensión del beneficio, sin embargo, parece ser discreta, y necesita ser confirmada en los ensayos clínicos randomizados, doble ciegos, controlados con placebo.

Bone marrow cell transplantation in Chagas' disease heart failure: report of the first human experience.

BACKGROUND: Heart failure due to Chagas' disease (HFCD) is a progressive inflammatory cardiomyopathy that affects millions of individuals in Latin America. Studies using mice models of HFCD indicate that bone marrow mononuclear cell transplantation (BMCT) may reduce inflammation, fibrosis, and improve myocardial function. OBJECTIVE: The purpose of this study was to evaluate, for the first time in humans, the safety and efficacy of BMCT to the myocardium of patients with HFCD. METHODS: A total of 28 HFCD patients (mean age 52.2 ± 9.9 years) with NYHA class III and IV were submitted to BMCT through intracoronary injection. Effects on the left ventricle ejection fraction (LVEF), functional capacity, quality-of-life, arrhythmias, biochemical, immunological, and neuro-humoral parameters, were evaluated. RESULTS: There were no complications directly related to the procedure. LVEF was 20.1 ± 6.8% and 28.3 ± 7.9%, p < 0.03 at baseline and 180 days after the procedure, respectively. In the same period, significant improvements were observed in the NYHA class (3.1 ± 0.3 to 1.8 ± 0.5; p < 0.001), quality-of-life (50.9 ± 11.7 to 25.1 ± 15.9; p < 0.001), and in the six-minute walking test (355 ± 136 m to 437 ± 94 m; p < 0,01). There were no changes in markers of immune or neurohormonal activation. No complications were registered. CONCLUSION: Our data suggest that the intracoronary injection of BMCT is safe and potentially effective in patients with HFCD. The extent of the benefit, however, appears to be small and needs to be confirmed in a larger randomized, double blind, placebo controlled clinical trial.

The close relationship between South African and Latin American HTLV type 1 strains corroborated in a molecular epidemiological study of the HTLV type 1 isolates from a blood donor cohort.

It has been difficult to explain why all HTLV-1 sequences in Salvador, a city in the northeast of Brazil, belong to the Transcontinental (A) subgroup of the Cosmopolitan (a) subtype, since according to historical data the vast majority of slaves brought to Brazil (through Salvador) came from west Africa, where only the western African subgroup (C) has been found. To shed more light on this subject we conducted a phylogenetic analysis of 23 isolates from blood donors of Salvador. DNA was extracted and submitted to a nested PCR for amplification of the entire LTR region. The PCR products were purified and sequenced on an automated sequencer. Neighbor-joining and maximum likelihood phylogenetic analyses were performed. None of the new sequences from Salvador clustered within the West-African subgroup C. Confirming previous results, all sequences belonged to the Transcontinental subgroup (A) of the Cosmopolitan subtype, and clustered in two Latin American clusters. In addition we showed sequences from southern Africa clustering in both Latin American clusters. One of the new sequences is ancestral to the larger Latin American cluster beta due to a duplication of a 12-bp long fragment, a finding that has not been previously described. These findings support the hypothesis that HTLV-1 isolates circulating in Latin America have a closer relationship to South African compared to West-African HTLV-1 strains. The 12-bp-long duplications in one of the sequences has no obvious clinical or biological implications yet.

[Sociodemographic, epidemiological and behavioral profile of women infected with HTLV-1 in Salvador, Bahia, an endemic area for HTLV]. / Perfil sociodemográfico, epidemiológico e comportamental de mulheres infectadas pelo HTLV-1 em Salvador-Bahia, uma área endêmica para o HTLV.

The objective was to describe the sociodemographic, epidemiological and behavioral characteristics of women infected with HTLV-1 (64) and uninfected women (66) in Salvador, Bahia. The serological diagnosis was obtained via Elisa, Western Blot and Immunofluorescence. Epidemiological and sociodemographic data were collected using a standardized questionnaire. The chi-squared or Fisher test was used for categorical data and ANOVA or Kruskal-Wallis (3 groups) and the T-test or Mann-Whitney (2 groups) were used for continuous data. Associated variables were adjusted using logistic regression. More than half (57.8%) of the seropositive women were asymptomatic. The symptomatic women (with HAM/TSP) had fewer years of education. Comparison between seronegative and seropositive women showed that blood transfusion, anal sex practices, first sexual intercourse before the age of 18 years and three or more sexual partners over women's lifetime were risk factors for HTLV-1 infection. The prevention of both sexual transmission and vertical transmission (breastfeeding) should be reinforced. Prenatal screening is of paramount importance.

Feasibility and safety of autologous bone marrow mononuclear cell transplantation in patients with advanced chronic liver disease.

AIM: To evaluate the safety and feasibility of bone marrow cell (BMC) transplantation in patients with chronic liver disease on the waiting list for liver transplantation. METHODS: Ten patients (eight males) with chronic liver disease were enrolled to receive infusion of autologous bone marrow-derived cells. Seven patients were classified as Child-Pugh B and three as Child-Pugh C. Baseline assessment included complete clinical and laboratory evaluation and abdominal MRI. Approximately 50 mL of bone marrow aspirate was prepared by centrifugation in a ficoll-hypaque gradient. At least of 100 millions of mononuclear-enriched BMCs were infused into the hepatic artery using the routine technique for arterial chemoembolization for liver tumors. Patients were followed up for adverse events up to 4 mo. RESULTS: The median age of the patients was 52 years (range 24-70 years). All patients were discharged 48 h after BMC infusion. Two patients complained of mild pain at the bone marrow needle puncture site. No other complications or specific side effects related to the procedure were observed. Bilirubin levels were lower at 1 (2.19 +/- 0.9) and 4 mo (2.10 +/- 1.0) after cell transplantation that baseline levels (2.78 +/- 1.2). Albumin levels 4 mo after BMC infusion (3.73 +/- 0.5) were higher than baseline levels (3.47 +/- 0.5). International normalized ratio (INR) decreased from 1.48 (SD = 0.23) to 1.43 (SD = 0.23) one month after cell transplantation. CONCLUSION: BMC infusion into hepatic artery of patients with advanced chronic liver disease is safe and feasible. In addition, a decrease in mean serum bilirubin and INR levels and an increase in albumin levels are observed. Our data warrant further studies in order to evaluate the effect of BMC transplantation in patients with advanced chronic liver disease.