Agreements and uncertainties in autologous haematopoietic stem cell mobilization and collection. A Spanish consensus document.

Although many experts position statements on autologous stem cell mobilization have been published, there are some aspects that are still under discussion. A Spanish Hematologist expert group was summoned to settle on agreements and uncertainties on PBSCs mobilization, including factors not always considered; as apheresis and cytometry key factors that determine a successful PBSC collection. This document reviews critical factors that define poor mobilizer patients and the tools to better collect the desired stem cells for a successful autologous haematopoietic stem cell transplant.

Peritumoral adipose tissue as a source of inflammatory and angiogenic factors in colorectal cancer.

PURPOSE: Obesity is a risk factor for the development of human colorectal cancer (CC). The aim of this work is to report the inflammatory and angiogenic scenario in lean (BMI < 25 kg/m2) and obese (BMI > 30 kg/m2) patients with and without CC and to assess the role of peritumoral adipose tissue in CC-induced inflammation. MATERIAL AND METHODS: Patients were divided in four experimental groups: obese patients with CC (OB-CC), lean patients with CC (LEAN-CC), obese patients without CC (OB), and lean patients without CC (LEAN). RESULTS: Plasma levels of pro-inflammatory cytokines (interleukin (IL)-6, IL-4, IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were increased in OB-CC patients. Peritumoral adipose tissue (TF) explants and cultured mature adipocytes secreted higher amounts of nitrites and nitrates than did control and non-tumoral (NTF) adipose tissue both alone and in response to lipopolysaccharide (LPS). Nitrite and nitrate secretion was also increased in TF explants from OB-CC patients compared with that from LEAN-CC patients. Gene expression of adiponectin, tumor necrosis factor alpha (TNF-α), insulin-like growth factor type I (IGF-I), cyclooxygenase-2 (COX-2), and peroxisome proliferator-activated receptor γ (PPAR-γ) was increased in TF explants from CC patients. LPS increased the gene expression of IL-6, IL-10, TNF-α, vascular endothelial growth factor (VEGF), and COX-2 in OB and in TF explants from OB-CC patients. COX-2 and PPAR-γ inhibition further increased LPS-induced release of nitrites and nitrates in TF explants and adipocytes from OB-CC patients. CONCLUSIONS: In conclusion, OB-CC patients have increased plasma levels of pro-inflammatory and angiogenic factors. TF from OB-CC patients shows an increased secretion of inflammatory markers compared with both TF from LEAN-CC and non-tumoral adipose tissue (AT) through a COX-2- and PPAR-γ-independent mechanism.

Results of allogeneic stem cell transplantation in the Spanish MDS registry: prognostic factors for low risk patients.

Although new agents have been approved for the treatment of MDS, the only curative approach is allogeneic hematopoietic stem cell transplantation (HSCT) and thus, in particular circumstances this procedure has been proposed as a treatment option for low risk patients. We have retrospectively analyzed the results of HSCT in 291 patients from the Spanish MDS registry with special attention to low risk MDS (LR-MDS) in order to define the variables that could impact their clinical evolution after transplantation. At 2 years OS was 51% and EFS was 50% (95% CI 0.7-4.5 years for OS and 95% CI 0.1-3.9 years for EFS). Among 43 LR-MDS, transplant-related mortality was 28%. At 3 years, OS was 67% (95% CI 264.7-8927.2 days for OS) and EFS was 64% (95% CI 0-9697.2 days for EFS). In the multivariate analysis only cytogenetics retained statistical significant effect on both OS (p=.047) and EFS (p=.046). Conditioning regimen could improve outcome among this subset of patients (OS 86% and RFS 100% for patients receiving RIC regimen). The present study confirms that specific disease characteristic as well as transplant characteristics have a significant impact on transplant outcome. Regarding low risk patients a non-myeloablative conditioning would be preferable especially in cases without high-risk cytogenetics.

Listeriosis durante el embarazo: importancia del tratamiento precoz / Listeriosis during pregnancy: Importance of early treatment

La infección por listeria monocytogenes durante la gestación tiene una repercusión grave en la evolución del embarazo.Ante una sospecha clínica, resulta indispensable iniciar un tratamiento precoz con ampicilina y gentamicina para evitar la infección neonatal secundaria a la bacteriemia materna.Describimos tres casos clínicos de listeriosis durante la gestación con distintos desenlaces en función de la precocidad del tratamiento (AU)

Listeria monocytogenes infection in pregnant women may have severe consequences for pregnancy outcome. Early antenatal treatment with ampicillin and gentamicin when there is clinical suspicion is highly recommended to avoid neonatal infection caused by maternal bacteremia. We describe three cases with distinct outcomes due to the different timing of treatment (AU)

Role of uterine artery Doppler in interpreting low PAPP-A values in first-trimester screening for Down syndrome in pregnancies at high risk of impaired placentation.

OBJECTIVES: Low maternal serum levels of pregnancy-associated plasma protein-A (PAPP-A) are associated with both increased risk of aneuploidies and impaired trophoblastic invasion, while high uterine artery (UtA) resistance is associated with impaired trophoblastic invasion but not with an increased risk of aneuploidies. The aim of this study was to determine whether high UtA resistance plays a role in explaining low PAPP-A levels in the absence of aneuploidies. METHODS: This was a prospective study of 116 singleton pregnancies at high risk for impaired placentation (having at least one major risk factor: prior history of pre-eclampsia, pregestational diabetes mellitus, chronic hypertension, chronic kidney disease, body mass index >30, autoimmune disorder, thrombophilia or recurrent pregnancy loss), booked for routine assessment of risk for aneuploidies by means of the first-trimester combined screening test (nuchal translucency thickness (NT) + PAPP-A + beta-human chorionic gonadotropin (beta-hCG)). Measurement of NT and the mean UtA pulsatility index (PI) were carried out at the 11 to 13 + 6-week scan. All values were calculated in multiples of the median (MoM) adjusted for gestational age. A cut-off risk of 1/270 at time of sampling was adopted to differentiate high- from low-risk groups for trisomy 21. RESULTS: There were 108 patients deemed to be at low risk for trisomy 21 and eight at high risk. None had chromosomal defects, giving a false-positive rate for trisomy 21 of 6.9%. The greatest differences between patients at low risk and those at high risk for trisomy 21 were found in their PAPP-A (0.98 vs. 0.38 MoM, P < 0.01) and beta-hCG (1.09 vs. 1.77 MoM, P = 0.04) values. Greater NT thickness (1.02 vs. 0.90 MoM) and higher mean UtA-PI (1.05 vs. 0.96 MoM) were recorded in the high-risk group, although the differences did not reach statistical significance (P = 0.19 and 0.40, respectively). After log-transformation there were no significant correlations between mean UtA-PI and NT and between mean UtA-PI and beta-hCG. There was a significant negative linear correlation between mean UtA-PI and PAPP-A (r = -0.331; P < 0.01). After adjusting the PAPP-A values by UtA-PI, the false-positive rate for trisomy 21 decreased to 2.6%. CONCLUSION: Mean UtA-PI at the 11 to 13 + 6-week scan may be an effect-modifier variable for PAPP-A that should be taken into account in the first-trimester combined screening for aneuploidies, at least in pregnancies at high risk for impaired placentation.

Both expanded and uncultured mesenchymal stem cells from MDS patients are genomically abnormal, showing a specific genetic profile for the 5q- syndrome.

The presence of cytogenetic aberrations on mesenchymal stem cells (MSC) from myelodysplastic syndrome (MDS) patients is controversial. The aim of the study is to characterize bone marrow (BM) derived MSC from patients with MDS using: kinetic studies, immunophenotyping, fluorescent in situ hybridization (FISH) and genetic changes by array-based comparative genomic hybridization (array-CGH). In all 36 cases of untreated MDS were studied. MDS-MSC achieved confluence at a significantly slower rate than donor-MSC, and the antigenic expression of CD105 and CD104 was lower. Array-CGH studies showed DNA genomic changes that were proved not to be somatic. These results were confirmed by FISH. To confirm that genomic changes were also present in freshly obtained MSCs they were enriched by sorting BM cells with the following phenotype: CD45(-)/CD73(++)/CD34(-)/CD271(++). They also showed genomic changes that were confirmed by FISH. To analyze the relationship of these aberrations with clinical-biological data an unsupervised hierarchical cluster analysis was performed, two clusters were identified: the first one included the 5q- syndrome patients, whereas the other incorporated other MDS. Our results show, for the first time that MSC from MDS display genomic aberrations, assessed by array-CGH and FISH, some of them specially linked to a particular MDS subtype, the 5q- syndrome.

Acceptability and use of sexual barrier products and lubricants among HIV-seropositive Zambian men.

This study assessed the acceptability and preference for sexual barrier and lubricant products among men in Zambia following trial and long-term use. It also examined the role of men's preferences as facilitators or impediments to product use for HIV transmission reduction within the Zambian context. HIV-seropositive and -serodiscordant couples were recruited from HIV voluntary counseling and testing centers in Lusaka between 2003 and 2006; 66% of those approached agreed to participate. HIV seropositive male participants participated in a product exposure group intervention (n = 155). Participants were provided with male and female condoms and vaginal lubricants (Astroglide [BioFilm, Inc., Vista, CA] & KY gels [Johnson & Johnson, Langhorne, PA], Lubrin suppositories [Kendwood Therapuetics, Fairfield, NJ]) over three sessions; assessments were conducted at baseline, monthly over 6 months and at 12 months. At baseline, the majority of men reported no previous exposure to lubricant products or female condoms and high (79%) levels of consistent male condom use in the last 7 days. Female condom use increased during the intervention, and male condom use increased at 6 months and was maintained over 12 months. The basis for decisions regarding lubricant use following product exposure was most influenced by a preference for communicating with partners; participant preference for lubricant products was distributed between all three products. Results illustrate the importance of development of a variety of products for prevention of HIV transmission and of inclusion of male partners in interventions to increase sexual barrier product use to facilitate barrier acceptability and use in Zambia.

Oral beclomethasone dipropionate for the treatment of gastrointestinal acute graft-versus-host disease (GVHD).

Acute graft-versus-host disease (aGVHD) remains one of the most severe complications after allogeneic transplantation; in particular, the presence of gut involvement has been related to increased mortality and poorer response. The use of systemic steroids remains the standard for first-line treatment despite its severe secondary effects. Beclomethasone dipropionate (BDP) is a topically active corticosteroid with low absorption, thereby avoiding many of the deleterious side effects associated with systemic steroids. In the present study we analyzed the efficacy of BDP in a series of 26 patients who were diagnosed with grade 1 and 2 gastrointestinal aGVHD. Twenty patients (77%) responded to BDP treatment, 17 (65.5%) reached complete remission (CR), and 3 (11.5%) showed partial response. Among those patients who reached CR, 5 relapsed, although 1 of them reached second CR after a second course of BDP; therefore, 13 (50%) of the 26 patients did not require systemic steroids to treat gastrointestinal aGVHD. CR rates in those showing gastrointestinal symptoms were 68% for patients with persistent nausea, 50% for those with vomiting, and 54% for those with diarrhea (P=.2). No patient included in the study developed any symptom related to adrenal axis suppression. Thirteen patients (50%) developed >or=1 infectious episode during the first 100 days after transplantation. Transplant-related mortality was 0% at 100 days, and overall transplant-related mortality was 30%, with only 2 patients dying due to infectious complications. Therefore, our study shows that monotherapy with oral BDP is an effective initial therapeutic approach for mild to moderate intestinal GVHD, which avoids complications related to systemic steroids.

Angiosarcoma in the small intestine. Apropos of a particular case.

Presentation of a case of small intestine primary angiosarcoma in a 70-year-old male. There is question of an extremely rare tumor in the gastrointestinal tract. Its symptomatology is similar to that of other tumors in the small intestine. An immunohistochemical study is usually essential for its anatomopathological diagnosis. The diagnosis is generally arrived at in its advanced stages, and that makes for a bad prognosis. The bibliography has been revised from this case on.

Sepsis: estudio comparativo en el tratamiento de las alteraciones de coagulación con concentrados de Antitrombina III o Heparina / Sepsis: Antitrombin III or Heparine therapy in disseminated intravascular coagulation, comparative study

Se efectuó el estudio en 48 pacientes con diagnóstico de sepsis, el mismo se hizo en todos los casos por el cuadro clínico y la confirmación bacteriológica, con aislamiento del germen por hemocultivo o cultivo de otras localizaciones. Se dividieron los pacientes en dos grupos distribuidos al azar, 24 pacientes fueron tratados con concentrados de AT III a las dosis de 1000 unidades cada 12 hs en infusión endovenosa durante 30 minutos, durante las primeras 48 hs. 24 recibieron heparina, 150 unidades por Kg por día en perfusión contínua durante 2 días, en el grupo con heparina si el paciente no mejoraba se mantenía la terapéutica más tiempo y si aparecían manifestaciones trombóticas (trombosis venosa profunda o tromboembolismo de pulmón) se aumentó la dosis a 500 unidades por Kg por día. A los pacientes se les efectuaron los siguientes controles de coagulación a las 0, 12, 24 y 48 hs: Tiempo de Quick, KPTT, Tiempo de Trombina, prueba de sulfato de protamina, recuento de plaquetas, determinación del factor II, V, VII-X y VIII, Pdf, D-Dimero, fibrógeno y AT III. Durante 7 días se siguió la evolución de los pacientes observando las complicaciones trombóticas, hemorrágicas y la mortalidad. En los resultados se pudo observar una mejoría en el grupo tratado con AT III en todos los parámetros de coagulación estudiados (P < 0,01), reducción de las hemorragias, trombosis y mortalidad, en este último caso cabe destacar que en el grupo tratado con AT III hubo 3 muertos contra 6 del grupo tratado con heparina, a pesar de ser el doble no es estadísticamente significativo, pero de aumentar el número de casos y mantenerse igual la proporción si llegaría a serlo (AU)

Sepsis: estudio comparativo en el tratamiento de las alteraciones de coagulación con concentrados de Antitrombina III o Heparina / Sepsis: Antitrombin III or Heparine therapy in disseminated intravascular coagulation, comparative study

Se efectuó el estudio en 48 pacientes con diagnóstico de sepsis, el mismo se hizo en todos los casos por el cuadro clínico y la confirmación bacteriológica, con aislamiento del germen por hemocultivo o cultivo de otras localizaciones. Se dividieron los pacientes en dos grupos distribuidos al azar, 24 pacientes fueron tratados con concentrados de AT III a las dosis de 1000 unidades cada 12 hs en infusión endovenosa durante 30 minutos, durante las primeras 48 hs. 24 recibieron heparina, 150 unidades por Kg por día en perfusión contínua durante 2 días, en el grupo con heparina si el paciente no mejoraba se mantenía la terapéutica más tiempo y si aparecían manifestaciones trombóticas (trombosis venosa profunda o tromboembolismo de pulmón) se aumentó la dosis a 500 unidades por Kg por día. A los pacientes se les efectuaron los siguientes controles de coagulación a las 0, 12, 24 y 48 hs: Tiempo de Quick, KPTT, Tiempo de Trombina, prueba de sulfato de protamina, recuento de plaquetas, determinación del factor II, V, VII-X y VIII, Pdf, D-Dimero, fibrógeno y AT III. Durante 7 días se siguió la evolución de los pacientes observando las complicaciones trombóticas, hemorrágicas y la mortalidad. En los resultados se pudo observar una mejoría en el grupo tratado con AT III en todos los parámetros de coagulación estudiados (P < 0,01), reducción de las hemorragias, trombosis y mortalidad, en este último caso cabe destacar que en el grupo tratado con AT III hubo 3 muertos contra 6 del grupo tratado con heparina, a pesar de ser el doble no es estadísticamente significativo, pero de aumentar el número de casos y mantenerse igual la proporción si llegaría a serlo

Cerebellar infarction from fibromuscular dysplasia and dissecting aneurysm of the vertebral artery. Report of a child.

Infarction in the vertebrobasilar system presenting as a posterior fossa mass lesion is extremely rare in children. We recently studied and treated a 9-year-old boy with cerebellar infarct produced by angiographically confirmed Type I fibromuscular dysplasia of the vertebral artery, complicated by a dissecting aneurysm. This case appears to be the first reported in the literature.

Comparative clinical evaluation of imipenem/cilastatin vs. cefotaxime in treatment of severe bacterial infections.

Adult patients with severe bacterial infections caused by organisms susceptible to imipenem and cefotaxime were given either imipenem/cilastatin sodium (MK0787/MK0791) or cefotaxime as a part of a multiclinic randomized study to evaluate the effectiveness, safety, and tolerability of imipenem/cilastatin. Clinical diagnoses included bacteremia, urinary tract infection, osteomyelitis, mediastinitis, lower respiratory tract infection, and soft tissue infection. Efficacy was evaluated for 10 patients given imipenem/cilastatin and for 10 patients given cefotaxime. Major pathogens isolated included Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella species, Streptococcus pneumoniae, Bacteroides fragilis, and Peptostreptococcus species. Satisfactory clinical responses were noted in 90% of the patients in both treatment groups. Eradication of the pathogen was achieved in nine of 10 patients treated with imipenem/cilastatin and in 10 of 10 patients treated with cefotaxime. No major adverse effects were found in patients in each treatment group. The results of this study suggest that imipenem/cilastatin sodium is a relatively safe and effective antibiotic for the treatment of adult patients with severe infections caused by susceptible organisms.