Pediatric septic thrombosis of intracranial venous sinuses: from diagnosis to discharge. Twenty years of experience. / Trombosis séptica pediátrica de senos venosos intracraneales: del diagnóstico al alta. Veinte años de experiencia.

INTRODUCTION: Septic thrombosis of intracranial venous sinuses (STSV) is a rare and severe complication of cranial infections. MATERIALS AND METHODS: The main objective of this paper is to describe the clinical data, diagnostic procedures, treatment and evolution of a series of cases of STSV. In addition, the current literature is reviewed. Observational retrospective study by review of medical histories (January 1995-December 2016). The data collected were: clinical, analytical, epidemiological, microbiological, radiological, management and follow-up. A descriptive and statistical analysis of the data was done. RESULTS: Twelve children were included (86,832 admissions studied). They have a median age of 4.5 years (range 1-13) with a median time of symptoms of 6 days (range 1-25). At admission, the clinical data were: fever (11/12), vomiting (9/12) and headache (8/12). They also showed bad general status 12/12, 7/12 acute otitis media and 5/12 VI cranial nerve paresis. The lumbar puncture was pathological in 4/12. The most frequently microorganism isolated was Streptococcus sp. Prothrombotic mutations were confirmed on 2/12. Cranial computed tomography allowed diagnosis in 9/12; the magnetic resonance imaging achieves that in 12/12. Previous neurological signs or time to diagnosis did not influence the appearance of other image complications. All received antibiotic treatment, heparin 10/12 and 11/12 surgery. There were no sequels. CONCLUSION: In our series otitis, headache, vomiting and fever were prevalent. Complementary tests allowed the suspect but the definitive diagnosis was obtained by neuroimaging. There were no sequels and the therapies were mainly wide broad-spectrum antibiotics, heparin, and surgical.

TITLE: Trombosis séptica pediátrica de senos venosos intracraneales: del diagnóstico al alta. Veinte años de experiencia.Introducción. La trombosis séptica de los senos venosos intracraneales (TSSV) es una complicación rara y grave de las infecciones craneales. Materiales y métodos. El objetivo principal de este trabajo es describir los datos clínicos, procedimientos diagnósticos, tratamiento y evolución de una serie de casos de TSSV. Además, se revisa la bibliografía actual. Es un estudio retrospectivo observacional mediante revisión de historias médicas (enero de 1995-diciembre de 2016). Los datos recogidos fueron: clínicos, analíticos, epidemiológicos, microbiológicos, radiológicos, de manejo y de seguimiento. Se realizó un análisis descriptivo y estadístico de los datos. Resultados. Se incluyó a 12 niños (86.832 ingresos estudiados). La mediana de edad fue de 4,5 años (rango: 1-13), con un tiempo medio de síntomas de 6 días (rango: 1-25). En el momento de la admisión, los datos clínicos fueron: fiebre (11/12), vómitos (9/12) y dolor de cabeza (8/12). También mostraron mal estado general, 12/12; otitis media aguda, 7/12; y paresia del VI par craneal, 5/12. La punción lumbar fue patológica en 4/12. El microorganismo más frecuentemente aislado fue Streptococcus spp. Se confirmaron mutaciones protrombóticas en 2/12. La tomografía computarizada craneal permitió el diagnóstico en 9/12; la resonancia magnética lo logró en 12/12. Los signos neurológicos anteriores o el tiempo de diagnóstico no influyeron en la aparición de otras complicaciones de la imagen. Recibieron tratamiento antibiótico 12/12; heparina, 10/12; y cirugía, 11/12. No hubo secuelas. Conclusión. En nuestra serie, la otitis, el dolor de cabeza, los vómitos y la fiebre fueron frecuentes. Las pruebas complementarias permitieron el diagnóstico de sospecha, pero el diagnóstico definitivo se obtuvo por neuroimagen. No hubo secuelas y las terapias fueron principalmente antibióticos de amplio espectro, heparina y cirugía.

Multi-center analysis of the effect of T-cell acute lymphoblastic leukemia subtype and minimal residual disease on allogeneic stem cell transplantation outcomes.

This study aims to provide a detailed analysis of allogeneic stem cell transplantation (allo-SCT) outcomes in a large T-cell acute lymphoblastic leukemia (T-ALL) cohort with a specific emphasis on the effects of pre-transplant minimal residual disease (MRD) and disease subtype, including the aggressive early-thymic precursor (ETP) subtype. Data from 102 allo-SCT patients with a diagnosis of T-ALL from three centers were retrospectively analyzed. Patients were grouped into four T-ALL subtypes: ETP, early, cortical and mature. At 3 years, overall survival (OS), PFS, non-relapse mortality and cumulative incidence (CI) progression were 35, 33, 11 and 55%, respectively. Patients transplanted in first complete remission (CR1) had a 3-year OS of 62% versus those transplanted in CR2 or greater (24%) (hazards ratio 1.6, P=0.2). Patients with MRD positivity at the time of transplant had significantly higher rates of progression compared with those with MRD negativity (76 vs 34%, hazards ratio 2.8, P=0.006). There was no difference in OS, PFS or cumulative incidence (CI) progression between disease subtypes, including ETP (n=16). ETP patients transplanted in CR1 (n=10) had OS of 47%, comparable to other disease subtypes, suggesting that allo-SCT can overcome the poor prognosis associated with ETP. MRD status at transplant was highly predictive of disease relapse, suggesting novel therapies are necessary to improve transplant outcomes.

Bendamustine added to allogeneic conditioning improves long-term outcomes in patients with CLL.

Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received bendamustine, fludarabine and rituximab (BFR) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR-treated patients vs only two (3%) FCR-treated patients did not experience severe neutropenia (P=<0.001). The 3-year overall survival estimates for the BFR and FCR groups were 82 and 51% (P=0.03), and the 3-year PFS estimates were 63% and 27% (P=0.001), respectively. The 2-year treatment-related mortality was 8 and 23% and the incidence of grade 3 or 4 GvHD was 4% and 10%, respectively. This study is the first to report that addition of bendamustine to alloSCT conditioning for CLL patients is associated with improved survival and lower mortality, myelosuppression, and GvHD.

Bevacizumab/high-dose chemotherapy with autologous stem-cell transplant for poor-risk relapsed or refractory germ-cell tumors.

BACKGROUND: High-dose chemotherapy (HDC) using sequential cycles of carboplatin/etoposide is curative for relapsed germ-cell tumors (GCT). However, outcomes of high-risk patients in advanced relapse remain poor. We previously developed a new HDC regimen combining infusional gemcitabine with docetaxel/melphalan/carboplatin (GemDMC), with preliminary high activity in refractory GCT. Given the high vascular endothelial growth factor expression in metastatic GCT and the synergy between bevacizumab and chemotherapy, we studied concurrent bevacizumab and sequential HDC using GemDMC and ifosfamide/carboplatin/etoposide (ICE) in patients with poor-risk relapsed or refractory disease. PATIENTS AND METHODS: Eligibility criteria included intermediate/high-risk relapse (Beyer Model), serum creatinine ≤ 1.8 mg/dl and adequate pulmonary/cardiac/hepatic function. Patients received sequential HDC cycles with bevacizumab preceding GemDMC (cycle 1) and ICE (cycle 2). The trial was powered to distinguish a target 50% 2-year relapse-free survival (RFS) from an expected 25% 2-year RFS in this population. RESULTS: We enrolled 43 male patients, median age 30 (20-49) years, with absolute refractory (N = 20), refractory (N = 17) or cisplatin-sensitive (N = 6) disease, after a median 3 (1-5) prior relapses. Disease status right before HDC was unresponsive (N = 24, progressive disease 22, stable disease 2), partial response with positive markers (PRm(+)) (N = 8), PRm(-) (N = 7) or complete response (N = 4). Main toxicities were mucositis and renal. Four patients (three with baseline marginal renal function) died from HDC-related complications. Tumor markers normalized in 85% patients. Resection of residual lesions (N = 13) showed necrosis (N = 4), mature teratoma (N = 2), necrosis/teratoma (N = 3) and viable tumor (N = 4). At median follow-up of 46 (9-84) months, the RFS and overall survival rates are 55.8% and 58.1%, respectively. CONCLUSIONS: Sequential bevacizumab/GemDMC-bevacizumab/ICE shows encouraging outcomes in heavily pretreated and refractory GCT, exceeding the results expected in this difficult to treat population. CLINICALTRIALSGOV: NCT00936936.

Informed consent in colonoscopy: A comparative analysis of 2 methods.

BACKGROUND: The manner in which informed consent is obtained varies. The aim of this study is to evaluate the level of knowledge about colonoscopy and comparing 2 methods of obtaining informed consent. MATERIALS AND METHODS: A comparative, cross-sectional, observational study was conducted on patients that underwent colonoscopy in a public hospital (Group A) and in a private hospital (Group B). Group A received information verbally from a physician, as well as in the form of printed material, and Group B only received printed material. A telephone survey was carried out one or 2 weeks later. RESULTS: The study included a total of 176 subjects (group A [n=55] and group B [n=121]). As regards education level, 69.88% (n=123) of the patients had completed university education, 23.29% (n= 41) secondary level, 5.68% (n=10) primary level, and the remaining subjects (n=2) had not completed any level of education. All (100%) of the subjects knew the characteristics of the procedure, and 99.43% were aware of its benefits. A total of 97.7% received information about complications, 93.7% named some of them, and 25% (n=44) remembered major complications. All the subjects received, read, and signed the informed consent statement before the study. There were no differences between the groups with respect to knowledge of the characteristics and benefits of the procedure, or the receipt and reading of the consent form. Group B responded better in relation to complications (P=.0027) and group A had a better recollection of the major complications (P<.0001). Group A had a higher number of affirmative answers (P<.0001). CONCLUSIONS: The combination of verbal and written information provides the patient with a more comprehensive level of knowledge about the procedure.

Comparison of outcomes at two institutions of patients with ALL receiving ex vivo T-cell-depleted or unmodified allografts.

We compared outcomes of adult patients receiving T-cell-depleted (TCD) hematopoietic SCT (HCT) without additional GVHD prophylaxis at Memorial Sloan Kettering Cancer Center (MSKCC, N=52), with those of patients receiving conventional grafts at MD Anderson Cancer Center (MDACC, N=115) for ALL in CR1 or CR2. Patients received myeloablative conditioning. Thirty-nine patients received anti-thymocyte globulin at MSKCC and 29 at MDACC. Cumulative incidence of grades 2-4 acute (P=0.001, 17.3% vs 42.6% at 100 days) and chronic GVHD (P=0.006, 13.5% vs 33.4% at 3 years) were significantly lower in the TCD group. The non-relapse mortality at day 100, 1 and 3 years was 15.4, 25.0 and 35.9% in the TCD group and 9.6, 23.6 and 28.6% in the unmodified group (P=0.368). There was no difference in relapse (P=0.107, 21.3% vs 35.5% at 3 years), OS (P=0.854, 42.6% vs 43.0% at 3 years) or RFS (P=0.653, 42.8% vs 35.9% at 3 years). In an adjusted model, age >50, cytogenetics and CR status were associated with inferior RFS (hazard ratio (HR)=2.16, P=0.003, HR=1.77, P=0.022, HR=2.47, P<0.001), whereas graft type was NS (HR=0.90, P=0.635). OS and RFS rates are similar in patients undergoing TCD or conventional HCT, but TCD effectively reduces the rate of GVHD.

Intravenous BU plus Mel: an effective, chemotherapy-only transplant conditioning regimen in patients with ALL.

We investigated the administration of i.v. BU combined with melphalan (Mel) in patients with ALL undergoing allogeneic hematopoietic SCT. Forty-seven patients with a median age of 33 years (range 20-61) received a matched sibling (n=27) or matched unrelated donor transplant (n=20) for ALL in first CR (n=26), second CR (n=13), or with more advanced disease (n=8). BU was infused daily for 4 days, either at a fixed dose of 130 mg/m² (5 patients) or using pharmacokinetic (PK) dose adjustment (42 patients), to target an average daily area-under-the-curve (AUC) of 5000 µmol/min, determined by a test dose of i.v. BU at 32 mg/m². This was followed by a rest day, then two daily doses of Mel at 70 mg/m². Stem cells were infused on the following day. The 2-year OS, PFS and non-relapse mortality (NRM) rates were 35% (95% confidence interval (CI), 23-51%), 31% (95% CI, 21-48%) and 37% (95% CI, 23-50%), respectively. Acute NRM at 100 days was favorable at 12% (95% CI, 5-24%); however, the 2-year NRM was significantly higher for patients older than 40 years, 58% vs 20%, mainly due to GVHD.

Clofarabine combined with busulfan provides excellent disease control in adult patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation.

We investigated the safety and early disease control data for i.v. busulfan (Bu) in combination with clofarabine (Clo) in patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation (SCT). Fifty-one patients (median age, 36 years; range, 20-64 years) received a matched sibling (n = 24), syngeneic (n = 2), or matched unrelated donor transplant (n = 25) for acute lymphoblastic leukemia in first complete remission (n = 30), second complete remission (n = 13), or active disease (n = 8). More than one-half of the patients had a high-risk cytogenetic profile, as defined by the presence of t(9;22) (n = 17), t(4;11) (n = 3), or complex cytogenetics (n = 7). Clo 40 mg/m(2) was given once daily, with each dose followed by pharmacokinetically dosed Bu infused over 3 hours daily for 4 days, followed by hematopoietic SCT 2 days later. The Bu dose was based on drug clearance, as determined by the patient's response to a 32-mg/m(2) Bu test dose given 48 hours before the high-dose regimen. The target daily area under the receiver-operating characteristic curve was 5500 µM/min for patients age <60 years and 4000 µM/min for those age ≥60 years. The regimen was well tolerated, with a 100-day nonrelapse mortality rate of 6%. With a median follow-up of 14 months among surviving patients (range, 6-28 months), the 1-year overall survival, disease-free survival, and nonrelapse mortality rates were 67% (95% confidence interval [CI], 55%-83%), 54% (95% CI, 41%-71%), and 32% (95% CI, 16%-45%), respectively. For patients undergoing SCT in first remission, these respective rates were 74%, 64%, and 25%. Our data indicate that the combination of Clo and Bu provides effective disease control while maintaining a favorable safety profile.

Evaluación de los acidos grasos n-3 de 18 especies de pescados marinos mexicanos como alimentos funcionales / n-3 fatty acid evaluation in eighteen Mexican marine fishes as functional food

The objective of the present work was to characterize the n-3 fatty acid composition of eighteen species of Mexican marine fishes and to evaluate their potential as functional food. Total lipids and fatty acid (FA) compositions were obtained of the edible portion of the fish, by solvent extraction and gas chromatography. Fifty percent of the studied species proceeded of the Mexican Pacific and the remainder from the Gulf of Mexico. The total lipid content varied from 0.76 to 7.13 g/100g. Averages of 58.51, 58.74 and 132.85 mg/100g of flesh were obtained for saturated, monounsaturated and polyunsaturated FA, respectively. In all the samples the n-3 fatty acids identified in order of abundance were (mg/100g), C22:6n-3 (DHA) (85.02), C20:5 n-3 (EPA)(16.22), C18:3 n-3 (ALA)(1.95) and the C20:3 n-3 was found only in four species (range from 0.08 to 12.99 mg/100g). Twenty-seven percent of the fishes exhibited low (4 to 40), 66% intermediate (70 to 170) and 7% high values (200 to 300 mg/100g) of n-3 FA. The latter species were identified as picuda (Sphyraena agentea) and sargo (Lagodon rhomboides). Since international standards recommend a daily regular consumption form 200 to 650 mg of EPA + DHA/day as beneficial for good health, it is therefore suggested as functional food.

Monosomy 16 as the sole abnormality in myeloid malignancies.

The majority of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients reported with chromosome 16 abnormalities had the inv(16)(p13q22) or t(16;16)(p13;q22) rearrangements, which were associated with a favorable prognosis. In contrast, del(16)(q22) was reported less commonly but was associated with a less favorable prognosis. We describe an 80-year-old woman who presented with MDS (refractory anemia). Chromosome analysis from bone marrow aspirate cultures showed monosomy 16 as the sole cytogenetic abnormality. Comparison of this patient with previously reported cases of monosomy 16 showed that this uncommon abnormality was associated with myeloid disorders. Monosomy 16 patients, similar to del(16)(q22) patients, tended to be elderly, presented with MDS or AML, and had a poor prognosis. The similarity in clinical course for del(16)(q22) and monosomy 16 patients suggests that the phenotype in both groups resulted from loss of important gene(s) on 16q, as distinct from the fusion gene product identified in the inv(16) and t(16;16) rearrangements.

Adenomatoid odontogenic tumour with features of calcifying epithelial odontogenic tumour. (The so-called combined epithelial odontogenic tumour.) Clinico-pathological report of 12 cases.

The combination of two odontogenic tumours is a rarely reported finding. To date only 10 cases of adenomatoid odontogenic tumour (AOT) combined with areas of calcifying epithelial odontogenic tumour (CEOT) have been published. This article describes the clinical, radiographical and microscopic findings of 12 cases of AOT, in which CEOT-like areas of variable sizes were found. These results suggest that such areas may be considered as a normal feature within the histomorphological spectrum of AOT.

Especificidad de la ecografía en el diagnóstico precoz de la hidatidosis humana / Echographic specificity in the early diagnosis of human hydatidosis

Se efectuaron catastros ecográficos en 132 pobladores asintomáticos de la Provincia de Rio Negro, Argentina. Un total de 76 casos fueron clasificados como probales hidatidosis. Se sometió a cirugía a 30 pacientes, confirmándose el diagnóstico en 28 casos (93.34% especificidad)

[Echographic specificity in the early diagnosis of human hydatidosis]. / Especificidad de la ecografía en el diagnóstico precoz de la hidatidosis humana.

Ultrasonography (US) were used for screening of hydatid disease in 1321 asymptomatic individuals fron Río Negro Province, Argentina. A total of 76 positive subjects were identified with possible hydatid disease. Surgery was performed in 30 patients, conforming in 28 of them sonographic diagnosis (93.34%).