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Introduction Healthcare personnel (HP) are frequently exposed to influenza and can be a source of transmission to patients and other workers, resulting in high-cost outbreaks for healthcare institutions. Objectives To analyse the presentation of HP with influenza-like illness (ILI) and the differences between individuals with influenza confirmed by polymerase chain reaction (PCR) and those with a negative test. The secondary objective was to evaluate the duration of symptomatology and work absenteeism as well as the vaccination rate of HP at a paediatric referral hospital. Methods A cross-sectional, descriptive study was conducted at a paediatric referral hospital. Clinical and epidemiological data on HP with ILI were collected between January and April 2016. Nasopharyngeal swab for influenza PCR was obtained from one in every three workers with ILI. Telephone follow-up was conducted to document duration of symptoms, complications and absenteeism. Results A total of 164 ILI episodes were evaluated in 162 HP. A swab was obtained in 59 cases, and influenza was detected in 30 cases. The clinical picture of HP with confirmed influenza was similar to that of HP with a negative PCR. Arthralgia was more common in those with influenza (90% vs. 58%), with a tendency towards statistical significance. No HP required hospitalization, and 78.5% were absent from work at least one day. Conclusions Influenza causes significant morbidity and absenteeism among HP. Influenza infection was confirmed in only half of HP with an ILI on whom a PCR was performed, suggesting that other respiratory viruses can cause a similar pattern. This article is protected by copyright. All rights reserved.

B-cell acute lymphoblastic leukemia (B-ALL) is a serious public health problem in the pediatric population worldwide, contributing to 85% of deaths from childhood cancers. Understanding the biology of the disease is crucial for its clinical management and the development of therapeutic strategies. In line with that observed in other malignancies, chronic inflammation may contribute to a tumor microenvironment resulting in the damage of normal processes, concomitant to development and maintenance of neoplastic cells. We report here that hematopoietic cells from bone marrow B-ALL have the ability to produce proinflammatory and growth factors, including TNFα, IL-1β, IL-12, and GM-CSF that stimulate proliferation and differentiation of normal stem and progenitor cells. Our findings suggest an apparently distinct CD13+CD33+population of leukemic cells contributing to a proinflammatory microenvironment that may be detrimental to long-term normal hematopoiesis within B-ALL bone marrow.

ResumenIntroducciónLa infección del tracto urinario en los niños es reconocida como una causa de morbilidad y de condiciones médicas crónicas, por lo que resulta indispensable conocer con claridad la patogénesis de esta enfermedad. Sin embargo, la resistencia creciente complica su tratamiento ya que aumenta la morbilidad, los costos, la estancia hospitalaria y el uso de fármacos de mayor espectro antimicrobiano. El propósito de este estudio fue determinar la susceptibilidad antimicrobiana de los uropatógenos aislados en niños.MétodosSe incluyeron en el estudio 457 niños que asistieron a la consulta externa y a urgencias del Hospital Infantil de México Federico Gómez, con síntomas de infección del tracto urinario baja no complicada. La orina fue tomada a la mitad del chorro o por cateterismo, y se realizó la identificación y la susceptibilidad antimicrobiana.ResultadosLos patógenos aislados con mayor frecuencia fueron: Escherichia coli (E. coli) (312, 68.3%), Enterococcus spp. (42, 11%), Klebsiella pneumoniae (K. pneumoniae) (40, 8.7%), Pseudomonas aeruginosa (P. aeruginosa) (34, 7.5%), Proteus mirabilis (P. mirabilis) (21, 4.5%), Enterobacter cloacae (8, 1.7%). La resistencia para trimetoprima/sulfametoxazol fue del 73.7, 62.2, 100, 52, 50%,respectivamente, para E. coli, K. pneumoniae, P. aeruginosa, P. mirabilis y Enterobacter spp., del 92.5% para Enterococcus faecalis (E. faecalis) y del 49.9% para Enterococcus faecium (E. faecium). Para ampicilina fue del 86.3, 45, 100, 47.9 y 66.6% para las mismas bacterias, respectivamente. Para ciprofloxacina del 33.8, 9, 18.8, 0 y 0%; para nitrofurantoína del 4.4, 13, 97.7, 70, 0% para enterobacterias, del 0% para E. faecalis y del 16.7% para E. faecium.ConclusionesLos antimicrobianos frecuentemente prescritos para el tratamiento empírico de la infección del tracto urinario no complicada demuestran resistencia importante o baja susceptibilidad cuando se les probó frente a las cepas aisladas.AbstractBackgroundUrinary tract infection in children is well recognized as a cause of acute morbidity and chronic medical conditions. As a result, appropriate use of antimicrobial agents, however, increases antibiotic resistance and complicates its treatment due to increased patient morbidity, costs, rates of hospitalization, and use of broader-spectrum antibiotics. The goal of this study was to determine antibiotic susceptibility to commonly used agents for urinary tract infection against recent urinary isolates.MethodsA total of 457 consecutive children attending the emergency room at the Hospital Infantil de México Federico Gómez with symptoms of uncomplicated lower urinary tract infection were eligible for inclusion. Patients who had had symptoms for≥7 days and those who had had previous episodes of urinary tract infection, received antibiotics or other complicated factors were excluded. Midstream and catheter urine specimens were collected. All isolates were identified and the in vitro activities of antimicrobials were determined.ResultsThe most frequently isolated urinary pathogens were as follows: Escherichia coli (E. coli) (312, 68.3%), Enterococcus spp. (42, 11%), Klebsiella pneumoniae (K. pneumoniae) (40, 8.7%), Pseudomonas aeruginosa (P. aeruginosa) (34, 7.5%), Proteus mirabilis (P. mirabilis) (21, 4.5%), Enterobacter cloacae (8, 1.7%). The resistance to trimetoprim/sulfametoxazol (%) was 73.7, 62.2, 100, 52, and 50, respectively, for E. coli, K. pneumoniae, P. aeruginosa, P. mirabilis and Enterobacter spp., 92.5 for Enterococcus faecalis (E. faecalis) and 49.9 for Enterococcus faecium (E. faecium). Ampicillin was 86.3, 45, 100, 47.9, and 66.6% for the same strains, ciprofloxacin 33.8, 9, 18.8, 0, 0%, nitrofurantoin 4.4, 13, 97.7, 70, 0%; to E. faecalis 0% and 16.7% to E. faecium.ConclusionsFrequently prescribed empirical agents for uncomplicated urinary tract infection demonstrate lowered in vitro susceptibilities when tested against recent clinical isolates.

In recent years, an increase of uropathogenic Escherichia coli (UPEC) strains with Multidrug-resistant (MDR) and Extensively Drug-resistant (XDR) profiles that complicate therapy for urinary tract infections (UTIs) has been observed and has directly impacted costs and extended hospital stays. The aims of this study were to determine MDR- and XDR-UPEC clinical strains, their virulence genes and their phylogenetic groups and to ascertain their relationship with integrons and genetic diversity. From a collection of 500 UPEC clinical strains, 103 were selected with MDR [79.61% (82/103)] and XDR [20.38% (21/103)] characteristics. MDR-UPEC clinical strains were mainly associated with phylogenetic groups D (54.87%) and B2 (39.02%) with a high percentage (≥70%) of several fimbrial genes (ecpA, fimH, csgA, and papGII), an iron uptake gene (chuA), and a toxin gene (hlyA). In addition, a moderate frequency (40-70%) of other genes (iutD, tosA, and bcsA) was observed. XDR-UPEC clinical strains were predominantly associated with phylogenetic groups B2 (47.61%) and D (42.85%), which grouped with ≥80 virulence genes, including ecpA, fimH, csgA, papGII, iutD, and chuA. A moderate frequency (40-70%) of the tosA and hlyA genes was observed. The class 1 and 2 integrons that were identified in the MDR- and XDR-UPEC strains were associated with phylogenetic groups D, B2 and A, while the XDR-UPEC strains that were associated with phylogenetic groups B2, D and A showed an extended-spectrum beta-lactamase (ESBL) phenotype. The modifying enzymes (aadA1, aadB, aacC, ant1, dfrA1, dfrA17 and aadA4) that were identified in the variable region of class 1 and 2 integrons from the MDR strains showed resistance to gentamycin (56.25% and 66.66%, respectively) and trimethoprim-sulfamethoxazole (84.61% and 66.66%, respectively). The MDR- and XDR-UPEC strains were distributed into seven clusters and were closely related to phylogenic groups B2 and D. The diversity analysis by PFGE showed 42.68% of clones of MDR-UPEC and no clonal association in the XDR-UPEC clinical strains. In conclusion, phylogenetic groups including virulence genes are widely associated with two integron classes (B2 and D) in MDR- and XDR-UPEC clinical strains.

Objective Introduction of pneumococcal conjugate vaccines (PCV) targeted against a limited number of serotypes substantially decreased invasive (IPD) and non-invasive pneumococcal diseases (NIPD) but it was accompanied by non-vaccine type replacement disease. After 9 years of introduction of PCV in Mexico, we analyze the evidence of the indirect effects on IPD and NIPD serotype distribution among groups not targeted to receive the vaccine. Methods From January 2000 to December 2014, pneumococcal strains isolated from IPD and NIPD cases from patients ≥5 years of age from participant hospitals of the SIREVA II (Sistema Regional de Vacunas) network were serotyped. A regression analysis was performed considering year and proportion of serotypes included in the different vaccine formulations (PCV7, PCV10 and PCV13). The slope was obtained for each regression line and their correspondent p-value. The proportion of each serotype in the pre-PCV7 and post-PCV7 periods was evaluated by χ2 test. Results From a total of 1147 pneumococcal strains recovered, 570 corresponded to the pre-PCV7 and 577 to the post-PCV7 periods. The proportion of vaccine serotypes included in the three PCV formulations decreased by 2.4, 2.6 and 1.3%, respectively per year during the study period. A significant increase of serotype 19A was observed in the post-vaccine period in all age groups. Conclusions A percentage of annual decline of serotypes causing IPD and NIPD included in PCV was detected among groups not targeted to receive the vaccine, probably due to herd effect. Considering pneumococcal serotype distribution is a dynamic process, we highlight the importance of surveillance programs.

Background and Aims Childhood acute leukemias (AL) are characterized by the excessive production of malignant precursor cells at the expense of effective blood cell development. The dominance of leukemic cells over normal progenitors may result in either direct suppression of functional hematopoiesis or remodeling of microenvironmental niches, contributing to BM failure and AL-associated mortality. We undertook this study to investigate the contents and functional activity of hematopoietic stem/progenitor cells (HSPC) and their relationship to immune cell production and risk status in AL pediatric patients. Methods Multiparametric flow cytometry of BM aspirates was performed to classify AL on the basis of lineage and differentiation stages and to analyze HSPC and immune cell frequencies. Controlled co-culture systems were conducted to evaluate functional lineage potentials of primitive cells. Statistical correlations and inter-group significant differences were established. Results Among 113 AL BM aspirates, 26.5% corresponded to ProB, 19.5% to PreB and 32% contain ProB and PreB differentiation stages, whereas nearly 9% of the cases were T- and 13% myeloid-lineage leukemias. We identified ProB-ALL as the subtype endowed with the highest relative contents of HSPC, whereas T-ALL and PreB-ALL showed a critically reduced size of both HSC and MLP compartments. Notably, lower cell frequencies of HSPC in ProB-ALL correlated to high-risk prognosis at disease debut. Conclusions HSPC abundance at initial diagnosis may aid to predict the clinical course of ALL and to identify high-risk patients. A clearer understanding of their population dynamics and functional properties in the leukemia setting will potentially pave the way for targeted therapies.

In recent years, an increase of uropathogenic Escherichia coli (UPEC) strains with Multidrug-resistant (MDR) and Extensively Drug-resistant (XDR) profiles that complicate therapy for urinary tract infections (UTIs) has been observed and has directly impacted costs and extended hospital stays. The aim of this study was to determine MDR- and XDR-UPEC clinical strains, their virulence genes, their phylogenetic groups and to ascertain their relationship with integrons and genetic diversity. From a collection of 500 UPEC strains, 103 were selected with MDR and XDR characteristics. MDR-UPEC strains were mainly associated with phylogenetic groups D (54.87%) and B2 (39.02%) with a high percentage (≥70%) of several fimbrial genes (ecpA, fimH, csgA, and papGII), an iron uptake gene (chuA), and a toxin gene (hlyA). In addition, a moderate frequency (40–70%) of other genes (iutD, tosA, and bcsA) was observed. XDR-UPEC strains were predominantly associated with phylogenetic groups B2 (47.61%) and D (42.85%), which grouped with ≥80 virulence genes, including ecpA, fimH, csgA, papGII, iutD, and chuA. A moderate frequency (40–70%) of the tosA and hlyA genes was observed. The class 1 and 2 integrons that were identified in the MDR- and XDR-UPEC strains were associated with phylogenetic groups D, B2, and A, while the XDR-UPEC strains that were associated with phylogenetic groups B2, D, and A showed an extended-spectrum beta-lactamase (ESBL) phenotype. The modifying enzymes (aadA1, aadB, aacC, ant1, dfrA1, dfrA17, and aadA4) that were identified in the variable region of class 1 and 2 integrons from the MDR strains showed resistance to gentamycin (56.25 and 66.66%, respectively) and trimethoprim-sulfamethoxazole (84.61 and 66.66%, respectively). The MDR- and XDR-UPEC strains were distributed into seven clusters and were closely related to phylogenic groups B2 and D. The diversity analysis by PFGE showed 42.68% of clones of MDR-UPEC and no clonal association in the XDR-UPEC strains. In conclusion, phylogenetic groups including virulence genes are widely associated with two integron classes (1 and 2) in MDR- and XDR-UPEC strains.

Indirect evidence of hemolysis has been described in patients with autoimmune thrombocytopenic purpura. In order to collect more data, another method to assess red blood cell destruction in these patients was employed: measurement of free haptoglobin levels. In 17 individuals with autoimmune thrombocytopenic purpura the levels of free haptoglobins were assessed after carefully ruling out microangiopathic hemolysis, systemic lupus erythematosus or overt Evans syndrome. Abnormally low levels of free haptoglobins were found in five individuals (29%) as indirect evidence of hemolysis. The long-term thrombocytopenia-free status was lower in patients with low haptoglobin levels than in those with normal levels (40 versus 58%). These data, added to previous evidence, support the observation of Evans made 50 years ago: "there is a spectrum-like relationship between primary thrombocytopenia and haemolytic anemia".". Accordingly, the concept of "attenuated" variants of the Evans syndrome could be entertained.

By virtue of their self-renewal and tightly regulated multi-lineage differentiation properties, hematopoietic stem cells (HSCs) generate the whole blood system throughout postnatal life. During malignant hematological disorders, including acute leukemias, a number of intrinsic and extrinsic cues influence the hematopoietic differentiation pathway and cooperate to make aberrant cell fate decisions concomitant with cell transformation. The cellular origin of these disorders is a fundamental matter in question. In keeping with the hierarchical model of tumor evolution, a conspicuous and unique leukemic stem cell (LSC) population is most likely the foundation of acute and chronic myeloid leukemias. In contrast, all B-cell differentiation stages in acute lymphoblastic leukemia (ALL) function as leukemia-initiating cells (LICs), are endowed with primitive stem cell properties and are apparently responsible for the long-term maintenance of tumor growth within the bone marrow (BM) and for relapse of the disease following remission. Furthermore, LICs reveal the ability to create irregular BM microenvironments that may result in proinflammatory scenarios with a permissive role by allowing leukemic cell development at the expense of normal hematopoiesis. This chapter outlines the recent findings contributing to the understanding of malignant hematopoiesis through the biology of early stem and progenitor cells in the context of abnormal microenvironments within leukemic BM. By unraveling the role of leukemic precursor cells in the initiation of local inflammatory processes leading to hematopoietic instability, we may learn about additional mechanisms co-participating in the etiology and maintenance of this pathological condition.

In recent years, the main reason for parasitological diagnosis was suspicion of a parasitic etiology. Currently, diagnosis and consultation are associated with co-morbidity with a hemato-oncological, autoimmune, immunodeficiency or post-transplant condition.Results collected from the Parasitology Laboratory of the Hospital Infantil de Mexico Federico Gómez from January 1990 to December 2010 were analyzed to determine the frequency and distribution of parasites and commensals per year and decade.There were 211,600 samples analyzed with a statistical media of 10,100 and a standard deviation of 3,500 samples. Percentage of observations for parasitic structures as well as commensals was 37.73% according to Pearson Chi square with a significant difference among percentages between decades (p0.0001).Behavioral tendency of intestinal parasitosis during the last two decades shows a change in frequency and genera from the agents that were reported at this pediatric health care level. The processing of epidemiologic information is important in order to determine the response of the parasitosis and its variations over time.

Acute leukemia (AL) is a heterogeneous group of diseases characterized by a disorganized clone proliferation of hematopoietic cells. Thymidine kinase (TK) is a cell enzyme involved in DNA synthesis and is considered a cellular proliferation marker in some solid tumors.A cross-sectional prospective and comparative study was performed in the Federico Gomez Children's Hospital in Mexico (HIMFG, in Spanish) in 125 samples of patients of the HIMFG with AL and 138 samples of children without leukemia. Serum TK levels were determined for both groups.Of the children with AL, 90 presented B-cell acute lymphoblastic leukemia (B-ALL); 13, T-cell acute lymphoblastic leukemia (T-ALL); and 22, acute myeloid leukemia (AML). A median (m) TK level of 23.7 IU (IQR 17-35.7) was observed in the group without AL and 91 IU (IQR 98-392) in the AL group. This difference was statistically significant (p0.0001). When analyzing TK levels according to the type of leukemia, the m was as follows: 68 IU (IQR 35-118) for B-ALL, 470 IU (IQR 88-750) for AML, and 1678 IU (IQR 288-2108) for T- ALL.TK is an enzyme showing heterogeneous levels in B-ALL although it is significantly increased in 90% of patients with T-ALL and AML.

Over a 36-month period, 46 consecutive Mexican mestizos with a clinical marker associated with a primary hypercoagulable state were prospectively assessed by searching for the sticky platelet syndrome (SPS), the activated protein C resistance (aPCR) phenotype, coagulation protein C activity and antigen, coagulation protein S, antithrombin III, plasminogen, tissue-type plasminogen activator activity, plasminogen activator inhibitor activity, plasminogen activator inhibitor type 1, IgG and IgM isotypes of antiphospholipid antibodies, homocysteine levels, the factor V gene Leiden, Cambridge, Hong Kong, and Liverpool mutations, the 677 C→T mutation in the 5,10-methylenetetrahydrofolatereductase (MTHFR), and the G20210A polymorphism in the 3′-untranslated region of the prothrombin gene. Of the 46 consecutive patients prospectively accrued in the study, only 12 (26%) were males, the median age being 38 years (range 10–63 years). In only four individuals (8%) could we not record any abnormality. In 5/42 patients with abnormal results (12%), a single abnormality was recorded, whereas in the remaining 37, two to five co-existing abnormalities were identified. We found 22 (48%) patients with the SPS, 11 (24%) with the aPCR phenotype, 5 (11%) with the factor V Leiden mutation, 7 (15%) with the prothrombin gene mutation, 29 (63%) with the MTHFR gene mutation, 11 (24%) with the factor V HR2 haplotype, 11 (24%) with antiphospholipid antibodies, 4 (9%) with PS deficiency, 6 (13%) with PC deficiency, one with the FV Hong Kong mutation, and one with AT-III deficiency. The results are consonant with the idea that most cases of thrombophilia in Mexico are multifactorial. Am. J. Hematol. 78:21–26, 2005. © 2004 Wiley-Liss, Inc.

We report our experience of allogeneic peripheral blood stem cell transplantation using non-myeloablative conditioning regimens delivered and supported on an outpatient basis. A group of 44 patients underwent 47 allograft procedures using peripheral blood stem cells. Approximately one third of the individuals did not require red blood cells transfusions: the median of transfused red blood cells units was 1 (range 0-10). In addition one out of three did not require platelet transfusions either, the median of platelet transfusions being 1 (range 0-6). In fourteen allografts (30%) neither red blood cells nor platelet transfusions were used. An inverse correlation was found between the number of CD34 cells infused and the PRBC and PLT transfusion requirements, those patients receiving high numbers of CD34 cells needing fewer transfusions of both PRBC and platelets. The possibility of conducting allografts without transfusion of blood products in some patients may result in a decrease in both cost and the risks stemming from exposure to human blood derivatives.

Use of myeloablative preparative therapy and allogeneic stem cell transplantation (alloSCT) as salvage therapy for adult patients with relapsed hematologic malignancies after autologous stem cell transplantation (autoSCT) is generally unsuccessful due to very high treatment-related mortality rates. We report here the outcome of HLA-matched related donor alloSCT following nonmyeloablative preparative therapy in two patients with Hodgkin's disease, relapsed after autologous stem cell graft. Times from autoSCT to alloSCT were 9 and 11 months, respectively. Preparative therapy consisted of the following: oral busulfan, 4 mg/kg on days -6 and -5; intravenous (i.v.) cyclophosphamide, 350 mg/m2 on days -4, -3 and, -2, and i.v. fludarabine, 30 mg/m2 on days -4, -3, and -2; oral cyclosporin A (CyA) 5 mg/kg was begun on day -1 and i.v. methotrexate 5 mg/m2 was delivered on days +1, +3, +5, and +11. Both patients achieved initial mixed chimerism as defined as > 1% donor peripheral white blood cells and did not receive prophylactic donor lymphocyte infusions; both showed conversion to final full-donor chimerism. Stage I acute graft-vs.-host disease occurred in one patient and both achieved sustained complete response. One patient died on day 233 as a consequence of drug-induced pulmonary toxicity, whereas the other patient remains in continued complete remission 513 days after allograft. This nonmyeloablative alloSCT strategy was well tolerated, was completed entirely on an out-patient basis, and can result in durable disease-free survival among patients with Hodgkin's disease after failed autoSCT. Further follow-up and evaluation of additional patients are required to conclusively establish the role of this strategy in treatment of hematologic malignancies after autologous transplantation.

During an 18-month period, 10 consecutive Mexican mestizos with a clinical marker associated with a primary hypercoagulable state were studied. The assessment of the sticky platelet syndrome (SPS) was done by the method described by Mammen. In addition, the activated protein C resistance phenotype, coagulation protein C activity and antigen, coagulation protein S, antithrombin III, plasminogen, tissue-type plasminogen activator activity, plasminogen activator inhibitor activity, plasminogen activator inhibitor type 1, IgG and IgM isotypes of anti-phospholipid antibodies, homocysteine levels, the factor V gene Leiden mutation, the 677 C->T mutation in the 5,10-methylen-tetrahydrofolate-reductase (MTHFR), and the G20210A polymorphism in the 3′-untranslated region of the prothrombin gene were studied. Six patients with the SPS were identified: only one displayed this as the single thrombophilic abnormality; in five others, additional thrombosis-prone conditions were found: heterozygosity for the MTHFR 677 gene mutation in five cases; and, in one case each, heterozygosity for the factor V Leiden mutation, heterozygosity for the factor II G20210A mutation, and antiphospholipid antibodies in another. Four of the six patients had a family history of thrombophilia. All patients were treated with aspirin and no new vasoocclusive episodes have been recorded. SPS in not an infrequent finding in Mexican mestizo thrombophilic patients and may contribute to thrombophilia.

Cytomegalovirus (CMV)-related deaths and data of clinically evident CMV disease were assessed in a group of 47 individuals given allogeneic non-myeloablative hematopoietic stem cell transplants (NST). IgG anti-CMV antibodies were found in 56% of the donors and 76% of the receptors. Prophylactic ganciclovir was given to only 12 of the recipients during 100 days after the graft. There were no CMV-related deaths and clinically overt CMV disease was not found in any individual. The follow up post-transplant period of the patients, ranges between 30 and 810 days (median 242 days), the actuarial median survival (SV) is above 810 days and has not been reached, whereas the 810-days SV is 60%. Eighteen patients (38%) died 30-480 days after the transplant; four failed to engraft and died because of progressive disease; three died as a consequence of graft versus host disease (GVHD), whereas eleven individuals had a relapse of the malignancy and died. It is possible that the reduced bone marrow damage during NST, the prompt recovery of both the hematopoiesis and immune function in this type of allografts and the use of peripheral blood hematopoietic stem cell (HSC) is responsible for the absence of CMV-related deaths and clinical disease despite a high prevalence of CMV infection in these individuals.

Several microorganisms produce nosocomial infections (NIs), among which Pseudomonas aeruginosa stands out as an opportunist pathogen with the capacity to develop multiresistance to first-choice antibiotics. From 2007 to 2013, forty-six NIs produced by P. aeruginosa were detected at a pediatric tertiary care hospital in Mexico with a significant mortality rate (17.39%). All isolates (n = 58/46 patients) were characterized by evaluating their response to several antibiotics as panresistant (PDR), extensively resistant (XDR), multiresistant (MDR) or sensitive (S). In addition, all isolates were typified through multilocus sequencing of seven genes: acsA, aroE, guaA, mutL, nuoD, ppsA and trpE. Furthermore, to establish the genetic relationships among these isolates, we carried out a phylogenetic inference analysis using maximum likelihood to construct a phylogenetic network. To assess evolutionary parameters, recombination was evaluated using the PHI test, and the ratio of nonsynonymous to synonymous substitutions was determined. Two of the strains were PDR (ST1725); 42 were XDR; four were MDR; and ten were S. Twenty-one new sequence types were detected. Thirty-three strains exhibited novel sequence type ST1725. The ratio of nonsynonym to synonym substitutions was 1:1 considering all genes. Phylogenetic analysis showed that the genetic relationship of the PDR, XDR and MDR strains was mainly clonal; however, the PHI test and the phylogenetic network suggest that recombination events occurred to produce a non-clonal population. This study aimed not only to determine the genetic diversity of clinical P. aeruginosa but also to provide a warning regarding the identification and spreading of clone ST1725, its ability to cause outbreaks with high mortality rates, and to remain in the hospital environment for over seven years. These characteristics highlight the need to identify clonal outbreaks, especially where high resistance to most antibiotics is observed, and control measures are needed. This study also represents the first report of the PDR ST1725.

Urinary tract infection in children is well recognized as a cause of acute morbidity and chronic medical conditions. As a result, appropriate use of antimicrobial agents, however, increases antibiotic resistance and complicates its treatment due to increased patient morbidity, costs, rates of hospitalization, and use of broader-spectrum antibiotics. The goal of this study was to determine antibiotic susceptibility to commonly used agents for urinary tract infection against recent urinary isolates.A total of 457 consecutive children attending the emergency room at the Hospital Infantil de México Federico Gómez with symptoms of uncomplicated lower urinary tract infection were eligible for inclusion. Patients who had had symptoms for≥7 days and those who had had previous episodes of urinary tract infection, received antibiotics or other complicated factors were excluded. Midstream and catheter urine specimens were collected. All isolates were identified and the in vitro activities of antimicrobials were determined.The most frequently isolated urinary pathogens were as follows: Escherichia coli (E. coli) (312, 68.3%), Enterococcus spp. (42, 11%), Klebsiella pneumoniae (K. pneumoniae) (40, 8.7%), Pseudomonas aeruginosa (P. aeruginosa) (34, 7.5%), Proteus mirabilis (P. mirabilis) (21, 4.5%), Enterobacter cloacae (8, 1.7%). The resistance to trimetoprim/sulfametoxazol (%) was 73.7, 62.2, 100, 52, and 50, respectively, for E. coli, K. pneumoniae, P. aeruginosa, P. mirabilis and Enterobacter spp., 92.5 for Enterococcus faecalis (E. faecalis) and 49.9 for Enterococcus faecium (E. faecium). Ampicillin was 86.3, 45, 100, 47.9, and 66.6% for the same strains, ciprofloxacin 33.8, 9, 18.8, 0, 0%, nitrofurantoin 4.4, 13, 97.7, 70, 0%; to E. faecalis 0% and 16.7% to E. faecium.Frequently prescribed empirical agents for uncomplicated urinary tract infection demonstrate lowered in vitro susceptibilities when tested against recent clinical isolates.

The features of the engraftment in 26 patients allografted using reduced-intensity conditioning regimen (8 with chronic myelogenous leukemia, 6 with acute myelogenous leukemia, 9 with acute lymphoblastic leukemia, 1 with hybrid acute leukemia, 1 with myelodysplasia and 1 with thalassemia major) were analyzed. Patients received a median of 10 x 10(8)/Kg mononuclear cells (range 1.6 to 22.9), and a median of 4.2 x 10(6)/Kg CD34 cells (range 0.3 to 14). There was a linear correlation between the number of infused mononuclear cells (MNC) and that of CD34 cells (r = 0.78, p = 0.002). Three patients (11%) failed to engraft; in those who engrafted, the median time to achieve > 500 granulocytes was 11 days (range 10 to 22), and the median time to achieve > 10,000 platelets was 12 days (range 10 to 41). The three patients who failed to engraft received less than 5 x 10(8)/Kg MNC (1.6, 4.6 and 4.9) and less than 0.5 x 10(6)/Kg CD34; however, five of eight patients who received less than 5 x 10(8)/Kg MNC still engrafted successfully. On the other hand, all the patients who received less than 0.5 x 10(6)/Kg CD34 cells failed to engraft. Within the group of patients who engrafted, it was found that those who received more than 7 x 10(6)/Kg CD34+ cells tended to earlier recover > 20 x 10(9)/L platelets (p = 0.02), and > 0.5 x 10(9)/L neutrophils (p = 0.06) before day 15, than those who received less than 7 x 10(6)/Kg CD34+ cells. No such association could be established between the number of MNC and the time for recovery. In these patients allografted using reduced-intensity conditioning regimens, the target doses of hematopoietic cell used were similar to those described for conventional allografts: The number of CD34 infused cells was significantly related to the possibility of failure to engraft and to the recovery rate of the hemopoiesis.

Background In some Caucasian populations it has been found that the C282Y hemochromatosis (HFE) gene mutation is a risk factor for the development of leukemia and other malignancies. Methods In a group of 50 Mexican mestizo patients and 153 normal controls, the HFE gene mutations H63D and C282Y were studied by means of ARMS-PCR. Results In the group of patients with leukemia we found a heterozygote for the C282Y mutation, seven heterozygotes for the H63D mutation, a double heterozygote for the H63D / C282Y mutation and 41 normal homozygotes. These data are not different from those observed in normal controls, where the allele frequencies were 0.062 and 0.013 for the H63D and C282Y HFE gene mutations, respectively. Conclusions These HFE gene mutations are not risk factors for the development of leukemia in Mexican mestizos.

Background Enterococcus faecium has recently emerged as a multidrug-resistant nosocomial pathogen involved in outbreaks worldwide. A high rate of resistance to different antibiotics has been associated with virulent clonal complex 17 isolates carrying the esp and hyl genes and the purK1 allele. Results Twelve clinical vancomycin-resistant Enterococcus faecium (VREF) isolates were obtained from pediatric patients at the Hospital Infantil de México Federico Gómez (HIMFG). Among these VREF isolates, 58.3% (7/12) were recovered from urine, while 41.7% (5/12) were recovered from the bloodstream. The VREF isolates showed a 100% rate of resistance to ampicillin, amoxicillin-clavulanate, ciprofloxacin, clindamycin, chloramphenicol, streptomycin, gentamicin, rifampicin, erythromycin and teicoplanin. In addition, 16.7% (2/12) of the isolates were resistant to linezolid, and 66.7% (8/12) were resistant to tetracycline and doxycycline. PCR analysis revealed the presence of the vanA gene in all 12 VREF isolates, esp in 83.3% (10/12) of the isolates and hyl in 50% (6/12) of the isolates. Phylogenetic analysis via molecular typing was performed using pulsed-field gel electrophoresis (PFGE) and demonstrated 44% similarity among the VREF isolates. MLST analysis identified four different sequence types (ST412, ST757, ST203 and ST612). Conclusion This study provides the first report of multidrug-resistant VREF isolates belonging to clonal complex 17 from a tertiary care center in Mexico City. Multidrug resistance and genetic determinants of virulence confer advantages among VREF in the colonization of their host. Therefore, the prevention and control of the spread of nosocomial infections caused by VREF is crucial for identifying new emergent subclones that could be challenging to treat in subsequent years.

Acute promyelocytic leukemia (APL) is a distinct type of acute myeloid leukemia (AML) characterized by chromosomal translocations involving the retinoid acid receptor α (RARA) gene on chromosome 17. APL is a relatively rare blood disease that is highly curable with current treatment strategies; however, patient outcomes are heterogeneous in countries with limited resources. Promyelocytic leukemia accounts for 20-25% of all AML cases in Latin American countries.We conducted a study from July 2007 to July 2012 and applied the IC-APL2006 protocol. This case study reports the results from eleven patients with AML M3 (five males and six females). In all cases, the diagnoses were made by aspirating bone marrow and evaluating the t(15:17) or t(11:17) transcript. In eight cases, the molecular biology-based diagnostics for the PLM-RARa transcript were positive, and they were negative in two cases. One patient was positive for the PLZF-RARa transcript.The mean WBC at the time of diagnosis was 10.1 x 10(9)/L, and the mean platelet count was 17.1 x 10(9)/L. The mean percentage of abnormal promyelocytes in the bone marrow aspirates was 68%. Of the eleven patients, four presented with disseminated intravascular coagulation. All of the patients began treatment with transretinoic acid (ATRA) (45 mg/m(2)/day), which led to 4 cases of ATRA syndrome. There were 2 relapses, and the patient died in one case. The remaining ten patients were alive after the median follow-up period of 33.6 months (range from 11 to 60 months).The authors report on a series of cases involving pediatric patients with AML M3 seen at a single institution; the patients were stratified and treated with a standard protocol to obtain satisfactory results. Although the number of patients is limited, the health outcomes are relevant. To our knowledge, this is the first series of pediatric APL patients in Mexico who were treated with the IC-APL2006 protocol.

We assessed the value of bone marrow biopsy prospectively in a group of 91 individuals with Hodgkin's disease. The median age of our population was 29 years (range 4-87 years); 59 were males. Most patients (45%) had nodular sclerosing disease and most patients (44%) were in pathological stage II at diagnosis. The bone marrow biopsy showed infiltration by Hodgkin's disease in only three individuals (3.3%); two of these patients displayed constitutional symptoms and had been assigned to stage III before the biopsy. In one case, bone marrow biopsy was the diagnostic procedure, which was performed as part of the investigation of fever of unknown origin. Follow-up periods ranged between 1 and 117 months (median 16 months). All patients achieved complete remission, seven patients relapsed and four were given autologous stem cell transplants. The median survival of the whole group was 117 months, while the 3500-day survival was 76%. As bone marrow biopsy was the diagnostic procedure in one case, bone marrow biopsy was a useful staging procedure in only 2.2% of patients (two out of 90 patients). We suggest that bone marrow biopsy should be only be performed as a staging procedure in a selected subset of patients with Hodgkin's disease (clinical stage III, B symptoms, etc.).

Of a group of 149 patients who underwent allogeneic stem cell transplantation using the “Mexican approach,” a nonablative preparative regimen, 49 individuals developed bone marrow relapse, and 8 patients developed extramedullary relapse (EMR). All EMR cases presented in patients who received allografts for myeloid malignancies. In contrast, bone marrow relapses presented in patients with myeloid or lymphoid malignancies. EMR presented 60 to 1010 days after the allograft and appeared in 3 cases as subcutaneous nodules in different parts of the body, in the vertebrae in 3 cases, and in the kidney and the breast in 1 case each. One patient had both subcutaneous nodules and epididymis EMR. When EMR was noted, acute graft-versus-host disease (GVHD) had presented in 4 patients, and limited forms of chronic GVHD were present in 3 patients. All but 1 of the patients were full chimeras when the EMR ensued, and the EMR preceded an overt hematologic relapse in all but 1 of the patients. Patients who experienced an overt hematologic relapse died 20 to 180 days (median, 40 days) after the EMR. The only individual alive 240 days after relapse shows no evidence of a full-blown hematologic relapse. An EMR after allogeneic hematopoietic stem cell transplantation usually has a bad prognosis and presents mainly in individuals with high-risk malignancies.

The results of the treatment of 14 patients with promyelocytic leukemia (PML) treated with all trans-retinoic acid (ATRA), combined chemotherapy (CT) and prophylactic prednisone are reported; the median age was 30 years (range 7 - 49). A complete remission (CR) was obtained in 13 / 14 patients (93%). All patients were given ATRA fully as outpatients; the CR was achieved after the administration of ATRA in five patients, whereas in the remaining eight, CT was required to achieve it. There were no instances of the ATRA syndrome. One patient relapsed with a PML/RAR-a negative PML 575 days after achieving the CR, failed to respond again to ATRA and died. The median overall (OS) and disease free survival (DFS) has not been reached, being above 4,000 days, whereas the 12-month DFS was 93%, the three and five years DFS being 85%. The treatment employed differs from others in: Oral prednisone is used prophylactically, ATRA is given on an outpatient basis and adriamycin is used instead of other anthracyclines. The results are similar to those obtained in other centers worldwide and it is possible that the prophylactic administration of prednisone precluded the development of the full-blown ATRA syndrome in this group of patients.

We have analyzed the transfusion requirements of a group of 132 peripheral blood stem cell transplants from a single institution (73 allografts and 59 autografts) over a 10-year period. The allografts were conducted using the 'Mexican' nonmyeloablative conditioning regimen, while the autografts were given single-day high-dose melphalan. For the allografts, the median number of transfused packed red blood (PRBC) cell units was 1 (range 0-22), while the median number of platelet transfusion (PLT) sessions was 1 (range 0-9); 45% of allografted individuals did not require PRBC transfusions and 35% did not require PLT. For autografts, the median number of PRBC units was 2 (range 0-21), while the median number of PLT was 2 (range 0-21); 33% of autografted individuals did not require PRBC and 25% did not require PLT. We conclude that, by using certain preparative regimens, both allo and auto hematopoietic stem cell grafts can be conducted without the transfusion of blood products.

The activated protein C resistance (APCr) phenotype is found in around 40% of thrombophilic Mexican Mestizo individuals; since only very few display the factor V gene Leiden (Arg506Gln) mutation, it was considered of interest looking for other factor V gene mutations associated to thrombophilia: The HR2 haplotype, the factor V Cambridge (Arg306Thr), the factor V Hong Kong (Arg306Gly) and the FV Liverpool (Ile359Thr). In 39 individuals, the FV Leiden was found in 10%, the HR2 haplotype in 28%, the FV Hong Kong in 2%, whereas the FV Cambridge and FV Liverpool gene mutations were not found in any individual. In the subset of 10 patients with the APCr phenotype, the FV Leiden mutation was found only in 4 (40%) whereas the HR2 haplotype in 3 (30%); all the patients with the factor V Leiden mutation and 27% of those with the HR2 phenotype displayed the APCr phenotype. It is concluded that these polymorphisms of the factor V gene are not major contributors to the thrombophilia observed in Mexican Mestizos and that additional mutations in the FV gene should be looked for in those who display the APCr phenotype.

Using the Mexican approach to conduct nonablative stem cell transplantation (NST), we have prospectively performed 58 allografts in individuals with various malignant and nonmalignant hematological diseases using sibling donors, either HLA identical (6/6) or compatible, with one mismatch (5/6). When comparing allografts obtained from HLA identical (n=40) or compatible (n=18) siblings, respectively, the overall median survival was found to be 33 vs 8 months (P0.01), the 52-month survival was 47 vs 38% (P0.2), the prevalence of acute graft-versus-host disease (GVHD) 57 vs 38%, that of chronic GVHD 25 vs 11% and the relapse rate 45 vs 55%. The two patients who failed to engraft were both 5/6 matches. Probably stemming from the low number of patients, and despite a trend toward worse results in patients allografted from HLA compatible (5/6) siblings, most differences in outcome were not significant. It seems that NST can be offered to individuals with either an HLA identical or a compatible sibling donor.

The impact of undernutrition in the outcome of treatment of children with ALL has been analyzed by several authors who have highlighted undernutrition as another relevant prognostic factor in children with acute lymphoblastic leukemia (ALL). There are, however, some papers which have not confirmed the prognostic value of malnutrition at diagnosis in children with ALL. Overall, data from 1,123 children with ALL worldwide support the concept of malnutrition at diagnosis being useful as a prognostic factor, whereas data from 1,271 children fail to support this concept. We here critically analyze the information of these publications referring to a total of 2,394 children with ALL. Detailed information was available only from 500 of the 2,394 patients, stemming from six publications; of these individuals, at diagnosis, 376 were well nourished and 124 were malnourished. In this subset of patients, the analysis of the data shows that the 5-year (or longer) overall survival of undernourished children (UNC) was 26%, whereas that of well-nourished children (WNC) was 59% (p0.001); along the same line the relative risk of dying during this period was 1.8 times higher for UNC than WNC (p0.01; Interval of Confidence [IC] 95%: 1.72-1.88). On the other hand, the censoring time of these 500 children is different: 293 were censored at 5 years after diagnosis, whereas 207 where censored at 8-10 years: The overall survival for each of these periods was also different: 36% versus 2% for UNC (p0.001), and 56% versus 63% (p0.10) for WNC, data which support the concept that the differences in survival are more apparent in UNC if the period of observation is extended. These data suggest that undernutrition at diagnosis by itself and without interacting with other variables, may be a significant prognostic factor in the long-term outcome of treatment of pediatric patients with ALL. After identifying these variables as important, imaginative approaches to the treatment of cancer in childhood in the years ahead may lead into the improvement of the results of these treatments.

A group of 21 consecutive patients aged 4-20 (median 13) years was prospectively allografted using a reduced intensity preparative regimen. The group included both malignant (acute lymphoblastic leukemia, acute myelogenous leukemia, and chronic myelogenous leukemia) and nonmalignant (aplastic anemia, Diamond-Blackfan anemia, thalassemia major and adrenoleukodystrophy) conditions. Follow-up times ranged between 16 and 1038 days. Four of 21 patients (9.5%) developed acute graft-versus-host disease, and 2 of them died, whereas limited chronic graft-versus-host disease was observed in 2 of 15 cases. The 100-day mortality was 19%. Median overall survival was above 1038 days, whereas the 34-month survival was 55%. These data show that reduced intensity stem cell transplantation in children permits rapid engraftment from siblings with little toxicity. © 2003 American Society for Blood and Marrow Transplantation Biology of Blood and Marrow Transplantation 9:157-161 (2003)

Background. The chronic myeloproliferative diseases (CMPDs) include chronic myelogenous leukemia (CML), primary (essential) thrombocythemia (PT), agnogenic myeloid metaplasia (AMM), and polycythemia vera (PV). Certain hematological malignancies have a different prevalence in our country than in countries with Caucasian populations. Data indicate that the prevalence of CML in our country is similar to that found in Caucasians; however, the prevalence of the other CMPDs has not been studied. Methods. In a total of 8069 individuals studied between June 1983 and March 2001 in the Centro de Hematologia y Medicina Interna de Puebla, we assessed the prevalence of CML, PT, AMM, and PV. Some of the clinical features of these individuals were also assessed. Results and Conclusions. Forty-nine patients with CML, 14 with PT, 7 with AMM, and 3 with PV were identified. The clinical presentations of these CMPDs were not different from those described in Caucasians. Conclusions.We found that CML was more than 3 times more frequent than PT, that both PV and AMM were exceptional, and that PT, AMM, and PV were significantly less frequent in Mexican than in Caucasian populations (P < .01).Int J Hematol. 2002;75:499–502.

Describimos dos pacientes con linfoma no Hodgking y niveles sericos elevados del antigeno CA-125: un caso de una mujer de 75 anos de edad con perdida de peso y leucoeritroblastosis con cifras de CA-125 de 165 U/ml (valores de referencia: o a 35). El segundo caso fue un hombre de 92 anos estudiado por perdida ponderal, astenia, adinamia y ascitis con cifras de CA-125 de 1.246 U/ml. Ambos pacientes fallecieron pronto despues de haberse hecho el diagnostico. Los niveles sericos de CA-125, considerado como un marcador de cancer de ovario, pueden incrementarse en pacientes con linfoma no Hodgkin, y hay datos que indican que este hallazgo puede ser un factor pronostico adverso.

The Mexican approach was used to conduct nonmyeloablative stem cell transplantation (SCT) in patients with various malignant and non-malignant hematologic diseases. Patients received a modified, low-intensity conditioning regimen, which included oral busulphan 4 mg/kg on Days −6 and −5, IV cyclophosphamide 350 mg/m2 on Days −4, −3, and −2, IV fludarabine 30 mg/m2 on Days −4, −3, and −2, oral cyclosporine A 5 mg/kg twice daily staring on Day −1 (continuing until Day 180), and IV methotrexate 5 mg/m2 on Days +1, +3, +5, and +11. Allografts were prospectively performed in 58 patients using sibling donors that were either human leukocyte antigen (HLA) identical (6/6) or compatible with 1 mismatch (5/6). In allografts where the donor was an HLA identical sibling (n = 40), the median overall survival was 33 months compared to 8 months when the donor was an HLA compatible sibling (n = 18; P