Evaluation of Liver Graft Recipient Workup in Predicting of Early Cardiovascular Events During Liver Transplantation: A Single-Center Experience.

BACKGROUND: Cardiovascular events (CVE) contribute to serious complications and death after liver transplantation (LT). Troponin I (TnI) level >0.07 mg/L and prior cardiac disease are known to be the independent predictors for posttransplant CVE. We evaluated single-center cardiac workup to predict early cardiovascular morbidity and mortality after LT. PATIENTS AND METHODS: We recruited 105 consecutive liver transplant recipients (male/female, 59/46; mean age, 51.66 ± 11.67 years). The cardiological assessment at evaluation for LT included medical history, electrocardiogram, echocardiography, Holter monitoring, and exercise test. We collected data regarding CVE including hypotonia with catecholamine usage, arrhythmia, sudden cardiac death, pulmonary edema, and myocardial infarction within 7 days after LT. RESULTS: CVE during LT occurred in 42 recipients (40%) and after LT in 9 patients (8.57%). Proposed cutoff level of TnI >0.07 mg/L did not correlate with CVE during operation (P = .73) or after LT (P = .47). CVE during LT was associated with arterial hypertension in medical history (P <.001), right ventricular systolic pressure (P< .05), and clinical scores: Child-Pugh (P = .04), Model for End-Stage Liver Disease (MELD) (P = .04), MELD incorporating serum sodium (P<.03), and integrated MELD score (P = .01). CVE after LT correlated only with arrhythmia (P<.001) and catecholamine usage (P < .05) perioperatively. Of interest, catecholamine usage during LT was associated with prolonged stay at the intensive care unit (P < .05). CONCLUSION: The single-center algorithm with noninvasive cardiac procedures without TnI assessment is optimal in evaluation before LT; however, medical history and severity of the liver disease are crucial for short-term cardiovascular morbidity after LT.

Troponin I Is Not a Predictor of Early Cardiovascular Morbidity in Liver Transplant Recipients.

BACKGROUND: Cardiovascular events (CVE) might occur in 20% to 70% of liver transplant recipients, and major CVE are associated with poor long-term survival. Overall, the ability to identify patients at the highest risk of death after liver transplantation (LT) has been improved. Abnormal pretransplant troponin I (TnI) level is regarded as one of predictors of postoperative CVE. We evaluated the number of early CVE after LT and the impact of pretransplant TnI on cardiovascular morbidity. PATIENTS AND METHODS: We prospectively enrolled 110 consecutive liver transplant recipients (M/F 67/43, age 53.3 ± 10.4 years, 32.7% with hepatitis C virus). Seven of them (6.4%) were on urgent protocol and 3 patients (2.7%) had re-LT. TnI level was measured at listing for LT and directly after LT; clinical outcomes were observed within the first 7 days after LT. RESULTS: CVE during LT occurred in 51 recipients (46.4%). CVE after LT at the intensive care unit were noticed in 13 patients (11.8%). One patient (0.9%) died in the first 7 days after LT. The level of TnI >0.07 did not correlate with CVE during operation and 7 days after LT (P > .05), but the subgroup with TnI >0.07 before LT had a trend with higher TnI after LT (P = .065). Recipients with hepatitis C virus had a trend for higher TnI after LT (P = .061). CVE directly after LT correlated significantly with Child-Pugh (P = .01), Model for End-Stage Liver Disease (MELD), MELD incorporating serum sodium, and integrated MELD scales (P < .001). CONCLUSION: In our single-center algorithm, TnI with canonical cutoff value of 0.07 was not an effective predictor for cardiac outcomes shortly after LT in our population.

Functional screening of Alzheimer risk loci identifies PTK2B as an in vivo modulator and early marker of Tau pathology.

A recent genome-wide association meta-analysis for Alzheimer's disease (AD) identified 19 risk loci (in addition to APOE) in which the functional genes are unknown. Using Drosophila, we screened 296 constructs targeting orthologs of 54 candidate risk genes within these loci for their ability to modify Tau neurotoxicity by quantifying the size of >6000 eyes. Besides Drosophila Amph (ortholog of BIN1), which we previously implicated in Tau pathology, we identified p130CAS (CASS4), Eph (EPHA1), Fak (PTK2B) and Rab3-GEF (MADD) as Tau toxicity modulators. Of these, the focal adhesion kinase Fak behaved as a strong Tau toxicity suppressor in both the eye and an independent focal adhesion-related wing blister assay. Accordingly, the human Tau and PTK2B proteins biochemically interacted in vitro and PTK2B co-localized with hyperphosphorylated and oligomeric Tau in progressive pathological stages in the brains of AD patients and transgenic Tau mice. These data indicate that PTK2B acts as an early marker and in vivo modulator of Tau toxicity.

Menstrual cycle disorders in female volleyball players.

The aim of this study was to examine the relation between increased physical activity and menstrual disorders in adolescent female volleyball players. The study was conducted on 210 Polish female volleyball players, aged 13-17 years, the authorship questionnaire was used. The results of the study showed that irregular menstruation occurred in 19% of girls, spotting between menstrual periods in 27% and heavy menstruation was reported in 33% of girls. Out of all volleyball female players participating in the study, 94 girls (45%) declared absence of menstrual periods after regular cycles. Statistical analysis showed that the more training hours per week, the bigger probability of the occurrence of irregular menstruation. It was concluded that the number of hours of volleyball training per week affects regularity of menstrual cycles in female volleyball players. The absence of menstruation might be caused by the duration of training per week or years of training.

Bordetella holmesii in children suspected of pertussis in Argentina.

We describe nine patients (eight aged <1 year) clinically diagnosed with pertussis yet laboratory-confirmed with Bordetella holmesii infections, a human pathogen normally isolated from blood. Most patients reported cough and cold symptoms. No death was reported. We report B. holmesii isolation in infants with respiratory symptoms in Argentina.

Clonal dissemination of Klebsiella pneumoniae ST258 harbouring KPC-2 in Argentina.

The present work describes the abrupt emergence of Klebsiella pneumoniae carbapenemase (KPC) and characterizes the first 79 KPC-producing enterobacteria from Argentina (isolated from 2006 to 2010). The emergence of bla(KPC-2) was characterized by two patterns of dispersion: the first was the sporadic occurrence in diverse enterobacteria from distant geographical regions, harbouring plasmids of different incompatibility groups and bla(KPC-2) in an unusual genetic environment flanked by ISKpn8-Δbla(TEM-1) and ISKpn6-like. bla(KPC-2) was associated with IncL/M transferable plasmids; the second was the abrupt clonal spread of K. pneumoniae ST258 harbouring bla(KPC-2) in Tn4401a.

Fluoroquinolone-resistant Streptococcus agalactiae isolates from Argentina.

Fluoroquinolone resistance is a growing problem that has only recently emerged in S. agalactiae. Between 2005-2007, WHONET--Argentina network evaluated levofloxacin susceptibility in 1128 clinical S. agalactiae isolates, 10 (0.9%) of which proved to be resistant. Nine of them had come from 5 hospitals (in Buenos Aires City and 4 Argentinean provinces) and recovered from urine (n=7) and vaginal screening cultures (n=2). Three strains were also resistant to macrolides, lincosamides and B streptogramins due to the ermA gene. All nine fluoroquinolone-resistant isolates bore the same two mutations, Ser79Phe in ParC and Ser81Leu in GyrA proteins. Genetic relationships were analyzed by Apal-PFGE and two clones were determined, A (n=6) and B (n=3). To our knowledge, these are the first fluoroquinolone-resistant S. agalactiae isolates detected in Latin America.

Vigilancia nacional de tos convulsa, coqueluche o pertussis: experiencia del hospital Garrahan y de los laboratorios nacionales de referencia / National vigilance program for whooping cough or pertussis: Experience of the Garrahan Hospital and national reference laboratories

Pertussis es una enfermedad particularmente grave en menores de 1 año. No sólo no se ha podido erradicar pese al uso de vacunas por más de cincuenta años, sino que en la actualidad ha reemergido. En junio del 2010 se registró uno de los mayores brotes de coqueluche de los Estados Unidos, con 910 casos confirmados. En la Argentina se ha venido registrando un aumento significativo de casos de pertussis. En este trabajo se presentan datos nacionales y de nuestro hospital confirmados por cultivo y/o métodos moleculares (PCR). Durante el período 2008-2010 se registraron anualmente en nuestro país entre 600 y 1.000 casos con sintomatología compatible y en el Hospital Garrahan entre 110 y 150. La confirmación se concretó en alrededor de 24% de los casos nacionales y entre un 7% y un 36,4% en el hospital. Los datos obtenidos en los laboratorios nacionales de referencia muestran un registro actual que vuelve a alcanzar los valores del 2008, luego de un descenso en el 2009. En el Hospital Garrahan, un aumento relativo en el número de casos sospechosos no confirmados podría estar vinculados a cuadros respiratorios compatibles con pertussis producidos por otros agentes etiológicos. Más allá de las variaciones anuales se puede observar la vigencia de esta enfermedad en la Argentina. Desde el punto de vista de la prevención es importante destacar que muchos de estos niños no habían recibido el esquema de vacunación completo (la mayoría de los casos se registró en menores de 6 meses). (AU)

Pertussis is a especially severe illness in infants. The use of vaccines during more than 50 years could not eradicate this illness, that now it has reemerged. In June 2010 one of the greatest outbreaks of coqueluche was recorded in the United States, with 910 confirmed cases. In Argentina, a significant increase of pertussis cases was recorded. In the present study both national and hospital data is presented, including cases confirmed by culture and/or molecular methods (PCR). During 2008-2010 between 600 and 1,000 cases were recorded in our country, and between 110 and 150 at the Hospital Garrahan. Confirmation was done in almost 24% of national cases and between 7% and 36.4% in the hospital. Data obtained by national reference laboratories showed that cases decreased from 2007 to 2008, to regain similar numbers in 2009. In the Hospital Garrahan a relative increase of non-confirmed suspected cases could be related to respiratory syndromes due to other agents but compatible with pertussis. Beyond annual fluctuations the prevalence of this illness in Argentina can be observed. From the prevention point of view it is very important to highlight that many of these children have not received the complete vaccination scheme (most of cases have been recorded in less than 6-month-old children) (AU)

Automated use of WHONET and SaTScan to detect outbreaks of Shigella spp. using antimicrobial resistance phenotypes.

Antimicrobial resistance is a priority emerging public health threat, and the ability to detect promptly outbreaks caused by resistant pathogens is critical for resistance containment and disease control efforts. We describe and evaluate the use of an electronic laboratory data system (WHONET) and a space-time permutation scan statistic for semi-automated disease outbreak detection. In collaboration with WHONET-Argentina, the national network for surveillance of antimicrobial resistance, we applied the system to the detection of local and regional outbreaks of Shigella spp. We searched for clusters on the basis of genus, species, and resistance phenotype and identified 19 statistical 'events' in a 12-month period. Of the six known outbreaks reported to the Ministry of Health, four had good or suggestive agreement with SaTScan-detected events. The most discriminating analyses were those involving resistance phenotypes. Electronic laboratory-based disease surveillance incorporating statistical cluster detection methods can enhance infectious disease outbreak detection and response.

Pertussis epidemiology in Argentina: trends over 2004-2007.

OBJECTIVES: Pertussis continues causing significant morbidity and mortality worldwide. Although its epidemiology has been studied in many developed countries, the current pertussis situation in South America is scarcely known. This review summarizes the most important recent data concerning pertussis in a country of South America, Argentina. METHODS: CDC criteria were used for pertussis diagnosis. Proportion of pertussis cases by age, immunization status, and immunization coverage rate evaluated at the Argentinean National Pertussis Reference Centers was reported. Bordetella pertussis isolates were characterized and compared with vaccine strains. RESULTS: From 2002 to nowadays, a steady increase of pertussis cases was observed. Most of these cases correspond to patients younger than six months old that received less than three doses of vaccine. However, cases in adolescent and adults have also been detected. For this situation, which is not peculiar to Argentina, several explanations have been proposed. Among them, the inability of current vaccines to induce long-lasting immunity is the most widely accepted as a cause of pertussis resurgence. Furthermore, antigenic divergence between local clinical isolates and vaccine strains may have aggravated the effect of waning immunity. CONCLUSIONS: Pertussis is an important problem for public health in Argentina. Divergence between vaccine strains and local isolates could contribute to the described pertussis epidemiology.

The peptidyl prolyl cis/trans isomerase Pin1 downregulates the Inhibitor of Apoptosis Protein Survivin.

The peptidyl prolyl cis-trans isomerase Pin1 and the Inhibitor of Apoptosis Protein (IAP) Survivin are two major proteins involved in cancer. They both modulate apoptosis, mitosis, centrosome duplication and neuronal development but until now no functional relationship has been reported between these two proteins. We tested Pin1-induced regulation of Survivin in neuroblastoma cells. Pin1 overexpression in SY5Y neuroblastoma cells decreased Survivin levels. Immunocytochemical studies indicated that they partially co-localized in interphase and mitotic cells. Co-immunoprecipitation further demonstrates the existence of a Pin1/Survivin complex. Pin1-induced effect on Survivin was confirmed in COS cells. RT-PCR and mutagenesis experiments suggested that this Pin1-induced decrease of Survivin occurred at the protein level. Survivin downregulation depended on the binding ability of Pin1 but was not related to the single Thr-Pro site, suggesting an indirect relationship into a protein complex. Finally, this functional regulation of Survivin by Pin1 is reciprocal since Pin1 silencing led to an increase in Survivin levels. The characterization of this functional relationship between Pin1 and Survivin might help to better understand mitosis control and cancer mechanisms.

[Consensus for antimicrobial susceptibility testing for Enterobacteriaceae. Subcommittee on Antimicrobials, SADEBAC (Argentinian Society of Clinical Bacteriology), Argentinian Association of Microbiology]. / Consenso sobre las pruebas de sensibilidad a los antimicrobianos en Enterobacteriaceae.

Taking into account previous recommendations from the National Committee for Clinical Laboratory Standards (NCCLS), the Antimicrobial Committee, Sociedad Argentina de Bacteriología Clínica (SADEBAC), Asociación Argentina de Microbiología (AAM), and the experience from its members and some invited microbiologists, a consensus was obtained for antimicrobial susceptibility testing and interpretation in most frequent enterobacterial species isolated from clinical samples in our region. This document describes the natural antimicrobial resistance of some Enterobacteriaceae family members, including the resistance profiles due to their own chromosomal encoded beta-lactamases. A list of the antimicrobial agents that should be tested, their position on the agar plates, in order to detect the most frequent antimicrobial resistance mechanisms, and considerations on which antimicrobial agents should be reported regarding to the infection site and patient characteristics are included. Also, a description on appropriate phenotypic screening and confirmatory test for detection of prevalent extended spectrum beta-lactamases in our region are presented. Finally, a summary on frequent antimicrobial susceptibility profiles and their probably associated resistance mechanisms, and some infrequent antimicrobial resistance profiles that deserve confirmation are outlined.

Consenso sobre las pruebas de sensibilidad a los antimicrobianos en Enterobacteriaceae / Consensus for antimicrobial susceptibility testing for Enterobacteriaceae

En este documento se elaboraron una serie de recomendaciones para el ensayo, lectura, interpretación e informe de las pruebas de sensibilidad a los antimicrobianos para las enterobacterias aisladas con mayor frecuencia de especímenes clínicos. Se adoptaron como base las recomendaciones del National Committee for Clinical Laboratory Standards (NCCLS) de los EEUU, los de la subcomisión de Antimicrobianos, de la Sociedad Argentina de Bacteriología Clínica (SADEBAC), división de la Asociación Argentina de Microbiología (AAM) y de un grupo de expertos invitados. En él se indican las resistencias naturales de los diferentes miembros que integran la familia Enterobacteriaceae y se analiza la actividad de las diferentes beta-lactamasas cromosómicas, propias de cada especie, sobre las penicilinas, cefalosporinas y carbapenemes. Se recomiendan los antimicrobianos que se deberían ensayar, ubicados estratégicamente, para detectar los mecanismos de resistencia más frecuentes y cuales se deberían informar de acuerdo a la especie aislada, el sitio de infección y el origen de la cepa (intra o extrahospitalario). Se detallan los métodos de "screening" y de confirmación fenotipíca para detectar beta-lactamasas de espectro extendido (BLEE) que son más adecuados a nuestra realidad. Por último, se mencionan patrones infrecuentes de sensibilidad/resistencia que deberían verificarse y los perfiles de sensibilidad que pueden hallarse en las distintas enterobacterias en relación con los probables mecanismos de resistencia. Se debe resaltar que el contenido de este documento debe ser considerado como recomendaciones realizadas por expertos argentinos basadas en una revisión de la literatura y datos personales.

Taking into account previous recommendations from the National Committee for Clinical Laboratory Standards (NCCLS), the Antimicrobial Committee, Sociedad Argentina de Bacteriología Clínica (SADEBAC), Asociación Argentina de Microbiología (AAM), and the experience from its members and some invited microbiologists, a consensus was obtained for antimicrobial susceptibility testing and interpretation in most frequent enterobacterial species isolated from clinical samples in our region. This document describes the natural antimicrobial resistance of some Enterobacteriaceae family members, including the resistance profiles due to their own chromosomal encoded beta-lactamases. A list of the antimicrobial agents that should be tested, their position on the agar plates, in order to detect the most frequent antimicrobial resistance mechanisms, and considerations on which antimicrobial agents should be reported regarding to the infection site and patient characteristics are included. Also, a description on appropriate phenotypic screening and confirmatory test for detection of prevalent extended spectrum beta-lactamases in our region are presented. Finally, a summary on frequent antimicrobial susceptibility profiles and their probably associated resistance mechanisms, and some infrequent antimicrobial resistance profiles that deserve confirmation are outlined.

First report of VanA Enterococcus gallinarum dissemination within an intensive care unit in Argentina.

Enterococcusgallinarum is intrinsically resistant to low levels of vancomycin and has been described as a colonizing microorganism causing bacteraemia and infection among immunosupresed patients. Between August 2000 and February 2001, 15 highly glycopeptide-resistant E. gallinarum isolates, one from blood and the remaining from rectal swabs, were recovered in a general hospital of Buenos Aires Province, Argentina. All isolates were characterized by biochemical assays, and displayed MICs of vancomycin in the range 16-128 mg/l and MICs of teicoplanin in the range 16-32 mg/l. In all cases, PCR analysis yield positive results for both vanC1 and vanA genes. E. gallinarum isolates were classified as two clonal types by SmaI-PFGE: clone A (n = 8) and clone B (n = 7) and both harboured a transferable vanA element.

Consenso sobre las pruebas de sensibilidad a los antimicrobianos en Enterobacteriaceae. / [Consensus for antimicrobial susceptibility testing for Enterobacteriaceae. Subcommittee on Antimicrobials, SADEBAC (Argentinian Society of Clinical Bacteriology), Argentinian Association of Microbiology]

Taking into account previous recommendations from the National Committee for Clinical Laboratory Standards (NCCLS), the Antimicrobial Committee, Sociedad Argentina de Bacteriología Clínica (SADEBAC), Asociación Argentina de Microbiología (AAM), and the experience from its members and some invited microbiologists, a consensus was obtained for antimicrobial susceptibility testing and interpretation in most frequent enterobacterial species isolated from clinical samples in our region. This document describes the natural antimicrobial resistance of some Enterobacteriaceae family members, including the resistance profiles due to their own chromosomal encoded beta-lactamases. A list of the antimicrobial agents that should be tested, their position on the agar plates, in order to detect the most frequent antimicrobial resistance mechanisms, and considerations on which antimicrobial agents should be reported regarding to the infection site and patient characteristics are included. Also, a description on appropriate phenotypic screening and confirmatory test for detection of prevalent extended spectrum beta-lactamases in our region are presented. Finally, a summary on frequent antimicrobial susceptibility profiles and their probably associated resistance mechanisms, and some infrequent antimicrobial resistance profiles that deserve confirmation are outlined.

Improvement of a latex agglutination test for the evaluation of oxacillin resistance in coagulase-negative staphylococci.

The "Slidex MRSA Detection" test (Denka Seiken, Japan) is a latex agglutination assay able to detect PBP2a. We evaluated its ability to differentiate mecA-positive from mecA-negative coagulase-negative staphylococci. We included 100 coagulase-negative staphylococci clinical isolates belonging to 9 species, 54 mecA positive and 46 mecA negative, as characterized by PCR. The specificity achieved using the manufacturer's instructions was 100%, but the sensitivity was only 57%. To increase sensitivity, we introduced modifications into the standard protocol. Using either large inocula or oxacillin induction before test performance, we achieved 100% sensitivity.

[Methicillin resistance detection in Staphylococcus aureus: comparison between conventional methods and MRSA-Screen latex agglutination technique]. / Detección de meticilino-resistencia en Staphylococcus aureus: comparación de métodos convencionales y aglutinación con MRSA-Screen latex.

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant pathogen that has emerged over the last four decades, causing both nosocomial and community-acquired infections. Rapid and accurate detection of methicillin resistance in S. aureus is important for the use of appropriate antimicrobial therapy and for the control of nosocomial spread of MRSA strains. We evaluated the efficiency of conventional methods for detection of methicillin resistance such as the disk diffusion, agar dilution, oxacillin agar screen test, and the latex agglutination test MRSA-Screen latex, in 100 isolates of S. aureus, 79 mecA positive and 21 mecA negative. The MRSA-Screen latex (Denka Seiken, Niigata, Japón), is a latex agglutination method that detects the presence of PLP-2a, product of mecA gene in S. aureus. The PCR of the mecA gene was used as the "gold standard" for the evaluation of the different methods tested. The percentages of sensitivity and specificity were as follows: disk difusión 97 and 100%, agar dilution 97 and 95%, oxacillin agar screen test 100 and 100%, and MRSA-Screen latex, 100 and 100 %. All methods presented high sensitivity and specificity, but MRSA-Screen latex had the advantage of giving a reliable result, equivalent to PCR, in only 15 minutes.