Predictors of packed red cell transfusion after isolated primary coronary artery bypass grafting – The experience of a single cardiac center: A prospective observational study

<p>Abstract</p> <p>Background</p> <p>Preoperative patients' characteristics can predict the need for perioperative blood component transfusion in cardiac surgical operations. The aim of this prospective observational study is to identify perioperative patient characteristics predicting the need for allogeneic packed red blood cell (PRBC) transfusion in isolated primary coronary artery bypass grafting (CABG) operations.</p> <p>Patients and Methods</p> <p>105 patients undergoing isolated, first-time CABG were reviewed for their preoperative variables and followed for intraoperative and postoperative data. Patients were 97 males and 8 females, with mean age 58.28 ± 10.97 years. Regression logistic analysis was used for identifying the strongest perioperative predictors of PRBC transfusion.</p> <p>Results</p> <p>PRBC transfusion was used in 71 patients (67.6%); 35 patients (33.3%) needed > 2 units and 14 (13.3%) of these needed > 4 units. Univariate analysis identified female gender, age > 65 years, body weight ≤ 70 Kg, BSA ≤ 1.75 m², BMI ≤ 25, preoperative hemoglobin ≤ 13 gm/dL, preoperative hematocrit ≤ 40%, serum creatinine > 100 μmol/L, Euro SCORE (standard/logistic) > 2, use of CPB, radial artery use, higher number of distal anastomoses, and postoperative chest tube drainage > 1000 mL as significant predictors. The strongest predictors using multivariate analysis were CPB use, hematocrit, body weight, and serum creatinine.</p> <p>Conclusion</p> <p>The predictors of PRBC transfusion after primary isolated CABG are use of CPB, hematocrit ≤ 40%, weight ≤ 70 Kg, and serum creatinine > 100 μmol/L. This leads to better utilization of blood bank resources and cost-efficient targeted use of expensive blood conservation modalities.</p

Effect of Investment in Malaria Control on Child Mortality in Sub-Saharan Africa in 2002–2008

BACKGROUND: Around 8.8 million children under-five die each year, mostly due to infectious diseases, including malaria that accounts for 16% of deaths in Africa, but the impact of international financing of malaria control on under-five mortality in sub-Saharan Africa has not been examined. METHODS AND FINDINGS: We combined multiple data sources and used panel data regression analysis to study the relationship among investment, service delivery/intervention coverage, and impact on child health by observing changes in 34 sub-Saharan African countries over 2002-2008. We used Lives Saved Tool to estimate the number of lives saved from coverage increase of insecticide-treated nets (ITNs)/indoor residual spraying (IRS). As an indicator of outcome, we also used under-five mortality rate. Global Fund investments comprised more than 70% of the Official Development Assistance (ODA) for malaria control in 34 countries. Each $1 million ODA for malaria enabled distribution of 50,478 ITNs [95$3.90 vs. $7.05). Increased ITN/IRS coverage in high-burden countries led to 3,575 lives saved per 1 million children, as compared with 914 lives in lower-burden countries. Impact of ITN/IRS coverage on under-five mortality was significant among major child health interventions such as immunisation showing that 10% increase in households with ITN/IRS would reduce 1.5 [95%CI: 0.3-2.8] child deaths per 1000 live births. CONCLUSIONS: Along with other key child survival interventions, increased ITNs/IRS coverage has significantly contributed to child mortality reduction since 2002. ITN/IRS scale-up can be more efficiently prioritized to countries where malaria is a major cause of child deaths to save greater number of lives with available resources

I-TRAP: A method to identify transcriptional regulator activated promoters

BACKGROUND: The differential expression of virulence genes is often used by microbial pathogens in adapting to the environment of their host. The differential expression of such sets of genes can be regulated by RNA polymerase sigma factors. Some sigma factors are differentially expressed, which can provide a means to identifying other differentially expressed genes such as those whose expression are controlled by the sigma factor. METHODS: To identify sigma factor-regulated genes, we developed a method, termed I-TRAP, for the identification of transcriptional regulator activated promoters. The I-TRAP method is based on the fact that some genes will be differentially expressed in the presence and absence of a transcriptional regulator. I-TRAP uses a DNA library in a promoter-trap vector that contains two reporter genes, one to allow the selection of active promoters in the presence of the transcriptional regulator and a second to allow screening for promoter activity in the absence of the transcriptional regulator. RESULTS: To illustrate the development and use of the I-TRAP approach, the construction of the vectors, host strains, and library necessary to identify SigmaE-regulated genes of Mycobacterium tuberculosis is described. CONCLUSION: The I-TRAP method should be a versatile and useful method for identifying and characterizing promoter activity under a variety of conditions and in response to various regulatory proteins. In our study, we isolated 360 clones that may contain plasmids carrying SigmaE-regulated promoters genes of M. tuberculosis

β-Lactam Resistance Response Triggered by Inactivation of a Nonessential Penicillin-Binding Protein

It has long been recognized that the modification of penicillin-binding proteins (PBPs) to reduce their affinity for β-lactams is an important mechanism (target modification) by which Gram-positive cocci acquire antibiotic resistance. Among Gram-negative rods (GNR), however, this mechanism has been considered unusual, and restricted to clinically irrelevant laboratory mutants for most species. Using as a model Pseudomonas aeruginosa, high up on the list of pathogens causing life-threatening infections in hospitalized patients worldwide, we show that PBPs may also play a major role in β-lactam resistance in GNR, but through a totally distinct mechanism. Through a detailed genetic investigation, including whole-genome analysis approaches, we demonstrate that high-level (clinical) β-lactam resistance in vitro, in vivo, and in the clinical setting is driven by the inactivation of the dacB-encoded nonessential PBP4, which behaves as a trap target for β-lactams. The inactivation of this PBP is shown to determine a highly efficient and complex β-lactam resistance response, triggering overproduction of the chromosomal β-lactamase AmpC and the specific activation of the CreBC (BlrAB) two-component regulator, which in turn plays a major role in resistance. These findings are a major step forward in our understanding of β-lactam resistance biology, and, more importantly, they open up new perspectives on potential antibiotic targets for the treatment of infectious diseases

Hospital variation in transfusion and infection after cardiac surgery: a cohort study

<p>Abstract</p> <p>Background</p> <p>Transfusion practices in hospitalised patients are being re-evaluated, in part due to studies indicating adverse effects in patients receiving large quantities of stored blood. Concomitant with this re-examination have been reports showing variability in the use of specific blood components. This investigation was designed to assess hospital variation in blood use and outcomes in cardiac surgery patients.</p> <p>Methods</p> <p>We evaluated outcomes in 24,789 Medicare beneficiaries in the state of Michigan, USA who received coronary artery bypass graft surgery from 2003 to 2006. Using a cohort design, patients were followed from hospital admission to assess transfusions, in-hospital infection and mortality, as well as hospital readmission and mortality 30 days after discharge. Multilevel mixed-effects logistic regression was used to calculate the intrahospital correlation coefficient (for 40 hospitals) and compare outcomes by transfusion status.</p> <p>Results</p> <p>Overall, 30% (95 CI, 20% to 42%) of the variance in transfusion practices was attributable to hospital site. Allogeneic blood use by hospital ranged from 72.5% to 100% in women and 49.7% to 100% in men. Allogeneic, but not autologous, blood transfusion increased the odds of in-hospital infection 2.0-fold (95% CI 1.6 to 2.5), in-hospital mortality 4.7-fold (95% CI 2.4 to 9.2), 30-day readmission 1.4-fold (95% CI 1.2 to 1.6), and 30-day mortality 2.9-fold (95% CI 1.4 to 6.0) in elective surgeries. Allogeneic transfusion was associated with infections of the genitourinary system, respiratory tract, bloodstream, digestive tract and skin, as well as infection with <it>Clostridium difficile</it>. For each 1% increase in hospital transfusion rates, there was a 0.13% increase in predicted infection rates.</p> <p>Conclusion</p> <p>Allogeneic blood transfusion was associated with an increased risk of infection at multiple sites, suggesting a system-wide immune response. Hospital variation in transfusion practices after coronary artery bypass grafting was considerable, indicating that quality efforts may be able to influence practice and improve outcomes.</p

Mycobacterium tuberculosis DosR Regulon Gene Rv0079 Encodes a Putative, ‘Dormancy Associated Translation Inhibitor (DATIN)’

Mycobacterium tuberculosis is a major human pathogen that has evolved survival mechanisms to persist in an immune-competent host under a dormant condition. The regulation of M. tuberculosis metabolism during latent infection is not clearly known. The dormancy survival regulon (DosR regulon) is chiefly responsible for encoding dormancy related functions of M. tuberculosis. We describe functional characterization of an important gene of DosR regulon, Rv0079, which appears to be involved in the regulation of translation through the interaction of its product with bacterial ribosomal subunits. The protein encoded by Rv0079, possibly, has an inhibitory role with respect to protein synthesis, as revealed by our experiments. We performed computational modelling and docking simulation studies involving the protein encoded by Rv0079 followed by in vitro translation and growth curve analysis experiments, involving recombinant E. coli and Bacille Calmette Guérin (BCG) strains that overexpressed Rv0079. Our observations concerning the interaction of the protein with the ribosomes are supportive of its role in regulation/inhibition of translation. We propose that the protein encoded by locus Rv0079 is a ‘dormancy associated translation inhibitor’ or DATIN

Local Microenvironment Provides Important Cues for Cell Differentiation in Lingual Epithelia

Transgenic Keratin14-rtTA-PTR mice specifically express Keratin14 (K14) in the tongue epithelia, as well as co-express EGFP and the dominant negative ΔTgfbr2 genes upon treatment with Doxycycline (Dox). As TGF-β signaling negatively regulates the stem cell cycle and proliferation, its disruption by Dox induction in these transgenic mice shortens the cell cycle and allows observation of the final fate of those mutated cell lineages within a short period of time. Here, we used inducible transgenic mice to track the K14+ cells through the cell migration stream by immunohistochemical an immunofluorescent imaging. We showed that these cells have different development patterns from the tip to posterior of the tongue, achieved presumably by integrating positional information from the microenvironment. The expression of the K14 gene was variable, depending on the location of the tongue and papillae. Disruption of TGF-β signaling in K14+ progenitor cells resulted in proliferation of stem cell pools

Tone burst-evoked otoacoustic emissions in neonates: normative data

<p>Abstract</p> <p>Background</p> <p>Tone-burst otoacoustic emissions (TBOAEs) have not been routinely studied in pediatric populations, although tone burst stimuli have greater frequency specificity compared with click sound stimuli. The present study aimed (1) to determine an appropriate stimulus level for neonatal TBOAE measurements when the stimulus center frequency was 1 kHz, (2) to explore the characteristics of 1 kHz TBOAEs in a neonatal population.</p> <p>Methods</p> <p>A total of 395 normal neonates (745 ears) were recruited. The study consisted of two parts, reflecting the two study aims. Part I included 40 normal neonatal ears, and TBOAE measurement was performed at five stimulus levels in the range 60–80 dB peSPL, with 5 dB incremental steps. Part II investigated the characteristics of the 1 kHz TBOAE response in a large group of 705 neonatal ears, and provided clinical reference criteria based on these characteristics.</p> <p>Results</p> <p>The study provided a series of reference parameters for 1 kHz TBOAE measurement in neonates. Based on the results, a suggested stimulus level and reference criteria for 1 kHz TBOAE measures with neonates were established. In addition, time-frequency analysis of the data gave new insight into the energy distribution of the neonatal TBOAE response.</p> <p>Conclusion</p> <p>TBOAE measures may be a useful method for investigating cochlear function at specific frequency ranges in neonates. However, further studies of both TBOAE time-frequency analysis and measurements in newborns are needed.</p

Troublesome Heterotopic Ossification after Central Nervous System Damage: A Survey of 570 Surgeries

BACKGROUND: Heterotopic ossification (HO) is a frequent complication after central nervous system (CNS) damage but has seldom been studied. We aimed to investigate features of HO for the first time in a large sample and the rate of early recurrence of HO in terms of the time of surgery. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively analyzed data from an anonymous prospective survey of patients undergoing surgery between May 1993 and November 2009 in our institution for troublesome HO related to acquired neurological disease. Demographic and HO characteristics and neurological etiologies were recorded. For 357 consecutive patients, we collected data on 539 first surgeries for HO (129 surgeries for multiple sites). During the follow-up, recurrences requiring another surgery appeared in 31 cases (5.8% [31/539]; 95% confidence interval [CI]: 3.8%-7.8%; 27 patients). Most HO requiring surgery occurred after traumatic brain injury (199 patients [55.7%]), then spinal cord injury (86 [24.0%]), stroke (42 [11.8%]) and cerebral anoxia (30 [8.6%]). The hip was the primary site of HO (328 [60.9%]), then the elbow (115 [21.3%]), knee (77 [14.3%]) and shoulder (19 [3.5%]). For all patients, 181 of the surgeries were performed within the first year after the CNS damage, without recurrence of HO. Recurrence was not associated with etiology (p = 0.46), sex (p = 1.00), age at CNS damage (p = 0.2), multisite localization (p = 0.34), or delay to surgery (p = 0.7). CONCLUSIONS/SIGNIFICANCE: In patients with CNS damage, troublesome HO and recurrence occurs most frequently after traumatic brain injury and appears frequently in the hip and elbow. Early surgery for HO is not a factor of recurrence

Coronary artery surgery: cardiotomy suction or cell salvage?

Coronary artery bypass grafting (CABG) today results in what may be regarded as acceptable levels of blood loss with many institutions avoiding allogeneic red cell transfusion in over 60% of their patients. The majority of cardiac surgeons employ cardiotomy suction to preserve autologous blood during on-pump coronary artery bypass surgery; however the use of cardiotomy suction is associated with a more pronounced systemic inflammatory response and a resulting coagulopathy as well as exacerbating the microembolic load. This leads to a tendency to increased blood loss, transfusion requirement and organ dysfunction. Conversely, the avoidance of cardiotomy suction in coronary artery bypass surgery is not associated with an increased transfusion requirement. There is therefore no indication for the routine use of cardiotomy suction in on-pump coronary artery surgery