Prenatal diagnosis of trisomy 1q21-qter: case report and review of literature

We report on a midtrimester fetus with multiple malformations, who was prenatally found to have pure partial trisomy 1q with duplication 1q21-qter. Prenatal ultrasound at 23 gestational weeks demonstrated craniofacial dysmorphism, ventriculomegaly, hand anomalies, and multiple visceral anomalies including cardiac defect, duodenal atresia, omphalocele, and urethral obstruction in the fetus. After pregnancy termination, external morphologic examination confirmed the sonographic characteristics, but autopsy was refused. Cytogenetic analysis (GTG banding) and subtelomeric probes (FISH) demonstrated an aberrant karyotype 46,XY,der(1)(1qter --> 1q21::1p36.3 --> 1qter) in a total of 139 amniotic fluid cells. Trisomy of the long arm of chromosome 1 is a rare condition. Large duplications of almost the entire 1q had so far been described in five mosaic cases. The present case and review of the literature suggest that duplication 1q21-qter is a serious condition with pre- or perinatal demise of all reported cases. This case further delineates the phenotype in trisomy 1q.     

The Macrophage Mediates the Renoprotective Effects of Endotoxin Preconditioning

Preconditioning is a preventative approach, whereby minimized insults generate protection against subsequent larger exposures to the same or even different insults. In immune cells, endotoxin preconditioning downregulates the inflammatory response and yet, preserves the ability to contain infections. However, the protective mechanisms of preconditioning at the tissue level in organs such as the kidney remain poorly understood. Here, we show that endotoxin preconditioning confers renal epithelial protection in various models of sepsis in vivo. We also tested the hypothesis that this protection results from direct interactions between the preconditioning dose of endotoxin and the renal tubules. This hypothesis is on the basis of our previous findings that endotoxin toxicity to nonpreconditioned renal tubules was direct and independent of immune cells. Notably, we found that tubular protection after preconditioning has an absolute requirement for CD14-expressing myeloid cells and particularly, macrophages. Additionally, an intact macrophage CD14-TRIF signaling pathway was essential for tubular protection. The preconditioned state was characterized by increased macrophage number and trafficking within the kidney as well as clustering of macrophages around S1 proximal tubules. These macrophages exhibited increased M2 polarization and upregulation of redox and iron-handling molecules. In renal tubules, preconditioning prevented peroxisomal damage and abolished oxidative stress and injury to S2 and S3 tubules. In summary, these data suggest that macrophages are essential mediators of endotoxin preconditioning and required for renal tissue protection. Preconditioning is, therefore, an attractive model to investigate novel protective pathways for the prevention and treatment of sepsis.     

Infections of cardiac implantable electronic devices: a retrospective multicenter observational study

Infections of cardiac implantable electronic devices (CIED) can cause significant morbidity, mortality, and financial burden. Although staphylococcal organisms account for most infections of these cardiac devices, approximately 20% of all CIED-related infections are caused by non-Staphylococcus species. Herein we describe and compare the demographics, clinical presentation, and outcomes of Staphylococcus aureus and non-staphylococcal infections of CIED.We performed a retrospective, multicenter, observational study of patients from 4 academic hospitals in Houston between 2002 and 2009. All 80 identified non-staphylococcal CIED-related infections were matched, at a 1:1 ratio, to S. aureus infections.Although the demographics and general comorbidities in the 2 study groups were relatively similar, the S. aureus group had a higher proportion of patients with coronary artery disease, diabetes mellitus, and end-stage renal disease. Additionally, 81% of S. aureus compared with only 48.5% of the non-staphylococcal CIED-related infections were health care-associated (p < 0.001). Furthermore, when compared to non-staphylococcal infections, the S. aureus group had more indwelling intravascular foreign material (p < 0.001), more rapid clinical progression (p < 0.001), and overall worse clinical presentation (p < 0.001). However, after stratifying by clinical presentation, the mortality rates in the 2 groups were similar (p = 0.45).Since approximately one-fifth of all CIED-related infections are caused by non-staphylococcal organisms, and untimely antibiotic treatment can result in serious complications, it may be prudent to broaden empiric antimicrobial therapy to cover both Gram-positive and -negative bacteria, until the causative organism is identified.     

Diagnostic accuracy of somatosensory evoked potential and electroencephalography during carotid endarterectomy

Background and Purpose: Perioperative stroke risk following carotid endarterectomy (CEA) is reported to be approximately 2–3%. The diagnostic accuracies of intraoperative EEG and SSEP monitoring during CEA have been studied separately. However, to date, the effectiveness of simultaneous EEG and SSEP monitoring during CEA has only been evaluated in small study populations. This study examined the diagnostic accuracy of combined EEG and SSEP monitoring in a large (N = 1165) patient population.

Methods: This study included 1165 patients who underwent CEA from 2000 to 2012 at the University of Pittsburgh Medical Center. The sensitivities, specificities, and diagnostic odds ratio of EEG and SSEP monitoring methods were examined separately and together. Receiver operating characteristic curves were plotted to assess sensitivity and specificity of single and combined Intraoperative monitoring (IONM) methods.

Results: Maximum sensitivity was obtained with multimodality monitoring with an IONM change in either EEG or SSEP of 50.00 (95% CI, 30.66–69.34). The specificity of simultaneous EEG and SSEP changes was 93.95 (95% CI, 92.28–95.35%). Maximum area under ROC curve obtained for IONM change in either EEG or SSEP was 0.660 (95% CI, 0.547–0.773, p-value 0.004).

Conclusion: The diagnostic accuracy of multimodality IONM during CEA is higher than an approach using single modality IONM. Simultaneous EEG and SSEP monitoring improves the likelihood of detecting periprocedural strokes after CEA. Neuro protective therapies to prevent periprocedural strokes can be based on changes in SSEP and EEG during CEA.     

Expanded access to investigational drugs: balancing patient safety with potential therapeutic benefits

Introduction: Expanded access is the use of an investigational product by patients with serious medical conditions without participation in a clinical trial. It is a complicated process involving the collaboration of many parties and pharmaceutical companies. Ongoing efforts focus on accelerating expanded access procedures in the best interest of patients with cancer.

Areas covered: We review the regulatory and ethical challenges encountered in efforts to optimize expanded access.

Expert opinion: In the era of personalized medicine, patients may benefit from novel therapeutic agents that demonstrate encouraging results in early studies. However, drug approval is a lengthy and cumbersome procedure that might exceed the time frame of a life-threatening disease. Expanded access provides options to patients with unmet needs. It may provide informative safety and efficacy data to the manufacturers and the scientific and regulatory organizations.

Ongoing efforts are being made by global governmental and scientific committees, regulatory agencies, and patient organizations to address the ethical and regulatory issues and to optimize the expanded access process. Their goal is to expand access to promising novel drugs for individual patients and to accelerate the necessary procedures while preserving patient safety.     

Combination of tigecycline and N-acetylcysteine reduces biofilm-embedded bacteria on vascular catheters

To assess the efficacy of an antibiofilm/antimicrobial agent combination, we incubated catheter segments colonized with one of six studied bacterial organisms in N-acetylcysteine, tigecycline, N-acetylcysteine-tigecycline, or saline. Segments were washed, sonicated, and cultured. N-acetylcysteine-tigecycline significantly decreased all viable biofilm-associated bacteria and was synergistic for methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis.     

Anti-Inflammatory properties of Salograviolide A purified from Lebanese plant Centaurea ainetensis

Background  

Anti-inflammatory activities of medicinal plants have largely been attributed to their content of sesquiterpene lactones (SLs). SLs are predominantly found in the sunflower family Asteraceae and have been isolated from many plants of this family, particularly Centaurea. The anti-inflammatory activities of extract of Centaurea ainetensis, a Lebanese endemic plant, and the isolated active molecule were assessed for their potential ant-inflammatory activities.