Different types of cannulation techniques are available for minimally invasive cardiac surgery. At our institution, we favor a femoral platform for most minimally invasive cardiac procedures. Here, ...we review our results utilizing this cannulation approach.
We retrospectively reviewed all minimally invasive valve surgeries that were performed at our institution between January 2009 and January 2015. Operative times, lengths of stay, postoperative complications, and mortality were analyzed.
We identified 2,645 consecutive patients. The mean age was 69.7 ± 12.77 years, and 1,412 patients (53.4%) were male. Three hundred fifty-eight patients (13.5%) had a history of cerebrovascular accident, 422 (16%) had previous heart surgery, and 276 (10.4%) had a history of peripheral vascular disease. The procedures performed were isolated aortic valve replacements (42.1%), isolated mitral valve operations (40.6%), tricuspid valve repairs (0.57%), double valve surgery (15%), triple valve surgery (0.3%), and ascending aortic aneurysm resection with and without circulatory arrest (5%). Femoral cannulation and central cannulation were utilized in 2,400 patients (90.7%) and 244 patients (9.3%), respectively. The median aortic cross-clamp time and cardiopulmonary bypass time were 81 minutes (interquartile range, 65 to 105) and 113 minutes (interquartile range, 92 to 142), respectively. The median postoperative hospital length of stay was 6 days (interquartile range, 5 to 9). There were 31 cerebrovascular accidents (1.17%), no aortic dissections, two compartment syndromes, two femoral arterial pseudoaneurysms, and 174 (6.65%) groin wound seromas. The overall 30-day mortality was 57 patients (2.15%).
Minimally invasive cardiac surgical procedures utilizing femoral cannulation techniques have a low risk of complications.
The tumor microenvironment plays an important role in modulating tumor progression. Earlier, we showed that S100A8/A9 proteins secreted by myeloid-derived suppressor cells (MDSC) present within ...tumors and metastatic sites promote an autocrine pathway for accumulation of MDSC. In a mouse model of colitis-associated colon cancer, we also showed that S100A8/A9-positive cells accumulate in all regions of dysplasia and adenoma. Here we present evidence that S100A8/A9 interact with RAGE and carboxylated glycans on colon tumor cells and promote activation of MAPK and NF-κB signaling pathways. Comparison of gene expression profiles of S100A8/A9-activated colon tumor cells versus unactivated cells led us to identify a small cohort of genes upregulated in activated cells, including Cxcl1, Ccl5 and Ccl7, Slc39a10, Lcn2, Zc3h12a, Enpp2, and other genes, whose products promote leukocyte recruitment, angiogenesis, tumor migration, wound healing, and formation of premetastatic niches in distal metastatic organs. Consistent with this observation, in murine colon tumor models we found that chemokines were upregulated in tumors, and elevated in sera of tumor-bearing wild-type mice. Mice lacking S100A9 showed significantly reduced tumor incidence, growth and metastasis, reduced chemokine levels, and reduced infiltration of CD11b(+)Gr1(+) cells within tumors and premetastatic organs. Studies using bone marrow chimeric mice revealed that S100A8/A9 expression on myeloid cells is essential for development of colon tumors. Our results thus reveal a novel role for myeloid-derived S100A8/A9 in activating specific downstream genes associated with tumorigenesis and in promoting tumor growth and metastasis.
Increasing evidence has demonstrated that epigenetic factors can profoundly influence gene expression and, in turn, influence resistance or susceptibility to disease. Epigenetic drugs, such as ...histone deacetylase (HDAC) inhibitors, are finding their way into clinical practice, although their exact mechanisms of action are unclear. To identify mechanisms associated with HDAC inhibition, we performed microarray analysis on brain and muscle samples treated with the HDAC1/3-targeting inhibitor, HDACi 4b. Pathways analyses of microarray datasets implicate DNA methylation as significantly associated with HDAC inhibition. Further assessment of DNA methylation changes elicited by HDACi 4b in human fibroblasts from normal controls and patients with Huntington’s disease (HD) using the Infinium HumanMethylation450 BeadChip revealed a limited, but overlapping, subset of methylated CpG sites that were altered by HDAC inhibition in both normal and HD cells. Among the altered loci of Y chromosome-linked genes, KDM5D , which encodes Lys (K)-specific demethylase 5D, showed increased methylation at several CpG sites in both normal and HD cells, as well as in DNA isolated from sperm from drug-treated male mice. Further, we demonstrate that first filial generation (F1) offspring from drug-treated male HD transgenic mice show significantly improved HD disease phenotypes compared with F1 offspring from vehicle-treated male HD transgenic mice, in association with increased Kdm5d expression, and decreased histone H3 Lys4 (K4) (H3K4) methylation in the CNS of male offspring. Additionally, we show that overexpression of Kdm5d in mutant HD striatal cells significantly improves metabolic deficits. These findings indicate that HDAC inhibitors can elicit transgenerational effects, via cross-talk between different epigenetic mechanisms, to have an impact on disease phenotypes in a beneficial manner.
Significance We demonstrate that histone deacetylase (HDAC) inhibition can elicit changes in DNA methylation in Huntington’s disease (HD) human fibroblasts, as well as in sperm from HD transgenic mice, in association with DNA methylation-related gene expression changes. We suggest that alterations in sperm DNA methylation lead to transgenerational effects, and, accordingly, we show that first filial generation (F1) offspring of HDAC inhibitor-treated male HD transgenic mice show improved HD disease phenotypes compared with F1 offspring from vehicle-treated male HD transgenic mice. These findings have significant implications for human health because they enforce the concept that ancestral drug exposure may be a major molecular factor that can affect disease phenotypes, yet in a positive manner. Further, we implicate Lys (K)-specific demethylase 5d expression in this phenomenon.
Pluripotent stem cells (PSCs) are defined by their potential to generate all cell types of an organism. The standard assay for pluripotency of mouse PSCs is cell transmission through the germline, ...but for human PSCs researchers depend on indirect methods such as differentiation into teratomas in immunodeficient mice. Here we report PluriTest, a robust open-access bioinformatic assay of pluripotency in human cells based on their gene expression profiles.
There is concern that the stresses of inducing pluripotency may lead to deleterious DNA mutations in induced pluripotent stem cell (iPSC) lines, which would compromise their use for cell therapies. ...Here we report comparative genomic analysis of nine isogenic iPSC lines generated using three reprogramming methods: integrating retroviral vectors, non-integrating Sendai virus and synthetic mRNAs. We used whole-genome sequencing and de novo genome mapping to identify single-nucleotide variants, insertions and deletions, and structural variants. Our results show a moderate number of variants in the iPSCs that were not evident in the parental fibroblasts, which may result from reprogramming. There were only small differences in the total numbers and types of variants among different reprogramming methods. Most importantly, a thorough genomic analysis showed that the variants were generally benign. We conclude that the process of reprogramming is unlikely to introduce variants that would make the cells inappropriate for therapy.
Rift Valley fever (RVF), a zoonotic vectorborne viral disease, causes loss of life among humans and livestock and an adverse effect on the economy of affected countries. Vaccination is the most ...effective way to protect livestock; however, during protracted interepidemic periods, farmers discontinue vaccination, which leads to loss of herd immunity and heavy losses of livestock when subsequent outbreaks occur. Retrospective analysis of the 2008-2011 RVF epidemics in South Africa revealed a pattern of continuous and widespread seasonal rainfall causing substantial soil saturation followed by explicit rainfall events that flooded dambos (seasonally flooded depressions), triggering outbreaks of disease. Incorporation of rainfall and soil saturation data into a prediction model for major outbreaks of RVF resulted in the correctly identified risk in nearly 90% of instances at least 1 month before outbreaks occurred; all indications are that irrigation is of major importance in the remaining 10% of outbreaks.
A promising new compound class for treating human malaria is the imidazolopiperazines (IZP) class. IZP compounds KAF156 (Ganaplacide) and GNF179 are effective against Plasmodium symptomatic asexual ...blood-stage infections, and are able to prevent transmission and block infection in animal models. But despite the identification of resistance mechanisms in P. falciparum, the mode of action of IZPs remains unknown. To investigate, we here combine in vitro evolution and genome analysis in Saccharomyces cerevisiae with molecular, metabolomic, and chemogenomic methods in P. falciparum. Our findings reveal that IZP-resistant S. cerevisiae clones carry mutations in genes involved in Endoplasmic Reticulum (ER)-based lipid homeostasis and autophagy. In Plasmodium, IZPs inhibit protein trafficking, block the establishment of new permeation pathways, and cause ER expansion. Our data highlight a mechanism for blocking parasite development that is distinct from those of standard compounds used to treat malaria, and demonstrate the potential of IZPs for studying ER-dependent protein processing.
Neuroendocrine (NE) phenotype, seen in >30% of prostate adenocarcinomas (PCa), and NE prostate tumors are implicated in aggressive prostate cancer. Formation of NE prostate tumors in the
TRAMP mouse ...model was suppressed in mice lacking the ubiquitin ligase Siah2, which regulates HIF-1α availability. Cooperation between HIF-1α and FoxA2, a transcription factor expressed in NE tissue, promotes recruitment of p300 to transactivate select HIF-regulated genes,
Hes6,
Sox9, and
Jmjd1a. These HIF-regulated genes are highly expressed in metastatic PCa and required for hypoxia-mediated NE phenotype, metastasis in PCa, and the formation of NE tumors. Tissue-specific expression of FoxA2 combined with Siah2-dependent HIF-1α availability enables a transcriptional program required for NE prostate tumor development and NE phenotype in PCa.
► Ubiquitin ligase Siah2 is required for NE prostate tumor development ► HIF1α and FoxA2 cooperation identifies tissue-specific HIF transcriptional synergy ► HIF1α/FoxA2 target genes are required for NE phenotype of prostate tumors ► HIF1α/FoxA2 target genes are highly expressed in metastatic prostate tumors
Introduction/Background
After its initial description in 1990, video-assisted thoracoscopic surgery (VATS) has emerged as the minimally invasive approach for lung resection in early lung cancer.
...Methods
A retrospective review of prospectively collected data on patients who underwent robotic pulmonary resection for cancer by a single surgeon, between years 2009 and 2013, was performed. Age, gender, type and duration of surgery, length of stay, estimated blood loss, early and late complications, follow-up time, and local recurrence were reviewed and analyzed descriptively.
Results
Three hundred and thirty-one patients underwent the procedure for pulmonary neoplasm. Two hundred and fifty-nine (79 %) patients underwent anatomic lobectomies, 56 (17 %) patients had wedge resection, while five (1.5 %) patients underwent pneumonectomy. In 11 patients, no pulmonary resection was performed for different reasons. Most common neoplasm was adenocarcinoma (185, 56 %). All procedures involved a systematic mediastinal and hilar lymph node exploration and removal of suspicious nodes. Twenty-six (6.9 %) procedures were converted to open thoracotomy. Mean duration of surgery was 185.63 min. Mean length of hospital stay was 5.52 days. Mean estimated blood loss (EBL) was 47.85 ml. Mean follow-up was 249.41 days (20–1550 days), and five (1.5 %) patients developed local recurrence. Early complications were seen in 29 patients (8.8 %), most commonly cardiac arrhythmias (20, 6 %).
Conclusion
Robotic video-assisted thoracoscopic surgery is feasible in lung lesions, with all the advantages of VATS in terms of decreased length of stay and decreased blood loss with local recurrence rate and complication rate comparable to open procedures. There is a clear need for more studies comparing the apparent advantages of robotic-assisted surgery with increased cost of technology.
Rice to Ruin Roy Williams, Alexander Lucas Lofton
03/2018
eBook
In the 1780s Jonathan Lucas, on a journey from his native England, shipwrecked near the Santee Delta of South Carolina, about forty miles north of Charleston. Lucas, the son of English mill owners ...and builders, found himself, fortuitously, near vast acres of swamp and marshland devoted to rice cultivation. When the labor-intensive milling process could not keep pace with high crop yields, Lucas was asked by planters to build a machine to speed the process. In 1787 he introduced the first highly successful water-pounding rice mill—creating the foundation of an international rice mill dynasty. In Rice to Ruin, Roy Williams III and Alexander Lucas Lofton recount the saga of the precipitous rise and ultimate fall of that empire. Lucas’s invention did for rice, South Carolina’s first great agricultural staple, what Eli Whitney did for cotton with his cotton gin. With his sons Jonathan Lucas II and William Lucas, Lucas built rice mills throughout the lowcountry. Eventually the rice kingdom extended to India, Egypt, and Europe after the younger Jonathan Lucas moved to London to be at the center of the international rice trade. Their lives were grand until the American Civil War and its aftermath. The end of slave labor changed the family’s fortunes. The capital tied up in slaves evaporated; the plantations and town houses had to be sold off one by one; and the rice fields once described as “the gold mines of South Carolina" often failed or were no longer planted. Disease and debt took its toll on the Lucas clan, and, in the decades that followed, efforts to regain the lost fortune proved futile. In the end the once-glorious Carolina gold rice fields that had brought riches left the family in ruin.
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