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1.
Thorac Cardiovasc Surg ; 71(4): 327-335, 2023 06.
Article in English | MEDLINE | ID: mdl-35785811

ABSTRACT

BACKGROUND: Pulmonary complications are the most common adverse event after lung resection, yet few large-scale studies have examined pertinent risk factors after video-assisted thoracoscopic surgery (VATS) lobectomy. Veterans, older and less healthy compared with nonveterans, represent a cohort that requires further investigation. Our objective is to determine predictors of pulmonary complications after VATS lobectomy in veterans. METHODS: A retrospective review was conducted on patients who underwent VATS lobectomy from 2008 to 2018 using the Veterans Affairs Surgical Quality Improvement Program database. Patients were divided into two cohorts based on development of a pulmonary complication within 30 days. Patient characteristics were compared via multivariable analysis to determine clinical predictors associated with pulmonary complication and reported as adjusted odds ratios (aORs) with 95% confidence intervals. Patients with preoperative pneumonia, ventilator dependence, and emergent cases were excluded. RESULTS: In 4,216 VATS lobectomy cases, 480 (11.3%) cases had ≥1 pulmonary complication. Preoperative factors independently associated with pulmonary complication included chronic obstructive pulmonary disease (COPD) (aOR = 1.37 [1.12-1.69]; p = 0.003), hyponatremia (aOR = 1.50 [1.06-2.11]; p = 0.021), and dyspnea (aOR = 1.33 [1.06-1.66]; p = 0.013). Unhealthy alcohol consumption was associated with pulmonary complication via univariable analysis (17.1 vs. 13.0%; p = 0.016). Cases with pulmonary complication were associated with increased mortality (12.1 vs. 0.8%; p < 0.001) and longer length of stay (12.0 vs. 6.8 days; p < 0.001). CONCLUSION: This analysis revealed several preoperative factors associated with development of pulmonary complications. It is imperative to optimize pulmonary-specific comorbidities such as COPD or dyspnea prior to VATS lobectomy. However, unhealthy alcohol consumption and hyponatremia were linked with development of pulmonary complication in our analysis and should be addressed prior to VATS lobectomy. Future studies should explore long-term consequences of pulmonary complications.


Subject(s)
Hyponatremia , Lung Neoplasms , Pulmonary Disease, Chronic Obstructive , Humans , Lung Neoplasms/surgery , Thoracic Surgery, Video-Assisted/adverse effects , Hyponatremia/complications , Hyponatremia/surgery , Pneumonectomy/adverse effects , Treatment Outcome , Postoperative Complications/etiology , Pulmonary Disease, Chronic Obstructive/complications , Retrospective Studies , Length of Stay , Lung , Dyspnea/complications , Dyspnea/surgery
2.
J Surg Res ; 275: 291-299, 2022 07.
Article in English | MEDLINE | ID: mdl-35313138

ABSTRACT

INTRODUCTION: Previous studies reported that increased hospital case volume improves outcomes after esophagectomy. Yet, the standard for high and low-volume hospitals varies in the literature. This study attempts to define the relationship between hospital operative volume and 30-day post-operative outcomes of esophagectomy in the Veterans Affairs (VA) system. METHODS: This is a retrospective review of patients that underwent esophagectomy from 2008 to 2019 utilizing the Veterans Affairs Surgical Quality Improvement Program Database. Receiver operating characteristic (ROC) analysis quantified an inflection point of optimal association between 30-day morbidity and mortality by facility volume. This point was used to separate cohorts for comparison of outcomes using 1:1 propensity score matching (PSM) to account for confounding covariates. RESULTS: Two thousand two hundred and twelve esophagectomies were performed from 2008 to 2019 and ROC analysis identified an inflection point at 43 cases (4 cases/y) where bidirectional operative volume significantly affected outcomes. Subsequent PSM resulted in 1718 cases utilized for analysis (n = 859 per cohort). Facility volume ≥4 cases/y was significantly associated with decreased odds of 30-day mortality (odds ratio(OR) = 0.57; P = 0.03), shorter length of stay (median 13 versus 14 d; P = 0.04) and longer operative times (6.5 versus 6.0 h; P < 0.001). CONCLUSIONS: VA hospitals that averaged ≥4 esophagectomies/y had significantly lower rates of mortality and length of stay. This volume threshold may serve as a benchmark to determine the optimal setting for esophageal resection. However, our findings also may reflect the benefits of cumulative operating room and multidisciplinary team experience at VA centers in conjunction with dedicated surgeons. Future studies should focus on long-term outcomes after esophagectomy in relation to hospital operative volume.


Subject(s)
Esophageal Neoplasms , Veterans , Esophageal Neoplasms/surgery , Esophagectomy/methods , Hospital Mortality , Hospitals, Low-Volume , Humans , Length of Stay , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies
3.
Thorac Cardiovasc Surg ; 70(4): 346-354, 2022 06.
Article in English | MEDLINE | ID: mdl-34044463

ABSTRACT

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) offers reduced morbidity compared with open thoracotomy (OT) for pulmonary surgery. The use of VATS over time has increased, but at a modest rate in civilian populations. This study examines temporal trends in VATS use and compares outcomes between VATS and OT in the Veterans Health Administration (VHA). METHODS: Patients who underwent pulmonary surgery (wedge or segmental resection, lobectomy, or pneumonectomy) at Veterans Affairs centers from 2008 to 2018 were retrospectively identified using the Veterans Affairs Surgical Quality Improvement Project database. The cohort was divided into OT and VATS and propensity score matched, taking into account the type of pulmonary resection, preoperative diagnosis, and comorbidities. Thirty-day postoperative outcomes were compared. The prevalence of VATS use and respective complications over time was also analyzed. RESULTS: A total of 16,895 patients were identified, with 5,748 per group after propensity matching. VATS had significantly lower rates of morbidity and a 2-day reduction in hospital stay. Whereas 76% of lung resections were performed open in 2008, nearly 70% of procedures were performed using VATS in 2018. While VATS was associated with an 8% lower rate of major complications compared with thoracotomy in 2008, patients undergoing VATS lung resection in 2018 had a 58% lower rate of complications (p < 0.001). CONCLUSIONS: VATS utilization at VHA centers has become the predominant technique used for pulmonary surgeries over time. OT patients had more complications and longer hospital stays compared with VATS. Over the study period, VATS patients had increasingly lower complication rates compared with open surgery.


Subject(s)
Lung Neoplasms , Veterans , Humans , Lung/surgery , Lung Neoplasms/complications , Lung Neoplasms/surgery , Pneumonectomy/adverse effects , Pneumonectomy/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Retrospective Studies , Thoracic Surgery, Video-Assisted/adverse effects , Thoracic Surgery, Video-Assisted/methods , Thoracotomy/adverse effects , Thoracotomy/methods , Treatment Outcome , United States/epidemiology
4.
J Card Surg ; 37(10): 3084-3090, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35822719

ABSTRACT

BACKGROUND: Cerebrovascular accident (CVA) after coronary artery bypass grafting (CABG) is a devastating complication. Patient comorbidities and intraoperative elements contribute to the risk of CVA. The aim of this study is to identify risk factors for CVA in Veterans undergoing CABG. METHODS: Veterans undergoing isolated CABG from 2008 to 2019 were retrospectively identified using the Veterans Affairs Surgical Quality Improvement Program (VASQIP) database. Thirty-day postoperative outcomes were observed. Univariate analysis followed by multivariable logistic regression identified independent risk factors for postoperative CVA. Receiver operating characteristic diagnostics identified optimal inflection points between continuous risk factors and odds of CVA. RESULTS: Twenty-eight thousand seven hundred fifty-seven patients met inclusion criteria. Incidence of CVA was 1.1% (310 cases). In multivariate analysis, preoperative cerebrovascular disease had the strongest association with postoperative CVA (adjusted odds ratio = 2.29; p < .001). There was an inverse relationship between CVA incidence and ejection fraction (EF), with EF of 35%-39% conferring a 2.11 times higher risk compared to EF >55% (p < .001). CVA incidence was not different in on-pump versus off-pump cases; however, after 104 min or more on bypass patients had a 55% greater adjusted odds of CVA (p < .001). Other risk factors included poor kidney function, prior myocardial infarction, and intra-aortic balloon pump use. CONCLUSION: The risk of CVA after CABG is multifactorial and involves multiple organ systems, including cardiac disease, poor renal function, and cerebrovascular disease, which was the strongest contributing risk factor. Optimization of these comorbidities and time on bypass may help improve clinical outcomes and lower the risk of this devastating complication.


Subject(s)
Cerebrovascular Disorders , Stroke , Veterans , Cerebrovascular Disorders/etiology , Coronary Artery Bypass/adverse effects , Humans , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Risk Factors , Stroke/epidemiology , Stroke/etiology , Treatment Outcome
5.
HPB (Oxford) ; 24(4): 478-488, 2022 04.
Article in English | MEDLINE | ID: mdl-34538739

ABSTRACT

BACKGROUND: Preoperative biliary drainage (PBD) has been advocated to address the plethora of physiologic derangements associated with cholestasis. However, available literature reports mixed outcomes and is based on largely outdated and/or single-institution studies. METHODS: Patients undergoing PBD prior to pancreaticoduodenectomy (PD) for periampullary malignancy between 2014-2018 were identified in the ACS-NSQIP pancreatectomy dataset. Patients with PBD were propensity-score-matched to those without PBD and 30-day outcomes compared. RESULTS: 8,970 patients met our inclusion criteria. 4,473 with obstruction and PBD were matched to 829 with no preoperative drainage procedure. In the non-jaundiced cohort, 711 stented patients were matched to 2,957 without prior intervention. PBD did not influence 30-day mortality (2.2% versus 2.4%) or major morbidity (19.8% versus 20%) in patients with obstructive jaundice. Superficial surgical site infections (SSIs) were more common with PBD (6.8% versus 9.2%), however, no differences in deep or organ-space SSIs were found. Patients without obstruction prior to PBD exhibited a 3-fold increase in wound dehiscence (0.5% versus 1.5%) additionally to increased superficial SSIs. CONCLUSION: PBD was not associated with an increase in 30-day mortality or major morbidity but increased superficial SSIs. PBD should be limited to symptomatic, profoundly jaundiced patients or those with a delay prior to PD.


Subject(s)
Duodenal Neoplasms , Jaundice, Obstructive , Drainage/adverse effects , Drainage/methods , Duodenal Neoplasms/surgery , Humans , Jaundice, Obstructive/etiology , Jaundice, Obstructive/surgery , Pancreatectomy , Pancreaticoduodenectomy , Postoperative Complications/etiology , Postoperative Complications/surgery , Preoperative Care/methods , Retrospective Studies , Treatment Outcome
6.
Anal Chem ; 92(16): 11186-11194, 2020 08 18.
Article in English | MEDLINE | ID: mdl-32806901

ABSTRACT

Thousands of per- and polyfluoroalkyl substances (PFAS) exist in the environment and pose a potential health hazard. Suspect and nontarget screening with liquid chromatography (LC)-high-resolution tandem mass spectrometry (HRMS/MS) can be used for comprehensive characterization of PFAS. To date, no automated open source PFAS data analysis software exists to mine these extensive data sets. We introduce FluoroMatch, which automates file conversion, chromatographic peak picking, blank feature filtering, PFAS annotation based on precursor and fragment masses, and annotation ranking. The software library currently contains ∼7 000 PFAS fragmentation patterns based on rules derived from standards and literature, and the software automates a process for users to add additional compounds. The use of intelligent data-acquisition methods (iterative exclusion) nearly doubled the number of annotations. The software application is demonstrated by characterizing PFAS in landfill leachate as well as in leachate foam generated to concentrate the compounds for remediation purposes. FluoroMatch had wide coverage, returning 27 PFAS annotations for landfill leachate samples, explaining 71% of the all-ion fragmentation (CF2)n related fragments. By improving the throughput and coverage of PFAS annotation, FluoroMatch will accelerate the discovery of PFAS posing significant human risk.


Subject(s)
Hydrocarbons, Fluorinated/analysis , Algorithms , Chromatography, Liquid/statistics & numerical data , Hydrocarbons, Fluorinated/chemistry , Small Molecule Libraries/chemistry , Software , Tandem Mass Spectrometry/statistics & numerical data , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/chemistry
7.
Metabolomics ; 16(5): 56, 2020 04 19.
Article in English | MEDLINE | ID: mdl-32307636

ABSTRACT

BACKGROUND: Understanding the interaction between organisms and the environment is important for predicting and mitigating the effects of global phenomena such as climate change, and the fate, transport, and health effects of anthropogenic pollutants. By understanding organism and ecosystem responses to environmental stressors at the molecular level, mechanisms of toxicity and adaptation can be determined. This information has important implications in human and environmental health, engineering biotechnologies, and understanding the interaction between anthropogenic induced changes and the biosphere. One class of molecules with unique promise for environmental science are lipids; lipids are highly abundant and ubiquitous across nearly all organisms, and lipid profiles often change drastically in response to external stimuli. These changes allow organisms to maintain essential biological functions, for example, membrane fluidity, as they adapt to a changing climate and chemical environment. Lipidomics can help scientists understand the historical and present biofeedback processes in climate change and the biogeochemical processes affecting nutrient cycles. Lipids can also be used to understand how ecosystems respond to historical environmental changes with lipid signatures dating back to hundreds of millions of years, which can help predict similar changes in the future. In addition, lipids are direct targets of environmental stressors, for example, lipids are easily prone to oxidative damage, which occurs during exposure to most toxins. AIM OF REVIEW: This is the first review to summarize the current efforts to comprehensively measure lipids to better understand the interaction between organisms and their environment. This review focuses on lipidomic applications in the arenas of environmental toxicology and exposure assessment, xenobiotic exposures and health (e.g., obesity), global climate change, and nutrient cycles. Moreover, this review summarizes the use of and the potential for lipidomics in engineering biotechnologies for the remediation of persistent compounds and biofuel production. KEY SCIENTIFIC CONCEPT: With the preservation of certain lipids across millions of years and our ever-increasing understanding of their diverse biological roles, lipidomic-based approaches provide a unique utility to increase our understanding of the contemporary and historical interactions between organisms, ecosystems, and anthropogenically-induced environmental changes.


Subject(s)
Climate Change , Ecosystem , Lipidomics , Lipids , Humans
8.
Heart Surg Forum ; 23(2): E225-E230, 2020 04 16.
Article in English | MEDLINE | ID: mdl-32364919

ABSTRACT

OBJECTIVE: Heart disease is still the leading cause of death for both men and women in the United States, and the rate of cardiovascular disease in veterans is even higher than in civilians. This study examines age-related outcomes for veterans undergoing cardiac surgeries at a single institution. METHODS: We included all veterans undergoing coronary artery bypass grafting (CABG) and/or valve surgery between 1997 to 2017 at a single Veterans Affairs (VA) medical center. We stratified this cohort into 4 age groups: ≤59 years old, 60-69 years old, 70-79 years old, and ≥80 years old. Outcomes in age groups were compared using standard statistical methods with the ≤59 years old group as reference. RESULTS: A total of 2,301 patients underwent open cardiac procedures at our institution. The frequency of simultaneous CABG and valve operations increased with age. Usage of cardiopulmonary bypass versus off-pump CABG and operative time was not associated with age. Increased pulmonary and renal complications as well as rates of postoperative arrhythmias all were associated with increasing age. There was no statistically significant difference in 30-day mortality. However, multivariable analysis adjusted for covariates showed all-cause mortality significantly was increased with older age groups (aHR ≥80 years old: 2.94 [2.07-4.17], P < .01; aHR 70-79 years old: 2.15 [1.63-2.83], P < 0.01, with ≤59 years old as reference). CONCLUSIONS: Older patients may have comparable perioperative mortality as their younger counterparts. However, age still is a significant predictor of all-cause mortality, pulmonary and renal complications, and postoperative arrhythmia, and should be considered as a major factor in preoperative risk assessment.


Subject(s)
Cardiac Surgical Procedures/adverse effects , Cardiovascular Diseases/surgery , Postoperative Complications/epidemiology , Risk Assessment/methods , Veterans , Age Distribution , Age Factors , Aged , Aged, 80 and over , Cardiovascular Diseases/epidemiology , Cause of Death/trends , Female , Humans , Incidence , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Survival Rate/trends , United States/epidemiology
9.
Heart Surg Forum ; 23(4): E531-E536, 2020 Jul 24.
Article in English | MEDLINE | ID: mdl-32726203

ABSTRACT

BACKGROUND: Studies of the civilian population with left main coronary artery disease (LMCAD) who underwent coronary artery bypass grafting (CABG) have shown 2% to 4.2% 30-day mortality. However, there is a lack of reporting from the veteran population. Here we analyze the outcomes of veterans with LMCAD who underwent CABG by a single surgeon at a single Veterans Affairs Medical Center (VAMC). METHODS: Veterans who underwent isolated CABG between 1998 to 2018 at a VAMC were further divided into a group with significant left main coronary artery disease (LMCAD) of stenosis greater than or equal to 50% and a group without left main coronary artery stenosis (non-LMCAD). The primary outcome was mortality. Secondary outcomes included postoperative complications. Multivariable regression analysis and Kaplan-Meier survival analysis were used to compare the two cohorts. RESULTS: The demographics and comorbidities are similar between the two cohorts except for higher average age and percentage of stroke in the LMCAD group (n = 509) compared to non-LMCAD (n = 927). Perioperative complications are comparable between the two groups except for increased length of stay (LOS) in the LMCAD group (12.9 ± 15.9 days versus 10.9 ± 9.0 days in non-LMCAD, P < .001). 30-day mortality in the LMCAD group is 4.1% versus 1.4% in non-LMCAD. However, Kaplan-Meier curves show no significant difference in adjusted overall survival throughout 15 years between the groups (P = .560). CONCLUSION: Veterans with LMCAD who underwent CABG have similar postoperative complications compared to non-LMCAD group. The 30-day mortality is higher in the LMCAD group; however, there is no difference in long-term survival.


Subject(s)
Coronary Artery Bypass/methods , Coronary Artery Disease/surgery , Drug-Eluting Stents , Veterans , Aged , Coronary Angiography , Coronary Artery Disease/diagnosis , Female , Follow-Up Studies , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome
10.
Heart Surg Forum ; 23(3): E323-E328, 2020 May 21.
Article in English | MEDLINE | ID: mdl-32524977

ABSTRACT

BACKGROUND: The Surgical Treatment for Ischemic Heart Failure (STICH) trial showed that surgical revascularization in ischemic cardiomyopathy (ICM) patients improves long-term mortality compared with medical treatment alone. This study examines how veterans with ICM undergoing revascularization fare against patients without ICM; it also examines the outcomes in the veteran population. METHODS: This is a retrospective review of a single-center database. From 2000 to 2018, 1,461 patients underwent isolated coronary artery bypass grafting (CABG). Two-hundred-one patients with an ejection fraction less than 35% were classified as the ICM cohort. The primary outcome was mortality. Secondary outcomes included postoperative complications. Subgroup analysis was performed within the ICM cohort comparing off-pump CABG (OPCAB) versus on-pump CABG (ONCAB). RESULTS: ICM patients had a higher incidence of myocardial infarction (MI), diabetes, chronic kidney disease (CKD), and preoperative intra-aortic balloon pump (IABP) use. The non-ICM cohort was more functionally independent. OPCAB was performed in 80.1% of ICM and 66.3% of non-ICM cohorts. There was no statistical difference between ICM and non-ICM cohorts in 30-day mortality (OR 1.94[0.79 - 4.75], P = .15). The ICM cohort had an increased 5-year mortality (OR 1.75[1.14 - 2.69], P = .01) and 10-year mortality (OR 1.71[1.09 - 2.67], P = .02). The ICM cohort showed improved, although not statistically significant, short-term mortality with OPCAB compared with ONCAB (3.1% versus 12.5%, OR 0.31[0.05 - 1.82], P = .20). CONCLUSION: Veterans with ICM undergoing CABG demonstrated similar short-term survival compared with non-ICM veterans. The long-term survival in the ICM cohort still is inferior to patients without ICM. There is a trend toward improved short-term survival in patients with ICM undergoing OPCAB.


Subject(s)
Coronary Artery Bypass/methods , Myocardial Ischemia/surgery , Veterans , Aged , Female , Hospital Mortality/trends , Humans , Male , Middle Aged , Myocardial Ischemia/diagnosis , Myocardial Ischemia/mortality , Retrospective Studies , Survival Rate/trends , Treatment Outcome , United States/epidemiology
11.
Aquaculture ; 5292020.
Article in English | MEDLINE | ID: mdl-33363294

ABSTRACT

A 9-week feeding trial was conducted with juvenile red drum, Sciaenops ocellatus, to evaluate the use of soy oil as a fish oil replacement. Three primary protein sources (fishmeal - FM, soybean meal - SBM, and soy protein concentrate - SPC) were utilized with 100% fish oil (FM, SBM, SPC), 75% fish oil (SBM, SPC), or 50% fish oil (FM, SBM, SPC) as the lipid source. Traditional growth and performance metrics (specific growth rate, feed consumption, feed conversion ratio) were tracked and tissue samples (liver, muscle, plasma, adipose, and brain) were collected for gas chromatography-based fatty acid profiling. Ten lipid metabolism related genes were analyzed for potential expression differences between dietary treatments in liver and muscle tissues and whole body and fillet tissues were sampled for proximate composition analyses. Forty- four fatty acids were measured by gas chromatography-flame ionization detector (GC-FID) and evaluated with principle component analysis and ANOVA to understand the dietary influence on lipid metabolism and health. Significant differences in growth rate were observed with the SBM 50% fish oil diet outperforming the FM 100% fish oil reference diet. All other soy protein-based diets performed statistically equivalent to both FM reference diets (100% and 50% fish oil) in regard to growth, however all soy protein-based formulations had significantly lower feed conversion ratios than the fishmeal-based references (p < .001). Gene expression differences were not significant in most cases, however often trended similarly as the observed performance. Fatty acid profiles differed as a function of oil source, with no apparent influence by protein source, with C18:2n-6 (linoleic acid) being-the primary differentiator. Overall, the six soy protein, fishmeal-free formulations performed equivalently or better than the fishmeal references with up to 50% of fish oil replaced by soybean oil.

12.
J Minim Access Surg ; 16(4): 429-430, 2020.
Article in English | MEDLINE | ID: mdl-31793448

ABSTRACT

A 69-year-old male presented with back tightness. Computed tomography revealed a 5 cm × 3 cm cystic para-oesophageal mass. A right robotic-assisted thoracoscopic resection was performed. Final pathology revealed a thoracic duct cyst (TDC). Robotic resection of a TDC has not been described in the literature previously but is shown in this report to be an effective and efficient way to perform the procedure. We suspect that robotic resection of mediastinal masses such as TDCs will become more common. Further studies comparing robotic to non-robotic resection of mediastinal masses would be helpful to determine the preferred treatment while minimising morbidity, length of stay and cost.

13.
Proc Natl Acad Sci U S A ; 113(38): E5588-97, 2016 09 20.
Article in English | MEDLINE | ID: mdl-27601680

ABSTRACT

The degeneracy of the genetic code allows nucleic acids to encode amino acid identity as well as noncoding information for gene regulation and genome maintenance. The rare arginine codons AGA and AGG (AGR) present a case study in codon choice, with AGRs encoding important transcriptional and translational properties distinct from the other synonymous alternatives (CGN). We created a strain of Escherichia coli with all 123 instances of AGR codons removed from all essential genes. We readily replaced 110 AGR codons with the synonymous CGU codons, but the remaining 13 "recalcitrant" AGRs required diversification to identify viable alternatives. Successful replacement codons tended to conserve local ribosomal binding site-like motifs and local mRNA secondary structure, sometimes at the expense of amino acid identity. Based on these observations, we empirically defined metrics for a multidimensional "safe replacement zone" (SRZ) within which alternative codons are more likely to be viable. To evaluate synonymous and nonsynonymous alternatives to essential AGRs further, we implemented a CRISPR/Cas9-based method to deplete a diversified population of a wild-type allele, allowing us to evaluate exhaustively the fitness impact of all 64 codon alternatives. Using this method, we confirmed the relevance of the SRZ by tracking codon fitness over time in 14 different genes, finding that codons that fall outside the SRZ are rapidly depleted from a growing population. Our unbiased and systematic strategy for identifying unpredicted design flaws in synthetic genomes and for elucidating rules governing codon choice will be crucial for designing genomes exhibiting radically altered genetic codes.


Subject(s)
Arginine/genetics , Escherichia coli/genetics , RNA, Messenger/genetics , Amino Acids/genetics , Codon/genetics , Genes, Essential/genetics , Genetic Code , Genome, Bacterial , Protein Biosynthesis/genetics , RNA, Messenger/biosynthesis
14.
Planta Med ; 83(3-04): 312-317, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27599262

ABSTRACT

Indiscriminate use of synthetic pesticides can be hazardous to both humans and the environment, but the use of natural products as a source of bio-based products, such as Melia azedarach extracts, is an interesting approach to overcome these hazards. Unfortunately, the limonoids found in M. azedarach with desired insecticidal properties (e.g. azadirachtin) may also be present with limonoids toxic to mammals. The goal of this report was to develop a fast and reliable MS-based experiment to characterize meliatoxins in crude extracts of M. azedarach, in order to provide unequivocal assessment of the safety for extracts for application in the field. MS and MS/MS experiments using MALDI ionization were evaluated as tools for the assignment of characteristic ions produced by each meliatoxin in crude extracts.The use of different experiments in combination, such as the analysis of fragment m/z 557 and [M + Na]+ (adducts ions m/z 681 and m/z 667), MALDI-MS can be used for detection of meliatoxins A1/B1 or A2/B2 in a crude extract and may be used to discriminate meliatoxins A from B, respectively. Subsequent MS/MS experiments can distinguish between the presence of group 1 and/or 2 in each class of meliatoxins classifying the proposed approach as a quick and efficient quality control method of meliatoxins in real M. azedarach samples.


Subject(s)
Limonins/chemistry , Melia azedarach/chemistry , Plant Extracts/chemistry , Fruit/chemistry , Limonins/analysis , Limonins/toxicity , Plant Extracts/isolation & purification , Plant Extracts/toxicity , Quality Control , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods , Tandem Mass Spectrometry/methods
15.
Nucleic Acids Res ; 42(7): 4779-90, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24452804

ABSTRACT

Selection has been invaluable for genetic manipulation, although counter-selection has historically exhibited limited robustness and convenience. TolC, an outer membrane pore involved in transmembrane transport in E. coli, has been implemented as a selectable/counter-selectable marker, but counter-selection escape frequency using colicin E1 precludes using tolC for inefficient genetic manipulations and/or with large libraries. Here, we leveraged unbiased deep sequencing of 96 independent lineages exhibiting counter-selection escape to identify loss-of-function mutations, which offered mechanistic insight and guided strain engineering to reduce counter-selection escape frequency by ∼40-fold. We fundamentally improved the tolC counter-selection by supplementing a second agent, vancomycin, which reduces counter-selection escape by 425-fold, compared colicin E1 alone. Combining these improvements in a mismatch repair proficient strain reduced counter-selection escape frequency by 1.3E6-fold in total, making tolC counter-selection as effective as most selectable markers, and adding a valuable tool to the genome editing toolbox. These improvements permitted us to perform stable and continuous rounds of selection/counter-selection using tolC, enabling replacement of 10 alleles without requiring genotypic screening for the first time. Finally, we combined these advances to create an optimized E. coli strain for genome engineering that is ∼10-fold more efficient at achieving allelic diversity than previous best practices.


Subject(s)
Bacterial Outer Membrane Proteins/genetics , Escherichia coli Proteins/genetics , Genetic Engineering/methods , Membrane Transport Proteins/genetics , Alleles , Biomarkers , Escherichia coli/genetics , Gene Deletion , Gene Duplication , Genome, Bacterial , High-Throughput Nucleotide Sequencing , Phenotype
16.
Am Surg ; 89(12): 5487-5491, 2023 Dec.
Article in English | MEDLINE | ID: mdl-36786011

ABSTRACT

BACKGROUND: Prior studies suggest similar efficacy between large-bore chest tube (CT) placement and small-bore pigtail catheter (PC) placement for the treatment of pleural space processes. This study examined reintervention rates of CT and PC in patients with pneumothorax, hemothorax, and pleural effusion. METHODS: This retrospective study examined patients from September 2015 through December 2020. Patients were identified using ICD codes for pneumothorax, hemothorax, or pleural effusion. Use of a pigtail catheter (≤14Fr) or surgical chest tube (≥20Fr) was noted. The primary outcome was overall reintervention rate within 30 days of tube insertion. Patients who died with a pleural drainage catheter in place, unrelated to complications from chest tube placement, were excluded. RESULTS: There were 1032 total patients in the study: 706 CT patients and 326 PC patients. The PC group was older with more comorbidities and more likely to have effusion as the indication for pleural drainage. Patients with PC were 2.35 times more likely to have the tube replaced or repositioned (P < .0001), 1.77 times more likely to require any reintervention (P = .001) and 2.09 times more likely to remain in the hospital >14 days (P < .0001) compared to patients with CT. CONCLUSION: PCs have a significantly higher reintervention rate compared to CT for the treatment of pneumothorax, hemothorax, and pleural effusion. Although PC are believed to cause less pain and tissue trauma, they do not necessarily drain the pleural space as well as CT. Decisions on which method of draining the chest should be made on a case-by-case basis.


Subject(s)
Pleural Effusion , Pneumothorax , Humans , Chest Tubes/adverse effects , Hemothorax/etiology , Hemothorax/surgery , Retrospective Studies , Pneumothorax/surgery , Pneumothorax/etiology , Catheters/adverse effects , Pleural Effusion/surgery , Drainage/methods
17.
Am Surg ; 89(4): 656-664, 2023 Apr.
Article in English | MEDLINE | ID: mdl-34346712

ABSTRACT

BACKGROUND: Veterans undergoing elective surgery for diverticular disease have an ostomy creation rate of 18%. The purpose of this study was to analyze the outcomes and timing of ostomy reversal surgery, perioperative complications, and differences between colostomy and ileostomy reversal outcomes. METHODS: A retrospective review of the Veterans Affairs Surgical Quality Improvement Project (VASQIP) database was performed. Patients undergoing elective colectomy for diverticular disease between 2004 and 2018 were identified. Demographics, comorbidities, ostomy type, time to reversal, and postoperative complications were analyzed. RESULTS: 4,198 patients underwent elective colectomy for diverticular disease, with 751 patients (17.9%) receiving an ostomy. Of patients who received an ostomy, 407 had ostomy reversal surgery within the Veterans Health Administration system (54.2%), with 243 colostomies, 149 ileostomies, and 15 unspecified. Median time to ostomy reversal was 5.0 months (interquartile range 3.2, 7.8). Complication rate after reversal was 23.1%; surgical site infection was most common (9.1%). Patients with American Society of Anesthesiologists classification >3 (adjusted odds ratio (aOR) = .40[.22-.72]), increasing age (aOR = .98[.97-.99]), laparoscopic index procedure (aOR = .42[.27-.63]), and hypertension (aOR = .63[.46-.87]) were less likely to have their ostomy reversed. There were no differences in postoperative complication rates after ostomy vs ileostomy reversals. Reversals after 4.6 months were associated with 3.4-times higher odds of complications. CONCLUSION: Ostomy creation and reversal rates are similar between the veteran and non-veteran populations in the United States. Delays in reversal surgery were associated with worse postoperative outcomes, which underscore the importance of close follow-up for patients with an ostomy after elective colectomy for diverticular disease.


Subject(s)
Diverticular Diseases , Ostomy , Humans , United States , United States Department of Veterans Affairs , Ostomy/adverse effects , Colostomy/adverse effects , Diverticular Diseases/complications , Retrospective Studies , Hospitals , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Colectomy/adverse effects
18.
Am Surg ; 89(4): 1254-1257, 2023 Apr.
Article in English | MEDLINE | ID: mdl-33596103

ABSTRACT

BACKGROUND: Traumatic duodenal injury is a rare, potentially devastating condition with challenging management decisions. Contemporary literature on operative management of duodenal injury is lacking. The purpose of this study is to assess optimal management strategies based on outcomes of patients with traumatic duodenal injury at a single trauma center. METHODS: A retrospective study of patients with traumatic duodenal injury from 2013-2020 at a level 1 trauma center was performed. Patient demographics, grade of injury as noted on CT scan or intraoperatively, surgical procedure(s) performed, and resultant outcomes were extracted. RESULTS: After excluding one patient due to death on arrival, 23 patients met inclusion criteria. Injuries consisted of grade 1 (n = 7), grade 2 (n = 2), grade 3 (n = 12), and grade 5 (n = 2); there were no grade 4 injuries. Patients were predominantly male (83%) with a median age of 30 years old. Nineteen patients (82%) underwent surgery. Four of nine patients (44%) with grade 1/2 injuries had hematomas and were managed non-operatively. The remaining five patients (56%) with grade 1/2 injuries underwent operation, which included primary repair (n = 3), duodenal exclusion (n = 1), and periduodenal drainage (n = 1). Of 12 patients with grade 3 injury, 6 underwent primary repair and 6 underwent resection. Three patients who underwent primary repair and one who underwent resection developed a duodenal leak. All patients with grade 5 injury (n = 2) underwent pancreaticoduodenectomy. CONCLUSION: Grade 1 and 2 duodenal hematomas can be managed non-operatively, while lacerations require operative repair. Outcomes may be better following resection in patients with grade 3 injury.


Subject(s)
Abdominal Injuries , Duodenal Diseases , Wounds, Nonpenetrating , Humans , Male , Adult , Female , Retrospective Studies , Duodenum/surgery , Duodenum/injuries , Abdominal Injuries/diagnosis , Abdominal Injuries/surgery , Wounds, Nonpenetrating/surgery , Hematoma
19.
Nat Protoc ; 18(2): 374-395, 2023 02.
Article in English | MEDLINE | ID: mdl-36411351

ABSTRACT

Genetic engineering and implantable bioelectronics have transformed investigations of cardiovascular physiology and disease. However, the two approaches have been difficult to combine in the same species: genetic engineering is applied primarily in rodents, and implantable devices generally require larger animal models. We recently developed several miniature cardiac bioelectronic devices suitable for mice and rats to enable the advantages of molecular tools and implantable devices to be combined. Successful implementation of these device-enabled studies requires microsurgery approaches that reliably interface bioelectronics to the beating heart with minimal disruption to native physiology. Here we describe how to perform an open thoracic surgical technique for epicardial implantation of wireless cardiac pacemakers in adult rats that has lower mortality than transvenous implantation approaches. In addition, we provide the methodology for a full biocompatibility assessment of the physiological response to the implanted device. The surgical implantation procedure takes ~40 min for operators experienced in microsurgery to complete, and six to eight surgeries can be completed in 1 d. Implanted pacemakers provide programmed electrical stimulation for over 1 month. This protocol has broad applications to harness implantable bioelectronics to enable fully conscious in vivo studies of cardiovascular physiology in transgenic rodent disease models.


Subject(s)
Cardiac Surgical Procedures , Pacemaker, Artificial , Animals , Mice , Rats , Cardiac Surgical Procedures/methods
20.
Semin Thorac Cardiovasc Surg ; 34(3): 892-901, 2022.
Article in English | MEDLINE | ID: mdl-34364946

ABSTRACT

Dysfunction of the right ventricle (RV) is common in patients with advanced left-sided valve disease and the significant impact of RV dysfunction on both short and long-term outcome is well established. However, considerations of RV function are largely absent in current management guidelines for valve disease and cardiac procedural risk models. As the indications and use of trans-catheter therapies rapidly expand for patients with acquired valvular disease, it is critical for clinicians to understand and consider RV function when making decisions for these patients. This review summarizes contemporary data on the assessment of RV function, the prognostic importance of baseline RV dysfunction on surgical and transcatheter procedures for acquired left-sided valvular disease, and the relative impact of these interventions on RV function. Baseline RV dysfunction is a powerful predictor of poor short- and long-term outcome after any therapeutic intervention for acquired left-sided cardiac valve disease. Surgical intervention for aortic or mitral valve disease is associated with a significant but transient decline in RV function, whereas trans-catheter procedures generally do not appear to have detrimental effects on either longitudinal or global RV function. Guidelines for therapy in patents with acquired left-sided valvular disease should account for RV dysfunction. Whereas surgical intervention in these patients leads to a predictable decline in RV function, trans-catheter therapies largely do not appear to have this effect. Further study is needed to determine the impact of these findings on current practice.


Subject(s)
Heart Valve Diseases , Ventricular Dysfunction, Right , Catheters , Heart Valve Diseases/diagnostic imaging , Heart Valve Diseases/surgery , Heart Ventricles/surgery , Humans , Treatment Outcome , Ventricular Dysfunction, Right/complications , Ventricular Dysfunction, Right/therapy , Ventricular Function, Right
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