Engineering control of bacterial cellulose production using a genetic toolkit and a new cellulose-producing strain.

Bacterial cellulose is a strong and ultrapure form of cellulose produced naturally by several species of the Acetobacteraceae Its high strength, purity, and biocompatibility make it of great interest to materials science; however, precise control of its biosynthesis has remained a challenge for biotechnology. Here we isolate a strain of Komagataeibacter rhaeticus (K. rhaeticus iGEM) that can produce cellulose at high yields, grow in low-nitrogen conditions, and is highly resistant to toxic chemicals. We achieved external control over its bacterial cellulose production through development of a modular genetic toolkit that enables rational reprogramming of the cell. To further its use as an organism for biotechnology, we sequenced its genome and demonstrate genetic circuits that enable functionalization and patterning of heterologous gene expression within the cellulose matrix. This work lays the foundations for using genetic engineering to produce cellulose-based materials, with numerous applications in basic science, materials engineering, and biotechnology.

Adiposity Is Associated with Gender-Specific Reductions in Left Ventricular Myocardial Perfusion during Dobutamine Stress.

BACKGROUND: Obesity and visceral adiposity are increasingly recognized risk factors for cardiovascular disease. Visceral fat may reduce myocardial perfusion by impairing vascular endothelial function. Women experience more anginal symptoms compared to men despite less severe coronary artery stenosis, as assessed by angiography. Women and men have different fat storage patterns which may account for the observed differences in cardiovascular disease. Therefore, our objective was to evaluate the relationship between visceral adipose tissue distributions and myocardial perfusion in men and women. METHODS: Visceral and subcutaneous fat distributions and myocardial perfusion were measured in 69 men and women without coronary artery disease using magnetic resonance imaging techniques. Myocardial perfusion index was quantified after first-pass perfusion with gadolinium contrast at peak dose dobutamine stress. RESULTS: We observed inverse relationships between female gender (r = -0.35, p = 0.003), pericardial fat (r = -0.36, p = 0.03), intraperitoneal fat (r = -0.37, p = 0.001), and retroperitoneal fat (r = -0.36, p = 0.002) and myocardial perfusion index. Visceral fat depots were not associated with reduced myocardial perfusion at peak dose dobutamine in men. However, in women, BMI (r = -0.33, p = 0.04), pericardial fat (r = -0.53, p = 0.02), subcutaneous fat (r = -0.39, p = 0.01) and intraperitoneal fat (r = -0.30, p = 0.05) were associated with reduced myocardial perfusion during dobutamine stress. CONCLUSIONS: Higher visceral fat volumes are associated with reduced left ventricular myocardial perfusion at peak dose dobutamine stress in women but not in men. These findings suggest that visceral fat may contribute to abnormal microcirculatory coronary artery perfusion syndromes, explaining why some women exhibit more anginal symptoms despite typically lower grade epicardial coronary artery stenoses than men.

Minimally invasive retrieval of patent foramen ovale closure device after device migration to the descending aorta.

Percutaneous treatment of patent foramen ovale with a septal closure device has become a common procedure, but it is associated with various complications. Migration of the device is uncommon, and migration through the aortic valve into the aorta is rare. Managing the migration of a patent foramen ovale occluder can be challenging; it usually requires surgical retrieval of the foreign body. We report a rare case in which a patient experienced migration of a large patent foramen ovale closure device to the descending aorta. Rarer still was its successful percutaneous management.

Effect of initial heart rate on cardiac troponin and ejection fraction in patients with non-ST segment elevation myocardial infarction.

BACKGROUND: Increased heart rate has shown to be associated with adverse cardiovascular outcomes. This aim of this study was to find the association of troponin level and ejection fraction (EF) with triage heart rate in patients with non-ST elevation myocardial infarction (NSTEMI). It was hypothesized that heart rate at triage will be independently associated with higher troponin level and lower EF after NSTEMI. METHODS: The association of maximum troponin level and left ventricular EF with triage heart rate after adjusting for other factors known to affect these variables was assessed. RESULTS: Participants had a mean age of 68 ± 10 years with 34% women. Unadjusted correlations using linear regression showed a correlation coefficient (r) of 0.21, P = 0.01, between heart rate and maximum troponin before cardiac catheterization and a correlation coefficient (r) of -0.26, P = 0.007, between heart rate and post-myocardial infarction EF. EF was divided into 4 categories, namely, <30%, 30% to 45%, 45% to 60% and >60%. Heart rate showed a progressive increase from higher EF to lower EF. A multivariate analysis was also performed for association of heart rate with troponin and EF separately after adjusting for other confounding factors (diabetes, hypertension, number of coronary vessels and previous myocardial infarction). All associations persisted at P ≤ 0.05. CONCLUSIONS: Triage heart rate is independently associated with higher troponin and lower EF in NSTEMI.

Aging reduces left atrial performance during adrenergic stress in middle aged and older patients.

BACKGROUND: During adrenergic stress, the influence of age on left atrial (LA) function is unknown. We hypothesized that aging decreases LA total emptying fraction (LAEF) during maximal adrenergic stress. The aim of the study was to determine the influence of aging on LA function during adrenergic stress in middle aged and older patients. METHODS: We enrolled 167 middle aged and elderly participants, and measured LA and left ventricular (LV) volumes using a multi-slice three-dimensional cine white blood cardiovascular magnetic resonance (CMR) technique before and during intravenous dobutamine infused to achieve 80% of the maximum heart rate response for age. Paired sample t-test was used to detect differences in LA and LV volumes between baseline and peak dose stage of dobutamine stress CMR, and multivariable linear regression was used to identify predictors of LA function. RESULTS: Participants averaged 68 ± 8 years in age, 53% were men, 25% exhibited coronary artery disease, 35% had diabetes, 9% had a remote history of atrial fibrillation, 90% had hypertension, and 11% had inducible LV wall motion abnormalities indicative of ischemia during dobutamine CMR. Increasing age correlated with LA volumes (maximal and minimal) and inversely correlated with LAEF at rest and after peak adrenergic stress. Age was an independent predictor of LAEF during adrenergic stress, even after accounting for gender, LV volumes, and other co-morbidities including inducible ischemia. CONCLUSIONS: Age is associated with a decrease in LA function during adrenergic stress even after adjusting for co-morbidities associated with cardiovascular disease and LV function.

Successful repair of a type 2 endoleak with coiling of inferior mesenteric artery.

BACKGROUND: One of the most common complications of endovascular aneurysm repair (EVAR) is type 2 endoleak. We describe a patient who presented with a recurrent endoleak despite initial intervention and was successfully treated with coil embolization of the inferior mesenteric artery (IMA). CASE REPORT: A 63-year-old Caucasian male was found to have a 7.5 cm abdominal aortic aneurysm (AAA) during a routine ultrasound of the kidneys. The patient successfully underwent EVAR with exclusion of the aneurysm sac. A computed tomographic (CT) scan was performed 30 days after the procedure, and showed presence of a large type 1a endoleak with slight enlargement of the sac. The endoleak was successfully repaired with 2 extension cuffs which resulted in resolution of the endoleak. A few months later, another CT scan was performed that showed a type 2 endoleak without enlargement of the sac; however, there was no reduction in the size of the sac. Multiplanar reconstruction was used and a small branch connecting the superior mesenteric artery (SMA) to the inferior mesenteric artery (IMA) through the marginal artery was found. A selective angiogram of the SMA was performed that showed filling of the aneurysm sac. A microcatheter was advanced through the SMA and marginal artery into the IMA. The IMA was occluded with coil embolization, resulting in resolution of the endoleak. CONCLUSION: Our case describes a patient who initially underwent treatment for type 1a endoleak and subsequently developed type 2 endoleak that was successfully treated with coil embolization of the IMA.

Wrist drop: an atypical presentation of renal cell carcinoma.

Renal cell carcinoma (RCC) causing metastasis to the skeletal muscles is extremely rare. The authors describe a patient with history of RCC treated 5 years ago with radical nephrectomy who presented with left arm swelling after receiving seasonal flu shot. He was initially diagnosed with cellulitis, treated with intravenous antibiotics and discharged home. One month later, he presented with persistent left arm swelling accompanied by wrist drop. Subsequently he developed increased swelling, decreased pulse and wrist drop. He was diagnosed with compartment syndrome, for which fasciotomy was performed, and tissue samples were sent for analysis. Histopathological analysis confirmed metastatic clear cell RCC. The authors described a literature review of previously described cases of metastasis of renal cell cancer to the skeletal muscles. The authors also discussed the rarity of muscle metastasis and unpredictable behavior of RCC after being dormant for long periods.

Intraperitoneal fat is associated with thickening of the thoracic aorta in individuals at high risk for cardiovascular events.

Increased intraperitoneal (IP) fat is associated with increased cardiovascular (CV) risk, but mechanisms for this increase in risk are not completely established. We performed this study to assess whether IP fat is associated with ascending aortic wall thickness (AOWT), a risk factor for CV events. Four hundred and forty-one consecutive participants, aged 55-85 years, with risk factors for CV events underwent magnetic resonance measures of AOWT and abdominal fat (subcutaneous (SC) fat + IP fat). For the ascending aorta, mean wall thickness of the 4th quartile of the IP fat was higher relative to the 1st quartile (P ≤ 0.001). This difference persisted after accounting for SC fat (P ≤ 0.001), as well as age, gender, height, weight, smoking, diabetes, hypertension, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), and C-reactive protein (CRP) (P < 0.03). Elevated IP fat volume is associated with an increase in ascending AOWT, a condition that promotes CV events in middle aged and elderly adults.

Predictors of in-hospital mortality in patients receiving thrombolytic therapy for pulmonary embolism.

Predictors of in-hospital mortality from massive pulmonary embolism (PE) were retrospectively assessed in 78 patients who received thrombolytic therapy. Mortality from PE was 19% (15 of 78). Mortality from PE was higher in those with shock, 36% (12 of 33) versus no shock, 7% (3 of 45; P = .001), 21% (7 of 34) with right ventricle (RV) hypokinesis, and 20% (13 of 64) with RV enlargement. Mortality was 14% (2 of 14) with normal cardiac troponin I (cTnI), 19% (4 of 21) with intermediate cTnI, and 22% (8 of 36) with high cTnI (comparisons between groups nonsignificant [NS]). Trends with combinations of risk factors showed the highest mortality with shock plus high cTnI plus RV hypokinesis (57%) or shock plus high cTnI plus RV enlargement (54%). In conclusion, among the single risk factors, shock was associated with the highest in-hospital mortality from PE and combinations with high cTnI and RV enlargement were associated with higher mortalities.

Elevated cardiac biomarkers with normal right ventricular size indicate an unlikely diagnosis of acute pulmonary embolism in stable patients.

The purpose of this investigation is to assess the prevalence of elevated cardiac biomarkers, with or without estimates of right ventricular (RV) size, in stable patients with acute pulmonary embolism (PE). Our hypothesis is that the combination of high levels of cardiac troponin I (cTnI), high creatine kinase isoenzyme MB (CK-MB), and normal size RV are sufficiently uncommon in stable patients with PE to make the diagnosis of PE unlikely. Retrospective review showed a high cTnI plus high CK-MB in 20 (3.4%) of 585 stable patients with acute PE. A high cTnI plus high CK-MB with normal RV size was shown in 5 (1.9%) of 264 patients. In stable patients with such findings, therefore, PE is unlikely and other diagnoses, particularly acute coronary syndrome, should be considered before pursuing a diagnosis of PE.

Prognostic value of D-dimer in stable patients with pulmonary embolism.

Prognosis of pulmonary embolism (PE) based on levels of D-dimer has shown mixed results, and data on in-hospital prognosis of stable patients are sparse. We assessed in-hospital prognosis in 292 stable patients with PE based on retrospective chart review using an arbitrarily selected value of D-dimer ≥5000 ng/mL as cut-off level. In-hospital mortality from PE was 0% (0 of 222) with D-dimer <5000 ng/mL compared with 2.9% (2 of 70) with D-dimer ≥5000 ng/mL (P = .06). In-hospital all-cause mortality was 2.3% (5 of 222) with D-dimer <5000 ng/mL compared with 2.9% (2 of 70) with D-dimer ≥5000 ng/mL (NS). Markedly elevated levels of D-dimer, therefore, did not indicate a high mortality from PE or all-cause mortality during hospitalization.

Prognosis based on creatine kinase isoenzyme MB, cardiac troponin I, and right ventricular size in stable patients with acute pulmonary embolism.

Prognosis of stable patients with acute pulmonary embolism (PE) has been assessed with cardiac troponin I (cTnI) and right ventricular (RV) function or size. Whether creatine kinase-MB isoenzyme (CK-MB) would add to the prognostic assessment is uncertain. We retrospectively assessed in-hospital mortality from PE in 392 stable patients to test the hypothesis that CK-MB would be of greater prognostic value than cTnI or RV size and we assessed whether combinations would increase prognostic value. CK-MB was high in 29 patients (7.4%); cTnI was high in 76 patients (19%) and intermediate in 78 patients (20%). The right ventricle was dilated in 128 patients (33%). Trends showed highest in-hospital mortality from PE in 4 of 29 (14%) with high CK-MB compared to 6 of 76 (7.9%) with high cTnI and 8 of 128 (6.3%) with RV dilatation (differences NS). High CK-MB and high cTnI provided added prognostic information only in patients with RV dilatation. Mortality with high CK-MB plus RV dilatation (4 of 19, 21%) tended to exceed mortality with high cTnI plus RV dilatation (5 of 39, 13%, NS). When CK-MB and cTnI were high and the right ventricle was dilated, PE mortality tended to be highest (4 of 14, 29%, NS). In conclusion, cardiac biomarkers contributed to prognosis only in patients with RV dilatation. CK-MB was the strongest predictor of death from PE but its prevalence was low, thus limiting its value as a single prognostic indicator. The combination of high CK-MB, high cTnI, and RV dilatation tended to indicate the highest mortality.

Prehospital delay and its impact on time to treatment in ST-elevation myocardial infarction.

PURPOSES: We performed this study to assess the impact of pre-hospital time on the patient's outcome. PROCEDURES: Starting from the symptoms onset, "total time to treatment" was divided into less than or equal to 120 minutes and more than 120 minutes ("pre-hospital time" of ≤ or > 30 minutes respectively). Adverse patient's outcomes were compared in the two subgroups. FINDINGS: Our patients had a mean age of 63 (±13) years. On-scene time (17.8 ± 9.4 minutes), was the biggest fraction of "pre-hospital time". Comparing the groups with "Total time to treatment" of >120 minutes vs. ±120 minutes ("pre-hospital time" of >30 vs. ≤30 minutes), mortalities were 4 vs. 0 and transfers to a tertiary care facility were 3 vs.1. CONCLUSIONS: Most of the pre-hospital time in STEMI was spent on the scene and we suggest "total time to treatment" as a core measure instead of "door to balloon time".

Renal sinus fat and poor blood pressure control in middle-aged and elderly individuals at risk for cardiovascular events.

Fat in the renal sinus (RS), a region of the kidney in which low pressure venous and lymphatic vessels are present, may indirectly influence blood pressure. The purpose of this study was to assess the association between RS fat and control of blood pressure on receipt of antihypertensive medications. A total of 205 participants aged 55 to 85 years at risk for cardiovascular events underwent MRI assessments of abdominal and RS fat, measurement of blood pressure, and determination of the number of prescribed antihypertensive medications. Multivariable linear regression was used to determine associations among RS fat, blood pressure, and the number of prescribed antihypertensive medications. Abdominal fat averaged 416±160 cm(3) (median and interquartile range of 396 cm(3) and 308 to 518 cm(3)); intraperitoneal fat averaged 141±73 cm(3) (median and interquartile range of 129 cm(3) and 86 to 194 cm(3)); and RS fat averaged 4.6±3.2 cm(3) (median and interquartile range of 4.2 cm(3) and 2.2 to 6.6 cm(3)). After accounting for age, sex, height, body mass index, and intraperitoneal fat, RS fat correlated with the number of prescribed antihypertensive medications (P=0.010), stage II hypertension (P=0.02), and renal size (P≤0.001). In conclusion, after accounting for other body fat depots and risk factors for hypertension, RS fat volume is associated with the number of prescribed antihypertensive medications and stage II hypertension. These results indicate that further studies are warranted to determine whether fat accumulation in the RS promotes hypertension.

Endovascular abdominal aortic aneurysm repair by interventional cardiologists--a community-based experience.

INTRODUCTION: Endovascular repair of abdominal aortic aneurysm (AAA) is a relatively recent technology. In comparison to the conventional open surgical treatment for AAA, endovascular AAA repair (EVAR) combines a less-invasive approach with lower morbidity and mortality. There have been few studies regarding the performance of this procedure in a community-based setting. We report our experience of EVAR performed primarily by interventional cardiologists in a community hospital. METHODS: In our community hospital setting, between September 2005 and November 2007, we included all patients who underwent EVAR by interventional cardiologists, with available on-site vascular surgical support. Clinical and serial computed angiographic imaging outcomes were followed by a retrospective chart review. Data collection tools included demographic and clinical characteristics, anatomical aneurysm features, length of stay, peri- and postprocedural complications, and mortality. RESULTS: A total of 71 consecutive patients had EVAR attempted. The endovascular stent placement was successful in 67 (93%) patients. Thirty-day mortality in this study was 1 of 71 (1.4%). All four procedural failures and the single periprocedural mortality occurred in women. Mean follow-up was 12 months. There were a total of six mortalities and among these four were women (P ≤ 0.001); however, multivariate analysis revealed loss of significant difference in mortality (P = 0.16). Major complications following EVAR were noted in 10 of 71 (14%) patients. CONCLUSION: EVAR can be successfully performed by experienced interventional cardiologists with vascular surgical support in a community-based setting. In our experience, there is acceptable rate of complications and mortality in a carefully selected patient population.

Iatrogenic intrapericardial diaphragmatic hernia diagnosed by cardiovascular magnetic resonance.

Intrapericardial diaphragmatic hernias are very uncommon and are most typically caused by high-force blunt trauma. Other iatrogenic causes such as prior surgical formation of a pericardial window have been described, but are exceedingly rare. We present a case of an intrapericardial diaphragmatic hernia in a patient with a prior pericardial window in which the diagnosis was unclear using conventional imaging modalities, but was established using cardiovascular magnetic resonance.

Massive pulmonary embolism and paradoxical migration during surgical embolectomy: role of transesophageal echocardiogram.

Patent foramen ovale (PFO) in the setting of venous thromboembolism is associated with paradoxical embolization. We describe a patient who presented with pulmonary embolism, underwent pulmonary embolectomy, and postoperatively developed paradoxical embolization to the lower extremity.A 27-year-old African American male presented to the hospital with shortness of breath and midsternal chest pain along with neck vein distention. A CT scan with contrast showed the presence of a saddle embolus in both pulmonary arteries. The next day, the patient developed right ventricular failure and hypotension. The patient was taken to the operating room for a pulmonary embolectomy. Postoperatively, the patient developed acute left lower extremity ischemia. The origin of the embolus was suspected to be cardiac. A transesophageal echocardiogram (TEE) revealed thrombus on the mitral valve and a PFO with right to left shunt. At this point vascular surgery for revascularization of the left lower extremity was performed. Two days later, the patient was taken for a repeat cardiac surgery and the left-sided thrombus was removed along with a closure of the PFO.This case signifies the importance of complete TEE and a search for PFO in patients with massive pulmonary embolism especially prior to surgical embolectomy because hemodynamic disturbances of pulmonary embolism and surgical embolectomy may cause migration of the thrombus from the right side to the left side of the heart.

Adverse effect of increased left ventricular wall thickness on five year outcomes of patients with negative dobutamine stress.

BACKGROUND: To determine if patients without dobutamine induced left ventricular wall motion abnormalities (WMA) but an increased LV end-diastolic wall thickness (EDWT) exhibit a favorable cardiac prognosis. RESULTS: Between 1999 and 2001, 175 patients underwent a dobutamine stress cardiovascular magnetic resonance (DCMR) procedure utilizing gradient-echo cines. Participants had a LV ejection fraction >55% without evidence of an inducible WMA during peak dobutamine/atropine stress. After an average of 5.5 years, all participants were contacted and medical records were reviewed to determine the post-DCMR occurrence of cardiac death, myocardial infarction (MI), and unstable angina (USA) or congestive heart failure (CHF) warranting hospitalization.In a multivariate analysis, that took into account Framingham and other risk factors associated with cardiac events, a cine gradient-echo derived LV EDWT > or =12 mm was associated independently with an increase in cardiac death and MI (HR 6.0, p = 0.0016), and the combined end point of MI, cardiac death, and USA or CHF warranting hospitalization (HR 3.0, p = 0.0005). CONCLUSION: Similar to echocardiography, CMR measures of increased LV wall thickness should be considered a risk factor for cardiac events in individuals receiving negative reports of inducible ischemia after dobutamine stress. Additional prognostic studies of the importance of LV wall thickness and mass measured with steady-state free precession techniques are warranted.