Preoperative imaging of glioblastoma patients using hyperpolarized 13C pyruvate: Potential role in clinical decision making.

BACKGROUND: Glioblastoma remains incurable despite treatment with surgery, radiation therapy, and cytotoxic chemotherapy, prompting the search for a metabolic pathway unique to glioblastoma cells.13C MR spectroscopic imaging with hyperpolarized pyruvate can demonstrate alterations in pyruvate metabolism in these tumors. METHODS: Three patients with diagnostic MRI suggestive of a glioblastoma were scanned at 3 T 1-2 days prior to tumor resection using a 13C/1H dual-frequency RF coil and a 13C/1H-integrated MR protocol, which consists of a series of 1H MR sequences (T2 FLAIR, arterial spin labeling and contrast-enhanced [CE] T1) and 13C spectroscopic imaging with hyperpolarized [1-13C]pyruvate. Dynamic spiral chemical shift imaging was used for 13C data acquisition. Surgical navigation was used to correlate the locations of tissue samples submitted for histology with the changes seen on the diagnostic MR scans and the 13C spectroscopic images. RESULTS: Each tumor was histologically confirmed to be a WHO grade IV glioblastoma with isocitrate dehydrogenase wild type. Total hyperpolarized 13C signals detected near the tumor mass reflected altered tissue perfusion near the tumor. For each tumor, a hyperintense [1-13C]lactate signal was detected both within CE and T2-FLAIR regions on the 1H diagnostic images (P = .008). [13C]bicarbonate signal was maintained or decreased in the lesion but the observation was not significant (P = .3). CONCLUSIONS: Prior to surgical resection, 13C MR spectroscopic imaging with hyperpolarized pyruvate reveals increased lactate production in regions of histologically confirmed glioblastoma.

Potential Excess Intravenous Antibiotic Therapy in the Setting of Gram-Negative Bacteremia.

(1) Background: Excessive intravenous therapy (EIV) is associated with negative consequences, but guidelines are unclear about when switching to oral therapy is appropriate. (2) Methods: This cohort included patients aged ≥18 years receiving ≥48 h of antimicrobial therapy for bacteremia due to Escherichia coli, Pseudomonas aeruginosa, Enterobacter, Klebsiella, Acinetobacter, or Stenotrophomonas maltophilia from 1/01/2008-8/31/2011. Patients with a polymicrobial infection or recurrent bacteremia were excluded. Potential EIV (PEIV) was defined as days of intravenous antibiotic therapy beyond having a normal WBC count for 24 h and being afebrile for 48 h until discharge or death. (3) Results: Sixty-nine percent of patients had PEIV. Patients who received PEIV were more likely to receive intravenous therapy until discharge (46 vs. 16%, p < 0.001). Receipt of PEIV was associated with a longer mean time to receiving oral antimicrobials (8.7 vs. 3 days, p < 0.001). The only factors that impacted EIV days in the multivariable linear regression model were the source of infection (urinary tract) (coefficient -1.54, 95%CI -2.82 to -0.26) and Pitt bacteremia score (coefficient 0.51, 95%CI 0.10 to 0.92). (4) Conclusions: PEIV is common in inpatients with Gram-negative bacteremia. Clinicians should look to avoid PEIV in the inpatient setting.

Characterization and compensation of f0 inhomogeneity artifact in spiral hyperpolarized 13 C imaging of the human heart.

PURPOSE: This study aimed to investigate the role of regional f0 inhomogeneity in spiral hyperpolarized 13 C image quality and to develop measures to alleviate these effects. METHODS: Field map correction of hyperpolarized 13 C cardiac imaging using spiral readouts was evaluated in healthy subjects. Spiral readouts with differing duration (26 and 45 ms) but similar resolution were compared with respect to off-resonance performance and image quality. An f0 map-based image correction based on the multifrequency interpolation (MFI) method was implemented and compared to correction using a global frequency shift alone. Estimation of an unknown frequency shift was performed by maximizing a sharpness objective based on the Sobel variance. The apparent full width half at maximum (FWHM) of the myocardial wall on [13 C]bicarbonate was used to estimate blur. RESULTS: Mean myocardial wall FWHM measurements were unchanged with the short readout pre-correction (14.1 ± 2.9 mm) and post-MFI correction (14.1 ± 3.4 mm), but significantly decreased in the long waveform (20.6 ± 6.6 mm uncorrected, 17.7 ± 7.0 corrected, P = .007). Bicarbonate signal-to-noise ratio (SNR) of the images acquired with the long waveform were increased by 1.4 ± 0.3 compared to those acquired with the short waveform (predicted 1.32). Improvement of image quality was observed for all metabolites with f0 correction. CONCLUSIONS: f0 -map correction reduced blur and recovered signal from dropouts, particularly along the posterior myocardial wall. The low image SNR of [13 C]bicarbonate can be compensated with longer duration readouts but at the expense of increased f0 artifacts, which can be partially corrected for with the proposed methods.

Imaging Acute Metabolic Changes in Patients with Mild Traumatic Brain Injury Using Hyperpolarized [1-13C]Pyruvate.

Traumatic brain injury (TBI) involves complex secondary injury processes following the primary injury. The secondary injury is often associated with rapid metabolic shifts and impaired brain function immediately after the initial tissue damage. Magnetic resonance spectroscopic imaging (MRSI) coupled with hyperpolarization of 13C-labeled substrates provides a unique opportunity to map the metabolic changes in the brain after traumatic injury in real-time without invasive procedures. In this report, we investigated two patients with acute mild TBI (Glasgow coma scale 15) but no anatomical brain injury or hemorrhage. Patients were imaged with hyperpolarized [1-13C]pyruvate MRSI 1 or 6 days after head trauma. Both patients showed significantly reduced bicarbonate (HCO3 -) production, and one showed hyperintense lactate production at the injured sites. This study reports the feasibility of imaging altered metabolism using hyperpolarized pyruvate in patients with TBI, demonstrating the translatability and sensitivity of the technology to cerebral metabolic changes after mild TBI.

Impact of Neostigmine and Sugammadex on Time to Leaving the Operating Room in a Community Hospital.

PURPOSE: The purpose of this study was to evaluate the impact of sugammadex on operating room (OR) times versus neostigmine in patients recovering from rocuronium or vecuronium induced neuromuscular blockade. METHODS: This retrospective cohort study evaluated patients 18 years or older with an American Society of Anesthesiologists (ASA) physical status of I-III who received sugammadex or neostigmine (January- October 2017) for reversal of rocuronium or vecuronium at a 500 bed, community hospital. Patients who were pregnant or breastfeeding were excluded. The primary outcome measure was the time from sugammadex or neostigmine administration to OR exit. The primary outcome was evaluated using a linear regression model adjusting for inpatient procedures, age, sex, body mass index, and ASA score. Secondary outcomes included the incidence of bradycardia as well as nausea and vomiting. RESULTS: The baseline characteristics of the patients in the cohort (sugammadex=134, neostigmine=143) were similar. The median time from drug administration to OR exit was similar for neostigmine and sugammadex (16 vs. 15.5 minutes, p=0.11). Sugammadex had a statistically significant reduction in time from drug administration to OR exit (coefficient -2.7 minutes, 95% confidence interval -5.2 to -0.2 minutes) in the multivariable linear regression model. Sugammadex had lower rates of bradycardia (5.6 vs. 2.2%) or nausea and vomiting (18 vs. 11%) that did not reach statistical significance. CONCLUSIONS: Sugammadex had statistically shorter OR exit times after drug administration in the cohort. The mean 2.7 minute benefit is unlikely to be clinically meaningful and limits its application in practice unless larger cohorts detect a benefit due to a significant reduction.in.adverse.events.

Impact of Neostigmine and Sugammadex on Time to Leaving the Operating Room in a Community Hospital.

PURPOSE: The purpose of this study was to evaluate the impact of sugammadex on operating room (OR) times versus neostigmine in patients recovering from rocuronium or vecuronium induced neuromuscular blockade. METHODS: This retrospective cohort study evaluated patients 18 years or older with an American Society of Anesthesiologists (ASA) physical status of I-III who received sugammadex or neostigmine (January- October 2017) for reversal of rocuronium or vecuronium at a 500 bed, community hospital. Patients who were pregnant or breastfeeding were excluded. The primary outcome measure was the time from sugammadex or neostigmine administration to OR exit. The primary outcome was evaluated using a linear regression model adjusting for inpatient procedures, age, sex, body mass index, and ASA score. Secondary outcomes included the incidence of bradycardia as well as nausea and vomiting. RESULTS: The baseline characteristics of the patients in the cohort (sugammadex=134, neostigmine=143) were similar. The median time from drug administration to OR exit was similar for neostigmine and sugammadex (16 vs. 15.5 minutes, p=0.11). Sugammadex had a statistically significant reduction in time from drug administration to OR exit (coefficient -2.7 minutes, 95% confidence interval -5.2 to -0.2 minutes) in the multivariable linear regression model. Sugammadex had lower rates of bradycardia (5.6 vs. 2.2%) or nausea and vomiting (18 vs. 11%) that did not reach statistical significance. CONCLUSIONS: Sugammadex had statistically shorter OR exit times after drug administration in the cohort. The mean 2.7 minute benefit is unlikely to be clinically meaningful and limits its application in practice unless larger cohorts detect a benefit due to a significant reduction.in.adverse.events.

Impact of piperacillin/tazobactam on nephrotoxicity in patients with Gram-negative bacteraemia.

Piperacillin/tazobactam (TZP) has been associated with nephrotoxicity in patients receiving vancomycin. Its impact on nephrotoxicity in patients with Gram-negative bacteraemia (GNB) is unclear. This study evaluated the impact of TZP on nephrotoxicity in patients with GNB. This retrospective cohort included patients aged ≥18 years receiving ≥48 h of therapy for bacteraemia due to Escherichia coli, Pseudomonas aeruginosa, Enterobacter, Klebsiella, Acinetobacter or Stenotrophomonas maltophilia from 1/01/2008-8/31/2011. Patients with baseline serum creatinine (SCr) ≥3.5 mg/dL, polymicrobial infection or recurrent bacteraemia were excluded. Nephrotoxicity was defined as a ≥0.5 mg/dL increase in SCr or ≥50% increase from baseline for ≥2 consecutive days. Any variable demonstrating a 10% change in exposure effect was retained in the final model. All variables biologically reasonable causes of nephrotoxicity were also considered for inclusion. The median age of the cohort (n = 292) was 76 years; 38.0% had a cancer diagnosis and ICU residence was common (21.9%). There was no difference in nephrotoxicity incidence based on days of TZP received (0 days, 13.6%; 1-2 days, 14.7%; 3-4 days, 6.9%; ≥5 days, 16.7%; P = 0.71). In multivariable analysis, baseline SCr, total body weight and vasopressor use were independently associated with nephrotoxicity. Duration of TZP was not associated with nephrotoxicity in multivariable analysis (1-2 days, OR = 0.91, 95% CI 0.39-2.12; 3-4 days, OR = 0.48, 95% CI 0.10-2.46; ≥5 days, OR = 0.57, 95% CI 0.11-3.02). In this cohort of GNB patients, duration of TZP was not associated with nephrotoxicity.

Fractured inferior vena cava filter strut presenting with ST-segment elevation and cardiac tamponade.

The fracture of an inferior vena cava filter strut and its migration to the heart is a rare sequela of implanted inferior vena cava filters. Perforation through the right ventricle into the pericardium with resultant cardiopulmonary compromise is even less frequent. We report the case of a 53-year-old man who presented with chest pain and hypotension consequent to cardiac tamponade. A fractured inferior vena cava filter strut had migrated and perforated his right ventricle. The fractured strut was successfully removed by means of cardiac surgery. Inferior vena cava filters should be placed when necessary to minimize the risk of pulmonary embolism, and regular radiologic monitoring should be performed; however, the eventual extraction of retrievable filters should be considered. In addition to discussing the patient's case, we briefly review the relevant medical literature.

Real-time ultrasound guidance facilitates transradial access: RAUST (Radial Artery access with Ultrasound Trial).

OBJECTIVES: This study sought to assess the utility of ultrasound (US) guidance for transradial arterial access. BACKGROUND: US guidance has been demonstrated to facilitate vascular access, but has not been tested in a multicenter randomized fashion for transradial cardiac catheterization. METHODS: We conducted a prospective multicenter randomized controlled trial of 698 patients undergoing transradial cardiac catheterization. Patients were randomized to needle insertion with either palpation or real-time US guidance (351 palpation, 347 US). Primary endpoints were the number of forward attempts required for access, first-pass success rate, and time to access. RESULTS: The number of attempts was reduced with US guidance [mean: 1.65 ± 1.2 vs. 3.05 ± 3.4, p < 0.0001; median: 1 (interquartile range [IQR]: 1 to 2) vs. 2 (1 to 3), p < 0.0001] and the first-pass success rate improved (64.8% vs. 43.9%, p < 0.0001). The time to access was reduced (88 ± 78 s vs. 108 ± 112 s, p = 0.006; median: 64 [IQR: 45 to 94] s vs. 74 [IQR: 49 to 120] s, p = 0.01). Ten patients in the control group required crossover to US guidance after 5 min of failed palpation attempts with 8 of 10 (80%) having successful sheath insertion with US. The number of difficult access procedures was decreased with US guidance (2.4% vs. 18.6% for ≥5 attempts, p < 0.001; 3.7% vs. 6.8% for ≥5min, p = 0.07). No significant differences were observed in the rate of operator-reported spasm, patient pain scores following the procedure, or bleeding complications. CONCLUSIONS: Ultrasound guidance improves the success and efficiency of radial artery cannulation in patients presenting for transradial catheterization. (Radial Artery Access With Ultrasound Trial [RAUST]; NCT01605292).

Aortic atheromas: current concepts and controversies-a review of the literature.

The frequent use of transesophageal echocardiogram (TEE) has led to the increased recognition of aortic atheromas. Retrospective and prospective follow-up studies have reported an association between aortic atheromas and stroke in the high-risk patient population, with complex plaques being more likely to embolize than simple plaques. However, TEE-based studies in the low-risk cohorts have failed to show a similar association. There is growing body of evidence suggesting that aortic atheroma is a marker of generalized atherosclerosis. Although magnetic resonance (MR) imaging and computed tomography (CT) scan are emerging as a powerful noninvasive tool for characterization of aortic atheromas, TEE is the imaging modality of choice. Currently, treatment of aortic atheromas is not well defined, and mixed outcomes have been reported for anticoagulation therapy with warfarin. Statins appear promising based on their plaque stabilization properties. However, there are no randomized control trials to establish the role of both anticoagulation and statins in patients with aortic atheromas, and are warranted in the future.

Cell transplantation for treatment of left-ventricular dysfunction due to ischemic heart failure: from bench to bedside.

Cell transplantation is an innovative technology that involves the implantation of a variety of myogenic and angiogenic cell types. The transplanted cells proliferate and augment left ventricular performance and therein ameliorate the heart failure symptoms. The concept of cell transplantation has followed the footsteps of angiogenesis starting as bench side research. The latter half of the decade saw the transformation of this potential mechanism to a promising therapy for ischemic heart failure. More than 150 patients have been treated with cellular transplantation worldwide. This novel application has the potential to revolutionize alternative therapeutic approaches to management of heart failure.

Optimal management of hyperlipidemia in primary prevention of cardiovascular disease.

Cardiovascular disease (CVD) in the developed countries continues to grow at an epidemic proportion. There are a significant number of young adults with no clinical evidence of CVD, but who have two or more risk factors that predispose them to CV events and death. Many of these risk factors are modifiable, and by controlling these factors, the CVD burden can be decreased significantly. Recent statistics have shown that, if all major forms of CVD were eliminated, the life expectancy would rise by almost 7 years. Hence it is imperative that primary prevention efforts should be initiated at a young age to avert decades of unattended risk factors. Hyperlipidemia has been linked to CVD almost a century ago. Since then various clinical trials have not only supported this link, but have also shown the CV benefits in aggressively treating patients with hyperlipidemia. In this generation, we have various therapeutic agents that are capable of reducing the elevated lipid levels. With drugs like statins, we are able to reduce the risk of CVD by about 30% and avoid major adverse events. Newer drugs are being researched and introduced in the treatment of hyperlipidemia in humans. These can be used in combination therapy resulting in optimal levels of lipids. The new National Cholesterol Education Program (NCEP)/Adult Treatment Panel III (ATP III) guidelines have come as a wake-up call to clinicians about primary prevention of CVD through strict lipid management and multifaceted risk management approach in the prevention of CVD.

Ischemic heart disease in women and the role of hormone therapy.

The prevalence of ischemic heart disease (IHD) has been increasing among the women in developed countries. The well recognized IHD excess in men has often obscured the fact that IHD is the leading cause of death in women. Women have atypical symptoms of IHD that lead to a delay in the diagnosis and an overall poor prognosis. Women have a delay in the onset of IHD due to the beneficial effects of their sex hormones. Postmenopausal women lose this beneficial effect of estrogen and undergo significant changes in their lipid profile, arterial pressure, glucose tolerance, and vascular reactivity that increase their risk for development of IHD. Recently there has been considerable interest in the sex hormones and their role in IHD in women. The general belief that hormone replacement therapy (HRT) has an overall beneficial effect on cardiovascular disease (CVD) in women and hence decreases CVD mortality and morbidity has not been shown in the recent multicenter prospective studies. With the availability of various types of estrogen and progestins, physicians prescribing these agents should take into consideration their varying effects on the cardiovascular system. Risk factor modifications should include diet, weight loss, regular exercise, smoking cessation and adequate control of hypertension (HTN), diabetes (DM) and hyperlipidemia. In the appropriate setting, treatment with proven beneficial agents like aspirin, beta-blockers, angiotensin converting enzyme (ACE) inhibitors and statins will help decrease the burden of IHD in women.

Current concepts of cardiovascular diseases in diabetes mellitus.

The incidence of diabetes has reached epidemic proportions across the world. In patients with diabetes, there is a two to four times increased risk of developing coronary artery disease (CAD). Diabetes seems to eliminate the protective benefits of hormones in women against CAD. Patients with type II diabetes also have hypertension, dyslipidemia, obesity, endothelial dysfunction and prothrombotic factors, called 'the metabolic syndrome'. Not only the incidence of CAD is higher in diabetes, the mortality of the diabetic patients after a cardiac event is significantly increased as compared to non-diabetics, including sudden death. Although in the past 35 years there has been a decline in the rate of death due to CAD in the general population, this has not been seen among patients with diabetes. Primary prevention can play an important role in decreasing the incidence of CAD in diabetic patients. Aggressive treatment of hyperlipidemia and hypertension is essential. Recent knowledge about the protective effects of aspirin, statins, angiotension converting enzyme inhibitors, and glitazones in the diabetic patients, if used appropriately will go a long way in primary and secondary prevention of CAD in patients with diabetes.