Albert P. Nguyen

Importance of Calcium-Binding Site 2 in Simian Virus 40 Infection

ABSTRACT The exposure of molecular signals for simian virus 40 (SV40) cell entry and nuclear entry has been postulated to involve calcium coordination at two sites on the capsid made of Vp1. The role of calcium-binding site 2 in SV40 infection was examined by analyzing four single mutants of site 2, the Glu160Lys, Glu160Arg, Glu157Lys (E157K), and Glu157Arg mutants, and an E157K-E330K combination mutant. The last three mutants were nonviable. All mutants replicated viral DNA normally, and all except the last two produced particles containing all three capsid proteins and viral DNA. The defect of the site 1-site 2 E157K-E330K double mutant implies that at least one of the sites is required for particle assembly in vivo. The nonviable E157K particles, about 10% larger in diameter than the wild type, were able to enter cells but did not lead to T-antigen expression. Cell-internalized E157K DNA effectively coimmunoprecipitated with anti-Vp1 antibody, but little of the DNA did so with anti-Vp3 antibody, and none was detected in anti-importin immunoprecipitate. Yet, a substantial amount of Vp3 was present in anti-Vp1 immune complexes, suggesting that internalized E157K particles are ineffective at exposing Vp3. Our data show that E157K mutant infection is blocked at a stage prior to the interaction of the Vp3 nuclear localization signal with importins, consistent with a role for calcium-binding site 2 in postentry steps leading to the nuclear import of the infecting SV40.

Measuring intensive care unit performance after sustainable growth rate reform: An example with the National Quality Forum metrics

BACKGROUND Performance measurement is essential for quality improvement and is inevitable in the shift to value-based payment. The National Quality Forum is an important clearinghouse for national performance measures in health care in the United States. AIM We reviewed the National Quality Forum library of performance measures to highlight measures that are relevant to critical care medicine, and we describe gaps and opportunities for the future of performance measurement in critical care medicine. CONCLUSION Crafting performance measures that address core aspects of critical care will be challenging, as current outcome and performance measures have problems with validity. Future quality measures will likely focus on interdisciplinary measures across the continuum of patient care.

Cardiac arrest due to torsades de pointes in a patient with complete heart block: the “R-on-T” phenomenon

A 59-year-old white man with type 2 diabetes mellitus and no regular medical care presented to the emergency department with syncope while driving. The patient denied palpitations, chest pain, or blurry vision prior to the event. After passing out, he reported no postictal symptoms. He reported having a “slow heart rate” over the last year. His heart rate in the emergency department was about 30 beats per minute, and an electrocardiogram showed intermittent complete heart block (Figure ​(Figure11). Figure 1 P waves are shown without correlation to QRS complexes. On examination he was afebrile, hypertensive (blood pressure of 189/78 mm Hg), bradycardic (heart rate of 46 beats per minute) with a normal respiratory rate (20 breaths per minute), and had a normal arterial oxygen saturation (SpO2 of 100% on 2 L/min nasal cannula). The patient was alert and oriented. He had no murmurs, rubs, or gallops. Complete blood count was within normal limits. His blood glucose was 220 mg/dL and serum potassium was 3.2 mEq/L, which was being repleted. His thyroid-stimulating hormone level was within normal limits and hemoglobin A1C was 7.7%. Upon arrival in the intensive care unit, he went into cardiac arrest. An electrocardiogram showed ventricular premature complexes (VPCs) triggering torsades de pointes (TdP) (Figure ​(Figure22). Chest compressions, atropine (1 mg intravenously), magnesium sulfate (1 g intravenously), and defibrillation were applied before he returned to his baseline rhythm of third-degree heart block. At the time of the cardiac arrest, the patients potassium and magnesium levels were 3.8 mEq/dL and 2 mg/dL, respectively. The patient was chemically paced with isoproterenol and transcutaneously paced following the event. Figure 2 (a) Initiation of torsades de pointes (TdP) with a ventricular premature complex (VPC) falling on the downslope of the T wave. Classic polymorphic ventricular tachycardia is seen after initiation. (b) TdP ultimately devolves into coarse ventricular fibrillation. ... Following the cardiac arrest, the patients transthoracic echocardiogram showed normal left ventricular systolic function, borderline left ventricular hypertrophy with associated mild impaired relaxation, and mild mitral regurgitation. The patient received definitive treatment with an implantation of a Medtronic Sensia DDD pacemaker and was discharged home 2 days later.

Should High-Frequency Ventilation in the Adult Be Abandoned?

High-frequency oscillatory ventilation (HFOV) can improve ventilation-perfusion matching without excessive alveolar tidal stretching or collapse-reopening phenomenon. This is an attractive feature in the ventilation of patients with ARDS. However, two recent large multi-center trials of HFOV failed to show benefits in this patient population. The following review addresses whether, in view of these trails, HFOV should be abandoned in the adult population?

Preoperative Functional Status Is Associated With Unplanned Intubations Following Thyroidectomies

BACKGROUND: Unplanned postoperative intubation is an important event that may influence the outcome of thyroid- and parathyroidectomies. We performed a focused study on the association of preoperative functional status with unplanned intubation outcomes in these relatively common surgeries. METHODS: Utilizing data from the National Surgical Quality Improvement Program database from 2007 to 2013, a propensity score-matched retrospective cohort study was performed assessing this outcome in the functionally independent versus dependent groups. Kaplan-Meier survival analysis and a Cox proportional hazards model were performed to assess the difference. RESULTS: There were a total of 98,035 thyroid- and parathyroidectomies identified from the National Surgical Quality Improvement Program from 2007 to 2013. After propensity score matching, there were 1,862 and 931 cases in the independent and dependent group, respectively. There were 11 versus 33 per 1,000 persons in the independent and dependent group, respectively, who experienced an unplanned intubation within 30 d following surgery (P < .001). The dependent group showed worse intubation-free survival over 30 d (P < .001). There were no differences in this outcome during postoperative days 0–1 (P = .17). Dependent functional status was statistically significantly associated with unplanned intubations up to 30 d postoperatively (hazard ratio 2.4, 95% CI 1.4–4.18, P = .002). CONCLUSIONS: Preoperative functional status is a good marker for identifying patients at risk for re-intubation after thyroid- and parathyroidectomy.

The impact of a daily “medication time out” in the Intensive Care Unit

Objective: Medical errors play a large role in preventable harms within our health care system. Medications administered in the ICU can be numerous, complex and subject to daily changes. We describe a method to identify medication errors with the potential to improve patient safety. Design: A quality improvement intervention featuring a daily medication time out for each patient was performed during rounds. Setting: A 12‐bed Cardiac Surgical ICU at a single academic institution with approximately 180 beds. Intervention: After each patient encounter, the current medication list for the patient was read aloud from the electronic medical record, and the team would determine if any were erroneous or missing. Medication changes were recorded and graded post‐hoc according to perceived significance. Results: This intervention resulted in 285 medication changes in 347 patient encounters. 179 of the 347 encounters (51.6%) resulted in at least one change. Of the changes observed, 40.4% were categorized as trivial, 50.5% as minor and 9.1% were considered to have significant potential impact on patient care. The average time spent per patient for this intervention was 1.24 (SD 0.65) minutes. Conclusions: A daily medication time out should be considered as an additional mechanism for patient safety in the ICU. Highlights:Medication errors are an important source of preventable patient harm.Structured checklist‐style interventions may help prevent errors.A daily team‐based “time out” intervention is a low‐cost method to decrease errors.In this study, a large number of medication changes were prompted by a “time out” intervention.

The Strong Cough: Is It a Signpost on the Road to Extubation or Just a Dead End?

In the field of medicine, success has been measured by patient survival. True victory, however, should be judged by the patients liberation and independence from further medical intervention. This is particularly true in critical care medicine and the fields prototypical intervention: mechanical

Hemodynamic Consequence of Hand Ventilation Versus Machine Ventilation During Transport After Cardiac Surgery

OBJECTIVES The hemodynamic consequences of ventilation of intubated patients during transport either by hand or using a transport ventilator have not been reported in patients after cardiac surgery. The authors hypothesized that bag-mask ventilation would alter end-tidal CO2 during transport and hemodynamic parameters in patients post-cardiac surgery. DESIGN A prospective, randomized trial. SETTING A university-affiliated tertiary care hospital. PARTICIPANTS Cardiac surgery patients. INTERVENTIONS Thirty-six patients were randomized to hand ventilation or machine ventilation. Hemodynamic variables including blood pressure, heart rate, peripheral saturation of oxygen, and end-tidal carbon dioxide (ETCO2) were measured in these patients prior to transport, every 2 minutes during transport and upon arrival in the intensive care unit (ICU). Pulmonary artery pressure (PA) pressures were measured at origin and at destination. MEASUREMENTS AND MAIN RESULTS Outcomes were changes from baseline in end-tidal CO2, hemodynamic changes from baseline and pulmonary artery pressure changes from origin to destination. The average transport time between the 2 groups was not different: 5 minutes for patients ventilated by hand and 5.47 minutes for patients ventilated with a transport ventilator (p = 0.369 by 2-sided t-test). The difference in all measured changes in ETCO2 between hand-ventilated and machine-ventilated patients during transport was 2.74 mmHg (p = 0.013). The difference between operating room and ICU ETCO2 from each cohort was 1.31 mmHg (p = 0.067). The difference in PAmean measured at origin and destination was 0.783 mmHg (p = 0.622). All other hemodynamic variables were not different during transport. CONCLUSIONS Hand ventilation during transport was associated with greater change from baseline of ETCO2 compared to machine ventilation during transport after cardiac surgery, but this did not translate into any difference in hemodynamic changes upon arrival in ICU. A hemodynamic benefit of machine transport ventilation to cardiac patients was not demonstrated.

Severity of Acute Kidney Injury in the Post-Lung Transplant Patient Is Associated With Higher Healthcare Resources and Cost

OBJECTIVE Perioperative risk factors and the clinical impact of acute kidney injury (AKI) and failure after lung transplantation are not well described. The incidences of AKI and acute renal failure (ARF), potential perioperative contributors to their development, and postdischarge healthcare needs were evaluated. DESIGN Retrospective. SETTING University hospital. PARTICIPANTS Patients undergoing lung transplantation between January 1, 2011 and December 31, 2015. MEASURED DATA The incidences of AKI and ARF, as defined using the Risk, Injury, Failure, Loss, End-Stage Renal Disease criteria, were measured. Perioperative events were analyzed to identify risk factors for renal compromise. A comparison of ventilator days, intensive care unit (ICU) and hospital lengths of stay (LOS), 1-year readmissions, and emergency department visits was performed among AKI, ARF, and uninjured patients. MEASUREMENTS AND MAIN RESULTS Ninety-seven patients underwent lung transplantation; 22 patients developed AKI and 35 patients developed ARF. Patients with ARF had significantly longer ICU LOS (12 days v 4 days, p < 0.001); ventilator days (4.5 days v 1 day, p < 0.001); and hospital LOS (22.5 days v 14 days, p < 0.001) compared with uninjured patients. Patients with AKI also had significantly longer ICU and hospital LOS. Patients with ARF had significantly more emergency department visits and hospital readmissions (2 v 1 readmissions, p = 0.002) compared with uninjured patients. A univariable analysis suggested that prolonged surgical time, intraoperative vasopressor use, and cardiopulmonary bypass use were associated with the highest increased risk for AKI. Intraoperative vasopressor use and cardiopulmonary bypass mean arterial pressure <60 mmHg were identified as independent risk factors by multivariable analysis for AKI. CONCLUSION The severity of AKI was associated with an increase in the use of healthcare resources after surgery and discharge. Certain risk factors appeared modifiable and may reduce the incidence of AKI and ARF.

627: PERIOPERATIVE EVENTS AFFECTING ACUTE RENAL FAILURE IN POST-LUNG TRANSPLANT PATIENTS

Crit Care Med 2016 • Volume 44 • Number 12 (Suppl.) 35% received living-related LTx while the rest received deceased organ grafts. The mean age was 4.6 y (6 m – 24y) and 55% were female. Almost one third of the 58 episodes met criteria for septic shock and 39% had multiple organ dysfunction syndrome. Approximately 52% of the patients required mechanical ventilation and 5% of the patients were placed on extracorporeal membrane oxygenation support. The primary sites of infection included blood (40%), respiratory tract (16%), peritonitis (14%). Culture results were documented as bacterial (68%), culture negative (13%), viral (7%), and fungal (2%). Of note, 36% of bacterial infections were due to MDROs, predominantly vancomycin resistant enterococcus and extend spectrum beta lactamase producers. No graft loss was attributable to sepsis. Mortality for this cohort was 5%. Conclusions: Compared to the general PICU population, liver transplant recipients are more likely to be septic but have lower mortality despite infection with MDROs. Knowledge about local bacterial epidemiology should guide initial empiric antibiotic therapy. Future studies are needed to identify potential risk factors in this cohort, including immunosuppression management.