Sunil K. Geevarghese

The relationship between delirium duration, white matter integrity, and cognitive impairment in intensive care unit survivors as determined by diffusion tensor imaging: the VISIONS prospective cohort magnetic resonance imaging study*.

Objective:Evidence is emerging that delirium duration is a predictor of long-term cognitive impairment in intensive care unit survivors. Relationships between 1) delirium duration and brain white matter integrity, and 2) white matter integrity and long-term cognitive impairment are poorly understood and could be explored using magnetic resonance imaging. Design, Setting, Patients:A two-center, prospective cohort study incorporating delirium monitoring, neuroimaging, and cognitive testing in intensive care unit survivors. Measurements:Delirium was evaluated with the Confusion Assessment Method for the Intensive Care Unit and cognitive outcomes were tested at 3 and 12-month follow-up. Following the intensive care unit stay, fractional anisotropy, a measure of white matter integrity, was calculated quantitatively using diffusion tensor imaging with a 3-T magnetic resonance imaging scanner at hospital discharge and 3-month follow-up. We examined associations between 1) delirium duration and fractional anisotropy and 2) fractional anisotropy and cognitive outcomes using linear regression adjusted for age and sepsis. Results:A total of 47 patients with a median age of 50 yrs completed the diffusion tensor imaging-magnetic resonance imaging protocol. Greater duration of delirium (3 vs. 0 days) was associated with lower fractional anisotropy (i.e., reduced fractional anisotropy = white matter disruption) in the genu (−0.02; p = .04) and splenium (−0.01; p = .02) of the corpus callosum and anterior limb of the internal capsule (−0.02; p =.01) at hospital discharge. These associations persisted at 3 months for the genu (−0.02; p =.02) and splenium (−0.01; p = .004). Lower fractional anisotropy in the anterior limb of internal capsule at discharge and in genu of corpus callosum at three months was associated with worse cognitive scores at 3 and 12 months. Conclusions:In this pilot investigation, delirium duration in the intensive care unit was associated with white matter disruption at both discharge and 3 months. Similarly, white matter disruption was associated with worse cognitive scores up to 12 months later. This hypothesis-generating investigation may help design future studies to explore these complex relationships in greater depth.

The association between brain volumes, delirium duration, and cognitive outcomes in intensive care unit survivors: the VISIONS cohort magnetic resonance imaging study*.

Objective:Delirium duration is predictive of long-term cognitive impairment in intensive care unit survivors. Hypothesizing that a neuroanatomical basis may exist for the relationship between delirium and long-term cognitive impairment, we conducted this exploratory investigation of the associations between delirium duration, brain volumes, and long-term cognitive impairment. Design, Setting, and Patients:A prospective cohort of medical and surgical intensive care unit survivors with respiratory failure or shock. Measurements:Quantitative high resolution 3-Tesla brain magnetic resonance imaging was used to calculate brain volumes at discharge and 3-month follow-up. Delirium was evaluated using the confusion assessment method for the intensive care unit; cognitive outcomes were tested at 3- and 12-month follow-up. Linear regression was used to examine associations between delirium duration and brain volumes, and between brain volumes and cognitive outcomes. Results:A total of 47 patients completed the magnetic resonance imaging protocol. Patients with longer duration of delirium displayed greater brain atrophy as measured by a larger ventricle-to-brain ratio at hospital discharge (0.76, 95% confidence intervals [0.10, 1.41]; p = .03) and at 3-month follow-up (0.62 [0.02, 1.21], p = .05). Longer duration of delirium was associated with smaller superior frontal lobe (−2.11 cm3 [−3.89, −0.32]; p = .03) and hippocampal volumes at discharge (−0.58 cm3 [−0.85, −0.31], p < .001)—regions responsible for executive functioning and memory, respectively. Greater brain atrophy (higher ventricle-to-brain ratio) at 3 months was associated with worse cognitive performances at 12 months (lower Repeatable Battery for the Assessment of Neuropsychological Status score −11.17 [−21.12, −1.22], p = .04). Smaller superior frontal lobes, thalamus, and cerebellar volumes at 3 months were associated with worse executive functioning and visual attention at 12 months. Conclusions:These preliminary data show that longer duration of delirium is associated with smaller brain volumes up to 3 months after discharge, and that smaller brain volumes are associated with long-term cognitive impairment up to 12 months. We cannot, however, rule out that smaller preexisting brain volumes explain these findings.

Phosphorus ans an early predictive factor in patients with acute liver failure1

Background. This study analyzes the prognostic significance of serum phosphorus in patients with acute liver failure (ALF). Methods. We performed a retrospective analysis of 112 patients with ALF. Univariate and bivariate analyses based on Kaplan-Meier recovery curves and a multivariate Classification Tree Structure Survival Analysis were performed to identify independent predictors of outcome. The variables analyzed were age, gender, race, ABO blood group, etiology of liver disease, grade of encephalopathy, serum bilirubin, prothrombin time, creatinine, serum phosphorus, phosphorus administered, phosphorus binders, and hemodialysis. Results. The median follow-up time was 5 days, the median age was 28 years, and 62% of the patients were female. The patients’ outcomes were as follows: 28% recovered, 52% required orthotopic liver transplantation, and 20% died. White patients showed the best prognosis (58% recovered in the first week), and Hispanics showed the worst prognosis (0.3% recovered at 1 week) (P =0.0001). Encephalopathy and bilirubin were significant predictors of recovery (P <0.0001 and P =0.004). The analysis of the serum phosphorus showed a statistically significant better prognosis in patients with low phosphorus (P <0.001). The recovery rate at 1 week was 74% in patients with serum phosphorus less than 2.5 mg/dL, 45% if phosphorus ranged between 2.5 to 5 mg/dL, and 0% if phosphorus was more than 5 mg/dL. The bivariate analysis on the effects of phosphorus administration showed that phosphorus replacement was associated with a significant improvement in recovery in patients with low (P <0.004) or normal serum phosphorus levels (P <0.017) Conclusions. Hypophosphatemia and early phosphorus administration are associated with a good prognosis in ALF, whereas hyperphosphatemia is predictive of poor recovery.

Renal Function in Primary Liver Transplant Recipients Receiving Neoral (Cyclosporine) Versus Prograf (Tacrolimus)

Immunosuppressive efficacy of Neoral and Prograf following primary hepatic transplantation was comparable. Incidence of rejection episodes, infectious complications, hypertension, and postoperative diabetes mellitus was comparable. Although clinical use of both immunosuppressants was associated with early compromise in renal function, no progressive renal dysfunction was observed.

Surgery and Anesthesia Exposure Is Not a Risk Factor for Cognitive Impairment After Major Noncardiac Surgery and Critical Illness.

Objective: The aim of this study was to determine whether surgery and anesthesia exposure is an independent risk factor for cognitive impairment after major noncardiac surgery associated with critical illness. Summary of Background Data: Postoperative cognitive impairment is a prevalent individual and public health problem. Data are inconclusive as to whether this impairment is attributable to surgery and anesthesia exposure versus patients’ baseline factors and hospital course. Methods: In a multicenter prospective cohort study, we enrolled ICU patients with major noncardiac surgery during hospital admission and with nonsurgical medical illness. At 3 and 12 months, we assessed survivors’ global cognitive function with the Repeatable Battery for the Assessment of Neuropsychological Status and executive function with the Trail Making Test, Part B. We performed multivariable linear regression to study the independent association of surgery/anesthesia exposure with cognitive outcomes, adjusting initially for baseline covariates and subsequently for in-hospital covariates. Results: We enrolled 1040 patients, 402 (39%) with surgery/anesthesia exposure. Median global cognition scores were similar in patients with surgery/anesthesia exposure compared with those without exposure at 3 months (79 vs 80) and 12 months (82 vs 82). Median executive function scores were also similar at 3 months (41 vs 40) and 12 months (43 vs 42). Surgery/anesthesia exposure was not associated with worse global cognition or executive function at 3 or 12 months in models incorporating baseline or in-hospital covariates (P > 0.2). Higher baseline education level was associated with better global cognition at 3 and 12 months (P < 0.001), and longer in-hospital delirium duration was associated with worse global cognition (P < 0.02) and executive function (P < 0.01) at 3 and 12 months. Conclusions: Cognitive impairment after major noncardiac surgery and critical illness is not associated with the surgery and anesthesia exposure but is predicted by baseline education level and in-hospital delirium.

Registration of liver images to minimally invasive intraoperative surface and subsurface data

Laparoscopic liver resection is increasingly being performed with results comparable to open cases while incurring less trauma and reducing recovery time. The tradeoff is increased difficulty due to limited visibility and restricted freedom of movement. Image-guided surgical navigation systems have the potential to help localize anatomical features to improve procedural safety and achieve better surgical resection outcome. Previous research has demonstrated that intraoperative surface data can be used to drive a finite element tissue mechanics organ model such that high resolution preoperative scans are registered and visualized in the context of the current surgical pose. In this paper we present an investigation of using sparse data as imposed by laparoscopic limitations to drive a registration model. Non-contact laparoscopicallyacquired surface swabbing and mock-ultrasound subsurface data were used within the context of a nonrigid registration methodology to align mock deformed intraoperative surface data to the corresponding preoperative liver model as derived from pre-operative image segmentations. The mock testing setup to validate the potential of this approach used a tissue-mimicking liver phantom with a realistic abdomen-port patient configuration. Experimental results demonstrates a range of target registration errors (TRE) on the order of 5mm were achieving using only surface swab data, while use of only subsurface data yielded errors on the order of 6mm. Registrations using a combination of both datasets achieved TRE on the order of 2.5mm and represent a sizeable improvement over either dataset alone.

The association between brain volumes, delirium duration, and cognitive outcomes in intensive care unit survivors

Objective:Delirium duration is predictive of long-term cognitive impairment in intensive care unit survivors. Hypothesizing that a neuroanatomical basis may exist for the relationship between delirium and long-term cognitive impairment, we conducted this exploratory investigation of the associations between delirium duration, brain volumes, and long-term cognitive impairment. Design, Setting, and Patients:A prospective cohort of medical and surgical intensive care unit survivors with respiratory failure or shock. Measurements:Quantitative high resolution 3-Tesla brain magnetic resonance imaging was used to calculate brain volumes at discharge and 3-month follow-up. Delirium was evaluated using the confusion assessment method for the intensive care unit; cognitive outcomes were tested at 3- and 12-month follow-up. Linear regression was used to examine associations between delirium duration and brain volumes, and between brain volumes and cognitive outcomes. Results:A total of 47 patients completed the magnetic resonance imaging protocol. Patients with longer duration of delirium displayed greater brain atrophy as measured by a larger ventricle-to-brain ratio at hospital discharge (0.76, 95% confidence intervals [0.10, 1.41]; p = .03) and at 3-month follow-up (0.62 [0.02, 1.21], p = .05). Longer duration of delirium was associated with smaller superior frontal lobe (−2.11 cm3 [−3.89, −0.32]; p = .03) and hippocampal volumes at discharge (−0.58 cm3 [−0.85, −0.31], p < .001)—regions responsible for executive functioning and memory, respectively. Greater brain atrophy (higher ventricle-to-brain ratio) at 3 months was associated with worse cognitive performances at 12 months (lower Repeatable Battery for the Assessment of Neuropsychological Status score −11.17 [−21.12, −1.22], p = .04). Smaller superior frontal lobes, thalamus, and cerebellar volumes at 3 months were associated with worse executive functioning and visual attention at 12 months. Conclusions:These preliminary data show that longer duration of delirium is associated with smaller brain volumes up to 3 months after discharge, and that smaller brain volumes are associated with long-term cognitive impairment up to 12 months. We cannot, however, rule out that smaller preexisting brain volumes explain these findings.

Impact of sandimmune, neoral, and prograf on rejection incidence and renal function in primary liver transplant recipients

Following primary liver transplantation, immunosuppressive efficacy of Neoral and Prograf was similar and superior to that of Sandimmune. Rejection incidence was statistically increased with Sandimmune therapy. Incidence of hypertension, posttransplant diabetes mellitus, and infectious complications was not statistically different. Although early compromise in renal function was associated with Sandimmune, Neoral, and Prograf immunosuppression, no progressive renal dysfunction was identified.

Consensus Conference on North American Training in Hepatopancreaticobiliary Surgery: A Review of the Conference and Presentation of Consensus Statements

The findings and recommendations of the North American consensus conference on training in hepatopancreaticobiliary (HPB) surgery held in October 2014 are presented. The conference was hosted by the Society for Surgical Oncology (SSO), the Americas Hepato‐Pancreatico‐Biliary Association (AHPBA), and the American Society of Transplant Surgeons (ASTS). The current state of training in HPB surgery in North America was defined through three pathways—HPB, surgical oncology, and solid organ transplant fellowships. Consensus regarding programmatic requirements included establishment of minimum case volumes and inclusion of quality metrics. Formative assessment, using milestones as a framework and inclusive of both operative and nonoperative skills, must be present. Specific core HPB cases should be defined and used for evaluation of operative skills. The conference concluded with a focus on the optimal means to perform summative assessment to evaluate the individual fellow completing a fellowship in HPB surgery. Presentations from the hospital perspective and the American Board of Surgery led to consensus that summative assessment was desired by the public and the hospital systems and should occur in a uniform but possibly modular manner for all HPB fellowship pathways. A task force composed of representatives of the SSO, AHPBA, and ASTS are charged with implementation of the consensus statements emanating from this consensus conference.

The Association between Brain Volumes, Delirium Duration and Cognitive Outcomes in Intensive Care Unit Survivors: A Prospective Exploratory Cohort Magnetic Resonance Imaging Study

Objective:Delirium duration is predictive of long-term cognitive impairment in intensive care unit survivors. Hypothesizing that a neuroanatomical basis may exist for the relationship between delirium and long-term cognitive impairment, we conducted this exploratory investigation of the associations between delirium duration, brain volumes, and long-term cognitive impairment. Design, Setting, and Patients:A prospective cohort of medical and surgical intensive care unit survivors with respiratory failure or shock. Measurements:Quantitative high resolution 3-Tesla brain magnetic resonance imaging was used to calculate brain volumes at discharge and 3-month follow-up. Delirium was evaluated using the confusion assessment method for the intensive care unit; cognitive outcomes were tested at 3- and 12-month follow-up. Linear regression was used to examine associations between delirium duration and brain volumes, and between brain volumes and cognitive outcomes. Results:A total of 47 patients completed the magnetic resonance imaging protocol. Patients with longer duration of delirium displayed greater brain atrophy as measured by a larger ventricle-to-brain ratio at hospital discharge (0.76, 95% confidence intervals [0.10, 1.41]; p = .03) and at 3-month follow-up (0.62 [0.02, 1.21], p = .05). Longer duration of delirium was associated with smaller superior frontal lobe (−2.11 cm3 [−3.89, −0.32]; p = .03) and hippocampal volumes at discharge (−0.58 cm3 [−0.85, −0.31], p < .001)—regions responsible for executive functioning and memory, respectively. Greater brain atrophy (higher ventricle-to-brain ratio) at 3 months was associated with worse cognitive performances at 12 months (lower Repeatable Battery for the Assessment of Neuropsychological Status score −11.17 [−21.12, −1.22], p = .04). Smaller superior frontal lobes, thalamus, and cerebellar volumes at 3 months were associated with worse executive functioning and visual attention at 12 months. Conclusions:These preliminary data show that longer duration of delirium is associated with smaller brain volumes up to 3 months after discharge, and that smaller brain volumes are associated with long-term cognitive impairment up to 12 months. We cannot, however, rule out that smaller preexisting brain volumes explain these findings.