Objective Delirium duration is predictive of long-term cognitive impairment (LTCI) in Intensive Care Unit (ICU) survivors. Hypothesizing that a neuroanatomical basis may exist for the relationship between delirium and LTCI, we conducted this exploratory investigation of the associations between delirium duration, brain volumes and LTCI. Design, Setting, and Patients A prospective cohort of medical and surgical ICU 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 three-month follow-up. Delirium was evaluated using the Confusion Assessment Method for the ICU; cognitive outcomes were tested at three- and twelve-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 MRI protocol. Patients with longer duration of delirium displayed greater brain atrophy as measured by a larger ventricle-to-brain ratio (VBR) at hospital discharge [0.76, 95% confidence intervals (CI) (0.10, 1.41); p=0.03] and at 3-month follow-up [0.62 (0.02, 1.21), p=0.05]. Longer duration of delirium was associated with smaller superior frontal lobe [−2.11 cm3 (−3.89, −0.32); p=0.03] and hippocampal volumes at discharge [−0.58 cm3 (−0.85, −0.31), p<0.001] – regions responsible for executive functioning and memory, respectively. Greater brain atrophy (higher VBR) at three months was associated with worse cognitive performances at twelve months [lower RBANS battery score −11.17 (−21.12, −1.22), p=0.04]. Smaller superior frontal lobes, thalamus, and cerebellar volumes at three months were associated with worse executive functioning and visual attention at twelve months. Conclusions These preliminary data show that longer duration of delirium is associated with smaller brain volumes up to three months after discharge, and that smaller brain volumes are associated with LTCI up to 12 months. We cannot, however, rule out that smaller preexisting brain volumes explain these findings.

Objective Evidence is emerging that delirium duration is a predictor of long-term cognitive impairment (LTCI) in Intensive Care Unit (ICU) survivors. Relationships between (a) delirium duration and brain white matter integrity, and (b) between white matter integrity and LTCI are poorly understood and could be explored using Magnetic Resonance Imaging (MRI). Design, Setting, Patients A two-center, prospective cohort study incorporating delirium monitoring, neuroimaging and cognitive testing in ICU survivors. Measurements Delirium was evaluated with the Confusion Assessment Method for the ICU (CAM-ICU) and cognitive outcomes were tested at 3 and 12-month follow-up. Following the ICU stay, Fractional Anisotropy (FA), a measure of white matter integrity, was calculated quantitatively using Diffusion Tensor Imaging (DTI) with a 3-Tesla MRI scanner at hospital discharge and three-month follow-up. We examined associations between (a) delirium duration and FA and (b) between FA and cognitive outcomes using linear regression adjusted for age and sepsis. Results A total of 47 patients with median age of 50 years completed the DTI-MRI protocol. Greater duration of delirium (3 vs. 0 days) was associated with lower FA (i.e. reduced FA=white matter disruption) in the genu (−0.02; p = 0.04) and splenium (−0.01; p = 0.02) of the corpus callosum and anterior limb of the internal capsule (−0.02; p = 0.01) at hospital discharge. These associations persisted at 3 months for the genu (−0.02; p= 0.02) and splenium (−0.01; p= 0.004). Lower FA in the anterior limb of internal capsule at discharge (−10.35; p= 0.05) and in genu of corpus callosum at three months (−8.81; p = 0.006) was associated with worse cognitive scores at 3 and 12 months. Conclusions In this pilot investigation, delirium duration in the ICU 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.

This multicenter phase I/II study evaluated the safety, pharmacokinetics, and antitumor effects of repeated doses of NV1020, a genetically engineered oncolytic herpes simplex virus, in patients with advanced metastatic colorectal cancer (mCRC). Patients with liver-dominant mCRC received four fixed NV1020 doses via weekly hepatic artery infusion, followed by two or more cycles of conventional chemotherapy. Phase I included cohorts receiving 3 × 10(6), 1 × 10(7), 3 × 10(7), and 1 × 10(8) plaque-forming units (PFU)/dose to determine the optimal biological dose (OBD) for phase II. Blind independent computed tomography scan review was based on RECIST (response evaluation criteria in solid tumors) to assess hepatic tumor response. Phase I and II enrolled 13 and 19 patients, respectively. Patients experienced transient mild-moderate febrile reactions after each NV1020 infusion. Grade 3/4 virus-related toxicity was limited to transient lymphopenia in two patients. NV1020 shedding was not detected. Simultaneous cytokine and grade 1 coagulation perturbations were dose-limiting at 1 × 10(8) PFU/dose, considered the OBD. All 22 OBD patients had previously received 5-fluorouracil; most had received oxaliplatin or irinotecan (50% had both), many with at least one targeted agent. After NV1020 administration, 50% showed stable disease. The best overall tumor control rate after chemotherapy was 68% (1 partial response, 14 stable disease); this did not correlate with baseline variables or chemotherapy. Median time to progression was 6.4 months (95% confidence interval: 2, 8.9); median overall survival was 11.8 months (95% confidence interval: 8.3, 20.7). One-year survival was 47.2%. We conclude that NV1020 stabilizes liver metastases with minimal toxicity in mCRC. It may resensitize metastases to salvage chemotherapy and extend overall survival. A randomized phase II/III trial now appears justified.

Orthotopic liver transplantation for HBV under combination viral prophylaxis results in survival rates equivalent to other indications. Pretransplant viral replication, UNOS status, and the presence of HCC are all sensitive markers for posttransplantation outcome. Viral prophylactic therapy has effectively reduced HBV recurrence and prolonged survival outcomes. The combination of HBIg and lamivudine is the prophylactic regimen of choice.

S urvivors of critical illness often have a prolonged form of cognitive dysfunction, characterized by new deficits or exacerbations of preexisting mild deficits in global cognition or executive function. The ramifications of this long-term cognitive impairment after critical illness are well known, especially among older adults. Delirium, a form of acute brain dysfunction, may be associated with long-term cognitive impairment. The use of sedative and analgesic medications may also contribute to long-term cognitive impairment. This multicenter, prospective cohort study was undertaken to estimate the prevalence of long-term cognitive impairment after critical illness and to determine if a longer duration of delirium in the hospital and higher doses of sedative and analgesic drugs are associated with more severe cognitive impairment up to a year after hospital discharge.Enrolled patients with respiratory failure, cardiogenic shock, or septic shock were in a medical or surgical intensive care unit (ICU). Two primary independent risk factors were assessed, specifically, the duration of delirium (number of hospital days with delirium) and the use of sedative or analgesic medications during hospitalization. Delirium was assessed with the Confusion Assessment Method for the ICU (CAM-ICU), which determines the presence or absence of delirium based on acute change or a fluctuation in mental status, inattention, disorganized thinking, and altered level of consciousness. Patients were assessed for global cognition and executive function at 3 and 12 months after discharge using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). This assessment is a battery for the evaluation of global cognition including individual domains of immediate and delayed memory, attention, visuospatial construction, and language. The population age-adjusted mean score and for the domains is 100 ± 15 on a scale ranging from 40 to 160, with lower scores indicating worse performance. Executive function was assessed with the Trail Making Test, Part B. The T score after adjustment for age, sex, and education is 50 on a scale of 0 to 100, with lower scores indicating worse executive function. Linear regression, with adjustment for potential confounders, was used to determine the associations of the duration of delirium and the use of sedative or analgesic agents with outcomes.Of the 821 patients (median age, 61 years), only 51 (6%) had signs of preexisting cognitive impairment. Delirium affected 606 patients (74%) during the hospital stay; the median duration of delirium was 4 days. At the 3-month follow-up, 448 (79%) of 569 surviving patients had cognitive testing; 382 (75%) of the 510 surviving patients were tested at 12 months. Median RBANS global cognition scores at 3 and 12 months were 79 and 80, respectively,~1.5 SDs below the age-adjusted population mean, and were similar to scores for patients with mild cognitive impairment. At 3 months, 40% of patients had global cognition scores similar to scores for patients with mo...

Hypophosphatemia and early phosphorus administration are associated with a good prognosis in ALF, whereas hyperphosphatemia is predictive of poor recovery.

Laparoscopic liver surgery is challenging to perform due to a compromised ability of the surgeon to localize subsurface anatomy in the constrained environment. While image guidance has the potential to address this barrier, intraoperative factors, such as insufflation and variable degrees of organ mobilization from supporting ligaments, may generate substantial deformation. The severity of laparoscopic deformation in humans has not been characterized, and current laparoscopic correction methods do not account for the mechanics of how intraoperative deformation is applied to the liver. We first measure the degree of laparoscopic deformation at two insufflation pressures over the course of laparoscopic-to-open conversion in 25 patients. With this clinical data alongside a mock laparoscopic phantom setup, we report a biomechanical correction approach that leverages anatomically load-bearing support surfaces from ligament attachments to iteratively reconstruct and account for intraoperative deformations. Laparoscopic deformations were significantly larger than deformations associated with open surgery, and our correction approach yielded subsurface target error of [Formula: see text] and surface error of [Formula: see text] using only sparse surface data with realistic surgical extent. Laparoscopic surface data extents were examined and found to impact registration accuracy. Finally, we demonstrate viability of the correction method with clinical data.

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.