Objective
The aim of this work was to investigate whether an imaging measure of corticospinal tract (CST) injury in the acute phase can predict motor outcome at 3 months in comparison to clinical ...assessment of initial motor impairment.
Methods
A two‐site prospective cohort study followed up a group of first‐ever ischemic stroke patients using the Upper‐Extremity Fugl‐Meyer (UE‐FM) Scale to measure motor impairment in the acute phase and at 3 months. A weighted CST lesion load (wCST‐LL) was calculated by overlaying the patient's lesion map on magnetic resonance imaging with a probabilistic CST constructed from healthy control subjects. Regression models were fit to assess the predictive value of wCST‐LL and compared with initial motor impairment.
Results
Seventy‐six patients (37 from cohort 1 and 39 from cohort 2) completed the study. wCST‐LL as well as assessment of motor impairment (UE‐FM) in the acute phase correlated with motor impairment (UE‐FM) at 3 months in both cohort 1 (R2 = 0.69 vs. R2 = 0.67; p = 0.43) and cohort 2 (R2 = 0.69 vs. R2 = 0.62; p = 0.25). In the severely impaired subgroup (defined as UE‐FM ≤ 10 at baseline), wCST‐LL correlated with outcomes significantly better than clinical assessment (R2 = 0.47 vs. R2 = 0.11; p = 0.03). In the nonseverely impaired subgroup, stroke patients recovered approximately 70% of their maximal recovery potential. All stroke patients in both cohorts had poor motor outcomes at 3 months (defined as UE‐FM ≤ 25) when wCST‐LL was ≥ 7.0 cc (positive predictive value was 100%).
Interpretation
wCST‐LL, an imaging biomarker determined in the acute phase, can predict poststroke motor outcomes at 3 months, especially in patients with severe impairment at baseline. Ann Neurol 2015;78:860–870
Multifocal hepatocellular carcinoma (HCC) differs biologically and immunologically from single-nodule HCC. Asian and European guidelines consider liver transplantation (LT) and partial hepatectomy ...(PH) as effective for T2 multifocal HCC, with preference toward LT, but few US studies compare these treatments directly. This propensity score-based observational study uses an established national cancer outcomes registry to compare overall survival in patients undergoing PH and LT for multifocal HCC.
Data from the 2020 National Cancer Database were obtained on patients who underwent LT or PH for multifocal stage 2 HCC within Milan criteria and without vascular invasion. Propensity score matching and Cox regression analysis was applied to evaluate overall survival in an observational cohort balanced by age, sex, treatment facility type, treatment year, prothrombin time, α-fetoprotein, comorbidity burden, liver fibrosis severity, and pretreatment creatinine and bilirubin levels.
Of 21,248 T2 HCC patients identified, 6,744 had multifocal tumors with largest tumor diameter <3 cm without major vascular invasion, with 1,267 and 181 having undergone LT and PH, respectively. Propensity score-matched Cox regression analysis associated LT with a hazard ratio of 0.39 (95% CI 0.30 to 0.50) relative to PH. Landmark analyses to account for a longer interval to LT demonstrated survival benefits of similar magnitude.
Although early-stage HCC can be effectively treated with either LT or PH, propensity score-matched analysis comparatively shows a survival benefit for LT in patients with multifocal HCC who are within the Milan criteria.
Frailty with sarcopenia in cirrhosis causes liver transplant wait‐list attrition and deaths. Regular physical activity is needed to protect patients with cirrhosis from frailty. We subjectively ...assess physical performance in selecting patients for transplant listing, but we do not know whether clinical assessments reflect the extent of activity patients actually perform. To investigate this question, 53 wait‐listed patients self‐assessed their performance of ordinary physical tasks using the Rosow‐Breslau survey, and clinicians assessed their physical performance status with the Karnofsky index. We compared these assessments with actual activity measured using an accelerometer/thermal sensing armband worn from 4 to 7 days. We found that their measured activity was among the lowest reported in chronic disease, similar to that of patients with advanced chronic pulmonary disease or renal failure. Their percentages of waking hours spent in sedentary, light, and moderate‐vigorous activity were 75.9% ± 18.9%, 18.9% ± 14.3%, and 4.9% ± 6.9%, respectively. Higher mean sedentary and lower mean moderate‐vigorous activity was significantly associated with 9 wait‐list deaths (P = 0.004). Compared with a range of 7000‐13,000 steps/day in healthy adults, patients' mean steps/day were 3164 ± 2842. Both their activity percentage and step data were typical of other severely inactive populations. Neither their Rosow‐Breslau scores (mean 2.3 ± 0.8, maximum 3.0) nor their Karnofsky scores (mean 79 ± 12, maximum 100) suggested major impairment or showed a correlation with patients' actual physical performance. In conclusion, physical activity in patients with cirrhosis wait‐listed for transplantation is highly sedentary. Self‐assessments and provider assessments of physical activity do not reliably indicate actual performance. Whether the gap between assessed and actual performance may be favorably modified by interventions to improve activity and ameliorate frailty merits further study. Liver Transplantation 22 1324–1332 2016 AASLD.
Frailty is a known risk factor for major life-threatening liver transplant complications, deaths, and waitlist attrition. Whether frailty indicates risk for adverse outcomes in cirrhosis short of ...lethality is not well defined. We hypothesized that clinical measurements of frailty using gait speed and grip strength would indicate the risk of subsequent hospitalization for the complications of cirrhosis.
We assessed frailty as gait speed and grip strength in a 1-year prospective study of 373 cirrhotic patients evaluated for or awaiting liver transplantation. We determined its association with the outcome of subsequent hospital days/100 days at risk for 7 major complications of cirrhosis. We tested potential covariate influences of Model for Endstage Liver Disease (MELD) and Child-Turcotte-Pugh (CTP) scores, age, sex, height, depression, narcotic use, vitamin D deficiency, and hepatocellular carcinoma using multivariable modeling.
Patients experienced 2.14 hospital days/100 days at risk, or 7.81 days/year. Frailty measured by gait speed was a strong risk factor for hospitalization for all cirrhosis complications. Each 0.1 m/s gait speed decrease was associated with 22% greater hospital days (P<0.001). Grip strength showed a similar but nonsignificant association. Gait speed remained independently significant when adjusted for MELD, CTP, and other covariates. At hospital costs of $4,000/day, patients with normal 1 m/s gait speed spent 6.2 days and $24,800/year; patients with 0.5 m/s speed spent 21.2 days and $84,800/year; and patients with 0.25 m/s speed spent 40.2 days and $160,800/year.
Frailty as measured by gait speed is an independent and potentially modifiable risk factor for cirrhosis complications requiring hospitalization. The potential clinical value of frailty measurements to help define such risk merits broader evaluation.
Frailty and sarcopenia are known risk factors for adverse liver transplant outcomes and mortality. We hypothesized that frailty or sarcopenia could identify the risk for common serious ...transplant-related adverse respiratory events.
For 107 patients (74 men, 33 women) transplanted over 1 year, we measured frailty with gait speed, chair stands, and Karnofsky Performance Scale (KPS) and sarcopenia with Skeletal Muscle Index on computed tomography at L3. We recorded the stress-tested cardiac double product as an index of cardiac work capacity. Outcomes included days of intubation, aspiration, clinical pneumonia, reintubation/tracheostomy, days to discharge, and survival. We modeled the outcomes using unadjusted regression and multivariable analyses controlled for (i) age, sex, and either Model for End-Stage Liver Disease-Na (MELDNa) or Child-Turcotte-Pugh scores, (ii) hepatocellular carcinoma status, and (iii) chronic obstructive pulmonary disease and smoking history. Subgroup analysis was performed for living donor liver transplant and deceased donor liver transplant recipients.
Gait speed was negatively associated with aspiration and pulmonary infection, both in unadjusted and MELDNa-adjusted models (adjusted odds ratio for aspiration 0.10 95% confidence interval CI 0.02-0.67 and adjusted odds ratio for pulmonary infection 0.12 95% CI 0.02-0.75). Unadjusted and MELDNa-adjusted models for gait speed (coefficient -1.47, 95% CI -2.39 to -0.56) and KPS (coefficient -3.17, 95% CI -5.02 to -1.32) were significantly associated with shorter intubation times. No test was associated with length of stay or need for either reintubation or tracheostomy.
Slow gait speed, an index of general frailty, indicates significant risk for post-transplant respiratory complications. Intervention to arrest or reverse frailty merits exploration as a potentially modifiable risk factor for improving transplant respiratory outcomes.
The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral ...activity.
Prospective weekly hospital stress survey, November 2020-June 2022.
Society of Critical Care Medicine's Discovery Severe Acute Respiratory Infection-Preparedness multicenter cohort study.
Thirteen hospitals across seven U.S. health systems.
None.
We analyzed 839 hospital-weeks of data over 85 pandemic weeks and five viral surges. Perceived overall hospital, ICU, and emergency department (ED) stress due to severe acute respiratory infection patients during the pandemic were reported by a mean of 43% ( sd , 36%), 32% (30%), and 14% (22%) of hospitals per week, respectively, and perceived care deviations in a mean of 36% (33%). Overall hospital stress was highly correlated with ICU stress (ρ = 0.82; p < 0.0001) but only moderately correlated with ED stress (ρ = 0.52; p < 0.0001). A county increase in 10 severe acute respiratory syndrome coronavirus 2 cases per 100,000 residents was associated with an increase in the odds of overall hospital, ICU, and ED stress by 9% (95% CI, 5-12%), 7% (3-10%), and 4% (2-6%), respectively. During the Delta variant surge, overall hospital stress persisted for a median of 11.5 weeks (interquartile range, 9-14 wk) after local case peak. ICU stress had a similar pattern of resolution (median 11 wk 6-14 wk after local case peak; p = 0.59) while the resolution of ED stress (median 6 wk 5-6 wk after local case peak; p = 0.003) was earlier. There was a similar but attenuated pattern during the Omicron BA.1 subvariant surge.
During the COVID-19 pandemic, perceived care deviations were common and potentially avoidable patient harm was rare. Perceived hospital stress persisted for weeks after surges peaked.
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive enlargement of kidney cysts leading to chronic kidney disease (CKD) and end-stage renal disease (ESRD). ...Identification of an early biomarker that can predict progression of CKD is urgently needed. In an earlier Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) study (a prospective, multicenter, observational analysis of 241 patients with ADPKD initiated in 2000), baseline height-adjusted total kidney volume (htTKV) was shown to be associated with development of CKD stage 3 after eight years of follow-up. Here we conducted an extended study and found that in a multivariable logistic regression model, baseline htTKV was shown to be a strong, independent predictor for the development of CKD after a median follow-up of 13 years. The odds ratio of reaching each CKD stage per 100 mL/m increment in htTKV was 1.38 (95% confidence interval 1.19-1.60) for stage 3, 1.42 (1.23-1.64) for stage 4, and 1.35 (1.18-1.55) for stage 5 or ESRD. Baseline htTKV was also associated with relative decreases in the glomerular filtration rate of 30%, and 57% or more. Moreover, the rate of change in htTKV was negatively correlated with the slope of the glomerular filtration rate. While ADPKD genotype was also associated with CKD outcomes, it was not an independent prognostic factor after adjusting for htTKV. Thus, baseline total kidney volume and the rate of kidney growth are strongly associated with the development of advanced stages of CKD. These findings support the use of total kidney volume as a prognostic and potentially monitoring biomarker in ADPKD.
Activation of host T cells that mediate allograft rejection is a 2-step process. The first occurs in secondary lymphoid organs where T cells encounter alloantigens presented by host DCs and ...differentiate to effectors. Antigen presentation at these sites occurs principally via transfer of intact, donor MHC-peptide complexes from graft cells to host DCs (cross-dressing) or by uptake and processing of donor antigens into allopeptides bound to self-MHC molecules (indirect presentation). The second step takes place in the graft, where effector T cells reengage with host DCs before causing rejection. How host DCs present alloantigens to T cells in the graft is not known. Using mouse islet and kidney transplantation models, imaging cytometry, and 2-photon intravital microscopy, we demonstrate extensive cross-dressing of intragraft host DCs with donor MHC-peptide complexes that occurred early after transplantation, whereas host DCs presenting donor antigen via the indirect pathway were rare. Cross-dressed DCs stably engaged TCR-transgenic effector CD8+ T cells that recognized donor antigen and were sufficient for sustaining acute rejection. In the chronic kidney rejection model, cross-dressing declined over time but was still conspicuous 8 weeks after transplantation. We conclude that cross-dressing of host DCs with donor MHC molecules is a major antigen presentation pathway driving effector T cell responses within allografts.
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cyst and kidney growth, which is hypothesized to cause loss of functioning renal mass and eventually end-stage kidney disease. ...However, the time course of decline in glomerular filtration rate (GFR) is poorly defined. The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease study is a 14-year observational cohort study of 241 adults with ADPKD. As an estimate of the rate of kidney growth, participants were stratified into 5 subclasses based on baseline age and magnetic resonance imaging measurements of total kidney volume (TKV) according to the method of Irazabal. GFR trajectories spanning over four decades of life were reconstructed and fitted using mixed polynomial models, which were validated using data from the HALT-PKD study. GFR trajectories were nonlinear, with a period of relative stability in most participants, followed by accelerating decline. The shape and slope of these trajectories were strongly associated with baseline Irazabal class. Patients with PKD1 mutations had a steeper GFR decline than patients with PKD2 mutations or with no detected mutation, largely mediated by the effect of genotype on Irazabal class. Thus, GFR decline in ADPKD is nonlinear, and its trajectory throughout adulthood can be predicted from a single measurement of kidney volume. These models can be used for clinical prognostication, clinical trial design, and patient selection for clinical interventions. Our findings support a causal link between growth in kidney volume and GFR decline, adding support for the use of TKV as a surrogate endpoint in clinical trials.
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Serum-biomarker based screening for pancreatic cancer could greatly improve survival in appropriately targeted high-risk populations.
Eighty-three circulating proteins were analyzed in sera of ...patients diagnosed with pancreatic ductal adenocarcinoma (PDAC, n = 333), benign pancreatic conditions (n = 144), and healthy control individuals (n = 227). Samples from each group were split randomly into training and blinded validation sets prior to analysis. A Metropolis algorithm with Monte Carlo simulation (MMC) was used to identify discriminatory biomarker panels in the training set. Identified panels were evaluated in the validation set and in patients diagnosed with colon (n = 33), lung (n = 62), and breast (n = 108) cancers.
Several robust profiles of protein alterations were present in sera of PDAC patients compared to the Healthy and Benign groups. In the training set (n = 160 PDAC, 74 Benign, 107 Healthy), the panel of CA 19-9, ICAM-1, and OPG discriminated PDAC patients from Healthy controls with a sensitivity/specificity (SN/SP) of 88/90%, while the panel of CA 19-9, CEA, and TIMP-1 discriminated PDAC patients from Benign subjects with an SN/SP of 76/90%. In an independent validation set (n = 173 PDAC, 70 Benign, 120 Healthy), the panel of CA 19-9, ICAM-1 and OPG demonstrated an SN/SP of 78/94% while the panel of CA19-9, CEA, and TIMP-1 demonstrated an SN/SP of 71/89%. The CA19-9, ICAM-1, OPG panel is selective for PDAC and does not recognize breast (SP = 100%), lung (SP = 97%), or colon (SP = 97%) cancer.
The PDAC-specific biomarker panels identified in this investigation warrant additional clinical validation to determine their role in screening targeted high-risk populations.
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