Mara, Kristin C

The lack of reliable, noninvasive methods to diagnose early nonalcoholic steatohepatitis (NASH) is a major unmet need. We aimed to determine the diagnostic accuracy of three‐dimensional magnetic resonance elastography (3D‐MRE), with shear stiffness measured at 60 Hz, damping ratio at 40 Hz, and magnetic resonance imaging proton density fat fraction (MRI‐PDFF) in the detection of NASH in individuals undergoing bariatric surgery. Obese adults at risk for NASH were enrolled between 2015 and 2017 (prospective cohort, n = 88) and 2010 and 2013 (retrospective cohort, n = 87). The imaging protocol consisted of multifrequency 3D‐MRE (mf3D‐MRE) with shear waves delivered at different frequencies to explore parameters that best correlated with histologic NASH, and MRI‐PDFF to estimate steatosis. The prospective cohort was used to establish the optimal mf3D‐MRE technical parameters for NASH detection. The two cohorts were then combined to derive predictive models of NASH and disease activity by nonalcoholic fatty liver disease activity score (NAS) using the three imaging parameters that correlated with NASH. A total of 175 patients (median age 45, 81% women, and 81 [46%] with histologic NASH) were used for model derivation. From the complex shear modulus output generated by mf3D‐MRE, the damping ratio at 40 Hz and shear stiffness at 60 Hz best correlated with NASH. The fat fraction obtained from MRI‐PDFF correlated with steatosis ( P < 0.05 for all). These three parameters were fit into a logistic regression model that predicted NASH with cross‐validated area under the receiver operating characteristic curve (AUROC) = 0.73, sensitivity = 0.67, specificity = 0.80, positive predictive value = 0.73 and negative predictive value = 0.74, and disease activity by NAS with cross‐validated AUROC = 0.82. Conclusion: The mf3D‐MRE allows identification of imaging parameters that predict early NASH and disease activity. This imaging biomarker represents a promising alternative to liver biopsy for NASH diagnosis and monitoring. The results provide motivation for further studies in nonbariatric cohorts.

AbstractBackgroundReliable and valid tools to screen for malnutrition in the intensive care unit (ICU) remain elusive. The sarcopenia index (SI) [(serum creatinine/serum cystatin C) × 100], could be an inexpensive, objective tool to predict malnutrition. We evaluated the SI as a screening tool for malnutrition in the ICU and compared it with the modified‐NUTRIC score.Materials and MethodsThis was a historical cohort study of ICU patients with stable kidney function admitted to Mayo Clinic ICUs between 2008 and 2015. Malnutrition was defined by the Subjective Global Assessment. Diagnostic performance was evaluated with the area under the receiver operating characteristic curve (AUC) and multivariable logistic regression.ResultsOf the 398 included patients, 181 (45%) had malnutrition, with 34 (9%) scored as severely malnourished. The SI was significantly lower in malnourished patients than in well‐nourished patients (64 ± 27 vs 72 ± 25; P = 0.002), and reductions in SI corresponded to increased malnutrition severity (P = 0.001). As a screening tool, the SI was an indicator of malnutrition risk (AUC 0.61) and performed slightly better than the more complex modified‐NUTRIC score (AUC = 0.57). SI cutoffs of 101 and 43 had >90% sensitivity and >90% specificity, respectively, for the prediction of malnutrition. Patients with a low SI (≤43) had a significantly higher risk of mortality (HR = 2.61, 95% CI 1.06–6.48, P = 0.038).ConclusionThe frequency of malnutrition was high in this critically ill population, and it was associated with a poor prognosis. The SI could be used to assess nutrition risk in ICU patients.

ObjectivesThe primary objective of this study was to determine whether pharmacist‐clinician collaborative (PCC) visits within 7 days after hospital discharge (early‐visit cohort) would reduce the risk of 30‐day hospital readmission compared with PCC visits eight or more days after hospital discharge (late‐visit cohort).MethodsThis retrospective study of adult primary care patients was conducted from July 26, 2013 to April 1, 2016. Patients who were included were receiving at least one medication that put them at high risk for emergent hospital admission and at least 10 total medications. A Cox proportional hazards model was used to assess 30‐day readmission risk between the two groups.ResultsThe early‐visit cohort included 393 patients; the late‐visit cohort included 109 patients. After adjusting for statistically different baseline characteristics and the LACE index score (which predicts the risk of death or unplanned readmission within 30 days after hospital discharge), 30‐day readmission risk was not significantly different between the late‐visit cohort and the early‐visit cohort (hazard ratio, 0.8; 95% confidence interval [CI], 0.34‐1.88; P = 0.61). Similarly, the difference was not significant 60 and 180 days after the PCC visit.ConclusionPatients in the early‐visit cohort had no greater risk of readmission 30 days after the visit than patients in the late‐visit cohort. Although previous research indicates that PCC visits may have significant benefits for decreasing readmission risk, delaying them may not increase the patient's risk. This finding may allow more flexibility in scheduling a pharmacist and a primary care clinician to meet with the patient.

Abstract Background: The GALAD score is a serum biomarker–based model that predicts the probability of having hepatocellular carcinoma (HCC) in patients with chronic liver disease. We aimed to assess the performance of the GALAD score in comparison with liver ultrasound for detection of HCC. Methods: A single-center cohort of 111 HCC patients and 180 controls with cirrhosis or chronic hepatitis B and a multicenter cohort of 233 early HCC and 412 cirrhosis patients from the Early Detection Research Network (EDRN) phase II HCC Study were analyzed. Results: The area under the ROC curve (AUC) of the GALAD score for HCC detection was 0.95 [95% confidence interval (CI), 0.93–97], which was higher than the AUC of ultrasound (0.82, P &lt;0.01). At a cutoff of −0.76, the GALAD score had a sensitivity of 91% and a specificity of 85% for HCC detection. The AUC of the GALAD score for early-stage HCC detection remained high at 0.92 (95% CI, 0.88–0.96; cutoff −1.18, sensitivity 92%, specificity 79%). The AUC of the GALAD score for HCC detection was 0.88 (95% CI, 0.85–0.91) in the EDRN cohort. The combination of GALAD and ultrasound (GALADUS score) further improved the performance of the GALAD score in the single-center cohort, achieving an AUC of 0.98 (95% CI, 0.96–0.99; cutoff −0.18, sensitivity 95%, specificity 91%). Conclusions: The performance of the GALAD score was superior to ultrasound for HCC detection. The GALADUS score further enhanced the performance of the GALAD score. Impact: The GALAD score was validated in the United States.

Background: Antibiotic therapy with a macrolide and β-lactam or a fluoroquinolone for the empirical treatment of community-acquired pneumonia (CAP) in an inpatient non–intensive care setting is recommended per guidelines. Studies show that these treatments have similar outcomes, including death, adverse effects, and bacterial eradication. However, a comparison of 30-day readmission rates between these treatments is limited. Study Question: To determine whether 30-day readmissions for patients treated for CAP in a regional hospital differed between a fluoroquinolone monotherapy and a β-lactam plus macrolide combination therapy. Study Design: Retrospective cohort study of patients aged ≥18 years with a CAP diagnosis who were admitted to the same regional hospital from December 1, 2011, through December 1, 2016. Measures and Outcomes: Patients receiving a third-generation cephalosporin plus macrolide were compared with those receiving a respiratory fluoroquinolone. Exclusion criteria were concurrent or recent use of the study antibiotics; death, transfer, or transition to hospice; and diagnosis of hospital-acquired pneumonia or health care–associated pneumonia. The collected data were 30-day readmission rates, antibiotic regimens, demographic characteristics, and pneumonia severity index and comorbidity scores. Association between treatment group and readmissions was assessed with logistic regression. Association between readmissions and individual data points between the 2 treatment groups was calculated with multivariate regression and odds ratio (95% confidence interval). Results: Of 432 patients, 171 met inclusion criteria (fluoroquinolone group, n = 101; β-lactam plus macrolide group, n = 70). Thirty-day readmissions were not significantly different between the fluoroquinolone group and β-lactam plus macrolide group (P = 0.58). Increased 30-day readmissions were independently associated with male sex and hospital length of stay (P < 0.05). Length of stay was approximately 3 days and did not differ between treatment groups. Conclusions: No difference was seen in 30-day readmissions between CAP patients who received fluoroquinolone monotherapy and those who received β-lactam plus macrolide combination therapy.

BACKGROUND: There is lack of consensus on post-operative surveillance for resected non-invasive intraductal papillary neoplasms (IPMNs). In this study we explored risk factors for subsequent PC in patients with MD-IPMN undergoing partial pancreatectomy. METHODS: We searched the Mayo Clinic surgical pathology database for all cases of resected MD-IPMN between 1997 and 2014. Cases with histologically confirmed main pancreatic duct involvement either isolated or in a mixed pattern with branch-duct involvement were included. Outcomes of PC in the remnant pancreas, and death related to MD-IPMN were assessed with survival analyses (Kaplan–Meier and Cox regression). RESULTS: Among the 179 patients with resected MD-IPMN the incidence of concomitant PC and high-grade dysplasia (HGD) in the resected specimen was 23 and 14%, respectively. The mean duration of follow-up was 4.31 years (range 0.12–13.5 years). Excluding 28 subjects who either underwent initial total pancreatectomy or partial pancreatectomy with surgical margins positive for PC/HGD, the 5-year incidence of subsequent PC was 12%, including 60.6% and 15.6% in those with initial PC and HGD, respectively. The 10-year incidence of PC was 21.2% overall, 60.6% for PC, 38.3% for HGD, and 3.0% for LGD. Risk of subsequent PC was significantly higher for those with initial PC compared with HGD (HR = 4.95, 95% CI: 1.63–15.03, p = 0.005 and for HGD compared with LGD (HR = 11.30, 95% CI: 1.55–82.26, p = 0.017). CONCLUSIONS: Patients with MD-IPMN with PC or HGD undergoing segmental pancreatectomy are at higher risk of subsequent PC and may benefit from post-operative surveillance. The post-operative surveillance intervals in resected MD-IPMNs need to be tailored based on dysplasia grade.

Sarcopenia and frailty are commonly encountered in patients with end‐stage liver disease and are associated with adverse clinical outcomes, including decompensation and wait‐list mortality. The impact of these entities in patients with differing disease etiologies has not been elucidated. We aim to ascertain the change in their prevalence over time on the wait list and determine their impact on hospitalization, delisting, and wait‐list survival, specifically for patients with nonalcoholic steatohepatitis (NASH) and alcoholic liver disease (ALD). Adult patients who were evaluated for their first liver transplant from 2014 to 2016 with a primary diagnosis of NASH (n = 136) or ALD (n = 129) were included. Computed tomography scans were used to determine the presence of sarcopenia and myosteatosis. Frailty was diagnosed using the Rockwood frailty index. Patients with NASH had a significantly lower prevalence of sarcopenia (22% versus 47%; P < 0.001) but a significantly higher prevalence of frailty (49% versus 34%; P = 0.03) when compared with patients with ALD at the time of listing. In patients with NASH, sarcopenia was not associated with adverse events, but a higher frailty score was associated with an increased length of hospitalization (P = 0.05) and an increased risk of delisting (P = 0.02). In patients with ALD, univariate analysis showed the presence of sarcopenia was associated with an increased risk of delisting (P = 0.01). In conclusion, sarcopenia and frailty occur with differing prevalence with variable impact on outcomes in wait‐listed patients with NASH and ALD.

AbstractBackgroundNephrotoxins contribute to 20%–40% of acute kidney injury (AKI) cases in the intensive care unit (ICU). The combination of piperacillin-tazobactam (PTZ) and vancomycin (VAN) has been identified as nephrotoxic, but existing studies focus on extended durations of therapy rather than the brief empiric courses often used in the ICU. The current study was performed to compare the risk of AKI with a short course of PTZ/VAN to with the risk associated with other antipseudomonal β-lactam/VAN combinations.MethodsThe study included a retrospective cohort of 3299 ICU patients who received ≥24 but ≤72 hours of an antipseudomonal β-lactam/VAN combination: PTZ/VAN, cefepime (CEF)/VAN, or meropenem (MER)/VAN. The risk of developing stage 2 or 3 AKI was compared between antibiotic groups with multivariable logistic regression adjusted for relevant confounders. We also compared the risk of persistent kidney dysfunction, dialysis dependence, or death at 60 days between groups.ResultsThe overall incidence of stage 2 or 3 AKI was 9%. Brief exposure to PTZ/VAN did not confer a greater risk of stage 2 or 3 AKI after adjustment for relevant confounders (adjusted odds ratio [95% confidence interval] for PTZ/VAN vs CEF/VAN, 1.11 [.85–1.45]; PTZ/VAN vs MER/VAN, 1.04 [.71–1.42]). No significant differences were noted between groups at 60-day follow-up in the outcomes of persistent kidney dysfunction (P = .08), new dialysis dependence (P = .15), or death (P = .09).ConclusionShort courses of PTZ/VAN were not associated with a greater risk of short- or 60-day adverse renal outcomes than other empiric broad-spectrum combinations.