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•NAFLD is associated with a nearly 2-fold increase in the overall risk of incident cancers.•The highest risk was noted in liver, uterine, stomach, pancreas and colon cancers.•Obesity ...in the absence of NAFLD had minimal impact on malignancy risk.
Cancer is a major cause of death in patients with non-alcoholic fatty liver disease (NAFLD). Obesity is a risk factor for cancers; however, the role of NAFLD in this association is unknown. We investigated the effect of NAFLD versus obesity on incident cancers.
We identified all incident cases of NAFLD in a US population between 1997-2016. Individuals with NAFLD were matched by age and sex to referent individuals from the same population (1:3) on the index diagnosis date. We ascertained the incidence of cancer after index date until death, loss to follow-up or study end. NAFLD and cancer were defined using a code-based algorithm with high validity and tested by medical record review. The association between NAFLD or obesity and cancer risk was examined using Poisson regression.
A total of 4,722 individuals with NAFLD (median age 54, 46% male) and 14,441 age- and sex-matched referent individuals were followed for a median of 8 (range 1–21) years, during which 2,224 incident cancers occurred. NAFLD was associated with 90% higher risk of malignancy: incidence rate ratio (IRR) = 1.9 (95% CI 1.3–2.7). The highest risk increase was noted in liver cancer, IRR = 2.8 (95% CI 1.6–5.1), followed by uterine IRR = 2.3 (95% CI 1.4–4.1), stomach IRR = 2.3 (95% CI 1.3–4.1), pancreas IRR = 2.0 (95% CI 1.2–3.3) and colon cancer IRR = 1.8 (95% CI 1.1–2.8). In reference to non-obese controls, NAFLD was associated with a higher risk of incident cancers (IRR = 2.0, 95% CI 1.5–2.9), while obesity alone was not (IRR = 1.0, 95% CI 0.8–1.4).
NAFLD was associated with increased cancer risk, particularity of gastrointestinal types. In the absence of NAFLD, the association between obesity and cancer risk is small, suggesting that NAFLD may be a mediator of the obesity-cancer association.
We studied the incidence of malignancies in a community cohort of adults with non-alcoholic fatty liver disease (NAFLD) in reference to age- and sex-matched adults without NAFLD. After 21 years of longitudinal follow-up, NAFLD was associated with a nearly 2-fold increase in the risk of developing cancers, predominantly of the liver, gastrointestinal tract and uterus. The association with increased cancer risk was stronger in NAFLD than obesity.
Diabetes increases the risk of liver disease progression and cirrhosis development in patients with nonalcoholic steatohepatitis (NASH). The association between diabetes and the risk of ...hepatocellular carcinoma (HCC) in NASH patients with cirrhosis is not well quantified. All patients with the diagnosis of NASH cirrhosis seen at Mayo Clinic Rochester between January 2006 and December 2015 were identified. All adult liver transplant registrants with NASH between 2004 and 2017 were identified using the United Network for Organ Sharing (UNOS)/Organ Procurement and Transplantation registry for external validation. Cox proportional hazard analysis was performed to investigate the association between diabetes and HCC risk. Among 354 Mayo Clinic patients with NASH cirrhosis, 253 (71%) had diabetes and 145 (41%) were male. Mean age at cirrhosis evaluation was 62. During a median follow‐up of 47 months, 30 patients developed HCC. Diabetes was associated with an increased risk of developing HCC in univariate (hazard ratio HR = 3.6; 95% confidence interval CI = 1.1‐11.9; P = 0.04) and multivariable analysis (HR = 4.2; 95% CI = 1.2‐14.2; P = 0.02). In addition, age (per decade, HR = 1.8; 95% CI = 1.2‐2.6; P < 0.01) and low serum albumin (HR = 2.1; 95% CI = 1.5‐2.9; P < 0.01) were significantly associated with an increased risk of developing HCC in multivariable analysis. Other metabolic risk factors, including body mass index, hyperlipidemia, and hypertension, were not associated with HCC risk. Among UNOS NASH registrants (N = 6,630), 58% had diabetes. Diabetes was associated with an increased risk of developing HCC in univariate (HR = 1.4; 95% CI = 1.1‐1.8; P < 0.01) and multivariable (HR = 1.3; 95% CI = 1.0‐1.7; P = 0.03) analysis. Conclusion: Diabetes is associated with an increased risk of HCC in patients with NASH cirrhosis.
Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection (CDI), with emerging data on intermediate and long-term safety.
A prospective ...survey-based study was conducted (September 2012–June 2018) in patients undergoing FMT for recurrent CDI. Data on demographics and comorbidities were abstracted from medical records. Patients were contacted at 1 week, 1 month, 6 months, 1 year (short-term), and ≥2 years post-FMT (long-term). Symptoms and new medical diagnoses were recorded at each time point. Data were weighted to account for survey nonresponse bias. Multivariate logistic regression models for adverse events were built using age (per 10-year increment), sex, time of survey, and comorbidities. P < .05 was considered statistically significant.
Overall, 609 patients underwent FMT; median age was 56 years (range, 18–94), 64.8% were women, 22.8% had inflammatory bowel disease (IBD). At short-term follow-up (n = 609), >60% of patients had diarrhea and 19%-33% had constipation. At 1 year, 9.5% reported additional CDI episodes. On multivariable analysis, patients with IBD, dialysis-dependent kidney disease, and multiple FMTs had higher risk of diarrhea; risk of constipation was higher in women and lower in IBD (all P < .05). For long-term follow-up (n = 447), median time of follow-up was 3.7 years (range, 2.0–6.8). Overall, 73 new diagnoses were reported: 13% gastrointestinal, 10% weight gain, 11.8% new infections (all deemed unrelated to FMT). Median time to infections was 29 months (range, 0–73) post-FMT.
FMT appears safe with low risk of transmission of infections. Several new diagnoses were reported, which should be explored in future studies.
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.
The natural history of lean nonalcoholic fatty liver disease (NAFLD) is not well-understood. Consequently, patient counseling and disease management are limited. We aimed to compare the natural ...history of lean, overweight, and obese NAFLD in a U.S. population with long-term follow-up.
All adults diagnosed with NAFLD in Olmsted County, MN between 1996 and 2016 were identified, and all subsequent medical events were ascertained using a medical record linkage system. Subjects were divided on the basis of body mass index (BMI) at NAFLD diagnosis into 3 groups: normal, overweight, and obese. The probability to develop cirrhosis, decompensation, malignancies, cardiovascular events, or death among the 3 groups was estimated by using the Aalen-Johansen method, treating death as a competing risk. The impact of BMI categories on these outcomes was explored by using Cox proportional hazards regression analysis.
A total of 4834 NAFLD individuals were identified: 414 normal BMI, 1189 overweight, and 3231 obese. Normal BMI NAFLD individuals were characterized by a higher proportion of women (66% vs 47%) and lower prevalence of metabolic comorbidities than the other 2 groups. In reference to obese, those with normal BMI NAFLD had a nonsignificant trend toward lower risk of cirrhosis (hazard ratio HR, 0.33, 95% confidence interval CI, 0.1-1.05). There were no significant differences in the risk of decompensation (HR, 0.79; 95% CI, 0.11-5.79), cardiovascular events (HR, 1.05; 95% CI, 0.73-1.51), or malignancy (HR, 0.87; 95% CI, 0.51-1.48). Compared with obese, normal BMI NAFLD had higher risk of all-cause mortality (HR, 1.96; 95% CI, 1.52-2.51).
NAFLD with normal BMI is associated with a healthier metabolic profile and possibly a lower risk of liver disease progression but similar risk of cardiovascular disease and malignancy than obese NAFLD.
Periacetabular osteotomy (PAO) is the most common treatment for symptomatic acetabular dysplasia, or developmental dysplasia of the hip (DDH), in skeletally mature patients. The purpose of this ...multicenter cohort study was to delineate the long-term radiographic natural history of the dysplastic hip following PAO.
We evaluated all patients undergoing PAO from 1996 to 2012 at 3 academic institutions in the United States. Inclusion criteria were PAO for DDH with a minimum 5-year radiographic follow-up. Exclusion criteria were PAO for isolated acetabular retroversion, neurogenic dysplasia, Legg-Calvé-Perthes disease, and prior hip surgery including osteotomies and arthroscopy. There were 288 patients, 83% of whom were women; the mean age and body mass index (BMI) were 29 years and 25 kg/m, respectively. The mean clinical and radiographic follow-up was 9.2 years (range, 5.0 to 21.1 years). Every preoperative and postoperative hip radiograph was assessed to determine the degree of osteoarthritis according to the Tönnis classification. Survivorship was analyzed by multistate modeling, enabling assessment of progression through the Tönnis grades rather than just individual transitions as with Kaplan-Meier techniques.
At the time of final follow-up, 144 patients (50%) had progressed at least 1 Tönnis grade, with 42 patients (14.6%) undergoing total hip arthroplasty. The mean number of years spent in each Tönnis grade following PAO was 19 for Tönnis grade 1, 8 for Tönnis grade 2, and 4 for Tönnis grade 3. The probability of progression to total hip arthroplasty increased significantly on the basis of a higher initial Tönnis grade (p < 0.001). The most marked difference occurred between Tönnis grade 0 or 1 and Tönnis grade 2; for Tönnis grade 1, the probability of progression to total hip arthroplasty at 5 and 10 years was 2% and 11%, respectively, compared with 23% and 53%, respectively, for Tönnis grade 2.
PAO effectively alters the natural history of DDH. Precise radiographic progression based on the Tönnis grade can now be used to ascribe prognosis for the native hip. Importantly, this investigation demonstrates a stark increase in progression to total hip arthroplasty within 10 years of PAO for patients with preoperative Tönnis grade-2 osteoarthritis compared with those with Tönnis grade-0 or 1 osteoarthritis.
Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Abstract
Purpose
With the implementation of a new electronic health record (EHR) system across Mayo Clinic, a project was approved to standardize and converge 9 region-specific large-volume infusion ...pump (LVP) drug libraries for Baxter SIGMA Spectrum pumps.
Summary
The objectives of the project were to (1) develop recommendations for identified variances in practice, (2) consolidate regional drug libraries into a converged enterprise library, (3) improve the drug library management process, and (4) maintain or exceed previous Dose Error Reduction System (DERS) compliance for infusions administered. Harmonization efforts with infusion pumps decreased the number of drug libraries maintained, reduced content maintenance time, and increased readiness for smart infusion pump–EHR interoperability. Seven of the 8 regions for which change in DERS compliance was assessed showed improved compliance relative to baseline in the 30-day postwashout period. Furthermore, when comparing pre- and postimplementation DERS compliance, the number of regions meeting the minimum compliance rate of 95% increased from 5 to 6 regions.
Conclusion
The project improved the drug library management process, allowed for DERS compliance to be accurately compared across regions, and ensured that patients across the enterprise receive the same standard of care with the administration of intravenous medications.
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.
Advances in surgical techniques have improved clinical outcomes and decreased complications. At the same time, heightened attention to care quality has resulted in increased identification of ...hospital-acquired adverse events. We evaluated these divergent effects on the reported safety of lung cancer resection.
We analyzed hospital-acquired adverse events in patients undergoing lung cancer resection using the National Hospital Discharge Survey (NHDS) database from 2001-2010. Demographics, diagnoses, and procedures data were abstracted using ICD-9 codes. We used the Agency for Healthcare Research and Quality (AHRQ) Patient Safety Indicators (PSI) to identify hospital-acquired adverse events. Weighted analyses were performed using t-tests and chi-square.
A total of 302,444 hospitalizations for lung cancer resection and were included in the analysis. Incidence of PSI increased over time (28% in 2001-2002 vs 34% in 2009-2010; P<0.001). Those with one or more PSI had increased in-hospital mortality (aOR = 11.1; 95% CI, 4.7-26.1; P<0.001) and prolonged hospitalization (12.5 vs 7.8 days; P<0.001). However, among those with PSI, in-hospital mortality decreased over time, from 17% in 2001-2002 to 2% in 2009-2010.
In a recent ten-year period, documented rates of adverse events associated with lung cancer resection increased. Despite this increase in safety events, we observed that mortality decreased. Because such metrics may be incorporated into hospital rankings and reimbursement considerations, adverse event coding consistency and content merit further evaluation.
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