Citations

SummaryBackgroundHepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti‐viral therapy affects survival after HCC diagnosis.MethodsThis was an international multicentre cohort study of 2518 HBV‐related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti‐viral therapy and cirrhosis on patients' risk of death.ResultsApproximately, 48% of patients received anti‐viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti‐viral therapy would have been indicated for >60% of the patients not on anti‐viral therapy based on American criteria. Patients with cirrhosis had lower 5‐year survival (34% vs 46%; P < 0.001) while patients receiving anti‐viral therapy had increased 5‐year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti‐viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001).ConclusionsAnti‐viral therapy improved overall survival in patients with HBV‐related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti‐viral therapy in HBV‐related HCC and better linkage‐to‐care for HBV patients are needed.

Background: Deficient soft tissue following total knee arthroplasty (TKA) can jeopardize outcome. The gastrocnemius flap is an important means of providing coverage of a knee with deficient soft tissue. There is a paucity of long-term studies on the use of the gastrocnemius flap in the setting of TKA. The purpose of this study was to review the outcomes after the use of pedicled gastrocnemius flaps for coverage of a soft-tissue defect at the time of TKA. Methods: Eighty-three patients in whom a gastrocnemius flap had been used to cover the site of a primary (n = 18) or revision (n = 65) TKA over a 25-year period were identified. There were 48 women (58%) and 35 men (42%) with a mean age and body mass index (BMI) of 65 years and 32.6 kg/m 2 . The mean wound size was 49 cm 2 , and the wound was most commonly located over the anterior aspect of the knee/patellar tendon (n = 33). Patients were followed to the time of implant or flap revision, amputation, or death or for a minimum of 2 years (mean, 8 years). Clinical outcomes were assessed using the Knee Society Score (KSS) for pain and the KSS for function. The Kaplan-Meier method was used to assess revision and amputation-free survival. Risk factors for amputation and revision were identified with Cox regression. Results: The 10-year revision and amputation-free survival rates following gastrocnemius flap coverage were 68% and 79%, respectively. The risk of implant failure was increased by morbid obesity (BMI of ≥40 kg/m 2 ) (hazard ratio [HR] = 2.82, 95% confidence interval [CI] = 1.09 to 7.32, p = 0.03) and ≥5 prior surgical procedures on the knee (HR = 2.68, 95% CI = 1.04 to 6.88, p = 0.04). The risk of amputation was increased in patients with ≥5 prior surgical procedures (HR = 10.76, 95% CI = 2.38 to 48.58, p = 0.002), an age of ≥65 years (HR = 4.94, 95% CI = 1.10 to 22.09, p = 0.03), and a wound size of ≥50 cm 2 (HR = 3.29, 95% CI = 1.14 to 9.53, p = 0.02). Preoperatively the mean KSSs for pain and function were 46 and 28, and these scores significantly (p < 0.05) improved to 78 and 43, respectively, at the time of follow-up. Conclusions: The gastrocnemius flap reliably provides coverage of components used in complex knee reconstruction. A history of multiple surgical procedures on the knee and larger soft-tissue defects increase the risk of revision TKA and of amputation. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Background: Right ventricular systolic dysfunction (RVD) often coexists with various cardiopulmonary diseases. However, the association between RVD and risk of sudden cardiac death (SCD) has not been well studied. This study examined the risk of SCD associated with RVD in patients with heterogeneous underlying cardiac diseases. Methods: The Mayo Clinic cardiac care unit database included 5463 consecutive patients with complete echocardiographic evaluation to assess right ventricular systolic function and RVD severity. Prospective surveillance follow-up was obtained for all patients. SCD was adjudicated when a malignant ventricular arrhythmia was documented as the primary rhythm leading to death. RESULTS: The prevalence of mild RVD and moderate-severe RVD was 14.9% and 17.1%, respectively. Patients with RVD were more likely to have a history of congestive heart failure, cardiac arrest, pulmonary disease, and lower baseline left ventricular ejection fraction compared with those with normal right ventricular systolic function. During a median follow-up of 14 months, the incidence of SCD was highest in patients with moderate-severe RVD (7.4% versus 4.4% in mild RVD versus 1.6% in normal right ventricular function; P <0.001). After adjustment for baseline characteristics, mild RVD (adjusted hazard ratio, 1.57; P =0.046) and moderate-severe RVD (adjusted hazard ratio, 1.91; P =0.006) were independently associated with an increased risk of SCD. Moderate-severe RVD remained an independent predictor of SCD for patients with left ventricular ejection fraction >35% without or with preexisting implantable cardioverter-defibrillator (adjusted hazard ratio, 4.12; P =0.003 and adjusted hazard ratio, 5.04; P <0.001, respectively). Conclusions: Presence of RVD in patients with a history of preexisting cardiac disease is an independent predictor of SCD irrespective of left ventricular ejection fraction.

Abstract BACKGROUND A decrease in diastolic blood pressure (DBP) with exercise is considered normal, but the significance of an increase in DBP has not been validated. Our aim was to determine the relationship of DBP increasing on a stress test regarding comorbidities and mortality. METHODS Our database was reviewed from 1993 to 2010 using the first stress test of a patient. Non-Minnesota residence, baseline cardiovascular (CV) disease, rest DBP &lt;60 or &gt;100 mm Hg, and age &lt;30 or ≥80 were exclusion criteria. DBP response was classified: normal if peak DBP–rest DBP &lt; 0, borderline 0–9, and abnormal ≥10 mm Hg. Mortality was determined from Mayo Clinic records and Minnesota Death Index. Logistic regression was used to determine the relationship of DBP response to the presence of comorbidities. Cox regression was used to determine total and CV mortality risk by DBP response. All analyses were adjusted for age, sex, and resting DBP. RESULTS Twenty thousand seven hundred sixty patients were included (51 ± 11 years, female n = 7,314). Rest/peak averaged DBP 82 ± 8/69 ± 15 mm Hg in normal vs. 79 ± 9/82 ± 9 mm Hg in borderline vs. 76 ± 9/92 ± 11 mm Hg in abnormal DBP response. There were 1,582 deaths (8%) with 557 (3%) CV deaths over 12 ± 5 years of follow-up. In patients with borderline and abnormal DBP response, odds ratios for obesity, hypertension, diabetes, and current smoking were significant, while hazard ratios for total and CV death were not significant compared with patients with normal DBP response. CONCLUSIONS DBP response to exercise is significantly associated with important comorbidities at the time of the stress test but does not add to the prognostic yield of stress test.

AbstractObjectivesBoth projection and dual‐energy (DE)‐based methods have been used for metal artifact reduction (MAR) in CT. The two methods can also be combined. The purpose of this work was to evaluate these three MAR methods using phantom experiments for five types of metal implants.Materials and MethodsFive phantoms representing spine, dental, hip, shoulder, and knee were constructed with metal implants. These phantoms were scanned using both single‐energy (SE) and DE protocols with matched radiation output. The SE data were processed using a projection‐based MAR (iMAR, Siemens) algorithm, while the DE data were processed to generate virtual monochromatic images at high keV (Mono+, Siemens). In addition, the DE images after iMAR were used to generate Mono+ images (DE iMAR Mono+). Artifacts were quantitatively evaluated using CT numbers at different regions of interest. Iodine contrast‐to‐noise ratio (CNR) was evaluated in the spine phantom. Three musculoskeletal radiologists and two neuro‐radiologists independently ranked the artifact reduction.ResultsThe DE Mono+ at high keV resulted in reduced artifacts but also lower iodine CNR. The iMAR method alone caused missing tissue artifacts in dental phantom. DE iMAR Mono+ caused wrong CT numbers in close proximity to the metal prostheses in knee and hip phantoms. All musculoskeletal radiologists ranked SE iMAR > DE iMAR Mono+ > DE Mono+ for knee and hip, while DE iMAR Mono+ > SE iMAR > DE Mono+ for shoulder. Both neuro‐radiologists ranked DE iMAR Mono+ > DE Mono+ > SE iMAR for spine and DE Mono+ > DE iMAR Mono+ > SE iMAR for dental.ConclusionsThe SE iMAR was the best choice for the hip and knee prostheses, while DE Mono+ at high keV was best for dental implants and DE iMAR Mono+ was best for spine and shoulder prostheses. Artifacts were also introduced by MAR algorithms.

Abstract Background Treatment-induced neuroendocrine prostate cancer (tNEPC) is an aggressive variant of late-stage metastatic castrate-resistant prostate cancer that commonly arises through neuroendocrine transdifferentiation (NEtD). Treatment options are limited, ineffective, and, for most patients, result in death in less than a year. We previously developed a first-in-field patient-derived xenograft (PDX) model of NEtD. Longitudinal deep transcriptome profiling of this model enabled monitoring of dynamic transcriptional changes during NEtD and in the context of androgen deprivation. Long non-coding RNA (lncRNA) are implicated in cancer where they can control gene regulation. Until now, the expression of lncRNAs during NEtD and their clinical associations were unexplored. Results We implemented a next-generation sequence analysis pipeline that can detect transcripts at low expression levels and built a genome-wide catalogue (n = 37,749) of lncRNAs. We applied this pipeline to 927 clinical samples and our high-fidelity NEtD model LTL331 and identified 821 lncRNAs in NEPC. Among these are 122 lncRNAs that robustly distinguish NEPC from prostate adenocarcinoma (AD) patient tumours. The highest expressed lncRNAs within this signature are H19, LINC00617, and SSTR5-AS1. Another 742 are associated with the NEtD process and fall into four distinct patterns of expression (NEtD lncRNA Class I, II, III, and IV) in our PDX model and clinical samples. Each class has significant (z-scores &gt;2) and unique enrichment for transcription factor binding site (TFBS) motifs in their sequences. Enriched TFBS include (1) TP53 and BRN1 in Class I, (2) ELF5, SPIC, and HOXD1 in Class II, (3) SPDEF in Class III, (4) HSF1 and FOXA1 in Class IV, and (5) TWIST1 when merging Class III with IV. Common TFBS in all NEtD lncRNA were also identified and include E2F, REST, PAX5, PAX9, and STAF. Interrogation of the top deregulated candidates (n = 100) in radical prostatectomy adenocarcinoma samples with long-term follow-up (median 18 years) revealed significant clinicopathological associations. Specifically, we identified 25 that are associated with rapid metastasis following androgen deprivation therapy (ADT). Two of these lncRNAs (SSTR5-AS1 and LINC00514) stratified patients undergoing ADT based on patient outcome. Discussion To date, a comprehensive characterization of the dynamic landscape of lncRNAs during the NEtD process has not been performed. A temporal analysis of the PDX-based NEtD model has for the first time provided this dynamic landscape. TFBS analysis identified NEPC-related TF motifs present within the NEtD lncRNA sequences, suggesting functional roles for these lncRNAs in NEPC pathogenesis. Furthermore, select NEtD lncRNAs appear to be associated with metastasis and patients receiving ADT. Treatment-related metastasis is a clinical consequence of NEPC tumours. Top candidate lncRNAs FENDRR, H19, LINC00514, LINC00617, and SSTR5-AS1 identified in this study are implicated in the development of NEPC. We present here for the first time a genome-wide catalogue of NEtD lncRNAs that characterize the transdifferentiation process and a robust NEPC lncRNA patient expression signature. To accomplish this, we carried out the largest integrative study that applied a PDX NEtD model to clinical samples. These NEtD and NEPC lncRNAs are strong candidates for clinical biomarkers and therapeutic targets and warrant further investigation.

Background Prognosis based on body fat percentage ( BF %) in patients with coronary artery disease has not been extensively studied. We tested the hypothesis that patients with coronary artery disease and increased BF % have a higher risk for major adverse cardiovascular events ( MACEs ) and that fat‐free mass is associated with better prognosis. Methods and Results We included 717 patients referred to cardiac rehabilitation after coronary artery disease events or procedures who underwent air displacement plethysmography to assess BF %; 75% were men, with a mean age 61.4±11.4 years and a mean body mass index of 30±5.4 kg/m 2 . Follow‐up was performed using a record linkage system. Patients were classified in sex‐specific quartiles of BF % and fat‐free mass index. The composite outcome of MACEs included acute coronary syndromes, coronary revascularization, stroke, or death from any cause. After a median follow‐up of 3.9 years, 201 patients had a MACE . After adjusting for covariates, body mass index was not associated with MACEs ( P =0.12). However, the risk of MACEs for those in the highest BF % quartile was nearly double when compared with those in the lowest quartile (hazard ratio, 1.89; 95% confidence interval, 1.30–2.77; P =0.0008). In contrast, fat‐free mass was inversely associated with MACEs . The risk of MACEs for those in the fourth fat‐free mass quartile was lower (adjusted hazard ratio, 0.53; 95% confidence interval, 0.35–0.82; P =0.004), when compared with those in the first quartile. Conclusions In patients with coronary artery disease, there is no obesity paradox when measuring BF % instead of body mass index. BF % is associated with a higher risk of MACEs , whereas fat‐free mass is associated with a lower risk of MACEs . Body mass index was not associated with MACEs .

INTRODUCTION: Obesity is associated with postnatal depression; however, the prevalence of postnatal depression in women after bariatric surgery has not been further evaluated. METHODS: For this observational investigation, women, ages 18-45 years, with pregnancy from 1989-2015 and bariatric surgery were identified using the Olmsted County Rochester Epidemiology Project and ICD-9 codes. Those with surgery after pregnancy and/or without permission to use their records were excluded. Charts were reviewed for maternal and infant characteristics and outcomes. Postnatal depression was identified from a positive screen, referral for mood disorder, antidepressant medication increase, suicidality, or provider diagnosis from delivery to 12 months postpartum. RESULTS: Ninety-one women with pregnancy >23 weeks after surgery and available data were reviewed. The average body mass index at time of surgery was 47±8.6 kg/m2 (N=88) and at time of pregnancy 32±6.6 kg/m2 (N=89). The average age at surgery was 29±4.1 years and at delivery 33±4.4 years. Roux-en-Y gastric bypass was the most common surgery (N=70, 77%). Pregnancy outcomes included: 14% preterm deliveries (<37 weeks, N=13), 67% vaginal deliveries (N=61), no stillbirths, and 97% singleton deliveries (N=88). Mean singleton birthweight was 3225 grams (±471, N=86). Postnatal depression was noted in 38% of women (N=35), which is significantly higher than that for obese women in general (13-18%) when a 1-sample proportion test is conducted for comparison (38%vs18%, p <0.0001). CONCLUSION: Postnatal depression may be increased in women with a history of bariatric surgery. Further investigation is needed, but particular care should be taken to screen and diagnose these high-risk women.