Atrial Fibrillation and the Prognostic Performance of Biomarkers in Heart Failure.

BACKGROUND: Consideration of circulating biomarkers for risk stratification in heart failure (HF) is recommended, but the influence of atrial fibrillation (AF) on prognostic performance of many markers is unclear. We investigated the influence of AF on the prognostic performance of circulating biomarkers in HF. METHODS: N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional-pro-atrial natriuretic peptide, C-type natriuretic peptide (CNP), NT-proCNP, high-sensitivity troponin-T, high-sensitivity troponin-I, mid-regional-propeptide adrenomedullin, co-peptin, growth differentiation factor-15, soluble Suppressor of Tumorigenicitiy (sST2), galectin-3, and procalcitonin plasma concentrations were measured in a prospective, multicenter study of adults with HF. AF was defined as a previous history of AF, and/or presence of AF/flutter on baseline 12-lead electrocardiogram. The primary outcome was the composite of HF-hospitalization or all-cause mortality at 2 years. RESULTS: Among 1099 patients (age 62 ± 12years, 28% female), 261(24%) patients had AF. Above-median concentrations of all biomarkers were independently associated with increased risk of the primary outcome. Significant interactions with AF were detected for galectin-3 and sST2. In considering NT-proBNP for additive risk stratification, sST2 (adjusted hazard ratio [AHR]1.85, 95%confidence interval [C.I.] 1.17-2.91) and galectin-3 (AHR1.85, 95%C.I. 1.09-2.45) were independently associated with increased primary outcome only in the presence of AF. The prognostic performance of sST2 was also stronger in AF for all-cause mortality (AF: AHR2.82, 95%C.I. 1.26-6.21; non-AF: AHR1.78, 95% C.I. 1.14-2.76 without AF), while galectin-3 predicted HF-hospitalization only in AF (AHR1.64, 95%C.I. 1.03-2.62). CONCLUSIONS: AF modified the prognostic utility of selected guideline-endorsed HF-biomarkers. Application of markers for prognostic purposes in HF requires consideration of the presence or absence of AF. CLINICAL TRIAL REGISTRATION: ACTRN12610000374066.

Contrasting biogeographical patterns in Margarella (Gastropoda: Calliostomatidae: Margarellinae) across the Antarctic Polar Front.

Members of the trochoidean genus Margarella (Calliostomatidae) are broadly distributed across Antarctic and sub-Antarctic ecosystems. Here we used novel mitochondrial and nuclear gene sequences to clarify species boundaries and phylogenetic relationships among seven nominal species distributed on either side of the Antarctic Polar Front (APF). Molecular reconstructions and species-delimitation analyses recognized only four species: M. antarctica (the Antarctic Peninsula), M. achilles (endemic to South Georgia), M. steineni (South Georgia and Crozet Island) and the morphologically variable M. violacea (=M. expansa, M. porcellana and M. pruinosa), with populations in southern South America, the Falkland/Malvinas, Crozet and Kerguelen Islands. Margarella violacea and M. achilles are sister species, closely related to M. steineni, with M. antarctica sister to all these. This taxonomy reflects contrasting biogeographic patterns on either side of the APF in the Southern Ocean. Populations of Margarella north of the APF (M. violacea) showed significant genetic variation but with many shared haplotypes between geographically distant populations. By contrast, populations south of the APF (M. antarctica, M. steineni and M. achilles) exhibited fewer haplotypes and comprised three distinct species, each occurring across a separate geographical range. We hypothesize that the biogeographical differences may be the consequence of the presence north of the APF of buoyant kelps - potential long-distance dispersal vectors for these vetigastropods with benthic-protected development - and their near-absence to the south. Finally, we suggest that the low levels of genetic diversity within higher-latitude Margarella reflect the impact of Quaternary glacial cycles that exterminated local populations during their maxima.

Synergy of Sex Differences in Visceral Fat Measured with CT and Tumor Metabolism Helps Predict Overall Survival in Patients with Renal Cell Carcinoma.

Purpose To determine if sex differences in abdominal visceral fat composition, measured by using computed tomography (CT), and tumor glucose metabolism, measured by gene expression, can help predict outcomes in patients with clear cell renal cell carcinoma (RCC). Materials and Methods This retrospective cohort study included 222 patients with clear cell RCC from The Cancer Imaging Atlas. By using CT, body fat was segmented into subcutaneous fat and visceral fat areas (VFAs) and normalized to total fat to obtain the relative VFA (rVFA) and relative subcutaneous fat area. Multivariate Cox proportional hazard regression models were performed to identify effects of rVFA on sex-specific survival. Expression profiles for 39 glycolytic genes in tumors from these patients were obtained from The Cancer Genome Atlas to determine sex differences in metabolism and compared with rVFA. Key mutations in clear cell RCC were analyzed for association with rVFA and tumor glycolytic profiles. Results Women with rVFA greater than 30.9% had an increased risk of death (hazard ratio, 3.66 [95% confidence interval: 1.64, 8.19]) for women vs 1.13 ([95% confidence interval: 0.58, 2.18] for men, P = .028). Glycolytic gene expression stratified both men and women, and the combination of low rVFA and low glycolysis identified 19 women with excellent overall survival (P < .001). SETD2 and BAP1 mutations were uniquely enriched in female tumors with high glycolysis (P = .036 and .001, respectively). No significant differences were identified in tumor mutations between patients with high and low rVFA. Conclusion Sex differences in visceral fat and tumor glucose metabolism may provide a new risk-stratification system for patients with clear cell RCC. © RSNA, 2018 Online supplemental material is available for this article.

Urinary hypoxia: an intraoperative marker of risk of cardiac surgery-associated acute kidney injury.

Background: Acute kidney injury (AKI) is common after cardiac surgery and profoundly affects postoperative mortality and morbidity. There are no validated methods to assess risk of AKI intraoperatively. Methods: We determined the association between postoperative AKI and intraoperative urinary oxygen tension (PO2), measured via a fiber optic probe in the tip of the urinary catheter, in 65 patients undergoing high-risk cardiac surgery requiring cardiopulmonary bypass (CPB). AKI was diagnosed by modified Kidney Disease: Improving Global Outcomes criteria. Results: Urinary PO2 fell during the operation, often reaching its nadir during rewarming or after weaning from CPB. Nadir urinary PO2 was lower in the 26 patients who developed AKI (mean ± SD, 8.9 ± 5.6 mmHg) than in the 39 patients who did not (14.9 ± 10.2 mmHg, P = 0.008). Patients who developed AKI had longer periods of urinary PO2 ≤15 and 10 mmHg than patients who did not. Odds of AKI increased when urinary PO2 fell to ≤10 mmHg {3.60 [95% confidence interval (CI) 1.27-10.21]} or ≤5 mmHg [3.60 (95% CI 1.04-12.42), P = 0.04] during the operation. When urinary PO2 fell to ≤15 mmHg, for more than or equal to the median duration for all patients (4.8 min/h surgery), the odds of AKI were 4.85 (95% CI 1.64-14.40), P = 0.004. The area under the receiver-operator curve for this parameter alone was 0.69, and was 0.89 when other variables with P ≤ 0.10 in univariable analysis were included in the model. Conclusion: Low urinary PO2 during adult cardiac surgery requiring CPB predicts AKI, so may identify patients in which intervention to improve renal oxygenation might reduce the risk of AKI.

Molecular basis of familial hypercholesterolemia.

PURPOSE OF REVIEW: To provide an overview about the molecular basis of familial hypercholesterolemia. RECENT FINDINGS: Familial hypercholesterolemia is a common hereditary cause of premature coronary heart disease. It has been estimated that 1 in every 250 individuals has heterozygous familial hypercholesterolemia and that fewer than 1% of patients with familial hypercholesterolemia have been identified across the globe. If heterozygous familial hypercholesterolemia is left untreated, it is likely that coronary heart disease will manifest clinically prior to the age of 55 years and that half of all patients will prematurely die from the consequences of myocardial infarction. It is crucial to understand the molecular basis of familial hypercholesterolemia to diagnose familial hypercholesterolemia properly. SUMMARY: The phenotype of familial hypercholesterolemia is caused by more than 1700 mutations the LDLR, apoB and PCSK9 genes, which explains approximately 85% of familial hypercholesterolemia cases. By means of next-generation sequencing, an increasing number of mutations in established and putative novel genes associated with this phenotype have been identified.

Clinical Features of Lysosomal Acid Lipase Deficiency.

OBJECTIVE: The aim of this study was to characterize key clinical manifestations of lysosomal acid lipase deficiency (LAL D) in children and adults. METHODS: Investigators reviewed medical records of LAL D patients ages ≥5 years, extracted historical data, and obtained prospective laboratory and imaging data on living patients to develop a longitudinal dataset. RESULTS: A total of 49 patients were enrolled; 48 had confirmed LAL D. Mean age at first disease-related abnormality was 9.0 years (range 0-42); mean age at diagnosis was 15.2 years (range 1-46). Twenty-nine (60%) were male patients, and 27 (56%) were <20 years of age at the time of consent/assent. Serum transaminases were elevated in most patients with 458 of 499 (92%) of alanine aminotransferase values and 265 of 448 (59%) of aspartate aminotransferase values above the upper limit of normal. Most patients had elevated low-density lipoprotein (64% patients) and total cholesterol (63%) at baseline despite most being on lipid-lowering therapies, and 44% had high-density lipoprotein levels below the lower limit of normal. More than half of the patients with liver biopsies (n = 31, mean age 13 years) had documented evidence of steatosis (87%) and/or fibrosis (52%). Imaging assessments revealed that the median liver volume was ∼1.15 multiples of normal (MN) and median spleen volume was ∼2.2 MN. Six (13%) patients had undergone a liver transplant (ages 9-43.5 years). CONCLUSION: This study provides the largest longitudinal case review of patients with LAL D and confirms that LAL D is predominantly a pediatric disease causing early and progressive hepatic dysfunction associated with dyslipidemia that often leads to liver failure and transplantation.

Basal renal O2 consumption and the efficiency of O2 utilization for Na+ reabsorption.

We examined how the presence of a fixed level of basal renal O2 consumption (Vo2(basal); O2 used for processes independent of Na(+) transport) confounds the utility of the ratio of Na(+) reabsorption (TNa(+)) to total renal Vo2 (Vo2(total)) as an index of the efficiency of O2 utilization for TNa(+). We performed a systematic review and additional experiments in anesthetized rabbits to obtain the best possible estimate of the fractional contribution of Vo2(basal) to Vo2(total) under physiological conditions (basal percent renal Vo2). Estimates of basal percent renal Vo2 from 24 studies varied from 0% to 81.5%. Basal percent renal Vo2 varied with the fractional excretion of Na(+) (FENa(+)) in the 14 studies in which FENa(+) was measured under control conditions. Linear regression analysis predicted a basal percent renal Vo2 of 12.7-16.5% when FENa(+) = 1% (r(2) = 0.48, P = 0.001). Experimentally induced changes in TNa(+) altered TNa(+)/Vo2(total) in a manner consistent with theoretical predictions. We conclude that, because Vo2(basal) represents a significant proportion of Vo2(total), TNa(+)/Vo2(total) can change markedly when TNa(+) itself changes. Therefore, caution should be taken when TNa(+)/Vo2(total) is interpreted as a measure of the efficiency of O2 utilization for TNa(+), particularly under experimental conditions where TNa(+) or Vo2(total) changes.

Determination of a perfusion threshold in experimental perforator flap surgery using indocyanine green angiography.

Indocyanine green (ICG) angiography has been used in the evaluation of flap perfusion but the viability threshold has not been elucidated. In this study, we determined the threshold by comparing perfusion, using ICG imaging (SPY imaging system, LifeCell Corporation), to clinical evidence of nonviability in rat abdominal perforator flaps. Abdominal flaps, based on a single perforator, were elevated and re-inset in Sprague-Dawley rats. ICG imaging and clinical assessments were conducted preoperatively, as well as 0, 24, and 48 hours postoperatively. SPY-Q software allowed standardization of the perforator's perfusion for comparison purposes. A total of 278 random percentage measurements were made from postoperative day 0 giving a mean (SE) percentage perfusion of 26.8% (1.6%) and 59.1% (1.3%), respectively, for necrosis and survival (P<0.05). We demonstrate that ICG angiography can be readily analyzed in a perforator flap environment allowing a determination of the perfusion threshold.

The role of hydrolases in the loss of firmness and of the changes in sugar content during the post-harvest maturation of Carica papaya L. var solo 8.

Fruit ripening is associated with many hydrolase activities involved in the softening of the fruit during the maturation. This study investigates the relationship between the loss of firmness along with the changes of sugar content and the enzymatic activities in Carica papaya L.var solo 8 during post-harvest storage. Three maturation stages (green immature: the fruit is entirely green, green mature: the fruit shows 1/32 yellow skin and fully mature: the fruit shows 1/8 yellow skin) have been selected and stored at 15, 22 and 28 °C. The reduction of fruit firmness, total sugar contents, refractive index (% Brix) and enzymatic activities were measured. Low enzymatic activities (0.035 µmol/min/mg) were recorded in fruit harvested at the green immature stage with no significant (p ≥ 0.05) effect on the softening while fruit harvested at the green mature and fully mature stages showed enzymatic activities 7 times as high as those of the green immature stage. These high enzymatic activities were responsible for the loss of firmness of the fruit. Accordingly, papayas at the green mature and fully mature stages displayed higher maxima of sugar content (4.8 g/100 g at 28 °C at day 12, and 10.2 g/100 g at 22 °C at day 8, respectively) at higher temperatures. Meanwhile in green immature papayas, the maximum was only 4.3 g/100 g at 22 °C and day 12 of storage. The results show that the loss of firmness of the papaya was highly related to the hydrolytic enzyme activities and the sweet taste to the presence of simple sugars such as galactose liberated from the polysaccharide complexes.

Novel Allograft in the Load-Bearing Portion of the Femoral Head.

Background: An osteochondral defect in the hip can be a painful and limiting pathologic process. The damaged joint may progress into premature osteoarthritis, further limiting a patient's functionality. Case Report: A 24-year-old male presented to the clinic with left hip pain. The patient had been involved in a motor vehicle accident 3 years prior to presentation to our clinic. His injury from the high-speed accident required intramedullary rod fixation for a right-sided (contralateral) subtrochanteric femur fracture. The patient complained of left groin pain when in a sitting position, with activities of daily living, and with exercise. He failed conservative management consisting of nonsteroidal anti-inflammatory drugs and physical therapy. Imaging on presentation demonstrated an osteochondral defect in the weight-bearing portion of the left femoral head consistent with an International Cartilage Repair Society grade 4b lesion, a cam lesion was noted on assessment of bone morphology, and magnetic resonance imaging revealed degenerative labral pathology. The patient was treated with surgical hip dislocation through a modified Hardinge approach, femoral head osteochondral allograft transplantation using a Missouri Osteochondral Preservation System (MOPS) graft, acetabuloplasty, femoral neck osteoplasty, and open labral repair. Conclusion: Femoral head osteochondral MOPS allograft transplantation is a viable technique for joint preservation in young patients with posttraumatic osteochondral defects of the femoral head.

Female-specific pancreatic cancer survival from CT imaging of visceral fat implicates glutathione metabolism in solid tumors.

RATIONALE AND OBJECTIVES: To identify if body composition, assessed with preoperative CT-based visceral fat ratio quantification as well as tumor metabolic gene expression, predicts sex-dependent overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: This was a retrospective analysis of preoperative CT in 98 male and 107 female patients with PDAC. Relative visceral fat (rVFA; visceral fat normalized to total fat) was measured automatically using software and corrected manually. Median and optimized rVFA thresholds were determined according to published methods. Kaplan Meier and log-rank tests were used to estimate OS. Multivariate models were developed to identify interactions between sex, rVFA, and OS. Unsupervised gene expression analysis of PDAC tumors from The Cancer Genome Atlas (TCGA) was performed to identify metabolic pathways with similar survival patterns to rVFA. RESULTS: Optimized preoperative rVFA threshold of 38.9% predicted significantly different OS in females with a median OS of 15 months (above threshold) vs 24 months (below threshold; p = 0.004). No significant threshold was identified in males. This female-specific significance was independent of age, stage, and presence of chronic pancreatitis (p = 0.02). Tumor gene expression analysis identified female-specific stratification from a five-gene signature of glutathione S-transferases. This was observed for PDAC as well as clear cell renal carcinoma and glioblastoma. CONCLUSION: CT-based assessments of visceral fat can predict pancreatic cancer OS in females. Glutathione S-transferase expression in tumors predicts female-specific OS in a similar fashion.

Comparison between the HyperArc™ technique and the CyberKnife® technique for stereotactic treatment of brain metastases.

PURPOSE: The purpose of this study was to compare the planimetric capacities between HyperArc™-based stereotactic radiosurgery and robotic radiosurgery system-based planning using CyberKnife® M6 for single and multiple cranial metastases. MATERIALS AND METHODS: We evaluated 51 treatment plans for cranial metastases, including 30 patients with a single lesion and 21 patients with multiple lesions, treated with the CyberKnife® M6. These treatment plans were optimized using the HyperArc™ (HA) system with the TrueBeam. The comparison of the quality of the treatment plans between the two treatment techniques (CyberKnife and HyperArc) was performed using the Eclipse treatment planning system. Dosimetric parameters were compared for target volumes and organs at risk. RESULTS: Coverage of the target volumes was equivalent between the two techniques, whereas median Paddick conformity index and median gradient index for all target volumes were 0.9 and 3.4, respectively for HyperArc plans, and 0.8 and 4.5 for CyberKnife plans (P<0.001). The median dose of gross tumor volume (GTV) for HyperArc and CyberKnife plans were 28.4 and 28.8, respectively. Total brain V18Gy and V12Gy-GTVs were 11cm3 and 20.2cm3 for HyperArc plans versus 18cm3 and 34.1cm3 for CyberKnife plans (P<0.001). CONCLUSION: The HyperArc provided better brain sparing, with a significant reduction in V12Gy and V18Gy, associated with a lower gradient index, whereas the CyberKnife gave a higher median GTV dose. The HyperArc technique seems to be more appropriate for multiple cranial metastases and for large single metastatic lesions.

Can we predict the cardiac benefit of deep inspiration breath hold for left breast and regional nodal irradiation?

PURPOSE: Deep inspiration breath hold (DIBH) is used to decrease the dose of radiotherapy delivered to the heart. There is a need to define criteria to select patients with the potential to derive a real clinical benefit from DIBH treatment. Our study's main goal was to investigate whether two CT-scan cardiac anatomical parameters, cardiac contact distance in the parasagittal plane (CCDps) and lateral heart-to-chest distance (HCD), were predictive of unmet dosimetric cardiac constraints for left breast and regional nodal irradiation (RNI). MATERIALS AND METHODS: This retrospective single-institution dosimetric study included 62 planning CT scans of women with left-sided breast cancer (BC) from 2016 to 2021. Two independent radiation oncologists measured HCD and CCDps twice to assess inter- and intra-observer reproducibility. Dosimetric constraints to be respected were defined, and dosimetric parameters of interest were collected for each patient. RESULTS: Mean heart dose was 7.9Gy. Inter-rater reproducibility between the two readers was considered excellent. The mean heart dose constraint<8Gy was not achieved in 25 patients (40%) and was achieved in 37 patients (60%). There was a significant correlation between mean heart dose and HCD (rs=-0.25, P=0.050) and between mean heart dose and CCDps (rs=0.25, P=0.047). The correlation between HCD and CCDps and unmet cardiac dosimetric constraints was not statistically significant. CONCLUSION: Our dosimetric analysis did not find that the cardiac anatomical parameters HCD and CCDps were predictive of unmet dosimetric cardiac constraints, nor that they were good predictors for cardiac exposure in left-sided BC radiotherapy comprising RNI.

Positional and rotational stability of the toric phakic intraocular lens under high +Gz environments.

BACKGROUND: Phakic intraocular lens (PIOL) implantation is a surgical option for correction of refractive errors. PIOLs can be use to correct myopia, hyperopia, and astigmatism. It is a surgical option available to patients in addition to methods such as laser cornea refractive surgery, e.g., laser assisted in-situ keratomileusis (LASIK) and photo-refractive keratectomy (PRK). Visian implantable collamer lens (ICL) are posterior chamber lenses which are surgically positioned in a phakic eye in the sulcus between the iris diaphragm and the natural crystalline lens. CASE REPORT: This case report describes the stability of Visian toric ICL in a candidate with bilateral implants under high +Gz force exposure in a human centrifuge trainer. The subject was sequentially exposed to three incremental +Gz profiles of +5 Gz, +7 Gz, and +9 Gz. Pre- and post-+Gz exposure, ophthalmic examination revealed no ICL displacement, implant touch or induced cataract, or change in refractive error. DISCUSSION: The rotational stability of the toric implants was also demonstrated by identical subjective refractions in both eyes taken pre- and post-+Gz, exposure. A search of the literature did not reveal any published articles on intraocular stability of ICL in the +Gz environment. This case report suggests that ICL may be considered an alternative to laser refractive surgery for patients subjected to a high +G, environment such as military aviators.

Hydrogenation of Cyclic 1,3-Diones to Their 1,3-Diols Using Heterogeneous Catalysts: Toward a Facile, Robust, Scalable, and Potentially Bio-Based Route.

Cyclopentane-1,3-diol (4b) has gained renewed attention as a potential building block for polymers and fuels because its synthesis from hemicellulose-derived 4-hydroxycyclopent-2-enone (3) was recently disclosed. However, cyclopentane-1,3-dione (4), which is a constitutional isomer of 3, possesses a higher chemical stability and can therefore afford higher carbon mass balances and higher yields of 4b in the hydrogenation reaction under more concentrated conditions. In this work, the hydrogenation of 4 into 4b over a commercial Ru/C catalyst was systematically investigated on a bench scale through kinetic studies and variation of reaction conditions. Herein, the temperature, H2-pressure, and the solvent choice were found to have significant effects on the reaction rate and suppression of undesired dehydration of 4. The cis-trans ratio of 4b is naturally generated as 7:3 in these reactions. However, at elevated reaction temperatures, 4b epimerizes, yielding more trans products. This effect was also studied and rationalized from a thermodynamic perspective using DFT. The combined optimized reaction conditions provided 78% yield for 4b, and successful applications to 8-fold scaled up reactions (40 g) and a substrate scope of several 1,3-diones demonstrate the general applicability of this catalytic approach.

Chemoselective formation of cyclo-aliphatic and cyclo-olefinic 1,3-diols via pressure hydrogenation of potentially biobased platform molecules using Knölker-type catalysts.

The hydrogenative conversions of the biobased platform molecules 4-hydroxycyclopent-2-enone and cyclopentane-1,3-dione to their corresponding 1,3-diols are established using a pre-activated Knölker-type iron catalyst. The catalyst exhibits a high selectivity for ketone reduction, and does not induce dehydration. Moreover, by using different substituents of the ligand, the cis-trans ratio of the products can be affected substantially. A decent compatibility of this catalytic system with various structurally related substrates is demonstrated.

Patellofemoral Arthroplasty.

BACKGROUND: Patellofemoral arthritis is a common cause of anterior knee pain and limits flexion-related activities of daily living and exercise. While frequently present in bicompartmental and tricompartmental osteoarthritis, patellofemoral arthritis can occur in isolation. Patellofemoral arthroplasty as a treatment option is gaining in popularity, especially with new implant designs. We report a case in which new inlay implants were used to resurface the patellofemoral joint in a patient with contralateral compromise secondary to a previous below-knee amputation. CASE REPORT: A 37-year-old female with a contralateral right below-knee amputation and progressive left patellofemoral arthritis had failed multiple conservative treatment modalities. She underwent isolated patellofemoral arthroplasty using an inlay-designed implant. The patient was followed for 2 years postoperatively. She noticed an immediate increase in her knee range of motion and her pain scores improved. Two years postoperatively, she demonstrated drastic improvement in all outcome measures: International Knee Documentation Committee score (16.1 to 88.5), Lysholm Knee Scoring Scale (22 to 100), Knee Injury and Osteoarthritis Outcome Score (KOOS) Symptoms (7.14 to 96.43), KOOS Pain (2.78 to 100), KOOS Activities of Daily Living (0 to 100), KOOS Sports (0 to 100), and KOOS Quality of Life (12.5 to 93.75). CONCLUSION: Inlay patellofemoral arthroplasty is a valid treatment option for isolated patellofemoral arthritis. Successful results can be achieved with this procedure after failure of conservative measures in patients with limited or no evidence of tibiofemoral arthritis.

Frequency of hepatic contour abnormalities and signs of portal hypertension at CT in patients receiving chemotherapy for breast cancer metastatic to the liver.

PURPOSE: This study aimed to determine the frequency of hepatic contour abnormalities and signs of portal hypertension at serial CT in patients receiving chemotherapy for breast cancer metastatic to the liver. MATERIALS AND METHODS: We retrospectively identified 91 women with breast cancer metastatic to the liver who received chemotherapy and underwent serial CT at our institution between 1998 and 2002. Two readers independently categorized hepatic contour abnormalities on the final CT examination as none, limited retraction, widespread retraction, or diffuse nodularity. Readers also recorded the development of hepatic atrophy or enlargement, ascites, portosystemic collateral veins, and splenomegaly. Interpretative discrepancies were resolved by consensus. Portal hypertension was defined as the presence of at least two of the following CT signs: simple ascites, portosystemic collateral veins, and splenomegaly. RESULTS: After a median follow-up interval of 15 months (range, 1-46), hepatic contour abnormalities were seen in 68 of 91 patients (75%) and consisted of limited retraction (n = 42), widespread retraction (n = 10), or diffuse nodularity (n = 16). Portal hypertension was found in 1 of 23 patients without contour abnormalities, in 1 of 42 patients with limited retraction, in none of 10 patients with widespread retraction, and in 6 of 16 patients with diffuse nodularity (P < .01). CONCLUSION: Hepatic contour abnormalities commonly develop at serial CT in patients undergoing chemotherapy for breast cancer metastatic to the liver and may be accompanied by signs of portal hypertension; the latter are particularly, but not exclusively, associated with the development of diffuse hepatic nodularity.

Thromboprophylaxis after hip fracture: evaluation of 3 pharmacologic agents.

We compared the clinical efficacy and side-effect profiles of aspirin, dextran 40, and low-molecular-weight heparin (enoxaparin) in preventing thromboembolic phenomena after hip fracture surgery. All patients admitted with a diagnosis of hip fracture to our institution between July 1, 1987, and December 31, 1999, were evaluated. Study inclusion criteria were age 65 years or older, previously ambulatory, cognitively intact, home-dwelling, and having a nonpathologic intertrochanteric or femoral neck fracture. Each patient received mechanical thromboprophylaxis (above-knee elastic stockings) and 1 pharmacologic agent (aspirin, dextran 40, or enoxaparin); patients who received aspirin were also given a calf sequential compression device. Meeting the selection criteria and included in the study were 917 patients. Findings included low incidence of thromboembolic phenomena (deep vein thrombosis, 0.5%-1.7%; pulmonary embolism, 0%-2.0%; fatal pulmonary embolism, 0%-0.5%) and no difference among the 3 pharmacologic agents in thromboembolic prophylaxis efficacy. Use of enoxaparin was associated with a significant increase (3.8%) in wound hematoma compared with dextran 40 (1.6%) and aspirin (2.4%) (P<.01). The 3 agents were found not to differ with respect to mortality, thromboembolic phenomena, hemorrhagic complications, or wound complications.

The prognostic value of highly sensitive cardiac troponin assays for adverse events in men and women with stable heart failure and a preserved vs. reduced ejection fraction.

AIMS: Circulating biomarkers are important in the diagnosis, risk stratification and management of patients with heart failure (HF). Given the current lack of biomarkers in HF with preserved ejection fraction (HFpEF), we aimed to investigate the prognostic performance of the newly developed high-sensitivity (hs) assays for cardiac troponin I (hsTnI) compared with troponin T (hsTnT) for adverse events in HFpEF vs. HF with reduced ejection fraction (HFrEF). Findings in these two HF subgroups were also compared with those in the recently defined HF with mid-range ejection fraction (HFmrEF) subgroup. METHODS AND RESULTS: Both hsTnI and hsTnT were measured in 1096 patients with HFrEF [left ventricular ejection fraction (LVEF) <50%; n = 853] or HFpEF (LVEF ≥50%; n = 243) enrolled in the Singapore Heart Failure Outcomes and Phenotypes (SHOP) study. Both troponin assays were more strongly associated with the composite endpoint (all-cause mortality or first rehospitalization for HF) in HFpEF than in HFrEF. The hsTnT assay provided the greatest additional prognostic value in HFpEF in comparison with hsTnI and NT-proBNP. TnI was more strongly associated with composite events in men with HFpEF [hazard ratio (HR) 3.33, 95% confidence interval (CI) 1.82-6.09; P < 0.001 per standard deviation (SD) increase in log-transformed hsTnI] than in women with HFpEF (HR 1.35, 95% CI 0.94-1.93; P = 0.10 per SD increase in log-transformed hsTnI). CONCLUSIONS: There is a potential role for the prognostic use of high-sensitivity troponin assays, particularly hsTnT, in men and women with HFpEF. The predictive association of hsTnI with outcome appears strongest in men with HFpEF.