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AbstractBackgroundDepression is highly prevalent in individuals with coronary artery disease (CAD) and increases the risk of future cardiac events and mortality. Sphingolipids have been implicated in the pathophysiology of both CAD and depression. This study assessed the association between plasma sphingolipid concentrations and depressive symptoms in CAD subjects.MethodsDepressive symptoms were measured using the depression subscale of the self‐reported Hospital Anxiety and Depression Scale (HADS). Sphingolipid concentrations were measured from fasting plasma samples using high‐performance liquid chromatography‐coupled electrospray ionization tandem mass spectrometry (LC/MS/MS). Linear regression models were used to assess associations between log‐transformed concentrations of plasma sphingolipids and depressive symptoms.ResultsA total of 111 CAD patients (mean (SD) age = 63.6 ± 6.4, 84.7% male) were included. In linear regression analyses, higher plasma concentrations of ceramides C16:0 (β = 0.204, p = .026) and C18:0 (β = 0.209, p = .023) and sphingomyelin SM18:1 (β = 0.210, p = .024) were significantly associated with higher HADS depression subscale score after adjusting for covariates.ConclusionSphingolipids, in particular the ceramide species C16:0 and C18:0 and the sphingomyelin species SM18:1, may be implicated in the pathophysiology of depression in CAD. The association between plasma sphingolipid concentrations and depression should be further examined in CAD patients and in other populations.

Background: Multi-ligament knee injury (MLKI) associated with knee dislocation can result in vascular injury. The purpose of this study was to compare knee function after MLKI between patients with a vascular injury requiring popliteal artery bypass grafting and patients without vascular involvement. Additionally, factors associated with poor knee function in patients who had MLKI with vascular injury were evaluated. Methods: This retrospective study identified patients with an MLKI between 1992 and 2014. Each patient who had a concomitant vascular injury requiring bypass grafting (vascular cohort, n = 16; mean age, 30.3 years) was matched to 2 patients without a vascular injury (control cohort, n = 32; mean age, 31.4 years) on the basis of age, knee dislocation (KD) grade, and peroneal nerve status. Fifteen patients in the vascular cohort and 26 patients in the control cohort had an isolated knee injury. Functional outcomes were assessed with physical examination of range of motion and ligamentous stability as well as patient-reported outcome scores. Results: The vascular cohort had a mean Lysholm score of 62.5 points (range, 16 to 100 points) and a mean International Knee Documentation Committee (IKDC) score of 59.7 points (range, 14.9 to 100 points) at a mean (and standard deviation) of 8.3 ± 5.0 years after surgery. The control cohort had a mean Lysholm score of 86.4 points (range, 51.0 to 100.0 points) and a mean IKDC score of 83.8 points (range, 35.6 to 100.0 points) at a mean of 6.0 ± 4.0 years. The vascular cohort had significantly lower Lysholm (p = 0.001) and IKDC (p = 0.002) scores than the control cohort. A body mass index (BMI) of >30 kg/m 2 was predictive of lower IKDC (p = 0.0009) and Lysholm (p = 0.0008) scores. Conclusions: Patients who sustain an MLKI with an associated popliteal artery injury requiring bypass grafting have significantly lower knee function scores than patients without vascular involvement. This information can be used to help counsel patients with combined multiple ligament and popliteal artery injuries. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Purpose This brief report describes a planned, interim, 6-patient toxicity analysis that confirms the safety of pemetrexed, carboplatin, radiation with subsequent surgery, as prescribed in the North Central Cancer Treatment Group trial N044E, in patients with locally advanced esophageal cancer. Methods Six patients with locally advanced, potentially resectable esophageal cancer received pemetrexed 500 mg/m 2 and carboplatin AUC = 6 on days 1 and 22 with 5040 centigray of concomitant radiation in 28 fractions over 5.5 weeks followed by esophagectomy as a prelude to a phase II multi-institutional trial. Results Only 1 of the 6 patients experienced a grade 4 adverse event (neutropenia). This patient also experienced a grade 3 depression. Of the remaining 5 patients, three experienced at least one grade 3 adverse event (neutropenia, nausea/vomiting, and esophagitis). There were no deaths. Incidentally, one patient manifested a complete pathologic response, three a partial pathologic response, and one stable disease. Conclusion These preliminary observations on safety suggest that this regimen can be further studied in this clinical setting.

Background Few studies have described the demographics and outcomes in patients with multiple cancers. Methods We reviewed the health records of patients with at least 3 invasive solid-tumor malignancies (lung, colorectal, pancreatic, prostate, breast, or ovarian) diagnosed between 1995 and 2014 at our institution. Results A total of 163 patients were identified. The median age at first cancer diagnosis was 61 years. Sixteen (10%) had a family history of cancer, and 7 (4%) had a cancer-predisposing syndrome. Most had early-stage malignancies and underwent a series of surgical resections. The median survival from the first cancer diagnosis was 14 years (95% confidence interval: 12–16). Forty-three percent developed 4 or more cancers. In univariate analyses, older age, male sex, smoking history, concurrent cancer, and stage IV disease were associated with worse survival; by contrast, breast cancer as the first cancer diagnosis yielded better survival. In multivariate analyses, older age, smoking history, and stage IV disease were associated with worse survival. Conclusions A small group of patients with no ostensible risk factors develop multiple early-stage cancers, receive curative therapy (often surgery), and live for years. These patients merit further study to ascertain the broader prevalence rates of individuals with multiple invasive cancers and to better understand factors that contribute to cancer risk.

Background: The reported rate of second anterior cruciate ligament (ACL) injuries (20%-30%), including graft failure and contralateral ACL tears, after ACL reconstruction (ACLR) or nonoperative therapy indicates that multiple factors may predispose patients to subsequent ACL injuries. Purpose: To determine the incidence of second ACL injuries in a population-based cohort over a 10-year observation period (2001-2010) and to identify factors that contribute to the risk of second injuries. Study Design: Descriptive epidemiological study. Methods: International Classification of Diseases, 9th Revision (ICD-9) codes relevant to the diagnosis of an ACL tear and the procedure code for ACLR were utilized to search the Rochester Epidemiology Project, a multidisciplinary county database, between the years of 2001 and 2010. The complete medical records for all cases were reviewed to confirm diagnosis and treatment details. A total of 914 unique patients with 1019 acute, isolated ACL tears were identified. These patients were stratified by primary and secondary tears, sex, age, activity level, side of injury, sex × side of injury, and graft type of reconstruction. Results: Second ACL tears were recorded in 141 (13.8%) of the 914 patients diagnosed with an ACL tear in Olmsted County, Minnesota, USA, from 2001 to 2010; 50.4% of these occurred in the contralateral knee. A noncontact mechanism was responsible for 76.4% of all ACL injuries. A second ACL injury was influenced by factors of sex × age group, treatment type × age group, and treatment type × activity level. Nonparametric analysis of graft disruption × graft type demonstrated that a higher prevalence of second ACL tears occurred with allografts compared with hamstring autografts ( P = .0054) and patellar tendon autografts ( P = .0001). Conclusion: The incidence of second ACL tears in this population-based cohort was 13.8%, and half occurred to the ACL of the contralateral knee. Statistically, second ACL injuries differed by sex, occurring in female patients younger than 25 years and male patients aged 26 to 45 years. Allografts continued to be associated with a greater risk of second ACL injuries compared with hamstring and patellar tendon autografts. Nonoperative treatment carried more risk of contralateral tears than ACLR.

SummaryObjectiveEvidence on the diagnostic performance of adrenal imaging is limited. We aimed to assess the diagnostic performance of unenhanced computed tomography (CT) and 18F‐fluorodeoxyglucose (18FDG) positron emission tomography (PET)/CT imaging in a high‐risk population for adrenal malignancy using an optimal reference standard.DesignRetrospective cohort study.MethodsImaging studies of patients with adrenal nodules who underwent adrenal biopsy and/or adrenalectomy between 1994 and 2014 were reviewed and compared to the reference standard of histology. Eighty % of patients presented with known or suspected extra‐adrenal malignancy.ResultsUnenhanced abdominal CT was performed in 353 patients with adrenal lesions; median size was 3 (0.7‐15) cm and median radiodensity was 33 (−21‐78) Hounsfield units (HU). Radiodensity of >10 HU diagnosed malignancy with a sensitivity of 100%, specificity of 33%, positive predictive value (PPV) of 72% and negative predictive value (NPV) of 100%. 18FDG‐PET/CT was performed in 89 patients; median tumour size was 2.1 (0.7‐9.2) cm. Maximum standardized uptake (SUV max) was higher in malignant lesions when compared to benign lesions (median=10 [2.3‐29.4] vs 3.7 [1.4‐24.5], respectively, P<.0001). Similarly, median SUV max lesion to SUV max liver ratio (ALR) in malignant lesions was higher than in benign lesions (median=3 [0.74‐13.4] vs 1.2 [0.5‐6.6], respectively, P<.0001). 18FDG‐PET/CT ALR >1.8 diagnosed malignancy with a sensitivity of 87%, specificity of 84%, PPV of 85% and NPV of 86%.ConclusionNoncontract CT radiodensity of ≤10 HU excludes malignancy even in a high‐risk population. For indeterminate adrenal lesions, given a superior specificity, 18FDG‐PET/CT could be considered as a second stage imaging study.