Clinical genomic profiling in the management of patients with soft tissue and bone sarcoma.

There are more than 70 distinct sarcomas, and this diversity complicates the development of precision-based therapeutics for these cancers. Prospective comprehensive genomic profiling could overcome this challenge by providing insight into sarcomas' molecular drivers. Through targeted panel sequencing of 7494 sarcomas representing 44 histologies, we identify highly recurrent and type-specific alterations that aid in diagnosis and treatment decisions. Sequencing could lead to refinement or reassignment of 10.5% of diagnoses. Nearly one-third of patients (31.7%) harbor potentially actionable alterations, including a significant proportion (2.6%) with kinase gene rearrangements; 3.9% have a tumor mutational burden ≥10 mut/Mb. We describe low frequencies of microsatellite instability (<0.3%) and a high degree of genome-wide loss of heterozygosity (15%) across sarcomas, which are not readily explained by homologous recombination deficiency (observed in 2.5% of cases). In a clinically annotated subset of 118 patients, we validate actionable genetic events as therapeutic targets. Collectively, our findings reveal the genetic landscape of human sarcomas, which may inform future development of therapeutics and improve clinical outcomes for patients with these rare cancers.

Hepatocyte growth factor is associated with greater risk of extracoronary calcification: results from the multiethnic study of atherosclerosis.

BACKGROUND: Hepatocyte growth factor (HGF) is a biomarker with potential for use in the diagnosis, treatment and prognostication of cardiovascular disease (CVD). Elevated HGF is associated with calcification in the coronary arteries. However, knowledge is limited on the role HGF may play in extracoronary calcification (ECC). This study examined whether HGF is associated with ECC in the aortic valve (AVC), mitral annulus (MAC), ascending thoracic aorta and descending thoracic aortic (DTAC). METHODS: At baseline, adults aged 45-84 years, free of CVD, in the Multi-Ethnic Study of Atherosclerosis had HGF and ECC measured by ELISA and cardiac CT scan, respectively. ECC measurements were repeated after an average of 2.4 years of follow-up. Prevalent ECC was defined as Agatston score >0 at baseline. Incident ECC was defined as Agatston score >0 at follow-up among participants with Agatston score=0 at baseline. We used Poisson and linear mixed-effects regression models to estimate the association between HGF and ECC, adjusted for sociodemographic and CVD risk factors. RESULTS: Of 6648 participants, 53% were women. Mean (SD) age was 62 (10) years. Median (IQR) of HGF was 905 (757-1087) pg/mL. After adjustment for CVD risk factors, the highest HGF levels (tertile 3) were associated with greater prevalence and extent of AVC, MAC and DTAC at baseline compared with the lowest tertile (tertile 1). Additionally, the risk of incident AVC and MAC increased by 62% and 45%, respectively, in demographic-adjusted models. However, the associations were not statistically significant in fully adjusted models. The highest HGF levels were also associated with 10% and 13% increase in MAC and DTAC progression, respectively, even after adjustment for CVD risk factors. CONCLUSION: Higher HGF levels were significantly associated with a greater risk of calcification at some extracoronary sites, suggesting an alternate biological pathway that could be targeted to reduce CVD risk.

Ten things to know about ten cardiovascular disease risk factors.

Given rapid advancements in medical science, it is often challenging for the busy clinician to remain up-to-date on the fundamental and multifaceted aspects of preventive cardiology and maintain awareness of the latest guidelines applicable to cardiovascular disease (CVD) risk factors. The "American Society for Preventive Cardiology (ASPC) Top Ten CVD Risk Factors 2021 Update" is a summary document (updated yearly) regarding CVD risk factors. This "ASPC Top Ten CVD Risk Factors 2021 Update" summary document reflects the perspective of the section authors regarding ten things to know about ten sentinel CVD risk factors. It also includes quick access to sentinel references (applicable guidelines and select reviews) for each CVD risk factor section. The ten CVD risk factors include unhealthful nutrition, physical inactivity, dyslipidemia, hyperglycemia, high blood pressure, obesity, considerations of select populations (older age, race/ethnicity, and sex differences), thrombosis/smoking, kidney dysfunction and genetics/familial hypercholesterolemia. For the individual patient, other CVD risk factors may be relevant, beyond the CVD risk factors discussed here. However, it is the intent of the "ASPC Top Ten CVD Risk Factors 2021 Update" to provide a succinct overview of things to know about ten common CVD risk factors applicable to preventive cardiology.

Favorable Cardiovascular Health Is Associated With Lower Hepatocyte Growth Factor Levels in the Multi-Ethnic Study of Atherosclerosis.

Introduction: Hepatocyte growth factor (HGF) is a cytokine released in response to endothelial injury and a potential biomarker of cardiovascular disease (CVD) risk. We examined the association between cardiovascular health (CVH) and HGF in a multi-ethnic cohort of adults free from CVD at baseline. Methods: This cross-sectional study conducted between 2020 and 2021 used MESA baseline examination data (2000-2002) from 6,490 US adults aged 45-84 years. The independent variable was CVH measured by the CVH score and number of ideal metrics. The score was derived from seven metrics: smoking, body mass index, physical activity, diet, total cholesterol, blood pressure and blood glucose. Each metric was scored 0 points (poor), 1 point (intermediate) and 2 points (ideal). The total CVH score ranged from 0 to 14. An inadequate score was 0-8, average, 9-10 and optimal, 11-14. The dependent variable was logarithmically transformed HGF. We used regression analyses to estimate associations between CVH and HGF adjusting for sociodemographic factors. Results: Participants' mean (SD) age was 62 (10) years. Fifty-three percent were female. A one-unit increment in the CVH score was significantly associated with 3% lower HGF levels. Average and optimal CVH scores were significantly associated with 8% and 12% lower HGF levels, respectively, compared to inadequate scores. Additionally, a greater number of ideal metrics was associated with lower HGF levels. Conclusion: Favorable CVH was significantly associated with lower HGF levels in this ethnically diverse cohort. Interventions aimed at promoting and preserving favorable CVH may reduce the risk of endothelial injury as indicated by lower serum HGF levels.

Nutrition and physical activity recommendations from the United States and European cardiovascular guidelines: a comparative review.

PURPOSE OF REVIEW: A healthy lifestyle throughout one's lifespan is the core foundation for both primary and secondary prevention of cardiovascular disease (CVD). Risk-based decisions for pharmacological therapy is added on-top of lifestyle management. Thus, understanding lifestyle-based recommendations is central to CVD prevention. RECENT FINDINGS: In 2018 and 2019, the American Heart Association (AHA) and American College of Cardiology (ACC) published new guidelines for lipid management and primary prevention of cardiovascular disease (CVD), respectively. The European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) published new guidelines on lipids and diabetes management in 2019. These guidelines provide recommendations on diet and lifestyle for reducing cardiovascular risk. Both encourage heart-healthy diets consistent with Mediterranean, DASH, or healthy vegetarian patterns. Both provide guidance for recommended physical activity levels but acknowledge any physical activity, even less than recommended, is better than inactivity. Although both ACC/AHA and ESC/EAS guidelines have similar approaches to achieve the same goal of CVD prevention, there were some differences between them. SUMMARY: In this review, we discussed similarities and differences between the American and European guidelines to familiarize clinicians with both sets of lifestyle recommendations in an effort to provide best practices in individualized patient-care for CVD prevention.

High neutrophil-to-lymphocyte ratio (NLR) is associated with treatment failure and death in patients who have melanoma treated with PD-1 inhibitor monotherapy.

BACKGROUND: An elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor survival in patients with cancer, including those who receive immunotherapies. The authors sought to investigate NLR as a biomarker of treatment outcomes in patients with melanoma who were treated with PD-1 inhibition. METHODS: Patients undergoing initial treatment with PD-1 inhibitor monotherapy for stage IV melanoma at a single center from 2012 to 2015 were included. Clinical characteristics and the NLR at baseline and before subsequent treatment cycles were collected. The time to treatment failure (TTF) and overall survival (OS) were evaluated using Kaplan-Meier and landmark analyses. RESULTS: Among 224 study patients, 63 (28%) had a baseline NLR ≥5. The baseline NLR was significantly associated with Eastern Cooperative Oncology Group performance status and the number of involved metastatic sites. With a median follow-up of 39 months in survivors, a baseline NLR ≥5 was independently associated with shorter OS (hazard ratio, 2.0; 95% CI, 1.3-2.9) and TTF (hazard ratio, 1.7; 95% CI, 1.2-2.4). An NLR increase ≥30% during the first 2 cycles of treatment was associated with worse OS (median, 47 vs 13.5 months; P < .001) and a trend toward shorter TTF (12.8 vs 5.9 months; P = .05). A combined baseline NLR ≥5 and an NLR increase ≥30% identified a small cohort with markedly shortened OS (median, 5.8 months) and TTF (median, 1.8 months). CONCLUSIONS: Elevated baseline NLR and an increased NLR early during treatment are prognostic for TTF and OS in patients who have melanoma treated with PD-1 inhibitor monotherapy. Combined, these biomarkers can widely risk-stratify patients for treatment failure and survival.

Invasive granulomatous cryptococcal sinusitis in an adult with multiple myeloma.

We report a case of cryptococcal sinusitis, a rare presentation of Cryptococcus neoformans infection in a patient with multiple myeloma. The objective of this case report is to highlight the utility of structural and functional imaging modalities in the differential diagnosis of sinonasal soft tissue masses in the immunocompromised patient population. PET-CT was the first imaging modality in this patient, who presented for routine follow-up staging of multiple myeloma, and was asymptomatic at the time of his presentation. PET-CT findings prompted further evaluation with MRI, to aid in the differential diagnosis with respect to a neoplastic versus infectious etiology. Ultimately, surgical excision with histopathology was required to provide definitive diagnosis. Final histopathology displayed yeast-organism staining consistent with Cryptococcus neoformans/gatti. The patient subsequently underwent treatment for this infection, along continued treatment for multiple myeloma. To our knowledge this is the first known case of cryptococcal sinusitis in a patient with neoplastic disease. Imaging represents an important tool to differentiate fungal infection from neoplasm in the immunocompromised patient population. As the population of immunocompromised patients continues to grow, the relevance of this diagnosis as well as the use of alternative imaging modalities is becoming more important in clinical practice.

How Are We Measuring Patient Satisfaction After Anterior Cruciate Ligament Reconstruction?

BACKGROUND: Reconstruction of the anterior cruciate ligament (ACL) is one of the most common orthopaedic operations in the United States. The long-term impact of ACL reconstruction is controversial, however, as longer term data have failed to demonstrate that ACL reconstruction helps alter the natural history of early onset osteoarthritis that occurs after ACL injury. There is significant interest in evaluating the value of ACL reconstruction surgeries. PURPOSE: To examine the quality of patient satisfaction reporting after ACL reconstruction surgery. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review of the MEDLINE database was performed using the PubMed interface. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines as well as the PRISMA checklist were employed. The initial search yielded 267 studies. The inclusion criteria were: English language, US patient population, clinical outcome study of ACL reconstruction surgery, and reporting of patient satisfaction included in the study. Study quality was assessed using the Newcastle-Ottawa scale. RESULTS: A total of 22 studies met the inclusion criteria. These studies comprised a total of 1984 patients with a mean age of 31.9 years at the time of surgery and a mean follow-up period of 59.3 months. The majority of studies were evidence level 4 (n = 18; 81.8%), had a mean Newcastle-Ottawa scale score of 5.5, and were published before 2006 (n = 17; 77.3%); 5 studies (22.7%) failed to clearly describe their method for determining patient satisfaction. The most commonly used method for assessing satisfaction was a 0 to 10 satisfaction scale (n = 11; 50.0%). Among studies using a 0 to 10 scale, mean satisfaction ranged from 7.4 to 10.0. Patient-reported outcome and objective functional measures for ACL stability and knee function were positively correlated with patient satisfaction. Degenerative knee change was negatively correlated with satisfaction. CONCLUSION: The level of evidence for studies reporting patient satisfaction is low, and the methodologies for reporting patient satisfaction are variable. Additionally, within the past decade there has been a significant decline in the inclusion of this outcome measure within published ACL studies. As sports surgeons are increasingly called on to demonstrate the value of operative procedures, attention should be paid to understanding and reporting patient satisfaction.