Metabolite profiling of human renal cell carcinoma reveals tissue-origin dominance in nutrient availability.

The tumor microenvironment is a determinant of cancer progression and therapeutic efficacy, with nutrient availability playing an important role. Although it is established that the local abundance of specific nutrients defines the metabolic parameters for tumor growth, the factors guiding nutrient availability in tumor compared to normal tissue and blood remain poorly understood. To define these factors in renal cell carcinoma (RCC), we performed quantitative metabolomic and comprehensive lipidomic analyses of tumor interstitial fluid (TIF), adjacent normal kidney interstitial fluid (KIF), and plasma samples collected from patients. TIF nutrient composition closely resembles KIF, suggesting that tissue-specific factors unrelated to the presence of cancer exert a stronger influence on nutrient levels than tumor-driven alterations. Notably, select metabolite changes consistent with known features of RCC metabolism are found in RCC TIF, while glucose levels in TIF are not depleted to levels that are lower than those found in KIF. These findings inform tissue nutrient dynamics in RCC, highlighting a dominant role of non-cancer driven tissue factors in shaping nutrient availability in these tumors.

Screening in serum-derived medium reveals differential response to compounds targeting metabolism.

A challenge for screening new anticancer drugs is that efficacy in cell culture models is not always predictive of efficacy in patients. One limitation of standard cell culture is a reliance on non-physiological nutrient levels, which can influence cell metabolism and drug sensitivity. A general assessment of how physiological nutrients affect cancer cell response to small molecule therapies is lacking. To address this, we developed a serum-derived culture medium that supports the proliferation of diverse cancer cell lines and is amenable to high-throughput screening. We screened several small molecule libraries and found that compounds targeting metabolic enzymes were differentially effective in standard compared to serum-derived medium. We exploited the differences in nutrient levels between each medium to understand why medium conditions affected the response of cells to some compounds, illustrating how this approach can be used to screen potential therapeutics and understand how their efficacy is modified by available nutrients.

Racial differences in phenotypic frailty assessment among general thoracic surgery patients.

Objectives: The American Association for Thoracic Surgery recommends using frailty assessments to identify patients at higher risk of perioperative morbidity and mortality. We evaluated what patient factors are associated with frailty in a thoracic surgery patient population. Methods: New patients aged more than 50 years who were evaluated in a thoracic surgery clinic underwent routine frailty screening with a modified Fried's Frailty Phenotype. Differences in demographics and comorbid conditions among frailty status groups were assessed with chi-square and Student t tests. Logistic regressions performed with binomial distribution assessed the association of demographic and clinical characteristics with nonfrail, frail, prefrail, and any frailty (prefrail/frail) status. Results: The study population included 317 patients screened over 19 months. Of patients screened, 198 (62.5%) were frail or prefrail. Frail patients undergoing thoracic surgery were older, were more likely single or never married, had lower median income, and had lower percent predicted diffusion capacity of the lungs for carbon monoxide and forced expiratory volume during 1 second (all P < .05). More non-Hispanic Black patients were frail and prefrail compared with non-Hispanic White patients (P = .003) and were more likely to score at least 1 point on Fried's Frailty Phenotype (adjusted odds ratio, 3.77; P = .02) when controlling for age, sex, number of comorbidities, median income, diffusion capacity of the lungs for carbon monoxide, and forced expiratory volume during 1 second. Non-Hispanic Black patients were more likely than non-Hispanic White patients to score points for slow gait and low activity (both P < .05). Conclusions: Non-Hispanic Black patients undergoing thoracic surgery are more likely to score as frail or prefrail than non-Hispanic White patients. This disparity stems from differences in activity and gait speed. Frailty tools should be examined for factors contributing to this disparity, including bias.

Enterobius vermicularis Appendiceal Colic.

Enterobius vermicularis associated appendiceal colic and acute appendicitis are rarely encountered in the United States. The 9-year-old patient described in this case presented with right lower quadrant abdominal pain, nausea, and vomiting consistent with acute appendicitis and was brought to the operating room for an appendectomy. Intraoperatively a pinworm, E. vermicularis, was visualized and the presumptive diagnosis of acute appendicitis was revised to E. vermicularis associated appendiceal colic. Retrospective review of the preoperative imaging demonstrates the first reported ultrasonographic image of pinworm inhabitance within the appendiceal lumen. The patient was treated postoperatively with a course of albendazole and recovered appropriately. This article reviews the geographic epidemiology, pathophysiology, surgical, and medical treatment recommendations in the management of E. vermicularis diseases of the appendix. Through dissemination of this ultrasonographic imaging, the authors hope to inform other providers about E. vermicularis associated appendiceal colic and reduce the incidence of avoidable surgeries.