The association between neighborhood disadvantage and frailty: A retrospective case series.

Background: Frailty predicts poorer outcomes in surgical patients. Recent studies have found socioeconomic status to be an important characteristic for surgical outcomes. We evaluated the association of Area Deprivation Index (ADI) and Social Vulnerability Index (SVI), two geospatial atlases that provide a multidimensional evaluation of neighborhood deprivation, with frailty in a surgery population. Design & methods: A retrospective study of patients undergoing routine frailty screening was conducted 12/2020-8/2022. Frailty was measured using Fried's Frailty Phenotype (FFP) and the five-item Modified Frailty Index (mFI-5). ADI and SVI quartiles were determined using patient residence. Logistic regression models were used to evaluated associations of FFP (frail only vs not frail) and mFI-5 (≥2 vs 0-1) with ADI and SVI (α = 0.05). Results: Of 372 screened patients, 41% (154) were women, median age was 68% (63-74), and 46% (170) identified as non-White. Across ADI and SVI quartiles, higher number of comorbidities, decreasing median income, and frailty were associated with increasing deprivation (p < 0.01). When controlling for age, sex, comorbidities, and BMI category, frailty by FFP was associated with the most deprived two quartiles of ADI (OR 2.61, CI: [1.35-5.03], p < 0.01) and the most deprived quartile of SVI (OR 2.33, [1.10-4.95], p < 0.05). These trends were also seen with mFI-5 scores ≥2 (ADI: OR 1.64, [1.02-2.63], p < 0.05; SVI: OR 1.71, [1.01-2.91], p < 0.05). Conclusions: Surgical patients living in socioeconomically deprived neighborhoods are more likely to be frail. Interventions may include screening of disadvantaged populations and resource allocation to vulnerable neighborhoods.

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.

Cancer cells convert nutrients into energy differently compared to healthy cells. This difference in metabolism allows them to grow and divide more quickly and sometimes to migrate to different areas of the body. The environment around cancer cells ­ known as the tumor microenvironment ­ contains a variety of different cells and blood vessels, which are bathed in interstitial fluid. This microenvironment provides nutrients for the cancer cells to metabolize, and therefore influences how well a tumor grows and how it might respond to treatment. Recent advances with techniques such as mass spectrometry, which can measure the chemical composition of a substance, have allowed scientists to measure nutrient levels in the tumor microenvironments of mice. However, it has been more difficult to conduct such studies in humans, as well as to compare the tumor microenvironment to the healthy tissue the tumors arose from. Abbott, Ali, Reinfeld et al. aimed to fill this gap in knowledge by using mass spectrometry to measure the nutrient levels in the tumor microenvironment of 55 patients undergoing surgery to remove kidney tumors. Comparing the type and levels of nutrients in the tumor interstitial fluid, the neighboring healthy kidney and the blood showed that nutrients in the tumor and healthy kidney were more similar to each other than those in the blood. For example, both the tumor and healthy kidney interstitial fluids contained less glucose than the blood. However, the difference between nutrient composition in the tumor and healthy kidney interstitial fluids was insignificant, suggesting that the healthy kidney and its tumor share a similar environment. Taken together, the findings indicate that kidney cancer cells must adapt to the nutrients available in the kidney, rather than changing what nutrients are available in the tissue. Future studies will be required to investigate whether this finding also applies to other types of cancer. A better understanding of how cancer cells adapt to their environments may aid the development of drugs that aim to disrupt the metabolism of tumors.

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.

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.

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.

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.