Melanoma Deaths by Thickness: Most Melanoma Deaths Are Not Attributable to Thin Melanomas.

INTRODUCTION: Previous population-based studies have reported that the majority of melanoma mortality is related to patients with thin (≤1 mm Breslow thickness) melanomas. The aim of the present study was to evaluate the relative proportion of melanoma-specific deaths across all stages of melanoma at diagnosis over the past 20 y in the United States. METHODS: A review of all cutaneous melanoma cases in the US Surveillance, Epidemiology, and End Results registry from 2004 to 2020 was performed. Breslow thickness was categorized as thin (≤1.0 mm), intermediate (>1-4 mm), or thick (>4 mm). All-cause deaths and melanoma-specific deaths were compared across tumor thickness and stage groups at diagnosis. Survival analysis was performed with nonmelanoma deaths considered as a competing risk to estimate the cumulative incidence of melanoma-specific death. RESULTS: Most melanoma deaths occurred in patients who initially presented with local disease (53%) compared to regional (36%) or distant (11%) disease (P < 0.001). However, most (66%) of the melanoma-specific deaths in patients who presented with localized disease were in those with intermediate or thick (i.e., Breslow thickness >1.0 mm) primary tumors compared to those with thin melanomas (34%). The cumulative incidence of melanoma-specific death at 10 y in patients with localized thin melanomas at the time of diagnosis was 2.6% (95% confidence intervals 2.5%-2.7%). CONCLUSIONS: The public health burden in terms of melanoma-specific mortality is related to patients with tumors >1 mm Breslow thickness, many of whom have regional and distant metastatic disease at the time of diagnosis, not patients with thin melanomas.

Fitness Beats Truth in the Evolution of Perception.

Does natural selection favor veridical percepts-those that accurately (if not exhaustively) depict objective reality? Perceptual and cognitive scientists standardly claim that it does. Here we formalize this claim using the tools of evolutionary game theory and Bayesian decision theory. We state and prove the "Fitness-Beats-Truth (FBT) Theorem" which shows that the claim is false: If one starts with the assumption that perception involves inference to states of the objective world, then the FBT Theorem shows that a strategy that simply seeks to maximize expected-fitness payoff, with no attempt to estimate the "true" world state, does consistently better. More precisely, the FBT Theorem provides a quantitative measure of the extent to which the fitness-only strategy dominates the truth strategy, and of how this dominance increases with the size of the perceptual space. The FBT Theorem supports the Interface Theory of Perception (e.g. Hoffman et al. in Psychon Bull Rev https://doi.org/10.3758/s13423-015-0890-8 , 2015), which proposes that our perceptual systems have evolved to provide a species-specific interface to guide adaptive behavior, and not to provide a veridical representation of objective reality.

On Visual Texture Preference: Can an Ecological Model Explain Why People Like Some Textures More Than Others?

What visual textures do people like and why? Here, we test whether the ecological valence theory proposed for color preferences can also predict people's preferences for visual texture. According to the theory, people should like visual textures associated with positive objects or entities and dislike visual textures associated with negative objects or entities. We compare the results for the ecological model with a more traditional texture-preference model based on computational features and find that the ecological model performs reasonably well considering its lower complexity, explaining 63% of the variance in the human preference data.

Hyperglycemia impairs atherosclerosis regression in mice.

Diabetic patients are known to be more susceptible to atherosclerosis and its associated cardiovascular complications. However, the effects of hyperglycemia on atherosclerosis regression remain unclear. We hypothesized that hyperglycemia impairs atherosclerosis regression by modulating the biological function of lesional macrophages. HypoE (Apoe(h/h)Mx1-Cre) mice express low levels of apolipoprotein E (apoE) and develop atherosclerosis when fed a high-fat diet. Atherosclerosis regression occurs in these mice upon plasma lipid lowering induced by a change in diet and the restoration of apoE expression. We examined the morphological characteristics of regressed lesions and assessed the biological function of lesional macrophages isolated with laser-capture microdissection in euglycemic and hyperglycemic HypoE mice. Hyperglycemia induced by streptozotocin treatment impaired lesion size reduction (36% versus 14%) and lipid loss (38% versus 26%) after the reversal of hyperlipidemia. However, decreases in lesional macrophage content and remodeling in both groups of mice were similar. Gene expression analysis revealed that hyperglycemia impaired cholesterol transport by modulating ATP-binding cassette A1, ATP-binding cassette G1, scavenger receptor class B family member (CD36), scavenger receptor class B1, and wound healing pathways in lesional macrophages during atherosclerosis regression. Hyperglycemia impairs both reduction in size and loss of lipids from atherosclerotic lesions upon plasma lipid lowering without significantly affecting the remodeling of the vascular wall.

Multi-institutional review of adverse events associated with irreversible electroporation in the treatment of locally advanced pancreatic cancer.

BACKGROUND: Irreversible electroporation is a novel approach for treating locally advanced pancreatic adenocarcinoma. However, this ablative technique is not without risk and has the potential to precipitate adverse events. The aim of this study was to delineate risk factors that increase this risk, as well as to elucidate the risk profile associated with irreversible electroporation in the setting of locally advanced pancreatic adenocarcinoma. METHODS: A review of our prospective multi-institutional database from December 2015 to March 2022 of patients with locally advanced pancreatic adenocarcinoma who underwent irreversible electroporation was analyzed for adverse events. These were then compared with a control population of patients undergoing pancreatectomy for adenocarcinoma. RESULTS: Adverse events occurred in 51 patients of the 201 patients treated with irreversible electroporation compared with 78 of the 200 patients treated with pancreatectomy. The irreversible electroporation group had a significantly greater incidence of postoperative ascites in stage 3C patients. The most common complications in the irreversible electroporation group were infectious (n = 13), gastrointestinal bleed (n = 11), and ascites (n = 7). Multivariate analysis demonstrated increased risk of severe (grade ≥3) adverse events in the irreversible electroporation cohort who received high dose, neoadjuvant radiation (hazard ratio, 2.4; 95% confidence interval, 1.4-5.4), irreversible electroporation electrodes bracketing the superior mesenteric artery, superior mesenteric vein, and portal venous vein (hazard ratio, 1.9; 95% confidence interval, 1.3-3.4), and who had a bile duct stent in place for >6 months (hazard ratio, 1.7; 95% confidence interval, 1.2-5.6). There were similar rates of 90-day mortality in both groups, irreversible electroporation 2.4% vs pancreatectomy 2.8%. CONCLUSION: This study revealed a 25% rate of adverse events associated with irreversible electroporation in locally advanced pancreatic adenocarcinoma, which was significantly less (P = .004) than the 39% rate of adverse events associated with pancreatectomy in early-stage disease. Certain unique adverse events in the irreversible electroporation group have been established and should be understood in the care of these patients.

ApoE suppresses atherosclerosis by reducing lipid accumulation in circulating monocytes and the expression of inflammatory molecules on monocytes and vascular endothelium.

OBJECTIVE: We investigated atheroprotective properties of apolipoprotein (apo) E beyond its ability to lower plasma cholesterol. We hypothesized that apoE reduces atherosclerosis by decreasing lipid accumulation in circulating monocytes and the inflammatory state of monocytes and the vascular endothelium. METHODS AND RESULTS: We developed mice with spontaneous hyperlipidemia with and without plasma apoE. Hypomorphic apoE mice deficient in low-density lipoprotein receptor (Apoe(h/h)Ldlr(-/-)) were compared to Apoe(-/-)Ldlr(-/-) mice. Despite 4-fold more plasma apoE than WT mice, Apoe(h/h)Ldlr(-/-) mice displayed similar plasma cholesterol as Apoe(-/-) Ldlr(-/-) mice but developed 4-fold less atherosclerotic lesions by 5 months of age. The aortic arch of Apoe(h/h)Ldlr(-/-) mice showed decreased endothelial expression of ICAM-1, PECAM-1, and JAM-A. In addition, Apoe(h/h)Ldlr(-/-) mice had less circulating leukocytes and proinflammatory Ly6C(high) monocytes. These monocytes had decreased neutral lipid content and reduced surface expression of ICAM-1, VLA-4, and L-Selectin. Apoe(h/h)Ldlr(-/-) mice displayed increased levels of apoA1-rich HDL that were potent in promoting cellular cholesterol efflux. CONCLUSIONS: Our findings suggest that apoE reduces atherosclerosis in the setting of hyperlipidemia by increasing plasma apoA1-HDL that likely contribute to reduce intracellular lipid accumulation and thereby the activation of circulating leukocytes and the vascular endothelium.

Adherence to surveillance colonoscopy guidelines in patients following curative-intent colorectal cancer resection.

BACKGROUND: Current guidelines recommend that patients who have undergone curative-intent resection for colorectal cancer (CRC) should undergo colonoscopy one year following their surgery or at six months post-operatively if a pre-operative colonoscopy was not performed due to an obstructing lesion. We sought to determine adherence to postoperative surveillance colonoscopy guidelines in our National Cancer Institute designated comprehensive cancer center and potentially identify factors associated with non-adherence. MATERIALS AND METHODS: A retrospective review of 100 patients who underwent curative-intent CRC resection was performed between 2013 and 2019. Patients were divided into two groups based upon adherence to surveillance colonoscopy guidelines. Demographic, tumor, and postoperative variables were analyzed. RESULTS: The median age of all patients was 62. Fifty-seven percent of patients were male. Thirty-eight patients underwent surveillance colonoscopy in accordance with current guidelines. Sixty-two patients did not undergo surveillance colonoscopy postoperatively or did so outside of the National Comprehensive Cancer Network guidelines. Factors associated with non-adherence to surveillance colonoscopy included presence of comorbidities, albumin less than 3.5, and performance of a pre-operative colonoscopy. CONCLUSIONS: Adherence to surveillance colonoscopy guidelines was low among our patients. Efforts should be directed toward patients at increased risk for non-adherence to surveillance colonoscopy guidelines.

Non-cancer clinical trials start-up metrics at an academic medical center: Implications for advancing research.

The primary goal for any clinical trial after it receives a funding notification is to receive regulatory approval and initiate the trial for recruitment. Every trial must go through documentation and regulatory process before it can start recruiting participants and collecting data; this initial process of review and approval is known as the study start-up process (SSU). We evaluated the average time taken for studies to receive approvals. Using data from clinical trials conducted at the University of Kansas Medical Center, various times to reach the start of the study were calculated based on the dates of individual study. The results of this analysis showed that chart review studies and investigator-initiated trials had a shorter time to activation than other types of studies. Additionally, single-center studies had a shorter activation time than multi-center studies. The analysis also demonstrated that the overall processing time consistently had been reduced over time.

Mitigation of reactive human cell adhesion on poly(dimethylsiloxane) by immobilized trypsin.

Occlusion or blockage of silicone shunts utilized in the treatment of hydrocephalus is a major challenge that is currently addressed by multiple shunt replacements. Shunt occlusion is caused by the adhesion and proliferation of reactive cells, such as glial and vascular cells, into the lumen of the catheter and on valve components. This in vitro study describes how the adhesive behavior of four human cell types on poly(dimethylsiloxane) (PDMS) surfaces can be suppressed by functionalization with trypsin, a proteolytic enzyme. The covalently conjugated trypsin retained its proteolytic activity and acted in a dose-dependent manner. Trypsin-modified PDMS surfaces supported significantly lower adhesion of normal human astrocytes, human microglia, human dermal fibroblasts, and human umbilical vein endothelial cells compared to unmodified PDMS surfaces (p < 0.0001). Immunofluorescence imaging of cellular fibronectin and quantitative adsorption experiments with serum components indicated that the PDMS surfaces immobilized with trypsin inhibited surface remodeling by all cell types and resisted protein adsorption. The impact of this work lies in the recognition that the well-known proteolytic characteristics of trypsin can be harnessed by covalent surface immobilization to suppress cell adhesion and protein adsorption.

Management of Distal Tibial Metaphyseal Fractures With the SIGN Intramedullary Nail in 3 Developing Countries.

OBJECTIVES: To evaluate the effectiveness of the Surgical Implant Generation Network (SIGN) intramedullary (IM) nail in distal tibial metaphyseal fractures. DESIGN: Retrospective Case Series. SETTING: Three Level I trauma centers in 3 different developing countries from 2009 to 2013. PATIENT/PARTICIPANTS: One hundred sixty patients with 162 distal tibial metaphyseal fractures (AO/OTA 43-A). INTERVENTION: SIGN IM nailing was performed using hand reaming and without the use of an image intensifier. MAIN OUTCOME MEASUREMENTS: The primary outcome measures were the rate of union and complications. The secondary outcome measures were the effect of open fractures on outcomes, effectiveness and safety of open reduction of closed fractures, and risk factors for the development of malalignment and possible solutions. RESULTS: The average age of patients was 35.3 years. Seventy-nine percent were male. Sixty percent of the fractures were closed. The mean time to surgery was 4.1 days. Fracture union occurred in 97.3% of fractures with an average time to union of 105 days. Open reduction of closed fractures was performed in 51 fractures. Nonunion occurred in 3 patients (1.8%). Acceptable alignment (<5 degrees deformity) was found in 134 fractures (83%). Infection occurred in 14 patients (8.6%). Revision surgery was required in 10 fractures (6.2%). CONCLUSIONS: In developing settings, distal metaphyseal tibial fractures can be managed successfully with the SIGN IM nail. There is an increased risk for complications (P = 0.001) and infection (P = 0.0004) in open fractures. Open reduction of closed distal tibia fractures is safe and effective. Malalignment can be improved with fibula stabilization but indications remain unclear. For surgeons interested in international mission work, the SIGN IM nail is an effective tool in managing distal tibial fractures. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.