Ambulances Required to Relieve Overcapacity Hospitals: A Novel Measure of Hospital Strain During the COVID-19 Pandemic in the United States.

STUDY OBJECTIVE: One in 4 deaths from COVID-19 has been attributed to hospital crowding. We simulated how many ambulances would be required to rebalance hospital load through systematic interhospital transfers. We assessed the potential feasibility of such a strategy and explored whether transfer requirement was a helpful measure and visualization of regional hospital crowding during COVID-19 surges. METHODS: Using data from the United States hospitals reporting occupancy to the Department of Health and Human Services from July 2020 to March 2022 and road network driving times, we estimated the number of ambulances required weekly to relieve overcapacity hospitals. RESULTS: During the peak week, which ended on January 8, 2021, approximately 1,563 ambulances would be needed for 15,389 simulated patient transports, of which 6,530 (42%) transports involved a 1-way driving time of more than 3 hours. Transfer demands were dramatically lower during most other weeks, with the median week requiring only 134 ambulances (interquartile range, 84 to 295) and involving only 116 transports with 1-way driving times above 3 hours (interquartile range, 4 to 548). On average, receiving hospitals were larger and located in more rural areas than sending hospitals. CONCLUSION: This simulation demonstrated that for most weeks during the pandemic, ambulance availability and bed capacity were unlikely to have been the main impediments to rebalancing hospital loads. Our metric provided an immediately available and much more complete measure of hospital system strain than counts of hospital admissions alone.

Beyond the 405 and the 5: Geographic Variations and Factors Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Positivity Rates in Los Angeles County.

BACKGROUND: To highlight geographic differences and the socio-structural determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test positivity within Los Angeles County (LAC). METHODS: A geographic information system was used to integrate, map, and analyze SARS-CoV-2 testing data reported by the LAC Department of Public Health and data from the American Community Survey. Structural determinants included race/ethnicity, poverty, insurance status, education, and population and household density. We examined which factors were associated with positivity rates, using a 5% test positivity threshold, with spatial analysis and spatial regression. RESULTS: Between 1 March and 30 June 2020 there were 843 440 SARS-CoV-2 tests and 86 383 diagnoses reported, for an overall positivity rate of 10.2% within the study area. Communities with high proportions of Latino/a residents, those living below the federal poverty line, and with high household densities had higher crude positivity rates. Age- adjusted diagnosis rates were significantly associated with the proportion of Latino/as, individuals living below the poverty line, and population and household density. CONCLUSIONS: There are significant local variations in test positivity within LAC and several socio-structural determinants contribute to ongoing disparities. Public health interventions, beyond shelter in place, are needed to address and target such disparities.

A clinical trial of intraoperative near-infrared imaging to assess tumor extent and identify residual disease during anterior mediastinal tumor resection.

BACKGROUND: The management of most solid tumors of the anterior mediastinum involves complete resection. Because of their location near mediastinal structures, wide resection is not possible; therefore, surgeons must use subjective visual and tactile cues to determine disease extent. This clinical trial explored intraoperative near-infrared (NIR) imaging as an approach to improving tumor delineation during mediastinal tumor resection. METHODS: Twenty-five subjects with anterior mediastinal lesions suspicious for malignancy were enrolled in an open-label feasibility trial. Subjects were administered indocyanine green (ICG) at a dose of 5 mg/kg, 24 hours before resection (via a technique called TumorGlow). The NIR imaging systems included Artemis (Quest, Middenmeer, the Netherlands) and Iridium (VisionSense Corp, Philadelphia, Pennsylvania). Intratumoral ICG uptake was evaluated. The clinical value was determined via an assessment of the ability of NIR imaging to detect phrenic nerve involvement or incomplete resection. Clinical and histopathologic variables were analyzed to determine predictors of tumor fluorescence. RESULTS: No drug-related toxicity was observed. Optical imaging added a mean of 10 minutes to case duration. Among the subjects with solid tumors, 19 of 20 accumulated ICG. Fluorescent tumors included thymomas (n = 13), thymic carcinomas (n = 4), and liposarcomas (n = 2). NIR feedback improved phrenic nerve dissection (n = 4) and identified residual disease (n = 2). There were no false-positives or false-negatives. ICG preferentially accumulated in solid tumors; this was independent of clinical and pathologic variables. CONCLUSIONS: NIR imaging for anterior mediastinal neoplasms is safe and feasible. This technology may provide a real-time tool capable of determining tumor extent and specifically identify phrenic nerve involvement and residual disease.

Intraoperative Near-infrared Imaging Can Identify Neoplasms and Aid in Real-time Margin Assessment During Pancreatic Resection.

OBJECTIVE: To determine if intraoperative near-infrared (NIR) imaging carries benefit in resection of pancreatic neoplasms. BACKGROUND: Resection of pancreatic malignancies is hindered by high rates of local and distant recurrence from positive margins and unrecognized metastases. Improved tumor visualization could improve outcomes. We hypothesized that intraoperative NIR imaging with a clinically approved optical contrast agent could serve as a useful adjunct in assessing margins and extent of disease during pancreatic resections. METHODS: Twenty patients were enrolled in an open-label clinical trial from July 2016 to May 2018. Subjects received second window indocyanine green (ICG) (2.5-5 mg/kg) 24 hours prior to pancreatic resection. NIR imaging was performed during staging laparoscopy and after pancreas mobilization in situ and following resection ex vivo. Tumor fluorescence was quantified using tumor-to-background ratio (TBR). Fluorescence at the specimen margin was compared to pathology evaluation. RESULTS: Procedures included 9 pancreaticoduodenectomies, 10 distal pancreatectomies, and 1 total pancreatectomy; 21 total specimens were obtained. Three out of 8 noninvasive tumors were fluorescent (mean TBR 2.59 ±â€Š2.57). Twelve out of 13 invasive malignancies (n = 12 pancreatic adenocarcinoma, n = 1 cholangiocarcinoma) were fluorescent (mean TBR 4.42 ±â€Š2.91). Fluorescence at the transection margin correlated with final pathologic assessment in 12 of 13 patients. Following neoadjuvant therapy, 4 of 5 tumors were fluorescent; these 4 tumors showed no treatment response on pathology assessment. One tumor had a significant treatment response and showed no fluorescence. CONCLUSIONS: Second window ICG reliably accumulates in invasive pancreatic malignancies and provides real-time feedback during pancreatectomy. NIR imaging may help to assess the response to neoadjuvant therapy.

Structural and Functional Role of Acetyltransferase hMOF K274 Autoacetylation.

Many histone acetyltransferases undergo autoacetylation, either through chemical or enzymatic means, to potentiate enzymatic cognate substrate lysine acetylation, although the mode and molecular role of such autoacetylation is poorly understood. The MYST family of histone acetyltransferases is autoacetylated at an active site lysine residue to facilitate cognate substrate lysine binding and acetylation. Here, we report on a detailed molecular investigation of Lys-274 autoacetylation of the human MYST protein Males Absent on the First (hMOF). A mutational scan of hMOF Lys-274 reveals that all amino acid substitutions of this residue are able to bind cofactor but are significantly destabilized, both in vitro and in cells, and are catalytically inactive for cognate histone H4 peptide lysine acetylation. The x-ray crystal structure of a hMOF K274P mutant suggests that the reduced stability and catalytic activity stems from a disordering of the residue 274-harboring a α2-ß7 loop. We also provide structural evidence that a C316S/E350Q mutant, which is defective for cognate substrate lysine acetylation; and biochemical evidence that a K268M mutant, which is defective for Lys-274 chemical acetylation in the context of a K274-peptide, can still undergo quantitative K274 autoacetylation. Together, these studies point to the critical and specific role of hMOF Lys-274 autoacetylation in hMOF stability and cognate substrate acetylation and argues that binding of Ac-CoA to hMOF likely drives Lys-274 autoacetylation for subsequent cognate substrate acetylation.

Tissue engineering of the stomach.

Tissue engineering combines engineering principles with the biological sciences to create functional replacement tissues. The underlying principle of tissue engineering is that isolated cells combined with biomaterials can form new tissues and organs in vitro and in vivo. This review focuses on stomach tissue engineering, which is a promising approach to the treatment of gastric cancer, the fourth most common malignancy in the world and the second-leading cause of cancer mortality worldwide. Although gastrectomy is a reliable intervention to achieve complete removal of cancer lesions, the limited capacity for food intake after resection results in lower quality of life for patients. To address this issue, we have developed a tissue-engineered stomach to increase the capacity for food intake by creating a new food reservoir. We have transplanted this neo-stomach as a substitute for the original native stomach in a rat model and confirmed functional adaptation. Furthermore, we have demonstrated the feasibility of transplanting a tissue-engineered gastric wall patch in a rat model to alleviate the complications after resection of a large area of the gastric wall. Although progress has been achieved, significant challenges remain to bring this approach to clinical practice. Here, we summarize our work and present the state of the art in stomach tissue engineering.

The association between county political inclination and obesity: Results from the 2012 presidential election in the United States.

OBJECTIVE: We examined whether stable, county-level, voter preferences were significantly associated with county-level obesity prevalence using data from the 2012 US Presidential election. County voting preference for the 2012 Republican Party presidential candidate was used as a proxy for voter endorsement of personal responsibility approaches to reducing population obesity risk versus approaches featuring government-sponsored, multi-sectoral efforts like those recommended by the Centers for Disease Control Centers for Disease Control (CDC, 2009). METHOD: Cartographic visualization and spatial analysis were used to evaluate the geographic clustering of obesity prevalence rates by county, and county-level support for the Republican Party candidate in the 2012 U.S. presidential election. The spatial analysis informed the spatial econometric approach employed to model the relationship between political preferences and other covariates with obesity prevalence. RESULTS: After controlling for poverty rate, percent African American and Latino populations, educational attainment, and spatial autocorrelation in the error term, we found that higher county-level obesity prevalence rates were associated with higher levels of support for the 2012 Republican Party presidential candidate. CONCLUSION: Future public health efforts to understand and reduce obesity risk may benefit from increased surveillance of this and similar linkages between political preferences and health risks.

Assessment of a tissue-engineered gastric wall patch in a rat model.

Stenosis or deformity of the remaining stomach can occur after gastrectomy and result in stomach malfunction. The objective of this study is to demonstrate the feasibility of transplanting a tissue-engineered gastric wall patch in a rat model to alleviate the complications after resection of a large area of the gastric wall. Tissue-engineered gastric wall patches were created from gastric epithelial organoid units and biodegradable polymer scaffolds. In the first treatment group, gastric wall defects were created in recipient rats and covered with fresh tissue-engineered gastric wall patches (simultaneous transplantation). In the second treatment group, the tissue-engineered gastric wall patches were frozen for 12weeks, and then transplanted in recipient rats (metachronous transplantation). Tissue-engineered gastric wall patches were successfully used as a substitute of the resected native gastric wall in both simultaneous and metachronous transplantation groups. The defrosted wall patches showed almost the same cell viability as the fresh ones. Twenty-four weeks after transplantation, the defect in the gastric wall was well-covered with tissue-engineered gastric wall patch, and the repaired stomach showed no deformity macroscopically in both groups. Histology showed continuous mucosa and smooth muscle layers at the tissue-engineered stomach wall margin. The feasibility of transplanting a tissue-engineered patch to repair a defect in the native gastric wall has been successfully shown in a rat model, thereby taking one step closer toward the transplantation of an entire tissue-engineered stomach in the future.

Inflammatory bowel disease induces inflammatory and pre-neoplastic changes in the prostate.

BACKGROUND: Inflammatory bowel disease (IBD) has been implicated as a risk factor for prostate cancer, however, the mechanism of how IBD leads to prostate tumorigenesis is not known. Here, we investigated whether chronic intestinal inflammation leads to pro-inflammatory changes associated with tumorigenesis in the prostate. METHODS: Using clinical samples of men with IBD who underwent prostatectomy, we analyzed whether prostate tumors had differences in lymphocyte infiltrate compared to non-IBD controls. In a mouse model of chemically-induced intestinal inflammation, we investigated whether chronic intestinal inflammation could be transferred to the wild-type mouse prostate. In addition, mouse prostates were evaluated for activation of pro-oncogenic signaling and genomic instability. RESULTS: A higher proportion of men with IBD had T and B lymphocyte infiltration within prostate tumors. Mice with chronic colitis showed significant increases in prostatic CD45 + leukocyte infiltration and elevation of three pro-inflammatory cytokines-TIMP-1, CCL5, and CXCL1 and activation of AKT and NF-kB signaling pathways. Lastly, mice with chronic colitis had greater prostatic oxidative stress/DNA damage, and prostate epithelial cells had undergone cell cycle arrest. CONCLUSIONS: These data suggest chronic intestinal inflammation is associated with an inflammatory-rich, pro-tumorigenic prostatic phenotype which may explain how gut inflammation fosters prostate cancer development in men with IBD.

Global tropical dry forest extent and cover: A comparative study of bioclimatic definitions using two climatic data sets.

There is a debate concerning the definition and extent of tropical dry forest biome and vegetation type at a global spatial scale. We identify the potential extent of the tropical dry forest biome based on bioclimatic definitions and climatic data sets to improve global estimates of distribution, cover, and change. We compared four bioclimatic definitions of the tropical dry forest biome-Murphy and Lugo, Food and Agriculture Organization (FAO), DryFlor, aridity index-using two climatic data sets: WorldClim and Climatologies at High-resolution for the Earth's Land Surface Areas (CHELSA). We then compared each of the eight unique combinations of bioclimatic definitions and climatic data sets using 540 field plots identified as tropical dry forest from a literature search and evaluated the accuracy of World Wildlife Fund tropical and subtropical dry broadleaf forest ecoregions. We used the definition and climate data that most closely matched field data to calculate forest cover in 2000 and change from 2001 to 2020. Globally, there was low agreement (< 58%) between bioclimatic definitions and WWF ecoregions and only 40% of field plots fell within these ecoregions. FAO using CHELSA had the highest agreement with field plots (81%) and was not correlated with the biome extent. Using the FAO definition with CHELSA climatic data set, we estimate 4,931,414 km2 of closed canopy (≥ 40% forest cover) tropical dry forest in 2000 and 4,369,695 km2 in 2020 with a gross loss of 561,719 km2 (11.4%) from 2001 to 2020. Tropical dry forest biome extent varies significantly based on bioclimatic definition used, with nearly half of all tropical dry forest vegetation missed when using ecoregion boundaries alone, especially in Africa. Using site-specific field validation, we find that the FAO definition using CHELSA provides an accurate, standard, and repeatable way to assess tropical dry forest cover and change at a global scale.

Geographical and socioeconomic disparities in opioid access in Mexico, 2015-19: a retrospective analysis of surveillance data.

BACKGROUND: In 2015, Mexico implemented regulatory changes and an electronic system to improve access to prescription opioids. We aimed to investigate trends in opioid dispensing after the implementation of these changes and assess how opioid dispensing varied geographically and by socioeconomic status. METHODS: In this retrospective analysis of prescription medication surveillance data, we analysed dispensing data for group 1 medications (all opioids, including morphine, methadone, hydromorphone, oxycodone, tapentadol, fentanyl, sufentanil, and remifentanil) obtained from the Federal Commission for the Protection against Sanitary Risk database for 32 states and six large metropolitan areas in Mexico. We calculated crude annual opioid prescriptions per 10 000 people at the national, state, and municipal levels. Adapting methods from the report of the Lancet Commission on Palliative Care and Pain Relief, we calculated the need for palliative opioids by state, and then assessed the observed opioid dispensing rates as a percentage of expected need by geographical socioeconomic status. Within the six major metropolitan areas, we mapped the geocoded location of opioid prescriptions and assessed the association between opioid dispensing and socioeconomic status as well as the association between opioid dispensing and time to US border crossing for areas on the US-Mexico border. FINDINGS: Between June 25, 2015, and Oct 7, 2019, opioid dispensing rates increased by an average of 13% (95% CI 6·8-19·6) per quarter (3 months). The overall national opioid dispensing rate during the study period was 26·3 prescriptions per 10 000 inhabitants. States with a higher socioeconomic status had higher opioid dispensing rates than states with lower socioeconomic status (rate ratio [RR] 1·88, 95% CI 1·33-2·58, p=0·00016) after controlling for the estimated opioid requirement per state, the presence of methadone clinics, and the presence of tertiary hospitals and cancer centres. The same association between opioid dispensing and socioeconomic status was observed in the metropolitan areas, and in those metropolitan areas on the US-Mexico border a 20% decrease (RR 0·80, 95% CI 0·75-0·86) in opioid dispensation was observed per each SD increase (SD 17·1 min) in travel time to the border. INTERPRETATION: Measures introduced by the Mexican federal Government to increase opioid access for patients with palliative care needs were only marginally successful in raising opioid prescription rates. Opioid access should be improved for patients with palliative care needs who live in geographical areas of lower socioeconomic status. FUNDING: US National Institutes of Health.

Inter-alpha inhibitor protein level in neonates predicts necrotizing enterocolitis.

OBJECTIVES: To compare inter-alpha inhibitor protein (IaIp) levels in neonates with proven necrotizing enterocolitis (NEC) and neonates with other, nonspecific abdominal disorders. STUDY DESIGN: This was a prospective observational study of neonates in the neonatal intensive care unit. NEC was diagnosed according to Bell's staging criteria. The nNeonates in the control group had a nonspecific abdominal disorder, but no radiographic evidence of NEC and no disease progression. All neonates with radiographically confirmed NEC were included. Plasma IaIp levels were quantitated by enzyme-linked immunosorbent assay. RESULTS: Seventeen neonates had confirmed NEC, and 34 neonates had nonspecific abdominal disorders that improved rapidly. Gestational age, postnatal age, weight, sex, maternal obstetric variables, rupture of membranes, and mode of delivery did not differ between the two groups. Mean IaIp level was significantly lower in the NEC group compared with the control group (137 ± 38 mg/L; 95% confidence interval [CI], 118-157 mg/L vs 258 ± 53 mg/L; 95% CI, 238-277 mg/L; P <.0001). CONCLUSIONS: The finding of significantly lower IaIp levels in neonates with NEC suggests that IaIp might be a useful, sensitive biomarker, allowing initiation of appropriate therapy and reducing antibiotic overuse in neonates with suspected but unproven NEC. Administration of IaIp may significantly reduce the severity of systemic inflammation and associated tissue injury.

Comparison of a Short Versus Long Stokes Shift Near-Infrared Dye During Intraoperative Molecular Imaging.

PURPOSE: Intraoperative molecular imaging (IMI) utilizes optical dyes that accumulate within tumors to assist with detection during a cancer operation. IMI can detect disease not visualized preoperatively, as well as positive margins. However, these dyes are limited by autofluorescence, signal reflection, and photon-scatter. We hypothesize that a novel dye with a wide separation between excitation and emission spectra, SS180, would help overcome these obstacles. PROCEDURES: Two targeted molecular contrast agents, OTL38 and SS180, were selected for this study. Both dyes had the same targeting ligand to folate receptor alpha (FRα). OTL38, a well-annotated IMI agent in human trials, has a Stokes shift of 22 nm, whereas SS180, the new dye, has a Stokes shift of 129 nm. Cell lines were tested for FRα expression and incubated with dyes to demonstrate receptor-dependent binding. Cells were incubated in various concentrations of the dyes to compare dose- and time-dependent binding. Finally, cells tagged with the dyes were injected subcutaneously in a murine model to estimate tumor burden necessary to generate fluorescent signal. RESULTS: Cellular studies demonstrated that SS180 binds cells in a dose-, receptor-, and time-dependent manner and exhibits higher mean fluorescence intensities by flow cytometry when compared with OTL38 for each time point and concentration. In an in vivo flank tumor model, SS180 had a higher tumor-to-background ratio (TBR) than OTL38, though not statistically significant (p = 0.08). Ex vivo, OTL38 had a higher TBR than SS180 (p = 0.02). The subcutaneous model revealed that SS180 had a higher TBR at 5 × 106 cells than OTL38 (p = 0.05). No toxicity was observed in the animals. CONCLUSIONS: SS180 exhibits greater TBRs in vivo, but not ex vivo. These findings suggest that SS180 may have weaker fluorescence, but superior contrast. Studies in large animal models and clinical trials may better elucidate the clinical value of a long Stokes shift.

Assessment of Racial/Ethnic and Income Disparities in the Prescription of Opioids and Other Controlled Medications in California.

Importance: Most drug epidemics in the United States have disproportionately affected nonwhite communities. Notably, the current opioid epidemic is heavily concentrated among low-income white communities, and the roots of this racial/ethnic phenomenon have not been adequately explained. Objective: To examine the degree to which differential exposure to opioids via the health care system by race/ethnicity and income could be driving the observed social gradient of the current opioid epidemic, as well as to compare the trends in the prevalence of prescription opioids with those observed for stimulants and benzodiazepines. Design, Setting, and Participants: This population-based study used 2011 through 2015 records from California's prescription drug monitoring program (Controlled Substance Utilization Review and Evaluation System), which longitudinally tracks all patients receiving controlled substance prescriptions in the state and contained unique records for 29.7 million individuals who received such a prescription from 2011 to 2015. Data were analyzed between January and May 2018. Exposures: A total of 1760 zip code tabulation areas (ZCTAs) in California, with associated racial/ethnic composition and per capita income. Main Outcomes and Measures: The percentage of individuals receiving at least 1 prescription each year was calculated for opioids, benzodiazepines, and stimulants. Results: A nearly 300% difference in opioid prescription prevalence across the race/ethnicity-income gradient was observed in California, with 44.2% of adults in the quintile of ZCTAs with the lowest-income/highest proportion-white population receiving at least 1 opioid prescription each year compared with 16.1% in the quintile with the highest-income/lowest proportion-white population and 23.6% of all individuals 15 years or older. Stimulant prescriptions were highly concentrated in mostly white high-income areas, with a prevalence of 3.8% among individuals in the quintile with the highest-income/highest proportion-white population and a prevalence of 0.6% in the quintile with the lowest-income/lowest proportion-white population. Benzodiazepine prescriptions did not have an income gradient but were concentrated in mostly white areas, with 15.7% of adults in the quintile of ZCTAs with the highest proportion-white population receiving at least 1 prescription each year compared with 7.0% among the quintile with the lowest proportion-white population. Conclusions and Relevance: The race/ethnicity and income pattern of opioid overdoses mirrored prescription rates, suggesting that differential exposure to opioids via the health care system may have induced the large, observed racial/ethnic gradient in the opioid epidemic. Across drug categories, controlled medications were much more likely to be prescribed to individuals living in majority-white areas. These discrepancies may have shielded nonwhite communities from the brunt of the prescription opioid epidemic but also represent disparities in treatment and access to all medications.

Modeling Epidermal Growth Factor Inhibitor-mediated Enhancement of Photodynamic Therapy Efficacy Using 3D Mesothelioma Cell Culture.

We have demonstrated that lung-sparing surgery with intraoperative photodynamic therapy (PDT) achieves remarkably extended survival for patients with malignant pleural mesothelioma (MPM). Nevertheless, most patients treated using this approach experience local recurrence, so it is essential to identify ways to enhance tumor response. We previously reported that PDT transiently activates EGFR/STAT3 in lung and ovarian cancer cells and inhibiting EGFR via erlotinib can increase PDT sensitivity. Additionally, we have seen higher EGFR expression associating with worse outcomes after Photofrin-mediated PDT for MPM, and the extensive desmoplastic reaction associated with MPM influences tumor phenotype and therapeutic response. Since extracellular matrix (ECM) proteins accrued during stroma development can alter EGF signaling within tumors, we have characterized novel 3D models of MPM to determine their response to erlotinib combined with Photofrin-PDT. Our MPM cell lines formed a range of acinar phenotypes when grown on ECM gels, recapitulating the locally invasive phenotype of MPM in pleura and endothoracic fascia. Using these models, we confirmed that EGFR inhibition increases PDT cytotoxicity. Together with emerging evidence that EGFR inhibition may improve survival of lung cancer patients through immunologic and direct cell killing mechanisms, these results suggest erlotinib-enhanced PDT may significantly improve outcomes for MPM patients.

A Clinical Trial of TumorGlow to Identify Residual Disease During Pleurectomy and Decortication.

BACKGROUND: Macroscopic complete resection can improve survival in a select group of patients with malignant pleural mesothelioma. During resection, differentiating residual tumor from inflammation or scar can be challenging. This trial evaluated near-infrared (NIR) intraoperative imaging using TumorGlow (a novel NIR imaging approach utilizing high-dose indocyanine green and delayed imaging) technology to improve detection of macroscopic residual disease. METHODS: Twenty subjects were enrolled in an open-label clinical trial of NIR intraoperative imaging with TumorGlow (Indocyanine Green for Solid Tumors [NCT02280954]). Twenty-four hours before pleural biopsy or pleurectomy and decortication (P/D), patients received intravenous indocyanine green. All specimens identified during standard-of-care surgical resection and with NIR imaging underwent histopathologic profiling and correlative microscopic fluorescent tomographic evaluation. For subjects undergoing P/D (n = 13), the hemithorax was evaluated with NIR imaging during P/D to assess for residual disease. When possible, additional fluorescent lesions were resected. RESULTS: Of 203 resected specimens submitted for evaluation, indocyanine green accumulated within 113 of 113 of resected mesothelioma specimens, with a mean signal-to-background fluorescence ratio of 3.1 (SD, 2.2 to 4.8). The mean signal-to-background fluorescence ratio of benign tissues was 2.2 (SD, 1.4 to 2.4), which was significantly lower than in malignant specimens (p = 0.001). NIR imaging identified occult macroscopic residual disease in 10 of 13 subjects. A median of 5.6 resectable residual deposits per patient (range, 0 to 11 deposits per patient), with a mean size of 0.3 cm (range, 0.1 to 1.5 cm), were identified. CONCLUSIONS: TumorGlow for malignant pleural mesothelioma is safe and feasible. Excellent sensitivity allows for to reliable detection of macroscopic residual disease during cytoreductive surgical procedures.

National trends and disparities of minimally invasive surgery for localized renal cancer, 2010 to 2015.

PURPOSE: To investigate national utilization trends of minimally-invasive partial nephrectomy (PN) and minimally-invasive radical nephrectomy (RN), and to identify disparities in the usage of these techniques across different sociodemographic subgroups. MATERIALS AND METHODS: A retrospective cohort study was conducted using the National Cancer Database to identify patients undergoing partial or RN for cT1N0M0 renal cancer diagnosed between 2010 and 2015. Main outcomes of interest were the utilizations of minimally-invasive (robotic and laparoscopic) PN and RN. RESULTS: A total of 46,346 and 37,712 subjects who underwent PN and RN, respectively, were analyzed. During the study interval, increased utilization of robotic surgery paralleled the decreased utilization of open surgery. Robotic PN increased from 35.2% to 63.7% and robotic RN increased from 10.3% to 26.3%. The utilization of laparoscopic surgery was decreasing for PN but stable for RN through the study period. In the PN cohort, multivariable logistic regression showed non-Hispanic black (odds ratio [OR] = 0.90 [95% CI, 0.84-0.96]) and Hispanic (OR = 0.91 [0.84-0.99]) subjects were associated with less utilization of minimally invasive surgery (MIS) (vs. non-Hispanic white). Younger (18-64 years) Medicare (OR = 0.83 [0.77-0.90]), Medicaid (OR = 0.80 [0.74-0.87]), and uninsured (OR = 0.55 [0.49-0.62]) were also associated with less utilization of MIS (vs. private insurance). Compared with low socioeconomic status (SES), upper middle (OR = 1.14 [1.07-1.21]) and high (OR = 1.24 [1.16-1.33]) SES were associated with higher utilization of MIS. Similar demographic, insurance, and SES-related disparities were identified in the RN cohort. CONCLUSIONS: Utilization of MIS for localized renal cancer has increased significantly and was mainly attributed to increased usage of robotic surgery. Racial/ethnic, insurance, and SES related disparities in MIS utilization were identified. Our findings demonstrate a targetable subgroup of patients who do not have the same access to advances in surgical technology.

Evaluation of Aminolevulinic Acid-Derived Tumor Fluorescence Yields Disparate Results in Murine and Spontaneous Large Animal Models of Lung Cancer.

Fluorescence guided surgery is an emerging technology that may improve accuracy of pulmonary resection for non-small cell lung cancer (NSCLC). Herein we explore optical imaging for NSCLC surgery using the well-studied protoporphyrin IX (PPIX)/5-aminiolevulinic acid (5-ALA) system. More specifically, we evaluate fluorescent patterns observed when using (1) commonly utilized in vitro and murine NSCLC models and with (2) spontaneous canine NSCLCs, which closely mimic human disease. Using flow cytometry and fluorescent microscopy, we confirmed that NSCLC models fluoresce after exposure to 5-ALA in vitro. High levels of fluorescence were similarly observed in murine tumors within 2 hours of systemic 5-ALA delivery. When evaluating this approach in spontaneous canine NSCLC, tumor fluorescence was observed in 6 of 7 canines. Tumor fluorescence, however, was heterogenous owing to intratumoral variations in cellularity and necrosis. Margin and lymph node detection was inaccurate. These data demonstrate the importance of incorporating reliable cancer models into preclinical evaluations of optical agents. Utilization of spontaneous large animal models of cancer may further provide an important intermediate in the path to human translation of optical contrast agents.

Near-infrared intraoperative imaging for minimally invasive pulmonary metastasectomy for sarcomas.

BACKGROUND: Complete pulmonary metastasectomy for sarcoma metastases provides patients an opportunity for long-term survival and possible cure. Intraoperative localization of preoperatively identified metastases and identification of occult lesions can be challenging. In this trial, we evaluated the efficacy of near-infrared (NIR) intraoperative imaging using second window indocyanine green during metastasectomy to identify known metastases and to detect occult nodules. METHODS: Thirty patients with pulmonary nodules suspicious for sarcoma metastases were enrolled in an open-label, feasibility study (NCT02280954). All patients received intravenous indocyanine green (5 mg/kg) 24 hours before metastasectomy. Patients 1 through 10 (cohort 1) underwent metastasectomy via thoracotomy to assess fluorescence patterns of nodules detected by traditional methods (preoperative imaging and intraoperative visualization/bimanual palpation). After confirming reliability within cohort 1, patients 11 through 30 (cohort 2) underwent video-assisted thoracic surgery metastasectomy with NIR imaging. RESULTS: In cohort 1, 14 out of 16 preoperatively identified pulmonary metastases (87.5%) displayed tumor fluorescence. Nonfluorescent metastases were deeper than fluorescent metastases (2.1 cm vs 1.3 cm; P = .03). Five out of 5 metastases identified during thoracotomy displayed fluorescence. NIR imaging identified 3 additional occult lesions in this cohort. In cohort 2, 33 out of 37 known pulmonary metastases (89.1%) displayed fluorescence. Nonfluorescent tumors were deeper than 2.0 cm (P = .007). NIR imaging identified 24 additional occult lesions. Of 24 occult lesions, 21 (87.5%) were confirmed metastases and the remaining 3 nodules were lymphoid aggregates. CONCLUSIONS: NIR intraoperative imaging with indocyanine green (5 mg/kg and 24 hours before surgery) localizes known sarcoma pulmonary metastases and identifies otherwise occult lesions. This approach may be a useful intraoperative adjunct to improve metastasectomy.