Wavelength-Dependent Bifunctional Plasmonic Photocatalysis in Au/Chalcopyrite Hybrid Nanostructures.

Excited, or "hot" charge carrier generation and transfer driven by the decay of localized surface plasmon resonances (LSPRs) are key steps in plasmonic photocatalysis. Hybrid structures that contain both metal and semiconductor building blocks facilitate the extraction of reactive charge carriers and their utilization for photoelectrocatalysis. Additional functionality arises from hybrid structures that combine noble metal nanostructures with semiconductor components, such as chalcopyrite (CuFeS2) nanocrystals (NCs), which by themselves support quasistatic resonances. In this work, we use a hybrid membrane to integrate Au nanorods (NRs) with a longitudinal LSPR at 745 nm and CuFeS2 NCs with a resonance peak at 490 nm into water-stable nanocomposites for robust and bifunctional photocatalysis of oxygen and hydrogen evolution reactions in a wavelength-dependent manner. Excitation of NRs or NCs in the nanocomposite correlates with increased hydrogen or oxygen evolution, respectively, consistent with a light-driven electron transfer between the metal and semiconductor building blocks, the direction of which depends on the wavelength. The bifunctional photoreactivity of the nanocomposite is enhanced by Cu(I)/Cu(II)-assisted catalysis on the surface of the NCs.

Effective Mass for Holes in Paramagnetic, Plasmonic Cu5FeS4 Semiconductor Nanocrystals.

The impact of a magneto-structural phase transition on the carrier effective mass in Cu5FeS4 plasmonic semiconductor nanocrystals was examined using Magnetic Circular Dichroism (MCD). Through MCD, the sample was confirmed as p-type from variable temperature studies from 1.8 - 75 K. Magnetic field dependent behavior is observed, showing an asymptotic behavior at high field with an m∗ value 5.98 m∗∕me at 10 T and 2.73 m∗∕me at 2 T. Experimentally obtained results are holistically compared to SQUID magnetization data and DFT results, highlighting a dependency on vacancy driven polaronic coupling, magnetocrystalline anisotropy, and plasmon coupling of the magnetic field all contributing to an overall decrease in the hole mean free path dependent on the magnetic field applied to Cu5FeS4.

Profiling of Adipose and Skeletal Muscle in Human Pancreatic Cancer Cachexia Reveals Distinct Gene Profiles with Convergent Pathways.

The vast majority of patients with pancreatic ductal adenocarcinoma (PDAC) suffer cachexia. Although cachexia results from concurrent loss of adipose and muscle tissue, most studies focus on muscle alone. Emerging data demonstrate the prognostic value of fat loss in cachexia. Here we sought to identify the muscle and adipose gene profiles and pathways regulated in cachexia. Matched rectus abdominis muscle and subcutaneous adipose tissue were obtained at surgery from patients with benign conditions (n = 11) and patients with PDAC (n = 24). Self-reported weight loss and body composition measurements defined cachexia status. Gene profiling was done using ion proton sequencing. Results were queried against external datasets for validation. 961 DE genes were identified from muscle and 2000 from adipose tissue, demonstrating greater response of adipose than muscle. In addition to known cachexia genes such as FOXO1, novel genes from muscle, including PPP1R8 and AEN correlated with cancer weight loss. All the adipose correlated genes including SCGN and EDR17 are novel for PDAC cachexia. Pathway analysis demonstrated shared pathways but largely non-overlapping genes in both tissues. Age related muscle loss predominantly had a distinct gene profiles compared to cachexia. This analysis of matched, externally validate gene expression points to novel targets in cachexia.

Extending the Near-Infrared Emission Range of Indium Phosphide Quantum Dots for Multiplexed In Vivo Imaging.

This report of the reddest emitting indium phosphide quantum dots (InP QDs) to date demonstrates tunable, near-infrared (NIR) photoluminescence (PL) as well as PL multiplexing in the first optical tissue window while avoiding toxic constituents. This synthesis overcomes the InP "growth bottleneck" and extends the emission peak of InP QDs deeper into the first optical tissue window using an inverted QD heterostructure, specifically ZnSe/InP/ZnS core/shell/shell nanoparticles. The QDs exhibit InP shell thickness-dependent tunable emission with peaks ranging from 515-845 nm. The high absorptivity of InP yields effective photoexcitation of the QDs with UV, visible, and NIR wavelengths. These nanoparticles extend the range of tunable direct-bandgap emission from InP-based nanostructures, effectively overcoming a synthetic barrier that has prevented InP-based QDs from reaching their full potential as NIR imaging agents. Multiplexed lymph node imaging in a mouse model demonstrates the potential of the NIR-emitting InP particles for in vivo imaging.

Incisional Hernia After Orthotopic Liver Transplantation: A Systematic Review and Meta-analysis.

BACKGROUND: Incisional hernia (IH) is a well-known complication of orthotopic liver transplantation. Despite wide recognition of the impact of this problem, the incidence remains imprecisely known. METHODS: The MEDLINE, EMBASE, Cochrane Central Register of Clinical Trials and Cochrane Database of Systematic Reviews databases were searched from their inception to November 2017 for abstracts documenting IH after orthotropic liver transplantation (OLT). The primary endpoint of this study was incidence of IH, secondary endpoints were time to hernia and recurrence. Three reviewers independently graded abstracts for inclusion in this review. Heterogeneity in combining data was assumed prior to pooling. Random-effects meta-analyses were performed to estimate percentages and 95% CIs. RESULTS: After a review of 77 abstracts, 18 studies were graded as relevant. The methodological quality of studies was assessed with a minimum Oxford Centre for Evidence-Based Medicine level of 2B. These represent a cohort of 981 patients with IH after OLT reported in the literature. A meta-analysis of studies meeting inclusion criteria shows mean incidence of 15.1% (CI 12.1%-18.2%). Aggregate recurrence rate reported in the literature is 12.4% (CI 4.3%-20.5%). Overall reported time to IH after OLT was 42.9 months. CONCLUSIONS: Although reported incidences of IH after OLT vary widely across studies, an overall incidence of 15.1% is reported. This is a relatively late complication after transplantation. Recurrence of hernia after initial repair is 12.4% within this patient population.

Controlled Synthesis and Exploration of CuxFeS4 Bornite Nanocrystals.

Plasmonic semiconductor nanocrystals (NCs) are a new and exciting class of materials that enable higher control of their localized surface plasmon resonance (LSPR) than metallic counterparts. Additionally, earth-abundant and non-toxic materials such as copper iron sulfides are gaining interest as alternatives to heavy metal-based semiconductor materials. Colloidal bornite (Cu5FeS4) is an interesting but underexplored example of a heavy metal-free plasmonic semiconductor. This report details the hot-injection synthesis of bornite yielding NCs ranging from 2.7 to 6.1 nm in diameter with stoichiometric control of the copper and iron content. The absorbance spectra of bornite NCs with different Cu:Fe ratios change at different rates as the particles oxidize and develop LSPR in the near-infrared region. X-ray photoelectron spectroscopy results indicate that oxidation produces sulfates rather than metal oxides as well as a decrease in the iron content within the NCs. Additionally, increasing iron content leads to decreases in carrier density and effective mass of the carrier, as determined by the Drude model. This controlled synthesis, combined with a further understanding of the relationship between the particle structure and optical properties, will enable the continued development and application of these fascinating heavy metal-free plasmonic semiconductor nanoparticles.

Correlating ZnSe Quantum Dot Absorption with Particle Size and Concentration.

The focus on heavy metal-free semiconductor nanocrystals has increased interest in ZnSe semiconductor quantum dots (QDs) over the past decade. Reliable and consistent incorporation of ZnSe cores into core/shell heterostructures or devices requires empirical fit equations correlating the lowest-energy electron transition (1S peak) to their size and molar extinction coefficients (ε). While these equations are known and heavily used for CdSe, CdTe, CdS, PbS, etc., they are not well established for ZnSe and are nonexistent for ZnSe QDs with diameters <3.5 nm. In this study, a series of ZnSe QDs with diameters ranging from 2 to 6 nm were characterized by small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), UV-vis spectroscopy, and microwave plasma atomic emission spectroscopy (MP-AES). SAXS-based size analysis enabled the practical inclusion of small particles in the evaluation, and elemental analysis with MP-AES elucidates a nonstoichiometric Zn:Se ratio consistent with zinc-terminated spherical ZnSe QDs. Using these combined results, empirical fit equations correlating QD size with its lowest-energy electron transition (i.e., 1S peak position), Zn:Se ratio, and molar extinction coefficients for 1S peak, 1S integral, and high-energy wavelengths are reported. Finally, the equations are used to track the evolution of a ZnSe core reaction. These results will enable the consistent and reliable use of ZnSe core particles in complex heterostructures and devices.

Identification of Potential Serum Protein Biomarkers and Pathways for Pancreatic Cancer Cachexia Using an Aptamer-Based Discovery Platform.

Patients with pancreatic ductal adenocarcinoma (PDAC) suffer debilitating and deadly weight loss, known as cachexia. Development of therapies requires biomarkers to diagnose, and monitor cachexia; however, no such markers are in use. Via Somascan, we measured ~1300 plasma proteins in 30 patients with PDAC vs. 11 controls. We found 60 proteins specific to local PDAC, 46 to metastatic, and 67 to presence of >5% cancer weight loss (FC ≥ |1.5|, p ≤ 0.05). Six were common for cancer stage (Up: GDF15, TIMP1, IL1RL1; Down: CCL22, APP, CLEC1B). Four were common for local/cachexia (C1R, PRKCG, ELANE, SOST: all oppositely regulated) and four for metastatic/cachexia (SERPINA6, PDGFRA, PRSS2, PRSS1: all consistently changed), suggesting that stage and cachexia status might be molecularly separable. We found 71 proteins that correlated with cachexia severity via weight loss grade, weight loss, skeletal muscle index and radiodensity (r ≥ |0.50|, p ≤ 0.05), including some known cachexia mediators/markers (LEP, MSTN, ALB) as well as novel proteins (e.g., LYVE1, C7, F2). Pathway, correlation, and upstream regulator analyses identified known (e.g., IL6, proteosome, mitochondrial dysfunction) and novel (e.g., Wnt signaling, NK cells) mechanisms. Overall, this study affords a basis for validation and provides insights into the processes underpinning cancer cachexia.

The Combination of Low Skeletal Muscle Mass and High Tumor Interleukin-6 Associates with Decreased Survival in Clear Cell Renal Cell Carcinoma.

Clear cell renal carcinoma (ccRCC) is frequently associated with cachexia which is itself associated with decreased survival and quality of life. We examined relationships among body phenotype, tumor gene expression, and survival. Demographic, clinical, computed tomography (CT) scans and tumor RNASeq for 217 ccRCC patients were acquired from the Cancer Imaging Archive and The Cancer Genome Atlas (TCGA). Skeletal muscle and fat masses measured from CT scans and tumor cytokine gene expression were compared with survival by univariate and multivariate analysis. Patients in the lowest skeletal muscle mass (SKM) quartile had significantly shorter overall survival versus the top three SKM quartiles. Patients who fell into the lowest quartiles for visceral adipose mass (VAT) and subcutaneous adipose mass (SCAT) also demonstrated significantly shorter overall survival. Multiple tumor cytokines correlated with mortality, most strongly interleukin-6 (IL-6); high IL-6 expression was associated with significantly decreased survival. The combination of low SKM/high IL-6 was associated with significantly lower overall survival compared to high SKM/low IL-6 expression (26.1 months vs. not reached; p < 0.001) and an increased risk of mortality (HR = 5.95; 95% CI = 2.86-12.38). In conclusion, tumor cytokine expression, body composition, and survival are closely related, with low SKM/high IL-6 expression portending worse prognosis in ccRCC.

Encapsulating Quantum Dots in Lipid-PEG Micelles and Subsequent Copper-Free Click Chemistry Bioconjugation.

The utility of quantum dots (QDs) for biological applications is predicated on stably dispersing the particles in aqueous media. During transfer from apolar organic solvents to water, the optical properties of the fluorescent nanoparticles must be maintained; additionally, the resulting colloid should be monodisperse and stable against aggregation. Furthermore, the hydrophilic coating should confer functional groups or conjugation handles to the QDs, as biofunctionalization is often critical to biosensing and bioimaging applications. Micelle encapsulation is an excellent technique for conferring hydrophilicity and conjugation handles to QDs. One interesting conjugation handle that can easily be added to the QDs is an azide group, which conjugates to strained alkynes via strain promoted azide-alkyne cycloaddition (SPAAC) reactions. SPAAC, or copper-free click chemistry, utilizes very mild reaction conditions, involves reactive groups that are bio-orthogonal, and is nearly quantitative. Micelle encapsulation is also very mild and preserves the optical properties of the QDs nearly perfectly. The combination of these approaches comprises a mild, effective, and straightforward approach to preparing functionalized QDs for biological applications.

Sustained treatment of retinal vascular diseases with self-aggregating sunitinib microparticles.

Neovascular age-related macular degeneration and diabetic retinopathy are prevalent causes of vision loss requiring frequent intravitreous injections of VEGF-neutralizing proteins, and under-treatment is common and problematic. Here we report incorporation of sunitinib, a tyrosine kinase inhibitor that blocks VEGF receptors, into a non-inflammatory biodegradable polymer to generate sunitinib microparticles specially formulated to self-aggregate into a depot. A single intravitreous injection of sunitinib microparticles potently suppresses choroidal neovascularization in mice for six months and in another model, blocks VEGF-induced leukostasis and retinal nonperfusion, which are associated with diabetic retinopathy progression. After intravitreous injection in rabbits, sunitinib microparticles self-aggregate into a depot that remains localized and maintains therapeutic levels of sunitinib in retinal pigmented epithelium/choroid and retina for more than six months. There is no intraocular inflammation or retinal toxicity. Intravitreous injection of sunitinib microparticles provides a promising approach to achieve sustained suppression of VEGF signaling and improve outcomes in patients with retinal vascular diseases.

Shell-Free Copper Indium Sulfide Quantum Dots Induce Toxicity in Vitro and in Vivo.

Semiconductor quantum dots (QDs) are attractive fluorescent contrast agents for in vivo imaging due to their superior photophysical properties, but traditional QDs comprise toxic materials such as cadmium or lead. Copper indium sulfide (CuInS2, CIS) QDs have been posited as a nontoxic and potentially clinically translatable alternative; however, previous in vivo studies utilized particles with a passivating zinc sulfide (ZnS) shell, limiting direct evidence of the biocompatibility of the underlying CIS. For the first time, we assess the biodistribution and toxicity of unshelled CIS and partially zinc-alloyed CISZ QDs in a murine model. We show that bare CIS QDs breakdown quickly, inducing significant toxicity as seen in organ weight, blood chemistry, and histology. CISZ demonstrates significant, but lower, toxicity compared to bare CIS, while our measurements of core/shell CIS/ZnS are consistent with literature reports of general biocompatibility. In vitro cytotoxicity is dose-dependent on the amount of metal released due to particle degradation, linking degradation to toxicity. These results challenge the assumption that removing heavy metals necessarily reduces toxicity: indeed, we find comparable in vitro cytotoxicity between CIS and CdSe QDs, while CIS caused severe toxicity in vivo compared to CdSe. In addition to highlighting the complexity of nanotoxicity and the differences between the in vitro and in vivo outcomes, these unexpected results serve as a reminder of the importance of assessing the biocompatibility of core QDs absent the protective ZnS shell when making specific claims of compositional biocompatibility.

Specialized care improves outcomes for patients with cirrhosis who require general surgical operations.

BACKGROUND: General surgical operations on patients with cirrhosis have historically been associated with high morbidity and mortality rates. This study examines a contemporary series of patients with cirrhosis undergoing general surgical procedures. METHODS: A retrospective evaluation of 358 cirrhotic patients undergoing general surgical operations at a single institution between 2004-2015 was performed. Thirty- and 90-day mortality along with complications and subsequent transplantation rates were examined. RESULTS: 358 cirrhotic patients were identified. The majority were Child-Turcotte-Pugh class (CTP) A (55.9%) followed by class B (32.4%) and class C (11.7%). Mean MELD score differed significantly between the groups (8.7 vs. 12.1 vs. 20.1; p<0.001). The most common operations were herniorrhaphy (29.9%), cholecystectomy (19.3%), and liver resection (14.5%). The majority of cases were performed semi-electively (68.4%), however, within the CTP C patients most cases were performed emergently (73.8%). Thirty and 90-day mortality for all patients were 5% and 6%, respectively. Mortality rates increased from CTP A to CTP C (30 day: 3.0% vs. 5.2% vs. 14.3%; p = 0.01; 90 day: 4.5% vs. 6.9% vs. 16.7%; p = 0.016). Additionally, 30-day mortality (12.8% vs. 2.3%; p<0.001), 90 day mortality (16.0% vs. 3.4%; p<0.001) were higher for emergent compared to elective cases. A total of 13 (3.6%) patients underwent transplantation ≤ 90 days from surgery. No elective cases resulted in an urgent transplantation. CONCLUSION: Performing general surgical operations on cirrhotic patients carries a significant morbidity and mortality. This contemporary series from a specialized liver center demonstrates improved outcomes compared to historical series. These data strongly support early referral of cirrhotic patients needing general surgical operation to centers with liver expertise to minimize morbidity and mortality.

Financial Burden of Liver Transplant vs Resection for Hepatocellular Carcinoma.

BACKGROUND: Liver transplant and liver resection are surgical treatments for hepatocellular carcinoma (HCC) performed with curative intent. While liver transplant provides longer survival when compared to resection, the financial burden on patients and payors is significantly greater. With the increase in health care costs and the emergence of high deductible insurance policies that increase out of pocket deductibles for patients, assessment of value-based treatment is warranted. METHODS: We compiled total billable events from diagnosis of HCC through resection (N = 20) or transplant (N = 24) to death or last reported encounter from January 2011 to December 2012. RESULTS: Patients with HCC receiving resection had a model of end stage liver disease of 10.2 ± 1.2, survival 652 days (3-1, 167 days), and billable encounters of $316,873 ($2904/day). HCC patients receiving a liver transplant had a greater liver injury (model of end stage liver disease of 19.2 ± 3.7), longer survival (1579 days), and higher billable encounters, $740,714 ($2889/day). The surgical procedure represented the largest cost category (28% and 26% resection vs transplant, respectively). The cost effectiveness of treatment was directly proportional to length of survival. In resection, patients who survived >30 days (85%) cost per day dropped to $432. Transplant patients who survived >2 years (75%) saw the cost per day drop to $462. CONCLUSION: The relative financial burdens of liver resection vs liver transplant for treating HCC are comparable in patients who survive beyond a certain threshold. Transplant patients survived longer, and survival beyond 2 years makes this approach cost effective. In a health care climate aiming to contain costs and evaluate value-based treatment paradigms, expected survival and financial burden should be included in the treatment decision analysis.

In Vivo Biosensing Using Resonance Energy Transfer.

Solution-phase and intracellular biosensing has substantially enhanced our understanding of molecular processes foundational to biology and pathology. Optical methods are favored because of the low cost of probes and instrumentation. While chromatographic methods are helpful, fluorescent biosensing further increases sensitivity and can be more effective in complex media. Resonance energy transfer (RET)-based sensors have been developed to use fluorescence, bioluminescence, or chemiluminescence (FRET, BRET, or CRET, respectively) as an energy donor, yielding changes in emission spectra, lifetime, or intensity in response to a molecular or environmental change. These methods hold great promise for expanding our understanding of molecular processes not just in solution and in vitro studies, but also in vivo, generating information about complex activities in a natural, organismal setting. In this review, we focus on dyes, fluorescent proteins, and nanoparticles used as energy transfer-based optical transducers in vivo in mice; there are examples of optical sensing using FRET, BRET, and in this mammalian model system. After a description of the energy transfer mechanisms and their contribution to in vivo imaging, we give a short perspective of RET-based in vivo sensors and the importance of imaging in the infrared for reduced tissue autofluorescence and improved sensitivity.

Role for targeted resection in the multidisciplinary treatment of metastatic gastrointestinal stromal tumor.

The management of advanced gastrointestinal stromal tumors (GISTs) has evolved in the modern era due to the discovery of c-kit mutations and the development of tyrosine kinase inhibitors (TKIs). Until the advent of TKIs such as imatinib, the median survival reported for patients with advanced GIST was 19 months. Although surgery is the treatment of choice for resectable primary GIST, its role in cases of recurrence and metastasis remains to be unclear. This review outlines the potential beneficial role of repeat surgical resection in the multidisciplinary treatment of advanced GIST in the era of TKIs.

Postoperative renal impairment is associated with increased length of stay for incisional hernia repair after liver transplantation.

BACKGROUND: Incisional hernia repair is the most common procedure after orthotopic liver transplantation. Although enhanced recovery protocols are increasingly employed, the post-orthotopic liver transplantation patient may not benefit from all aspects of these models. The aim of the present study is to assess which perioperative interventions and patient factors affect hospital length of stay in a cohort of post-orthotopic liver transplantation patients undergoing incisional hernia repair. METHODS: We conducted a retrospective review of a series of adult patients undergoing incisional hernia repair after orthotopic liver transplantation. The primary endpoint was length of stay. Results were stratified by demographic, intraoperative, and postoperative variables. RESULTS: Eleven percent (172/1523) of patients who received orthotopic liver transplantation during the study period underwent subsequent incisional hernia repair. Median length of stay was 5 days (range 2-50). The strongest predictor of length of stay was postoperative renal function. Despite liberal intraoperative administration of volume (median 642 mL/h) and brisk intraoperative urine output (median 72 mL/h), postoperative acute kidney injury occurred in 48% of patients. Those that developed acute kidney injury received less intraoperative volume (6 vs 8.5 mL/kg/h; P = .031) and the severity of postoperative renal injury was inversely related to the amount intraoperative volume given. CONCLUSIONS: In patients undergoing incisional hernia repair after orthotopic liver transplantation, postoperative renal function is frequently impaired. Although many aspects of current ERAS protocols may be applied to post-transplant patients, restrictive intraoperative fluid administration strategies should be employed with caution given a high propensity for the development of post-operative acute kidney injury in this complex population.

Outcomes of pancreatoduodenectomy in the cirrhotic patient: risk stratification and meta-analysis.

BACKGROUND: Cirrhosis increases the risk of perioperative mortality in gastrointestinal surgery. Though cirrhosis is sometimes considered a contraindication to pancreatoduodenectomy (PD), few data are available in this patient population. The aim of the present study is to identify predictors of outcome in cirrhotic patients undergoing PD. METHODS: Patients undergoing PD with biopsy-proved cirrhosis were evaluated. Primary endpoints were morbidity and mortality. Child score, MELD score, and radiographic evidence of portal hypertension (pHTN) were assessed for accuracy in preoperative risk stratification. A systematic review of the literature with meta-analysis was also performed to query morbidity and mortality of patients with cirrhosis reported to undergo PD. RESULTS: Between 2005 and 2015, 36 cirrhotic patients underwent PD; three year follow-up was complete. Median Child score was 6 (range 5-10); median MELD score was 9 (range 7-18). Perioperative (90-day) mortality was 6/36. Median survival was 37 months (range 0.2-116). MELD ≥ 10 was associated with increased mortality (4/13 vs. 2/13, p = 0.004). Irrespective of Child or MELD score, those with pHTN had poor outcomes including significantly greater intraoperative blood loss, increased incidence of major complication, and length of stay. Postoperative mortality was significantly higher with pHTN (3/16 vs. 1/13, p = 0.012). CONCLUSION: Pancreatoduodenectomy may be considered in carefully selected cirrhotic patients. MELD ≥ 10 predicts increased risk of postoperative mortality. Specific attention should be afforded to patients with preoperative radiographic evidence of portal hypertension as this group experiences poor outcomes irrespective of MELD or Child score.

Sensing with photoluminescent semiconductor quantum dots.

Fluorescent sensors benefit from high signal-to-noise and multiple measurement modalities, enabling a multitude of applications and flexibility of design. Semiconductor nanocrystal quantum dots (QDs) are excellent fluorophores for sensors because of their extraordinary optical properties. They have high thermal and photochemical stability compared to organic dyes or fluorescent proteins and are extremely bright due to their large molar cross-sections. In contrast to organic dyes, QD emission profiles are symmetric, with relatively narrow bandwidths. In addition, the size tunability of their emission color, which is a result of quantum confinement, make QDs exceptional emitters with high color purity from the ultra-violet to near infrared wavelength range. The role of QDs in sensors ranges from simple fluorescent tags, as used in immunoassays, to intrinsic sensors that utilize the inherent photophysical response of QDs to fluctuations in temperature, electric field, or ion concentration. In more complex configurations, QDs and biomolecular recognition moieties like antibodies are combined with a third component to modulate the optical signal via energy transfer. QDs can act as donors, acceptors, or both in energy transfer-based sensors using Förster resonance energy transfer (FRET), nanometal surface energy transfer (NSET), or charge or electron transfer. The changes in both spectral response and photoluminescent lifetimes have been successfully harnessed to produce sensitive sensors and multiplexed devices. While technical challenges related to biofunctionalization and the high cost of laboratory-grade fluorimeters have thus far prevented broad implementation of QD-based sensing in clinical or commercial settings, improvements in bioconjugation methods and detection schemes, including using simple consumer devices like cell phone cameras, are lowering the barrier to broad use of more sensitive QD-based devices.

Three cachexia phenotypes and the impact of fat-only loss on survival in FOLFIRINOX therapy for pancreatic cancer.

BACKGROUND: By the traditional definition of unintended weight loss, cachexia develops in ~80% of patients with pancreatic ductal adenocarcinoma (PDAC). Here, we measure the longitudinal body composition changes in patients with advanced PDAC undergoing 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin therapy. METHODS: We performed a retrospective review of 53 patients with advanced PDAC on 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin as first line therapy at Indiana University Hospital from July 2010 to August 2015. Demographic, clinical, and survival data were collected. Body composition measurement by computed tomography (CT), trend, univariate, and multivariate analysis were performed. RESULTS: Among all patients, three cachexia phenotypes were identified. The majority of patients, 64%, had Muscle and Fat Wasting (MFW), while 17% had Fat-Only Wasting (FW) and 19% had No Wasting (NW). NW had significantly improved overall median survival (OMS) of 22.6 months vs. 13.0 months for FW and 12.2 months for MFW (P = 0.02). FW (HR = 5.2; 95% confidence interval = 1.5-17.3) and MFW (HR = 1.8; 95% confidence interval = 1.1-2.9) were associated with an increased risk of mortality compared with NW. OMS and risk of mortality did not differ between FW and MFW. Progression of disease, sarcopenic obesity at diagnosis, and primary tail tumours were also associated with decreased OMS. On multivariate analysis, cachexia phenotype and chemotherapy response were independently associated with survival. Notably, CT-based body composition analysis detected tissue loss of >5% in 81% of patients, while the traditional definition of >5% body weight loss identified 56.6%. CONCLUSIONS: Distinct cachexia phenotypes were observed in this homogeneous population of patients with equivalent stage, diagnosis, and first-line treatment. This suggests cellular, molecular, or genetic heterogeneity of host or tumour. Survival among patients with FW was as poor as for MFW, indicating adipose tissue plays a crucial role in cachexia and PDAC mortality. Adipose tissue should be studied for its mechanistic contributions to cachexia.