Lifileucel, an Autologous Tumor-infiltrating Lymphocyte Monotherapy, in Patients with Advanced Non-small Cell Lung Cancer Resistant to Immune Checkpoint Inhibitors.

In this phase 2 multicenter study, we evaluated the efficacy and safety of lifileucel (LN-145), an autologous tumor-infiltrating lymphocyte cell therapy, in patients with metastatic non-small cell lung cancer (mNSCLC) who had received prior immunotherapy and progressed on their most recent therapy. The median number of prior systemic therapies was 2 (range, 1-6). Lifileucel was successfully manufactured using tumor tissue from different anatomic sites, predominantly lung. The objective response rate was 21.4% (6/28). Responses occurred in tumors with profiles typically resistant to immunotherapy, such as PD-L1-negative, low tumor mutational burden, and STK11 mutation. Two responses were ongoing at the time of data cutoff, including one complete metabolic response in a PD-L1-negative tumor. Adverse events were generally as expected and manageable. Two patients died of treatment-emergent adverse events: cardiac failure and multiple organ failure. Lifileucel is a potential treatment option for patients with mNSCLC refractory to prior therapy.

A Voucher Flora of Diatoms from Fens in the Tanana River Floodplain, Alaska.

Climate change and human activities may alter the structure and function of boreal peatlands by warming waters and changing their hydrology. Diatoms can be used to assess or track these changes. However, effective biomonitoring requires consistent, reliable identification. To address this need, this study developed a diatom voucher flora of species found across a boreal fen gradient (e.g., vegetation) in interior Alaskan peatlands. Composite diatom samples were collected bi-weekly from three peatland complexes over the 2017 summer. The morphological range of each taxon was imaged. The fens contained 184 taxa across 38 genera. Eunotia (45), Gomphonema (23), and Pinnularia (20) commonly occurred in each peatland. Tabellaria was common in the rich and moderate fen but sparse in the poor fen. Eunotia showed the opposite trend. Approximately 11% of species are potentially novel and 25% percent matched those at risk or declining in status on the diatom Red List (developed in Germany), highlighting the conservation value of boreal wetlands. This voucher flora expands knowledge of regional diatom biodiversity and provides updated, verifiable taxonomic information for inland Alaskan diatoms, building on Foged's 1981 treatment. This flora strengthens the potential to effectively track changes in boreal waterways sensitive to climate change and anthropogenic stressors.

Characterization of algal community composition and structure from the nearshore environment, Lake Tahoe (United States).

Periphyton assemblages from the nearshore environment of the west (California) side of Lake Tahoe, were analyzed to determine their taxonomic composition and community structure across habitats and seasons. Lake Tahoe is the second deepest lake in the US and an iconic oligotrophic subalpine lake with remarkable transparency. It has experienced offshore cultural eutrophication since the 1960s with observations of nuisance nearshore algal growth since the mid 2000s attributed to anthropogenic stressors. Samplings from November 2019-September 2020 provide useful snapshots against which older monitoring may be contextualized. A voucher flora, complete with descriptions, photo-documentation and referencing to species concepts employed, was created as a method of providing reproducible identification and enumeration of algal species, and more seamless reconciliation of detailed taxonomic data with future monitoring projects. The eulittoral zone (0-2 m) is seasonally dominated by elongate araphid (Synedra, Ulnaria) and stalked or entubed diatoms (Gomphonema, Cymbella, Encyonema). The sublittoral zone (>2 m) is dominated by a nitrogen-fixing Epithemia-cyanobacteria assemblage with less seasonal changes in dominance and composition that expanded to impinge on the 2 m depths of the eulittoral zone in the Fall. Sublittoral epipsammic samples, despite their proximity to rocks, had a very distinct diatom composition and high species dominance, similar to what was seen in the Fall eulittoral samples, with high numbers of Staurosirella chains and small biraphid diatoms. The deeper samples at 30 and 50 m contained high numbers of live Epithemia, and indicate a thriving sublittoral assemblage at these greater depths, but with less biomass. The 2019-20 data show many of the same diatom taxa observed in the 1970's and 1980's but with changes in species dominance. Notably, there was less of the green alga Mougeotia, when compared to the 1970's data, and a higher dominance by nitrogen fixing Epithemia in the sublittoral zone, persisting year-round. These new data show roughly double the algal species biodiversity that had been documented previously in the Lake Tahoe nearshore, and is largely attributed to the methods employed. Adopting these new methods in future monitoring efforts should improve harmonization of taxonomic data and help advance our knowledge of the contributions to nearshore cultural eutrophication.

Protective effects of blueberries on vascular function: A narrative review of preclinical and clinical evidence.

Blueberries are rich in nutrients and (poly)phenols, popular with consumers, and a major agricultural crop with year-round availability supporting their use in food-based strategies to promote human health. Accumulating evidence indicates blueberry consumption has protective effects on cardiovascular health including vascular dysfunction (i.e., endothelial dysfunction and arterial stiffening). This narrative review synthesizes evidence on blueberries and vascular function and provides insight into underlying mechanisms with a focus on oxidative stress, inflammation, and gut microbiota. Evidence from animal studies supports beneficial impacts on vascular function. Human studies indicate acute and chronic blueberry consumption can improve endothelial function in healthy and at-risk populations and may modulate arterial stiffness, but that evidence is less certain. Results from cell, animal, and human studies suggest blueberry consumption improves vascular function through improving nitric oxide bioavailability, oxidative stress, and inflammation. Limited data in animals suggest the gut microbiome mediates beneficial effects of blueberries on vascular function; however, there is a paucity of studies evaluating the gut microbiome in humans. Translational evidence indicates anthocyanin metabolites mediate effects of blueberries on endothelial function, though this does not exclude potential synergistic and/or additive effects of other blueberry components. Further research is needed to establish the clinical efficacy of blueberries to improve vascular function in diverse human populations in a manner that provides mechanistic information. Translation of clinical research to the community/public should consider feasibility, social determinants of health, culture, community needs, assets, and desires, barriers, and drivers to consumption, among other factors to establish real-world impacts of blueberry consumption.

Density declines, richness increases, and composition shifts in stream macroinvertebrates.

Documenting trends of stream macroinvertebrate biodiversity is challenging because biomonitoring often has limited spatial, temporal, and taxonomic scopes. We analyzed biodiversity and composition of assemblages of >500 genera, spanning 27 years, and 6131 stream sites across forested, grassland, urban, and agricultural land uses throughout the United States. In this dataset, macroinvertebrate density declined by 11% and richness increased by 12.2%, and insect density and richness declined by 23.3 and 6.8%, respectively, over 27 years. In addition, differences in richness and composition between urban and agricultural versus forested and grassland streams have increased over time. Urban and agricultural streams lost the few disturbance-sensitive taxa they once had and gained disturbance-tolerant taxa. These results suggest that current efforts to protect and restore streams are not sufficient to mitigate anthropogenic effects.

Modeling Lake Recovery Lag Times Following Influent Phosphorus Loading Reduction.

Internal feedback of nutrients may impede timely improvement in lake water quality. We describe a parsimonious, mechanistic framework for modeling lag times to recovery of phosphorus-enriched lakes, given decreases in external loading. The approach assumes first-order kinetics in a two-compartment system taking account of phosphorus storage in and loading from benthic sediments. Bayesian parameter modeling, published sediment phosphorus release rates, and a prior dynamic calibration for one lake are used to derive estimates of key parameters. Applications are developed for an example lake, as are maps displaying estimated times to attainment of a phosphorus criterion in lakes across a midwestern state, and lag time estimates for fractional water column concentration decrease averaged over HUC-8s. Mean lag times to 50 and 75% declines in water column phosphorus concentration were estimated as 13.1 and 39.0 years respectively, across more than 70,000 lentic water bodies in the continental United States.

Daily blueberry consumption for 12 weeks improves endothelial function in postmenopausal women with above-normal blood pressure through reductions in oxidative stress: a randomized controlled trial.

Estrogen-deficient postmenopausal women have oxidative stress-mediated suppression of endothelial function that is exacerbated by high blood pressure. Previous research suggests blueberries may improve endothelial function through reductions in oxidative stress, while also exerting other cardiovascular benefits. The objective of this study was to examine the efficacy of blueberries to improve endothelial function and blood pressure in postmenopausal women with above-normal blood pressure, and to identify potential mechanisms for improvements in endothelial function. A randomized, double-blind, placebo-controlled, parallel-arm clinical trial was performed, where postmenopausal women aged 45-65 years with elevated blood pressure or stage 1-hypertension (total n = 43, endothelial function n = 32) consumed 22 g day-1 of freeze-dried highbush blueberry powder or placebo powder for 12 weeks. Endothelial function was assessed at baseline and 12 weeks through ultrasound measurement of brachial artery flow-mediated dilation (FMD) normalized to shear rate area under the curve (FMD/SRAUC) before and after intravenous infusion of a supraphysiologic dose of ascorbic acid to evaluate whether FMD improvements were mediated by reduced oxidative stress. Hemodynamics, arterial stiffness, cardiometabolic blood biomarkers, and plasma (poly)phenol metabolites were assessed at baseline and 4, 8, and 12 weeks, and venous endothelial cell protein expression was assessed at baseline and 12 weeks. Absolute FMD/SRAUC was 96% higher following blueberry consumption compared to baseline (p < 0.05) but unchanged in the placebo group (p > 0.05), and changes from baseline to 12 weeks were greater in the blueberry group than placebo (+1.09 × 10-4 ± 4.12 × 10-5vs. +3.82 × 10-6 ± 1.59 × 10-5, p < 0.03, respectively). The FMD/SRAUC response to ascorbic acid infusion was lower (p < 0.05) at 12 weeks compared to baseline in the blueberry group with no change in the placebo group (p > 0.05). The sum of plasma (poly)phenol metabolites increased at 4, 8, and 12 weeks in the blueberry group compared to baseline, and were higher than the placebo group (all p < 0.05). Increases in several plasma flavonoid and microbial metabolites were also noted. No major differences were found for blood pressure, arterial stiffness, blood biomarkers, or endothelial cell protein expression following blueberry consumption. These findings suggest daily consumption of freeze-dried blueberry powder for 12 weeks improves endothelial function through reduced oxidative stress in postmenopausal women with above-normal blood pressure. The clinical trial registry number is NCT03370991 (https://clinicaltrials.gov).

Non-viral precision T cell receptor replacement for personalized cell therapy.

T cell receptors (TCRs) enable T cells to specifically recognize mutations in cancer cells1-3. Here we developed a clinical-grade approach based on CRISPR-Cas9 non-viral precision genome-editing to simultaneously knockout the two endogenous TCR genes TRAC (which encodes TCRα) and TRBC (which encodes TCRß). We also inserted into the TRAC locus two chains of a neoantigen-specific TCR (neoTCR) isolated from circulating T cells of patients. The neoTCRs were isolated using a personalized library of soluble predicted neoantigen-HLA capture reagents. Sixteen patients with different refractory solid cancers received up to three distinct neoTCR transgenic cell products. Each product expressed a patient-specific neoTCR and was administered in a cell-dose-escalation, first-in-human phase I clinical trial ( NCT03970382 ). One patient had grade 1 cytokine release syndrome and one patient had grade 3 encephalitis. All participants had the expected side effects from the lymphodepleting chemotherapy. Five patients had stable disease and the other eleven had disease progression as the best response on the therapy. neoTCR transgenic T cells were detected in tumour biopsy samples after infusion at frequencies higher than the native TCRs before infusion. This study demonstrates the feasibility of isolating and cloning multiple TCRs that recognize mutational neoantigens. Moreover, simultaneous knockout of the endogenous TCR and knock-in of neoTCRs using single-step, non-viral precision genome-editing are achieved. The manufacture of neoTCR engineered T cells at clinical grade, the safety of infusing up to three gene-edited neoTCR T cell products and the ability of the transgenic T cells to traffic to the tumours of patients are also demonstrated.

A web-based tool for assessing the condition of benthic diatom assemblages in streams and rivers of the conterminous United States.

Benthic diatom assemblages are known to be indicative of water quality but have yet to be widely adopted in biological assessments in the United States due to several limitations. Our goal was to address some of these limitations by developing regional multi-metric indices (MMIs) that are robust to inter-laboratory taxonomic inconsistency, adjusted for natural covariates, and sensitive to a wide range of anthropogenic stressors. We aggregated bioassessment data from two national-scale federal programs and used a data-driven analysis in which all-possible combinations of 2-7 metrics were compared for three measures of performance. After ranking the best-performing MMIs, we selected the final MMIs by evaluating stress-response relations in independent regional datasets of diatom samples paired with measures of several water-quality stressors, including herbicides and streamflow flashiness. Each regional MMI performed well at calibration sites and represented diverse aspects of the structure and function of diatom communities. Most metrics included in the best MMIs were modeled to account for natural variation including climate, topography, soil characteristics, lithology, and groundwater influence on streamflow. MMI performance improved with higher numbers of component metrics, but this effect diminished beyond six metrics. Component metrics of MMIs were associated with a broad suite of measured stressors in every region, including salinity, nutrients, herbicides, and streamflow flashiness. We provide a web-based software application that allows users in the conterminous United States to apply our MMIs to their own datasets and compare MMI scores from their sites to a broader regional context.

A harmonized dataset of sediment diatoms from hundreds of lakes in the northeastern United States.

Sediment diatoms are widely used to track environmental histories of lakes and their watersheds, but merging datasets generated by different researchers for further large-scale studies is challenging because of taxonomic discrepancies caused by rapidly evolving diatom nomenclature and taxonomic concepts. We collated five datasets of lake sediment diatoms from the Northeastern USA using a harmonization process which included updating synonyms, tracking the identity of inconsistently identified taxa, and grouping those that could not be resolved taxonomically. Each harmonization step led to an increase in variation explained by environmental variables and a parallel reduction of variation attributable to taxonomic inconsistency. To maximize future use of the data and underlying specimens we provide the original and harmonized counts for 1327 core samples from 607 lakes, name translation schemes, sample metadata, specimen museum locations, and the Northeast Lakes Voucher Flora, which is a set of light microscope images grouped into 1154 morphological operational taxonomic units. Post-hoc harmonization enables data quality control when other approaches (e.g., upfront management of taxonomic consistency) are not possible.

Diatoms.org: supporting taxonomists, connecting communities.

Consistent identification of diatoms is a prerequisite for studying their ecology, biogeography, and successful application as environmental indicators. However, taxonomic consistency among observers has been difficult to achieve, because taxonomic information is scattered across numerous literature sources, presenting challenges to the diatomist. First, literature is often inaccessible because of cost, or its location in journals that are not widely circulated. Second, taxonomic revisions of diatoms are taking place faster than floras can be updated. Finally, taxonomic information is often contradictory across literature sources. These issues can be addressed by developing a content creation community dedicated to making taxonomic, ecological, and image-based data freely available for diatom researchers. Diatoms.org represents such a content curation community, providing open, online access to a vast amount of recent and historical information on North American diatom taxonomy and ecology. The content curation community aggregates existing taxonomic information, creates new content, and provides feedback in the form of corrections and notice of literature with nomenclatural changes. The website not only addresses the needs of experienced diatom scientists for consistent identification, but is also designed to meet users at their level of expertise, including engaging the lay public in the importance of diatom science. The website now contains over 1000 species pages contributed by over 100 content contributors, from students to established scientists. The project began with the intent to provide accurate information on diatom identification, ecology, and distribution using an approach that incorporates engaging design, user feedback, and advanced data access technology. In retrospect, the project that began as an "extended electronic book" has emerged not only as a means to support taxonomists, but for practitioners to communicate and collaborate, expanding the size of and benefits to the content curation community. In this paper, we outline the development of diatoms.org, document key elements of the project, examine ongoing challenges, and consider the unexpected emergent properties, including the value of diatoms.org as a source of data. Ultimately, if the field of diatom taxonomy, ecology, and biodiversity is to be relevant, a new generation of taxonomists needs to be trained and employed using new tools. We propose that diatoms.org is in a key position to serve as a hub of training and continuity for the study of diatom biodiversity and aquatic conditions.

Cancer-cell-secreted miR-122 suppresses O-GlcNAcylation to promote skeletal muscle proteolysis.

A decline in skeletal muscle mass and low muscular strength are prognostic factors in advanced human cancers. Here we found that breast cancer suppressed O-linked N-acetylglucosamine (O-GlcNAc) protein modification in muscle through extracellular-vesicle-encapsulated miR-122, which targets O-GlcNAc transferase (OGT). Mechanistically, O-GlcNAcylation of ryanodine receptor 1 (RYR1) competed with NEK10-mediated phosphorylation and increased K48-linked ubiquitination and proteasomal degradation; the miR-122-mediated decrease in OGT resulted in increased RYR1 abundance. We further found that muscular protein O-GlcNAcylation was regulated by hypoxia and lactate through HIF1A-dependent OGT promoter activation and was elevated after exercise. Suppressed O-GlcNAcylation in the setting of cancer, through increasing RYR1, led to higher cytosolic Ca2+ and calpain protease activation, which triggered cleavage of desmin filaments and myofibrillar destruction. This was associated with reduced skeletal muscle mass and contractility in tumour-bearing mice. Our findings link O-GlcNAcylation to muscular protein homoeostasis and contractility and reveal a mechanism of cancer-associated muscle dysregulation.

Neoantigen-specific CD4+ T cells in human melanoma have diverse differentiation states and correlate with CD8+ T cell, macrophage, and B cell function.

CD4+ T cells that recognize tumor antigens are required for immune checkpoint inhibitor efficacy in murine models, but their contributions in human cancer are unclear. We used single-cell RNA sequencing and T cell receptor sequences to identify signatures and functional correlates of tumor-specific CD4+ T cells infiltrating human melanoma. Conventional CD4+ T cells that recognize tumor neoantigens express CXCL13 and are subdivided into clusters expressing memory and T follicular helper markers, and those expressing cytolytic markers, inhibitory receptors, and IFN-γ. The frequency of CXCL13+ CD4+ T cells in the tumor correlated with the transcriptional states of CD8+ T cells and macrophages, maturation of B cells, and patient survival. Similar correlations were observed in a breast cancer cohort. These results identify phenotypes and functional correlates of tumor-specific CD4+ T cells in melanoma and suggest the possibility of using such cells to modify the tumor microenvironment.

Prognostic Value of Early Fluorodeoxyglucose-Positron Emission Tomography Response Imaging and Peripheral Immunologic Biomarkers: Substudy of a Phase II Trial of Risk-Adaptive Chemoradiation for Unresectable Non-Small Cell Lung Cancer.

Purpose: We sought to examine the prognostic value of fluorodeoxyglucose-positron emission tomography (PET) imaging during chemoradiation for unresectable non-small cell lung cancer for survival and hypothesized that tumor PET response is correlated with peripheral T-cell function. Methods and Materials: Forty-five patients with American Joint Committee on Cancer version 7 stage IIB-IIIB non-small cell lung cancer enrolled in a phase II trial and received platinum-doublet chemotherapy concurrent with 6 weeks of radiation (NCT02773238). Fluorodeoxyglucose-PET was performed before treatment start and after 24 Gy of radiation (week 3). PET response status was prospectively defined by multifactorial radiologic interpretation. PET responders received 60 Gy in 30 fractions, while nonresponders received concomitant boosts to 74 Gy in 30 fractions. Peripheral blood was drawn synchronously with PET imaging, from which germline DNA sequencing, T-cell receptor sequencing, and plasma cytokine analysis were performed. Results: Median follow-up was 18.8 months, 1-year overall survival (OS) 82%, 1-year progression-free survival 53%, and 1-year locoregional control 88%. Higher midtreatment PET total lesion glycolysis was detrimental to OS (1 year 87% vs 63%, P < .001), progression-free survival (1 year 60% vs 26%, P = .044), and locoregional control (1 year 94% vs 65%, P = .012), even after adjustment for clinical/treatment factors. Twenty-nine of 45 patients (64%) were classified as PET responders based on a priori definition. Higher tumor programmed death-ligand 1 expression was correlated with response on PET (P = .017). Higher T-cell receptor richness and clone distribution slope were associated with improved OS (P = .018-0.035); clone distribution slope was correlated with PET response (P = .031). Conclusions: Midchemoradiation PET imaging is prognostic for survival; PET response may be linked to tumor and peripheral T-cell biomarkers.

Performance status (PS) as a predictor of poor response to immune checkpoint inhibitors (ICI) in recurrent/metastatic head and neck cancer (RMHNSCC) patients.

BACKGROUND: Anti-PD1 checkpoint inhibitors (ICI) represent an established standard-of-care for patients with recurrent/metastatic head and neck squamous cell carcinoma (RMHNSCC). Landmark studies excluded patients with ECOG performance status (PS) ≥2; the benefit of ICI in this population is therefore unknown. METHODS: We retrospectively reviewed RMHNSCC patients who received 1+ dose of ICI at our institution between 2013 and 2019. Demographic and clinical data were obtained; the latter included objective response (ORR), toxicity, and any unplanned hospitalization (UH). Associations were explored using uni- and multivariate analysis. Overall survival (OS) was estimated using a Cox proportional hazards model; ORR, toxicity, and UH were evaluated with logistic regression. RESULTS: Of the 152 patients, 29 (19%) had an ECOG PS ≥2. Sixty-six (44%) experienced toxicity; 54 (36%) had a UH. A multivariate model for OS containing PS, smoking status, and HPV status demonstrated a strong association between ECOG ≥2 and shorter OS (p < 0.001; HR = 3.30, CI = 2.01-5.41). An association between OS and former (vs. never) smoking was also seen (p < 0.001; HR = 2.17, CI = 1.41-3.35); current smoking did not reach statistical significance. On univariate analysis, poor PS was associated with inferior ORR (p = 0.03; OR = 0.25, CI = 0.06-0.77) and increased UH (p = 0.04; OR = 2.43, CI = 1.05-5.71). There was no significant association between toxicity and any patient characteristic. CONCLUSIONS: We observed inferior OS, ORR, and rates of UH among ICI-treated RMHNSCC patients with ECOG 2/3. Our findings help frame discussion of therapeutic options in this poor-risk population.

Impact of HPV status on immune responses in head and neck squamous cell carcinoma.

The main objective of our study was to understand the impact of immune cell composition and the tumor-reactivity of tumor infiltrating lymphocytes (TIL) in HPV-positive (HPV+) and HPV-negative (HPV-) head and neck squamous cell carcinoma (HNSCC). TIL cultures were established from primary HNSCC tumors, the T cell subsets were phenotypically characterized using flow cytometry, and Interferon (IFN)-γ ELISA assay was used to determine TIL function. NanoString Immune Profiler was used to determine an immune signature by HPV-status, and multiplex immunohistochemistry (MIHC) was used to quantify immune cell distributions and their spatial relationships. Results showed that HPV+ and HPV- HNSCC had similar capacity to expand IFN-γ reactive TIL populations, and these TIL populations had similar characteristics. NanoString analysis revealed increased differential expression of genes related to B cell functions in HPV+ HNSCC, which were significant at a Benjamini-Yekutieli adjusted p-value of < 0.001. MIHC also displayed increased CD8+ T cell and CD19/CD20+ B cell densities in the tumor region of HPV+ HNSCC as opposed to HPV- HNSCC (p < 0.01). Increases in a combined metric of tumor B cell content and stromal plasma cell content was associated with increased progression-free survival in HPV- HNSCC patients treated with immune checkpoint inhibitor therapy (p = 0.03). In summary, TIL populations expanded from HPV+ and HPV- HNSCC displayed similar IFN-γ reactivity. However, we identified a strong B-cell signature present within HPV+ HNSCC, and higher B and plasma cell content associated with improved PFS in HPV- HNSCC patients treated with immune checkpoint inhibitors.

Associating sleep problems with advanced cancer diagnosis, and immune checkpoint treatment outcomes: a pilot study.

BACKGROUND: Sleep problems (SP) are common in cancer patients but have not been previously assessed in patients receiving immune checkpoint inhibitors (ICI). METHODS: We collected questionnaire data on sleep apnea risk, insomnia, and general sleep patterns. We used an adjusted multivariate Poisson regression to calculate prevalence ratios (PRs) and associated 95% confidence intervals (CIs) for associations between these SP and metastatic versus localized cancer stage (M1 vs. M0), and adjusted logistic regression models to calculate ORs for associations between SP with the number of ICI infusions completed (6 + vs. < 6). RESULTS: Among 32 patients who received ICI treatment, the prevalence of low, intermediate, and high-risk OSA risk was 36%, 42%, and 21%, respectively. Overall, 58% of participants reported clinically significant insomnia. We did not find a significant association between intermediate or high risk OSA (vs. low risk) and metastatic cancer status (PR = 1.01 (95% CI: 0.28, 3.67)). Patients in the cohort who reported taking > 15 min to fall asleep were 3.6 times more likely to be diagnosed with metastatic cancer compared to those reporting shorter sleep latency (95% CI (1.74, 7.35)). We did not find a significant association between SP and number of ICI infusions completed. CONCLUSION: Our data associating sleep apnea risk, insomnia, and sleep patterns with more advanced cancer encourages further exploration in larger-scale observational studies and suggests interventional clinical trials focused on sleep quality improvement that could result in better outcomes for these patients.

High End-of-Life Health Care Utilization in a Contemporary Cohort of Head and Neck Cancer Patients Treated with Immune Checkpoint Inhibitors.

Background/Objective: End-of-life health care utilization (EOLHCU) is largely uncharacterized among patients with recurrent/metastatic head and neck squamous cell carcinomas (RMHNSCC), particularly now that immune checkpoint inhibitors (ICI) have been introduced to the treatment landscape. We examined this in a single-institution, retrospective study. Design/Settings: We utilized a database of deceased, ICI-treated RMHNSCC patients to obtain demographic and EOLHCU data, the latter of which included advanced care plan documentation (ACPD) and systemic therapy or emergency room (ER)/hospital/intensive care unit (ICU) admission within 30 days of death (DOD). This was compared with a cohort of deceased thoracic malignancy (TM) patients in an exploratory analysis. Multivariate analysis was performed to examine for association between patient factors (such as age, Eastern Cooperative Oncology Group (ECOG) performance status, or smoking status) and overall survival (OS); associations between the said patient factors and EOLHCU were also evaluated. This study was conducted at an academic, tertiary center in the United States. Results: The RMHNSCC patients (n = 74) were more likely to have ACPD (p < 0.01), an emergency department visit (p < 0.01), and/or hospital admission (p < 0.01) within 30 DOD relative to the TM group. There was no difference in ICU admissions, ICU deaths, or systemic therapy at end of life (EOL). The OS declined in association with ECOG performance status (PS) and smoking. No association was observed between patient factors and any EOLHCU metric. Conclusions: At our center, patients with ICI-treated RMHNSCC have higher rates of both ACPD and EOLHCU, suggesting high symptom burden and representing opportunities for further study into supportive care augmentation.

Resources and Practices to Improve Diatom Data Quality.

Environmental programs in the United States face technical challenges that inhibit the ability to use diatoms in water quality monitoring and assessment projects. Specifically, inconsistent taxonomy can obscure diatom responses to environmental variables. Problems are the result of (1) limited access to a common set of taxonomic references, especially those that are geographically relevant, (2) inefficient enumeration protocols, (3) lack of complete and transparent documentation of taxa, and (4) limited opportunities for continued education, training, and knowledge sharing. However, robust resources and practices are available to improve diatom data quality and interpretation. Several resources improve diatom data quality, including a publicly accessible taxonomic reference (diatoms.org) and recommended practices. These practices include adoption of the voucher floras, random sample assignment, replicate microscope slides, and improved quality control. Finally, the Society for Freshwater Science Diatom Taxonomic Certification Committee is developing educational materials and certification exams to support practitioner training and to increase the diatom research knowledge base. The resources and practices in this article are broadly applicable to improving basic and applied research on diatoms worldwide.

A Phase II study of nab-Paclitaxel (nab-P) in patients with advanced non-small cell lung cancer with EGFR mutations after frontline tyrosine kinase inhibitor therapy.

BACKGROUND: Patients with metastatic non-small cell lung cancer (NSCLC) harboring a sensitizing EGFR mutation have effective targeted therapy options initially but most patients eventually progress and receive cytotoxic chemotherapy. In this single-institution phase II study, we evaluated the role of nab-paclitaxel monotherapy in this patient population. PATIENTS AND METHODS: Patients with metastatic NSCLC with an activating EGFR mutation whose disease progressed after frontline tyrosine kinase inhibitor therapy and who were chemotherapy naïve received nab-paclitaxel 125 mg/m2 on days 1, 8 and 15 in a 28-day cycle. The primary endpoint was response rate per RECIST 1.1 and secondary endpoints were duration of response, progression free survival, toxicity and overall survival. RESULTS: A total of 27 patients were enrolled and 21 patients were evaluable for response. Median age was 65 (range 52-81), 69% of patients were women, 42% of patients did not having a smoking history. 31% of patients had central nervous system (CNS) metastatic disease at baseline. Confirmed partial response was documented in 9 of 26 patients (35%, 95% CI 17-56) and disease control rate was 58% (95% CI 35-73). CNS was a common first site of progression. Median progression free survival was 4.0 months (95% CI 1.8-5.2). No new safety signals were observed. CONCLUSION: Single agent nab-paclitaxel showed modest antitumor activity in patients with EGFR mutation positive NSCLC and may be an option in patients who are platinum ineligible. Patients often progressed in the CNS and the results underscores the importance of CNS activity of systemic therapies in this patient population.