Shared Features Underlying Compact Genomes and Extreme Habitat Use in Chironomid Midges.

Nonbiting midges (family Chironomidae) are found throughout the world in a diverse array of aquatic and terrestrial habitats, can often tolerate harsh conditions such as hypoxia or desiccation, and have consistently compact genomes. Yet we know little about the shared molecular basis for these attributes and how they have evolved across the family. Here, we address these questions by first creating high-quality, annotated reference assemblies for Tanytarsus gracilentus (subfamily Chironominae, tribe Tanytarsini) and Parochlus steinenii (subfamily Podonominae). Using these and other publicly available assemblies, we created a time-calibrated phylogenomic tree for family Chironomidae with outgroups from order Diptera. We used this phylogeny to test for features associated with compact genomes, as well as examining patterns of gene family evolution and positive selection that may underlie chironomid habitat tolerances. Our results suggest that compact genomes evolved in the common ancestor of Chironomidae and Ceratopogonidae and that this occurred mainly through reductions in noncoding regions (introns, intergenic sequences, and repeat elements). Significantly expanded gene families in Chironomidae included biological processes that may relate to tolerance of stressful environments, such as temperature homeostasis, carbohydrate transport, melanization defense response, and trehalose transport. We identified several positively selected genes in Chironomidae, notably sulfonylurea receptor, CREB-binding protein, and protein kinase D. Our results improve our understanding of the evolution of small genomes and extreme habitat use in this widely distributed group.

Disparities in Access to Multidisciplinary Cancer Consultations and Treatment for Patients With Early-Stage Non-Small Cell Lung Cancer: A SEER-Medicare Analysis.

PURPOSE: Disparities in access to a multidisciplinary cancer consultation (MDCc) persist, and the role of physician relationships remains understudied. This study examined the extent to which multilevel factors, including patient characteristics and patient-sharing network measures reflecting the structure of physician relationships, are associated with an MDCc and receipt of stereotactic body radiation therapy versus surgery among patients with early-stage non-small cell lung cancer (NSCLC). METHODS AND MATERIALS: In this cross-sectional study, we analyzed Surveillance, Epidemiology, and End Results (SEER)-Medicare data for patients diagnosed with stage I-IIA NSCLC from 2016 to 2017. We assembled patient-sharing networks and identified cancer specialists who were locally unique for their specialty, herein referred to as linchpins. The proportion of linchpin cancer specialists for each hospital referral region (HRR) was calculated as a network-based measure of specialist scarcity. We used multilevel multinomial logistic regression to estimate associations between study variables and receipt of an MDCc and multilevel logistic regression to examine the relationship between patient receipt of an MDCc and initial treatment. RESULTS: Our study included 6120 patients with stage I-IIA NSCLC, of whom 751 (12.3%) received an MDCc, 1729 (28.3%) consulted only a radiation oncologist, 2010 (32.8%) consulted only a surgeon, and 1630 (26.6%) consulted neither specialist within 2 months of diagnosis. Compared with patients residing in an HRR with a low proportion of linchpin surgeons, those residing in an HRR with a high proportion of linchpin surgeons had a 2.99 (95% CI, 1.87-4.78) greater relative risk of consulting only a radiation oncologist versus receiving an MDCc and a 2.70 (95% CI, 1.68-4.35) greater relative risk of consulting neither specialist versus receiving an MDCc. Patients who received an MDCc were 5.32 times (95% CI, 4.27-6.63) more likely to receive stereotactic body radiation therapy versus surgery. CONCLUSIONS: Physician networks are associated with receipt of an MDCc and treatment, underscoring the potential for leveraging patient-sharing network analysis to improve access to lung cancer care.

Disentangling the drivers of decadal body size decline in an insect population.

While climate warming is widely predicted to reduce body size of ectotherms, evidence for this trend is mixed. Body size depends not only on temperature but also on other factors, such as food quality and intraspecific competition. Because temperature trends or other long-term environmental factors may affect population size and food sources, attributing trends in average body size to temperature requires the separation of potentially confounding effects. We evaluated trends in the body size of the midge Tanytarsus gracilentus and potential drivers (water temperature, population size, and food quality) between 1977 and 2015 at Lake Mývatn, Iceland. Although temperatures increased at Mývatn over this period, there was only a slight (non-significant) decrease in midge adult body size, contrary to theoretical expectations. Using a state-space model including multiple predictors, body size was negatively associated with both water temperature and midge population abundance, and it was positively associated with 13 C enrichment of midges (an indicator of favorable food conditions). The magnitude of these effects were similar, such that simultaneous changes in temperature, abundance, and carbon stable isotopic signature could counteract each other in the long-term body size trend. Our results illustrate how multiple factors, all of which could be influenced by global change, interact to affect average ectotherm body size.

Unspoken Truths: Mental Health Among Academic Surgeons.

OBJECTIVE: To characterize the current state of mental health within the surgical workforce in the United States. BACKGROUND: Mental illness and suicide is a growing concern in the medical community; however, the current state is largely unknown. METHODS: Cross-sectional survey of the academic surgery community assessing mental health, medical error, and suicidal ideation. The odds of suicidal ideation adjusting for sex, prior mental health diagnosis, and validated scales screening for depression, anxiety, post-traumatic stress disorder (PTSD), and alcohol use disorder were assessed. RESULTS: Of 622 participating medical students, trainees, and surgeons (estimated response rate=11.4%-14.0%), 26.1% (141/539) reported a previous mental health diagnosis. In all, 15.9% (83/523) of respondents screened positive for current depression, 18.4% (98/533) for anxiety, 11.0% (56/510) for alcohol use disorder, and 17.3% (36/208) for PTSD. Medical error was associated with depression (30.7% vs. 13.3%, P <0.001), anxiety (31.6% vs. 16.2%, P =0.001), PTSD (12.8% vs. 5.6%, P =0.018), and hazardous alcohol consumption (18.7% vs. 9.7%, P =0.022). Overall, 13.2% (73/551) of respondents reported suicidal ideation in the past year and 9.6% (51/533) in the past 2 weeks. On adjusted analysis, a previous history of a mental health disorder (aOR: 1.97, 95% CI: 1.04-3.65, P =0.033) and screening positive for depression (aOR: 4.30, 95% CI: 2.21-8.29, P <0.001) or PTSD (aOR: 3.93, 95% CI: 1.61-9.44, P =0.002) were associated with increased odds of suicidal ideation over the past 12 months. CONCLUSIONS: Nearly 1 in 7 respondents reported suicidal ideation in the past year. Mental illness and suicidal ideation are significant problems among the surgical workforce in the United States.

Gene modules and genes associated with postoperative atrial fibrillation: weighted gene co-expression network analysis and circRNA-miRNA-mRNA regulatory network analysis.

Background: Atrial fibrillation (AF) is the most common complication in patients undergoing cardiac surgery. However, the pathogenesis of postoperative AF (POAF) is elusive, and research related to this topic is sparse. Our study aimed to identify key gene modules and genes and to conduct a circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) regulatory network analysis of POAF on the basis of bioinformatic analysis. Methods: The GSE143924 and GSE97455 data sets from the Gene Expression Omnibus (GEO) database were analyzed. Weighted gene co-expression network analysis (WGCNA) was used to identify the key gene modules and genes related to POAF. A circRNA-miRNA-mRNA regulatory network was also built according to differential expression analysis. Functional enrichment analysis was further performed according to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Results: WGCNA identified 2 key gene modules and 44 key genes that were significantly related to POAF. Functional enrichment analysis of these key genes implicated the following important biological processes (BPs): endosomal transport, protein kinase B signaling, and transcription regulation. The circRNA-miRNA-mRNA regulatory network suggested that KLF10 may take critical part in POAF. Moreover, 2 novel circRNAs, hsa_circRNA_001654 and hsa_circRNA_005899, and 2 miRNAs, hsa-miR-19b-3p and hsa-miR-30a-5p, which related with KLF10, were involved in the network. Conclusions: Our study provides foundational expression profiles following POAF based on WGCNA. The circRNA-miRNA-mRNA network offers insights into the BPs and underlying mechanisms of POAF.

Double trouble: How sectarian and national narcissism relate differently to collective violence beliefs in Lebanon.

Collective narcissism is a belief in ingroup greatness which is contingent on external validation. A lack of research on collective narcissism amongst non-Western contexts and minority groups remains a challenge for the field. However, here we test two types of collective narcissism (sectarian and national) as differential predictors of two dimensions of collective violence beliefs (against outgroup members and leaders) in a large, diverse, community sample from Lebanon (N = 778). We found that sectarian narcissism (narcissism related to smaller political and religious ingroup identity) predicted support for collective violence against members of different sects, while national narcissism predicted opposition to such collective violence. Neither form of collective narcissism had any significant relationship with collective violence against outgroup leaders. We controlled for both sectarian and national identification and found no significant effects in predicting either one of the two dimensions of collective violence beliefs. In this non-Western context, in which a coherent national identity is undermined by sectarianism, national narcissism seems to be a progressive motivator for unity and social change, while sectarian narcissism is rather associated with extreme attitudes, such as support for collective violence.

Correlates of support for international vaccine solidarity during the COVID-19 pandemic: Cross-sectional survey evidence from Germany.

During the COVID-19 pandemic, many residents of high-income countries (HICs) were eligible for COVID-19 vaccine boosters, while many residents of lower-income countries (LICs) had not yet received a first dose. HICs made some efforts to contribute to COVID-19 vaccination efforts in LICs, but these efforts were limited in scale. A new literature discusses the normative importance of an international redistribution of vaccines. Our analysis contributes an empirical perspective on the willingness of citizens in a HIC to contribute to such efforts (which we term international vaccine solidarity). We analyse the levels and predictors of international vaccine solidarity. We surveyed a representative sample of German adults (n = 2019) who participated in a two-wave YouGov online survey (w1: Sep 13-21, 2021 and w2: Oct 4-13, 2021). International vaccine solidarity is measured by asking respondents preferences for sharing vaccine supplies internationally versus using that supply as boosters for the domestic population. We examine a set of pre-registered hypotheses. Almost half of the respondents in our sample (48%) prioritize giving doses to citizens in less developed countries. A third of respondents (33%) prefer to use available doses as boosters domestically, and a fifth of respondents (19%) did not report a preference. In line with our hypotheses, respondents higher in cosmopolitanism and empathy, and those who support domestic redistribution exhibit more support for international dose-sharing. Older respondents (who might be more at risk) do not consistently show less support for vaccine solidarity. These results help us to get a better understanding of the way citizens' form preferences about a mechanism that redistributes medical supplies internationally during a global crisis.

The Effect of Lung Resection for NSCLC on Circulating Immune Cells: A Pilot Study.

This pilot study sought to evaluate the circulating levels of immune cells, particularly regulatory T-cell (Treg) subsets, before and after lung resection for non-small cell lung cancer. Twenty-five patients consented and had specimens collected. Initially, peripheral blood of 21 patients was collected for circulating immune cell studies. Two of these patients were excluded due to technical issues, leaving 19 patients for the analyses of circulating immune cells. Standard gating and high-dimensional unsupervised clustering flow cytometry analyses were performed. The blood, tumors and lymph nodes were analyzed via single-cell RNA and TCR sequencing for Treg analyses in a total of five patients (including four additional patients from the initial 21 patients). Standard gating flow cytometry revealed a transient increase in neutrophils immediately following surgery, with a variable neutrophil-lymphocyte ratio and a stable CD4-CD8 ratio. Unexpectedly, the total Treg and Treg subsets did not change with surgery with standard gating in short- or long-term follow-up. Similarly, unsupervised clustering of Tregs revealed a dominant cluster that was stable perioperatively and long-term. Two small FoxP3hi clusters slightly increased following surgery. In the longer-term follow-up, these small FoxP3hi Treg clusters were not identified, indicating that they were likely a response to surgery. Single-cell sequencing demonstrated six CD4+FoxP3+ clusters among the blood, tumors and lymph nodes. These clusters had a variable expression of FoxP3, and several were mainly, or only, present in tumor and lymph node tissue. As such, serial monitoring of circulating Tregs may be informative, but not completely reflective of the Tregs present in the tumor microenvironment.

Personality in juvenile Atlantic cod ecotypes and implications for fisheries management.

Animals show among-individual variation in behaviors, including migration behaviors, which are often repeatable across time periods and contexts, commonly termed "personality." These behaviors can be correlated, forming a behavioral syndrome. In this study, we assessed the repeatability and correlation of different behavioral traits, i.e., boldness, exploration, and sociality, and the link to feeding migration patterns in Atlantic cod juveniles. To do so, we collected repeated measurements within two short-term (3 days) and two long-term (2 months) intervals of these personality traits and genotypes of the Pan I locus, which is correlated with feeding migration patterns in this species. We found high repeatabilities for exploration behavior in the short- and long-term intervals, and a trend for the relationship between exploration and the Pan I locus. Boldness and sociality were only repeatable in the second short-term interval indicating a possible development of stability over time and did not show a relation with the Pan I locus. We found no indication of behavioral syndromes among the studied traits. We were unable to identify the existence of a migration syndrome for the frontal genotype, which is the reason that the link between personality and migration remains inconclusive, but we demonstrated a possible link between exploration and the Pan I genotype. This supports the need for further research that should focus on the effect of exploration tendency and other personality traits on cod movement, including the migratory (frontal) ecotype to develop management strategies based on behavioral units, rather than treating the population as a single homogeneous stock.

Food Deserts Increase Readmission After Esophagectomy for Cancer: A Multi-institutional Study.

BACKGROUND: Food deserts are low-income census tracts with poor access to supermarkets and are associated with worse outcomes in breast, colon, and a small number of esophageal cancer patients. This study investigated residency in food deserts on readmission rates in a multi-institutional cohort of esophageal cancer patients undergoing trimodality therapy. METHODS: A retrospective review of patients who underwent trimodality therapy at 6 high-volume institutions from January 2015 to July 2019 was performed. Food desert status was defined by the United States Department of Agriculture by patient ZIP Code. The primary outcome was 30-day readmission after esophagectomy. Multilevel, multivariable logistic regression was used to model readmission on food desert status adjusted for diabetes, insurance type, length of stay, and any complication, treating the institution as a random factor. RESULTS: Of the 453 records evaluated, 425 were included in the analysis. Seventy-three patients (17.4%) resided in a food desert. Univariate analysis demonstrated food desert patients had significantly increased 30-day readmission. No differences were seen in length of stay, complications, or 30-day mortality. In the adjusted logistic regression model, residing in a food desert remained a significant risk factor for readmission (odds ratio, 2.11; 95% CI, 1.07-4.15). There were no differences in 30-day, 90-day, or 1-year mortality based on food desert status, although readmission was associated with worse 90-day and 1-year mortality. CONCLUSIONS: Food desert residence was associated with 30-day readmission after esophagectomy in patients undergoing trimodality treatment for esophageal cancer in this multi-institutional population. Identification of patients residing in a food desert may allow surgeons to focus preventative interventions during treatment and postoperatively to improve outcomes.

Vaccine attributes and vaccine uptake in Hungary: evidence from a conjoint experiment.

BACKGROUND: In an ongoing public health crisis, the question of why some people are unwilling to take vaccines with particular attributes is an especially pertinent one, since low rates of vaccination mean that it will take longer for many nations to exit the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In this article, we conduct a pre-registered conjoint experiment in Hungary (N = 2512), where respondents were asked about their attitudes towards hypothetical COVID-19 vaccines whose characteristics varied across a number of attributes. RESULTS: Results indicate that vaccine attributes matter for the likelihood of uptake when it comes to the prevalence of severe side effects, efficacy and country of origin. Moreover, we find that our pre-treatment measure of institutional trust moderates the effect of our treatment, as differences in vaccine attributes are larger for those with robust levels of institutional trust compared to those with weaker levels. CONCLUSION: Our findings suggest that institutional trust matters when it comes to understanding the relationship between vaccine attributes and likelihood of uptake.

Lessons learned by thoracic surgeons during the COVID-19 pandemic.

Background: The scale of the coronavirus disease 2019 (COVID-19) pandemic has necessitated healthcare systems to adapt and evolve, altering physician roles and expectations. Thoracic surgeons have seen practice changes from new COVID-19 consults to necessary delay and triage of elective care. The goal of this study was to understand the impact of COVID-19 on thoracic surgeon experiences in order to anticipate roles and changes in practice in future such circumstances. Methods: Semi-structured, qualitative individual telephone interviews were conducted with thoracic surgeons. Interviews were structured to understand how surgeons were impacted by the COVID-19 pandemic and to record lessons learned. Interviews were conducted until thematic saturation was achieved. Data were analyzed using matrix analysis. Results: Eleven board-certified general thoracic surgeons from nine institutions were interviewed. Thoracic surgeon roles in COVID-19 care included critical care delivery, performing tracheostomies and establishing related protocols, and interventions for long-term airway complications. Attention was called to the impact of the pandemic on thoracic cancer: patients avoided hospitals because of concern over COVID-19, delaying care. Conclusions: Thoracic surgeons played a critical role in the COVID-19 pandemic response in both technical patient care and administrative capacities. Primary care responsibilities included the development, administration and delivery of tracheostomy protocols, and the care of down-stream airway complications. Thoracic surgeons were critical in triage decisions to minimize the impact of COVID-19 on thoracic cancer care. Lessons learned during the COVID-19 pandemic may provide insight into opportunities to promote collaboration in thoracic surgery and facilitate improved care delivery in future settings of resource limitation.

The Ability of Near-Infrared Spectroscopy to Identify Vulnerable Patients and Plaques: A Systematic Review and Meta-Analysis.

Previous studies have analyzed the efficacy of near-infrared spectroscopy-derived lipid core burden index (LCBI) in quantifying and identifying high-risk plaques and patients at increased risk of future major adverse cardiac outcomes/major adverse cardiovascular and cerebrovascular events. A maxLCBI4mm of 400 or greater seems to be an effective threshold for classifying at-risk plaques. This meta-analysis provides a more precise odds ratio with a narrow standard deviation that can be used to guide future studies.

Demographic Basis of Spatially Structured Fluctuations in a Threespine Stickleback Metapopulation.

AbstractUncovering the demographic basis of population fluctuations is a central goal of population biology. This is particularly challenging for spatially structured populations, which require disentangling synchrony in demographic rates from coupling via movement between locations. In this study, we fit a stage-structured metapopulation model to a 29-year time series of threespine stickleback abundance in the heterogeneous and productive Lake Mývatn, Iceland. The lake comprises two basins (North and South) connected by a channel through which the stickleback disperse. The model includes time-varying demographic rates, allowing us to assess the potential contributions of recruitment and survival, spatial coupling via movement, and demographic transience to the population's large fluctuations in abundance. Our analyses indicate that recruitment was only modestly synchronized between the two basins, whereas survival probabilities of adults were more strongly synchronized, contributing to cyclic fluctuations in the lake-wide population size with a period of approximately 6 years. The analyses further show that the two basins were coupled through movement, with the North Basin subsidizing the South Basin and playing a dominant role in driving the lake-wide dynamics. Our results show that cyclic fluctuations of a metapopulation can be explained in terms of the combined effects of synchronized demographic rates and spatial coupling.

Reasons for Long-term Opioid Prescriptions After Guideline-directed Opioid Prescribing and Excess Opioid Pill Disposal.

OBJECTIVES: The aim of this study was to determine the frequency and reasons for long-term opioid prescriptions (rxs) after surgery in the setting of guideline-directed prescribing and a high rate of excess opioid disposal. BACKGROUND: Although previous studies have demonstrated that 5% to 10% of opioid-naïve patients prescribed opioids after surgery will receive long-term (3-12 months after surgery) opioid rxs, little is known about the reasons why long-term opioids are prescribed. METHODS: We studied 221 opioid-naïve surgical patients enrolled in a previously reported prospective clinical trial which used a patient-centric guideline for discharge opioid prescribing and achieved a high rate of excess opioid disposal. Patients were treated on a wide variety of services; 88% of individuals underwent cancer-related surgery. Long-term opioid rxs were identified using a Prescription Drug Monitoring Program search and reasons for rxs and opioid adverse events were ascertained by medical record review. We used a consensus definition for persistent opioid use: opioid rx 3 to 12 months after surgery and >60day supply. RESULTS: 15.3% (34/221) filled an opioid rx 3 to 12 months after surgery, with 5.4% and 12.2% filling an rx 3 to 6 and 6 to 12 months after surgery, respectively. The median opioid rx days supply per patient was 7, interquartile range 5 to 27, range 1 to 447 days. The reasons for long-term opioid rxs were: 51% new painful medical condition, 40% new surgery, 6% related to the index operation; only 1 patient on 1 occasion was given an opioid rx for a nonspecific reason. Five patients (2.3%) developed persistent opioid use, 2 due to pain from recurrent cancer, 2 for new medical conditions, and 1 for a chronic abscess. CONCLUSIONS: In a group of prospectively studied opioid-naïve surgical patients discharged with guideline-directed opioid rxs and who achieved high rates of excess opioid disposal, no patients became persistent opioid users solely as a result of the opioid rx given after their index surgery. Long-term opioid use did occur for other, well-defined, medical or surgical reasons.

Genome-phenotype-environment associations identify signatures of selection in a panmictic population of threespine stickleback.

Adaptive genetic divergence occurs when selection imposed by the environment causes the genomic component of the phenotype to differentiate. However, genomic signatures of natural selection are usually identified without information on which trait is responding to selection by which selective agent(s). Here, we integrate whole-genome sequencing with phenomics and measures of putative selective agents to assess the extent of adaptive divergence in threespine stickleback occupying the highly heterogeneous lake Mývatn, NE Iceland. We find negligible genome wide divergence, yet multiple traits (body size, gill raker structure and defence traits) were divergent along known ecological gradients (temperature, predatory bird densities and water depth). SNP based heritability of all measured traits was high (h2  = 0.42-0.65), indicating adaptive potential for all traits. Environment-association analyses further identified thousands of loci putatively involved in selection, related to genes linked to, for instance, neuron development and protein phosphorylation. Finally, we found that loci linked to water depth were concurrently associated with pelvic spine length variation - supporting the conclusion that divergence in pelvic spine length occurred in the face of gene flow. Our results suggest that whilst there is substantial genetic variation in the traits measured, phenotypic divergence of Mývatn stickleback is mostly weakly associated with environmental gradients, potentially as a result of substantial gene flow. Our study illustrates the value of integrative studies that combine genomic assays of multivariate trait variation with landscape genomics.

Reconstructing midge consumer-resource dynamics using carbon stable isotope signatures of archived specimens.

Population cycles can be caused by consumer-resource interactions. Confirming the role of consumer-resource interactions, however, can be challenging due to an absence of data for the resource candidate. For example, interactions between midge larvae and benthic algae likely govern the high-amplitude population fluctuations of Tanytarsus gracilentus in Lake Mývatn, Iceland, but there are no records of benthic resources concurrent with adult midge population counts. Here, we investigate consumer population dynamics using the carbon stable isotope signatures of archived T. gracilentus specimens collected from 1977 to 2015, under the assumption that midge δ13 C values reflect those of resources they consumed as larvae. We used the time series for population abundance and δ13 C to estimate interactions between midges and resources while accounting for measurement error and possible preservation effects on isotope values. Results were consistent with consumer-resource interactions: high δ13 C values preceded peaks in the midge population, and δ13 C values tended to decline after midges reached high abundance. One interpretation of this dynamic coupling is that midge isotope signatures reflect temporal variation in benthic algal δ13 C values, which we expected to mirror primary production. Following from this explanation, high benthic production (enriched δ13 C values) would contribute to increased midge abundance, and high midge abundance would result in declining benthic production (depleted δ13 C values). An additional and related explanation is that midges deplete benthic algal abundance once they reach peak densities, causing midges to increase their relative reliance on other resources including detritus and associated microorganisms. Such a shift in resource use would be consistent with the subsequent decline in midge δ13 C values. Our study adds evidence that midge-resource interactions drive T. gracilentus fluctuations and demonstrates a novel application of stable isotope time-series data to understand consumer population dynamics.

Reducing Unnecessary Type and Screens Prior to Thoracic Surgery: A Quality Improvement Initiative.

INTRODUCTION: Previous work identified that routine preoperative type and screen (T&S) testing before elective thoracic surgery is overutilized. We hypothesized that instituting a quality improvement (QI) initiative to change practice would significantly reduce this unnecessary testing, reduce costs, and improve healthcare efficiency. MATERIALS AND METHODS: A QI initiative was developed at a single, academic center to reduce empiric T&S ordering before elective anatomic lung resections. Two interventions were implemented: 1) education based on current institutional data and 2) an electronic medical record order set modification. Utilization of T&S testing, blood transfusion data, and perioperative outcomes were tracked and compared between a preintervention group (2015-2018) and a postintervention group (2020-2021). Cost data were derived from institutional charges and Centers for Medicare & Medicaid Services fee schedules. RESULTS: Of the 553 patients included: 420 were in the preintervention group and 133 were in the postintervention group. The rate of routine T&Ss significantly dropped after implementing the QI initiative (97 versus 20%, P ≤ 0.001). Additionally, no difference in blood transfusion rate was observed (4.3 versus 2.3%, P = 0.29), and there were no differences noted in postoperative complications (P = 0.82), 30-day readmission (P = 0.29), or mortality (P = 0.96). Based on current volumes of ∼200 anatomic lung resections/year, estimated cost savings from reducing T&S testing from 97 to 20% would be at least $40,000 a year. CONCLUSIONS: Our QI initiative significantly reduced the use of routine T&S testing. This practice change was achieved while maintaining excellent outcomes demonstrating routine preoperative T&S testing can be safely reduced in most elective thoracic surgery.

Tumour, whole-blood, plasma and tissue concentrations of metformin in lung cancer patients.

AIM: Metformin is used for the management of type 2 diabetes mellitus (T2DM) and is being tested clinically as an anticancer agent. Metformin concentrations safely achievable in human solid tissues including tumours are unknown. This study was designed to determine metformin concentration in tissue compartments as a function of dose to inform rational dosing in preclinical models and interpretation of clinical results." METHODS: Subjects with solid tumours to be treated by resection and either (A) willingness to take metformin for 7-10 days before surgery or (B) taking metformin for T2DM were eligible. Whole blood, plasma, tumour, tumour-adjacent uninvolved tissue and subcutaneous adipose tissue were obtained for liquid chromatography with tandem mass spectrometry to measure metformin concentrations. RESULTS: All subjects had primary lung tumours. Metformin dose was significantly correlated with drug concentrations in all tissues analysed. Intersubject metformin concentrations varied by over two orders of magnitude. Metformin concentrations were significantly higher in tumour tissues and lower in adipose tissues compared to other tissues. Concentrations in blood and plasma were significantly correlated with concentrations in solid tissues. CONCLUSION: Metformin accumulates in cellular compartments. Concentrations observed in plasma, blood, lung and tumour tissues in subjects treated with US Food and Drug Administration-approved doses for T2DM are lower than those typically used in tissue culture studies. However, such tissue concentrations are in line with those found within cultured cells treated with supra-pharmacological doses of metformin. Given the large intersubject variability in metformin concentrations, it is imperative to determine whether there is an association between tissue metformin concentration and anticancer activity in humans.