Human microglial state dynamics in Alzheimer's disease progression.

Altered microglial states affect neuroinflammation, neurodegeneration, and disease but remain poorly understood. Here, we report 194,000 single-nucleus microglial transcriptomes and epigenomes across 443 human subjects and diverse Alzheimer's disease (AD) pathological phenotypes. We annotate 12 microglial transcriptional states, including AD-dysregulated homeostatic, inflammatory, and lipid-processing states. We identify 1,542 AD-differentially-expressed genes, including both microglia-state-specific and disease-stage-specific alterations. By integrating epigenomic, transcriptomic, and motif information, we infer upstream regulators of microglial cell states, gene-regulatory networks, enhancer-gene links, and transcription-factor-driven microglial state transitions. We demonstrate that ectopic expression of our predicted homeostatic-state activators induces homeostatic features in human iPSC-derived microglia-like cells, while inhibiting activators of inflammation can block inflammatory progression. Lastly, we pinpoint the expression of AD-risk genes in microglial states and differential expression of AD-risk genes and their regulators during AD progression. Overall, we provide insights underlying microglial states, including state-specific and AD-stage-specific microglial alterations at unprecedented resolution.

Epigenomic dissection of Alzheimer's disease pinpoints causal variants and reveals epigenome erosion.

Recent work has identified dozens of non-coding loci for Alzheimer's disease (AD) risk, but their mechanisms and AD transcriptional regulatory circuitry are poorly understood. Here, we profile epigenomic and transcriptomic landscapes of 850,000 nuclei from prefrontal cortexes of 92 individuals with and without AD to build a map of the brain regulome, including epigenomic profiles, transcriptional regulators, co-accessibility modules, and peak-to-gene links in a cell-type-specific manner. We develop methods for multimodal integration and detecting regulatory modules using peak-to-gene linking. We show AD risk loci are enriched in microglial enhancers and for specific TFs including SPI1, ELF2, and RUNX1. We detect 9,628 cell-type-specific ATAC-QTL loci, which we integrate alongside peak-to-gene links to prioritize AD variant regulatory circuits. We report differential accessibility of regulatory modules in late AD in glia and in early AD in neurons. Strikingly, late-stage AD brains show global epigenome dysregulation indicative of epigenome erosion and cell identity loss.

Regulatory genomic circuitry of human disease loci by integrative epigenomics.

Annotating the molecular basis of human disease remains an unsolved challenge, as 93% of disease loci are non-coding and gene-regulatory annotations are highly incomplete1-3. Here we present EpiMap, a compendium comprising 10,000 epigenomic maps across 800 samples, which we used to define chromatin states, high-resolution enhancers, enhancer modules, upstream regulators and downstream target genes. We used this resource to annotate 30,000 genetic loci that were associated with 540 traits4, predicting trait-relevant tissues, putative causal nucleotide variants in enriched tissue enhancers and candidate tissue-specific target genes for each. We partitioned multifactorial traits into tissue-specific contributing factors with distinct functional enrichments and disease comorbidity patterns, and revealed both single-factor monotropic and multifactor pleiotropic loci. Top-scoring loci frequently had multiple predicted driver variants, converging through multiple enhancers with a common target gene, multiple genes in common tissues, or multiple genes and multiple tissues, indicating extensive pleiotropy. Our results demonstrate the importance of dense, rich, high-resolution epigenomic annotations for the investigation of complex traits.

GENCODE: reference annotation for the human and mouse genomes in 2023.

GENCODE produces high quality gene and transcript annotation for the human and mouse genomes. All GENCODE annotation is supported by experimental data and serves as a reference for genome biology and clinical genomics. The GENCODE consortium generates targeted experimental data, develops bioinformatic tools and carries out analyses that, along with externally produced data and methods, support the identification and annotation of transcript structures and the determination of their function. Here, we present an update on the annotation of human and mouse genes, including developments in the tools, data, analyses and major collaborations which underpin this progress. For example, we report the creation of a set of non-canonical ORFs identified in GENCODE transcripts, the LRGASP collaboration to assess the use of long transcriptomic data to build transcript models, the progress in collaborations with RefSeq and UniProt to increase convergence in the annotation of human and mouse protein-coding genes, the propagation of GENCODE across the human pan-genome and the development of new tools to support annotation of regulatory features by GENCODE. Our annotation is accessible via Ensembl, the UCSC Genome Browser and https://www.gencodegenes.org.

Histopathological characterisation of trunk-dominant canine pemphigus foliaceus, and comparison with classic facial and insecticide-triggered forms.

BACKGROUND: While the clinical features were described recently, the histopathological characterisation of trunk-dominant canine pemphigus foliaceus (PF) is lacking, and whether it differs from classic facial or insecticide-triggered PF is unknown. HYPOTHESIS/OBJECTIVES: This study describes the histopathological findings of trunk-dominant PF, and compares the results to classic facial and insecticide-triggered PF. ANIMALS: Skin biopsies from 103 dogs with clinically characterised trunk-dominant (n = 33), classic facial (n = 26) and insecticide-triggered PF (n = 44) were included. MATERIALS AND METHODS: Histological sections, randomised and blinded, were scored for over 50 morphological parameters of pustules, epidermis, dermis, adnexa and crusts. Intact pustule area and width were measured by digital microscopy. RESULTS: In trunk-dominant PF, 77 intact pustules were predominantly subcorneal (0.0019-1.940 mm2 area, 0.0470-4.2532 mm wide), and contained from one to over 100 acantholytic keratinocytes. Pustules had boat acantholytic cells, corneocytes, perinuclear eosinophilic rings, neutrophil rosettes, acantholytic cell necrosis, rafts, cling-ons and/or eosinophils. Peripustular epidermal spongiosis, necrosis and lymphocyte exocytosis occurred, as did follicular pustules. Mixed dermal inflammation often contained eosinophils. Trunk-dominant PF did not differ from the other PF groups except for few parameters, such as having fewer rafts (p = 0.003). Additional autoimmune inflammatory patterns occurred in all PF groups. CONCLUSIONS AND CLINICAL RELEVANCE: Trunk-dominant PF and other canine PF variants are histologically similar, which indicates shared pathomechanisms. The identification of common boat acantholytic cells and corneocyte separation has implications for the mechanisms of acantholysis. The diversity of histopathological and polyautoimmunity features support complicated immune mechanisms. Finally, results indicate that diagnostic biopsies cannot differentiate between these PF variants in dogs.

Survival After Adrenalectomy for Metastatic Lung Cancer.

BACKGROUND: Adrenal metastasectomy is associated with increased survival in non-small cell lung cancer (NSCLC) with isolated adrenal metastases. Although clinical use of adrenal metastasectomy has expanded, indications remain poorly defined. The aim of this study was to evaluate the clinical benefit of adrenal metastasectomy for all lung cancer subtypes. PATIENTS AND METHODS: We performed a retrospective cohort study of patients who underwent adrenal metastasectomy for metastatic lung cancer at six institutions between 2001 and 2015. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Cox proportional hazards regressions and Kaplan-Meier survival analysis were performed. RESULTS: For 122 patients, the mean age was 60.5 years and 49.2% were female. Median time to detection of the metastasis was 11 months, and 41.8% were ipsilateral to the primary lung cancer. Median DFS was 40 months (1 year: 64.8%; 5 year: 42.9%). Factors associated with longer DFS included primary tumor resection [hazard ratio (HR): 0.001; p = 0.005], longer time to adrenal metastasis (HR: 0.94; p = 0.005), and ipsilateral metastases (HR: 0.13; p = 0.004). Shorter DFS corresponded with older age (HR: 1.11; p = 0.01), R1 resection (HR: 8.94; p = 0.01), adjuvant radiation (HR: 9.45; p = 0.02), and open adrenal metastasectomy (HR: 10.0; p = 0.03). Median OS was 47 months (1 year: 80.2%; 5 year: 35.2%). Longer OS was associated with ipsilateral metastasis (HR: 0.55; p = 0.02) and adjuvant chemotherapy (HR: 0.35; p = 0.02). Shorter OS was associated with extra-adrenal metastases at adrenalectomy (HR: 3.52; p = 0.007), small cell histology (HR: 15.0; p = 0.04), and lung radiation (HR: 3.37; p = 0.002). DISCUSSION: Durable survival was observed in patients undergoing adrenal metastasectomy and should be considered for isolated adrenal metastases of NSCLC. Small cell histology and extra-adrenal metastases are relative contraindications to adrenal metastasectomy.

Quality of Life in Patients with Benign Non-Toxic Goiter After Surgical Intervention: A Systematic Review and Meta-Analysis.

BACKGROUND: Prior studies evaluating health-related quality of life (HR-QoL) outcomes in patients undergoing surgery for benign non-toxic goiter have used different instruments and time points, leading to conflicting results. We sought to systematically review the differences in HR-QoL among patients with BNTG at baseline and 6 months after surgery, using exclusively the ThyPRO questionnaire. METHODS: A systematic search was performed using PubMed, Embase, Web of Science, Cochrane Central, CINAHL, and PsycINFO for papers reporting the assessment of HR-QoL utilizing ThyPRO. Data were meta-analyzed using a random-effects model, and pooled estimates were calculated using weighted mean differences (WMD) between baseline and 6 months after surgery. We assessed the quality and risk of bias of the studies using the Robins-I tool and previously published minimally important change (MIC) values to assess clinical significance. RESULTS: Six papers met the predefined inclusion criteria, describing a total of 496 patients. Meta-analysis demonstrated improved QoL in all thirteen domains of ThyPRO six months post-surgical intervention compared to baseline. Specifically, the largest improvement in QoL was seen in the domains of overall QoL, WMD -25.84 (95% CI -29.70, -21.98, p < 0.001, I2 = 23%), goiter symptoms, 23.96 (95% CI -30.29, -17.64, p < 0.001, I2 = 91%), and tiredness, -16.20 (95% CI -19.23, -13.16, p < 0.001, I2 = 3%). The differences in scores 9 of 13 domains were clinically significant based on MIC. CONCLUSIONS: Disease-specific HR-QoL improved in all ThyPRO domains after surgery in patients with BNTG. Future studies of QoL in thyroid surgery patients will benefit from a standard questionnaire and improved reporting of covariates including complications to ensure comparability across studies.

Optimized cell growth and poly(3-hydroxybutyrate) synthesis from saponified spent coffee grounds oil.

Spent coffee ground (SCG) oil is an ideal substrate for the biosynthesis of polyhydroxyalkanoates (PHAs) by Cupriavidus necator. The immiscibility of lipids with water limits their bioavailability, but this can be resolved by saponifying the oil with potassium hydroxide to form water-soluble fatty acid potassium salts and glycerol. Total saponification was achieved with 0.5 mol/L of KOH at 50 °C for 90 min. The relationship between the initial carbon substrate concentration (C0) and the specific growth rate (µ) of C. necator DSM 545 was evaluated in shake flask cultivations; crude and saponified SCG oils were supplied at matching initial carbon concentrations (C0 = 2.9-23.0 g/L). The Han-Levenspiel model provided the closest fit to the experimental data and accurately described complete growth inhibition at 32.9 g/L (C0 = 19.1 g/L) saponified SCG oil. Peak µ-values of 0.139 h-1 and 0.145 h-1 were obtained with 11.99 g/L crude and 17.40 g/L saponified SCG oil, respectively. Further improvement to biomass production was achieved by mixing the crude and saponified substrates together in a carbon ratio of 75:25% (w/w), respectively. In bioreactors, C. necator initially grew faster on the mixed substrates (µ = 0.35 h-1) than on the crude SCG oil (µ = 0.23 h-1). After harvesting, cells grown on crude SCG oil obtained a total biomass concentration of 7.8 g/L and contained 77.8% (w/w) PHA, whereas cells grown on the mixed substrates produced 8.5 g/L of total biomass and accumulated 84.4% (w/w) of PHA. KEY POINTS: • The bioavailability of plant oil substrates can be improved via saponification. • Cell growth and inhibition were accurately described by the Han-Levenpsiel model. • Mixing crude and saponified oils enable variation of free fatty acid content.

Adrenalectomy for Secondary Malignancy: Patients, Outcomes, and Indications.

OBJECTIVE: The goal of this study was to examine a multi-institutional experience with adrenal metastases to describe survival outcomes and identify subpopulations who benefit from adrenal metastasectomy. BACKGROUND: Adrenalectomy for metastatic disease is well-described, although indications and outcomes are incompletely defined. METHODS: A retrospective cohort study was performed of patients undergoing adrenalectomy for secondary malignancy (2002-2015) at 6 institutions. The primary outcomes were disease free survival (DFS) and overall survival (OS). Analysis methods included Kaplan-Meier and Cox proportional hazards. RESULTS: Of 269 patients, mean age was 60.1 years; 50% were male. The most common primary malignancies were lung (n = 125, 47%), renal cell (n = 38, 14%), melanoma (n = 33, 12%), sarcoma (n = 18, 7%), and colorectal (n = 12, 5%). The median time to detection of adrenal metastasis after initial diagnosis of the primary tumor was 17 months (interquartile range: 6-41). Post-adrenalectomy, the median DFS was 18 months (1-year DFS: 54%, 5-year DFS: 31%). On multivariable analysis, lung primary was associated with longer DFS [hazard ratio (HR): 0.49, P = 0.008). Extra-adrenal oligometastatic disease at initial presentation (HR: 1.84, P = 0.016), larger tumor size (HR: 1.07, P = 0.013), chemotherapy as treatment of the primary tumor (HR: 2.07 P = 0.027) and adjuvant chemotherapy (HR: 1.95, P = 0.009) were associated with shorter DFS. Median OS was 53 months (1-year OS: 83%, 5-year OS: 43%). On multivariable analysis, extra-adrenal oligometastatic disease at adrenalectomy (HR: 1.74, P = 0.031), and incomplete resection of adrenal metastasis (R1 margins; HR: 1.62, P = 0.034; R2 margins; HR: 5.45, P = 0.002) were associated with shorter OS. CONCLUSIONS: Durable survival is observed in patients undergoing adrenal metastasectomy and should be considered for subjects with isolated adrenal metastases.

A survey and evaluations of histogram-based statistics in alignment-free sequence comparison.

MOTIVATION: Since the dawn of the bioinformatics field, sequence alignment scores have been the main method for comparing sequences. However, alignment algorithms are quadratic, requiring long execution time. As alternatives, scientists have developed tens of alignment-free statistics for measuring the similarity between two sequences. RESULTS: We surveyed tens of alignment-free k-mer statistics. Additionally, we evaluated 33 statistics and multiplicative combinations between the statistics and/or their squares. These statistics are calculated on two k-mer histograms representing two sequences. Our evaluations using global alignment scores revealed that the majority of the statistics are sensitive and capable of finding similar sequences to a query sequence. Therefore, any of these statistics can filter out dissimilar sequences quickly. Further, we observed that multiplicative combinations of the statistics are highly correlated with the identity score. Furthermore, combinations involving sequence length difference or Earth Mover's distance, which takes the length difference into account, are always among the highest correlated paired statistics with identity scores. Similarly, paired statistics including length difference or Earth Mover's distance are among the best performers in finding the K-closest sequences. Interestingly, similar performance can be obtained using histograms of shorter words, resulting in reducing the memory requirement and increasing the speed remarkably. Moreover, we found that simple single statistics are sufficient for processing next-generation sequencing reads and for applications relying on local alignment. Finally, we measured the time requirement of each statistic. The survey and the evaluations will help scientists with identifying efficient alternatives to the costly alignment algorithm, saving thousands of computational hours. AVAILABILITY: The source code of the benchmarking tool is available as Supplementary Materials.

Look4TRs: a de novo tool for detecting simple tandem repeats using self-supervised hidden Markov models.

MOTIVATION: Simple tandem repeats, microsatellites in particular, have regulatory functions, links to several diseases and applications in biotechnology. There is an immediate need for an accurate tool for detecting microsatellites in newly sequenced genomes. The current available tools are either sensitive or specific but not both; some tools require adjusting parameters manually. RESULTS: We propose Look4TRs, the first application of self-supervised hidden Markov models to discovering microsatellites. Look4TRs adapts itself to the input genomes, balancing high sensitivity and low false positive rate. It auto-calibrates itself. We evaluated Look4TRs on 26 eukaryotic genomes. Based on F measure, which combines sensitivity and false positive rate, Look4TRs outperformed TRF and MISA-the most widely used tools-by 78 and 84%. Look4TRs outperformed the second and the third best tools, MsDetector and Tantan, by 17 and 34%. On eight bacterial genomes, Look4TRs outperformed the second and the third best tools by 27 and 137%. AVAILABILITY AND IMPLEMENTATION: https://github.com/TulsaBioinformaticsToolsmith/Look4TRs. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Time to Surgery and Thyroid Cancer Survival in the United States.

BACKGROUND: Longer time to surgery worsens survival in multiple malignancies, including lung, colorectal, and breast cancers, but limited data exist for well-differentiated thyroid cancer. We sought to investigate the impact of time to surgery on overall survival in patients with papillary thyroid cancer. METHODS: In a retrospective cohort study of the National Cancer Database, we used Cox proportional hazard models to investigate overall survival as a function of time between diagnosis and surgery for adults with papillary thyroid cancer, adjusting for demographic, patient, and cancer-related variables. Time to surgery was investigated both as a continuous variable and as intervals of 0-90 days, 90-180 days, and > 180 days. Subgroup analyses were conducted by T stage. RESULTS: Overall, 103,812 adults with papillary thyroid cancer were included from 2004 to 2016. Median follow-up was 55.2 months (interquartile range 28.4-89.5). Increasing time to surgery was associated with increased mortality: delaying by 91-180 days increased the risk by 30% (adjusted hazard ratio [aHR] 1.30, 95% CI 1.19-1.43) and delaying by over 180 days increased the risk by 94% (aHR 1.94, 95% CI 1.68-2.24). Five-year overall survival was 95.7% for 0-90 days, 93.0% for 91-180 days, and 87.9% for over 180 days. On subgroup analysis, increasing delay was associated with worse overall survival for T1, T2, and T3 tumors, but not T4 tumors. CONCLUSIONS: Increasing time to surgery in papillary thyroid cancer is associated with reduced overall survival. Further research is necessary to assess the impact of surgical delay on disease-specific survival.

Diagnostic Impact of Adrenal Vein Sampling in Adrenal Cushing's Syndrome.

BACKGROUND: Adrenal Cushing's syndrome is characterized by ACTH-independent hypercortisolism. Adrenal vein sampling (AVS) is not routinely employed prior to management decisions, and few studies have investigated the value of AVS in this population. We assessed whether AVS provides a diagnostic benefit for treatment planning. MATERIALS AND METHODS: Six patients with imaging and biochemical evidence of adrenal Cushing's syndrome undergoing AVS at our institution from 2015 to 2020 were analyzed retrospectively, including demographic and clinical characteristics. AVS lateralization index was determined by comparing the (cortisol/ipsilateral reference hormone) ratios of both adrenal veins. lateralization index of 2 or greater was considered diagnostic of unilateral disease. Post-management clinical improvement was defined as serum cortisol normalization, symptomatic improvement, or both. RESULTS: Cross-sectional imaging noted bilateral adrenal enlargement or nodules in three patients, and unilateral nodules in three patients. AVS results were discordant with imaging in three patients. Treatment included medical management in two patients, percutaneous radiofrequency ablation in one patient, and laparoscopic adrenalectomy in two patients. One patient was lost to follow up. AVS results aided management planning in five patients, definitively changing treatment from surgery to medical management in one patient. All five patients demonstrated clinical improvement. CONCLUSIONS: AVS offered useful information for determining appropriate management of adrenal Cushing's syndrome, especially distinguishing unilateral from bilateral disease. Even in bilateral disease, AVS may show a dominant gland, potentially allowing a staged unilateral adrenalectomy, before assessing the need for completion adrenalectomy or medical management. Larger studies are needed to better establish whether AVS offers significant benefit for this population.

Decreasing Surgical Management of Secondary Hyperparathyroidism in the United States.

BACKGROUND: Secondary hyperparathyroidism (SHPT) commonly occurs in end-stage renal disease (ESRD), leading to vascular calcification and increased mortality. For SHPT refractory to medical management, parathyroidectomy improves symptoms and decreases mortality. Medical management has changed with the release of new guidelines and advent of novel medications. We investigate recent national trends in parathyroidectomy for SHPT. MATERIALS AND METHODS: We used the National/Nationwide Inpatient Sample from 2004 to 2016 to identify hospitalizations including parathyroidectomy for SHPT and calculated parathyroidectomy rates utilizing data from the United States Renal Data System. Subgroup analysis was conducted by race. Risk factors for in-hospital mortality were identified with purposeful selection and multivariable logistic regression. RESULTS: From 2004 to 2016, the rate of parathyroidectomies for SHPT per 1000 ESRD patients decreased from 6.07 (95% CI: 4.83-7.32) to 3.67 (95% CI: 3.33-4.00). Black patients underwent parathyroidectomy for SHPT at a 1.8-fold higher rate than white and Hispanic patients (5.59 versus 3.04 and 3.07). Almost all tracked comorbidities increased in prevalence. In-hospital mortality trended lower (1.5% to 0.8%, P = 0.051). Risk factors for in-hospital mortality included weight loss (OR 4.19, 95% CI: 2.00-8.78) and cardiac arrhythmia (OR 3.38, 95% CI: 1.66-6.91), while additional calendar year (OR = 0.87, 95% CI: 0.80-0.95) was protective. CONCLUSIONS: The etiology of the declining parathyroidectomy rate for SHPT is unclear; possible factors include changing guidelines emphasizing medical management, widespread availability of cinacalcet, changing practice patterns, and inadequate surgical referral.

Can Cytologic and Sonographic Features Help Prevent Overtreatment of Bethesda V Thyroid Nodules?

BACKGROUND: Although nearly half of thyroid nodules with Bethesda V cytology (suspicious for malignancy) may be benign or harbor low-grade neoplasms that can be sufficiently treated with lobectomy, many patients with Bethesda V cytology continue to be treated with total thyroidectomy. The objectives of this study were to establish whether cytomorphologic and ultrasonographic features can determine appropriate surgery for thyroid nodules with Bethesda V cytology and how often patients are overtreated with total instead of partial thyroidectomy. METHODS: Utilizing a 10-y prospective database starting January 1, 2004, cytomorphologic and ultrasonographic features of thyroid nodules with Bethesda V cytology were reviewed. Overtreatment was defined as total thyroidectomy when histopathology revealed benign nodule, noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) or a unilateral < 4 cm low risk cancer. RESULTS: Sixty-three patients were included in the study. Seventeen (27%) had benign, 14 (22%) NIFTP, and 32 (51%) malignant nodules. On cytology, nuclear pseudoinclusions, and on ultrasound, taller-than-wide configuration, were more common in malignant than benign or NIFTP nodules. Among 56 patients who underwent total thyroidectomy, 14 and 11 had a benign or NIFTP nodule, respectively, and 13 had a unilateral < 4 cm low risk cancer, suggesting that 68% (38/56) were overtreated. CONCLUSIONS: Total thyroidectomy for Bethesda V thyroid nodules may result in overtreatment in more than half of the patients. Although certain cytomorphologic and ultarsonographic features may be helpful in determining appropriate surgery for Bethesda V thyroid nodules, additional characteristics are needed to reduce overtreatment of these nodules.

Public Perceptions of Transoral Endocrine Surgery and their Influence on Choice of Operative Approach.

BACKGROUND: Transoral Endocrine Surgery (TES) represents an alternative to the open approach with no visible scar. Studies have shown TES has a safety profile similar to the open approach, but adoption has been limited. Public perception and preference for TES are factors associated with adoption that have not been explored. Here we aim to understand the perception of TES by the public and factors which influence decision making. MATERIALS AND METHODS: A 38-question survey was designed to assess factors which influence willingness to pursue TES. The survey was distributed utilizing Amazon Mechanical Turk (MTurk), a crowdsourcing marketplace in which individuals perform tasks virtually based on interest. Descriptive analyses, Pearson chi-squared tests, Student's t-tests, and multivariate logistic regression were performed to evaluate theoretical decision to pursue TES. RESULTS: Respondents (n = 795) were 47% female, 78% white, 70% held a college degree or higher, and had a mean age of 37. The majority (69%) preferred a mouth incision over a neck incision. Respondents were willing to pursue TES for a theoretical cancer despite increased cost (52%) and longer operative time (70%). Respondents top two most important surgical factors were safety and experience. CONCLUSIONS: Our data suggest the general public is willing to pursue TES and factors thought to be barriers to choosing TES may not deter the public. An informed discussion with appropriately-selected patients should be had between the patient and surgeon regarding specific surgical and postoperative differences including risks, safety, and experience.

Patient-Reported Financial Burden in Thyroid Cancer.

BACKGROUND: The incidence of thyroid cancer is increasing at a rapid rate. Prior studies have demonstrated financial burden and decreased quality of life in patients with thyroid cancer. Here, we characterize patient-reported financial burden in patients with thyroid cancer over a 28y period. MATERIALS AND METHODS: Patients who underwent thyroidectomy for thyroid cancer from 1990-2018 completed a phone survey assessing financial burden and its related psychological financial hardship. Descriptive statistics were performed to characterize these outcomes and correlation with sociodemographic data was assessed. RESULTS: Respondents (N = 147) were 73% female, 75% white, and had a median follow up of 7 y. The majority had a full-time job (59%) and private insurance (81%) at the time of diagnosis. Overall, 16% of respondents reported financial burden and 50% reported psychological financial hardship. Those reporting financial burden were disproportionately impacted by psychological financial hardship (87% versus 43%, P < 0.001). One in four (25%) respondents reported not being adequately informed about costs. CONCLUSIONS: Financial burdens are important outcomes of thyroid cancer which occur even among patients with protective financial factors, suggesting an even greater impact on the general population of patients with thyroid cancer. Further research is needed to explore the intersection of financial burden, cost, and quality of life.

Community- versus hospital-acquired acute kidney injury in hospitalised COVID-19 patients.

BACKGROUND: Acute kidney injury (AKI) is a recognised complication of coronavirus disease 2019 (COVID-19), yet the reported incidence varies widely and the associated risk factors are poorly understood. METHODS: Data was collected on all adult patients who returned a positive COVID-19 swab while hospitalised at a large UK teaching hospital between 1st March 2020 and 3rd June 2020. Patients were stratified into community- and hospital-acquired AKI based on the timing of AKI onset. RESULTS: Out of the 448 eligible patients with COVID-19, 118 (26.3 %) recorded an AKI during their admission. Significant independent risk factors for community-acquired AKI were chronic kidney disease (CKD), diabetes, clinical frailty score and admission C-reactive protein (CRP), systolic blood pressure and respiratory rate. Similar risk factors were significant for hospital-acquired AKI including CKD and trough systolic blood pressure, peak heart rate, peak CRP and trough lymphocytes during admission. In addition, invasive mechanical ventilation was the most significant risk factor for hospital-acquired AKI (adjusted odds ratio 9.1, p < 0.0001) while atrial fibrillation conferred a protective effect (adjusted odds ratio 0.29, p < 0.0209). Mortality was significantly higher for patients who had an AKI compared to those who didn't have an AKI (54.3 % vs. 29.4 % respectively, p < 0.0001). On Cox regression, hospital-acquired AKI was significantly associated with mortality (adjusted hazard ratio 4.64, p < 0.0001) while community-acquired AKI was not. CONCLUSIONS: AKI occurred in over a quarter of our hospitalised COVID-19 patients. Community- and hospital-acquired AKI have many shared risk factors which appear to converge on a pre-renal mechanism of injury. Hospital- but not community acquired AKI was a significant risk factor for death.

Overcoming a Hostile Work and Learning Environment in Academic Surgery-Tools for Change at Every Level.

Mistreatment has been documented as a negative factor in the learning environment for the past 30 y but little progress has been made to determine an effective way to significantly improve these interactions. Faculty may also be victims of a hostile work environment as well, although frequency has not been well-measured or reported. In fact, it may be difficult to identify and address mistreatment and hostility in the work place within the commonly established surgical culture. Thus, efforts to define, identify, and address workplace mistreatment or hostility are crucial to the success of the academic surgical environment. This article summarizes presentations and panel discussion that took place at the 2019 Academic Surgical Congress organized by the Association for Academic Surgery and the Society of University Surgeons. Definitions of mistreatment and hostility were provided, as well as information regarding occurrence. Tools for addressing mistreatment in the work environment and tips for creating a positive environment were presented and discussed.

Identification of Specific Educational Targets to Improve the Student Surgical Clerkship Experience.

BACKGROUND: This study describes the relationship between medical student perception of surgery, frequency of positive surgery clerkship activities, and overall surgical clerkship experience. METHODS: Medical students at four academic hospitals completed pre- and post-clerkship surveys assessing 1) surgery clerkship activities/experiences and 2) perceptions of surgery during the 2017-2018 academic year. RESULTS: Ninety-one percent of students completed both a pre- and post-clerkship survey (n = 162 of 179). Student perception of surgery significantly improved across the clerkship overall (P < 0.0001) and for 7 of 21 specific items. Eighty-six percent of students agreed that the clerkship was a meaningful experience. Sixty-six percent agreed that the operating room was a positive learning environment. Multivariable logistic regression identified one-on-one mentoring from a resident (OR [95% CI] = 2.12 [1.11-4.04], P = 0.02) and establishing a meaningful relationship with a surgical patient (OR = 2.21 [1.12-4.37], P = 0.02) as activities predictive of student agreement that the surgical clerkship was meaningful. Making an incision (OR = 2.92 [1.54-5.56], P = 0.001) and assisting in dissection (OR = 1.67 [1.03-2.69], P = 0.035) were predictive of student agreement that the operating room was a positive learning environment. Positive student perception of surgery before the clerkship was associated with increased frequency of positive clerkship activities including operative involvement (r = 0.26, P = 0.001) and relationships with surgical attendings (r = 0.20, P = 0.01), residents (r = 0.41, P < 0.0001), and patients (r = 0.24, P = 0.003). CONCLUSIONS: Interventions to improve surgery clerkship quality should target enhancing student relationships with residents and surgical patients as well as providing opportunity for student operative involvement beyond just suturing. In addition, fostering positive perceptions of surgery in the preclinical period may increase meaningfulness and experience with the later surgery clerkship.