The cholesterol pathway: impact on immunity and cancer.

Cholesterol is a multifaceted metabolite that is known to modulate processes in cancer, atherosclerosis, and autoimmunity. A common denominator between these diseases appears to be the immune system, in which many cholesterol-associated metabolites impact both adaptive and innate immunity. Many cancers display altered cholesterol metabolism, and recent studies demonstrate that manipulating systemic cholesterol metabolism may be useful in improving immunotherapy responses. However, cholesterol can have both proinflammatory and anti-inflammatory roles in mammals, acting via multiple immune cell types, and depending on context. Gaining mechanistic insights into various cholesterol-related metabolites can improve our understanding of their functions and extensive effects on the immune system, and ideally will inform the design of future therapeutic strategies against cancer and/or other pathologies.

How local partisan context conditions prosocial behaviors: Mask wearing during COVID-19.

Does local partisan context influence the adoption of prosocial behavior? Using a nationwide survey of 60,000 adults and geographic data on over 180 million registered voters, we investigate whether neighborhood partisan composition affects a publicly observable and politicized behavior: wearing a mask. We find that Republicans are less likely to wear masks in public as the share of Republicans in their zip codes increases. Democratic mask wearing, however, is unaffected by local partisan context. Consequently, the partisan gap in mask wearing is largest in Republican neighborhoods, and less apparent in Democratic areas. These effects are distinct from other contextual effects such as variations in neighborhood race, income, or education. In contrast, partisan context has significantly reduced influence on unobservable public health recommendations like COVID-19 vaccination and no influence on nonpoliticized behaviors like flu vaccination, suggesting that differences in mask wearing reflect the publicly observable and politicized nature of the behavior instead of underlying differences in dispositions toward medical care.

Appropriateness of ChatGPT in Answering Heart Failure Related Questions.

BACKGROUND: Heart failure requires complex management, and increased patient knowledge has been shown to improve outcomes. This study assessed the knowledge of Chat Generative Pre-trained Transformer (ChatGPT) and its appropriateness as a supplemental resource of information for patients with heart failure. METHOD: A total of 107 frequently asked heart failure-related questions were included in 3 categories: "basic knowledge" (49), "management" (41) and "other" (17). Two responses per question were generated using both GPT-3.5 and GPT-4 (i.e., two responses per question per model). The accuracy and reproducibility of responses were graded by two reviewers, board-certified in cardiology, with differences resolved by a third reviewer, board-certified in cardiology and advanced heart failure. Accuracy was graded using a four-point scale: (1) comprehensive, (2) correct but inadequate, (3) some correct and some incorrect, and (4) completely incorrect. RESULTS: GPT-4 provided 107/107 (100%) responses with correct information. Further, GPT-4 displayed a greater proportion of comprehensive knowledge for the categories of "basic knowledge" and "management" (89.8% and 82.9%, respectively). For GPT-3, there were two total responses (1.9%) graded as "some correct and incorrect" for GPT-3.5, while no "completely incorrect" responses were produced. With respect to comprehensive knowledge, GPT-3.5 performed best in the "management" category and "other" category (prognosis, procedures, and support) (78.1%, 94.1%). The models also provided highly reproducible responses, with GPT-3.5 scoring above 94% in every category and GPT-4 with 100% for all answers. CONCLUSIONS: GPT-3.5 and GPT-4 answered the majority of heart failure-related questions accurately and reliably. If validated in future studies, ChatGPT may serve as a useful tool in the future by providing accessible health-related information and education to patients living with heart failure. In its current state, ChatGPT necessitates further rigorous testing and validation to ensure patient safety and equity across all patient demographics.

Effects of blended learning training for oncology physicians to advise their patients about complementary and integrative therapies: results from the multicenter cluster-randomized KOKON-KTO trial.

BACKGROUND: Many oncology physicians are confronted with the topic of complementary and integrative medicine (CIM) by cancer patients. This study examined whether a blended learning (e-learning and a workshop) to train oncology physicians in providing advice on CIM therapies to their cancer patients, in addition to distributing an information leaflet about reputable CIM websites, had different effects on physician-reported outcomes in regard to consultations compared with only distributing the leaflet. METHODS: In a multicenter, cluster-randomized trial, 48 oncology physicians were randomly allocated to an intervention group (CIM consultation and an information leaflet) or a control group (information leaflet only). After the training, the oncology physicians conducted 297 consultations with their cancer patients. Measurements were assessed at oncology physician, physician-patient-interaction (measured by external reviewers), and patient levels. This analysis focused on the physician outcomes of stress reaction and perceived consultation skill competency. In addition, qualitative interviews were conducted with a subsample of oncology physicians who experienced both, the intervention and control condition. RESULTS: The oncology physicians in the intervention group showed a lower stress reaction in all measured dimensions after CIM consultations than those in the control group. There was no significant difference between oncology physicians in the intervention and control groups regarding the perceived consultation skill competency (overburden: intervention 1.4 [95% CI: 0.7;2.1]; control 2.1 [95% CI: 1.4;2.7], tension: 1.3 [95% CI: 0.7;2.0] vs. 1.9 [95% CI: 1.3;2.5], and discomfort with consultation situations: 1.0 [95% CI: 0.4;1.7]; vs. 1.7 [95% CI: 1.2;2.3]). The qualitative data showed that only providing the leaflet seemed impersonal to oncology physicians, while the training made them feel well prepared to conduct a full conversation about CIM and provide the information leaflet. CONCLUSIONS: In our exploratory study providing structured CIM consultations showed positive effects on the perceived stress of oncology physicians, and the training was subjectively experienced as an approach that improved physician preparation for advising cancer patients about CIM, however no effects regarding perceived consultation skill competency were found. TRIAL REGISTRATION: The trial registration number of the KOKON-KTO study is DRKS00012704 in the German Clinical Trials Register (Date of registration: 28.08.2017).

Chronic Engineered Nanoparticle Additions Alter Insect Emergence and Result in Metal Flux from Aquatic Ecosystems into Riparian Food Webs.

Freshwater ecosystems are exposed to engineered nanoparticles (NPs) through discharge from wastewater and agricultural runoff. We conducted a 9-month mesocosm experiment to examine the combined effects of chronic NP additions on insect emergence and insect-mediated contaminant flux to riparian spiders. Two NPs (copper, gold, plus controls) were crossed by two levels of nutrients in 18 outdoor mesocosms open to natural insect and spider colonization. We collected adult insects and two riparian spider genera, Tetragnatha and Dolomedes, for 1 week on a monthly basis. We estimated a significant decrease in cumulative insect emergence of 19% and 24% after exposure to copper and gold NPs, irrespective of nutrient level. NP treatments led to elevated copper and gold tissue concentrations in adult insects, which resulted in terrestrial fluxes of metals. These metal fluxes were associated with increased gold and copper tissue concentrations for both spider genera. We also observed about 25% fewer spiders in the NP mesocosms, likely due to reduced insect emergence and/or NP toxicity. These results demonstrate the transfer of NPs from aquatic to terrestrial ecosystems via emergence of aquatic insects and predation by riparian spiders, as well as significant reductions in insect and spider abundance in response to NP additions.

Left atrial Thrombus formation after discontinuation of anticoagulation in patient with severe bioprosthetic mitral stenosis.

BACKGROUND: Mitral valve stenosis can be a highly symptomatic condition with significant complications if left untreated. In such cases, mitral valve replacement with a bioprosthetic or mechanical valve may be a viable solution to prevent progressive disease. Current guidelines do not recommend continued anticoagulation beyond 6 months for patients who have undergone bioprosthetic valve replacement without a separate indication for anticoagulation. With this case discussion we aim to 1) Review the current indications for anticoagulation for bioprosthetic mitral valves in patients without atrial fibrillation and 2) Discuss the constellation of comorbidities that may affect the decision to begin anticoagulation therapy. CASE PRESENTATION: We present a case describing a 55-year-old male with end-stage renal disease, coronary artery disease with coronary artery bypass graft surgery, and bioprosthetic mitral valve replacement 2 years prior with rapid degeneration of the replaced valve and on warfarin without a clear indication for anticoagulation. The patient was admitted for symptomatic, severe mitral stenosis and consideration of transcatheter mitral valve-in-valve replacement. During hospital admission, warfarin was discontinued and replaced with prophylactic anticoagulation. However, 8 days after warfarin cessation an intraoperative transesophageal echocardiography revealed a newly developed large left atrial thrombus leading to cancellation of the planned operation. CONCLUSIONS: This patient developed a left atrial thrombus after discontinuing warfarin in the setting of rapidly deteriorating bioprosthetic valve stenosis and vascular comorbidities. The decision to discontinue warfarin was made in concordance with current guidelines, which do not indicate systemic anticoagulation post 3-6 months after bioprosthetic valve replacement without separate indication for anticoagulation. This case identifies the need to investigate rebound hypercoagulability and further risk stratify comorbidities which may independently increase the risk of clot formation in the setting of severe mitral valve stenosis.

Ultrasound Examination Without Axial Imaging is Sufficient for Preoperative Planning in Transcarotid Artery Revascularization (TCAR).

BACKGROUND: Duplex ultrasound is frequently used to determine the degree of carotid stenosis. However, axial imaging is typically obtained for operative planning for transcarotid artery revascularization (TCAR). We examined if ultrasound alone is sufficient before TCAR. METHODS: Data from the Vascular Quality Initiative TCAR Surveillance Project registry between 2016 and 2021 was obtained. Patients were divided into 2 groups-those with preoperative ultrasound-alone (US) and those with additional axial imaging (AX). Perioperative outcomes were compared utilizing univariate Chi-square, independent t-test, multivariate logistic regression, and Kaplan-Meier analysis. RESULTS: There were 3,418 patients identified: 682 in the US group and 2,736 in the AX group. More preoperative hypertension was reported in US (16.1% vs. 10.2%, P < 0.001) while cardiovascular disease (23% vs. 28.9%, P = 0.006) and prior ipsilateral stroke (22% vs. 32.7%, P = 0.002) were more prevalent in AX. More patients had history of contralateral carotid endarterectomy (13.6% vs. 16.7%, P = 0.035) or either ipsilateral (2.6% vs. 1.2%, P = 0.002) or contralateral (7.9% vs. 4.9%, P = 0.008) carotid artery stenting in the US group. Lower preoperative creatinine was reported in the US cohort (1.09 ± 0.01 vs. 1.18 ± 0.02, P < 0.001) while more were symptomatic in AX (28.2% vs. 36.2%, P < 0.001). There were no significant differences between lesion characteristics or operative decision making. A slightly higher total procedure time was seen in AX (73.7 ± 0.6 vs. 68.6 ± 1.3 min, P = 0.017). No differences were seen in perioperative transient ischemic attack/stroke or other immediate complications. At 2-year follow-up, both groups reported no significant differences in stroke-free survival (P = 0.750) and independent functional status remained near-identical (97.3% vs. 97.4%, P = 0.921). Kaplan-Meier analysis yielded no significant difference between mortality at 2 years (P = 0.563). Bivariate logistic regression modeling did reveal a statistically significant increase in likelihood of long-term ipsilateral stroke (odds ratio 1.77, P = 0.015) and non stroke-related complication in the postoperative period (odds ratio 4.81, P = 0.005). However, only a statistically significant relationship persisted in non-stroke complication when the model was controlled for between-group differences. CONCLUSIONS: No significant differences in postoperative or long-term complications were noted with additional AX in preoperative TCAR planning. Thus, duplex ultrasound offers a safe and effective alternative for those with contraindication or axial imaging.

Adversarial super-resolution of climatological wind and solar data.

Accurate and high-resolution data reflecting different climate scenarios are vital for policy makers when deciding on the development of future energy resources, electrical infrastructure, transportation networks, agriculture, and many other societally important systems. However, state-of-the-art long-term global climate simulations are unable to resolve the spatiotemporal characteristics necessary for resource assessment or operational planning. We introduce an adversarial deep learning approach to super resolve wind velocity and solar irradiance outputs from global climate models to scales sufficient for renewable energy resource assessment. Using adversarial training to improve the physical and perceptual performance of our networks, we demonstrate up to a [Formula: see text] resolution enhancement of wind and solar data. In validation studies, the inferred fields are robust to input noise, possess the correct small-scale properties of atmospheric turbulent flow and solar irradiance, and retain consistency at large scales with coarse data. An additional advantage of our fully convolutional architecture is that it allows for training on small domains and evaluation on arbitrarily-sized inputs, including global scale. We conclude with a super-resolution study of renewable energy resources based on climate scenario data from the Intergovernmental Panel on Climate Change's Fifth Assessment Report.

Studying Regioisomer Formation in the Pd-Catalyzed Fluorination of Cyclic Vinyl Triflates: Evidence for in situ Ligand Modification.

Pd-catalyzed nucleophilic fluorination reactions are important methods for the synthesis of fluoroarenes and fluoroalkenes. However, these reactions can generate a mixture of regioisomeric products that are often difficult to separate. While investigating the Pd-catalyzed fluorination of cyclic vinyl triflates, we observed that the addition of a substoichiometric quantity of TESCF3 significantly improved the regioselectivity of the reaction. Herein, we report a combined experimental and computational study on the mechanism of this transformation focusing on the role of TESCF3 . The poor regioselectivity of the reaction in the absence of additives results from the formation of LPd-cyclohexyne complexes (L=biaryl monophosphine ligand). When TESCF3 is added to the reaction mixture, the generation of the Pd-cyclohexyne complexes is diminished by an unexpected pathway involving the dearomatization of the ligand by nucleophilic attack from a trifluoromethyl anion (CF3 - ).

Metabolic Rewiring by Loss of Sirt5 Promotes Kras-Induced Pancreatic Cancer Progression.

BACKGROUND & AIMS: SIRT5 plays pleiotropic roles via post-translational modifications, serving as a tumor suppressor, or an oncogene, in different tumors. However, the role SIRT5 plays in the initiation and progression of pancreatic ductal adenocarcinoma (PDAC) remains unknown. METHODS: Published datasets and tissue arrays with SIRT5 staining were used to investigate the clinical relevance of SIRT5 in PDAC. Furthermore, to define the role of SIRT5 in the carcinogenesis of PDAC, we generated autochthonous mouse models with conditional Sirt5 knockout. Moreover, to examine the mechanistic role of SIRT5 in PDAC carcinogenesis, SIRT5 was knocked down in PDAC cell lines and organoids, followed by metabolomics and proteomics studies. A novel SIRT5 activator was used for therapeutic studies in organoids and patient-derived xenografts. RESULTS: SIRT5 expression negatively regulated tumor cell proliferation and correlated with a favorable prognosis in patients with PDAC. Genetic ablation of Sirt5 in PDAC mouse models promoted acinar-to-ductal metaplasia, precursor lesions, and pancreatic tumorigenesis, resulting in poor survival. Mechanistically, SIRT5 loss enhanced glutamine and glutathione metabolism via acetylation-mediated activation of GOT1. A selective SIRT5 activator, MC3138, phenocopied the effects of SIRT5 overexpression and exhibited antitumor effects on human PDAC cells. MC3138 also diminished nucleotide pools, sensitizing human PDAC cell lines, organoids, and patient-derived xenografts to gemcitabine. CONCLUSIONS: Collectively, we identify SIRT5 as a key tumor suppressor in PDAC, whose loss promotes tumorigenesis through increased noncanonic use of glutamine via GOT1, and that SIRT5 activation is a novel therapeutic strategy to target PDAC.

The Impact of COVID-19 on Routine Medical Care and Cancer Screening.

BACKGROUND: COVID-19 restrictions and fear dramatically changed the use of medical care. Understanding the magnitude of cancelled and postponed appointments and associated factors can help identify approaches to mitigate unmet need. OBJECTIVE: To determine the proportion of medical visits cancelled or postponed and for whom. We hypothesized that adults with serious medical conditions and those with higher anxiety, depressive symptoms, and avoidance-oriented coping would have more cancellations/postponements. DESIGN: Four nationally representative cross-sectional surveys conducted online in May, July, October, and December 2020. PARTICIPANTS: 59,747 US adults who completed 15-min online surveys. 69% cooperation rate. MEASURES: Physical and mental health visits and cancer screening cancelled or postponed over prior 2 months. Plan to cancel or postpone visits over the next 2 months. Relationship with demographics, medical conditions, local COVID-19 death rate, anxiety, depressive symptoms, coping, intolerance of uncertainty, and perceived COVID-19 risk. KEY RESULTS: Of the 58% (N = 34,868) with a medical appointment during the 2 months before the survey, 64% had an appointment cancelled or postponed in May, decreasing to 37% in December. Of the 41% of respondents with scheduled cancer screening, 20% cancelled/postponed, which was stable May to December. People with more medical conditions were more likely to cancel or postpone medical visits (OR 1.19 per condition, 95% CI 1.16, 1.22) and cancer screening (OR 1.20, 95% CI 1.15, 1.24). Race, ethnicity, and income had weak associations with cancelled/postponed visits, local death rate was unrelated, but anxiety and depressive symptoms were strongly related to cancellations, and this grew between May and December. CONCLUSIONS: Cancelled medical care and cancer screening were more common among persons with medical conditions, anxiety and depression, even after accounting for COVID-19 deaths. Outreach and support to ensure that patients are not avoiding needed care due to anxiety, depression and inaccurate perceptions of risk will be important.

Thoracic Endovascular Aortic Repair for Iatrogenic Injury of the Thoracic Aorta.

PURPOSE: Address iatrogenic injury to the descending thoracic aorta by breached spinal screws through a novel approach of concomitant spinal screw removal and thoracic endovascular repair (TEVAR) placement. CASE REPORT: A 36-year-old female with idiopathic scoliosis underwent T4 to L3 bilateral pedicle instrumentation with spinal fusion and correction of scoliosis deformity. Ten months post-operative, she continued to complain of mid-thoracic pain; computed tomography (CT) angiography revealed protrusion of the left T5 and T6 transpedicular screws into her descending thoracic aorta by 3 and 5 mm, respectively. She was taken to the odds ratio (OR) in a combination case with vascular and neurosurgery. Positioned in the right lateral decubitus position, TEVAR was successfully deployed while neurosurgery concurrently removed the invading spinal screws via posterior spinal exposure. Neurosurgery then completely revised the spinal hardware during the same operation. The patient progressed well throughout the remainder of her hospital stay and was discharged on postoperative day 4. Two-year angiography demonstrated a well-placed TEVAR with no extravasation or aortic abnormality. CONCLUSIONS: In the setting of iatrogenic aortic injury due to pedicle screws, concomitant TEVAR and spinal screw removal is a safe and feasible treatment option that allows for spinal reconstruction to occur without multiple trips to the operating room.

SARS-CoV-2 infections in professional orchestra and choir musicians-a prospective cohort study.

During the COVID-19 pandemic, rehearsal and concert activities of professional orchestras and choirs were severely restricted based on the assumption of particularly high infection risks associated with wind instruments and singing. Therefore, our primary objective was to determine the incidence of SARS-CoV-2 infections in orchestra and choir musicians compared to controls. We also assessed influenza, flu, upper respiratory tract infections, and course of illness. Musicians from professional orchestras and choirs and controls from 23 institutions throughout Germany were included in a prospective cohort study. Data were collected from October 2020 to June 2021 by weekly online surveys. A mixed-effects cox proportional hazards model was used to assess the effect of exposure by professional activity on SARS-CoV-2 infection. In 1,097 participants (46.7 years (SD 10.3); 46.8% female; 705 orchestra, 154 choir, and 238 control subjects) 40 SARS-CoV-2 infections occurred. Cases per person-years were 0.06 in orchestras, 0.11 in choirs, and 0.03 in controls. Hazard ratios compared to controls were 1.74 (95% CI 0.58 to 5.25, p = 0.320) for orchestra musicians and 2.97 (0.87 to 10.28, p = 0.087) for choir singers. Infection source was suspected predominantly in private contexts. Disease courses were mild to moderate. Other respiratory infections were reported in 6.1% of study weeks in orchestras, 10.1% in choirs, and 8.0% in controls. Sick leave days of total study days were 0.5, 2.1 and 1.3%, respectively. This epidemiologic study during the pandemic in professional musicians indicates no increased risk of SARS-CoV-2 infections in orchestra musicians and a trend towards increased risk in choir singers compared to controls. However, the exact routes of infection could not be validated. If appropriate hygiene concepts are adhered to, safe orchestra and choir activity appears possible in pandemic times.

Staging Endovascular Thoracic and Thoracoabdominal Aortic Aneurysm Repairs and the Risk of Post-operative Spinal Cord Ischemia.

OBJECTIVE: Staged aortic aneurysm repair is one method used to decrease the risk of spinal cord ischemia (SCI) following endovascular aortic intervention. Sequential sacrifice of arteries perfusing the spine may allow for improved spinal perfusion through the development of collateral networks over time. To evaluate the impact of staging endovascular aortic aneurysm repairs on SCI, we conducted a conservative analysis of Vascular Quality Initiative (VQI) data. METHODS: De-identified VQI data were queried for cases of endovascular thoracic and thoracoabdominal aneurysm repairs from year 2014 to 2019. Cases were selected based on inclusion criteria: aneurysmal disease, no ruptures, no prior aortic surgeries, no retreatments, and only cases with complete data on aortic zones and SCI. Chi-square, Student's t-tests, and Mann-Whitney U tests were used for univariable analyses, as appropriate. Logistic regression analyses were used to identify independent predictors of outcome. RESULTS: There were 116 staged aortic repairs (SARs) (8.2%) performed out of a total of 1421 endovascular aortic repairs that fit study criteria. The overall rate of SCI within the study cohort was 3.4% (n = 48). The distribution of SARs and SCI events according to aortic zone coverage are displayed in Table 1. Patients who underwent staged endovascular aortic repairs had higher rates of SCI, pre-op spinal drain placement, non-African-American race, COPD, smoking history, positive stress tests, aspirin and statin use, increased estimated blood loss, physician-modified endografts, number of aortic zones covered, lower pre-op hemoglobin levels, larger aneurysm sac size, fusiform aneurysms, and longer total procedure times, Table 2. After adjusting for factors associated with SCI, a priori, and factors with a P < 0.1 univariable analysis, SAR was not associated with SCI (odds ratio [OR] = 1.86, 95% confidence interval [CI] = 0.77-4.50, P = 0.17). Of the six factors associated with SCI on univariable analysis, only procedure time ≥6 hours (OR = 2.49, 95% CI = 1.09-5.70, P = 0.031) and the number of aortic zones covered (OR = 1.15, 95% CI = 1.00-1.32, P = 0.047) were predictive of SCI. Staged repairs had a lower proportion of permanent SCI (38%, 3 of 8 cases) compared with repairs that were not staged (68%, 27 of 40 cases), with a relative risk reduction of 44% for those who developed SCI, P = 0.21. CONCLUSIONS: In a large national data set, SARs were performed for patients with more extensive aortic disease. SARs were only performed in about 8% of cases and the rate of SCI remained low. After adjusting for baseline comorbidities, extent of aortic disease, and other factors that may potentiate SCI, staged aortic aneurysm repair had a similar risk of SCI compared with non-staged repairs. However, there was a trend toward decreased permanent SCI risk in the SAR group.

Effects of training oncology physicians advising patients on complementary and integrative therapies on patient-reported outcomes: A multicenter, cluster-randomized trial.

BACKGROUND: Many patients with cancer do not disclose complementary medicine use but want their physician's advice on this matter. This study evaluated whether using blended learning (e-learning plus a workshop) to train oncology physicians in providing advice on complementary and integrative medicine (CIM) therapies to their patients with cancer, in addition to distributing an information leaflet on reputable CIM websites, had different effects on patient-reported outcomes for the consultation than only distributing the leaflet. METHODS: In this multicenter, cluster-randomized trial, patients from private practices/hospital departments, recruited by 48 oncology physicians randomly allocated to an intervention group (CIM consultation plus information leaflet) or a control group (information leaflet), received CIM information. Patient-reported outcomes included satisfaction (Patient Satisfaction With Information on Cancer Treatment), readiness to make a decision (Preparation for Decision Making), and physician-patient communication (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and Communication 26 [EORTC QLQ-COMU26]) for the consultation. Qualitative interviews were conducted with a physician subsample. RESULTS: A total of 291 patients (128 in the intervention group and 169 in the control group) advised by 41 physicians participated. Patients in the intervention group rated physician-patient communication higher on all EORTC QLQ-COMU26 scales (mean total score, 84.3 [95% CI, 79.5-89.2] vs 73.6 [95% CI, 69.3-78.0]; P = .002), were more satisfied with the advice (mean, 4.2 [95% CI, 4.0-4.4] vs 3.7 [95% CI, 3.5-3.8]; P < .001), and were readier to make a decision (mean, 63.5 [95% CI, 57.4-69.6] vs 53.2 [95% CI, 47.8-58.7]; P = .016) than the control group. Physicians who reported patients in both settings seemed satisfied with the advice given. CONCLUSIONS: This study evaluated a novel education intervention for training oncology physicians in providing CIM advice in routine care. Providing structured CIM consultations had positive effects on patient satisfaction, readiness to make decisions, and physician-patient communication.

Age-based outcomes of autogenous fistulas for hemodialysis access.

BACKGROUND: Hemodialysis (HD) dependence and autogenous fistula use for HD span the spectrum of age. This study examines age-related outcomes of autogenous fistulas for HD access in a large population-based cohort of patients. METHODS: A retrospective cohort study of all patients who initiated HD in the United States Renal Database System (2007-2014). χ2 tests, t tests, Kaplan-Meier, log-rank tests, multivariable logistic, and Cox regression analyses were employed to evaluate access maturation, interventions, patency, and mortality. RESULTS: Of the 303,281 patients studied, 48,892 (16.1%) were younger than 50 years, 55,817 (18.4%) were 50 to 59 years, 79,138 (26.1%) were 60 to 69 years, 75,200 (24.8%) were 70 to 79 years, and 44,234 (14.6%) were 80 years or older. There was a decrease in autogenous fistula maturation with increasing age. Primary patency at 5 years comparing patients <50 vs 50 to 59 vs 60 to 69 vs 70 to 79 vs 80+ years was 24% vs 23% vs 21% vs 20% vs 18% (P < .001). Primary assisted patency at 5 years was 38% vs 40% vs 37% vs 35% vs 33% (P < .001). Secondary patency at 5 years was 48% vs 50% vs 47% vs 45% vs 42% (P < .001). The risk-adjusted analyses revealed a progressive decrease in primary, primary assisted, and secondary patency with increasing age. As expected, patient survival decreased with increasing age. CONCLUSIONS: In this population-based cohort of HD patients, there was a decrease in autogenous fistula maturation, primary patency, primary assisted patency, secondary patency, and patient survival with increasing age. Despite the relative decline in outcomes associated with older age, decisions about arteriovenous access creation in older patients should be individualized, taking overall clinical status and outcomes of alternatives modes of access into consideration.

FLASH: a next-generation CRISPR diagnostic for multiplexed detection of antimicrobial resistance sequences.

The growing prevalence of deadly microbes with resistance to previously life-saving drug therapies is a dire threat to human health. Detection of low abundance pathogen sequences remains a challenge for metagenomic Next Generation Sequencing (NGS). We introduce FLASH (Finding Low Abundance Sequences by Hybridization), a next-generation CRISPR/Cas9 diagnostic method that takes advantage of the efficiency, specificity and flexibility of Cas9 to enrich for a programmed set of sequences. FLASH-NGS achieves up to 5 orders of magnitude of enrichment and sub-attomolar gene detection with minimal background. We provide an open-source software tool (FLASHit) for guide RNA design. Here we applied it to detection of antimicrobial resistance genes in respiratory fluid and dried blood spots, but FLASH-NGS is applicable to all areas that rely on multiplex PCR.

Evaluating the contribution of rare variants to type 2 diabetes and related traits using pedigrees.

A major challenge in evaluating the contribution of rare variants to complex disease is identifying enough copies of the rare alleles to permit informative statistical analysis. To investigate the contribution of rare variants to the risk of type 2 diabetes (T2D) and related traits, we performed deep whole-genome analysis of 1,034 members of 20 large Mexican-American families with high prevalence of T2D. If rare variants of large effect accounted for much of the diabetes risk in these families, our experiment was powered to detect association. Using gene expression data on 21,677 transcripts for 643 pedigree members, we identified evidence for large-effect rare-variant cis-expression quantitative trait loci that could not be detected in population studies, validating our approach. However, we did not identify any rare variants of large effect associated with T2D, or the related traits of fasting glucose and insulin, suggesting that large-effect rare variants account for only a modest fraction of the genetic risk of these traits in this sample of families. Reliable identification of large-effect rare variants will require larger samples of extended pedigrees or different study designs that further enrich for such variants.

Traumatic cervical spine fracture patterns on CT: a retrospective analysis at a level 1 trauma center.

PURPOSE: The purpose of our study was to determine common acute traumatic cervical spine fracture patterns on CT cervical spine (CTCS). METHODS: We retrospectively reviewed 1091 CTCS positive for traumatic fractures performed over a 10-year period at a level 1 trauma center. Fractures were classified by vertebral level, laterality, and anatomic location (anterior/posterior arch, body, odontoid, pedicle, facet, lateral mass, lamina, spinous process, transverse foramina, and transverse processes). RESULTS: C2 was the most commonly fractured vertebra (38% of all studies), followed by C7 (32.4%). 48.7% of studies had upper cervical spine (C1 and/or C2) fractures. 39.7% of positive studies involved > 1 vertebral level. Conditioned on fractures at one cervical level, the probability of fracture was greatest at adjacent levels with a 50% chance of sustaining a C7 fracture with C6 fracture. However, 31.3% (136) of studies with multi-level fractures had non-contiguous fractures. The most common isolated vertebral process fracture was of the transverse process, seen in 89 (8.2%) studies at a single level, 27 (2.5%) studies at multiple levels. Subaxial spine vertebral process fractures outnumbered body fractures with progressive dominance of vertebral process fracture down the spine. CONCLUSION: C2 was the most commonly fractured vertebral level. Multi-level traumatic cervical spine fractures constituted 40% of our cohort, most commonly at C6/C7 and C1/C2. Although the conditional probability of concurrent fracture in studies with multi-level fractures was greatest in contiguous levels, nearly one-third of multi-level fractures involved non-contiguous fractures.

Canine calvarial subperiosteal hematomas are fluid to soft tissue attenuating mass-like lesions with smoothly marginated peripheral mineralization on CT.

Subperiosteal hematomas are accumulations of blood between a bone and the periosteum leading to elevation of the periosteum. When ossified they have a mineralized outer rim. For this retrospective, multi-institutional case series, medical records were searched to identify dogs that underwent CT for focal calvarial swellings noted acutely after trauma. A total of four dogs were included. Computed tomography images were reviewed for each case. The focal swellings had progressed in size during the weeks after the head trauma until the time of imaging. Findings in all cases included a fluid to soft tissue attenuating mass-like lesion with smoothly marginated peripheral mineralization. Diagnosis was confirmed in two cases by cytology and/or histopathology. Therefore, authors recommend that subperiosteal hematoma be included in the differential diagnosis list for dogs with these clinical and CT characteristics. Based on our review of the literature, this is the first report to describe the CT features of calvarial subperiosteal hematomas in dogs.