Cardiovascular disease risk factors and their associations with inflammation among US adolescents: NHANES, 2015 to March 2020.

INTRODUCTION: The prevalence of obesity and glycemic dysfunction in adolescents has increased over the past several decades but less is known on how these conditions are associated with systemic inflammation in this population. This study determined the associations between cardiovascular disease (CVD) risk factors and inflammation among a nationally representative sample of US. adolescents. RESEARCH DESIGN AND METHODS: Cross-sectional analyses were conducted among 2693 adolescents aged 12-19 years who participated in the 2015 to March 2020 National Health and Nutrition Examination Surveys. Chronic inflammation was determined using laboratory measures for high-sensitivity C reactive protein (hs-CRP). Adjusted ORs (aOR, 95% CI) were calculated from logistic regression models to determine the association between CVD risk factors (obesity, overweight, dysglycemia, hypertension, hyperlipidemia) and elevated hs-CRP (>3.0 mg/L) while controlling for sociodemographic characteristics and other CVD risk factors. RESULTS: Overall, 15.3% of adolescents had elevated hs-CRP. Adolescents who were older (16-19 years vs 12-15 years), obese, had A1c ≥5.7% (≥39 mmol/mol), high total cholesterol, or low high-density lipoprotein had hs-CRP distributions that were more high risk (χ2 p value <0.001). Adolescents with obesity or A1c ≥5.7% had a sixfold and a nearly twofold higher odds of elevated hs-CRP compared those without obesity and A1c <5.7% after full adjustment (aOR=6.39, 4.64 to 8.79 and aOR=1.70, 1.05 to 3.06, respectively). Adolescents with hypertension or hyperlipidemia were significantly more likely to have elevated hs-CRP compared with those without these conditions after adjustment for sociodemographic characteristics (aOR=2.46, 1.08 to 5.60 and aOR=2.19, 1.36 to 3.54, respectively), but the association was not significant after further adjustment for obesity. CONCLUSIONS: Among US adolescents, obesity was strongly associated with elevated hs-CRP, a marker for future CVD risk. Given the obesity epidemic and the marked proportion with elevated CRP, concern should be given to future CVD risk in younger adults.

American Society for Gastrointestinal Endoscopy guideline on the role of endoscopy in the management of chronic pancreatitis: summary and recommendations.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based approach for the role of endoscopy in the management of chronic pancreatitis (CP). This document was developed using the Grading of Recommendations Assessment, Development and Evaluation framework. The guideline addresses effectiveness of endoscopic therapies for the management of pain in CP, including celiac plexus block, endoscopic management of pancreatic duct (PD) stones and strictures, and adverse events such as benign biliary strictures (BBSs) and pseudocysts. In patients with painful CP and an obstructed PD, the ASGE suggests surgical evaluation in patients without contraindication to surgery before initiation of endoscopic management. In patients who have contraindications to surgery or who prefer a less-invasive approach, the ASGE suggests an endoscopic approach as the initial treatment over surgery, if complete ductal clearance is likely. When a decision is made to proceed with a celiac plexus block, the ASGE suggests an EUS-guided approach over a percutaneous approach. The ASGE suggests indications for when to consider ERCP alone or with pancreatoscopy and extracorporeal shock wave lithotripsy alone or followed by ERCP for treating obstructing PD stones based on size, location, and radiopacity. For the initial management of PD strictures, the ASGE suggests using a single plastic stent of the largest caliber that is feasible. For symptomatic BBSs caused by CP, the ASGE suggests the use of covered metal stents over multiple plastic stents. For symptomatic pseudocysts, the ASGE suggests endoscopic therapy over surgery. This document clearly outlines the process, analyses, and decision processes used to reach the final recommendations and represents the official ASGE recommendations on the above topics.

COVID-19 deaths in dental occupations and other healthcare occupations among U.S. decedents in 2020.

BACKGROUND: Early studies during the COVID-19 pandemic suggested dental occupations were among the highest risk for exposure to SARs-CoV-2 because of multiple factors increasing exposure, including close proximity to unmasked patients and performance of aerosol-generating procedures. However, to date, few studies have investigated COVID-19 deaths in United States dental occupations, and compared COVID-19 deaths among healthcare occupations. METHODS: We analyzed 2020 mortality data collected by the National Center for Health Statistics' National Vital Statistics System. Multivariable logistic regression was used to generate odds ratios (ORs) and 95% confidence intervals for COVID-19 as the underlying cause of death in relation to occupation in working-age decedents (≤65 years), after adjusting for age, sex, race/ethnicity, education, and medical conditions associated with severe COVID-19. RESULTS: Dental occupations did not have significantly higher risk for COVID-19 death when compared to all other occupations combined. Among healthcare occupations with frequent, direct patient- or client interactions, LPNs and LVNs, and speech and language pathologists had significantly elevated adjusted ORs for COVID-19 death when compared to dentists, dental hygienists, or dental assistants. Similarly, nurse practitioners had significantly higher ORs for COVID-19 mortality than dentists or dental hygienists, and approached significance when compared to dental assistants. Conversely, massage therapists and other health diagnosing and treating practitioners had significantly lower adjusted ORs for COVID-19 death compared with dental occupations. CONCLUSION: Our study highlights potential differences in work-related transmission of SARs-CoV-2 and subsequent COVID-19 deaths in healthcare occupations, and furthers a previously limited understanding of COVID-19 deaths in healthcare occupations in 2020, before COVID-19 vaccine availability. Our results indicate that dental occupations were not among the highest, nor lowest risk, healthcare occupations for COVID-19 deaths in 2020, despite their known risks of direct exposure.

Probabilistic Estimation of Cadence and Walking Speed From Floor Vibrations.

OBJECTIVE: This research aims to extract human gait parameters from floor vibrations. The proposed approach provides an innovative methodology on occupant activity, contributing to a broader understanding of how human movements interact within their built environment. METHODS AND PROCEDURES: A multilevel probabilistic model was developed to estimate cadence and walking speed through the analysis of floor vibrations induced by walking. The model addresses challenges related to missing or incomplete information in the floor acceleration signals. Following the Bayesian Analysis Reporting Guidelines (BARG) for reproducibility, the model was evaluated through twenty-seven walking experiments, capturing floor vibration and data from Ambulatory Parkinson's Disease Monitoring (APDM) wearable sensors. The model was tested in a real-time implementation where ten individuals were recorded walking at their own selected pace. RESULTS: Using a rigorous combined decision criteria of 95% high posterior density (HPD) and the Range of Practical Equivalence (ROPE) following BARG, the results demonstrate satisfactory alignment between estimations and target values for practical purposes. Notably, with over 90% of the 95% HPD falling within the region of practical equivalence, there is a solid basis for accepting the estimations as probabilistically aligned with the estimations using the APDM sensors and video recordings. CONCLUSION: This research validates the probabilistic multilevel model in estimating cadence and walking speed by analyzing floor vibrations, demonstrating its satisfactory comparability with established technologies such as APDM sensors and video recordings. The close alignment between the estimations and target values emphasizes the approach's efficacy. The proposed model effectively tackles prevalent challenges associated with missing or incomplete data in real-world scenarios, enhancing the accuracy of gait parameter estimations derived from floor vibrations. CLINICAL IMPACT: Extracting gait parameters from floor vibrations could provide a non-intrusive and continuous means of monitoring an individual's gait, offering valuable insights into mobility and potential indicators of neurological conditions. The implications of this research extend to the development of advanced gait analysis tools, offering new perspectives on assessing and understanding walking patterns for improved diagnostics and personalized healthcare.Clinical and Translational Impact Statement: This manuscript introduces an innovative approach for unattended gait assessments with potentially significant implications for clinical decision-making. By utilizing floor vibrations to estimate cadence and walking speed, the technology can provide clinicians with valuable insights into their patients' mobility and functional abilities in real-life settings. The strategic installation of accelerometers beneath the flooring of homes or care facilities allows for uninterrupted daily activities during these assessments, reducing the reliance on specialized clinical environments. This technology enables continuous monitoring of gait patterns over time and has the potential for integration into healthcare platforms. Such integration can enhance remote monitoring, leading to timely interventions and personalized care plans, ultimately improving clinical outcomes. The probabilistic nature of our model enables uncertainty quantification in the estimated parameters, providing clinicians with a nuanced understanding of data reliability.

Perioperative risks associated with administration of andexanet alfa during emergency cardiac surgery with circulatory arrest.

This case report describes the perioperative course of a patient undergoing emergency repair of acute type A thoracic aortic dissection. Andexanet alfa was administered intraoperatively to obtain a dry operative field for right axillary artery exposure and cannulation. Andexanet alfa-induced heparin resistance resulted in cardiopulmonary bypass circuit and pericardial thrombosis requiring more than 400,000 units of unfractionated heparin and antithrombin III to overcome. Postoperatively, excessive chest tube output was observed secondary to protracted heparin rebound requiring continuous dosing of protamine. This case demonstrates the significant challenging perioperative, not just intraoperative, hazards associated with intraoperative andexanet alfa use during emergency cardiac surgery with cardiopulmonary bypass.

Impact of eccentric cycling in coronary rehabilitation program: a pragmatic randomized controlled trial versus conventional rehabilitation.

BACKGROUND: This randomized controlled trial examined the feasibility of adding eccentric exercise to a conventional cardiac rehabilitation program (CCRP) for coronary heart disease patients. METHODS: Ninety-three patients were randomly assigned to either the MIX group (eccentric ergometer + CCRP) or the CON group (concentric ergometer + CCRP) for 7 weeks. Training effectiveness was assessed based on "good responders" showing improved functional capacities, such as 6-minute walk test (6MWT) distance and maximal voluntary contraction of the plantar flexors (ankle MVC). Safety was monitored with a visual analog scale for muscle soreness, perceived exertion, and heart rate during training. RESULTS: The proportion of good responders was similar between groups (26% in MIX, 29% in CON, P=0.744). Both groups improved in 6MWT (CON: 12.6%, MIX: 16.14%) and ankle MVC (CON: 15.5%, MIX: 11.30%), with no significant differences. Exercise tolerance did not differ significantly between the groups, but perceived effort was significantly lower in the MIX group (P<0.0001) compared to the CON group. CONCLUSIONS: Integrating eccentric exercise into cardiac rehabilitation is safe and well-tolerated. Nevertheless, this study did not find significant advantages over conventional programs for coronary heart disease patients. Further research should explore specific patient groups or conditions where eccentric exercise may be more beneficial, emphasizing personalized prescriptions and gradual workload progression for better cardiac rehabilitation outcomes.

Hyperfibrinolysis during the treatment of rhabdomyosarcoma.

Background: Coagulopathies are frequently observed in alveolar rhabdomyosarcoma (ARMS), with disseminated intravascular coagulation (DIC) being the most common presentation. However, hyperfibrinolysis represents a distinct but often overlapping and potentially life-threatening subset of coagulation disorders that requires specific diagnostic and management approaches. Key Clinical Question: How can clinicians identify hyperfibrinolysis and what are the implications for management? Clinical Approach: This case report describes a 25-year-old man with metastatic ARMS arising from the prostate who developed persistent gross hematuria one week after initiating chemotherapy. A comprehensive coagulation workup was performed, including assessment of platelet count, prothrombin time, activated partial thromboplastin time, fibrinogen, D-dimer, and fibrin degradation products. Management included repletion of fibrinogen and the use of anti-fibrinolytic agents. Conclusion: Recognizing hyperfibrinolysis in ARMS patients is crucial for appropriate management. Clinicians should maintain a high index of suspicion for hyperfibrinolysis in ARMS patients presenting with severe coagulation abnormalities, particularly those with prostatic involvement or undergoing chemotherapy. In cases of primary hyperfibrinolysis, antifibrinolytic agents may be considered, whereas they are generally contraindicated in DIC.

CD4+ T cell-associated cytokines induce a chronic pro-inflammatory phenotype in induced pluripotent stem cell-derived midbrain astrocytes.

Astrocytes are mediators of homeostasis but contribute to neuroinflammation in Parkinson's disease (PD). Mounting evidence suggests involvement of peripheral immune cells in PD pathogenesis. Therefore, this study aimed to determine the potential role of peripheral immune secreted cytokines in modulating midbrain astrocyte reactivity. Human iPSC-derived midbrain astrocytes were exposed to 5% and 10% CD4+ T cell conditioned media (CD4CM) for 24 h, 72 h, and 7 days to assess chronic exposure. Additionally, astrocytes were exposed to the Th17 cell cytokine, IL-17A (10 ng/mL), alone and in combination with TNF-α (0.3 ng/mL) to assess potential synergistic effects of both cytokines at 24 h, 72 h, and 7 days. CD4CM induced acute and chronic alterations in midbrain astrocytes. Increased NFκB translocation to the nucleus, increased expression of the pro-inflammatory genes, IL-1ß, CXCL10 at 24 h, C3, LCN2, IL-6 at 24 and 48 h, as well as an increase in their release of pro-inflammatory cytokines IL-6 and CXCL10 at both these time points were observed. A synergistic response to the combination of IL-17A and TNF-α on increasing inflammatory gene expression and cytokine release occurred. IL-17A and TNF-α increased intensity of S100ß at 24 h, decreased nuclear area and increased circularity of astrocytes at 72 h. A synergistic effect on γH2AX intensity at 72 h and an increase in LDH release at 7 days was observed. Our results demonstrate that IL-17A and TNF-α act synergistically, enhancing midbrain astrocyte reactivity to a similar degree as CD4CM. This highlights the importance of the peripheral immune secreted cytokines in increasing the reactivity status of midbrain astrocytes, implicating their role in PD.

Feasibility and preliminary effects of the Fit2ThriveMB pilot physical activity promotion intervention on physical activity and patient reported outcomes in individuals with metastatic breast cancer.

PURPOSE: Physical activity research among patients with metastatic breast cancer (MBC) is limited. This study examined the feasibility and potential benefits of Fit2ThriveMB, a tailored mHealth intervention. METHODS: Insufficiently active individuals with MBC (n = 49) were randomized 1:1 to Fit2ThriveMB (Fit2ThriveMB app, Fitbit, and weekly coaching calls) or Healthy Lifestyle attention control (Cancer.Net app and weekly calls) for 12 weeks. Fit2ThriveMB aimed to increase daily steps via an algorithm tailored to daily symptom rating and step goal attainment. The primary outcome was feasibility defined as ≥ 80% completion rate. Secondary feasibility metrics included meeting daily step goal and wearing the Fitbit ≥ 70% of study days, fidelity, adherence to intervention features and safety. Secondary outcomes included physical activity, sedentary time, patient reported outcomes (PROs), health-related quality of life (QOL) and social cognitive theory constructs. A subsample (n = 25) completed functional performance tests via video conferencing. RESULTS: The completion rate was 98% (n = 1 died). No related adverse events were reported. Fit2ThriveMB participants (n = 24) wore the Fitbit 92.7%, met their step goal 53.1%, set a step goal 84.6% and used the app 94.1% of 84 study days. Intent-to-treat analyses indicated trends toward improvements in activity, QOL, and some PROs, social cognitive theory constructs, and functional performance tests favoring the Fit2ThriveMB group. Significant effects favoring Fit2ThriveMB were observed for self-efficacy and goal-setting. However, some PROs and functional performance improvements favored the control group (p-values > 0.05). CONCLUSIONS: Fit2ThriveMB is feasible and safe for patients with MBC and warrants further evaluation in randomized controlled trials with larger sample sizes. Registration Clinicaltrials.gov NCT04129346, https://clinicaltrials.gov/ct2/show/NCT04129346.

Are clinics not affiliated with a Menopause Society Certified Practitioner more likely to offer guideline-nonconcordant treatment compared to clinics affiliated with a Menopause Society Certified Practitioner?

OBJECTIVE: To identify clinics in Ohio, Michigan, and Pennsylvania that advertise menopause treatment on their website and evaluate whether clinics not affiliated with a Menopause Society Certified Practitioner (MSCP) are more likely to offer guideline-nonconcordant treatment compared to clinics affiliated with an MSCP. METHODS: We performed an Internet search to identify clinics advertising on their website menopause treatment in Ohio, Michigan, and Pennsylvania. We checked clinic personnel against The Menopause Society directory of practitioners to determine if the clinic was affiliated with an MSCP. RESULTS: We identified 174 clinics (41% in OH, 28% in PA, and 31% in MI). Thirteen percent of clinics were affiliated with an MSCP. Clinics with an MSCP are significantly less likely to advertise hormone testing (primary outcome; odds ratio [OR], 0.11; 95% confidence interval, 0.02-0.39), compounded hormone therapy (OR, 0.06; 95% confidence interval, 0.001-0.41), and bioidentical hormone therapy (OR, 0.07; 95% confidence interval, 0.001-0.26), compared to clinics without an MSCP-affiliated clinics that are also less likely to advertise that hormone therapy will help maintain youth or help with weight loss. CONCLUSIONS: Our pilot study has shown that in the states of Ohio, Michigan, and Pennsylvania, clinics with an MSCP were more likely to advertise on their website an adherence to The Menopause Society's guidelines and not advertise for compounded or bioidentical hormones, recommend hormone testing, or advertise hormones for a youthful appearance or weight loss.

Breast Arterial Calcifications on Mammography: Awareness and Reporting Preferences Amongst Referring Physicians in Canada.

Purpose: Breast arterial calcifications (BAC) on mammography have been correlated with increased cardiovascular risk. The Canadian Society of Breast Imaging released a position statement on BAC reporting in January 2023. This study evaluates the awareness of the clinical significance of BAC and reporting preferences of referring physicians in Canada. Methods: A 15-question survey was distributed to Canadian physicians who may review mammography results via regional and subspecialty associations and on social media following local institutional ethical approval. Responses were collected over 10 weeks from February to April 2023. Results: Seventy-two complete responses were obtained. We are unable to determine the response rate, given the means of distribution. Only 17% (12/72) of responding physicians were previously aware of the association between BAC and increased cardiovascular risk, and 51% (37/72) preferred the inclusion of BAC in the mammography report. Fifty-six percent (40/72) indicated that BAC reporting would prompt further investigation, and 63% (45/72) would inform patients that their mammogram showed evidence of BAC. Sixty-nine percent (50/72) would find grading of BAC beneficial and 71% (51/72) agreed that there is a need for national guidelines. Conclusion: Less than a quarter of responding Canadian referring physicians were previously aware of the association between BAC and cardiovascular risk, although half of respondents indicated a preference for BAC reporting on mammography. Most participating physicians would inform their patients of the presence of BAC and consider further cardiovascular risk management. There was consensus that a national BAC grading system and clinical management guidelines would be beneficial.

Reversal of direct oral anticoagulants: guidance from the SSC of the ISTH.

The currently approved direct oral anticoagulants (DOACs) are increasingly used in clinical practice. Although serious bleeding risks are lower with DOACs than with vitamin K antagonists, bleeding remains the most frequent side effect. Andexanet alfa and idarucizumab are the currently approved specific reversal agents for oral factor (F)Xa inhibitors and dabigatran, respectively. Our prior guidance document was published in 2016, but with more information available on the utility and increased use of these reversal agents and other bleeding management strategies, we have updated this International Society on Thrombosis and Haemostasis guidance document on DOAC reversal. In this narrative review, we compare the mechanism of action of specific and nonspecific reversal agents, review the clinical data supporting their use, and provide guidance on when reversal is indicated. In addition, we briefly discuss the reversal of oral FXIa inhibitors, a new class of DOACs currently under clinical development.

Genetic Ancestry and Self-Reported "Skin Color/Race" in the Urban Admixed Population of São Paulo City, Brazil.

Epidemiological studies frequently classify groups based on phenotypes like self-reported skin color/race, which inaccurately represent genetic ancestry and may lead to misclassification, particularly among individuals of multiracial backgrounds. This study aimed to characterize both global and local genome-wide genetic ancestries and to assess their relationship with self-reported skin color/race in an admixed population of Sao Paulo city. We analyzed 226,346 single-nucleotide polymorphisms from 841 individuals participating in the population-based ISA-Nutrition study. Our findings confirmed the admixed nature of the population, demonstrating substantial European, significant Sub-Saharan African, and minor Native American ancestries, irrespective of skin color. A correlation was observed between global genetic ancestry and self-reported color-race, which was more evident in the extreme proportions of African and European ancestries. Individuals with higher African ancestry tended to identify as Black, those with higher European ancestry tended to identify as White, and individuals with higher Native American ancestry were more likely to self-identify as Mixed, a group with diverse ancestral compositions. However, at the individual level, this correlation was notably weak, and no deviations were observed for specific regions throughout the individual's genome. Our findings emphasize the significance of accurately defining and thoroughly analyzing race and ancestry, especially within admixed populations.

Evaluation of knowledge and practices on antibiotic use: a cross-sectional study on self-reported adherence to short-term antibiotic utilization among patients visiting level-1 hospitals in Lusaka, Zambia.

Background: Antimicrobial resistance (AMR) is a global public health problem affecting healthcare systems. Short-term antibiotic non-adherence is thought to be one of the factors contributing to antibiotic resistance. This study aimed to evaluate knowledge and practices towards short-term antibiotic use on self-reported adherence among patients visiting level-1 hospitals in Lusaka, Zambia. Methods: This was a multicentre institutional-based cross-sectional study conducted among 385 adult participants from 11 September to 30 September 2023 using an adopted structured questionnaire. Analysis of the data involved descriptive and inferential statistics, where significance was determined at P < 0.05. Results: Of the 335 participants, 56.7% displayed good knowledge and 77.3% low adherence towards antibiotic use. 54.6% thought that antibiotics were effective for viral infections, and 43.9% correctly recognized the definition of AMR. Being in formal employment (crude OR: 2.5, CI: 1.08-5.78, P: 0.032) was significantly associated with a higher likelihood of good knowledge about antibiotics while being divorced (adjusted OR: 2.5, CI: 1.23-6.10, P: 0.013) and having good knowledge (adjusted OR: 2.9, CI: 1.73-5.10, P = 0.048) were significantly associated with a higher likelihood of adherence to antibiotics. Regarding antibiotic practices, half (50. 0%) of the respondents had utilized antibiotics in the previous year while 58.2% had taken antibiotics for addressing a common cold. Furthermore, 74% reported to have bought antibiotics without a prescription. Conclusions: This study found that participants attending level-1 hospitals had relatively good knowledge and poor adherence towards antibiotic use. Additionally, the participants demonstrated poor antibiotic use practices in almost all statements related to antibiotic usage.

Electronic alerts to improve management of heparin-induced thrombocytopenia.

Background: Heparin-induced thrombocytopenia (HIT) is a difficult clinicopathologic diagnosis to make and to treat. Delays in identification and appropriate treatment can lead to increased morbidity and mortality. Objectives: To use electronic health alert interventions to improve provider diagnosis and management of heparin-induced thrombocytopenia through guideline-based, accurate care delivery. Methods: This quality improvement initiative developed 3 electronic health record-based interventions at our 750-bed academic medical center to improve the initial management of suspected HIT between 2018 and 2021: 1. an interruptive alert to recommend discontinuation of active heparin products when signing a heparin-platelet factor 4 test (PF4) order, 2. integrated 4T score calculation in the heparin-PF4 test order, and 3. interruptive alert suggesting not to order heparin-PF4 tests when the 4T score is <4. Changes in practice were assessed over defined time periods pre and post each intervention. Results: Intervention 1 resulted in heparin discontinuation in more patients, with 65% (191 heparin orders/293 heparin-PF4 enzyme-linked immunosorbent assay tests) of cases continuing heparin prealert and only 54% (127 heparin orders/235 heparin-PF4 enzyme-linked immunosorbent assay tests) postinterruptive alert (95% CI 2.3-19.9; P = .015). Intervention 2 increased appropriate heparin-PF4 test ordering from 40.4% (110/272) preintervention to 79.1% (246/311) (95% CI 30.9-46.4; P < .00001) postintervention, with inappropriate PF4 ordering defined as testing when 4T score was <4. Intervention 3 did not lead to reduction in heparin-PF4 testing in the control group (96 inappropriate orders/402 total orders, 24%) compared to the randomized alert group (56 inappropriate orders/298 total orders; 19%) (95% CI -1.2 to 11.5; P = .13). Conclusion: Implementation of unique electronic health record interventions, including both diagnostic and management interventions, led to improved guideline-based, accurate care delivery with 4T score calculation and cessation of heparin for patients with suspected HIT.

TEMPORARY REMOVAL: American Society for Gastrointestinal Endoscopy guideline on the role of therapeutic EUS in the management of biliary tract disorders: summary and recommendations.

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Faecal immunochemical tests can improve colonoscopy triage in patients with iron deficiency: A systematic review and meta-analysis.

BACKGROUND: Use of the faecal immunochemical test (FIT) to triage patients with iron deficiency (ID) for colonoscopy due to suspected colorectal cancer (CRC) may improve distribution of colonoscopic resources. We reviewed the diagnostic performance of FIT for detecting advanced colorectal neoplasia, including CRC and advanced pre-cancerous neoplasia (APCN), in patients with ID, with or without anaemia. METHODS: We performed a systematic review of three databases for studies comprising of patients with ID, with or without anaemia, completing a quantitative FIT within six months prior to colonoscopy, where test performance was compared against the reference standard colonoscopy. Random effects meta-analyses determined the diagnostic performance of FIT for advanced colorectal neoplasia. RESULTS: Nine studies were included on a total of n=1761 patients with ID, reporting FIT positivity thresholds between 4-150 µg haemoglobin/g faeces. Only one study included a non-anaemic ID (NAID) cohort. FIT detected CRC and APCN in ID patients with 90.7 % and 49.3 % sensitivity, and 81.0 % and 82.4 % specificity, respectively. FIT was 88.0 % sensitive and 83.4 % specific for CRC in patients with ID anaemia at a FIT positivity threshold of 10 µg haemoglobin/g faeces. CONCLUSIONS: FIT shows high sensitivity for advanced colorectal neoplasia and may be used to triage those with ID anaemia where colonoscopic resources are limited, enabling those at higher risk of CRC to be prioritised for colonoscopy. There is a need for further research investigating the diagnostic performance of FIT in NAID patients.

Portal Vein Doppler Is a Sensitive Marker for Evaluating Venous Congestion in End-Stage Kidney Disease.

INTRODUCTION: Determining ultrafiltration volume in patients undergoing intermittent hemodialysis (IHD) is an essential component in the assessment and management of volume status. Venous excess ultrasound (VExUS) is a novel tool used to quantify the severity of venous congestion at the bedside. Given the high prevalence of pulmonary hypertension in patients with end-stage kidney disease (ESKD), venous Doppler could represent a useful tool to monitor decongestion in these patients. METHODS: This is a prospective observational study conducted in ESKD patients who were admitted to the hospital requiring IHD and ultrafiltration. Inferior vena cava maximum diameter (IVCd), portal vein Doppler (PVD), and hepatic vein Doppler (HVD) were performed in all patients before and after a single IHD session. RESULTS: Forty-one patients were included. The prevalence of venous congestion was 88% based on IVCd and 63% based on portal vein pulsatility fraction (PVPF). Both mean IVCd and PVPF displayed a significant improvement after ultrafiltration. The percent decrease in PVPF was significantly larger than the percent decrease in IVCd. HVD alterations did not significantly improve after ultrafiltration. CONCLUSIONS: Our study revealed a high prevalence of venous congestion in hospitalized ESKD patients undergoing hemodialysis. After a single IHD session, there was a significant improvement in both IVCd and PVPF. HVD showed no significant improvement with one IHD session. PVPF changes were more sensitive than IVCd changes during volume removal. This study suggests that, due to its rapid response to volume removal, PVD, among the various components of the VExUS grading system, could be more effective in monitoring real-time decongestion in patients undergoing IHD.

The genomic and cellular basis of biosynthetic innovation in rove beetles.

How evolution at the cellular level potentiates macroevolutionary change is central to understanding biological diversification. The >66,000 rove beetle species (Staphylinidae) form the largest metazoan family. Combining genomic and cell type transcriptomic insights spanning the largest clade, Aleocharinae, we retrace evolution of two cell types comprising a defensive gland-a putative catalyst behind staphylinid megadiversity. We identify molecular evolutionary steps leading to benzoquinone production by one cell type via a mechanism convergent with plant toxin release systems, and synthesis by the second cell type of a solvent that weaponizes the total secretion. This cooperative system has been conserved since the Early Cretaceous as Aleocharinae radiated into tens of thousands of lineages. Reprogramming each cell type yielded biochemical novelties enabling ecological specialization-most dramatically in symbionts that infiltrate social insect colonies via host-manipulating secretions. Our findings uncover cell type evolutionary processes underlying the origin and evolvability of a beetle chemical innovation.