Hybrid and enhanced electrokinetic system for soil remediation from heavy metals and organic matter.

The electrokinetic (EK) process has been proposed for soil decontamination from heavy metals and organic matter. The advantages of the EK process include the low operating energy, suitability for fine-grained soil decontamination, and no need for excavation. During the last three decades, enhanced and hybrid EK systems were developed and tested for improving the efficiency of contaminants removal from soils. Chemically enhanced-EK processes exhibited excellent efficiency in removing contaminants by controlling the soil pH or the chemical reaction of contaminants. EK hybrid systems were tested to overcome environmental hurdles or technical drawbacks of decontamination technologies. Hybridization of the EK process with phytoremediation, bioremediation, or reactive filter media (RFM) improved the remediation process performance by capturing contaminants or facilitating biological agents' movement in the soil. Also, EK process coupling with solar energy was proposed to treat off-grid contaminated soils or reduce the EK energy requirements. This study reviews recent advancements in the enhancement and hybrid EK systems for soil remediation and the type of contaminants targeted by the process. The study also covered the impact of operating parameters, imperfect pollution separation, and differences in the physicochemical characteristics and microstructure of soil/sediment on the EK performance. Finally, a comparison between various remediation processes was presented to highlight the pros and cons of these technologies.

Simplified Nomenclature and Projection Diagrams of Chiral Cubane Analogs.

A simplified nomenclature for chiral cubane analogs is proposed where analogs with a clockwise systematic continuous numbering of the cubane core are designated as (C)-, and analogs with an anticlockwise continuous numbering of the cubane core are designated as (A)-. This method is accurate, allows for the rapid conversion of the chemical name to a structure, and it eliminates the need to designate the stereochemistry of each of the 8 carbons of cubane.

'Whole-Body' Perspectives of Schizophrenia and Related Psychotic Illness: miRNA-143 as an Exemplary Molecule Implicated across Multi-System Dysfunctions.

A wide array of biological abnormalities in psychotic illness appear to reflect non-cerebral involvement. This review first outlines the evidence for such a whole-body concept of schizophrenia pathobiology, focusing particularly on cardiovascular disease, metabolic syndrome and diabetes, immunity and inflammation, cancer, and the gut-brain axis. It then considers the roles of miRNAs in general and of miRNA-143 in particular as they relate to the epidemiology, pathobiology, and treatment of schizophrenia. This is followed by notable evidence that miRNA-143 is also implicated in each of these domains of cardiovascular disease, metabolic syndrome and diabetes, immunity and inflammation, cancer, and the gut-brain axis. Thus, miRNA-143 is an exemplar of what may be a class of molecules that play a role across the multiple domains of bodily dysfunction that appear to characterize a whole-body perspective of illness in schizophrenia. Importantly, the existence of such an exemplary molecule across these multiple domains implies a coordinated rather than stochastic basis. One candidate process would be a pleiotropic effect of genetic risk for schizophrenia across the whole body.

The auronidin flavonoid pigments of the liverwort Marchantia polymorpha form polymers that modify cell wall properties.

Plant adaptation from aquatic to terrestrial environments required modifications to cell wall structure and function to provide tolerance to new abiotic and biotic stressors. Here, we investigate the nature and function of red auronidin pigment accumulation in the cell wall of the liverwort Marchantia polymorpha. Transgenic plants with auronidin production either constitutive or absent were analysed for their cell wall properties, including fractionation of polysaccharide and phenolic components. While small amounts of auronidin and other flavonoids were loosely associated with the cell wall, the majority of the pigments were tightly associated, similar to what is observed in angiosperms for polyphenolics such as lignin. No evidence of covalent binding to a polysaccharide component was found: we propose auronidin is present in the wall as a physically entrapped large molecular weight polymer. The results suggested auronidin is a dual function molecule that can both screen excess light and increase wall strength, hydrophobicity and resistance to enzymatic degradation by pathogens. Thus, liverworts have expanded the core phenylpropanoid toolkit that was present in the ancestor of all land plants, to deliver a lineage-specific solution to some of the environmental stresses faced from a terrestrial lifestyle.

BOATMAP: Bayesian Optimization Active Targeting for Monomorphic Arrhythmia Pace-mapping.

Recent advances in machine learning and deep learning have presented new opportunities for learning to localize the origin of ventricular activation from 12-lead electrocardiograms (ECGs), an important step in guiding ablation therapies for ventricular tachycardia. Passively learning from population data is faced with challenges due to significant variations among subjects, and building a patient-specific model raises the open question of where to select pace-mapping data for training. This work introduces BOATMAP, a novel active learning approach designed to provide clinicians with interpretable guidance that progressively assists in locating the origin of ventricular activation from 12-lead ECGs. BOATMAP inverts the input-output relationship in traditional machine learning solutions to this problem and learns the similarity between a target ECG and a paced ECG as a function of the pacing site coordinates. Using Gaussian processes (GP) as a surrogate model, BOATMAP iteratively refines the estimated similarity landscape while providing suggestions to clinicians regarding the next optimal pacing site. Furthermore, it can incorporate constraints to avoid suggesting pacing in non-viable regions such as the core of the myocardial scar. Tested in a realistic simulation environment in various heart geometries and tissue properties, BOATMAP demonstrated the ability to accurately localize the origin of activation, achieving an average localization accuracy of 3.9±3.6mm with only 8.0±4.0 pacing sites. BOATMAP offers real-time interpretable guidance for accurate localization and enhancing clinical decision-making.

The evolution of flavonoid biosynthesis.

The flavonoid pathway is characteristic of land plants and a central biosynthetic component enabling life in a terrestrial environment. Flavonoids provide tolerance to both abiotic and biotic stresses and facilitate beneficial relationships, such as signalling to symbiont microorganisms, or attracting pollinators and seed dispersal agents. The biosynthetic pathway shows great diversity across species, resulting principally from repeated biosynthetic gene duplication and neofunctionalization events during evolution. Such events may reflect a selection for new flavonoid structures with novel functions that enable occupancy of varied ecological niches. However, the biochemical and genetic diversity of the pathway also likely resulted from evolution along parallel trends across land plant lineages, producing variant compounds with similar biological functions. Analyses of the wide range of whole-plant genome sequences now available, particularly for archegoniate plants, have enabled proposals on which genes were ancestral to land plants and which arose within the land plant lineages. In this review, we discuss the emerging proposals for how the flavonoid pathway may have evolved and diversified. This article is part of the theme issue 'The evolution of plant metabolism'.

Interactive Journal Club: A Learning Method to Enhance Collaboration and Participation among Medical Students.

Objectives: This quality improvement study aimed to explore the viability of a learning pedagogy for medical students, the interactive journal club (IJC), in stimulating active learning and engagement among learners. The study intends to explore the benefits provided by the IJC when compared to traditional learning methods (e.g., traditional journal clubs). It attempts to highlight the importance of didactics which focus on active learning and interactive engagement between learners. Methods: The IJC was implemented as a course requirement in HI 201: Health Informatics, a midyear elective course at the College of Medicine, University of the Philippines Manila. A class of MD-PhD (Molecular Medicine) students was divided into two separate groups: the designated leaders who presented the article and moderated the discussion, and the audience who did not read the article beforehand yet were involved in its critical analysis. The IJC was conducted twice in two different sections of MD-PhD (Molecular Medicine) students, across two different midyear terms, Midyear Term 2021, and Midyear Term 2022. Reflection papers were collected and the responses through this requirement were collated before the primary takeaways were extrapolated. A survey was also sent out to the students of each class to itemize the consolidated feedback of students on the proposed didactic. Results: The overall process of IJC was deemed both exciting and stimulating. The learning pedagogy provided an alternative platform for active learning, fostering a student-centered approach that placed a heavy emphasis on critical thinking. One major challenge identified in the implementation of the educational design was the heavy reliance on student participation which was identified to, at times, be a difficult factor to overcome. In order to improve its implementation, expectations may be set at the beginning and assessed at the end of the session. In addition, a pre- and post-questionnaire may be given to assess the perceived usefulness of this new method for qualitative comparison. Conclusion: Interactive and student-centered modes of learning are empirical for the improvement of literature appraisal, journal presentation, and evidence-based critical thinking among medical students. IJCs may be utilized as an alternative and effective learning strategy in teaching pertinent skills expected of a proper physician. When compared to traditional pedagogies, IJCs provide a platform for deeper learning and enable the achievement of learning outcomes, with learner engagement as the focal point. Future attempts at executing IJCs may consider the implementation of learning outcomes setting, and the use of pre- and post- IJC surveys to assess the effectiveness of the modality.

Consensus molecular subtyping of metastatic colorectal cancer expands biomarker-directed therapeutic benefit for patients with CMS1 and CMS2 tumors.

BACKGROUND: We developed a whole transcriptome sequencing (WTS)-based Consensus Molecular Subtypes (CMS) classifier using FFPE tissue and investigated its prognostic and predictive utility in a large clinico-genomic database of CRC patients (n = 24,939). METHODS: The classifier was trained against the original CMS datasets using an SVM model and validated in an independent blinded TCGA dataset (88.0% accuracy). Kaplan-Meier estimates of overall survival (OS) and time-on-treatment (TOT) were calculated for each CMS (p < 0.05 considered significant). RESULTS: CMS2 tumors were enriched on left-side of colon and conferred the longest median OS. In RAS-wildtype mCRC, left-sided tumors and CMS2 classification were associated with longer TOT with anti-EGFR antibodies (cetuximab and panitumumab). When restricting to only CMS2, there was no significant difference in TOT between right- versus left-sided tumors. CMS1 tumors were associated with a longer median TOT with pembrolizumab relative to other CMS groups, even when analyzing only microsatellite stable (MSS) tumors. DISCUSSION: A WTS-based CMS classifier allowed investigation of a large multi-institutional clinico-genomic mCRC cohort, suggesting anti-EGFR therapy benefit for right-sided RAS-WT CMS2 tumors and immune checkpoint inhibitor benefit for MSS CMS1. Routine CMS classification of CRC provides important treatment associations that should be further investigated.

Bimetallic catalyst system for the degradation of PCBs in sediments.

In this paper, we report the successful application of a patent-pending reduced bimetallic nanoparticle catalytic system developed for the remediation of polychlorinated biphenyl (PCB)-contaminated sediment and aquatic media. The formation of bimetallic nanoparticles associated with the granular activated carbon (GAC) were confirmed by high-resolution transmission electron microscopy. X-ray photoelectron spectroscopy showed the presence of the bimetallic matrix in reduced, albeit mixed, states. In the degradation studies, the bimetallic nanoparticles were deposited on a GAC substrate and utilized to treat both a surrogate PCB, 2-Chlorobiphenyl (2-CBP) in water and contaminated bottom-river sediments collected from a site with mixed-congener PCB contamination. The degradation studies on non-degassed water contaminated with 2-CBP at room temperature showed a high yield of 2-CBP degradation to biphenyl and phenol. Results from the bottom-river sediments contaminated with PCBs (tested in laboratory environment at ambient temperature and atmospheric conditions, not degassed) have indicated the bimetallic catalyst has great promise for remedial application in sediment and aquatic media. Results illustrate that this newly-developed and patent-pending catalytic system degrades PCBs through stepwise dichlorination, with expected byproducts such as biphenyl and phenol leading to mineralization of the PCBs.

Characterization of neural networks involved in transdiagnostic emotion dysregulation from a pilot randomized controlled trial of a neurostimulation-enhanced behavioral intervention.

BACKGROUND: Emotional dysregulation is a serious and impairing mental health problem. We examined functional activity and connectivity of neural networks involved in emotional dysregulation at baseline and following a pilot neurostimulation-enhanced cognitive restructuring intervention in a transdiagnostic clinical adult sample. METHODS: Neuroimaging data were analyzed from adults who scored 89 or higher on the Difficulties with Emotion Regulation (DERS) scale and had at least one DSM-5 diagnosis. These participants were part of a pilot randomized, double-blind, placebo-controlled trial combining a single therapeutic session of cognitive restructuring with active or sham transcranial magnetic stimulation over the dorsolateral prefrontal cortex. During the study, participants engaged in an emotional regulation task using personalized autobiographical stressors while undergoing functional magnetic resonance imaging (fMRI) before and after the pilot intervention. The fMRI task required participants to either experience the emotions associated with the memories or apply cognitive restructuring strategies to reduce their distress. RESULTS: Whole-brain fMRI results during regulation at baseline revealed increased activation in the dorsal frontoparietal network but decreased activation in the supplementary motor area, cingulate cortex, insula, and ventrolateral prefrontal cortex (vlPFC). Emotion dysregulation was associated with greater vmPFC and amygdala activation and functional connectivity between these regions. The strength of functional connectivity between the dlPFC and other frontal regions was also a marker of emotional dysregulation. Preliminary findings from a subset of participants who completed the follow-up fMRI scan showed that active neurostimulation improved behavioral indices of emotion regulation more than sham stimulation. A whole-brain generalized psychophysiological interaction analysis indicated that active neurostimulation selectively increased occipital cortex connectivity with both the insula and the dlPFC. Region-of-interest functional connectivity analyses showed that active neurostimulation selectively increased dlPFC connectivity with the insula and orbitofrontal cortex (OFC). CONCLUSION: Insufficient neural specificity during the emotion regulation process and over-involvement of frontal regions may be a marker of emotional dysregulation across disorders. OFC, vlPFC, insula activity, and connectivity are associated with improved emotion regulation in transdiagnostic adults. In this pilot study, active neurostimulation led to neural changes in the emotion regulation network after a single session; however, the intervention findings are preliminary, given the small sample size. These functional network properties can inform future neuroscience-driven interventions and larger-scale studies.

Tumor specimen cold ischemia time impacts molecular cancer drug target discovery.

Tumor tissue collections are used to uncover pathways associated with disease outcomes that can also serve as targets for cancer treatment, ideally by comparing the molecular properties of cancer tissues to matching normal tissues. The quality of such collections determines the value of the data and information generated from their analyses including expression and modifications of nucleic acids and proteins. These biomolecules are dysregulated upon ischemia and decompose once the living cells start to decay into inanimate matter. Therefore, ischemia time before final tissue preservation is the most important determinant of the quality of a tissue collection. Here we show the impact of ischemia time on tumor and matching adjacent normal tissue samples for mRNAs in 1664, proteins in 1818, and phosphosites in 1800 cases (tumor and matching normal samples) of four solid tumor types (CRC, HCC, LUAD, and LUSC NSCLC subtypes). In CRC, ischemia times exceeding 15 min impacted 12.5% (mRNA), 25% (protein), and 50% (phosphosites) of differentially expressed molecules in tumor versus normal tissues. This hypoxia- and decay-induced dysregulation increased with longer ischemia times and was observed across tumor types. Interestingly, the proteomics analysis revealed that specimen ischemia time above 15 min is mostly associated with a dysregulation of proteins in the immune-response pathway and less so with metabolic processes. We conclude that ischemia time is a crucial quality parameter for tissue collections used for target discovery and validation in cancer research.

A multicenter study of clinical outcomes and volumetric trends in suspected microprolactinomas.

The diagnosis of pituitary microprolactinomas is often obscured by relatively low levels of elevated prolactin compared to macroprolactinomas. This may lead to varying patterns of medical therapy versus observation. We sought to correlate prolactin levels in suspected microprolactinomas with tumor volumes and clinical outcomes. This was a multicenter retrospective study of patients with pituitary microadenomas with baseline prolactin levels > 18ng/ml for males and > 30ng/ml for females. A linear-mixed model was used to depict changes in tumor volume over time. There were 65 patients with a mean tumor volume of 95.9mm3 and mean prolactin level of 59.4ng/ml. There were significantly higher prolactin levels in patients with tumors above the mean volume versus below (74.0 versus 53.4ng/ml, p = 0.027). 26 patients were observed, 31 were treated with anti-dopaminergic therapy, and 8 had surgery. There were significantly greater baseline prolactin levels for patients who were treated surgically (mean 86.4ng/ml) than those treated medically (mean 61.7 g/ml) or observed (mean 48.5ng/ml) (p = 0.02). Among the 26 patients who were surveilled, 13 patients demonstrated spontaneous tumor shrinkage, 12 remained stable, and 1 patient's tumor grew but was lost to follow-up. Linear mixed modeling demonstrated a statistically significant rate of tumor shrinkage over time of 3.67mm3/year (p = 0.03). When analyzing patients who were observed versus those requiring surgery after initially being surveilled, there were significantly greater baseline PRL/volume ratios in surgical patients versus those observed (8.1 ng/ml/mm3 versus 2.4 ng/ml/mm3, p = 0.025). Suspected microprolactinomas may demonstrate more convincingly elevated prolactin levels when measuring over 95.9mm3. Tumors with baseline prolactin levels over 50ng/ml may be more inclined to undergo medical treatment. In tumors with levels below 50ng/ml, it may be reasonable to undergo surveillance as these tumors tend to spontaneously shrink over time. In tumors that are surveilled, an elevated baseline PRL/volume ratio of > 8 ng/ml/mm3 may be indicate serial tumor growth that may necessitate medical and/or surgical intervention.

Loss of normal facial asymmetry in schizophrenia and bipolar disorder: Implications for development of brain asymmetry in psychotic illness.

Development of the craniofacies occurs in embryological intimacy with development of the brain and both show normal left-right asymmetries. While facial dysmorphology occurs to excess in psychotic illness, facial asymmetry has yet to be investigated as a putative index of brain asymmetry. Ninety-three subjects (49 controls, 22 schizophrenia, 22 bipolar disorder) received 3D laser surface imaging of the face. On geometric morphometric analysis with (x, y, z) visualisations of statistical models for facial asymmetries, in controls the upper face and periorbital region, which share embryological intimacy with the forebrain, showed marked asymmetries. Their geometry included: along the x-axis, rightward asymmetry in its dorsal-medial aspects and leftward asymmetry in its ventral-lateral aspects; along the z-axis, anterior protrusion in its right ventral-lateral aspect. In both schizophrenia and bipolar disorder these normal facial asymmetries were diminished, with residual retention of asymmetries in bipolar disorder. This geometry of normal facial asymmetries shows commonalities with that of normal frontal lobe asymmetries. These findings indicate a trans-diagnostic process that involves loss of facial asymmetries in both schizophrenia and bipolar disorder. Embryologically, they implicate loss of face-brain asymmetries across gestational weeks 7-14 in processes that involve genes previously associated with risk for schizophrenia.

Current experience and future potential of facilitating access to digital NHS primary care services in England: the Di-Facto mixed-methods study.

Background: Current National Health Service policy in England encourages enhanced digital access in primary care service provision. In this study, we investigate 'digital facilitation' - that range of processes, procedures and personnel which seeks to support National Health Service primary care patients in their uptake and use of online services. Objectives: Identify, characterise and explore the potential benefits and challenges associated with different models of digital facilitation currently in use in general practice which are aimed at improving patient access to online services in general practice in England. Use the resulting intelligence to design a framework for future evaluations of the effectiveness and cost effectiveness of such interventions. Explore how patients with mental health conditions experience digital facilitation and gauge their need for this support. Design: Observational mixed-methods study (literature review, surveys, ethnographic observation and interviews); formal synthesis of findings. Setting: General practice in four regions of England. Participants: Practice survey: 156 staff. Patient survey: 3051 patients. Mental health survey: 756 patients. General practitioner patient survey: 3 million responders. Ethnographic case-studies: 8 practices; interviews with 36 staff, 33 patients and 10 patients with a mental health condition. Stakeholder interviews: 19 participants. Intervention: Digital facilitation as undertaken in general practice. Main outcome measures: Patient and practice staff reported use of, and views of, digital facilitation. Data sources: Surveys, qualitative research; national General Practitioner Patient Survey (2019-22). Review methods: Scoping-review methodology applied to academic and grey literature published 2015-20. Results: While we did find examples of digital facilitation in routine practice, these often involved using passive or reactive modes of support. The context of COVID, and the necessary acceleration (at that time) of the move to a digital-first model of primary care, shaped the way digital facilitation was delivered. There was lack of clarity over where the responsibility for facilitation efforts lay; it was viewed as the responsibility of 'others'. Patients living with mental health conditions had similar needs and experiences regarding digital facilitation to other patients. Limitations: The context of the COVID pandemic placed limitations on the project. Fewer practices responded to the practice survey than anticipated; reconfiguration of general practices to support COVID measures was a key consideration during non-participant observation with social distancing and other measures still in place during fieldwork. Conclusions: Digital facilitation, while not a widely recognised concept, is important in supporting the move to a National Health Service with enhanced digital opportunities and enhanced digital access. General practice staff are allocating resources to provide such efforts in general practices in England. The establishment of clear lines of responsibility, the development of digital tools and platforms that work for patients and practice staff, and investment in staff time and training are needed if digital facilitation is to support the intended digital revolution. Future work: We did not find one single dominant or preferred model of digital facilitation which might reasonably be considered to form the basis of an intervention to be tested. Rather, there is a need to co-develop such an intervention with patients, general practice staff and relevant policy experts. We outline a framework for a future evaluation of such an intervention. Study registration: This study is registered as ResearchRegistry6523 (www.researchregistry.com/browse-the-registry#home/?view_2_search=Di-Facto&view_2_page=1) and PROSPERO CRD42020189019 (www.crd.york.ac.uk/prospero/display_record.php?RecordID=189019). Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: NIHR128268) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 32. See the NIHR Funding and Awards website for further award information.

Online services are common in the National Health Service. This research looked at 'digital facilitation' in general practices. Digital facilitation is about supporting National Health Service patients in their use of online services. We aimed to understand how much digital facilitation is being used by general practices. We also looked at how digital facilitation happens and if it affects the number of people using online services. We looked at previous research to help us understand what approaches have been used to support patients to use online services. We used surveys to ask staff at general practices what they were already doing, and to ask patients about their experiences. We observed digital facilitation in general practices and spoke to patients and staff to help us understand the benefits and challenges of different approaches. We combined findings from the three stages outlined above to identify key aspects of digital facilitation. All stages of our research included discussions with the project's patient advisory group. We found that digital facilitation is seen as important and has many forms. Most general practices are using passive and reactive types of facilitation. An example of passive facilitation, initiated by the service but not involving direct inter-personal interaction, is the use of text messaging relating to ordering of repeat prescriptions online. An example of reactive facilitation is providing a response to a patient-initiated query regarding online access. There is clear scope to develop a more proactive approach to facilitation that actively engages patients. Our research highlights a lack of clarity over who is responsible for digital facilitation. Different people (patients, staff, policy-makers) often think that the responsibility lies with others. Investment in digital facilitation is needed. Tools and platforms for digital facilitation that meet patients' and general practices' needs should be developed.

Symptomatic, Massive Right-Sided Splenic Heterotopia Masquerading as a Renal Cell Carcinoma With Metastasis.

Heterotopic splenic tissue is a rare phenomenon that can occur in the abdomen and mimic renal or gastrointestinal tumors on imaging. We describe a 24-year-old woman who initially presented with right flank pain, urinary frequency, intermittency, and nocturia. The patient was found to have a large mass distorting and displacing the right kidney, thought to be renal cell carcinoma with concern for metastasis to the ileocecal junction based on radiographic imaging. The patient underwent right radical nephrectomy with right adrenalectomy and partial colon resection to remove the ileocecal mass. Pathological examination revealed the renal mass to be splenic tissue and the ileocecal mass to be a dermoid cyst, with no evidence of renal malignancy. This is an exceptional demonstration of a right-sided splenic heterotopia of remarkably large size sufficient to cause symptoms of a mass effect.

Herbivore kairomones affect germination speed, seedling growth, and herbivory.

Seeds and seedlings are particularly vulnerable to herbivory. Unlike mature plants, which can wait until herbivory is experienced to induce defense, seeds and seedlings face mortality if they wait. Slug mucus functions as a kairomone, a non-attack-related substance emitted by consumers that is detected by a prey species (in this case, plants). While snail mucus has been shown to induce defense in seedlings, it is not widely confirmed whether slugs have the same effect and whether seeds can also detect and react to such herbivore cues. We investigated how exposure to Arion subfuscus mucus affected growth and defense in Brassica nigra seeds and seedlings. Seeds exposed to slug mucus germinated 5% faster than control (water only) seeds, but the resulting seedlings weighed 16% less than control seedlings. To test whether this difference results from herbivore-exposed plants allocating energy from growth to defense, we conducted choice bioassays assessing slug preference for control seedlings versus seedlings that were either (A) exposed to mucus only as a seed; or (B) exposed to mucus as a seed and seedling. While slugs did not differentiate between control seedlings and ones exposed to herbivore cues only as a seed, they ate 88% less biomass of seedlings exposed to mucus as both seeds and seedlings. These results suggest that slug mucus induces changes in plant traits related to defense and growth/competitive ability. Future research should determine the chemical mechanisms of this induced defense.

Epidemiology and timing of infectious complications from battlefield-related burn injuries.

BACKGROUND: Infections are the most frequent complication and cause of mortality in burn patients. We describe the epidemiology and outcomes of infections among deployed U.S. military personnel with burns. METHODS: Military personnel who sustained a burn injury in Iraq or Afghanistan (2009-2014) and were admitted to the Burn Center at U.S. Army Institute of Surgical Research at Brooke Army Medical Center were included in the analysis. RESULTS: The study population included 144 patients who were primarily young (median 24 years) males (99 %) with combat-related burns (62 %) sustained via a blast (57 %), resulting in a median total body surface area burned (TBSA) of 6 % (IQR 3-14 %). Twenty-six (18 %) patients developed infections, with pneumonia being the predominant initial infection (= 16), followed by skin and soft-tissue infections (SSTI, = 6), bloodstream infections (BSI, = 3), and intra-abdominal infections (IAI, = 1). Initial infections were diagnosed at a median of 4 days (IQR 3-5) post-injury for pneumonia, 7 days (IQR 4-12) for SSTIs, 7 days (IQR 6-7) for BSI, and 17 days for IAI. Patients with infections were more severely injured with greater TBSA (median 31 % vs 5 %), more inhalation injury (38 % vs 12 %), and longer time to definitive surgical management (median of 34 days vs 9) compared to those who did not develop infections (p < 0.001). Among patients with inhalation injury, a higher proportion developed pneumonia (42 %) compared to those without inhalation injury (5 %; p < 0.001). Five patients developed an invasive fungal infection. Gram-negative bacilli were most frequently recovered, with 32 % of Gram-negative isolates being multidrug-resistant. Four patients died, of whom all had ≥ 4 infections. CONCLUSIONS: Military personnel with burn injuries who developed infections were more severely injured with greater TBSA and inhalation injury. Improved understanding of risk factors for burn-related infections in combat casualties is critical for effective management.

Development and Optimization of a Bladder Cancer Algorithm Using SEER-Medicare Claims Data.

PURPOSE: Categorizing patients with cancer by their disease stage can be an important tool when conducting administrative claims-based studies. As claims databases frequently do not capture this information, algorithms are increasingly used to define disease stage. To our knowledge, to date, no study has used an algorithm to categorize patients with bladder cancer (BC) by disease stage (non-muscle-invasive BC [NMIBC], muscle-invasive BC [MIBC], or locally advanced/metastatic urothelial carcinoma [la/mUC]) in a US-based health care claims database. METHODS: A claims-based algorithm was developed to categorize patients by disease stage on the basis of the administrative claims portion of the SEER-Medicare linked data. The algorithm was validated against a reference SEER registry, and the algorithm's parameters were iteratively modified to improve its performance. Patients were included if they had an initial diagnosis of BC between January 2016 and December 2017 recorded in SEER registry data. Medicare claims data were available for these patients until December 31, 2019. The algorithm was evaluated by assessing percentage agreement, Cohen's kappa (κ), specificity, positive predictive value (PPV), and negative predictive value (NPV) against the SEER categorization. RESULTS: A total of 15,484 patients with SEER-confirmed BC were included: 10,991 (71.0%) with NMIBC, 3,645 (23.5%) with MIBC, and 848 (5.5%) with la/mUC. After multiple rounds of algorithm optimization, the final algorithm had an agreement of 82.5% with SEER, with a κ of 0.58, a PPV of 87.0% for NMIBC, and 76.8% for MIBC and a high NPV for la/mUC of 98.0%. CONCLUSION: This claims-based algorithm could be a useful approach for researchers conducting claims-based studies categorizing patients with BC at diagnosis.