Lipid nanoparticle structure and delivery route during pregnancy dictate mRNA potency, immunogenicity, and maternal and fetal outcomes.

Treating pregnancy-related disorders is exceptionally challenging because the threat of maternal and/or fetal toxicity discourages the use of existing medications and hinders new drug development. One potential solution is the use of lipid nanoparticle (LNP) RNA therapies, given their proven efficacy, tolerability, and lack of fetal accumulation. Here, we describe LNPs for efficacious mRNA delivery to maternal organs in pregnant mice via several routes of administration. In the placenta, our lead LNP transfected trophoblasts, endothelial cells, and immune cells, with efficacy being structurally dependent on the ionizable lipid polyamine headgroup. Next, we show that LNP-induced maternal inflammatory responses affect mRNA expression in the maternal compartment and hinder neonatal development. Specifically, pro-inflammatory LNP structures and routes of administration curtailed efficacy in maternal lymphoid organs in an IL-1ß-dependent manner. Further, immunogenic LNPs provoked the infiltration of adaptive immune cells into the placenta and restricted pup growth after birth. Together, our results provide mechanism-based structural guidance on the design of potent LNPs for safe use during pregnancy.

Advances in proteomics methods for the analysis of exhaled breath condensate.

The analysis of exhaled breath condensate (EBC) demonstrates a promising avenue of minimally invasive biopsies for diagnostics. EBC is obtained by cooling exhaled air and collecting the condensation to be utilized for downstream analysis using various analytical methods. The aqueous phase of breath contains a large variety of miscible small compounds including polar electrolytes, amino acids, cytokines, chemokines, peptides, small proteins, metabolites, nucleic acids, and lipids/eicosanoids-however, these analytes are typically present at minuscule levels in EBC, posing a considerable technical challenge. Along with recent improvements in devices for breath collection, the sensitivity and resolution of liquid chromatography coupled to online mass spectrometry-based proteomics has attained subfemtomole sensitivity, vastly enhancing the quality of EBC sample analysis. As a result, proteomics analysis of EBC has been expanding the field of breath biomarker research. We present an au courant overview of the achievements in proteomics of EBC, the advancement of EBC collection devices, and the current and future applications for EBC biomarker analysis.

Sleep disturbances and interrelationship between persons with dementia and family caregivers: The lived experiences of Korean American Dyads.

BACKGROUND: Little research has investigated sleep quality in dyadic interrelationships between persons with dementia (PWD) and family caregivers, particularly among immigrant ethnic minorities, such as Korean Americans. PURPOSE: The study aimed to describe lived experiences of sleep disturbances and sleep interrelationships between Korean American PWD and their family caregivers. METHODS: A descriptive qualitative design used semi-structured interviews with cohabitating PWD-caregiver dyads. RESULTS: Eleven Korean American dyads participated (PWD mean age: 82.7, SD=2.3; caregivers mean age: 69.1, SD=10.2). Major themes included (1) linked sleep disturbances between PWD and caregivers, (2) interrelationship in dyads, (3) language challenges within and outside the dyads, and (4) strategies that improve sleep quality for dyads. CONCLUSION: Findings demonstrated bidirectional influences in dyadic sleep disturbances, where caregiving reciprocally impacted PWD sleep as part of an interactional unit. Communication barriers and limited community resources posed challenges for these dyads. Future sleep interventions should consider culturally competent, dyadic approaches.

Artificial Intelligence-Driven Morphology-Based Enrichment of Malignant Cells from Body Fluid.

Cell morphology is a fundamental feature used to evaluate patient specimens in pathologic analysis. However, traditional cytopathology analysis of patient effusion samples is limited by low tumor cell abundance coupled with the high background of nonmalignant cells, restricting the ability of downstream molecular and functional analyses to identify actionable therapeutic targets. We applied the Deepcell platform that combines microfluidic sorting, brightfield imaging, and real-time deep learning interpretations based on multidimensional morphology to enrich carcinoma cells from malignant effusions without cell staining or labels. Carcinoma cell enrichment was validated with whole genome sequencing and targeted mutation analysis, which showed a higher sensitivity for detection of tumor fractions and critical somatic variant mutations that were initially at low levels or undetectable in presort patient samples. Our study demonstrates the feasibility and added value of supplementing traditional morphology-based cytology with deep learning, multidimensional morphology analysis, and microfluidic sorting.

Carbonate Coprecipitation for Cd and Zn Treatment and Evaluation of Heavy Metal Stability Under Acidic Conditions.

Mining wastes or combustion ash are materials of high carbon sequestration potential but are also known for their toxicity in terms of heavy metal content. To utilize such waste materials for engineered carbon mineralization purposes, there is a need to investigate the fate and mobility of toxic metals. This is a study of the coprecipitation of metals with calcium carbonate for environmental heavy metal mitigation. The study also examines the stability of precipitated phases under environmentally relevant acid conditions. For a wide range of cadmium (Cd) and zinc (Zn) concentrations (10 to 5000 mg/L), induced coprecipitation led to greater than 99% uptake from water. The calcium carbonate phases were found to contain amounts as high as 9.9 wt % (Cd) and 17 wt % (Zn), as determined by novel synchrotron techniques, including X-ray fluorescence element mapping and three-dimensional (3D) nanotransmission X-ray microscopy (TXM). TXM imaging revealed first-of-a-kind observations of chemical gradients and internal nanoporosity within particles. These observations provided new insights into the mechanisms leading to the retention of coprecipitated heavy metals during the dissolution of calcite in acidic (pH 4) solutions. These observations highlight the feasibility of utilizing carbonate coprecipitation as an engineered approach to the durable sequestration of toxic metals.

Effects of the multi-channeled oral irrigation (MCOI) unit in preventing dental plaque formation and gingivitis: A randomized controlled trial.

PURPOSE: To evaluate the efficacy of COMORAL a new multi-channeled oral irrigation (MCOI) unit with pulsating water jet, in plaque score reduction and gingivitis. METHODS: This was a single-blinded clinical randomized controlled trial (NCT05031260). Forty-two healthy subjects between 18 to 35 years old were initially recruited, and the control group (n = 20) and the intervention group (n = 17) were randomly assigned. Both groups were asked to brush their teeth one or two times a day without any supplementary oral hygiene products while the intervention group used COMORAL 3 times a day, 5 days a week. Clinical indices including gingival index (GI), plaque index (PI), bleeding on probing (BOP), pocket depth (PD), gingival recession (GR), and clinical attachment loss (CAL) were obtained at the baseline (D0), day 14 (D14), and day 28 (D28). Saliva was collected to examine the presence of periodontal pathogens. The repeated measures analysis of variance or generalized estimating equation was used to compare the interaction between groups and time points. The independent t-test or Mann-Whitney test were used for intergroup differences at each time point. RESULTS: At V0, PI, GI, BOP, and PD scores showed no differences between the two groups. At V1 and V2, these scores showed significant difference between two groups (P < 0.05) such that the intervention group showed gradual decreases while the control group showed no change. There were no differences in GR, CAL, and periodontal pathogens between the two groups. COMORAL showed improvement in reducing gingival inflammation and dental plaque formation adjuvant to routine toothbrushing in healthy adults. CLINICAL SIGNIFICANCE: The results of this study can be useful to clinicians when selecting oral hygiene devices that can help improve patients' routine oral hygiene practice and their overall oral health.

NANOG regulates epithelial-mesenchymal transition via AMPK/mTOR signalling pathway in ovarian cancer SKOV-3 and A2780 cells.

NANOG engages with tumour initiation and metastasis by regulating the epithelial-mesenchymal transition (EMT) in epithelial ovarian cancer (EOC). However, its role in association with pAMPKα, and its clinical significance in EOC have not been elucidated even though AMPK is known to degrade NANOG in various human cancers. Hence, we investigated the role of pAMPKα and its association with NANOG as potential prognostic biomarkers in EOC. Both NANOG and pAMPKα expression were significantly overexpressed in EOCs comparing nonadjacent normal epithelial tissues, benign tissues, and borderline tumours. NANOG overexpression was significantly associated with poor disease-free survival (DFS) and overall survival (OS), whereas pAMPKα overexpression was associated with good DFS and OS. Importantly, multivariate analysis revealed that the combination of high NANOG and low pAMPKα expression was a poor independent prognostic factor for DFS and was associated with platinum resistance. In ovarian cancer cell lines, siRNA-mediated NANOG knockdown diminished migration and invasion properties by regulating the EMT process via the AMPK/mTOR signalling pathway. Furthermore, treatment with AMPK activator suppressed expression of stemness factors such as NANOG, Oct4 and Sox2. Collectively, these findings established that the combination of high NANOG and low pAMPKα expression was associated with EOC progression and platinum resistance, suggesting a potential prognostic biomarker for clinical management in EOC patients.

RNA sequencing and bioinformatics analysis revealed PACSIN3 as a potential novel biomarker for platinum resistance in epithelial ovarian cancer.

BACKGROUND: Failure to respond to treatment in epithelial ovarian cancer can often be attributed to platinum-based chemotherapy resistance. However, the possible mechanisms or candidate biomarkers associated with platinum resistance are yet to be elucidated, even though many researchers have performed related studies. METHODS: We performed RNA sequencing of clinical specimens obtained from patients with platinum-sensitive or resistant epithelial ovarian cancer (EOC). Furthermore, various bioinformatics approaches, including spatial analysis of functional enrichment, were used to identify key regulators and associated underlying mechanisms of platinum resistance in EOC. RESULTS: Through RNA-sequencing, we identified 263 differentially expressed genes (98 upregulated and 165 downregulated) and subjected them to Gene Oncology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, which were characterized to the traditional platinum-resistant characteristics. Subsequently, the gene interaction network and module analysis by spatial analysis of functional enrichment software demonstrated protein kinase C and casein kinase substrate in neurons 3 (PACSIN3) as the only upregulated hub gene, and neurotensin (NTS) and KIAA0319 as downregulated hub genes in platinum-resistant EOC. We selected PACSIN3 for further analysis because it has not been studied in relation to response to platinum-based chemotherapy. PACSIN3 was significantly upregulated in ovarian cancer cells compared to immortalized human ovarian surface epithelial cells. In addition, cisplatin-induced apoptosis was measured in PACSIN3 knockout OVCA433 and BRCA-mutated EOC cell line, SNU251, by a fluorescence-activated cell sorting-based Annexin-V/propium iodide double staining assay, which revealed a significant increase in apoptosis. CONCLUSIONS: Taken together, the present study presents PACSIN3 as a promising predictive biomarker associated with platinum resistance, especially in BRCA-mutated epithelial ovarian cancers.

Semisupervised Training of a Brain MRI Tumor Detection Model Using Mined Annotations.

Background Artificial intelligence (AI) applications for cancer imaging conceptually begin with automated tumor detection, which can provide the foundation for downstream AI tasks. However, supervised training requires many image annotations, and performing dedicated post hoc image labeling is burdensome and costly. Purpose To investigate whether clinically generated image annotations can be data mined from the picture archiving and communication system (PACS), automatically curated, and used for semisupervised training of a brain MRI tumor detection model. Materials and Methods In this retrospective study, the cancer center PACS was mined for brain MRI scans acquired between January 2012 and December 2017 and included all annotated axial T1 postcontrast images. Line annotations were converted to boxes, excluding boxes shorter than 1 cm or longer than 7 cm. The resulting boxes were used for supervised training of object detection models using RetinaNet and Mask region-based convolutional neural network (R-CNN) architectures. The best-performing model trained from the mined data set was used to detect unannotated tumors on training images themselves (self-labeling), automatically correcting many of the missing labels. After self-labeling, new models were trained using this expanded data set. Models were scored for precision, recall, and F1 using a held-out test data set comprising 754 manually labeled images from 100 patients (403 intra-axial and 56 extra-axial enhancing tumors). Model F1 scores were compared using bootstrap resampling. Results The PACS query extracted 31 150 line annotations, yielding 11 880 boxes that met inclusion criteria. This mined data set was used to train models, yielding F1 scores of 0.886 for RetinaNet and 0.908 for Mask R-CNN. Self-labeling added 18 562 training boxes, improving model F1 scores to 0.935 (P < .001) and 0.954 (P < .001), respectively. Conclusion The application of semisupervised learning to mined image annotations significantly improved tumor detection performance, achieving an excellent F1 score of 0.954. This development pipeline can be extended for other imaging modalities, repurposing unused data silos to potentially enable automated tumor detection across radiologic modalities. © RSNA, 2022 Online supplemental material is available for this article.

Laboratory parameters and outcomes in hospitalized adults with COVID-19: a scoping review.

BACKGROUND: Laboratory parameters and the associated clinical outcomes have been an area of focus in COVID-19 research globally. PURPOSE: We performed a scoping review to synthesize laboratory values described in the literature and their associations with mortality and disease severity. METHODS: We identified all primary studies involving laboratory values with clinical outcomes as a primary endpoint by performing data searches in various systematic review databases until 10th August, 2020. Two reviewers independently reviewed all abstracts (13,568 articles) and full text (1126 articles) data. A total of 529 studies involving 165,020 patients from 28 different countries were included. Investigation of the number of studies and patients from a geographical perspective showed that the majority of published literature from January-March 2020 to April-June 2020 was from Asia, though there was a temporal shift in published studies to Europe and the Americas. For each laboratory value, the proportion of studies that noted a statistically significant (p < 0.05) correlation with adverse clinical outcomes (e.g., mortality, disease severity) was tabulated. RESULTS AND CONCLUSION: Among frequently reported laboratory values, blood urea nitrogen was the most often reported predictor of mortality (91%); neutrophil-to-lymphocyte ratio was the most frequent statistically significant laboratory parameter in predicting disease severity (96%). This review highlights the temporal progression of laboratory value frequencies, as well as potentially distinct utilities of different markers for clinical outcomes of COVID-19. Future research pathways include using this collected data for focused quantitative meta-analyses of particular laboratory values correlated with clinical outcomes of mortality and disease severity.

Patient and Provider Satisfaction with Telemedicine in a Comprehensive Weight Management Program.

Introduction: Telemedicine use became widespread at our weight management center in 2020 due to the coronavirus disease 2019 (COVID-19) pandemic. Objectives: The objective of this study was to determine patient and provider satisfaction with telemedicine visits at a community-based hospital in the United States. Methods: Patients and providers were electronically surveyed at the end of 2020 regarding telemedicine visit experiences. These visits took place throughout the majority of 2020 during the COVID-19 pandemic. Results: A total of 85.7% (6) of providers reported spending the same or less time on telemedicine visits compared with in-person visits. All providers were either somewhat or very satisfied with the interpersonal connections made in telemedicine visits. All providers wished to see telemedicine visits continued in the future. A total of 355 patients responded. Over 90% of participants reported feeling comfortable speaking to their provider about personal issues through telemedicine. Around 73.2% of patients were very satisfied with their telemedicine visit. Around 69.8% of patients report that they would like to use either primarily telemedicine visits or a combination of telemedicine and in-person visits when it is safe to return to in-person care. Conclusions: Patients and providers exhibited high levels of satisfaction with telemedicine use in a weight management center. They both wish to see these visit types offered in the future. Patients who saved more than 30 min of time traveling with a telemedicine visit were significantly more likely to show high levels of satisfaction. Patients who found it easier to connect with the virtual platforms also were significantly more likely to have higher satisfaction levels.

Design of BET Inhibitor Bottlebrush Prodrugs with Superior Efficacy and Devoid of Systemic Toxicities.

Prodrugs engineered for preferential activation in diseased versus normal tissues offer immense potential to improve the therapeutic indexes (TIs) of preclinical and clinical-stage active pharmaceutical ingredients that either cannot be developed otherwise or whose efficacy or tolerability it is highly desirable to improve. Such approaches, however, often suffer from trial-and-error design, precluding predictive synthesis and optimization. Here, using bromodomain and extra-terminal (BET) protein inhibitors (BETi)-a class of epigenetic regulators with proven anticancer potential but clinical development hindered in large part by narrow TIs-we introduce a macromolecular prodrug platform that overcomes these challenges. Through tuning of traceless linkers appended to a "bottlebrush prodrug" scaffold, we demonstrate correlation of in vitro prodrug activation kinetics with in vivo tumor pharmacokinetics, enabling the predictive design of novel BETi prodrugs with enhanced antitumor efficacies and devoid of dose-limiting toxicities in a syngeneic triple-negative breast cancer murine model. This work may have immediate clinical implications, introducing a platform for predictive prodrug design and potentially overcoming hurdles in drug development.

TB notification rates across parliamentary constituencies in India: a step towards data-driven political engagement.

OBJECTIVE: National averages obscure geographic variation in program performance. We determined Parliamentary Constituency (PC)-wise estimates of TB notification to guide political engagement. METHODS: We extracted district-level TB notification data from the 2018 annual TB report. We derived PC-level estimates by building a 'cross-walk' between districts and PCs using boundary shapefiles. We described the spatial distribution of the PC-wise estimates of Total Notification Rate and percentage of Private Sector Notification. RESULTS: The median PC-wise Total Notification Rate was 126.24/100 000 (IQR: 94.86/100 000, 162.22/100 000). The median PC-wise Percentage Private Sector Notification was 18.03% (IQR: 9.56%, 26.84%). Only 16 (2.94%) PCs met the target of 50% private sector notification. Most of high notification rates in PCs were driven by high notification in public sector. There was geographic - both interstate and within state inter-PC - variation in the estimates of these indicators. The study identified some geographic patterns of notification - high positive outlier PCs with adjoining PCs in lower deciles of notification rates, intra-state differences in PC performance, and similarities in notification rates of adjoining PCs in different states. CONCLUSION: In addition to regional inequality, the study identified geospatial patterns that can aid in the formulation of suitable interventions. These include decongestion of overburdened facilities by strengthening poorly performing units. The PCs with a high percentage Private Sector Notification can act as role models for neighbouring PCs to improve private sector engagement. MPs can play a crucial role in mobilising additional resources, creating awareness, and establishing inter-PC and inter-state collaboration to improve TB program performance.

Altered Mental Status: An Important but Overlooked Presenting Symptom of COVID-19 in Older Adults.

OBJECTIVES: To determine whether altered mental status (AMS) as a presenting symptom in older adults with COVID-19 is independently associated with adverse outcomes. METHODS: A retrospective single center observational study of admitted patients (n = 421) age greater than 60 and a positive COVID-19 test. Outcomes included mortality, intubation, acute respiratory distress syndrome, acute kidney injury, and acute cardiac injury. Multivariate regression analysis was used to determine if presenting with AMS was associated with adverse outcomes. RESULTS: There was an increased risk of mortality (RR 1.29, 95% CI 1.05-1.57), intubation (RR 1.52, 95% CI 1.09-2.12) and AKI (RR 1.42, 95% CI 1.13-1.78) in patients that presented with AMS. CONCLUSIONS: During a global pandemic, prognostic indicators are vital to help guide the clinical course of patients, reduce healthcare cost, and preserve life. Our study suggests that AMS can play a major role in diagnostic algorithms in older adults with COVID-19.

Predictive modeling of spread in adult-onset isolated dystonia: Key properties and effect of tremor inclusion.

BACKGROUND AND PURPOSE: Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. The aims of this study were: (i) to develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; and (ii) to evaluate whether presence of tremor associated with dystonia influences model predictions of spread. METHODS: Adult-onset isolated dystonia participants with focal onset from the Dystonia Coalition Natural History Project database were included. We developed two prediction models, one with dystonia as sole disease manifestation ("dystonia-only") and one accepting dystonia OR tremor in any body part as disease manifestations ("dystonia OR tremor"). Demographic and clinical predictors were selected based on previous evidence, clinical plausibility of association with spread, or both. We used logistic regressions and evaluated model discrimination and calibration. Internal validation was carried out based on bootstrapping. RESULTS: Both predictive models showed an area under the curve of 0.65 (95% confidence intervals 0.62-0.70 and 0.62-0.69, respectively) and good calibration after internal validation. In both models, onset of dystonia in body regions other than the neck, older age, depression and history of neck trauma were predictors of spread. CONCLUSIONS: This predictive modeling of spread in adult-onset isolated dystonia based on accessible predictors (demographic and clinical) can be easily implemented to inform individuals' risk of spread. Because tremor did not influence prediction of spread, our results support the argument that tremor is a part of the dystonia syndrome, and not an independent or coincidental disorder.

Low diagnostic yield in follow-up MR imaging in patients with spontaneous intracerebral hemorrhage with a negative initial MRI.

PURPOSE: Follow-up MRI/MRA is historically obtained as outpatient when patients with a spontaneous intracerebral hemorrhage (ICH) have an initial MRI/MRA that is negative for an underlying structural lesion. However, the utility of repeating MR imaging in a delayed fashion remains uncertain. METHODS: We retrospectively reviewed 396 patients with spontaneous ICH admitted at our institution between 2015 and 2017 and selected those whose initial MRI/MRA was negative for an underlying structural lesion and those who underwent follow-up MR imaging in a delayed fashion. RESULTS: A total of 113 patients met the study criteria. The average age of those with negative follow-up MRI/MRA was 65.0 ± 12.6 (IQR: 55.0-74.0) years old. None of the 113 patients with a negative inpatient MRI/MRA had an underlying structural lesion on follow-up MRI/MRA (0%, 95% CI 0.0-0.032, p < 0.001). The mean time of the follow-up imaging from the initial study was 105.7 days (median: 62 days; IQR: 42.5-100.5). Of the 113, 83 (73.5%) underwent follow-up MRI with and without gadolinium, while 30 (26.5%) patients did not receive gadolinium. CONCLUSION: Delayed follow-up MRI in patients with a negative initial MRI/MRA for workup of spontaneous ICH was not diagnostic in any of the patients included in the study. Our study suggests that a routine follow-up MRI for this patient population is not necessary.

Non-invasive positive pressure ventilation versus endotracheal intubation in treatment of COVID-19 patients requiring ventilatory support.

IMPORTANCE: Initial guidelines recommended prompt endotracheal intubation rather than non-invasive ventilation (NIV) for COVID-19 patients requiring ventilator support. There is insufficient data comparing the impact of intubation versus NIV on patient-centered outcomes of these patients. OBJECTIVE: To compare all-cause 30-day mortality for hospitalized COVID-19 patients with respiratory failure who underwent intubation first, intubation after NIV, or NIV only. DESIGN: Retrospective study of patients admitted in March and April of 2020. SETTING: A teaching hospital in Brooklyn, New York City. PARTICIPANTS: Adult COVID-19 confirmed patients who required ventilator support (non-invasive ventilation and/or endotracheal intubation) at discretion of treating physician, were included. EXPOSURES: Patients were categorized into three exposure groups: intubation-first, intubation after NIV, or NIV-only. PRIMARY OUTCOME: 30-day all-cause mortality, a predetermined outcome measured by multivariable logistic regression. Data are presented with medians and interquartile ranges, or percentages with 95% confidence intervals, for continuous and categorical variables, respectively. Covariates for the model were age, sex, qSOFA score ≥ 2, presenting oxygen saturation, vasopressor use, and greater than three comorbidities. A secondary multivariable model compared mortality of all patients that received NIV (intubation after NIV and NIV-only) with the intubation-first group. RESULTS: A total of 222 were enrolled. Overall mortality was 77.5% (95%CI, 72-83%). Mortality for intubation-first group was 82% (95%CI, 73-89%; 75/91), for Intubation after NIV was 84% (95%CI, 70-92%; 37/44), and for NIV-only was 69% (95%CI, 59-78%; 60/87). In multivariable analysis, NIV-only was associated with decreased all-cause mortality (odds ratio [OR]: 0.30, 95%CI, 0.13-0.69). No difference in mortality was observed between intubation-first and intubation after NIV. Secondary analysis found all patients who received NIV to have lower mortality than patients who were intubated only (OR: 0.44, 95%CI, 0.21-0.95). CONCLUSIONS & RELEVANCE: Utilization of NIV as the initial intervention in COVID-19 patients requiring ventilatory support is associated with significant survival benefit. For patients intubated after NIV, the mortality rate is not worse than those who undergo intubation as their initial intervention.

Impact of Blood Transfusion in Free Flap Breast Reconstruction Using Propensity Score Matching.

BACKGROUND: Microvascular thrombosis has been associated with cytokine release and inflammatory syndromes which can occur as a result of blood transfusions. This phenomenon could potentially lead to complications in breast free flap reconstruction. The aim of this study was to evaluate the impact of perioperative blood transfusion in free flap breast reconstruction using large population analysis. METHODS: The American College of Surgeons National Quality Improvement Program database was queried for delayed free flap breast reconstructions performed in 2016. The study population was divided based on perioperative blood transfusion within 24 hours of the start of the operation. Propensity score matching analysis was used to ensure homogeneity between the two study groups. Primary outcome was unplanned return to the operating room (OR) within 30 days. Secondary outcomes were readmission and complications. RESULTS: A total of 1,256 patients were identified. Out of those, 91 patients received a perioperative blood transfusion. All the patients received only one unit of PRBC within the first 24 hours. Those patients were matched with similar patients who did not receive a transfusion on a ratio of 1:3 (273 patients). Patients who received a transfusion had a significantly higher incidence of reoperation (42 vs. 10%, p < 0.001). Patients who received a transfusion were more likely to return to the OR after 48 hours from the initial operation (13 vs. 5%, p = 0.001). All returns to the OR were due to flap-related complications. Perioperative blood transfusion increased the incidence of wound dehiscence (9 vs. 2%, p = 0.041) but had no protective effect on the development of other postoperative complications. CONCLUSION: Perioperative blood transfusion in free flap breast reconstruction is associated with an increased probability of flap-related complications and subsequent return to the OR without decreasing the probability of developing other systemic postoperative complications.

The impact of obesity on COVID-19 complications: a retrospective cohort study.

BACKGROUND: Obesity is an epidemic in New York City, the global epicenter of the coronavirus pandemic. Previous studies suggest that obesity is a possible risk factor for adverse outcomes in COVID-19. OBJECTIVE: To elucidate the association between obesity and COVID-19 outcomes. DESIGN: Retrospective cohort study of COVID-19 hospitalized patients tested between March 10 and April 13, 2020. SETTING: SUNY Downstate Health Sciences University, a COVID-only hospital in New York. PARTICIPANTS: In total, 684 patients were tested for COVID-19 and 504 were analyzed. Patients were categorized into three groups by BMI: normal (BMI 18.50-24.99), overweight (BMI 25.00-29.99), and obese (BMI ≥ 30.00). MEASUREMENTS: Primary outcome was 30-day in-hospital mortality, and secondary outcomes were intubation, acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), and acute cardiac injury (ACI). RESULTS: There were 139 patients (27%) with normal BMI, 150 patients who were overweight (30%), and 215 patients with obesity (43%). After controlling for age, gender, diabetes, hypertension, and qSOFA score, there was a significantly increased risk of mortality in the overweight (RR 1.4, 95% CI 1.1-1.9) and obese groups (RR 1.3, 95% CI 1.0-1.7) compared with those with normal BMI. Similarly, there was a significantly increased relative risk for intubation in the overweight (RR 2.0, 95% CI 1.2-3.3) and obese groups (RR 2.4, 95% CI 1.5-4.0) compared with those with normal BMI. Obesity did not affect rates of AKI, ACI, or ARDS. Furthermore, obesity appears to significantly increase the risk of mortality in males (RR 1.4, 95% CI 1.0-2.0, P = 0.03), but not in females (RR 1.2, 95% CI 0.77-1.9, P = 0.40). CONCLUSION: This study reveals that patients with overweight and obesity who have COVID-19 are at increased risk for mortality and intubation compared to those with normal BMI. These findings support the hypothesis that obesity is a risk factor for COVID-19 complications and should be a consideration in management of COVID-19.

Acid Erosion of Carbonate Fractures and Accessibility of Arsenic-Bearing Minerals: In Operando Synchrotron-Based Microfluidic Experiment.

Underground flows of acidic fluids through fractured rock can create new porosity and increase accessibility to hazardous trace elements such as arsenic. In this study, we developed a custom microfluidic cell for an in operando synchrotron experiment using X-ray attenuation. The experiment mimics reactive fracture flow by passing an acidic fluid over a surface of mineralogically heterogeneous rock from the Eagle Ford shale. Over 48 h, calcite was preferentially dissolved, forming an altered layer 200-500 µm thick with a porosity of 63-68% and surface area >10× higher than that in the unreacted shale as shown by xCT analyses. Calcite dissolution rate quantified from the attenuation data was 3 × 10-4 mol/m2s and decreased to 3 × 10-5 mol/m2s after 24 h because of increasing diffusion limitations. Erosion of the fracture surface increased access to iron-rich minerals, thereby increasing access to toxic metals such as arsenic. Quantification using XRF and XANES microspectroscopy indicated up to 0.5 wt % of As(-I) in arsenopyrite and 1.2 wt % of As(V) associated with ferrihydrite. This study provides valuable contributions for understanding and predicting fracture alteration and changes to the mobilization potential of hazardous metals and metalloids.