Now showing items 1-20 of 4509

    • Isolated Antineutrophil Cytoplasmic Antibody-Associated Coronary Vasculitis and Valvulitis

      Kim, Yoon Kook; Chekka, Praveen; Mysore, Manu; Childress, James; Alfaraidhy, Maha; Thomas, Afton; Taylor, Bradley; Mikdashi, Jamal; Liu, Stanley; Wang, Libin (Elsevier Inc., 2021-02-10)
      A 30-year-old woman presented with angina pectoris. Coronary angiography revealed severe stenosis in the left main and right coronary arteries that did not improve with intracoronary nitroglycerin. Coronary computed tomography angiography and positron emission tomography revealed coronary ostia inflammation and aortic root fat stranding. She was diagnosed with vasculitis and valvulitis and received immunotherapy and coronary bypass. (Level of Difficulty: Advanced.).
    • Complete percutaneous decannulation from femoral venoarterial extracorporeal membrane oxygenation

      Shah, Aakash; Ghoreishi, Mehrdad; Taylor, Bradley S; Toursavadkohi, Shahab; Kaczorowski, David J (Elsevier Inc., 2020-11-21)
      Objectives: To evaluate the clinical outcomes and perioperative complications associated with complete percutaneous decannulation of femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO) with the MANTA closure device. Methods: This is a retrospective analysis of a single surgeon consecutive series of 14 patients at a single center who underwent decannulation from VA-ECMO, 10 of whom underwent a percutaneous method of femoral cannula removal. Results: After a mean duration of VA-ECMO support of 7.4 ± 3.8 days, all 10 patients, with arterial cannulas ranging in size from 17 to 21 Fr, underwent percutaneous decannulation with the MANTA closure device, with immediate hemostasis. One patient had acute lower limb ischemia that was recognized intraoperatively and successfully treated with suction embolectomy. Two patients had a pseudoaneurysm at the distal perfusion catheter site recognized on perioperative imaging studies, one resolving with observation and the other necessitating thrombin injection. One patient had a hematoma that resolved with observation. Conclusions: Percutaneous decannulation from VA-ECMO using the MANTA large-bore vascular closure device is feasible and results in immediate hemostasis with excellent angiographic results.
    • Pre-operative fluid resuscitation in the emergency general surgery septic patient: does it really matter?

      Moran, Benjamin; Major, Erin; Kufera, Joseph A; Tisherman, Samuel A; Diaz, Jose (Springer Nature, 2021-07-22)
      Objective: Emergency general surgery (EGS) patients presenting with sepsis remain a challenge. The Surviving Sepsis Campaign recommends a 30 mL/kg fluid bolus in these patients, but recent studies suggest an association between large volume crystalloid resuscitation and increased mortality. The optimal amount of pre-operative fluid resuscitation prior to source control in patients with intra-abdominal sepsis is unknown. This study aims to determine if increasing volume of resuscitation prior to surgical source control is associated with worsening outcomes. Methods: We conducted an 8-year retrospective chart review of EGS patients undergoing surgery for abdominal sepsis within 24 h of admission. Patients in hemorrhagic shock and those with outside hospital index surgeries were excluded. We grouped patients by increasing pre-operative resuscitation volume in 10 ml/kg intervals up to > 70 ml/kg and later grouped them into < 30 ml/kg or ≥ 30 ml/kg. A relative risk regression model compared amounts of fluid administration. Mortality was the primary outcome measure. Secondary outcomes were time to operation, ventilator days, and length of stay (LOS). Groups were compared by quick Sequential Organ Failure Assessment (qSOFA) and SOFA scoring systems. Results: Of the 301 patients included, the mean age was 55, 51% were male, 257 (85%) survived to discharge. With increasing fluid per kg (< 10 to < 70 ml/kg), there was an increasing mortality per decile, 8.8% versus 31.6% (p = 0.004). Patients who received < 30 mL/kg had lower mortality (11.3 vs 21%) than those who received > 30 ml/kg (p = 0.02). These groups had median qSOFA scores (1.0 vs. 1.0, p = 0.06). There were no differences in time to operation (6.1 vs 4.9 h p = 0.11), ventilator days (1 vs 3, p = 0.08), or hospital LOS (8 vs 9 days, p = 0.57). Relative risk regression correcting for age and physiologic factors showed no significant differences in mortality between the fluid groups. Conclusions: Greater pre-operative resuscitation volumes were initially associated with significantly higher mortality, despite similar organ failure scores. However, fluid volumes were not associated with mortality following adjustment for other physiologic factors in a regression model. The amount of pre-operative volume resuscitation was not associated with differences in time to operation, ventilator days, ICU or hospital LOS.
    • Association of Baseline Urinary Metabolic Biomarkers with ADPKD Severity in TAME-PKD Clinical Trial Participants

      Hallows, Kenneth R; Althouse, Andrew D; Li, Hui; Saitta, Biagio; Abebe, Kaleab Z; Bae, Kyongtae T; Miskulin, Dana C; Perrone, Ronald D; Seliger, Stephen L; Watnick, Terry J (American Society of Nephrology, 2021-05-27)
      Background: Recent work suggests that dysregulated cellular metabolism may play a key role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). The TAME-PKD clinical trial is testing the safety, tolerability, and efficacy of metformin, a regulator of cell metabolism, in patients with ADPKD. This study investigates the cross-sectional association of urinary metabolic biomarkers with ADPKD severity among TAME-PKD trial participants at baseline. Methods: Concentrations of total protein, targeted metabolites (lactate, pyruvate, succinate, and cAMP), and key glycolytic enzymes (pyruvate kinase M2 [PKM2], lactate dehydrogenase A [LDHA], and pyruvate dehydrogenase kinase 1 [PDK1]) were measured by ELISA, enzymatic assays, and immunoblotting in baseline urine specimens of 95 TAME-PKD participants. These analytes, normalized by urinary creatinine or osmolality to estimate excretion, were correlated with patients’ baseline height-adjusted total kidney volumes (htTKVs) by MRI and eGFR. Additional analyses were performed, adjusting for participants’ age and sex, using multivariable linear regression. Results: Greater htTKV correlated with lower eGFR (r=−0.39; P=0.0001). Urinary protein excretion modestly correlated with eGFR (negatively) and htTKV (positively). Urinary cAMP normalized to creatinine positively correlated with eGFR. Among glycolytic enzymes, PKM2 and LDHA excretion positively correlated with htTKV, whereas PKM2 excretion negatively correlated with eGFR. These associations remained significant after adjustments for age and sex. Moreover, in adjusted models, succinate excretion was positively associated with eGFR, and protein excretion was more strongly associated with both eGFR and htTKV in patients <43 years old. Conclusions: Proteinuria correlated with ADPKD severity, and urinary excretion of PKM2 and LDHA correlated with ADPKD severity at baseline in the TAME-PKD study population. These findings are the first to provide evidence in human urine samples that upregulated glycolytic flux is a feature of ADPKD severity. Future analysis may reveal if metformin treatment affects both disease progression and the various urinary metabolic biomarkers in patients throughout the study.
    • Hyperspectral Mapping for the Detection of SARS-CoV-2 Using Nanomolecular Probes with Yoctomole Sensitivity

      Alafeef, Maha; Moitra, Parikshit; Dighe, Ketan; Pan, Dipanjan (American Chemical Society, 2021-07-19)
      Efficient monitoring of SARS-CoV-2 outbreak requires the use of a sensitive and rapid diagnostic test. Although SARS-CoV-2 RNA can be detected by RT-qPCR, the molecular-level quantification of the viral load is still challenging, time-consuming, and labor-intensive. Here, we report an ultrasensitive hyperspectral sensor (HyperSENSE) based on hafnium nanoparticles (HfNPs) for specific detection of COVID-19 causative virus, SARS-CoV-2. Density functional theoretical calculations reveal that HfNPs exhibit higher changes in their absorption wavelength and light scattering when bound to their target SARS-CoV-2 RNA sequence relative to the gold nanoparticles. The assay has a turnaround time of a few seconds and has a limit of detection in the yoctomolar range, which is 1 000 000-fold times higher than the currently available COVID-19 tests. We demonstrated in ∼100 COVID-19 clinical samples that the assay is highly sensitive and has a specificity of 100%. We also show that HyperSENSE can rapidly detect other viruses such as influenza A H1N1. The outstanding sensitivity indicates the potential of the current biosensor in detecting the prevailing presymptomatic and asymptomatic COVID-19 cases. Thus, integrating hyperspectral imaging with nanomaterials establishes a diagnostic platform for ultrasensitive detection of COVID-19 that can potentially be applied to any emerging infectious pathogen.
    • Transcriptomic Profiling of Control and Thyroid-Associated Orbitopathy (TAO) Orbital Fat and TAO Orbital Fibroblasts Undergoing Adipogenesis

      Kim, Dong Won; Taneja, Kamil; Hoang, Thanh; Santiago, Clayton P; McCulley, Timothy J; Merbs, Shannath L; Mahoney, Nicholas R; Blackshaw, Seth; Rajaii, Fatemeh (Association for Research in Vision and Ophthalmology, Inc. (ARVO), 2021-07-16)
      Purpose: Orbital fat hyperplasia commonly occurs in thyroid-associated orbitopathy (TAO). To understand molecular mechanisms underlying orbital adipogenesis, we used transcriptomics to compare gene expression in controls and patients with TAO, as well as in orbital fibroblasts (OFs) undergoing adipogenic differentiation. Methods: We performed bulk RNA sequencing (RNA-Seq) on intraconal orbital fat from controls and patients with TAO. We treated cultured OFs derived from patients with TAO with adipogenic media to induce adipogenesis. We used single nucleus RNA-Seq (snRNA-Seq) to profile treated and control OFs, identifying genes that are dynamically expressed during orbital adipogenesis in vitro, and compared these results to data from control and TAO orbital fat. Results: Gene expression profiles in control and TAO orbital fat are distinct. Signaling pathways including PI3K-Akt signaling, cAMP signaling, AGE-RAGE signaling, regulation of lipolysis, and thyroid hormone signaling are enriched in orbital fat isolated from patients with TAO. SnRNA-Seq of orbital fibroblasts undergoing adipogenesis reveals differential expression of the adipocyte-specific genes FABP4/5, APOE, PPARG, and ADIPOQ during adipogenic differentiation. The insulin-like growth factor-1 receptor and Wnt signaling pathways appear to be enriched early in adipogenesis. Gene modules that are enriched in TAO orbital fat are upregulated in orbital adipocytes during differentiation in vitro, whereas genes that are enriched in control orbital fat are enriched in undifferentiated OFs. Conclusions: We identified pathways enriched in TAO orbital fat, and dynamic changes in gene expression that occur during adipogenic differentiation of orbital fibroblasts. These findings may help guide functional studies of genes and pathways critical for orbital adipogenesis.
    • Preventing Thrombohemorrhagic Complications of Heparinized COVID-19 Patients Using Adjunctive Thromboelastography: A Retrospective Study

      Bunch, Connor M; Thomas, Anthony V; Stillson, John E; Gillespie, Laura; Khan, Rashid Z; Zackariya, Nuha; Shariff, Faadil; Al-Fadhl, Mahmoud; Mjaess, Nicolas; Miller, Peter D; et al. (MDPI AG, 2021-07-14)
      Background: The treatment of COVID-19 patients with heparin is not always effective in preventing thrombotic complications, but can also be associated with bleeding complications, suggesting a balanced approach to anticoagulation is needed. A prior pilot study supported that thromboelastography and conventional coagulation tests could predict hemorrhage in COVID-19 in patients treated with unfractionated heparin or enoxaparin, but did not evaluate the risk of thrombosis. Methods: This single-center, retrospective study included 79 severely ill COVID-19 patients anticoagulated with intermediate or therapeutic dose unfractionated heparin. Two stepwise logistic regression models were performed with bleeding or thrombosis as the dependent variable, and thromboelastography parameters and conventional coagulation tests as the independent variables. Results: Among all 79 patients, 12 (15.2%) had bleeding events, and 20 (25.3%) had thrombosis. Multivariate logistic regression analysis identified a prediction model for bleeding (adjusted R2 = 0.787, p < 0.001) comprised of increased reaction time (p = 0.016), decreased fibrinogen (p = 0.006), decreased D-dimer (p = 0.063), and increased activated partial thromboplastin time (p = 0.084). Multivariate analysis of thrombosis identified a weak prediction model (adjusted R2 = 0.348, p < 0.001) comprised of increased D-dimer (p < 0.001), decreased reaction time (p = 0.002), increased maximum amplitude (p < 0.001), and decreased alpha angle (p = 0.014). Adjunctive thromboelastography decreased the use of packed red cells (p = 0.031) and fresh frozen plasma (p < 0.001). Conclusions: Significantly, this study demonstrates the need for a precision-based titration strategy of anticoagulation for hospitalized COVID-19 patients. Since severely ill COVID-19 patients may switch between thrombotic or hemorrhagic phenotypes or express both simultaneously, institutions may reduce these complications by developing their own titration strategy using daily conventional coagulation tests with adjunctive thromboelastography.
    • Strength Training to Prevent Falls in Older Adults: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

      Claudino, João Gustavo; Afonso, José; Sarvestan, Javad; Lanza, Marcel Bahia; Pennone, Juliana; Filho, Carlos Alberto Cardoso; Serrão, Julio Cerca; Espregueira-Mendes, João; Vasconcelos, Ana Luiza Vilefort; de Andrade, Monique Paula; et al. (MDPI AG, 2021-07-20)
      We performed a systematic review with meta-analysis of randomized controlled trials (RCTs) to assess the effects of strength training (ST), as compared to alternative multimodal or unimodal exercise programs, on the number of falls in older adults (≥60 years). Ten databases were consulted (CINAHL, Cochrane Library, EBSCO, EMBASE, PEDro, PubMed, Scielo, Scopus, SPORTDiscus and Web of Science), without limitations on language or publication date. Eligibility criteria were as follows: RCTs with humans ≥60 years of age of any gender with one group performing supervised ST and a group performing another type of exercise training, reporting data pertaining falls. Certainty of evidence was assessed with Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Meta-analysis used a random effects model to calculate the risk ratio (RR) for number of falls. Five RCTs with six trials were included (n = 543, 76% women). There was no difference between ST and alternative exercise interventions for falls (RR = 1.00, 95% CI 0.77-1.30, p = 0.99). The certainty of evidence was very low. No dose-response relationship could be established. In sum, ST showed comparable RR based on number of falls in older adults when compared to other multimodal or unimodal exercise modalities, but evidence is scarce and heterogeneous, and additional research is required for more robust conclusions. Registration: PROSPERO CRD42020222908.
    • Reporting stAndards for research in PedIatric Dentistry (RAPID): an expert consensus-based statement

      Jayaraman, Jayakumar; Dhar, Vineet; Donly, Kevin J; Priya, Ekta; Raggio, Daniela P; Childers, Noel K; Wright, Timothy J; Nagendrababu, Venkateshbabu; Clarke, Mike; King, Nigel; et al. (Springer Nature, 2021-07-23)
      Background: Reporting guidelines for different study designs are currently available to report studies with accuracy and transparency. There is a need to develop supplementary guideline items that are specific to areas within Pediatric Dentistry. This study aims to develop Reporting stAndards for research in PedIatric Dentistry (RAPID) guidelines using a pre-defined expert consensus-based Delphi process. Methods: The development of the RAPID guidelines was based on the Guidance for Developers of Health Research Reporting Guidelines. Following a comprehensive search of the literature, the Executive Group identified ten themes in Pediatric Dentistry and compiled a draft checklist of items under each theme. The themes were categorized as: General, Oral Medicine, Pathology and Radiology, Children with Special Health Care Needs, Sedation and Hospital Dentistry, Behavior Guidance, Dental Caries, Preventive and Restorative Dentistry, Pulp Therapy, Traumatology, and Interceptive Orthodontics. A RAPID Delphi Group (RDG) was formed comprising of 69 members from 15 countries across six continents. Items were scored using a 9-point rating Likert scale. Items achieving a score of seven and above, marked by at least 70% of RDG members were accepted into the RAPID checklist items. Weighted mean scores were calculated for each item. Statistical significance was set at p < 0.05 and one-way ANOVA was used to calculate the difference in the weighted mean scores between the themes. Results: The final RAPID checklist comprised of 128 items that were finalized and approved by the RDG members in the online consensus meeting. The percentage for high scores (scores 7 to 9) ranged from 69.57 to 100% for individual items. The overall weighted mean score of the final items ranged from 7.51 to 8.28 (out of 9) and the difference was statistically significant between the themes (p < 0.05). Conclusions: The RAPID statement provides guidance to researchers, authors, reviewers and editors, to ensure that all elements relevant to particular studies are adequately reported.
    • Periodontal Disease and Incident CKD in US Hispanics/Latinos: The Hispanic Community Health Study/Study of Latinos

      Toth-Manikowski, Stephanie M.; Ricardo, Ana C.; Salazar, Christian R.; Chen, Jinsong; Khambaty, Tasneem; Liu, Jannel; Singer, Richard H.; Youngblood, Marston E.; Cai, Jianwen; Kaste, Linda M.; et al. (Elsevier Ltd., 2021-07-3)
      Rationale & Objective: Recent studies suggest that periodontal disease may be associated with incident chronic kidney disease (CKD). However, studies have focused on older populations, and US Hispanics/Latinos were not well represented. Study Design: Observational cohort. Setting & Participants: We analyzed data from the Hispanic Community Health Study/Study of Latinos who completed a baseline visit with a periodontal examination and a follow-up visit, and did not have CKD at baseline. Predictors: Predictors included ≥30% of sites with clinical attachment loss ≥3 mm, ≥30% of sites with probing depth ≥4 mm, percentage of sites with bleeding on probing, and absence of functional dentition (<21 permanent teeth present). Outcomes: Outcomes were incident low estimated glomerular filtration rate (eGFR) (eGFR <60 mL/min/1.73 m2 and decline in eGFR ≥1 mL/min/year); incident albuminuria (urine albumin:creatinine ratio [ACR] ≥30 mg/g); and change in eGFR and ACR. Analytic Approach: Poisson and linear regression. Results: For the sample (n = 7.732), baseline mean age was 41.5 years, 45.2% were male, 11.7% had ≥30% of sites with clinical attachment loss ≥3 mm, 5.1% had ≥30% of sites with probing depth ≥4 mm, 30.7% had ≥50% of sites with bleeding on probing, and 16.2% had absent functional dentition. During a median follow-up of 5.9 years, 149 patients developed low eGFR and 415 patients developed albuminuria. On multivariable analysis, presence versus absence of ≥30% of sites with probing depth ≥4 mm and absence of functional dentition were each associated with increased risk for incident low eGFR (incident density ratio, 2.31; 95% CI, 1.14-4.65 and 1.65, 95% CI, 1.01-2.70, respectively). None of the other predictors were associated with outcomes. Limitations: Only a single kidney function follow-up measure. Conclusions: In this cohort of US Hispanics/Latinos, we found that select measures of periodontal disease were associated with incident low eGFR. Future work is needed to assess whether the treatment of periodontal disease may prevent CKD.
    • Predictors of Severe COVID-19 in Patients With Diabetes: A Multicenter Review

      Kristan, Megan M; Kim, Yoon K; Nelson, Toby; Moxley, Meaghan C; Yip, Terry Cheuk-Fung; Munir, Kashif; Malek, Rana (Elsevier B.V., 2021-06-06)
      Objective: Diabetes is an independent risk factor for severe SARS-CoV-2 infections. This study aims to elucidate the risk factors predictive of more severe outcomes in patients with diabetes by comparing the clinical characteristics of those requiring inpatient admissions with those who remain outpatient. Methods: A retrospective review identified 832 patients—631 inpatients and 201 outpatients—with diabetes and a positive SARS-CoV-2 test result between March 1 and June 15, 2020. Comparisons between the outpatient and inpatient cohorts were conducted to identify risk factors associated with severity of disease determined by admission rate and mortality. Previous dipeptidyl peptidase 4 inhibitor use and disease outcomes were analyzed. Results: Risk factors for increased admission included older age (odds ratio [OR], 1.04 [95% CI, 1.01-1.06]; P = .003), the presence of chronic kidney disease (OR, 2.32 [1.26-4.28]; P = .007), and a higher hemoglobin A1c at the time of admission (OR, 1.25 [1.12-1.39]; P < .001). Lower admission rates were seen in those with commercial insurance. Increased mortality was seen in individuals with older age (OR, 1.09 [1.07-1.11]; P < .001), higher body mass index number (OR, 1.04 [1.01-1.07]; P = .003), and higher hemoglobin A1c value at the time of diagnosis of COVID-19 (OR, 1.12 [1.01-1.24]; P = .028) and patients requiring hospitalization. Lower mortality was seen in those with hyperlipidemia. Dipeptidyl peptidase 4 inhibitor use prior to COVID-19 infection was not associated with a decreased hospitalization rate. Conclusion: This retrospective review offers the first analysis of outpatient predictors for admission rate and mortality of COVID-19 in patients with diabetes. © 2021 AACE
    • Lymph node fibroblastic reticular cells steer immune responses

      Li, Lushen; Wu, Jing; Abdi, Reza; Jewell, Christopher M; Bromberg, Jonathan S (Elsevier Ltd., 2021-07-10)
      Lymph nodes (LNs), where immune responses are initiated, are organized into distinctive compartments by fibroblastic reticular cells (FRCs). FRCs imprint immune responses by supporting LN architecture, recruiting immune cells, coordinating immune cell crosstalk, and presenting antigens. Recent high-resolution transcriptional and histological analyses have enriched our knowledge of LN FRC genetic and spatial heterogeneities. Here, we summarize updated anatomic, phenotypic, and functional identities of FRC subsets, delve into topological and transcriptional remodeling of FRCs in inflammation, and illustrate the crosstalk between FRCs and immune cells. Discussing FRC functions in immunity and tolerance, we highlight state-of-the-art FRC-based therapeutic approaches for maintaining physiological homeostasis, steering protective immunity, inducing transplantation tolerance, and treating diverse immune-related diseases. © 2021
    • Procedural Telementoring in Rural, Underdeveloped, and Austere Settings: Origins, Present Challenges, and Future Perspectives

      Wachs, Juan P; Kirkpatrick, Andrew W; Tisherman, Samuel A (Annual Reviews Inc., 2021-03-26)
      Telemedicine is perhaps the most rapidly growing area in health care. Approximately 15 million Americans receive medical assistance remotely every year. Yet rural communities face significant challenges in securing subspecialist care. In the United States, 25% of the population resides in rural areas, where less than 15% of physicians work. Current surgery residency programs do not adequately prepare surgeons for rural practice. Telementoring, wherein a remote expert guides a less experienced caregiver, has been proposed to address this challenge. Nonetheless, existing mentoring technologies are not widely available to rural communities, due to a lack of infrastructure and mentor availability. For this reason, some clinicians prefer simpler and more reliable technologies. This article presents past and current telementoring systems, with a focus on rural settings, and proposes aset of requirements for such systems. We conclude with a perspective on the future of telementoring systems and the integration of artificial intelligence within those systems. © Copyright 2021 by Annual Reviews.
    • Postoperative complications of endovascular blunt thoracic aortic injury repair

      Abdou, Hossam; Elansary, Noha N.; Darko, Louisa; Dubose, Joseph J.; Scalea, Thomas M.; Morrison, Jonathan J.; Kundi, Rishi (BMJ Publishing Group, 2021-07-15)
      Background: Thoracic endovascular aortic repair (TEVAR) has become the standard of care for thoracic aortic aneurysms and increasingly for blunt thoracic aortic injury (BTAI). Postoperative complications, including spinal cord ischemia and paraplegia, have been shown to be less common with elective TEVAR than with open thoracic or thoracoabdominal repair. Although small cohort studies exist, the postoperative complications of endovascular repair of traumatic aortic injury have not been described through large data set analysis. Methods: A retrospective cohort analysis was performed of the American College of Surgeons Trauma Quality Improvement Program registry spanning from 2007 to 2017. All patients with BTAI who underwent TEVAR, as indicated by the Abbreviated Injury Scale or the International Classification of Diseases (ICD-9 or ICD-10), were included. Categorical data were presented as proportions and continuous data as mean and SD. OR was calculated for each postoperative complication. Results: 2990 patients were identified as having undergone TEVAR for BTAI. The postoperative incidence of stroke was 2.8% (83), and 4.7% (140) of patients suffered acute kidney injury or renal failure. The incidence of spinal cord ischemia was 1.9% (58), whereas 0.2% (7) of patients suffered complete paraplegia. Renal events and stroke were found to occur significantly more frequently in those undergoing TEVAR (OR 1.758, 1.449-2.134 and OR 2.489, 1.917-3.232, respectively). Notably, there was no difference between TEVAR and non-operative BTAI incidences of spinal cord ischemia or paraplegia (OR 1.061, 0.799-1.409 and OR 1.698, 0.728-3.961, respectively). Discussion: Postoperative intensive care unit care of patients after BTAI has historically focused on awareness of spinal cord ischemia. Our analysis suggests that after endovascular repair of blunt aortic trauma, care should involve vigilance primarily against postoperative cerebrovascular and renal events. Further study is warranted to develop guidelines for the intensivist managing patients after TEVAR for BTAI. Level of evidence Level III. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
    • Digital Consultations During COVID-19: A Multiperspective Mixed-Methods Study in an Integrative Medicine Setting in Switzerland

      Barth, Jürgen; Canella, Claudia; Oehler, Manuela; Witt, Claudia M (Mary Ann Liebert Inc., 2021-07-12)
      Objective: We evaluated digital consultations at a University Hospital in Switzerland within an integrative medicine outpatient setting. Patients' and treatment providers' (physicians and therapists) evaluated digital conversation-based consultations as well as the digital delivery of practical exercises. Methods: Digital consultations between March 15, 2020 and April 30, 2020 were identified. Between June and July 2020, patients and treatment providers completed online questionnaires addressing challenges and advantages of their digital consultations. Both groups documented their satisfaction and working alliance (Working Alliance Inventory). In addition, semistructured qualitative interviews with treatment providers were conducted. Findings: A total of 82 online surveys (response rate 47%) about the digital consultations were available for analyses, with 60 patients correctly identifying at least one treatment provider, and 9 interviews were performed. Patients and treatment providers overall evaluated the new setting of digital consultation as feasible and an efficient consultation format. Interestingly, the working alliance was rated as good. Technical problems were mentioned as the main challenge and the delivery of practical exercises in digital consultations was seen more challenging than having digital conversation-based consultations. Conclusion: Digital consultations were established with overall positive evaluations and with a good working alliance between patients and providers. For the delivery of practical exercises it might be required to develop more innovative digital settings to overcome shortcomings of the digital format. Hybrid settings that combine the best of both settings could be a good option for future in postpandemic times.
    • Evaluating the Sulfate Radical Anion as a New Reagent for In-Cell Fast Photochemical Oxidation of Proteins

      McKenzie-Coe, Alan A; Johnson, Danté T; Peacock, Riley B; Zhang, Zhihui; Jones, Lisa M (American Chemical Society, 2021-06-25)
      Fast photochemical oxidation of proteins (FPOP) has demonstrated the ability to inform on the higher order structure of proteins. Recent technological advances have extended FPOP to live cells (IC-FPOP) using multiple cell lines and in vivo (IV-FPOP) using C. elegans. These innovations allow proteins to be studied in their native cellular environment. Hydroxyl radicals are generated via the photoloysis of hydrogen peroxide. Hydrogen peroxide is a signaling molecule that can induce changes to some proteins in the cell limiting the proteins that can be studied by IC-FPOP. Here, we evaluate the sulfate radical anion as a footprinting label in IC-FPOP with sodium persulfate as the precursor. Our findings show a 1.5-fold increase in the number of modified proteins compared to IC-FPOP using hydroxyl radicals at the same precursor concentration demonstrating the amenability of this radical with IC-FPOP.
    • Treating the endotheliopathy of SARS-CoV-2 infection with plasma: Lessons learned from optimized trauma resuscitation with blood products

      Pati, Shibani; Fennern, Erin; Holcomb, John B; Barry, Mark; Trivedi, Alpa; Cap, Andrew P; Martin, Matthew J; Wade, Charles; Kozar, Rosemary; Cardenas, Jessica C; et al. (Wiley-Blackwell, 2021-07-16)
    • Reply: Expected Disability From Isolated Small Airway Disease

      Falvo, Michael J; Sotolongo, Anays M; Osinubi, Omowunmi Y; Helmer, Drew A; Galvin, Jeffrey R; Franks, Teri J (Association of Military Surgeons of the US, 2021-07-01)
    • Insights into substrate recognition and specificity for IgG by Endoglycosidase S2

      Aytenfisu, Asaminew H; Deredge, Daniel; Klontz, Erik H; Du, Jonathan; Sundberg, Eric J; MacKerell, Alexander D (Public Library of Science, 2021-07-26)
      Antibodies bind foreign antigens with high affinity and specificity leading to their neutralization and/or clearance by the immune system. The conserved N-glycan on IgG has significant impact on antibody effector function, with the endoglycosidases of Streptococcus pyogenes deglycosylating the IgG to evade the immune system, a process catalyzed by the endoglycosidase EndoS2. Studies have shown that two of the four domains of EndoS2, the carbohydrate binding module (CBM) and the glycoside hydrolase (GH) domain site are critical for catalytic activity. To yield structural insights into contributions of the CBM and the GH domains as well as the overall flexibility of EndoS2 to the proteins’ catalytic activity, models of EndoS2-Fc complexes were generated through enhanced-sampling molecular-dynamics (MD) simulation and site-identification by ligand competitive saturation (SILCS) docking followed by reconstruction and multi-microsecond MD simulations. Modeling results predict that EndoS2 initially interacts with the IgG through its CBM followed by interactions with the GH yielding catalytically competent states. These may involve the CBM and GH of EndoS2 simultaneously interacting with either the same Fc CH2/CH3 domain or individually with the two Fc CH2/CH3 domains, with EndoS2 predicted to assume closed conformations in the former case and open conformations in the latter. Apo EndoS2 is predicted to sample both the open and closed states, suggesting that either complex can directly form following initial IgG-EndoS2 encounter. Interactions of the CBM and GH domains with the IgG are predicted to occur through both its glycan and protein regions. Simulations also predict that the Fc glycan can directly transfer from the CBM to the GH, facilitating formation of catalytically competent complexes and how the 734 to 751 loop on the CBM can facilitate extraction of the glycan away from the Fc CH2/CH3 domain. The predicted models are compared and consistent with Hydrogen/Deuterium Exchange data. In addition, the complex models are consistent with the high specificity of EndoS2 for the glycans on IgG supporting the validity of the predicted models.
    • Genetic Variations in the Transforming Growth Factor-β1 Pathway May Improve Predictive Power for Overall Survival in Non-small Cell Lung Cancer

      Zhang, Hong; Wang, Weili; Pi, Wenhu; Bi, Nan; DesRosiers, Colleen; Kong, Fengchong; Cheng, Monica; Yang, Li; Lautenschlaeger, Tim; Jolly, Shruti; et al. (Frontiers Media S.A., 2021-07-07)
      Purpose: Transforming growth factor-β1 (TGF-β1), a known immune suppressor, plays an important role in tumor progression and overall survival (OS) in many types of cancers. We hypothesized that genetic variations of single nucleotide polymorphisms (SNPs) in the TGF-β1 pathway can predict survival in patients with non-small cell lung cancer (NSCLC) after radiation therapy. Materials and Methods: Fourteen functional SNPs in the TGF-β1 pathway were measured in 166 patients with NSCLC enrolled in a multi-center clinical trial. Clinical factors, including age, gender, ethnicity, smoking status, stage group, histology, Karnofsky Performance Status, equivalent dose at 2 Gy fractions (EQD2), and the use of chemotherapy, were first tested under the univariate Cox's proportional hazards model. All significant clinical predictors were combined as a group of predictors named "Clinical." The significant SNPs under the Cox proportional hazards model were combined as a group of predictors named "SNP." The predictive powers of models using Clinical and Clinical + SNP were compared with the cross-validation concordance index (C-index) of random forest models. Results: Age, gender, stage group, smoking, histology, and EQD2 were identified as significant clinical predictors: Clinical. Among 14 SNPs, BMP2:rs235756 (HR = 0.63; 95% CI:0.42-0.93; p = 0.022), SMAD9:rs7333607 (HR = 2.79; 95% CI 1.22-6.41; p = 0.015), SMAD3:rs12102171 (HR = 0.68; 95% CI: 0.46-1.00; p = 0.050), and SMAD4: rs12456284 (HR = 0.63; 95% CI: 0.43-0.92; p = 0.016) were identified as powerful predictors of SNP. After adding SNP, the C-index of the model increased from 84.1 to 87.6% at 24 months and from 79.4 to 84.4% at 36 months. Conclusion: Genetic variations in the TGF-β1 pathway have the potential to improve the prediction accuracy for OS in patients with NSCLC.