Computational identification of ultra-conserved elements in the human genome: a hypothesis on homologous DNA pairing.

Thousands of prolonged sequences of human ultra-conserved non-coding elements (UCNEs) share only one common feature: peculiarities in the unique composition of their dinucleotides. Here we investigate whether the numerous weak signals emanating from these dinucleotide arrangements can be used for computational identification of UCNEs within the human genome. For this purpose, we analyzed 4272 UCNE sequences, encompassing 1 393 448 nucleotides, alongside equally sized control samples of randomly selected human genomic sequences. Our research identified nine different features of dinucleotide arrangements that enable differentiation of UCNEs from the rest of the genome. We employed these nine features, implementing three Machine Learning techniques - Support Vector Machine, Random Forest, and Artificial Neural Networks - to classify UCNEs, achieving an accuracy rate of 82-84%, with specific conditions allowing for over 90% accuracy. Notably, the strongest feature for UCNE identification was the frequency ratio between GpC dinucleotides and the sum of GpG and CpC dinucleotides. Additionally, we investigated the entire pool of 31 046 SNPs located within UCNEs for their representation in the ClinVar database, which catalogs human SNPs with known phenotypic effects. The presence of UCNE-associated SNPs in ClinVar aligns with the expectation of a random distribution, emphasizing the enigmatic nature of UCNE phenotypic manifestation.

Diabetes increases risk of lumbar spinal fusion complications: association with altered structure of newly formed bone at the fusion site.

Diabetes predisposes to spine degenerative diseases often requiring surgical intervention. However, the statistics on the prevalence of spinal fusion success and clinical indications leading to the revision surgery in diabetes are conflicting. The purpose of the presented retrospective observational study was to determine the link between diabetes and lumbar spinal fusion complications using a database of patients (n = 552, 45% male, age 54 ± 13.7 years) residing in the same community and receiving care at the same health care facility. Outcome measures included clinical indications and calculated risk ratio (RR) for revision surgery in diabetes. Paravertebral tissue recovered from a non-union site of diabetic and nondiabetic patients was analyzed for microstructure of newly formed bone. Diabetes increased the RR for revision surgery due to non-union complications (2.80; 95% CI, 1.12-7.02) and degenerative processes in adjacent spine segments (2.26; 95% CI, 1.45-3.53). In diabetes, a risk of revision surgery exceeded the RR for primary spinal fusion surgery by 44% (2.36 [95% CI, 1.58-3.52] vs 1.64 [95% CI, 1.16-2.31]), which was already 2-fold higher than diabetes prevalence in the studied community. Micro-CT of bony fragments found in the paravertebral tissue harvested during revision surgery revealed structural differences suggesting that newly formed bone in diabetic patients may be of compromised quality, as compared with that in nondiabetic patients. In conclusion, diabetes significantly increases the risk of unsuccessful lumbar spine fusion outcome requiring revision surgery. Diabetes predisposes to the degeneration of adjacent spine segments and pseudoarthrosis at the fusion sites, and affects the structure of newly formed bone needed to stabilize fusion.

Differences in Responses of Immunosuppressed Kidney Transplant Patients to Moderna mRNA-1273 versus Pfizer-BioNTech.

Immunosuppressed kidney transplant (KT) recipients produce a weaker response to COVID-19 vaccination than immunocompetent individuals. We tested antiviral IgG response in 99 KT recipients and 66 healthy volunteers who were vaccinated with mRNA-1273 Moderna or BNT162b2 Pfizer-BioNTech vaccines. A subgroup of participants had their peripheral blood leukocytes (PBLs) evaluated for the frequency of T helper 1 (Th1) cells producing IL-2, IFN-γ and/or TNF-α, and IL-10-producing T-regulatory 1 (Tr) cells. Among KT recipients, 45.8% had anti-SARS-CoV-2 IgG compared to 74.1% of healthy volunteers (p = 0.009); also, anti-viral IgG levels were lower in recipients than in volunteers (p = 0.001). In terms of non-responders (≤2000 U/mL IgG), Moderna's group had 10.8% and Pfizer-BioNTech's group had 34.3% of non-responders at 6 months (p = 0.023); similarly, 15.7% and 31.3% were non-responders in Moderna and Pfizer-BioNTech groups at 12 months, respectively (p = 0.067). There were no non-responders among controls. Healthy volunteers had higher Th1 levels than KT recipients, while Moderna produced a higher Th1 response than Pfizer-BioNTech. In contrast, the Pfizer-BioNTech vaccine induced a higher Tr1 response than the Moderna vaccine (p < 0.05); overall, IgG levels correlated with Th1(fTTNF-α)/Tr1(fTIL-10) ratios. We propose that the higher number of non-responders in the Pfizer-BioNTech group than the Moderna group was caused by a more potent activity of regulatory Tr1 cells in KT recipients vaccinated with the Pfizer-BioNTech vaccine.

The efficacy of non-pharmacological and non-pacing therapies in preventing vasovagal syncope: Tilt training, physical counter pressure maneuvers, and yoga - A systematic review and meta-analysis.

BACKGROUND: Vasovagal syncope (VVS) is a prevalent condition characterized by a sudden drop in blood pressure and heart rate, leading to a brief loss of consciousness and postural control. Recurrent episodes of VVS significantly impact the quality of life and are a common reason for emergency department visits. Non-pharmacological interventions, such as tilt training, physical counter pressure maneuvers, and yoga, have been proposed as potential treatments for VVS. However, their efficacy in preventing VVS remains uncertain. METHODS: A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Web of Science, and Embase were searched up to March 2023 for randomized controlled trials comparing non-pharmacological interventions with control in preventing VVS recurrence. The primary outcome was the recurrence rate of VVS episodes. RESULTS: A total of 1130 participants from 18 studies were included in the meta-analysis. The overall mean effect size for non-pharmacological interventions versus control was 0.245 (95 % CI: 0.128-0.471, p-value <0.001). Subgroup analysis showed that yoga had the largest effect size (odds ratio 0.068, 95 % CI: 0.018-0.250), while tilt training had the lowest effect size (odds ratio 0.402, 95 % CI: 0.171-0.946) compared to control. Physical counter pressure maneuvers demonstrated an odds ratio of 0.294 (95 % CI: 0.165-0.524) compared to control. CONCLUSION: Non-pharmacological interventions show promise in preventing recurrent VVS episodes. Yoga, physical counter pressure maneuvers, and tilt training can be considered as viable treatment options. Further research, including randomized studies comparing pharmacological and non-pharmacological approaches, is needed to evaluate the safety and efficacy of these interventions for VVS treatment.

Safety and Efficacy of Direct Oral Anticoagulant in Addition to Antiplatelet Therapy After Acute Coronary Syndrome: A Systemic Review and Meta-analysis of 53,869 Patients.

INTRODUCTION: Significant progress has been made in the management of patients with acute coronary syndrome (ACS) during the past few decades. However, the role of direct oral anticoagulants (DOACs) in post-ACS prophylactic therapy remains unknown. This study aims to assess the efficacy and safety of DOACs plus antiplatelet treatment (APT) after ACS. METHODS: A systematic literature search was conducted to identify randomized clinical trials comparing DOACs plus APT with APT alone after ACS. The primary efficacy end points were cardiovascular mortality, myocardial infarction, all-cause mortality, and stroke and systemic embolization (SSE). The primary safety end point was major bleeding. The random-effects model was used to calculate relative risk (RR) and corresponding 95% CIs. RESULTS: Nine trials with a total of 53,869 patients were identified, with 33,011 (61.2%) in the DOACs plus APT group and 20,858 (38.8%) in the APT alone group. The use of DOACs did not decrease the risk of cardiovascular death (RR = 0.87; 95% CI, 0.75-1.01; P = 0.08; I2 = 0%) or myocardial infarction (RR = 0.90; 95% CI, 0.80-1.02; P = 0.10; I2 = 6%). However, the risk of SSE was significantly lower in patients who received DOACs plus APT compared with APT alone (RR = 0.67; 95% CI, 0.50-0.90; P = 0.008). Moreover, all-cause mortality was significantly lower in the DOACs plus APT group (RR = 0.83; 95% CI, 0.71-98; P = 0.03; I2 = 0%). However, the risk of major bleeding was significantly higher in patients treated with DOACs plus APT compared with APT alone (RR = 2.53; 95% CI, 1.96-3.26; P < 0.01; I2 = 0%), as was the risk of nonmajor bleeding (RR = 2.27; 95% CI, 1.51-3.41; P < 0.01). IMPLICATIONS: DOACs plus APT for the prevention of left ventricular thrombus in patients with ACS were associated with a lower risk of SSE and all-cause mortality but increased the risk of major and nonmajor bleeding. The benefits and risks of this approach should be weighed based on a patient's individual clinical characteristics.

Comparing EUS-directed Transgastric ERCP (EDGE) Versus Laparoscopic-Assisted ERCP Versus Enteroscopic ERCP: A Network Meta-analysis.

BACKGROUND: Management of choledocholithiasis in patients with Roux-en-Y gastric bypass surgery is challenging. This study aims to compare technical success rates, adverse events, and procedural time between 3 current approaches: endoscopic ultrasound-directed transgastric Endoscopic retrograde cholangiopancreatography (ERCP) (EDGE), enteroscopy-assisted ERCP (E-ERCP), and laparoscopic-assisted ERCP (LA-ERCP). METHODS: A systematic search of 5 databases was conducted. Direct and network meta-analyses were performed to compare interventions using the random effects model. A significance threshold of P < 0.05 was applied. RESULTS: Sixteen studies were included. On direct meta-analysis, technical success rates were comparable between EDGE and LA-ERCP (odds ratio: 0.768, CI: 0.196-3.006, P = 0.704, I2 = 14.13%). However, EDGE and LA-ERCP showed significantly higher success rates than E-ERCP. No significant differences in adverse events were found between EDGE versus LA-ERCP, EDGE versus E-ERCP, and LA-ERCP versus E-ERCP on direct meta-analysis. In terms of procedural time, EDGE was significantly shorter than E-ERCP [mean difference (MD): -31 minutes, 95% CI: -40.748 to -21.217, P < 0.001, I2 = 19.89%), and E-ERCP was shorter than LA-ERCP (MD: -44.567 minutes, 95% CI: -76.018 to -13.116, P = 0.005, I2 = 0%). EDGE also demonstrated a significant time advantage over LA-ERCP (MD: -78.145 minutes, 95% CI: -104.882 to -51.407, P < 0.001, I2 = 0%). All findings were consistent with network meta-analysis on random effects model. The heterogeneity of the model was low. CONCLUSIONS: EDGE and LA-ERCP showed superior technical success rates compared with E-ERCP. Adverse events did not significantly differ among the three approaches. Furthermore, EDGE demonstrated the shortest procedural duration. We recommend considering EDGE as a first-choice procedure.

Assessing the Ethical Concerns of Medical Students in the Gross Anatomy Lab.

OBJECTIVES: Cadaver dissection has become the gold-standard for anatomical education in US medical schools. Ethical issues regarding cadavers may not be as obvious as in living patients, which can lead to their potential neglect in medical school curricula. In this study, we assessed the different ethical concerns (ECs) of medical students regarding cadavers in the gross anatomy lab (GAL), gathered student information, including self-reported academic performance (AP) in the GAL, and determined the best predictors for a student's EC. METHODS: All second-year medical students at the University of Toledo were invited to complete an anonymous, online-survey. Participants were presented with 10 hypothetical but realistic lab scenarios and asked to rate their EC for each on a 5-point Likert scale. Gender, age, and scores received in the GAL course were also collected. A multiple linear regression model was used to find the best predictors of the total EC score. RESULTS: A total of 112 (63%) responses to the online-survey were recorded. The highest EC was for Q7: Taking pictures of the cadaver. The lowest EC was for Q10: The dissection of cadavers itself is an EC. Gender was the best predictor of total EC, followed by age. Female total EC was significantly higher than that for males (35.8 ± 5.5 vs 33.1 ± 7.9). Female scores for Q1 and Q2 were significantly higher than those for males. Total EC for students in the age group 25 to 34 was significantly higher than those in the age group 18 to 24 (35.9 ± 6.1 vs 33.9 ± 7.2). No significant difference was found for individual scenarios. AP was not significantly related to the total score or the scores of the individual scenarios. CONCLUSION: The significant differences in ECs of medical students found in our study indicate that not all students have the same outlook towards the GAL specifically and ECs generally.

Association between Body Mass Index and Hospital Outcomes for COVID-19 Patients: A Nationwide Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused significant morbidity and mortality worldwide. There is limited information describing the hospital outcomes of COVID-19 patients in regard to specific body mass index (BMI) categories. METHODS: We utilized the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS) 2020 database to collect information on patients hospitalized for COVID-19 in the United States. Using the International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) coding system, adult patients (≥18 years of age) with a primary hospitalization for COVID-19 were identified. Adjusted analyses were performed to assess for mortality, morbidity, and resource utilization, and compare the outcomes among patients categorized according to BMI. RESULTS: A total of 305,284 patients were included in this study. Of them, 248,490 had underlying obesity, defined as BMI ≥ 30. The oldest patients were observed to have BMI < 19, while youngest patients were in the BMI > 50 category. BMI < 19 category had the highest crude in-hospital mortality rate. However, after adjusted regression, patients with BMI > 50 (adjusted odds ratio (aOR) 1.63, 95% CI 1.48-1.79, p-value < 0.001) had the highest increased odds, at 63%, of in-hospital mortality compared to all other patients in the study. Patients with BMI > 50 also had the highest increased odds of needing invasive mechanical ventilation (IMV) and mortality associated with IMV compared to all other patient, by 37% and 61%, respectively. Obese patients were noted to have shorter average hospital length of stay (LOS), by 1.07 days, compared to non-obese patients, but there was no significant difference in average hospitalization charges. CONCLUSION: Among obese patients primarily hospitalized with COVID-19, those with BMI ≥ 40 had significantly increased rates of all-cause in-hospital mortality, need for IMV, mortality associated with IMV, and septic shock. Overall, obese patients had shorter average hospital LOS, however, did not have significantly higher hospitalization charges.

Use of ultraviolet light in graduate medical education to assess confidence among residents and fellows in handwashing instruction.

Background: Coronavirus disease 2019 (COVID-19) has made it imperative to focus on strategies to improve hand hygiene to minimize threats of viral transmission in hospitals. Objective: We investigated the potential of using ultraviolet (UV) light as a visual tool in hand-hygiene education to bring awareness of individual handwashing effectiveness to healthcare workers. Methods: In 2020, 117 individuals participated in the simulation and completed surveys on proper handwashing technique. Of these, 114 were first-year residents and fellows. Surveys of confidence in hand hygiene were obtained before and after formal hand-hygiene education utilizing UV light with Glo Germ lotion. The UV light and Glo Germ lotion were used to identify deficiencies in individual handwashing technique. Results: With a total response rate of 97.4%, first-year residents and fellows demonstrated a significant decrease in handwashing confidence in pre- and posteducation surveys. Study participants who had had formal hand-hygiene training in the previous 3 years also indicated confidence in hand hygiene similar to those who had not had previous hand-hygiene training. Conclusions: Overall, resident interns and fellows may have falsely elevated their hand-hygiene confidence levels. However, conclusions regarding the confidence of residents and fellows individually could not be made due to sample size. Many healthcare personnel practice improper handwashing techniques, which may be improved with education and training that includes UV light.

Extracellular sulfatase-2 is overexpressed in rheumatoid arthritis and mediates the TNF-α-induced inflammatory activation of synovial fibroblasts.

Extracellular sulfatase-2 (Sulf-2) influences receptor-ligand binding and subsequent signaling by chemokines and growth factors, yet Sulf-2 remains unexplored in inflammatory cytokine signaling in the context of rheumatoid arthritis (RA). In the present study, we characterized Sulf-2 expression in RA and investigated its potential role in TNF-α-induced synovial inflammation using primary human RA synovial fibroblasts (RASFs). Sulf-2 expression was significantly higher in serum and synovial tissues from patients with RA and in synovium and serum from hTNFtg mice. RNA sequencing analysis of TNF-α-stimulated RASFs showed that Sulf-2 siRNA modulated ~2500 genes compared to scrambled siRNA. Ingenuity Pathway Analysis of RNA sequencing data identified Sulf-2 as a primary target in fibroblasts and macrophages in RA. Western blot, ELISA, and qRT‒PCR analyses confirmed that Sulf-2 knockdown reduced the TNF-α-induced expression of ICAM1, VCAM1, CAD11, PDPN, CCL5, CX3CL1, CXCL10, and CXCL11. Signaling studies identified the protein kinase C-delta (PKCδ) and c-Jun N-terminal kinase (JNK) pathways as key in the TNF-α-mediated induction of proteins related to cellular adhesion and invasion. Knockdown of Sulf-2 abrogated TNF-α-induced RASF proliferation. Sulf-2 knockdown with siRNA and inhibition by OKN-007 suppressed the TNF-α-induced phosphorylation of PKCδ and JNK, thereby suppressing the nuclear translocation and DNA binding activity of the transcription factors AP-1 and NF-κBp65 in human RASFs. Interestingly, Sulf-2 expression positively correlated with the expression of TNF receptor 1, and coimmunoprecipitation assays demonstrated the binding of these two proteins, suggesting they exhibit crosstalk in TNF-α signaling. This study identified a novel role of Sulf-2 in TNF-α signaling and the activation of RA synoviocytes, providing the rationale for evaluating the therapeutic targeting of Sulf-2 in preclinical models of RA.

Contributing Factors to Operating Room Delays Identified from an Electronic Health Record: A Retrospective Study.

The operating room (OR) is considered a major cost center and revenue generator for hospitals. Multiple factors contribute to OR delays and impact patient safety, patient satisfaction scores, and hospital financial performance. Reducing OR delays allows better utilization of OR resources and staffing and improves patient satisfaction while decreasing operating costs. Accurate scheduling can be the basis to achieve these goals. The objective of this initial study was to identify factors not normally documented in the electronic health record (EHR) that may contribute to or be indicators of OR delays. Materials and Methods. A retrospective data analysis was performed analyzing 67,812 OR cases from 12 surgical specialties at a small university medical center from 2010 through the first quarter of 2017. Data from the hospital's EHR were exported and subjected to statistical analysis using Statistical Analysis System (SAS) software (SAS Institute, Cary, NC). Results. Statistical analysis of the extracted EHR data revealed factors that were associated with OR delays including, surgical specialty, preoperative assessment testing, patient body mass index, American Society of Anesthesiologists (ASA) physical status classification, daily procedure count, and calendar year. Conclusions. Delays hurt OR efficiency on many levels. Identifying those factors may reduce delays and better accommodate the needs of surgeons, staff, and patients thereby leading to improved patient's outcomes and patient satisfaction. Reducing delays can decrease operating costs and improve the financial position of the operating theater as well as that of the hospital. Anesthesiology teams can play a key role in identifying factors that cause delays and implementing mitigating efficiencies.

AngioVac for Vegetation Debulking in Right-sided Infective Endocarditis: A Systematic Review and Meta-Analysis.

To investigate the utility of AngioVac-assisted vegetation debulking (AVD) in right sided infective endocarditis (RSIE). AngioVac is a vacuum-based device that was approved in 2014 for the percutaneous removal of undesirable materials from the intravascular system. Although there are multiple reports on the use of the AngioVac device to aspirate right-sided heart chamber thrombi, data on its use to treat RSIE is limited. We performed a comprehensive literature search for studies that evaluated the utility of AVD. The primary outcomes of our study were the procedural success, defined as the ability of AngioVac to produce residual vegetation size <50% (RVS<50%) without serious procedural complications, and the clinical success, defined as composite of RVS<50%, in-hospital survival, absence of recurrent bacteremia, and valve function not requiring further intervention. The secondary outcomes included the individual components of the primary outcomes and average length of hospital stay. The pooled means and proportions of our data were analyzed using random effects model, generic inverse variance method, and represented with 95% confidence intervals (CIs). A total of 44 studies, including 301 patients (mean age: 44.6 ± 18.2 years, 71.6% males) were included. Procedural success was achieved in 89.2% of patients (95% CI:82.3%-93.6%, I2 = 0%). Clinical success was achieved in 79.1% of patients (95% CI:67.9%-87.2%, I2 = 15%). Overall survival rate was 89.7% (95% CI:83.1%-93.9%%, I2 = 9%). Our meta-analysis demonstrates that AVD is a promising therapeutic option for RSIE offering a high success rate with an acceptable complication rate across a wide range of patients.

Neuromuscular function of the shoulder girdle and upper extremity musculature in individuals with a history of glenohumeral labral repair.

The purpose of this study was to compare neuromuscular function in the upper extremity musculature between individuals with glenohumeral labrum repair and uninjured controls. This cross-sectional study examined 16 individuals with a primary, unilateral glenohumeral labral repair (male/female: 13/3, age: 24.1 ± 5.0 years, time from surgery: 36.7 ± 33.3 months) and 14 uninjured individuals (male/female: 11/3, age: 23.8 ± 2.7 years) matched by age, sex, activity level, and limb dominance participated. Mass-normalized shoulder abduction and wrist flexion maximal voluntary isometric contraction (MVIC) torque, motoneuron pool excitability of the flexor carpi radialis (Hoffmann reflex), and corticospinal excitability of the upper trapezius, middle deltoid, and flexor carpi radialis (active motor threshold [AMT]) were evaluated. Dependent and independent t-tests were used to assess between-limb and between-group comparisons. Cohen's d effect sizes with 95% confidence intervals were used to quantify the magnitude of differences observed. Within the injured group, the involved limb had lesser shoulder abduction MVIC torque (p < 0.001, d = 1.16) and higher AMT for the upper trapezius (p = 0.01, d = 0.81) compared with the contralateral limb. The labral repair group had lesser shoulder abduction MVIC torque (p < 0.001, d = 1.17) and Hoffmann reflex (p = 0.01, d = 0.99), as well as higher AMT for the upper trapezius (p < 0.001, d = 1.23) in their involved limb compared with the control group. Large magnitude neuromuscular impairments are present beyond 6 months from glenohumeral labral repair, suggesting potential origins of impairments to be addressed during post-operative rehabilitation.

Improving Access to HLA-Matched Kidney Transplants for African American Patients.

Introduction: Kidney transplants fail more often in Black than in non-Black (White, non-Black Hispanic, and Asian) recipients. We used the estimated physicochemical immunogenicity for polymorphic amino acids of donor/recipient HLAs to select weakly immunogenic kidney transplants for Black vs. White or non-Black patients. Methods: OPTN data for 65,040 donor/recipient pairs over a 20-year period were used to calculate the individual physicochemical immunogenicity by hydrophobic, electrostatic and amino acid mismatch scores (HMS, EMS, AMS) and graft-survival outcomes for Black vs. White or vs. non-Black recipients, using Kaplan-Meier survival and Cox regression analyses. Simulations for re-matching recipients with donors were based on race-adjusted HMS thresholds with clinically achievable allocations. Results: The retrospective median kidney graft survival was 12.0 years in Black vs. 18.6 years in White (6.6-year difference; p>0.001) and 18.4 years in non-Black (6.4-year difference; p>0.01) recipients. Only 0.7% of Blacks received transplants matched at HLA-A/B/DR/DQ (HMS=0) vs. 8.1% in Whites (p<0.001). Among fully matched Blacks (HMS=0), graft survival was 16.1-years and in well-matched Blacks (HMS ≤ 3.0) it was 14.0-years. Whites had 21.6-years survival at HMS ≤ 3.0 and 18.7-years at HMS ≤ 7.0 whereas non-Blacks had 22.0-year at HMS ≤ 3.0 and 18.7-year at HMS ≤ 7.0, confirming that higher HMS thresholds produced excellent survival. Simulation of ABO-compatible donor-recipient pairs using race-adjusted HMS thresholds identified weakly immunogenic matches at HMS=0 for 6.1% Blacks and 18.0% at HMS ≤ 3.0. Despite prioritizing Black patients, non-Black patients could be matched at the same level as in current allocation (47.0% vs 56.5%, at HMS ≤ 7.0). Conclusions: Race-adjusted HMS (EMS, AMS)-based allocation increased the number of weakly immunogenic donors for Black patients, while still providing excellent options for non-Black recipients.

Platelet Storage Pool Deficiency and Elevated Inflammatory Biomarkers Are Prevalent in Postural Orthostatic Tachycardia Syndrome.

A significant number of postural orthostatic tachycardia syndrome (POTS) patients have platelet delta granule storage pool deficiency (δ-SPD). The etiology of POTS is unknown but a number of laboratories, including ours, have reported elevations of G-protein-coupled adrenergic receptor and muscarinic acetylcholine receptor autoantibodies in POTS patients, detected by a variety of techniques, suggesting that the disorder is an autoimmune condition. Thus, it could also be considered an inflammatory disease. In a pilot study, we investigated a limited number of platelet-related cytokines and chemokines and discovered many that were elevated. This case−control study validates our pilot study results that POTS patients have an activated innate immune system. Plasma of 35 POTS patients and 35 patients with unexplained bleeding symptoms and categorized as "non-POTS" subjects was analyzed by multiplex flow cytometry to quantify 16 different innate immune system cytokines and chemokines. Electron microscopy was used to quantify platelet dense granules. Ten of 16 biomarkers of inflammation were elevated in plasma from POTS patients compared to non-POTS subjects, with most of the differences extremely significant, with p values < 0.0001. Of particular interest were elevations of IL-1ß and IL-18 and decreased or normal levels of type 1 interferons in POTS patients, suggesting that the etiology of POTS might be autoinflammatory. All POTS patients had δ-SPD. With a growing body of evidence that POTS is an autoimmune disease and having elevations of the innate immune system, our results suggest a potential T-cell-mediated autoimmunity in POTS characteristic of a mixed-pattern inflammatory disease similar to rheumatoid arthritis.

Home Health Care Utilization Trend, Predictors, and Association With Early Rehospitalization Following Endovascular Transcatheter Aortic Valve Replacement.

BACKGROUND/PURPOSE: Home healthcare (HHC) utilization is associated with higher rates of rehospitalization in patients with heart failure and transcatheter mitral valve repair. This study sought to assess the utilization, predictors, and the association of HHC with 30-day readmission in patients undergoing transcatheter aortic valve replacement (TAVR). METHODS/MATERIALS: We queried the Nationwide Readmission Database from January 2012 to December 2017 for TAVR discharges with and without HHC referral. Using multivariate analysis, we identified predictors of HHC utilization, and its association with outcomes. RESULTS: Of 60,950 TAVR discharges, 21,724 (35.7%) had HHC referral. On multivariable analysis, female sex (OR, 1.34; 95% CI, 1.29-1.40), non-elective admission (OR, 1.49; 95% CI, 1.42-1.56), diabetes mellitus (OR, 1.09; 95% CI, 1.05-1.13), prior stroke (OR, 1.06; 95% CI, 1.01-1.12), anemia (OR, 1.16; 95% CI, 1.11-1.21), and in-hospital complications including cardiogenic shock (OR, 1.37; 95% CI, 1.16-1.50), cardiac arrest (OR, 1.22; 95% CI, 1.00-1.50), stroke (OR, 2.62; 95% CI, 2.20-3.18), and new Permanent pacemaker (OR, 1.49; 95% CI, 1.41-1.58) were identified as independent predictors of HHC referral. HHC utilization was associated with longer median length of stay (4 days vs. 2 days, P < 0.001), higher rate of 30-day all-cause (15.5% vs. 10.6%, P < 0.001) and heart failure (2.1%vs. 1.1%, P < 0.001) readmission rates compared to those without HHC. CONCLUSIONS: Our study identified a vulnerable group of TAVR patients that are at higher risk of 30-day readmission. Evidence-based interventions proven effective in reducing the burden of readmissions should be pursed in these patients to improve outcomes and quality of life.

A novel assay that characterizes properdin function shows neutrophil-derived properdin has a distinct oligomeric distribution.

Properdin acts as an essential positive regulator of the alternative pathway of complement by stabilizing enzymatic convertases. Identical properdin monomers form head-to-tail associations of oligomers in a reported 20:54:26 ratio (most often described as an approximate 1:2:1 ratio) of tetramers (P4), trimers (P3), and dimers (P2), in blood, under normal physiological conditions. Oligomeric size is proportional to properdin function with tetramers being more active, followed by trimers and dimers. Neutrophils are the most abundant granulocyte, are recruited to inflammatory microenvironments, and are a significant source of properdin, yet the ratio of properdin oligomers released from neutrophils is unknown. The oligomer ratio of neutrophil-derived properdin could have functional consequences in local microenvironments where neutrophils are abundant and complement drives inflammation. We investigated the oligomer properties of neutrophil-derived properdin, as compared to that of normal human sera, using a novel ELISA-based method that detects function of properdin in a way that was proportional to the oligomeric size of properdin (i.e., the larger the oligomer, the higher the detected function). Unexpectedly, neutrophil-derived properdin had 5-fold lower function than donor-matched serum-derived properdin. The lower function was due to a lower percentage of tetramers/trimers and more dimers, indicating a significantly different P4:P3:P2 ratio in neutrophil-derived properdin (18:34:48) as compared to donor-matched serum (29:43:29). Release of lower-order oligomers by neutrophils may constitute a novel regulatory mechanism to control the rate of complement activation in cellular microenvironments. Further studies to determine the factors that affect properdin oligomerization and whether, or how, the predominant dimers in neutrophil-derived properdin, assimilate to the ~1:2:1 ratio found in serum are warranted.

In-Hospital Mortality and Morbidity in Cancer Patients with COVID-19: A Nationwide Analysis from the United States.

Background: Coronavirus disease 2019 (COVID-19) caused significant mortality and mortality worldwide. There is limited information describing the outcomes of COVID-19 in cancer patients. Methods: We utilized the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (NIS) 2020 database to collect information on cancer patients hospitalized for COVID-19 in the United States. Using the International Classification of Diseases, 10th revision, Clinical Modification (ICD-10-CM) coding system, adult (≥18 years) patients with COVID-19 were identified. Adjusted analyses were performed to assess for mortality, morbidity, and resource utilization among cancer patients. Results: A total of 1,050,045 patients were included. Of them, 27,760 had underlying cancer. Cancer patients were older and had more comorbidities. The all-cause in-hospital mortality rate in cancer patients was 17.58% vs. 11% in non-cancer. After adjusted logistic regression, cancer patients had a 21% increase in the odds of all-cause in-hospital mortality compared with those without cancer (adjusted odds ratio (aOR) 1.21, 95%CI 1.12−1.31, p-value < 0.001). Additionally, an increased odds in acute respiratory failure rate was found (aOR 1.14, 95%CI 1.06−1.22, p-value < 0.001). However, no significant differences were found in the odds of septic shock, acute respiratory distress syndrome, and mechanical ventilation between the two groups. Additionally, no significant differences in the mean length of hospital stay and the total hospitalization charges between cancer and non-cancer patients. Conclusion: Cancer patients hospitalized for COVID-19 had increased odds of all-cause in hospital mortality and acute respiratory failure compared with non-cancer patients.

Corrigendum: Ets-2 Propagates IL-6 Trans-Signaling Mediated Osteoclast-Like Changes in Human Rheumatoid Arthritis Synovial Fibroblast.

[This corrects the article DOI: 10.3389/fimmu.2021.746503.].