Publications by authors named "Brandon Michael Henry"

137 Publications

Outcomes of extracorporeal life support for respiratory failure in children with primary immunodeficiencies.

Perfusion 2021 Jul 19:2676591211033946. Epub 2021 Jul 19.

The Heart Institute, Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.

Objective: Extracorporeal Membrane Oxygenation (ECMO) may serve as a life-saving rescue therapy in critically ill children with respiratory failure. While survival rates of ECMO in children with secondary immunodeficiency is considered relatively poor, survival rates in children with primary immunodeficiencies (PID) has yet to be thoroughly investigated.

Design: Retrospective analysis of prospectively collected data from children (29 days-18 years old). PID patients were identified by using International Classification of Diseases (ICD) codes.

Setting: Data were retrieved from Extracorporeal Life Support Organization Registry (1989-2018).

Interventions: ECMO for a pulmonary support indication. The survival-to-discharge rate was calculated and factors influencing outcomes were compared between survivors and non-survivors.

Measurements And Main Results: A total of 73 eligible ECMO runs were included. The survival-to-discharge rate in pediatric PID patients was 45.2%. No differences were noted in survival based on type of immunodeficiency (p = 0.42) or decade of support (p = 0.98). There was no difference in the rate of pre-ECMO infection in survivors versus non-survivors (p = 0.69). The survival-to-discharge rate in patients with a culture positive infection during the ECMO run was 45.0% versus 45.3% in those with no infection (p = 0.98). In multivariate analysis, only cardiac complications (OR 5.09, 95% CI: 1.15-22.53), pulmonary complications (OR: 13.00, 95% CI: 1.20-141.25), and neurologic complications (OR: 9.86, 95% CI: 1.64-59.21) were independently associated with increased mortality.

Conclusion: Children with a PID who require extracorporeal life support due to respiratory failure have a reasonable chance of survival and should be considered candidates for ECMO. The presence of a pre-ECMO infection should not be considered an ECMO contraindication.
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http://dx.doi.org/10.1177/02676591211033946DOI Listing
July 2021

Is Lupus Anticoagulant a Significant Feature of COVID-19? A Critical Appraisal of the Literature.

Semin Thromb Hemost 2021 Jun 15. Epub 2021 Jun 15.

Section of Clinical Biochemistry, University of Verona, Verona, Italy.

The term "lupus anticoagulant (LA)" identifies a form of antiphospholipid antibodies (aPLs) causing prolongation of clotting tests in a phospholipid concentration-dependent manner. LA is one of the laboratory criteria identified in patients with antiphospholipid (antibody) syndrome (APS). The presence of LA in patients with APS represents a significant risk factor for both thrombosis and pregnancy morbidity. There have been several reports of similarities between some of the pathophysiological features of COVID-19 and APS, in particular the most severe form, catastrophic APS. There have also been many reports identifying various aPLs, including LA, in COVID-19 patients. Accordingly, a very pertinent question arises: "Is LA a feature of COVID-19 pathology?" In this review, we critically appraise the literature to help answer this question. We conclude that LA positivity is a feature of COVID-19, at least in some patients, and potentially those who are the sickest or have the most severe infection. However, many publications have failed to appropriately consider the many confounders to LA identification, being assessed using clot-based assays such as the dilute Russell viper venom time, the activated partial thromboplastin time (aPTT), and the silica clotting time. First, most patients hospitalized with COVID-19 are placed on anticoagulant therapy, and those with prior histories of thrombosis would possibly present to hospital already on anticoagulant therapy. All anticoagulants, including vitamin K antagonists, heparin (both unfractionated heparin and low-molecular-weight heparin), and direct oral anticoagulants affect these clot-based assays. Second, C-reactive protein (CRP) is highly elevated in COVID-19 patients, and also associated with severity. CRP can also lead to false-positive LA, particularly with the aPTT assay. Third, persistence of aPL positivity (including LA) is required to identify APS. Fourth, those at greatest risk of thrombosis due to aPL are those with highest titers or multiple positivity. Most publications either did not identify anticoagulation and/or CRP in their COVID-19 cohorts or did not seem to account for these as possible confounders for LA detection. Most publications did not assess for aPL persistence, and where persistence was checked, LA appeared to represent transient aPL. Finally, high titer aPL or multiple aPL positivity were in the minority of COVID-19 presentations. Thus, at least some of the reported LAs associated with COVID-19 are likely to be false positives, and the relationship between the detected aPL/LA and COVID-19-associated coagulopathy remains to be resolved using larger and better studies.
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http://dx.doi.org/10.1055/s-0041-1729856DOI Listing
June 2021

COVID-19 and Antiphospholipid Antibodies: Time for a Reality Check?

Semin Thromb Hemost 2021 Jun 15. Epub 2021 Jun 15.

Section of Clinical Biochemistry, University of Verona, Verona, Italy.

Antiphospholipid antibodies (aPL) comprise a panel of autoantibodies that reflect a potential prothrombotic risk in several autoimmune conditions, most notably antiphospholipid (antibody) syndrome (APS). aPL can be divided into those that form part of the laboratory criteria for APS, namely, lupus anticoagulant (LA), as well as anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I antibodies (aβ2GPI) of the immunoglobulin G and M classes, and those that form a group considered as "noncriteria antibodies." The noncriteria antibodies include, for example, antiphosphatidylserine antibodies (aPS), antiprothrombin antibodies (aPT), and antiphosphatidylserine/prothrombin complex antibodies (aPS/PT). COVID-19 (coronavirus disease 2019) represents a prothrombotic disorder, and there have been several reports of various aPL being present in COVID-19 patients. There have also been similarities drawn between some of the pathophysiological features of COVID-19 and APS, in particular, the most severe form, catastrophic APS (CAPS). In this review, we critically appraise the literature on aPL and COVID-19. This is a companion piece to a separate review focused on LA. In the current review, we primarily concentrate on the so-called solid phase identifiable aPL, such as aCL and aβ2GPI, but also reflect on noncriteria aPL. We conclude that aPL positivity may be a feature of COVID-19, at least in some patients, but in general, identified "solid-phase" aPL are of low titer and not able to be well-linked to the thrombotic aspects of COVID-19. Also, most publications did not assess for aPL persistence, and where persistence was checked, the findings appeared to represent transient aPL. Importantly, high-titer aPL or multiple aPL positivity (including double, triple) were in the minority of COVID-19 presentations, and thus discount any widespread presence of APS, including the most severe form CAPS, in COVID-19 patients.
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http://dx.doi.org/10.1055/s-0041-1728832DOI Listing
June 2021

Anti-SARS-CoV-2 Antibodies Testing in Recipients of COVID-19 Vaccination: Why, When, and How?

Diagnostics (Basel) 2021 May 25;11(6). Epub 2021 May 25.

Department of Medicine-DIMED, Medical School, University of Padova, 37126 Verona, Italy.

Although universal vaccination is one of the most important healthcare strategies for limiting SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) circulation and averting the huge number of hospitalizations and deaths due to coronavirus disease 2019 (COVID-19), significant inter-individual variability of COVID-19 vaccines' efficacies has been described, mostly due to heterogeneous immune response in recipients. This opinion paper hence aims to discuss aspects related to the opportunity of monitoring anti-SARS-CoV-2 antibodies before and after COVID-19 vaccination, highlighting the pros and cons of this strategy. In summary, the advantages of anti-SARS-CoV-2 antibodies' testing in recipients of COVID-19 vaccination encompass an assessment of baseline seroprevalence of SARS-CoV-2 infection in non-vaccinated individuals; early identification of low or non-responders to COVID-19 vaccination; and timely detection of faster decay of anti-SARS-CoV-2 antibody levels. In contrast, potential drawbacks to date include an unproven equivalence between anti-SARS-CoV-2 antibody titer, neutralizing activity, and vaccine efficiency; the lack of cost-effective analyses of different testing strategies; the enormous volume of blood drawings and increase of laboratory workload that would be needed to support universal anti-SARS-CoV-2 antibodies testing. A potential solution entails the identification of cohorts to be prioritized for testing, including those at higher risk of being infected by variants of concern, those at higher risk of unfavorable disease progression, and subjects in whom vaccine immunogenicity may be expectedly lower and/or shorter.
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http://dx.doi.org/10.3390/diagnostics11060941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228868PMC
May 2021

Serum ACE activity and plasma ACE concentration in patients with SARS-CoV-2 infection.

Scand J Clin Lab Invest 2021 07 18;81(4):272-275. Epub 2021 May 18.

Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, OH, USA.

Significant controversy has arisen over the role of the renin-angiotensin-aldosterone system (RAAS) in COVID-19 pathophysiology. In this prospective, observational study, we evaluated plasma angiotensin converting enzyme (ACE) concentration and serum ACE activity in 52 adults with laboratory-confirmed SARS-CoV-2 infection and 27 non-COVID-19 sick controls. No significant differences were observed in ACE activity in COVID-19 patients versus non-COVID-19 sick controls (41.1 [interquartile range (IQR): 23.0-55.2] vs. 42.9 [IQR 13.6-74.2] U/L,  = .649, respectively). Similarly, no differences were observed in ACE concentration in COVID-19 patients versus non-COVID-19 sick controls (108.4 [IQR: 95.8-142.2] vs. 133.8 [IQR: 100.2-173.7] μg/L,  = .059, respectively). Neither ACE activity ( = .751), nor ACE concentration ( = .283) was associated with COVID-19 severity. Moreover, neither ACE activity, nor ACE concentration was correlated with any inflammatory biomarkers.
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http://dx.doi.org/10.1080/00365513.2021.1926536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146290PMC
July 2021

The complicated relationships of heparin-induced thrombocytopenia and platelet factor 4 antibodies with COVID-19.

Int J Lab Hematol 2021 May 17. Epub 2021 May 17.

Section of Clinical Biochemistry, University of Verona, Verona, Italy.

COVID-19 (coronavirus disease 2019) represents a prothrombotic disorder, and there have been several reports of platelet factor 4/heparin antibodies being present in COVID-19-infected patients. This has thus been identified in some publications as representing a high incidence of heparin-induced thrombocytopenia (HIT), whereas in others, findings have been tempered by general lack of functional reactivity using confirmation assays of serotonin release assay (SRA) or heparin-induced platelet aggregation (HIPA). Moreover, in at least two publications, data are provided suggesting that antibodies can arise in heparin naïve patients or that platelet activation may not be heparin-dependent. From this literature, we would conclude that platelet factor 4/heparin antibodies can be observed in COVID-19-infected patients, and they may occur at higher incidence than in historical non-COVID-19-infected cohorts. However, the situation is complex, since not all platelet factor 4/heparin antibodies may lead to platelet activation, and not all identified antibodies are heparin-dependent, such that they do not necessarily reflect "true" HIT. Most recently, a "HIT-like" syndrome has reported in patients who have been vaccinated against COVID-19. Accordingly, much more is yet to be learnt about the insidious disease that COVID-19 represents, including autoimmune outcomes in affected patients.
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http://dx.doi.org/10.1111/ijlh.13582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239595PMC
May 2021

Complement levels at admission as a reflection of coronavirus disease 2019 (COVID-19) severity state.

J Med Virol 2021 09 19;93(9):5515-5522. Epub 2021 May 19.

Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

Complement system hyperactivation has been proposed as a potential driver of adverse outcomes in severe acute respiratory syndrome coronavirus 2 infected patients, given prior research of complement deposits found in tissue and blood samples, as well as evidence of clinical improvement with anticomplement therapy. Its role in augmenting thrombotic microangiopathy mediated organ damage has also been implicated in coronavirus disease 2019 (COVID-19). This study aimed to examine associations between complement parameters and progression to severe COVID-19 illness, as well as correlations with other systems. Blood samples of COVID-19 patients presenting to the emergency department (ED) were analyzed for a wide panel of complement and inflammatory biomarkers. The primary outcome was COVID-19 severity at index ED visit, while the secondary outcome was peak disease severity over the course of illness. Fifty-two COVID-19 patients were enrolled. C3a (p = 0.018), C3a/C3 ratio (p = 0.002), and sC5b-9/C3 ratio (p = 0.021) were significantly elevated in with severe disease at ED presentation. Over the course of illness, C3a (p = 0.028) and C3a/C3 ratio (p = 0.003) were highest in the moderate severity group. In multivariate regression controlled for confounders, complement hyperactivation failed to predict progression to severe disease. C3a, C3a/C3 ratio, and sC5b-9/C3 ratio were correlated positively with numerous inflammatory biomarkers, fibrinogen, and VWF:Ag, and negatively with plasminogen and ADAMTS13 activity. We found evidence of complement hyperactivation in COVID-19, associated with hyperinflammation and thrombotic microangiopathy. Complement inhibition should be further investigated for potential benefit in patients displaying a hyperinflammatory and microangiopathic phenotype.
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http://dx.doi.org/10.1002/jmv.27077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242600PMC
September 2021

Pooled analysis of mid-regional pro-adrenomedullin values in COVID-19 patients with critical illness.

Intern Emerg Med 2021 May 7. Epub 2021 May 7.

Cardiac Intensive Care Unit, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

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http://dx.doi.org/10.1007/s11739-021-02756-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104917PMC
May 2021

Increased VWF and Decreased ADAMTS-13 in COVID-19: Creating a Milieu for (Micro)Thrombosis.

Semin Thromb Hemost 2021 Jun 23;47(4):400-418. Epub 2021 Apr 23.

Section of Clinical Biochemistry, University of Verona, Verona, Italy.

von Willebrand factor (VWF) is a large adhesive multimeric protein involved in hemostasis. The larger the size (or number of VWF multimers), the greater the functionality of the protein. A deficiency or defect of VWF can lead to von Willebrand disease (VWD) and cause bleeding. Conversely, an increase in VWF may create an environment that promotes thrombosis. ADAMS-13 ( isintegrin nd etalloproteinase with a hrombopondin type 1 motif, member ), sometimes called VWF-cleaving protease, is primarily responsible for controlling the size of VWF. The most severe deficiency (<10% of normal levels) of ADAMTS-13 arises in thrombotic thrombocytopenic purpura, a condition characterized by the presence of ultralarge VWF and clinically resulting in enhanced risk of thrombosis. However, ADAMTS-13 deficiency may result from other pathological processes. Of relevance is the recent finding that COVID-19 (coronavirus disease 2019) is associated with both increased levels and activity of VWF as well as generally decreased (or occasionally normal) activity levels of ADAMTS-13. Thus, in COVID-19 there is an alteration in the VWF/ADAMTS-13 axis, most often described by increased VWF/ADAMTS-13 ratio (or reduced ADAMTS-13/VWF ratio). COVID-19 is also associated with high prothrombotic risk. Thus, the imbalance of VWF and ADAMTS-13 in COVID-19 may be providing a milieu that promotes (micro)thrombosis, in a clinical picture resembling a secondary thrombotic microangiopathy in some patients. This review therefore assesses the literature on VWF, ADAMTS-13, and COVID-19. Whenever reported in COVID-19, VWF has always been identified as raised (compared with normal reference ranges or control populations). Reports have included VWF level (i.e., VWF antigen) and in some cases one or more VWF "activity" (e.g., collagen binding; platelet glycoprotein Ib [GPIb] binding, using ristocetin cofactor or more modern versions including VWF:GPIbR [recombinant] and VWF:GPIbM [mutant]). Whenever reported, ADAMTS-13 has been reported as "normal" or reduced; however, it should be recognized that "normal" levels may still identify a relative reduction in individual cases. Some reports also discuss the raised VWF/ADAMTS-13 (or reduced ADAMTS-13/VWF) ratio, but very few provide actual numerical data.
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http://dx.doi.org/10.1055/s-0041-1727282DOI Listing
June 2021

Cytokeratin 18 cell death assays as biomarkers for quantification of apoptosis and necrosis in COVID-19: a prospective, observational study.

J Clin Pathol 2021 Mar 31. Epub 2021 Mar 31.

Department of Emergency Medicine, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.

Background: The mechanism by which SARS-CoV-2 triggers cell damage and necrosis are yet to be fully elucidated. We sought to quantify epithelial cell death in patients with COVID-19, with an estimation of relative contributions of apoptosis and necrosis.

Methods: Blood samples were collected prospectively from adult patients presenting to the emergency department. Circulating levels of caspase-cleaved (apoptosis) and total cytokeratin 18 (CK-18) (total cell death) were determined using M30 and M65 enzyme assays, respectively. Intact CK-18 (necrosis) was estimated by subtracting M30 levels from M65.

Results: A total of 52 COVID-19 patients and 27 matched sick controls (with respiratory symptoms not due to COVID-19) were enrolled. Compared with sick controls, COVID-19 patients had higher levels of M65 (p = 0.046, total cell death) and M30 (p = 0.0079, apoptosis). Hospitalised COVID-19 patients had higher levels of M65 (p= 0.014) and intact CK-18 (p= 0.004, necrosis) than discharged patients. Intensive care unit (ICU)-admitted COVID-19 patients had higher levels of M65 (p= 0.004), M30 (p= 0.004) and intact CK-18 (p= 0.033) than hospitalised non-ICU admitted patients. In multivariable logistic regression, elevated levels of M65, M30 and intact CK-18 were associated with increased odds of ICU admission (OR=22.05, p=0.014, OR=19.71, p=0.012 and OR=14.12, p=0.016, respectively).

Conclusion: Necrosis appears to be the main driver of hospitalisation, whereas apoptosis and necrosis appear to drive ICU admission. Elevated levels CK-18 levels are independent predictors of severe disease, and could be useful for risk stratification of COVID-19 patients and in assessment of therapeutic efficacy in early-phase COVID-19 clinical trials.
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http://dx.doi.org/10.1136/jclinpath-2020-207242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025250PMC
March 2021

Utility of Google Trends in anticipating COVID-19 outbreaks in Poland.

Pol Arch Intern Med 2021 04 26;131(4):389-392. Epub 2021 Mar 26.

Department of Bioinformatics and Public Health, Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Kraków, Poland

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http://dx.doi.org/10.20452/pamw.15894DOI Listing
April 2021

Surgical anatomy of the accessory middle colic artery: a meta-analysis with implications for splenic flexure cancer surgery.

Colorectal Dis 2021 Jul 25;23(7):1712-1720. Epub 2021 Mar 25.

Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Aim: Surgical resection of splenic flexure cancers (SFCs) is technically demanding due to the complex regional anatomy, characterized by the presence of embryological adhesions, close proximity to the pancreas and spleen, and a highly heterogeneous arterial supply and lymphatic drainage. The accessory middle colic artery (AMCA) is increasingly being recognized as an important source of blood supply to the splenic flexure. The aim of this study is to determine the prevalence and anatomical features of the AMCA.

Method: A systematic search of the scientific literature was conducted on PubMed and Embase from inception to November 2020 to identify potentially eligible studies. Data were extracted and prevalence was pooled into a meta-analysis using MetaXL and Meta-Analyst software.

Results: A total of 16 studies (n = 2203 patients) were included. The pooled prevalence (PP) of the AMCA was 25.4% (95% CI 18.1-33.4). Its prevalence was higher in patients without a left colic artery (LCA) (PP = 83.2%; 95% CI 70.4-93.1). The commonest origin for the AMCA was the superior mesenteric artery (PP = 87.9%; 95% CI 86.4-90.7). The AMCA shared a common trunk/gave rise to pancreatic branches in 23.1% of cases (95% CI 15.3-31.9).

Conclusion: The AMCA contributes to the vascularization of the splenic flexure in approximately 25% of individuals, and may be an important feeder artery to SFCs, especially in the absence of a LCA. Preoperative identification of this artery is important to ensure optimal surgery for SFC and minimize complications.
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http://dx.doi.org/10.1111/codi.15630DOI Listing
July 2021

Laparoscopic surgery during the COVID-19 pandemic: detection of SARS-COV-2 in abdominal tissues, fluids, and surgical smoke.

Langenbecks Arch Surg 2021 Jun 6;406(4):1007-1014. Epub 2021 Mar 6.

School of Medicine, College of Health Sciences, University of Nairobi, Nairobi, Kenya.

Background: There are still concerns over the safety of laparoscopic surgery in coronavirus disease 2019 (COVID-19) patients due to the potential risk of viral transmission through surgical smoke/laparoscopic pneumoperitoneum.

Methods: We performed a systematic review of currently available literature to determine the presence of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in abdominal tissues or fluids and in surgical smoke.

Results: A total of 19 studies (15 case reports and 4 case series) comprising 29 COVID-19 patients were included. The viral RNA was positively identified in 11 patients (37.9%). The samples that tested positive include the peritoneal fluid, bile, ascitic fluid, peritoneal dialysate, duodenal wall, and appendix. Similar samples, together with the omentum and abdominal subcutaneous fat, tested negative in the other patients. Only one study investigated SARS-COV-2 RNA in surgical smoke generated during laparoscopy, reporting negative findings.

Conclusions: There are conflicting results regarding the presence of SARS-COV-2 in abdominal tissues and fluids. No currently available evidence supports the hypothesis that SARS-COV-2 can be aerosolized and transmitted through surgical smoke. Larger studies are urgently needed to corroborate these findings.
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http://dx.doi.org/10.1007/s00423-021-02142-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936592PMC
June 2021

Link between cardiovascular disease and the risk of falling: a comprehensive review of the evidence.

Pol Arch Intern Med 2021 04 25;131(4):369-376. Epub 2021 Feb 25.

Department of Physiology, Faculty of Medicine, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain

Falls are associated with increased morbidity and mortality, rising hospital readmission rates, decreased patient independence, and strained healthcare resources. In aged populations and individuals with multimorbidity, cardiovascular conditions may contribute towards an increased propensity to fall. The prevalence of cardiovascular conditions generally increases with age, and understanding potential fall risk factors may help to minimize the risk of falls and develop preventive interventions. Acting on even one such risk factor or introducing an appropriate intervention may reduce the overall propensity for a patient to fall. Further prevention strategies primed towards cardiovascular ailments should be elucidated and trialed.
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http://dx.doi.org/10.20452/pamw.15849DOI Listing
April 2021

The anti-inflammatory cytokine response characterized by elevated interleukin-10 is a stronger predictor of severe disease and poor outcomes than the pro-inflammatory cytokine response in coronavirus disease 2019 (COVID-19).

Clin Chem Lab Med 2021 02 26;59(3):599-607. Epub 2020 Nov 26.

Department of Emergency Medicine, University of Cincinnati, Cincinnati, OH, USA.

Objectives: Severe coronavirus disease 2019 (COVID-19) is associated with a dysregulated immune state. While research has focused on the hyperinflammation, little research has been performed on the compensatory anti-inflammatory response. The aim of this study was to evaluate the anti-inflammatory cytokine response to COVID-19, by assessing interleukin-10 (IL-10) and IL-10/lymphocyte count ratio and their association with outcomes.

Methods: Adult patients presenting to the emergency department (ED) with laboratory-confirmed COVID-19 were recruited. The primary endpoint was maximum COVID-19 severity within 30 days of index ED visit.

Results: A total of 52 COVID-19 patients were enrolled. IL-10 and IL-10/lymphocyte count were significantly higher in patients with severe disease (p<0.05), as well as in those who developed severe acute kidney injury (AKI) and new positive bacterial cultures (all p≤0.01). In multivariable analysis, a one-unit increase in IL-10 and IL-10/lymphocyte count were associated with 42% (p=0.031) and 32% (p=0.013) increased odds, respectively, of severe COVID-19. When standardized to a one-unit standard deviations scale, an increase in the IL-10 was a stronger predictor of maximum 30-day severity and severe AKI than increases in IL-6 or IL-8.

Conclusions: The hyperinflammatory response to COVID-19 is accompanied by a simultaneous anti-inflammatory response, which is associated with poor outcomes and may increase the risk of new positive bacterial cultures. IL-10 and IL-10/lymphocyte count at ED presentation were independent predictors of COVID-19 severity. Moreover, elevated IL-10 was more strongly associated with outcomes than pro-inflammatory IL-6 or IL-8. The anti-inflammatory response in COVID-19 requires further investigation to enable more precise immunomodulatory therapy against SARS-CoV-2.
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http://dx.doi.org/10.1515/cclm-2020-1284DOI Listing
February 2021

Protective Effects of Statins Administration in European and North American Patients Infected with COVID-19: A Meta-Analysis.

Semin Thromb Hemost 2021 Jun 22;47(4):392-399. Epub 2021 Jan 22.

Section of Clinical Biochemistry, Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Italy.

Severe acute respiratory syndrome coronavirus 2 has spread rapidly throughout the world, becoming an overwhelming global health emergency. The array of injuries caused by this virus is broad and not limited to the respiratory system, but encompassing also extensive endothelial and systemic tissue damage. Since statins effectively improve endothelial function, these drugs may have beneficial effects in patients with coronavirus disease 2019 (COVID-19). Therefore, this investigation aimed to provide an updated overview on the interplay between statins and COVID-19, with particular focus on their potentially protective role against progression toward severe or critical illness and death. A systematic electronic search was performed in Scopus and PubMed up to present time. Data on statins use and COVID-19 outcomes especially in studies performed in Europe and North America were extracted and pooled. A total of seven studies met our inclusion criteria, totaling 2,398 patients (1,075 taking statins, i.e., 44.8%). Overall, statin usage in Western patients hospitalized with COVID-19 was associated with nearly 40% lower odds of progressing toward severe illness or death (odds ratio: 0.59; 95% confidence interval: 0.35-0.99). After excluding studies in which statin therapy was started during hospital admission, the beneficial effect of these drugs was magnified (odds ratio: 0.51; 95% confidence interval: 0.41-0.64). In conclusion, although randomized trials would be necessary to confirm these preliminary findings, current evidence would support a favorable effect of statins as adjuvant therapy in patients with COVID-19. Irrespective of these considerations, suspension of statin therapy seems highly unadvisable in COVID-19 patients.
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http://dx.doi.org/10.1055/s-0040-1722307DOI Listing
June 2021

Surgical anatomy of sigmoid arteries: A systematic review and meta-analysis.

Surgeon 2021 Jan 5. Epub 2021 Jan 5.

Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH, 45229, USA.

Background: The purpose of this systematic review and meta-analysis was to determine the prevalence of the number of sigmoid arteries (SA) and variations in their origins.

Methods: A thorough systematic search of literature through February 2020 was conducted on major electronic databases to identify eligible studies. Data were extracted and pooled into a meta-analysis using Metafor package in R. The primary outcome was the variations in the SA origin (according to modified Zebrowski classification), and the secondary outcome was the prevalence of the number of SA.

Results: A total of 22 studies (n = 2653 patients) were included. Type 1 modified Zebrowski (separated origins or common trunk of the SA originating from descending recto-sigmoid trunk (DRST)) was the most common origin type of the SA (pooled prevalence estimate (PPE) = 49.67% (95% CI 32. 67- 66.71)), while type 3 (separated origins or common trunk of 1 or 2 SA originating from DRST or superior rectal artery (SRA) and 1 or 2 SA originating from DRST or SRA) was the least common (PPE = 0.18%; 95% CI 0.00-2.82)). Of the Type 1 variants, the not specified (N.S) variant was by far the most prevalent. The number of SA ranged from one to five, with three being the mode (PPE = 42.3%).

Conclusion: This is the most comprehensive analysis of arterial vascular anatomy of the sigmoid colon. In light of the highly variable anatomical pattern displayed by the SA, thorough pre-operative knowledge of their anatomy can be crucial in minimizing incidences of iatrogenic injury.
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http://dx.doi.org/10.1016/j.surge.2020.11.012DOI Listing
January 2021

Evaluation of PCL rapid point of care antigen test for detection of SARS-CoV-2 in nasopharyngeal swabs.

J Med Virol 2021 04 6;93(4):1920-1922. Epub 2021 Jan 6.

The Heart Institute, Cincinnati Children's Hospital Medical Center, Ohio, USA.

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http://dx.doi.org/10.1002/jmv.26765DOI Listing
April 2021

Outcomes of Multiple Runs of Extracorporeal Membrane Oxygenation: An analysis of the Extracorporeal Life Support Registry.

J Intensive Care Med 2020 Dec 22:885066620981903. Epub 2020 Dec 22.

Divisions of Cardiology and Critical Care Medicine, Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Objective: When patients deteriorate after decannulation from extracorporeal membrane oxygenation (ECMO), a second run of extracorporeal support may be considered. However, repeat cannulation can be difficult and poor outcomes associated with multiple ECMO runs are a concern. The aim of this study was to evaluate outcomes and identify factors associated with survival and mortality in cases of multiple runs of extracorporeal membrane oxygenation.

Design: Retrospective cohort analysis of the Extracorporeal Life Support Organization Registry.

Setting: The Extracorporeal Life Support Organization's registry was queried for neonates, children, and adults receiving 2 or more runs of ECMO during the same hospitalization, for any indication, from 1998 to 2015.

Patients: 1,818 patients from the Extracorporeal Life Support Organization Registry.

Results: Of the 1,818 patients, 1,648 underwent 2 runs and 170 underwent 3 or more runs of ECMO. The survival to discharge rate was 36.7% for 2 runs and 29.4% for 3 or more runs. No significant differences in survival were detected in analysis by decade of ECMO run (p = 0.21). Pediatric patients had less mortality than adults (OR: 0.45, 95%CI: 0.24-0.82). Cardiac support on the first run portrayed worse mortality than pulmonary support regardless of final run indication (OR:1.38, 95%CI: 1.09-1.75). Across all age groups, patients receiving pulmonary support on the last run tended to have higher survival rates regardless of support type on the first run. The only first run complication independently predictive of mortality on the final run was renal complications (OR: 1.60, 95%CI: 1.28-1.99).

Conclusions: Though the use of multiple runs of ECMO is growing, outcomes remain poor for most cohorts. Survival decreases with each additional run. Patients requiring additional runs for a pulmonary indication should be considered prime candidates. Renal complications on the first run significantly increases the risk of mortality on subsequent runs, and as such, careful consideration should be applied in these cases.
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http://dx.doi.org/10.1177/0885066620981903DOI Listing
December 2020

ADAMTS13 activity to von Willebrand factor antigen ratio predicts acute kidney injury in patients with COVID-19: Evidence of SARS-CoV-2 induced secondary thrombotic microangiopathy.

Int J Lab Hematol 2021 Jul 3;43 Suppl 1:129-136. Epub 2020 Dec 3.

Department of Emergency Medicine, University of Cincinnati, Cincinnati, OH, USA.

Introduction: Severe COVID-19 is often compounded by a prothrombotic state that is associated with poor outcomes. In this investigation, we aimed to evaluate ADAMTS13 activity, von Willebrand factor level (VWF:Ag), and the corresponding ADAMTS13 activity/VWF:Ag ratio, in patients with COVID-19 and for associations with disease progression and acute kidney injury (AKI).

Methods: Patients presenting to the emergency department (ED) with COVID-19 were enrolled in this prospective, observational study. ADAMTS13 activity and VWF:Ag were measured at index ED visit. The primary endpoint was severe AKI defined by KDIGO stage 2 + 3 criteria, while the secondary endpoint was peak 30-day COVID-19 severity.

Results: A total of 52 adult COVID-19 patients were enrolled. Overall, we observed that 23.1% of the cohort had a relative deficiency in ADAMTS13 activity, while 80.8% had elevated VWF:Ag. The ADAMTS13 activity/VWF:Ag ratio was significantly lower in patients with severe AKI (P = .002) and those who developed the severe form of COVID-19 (P = .020). The ADAMTS13 activity/VWF:Ag ratio was negatively correlated with age (P < .001) and LDH (P < .001), while positively correlated with hemoglobin (P = .041). After controlling for confounders, a one-unit increase in ADAMTS13/VWF:Ag ratio was associated with 20% decreased odds of severe AKI.

Conclusion: A low ADAMTS13 activity:VWF:Ag ratio at ED presentation is associated with progression to severe COVID-19 disease and severe AKI, with a pattern suggestive of a secondary microangiopathy. Further interventional studies should be conducted to assess the restoration of ADAMTS13:VWF:Ag ratio in hospitalized patients with COVID-19.
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http://dx.doi.org/10.1111/ijlh.13415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753610PMC
July 2021

Anatomical variations of the pyramidalis muscle: a systematic review and meta-analysis.

Surg Radiol Anat 2021 Apr 24;43(4):595-605. Epub 2020 Nov 24.

Georgia Baptist College of Nursing, Mercer University, 3001 Mercer University Drive, Atlanta, GA, 30341, USA.

Purpose: To provide a comprehensive evidence-based assessment of the anatomical characteristics of the pyramidalis muscle (PM).

Materials And Methods: A thorough systematic search of the literature through August 31st 2020 was conducted on major electronic databases PubMed, Scopus and Web of Science (WOS) to identify studies eligible for inclusion. Data were extracted and pooled into a meta-analysis using MetaFor package in R and MetaXL. A random-effects model was applied. The primary outcome of interest was the prevalence of PM. The secondary outcomes were the dimensions (length and width) of the PM.

Results: A total of 11 studies (n = 787 patients; 1548 sides) were included in the meta-analysis. The multinomial pooled prevalence estimate (PPE) for a bilateral absence of the PM was 11.3% (95% CI [7.2%, 16.2%], 82.3% (95% CI [76.2%, 87.6%]) for a bilateral presence, and 6.3% (95% CI [3.3%, 10.2%]) for a unilateral presence. Of four studies (n = 37 patients) that reported the side of a unilateral presence, the PPE of a unilateral right-side presence was 42.2% (95% CI [23.0%, 62.3%]) compared to 57.8% for a unilateral left-side presence (95% CI [37.7%, 77.0%]). The mean length of the PM displayed high levels of heterogeneity, ranging from 3.12 to 12.50 cm.

Conclusion: The pyramidalis muscle is a rather constant anatomical structure being present in approximately 90% of individuals.
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http://dx.doi.org/10.1007/s00276-020-02622-4DOI Listing
April 2021

Congenital Anomalies of the Tracheobronchial Tree: A Meta-Analysis and Clinical Considerations.

Ann Thorac Surg 2021 07 4;112(1):315-325. Epub 2020 Nov 4.

International Evidence-Based Anatomy Working Group, Krakow, Poland; Cardiac Intensive Care Unit, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address:

Background: The aim of this study was to determine the prevalence and anatomic features of major tracheobronchial anomalies.

Methods: Major electronic databases were systematically searched to identify eligible studies. Data were extracted and pooled into a meta-analysis. The primary outcome was the prevalence of major tracheobronchial anomalies, specifically tracheal bronchus (TB) and accessory cardiac bronchus (ACB). Secondary outcomes included the origin and types of TB and ACB.

Results: A total of 27 studies (n = 119,695 patients) were included. A TB was present in 0.99% (95% confidence interval, 0.67 to 1.37) of patients, and an ACB was present in 0.14% (95% confidence interval, 0.09 to 0.20). The overall prevalence of TB was higher in imaging than in operative studies (1.81% vs 0.82%). It was also higher in pediatric (2.55%) than in adult studies (0.50%). Patients with other congenital anomalies were 15 times more likely to have a TB (odds ratio 14.89; 95% confidence interval, 7.09 to 31.22). The most common origin of TBs was from the trachea (81.42%), primarily from the right side (96.43%). The most common origin of ACBs was from the intermediate bronchus (74.32%). The ACBs terminated as blind-ending diverticulum in two thirds of cases.

Conclusions: Major tracheobronchial anomalies are present in approximately 1% of the population, although the prevalence is higher among pediatric patients and patients with accompanying congenital anomalies. Although rare, major tracheobronchial anomalies can be associated with significant respiratory morbidities and present challenges during airway management in surgical and critical care patients. Establishing a preoperative diagnosis of these variations is essential for planning and implementing an appropriate airway management strategy to minimize attendant complications.
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http://dx.doi.org/10.1016/j.athoracsur.2020.08.060DOI Listing
July 2021

Response to: Is newly diagnosed diabetes a stronger risk factor than pre-existing diabetes for COVID-19 severity?

J Diabetes 2021 02 18;13(2):179-180. Epub 2020 Nov 18.

Cardiac Intensive Care Unit, The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.

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http://dx.doi.org/10.1111/1753-0407.13127DOI Listing
February 2021

Red Blood Cell Distribution Width (RDW) Predicts COVID-19 Severity: A Prospective, Observational Study from the Cincinnati SARS-CoV-2 Emergency Department Cohort.

Diagnostics (Basel) 2020 Aug 21;10(9). Epub 2020 Aug 21.

Section of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University of Verona, 37129 Verona, Italy.

Since previous evidence has demonstrated that red blood cell distribution width (RDW) may be a useful prognostic parameter in many critical illnesses and infectious diseases, we investigated the utility of RDW for monitoring patients with coronavirus disease 2019 (COVID-19). The study population consisted of 49 COVID-19 patients, including 16 (32.6%) with severe illness, 12 (24.5%) with severe acute kidney injury (AKI), and 8 (16.3%) requiring renal replacement therapy (RRT). The predictive value of blood tests, performed during emergency department evaluation, was then addressed. A progressive increase of RDW was observed with advancing COVID-19 severity. The area under the curve (AUC) of RDW was 0.73 for predicting severe illness, 0.80 for severe AKI, and 0.83 for RRT, respectively. In multivariate analysis, elevated RDW was associated with 9-fold and 16-fold increased odds of severe COVID-19 and AKI, respectively. The results of this study suggest that RDW should be part of routine laboratory assessment and monitoring of COVID-19.
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http://dx.doi.org/10.3390/diagnostics10090618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554711PMC
August 2020

Validation of the Corona-Score for rapid identification of SARS-CoV-2 infections in patients seeking emergency department care in the United States.

Clin Chem Lab Med 2020 08 10;58(12):e311-e313. Epub 2020 Aug 10.

Department of Emergency Medicine, University of Cincinnati, Cincinnati, OH, USA.

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http://dx.doi.org/10.1515/cclm-2020-1121DOI Listing
August 2020

Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: A pooled analysis.

Am J Emerg Med 2020 09 27;38(9):1722-1726. Epub 2020 May 27.

Section of Clinical Biochemistry, Department of Neuroscience, Biomedicine and Movement, University of Verona, Verona, Italy.

Coronavirus disease 2019 (COVID-19) infection has now reached a pandemic state, affecting more than a million patients worldwide. Predictors of disease outcomes in these patients need to be urgently assessed to decrease morbidity and societal burden. Lactate dehydrogenase (LDH) has been associated with worse outcomes in patients with viral infections. In this pooled analysis of 9 published studies (n = 1532 COVID-19 patients), we evaluated the association between elevated LDH levels measured at earliest time point in hospitalization and disease outcomes in patients with COVID-19. Elevated LDH levels were associated with a ~6-fold increase in odds of developing severe disease and a ~16-fold increase in odds of mortality in patients with COVID-19. Larger studies are needed to confirm these findings.
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http://dx.doi.org/10.1016/j.ajem.2020.05.073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251362PMC
September 2020

External versus internal cardioversion for atrial fibrillation: a meta-analysis of randomized controlled trials.

J Interv Card Electrophysiol 2020 Jul 31. Epub 2020 Jul 31.

Division of Cardiology, Department of Medicine, Creighton University School of Medicine, 7500 Mercy Road, Omaha, NE, USA.

Background: Patients with atrial fibrillation (AF) often require rhythm control strategy for amelioration of symptoms. It is unclear if there is any difference between external cardioversion (ECV) and internal cardioversion (ICV) for successful conversion of AF to normal sinus rhythm.

Methods: We performed a meta-analysis of published randomized controlled trials (RCTs) evaluating success of cardioversion using ECV versus ICV.

Results: In the pooled analysis of 5 RCTS, there was no difference in success of cardioversion using ECV versus ICV (OR 1.69, 95% CI 0.24-11.83, p = 0.6). In the subgroup analysis, there was no difference between ECV and direct electrode ICV (OR 0.41, 95% CI 0.09-1.83, p = 0.24). However, ECV was significantly better compared with ICV using ICD (OR 11.97, 95% CI 1.87-76.73, p = 0.009).

Conclusions: There was no difference between ECV versus ICV in effectiveness for termination of AF. Larger well-designed randomized controlled trials are needed to confirm our findings.
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http://dx.doi.org/10.1007/s10840-020-00836-5DOI Listing
July 2020
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