Anti-SARS-CoV-2 Antibody Levels Measured by the AdviseDx SARS-CoV-2 Assay Are Concordant with Previously Available Serologic Assays but Are Not Fully Predictive of Sterilizing Immunity.

With the availability of widespread SARS-CoV-2 vaccination, high-throughput quantitative anti-spike protein serological testing will likely become increasingly important. Here, we investigated the performance characteristics of the recently FDA-authorized semiquantitative anti-spike protein AdviseDx SARS-CoV-2 IgG II assay compared to the FDA-authorized anti-nucleocapsid protein Abbott Architect SARS-CoV-2 IgG, Roche Elecsys anti-SARS-CoV-2-S, EuroImmun anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA), and GenScript surrogate virus neutralization assays and examined the humoral response associated with vaccination, natural protection, and vaccine breakthrough infection. The AdviseDx assay had a clinical sensitivity at 14 days after symptom onset or 10 days after PCR detection of 95.6% (65/68; 95% confidence interval [CI], 87.8 to 98.8%), with two discrepant individuals seroconverting shortly thereafter. The AdviseDx assay demonstrated 100% positive percent agreement with the four other assays examined using the same symptom onset or PCR detection cutoffs. Using a recently available WHO international standard for anti-SARS-CoV-2 antibody, we provide assay unit conversion factors to international units for each of the assays examined. We performed a longitudinal survey of healthy vaccinated individuals, finding that median AdviseDx immunoglobulin levels peaked 7 weeks after first vaccine dose at approximately 4,000 IU/ml. Intriguingly, among the five assays examined, there was no significant difference in antigen binding level or neutralizing activity between two seropositive patients protected against SARS-CoV-2 infection in a previously described fishing vessel outbreak and five health care workers who experienced vaccine breakthrough of SARS-CoV-2 infection, all with variants of concern. These findings suggest that protection against SARS-CoV-2 infection cannot currently be predicted exclusively using in vitro antibody assays against wild-type SARS-CoV-2 spike. Further work is required to establish protective correlates for SARS-CoV-2 infection.

Evaluation of Cell-Based and Surrogate SARS-CoV-2 Neutralization Assays.

Determinants of protective immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection require the development of well-standardized, reproducible antibody assays. This need has led to the emergence of a variety of neutralization assays. Head-to-head evaluation of different SARS-CoV-2 neutralization platforms could facilitate comparisons across studies and laboratories. Five neutralization assays were compared using 40 plasma samples from convalescent individuals with mild to moderate coronavirus disease 2019 (COVID-19): four cell-based systems using either live recombinant SARS-CoV-2 or pseudotyped viral particles created with lentivirus (LV) or vesicular stomatitis virus (VSV) packaging and one surrogate enzyme-linked immunosorbent assay (ELISA)-based test that measures inhibition of the spike protein receptor binding domain (RBD) binding its receptor human angiotensin converting enzyme 2 (hACE2). Vero cells, Vero E6 cells, HEK293T cells expressing hACE2, and TZM-bl cells expressing hACE2 and transmembrane serine protease 2 were tested. All cell-based assays showed 50% neutralizing dilution (ND50) geometric mean titers (GMTs) that were highly correlated (Pearson r = 0.81 to 0.89) and ranged within 3.4-fold. The live virus assay and LV pseudovirus assays with HEK293T/hACE2 cells showed very similar mean titers, 141 and 178, respectively. ND50 titers positively correlated with plasma IgG targeting SARS-CoV-2 spike protein and RBD (r = 0.63 to 0.89), but moderately correlated with nucleoprotein IgG (r = 0.46 to 0.73). ND80 GMTs mirrored ND50 data and showed similar correlation between assays and with IgG concentrations. The VSV pseudovirus assay and LV pseudovirus assay with HEK293T/hACE2 cells in low- and high-throughput versions were calibrated against the WHO SARS-CoV-2 IgG standard. High concordance between the outcomes of cell-based assays with live and pseudotyped virions enables valid cross-study comparison using these platforms.

Improving the efficacy of exome sequencing at a quaternary care referral centre: novel mutations, clinical presentations and diagnostic challenges in rare neurogenetic diseases.

BACKGROUND: We used a multimodal approach including detailed phenotyping, whole exome sequencing (WES) and candidate gene filters to diagnose rare neurological diseases in individuals referred by tertiary neurology centres. METHODS: WES was performed on 66 individuals with neurogenetic diseases using candidate gene filters and stringent algorithms for assessing sequence variants. Pathogenic or likely pathogenic missense variants were interpreted using in silico prediction tools, family segregation analysis, previous publications of disease association and relevant biological assays. RESULTS: Molecular diagnosis was achieved in 39% (n=26) including 59% of childhood-onset cases and 27% of late-onset cases. Overall, 37% (10/27) of myopathy, 41% (9/22) of neuropathy, 22% (2/9) of MND and 63% (5/8) of complex phenotypes were given genetic diagnosis. Twenty-seven disease-associated variants were identified including ten novel variants in FBXO38, LAMA2, MFN2, MYH7, PNPLA6, SH3TC2 and SPTLC1. Single-nucleotide variants (n=10) affected conserved residues within functional domains and previously identified mutation hot-spots. Established pathogenic variants (n=16) presented with atypical features, such as optic neuropathy in adult polyglucosan body disease, facial dysmorphism and skeletal anomalies in cerebrotendinous xanthomatosis, steroid-responsive weakness in congenital myasthenia syndrome 10. Potentially treatable rare diseases were diagnosed, improving the quality of life in some patients. CONCLUSIONS: Integrating deep phenotyping, gene filter algorithms and biological assays increased diagnostic yield of exome sequencing, identified novel pathogenic variants and extended phenotypes of difficult to diagnose rare neurogenetic disorders in an outpatient clinic setting.

Open Endoaneurysmorrhaphy of 9-cm Ruptured Popliteal Aneurysm 7 Years after Initial Repair.

BACKGROUND: A previously repaired right popliteal artery aneurysm via a medial approach with proximal and distal ligation and interval bypass re-presented 7 years after the initial repair with a ruptured 9 × 25.5 cm right popliteal aneurysm. METHODS: Surgical repair was complex due to the large size of the aneurysm. Technique and management of popliteal aneurysm repair are discussed, along with a review of the current literature. RESULTS: A 58-year-old male with a 3.5 cm popliteal artery aneurysm was initially treated with end-to-end prosthetic bypass and proximal/distal aneurysm ligation from a medial-approach without complication. Seven years later, he presented with a 9-cm popliteal aneurysm rupture. Posterior approach endoaneurysmorrhaphy repair was far more complicated than expected with massive blood loss. Despite this, he was discharged without complication POD #5, but on POD #19 presented with cellulitis and underwent incision and drainage of retained hematoma with cultures positive for Strep dysgalactiae. With appropriate treatment, he was healed in 3 months. CONCLUSIONS: Surgical repair of large popliteal aneurysms can be challenging, but continued aneurysmal degeneration is a potential consequence if the sac continues to be pressurized from patent geniculate arteries. Surgical repair of large popliteal artery aneurysms is complex and requires adjunctive techniques to maximize success. A posterior approach is described and the literature reviewed to support recommendations for primary popliteal artery aneurysm repair and repair of large degenerated popliteal artery aneurysms. We recommend primary popliteal artery aneurysm repair from a posterior approach with endoaneurysmorrhaphy and an interposition bypass. For ruptured large popliteal artery aneurysms, there is a high risk of hemorrhage and wound complications. Therefore, we recommend the use of a tourniquet, surgical drain and to consider the collection of intraoperative cultures to guide potential antibiotic management.

Comparison of vergence mechanisms between university students with good and poor sleep quality.

AIM: To compare the vergence mechanisms between good and poor sleepers in university students. METHODS: A total of 64 university students were recruited in this study. The validated Malay version of Pittsburgh Sleep Quality Index questionnaire (PSQI-M) was used to measure the participants' sleep quality over the past month. Participants were categorized as good sleepers (n=32) and poor sleepers (n=32) based on the PSQI-M scores. Heterophoria and fusional vergences were measured at distance and near. Mann-Whitney U test was used to compare heterophoria, negative fusional vergence (NFV), and positive fusional vergence (PFV) at distance and near between good and poor sleepers. Spearman correlation analysis was used to study the relationship between PSQI-M score and PFV at distance. RESULTS: Both distance and near heterophorias were not significantly different between good and poor sleepers (P>0.05). There was a difference in distance PFV (P<0.05) between good and poor sleepers, but not in distance NFV, near NFV, and near PFV (P>0.05). Distance PFV was negatively correlated with PSQI-M score (rs=-0.33, P<0.05). CONCLUSION: University students with poor sleep quality demonstrates a reduced ability to maintain fusion with increasing convergence demand at distance. Sleep quality assessment during binocular vision examination in university students is recommended.

Rescue of immediate post-transcarotid artery revascularization carotid stent thrombosis due to clopidogrel resistance using flow-reversal and aspiration thrombectomy.

An 84-year-old patient developed immediate thrombosis of his carotid stent in recovery after transcarotid artery revascularization. In the present report, the technical details about intraoperative management for neurovascular rescue using the transcarotid artery revascularization flow-reversal system are described. The patient was determined to have clopidogrel resistance. Intraoperative medical management is also discussed. The current alternative intravenous and oral antiplatelet therapies such as glycoprotein IIb/IIIa and P2Y12 inhibitors are explored. The debate regarding preoperative antiplatelet resistance testing remains ambiguous, and increasing studies have demonstrated the safety and efficacy of alternatives to clopidogrel. Despite an unpredictable and devastating complication, the patient's outcome was successful using contemporary strategies.

Transient use of hemolymph for hydraulic wing expansion in cicadas.

Insect wings must be flexible, light, and strong to allow dynamic behaviors such as flying, mating, and feeding. When winged insects eclose into adults, their wings unfold, actuated hydraulically by hemolymph. Flowing hemolymph in the wing is necessary for functioning and healthy wings, both as the wing forms and as an adult. Because this process recruits the circulatory system, we asked, how much hemolymph is pumped into wings, and what happens to the hemolymph afterwards? Using Brood X cicadas (Magicicada septendecim), we collected 200 cicada nymphs, observing wing transformation over 2 h. Using dissection, weighing, and imaging of wings at set time intervals, we found that within 40 min after emergence, wing pads morphed into adult wings and total wing mass increased to ~ 16% of body mass. Thus, a significant amount of hemolymph is diverted from body to wings to effectuate expansion. After full expansion, in the ~ 80 min after, the mass of the wings decreased precipitously. In fact, the final adult wing is lighter than the initial folded wing pad, a surprising result. These results demonstrate that cicadas not only pump hemolymph into the wings, they then pump it out, producing a strong yet lightweight wing.

Prophylactic versus therapeutic dose anticoagulation effects on survival among critically ill patients with COVID-19.

INTRODUCTION: Although patients with severe COVID-19 are known to be at high risk of developing thrombotic events, the effects of anticoagulation (AC) dose and duration on in-hospital mortality in critically ill patients remain poorly understood and controversial. The goal of this study was to investigate survival of critically ill COVID-19 patients who received prophylactic or therapeutic dose AC and analyze the mortality rate with respect to detailed demographic and clinical characteristics. MATERIALS AND METHODS: We conducted a retrospective, observational study of critically ill COVID-19 patients admitted to the ICU at Stony Brook University Hospital in New York who received either prophylactic (n = 158) or therapeutic dose AC (n = 153). Primary outcome was in-hospital death assessed by survival analysis and covariate-adjusted Cox proportional hazard model. RESULTS: For the first 3 weeks of ICU stay, we observed similar survival curves for prophylactic and therapeutic AC groups. However, after 3 or more weeks of ICU stay, the therapeutic AC group, characterized by high incidence of acute kidney injury (AKI), had markedly higher death incidence rates with 8.6 deaths (95% CI = 6.2-11.9 deaths) per 1,000 person-days and about 5 times higher risk of death (adj. HR = 4.89, 95% CI = 1.71-14.0, p = 0.003) than the prophylactic group (2.4 deaths [95% CI = 0.9-6.3 deaths] per 1,000 person-days). Among therapeutic AC users with prolonged ICU admission, non-survivors were characterized by older males with depressed lymphocyte counts and cardiovascular disease. CONCLUSIONS: Our findings raise the possibility that prolonged use of high dose AC, independent of thrombotic events or clinical background, might be associated with higher risk of in-hospital mortality. Moreover, AKI, age, lymphocyte count, and cardiovascular disease may represent important risk factors that could help identify at-risk patients who require long-term hospitalization with therapeutic dose AC treatment.

Clinical predictors of acute cardiac injury and normalization of troponin after hospital discharge from COVID-19.

BACKGROUND: Although acute cardiac injury (ACI) is a known COVID-19 complication, whether ACI acquired during COVID-19 recovers is unknown. This study investigated the incidence of persistent ACI and identified clinical predictors of ACI recovery in hospitalized patients with COVID-19 2.5 months post-discharge. METHODS: This retrospective study consisted of 10,696 hospitalized COVID-19 patients from March 11, 2020 to June 3, 2021. Demographics, comorbidities, and laboratory tests were collected at ACI onset, hospital discharge, and 2.5 months post-discharge. ACI was defined as serum troponin-T (TNT) level >99th-percentile upper reference limit (0.014ng/mL) during hospitalization, and recovery was defined as TNT below this threshold 2.5 months post-discharge. Four models were used to predict ACI recovery status. RESULTS: There were 4,248 (39.7%) COVID-19 patients with ACI, with most (93%) developed ACI on or within a day after admission. In-hospital mortality odds ratio of ACI patients was 4.45 [95%CI: 3.92, 5.05, p<0.001] compared to non-ACI patients. Of the 2,880 ACI survivors, 1,114 (38.7%) returned to our hospitals 2.5 months on average post-discharge, of which only 302 (44.9%) out of 673 patients recovered from ACI. There were no significant differences in demographics, race, ethnicity, major commodities, and length of hospital stay between groups. Prediction of ACI recovery post-discharge using the top predictors (troponin, creatinine, lymphocyte, sodium, lactate dehydrogenase, lymphocytes and hematocrit) at discharge yielded 63.73%-75.73% accuracy. INTERPRETATION: Persistent cardiac injury is common among COVID-19 survivors. Readily available patient data accurately predict ACI recovery post-discharge. Early identification of at-risk patients could help prevent long-term cardiovascular complications. FUNDING: None.

Simulation in surgical education.

Simulation is becoming an important tool in surgical education. Surgical faculty have been forced to modify how they teach technical skills. Instead of a complete reliance on teaching in the operating room, a structured curriculum and dedicated time in the simulation center are being used in many centers. Some of the advantages of this approach include the ability to learn and practice new procedures in a safe and nurturing environment. The disadvantages include the significant cost of virtual reality simulators and the competition, between various training programs, to gain access to simulation.

Neural network analysis of clinical variables predicts escalated care in COVID-19 patients: a retrospective study.

This study sought to identify the most important clinical variables that can be used to determine which COVID-19 patients hospitalized in the general floor will need escalated care early on using neural networks (NNs). Analysis was performed on hospitalized COVID-19 patients between 7 February 2020 and 4 May 2020 in Stony Brook Hospital. Demographics, comorbidities, laboratory tests, vital signs and blood gases were collected. We compared those data obtained at the time in emergency department and the time of intensive care unit (ICU) upgrade of: (i) COVID-19 patients admitted to the general floor (N = 1203) vs. those directly admitted to ICU (N = 104), and (ii) patients not upgraded to ICU (N = 979) vs. those upgraded to the ICU (N = 224) from the general floor. A NN algorithm was used to predict ICU admission, with 80% training and 20% testing. Prediction performance used area under the curve (AUC) of the receiver operating characteristic analysis (ROC). We found that C-reactive protein, lactate dehydrogenase, creatinine, white-blood cell count, D-dimer and lymphocyte count showed temporal divergence between COVID-19 patients hospitalized in the general floor that were upgraded to ICU compared to those that were not. The NN predictive model essentially ranked the same laboratory variables to be important predictors of needing ICU care. The AUC for predicting ICU admission was 0.782 ± 0.013 for the test dataset. Adding vital sign and blood-gas data improved AUC (0.822 ± 0.018). This work could help frontline physicians to anticipate downstream ICU need to more effectively allocate healthcare resources.

Adventitial cystic disease in the external iliac artery of a 29-year-old man.

Adventitial cystic disease (ACD) is an uncommon condition that generally occurs at the popliteal artery but, rarely, can occur in the external iliac artery. To date, only eight cases of ACD occurring in the external iliac artery have been reported. We have reported the case of a 29-year-old man who had presented with new-onset claudication. Despite an extensive imaging workup, ACD was not confirmed until the gross intraoperative examination. We have reported our process of diagnosis and treatment in addition to that reported in previous studies to enhance the historical fund of knowledge for this rare pathology.

Ruptured abdominal aortic aneurysm repair in pediatric Marfan syndrome patient.

Marfan syndrome is a well-described autosomal dominant connective tissue disorder with a constellation of anatomic characteristics including aortic degeneration as a result of the spontaneous mutation of the fibrillin gene, FBN1. Whereas life-threatening dissection and ascending aneurysmal rupture have been thoroughly documented in the literature, aneurysms of the abdominal aorta and those present in the pediatric population have only rarely been reported. In this case report, we describe presentation, successful open surgical repair, and recovery of a pediatric Marfan syndrome patient with a ruptured abdominal aortic aneurysm.

Organ protection during aortic cross-clamping.

Open surgical repair of an aortic aneurysm requires aortic cross-clamping, resulting in temporary ischemia of all organs and tissues supplied by the aorta distal to the clamp. Major complications of open aneurysm repair due to aortic cross-clamping include renal ischemia-reperfusion injury and postoperative colonic ischemia in case of supra- and infrarenal aortic aneurysm repair. Ischemia-reperfusion injury results in excessive production of reactive oxygen species and in oxidative stress, which can lead to multiple organ failure. Several perioperative protective strategies have been suggested to preserve renal function during aortic cross-clamping, such as pharmacotherapy and therapeutic hypothermia of the kidneys. In this chapter, we will briefly discuss the pathophysiology of ischemia-reperfusion injury and the preventative measures that can be taken to avoid abdominal organ injury. Finally, techniques to minimize the risk of complications during and after open aneurysm repair will be presented.

Thoracic sympathectomy for upper extremity ischemia.

INTRODUCTION: Thoracic sympathectomy is performed in the management of a variety of disorders of the upper extremity. To evaluate the contemporary results of thoracic sympathectomy for upper extremity ischemia a systematic review of the literature was conducted. EVIDENCE AQUISITION: We performed a PubMed, EMBASE and Cochrane search of the literature written in the English language from January 1975 to December 2015. All articles presenting original patient data regarding the effect of treatment on symptoms or on the healing of ulcers were eligible for inclusion. Individual analyses for Primary Raynaud's Disease (PRD) and Secondary Raynaud's Phenomenon (SRP) were performed. EVIDENCE SYNTHESIS: We included 6 prospective and 23 retrospective series with a total of 753 patients and 1026 affected limbs. Early beneficial effects of thoracic sympathectomy were noticed in 63-100% (median 94%) of all patients, in 73-100% (median 98%) of PRD patients and in 63-100% (median 94%) of SRP patients. The beneficial effect was noted to lessen over time. Long-term beneficial effects were reported in 13-100% (median 75%) of all patients, in 22-100% (median 58%) of PRD patients, and in 13-100% (median 79%) of SRD patients. Complete or improved ulcer healing was achieved in 33-100% and 25-67% respectively, of all patients. CONCLUSIONS: Thoracic sympathectomy can be beneficial in the treatment of upper extremity ischemia in select patients. Although the effect in patients with PRD will lessen over time, it may still reduce the severity of symptoms. In SRD, effects are more often long-lasting. In addition, thoracic sympathectomy may maximize tissue preservation or prevent amputation in cases of digital ulceration.