An immune-protein signature combining TRAIL, IP-10 and CRP for accurate prediction of severe COVID-19 outcome

BACKGROUNDAccurately identifying COVID-19 patients at-risk to deteriorate remains challenging. Tools integrating host-protein expression have proven useful in determining infection etiology and hold potential for prognosticating disease severity. METHODSAdults with COVID-19 were recruited at medical centers in Israel, Germany, and the United States. Severe outcome was defined as intensive care unit admission, non-invasive or invasive ventilation, or death. Tumor necrosis factor related apoptosis inducing ligand (TRAIL) and interferon gamma inducible protein-10 (IP-10; also known as CXCL10) and C-reactive protein (CRP) were measured using an analyzer providing values within 15 minutes. A signature indicating the likelihood of severe outcome was derived generating a score (0-100). Patients were assigned to 4 score bins. RESULTSBetween March and November 2020, 518 COVID-19 patients were enrolled, of whom 394 were eligible, 29% meeting a severe outcome. The signatures area under the receiver operating characteristic curve (AUC) was 0.86 (95% confidence interval: 0.81-0.91). Performance was not confounded by age, sex, or comorbidities and superior to IL-6 (AUC 0.77; p = 0.033) and CRP (AUC 0.78; p < 0.001). Likelihood of severe outcome increased significantly (p < 0.001) with higher scores. The signature differentiated patients who further deteriorated after meeting a severe outcome from those who improved (p = 0.004) and projected 14-day survival probabilities (p < 0.001). CONCLUSIONThe derived immune-protein signature combined with a rapid measurement platform is an accurate predictive tool for early detection of COVID-19 patients at-risk for severe outcome, facilitating timely care escalation and de-escalation and appropriate resource allocation. FUNDINGMeMed funded the study

Real-time IP-10 measurements as a new tool for inflammation regulation within a clinical decision support protocol for managing severe COVID-19 patients

The challenge of treating severely ill COVID-19 patients is particularly great due to the need to simultaneously manage oxygenation and the inflammatory state without compromising viral clearance. Currently, there are many tools to aid in oxygen management and in monitoring viral replication. However, predictive biomarkers for monitoring the host immune response across COVID-19 disease stages and specifically, for titrating immunomodulatory therapy are lacking. We utilized a recently cleared platform (MeMed Key) that enables rapid and easy serial measurement of IP-10, a host protein implicated in lung injury due to viral-induced hyperinflammation. A dynamic clinical decision support protocol was employed for managing SARS-CoV-2 positive patients admitted to a COVID-19 dedicated medical center run by Clalit Health Services. This is the first protocol to include real-time measurements of IP-10 as a potential aid for regulating inflammation. Overall, 502 serial real-time IP-10 measurements were performed on 52 patients recruited between 7th April 2020 to 10th May 2020, with 12 patients admitted to the intensive care unit (ICU). IP-10 levels correlated with increased COVID-19 severity score and ICU admission. Within the ICU admitted patients, the number of days with IP-10 measurements >1,000 pg/ml was associated with mortality. Upon administration of corticosteroid immunomodulatory therapy, a significant decrease in IP-10 levels was observed. Real-time IP-10 monitoring represents a new tool to aid in management and therapeutic decisions relating to the inflammatory status of COVID-19 patients.

Accelerated versus standard corneal collagen crosslinking combined with same day phototherapeutic keratectomy and single intrastromal ring segment implantation for keratoconus.

AIM: To compare the results of same day transepithelial phototherapeutic keratectomy (t-PTK) and single inferior intracorneal ring segment (ICRS) combined with standard versus accelerated corneal collagen crosslinking (CXL) for keratoconus. METHODS: All consecutive progressive keratoconus eyes that underwent standard or accelerated CXL treatment preceded by same day t-PTK and placement of a single inferior ICRS and had 6  and 12 months of follow-up were reviewed retrospectively. Eyes were classified into two groups, the 'standard' and the 'accelerated' group, accordingly. Visual, refractive and topographic data prior to surgery and at 6 and 12 months post-treatment were analysed. RESULTS: Sixteen eyes were included in each of the standard and the accelerated groups. Mean patient age was 27.5±8.5 years and 30.5±10.7 years (p=0.38) in the standard and accelerated groups, respectively. There was a significant improvement in uncorrected distance visual acuity, refractive cylinder and all examined corneal parameters in both groups 12 months postsurgery. The corrected distance visual acuity and manifest refraction spherical equivalent showed a significant improvement after 12 months of follow-up only in the accelerated group. However, mean changes in all evaluated parameters did not differ significantly between the two groups. CONCLUSIONS: A combined treatment of accelerated CXL preceded by same day t-PTK and single ICRS is as effective as the combined treatment using standard CXL for visual rehabilitation in progressive keratoconus.

EndoGlide versus EndoSerter for the insertion of donor graft in descemet stripping automated endothelial keratoplasty.

PURPOSE: To compare 2 lenticule insertion methods currently in use for Descemet stripping automated endothelial keratoplasty (DSAEK). DESIGN: Prospective randomized single-masked study. PATIENTS AND METHODS: Twenty patients with Fuchs endothelial dystrophy and pseudophakic bullous keratopathy undergoing DSAEK surgery were included and randomized to the use of either EndoGlide or EndoSerter as a delivery method for the donor lenticule. Post surgery, patients were monitored for up to 1 year. Evaluation included corrected distance visual acuity (CDVA) and refraction. Specular microscopy images were obtained at the 6- and 12-month visits. Complications, including rebubbling rate, graft dislocation, and graft failure, were recorded. RESULTS: Twenty eyes were randomized to receive the Tan EndoGlide or the EndoSerter injector for lenticule insertion. Mean patient age was 65.9±8.4 years and 70.3±9.8 years in the Tan EndoGlide and EndoSerter groups, respectively (P=.3). Two eyes in each group needed rebubbling. The mean endothelial cell loss, including the rebubbled eyes, at the 12-month visit was 1093±629 cells/mm2 (range: 239-2109 cells/mm2, mean percentage cell loss 41.2%) and 877±566 cells/mm2 (range: 116-1851 cells/mm2, mean percentage cell loss 31.4%) in the Tan EndoGlide and EndoSerter groups, respectively (P=.45). Mean CDVA did not show a statistically significant difference between the 2 groups at the 6- or 12-month visit. CONCLUSION: The EndoSerter shows comparable results to the Tan EndoGlide. However, further investigation is warranted in order to validate these findings.

Collagen crosslinking after radial keratotomy.

PURPOSE: The aim of this study was to report the outcomes of corneal collagen crosslinking (CXL) after previous radial keratotomy (RK) in patients with decreasing visual acuity and/or diurnal visual fluctuations. METHODS: The charts of all patients who had undergone CXL because of a worsening corrected distance visual acuity (CDVA) and/or diurnal visual fluctuations after RK were reviewed retrospectively. Uncorrected distance visual acuity, CDVA, manifest refraction, and corneal topography were recorded preoperatively and at 1, 3, 6, and 12 months after the procedure. RESULTS: Nine eyes of 6 patients that had undergone an RK 15 to 23 years before the CXL were included in the study. In 5 patients (8 out of 9 eyes), discontinuation of diurnal visual fluctuation was reported between 6 and 12 months after the CXL. The mean uncorrected distance visual acuities pre and 12 months after the CXL were 0.7 logarithm of the minimum angle of resolution (logMAR) and 0.6 logMAR, respectively (P = 0.3). The mean CDVAs pre and 12 months after the CXL were 0.2 logMAR and 0.1 logMAR (P = 0.5), respectively. The mean average keratometry pre and 12 months after the CXL were 40.1 and 39.1 diopters (P = 0.06), respectively. The mean corneal astigmatism values pre and 12 months after the CXL were 2.3 and 1.9 diopters (P = 0.06), respectively. The mean manifest refraction spherical equivalents (MRSEs) before and 12 months after the CXL were +1.4 and +2.5 (P = 0.1), respectively. CONCLUSIONS: CXL is a safe and effective method to restore corneal stability in eyes with a history of RK. However, some of the effect that was achieved at the 6-month visit was blunted at the 12-month visit. Therefore, a longer follow-up is necessary to validate these findings.

Müller's muscle-conjunctival resection for upper eyelid ptosis: correlation between amount of resected tissue and outcome.

AIMS: To explore the relationship between the amount of resected Müller's muscle-conjunctiva (MMCR) and clinical outcome in patients undergoing upper eyelid ptosis surgery. METHODS: 49 patients underwent 87 MMCR surgeries. The total areas of the specimen and of MM were measured in pixels. RESULTS: The average percentage of muscle tissue in relation to total excised tissue was 21%. Intraoperative MMC tissue measurements and postoperative improvement in eyelid position (delta marginal reflex distance 1 (MRD1)) were positively correlated (R=0.427, p=0.09). There was a weak correlation between total areas measured on the histological slides and the intraoperative MMCR values (R=0.3, p=0.057). Total histological areas did not correlate with the delta change in eyelid position or with the amount and percentage of resected muscle tissue and the extent of improvement in eyelid position (delta MRD1) or final eyelid position (postoperative MRD1). CONCLUSIONS: Post-MMCR improvement in eyelid positions did not correlate with the percentage of MM in the excised tissue. We believe that the mechanism responsible for surgical outcome is plication or scarring of the posterior lamella and not the amount of resected MM. More lift in eyelid position can be anticipated when more tissue is excised by MMCR, and not when more muscle is excised.