Comprehensive Immune Profiling Reveals CD56+ Monocytes and CD31+ Endothelial Cells Are Increased in Severe COVID-19 Disease.

Immune response dysregulation plays a key role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis. In this study, we evaluated immune and endothelial blood cell profiles of patients with coronavirus disease 2019 (COVID-19) to determine critical differences between those with mild, moderate, or severe COVID-19 using spectral flow cytometry. We examined a suite of immune phenotypes, including monocytes, T cells, NK cells, B cells, endothelial cells, and neutrophils, alongside surface and intracellular markers of activation. Our results showed progressive lymphopenia and depletion of T cell subsets (CD3+, CD4+, and CD8+) in patients with severe disease and a significant increase in the CD56+CD14+Ki67+IFN-γ+ monocyte population in patients with moderate and severe COVID-19 that has not been previously described. Enhanced circulating endothelial cells (CD45-CD31+CD34+CD146+), circulating endothelial progenitors (CD45-CD31+CD34+/-CD146-), and neutrophils (CD11b+CD66b+) were coevaluated for COVID-19 severity. Spearman correlation analysis demonstrated the synergism among age, obesity, and hypertension with upregulated CD56+ monocytes, endothelial cells, and decreased T cells that lead to severe outcomes of SARS-CoV-2 infection. Circulating monocytes and endothelial cells may represent important cellular markers for monitoring postacute sequelae and impacts of SARS-CoV-2 infection during convalescence and for their role in immune host defense in high-risk adults after vaccination.

A longitudinal SARS-CoV-2 biorepository for COVID-19 survivors with and without post-acute sequelae.

BACKGROUND: SARS-CoV-2 has swept across the globe, causing millions of deaths worldwide. Though most survive, many experience symptoms of COVID-19 for months after acute infection. Successful prevention and treatment of acute COVID-19 infection and its associated sequelae is dependent on in-depth knowledge of viral pathology across the spectrum of patient phenotypes and physiologic responses. Longitudinal biobanking provides a valuable resource of clinically integrated, easily accessed, and quality-controlled samples for researchers to study differential multi-organ system responses to SARS-CoV-2 infection, post-acute sequelae of COVID-19 (PASC), and vaccination. METHODS: Adults with a history of a positive SARS-CoV-2 nasopharyngeal PCR are actively recruited from the community or hospital settings to enroll in the Northern Colorado SARS-CoV-2 Biorepository (NoCo-COBIO). Blood, saliva, stool, nasopharyngeal specimens, and extensive clinical and demographic data are collected at 4 time points over 6 months. Patients are assessed for PASC during longitudinal follow-up by physician led symptom questionnaires and physical exams. This clinical trial registration is NCT04603677 . RESULTS: We have enrolled and collected samples from 119 adults since July 2020, with 66% follow-up rate. Forty-nine percent of participants assessed with a symptom surveillance questionnaire (N = 37 of 75) had PASC at any time during follow-up (up to 8 months post infection). Ninety-three percent of hospitalized participants developed PASC, while 23% of those not requiring hospitalization developed PASC. At 90-174 days post SARS-CoV-2 diagnosis, 67% of all participants had persistent symptoms (N = 37 of 55), and 85% percent of participants who required hospitalization during initial infection (N = 20) still had symptoms. The most common symptoms reported after 15 days of infection were fatigue, loss of smell, loss of taste, exercise intolerance, and cognitive dysfunction. CONCLUSIONS: Patients who were hospitalized for COVID-19 were significantly more likely to have PASC than those not requiring hospitalization, however 23% of patients who were not hospitalized also developed PASC. This patient-matched, multi-matrix, longitudinal biorepository from COVID-19 survivors with and without PASC will allow for current and future research to better understand the pathophysiology of disease and to identify targeted interventions to reduce risk for PASC. Registered 27 October 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04603677 .

Optimal Timing of First Abdominal Radiography after Gastrografin Administration for Small Bowel Obstruction.

BACKGROUND: Water-soluble contrast agent (WSCA) administration is commonly used to evaluate adhesive small bowel obstruction (SBO) either via a challenge or follow-through study. This analysis aimed to determine optimal timing to first abdominal radiograph after WSCA administration. MATERIALS AND METHODS: A post hoc review of the Eastern Association for the Surgery of Trauma SBO database was used to compare data from two institutions using different methodologies, either the small bowel follow through method or the challenge method, from March 2015-January 2018. The primary outcome was timing of contrast into the colon. Outcomes were also analyzed. A multivariate regression analysis controlled for age, sex, body mass index, previous SBO admissions, and abdominal surgeries. RESULTS: A total of 236 patients met inclusion and exclusion criteria (A, 119; B, 117). There were minor demographic differences between cohorts and no significant differences between institutions regarding the confirmed presence of WSCA in the colon, rates of operative intervention, length of operation, hospital length of stay, or 30-d readmission rates.Institution A, where the challenge method was practiced, had 95 (80%) patients with contrast to colon overall; four of 95 (4%) patients had confirmed contrast to colon at or before 7 h, and 89 of 95 (94%) patients had confirmed contrast to colon between 7.1 and 10 h. Institution B, where the small bowel follow through method was practiced, had 94 (80%) patients with contrast to colon overall; 73 of 94 (78%) patients had confirmed contrast to colon at or before 7 h, and 15 of 94 (16%) patients had confirmed contrast to colon between 7.1 and 10 h. CONCLUSIONS: Either method is effective for evaluation of SBO. Adding a radiograph at 4 h is feasible, could promote earlier disposition, be conducted as part of an emergency department protocol, and possibly allow for the selection of patients who are candidates for outpatient treatment.

Modern Day Bicruciate-Retaining Total Knee Arthroplasty: A Short-Term Review of 146 Knees.

BACKGROUND: Bicruciate retaining (BCR) implants were first proposed in the 1960s with the polycentric knee. Given the technical difficulty of implanting these devices, and the mixed results at the time, the BCR concept had stalled, until recently. This study seeks to provide a short-term review of the BCR implant design, describe patient-reported outcomes, and discuss key aspects to ensure successful implantation of the modern-day BCR implant design. METHODS: Between October 2014 and December 2016, the senior author performed 146 primary total knee arthroplasties using BCR implants. Arthritic knees, with minimal soft tissue damage and an intact anterior cruciate ligament, were the general indications used for this cohort. All patients implanted with the BCR device were included in this analysis. One hundred forty-six (100%) BCR knees were available for follow-up at an average of 12 months (range, 1-33 months) postoperatively. RESULTS: Ninety-one percent of respondents reported their knee always or sometime feels normal, with only 9% of respondents reporting their knee never feels normal. Our study reports 94% of patients reported neutral satisfaction or higher, with only 6% of patients reporting dissatisfaction and 1% reported being very dissatisfied. Of all 146 BCR devices implanted, there were 2 (1.4%) revisions and 1 (0.7%) reoperation, a manipulation under anesthesia. CONCLUSION: This is the largest consecutive series of BCR total knee arthroplasties using the modern-day implant design with 1-year follow-up in the United States. The results of our study show great patient-reported satisfaction, function, and short-term outcomes for patients implanted with the new BCR design.

Eight Hundred Twenty-Five Medial Mobile-Bearing Unicompartmental Knee Arthroplasties: The First 10-Year US Multi-Center Survival Analysis.

BACKGROUND: FDA approval for the Oxford phase III device was approved for use in the United States in 2004. This study seeks to provide the first long-term, large patient sample size, Oxford phase III multi-site survivorship study in the United States, investigating patient reported outcomes of pain and function, while also providing an in-depth analysis of causes for revision, and finally addressing recent advancements that can help aid the unicompartmental knee arthroplasty (UKA) process and further improve partial knee survivorship. METHODS: Between July 2004 and December 2006, 5 surgeons from around the United States performed medial UKA through the minimally invasive surgical approach, on 825 knees in 695 patients. This was a consecutive series of primary UKAs using the phase III mobile bearing; cemented Oxford Knee (Zimmer Biomet, Warsaw, IN), implanted utilizing phase III instrumentation. UKA survivorship considered all revisions as the end point. Implant survivorship eliminated revisions at which the original Oxford implant was determined to be well fixated and functional intra-operatively. RESULTS: A total of 93 knees were revised in this study. Mean follow-up was 9.7 years (6-12). Implant survivorship at year 10 was 90% (confidence interval 2.7%). UKA survivorship at year 10 was 85% (confidence interval 3.8%). Average preoperative American Knee Society Score (knee score) was 49 and rose to 90 postoperatively (standard deviations 16 and 18, respectively). Average preoperative American Knee Society Score (function score) was 55 and rose to 77 postoperatively (standard deviations 15 and 28, respectively). CONCLUSION: This was the first large-scale, 10-year, multi-site follow-up of the Oxford mobile-bearing medial UKA undertaken in the United States, displaying good survivorship and excellent patient outcomes.

A Comparison of 2 Tibial Inserts of Different Constraint for Cruciate-Retaining Primary Total Knee Arthroplasty: An Additional Tool for Balancing the Posterior Cruciate Ligament.

BACKGROUND: Frequently, a normal posterior-cruciate ligament (PCL) is removed at the surgeon's discretion, converting the normal 4-ligament knee to a 2-ligament knee, thus eliminating the need to balance all 4 ligaments. The development of modular tibial components has led to the availability of differing polyethylene inserts that permit adjustment to the flexion gap independent of the extension gap, permitting PCL balancing not previously available. The purpose of this study is to analyze a specific cruciate-retaining (CR) prosthesis which has 2 polyethylene inserts intended for CR knee use. METHODS: Between February 2004 and February 2013, the senior author (R.H.E.) has performed 930 total knee arthroplasties using the CR flat insert and 424 knees using the CR lipped insert. The inserts were selected during surgery, based on the assessed tension and function of the PCL. The patients were followed up as part of a prospective total joint program with the Knee Society clinical scoring, range of motion, complications, revisions, preoperative coronal deformity, gender, body mass index, and status of the anterior-cruciate ligament intraoperatively. RESULTS: The average Knee Score was 92.4 for the flat group and 92.1 for the lipped group. Average knee flexion was 116.2° for the flat group and 114.4° for the lipped group (P=.2). Average knee extension (flexion deformity) was 2.1° for the flat group and 0.9° for the lipped group CONCLUSION: The results reported here show that clinical outcomes and survivorship were no different for either insert option, leading to indirect evidence that appropriate soft tissue balance had been achieved.

Optimal Duration of Antibiotics Following Appendectomy for Patients With Complicated Appendicitis.

BACKGROUND: Complicated appendicitis patients typically undergo appendectomy followed by antibiotics. The optimal course of antibiotics for complicated appendicitis is poorly defined. METHODS: Data were collected from patients presenting with acute appendicitis and underwent appendectomy at the index hospitalization (2015-2017). Primary outcomes were readmission rate, superficial surgical site infection (SSI), deep space infection (DSI), which includes abscess. Length of post-operative antibiotic use was recorded and an average intent-to-treat (ITT) by operative grade was calculated. RESULTS: Two hundred seventy-two patients (23%) were diagnosed with complicated appendicitis. SSI occurred in 4% of patients (n = 11); SSI rates ranged from 0% to 14.6% by ITT group with 3-4 days being the lowest (0%) and <3 days the highest (14.6%) (P = .008). DSI including abscesses occurred in 27 (9.9%) patients; least frequently in the 5-6 day ITT group (7.4%). Length of stay (LOS) was significantly related to longer antibiotic use (P < .001) and increasing operative grade (P < .01). CONCLUSIONS: Given the lower incidence of postoperative complications between 3 and 6 days and no added benefit for ITT >6 days, we recommend limiting antibiotic treatment to 3-6 days for all complicated appendicitis cases with additional workup warranted if infectious symptoms persist.

Non-invasive, Zip Type Skin Closure Device vs. Conventional Staples in Total Knee Arthroplasty: Which Method Holds Greater Potential for Bundled Payments?

INTRODUCTION: A new, noninvasive zip surgical skin closure device has recently been introduced into the market and introduces a new alternative to the traditional staple closure method which has dominated the industry for many years. METHODS: This was a retrospective chart review and case study of a consecutive series of 130 patients who underwent primary total knee arthroplasty (TKA) from April 2016 to November 2016. The first 65 patients in this series underwent a primary TKA utilizing the standard staple closure method (staple group). The next 65 patients underwent a primary TKA through the new zip surgical skin closure method (zip group). Charts were reviewed for incision-related phone calls to the clinic, additional clinic visits due to incision concerns, antibiotic prescriptions due to incision complications, and incision-related emergency room (ER) admits. RESULTS: The staple group had a significantly higher amount of incision-related phone calls made to the clinic as compared to the zip group (20 versus 8, P < .05, respectively). The staple group also had more incision-related ER admits, more incision-related clinic visits, and more antibiotics prescribed due to incisional complications than the zip group (1 versus 0, 5 versus 2, and 4 versus 1, respectively), although it was not proven to be significant (P > .05). CONCLUSION: This is the largest patient cohort study comparing the noninvasive zip-type closure device to staple closures in TKA cases and provides insight on how a simple change in the closure methodology can lead to many potential downstream savings when considering a bundled payment model.