Dysregulated platelet function in patients with postacute sequelae of COVID-19.

BACKGROUND: Postacute sequelae of COVID-19 (PASC), also referred to as "Long COVID", sometimes follows COVID-19, a disease caused by SARS-CoV-2. Although SARS-CoV-2 is well known to promote a prothrombotic state, less is known about the thrombosis risk in PASC. Our objective was to evaluate platelet function and thrombotic potential in patients following recovery from SARS-CoV-2, but with clear symptoms of patients with PASC. METHODS: patients with PASC and matched healthy controls were enrolled in the study on average 15 months after documented SARS-CoV-2 infection. Platelet activation was evaluated by light transmission aggregometry (LTA) and flow cytometry in response to platelet surface receptor agonists. Thrombosis in platelet-deplete plasma was evaluated by Factor Xa activity. A microfluidics system assessed thrombosis in whole blood under shear stress conditions. RESULTS: A mild increase in platelet aggregation in patients with PASC through the thromboxane receptor was observed, and platelet activation through the glycoprotein VI (GPVI) receptor was decreased in patients with PASC compared to age- and sex-matched healthy controls. Thrombosis under shear conditions as well as Factor Xa activity were reduced in patients with PASC. Plasma from patients with PASC was an extremely potent activator of washed, healthy platelets - a phenomenon not observed when stimulating healthy platelets after incubation with plasma from healthy individuals. CONCLUSIONS: patients with PASC show dysregulated responses in platelets and coagulation in plasma, likely caused by a circulating molecule that promotes thrombosis. A hitherto undescribed protective response appears to exist in patients with PASC to counterbalance ongoing thrombosis that is common to SARS-CoV-2 infection.

Health-Related Quality of Life for Patients with Post-Acute COVID-19 Syndrome: Identification of Symptom Clusters and Predictors of Long-Term Outcomes.

BACKGROUND: Following COVID-19 infection, as many as a third of patients have long-term symptoms, known as post-acute sequelae (PASC). The mechanisms contributing to PASC remain largely unknown and, due to the heterogeneity of symptoms, treating PASC provides unique challenges. OBJECTIVE: Our study sought to (1) identify clinical symptom profiles based on PROMIS Global Health (GH) items, (2) evaluate demographic and clinical differences across profiles, and (3) identify predictors of change in health-related quality of life (HRQL) over time. DESIGN: This was an observational cohort study of patients with PASC who completed PROMIS-GH between 2/11/21 and 12/3/21 as part of routine care, with data extracted from the electronic health record. PARTICIPANTS: There were 1407 adult patients (mean age 49.6 ± 13.7, 73% female, 81% White race) with PASC seen in the recovery clinic between 2/11/21 and 12/3/21, with 1129 (80.2%) completing PROMIS-GH as routine care. MAIN MEASURES: HRQL was measured with PROMIS-GH at initial visit and after 12 months. KEY RESULTS: Latent profile analysis identified symptom classes based on five PROMIS-GH items (mental health, ability to carry out physical activities, pain, fatigue, and emotional problems). Four latent profiles were identified: (1) "Poor HRQL" (n = 346), (2) "Mixed HRQL: good mental/poor physical" (n = 232), (3) "Mixed HRQL: poor mental/good physical" (n = 324), and (4) "Good HRQL" (n = 227). Demographics and comorbidities varied significantly across profile with patients with more severe COVID-19 infection more likely to be in profiles 1 and 2. Overall, patients improved 2 T-score points on PROMIS-GH after 12 months, with differences by profile. Predictors of improved HRQL included profile, lower body mass index, and fewer COVID symptoms. CONCLUSIONS: Patients with PASC have distinct HRQL symptom profiles which were able to differentiate across COVID-19 severity and symptoms. Improvement over 12 months differed by profile. These profiles may be used to better understand the mechanisms behind PASC. Future research should evaluate their ability to guide treatment decisions to improve HRQL.

Dysregulated Platelet Function in Patients with Post-Acute Sequelae of COVID-19.

Background: Post-acute sequelae of COVID-19 (PASC), also referred as Long-COVID, sometimes follows COVID-19, a disease caused by SARS-CoV-2. While SARS-CoV-2 is well-known to promote a prothrombotic state, less is known about the thrombosis risk in PASC. Aim: Our objective was to evaluate the platelet function and thrombotic potential in patients following recovery from SARS-CoV-2 with clear symptoms of PASC. Methods: PASC patients and matched healthy controls were enrolled in the study on average 15 months after documented SARS-CoV-2 infection. Platelet activation was evaluated by Light Transmission Aggregometry (LTA) and flow cytometry in response to platelet surface receptor agonists. Thrombosis in platelet-deplete plasma was evaluated by Factor Xa activity. A microfluidics system assessed thrombosis in whole blood under shear stress conditions. Results: A mild increase in platelet aggregation in PASC patients through the thromboxane receptor was observed and platelet activation through the glycoprotein VI (GPVI) receptor was decreased in PASC patients compared to age- and sex-matched healthy controls. Thrombosis under shear conditions as well as Factor Xa activity were reduced in PASC patients. Plasma from PASC patients was an extremely potent activator of washed, healthy platelets - a phenomenon not observed when stimulating healthy platelets after incubation with plasma from healthy individuals. Conclusions: PASC patients show dysregulated responses in platelets and coagulation in plasma, likely caused by a circulating molecule that promotes thrombosis. A hitherto undescribed protective response appears to exists in PASC patients to counterbalance ongoing thrombosis that is common to SARS-CoV-2 infection.

A case series of image-guided percutaneous drainage of abdominal aortic graft infection as bridge therapy.

INTRODUCTION: Aortic graft infection (AGI) is a rare complication following endovascular aneurysm repair and is associated with substantial morbidity and mortality. The traditional management of AGI is intravenous antibiotic therapy and surgical explantation. In this case series, percutaneous drainage was used as a bridge therapy in the treatment of AGI. METHODS: We report two cases, 78-year-old male and 57-year-old female, in whom image-guided percutaneous drainage was used to treat AGI in two contrasting contexts. Informed consent was obtained from both cases/relatives for publication. RESULTS: Both cases underwent successful percutaneous drainage of AGI utilized as a bridge therapy before definitive surgical reconstruction and graft explantation. Each patient had a different outcome. In the first case, the patient's comorbidities and severe disease state could not be overcome, resulting in his death. The second patient benefitted from the percutaneous drainage by allowing her more time ameliorate her malnutrition before definitive surgery. CONCLUSION: Data on the outcomes of percutaneous drainage of AGI is limited. The successful procedure described in this case series emphasizes the need to conduct more research to evaluate the safety and efficacy of this treatment approach before the surgical explantation.

A Post-Pandemic Enigma: The Cardiovascular Impact of Post-Acute Sequelae of SARS-CoV-2.

COVID-19 has become the first modern-day pandemic of historic proportion, affecting >600 million individuals worldwide and causing >6.5 million deaths. While acute infection has had devastating consequences, postacute sequelae of SARS-CoV-2 infection appears to be a pandemic of its own, impacting up to one-third of survivors and often causing symptoms suggestive of cardiovascular phenomena. This review will highlight the suspected pathophysiology of postacute sequelae of SARS-CoV-2, its influence on the cardiovascular system, and potential treatment strategies.

Impact of a standardized order set and medication-use process on medication error rates in sexual assault patients presenting to the emergency department for HIV nonoccupational postexposure prophylaxis.

PURPOSE: To evaluate the impact of a standardized order set and medication-use process on antiretroviral medication errors in sexual assault (SA) patients presenting to the emergency department (ED) for nonoccupational postexposure prophylaxis (nPEP). METHODS: In November 2019, a multidisciplinary group collaborated on an initiative to improve the nPEP medication-use process for SA patients presenting to the EDs within a large integrated health system. Electronic medical records of patients 13 years of age or older who presented for SA examination and were prescribed nPEP during the pre- (February 2018-August 2019) and poststandardization (February 2020-August 2021) periods were included. The primary objective was to compare the proportion of patients experiencing a medication error before and after SA/nPEP process standardization. Data regarding the following medication errors were evaluated: incomplete regimen; inappropriate/duplicative regimen; dosing, frequency, or quantity prescribed error; and initiation of nPEP without an HIV test. RESULTS: Two hundred six patients met criteria for inclusion. A higher proportion of patients experienced medication errors in the prestandardization group relative to the poststandardization group (46.5% vs 11.9%, P < 0.001). Fifty-five errors were observed in the prestandardization group, compared to 16 errors in the poststandardization group. The majority of errors in the prestandardization group were directly related to antiretroviral regimens, while the majority of errors in the poststandardization group involved initiation of nPEP without an HIV test. CONCLUSION: The standardization of the SA/nPEP process was associated with significantly lower medication error rates. Optimization of medication-use technology is an effective strategy in reducing medication errors.

Multidisciplinary Approach to Improve Human Immunodeficiency Virus and Syphilis Testing Rates in Emergency Departments.

Background: Best practice guidelines recommend that patients at risk for sexually transmitted infections (STIs), such as gonorrhea (GC) and chlamydia, should also be tested for human immunodeficiency virus (HIV) and syphilis. This prospective quality assurance study aimed to increase HIV and syphilis testing rates in emergency departments (EDs) across the Cleveland Clinic Health System from January 1, 2020 through January 1, 2022. Methods: A multidisciplinary team of emergency medicine, infectious diseases, pharmacy, and microbiology personnel convened to identify barriers to HIV and syphilis testing during ED encounters at which GC/chlamydia were tested. The following interventions were implemented in response: rapid HIV testing with new a workflow for results follow-up, a standardized STI-screening order panel, and feedback to clinicians about ordering patterns. Results: There were 57 797 ED visits with GC/chlamydia testing completed during the study period. Human immunodeficiency virus testing was ordered at 5% of these encounters before the interventions were implemented and increased to 8%, 23%, and 36% after each successive intervention. Syphilis testing increased from 9% before the interventions to 12%, 28%, and 39% after each successive intervention. In multivariable analyses adjusted for age, gender, and location, the odds ratio for HIV and syphilis testing after all interventions was 11.72 (95% confidence interval [CI], 10.82-12.71; P ≤.001) and 6.79 (95% CI, 6.34-7.27; P ≤.001), respectively. Conclusions: The multidisciplinary intervention resulted in improved testing rates for HIV and syphilis.

Clinical presentation and course of COVID-19.

Information about the clinical presentation and course of COVID-19 is evolving rapidly. On presentation, cough and fever predominate, but extrapulmonary symptoms are also common; in some patients, loss of sense of smell may be an early but favorable sign. The mortality rate varies widely in different reports but should become clearer as more data are collected. Risk factors for severe disease and death include comorbid conditions such as hypertension, cardiovascular disease, diabetes mellitus, and chronic obstructive pulmonary disease. Other implicated factors include older age, obesity, end-stage renal disease, and a higher neutrophil-lymphocyte ratio.

Transmission and risk factors of OF COVID-19.

SARS-CoV-2, the virus that causes COVID-19, is transmitted through respiratory secretions and saliva. The virus can also live for short periods of time (1 to several hours) on fomites such as doorknobs, handrails, and tables. Aerosolization of the virus can occur during procedures including bronchoscopy, endotracheal intubation, and administration of nebulized treatments. Asymptomatic shedding of the virus does occur and may account for up to 60% of cases. Risk factors for a more severe course of COVID-19 include age 65 and older, living in a nursing home or long term care facility, chronic lung disease, and others.

Problems with the problem list: challenges of transparency in an era of patient curation.

In recent years, the OpenNotes movement and other changes in healthcare have driven institutions to make medical records increasingly transparent. As patients have begun to question and request changes to their Problem Lists, clinicians have come to face the ever more frequent challenge of discerning which changes to make and which to refuse. Now clinicians and patients together choose the list of problems that represent the patient's current state of health and illness. As the physician's role slides closer to consultant and the medical paternalism of the twentieth century falls further into the background of our technology-infused present, who holds the power of delineating a patient's clinical identity? This paper examines the ethical and practical dimensions of this question and proposes a research agenda that aims to answer it. Such explorations are essential to ensuring that the physician remains relevant to patient's notions of health, illness, intervention, and healing.

Are Prophylactic Perioperative Antibiotics Required for Isolated Forefoot Procedures, Such as Hammertoes?

RECOMMENDATION: Though limited clinical data exists, the administration of perioperative antibiotics is not required for isolated forefoot procedures in the absence of any risk factors, such as immunodeficiency or diabetes mellitus. LEVEL OF EVIDENCE: Moderate. DELEGATE VOTE: Agree: 67%, Disagree: 25%, Abstain: 8% (Super Majority, Weak Consensus).

Is There a Role for the Use of Dilute Povidone-Iodine (Betadine) Irrigation or Other Antiseptic Irrigation Solutions During Total Ankle Arthroplasty (TAA) or Other Foot and Ankle Procedures?

RECOMMENDATION: With regard to total ankle arthroplasty (TAA), there is a lack of evidence to recommend for or against the use of betadine solution. LEVEL OF EVIDENCE: Consensus. DELEGATE VOTE: Agree: 100%, Disagree: 0%, Abstain: 0% (Unanimous, Strongest Consensus).

Tumor necrosis factor receptor associated periodic fever syndrome with photographic evidence of various skin disease and unusual phenotypes: case report and literature review.

OBJECTIVES: To report a case of tumor necrosis factor receptor associated periodic fever syndrome (TRAPS) with unusual clinical phenotypes and a systematic review. METHODS: The relevant English literature of TRAPS was searched using the keywords TRAPS, autoinflammatory disease, and gene mutation. Original and review articles were reviewed and the clinical scenarios were exemplified with a case report. RESULTS: A 58-year-old Jewish woman with Eastern European Ashkenazic background presented with photographic evidence of various skin disease, including previously unreported vesicles and alopecia, as well as other systemic manifestations. The complaints of urinary foreign bodies prompted a discovery of ureteral strictures with atypia perhaps from autoinflammation. A R92Q gene mutation of TNFRSFA1 was detected. The clinical manifestations of this disease are protean and its pathogenesis is complex, involving the interaction of wild-type and mutated gene products, innate immune system, and proinflammatory cytokines. Glucocorticoid and anticytokine therapy is generally efficacious but some cases remain refractory to the current treatment. CONCLUSIONS: TRAPS is a systemic autoinflammatory disease with variable clinical phenotypes associated with gene mutations. Recognition of the unusual phenotypes may enhance early accurate diagnosis.