Risk of thrombosis with thrombocytopenia syndrome after COVID-19 vaccination prior to the recognition of vaccine-induced thrombocytopenia and thrombosis: A self-controlled case series study in England.

Background: Several studies have found increased risks of thrombosis with thrombocytopenia syndrome (TTS) following the ChAdOx1 vaccination. However, case ascertainment is often incomplete in large electronic health record (EHR)-based studies. Objectives: To assess for an association between clinically validated TTS and COVID-19 vaccination. Methods: We used the self-controlled case series method to assess the risks of clinically validated acute TTS after a first COVID-19 vaccine dose (BNT162b2 or ChAdOx1) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Case ascertainment was performed uninformed of vaccination status via a retrospective clinical review of hospital EHR systems, including active ascertainment of thrombocytopenia. Results: One hundred seventy individuals were admitted to the hospital for a TTS event at the study sites between January 1 and March 31, 2021. A significant increased risk (relative incidence [RI], 5.67; 95% confidence interval [CI], 1.02-31.38) of TTS 4 to 27 days after ChAdOx1 was observed in the youngest age group (18- to 39-year-olds). No other period had a significant increase, although for ChAdOx1 for all ages combined the RI was >1 in the 4- to 27- and 28- to 41-day periods (RI, 1.52; 95% CI, 0.88-2.63; and (RI, 1.70; 95% CI, 0.73-3.8, respectively). There was no significant increased risk of TTS after BNT162b2 in any period. Increased risks of TTS following a positive SARS-CoV-2 test occurred across all age groups and exposure periods. Conclusions: We demonstrate an increased risk of TTS in the 4 to 27 days following COVID-19 vaccination, particularly for ChAdOx1. These risks were lower than following SARS-CoV-2 infection. An alternative vaccine may be preferable in younger age groups in whom the risk of postvaccine TTS is greatest.

Thoracic aortic syndromes in the emergency department: recognition and management.

Acute aortic syndromes include aortic dissection, penetrating atherosclerotic ulcer, and intramural hematomas, but aortic dissection is the most common and the deadliest. This review summarizes the latest evidence on developing a differential for aortic dissection when common complaints, such as chest pain, abdominal pain, and syncope are also present. Recent evidence on the optimal uses of emergency department imaging studies and risk stratification tools are reviewed, along with special considerations in the management of penetrating atherosclerotic ulcer and intramural hematoma. Pharmacologic therapies for managing hemodynamic parameters and shock, and indications for operative intervention are also reviewed, along with cutting-edge diagnostic and treatment options on the horizon.

Infective endocarditis: identification and management in the emergency department.

Recognition of infective endocarditis in the emergency department continues to be a challenge, as its signs and symptoms can be subtle, laboratory results are limited, and it can involve or lead to many other serious conditions. With the increase in use of medical access devices, implantable cardiac devices, and the rise of intravenous drug use, the epidemiology of infective endocarditis is changing. Diagnostic imaging has evolved, and the use of point-of-care ultrasound and transthoracic echocardiography are critical in making an early diagnosis. This review provides a best-evidence approach to diagnostic strategies, antibiotic recommendations, and surgical treatment recommendations for infective endocarditis.

Renal Infarct After Endovascular Abdominal Aortic Aneurysm Repair: Consider in Back Pain Differential.

As hypertension, obesity, and hyperlipidemia become more widespread, the prevalence of abdominal aortic aneurysms (AAA) has also increased.1 Traditionally those with multiple comorbidities - also those with greatest AAA mortality - were considered too high risk for operative repair. In recent decades, however, endovascular abdominal aortic aneurysm repair (EVAR) has become a popular option, especially for high-risk patients. Overall, short-term outcomes are comparable to traditional open repair despite higher patient baseline risk. However, EVAR comes with its own risks, which the emergency physician should be aware of. Here, we present a rare complication of EVAR: device thrombosis with subsequent renal infarct.

Community hospital experience in the emergency management of COVID-19: Preventing morbidity and preserving resources.

An incredible amount of information has been published regarding inpatient management of patients with COVID-19. Although this is vitally important, critical interventions that occur in the emergency department (ED) can have a profound impact on the individual patient and the healthcare system as a whole.  Much has been written regarding care in large centers, but there has been little discussion regarding similar patients in community settings. Prior to the pandemic, large centers were able to accept patients that outstripped the resources in community hospital settings, but currently we foresee that many community centers will begin to manage more complex cases without referral. As physicians in a medium-sized community academic center, we aim to enumerate community-hospital-relevant guidance for ED care that focuses on adherence to available evidence-based medicine, including early aggressive supplemental oxygenation, awake proning, and methods to improve oxygenation and ultimately delay intubation as long as safely possible.  Equally importantly, it was recognized early that adjustments to medication regimens (eg, sedation) and personal protective equipment (PPE) use must be made in the ED to conserve those same resources for long-term use in inpatient units and improve the functionality of the hospital system as a whole. It is our hope that this article may serve as a framework for similar community-based hospitals to create their own protocols to optimize resource utilization, staff safety, and patient care.

Delayed Diagnosis of Spinal Tuberculosis in a 44-year-old Male with Acute on Chronic Low Back Pain.

Spinal tuberculosis (STB), also known as tuberculous spondylitis, tuberculous vertebral osteomyelitis, or Pott's disease is a rare subset of extrapulmonary tuberculosis. Although rare in developed countries, STB is an important diagnosis for the emergency physician to consider. We report a case of a 44-year-old African-American male with STB presenting as an acute exacerbation of chronic low back pain complicated by urinary retention and difficulty ambulating. Our patient had no known predisposing risk factors for tuberculosis. This patient's STB was mistakenly diagnosed as nontuberculous vertebral osteomyelitis. This is not uncommon, as it is often difficult to distinguish the two clinically. This patient experienced advanced neurologic features at the time of initial presentation, which improved with surgical decompression. Ultimately, he re-presented to the emergency department 10 days after hospital discharge with recurrence of symptoms due to inaccurate antimicrobial selection. The diagnosis may hinge on the astute physician recognizing the characteristic, albeit subtle, imaging findings of STB.

Posterior Shoulder Dislocation During Morning PT: A Case Report.

Posterior shoulder dislocation should be considered in the differential diagnosis of acute shoulder pain and immobility following trauma. Although far less common then the anterior dislocation, it is associated with high rates of comorbidity. Seventy-nine percent of posterior shoulder dislocations are missed on initial presentation, which is partially responsible for the high rate of comorbidity associated with these injuries. The mechanism of injury is varied from generalized seizure to minor trauma, which adds to the complexity of the diagnosis. There is a well-documented "vulnerable position" described as injury to the arm while it is in a flexed, adducted, and internally rotated position that is highly associated with posterior shoulder dislocation. The plain film scapular Y is the most clinically significant imaging and can be used alone to diagnose the injury, although ancillary imaging such as magnetic resonance imaging is often warranted. Once this rare condition has been diagnosed, there are a number of appropriate reduction techniques available to the health care provider. Presented here is a case of posterior shoulder dislocation that occurred while doing pushups for routine morning physical training. Also discussed are keys to recognition and treatment as well as a brief discussion of associated complications of the injury.

Brugada pattern exposed with administration of amiodarone during emergent treatment of ventricular tachycardia.

BACKGROUND: Brugada pattern is a well-known pathological finding on electrocardiogram (ECG) which increases the likelihood of cardiac arrest due to ventricular arrhythmia. These cases generally present in younger patients without evidence of an electrolyte abnormality, structural heart disease, or cardiac ischemia. In many instances, this pattern is either hidden on initial presentation or presents as an incidental finding on an EKG. Often times the Brugada syndrome leads to sudden cardiac death or more rarely can be unmasked with a class 1A or 1C anti-arrhythmic agent. Here, we present a distinctive case in which the pattern was exposed by amiodarone during the emergent treatment of Ventricular Tachycardia (VT). CASE REPORT: A 34-year-old female, without significant cardiac history, presented to the Emergency Department after multiple near syncopal episodes at home. Initial ECG showed VT vs. SVT. After a failed trial of adenosine, the patient was treated with 150 mg amiodarone and became hypotensive needing an electrical cardioversion. After becoming bradycardic, the amiodarone drip was discontinued and she was admitted to the MICU. An echocardiogram and left heart catheterization showed no evidence of coronary artery disease or decreased ejection fraction. The patient's ECG now showed a subtle Brugada Type 3 pattern and she received a dual chamber AICD upon discharge. CONCLUSION: This case emphasizes the awareness needed to seek out this pattern on subsequent ECG's. With the high lethality of Brugada, the emergency physician must recognize that multiple drugs can evoke this pattern after initial presentation.

Headache with Aura: A case report of ocular melanoma.

BACKGROUND: Headaches and visual complaints are common conditions encountered in the emergency department. While a patient's age, risk factors, and comorbidities often aid in risk stratification and guide emergency department evaluation, atypical presentations of serious disease may still occur in young otherwise healthy patients CASE: In this vignette we discuss a case of ocular (choroidal) melanoma in a 21 year-old female patient who presented with recurrent photopsia and headaches. DISCUSSION: Ocular melanoma is the most common non-skin melanoma and should be considered by the emergency physician for patients with visual deficits. Likely presentations and risk factors for ocular melanoma will be discussed as well as emergency department and specialty management.

Screening of primary gp120 immunogens to formulate the next generation polyvalent DNA prime-protein boost HIV-1 vaccines.

Our previous preclinical studies and a Phase I clinical trial DP6-001 have indicated that a polyvalent Env formulation was able to elicit broadly reactive antibody responses including low titer neutralizing antibody responses against viral isolates of subtypes A, B, C and AE. In the current report, a panel of 62 gp120 immunogens were screened in a rabbit model to identify gp120 immunogens that can elicit improved binding and neutralizing antibody responses and some of them can be included in the next polyvalent formulation. Only about 19% of gp120 immunogens in this panel were able to elicit neutralizing antibodies against greater than 50% of the viruses included in a high throughput PhenoSense neutralization assay when these immuongens were tested as a DNA prime followed by a fixed 5-valent gp120 protein vaccine boost. The new polyvalent formulation, using five gp120 immunogens selected from this subgroup, elicited improved quality of antibody responses in rabbits than the previous DP6-001 formulation. More significantly, this new polyvalent formulation elicited higher antibody responses against a panel of gp70V1/V2 antigens expressing V1/V2 sequences from diverse subtypes. Bioinformatics analysis supports the design of a 4-valent or 5-valent formulation using gp120 immunogens from this screening study to achieve a broad coverage against 16 HIV-1 subtypes.

Polyvalent DNA vaccines expressing HA antigens of H5N1 influenza viruses with an optimized leader sequence elicit cross-protective antibody responses.

Highly pathogenic avian influenza A (HPAI) H5N1 viruses are circulating among poultry populations in parts of Asia, Africa, and the Middle East, and have caused human infections with a high mortality rate. H5 subtype hemagglutinin (HA) has evolved into phylogenetically distinct clades and subclades based on viruses isolated from various avian species. Since 1997, humans have been infected by HPAI H5N1 viruses from several clades. It is, therefore, important to develop strategies to produce protective antibody responses against H5N1 viruses from multiple clades or antigenic groups. In the current study, we optimized the signal peptide design of DNA vaccines expressing HA antigens from H5N1 viruses. Cross reactivity analysis using sera from immunized rabbits showed that antibody responses elicited by a polyvalent formulation, including HA antigens from different clades, was able to elicit broad protective antibody responses against multiple key representative H5N1 viruses across different clades. Data presented in this report support the development of a polyvalent DNA vaccine strategy against the threat of a potential H5N1 influenza pandemic.

Antibody responses elicited through homologous or heterologous prime-boost DNA and protein vaccinations differ in functional activity and avidity.

Using a gp120 envelope glycoprotein from the JR-FL strain of human immunodeficiency virus-1 (HIV-1) as a model antigen, the goal of the current study was to evaluate the level and quality of antibody responses elicited by different prime-boost vaccination regimens (protein only, DNA only, DNA plus protein) in rabbits. Our data demonstrated that incorporating DNA immunization as a prime in a heterologous prime-boost regimen was able to elicit a more diverse and conformational epitope profile, higher antibody avidity, and improved neutralizing activity than immunization with only protein. Additionally, this improved neutralizing activity was observed in spite of similar antibody specificities and avidities seen when only DNA vaccination was used, providing additional evidence that the use of a combination immunization regimen increases the protective antibody response. Insights gained from the current study confirmed that the heterologous DNA prime-protein boost approach is effective in eliciting not only high level but also improved quality of antigen-specific antibody responses, and thus may offer a new technology platform to develop better and safer subunit vaccines.

Intramuscular delivery of a cholera DNA vaccine primes both systemic and mucosal protective antibody responses against cholera.

Cholera is a potentially lethal diarrhea disease caused by the gram-negative bacterium Vibrio cholerae. The need for an effective cholera vaccine is clearly indicated but the challenges of eliciting both systemic and mucosal immune responses remains a significant challenge. In the current report, we discovered that a DNA vaccine expressing a protective cholera antigen, cholera toxin B subunit (CTB), delivered parenterally can elicit both systemic and mucosal anti-CTB antibody responses in mice. The priming effect by DNA immunization was demonstrated by higher mucosal antibody responses following one boost with the inactivated cholera vaccine (KWC-B) delivered orally when compared to the twice oral administration of KWC-B alone. This finding indicates that DNA vaccines delivered parenterally are effective in eliciting mucosal protective immune responses--a unique advantage for DNA vaccination that has not yet been well realized and should bring value to the development of novel vaccination approaches against mucosally transmitted diseases.

High ER stress in beta-cells stimulates intracellular degradation of misfolded insulin.

Endoplasmic reticulum (ER) stress, which is caused by the accumulation of misfolded proteins in the ER, elicits an adaptive response, the unfolded protein response (UPR). One component of the UPR, the endoplasmic reticulum-associated protein degradation (ERAD) system, has an important function in the survival of ER stressed cells. Here, we show that HRD1, a component of the ERAD system, is upregulated in pancreatic islets of the Akita diabetes mouse model and enhances intracellular degradation of misfolded insulin. High ER stress in beta-cells stimulated mutant insulin degradation through HRD1 to protect beta-cells from ER stress and ensuing death. If HRD1 serves the same function in humans, it may serve as a target for therapeutic intervention in diabetes.