Long-term quantitative assessment of anti-SARS-CoV-2 spike protein immunogenicity (QUASI) after COVID-19 vaccination in older people living with HIV (PWH).

BACKGROUND: The durability of immune responses to COVID-19 vaccines among older people living with HIV (PWH) is clinically important. METHODS: We aimed to assess vaccine-induced humoral immunity and durability in older PWH (≥ 55 years, n = 26) over 6 months (post-initial BNT162b2 series). A secondary and exploratory objective was to assess T-cell response and BNT162b2 booster reactogenicity, respectively. Our Visit 1 (3 weeks post-initial BNT162b2 dose) SARS-CoV-2 humoral immunity results are previously reported; these subjects were recruited for Visit 2 [2 weeks (+ 1 week window) post-second vaccination] and Visit 3 [6 months (± 2 week window) post-initial vaccination] in a single-center longitudinal observational study. Twelve participants had paired Visit 2/3 SARS-CoV-2 Anti-Spike IgG data. At Visit 3, SARS-CoV-2 Anti-Spike IgG testing occurred, and 5 subjects underwent T-cell immune response evaluation. Thereafter, subjects were offered BNT162b2 booster (concurrent day outside our study) per US FDA/CDC guidance; reactogenicity was assessed. The primary study outcome was presence of detectable Visit 3 SARS-CoV-2 Anti-Spike-1-RBD IgG levels. Secondary and exploratory outcomes were T-cell immune response and BNT162b2 booster reactogenicity, respectively. Wilcoxon signed-rank tests analyzed median SARS-CoV-2 Anti-Spike IgG 6-month trends. RESULTS: At Visit 3, 26 subjects underwent primary analysis with demographics noted: Median age 61 years; male n = 16 (62%), female n = 10 (38%); Black n = 13 (50%), White n = 13 (50%). Most subjects (n = 20, 77%) had suppressed HIV viremia on antiretroviral therapy, majority (n = 24, 92%) with CD4 > 200 cells/µL. At Visit 3, 26/26 (100%) had detectable Anti-Spike-1-RBD (≥ 0.8 U/mL). Among 12 subjects presenting to Visit 2/3, median SARS-CoV-2 Anti-Spike 1-RBD was 2087 U/mL at Visit 2, falling to 581.5 U/mL at Visit 3 (p = 0.0923), with a median 3.305-fold decrease over 6 months. Among subjects (n = 5) with 6-month T-cell responses measured, all had detectable cytokine-secreting anti-spike CD4 responses; 3 had detectable CD4 + Activation induced marker (AIM) + cells. Two had detectable cytokine-secreting CD8 responses, but all had positive CD8 + AIM + cells. CONCLUSIONS: Among older PWH, SARS-CoV-2 Anti-Spike IgG and virus-specific T-cell responses are present 6 months post-primary BNT162b2 vaccination, and although waning, suggest retention of some degree of long-term protective immunity.

The Benefit of Routine Axillary Sonographic Assessment in cN0 Breast Cancer Patients.

Objective: Axillary ultrasound (US) is often part of the routine assessment of the clinically negative axilla in primary breast cancer, which determines the extent of axillary surgery to be performed. This study aims to ascertain the burden of disease in the axilla of patients with a normal clinical examination (cN0) but with US detected metastatic axillary lymph nodes. Materials and Methods: We retrospectively identified 345 female patients who underwent axillary lymph node dissection, following a positive lymph node biopsy, between January 2015 and August 2019.Eighty-nine of those had a positive biopsy prior to surgery. They were divided into two groups: Those with clinically palpable axillary disease preoperatively, cN1 (n = 41), and those with a normal clinical axillary examination, cN0 (n = 48). We assessed the number of positive axillary lymph nodes dissected in the two groups. Results: In the cN0 group the mean value of excised disease-positive axillary lymph nodes was 3.6, while in the cN1 group it was 8.0 (p<0.01). However, further analysis showed that 25 patients of the cN0 who had T1/T2 tumors had ≥3 positive lymph nodes. Conclusion: Our study suggests that the presence of clinically palpable axillary lymph nodes appears to be correlated to a higher number of positive lymph nodes. However, in cases of non-palpable sonographically positive lymph nodes there might still be significant axillary disease, even in T1 and T2 tumors. Therefore we still support the routine use of preoperative sonographic assessment of the axilla for early breast cancer.

Postural Orthostatic Tachycardia Syndrome (POTS): A critical assessment.

Although diagnostic criteria have been developed characterizing postural orthostatic tachycardia syndrome (POTS), no single set of criteria is universally accepted. Furthermore, there are gaps in the present criteria used to identify individuals who have this condition. The reproducibility of the physiological findings, the relationship of symptoms to physiological findings, the presence of symptoms alone without any physiological findings and the response to various interventions confuse rather than clarify this condition. As many disease entities can be confused with POTS, it becomes critical to identify what this syndrome is. What appears to be POTS may be an underlying condition that requires specific therapy. POTS is not simply orthostatic intolerance and symptoms or intermittent orthostatic tachycardia but the syndrome needs to be characterized over time and with reproducibility. Here we address critical issues regarding the pathophysiology and diagnosis of POTS in an attempt to arrive at a rational approach to categorize the syndrome with the hope that it may help both better identify individuals and better understand approaches to therapy.

Ambulatory electrocardiogram monitoring for syncope and collapse: a comparative assessment of clinical practice in UK and Germany.

Aims: Diagnostic ambulatory electrocardiogram (AECG) monitoring is widely used for evaluating syncope/collapse. In Europe, two sets of practice guidelines [National Institute for Health and Clinical Excellence (NICE) and European Society of Cardiology (ESC)] provide recommendations concerning optimal selection of AECG devices. However, whether practising physicians' select AECGs based on published guidelines is unclear. This study examined AECG use by Emergency Department (EDs) physicians and cardiologists in two European countries: Germany (D) and United Kingdom (UK). Methods and Results: A quantitative survey was undertaken in which 177 respondents participated (ED: UK 33, Germany 40; Cardiology: UK 54, Germany 50). The choice of AECG technology varied by specialty. Thus, among EDs, despite patients having daily symptoms, 20% (UK), 31% (D) of respondents chose an AECG other than Holter monitor. Conversely, when monitoring for infrequent events (

Ambulatory diagnostic ECG monitoring for syncope and collapse: An assessment of clinical practice in the United States.

INTRODUCTION: Diagnostic ambulatory electrocardiogram (AECG) monitoring is widely used for evaluating syncope and collapse, and practice guidelines provide recommendations regarding optimal AECG device selection. However, whether physicians utilize AECGs in accordance with the pertinent guidelines is unclear. This study assessed utilization of AECG monitoring systems for syncope and collapse diagnosis by physicians in the United States. METHODS AND RESULTS: A quantitative survey was undertaken of physicians comprising multiple specialties (emergency department, n = 35; primary care, n = 35; hospitalists, n = 30; neurologists, n = 30; nonimplanting, n = 34, and implanting-cardiologists, n = 35). Depending on specialty, respondents reported that neural-reflex and orthostatic causes accounted for 17-23%, cardiac causes for 12-20%, and "neurological causes" (specifically psychogenic pseudo-syncope/pseudo-seizures and acute cerebrovascular conditions) for 7-12% of their syncope/collapse cases. The choice of AECG technology varied by specialty. Thus, despite patients having daily symptoms, 25% of respondents chose an AECG technology other than a Holter-type monitor. Conversely, when monitoring for infrequent events (e.g., less than monthly), 12-18% indicated that they would choose a 24- to 48-hour Holter, 20-34% would choose either a conventional event recorder or a mobile cardiac telemetry system, and only 53-65% would select an insertable cardiac monitor. CONCLUSIONS: In evaluation of syncope/collapse, most U.S. clinicians across specialties use AECGs appropriately, but in a substantial minority there remains discordance between choice of AECG technology and guideline-based recommendations.

European Heart Rhythm Association Summit report 2014.

Across Europe, the role of the welfare state is constantly being questioned and even eroded. At the same time, funding sources for post-graduate medical education and training are under attack as regulators review the working relationships between physicians and industry. Both of these issues have profound consequences for cardiologists and their patients, and were, therefore, chosen as the themes of the European Heart Rhythm Association (EHRA) 2014 Spring Summit held at Heart House, Sophia Antipolis, 25-26 March 2014. The meeting noted that some of the changes are already affecting patient care standards and that this is exacerbated by a reduction in research and education programmes. The principle conclusion was that EHRA must find better means of engagement with the authorities across Europe to ensure that its views are considered and that ethical patient care is preserved. Participants were particularly alarmed by the example from Sweden in which future healthcare planning appears to exclude the views of physicians, although this is not yet the case in other countries. The demand for greater transparency in relationships between physicians and industry was also discussed. Although intended to eliminate corruption, concern was expressed that such moves would cause long-term damage to education and research, threatening the future of congresses, whose role in these areas appears underestimated by the authorities.

The Value of Tilt Testing and Autonomic Nervous System Assessment.

Tilt testing for the investigation of syncope was introduced in 1986. Since then, it has propagated worldwide as a routine test to determine the cause of transient loss of consciousness when that event has not been diagnosed by history, including that of a witness, physical examination, supine and erect blood pressures, and 12-lead electrocardiogram. Tilt testing allows reproduction of syncope with monitoring of physiologic parameters including electrocardiogram, beat-to-beat blood pressure, electroencephalogram, and middle cerebral artery blood-flow velocity. As a result, much has been learned about syncope.

Epidemiology and economic impact of cardiac syncope in western countries.

This article updates our current understanding of the epidemiology and economic impact of syncope in western countries. Unfortunately, both of these aspects of syncope are inadequately understood; in part the problem is due to the difficulty in public health data separating 'true syncope' from conditions that cause other forms of transient loss of consciousness. However, in certain respects, the epidemiology of syncope is becoming clearer. Similarly, we have come to understand that the economic impact of syncope is substantial and is much larger than is necessary, primarily because management, especially excessive hospitalization, often remains suboptimal.

When is a "free" registrar in clinic not free?

OBJECTIVE: To investigate whether using registrars (doctors undergoing higher specialist training, whose salary is reimbursed) rather than consultants in outpatient clinics saves money DESIGN: Development of a formula calculating the economic breakeven point and application to retrospective audit data from 273 outpatient consultations. SETTING: General cardiology outpatient clinic in a secondary and tertiary referral NHS hospital. Outcomes Difference in probability of a registrar and a consultant making a diagnostic decision that completes a clinical episode. Use of UK costings for consultant salaries and outpatient attendances to determine the economic breakeven point. RESULTS: The formula showed that if a registrar's episode completing probability is 12 percentage points lower than that of a consultant, then using a registrar costs the hospital more. Real life data showed that episode completion probabilities are 43 percentage points lower for registrars than for consultants (26% versus 69%, 95% CI 32% to 54%, P<0.0001). CONCLUSION: It is wrong to assume that external reimbursement of registrar salaries makes them a money saving option for staffing clinics. The apparent service role of a registrar can be a disservice.

Cardiac pacemaker lead extraction using conventional techniques:a single centre experience.

BACKGROUND: New methods of lead extraction using laser sheath devices are under evaluation but these techniques are not available in the majority of centres and have cost implications. Furthermore, in the absence of comparative randomised trials, registry experience with new devices must be judged against contemporary data using conventional methods. We report a single centre series of pacemaker lead extraction using conventional methods. STUDY POPULATION: Attempted extraction of 165 leads during 95 procedures in 80 patients. Leads had been in place (dwell time) for a mean of 76 months (range 0.2-248.4 months). Indications for lead extraction: infection (41.1%), skin erosion (9.5%), advisory leads (12.6%), faulty leads (12.6%), other (24.2%). Extraction techniques: traction and/or locking stylets and dilator sheaths (89.7%), Byrd workstation (6.1%) and open thoracotomy (4.8%). RESULTS: Complete removal was achieved for 143 leads (86.7%), partial removal in 12 leads (7.3%) and 10 (6.1%) could not be removed. A shorter lead dwell time was associated with extraction success in both univariate (p=0.0004) and multivariate analyses (p<0.0001). There was a trend for a higher rate of success in atrial rather than ventricular leads (93.2% v 80.9%, p=0.052). Active fixation, patient gender, age and indication for lead extraction had no bearing on outcome. COMPLICATIONS: There were no deaths. Major complications occurred in 3 patients (3.2%): pericardial tamponade (1), pulmonary embolus (1) and stroke (1). Significant bleeding (requiring blood transfusion) occurred in 11 procedures (12%). CONCLUSIONS: Cardiac lead extraction using conventional methods has a high success rate of 86.7%. Success was significantly related to a shorter lead dwell time. Further prospective randomised trials are needed to compare traditional techniques with laser extraction both in terms of clinical outcome and cost-effectiveness.