Role of aortic valve replacement in moderate aortic stenosis: a 10-year outcomes study.

OBJECTIVE: Patients with moderate aortic stenosis (AS) exhibit high morbidity and mortality. Limited evidence exists on the role of aortic valve replacement (AVR) in this patient population. To investigate the benefit of AVR in moderate AS on survival and left ventricular function. METHODS: In a retrospective cohort study, patients with moderate AS between 2008 and 2016 were selected from the Cleveland Clinic echocardiography database and followed until 2018. Patients were classified as receiving AVR or managed medically (clinical surveillance). All-cause and cardiovascular mortality were assessed by survival analyses. Temporal haemodynamic and structural changes were assessed with longitudinal analyses using linear mixed effects models. RESULTS: We included 1421 patients (mean age, 75.3±5.4 years and 39.9% women) followed over a median duration of 6 years. Patients in the AVR group had lower risk of all-cause (adjusted HR (aHR)=0.51, 95% CI: 0.34 to 0.77; p=0.001) and cardiovascular mortality (aHR=0.50, 95% CI: 0.31 to 0.80; p=0.004) compared with those in the clinical surveillance group irrespective of sex, receipt of other open-heart surgeries and underlying malignancy. These findings were seen only in those with preserved left ventricular ejection fraction (LVEF) ≥50%. Further, patients in the AVR group had a significant trend towards an increase in LVEF and a decrease in right ventricular systolic pressure compared with those in the clinical surveillance group. CONCLUSIONS: In patients with moderate AS, AVR was associated with favourable clinical outcomes and left ventricular remodelling.

Gray Rainbows.

"You fooled me. I never dreamt," George said to the pasty gray face in the mirror. As a child, he had worked out complicated schemes of how the world must be constructed. This led to that, and that led to this. When this and that no longer fit together, he began to squint, and limit his view to the essential. At any moment, the sky might break open and rain body parts and end times. He never imagined that it would be colors that would give way.

Lost in Translation.

"Scleroderma," the rheumatologist said after examining my stiff swollen arms and legs. "Unfortunately, given your biomarkers, it's likely to get worse before it gets better, but you never know." She gave a quick rundown of what I might expect-rapidly progressive skin and joint tightening, GI symptoms, high likelihood of multi-organ involvement…. "Let's hope for the best." She paused, then asked if I had any questions.

Antiplatelet Therapy, Abdominal Aortic Aneurysm Progression, and Clinical Outcomes.

Importance: Preclinical studies suggest a potential role for aspirin in slowing abdominal aortic aneurysm (AAA) progression and preventing rupture. Evidence on the clinical benefit of aspirin in AAA from human studies is lacking. Objective: To investigate the association of aspirin use with aneurysm progression and long-term clinical outcomes in patients with AAA. Design, Setting, and Participants: This was a retrospective, single-center cohort study. Adult patients with at least 2 available vascular ultrasounds at the Cleveland Clinic were included, and patients with history of aneurysm repair, dissection, or rupture were excluded. All patients were followed up for 10 years. Data were analyzed from May 2022 to July 2023. Main Outcomes and Measures: Clinical outcomes were time-to-first occurrence of all-cause mortality, major bleeding, or composite of dissection, rupture, and repair. Multivariable-adjusted Cox proportional-hazard regression was used to estimate hazard ratios (HR) for all-cause mortality, and subhazard ratios competing-risk regression using Fine and Gray proportional subhazards regression was used for major bleeding and composite outcome. Aneurysm progression was assessed by comparing the mean annualized change of aneurysm diameter using multivariable-adjusted linear regression and comparing the odds of having rapid progression (annual diameter change >0.5 cm per year) using logistic regression. Results: A total of 3435 patients (mean [SD] age 73.7 [9.0] years; 2672 male patients [77.5%]; 120 Asian, Hispanic, American Indian, or Pacific Islander patients [3.4%]; 255 Black patients [7.4%]; 3060 White patients [89.0%]; and median [IQR] follow-up, 4.9 [2.5-7.5] years) were included in the final analyses, of which 2150 (63%) were verified to be taking aspirin by prescription. Patients taking aspirin had a slower mean (SD) annualized change in aneurysm diameter (2.8 [3.0] vs 3.8 [4.2] mm per year; P = .001) and lower odds of having rapid aneurysm progression compared with patients not taking aspirin (adjusted odds ratio, 0.64; 95% CI, 0.49-0.89; P = .002). Aspirin use was not associated with risk of all-cause mortality (adjusted HR [aHR], 0.92; 95% CI, 0.79-1.07; P = .32), nor was aspirin use associated with major bleeding (aHR, 0.88; 95% CI, 0.76-1.03; P = .12), or composite outcome (aHR, 1.16; 95% CI, 0.93-1.45; P = .09) at 10 years. Conclusions: In this retrospective study of a clinical cohort of 3435 patients with objectively measured changes in aortic aneurysm growth, aspirin use was significantly associated with slower progression of AAA with a favorable safety profile.

The 15-valent pneumococcal conjugate vaccine V114 induces cross-reactive antibodies against pneumococcal serotype 6C.

Pneumococcal serogroups consist of structurally related serotypes, and serotype-specific antibodies can cross-react against other serotypes within the same serogroup. Cross-reactivity of vaccine-induced serotype 6A antibodies, and, to a lesser extent, serotype 6B antibodies, to serotype 6C has been demonstrated following receipt of the 13-valent pneumococcal conjugate vaccine (PCV13), which contains serotypes 6A and 6B. V114 is a 15-valent PCV containing the 13 PCV13 serotypes plus two additional serotypes, 22F and 33F. This study assessed cross-reactivity to serotype 6C in recipients of V114 and PCV13 as well as specificity of opsonophagocytic activity (OPA) responses in serogroup 6. Following receipt of V114 or PCV13, the observed OPA geometric mean titers to serotypes 6A, 6B, and 6C were comparable across both vaccination groups (post-single dose in adults ≥50 years of age [n = 250] and from pre- to post-dose 4 in pediatric participants 12-15 months of age [n = 150]). Based on OPA inhibition studies, V114 induced cross-reactive antibodies to serotype 6C in adult and pediatric populations that were specific and comparable to those induced by PCV13. Based on experience with PCV13, V114 may also provide comparable protection against pneumococcal disease caused by serotype 6C; however, this will have to be evaluated in real-world studies.

Double Talk.

In this series of short essays, stories, poems, and personal observations, Robert A. Burton, neurologist and writer, uses both fiction and nonfiction to explore many paradoxes and contradictions inherent in scientific inquiry. A novelist as well as author of On Being Certain and A Skeptic's Guide to the Mind, Burton brings story to science and science to story.

Characteristics and outcomes of adverse events after COVID-19 vaccination.

OBJECTIVES: BNT-162b2, mRNA-1273, and Ad26.COV2.S vaccines data regarding adverse events (AEs) are scarce. In this report, we aimed to describe fatal and non-fatal possible AEs after COVID-19 vaccine administration. METHODS: An observational multicenter study investigating the causes of emergency department visits and hospital admissions within 10 days of COVID-19 vaccination. Patients who received first or second doses of COVID-19 vaccines and presented to the emergency department (ED), as well as those admitted to the hospitals or intensive care units (ICUs) were included. Causes of ED, hospital, and ICU admissions and discharges were collected based on the International Classification of Diseases, Tenth Revision (ICD-10) coding system. RESULTS: Between December 2020 and March 2021, 1842 patients visited the ED within 10 days of COVID-19 vaccine administration. The mean age was 70.3 years. Overall, 1221 patients presented after the first dose of the vaccine and 653 after the second dose. Trauma (14.9%), hypertensive emergency/urgency (7.8%), generalized pain and arthralgia (5.7%), and chest pain (4.4%) were the most common causes of presentation to the ED. Of all ED presentations, mortality rate was at 2.2% (41 patients) with a median follow-up time of 68.0 days, versus 2.6% in unvaccinated ED patients. Postvaccination acute hypoxemic respiratory failure (46.3%), septic shock (24.4%), and cardiogenic shock (12.2%) were the most common causes of death. CONCLUSION: Although reported AEs are not necessarily caused by the vaccination, this study provides further information about possible AEs after COVID-19 immunization, especially those requiring hospital admission. This study also supports prior data that serious AEs post vaccination are much lower than primary COVID-19 infections. Further studies are needed to investigate causalities between vaccines and reported AEs across all age groups.

Effect of aspirin on short-term outcomes in hospitalized patients with COVID-19.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is an ongoing viral pandemic marked by increased risk of thrombotic events. However, the role of platelets in the elevated observed thrombotic risk in COVID-19 and utility of antiplatelet agents in attenuating thrombosis is unknown. We aimed to determine if the antiplatelet effect of aspirin may mitigate risk of myocardial infarction, cerebrovascular accident, and venous thromboembolism in COVID-19. We evaluated 22,072 symptomatic patients tested for COVID-19. Propensity-matched analyses were performed to determine if treatment with aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) affected thrombotic outcomes in COVID-19. Neither aspirin nor NSAIDs affected mortality in COVID-19. Thus, aspirin does not appear to prevent thrombosis and death in COVID-19. The mechanisms of thrombosis in COVID-19, therefore, appear distinct and the role of platelets as direct mediators of SARS-CoV-2-mediated thrombosis warrants further investigation.

Does inpatient hyperglycemia predict a worse outcome in COVID-19 intensive care unit patients?

BACKGROUND: We undertook this study to evaluate the association between hyperglycemia and outcomes in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). METHODS: We conducted a multicenter retrospective study involving all adults with COVID-19 admitted to the ICU between March and May 2020. Patients were divided into normoglycemic (average blood glucose <140 mg/dL) and hyperglycemic (average blood glucose ≥140 mg/dL) groups. Outcomes such as mortality, need and duration of mechanical ventilation, and length of hospital and ICU stays were measured. RESULTS: Among 495 patients, 58.4% were male with a median age of 68 years (interquartile range [IQR]: 58.00-77.00), and baseline average blood glucose was 186.6 (SD ± 130.8). Preexisting diabetes was present in 35.8% of the studied cohort. Combined ICU and hospital mortality rates were 23.8%; mortality and mechanical ventilation rates were significantly higher in the hyperglycemic group with 31.4% vs 16.6% (P = .001) and 50.0% vs 37.2% (P = .004), respectively. Age above 60 years (hazard ratio [HR] 3.21; 95% CI 1.78, 5.78) and hyperglycemia (HR 1.79; 95% CI 1.14, 2.82) were the only significant predictors of in-hospital mortality. Increased risk for hyperglycemia was found in patients with steroid use (odds ratio [OR] 1.521; 95% CI 1.054, 2.194), triglycerides ≥150 mg/dL (OR 1.62; 95% CI 1.109, 2.379), and African American race (OR 0.79; 95% CI 0.65, 0.95). CONCLUSIONS: Hyperglycemia in patients with COVID-19 is significantly associated with a prolonged ICU length of stay, higher need of mechanical ventilation, and increased risk of mortality in the critical care setting. Tighter blood glucose control (≤140 mg/dL) might improve outcomes in COVID-19 critically ill patients; evidence from ongoing clinical trials is needed.

Plague Journal.

Given a strong family history of early heart attacks, the future has always been an iffy proposition. Miraculously, I have bypassed the early off-ramps and find myself approaching 80, stents in place, considering the very real but previously unimaginable possibility of still more. But what kind of more? With dopamine on the wane and no longer supercharged by the push and shove of unbridled ambition and pride, bigger and grander are out of the question. Tired clichés poke through the widening cracks in my thinking to become uninvited bulletins of compromise and consolation. Be grateful. Relax, reminisce, enjoy sunsets, learn the backyard birds' names, maybe even sing to them, and count blessings.

When Will the News be Bad Enough?

The cardiac rehab nurse calls out each of our group's blood pressures and pulse rates. It is my first posthospitalization class and I am relieved to be in the middle of the pack. Although fully aware that numbers are not fate, I cannot help wondering if the worst performers will fully satisfy the dark needs of heart disease statistics. I presume that others are making similar calculations, yet wince at the ugly direction of my mind. Maybe it is not necessary to do better than another; if we take our meds, eat wisely, and exercise to the max, it is possible that our entire group will do well.

Assignment of opsonic values to pneumococcal reference serum 007sp and a second pneumococcal OPA calibration serum panel (Ewha QC sera panel B) for 11 serotypes.

Pneumococcal conjugate vaccines (PCVs) have been effective in reducing the disease burden caused by Streptococcus pneumoniae. The first licensed PCV (PCV7) was composed of capsular polysaccharides from seven serotypes. This was followed by PCV10, then PCV13, and currently there are a number of higher valency vaccines in development. As part of licensure, new vaccine iterations require assessment of immunogenicity. Since some antibodies can be non-functional, measuring functional antibodies is desirable. To meet this need, opsonophagocytic assays (OPAs) have been developed. Previous studies have shown there can be significant variations in OPA results from different laboratories. We have previously shown that standardizing OPA data using reference serum 007sp can decrease this variation. To extend this approach to additional serotypes, a panel of sera was tested by five laboratories using a multiplexed OPA for serotypes 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20B, 22F, and 33F. Each sample was tested in five runs with 007sp tested three times in each run. Results were analyzed using a mixed effects ANOVA model. Standardization of the results significantly decreased the inter-laboratory variation for some serotypes. For serotypes 2, 8, and 11A, the variability was reduced by 40%, 45%, and 40%, respectively. For serotypes 12F, 17F, and 20B, the reductions were more modest (14%, 19%, and 24%, respectively). Standardization had little effect for the remaining serotypes. In many cases, the impact of normalization was blunted by the results from five sera that were collected after an extended post-vaccination interval. We have previously reported consensus values for 007sp for 13 serotypes, as well as the creation of a calibration serum panel ("Ewha Panel A"). Here, we report consensus values for 11 additional serotypes for 007sp and the creation of a second serum panel ("Ewha Panel B"). These consensus values will facilitate the development of next-generation PCVs.

Clinical characteristics and outcomes of critically Ill patients with COVID-19 in Northeast Ohio: low mortality and length of stay.

BACKGROUND: Published coronavirus disease 2019 (COVID-19) reports suggest higher mortality with increasing age and comorbidities. Our study describes the clinical characteristics and outcomes for all intensive care unit (ICU) patients admitted across the Cleveland Clinic enterprise, a 10-hospital health care system in Northeast Ohio, serving more than 2.7 million people. METHODS: We analyzed the quality data registry for clinical characteristics and outcomes of all COVID-19-confirmed ICU admissions. Differences in outcomes from other health care systems and published cohorts from other parts of the world were delineated. RESULTS: Across our health care system, 495 COVID-19 patients were admitted from March 15 to June 1, 2020. Mean patient age was 67.3 years, 206 (41.6%) were females, and 289 (58.4%) were males. Mean Acute Physiology Score was 45.3, and mean Acute Physiology and Chronic Health Evaluation III score was 60.5. In total, 215 patients (43.3%) were intubated for a mean duration of 9.2 days. Mean ICU and hospital length of stay were 7.4 and 13.9 days, respectively, while mean ICU and hospital mortality rates were 18.4% and 23.8%. CONCLUSIONS: Our health care system cohort is the fourth largest to be reported. Lower ICU and hospital mortality and length of stay were seen compared to most other published reports. Better preparedness and state-level control of the surge in COVID-19 infections are likely the reasons for these better outcomes. Future research is needed to further delineate differences in mortality and length of stay across health care systems and over time.