Neutralizing antibodies against the SARS-CoV-2 Delta and Omicron variants following heterologous CoronaVac plus BNT162b2 booster vaccination.

The recent emergence of the SARS-CoV-2 Omicron variant is raising concerns because of its increased transmissibility and its numerous spike mutations, which have the potential to evade neutralizing antibodies elicited by COVID-19 vaccines. Here we evaluated the effects of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of participants who had received a two-dose regimen of CoronaVac, an inactivated vaccine used globally. We found that a heterologous CoronaVac prime vaccination of two doses followed by a BNT162b2 booster induces elevated virus-specific antibody levels and potent neutralization activity against the ancestral virus and the Delta variant, resembling the titers obtained after two doses of mRNA vaccines. Although neutralization of Omicron was undetectable in participants who had received a two-dose regimen of CoronaVac, the BNT162b2 booster resulted in a 1.4-fold increase in neutralization activity against Omicron compared with the two-dose mRNA vaccine. Despite this increase, neutralizing antibody titers were reduced by 7.1-fold and 3.6-fold for Omicron compared with the ancestral strain and the Delta variant, respectively. These findings have immediate implications for multiple countries that previously used a CoronaVac regimen and reinforce the idea that the Omicron variant is associated with immune escape from vaccines or infection-induced immunity, highlighting the global need for vaccine boosters to combat the impact of emerging variants.

Dramatic resolution of disseminated pyoderma gangrenosum associated with monoclonal gammopathy after therapy with bortezomib and dexamethasone.

Pyoderma gangrenosum (PG) is an uncommon inflammatory and ulcerative skin disorder, which is commonly associated with systemic conditions such as inflammatory bowel disease, arthritis and haematological malignancies. It is widely stated that control of the underlying diseases may lead to resolution of PG. However, standard of care dictates that patients suffering with monoclonal gammopathy of undetermined significance or smouldering multiple myeloma (MM) should not receive therapy unless they progress to symptomatic MM. Here, we report a woman in her 40s with a disseminated corticodependent PG, resistant to any treatment attempted, including anti-tumoral necrosis factor (TNF) therapy in which bortezomib-dexamethasone regimen results in dramatic healing of all lesions in only a month. This case supports the belief that treatment of the underlying monoclonal gammopathy could be necessary when PG presents as an aggressive, non-responding skin disease.

Comparison of pharmacological treatment alone versus treatment combined with cardiac resynchronization therapy in patients over 75 years.

BACKGROUND: The role of cardiac resynchronization therapy (CRT) in patients aged ≥75 years is not well established. METHODS: We identified 607 patients aged ≥75 years with left ventricular ejection fraction (LVEF) of ≤35 %, of whom 78 met the guidelines for indication of CRT. Based on the decision of the patients or attending cardiologists, 34 patients received a CRT defibrillator (CRT-D). RESULTS: The age of patients with a CRT indication was 80 ± 4 years, and 73 % were males. As compared with patients on medical therapy, CRT-D patients were younger (79 ± 3 vs. 83 ± 4, P < 0.001), had lower LVEF (23 ± 7 vs. 27 ± 7 %, P = 0.008) and higher rate of decompensated heart failure episodes (77 vs. 55 %, P = 0.04), were more frequently New York Heart Association (NYHA) class III-IV (53 vs. 25 %, P = 0.01), and were more likely to be on beta-blockers (88 vs. 66 %, P = 0.023), anticoagulants (61 vs. 32 % P = 0.02), and anti-aldosterone drugs (82 vs. 50 %, P = 0.003). After a median follow-up of 26 months, seven patients in the CRT-D group (21 %) and 20 non-CRT patients (46 %) died (hazard ratio (HR) 0.16 [95 % confidence interval (CI) 0.06-0.46]). The end point of mortality or hospitalization was not reduced because of a similar rate of hospitalizations for heart failure of CRT-D patients. Four CRT-D patients (12 %) had received appropriate device therapy, and one had been inappropriately discharged. During follow-up, 44 % of CRT-D patients improved their LVEF by >40 %. CONCLUSION: CRT-D is potentially of benefit in terms of mortality in our population; this effect persists after correction for use of beta-blockers. In patients ≥75 years, CRT indications should be similar to those accepted for younger subjects.

Silent ischaemic brain lesions related to atrial high rate episodes in patients with cardiac implantable electronic devices.

AIMS: Monitoring capabilities of cardiac implantable electronic devices have revealed that a large proportion of patients present silent atrial fibrillation (AF) detected as atrial high rate episodes (AHREs). Atrial high rate episodes >5 min have been linked to increased risk of clinical stroke, but a high proportion of ischaemic brain lesions (IBLs) could be subclinical. METHODS AND RESULTS: We prospectively analysed the incidence of AHRE > 5 min in 109 patients (56% men, aged 74 ± 9 years) and the presence of silent IBL on computed tomography (CT) scan. Mean CHADS2 and CHA2DS2VASc scores were 2.3 ± 1.3 and 3.9 ± 1.6, respectively. Seventy-five patients (69%) had no history of AF or stroke/transient ischaemic attack (TIA). After 12 months, 28 patients (25.7%) showed at least one AHRE. Patients with AHREs were more likely to have history of AF. Computed tomography scan showed silent IBL in 28 (25.7%). The presence of IBL was significantly related to older patients, prior history of AF or stroke/TIA, higher CHADS2 or CHA2DS2VASc scores, and the presence of AHRE. Multivariable analysis demonstrated that AHRE was an independent predictor for silent IBL in overall population [hazard ratio (HR) 3.05 (1.06-8.81; P < 0.05)] but also in patients without prior history of AF or stroke/TIA [HR 9.76 (1.76-54.07; P < 0.05)]. CONCLUSION: Cardiac implantable electronic devices can accurately detect AF as AHRE. Atrial high rate episodes were associated to a higher incidence of silent IBL on CT scan. Atrial high rate episodes represent a kind of silent AF where management recommendations are lacking despite the fact that a higher embolic risk is present.

Limitations of the AutoCapture™ Pacing System in patients with cardiac stimulation devices.

AIMS: AutoCapture (St Jude Medical) is a technological development that confirms ventricular capture analysing the evoked response after a pacing impulse and adjusts the energy output to changes in the stimulation threshold. Although this algorithm is aimed to assure capture minimizing energy consumption, some patients might not benefit from it. The objective of this study is to identify them. METHODS AND RESULTS: Long-term AutoCapture efficiency was assessed using the data recorded in the programmer reports of patients undergoing scheduled pacemaker check-ups during 2012 in our institution. We have evaluated 160 consecutive patients (58% men) aged 78 ± 9 years. Pacemaker stimulation mode was DDD in 116 patients (72.5%) and VVI in 44 patients (27.5%). During the scheduled visits for pacemaker check-up, 73 patients (45.6%) showed abnormalities in the long-term AutoCapture function report (high variability in the AutoCapture stimulation threshold and/or out-of-range values). After multivariate analysis, abnormal AutoCapture pattern was associated to the presence of atrial fibrillation [odds ratio (OR) 3.96 (1.59-9.82; P < 0.05)]; and a ventricular pacing ≤25% of the time [OR 4.80 (2.09-11.05; P < 0.05)]. AutoCapture abnormalities were also described in three (1.8%) patients with very low stimulation threshold. CONCLUSION: Although AutoCapture algorithm has shown both efficacy and safety, our findings suggest that some patients with atrial fibrillation or those requiring ventricular pacing ≤25% of the time may not benefit from it. Activation of the algorithm should be individualized according to the patient's characteristics and long-term AutoCapture pattern checked in the routine follow-up.

[Asymptomatic severe aortic stenosis: a reopened debate]. / Estenosis aórtica grave asintomática: un debate todavía abierto.

Aortic stenosis is a complex disease. About 2-7% of the population over 65 years of age is affected by its degenerative form. In patients with severe aortic stenosis presenting with symptoms or left ventricle ejection fraction (LVEF)<.50, aortic valve replacement is indicated. Management and timing of surgery in asymptomatic patients with preserved LVEF is still a matter of debate. Recent published data show that about one third of these patients present with low left ventricle stroke volume, which may affect survival. For this reason, and considering that aortic valve replacement is in most cases a low risk procedure, early surgery in this subgroup is a strategy that deserves to be taken into account. In this review we report on these recent findings, which allow understanding why patients with asymptomatic severe aortic stenosis should not be considered and treated as a homogenous population.