Association between HMGB1 and asthma: a literature review.

BACKGROUND: Recently, some studies demonstrated that HMGB1, as proinflammatory mediator belonging to the alarmin family, has a key role in different acute and chronic immune disorders. Asthma is a complex disease characterised by recurrent and reversible airflow obstruction associated to airway hyper-responsiveness and airway inflammation. OBJECTIVE: This literature review aims to analyse advances on HMGB1 role, employment and potential diagnostic application in asthma. METHODS: We reviewed experimental studies that investigated the pathogenetic role of HMGB in bronchial airway hyper-responsiveness, inflammation and the correlation between HMGB1 level and asthma. RESULTS: A total of 19 studies assessing the association between HMGB1 and asthma were identified. CONCLUSIONS: What emerged from this literature review was the confirmation of HMGB-1 involvement in diseases characterised by chronic inflammation, especially in pulmonary pathologies. Findings reported suggest a potential role of the alarmin in being a stadiation method and a marker of therapeutic efficacy; finally, inhibiting HMGB1 in humans in order to contrast inflammation should be the aim for future further studies.

Spike on T wave! What went wrong?

An 80-year-old male, who previously received a dual chamber pacemaker, was referred to our ambulatory for dizziness and fatigue. The ECG obtained showed sinus rhythm, highly variable atrioventricular (AV) interval and alternation between spontaneous and paced ventricular complexes. A spike on the ascending part of the T wave was observed, suggesting ventricular undersensing. However, telemetry-supported pacemaker control showed inconstant atrial undersensing.

SafeR and escape junctional rhythm: A singular trigger for pacemaker-mediated tachycardia.

A 70-year-old man, who previously received a dual chamber pacemaker for paroxysmal AV block (Sorin Symphony DR 2550), was noted on telemetry to have multiple episodes of rapid ventricular pacing at approximately 120bpm. Evaluation of the telemetry strips revealed that all of the rapid ventricular pacing episodes were initiated by brief runs of escape junctional rhythm. Programmed bradycardia parameters were AAI SafeR with lower rate limit of 50bpm.

Delivering Simulation Activities Safely: What if We Hurt Ourselves?

SUMMARY STATEMENT: Although a focus on the learner rightly remains in any teaching environment, the psychological safety of everyone involved in the conduct of experiential learning and critical academic scholarship is important. Education literature suggests that faculty are just as prone to psychological harm as their learners. This commentary describes adverse experiences from a simulation-based education event that took place at an Australasian interprofessional and cross-domain simulation workshop. Event facilitators explored the notion of the "safe container" but, in the process, were themselves exposed to psychological injury. We summarize an ostensibly complex simulation activity with unintended sequelae, the ethical concerns surrounding the faculty care, and from lessons learned, present an extended conceptualization of the safe container including broader parameters around the preparation of all involved in the delivery of simulation-based activities. Our goals in sharing this case is to encourage the community to become more vigilant regarding the unintended consequences of our simulation activities and to encourage open reporting and discussion of such incidents for the betterment of the field.

Effects of Carfilzomib Therapy on Left Ventricular Function in Multiple Myeloma Patients.

Background: Carfilzomib improves the prognosis of multiple myeloma (MM) patients but significantly increases cardiovascular toxicity. The timing and effect of Carfilzomib therapy on the left ventricular function is still under investigation. We sought to assess the echocardiographic systo-diastolic changes, including global longitudinal strain (GLS), in patients treated with Carfilzomib and to identify predictors of increased risk of cardiovascular adverse events (CVAEs) during therapy. Methods: Eighty-eight patients with MM performed a baseline cardiovascular evaluation comprehensive of transthoracic echocardiogram (TTE) before the start of Carfilzomib therapy and after 6 months. All patients were clinically followed up to early identify the occurrence of CVAEs during the whole therapy duration. Results: After Carfilzomib treatment, mean GLS slightly decreased (-22.2% ± 2.6 vs. -21.3% ± 2.5; p < 0.001). Fifty-eight percent of patients experienced CVAEs during therapy: 71% of them had uncontrolled hypertension, and 29% had major CVAEs or CV events not related to arterial hypertension. GLS variation during therapy was not related to an increased risk of CVAEs; however, patients with baseline GLS ≥ -21% and/or left ventricular ejection fraction (LVEF) ≤ 60% had a greater risk of major CVAEs (OR = 6.2, p = 0.004; OR = 3.7, p = 0.04, respectively). Carfilzomib led to a higher risk of diastolic dysfunction (5.6 vs. 13.4%, p = 0.04) and to a rise in E/e' ratio (8.9 ± 2.7 vs. 9.7 ± 3.7; p = 0.006). Conclusion: Carfilzomib leads to early LV function impairment early demonstrated by GLS changes and diastolic dysfunction. Baseline echocardiographic parameters, especially GLS and LVEF, might improve cardiovascular risk stratification before treatment.

Cardiovascular Organ Damage and Blood Pressure Levels Predict Adverse Events in Multiple Myeloma Patients Undergoing Carfilzomib Therapy.

Carfilzomib is a second-generation proteasome inhibitor approved for the treatment of multiple myeloma (MM). It seems to determine cardiovascular toxicity, primarily arterial hypertension. No predictive factors for cardiovascular adverse events (CVAEs) are known in patients affected by multiple myeloma treated with carfilzomib. We evaluated the role of cardiovascular organ damage parameters to predict CVAEs in MM patients taking carfilzomib. Seventy patients affected by MM were prospectively enrolled. A comprehensive cardiovascular evaluation was performed before carfilzomib therapy; they underwent a transthoracic echocardiogram and the assessment of carotid-femoral pulse wave velocity. All the patients were followed up (FU) to determine the incidence of CVAEs. The mean age was 60.3 ± 8.2, and 51% were male. The median FU was 9.3 (4.3; 20.4) months. A proportion of 33% experienced CVAEs, 91% of them had uncontrolled hypertension, 4.5% acute coronary syndrome, and 4.5% cardiac arrhythmias. Subjects with CVAEs after carfilzomib treatment had significantly higher blood pressure values, left ventricular mass (98 ± 23 vs. 85 ± 17 g/m2, p = 0.01), and pulse wave velocity (8.5 ± 1.7 vs. 7.5 ± 1.6 m/s, p = 0.02) at baseline evaluation compared to the others. Furthermore, baseline uncontrolled blood pressure, left ventricular hypertrophy, and pulse wave velocity ≥ 9 m/s were able to identify patients at higher risk of developing CVAEs during FU. These preliminary findings indicate that blood pressure control, left ventricular mass, and pulse wave velocity may predict CVAEs in MM patients treated with carfilzomib.