Citations

Abstract Spontaneous coronary artery dissection is an unusual, but increasingly recognized, cause of acute coronary syndrome. It is a potentially fatal disorder that predominantly (>90% of cases) affects women, who are about 20 years younger (age 45–52 years) than those presenting with an acute coronary syndrome due to atherosclerotic coronary artery disease, and is the commonest cause of myocardial infarction associated with pregnancy. With the advent of improved coronary artery imaging modalities, including invasive coronary angiography, intravascular ultrasonography (IVUS), and optical coherence tomography (OCT), spontaneous coronary artery dissection is being increasingly diagnosed. It is typically due to a spontaneous bleed in the tunica media of an epicardial coronary artery, with or without an intimal tear, that results in an intramural haematoma; the latter, in turn causing a separation or dissection of the lamellae formed by the layers of smooth muscle cells of the tunica media, which can propagate longitudinally. Although coronary artery dissection can be due to atherosclerotic disease that may, in fact, present spontaneously, or to trauma, or guidewire-induced intimal injury, the understanding that the entity now known as spontaneous coronary artery dissection is an idiopathic disorder that is not associated with atherosclerosis or trauma, and is not iatrogenic, is one that has emerged only relatively recently (last 10–15 years). This raises the question, what is the provenance of spontaneous coronary artery dissection as it is now defined and understood? Here, this issue is addressed by a detailed consideration of the medical literature from 1800.

Abstract Objective: To define the incidence of donor-derived infection (DDI) in recipients of solid organ transplant (SOT) from donors with positive blood cultures and to assess the impact of shorter versus longer duration of targeted preemptive antibiotic therapy (PAT). Design: Retrospective, single-center, cohort study. Setting: Mayo Clinic Arizona. Patients: Recipients transplanted between 1/1/2019 and 7/1/2024 who received an organ from a donor with positive blood cultures. Methods: The primary outcome was incidence of DDI. Secondary outcomes included duration of PAT and incidence of donor blood culture contamination. Results: Among 199 SOT recipients from 167 unique donors with positive blood cultures, two recipients developed confirmed DDI within 30 days of SOT. Both cases were gram negative bacillary bacteremia not treated in donors and occurred immediately posttransplant prior to adequate recipient PAT. Six-month graft survival and recipient survival were 96.5% and 97.5% respectively. 139 recipients (69.8%) received PAT for a median duration of 7 days. There was no difference in rate of infections between recipients provided with ≤7 days versus 8–14 days of PAT for donor blood cultures; however, recipients who received 8–14 days had more Clostridioides difficile infections (CDIs) within 60 days of SOT (7.7% vs 1.5% ≤ 7 days, P = .040) and were more often discharged on intravenous antibiotics (32.3% vs 11.3%, P < .001). Conclusion: We observed a low rate of DDI following receipt of organs from donors with positive blood cultures. DDI occurred in cases without adequate donor/recipient treatment. Longer durations of targeted PAT resulted in more CDI and intravenous antibiotics on discharge.

Preeclampsia is a pregnancy-specific hypertensive disorder affecting up to 5% of pregnancies worldwide and is one of the leading causes of maternal and fetal morbidity and mortality globally. It is increasingly recognized that preeclampsia, from both clinical and pathophysiological standpoints, is a heterogeneous disease and that several mechanisms may lead to a clinical syndrome of hypertension, systemic disease, and proteinuria. Beyond its acute obstetric consequences, preeclampsia confers a significantly increased risk of future hypertension, cardiovascular disease, chronic kidney disease, and multimorbidity. Distinct underlying pathological mechanisms at the time of pregnancy may not only define clinical presentation and subtype of preeclampsia but may also make varying contributions to future cardiovascular and kidney disease. Emerging evidence implicates cellular senescence, a state of irreversible cell-cycle arrest accompanied by a proinflammatory senescence-associated secretory phenotype, as one of the mechanisms of preeclampsia that may serve as a mechanistic link between preeclampsia, accelerated cardiovascular aging, and future cardiovascular and kidney disease. This review synthesizes current evidence supporting the role of senescence in the pathophysiology of preeclampsia, demonstrated as accelerated epigenetic aging, increased senescence burden, and mesenchymal stem cell dysfunction, and discusses how persistence of senescence and propagation of senescent cells may contribute to vascular dysfunction decades after affected pregnancies. We further explore the translational implications of senolytic and senomorphic therapies as potential disease-modifying strategies in women with a history of preeclampsia.

ABSTRACT Background Quality of life and symptom burden of patients with myelofibrosis are well recognized and compounded in those with anemia; however, the effects of transfusion burden or anemia severity on quality of life have not been comprehensively characterized. This post hoc descriptive analysis explored the association between transfusion status or hemoglobin improvement and patient‐reported outcomes (PROs). Methods The analysis used pooled populations across treatment arms from 3 clinical trials (SIMPLIFY‐1, SIMPLIFY‐2, MOMENTUM); sample sizes for each PRO measure were dependent on the trials in which they were administered. Results At both baseline and week 24, transfusion independence was associated with umerically greater mean SF ‐36v2 and EORTC QLQ ‐ C30 scores than transfusion dependence; in the subgroup that was transfusion dependent at baseline, those who achieved transfusion independence at week 24 had greater PRO improvements than those who remained reliant on transfusions. Regardless of transfusion status, patients who achieved a hemoglobin improvement ≥ 1, ≥ 1.5, or ≥ 2 g/ dL from baseline also had clinically meaningful improvements in quality of life (assessed via mean EQ ‐ 5D ‐ 5L or SF ‐36v2 scores) and symptoms (assessed via PGIC or MPN ‐ SAF / MFSAF Total Symptom Score) at week 24 compared with those who did not. Conclusions Collectively, these results provide preliminary insights into the associations of transfusion status and anemia severity with quality of life in myelofibrosis; as current PRO measures do not directly evaluate the relationship between symptoms such as fatigue and anemia, development of new measures to more comprehensively capture the patient experience for those with anemia in myelofibrosis may be warranted. Trial Registration NCT01969838, NCT02101268, NCT04173494

We report a case of a 63-year-old male with metastatic hepatic PEComa harboring TSC2 and NF2 mutations who achieved a durable partial response to everolimus with only mild adverse effects. This case highlights the value of genomic profiling and the efficacy of mTOR inhibitors in hepatic PEComa management.

A 57-year-old woman with a ROS1-rearranged NSCLC patient demonstrated a Lazarus response to crizotinib but later developed recurrent pulmonary embolism (PE) with right ventricular (RV) failure. This incident highlights the potential crizotinib-related thrombotic risk and the need for appropriate monitoring of vascular complications, particularly in limited-option settings such as Thailand.

ABSTRACT Background Delirium predicts adverse outcomes in older emergency department (ED) patients, but many acutely ill patients without delirium have underlying cognitive impairment that goes unrecognized. Whether cognitive impairment screening improves risk prediction beyond delirium remains uncertain. We compared practical bedside screening strategies for delirium, cognitive impairment, or both for predicting 90‐day functional decline and mortality in older adults admitted from the ED. Methods A prospective cohort comprising patients aged ≥ 65 years admitted from the ED of a large hospital in São Paulo, Brazil. Trained professionals screened for delirium using the brief Confusion Assessment Method (bCAM) and for cognitive impairment using the 10‐point Cognitive Screener (10‐CS). Patients were classified as having normal cognition (bCAM negative, 10‐CS > 5), delirium (bCAM positive), or cognitive impairment without delirium (bCAM negative, 10‐CS ≤ 5). Blinded investigators assessed decline in basic activities of daily living (ADL) and mortality within 90 days of admission. Fine‐Gray models (death as a competing risk) and Cox models estimated associations with outcomes, adjusting for sociodemographic and clinical factors. Results Among 830 patients (mean age = 80 ± 9 years; women = 47%), 427 (51.5%) had normal cognition, 171 (20.6%) had delirium, and 232 (27.9%) had cognitive impairment without delirium. Among delirium‐negative patients with cognitive impairment, 52% had no documented dementia diagnosis or reported memory problems. Compared with normal cognition, cognitive impairment without delirium was associated with 90‐day functional ADL decline (sub‐HR = 1.60; 95% CI = 1.03–2.49) and mortality (HR = 2.31; 95% CI = 1.18–4.51), with risks similar to those observed in delirium. A staged strategy (bCAM first, then 10‐CS if bCAM negative) showed higher discrimination than delirium‐only or 10‐CS‐only screening. Conclusions Cognitive impairment without delirium is common, often unrecognized, and predicts 90‐day adverse outcomes in older patients admitted from the ED. A brief staged screening strategy integrating delirium assessment with cognitive impairment testing among delirium‐negative patients may enhance early detection of cognitive vulnerability and support care planning.

The brain is a highly recurrent, nonlinear network hypothesized to remain near the edge of chaos for optimal performance. Excitation and inhibition must be balanced precisely within every neuron to ensure a consistent level of dynamical stability and rich dynamics during transition to chaos. However, analysis of biologically realistic synaptic weight matrices suggests that sparsity and low-dimensional structure interact such that there is no known synaptic balancing rule that constrains the stability (i.e., eigenvalues) of the network while also preserving computationally useful, low-dimensional structure. Further, even if a network were well-balanced, external stimuli interact with the nonlinear activation functions to unbalance the network in real time. Therefore, the brain must utilize dynamic, rather than static, mechanisms to actively regulate its level of stability. We propose that two specific adaptation mechanisms, spike frequency adaptation (SFA) and short-term synaptic depression (STD), continuously modulate the effective connectivity, keeping the brain near the edge of chaos and reducing dynamical fluctuations caused by stimuli. This theoretical framework links intrinsic and synaptic negative feedback mechanisms to network-level dynamics. This offers an explanation of why data-driven modeling of human brain signals, an exciting and useful method in epilepsy and anesthesiology research, seems to require linear time-varying (LTV) models which are refit every half second: difficult to observe adaptation processes interact with nonlinearities to make connectivity effectively dynamic at the macroelectrode scale. We suggest that compromised adaptation may underlie neurological conditions characterized by altered excitability, and that targeted brain stimulation could be used to probe the regulatory action of adaptation.