Julia C. Slovis

Background and Objective:: Herpes zoster (HZ), also known as shingles, is caused by reactivation of the latent varicella-zoster virus. HZ commonly manifests as a painful rash but may lead to more severe complications. An estimated 1 million cases of HZ occur annually in the United States, with adults aged ≥50 years, women, and individuals living with certain underlying conditions at increased risk compared with the general population. This narrative review aims to support the provision of comprehensive HZ-preventive care to female patients through consolidating evidence on risk factors for HZ and current prevention practices. Risk Factors for HZ:: Evidence shows that women are at an increased risk of developing HZ and related complications. A variety of risk factors may contribute to this increased risk among women. Some are specific to women, including certain cancers. Other risk factors include chronic conditions and immune diseases with increased prevalence among women, such as rheumatoid arthritis and systemic lupus erythematosus. HZ Prevention Practices:: Gaps in HZ prevention persist, including in recombinant zoster vaccine uptake and disparities in vaccination uptake by race and ethnicity. Various methods have been proposed that aim to address gaps in prevention, including approaching vaccination outside of the traditional primary care setting and considering the educational and resource needs of women’s health providers. Guidelines and resources from the Centers for Disease Control and Prevention and medical societies are among the tools available to primary care providers and specialists in the women’s health space, such as obstetricians/gynecologists and oncologists, to support the incorporation of HZ-preventive care into clinicians’ practices.

Despite improvements in survival after illnesses requiring extracorporeal life support, cerebral injury continues to hinder successful outcomes. Cerebral autoregulation (CA) is an innate protective mechanism that maintains constant cerebral blood flow in the face of varying systemic blood pressure. However, it is impaired in certain disease states and, potentially, following initiation of extracorporeal circulatory support. In this review, we first discuss patient-related factors pertaining to venovenous and venoarterial extracorporeal membrane oxygenation (ECMO) and their potential role in CA impairment. Next, we examine factors intrinsic to ECMO that may affect CA, such as cannulation, changes in pulsatility, the inflammatory and adaptive immune response, intracranial hemorrhage, and ischemic stroke, in addition to ECMO management factors, such as oxygenation, ventilation, flow rates, and blood pressure management. We highlight potential mechanisms that lead to disruption of CA in both pediatric and adult populations, the challenges of measuring CA in these patients, and potential associations with neurological outcome. Altogether, we discuss individualized CA monitoring as a potential target for improving neurological outcomes in extracorporeal life support.

Background: Pediatric neurological injury and disease is a critical public health issue due to increasing rates of survival from primary injuries (e.g., cardiac arrest, traumatic brain injury) and a lack of monitoring technologies and therapeutics for the treatment of secondary neurological injury. Translational, preclinical research facilitates the development of solutions to address this growing issue but is hindered by a lack of available data frameworks and standards for the management, processing, and analysis of multimodal data sets. Methods: Here, we present a generalizable data framework that was implemented for large animal research at the Children’s Hospital of Philadelphia to address this technological gap. The presented framework culminates in an interactive dashboard for exploratory analysis and filtered data set download. Results: Compared with existing clinical and preclinical data management solutions, the presented framework accommodates heterogeneous data types (single measure, repeated measures, time series, and imaging), integrates data sets across various experimental models, and facilitates dynamic visualization of integrated data sets. We present a use case of this framework for predictive model development for intra-arrest prediction of cardiopulmonary resuscitation outcome. Conclusions: The described preclinical data framework may serve as a template to aid in data management efforts in other translational research labs that generate heterogeneous data sets and require a dynamic platform that can easily evolve alongside their research.

Background Significant long-term neurologic disability occurs in survivors of pediatric cardiac arrest, primarily due to hypoxic-ischemic brain injury. Postresuscitation care focuses on preventing secondary injury and the pathophysiologic cascade that leads to neuronal cell death. These injury processes include reperfusion injury, perturbations in cerebral blood flow, disturbed oxygen metabolism, impaired autoregulation, cerebral edema, and hyperthermia. Postresuscitation care also focuses on early injury stratification to allow clinicians to identify patients who could benefit from neuroprotective interventions in clinical trials and enable targeted therapeutics. Methods In this review, we provide an overview of postcardiac arrest pathophysiology, explore the role of neuromonitoring in understanding postcardiac arrest cerebral physiology, and summarize the evidence supporting the use of neuromonitoring devices to guide pediatric postcardiac arrest care. We provide an in-depth review of the neuromonitoring modalities that measure cerebral perfusion, oxygenation, and function, as well as neuroimaging, serum biomarkers, and the implications of targeted temperature management. Results For each modality, we provide an in-depth review of its impact on treatment, its ability to stratify hypoxic-ischemic brain injury severity, and its role in neuroprognostication. Conclusion Potential therapeutic targets and future directions are discussed, with the hope that multimodality monitoring can shift postarrest care from a one-size-fits-all model to an individualized model that uses cerebrovascular physiology to reduce secondary brain injury, increase accuracy of neuroprognostication, and improve outcomes.

Background: The primary objective was to develop a porcine model of prolonged (30 or 60 minutes) pediatric cardiopulmonary resuscitation (CPR) followed by 22‐ to 24‐hour survival with extracorporeal life support, and secondarily to evaluate differences in neurologic injury. Methods and Results: Ten‐kilogram, 4‐week‐old female piglets were used. First, model development established the technique (n=8). Then, a pilot study was conducted (n=15). After 80% survival was achieved in the final 5 pilot animals, a proof‐of‐concept randomized study was completed (n=11). Shams (n=6) underwent anesthesia only. Severe neurological injury was determined by a composite score of mitochondrial function, neuropathology, and cerebral metabolism: scale of 0–6 (severe: >3). Among 15 piglets in the pilot study, overall survival was 10 (67%); of the final 5, overall survival was 4 (80%). Eleven piglets were then randomized to 60 (CPR60, n=5) or 30 minutes of CPR (CPR30, n=5); 1 animal was excluded from prerandomization for intra‐abdominal hemorrhage (10/11, 91% survival). Three of 5 animals in the CPR60 group had severe neurological injury scores versus 1 of 5 in the CPR30 group ( P =0.52). During ECMO, CPR60 animals had lower pH (CPR60: 7.4 [IQR 7.4–7.4] versus CPR30: 7.5 [IQR 7.4–7.5], P =0.022), higher lactate (CPR60: 6.8 [IQR 6.8–11] versus CPR30: 4.2 [IQR 4.1–4.3] mmol/L; P =0.012), and higher ICP (CPR60: 19.3 [IQR 11.7–29.3] versus CPR30: 7.9 [IQR 6.7–9.3] mm Hg; P =0.037). Both groups had greater mitochondrial injury than shams (CPR60: P P <0.001). CPR60 did not differ from CPR30 in mitochondrial respiration, neuropathology, or cerebral metabolism. Conclusions: A pediatric porcine model of extracorporeal cardiopulmonary resuscitation after 60 and 30 minutes of CPR consistently resulted in 24‐hour survival with more severe lactic acidosis in the 60‐minute cohort.

Background: While epinephrine is the mainstay of therapy during cardiopulmonary resuscitation, it is potentially detrimental to the cerebral vasculature and ineffective in certain populations. This study compares a rescue dose of vasopressin to a rescue dose of epinephrine after ineffective initial doses of epinephrine in diverse models of pediatric in-hospital cardiac arrest. 67 one- to three-month old female swine (10-30kg) in six experimental cohorts from one laboratory received hemodynamic-directed CPR, a resuscitation method where high quality chest compressions are provided and vasopressor administration is titrated to coronary perfusion pressure (CoPP) ³20 mmHg. Vasopressors are given when CoPP is Results: Increases in CoPP and cerebral blood flow (CBF) were greater with vasopressin rescue than epinephrine rescue (CoPP: +8.16 [4.35, 12.06] mmHg vs. +5.43 [1.56, 9.82] mmHg, p=0.022; CBF: +14.58 [-0.05, 38.12] vs. +0.00 [-0.77, 18.24] perfusion units (PFU), p=0.005). Twenty animals (30%) failed to achieve CoPP ³20 mmHg after two doses of epinephrine; 9/20 (45%) non-responders achieved CoPP ³20 mmHg after vasopressin. Among all animals, the increase in CBF was greater with vasopressin (+14.58 [-0.58, 38.12] vs. 0.00 [-0.77, 18.24] PFU, p=0.005).Conclusions: CoPP and CBF rose significantly more after rescue vasopressin than after rescue epinephrine. Importantly, CBF increased after vasopressin rescue, but not after epinephrine rescue. In the 30% that failed to meet CoPP of 20mmHg after two doses of epinephrine, 45% achieved target CoPP with a single rescue vasopressin dose.