Recent Publications by CFE Educators

BACKGROUND

Prognostic markers for meningioma are needed to risk-stratify patients and guide postoperative surveillance and adjuvant therapy.

OBJECTIVE

To identify a prognostic gene signature for meningioma recurrence and mortality after resection using targeted gene-expression analysis.

METHODS

Targeted gene-expression analysis was used to interrogate a discovery cohort of 96 meningiomas and an independent validation cohort of 56 meningiomas with comprehensive clinical follow-up data from separate institutions. Bioinformatic analysis was used to identify prognostic genes and generate a gene-signature risk score between 0 and 1 for local recurrence.

RESULTS

We identified a 36-gene signature of meningioma recurrence after resection that achieved an area under the curve of 0.86 in identifying tumors at risk for adverse clinical outcomes. The gene-signature risk score compared favorably to World Health Organization (WHO) grade in stratifying cases by local freedom from recurrence (LFFR, P  .001 vs .09, log-rank test), shorter time to failure (TTF, F-test, P  .0001), and overall survival (OS, P  .0001 vs .07) and was independently associated with worse LFFR (relative risk [RR] 1.56, 95% CI 1.30-1.90) and OS (RR 1.32, 95% CI 1.07-1.64), after adjusting for clinical covariates. When tested on an independent validation cohort, the gene-signature risk score remained associated with shorter TTF (F-test, P = .002), compared favorably to WHO grade in stratifying cases by OS (P = .003 vs P = .10), and was significantly associated with worse OS (RR 1.86, 95% CI 1.19-2.88) on multivariate analysis.

CONCLUSION

The prognostic meningioma gene-expression signature and risk score presented may be useful for identifying patients at risk for recurrence.

OBJECTIVE

To review the virology, immunology, epidemiology, clinical manifestations, and treatment of the following 3 major zoonotic coronavirus epidemics: severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19).

DATA SOURCES

Published literature obtained through PubMed database searches and reports from national and international public health agencies.

STUDY SELECTIONS

Studies relevant to the basic science, epidemiology, clinical characteristics, and treatment of SARS, MERS, and COVID-19, with a focus on patients with asthma, allergy, and primary immunodeficiency.

RESULTS

Although SARS and MERS each caused less than a thousand deaths, COVID-19 has caused a worldwide pandemic with nearly 1 million deaths. Diagnosing COVID-19 relies on nucleic acid amplification tests, and infection has broad clinical manifestations that can affect almost every organ system. Asthma and atopy do not seem to predispose patients to COVID-19 infection, but their effects on COVID-19 clinical outcomes remain mixed and inconclusive. It is recommended that effective therapies, including inhaled corticosteroids and biologic therapy, be continued to maintain disease control. There are no reports of COVID-19 among patients with primary innate and T-cell deficiencies. The presentation of COVID-19 among patients with primary antibody deficiencies is variable, with some experiencing mild clinical courses, whereas others experiencing a fatal disease. The landscape of treatment for COVID-19 is rapidly evolving, with both antivirals and immunomodulators demonstrating efficacy.

CONCLUSION

Further data are needed to better understand the role of asthma, allergy, and primary immunodeficiency on COVID-19 infection and outcomes.

BACKGROUND/OBJECTIVES

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause kidney injury, especially in older adults. However, previously reported associations between NSAID use and kidney health outcomes are inconsistent and limited by reliance on serum creatinine-based GFR estimates. This analysis investigated the association of NSAID use with kidney damage in older adults using multiple kidney health measures.

DESIGN

Cross-sectional and longitudinal analyses.

SETTING

Multicenter, community-based cohort.

PARTICIPANTS

Two thousand nine hundred and ninty nine older adults in the Health ABC Study. A subcohort (n = 500) was randomly selected for additional biomarker measurements.

EXPOSURE

Prescription and over-the-counter NSAID use ascertained by self-report.

MEASUREMENTS

Baseline estimated glomerular filtration rate (eGFR) by cystatin C (cysC), urine albumin-to-creatinine ratio (ACR), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) were measured in 2,999 participants; alpha-1 microglobulin (α1m), neutrophil gelatinase-associated lipocalin (NGAL), propeptide type III procollagen (PIIINP), and uromodulin (UMOD) were measured in 500 participants. GFR was estimated three times over 10 years and expressed as percent change per year.

RESULTS

Participants had a mean age of 74 years, 51% were female, and 41% African-American. No eGFR differences were detected between NSAID users (n = 655) and non-users (n = 2,344) at baseline (72 ml/min/1.73 m in both groups). Compared to non-users, NSAID users had lower adjusted odds of having ACR greater than 30 mg/g (0.67; 95% confidence interval (CI) = 0.51-0.89) and lower mean urine IL-18 concentration at baseline (-11%; 95% CI = -4% to -18%), but similar mean KIM-1 (5%; 95% CI = -5% to 14%). No significant differences in baseline concentrations of the remaining urine biomarkers were detected. NSAID users and non-users did not differ significantly in the rate of eGFR decline (-2.2% vs -2.3% per year).

CONCLUSION

Self-reported NSAID use was not associated with kidney dysfunction or injury based on multiple measures, raising the possibility of NSAID use without kidney harm in ambulatory older adults. More research is needed to define safe patterns of NSAID consumption.

OBJECTIVE

To study the pregnancy outcomes, including obstetric complications and fetal outcomes, in pregnant women with epilepsy (WWE) treated with direct brain-responsive neurostimulation (RNS System).

METHODS

Retrospective review of obstetric outcomes and fetal outcomes in WWE treated with the RNS System at nine comprehensive epilepsy centers in the United States from 2014-2020. In addition, changes in seizure frequency, anti-seizure medications, and RNS System setting adjustments during pregnancy were investigated.

RESULTS

A total of 10 subjects and 14 pregnancies were identified. The mean age at conception was 30.6 ± 4.3 years old. The mean age at implantation was 29.8 ± 4.4 years old. The mean stimulation charge densities ranged from 1.0 to 3.0 μC/cm during pregnancy. Obstetric complications included recurrent miscarriage (1 patient), cesarean section (3 patients) due to preeclampsia, non-reassuring fetal heart rate tracing or prolonged labor, preterm birth (1 patient), and preeclampsia (1 patient). No still birth, gestational hypertension, gestational diabetes, eclampsia, or maternal mortality were observed. No RNS System-exposed pregnancies had major congenital malformations. One offspring had a minor congenital anomaly of cryptorchidism in a pregnancy complicated with risk factors of advanced maternal age and bicornuate uterus.

SIGNIFICANCE

The present study is the first report of RNS System-exposed pregnancies in WWE to date. No major congenital malformations were identified. All of the obstetric complications were within the expected range of those in WWE based on previously published data. The sample size of our study is small, so accumulation of additional cases will further help depict the safety profile of treatment with the RNS System during pregnancy.

PURPOSE

The reported conversion rates for minimally invasive distal pancreatectomy (MIDP) range widely from 2 to 38%. The identification of risk factors for conversion may help surgeons during preoperative planning and patient counseling. Moreover, the impact of conversion on outcomes of MIDP is unknown.

METHODS

A systematic review was conducted as part of the 2019 Miami International Evidence-Based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR). The PubMed, Cochrane, and Embase databases were searched for studies concerning conversion to open surgery in MIDP.

RESULTS

Of the 828 studies screened, eight met the eligibility criteria, resulting in a combined dataset including 2592 patients after MIDP. The overall conversion rate was 17.1% (range 13.0-32.7%) with heterogeneity between studies associated with the definition of conversion adopted. Only one study divided conversion into elective and emergency conversion. The main indications for conversion were vascular involvement (23.7%), concern for oncological radicality (21.9%), and bleeding (18.9%). The reported risk factors for conversion included a malignancy as an indication for surgery, the proximity of the tumor to vascular structures in preoperative imaging, higher BMI or visceral fat, and multi-organ resection or extended resection. Contrasting results were seen in terms of blood loss and length of stay in comparing converted MIDP and completed MIDP patients.

CONCLUSION

The identified risk factors for conversion from this study can be used for patient selection and counseling. Surgeon experience should be considered when contemplating MIDP for a complex patient. Future studies should divide conversion into elective and emergency conversion.

BACKGROUND

With funding from the United States Health Resources Service Administration (HRSA), a consortium of health professional training institutions from Africa developed HIV-specific, interprofessional, team-based educational resources to better support trainees during the transition period between pre-service training and professional practice.

METHODS

Ten faculty members representing nine medical and nursing schools in sub-Saharan Africa (SSA) developed a training package of modules focused on core clinical, public health, interprofessional education (IPE), and quality improvement (QI) domains related to HIV service delivery. Curriculum development was informed by a rapid needs assessment of existing tools and future needs for HIV education across 27 SSA health professions training institutions. A total of 17 modules were developed, targeted at newly qualified health care professionals to be taught in a series of two-day workshops meant to complement existing institution specific HIV-curricula.

RESULTS

Between April and July 2019, a comprehensive case-based HIV training package was developed to support trainees in transition from pre-service training to independent professional practice. Each module, addressing different elements of interprofessional practice, was intended to be delivered in an interprofessional format. Thus far, 70 health professions training institutions in 14 countries have implemented the program; 547 educators facilitated STRIPE workshops, with a total of 5027 learners trained between September 2019 and September 2020.

CONCLUSIONS

To our knowledge this is the first IPE HIV-specific curriculum explicitly focused on enhancing the quality of training provided to graduating health care professionals working in SSA. The collaborative, cross-institutional, interprofessional approach to curriculum development provides a benchmark for how best-practice approaches to education can be disseminated in SSA.