Recent Publications by CFE Educators

BACKGROUND AND PURPOSE

Diffuse midline gliomas with histone H3 K27M mutation are biologically aggressive tumors with poor prognosis defined as a new diagnostic entity in the 2016 World Health Organization Classification of Tumors of the Central Nervous System. There are no qualitative imaging differences (enhancement, border, or central necrosis) between histone H3 wildtype and H3 K27M-mutant diffuse midline gliomas. Herein, we evaluated the utility of diffusion-weighted imaging to distinguish H3 K27M-mutant from histone H3 wildtype diffuse midline gliomas.

MATERIALS AND METHODS

We identified 31 pediatric patients (younger than 21 years of age) with diffuse gliomas centered in midline structures that had undergone assessment for histone H3 K27M mutation. We measured ADC within these tumors using a voxel-based 3D whole-tumor measurement method.

RESULTS

Our cohort included 18 infratentorial and 13 supratentorial diffuse gliomas centered in midline structures. Twenty-three (74%) tumors carried H3-K27M mutations. There was no difference in ADC histogram parameters (mean, median, minimum, maximum, percentiles) between mutant and wild-type tumors. Subgroup analysis based on tumor location also did not identify a difference in histogram descriptive statistics. Patients who survived 1 year after diagnosis had lower median ADC (1.10 × 10mm/s; 95% CI, 0.90-1.30) compared with patients who survived >1 year (1.46 × 10mm/s; 95% CI, 1.19-1.67; .06). Average ADC values for diffuse midline gliomas were 1.28 × 10mm/s (95% CI, 1.21-1.34) and 0.86 × 10mm/s (95% CI, 0.69-1.01) for hemispheric glioblastomas with .05.

CONCLUSIONS

Although no statistically significant difference in diffusion characteristics was found between H3-K27M mutant and H3 wildtype diffuse midline gliomas, lower diffusivity corresponds to a lower survival rate at 1 year after diagnosis. These findings can have an impact on the anticipated clinical course for this patient population and offer providers and families guidance on clinical outcomes.

Psoriasis is a chronic, multisystem, inflammatory disease that affects approximately 1% of children, with onset most common during adolescence. This guideline addresses important clinical questions that arise in psoriasis management and provides evidence-based recommendations. Attention will be given to pediatric patients with psoriasis, recognizing the unique physiology, pharmacokinetics, and patient-parent-provider interactions of patients younger than 18 years old. The topics reviewed here mirror those discussed in the adult guideline sections, excluding those topics that are irrelevant to, or lack sufficient information for, pediatric patients.

OBJECTIVES

To investigate the efficacy and safety of ixekizumab for up to 52 weeks in two phase 3 studies of patients with active radiographic axial spondyloarthritis (r-axSpA) who were biological disease-modifying antirheumatic drug (bDMARD)-naive (COAST-V) or tumour necrosis factor inhibitor (TNFi)-experienced (COAST-W).

METHODS

Adults with active r-axSpA were randomised 1:1:1:1 (n=341) to 80 mg ixekizumab every 2 (IXE Q2W) or 4 weeks (IXE Q4W), placebo (PBO) or 40 mg adalimumab Q2W (ADA) in COAST-V and 1:1:1 (n=316) to IXE Q2W, IXE Q4W or PBO in COAST-W. At week 16, patients receiving ixekizumab continued their assigned treatment; patients receiving PBO or ADA were rerandomised 1:1 to IXE Q2W or IXE Q4W (PBO/IXE, ADA/IXE) through week 52.

RESULTS

In COAST-V, Assessment of SpondyloArthritis international Society 40 (ASAS40) responses rates (intent-to-treat population, non-responder imputation) at weeks 16 and 52 were 48% and 53% (IXE Q4W); 52% and 51% (IXE Q2W); 36% and 51% (ADA/IXE); 19% and 47% (PBO/IXE). Corresponding ASAS40 response rates in COAST-W were 25% and 34% (IXE Q4W); 31% and 31% (IXE Q2W); 14% and 39% (PBO/IXE). Both ixekizumab regimens sustained improvements in disease activity, physical function, objective markers of inflammation, QoL, health status and overall function up to 52 weeks. Safety through 52 weeks of ixekizumab was consistent with safety through 16 weeks.

CONCLUSION

The significant efficacy demonstrated with ixekizumab at week 16 was sustained for up to 52 weeks in bDMARD-naive and TNFi-experienced patients. bDMARD-naive patients initially treated with ADA demonstrated further numerical improvements after switching to ixekizumab. Safety findings were consistent with the known safety profile of ixekizumab.

TRIAL REGISTRATION NUMBER

NCT02696785/NCT02696798.

INTRODUCTION

Metformin may be associated with reduced colorectal cancer (CRC) risk, but findings from previous studies have been inconsistent and had insufficient sample sizes to examine whether the association differs by anatomic site. This study examined whether metformin was associated with reduced CRC risk, both overall and stratified by anatomic site, in a large sample of persons with diabetes who underwent colonoscopy.

METHODS

We performed a case-control study of US Veterans with prevalent diabetes who underwent colonoscopy between 1999 and 2014 using Department of Veterans Affairs electronic health record data. Cases were defined by presence of CRC at colonoscopy, while controls had normal colonoscopy. The primary exposure was metformin use at time of colonoscopy (yes/no). Association of metformin exposure with CRC (further stratified by proximal, distal, or rectal subsite) was examined using multivariable and multinomial logistic regression and summarized by odds ratios (ORs) with 95% confidence intervals (CIs).

RESULTS

We included 6,650 CRC patients and 454,507 normal colonoscopy patients. CRC cases were older and had lower metformin exposure. Metformin was associated with 8% relative reduction in CRC odds (OR: 0.92, 95% CI: 0.87-0.96). By subsite, metformin was associated with a 14% statistically significant reduced rectal cancer odds (OR: 0.86, 95% CI: 0.78-0.94) but no reduced distal or proximal cancer odds.

DISCUSSION

Metformin was associated with reduced CRC odds-particularly rectal cancer-in a large sample of persons with diabetes undergoing colonoscopy.

Idiopathic pulmonary fibrosis (IPF) is characterized by the transforming growth factor (TGF)-β-dependent differentiation of lung fibroblasts into myofibroblasts, leading to excessive deposition of extracellular matrix proteins, which distort lung architecture and function. Metabolic reprogramming in myofibroblasts is emerging as an important mechanism in the pathogenesis of IPF, and recent evidence suggests that glutamine metabolism is required in myofibroblasts, although the exact role of glutamine in myofibroblasts is unclear. In the present study, we demonstrate that glutamine and its conversion to glutamate by glutaminase are required for TGF-β-induced collagen protein production in lung fibroblasts. We found that metabolism of glutamate to α-ketoglutarate by glutamate dehydrogenase or the glutamate-pyruvate or glutamate-oxaloacetate transaminases is not required for collagen protein production. Instead, we discovered that the glutamate-consuming enzymes phosphoserine aminotransferase 1 (PSAT1) and aldehyde dehydrogenase 18A1 (ALDH18A1)/Δ-pyrroline-5-carboxylate synthetase (P5CS) are required for collagen protein production by lung fibroblasts. PSAT1 is required for glycine production, whereas ALDH18A1/P5CS is required for proline production. Consistent with this, we found that TGF-β treatment increased cellular concentrations of glycine and proline in lung fibroblasts. Our results suggest that glutamine metabolism is required to promote amino acid biosynthesis and not to provide intermediates such as α-ketoglutarate for oxidation in mitochondria. In support of this, we found that inhibition of glutaminolysis has no effect on cellular oxygen consumption and that knockdown of oxoglutarate dehydrogenase has no effect on the ability of fibroblasts to produce collagen protein. Our results suggest that amino acid biosynthesis pathways may represent novel therapeutic targets for treatment of fibrotic diseases, including IPF.

OBJECTIVES

The purpose of this study was to evaluate the feedback of participants upon laparoscopic liver surgery (LLS) course on Thiel-embalmed human bodies.

METHODS

From 2010 to 2017, ten LLS masterclasses have been organized by the Department of Hepatobiliary Surgery at Ghent University Hospital. A 23-question anonymous survey was electronically sent to 119 participants between November 2017 and January 2018, exploring their characteristics and asking for evaluation of the course. The obstacles for implementing LLS in their centers have been assessed.

RESULTS

Sixty-four surgeons (53.8%) responded to the survey; 42 (65.6%) were employed at a university hospital; and 39 (60.9%) were in the first decade of their practice as a consultant surgeon. Forty-three (67.2%) surgeons reported an increased percentage of LLS cases afterward. Training on Thiel cadavers was considered superior (49.2%) to other training options including proctoring in the operating room (34.9%), virtual reality (6.3%), video training (4.8%) and practicing on pigs (4.8%). Obstacles identified contained inadequate training, patient's referral pattern, financial issues, lack of dedicated surgical team and time constrains.

CONCLUSIONS

This survey revealed that a structured short-time program incorporating interactive discussion, live operations and hands-on training on human bodies under proctorship may enhance efficient training in laparoscopic liver surgery. In a step forward for upcoming courses, the importance of team building has to be addressed.

PURPOSE

To examine the impact of professional background and gender of a resuscitation team leader on residents' perceptions of leadership skills.

METHOD

The authors video-recorded a scripted, simulated resuscitation scenario twice, with either a male or a female team leader. They copied each video and labeled the leader as physician (MD) or nurse practitioner (NP), creating 4 conditions: female NP, female MD, male NP, or male MD. The authors recruited resident participants from 5 specialties at 4 institutions; they randomly assigned residents to view one version of the video and rate the team leader's performance using the Ottawa Crisis Resource Management Global Rating Scale (Ottawa CRM) in an online survey. The authors conducted 2-way ANOVA to examine interactions between team leader gender and profession on Ottawa CRM ratings.

RESULTS

One hundred sixty residents responded (89 females, 71 males). A statistically significant main effect of team leader gender on residents' ratings was found in 2 of the 6 Ottawa CRM domains, leadership (F1,156 = 6.97, P = .009) and communication skills (F1,156 = 8.53, P = .004), due to lower ratings for female than male leaders (5.29 ± 0.95 vs 5.74 ± 1.17; 5.05 ± 1.20 vs 5.57 ± 1.06). There was no effect of profession on ratings and no significant interaction between profession and gender of the team leader on ratings for any of the domains.

CONCLUSIONS

These findings indicate bias among residents against females as team leaders. Mitigating such bias is essential to successfully establish shared leadership models in health care.

BACKGROUND

Little is documented about the experiences of pregnancy for transgender and gender-diverse individuals. There is scant clinical guidance for providing prepregnancy, prenatal, intrapartum, and postpartum care to transgender and gender-diverse people who desire pregnancy.

CASE

Our team provided perinatal care to a 20-year-old transgender man, which prompted collaborative advocacy for health care systems change to create gender-affirming patient experiences in the perinatal health care setting.

CONCLUSION

Systems-level and interpersonal-level interventions were adopted to create gender-affirming and inclusive care in and around pregnancy. Basic practices to mitigate stigma and promote gender-affirming care include staff trainings and query and use of appropriate name and pronouns in patient interactions and medical documentation. Various factors are important to consider regarding testosterone therapy for transgender individuals desiring pregnancy.