Rural Emergency Medical Services Clinicians' Perceptions and Preferences in Receiving Clinical Feedback From Hospitals: A Qualitative Needs Assessment.

OBJECTIVE: Emergency medical services (EMS) clinicians experience dissatisfaction with the quality and quantity of clinical feedback from hospitals. Satisfaction is further diminished by the lack of a standardized systems approach. The purpose of this study was to identify rural clinicians' perceptions and preferences regarding clinical feedback received from hospitals, the delivery mechanisms, and its impact on their relationships with health care organizations. METHODS: This was a qualitative study focused on EMS clinicians involved in rural prehospital care at a single Midwestern academic medical center. Using a phenomenological framework, semi-structured interviews were conducted with medical directors, service directors, fire captains, air medical personnel, emergency medical responders, emergency medical technicians, advanced emergency medical technicians, and paramedics, all of whom were selected through purposive sampling. Interviews were recorded, transcribed, and independently coded by two trained reviewers. RESULTS: Twenty participants (11 frontline clinicians and 9 administrative staff members) with a wide range of clinical experience from 14 air and ground EMS agencies were interviewed. Emerging themes included: (1) the value or usefulness of feedback; (2) desired feedback system characteristics; (3) barriers to receiving feedback; (4) utilization and application of feedback; and (5) the feedback's impact on the relationship with health care organizations. Participants felt that clinical feedback from hospitals was especially important as a method of improving quality of care, though was rarely provided. Professional development was seen as a major benefit of receiving clinical feedback from hospitals. CONCLUSION: Our results suggest that consistent clinical feedback provided by hospitals was valued. Establishing a culture of providing organized feedback to practicing rural EMS clinicians is important for professional development and can strengthen the relationships between EMS clinicians and hospitals. These study findings can assist in the development and implementation of a standardized feedback instrument to benefit rural EMS clinicians, patients, and the health care system as a whole.

Improving Outcomes in Patients Sent to the Emergency Department from Outpatient Providers: A Receiver-Driven Handoff Process Improvement.

BACKGROUND: Outpatient providers refer to emergency departments (EDs) due to findings requiring assessment beyond existing capabilities. However, poor communication surrounding these transitions may hinder safety and timeliness of emergency care. Receiver-driven handoff (RDH) is a process that helps ensure that all pertinent information is shared. This quality improvement project aimed to (1) improve knowledge of RDH, (2) increase satisfaction and perceptions surrounding RDH, (3) modify behaviors in relation to RDH, and (4) decrease referred patients leaving without being seen (LWBS). METHODS: The Iowa Model and Implementation Framework guided this evidence-based quality improvement project. A multidisciplinary team developed and implemented a standardized RDH process consisting of screening to determine whether a patient was referred to the ED, review of electronic health record (EHR), and use of EHR documentation. Process measures were collected via questionnaire pre- and postimplementation and were analyzed quantitatively. Outcome measures were trended by a statistical process control p-chart, which was developed to demonstrate changes in the percentage of patients who were referred to the ED from the outpatient setting and LWBS. RESULTS: The average response for the question "How satisfied are you with the handoff of patient information from referring clinic providers to the ED?" increased from 1.51 preintervention to 2.04 postintervention (p = 0.005). Respondents rated the information received during handoff higher postintervention (2.12 vs. 2.52, p = 0.04). Compliance with screening for referral to the ED was 84.0%. The proportion of patients LWBS after referral decreased by 6.2 percentage points (p < 0.001). CONCLUSION: Using RDH in conjunction with a standardized triage screening may improve quality of information shared during this vulnerable transition and may assist in reduction of referred patients LWBS. The RDH process should be adapted into everyday workflow to ensure sustainability and effectiveness.

Results of a randomized controlled trial of a decision support intervention for disclosing maternal BRCA genetic test results to children and adolescents.

Objective: Evaluate the impact of a targeted family communication intervention for mothers undergoing genetic counseling and testing (GCT) for BRCA gene alterations. Methods: Following BRCA GCT, mothers (N = 204; M age = 45 y) were randomized to either a control condition (self-help print materials) or intervention (printed decision support guide, based on behavioral decision making theory in health care) for supporting choices about disclosing maternal genetic test results to children and adolescents. Behavioral assessments were administered prior to maternal GCT and after receipt of results: primary outcomes were maternal disclosure to children and parent-child communication quality. Results: Mothers in the intervention were > 2x likely to disclose their BRCA test results to their children compared to those in the control condition (odds ratio [OR] = 2.33, 95% confidence interval [CI] = 1.06, 5.10; p = .04). This effect was moderated by children's ages: mothers of preteens (<13 y) assigned to the intervention were >3x likely to disclose their results (OR = 3.74, 95% CI = 1.49, 9.41; p = .005). In adjusted models, intervention was also associated with favorable changes in the quality of parent-child communication (95% CI = 0.30, 9.00; p < .05). Conclusion: Decision support improves parent-child communication outcomes about GCT for hereditary breast-ovarian cancer. Innovation: This trial is among the first to empirically evaluate the outcomes of a behavioral intervention to support family communication of maternal BRCA risk information to children.

Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) infection causes considerable illness in older adults. The efficacy and safety of an investigational bivalent RSV prefusion F protein-based (RSVpreF) vaccine in this population are unknown. METHODS: In this ongoing, phase 3 trial, we randomly assigned, in a 1:1 ratio, adults (≥60 years of age) to receive a single intramuscular injection of RSVpreF vaccine at a dose of 120 µg (RSV subgroups A and B, 60 µg each) or placebo. The two primary end points were vaccine efficacy against seasonal RSV-associated lower respiratory tract illness with at least two or at least three signs or symptoms. The secondary end point was vaccine efficacy against RSV-associated acute respiratory illness. RESULTS: At the interim analysis (data-cutoff date, July 14, 2022), 34,284 participants had received RSVpreF vaccine (17,215 participants) or placebo (17,069 participants). RSV-associated lower respiratory tract illness with at least two signs or symptoms occurred in 11 participants in the vaccine group (1.19 cases per 1000 person-years of observation) and 33 participants in the placebo group (3.58 cases per 1000 person-years of observation) (vaccine efficacy, 66.7%; 96.66% confidence interval [CI], 28.8 to 85.8); 2 cases (0.22 cases per 1000 person-years of observation) and 14 cases (1.52 cases per 1000 person-years of observation), respectively, occurred with at least three signs or symptoms (vaccine efficacy, 85.7%; 96.66% CI, 32.0 to 98.7). RSV-associated acute respiratory illness occurred in 22 participants in the vaccine group (2.38 cases per 1000 person-years of observation) and 58 participants in the placebo group (6.30 cases per 1000 person-years of observation) (vaccine efficacy, 62.1%; 95% CI, 37.1 to 77.9). The incidence of local reactions was higher with vaccine (12%) than with placebo (7%); the incidences of systemic events were similar (27% and 26%, respectively). Similar rates of adverse events through 1 month after injection were reported (vaccine, 9.0%; placebo, 8.5%), with 1.4% and 1.0%, respectively, considered by the investigators to be injection-related. Severe or life-threatening adverse events were reported in 0.5% of vaccine recipients and 0.4% of placebo recipients. Serious adverse events were reported in 2.3% of participants in each group through the data-cutoff date. CONCLUSIONS: RSVpreF vaccine prevented RSV-associated lower respiratory tract illness and RSV-associated acute respiratory illness in adults (≥60 years of age), without evident safety concerns. (Funded by Pfizer; RENOIR ClinicalTrials.gov number, NCT05035212; EudraCT number, 2021-003693-31.).

Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants.

BACKGROUND: Whether vaccination during pregnancy could reduce the burden of respiratory syncytial virus (RSV)-associated lower respiratory tract illness in newborns and infants is uncertain. METHODS: In this phase 3, double-blind trial conducted in 18 countries, we randomly assigned, in a 1:1 ratio, pregnant women at 24 through 36 weeks' gestation to receive a single intramuscular injection of 120 µg of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine or placebo. The two primary efficacy end points were medically attended severe RSV-associated lower respiratory tract illness and medically attended RSV-associated lower respiratory tract illness in infants within 90, 120, 150, and 180 days after birth. A lower boundary of the confidence interval for vaccine efficacy (99.5% confidence interval [CI] at 90 days; 97.58% CI at later intervals) greater than 20% was considered to meet the success criterion for vaccine efficacy with respect to the primary end points. RESULTS: At this prespecified interim analysis, the success criterion for vaccine efficacy was met with respect to one primary end point. Overall, 3682 maternal participants received vaccine and 3676 received placebo; 3570 and 3558 infants, respectively, were evaluated. Medically attended severe lower respiratory tract illness occurred within 90 days after birth in 6 infants of women in the vaccine group and 33 infants of women in the placebo group (vaccine efficacy, 81.8%; 99.5% CI, 40.6 to 96.3); 19 cases and 62 cases, respectively, occurred within 180 days after birth (vaccine efficacy, 69.4%; 97.58% CI, 44.3 to 84.1). Medically attended RSV-associated lower respiratory tract illness occurred within 90 days after birth in 24 infants of women in the vaccine group and 56 infants of women in the placebo group (vaccine efficacy, 57.1%; 99.5% CI, 14.7 to 79.8); these results did not meet the statistical success criterion. No safety signals were detected in maternal participants or in infants and toddlers up to 24 months of age. The incidences of adverse events reported within 1 month after injection or within 1 month after birth were similar in the vaccine group (13.8% of women and 37.1% of infants) and the placebo group (13.1% and 34.5%, respectively). CONCLUSIONS: RSVpreF vaccine administered during pregnancy was effective against medically attended severe RSV-associated lower respiratory tract illness in infants, and no safety concerns were identified. (Funded by Pfizer; MATISSE ClinicalTrials.gov number, NCT04424316.).

Long-Term Adaptation Among Adolescent and Young Adult Children to Familial Cancer Risk.

BACKGROUND: It is important to examine adolescent and young adult (AYA) children's long-term psychosocial and behavioral adaptation to disclosure of maternal BRCA-positive carrier status (BRCA+) to inform approaches for familial cancer risk communication, education, and counseling. METHODS: Mothers underwent BRCA genetic testing 1 to 5 years earlier. Group differences in AYAs' self-reported outcomes were analyzed by maternal health and carrier status, and child age and sex. RESULTS: A total of N = 272 AYAs were enrolled: 76.1% of their mothers were breast or ovarian cancer survivors and 17.3% were BRCA+. AYAs' cancer risk behavior (tobacco and alcohol use, physical activity) and psychologic distress levels did not vary by maternal status. In bivariate analyses, AYAs of cancer-surviving mothers believed themselves to be at greater risk for, and were more knowledgeable about, cancer than AYAs of mothers without cancer. AYAs of BRCA+ mothers were more concerned about cancer, held stronger beliefs about genetic risk, and placed a higher value on learning about genetics. In adjusted models, maternal cancer history (not BRCA+) remained associated with AYAs' greater perceptions of cancer risk (P = .002), and knowledge about cancer (P = .03) and its causes (P = .002). CONCLUSIONS: Disclosing maternal BRCA+ status did not influence children's lifestyle behavior or adversely affect quality of life long term. AYAs of BRCA+ mothers were more aware of and interested in genetic risk information. Such families may benefit from support to promote open communication about genetic testing choices.

Spontaneous epiglottic hematoma secondary to direct oral anticoagulant.

Spontaneous hemorrhage is a known risk for patients on anticoagulation therapy. Most previous spontaneous airway hemorrhage cases reported involve warfarin, and of the few that involved a direct oral anticoagulant, none involved the epiglottis. The following case describes a spontaneous epiglottic hematoma in a patient one week after starting a direct oral anticoagulant. An 85-year-old man presented to the emergency department with acute onset of neck swelling, odynophagia and sublingual ecchymosis. Evaluation in the emergency department included advanced imaging of the neck and consultation with otolaryngology. Flexible fiberoptic laryngoscopy showed a markedly enlarged and ecchymotic epiglottis. The patient received medical management including rivaroxaban reversal, steroids, and broad-spectrum antibiotics, but no airway management was deemed necessary. After close monitoring, the patient was discharged on hospital day two. Further research and risk profiling could benefit patients and emergency clinicians when considering spontaneous hemorrhage in the airway in patients taking a direct oral anticoagulant.

Clinical Impact of Pathogenic Variants in DNA Damage Repair Genes beyond BRCA1 and BRCA2 in Breast and Ovarian Cancer Patients.

Consensus guidelines for hereditary breast and ovarian cancer include management recommendations for pathogenic/likely pathogenic (P/LP) variants in ATM, CHEK2, PALB2, and other DNA damage repair (DDR) genes beyond BRCA1 or BRCA2. We report on clinical management decisions across three academic medical centers resulting from P/LP findings in DDR genes in breast/ovarian cancer patients. Among 2184 patients, 156 (7.1%) carried a P/LP variant in a DDR gene. Clinical follow-up information was available for 101/156 (64.7%) patients. Genetic test result-based management recommendations were made for 57.8% (n = 59) of patients and for 64.7% (n = 66) of patients' family members. Most recommendations were made for moderate-to-high risk genes and were consistent with guidelines. Sixty-six percent of patients (n = 39/59) implemented recommendations. This study suggests that P/LP variants in DDR genes beyond BRCA1 and BRCA2 can change clinical management recommendations for patients and their family members, facilitate identification of new at-risk carriers, and impact treatment decisions. Additional efforts are needed to improve the implementation rates of genetic-testing-based management recommendations for patients and their family members.

Informed or anxious: patient preferences for release of test results of increasing sensitivity on electronic patient portals.

Worldwide, governments and healthcare systems are moving towards increased transparency to improve care quality, increase patient engagement, and decrease costs. For example, the American 21st Century Cures Act Final Rule requires providers to grant patients access to their electronic medical record. Unfortunately, limited research guides release of test results to online patient portals, especially concerning emotionally sensitive information. To address this gap, we surveyed the largest patient sample published to date. This cross-sectional survey project was conducted by the Market Research & Insights and Office of Patient Experience departments at a large academic medical center. Data were analyzed in SPSS using descriptive statistics and Z-tests. Of 8030 respondents, 74% and 57% accepted first learning their results online for cholesterol and strep throat tests, respectively. Most prefer in-person appointments for more serious tests detecting cancer (54%) and fetal miscarriage (53%). Excluding sexually transmitted disease (STD) testing, there are no clinically significant differences in preference between respondents previously diagnosed with the condition in question and respondents without such experience. When weighing the possibility of a 3-week wait to hear from their provider, most patients want automatic release of cholesterol (94%), strep throat (90%), genetic (68%), and STD (60%) test results, but the majority say it is unacceptable to receive Alzheimer's (52%), fetal miscarriage (51%), and cancer (59%) test results this way. Electronic results release is acceptable for less serious tests, but not for more consequential tests. Providers should consider patient preferences when developing policies to increase healthcare transparency. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12553-021-00628-5.

Pathogenicity of VHL variants in families with non-syndromic von Hippel-Lindau phenotypes: An integrated evaluation of germline and somatic genomic results.

Von Hippel-Lindau (VHL) syndrome is a hereditary tumor syndrome associated with germline loss-of-function pathogenic variants (PVs) in the VHL gene. VHL is classically associated with a high penetrance for many different tumor types. The same tumors may be sporadic in the setting of somatic VHL PVs. With more large-scale genome sequencing, variants with low penetrance or variable expressivity are identified. This has introduced challenges in patient management and the clinical interpretation of germline VHL variants identified in non-classic families. Herein, we report individuals from 3 non-classic families with VHL variants who presented with unexpected or non-syndromic phenotypes, but often with a VHL component tumor. In family 1, two siblings, age 61, with pathogenic VHL p.Leu188Val presented with clear cell renal cell carcinoma and lobular breast cancer. In family 2, the proband, age 82, was found to have pathogenic germline VHL p.Tyr98His on testing for metastatic bladder cancer. In family 3, four members carried germline VHL p.Pro81Ser (variant of uncertain significance), after the proband, age 40, presented with cerebellar hemangioblastoma. None of the individuals in the above three families met clinical criteria of classic VHL, suggesting germline VHL p.Leu188Val, p.Y98H, and p.Tyr98His may be low penetrant variants. Large studies are needed to evaluate penetrance and possible effect of genetic and non-genetic modifiers. Somatic sequencing performed on their respective tumors could help discern the etiology of the component tumors, highlighting the role of somatic evaluation in these cases. Paired examination of somatic and germline findings provided a more complete landscape of genome alterations in cancer development.

Fully Actuated Body-Mounted Robotic System for MRI-Guided Lower Back Pain Injections: Initial Phantom and Cadaver Studies.

This paper reports the improved design, system integration, and initial experimental evaluation of a fully actuated body-mounted robotic system for real-time MRI-guided lower back pain injections. The 6-DOF robot is composed of a 4-DOF needle alignment module and a 2-DOF remotely actuated needle driver module, which together provide a fully actuated manipulator that can operate inside the scanner bore during imaging. The system minimizes the need to move the patient in and out of the scanner during a procedure, and thus may shorten the procedure time and streamline the clinical workflow. The robot is devised with a compact and lightweight structure that can be attached directly to the patient's lower back via straps. This approach minimizes the effect of patient motion by allowing the robot to move with the patient. The robot is integrated with an image-based surgical planning module. A dedicated clinical workflow is proposed for robot-assisted lower back pain injections under real-time MRI guidance. Targeting accuracy of the system was evaluated with a real-time MRI-guided phantom study, demonstrating the mean absolute errors (MAE) of the tip position to be 1.50±0.68mm and of the needle angle to be 1.56±0.93°. An initial cadaver study was performed to validate the feasibility of the clinical workflow, indicating the maximum error of the position to be less than 1.90mm and of the angle to be less than 3.14°.

Structure-property studies of an imidazoquinoline chemotype with antitrypanosomal activity.

Human African trypanosomiasis is a neglected tropical disease (NTD) that is fatal if left untreated. Although approximately 13 million people live in moderate- to high-risk areas for infection, current treatments are plagued by problems with safety, efficacy, and emerging resistance. In an effort to fill the drug development pipeline for HAT, we have expanded previous work exploring the chemotype represented by the compound NEU-1090, with a particular focus on improvement of absorption, distribution, metabolism and elimination (ADME) properties. These efforts resulted in several compounds with substantially improved aqueous solubility, although these modifications typically resulted in a loss of trypanosomal activity. We herein report the results of our investigation into the antiparasitic activity, toxicity, and ADME properties of this class of compounds in the interest of informing the NTD drug discovery community and avoiding duplication of effort.

Improvement of Aqueous Solubility of Lapatinib-Derived Analogues: Identification of a Quinolinimine Lead for Human African Trypanosomiasis Drug Development.

Lapatinib, an approved epidermal growth factor receptor inhibitor, was explored as a starting point for the synthesis of new hits against Trypanosoma brucei, the causative agent of human African trypanosomiasis (HAT). Previous work culminated in 1 (NEU-1953), which was part of a series typically associated with poor aqueous solubility. In this report, we present various medicinal chemistry strategies that were used to increase the aqueous solubility and improve the physicochemical profile without sacrificing antitrypanosomal potency. To rank trypanocidal hits, a new assay (summarized in a cytocidal effective concentration (CEC50)) was established, as part of the lead selection process. Increasing the sp3 carbon content of 1 resulted in 10e (0.19 µM EC50 against T. brucei and 990 µM aqueous solubility). Further chemical exploration of 10e yielded 22a, a trypanocidal quinolinimine (EC50: 0.013 µM; aqueous solubility: 880 µM; and CEC50: 0.18 µM). Compound 22a reduced parasitemia 109 fold in trypanosome-infected mice; it is an advanced lead for HAT drug development.

Recognizing and Managing Children with a Pediatric Cancer Predisposition Syndrome: A Guide for the Pediatrician.

It is estimated that at least 8% to 10% of children diagnosed with cancer have an inherited cancer predisposition syndrome. Pediatricians may be called upon to (1) identify children with symptoms suggestive of cancer that require further diagnostic testing, (2) identify children who should be referred to cancer genetics based on their personal and family histories, and (3) provide primary care to children who have an inherited cancer syndrome. This review article provides a list of clinical warning signs suggestive of childhood malignancy, discusses the personal and family history "red flags" suggestive of hereditary cancer, offers checklists to help identify patients who are candidates for cancer genetics evaluation, and describes features of the major pediatric cancer syndromes involving solid tumors and surveillance guidelines. This review aims to provide the pediatrician with the tools needed to recognize, refer, and help manage children at risk for pediatric cancer syndromes. [Pediatr Ann. 2018;47(5):e204-e216.].

DICER1 and Associated Conditions: Identification of At-risk Individuals and Recommended Surveillance Strategies.

Pathogenic germline DICER1 variants cause a hereditary cancer predisposition syndrome with a variety of manifestations. In addition to conferring increased cancer risks for pleuropulmonary blastoma (PPB) and ovarian sex cord-stromal tumors, particularly Sertoli-Leydig cell tumor, individuals with pathogenic germline DICER1 variants may also develop lung cysts, cystic nephroma, renal sarcoma and Wilms tumor, nodular hyperplasia of the thyroid, nasal chondromesenchymal hamartoma, ciliary body medulloepithelioma, genitourinary embryonal rhabdomyosarcoma, and brain tumors including pineoblastoma and pituitary blastoma. In May 2016, the International PPB Registry convened the inaugural International DICER1 Symposium to develop consensus testing and surveillance and treatment recommendations. Attendees from North America, Europe, and Russia provided expert representation from the disciplines of pediatric oncology, endocrinology, genetics, genetic counseling, radiology, pediatric surgery, pathology, and clinical research. Recommendations are provided for genetic testing; prenatal management; and surveillance for DICER1-associated pulmonary, renal, gynecologic, thyroid, ophthalmologic, otolaryngologic, and central nervous system tumors and gastrointestinal polyps. Risk for most DICER1-associated neoplasms is highest in early childhood and decreases in adulthood. Individual and caregiver education and judicious imaging-based surveillance are the primary recommended approaches. These testing and surveillance recommendations reflect a consensus of expert opinion and current literature. As DICER1 research expands, guidelines for screening and treatment will continue to be updated. Clin Cancer Res; 24(10); 2251-61. ©2018 AACR.

Key High-efficiency Practices of Emergency Department Providers: A Mixed-methods Study.

OBJECTIVE: The objective of this study was to determine specific provider practices associated with high provider efficiency in community emergency departments (EDs). METHODS: A mixed-methods study design was utilized to identify key behaviors associated with efficiency. Stage 1 was a convenience sample of 16 participants (ED medical directors, nurses, advanced practice providers, and physicians) identified provider efficiency behaviors during semistructured interviews. Ninety-nine behaviors were identified and distilled by a group of three ED clinicians into 18 themes. Stage 2 was an observational study of 35 providers was performed in four (30,000- to 55,000-visit) community EDs during two 4-hour periods and recorded in minute-by-minute observation logs. In Stage 3, each behavior or practice from Stage 1 was assigned a score within each observation period. Behaviors were tested for association with provider efficiency (relative value units/hour) using linear univariate generalized estimating equations with an identity link, clustered on ED site. RESULTS: Five ED provider practices were found to be positively associated with efficiency: average patient load, using name of team member, conversations with health care team, visits to patient rooms, and running the board. Two behaviors, "inefficiency practices," demonstrated significant negative correlations: non-work-related tasks and documentation on patients no longer in the ED. CONCLUSIONS: Average patient load, running the board, conversations with team member, and using names of team members are associated with enhanced provider productivity. Identification of behaviors associated with efficiency can be utilized by medical directors, clinicians, and trainees to improve personal efficiency or counsel team members.

Genetic Counselor Recommendations for Cancer Predisposition Evaluation and Surveillance in the Pediatric Oncology Patient.

As the understanding of the genetic etiology of childhood cancers increases, the need for the involvement of experts familiar with the provision of genetic counseling for this population is paramount. In October 2016, the American Association for Cancer Research organized the AACR Childhood Cancer Predisposition Workshop in which international experts in pediatric cancer predisposition met to establish surveillance guidelines for children with cancer predisposition. Identifying for whom, when, why, and how these cancer predisposition surveillance guidelines should be implemented is essential. Genetic counselors invited to this workshop provide a genetic counseling framework for oncology professionals in this article. Points of entry and recommendations regarding the provision and timing of the initial and subsequent genetic counseling sessions are addressed. The genetic counseling and testing processes are reviewed, and the psychologic impact related to surveillance is explored. Pediatric cancer genetics will continue to grow and evolve as a field, and genetic counseling services will be vital to ensure appropriate identification and management of at-risk children moving forward. Clin Cancer Res; 23(13); e91-e97. ©2017 AACRSee all articles in the online-only CCR Pediatric Oncology Series.

PTEN, DICER1, FH, and Their Associated Tumor Susceptibility Syndromes: Clinical Features, Genetics, and Surveillance Recommendations in Childhood.

PTEN hamartoma tumor syndrome (PHTS), DICER1 syndrome, and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome are pleiotropic tumor predisposition syndromes that include benign and malignant neoplasms affecting adults and children. PHTS includes several disorders with shared and distinct clinical features. These are associated with elevated lifetime risk of breast, thyroid, endometrial, colorectal, and renal cancers as well as melanoma. Thyroid cancer represents the predominant cancer risk under age 20 years. DICER1 syndrome includes risk for pleuropulmonary blastoma, cystic nephroma, ovarian sex cord-stromal tumors, and multinodular goiter and thyroid carcinoma as well as brain tumors including pineoblastoma and pituitary blastoma. Individuals with HLRCC may develop multiple cutaneous and uterine leiomyomas, and they have an elevated risk of renal cell carcinoma. For each of these syndromes, a summary of the key syndromic features is provided, the underlying genetic events are discussed, and specific screening is recommended. Clin Cancer Res; 23(12); e76-e82. ©2017 AACRSee all articles in the online-only CCR Pediatric Oncology Series.