Management of Atopy with Dupilumab and Omalizumab in CADINS Disease.

The caspase activation and recruitment domain 11 (CARD11) gene encodes a scaffold protein required for lymphocyte antigen receptor signaling. Dominant-negative, loss-of-function (LOF) pathogenic variants in CARD11 result in CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease. Patients with CADINS suffer with severe atopic manifestations including atopic dermatitis, food allergy, and chronic spontaneous urticaria in addition to recurrent infections and autoimmunity. We assessed the response of dupilumab in five patients and omalizumab in one patient with CADINS for the treatment of severe atopic symptoms. CARD11 mutations were validated for pathogenicity using a T cell transfection assay to assess the impact on activation-induced signaling to NF-κB. Three children and three adults with dominant-negative CARD11 LOF mutations were included. All developed atopic disease in infancy or early childhood. In five patients, atopic dermatitis was severe and recalcitrant to standard topical and systemic medications; one adult suffered from chronic spontaneous urticaria. Subcutaneous dupilumab was initiated to treat atopic dermatitis and omalizumab to treat chronic spontaneous urticaria. All six patients had rapid and sustained improvement in atopic symptoms with no complications during the follow-up period. Previous medications used to treat atopy were able to be decreased or discontinued. In conclusion, treatment with dupilumab and omalizumab for severe, refractory atopic disease in patients with CADINS appears to be effective and well tolerated in patients with CADINS with severe atopy.

Risk factors and outcomes of melanoma in children and adolescents: A retrospective multicenter study.

BACKGROUND: Pediatric melanoma presents with distinct clinical features compared to adult disease. OBJECTIVE: Characterize risk factors and negative outcomes in pediatric melanoma. METHODS: Multicenter retrospective study of patients under 20 years diagnosed with melanoma between January 1, 1995 and June 30, 2015 from 11 academic medical centers. RESULTS: Melanoma was diagnosed in 317 patients, 73% of whom were diagnosed in adolescence (age ≥11). Spitzoid (31%) and superficial spreading (26%) subtypes were most common and 11% of cases arose from congenital nevi. Sentinel lymph node biopsy was performed in 68% of cases and positive in 46%. Fatality was observed in 7% of cases. Adolescent patients with melanoma were more likely to have family history of melanoma (P = .046) compared to controls. LIMITATIONS: Retrospective nature, cohort size, control selection, and potential referral bias. CONCLUSION: Pediatric melanoma has diverse clinical presentations. Better understanding of these cases and outcomes may facilitate improved risk stratification of pediatric melanoma.

Understanding vessel noise across a network of marine protected areas.

Protected areas are typically managed as a network of sites exposed to varying anthropogenic conditions. Managing these networks benefits from monitoring of conditions across sites to help prioritize coordinated efforts. Monitoring marine vessel activity and related underwater radiated noise impacts across a network of protected areas, like the U.S. National Marine Sanctuary system, helps managers ensure the quality of habitats used by a wide range of marine species. Here, we use underwater acoustic detections of vessels to quantify different characteristics of vessel noise at 25 locations within eight marine sanctuaries including the Hawaiian Archipelago and the U.S. east and west coasts. Vessel noise metrics, including temporal presence and sound levels, were paired with Automatic Identification System (AIS) vessel tracking data to derive a suite of robust vessel noise indicators for use across the network of marine protected areas. Network-wide comparisons revealed a spectrum of vessel noise conditions that closely matched AIS vessel traffic composition. Shifts in vessel noise were correlated with the decrease in vessel activity early in the COVID-19 pandemic, and vessel speed reduction management initiatives. Improving our understanding of vessel noise conditions in these protected areas can help direct opportunities for reducing vessel noise, such as establishing and maintaining noise-free periods, enhancing port efficiency, engaging with regional and international vessel quieting initiatives, and leveraging co-benefits of management actions for reducing ocean noise.

A comparative analysis of RAS variants in patients with disorders of somatic mosaicism.

PURPOSE: RAS genes (HRAS, KRAS, and NRAS) are commonly found to be mutated in cancers, and activating RAS variants are also found in disorders of somatic mosaicism (DoSM). A survey of the mutational spectrum of RAS variants in DoSM has not been performed. METHODS: A total of 938 individuals with suspected DoSM underwent high-sensitivity clinical next-generation sequencing-based testing. We investigated the mutational spectrum and genotype-phenotype associations of mosaic RAS variants. RESULTS: In this article, we present a series of individuals with DoSM with RAS variants. Classic hotspots, including Gly12, Gly13, and Gln61 constituted the majority of RAS variants observed in DoSM. Furthermore, we present 12 individuals with HRAS and KRAS in-frame duplication/insertion (dup/ins) variants in the switch II domain. Among the 18.3% individuals with RAS in-frame dup/ins variants, clinical findings were mainly associated with vascular malformations. Hotspots were associated with a broad phenotypic spectrum, including vascular tumors, vascular malformations, nevoid proliferations, segmental overgrowth, digital anomalies, and combinations of these. The median age at testing was higher and the variant allelic fraction was lower in individuals with in-frame dup/ins variants than those in individuals with mosaic RAS hotspots. CONCLUSION: Our work provides insight into the allelic and clinical heterogeneity of mosaic RAS variants in nonmalignant conditions.

Health literacy in pediatric dermatology: challenges and opportunities.

PURPOSE OF REVIEW: Health literacy influences how children and families participate in their medical care, use health services, and overall health outcomes. Health literacy is underexplored in pediatric dermatology. In this scoping review, we provide examples of how limited health literacy can be a barrier to patient care in pediatric dermatology and how to mitigate its effects. RECENT FINDINGS: Limited health literacy is associated with worse health outcomes, decreased medication adherence, and decreased use of the healthcare system versus those with adequate health literacy. Materials created to help patients understand their medical conditions and treatment options often are written at a reading level far above that of the average patient and caregiver. Given the reading level of patient-facing materials, those with limited health literacy are more susceptible to medication administration errors, with omissions or incorrect dosing being most frequent to occur. There is limited research about how skills related to health literacy, including numeracy and electronic health literacy, can be addressed in pediatric dermatology. SUMMARY: Health literacy impacts patient care, treatment, and adherence in pediatric dermatology. This article gives examples of how to address common challenges in the pediatric dermatology clinic and presents areas for further research and improvement.

"When Appearances Matter: A Taxonomy and Ethics for Demographic-Based Provider Requests".

Requests by patients for providers of specific demographic backgrounds pose an ongoing challenge for hospitals, policymakers, and ethicists. These requests may stem from a wide variety of motivations; some may be consistent with broader societal values, although many others may reflect prejudices inconsistent with justice, equity, and decency. This paper proposes a taxonomy designed to assist healthcare institutions in addressing such cases in a consistent and equitable manner. The paper then reviews a range of ethical and logistical challenges raised by such requests and proposed guidance to consider when reviewing and responding to them.

Smartphone-based Assessment of Preoperative Decision Conflict and Postoperative Physical Activity Among Patients Undergoing Cancer Surgery: A Prospective Cohort Study.

OBJECTIVE: To determine the prevalence of clinically significant decision conflict (CSDC) among patients undergoing cancer surgery and associations with postoperative physical activity, as measured through smartphone accelerometer data. BACKGROUND: Patients with cancer face challenging treatment decisions, which may lead to CSDC. CSDC negatively affects patient-provider relationships, psychosocial functioning, and health-related quality of life; however, physical manifestations of CSDC remain poorly characterized. METHODS: Adult smartphone-owners undergoing surgery for breast, skin-soft-tissue, head-and-neck, or abdominal cancer (July 2017-2019) were approached. Patients downloaded the Beiwe application that delivered the Decision Conflict Scale (DCS) preoperatively and collected smartphone accelerometer data continuously from enrollment through 6 months postop-eratively. Restricted-cubic-spline regression, adjusting for a priori potential confounders (age, type of surgery, support status, and postoperative complications) was used to determine trends in postoperative daily physical activity among patients with and without CSDC (DCS score >25/100). RESULTS: Among 99 patients who downloaded the application, 85 completed the DCS (86% participation rate). Twenty-three (27%) reported CSDC. These patients were younger (mean age 48.3 years [standard deviation 14.2]-vs-55.0 [13.3], P = 0.047) and more frequently lived alone (22%-vs-6%, P = 0.042). There were no differences in preoperative physical activity (115.4 minutes [95%CI 90.9, 139.9]-vs-110.8 [95%CI 95.7, 126.0], P = 0.753). Adjusted postoperative physical activity was lower among patients reporting CSDC at 30 days (difference 33.1 minutes [95%CI 5.93,60.2], P = 0.017), 60 days 35.5 [95%CI 8.50, 62.5], P = 0.010 and 90 days 31.8 [95%CI 5.44, 58.1], P = 0.018 postoperatively. CONCLUSIONS: CSDC was prevalent among patients who underwent cancer surgery and associated with lower postoperatively daily physical activity. These data highlight the importance of addressing modifiable decisional needs of patients through enhanced shared decision-making.

Anatomy and dietary specialization influence sensory behaviour among sympatric primates.

Senses form the interface between animals and environments, and provide a window into the ecology of past and present species. However, research on sensory behaviours by wild frugivores is sparse. Here, we examine fruit assessment by three sympatric primates (Alouatta palliata, Ateles geoffroyi and Cebus imitator) to test the hypothesis that dietary and sensory specialization shape foraging behaviours. Ateles and Cebus groups are comprised of dichromats and trichromats, while all Alouatta are trichomats. We use anatomical proxies to examine smell, taste and manual touch, and opsin genotyping to assess colour vision. We find that the frugivorous spider monkeys (Ateles geoffroyi) sniff fruits most often, omnivorous capuchins (Cebus imitator), the species with the highest manual dexterity, use manual touch most often, and that main olfactory bulb volume is a better predictor of sniffing behaviour than nasal turbinate surface area. We also identify an interaction between colour vision phenotype and use of other senses. Controlling for species, dichromats sniff and bite fruits more often than trichromats, and trichromats use manual touch to evaluate cryptic fruits more often than dichromats. Our findings reveal new relationships among dietary specialization, anatomical variation and foraging behaviour, and promote understanding of sensory system evolution.

Survival After Adrenalectomy for Metastatic Lung Cancer.

BACKGROUND: Adrenal metastasectomy is associated with increased survival in non-small cell lung cancer (NSCLC) with isolated adrenal metastases. Although clinical use of adrenal metastasectomy has expanded, indications remain poorly defined. The aim of this study was to evaluate the clinical benefit of adrenal metastasectomy for all lung cancer subtypes. PATIENTS AND METHODS: We performed a retrospective cohort study of patients who underwent adrenal metastasectomy for metastatic lung cancer at six institutions between 2001 and 2015. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Cox proportional hazards regressions and Kaplan-Meier survival analysis were performed. RESULTS: For 122 patients, the mean age was 60.5 years and 49.2% were female. Median time to detection of the metastasis was 11 months, and 41.8% were ipsilateral to the primary lung cancer. Median DFS was 40 months (1 year: 64.8%; 5 year: 42.9%). Factors associated with longer DFS included primary tumor resection [hazard ratio (HR): 0.001; p = 0.005], longer time to adrenal metastasis (HR: 0.94; p = 0.005), and ipsilateral metastases (HR: 0.13; p = 0.004). Shorter DFS corresponded with older age (HR: 1.11; p = 0.01), R1 resection (HR: 8.94; p = 0.01), adjuvant radiation (HR: 9.45; p = 0.02), and open adrenal metastasectomy (HR: 10.0; p = 0.03). Median OS was 47 months (1 year: 80.2%; 5 year: 35.2%). Longer OS was associated with ipsilateral metastasis (HR: 0.55; p = 0.02) and adjuvant chemotherapy (HR: 0.35; p = 0.02). Shorter OS was associated with extra-adrenal metastases at adrenalectomy (HR: 3.52; p = 0.007), small cell histology (HR: 15.0; p = 0.04), and lung radiation (HR: 3.37; p = 0.002). DISCUSSION: Durable survival was observed in patients undergoing adrenal metastasectomy and should be considered for isolated adrenal metastases of NSCLC. Small cell histology and extra-adrenal metastases are relative contraindications to adrenal metastasectomy.

Tumor predisposition: what's the skin got to do with it?

PURPOSE OF REVIEW: Recognition of skin findings associated with tumor predisposition syndromes can prompt early evaluation and surveillance and improve management. Additionally, knowing when to test and when to defer performing genetic testing can streamline management. This article reviews tumor predisposition syndromes with recently characterized skin findings and disorders for which early recognition and counseling can impact the course of disease. RECENT FINDINGS: Café au lait macules (CALMs) are important in many tumor predisposition syndromes, and 'atypical' CALMs are associated with constitutional mismatch repair deficiency and Fanconi anemia. Melanoma predisposition syndromes caused by pathogenic variants in POT1 and BAP1 are more recently described, and both are associated with Spitzoid tumors. Somatic pathogenic variants can cause segmental nevoid basal cell carcinoma syndrome and a mosaic form of Peutz-Jeghers syndrome. Patients with PTEN hamartoma syndrome have increased risk for melanoma but this might not occur until adulthood. SUMMARY: The cutaneous manifestations of tumor predisposition syndromes can aid diagnosis. Early photoprotection is key to modifying a main risk factor for skin cancer in many of these syndromes. Implementing surveillance guidelines facilitates early detection of tumors.

The sensory ecology of primate food perception, revisited.

Twenty years ago, Dominy and colleagues published "The sensory ecology of primate food perception," an impactful review that brought new perspectives to understanding primate foraging adaptations. Their review synthesized information on primate senses and explored how senses informed feeding behavior. Research on primate sensory ecology has seen explosive growth in the last two decades. Here, we revisit this important topic, focusing on the numerous new discoveries and lines of innovative research. We begin by reviewing each of the five traditionally recognized senses involved in foraging: audition, olfaction, vision, touch, and taste. For each sense, we provide an overview of sensory function and comparative ecology, comment on the state of knowledge at the time of the original review, and highlight advancements and lingering gaps in knowledge. Next, we provide an outline for creative, multidisciplinary, and innovative future research programs that we anticipate will generate exciting new discoveries in the next two decades.

The emergence noise reduction quality improvement initiative to enhance patient safety and quality of care.

BACKGROUND: Operating room noise levels may hinder staff communication and cause distractions for providers, endangering patient safety. Owing to concerns of unacceptable noise levels during emergence from general anesthesia, our institution developed a quality improvement project. The SMART aim of this initiative was to decrease the average decibel noise level measured during emergence from general anesthesia in our operating rooms from 65.65 to 63 decibels and the maximum decibel noise level from 81.64 to 75 decibels over approximately 3 months. METHODS: A multidisciplinary team completed this project utilizing improvement science methodology from The Model for Improvement, including interventions tested via Plan-Do-Study-Act cycles. Data were measured, collected manually, and entered in an Excel spreadsheet. Data were analyzed using statistical process control methods, including a Run Chart. Our measures were the average and maximum decibel noise levels during emergence from general anesthesia. RESULTS: Several interventions were associated with a decrease in the average and maximum decibel noise levels. Interventions included educational presentations to perioperative staff; the operating room nurse taking the role of pausing any music; and the utilization of an audible and visual decibel alarm meter to sound and blink lights when the noise level is too high. During the initiative, the average (and maximum) decibel noise levels during emergence from general anesthesia in our operating rooms decreased from 65.65 (81.84) to 61.5 (76.44). CONCLUSIONS: This improvement project was associated with a decrease in decibel noise levels during emergence. We enhanced a process and encouraged culture change at an academic pediatric hospital to enhance the safety of our care.

Immunosuppressant-associated eruptions in pediatric inflammatory bowel disease: A case-control study.

Paradoxically, immunosuppressive therapy for inflammatory bowel disease (IBD) can induce psoriasiform or eczematous eruptions. This case-control study identified infliximab exposure, Crohn's disease, and history of inflammatory skin conditions as significant risk factors for these eruptions in children with IBD. Our results also showed possible trends in age and race.

Antifibrinolytics Are Not Associated With Reduced Blood Loss in Minimally-Invasive Endoscopic-Assisted Craniectomy for Repair of Single-Suture Craniosynostosis.

ABSTRACT: Minimally-invasive endoscopic-assisted craniectomy (EAC) achieves similar functional and cosmetic outcomes, whereas reducing morbidity risk that is often associated with complex cranial vault reconstruction. Antifibrinolytics (AF) usage to limit blood loss and transfusion requirements during complex cranial vault reconstruction has been studied extensively; however, studies are limited for AF therapy in EAC. The aim of this single-center retrospective observational cohort pilot study was to evaluate whether the use of AF was associated with reduced blood loss in infants undergoing EAC. The authors hypothesized that there would be no difference in blood loss between patients who received AF and those that did not receive AF during EAC. Non-syndromic patients who underwent single-suture EAC were retrospectively evaluated. Primary outcome measure was intraoperative calculated blood loss (mL/kg). Secondary outcome measures included perioperative red blood cells transfusion volumes, number of blood donor exposures, and pediatric intensive care unit and total hospital length of stay. Study cohort demographic and outcome data were analyzed; Fisher exact test was used for categorical data, Student t test was used for continuous data. A P value of <0.05 was considered statistically significant. Forty-nine EAC patients were included in the study with 34 patients in the AF cohort and 15 patients in the non-AF cohort. There were no significant differences in demographics between the 2 groups. Additionally, there was no significant difference in intraoperative calculated blood loss or any secondary outcome measure. In our single-suture EAC study cohorts, AF administration was not associated with a decrease in blood loss when compared to those that did not receive AF therapy.

Efficacy of a commercial dry sleeve cryotherapy system for cooling the equine metacarpus.

OBJECTIVE: To determine the ability of a commercial cryotherapy system (Game Ready Equine) to cool the metacarpal subcutaneous tissue and the superficial digital flexor tendon (SDFT) in horses. STUDY DESIGN: Experimental study. ANIMALS OR SAMPLE POPULATION: Six healthy adult horses. METHODS: Thermocouples were implanted into the metacarpal subcutaneous tissues and the SDFT of six horses. Two treatments (cryotherapy or cryotherapy with 5-50 mmHg intermittent compression) were randomly assigned to forelimbs and performed for 20 minutes. Temperatures were compared to the target range of 10-19°C and between groups. RESULTS: Only one limb in the cryotherapy/compression group reached the target range after cryotherapy. Temperatures did not differ between treatment groups at time 0. Lowest temperatures achieved in the subcutaneous tissue (p = .0043) and SDFT (p = .005) were 4.9 and 7.6°C lower when intermittent compression was applied. Similarly, applying compression induced a maximum change in temperature of approximately 7.0°C in the subcutaneous tissue (p = .014) and 10.2°C in the SDFT (p = .0001). CONCLUSION: The cryotherapy system did not cool equine subcutaneous tissue or SDFT to the target temperature range, except in one limb. Combining cryotherapy with intermittent compression did result in lower temperatures and a greater change in temperature of the subcutaneous tissue and SDFT. CLINICAL SIGNIFICANCE: When using this cryotherapy system, the addition of intermittent compression should be considered to achieve lower temperatures and potentially greater reduction in inflammation. Further studies are warranted to determine the effect of longer treatment times, higher compression settings, and the optimal temperature for benefits in normal and diseased equine tissues.

Adrenalectomy for Secondary Malignancy: Patients, Outcomes, and Indications.

OBJECTIVE: The goal of this study was to examine a multi-institutional experience with adrenal metastases to describe survival outcomes and identify subpopulations who benefit from adrenal metastasectomy. BACKGROUND: Adrenalectomy for metastatic disease is well-described, although indications and outcomes are incompletely defined. METHODS: A retrospective cohort study was performed of patients undergoing adrenalectomy for secondary malignancy (2002-2015) at 6 institutions. The primary outcomes were disease free survival (DFS) and overall survival (OS). Analysis methods included Kaplan-Meier and Cox proportional hazards. RESULTS: Of 269 patients, mean age was 60.1 years; 50% were male. The most common primary malignancies were lung (n = 125, 47%), renal cell (n = 38, 14%), melanoma (n = 33, 12%), sarcoma (n = 18, 7%), and colorectal (n = 12, 5%). The median time to detection of adrenal metastasis after initial diagnosis of the primary tumor was 17 months (interquartile range: 6-41). Post-adrenalectomy, the median DFS was 18 months (1-year DFS: 54%, 5-year DFS: 31%). On multivariable analysis, lung primary was associated with longer DFS [hazard ratio (HR): 0.49, P = 0.008). Extra-adrenal oligometastatic disease at initial presentation (HR: 1.84, P = 0.016), larger tumor size (HR: 1.07, P = 0.013), chemotherapy as treatment of the primary tumor (HR: 2.07 P = 0.027) and adjuvant chemotherapy (HR: 1.95, P = 0.009) were associated with shorter DFS. Median OS was 53 months (1-year OS: 83%, 5-year OS: 43%). On multivariable analysis, extra-adrenal oligometastatic disease at adrenalectomy (HR: 1.74, P = 0.031), and incomplete resection of adrenal metastasis (R1 margins; HR: 1.62, P = 0.034; R2 margins; HR: 5.45, P = 0.002) were associated with shorter OS. CONCLUSIONS: Durable survival is observed in patients undergoing adrenal metastasectomy and should be considered for subjects with isolated adrenal metastases.

Somatic PIK3R1 variation as a cause of vascular malformations and overgrowth.

PURPOSE: Somatic activating variants in the PI3K-AKT pathway cause vascular malformations with and without overgrowth. We previously reported an individual with capillary and lymphatic malformation harboring a pathogenic somatic variant in PIK3R1, which encodes three PI3K complex regulatory subunits. Here, we investigate PIK3R1 in a large cohort with vascular anomalies and identify an additional 16 individuals with somatic mosaic variants in PIK3R1. METHODS: Affected tissue from individuals with vascular lesions and overgrowth recruited from a multisite collaborative network was studied. Next-generation sequencing targeting coding regions of cell-signaling and cancer-associated genes was performed followed by assessment of variant pathogenicity. RESULTS: The phenotypic and variant spectrum associated with somatic variation in PIK3R1 is reported herein. Variants occurred in the inter-SH2 or N-terminal SH2 domains of all three PIK3R1 protein products. Phenotypic features overlapped those of the PIK3CA-related overgrowth spectrum (PROS). These overlapping features included mixed vascular malformations, sandal toe gap deformity with macrodactyly, lymphatic malformations, venous ectasias, and overgrowth of soft tissue or bone. CONCLUSION: Somatic PIK3R1 variants sharing attributes with cancer-associated variants cause complex vascular malformations and overgrowth. The PIK3R1-associated phenotypic spectrum overlaps with PROS. These data extend understanding of the diverse phenotypic spectrum attributable to genetic variation in the PI3K-AKT pathway.

Time to Surgery and Thyroid Cancer Survival in the United States.

BACKGROUND: Longer time to surgery worsens survival in multiple malignancies, including lung, colorectal, and breast cancers, but limited data exist for well-differentiated thyroid cancer. We sought to investigate the impact of time to surgery on overall survival in patients with papillary thyroid cancer. METHODS: In a retrospective cohort study of the National Cancer Database, we used Cox proportional hazard models to investigate overall survival as a function of time between diagnosis and surgery for adults with papillary thyroid cancer, adjusting for demographic, patient, and cancer-related variables. Time to surgery was investigated both as a continuous variable and as intervals of 0-90 days, 90-180 days, and > 180 days. Subgroup analyses were conducted by T stage. RESULTS: Overall, 103,812 adults with papillary thyroid cancer were included from 2004 to 2016. Median follow-up was 55.2 months (interquartile range 28.4-89.5). Increasing time to surgery was associated with increased mortality: delaying by 91-180 days increased the risk by 30% (adjusted hazard ratio [aHR] 1.30, 95% CI 1.19-1.43) and delaying by over 180 days increased the risk by 94% (aHR 1.94, 95% CI 1.68-2.24). Five-year overall survival was 95.7% for 0-90 days, 93.0% for 91-180 days, and 87.9% for over 180 days. On subgroup analysis, increasing delay was associated with worse overall survival for T1, T2, and T3 tumors, but not T4 tumors. CONCLUSIONS: Increasing time to surgery in papillary thyroid cancer is associated with reduced overall survival. Further research is necessary to assess the impact of surgical delay on disease-specific survival.

Non-medullary Thyroid Cancer Susceptibility Genes: Evidence and Disease Spectrum.

BACKGROUND: The prevalence of non-medullary thyroid cancer (NMTC) is increasing worldwide. Although most NMTCs grow slowly, conventional therapies are less effective in advanced tumors. Approximately 5-15% of NMTCs have a significant germline genetic component. Awareness of the NMTC susceptibility genes may lead to earlier diagnosis and better cancer prevention. OBJECTIVE: The aim of this study was to provide the current panorama of susceptibility genes associated with NMTC and the spectrum of diseases associated with these genes. METHODS: Twenty-five candidate genes were identified by searching for relevant studies in PubMed. Each candidate gene was carefully checked using six authoritative genetic resources: ClinGen, National Comprehensive Cancer Network guidelines, Online Mendelian Inheritance in Man, Genetics Home Reference, GeneCards, and Gene-NCBI, and a validated natural language processing (NLP)-based literature review protocol was used to further assess gene-disease associations where there was ambiguity. RESULTS: Among 25 candidate genes, 10 (APC, DICER1, FOXE1, HABP2, NKX2-1, PRKAR1A, PTEN, SDHB, SDHD, and SRGAP1) were verified among the six genetic resources. Two additional genes, CHEK2 and SEC23B, were verified using the NLP protocol. Seventy-nine diseases were found to be associated with these 12 NMTC susceptibility genes. The following diseases were associated with more than one NMTC susceptibility gene: colorectal cancer, breast cancer, gastric cancer, kidney cancer, gastrointestinal stromal tumor, paraganglioma, pheochromocytoma, and benign skin conditions. CONCLUSION: Twelve genes predisposing to NMTC and their associated disease spectra were identified and verified. Clinicians should be aware that patients with certain pathogenic variants may require more aggressive surveillance beyond their thyroid cancer risk.

Smartphone Global Positioning System (GPS) Data Enhances Recovery Assessment After Breast Cancer Surgery.

PURPOSE: We sought to determine whether smartphone GPS data uncovered differences in recovery after breast-conserving surgery (BCS) and mastectomy, and how these data aligned with self-reported quality of life (QoL). METHODS: In a prospective pilot study, adult smartphone-owners undergoing breast surgery downloaded an application that continuously collected smartphone GPS data for 1 week preoperatively and 6 months postoperatively. QoL was assessed with the Short-Form-36 (SF36) via smartphone delivery preoperatively and 4 and 12 weeks postoperatively. Endpoints were trends in daily GPS-derived distance traveled and home time, as well as SF36 Physical (PCS) and Mental Component Scores (MCS) comparing BCS and mastectomy patients. RESULTS: Thirty-one patients were included. Sixteen BCS and fifteen mastectomy patients were followed for a mean of 201 (SD 161) and 174 (107) days, respectively. There were no baseline differences in demographics, PCS/MCS, home time, or distance traveled. Through 12 weeks postoperatively, mastectomy patients spent more time at home [e.g., week 4: 16.7 h 95% CI (14.3, 19.6) vs. 11.0 h (9.4, 12.9), p < 0.001] and traveled shorter distances [e.g., week 4: 52.5 km 95% CI (36.1, 76.0) vs. 107.7 km (75.8-152.9), p = 0.009] compared with BCS patients. There were no significant QoL differences throughout the study as measured by the MCS [e.g., week 4 difference: 7.83 95% CI (- 9.02, 24.7), p = 0.362] or PCS [e.g., week 4 difference: 8.14 (- 6.67, 22.9), p = 0.281]. GPS and QoL trends were uncorrelated (ρ < ± 0.26, p > 0.05). CONCLUSIONS: Differences in BCS and mastectomy recovery were successfully captured using smartphone GPS data. These data may describe currently unmeasured aspects of physical and mental recovery, which could supplement traditional and QoL outcomes to inform shared decision-making.