Activated T cells secrete an alternatively spliced form of common γ-chain that inhibits cytokine signaling and exacerbates inflammation.

The common γ-chain (γc) plays a central role in signaling by IL-2 and other γc-dependent cytokines. Here we report that activated T cells produce an alternatively spliced form of γc mRNA that results in protein expression and secretion of the γc extracellular domain. The soluble form of γc (sγc) is present in serum and directly binds to IL-2Rß and IL-7Rα proteins on T cells to inhibit cytokine signaling and promote inflammation. sγc suppressed IL-7 signaling to impair naive T cell survival during homeostasis and exacerbated Th17-cell-mediated inflammation by inhibiting IL-2 signaling upon T cell activation. Reciprocally, the severity of Th17-cell-mediated inflammatory diseases was markedly diminished in mice lacking sγc. Thus, sγc expression is a naturally occurring immunomodulator that regulates γc cytokine signaling and controls T cell activation and differentiation.

Local Recurrence Rates of Extramammary Paget Disease Are Lower After Mohs Micrographic Surgery Compared With Wide Local Excision: A Systematic Review and Meta-Analysis.

BACKGROUND: Extramammary Paget disease (EMPD) is a rare, slow growing neoplasm that presents most commonly in the anogenital region of older adults. OBJECTIVE: To analyze the difference in local recurrence rates of EMPD in patients treated with wide local excision (WLE) versus Mohs micrographic surgery (MMS). MATERIALS AND METHODS: A systematic review of the literature and meta-analysis were performed. Inclusion criteria were adults greater than 18 years of age with a diagnosis of EMPD who have undergone surgical intervention and had follow-up data. Studies were independently reviewed by 2 coinvestigators with discrepancies resolved by the principal investigator. RESULTS: Twenty-seven studies met the inclusion criteria. Patients had a 2.67 times higher chance of local recurrence after WLE than MMS (95% confidence interval [CI]:1.47, 4.85; p = .001). Meta-analysis of single-arm studies revealed a 7.3% local recurrence rate after MMS (95% CI: 0.039, 0.107; p < .001) versus a 26.3% recurrence rate after WLE (95% CI: 0.149, 0.376; p < .001). After excluding recurrent tumors, the odds ratio for recurrence in WLE versus MMS was 2.3 (95% CI: 0.285, 18.43, p = .435). CONCLUSION: There is a clinically and statistically increased risk of local recurrence of EMPD after WLE compared with MMS.

Surgical versus conservative management of tongue lacerations in the acute care setting: A systematic review of the literature.

Objective: The objective of this study was to determine whether suturing or conservative management of tongue lacerations results in differences in wound healing and functional outcome. The secondary aim was to identify whether antibiotics are required in the treatment of tongue lacerations. Methods: Studies published between December 1954 and August 2020 were extracted from MEDLINE via PubMed, Embase via OVID, CINAHL via EBSCO, Web of Science, and the Cochrane Library and evaluated for inclusion based on predetermined inclusion and exclusion criteria by two independent reviewers in accordance with PRISMA guidelines. Results: The search yielded a total of 16,111 articles, 124 of which were evaluated by full-text review, resulting in 11 articles included in this systematic review representing 142 unique cases of tongue lacerations. At least 26 lacerations (18.3%) included penetration of the muscle layer of the tongue, and 24 (16.9%) were classified as full-thickness lacerations. Thirty-five of the 142 tongue lacerations (24.6%) were sutured. The remaining lacerations underwent some form of conservative management. The majority of studies reported excellent healing of tongue lacerations regardless of the management method, with minimal scarring and excellent return to normal functional status. No cases of infection were reported. Conclusions: Current literature is inconsistent with regards to indications and guidelines for primary repair of tongue lacerations. The majority of tongue lacerations reported in the literature heal with excellent outcomes regardless of management method. Physician judgement along with patient and parental preference based on potential risks of the procedure should be used when deciding whether a tongue laceration requires primary repair. Tongue lacerations in otherwise healthy individuals are at very low risk of infection.

Vulvar apocrine hidradenocarcinoma arising in a hidradenoma papilliferum-A case report.

Hidradenoma papilliferum (HP) is a benign adnexal neoplasm of the vulva that typically presents as a unilateral, flesh-colored papule in the labium majus in middle-aged Caucasian women. It is considered to be a close counterpart of the intraductal papilloma of the breast. Malignant transformation is rare with few reports in the literature. We present a case of vulvar mammary-type apocrine hidradenocarcinoma arising in an HP.

Drug reaction with eosinophilia and systemic symptoms (DRESS) in the pediatric population: A systematic review of the literature.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a drug-induced hypersensitivity reaction that can have fatal complications. Although substantial data exist regarding DRESS in adults, to our knowledge, a systematic review of available literature has not been performed in children. OBJECTIVE: To review available data on DRESS in the pediatric population. METHODS: A systematic literature review was performed for pediatric (aged <18 years) patients with DRESS. RESULTS: We included 82 articles with 148 patients; of these, 97.9% experienced a skin rash, and the liver was the second most common organ involved (84.5%). Among 143 patients for which a treatment regimen was reported, 85.3% were treated with systemic steroids. Intravenous immunoglobulin alone failed to improve symptoms in 5 patients who were initially misdiagnosed, whereas those treated with intravenous immunoglobulin and steroids (2.7%) showed rapid clinical improvement. The mortality rate was low (3.0%). Complications included multiorgan failure and acute respiratory distress syndrome. LIMITATIONS: Limitations included limited availability of data for statistical analysis. CONCLUSION: Pediatric DRESS commonly involves the liver. With treatment, the prognosis is commonly good, but serious complications may occur. Corticosteroids, possibly in conjunction with intravenous immunoglobulin in severe cases, may serve as an effective, valuable treatment of pediatric DRESS.

Microvascular lining options for subtotal and total nasal reconstruction: A scoping review.

BACKGROUND: Restoration of nasal lining is essential in reconstruction of subtotal/total nasal defects. When local flaps are inadequate, a microvascular flap should be used. The purpose of this scoping review is to map the literature and identify the described flap options for subtotal/total nasal reconstruction. Further to that, we will summarize the stated advantages and disadvantages, evaluate functional and esthetic outcomes, and appraise the current body of literature. METHODS: An electronic literature search was completed. Studies required adult patients with subtotal/total nasal defects and lining reconstruction with microvascular free flap. Two independent reviewers completed screening and data extraction. Flap characteristics, advantages, disadvantages, functional and esthetic outcomes were reviewed. Two independent reviewers evaluated study quality. RESULTS: Of 305 initial articles, 22 studies were included (13 case reports, 9 case series) accounting for 65 flaps. Microvascular flaps varied by composition and anatomical location. For functional outcome, 13 studies used clinical exam by surgeon, 5 reported patient being satisfied, 3 studies used endoscopy, and 1 study used nasometry. Assessing esthetic outcome, 13 studies used clinical exam by surgeon, 5 studies reported patient being satisfied, 1 study used patient-reported outcome measures, and 16 studies included photos. Study quality (modified CARE and PROCESS checklists) was deemed poor. Quality of available evidence was level IV. CONCLUSIONS: Microvascular free flaps for nasal reconstruction, confer an overall satisfactory functional and esthetic outcome. All studies lack a systematic and comprehensive approach to assessing and reporting these outcomes. Future research should provide objective assessment and utilize patient reported outcome measures.

Dermatologic manifestations of solid organ transplantation-associated graft-versus-host disease: A systematic review.

BACKGROUND: Graft-versus-host-disease (GVHD) after solid organ transplantation (SOT) is extremely rare. OBJECTIVE: To investigate the dermatologic manifestations and clinical outcomes of SOT GVHD. METHODS: Systematic literature review of SOT GVHD. RESULTS: After full-text article review, we included 61 articles, representing 115 patients and 126 transplanted organs. The most commonly transplanted organ was the liver (n = 81). Among 115 patients, 101 (87.8%) developed skin involvement. The eruption appeared an average of 48.3 days (range, 3-243 days) posttransplant and was pruritic in 5 of 101 (4.9%) cases. The eruption was described as morbilliform in 2 patients (1.9%), confluent in 6 (5.9%), and desquamative in 4 (3.9%) cases. In many cases, specific dermatologic descriptions were lacking. The mortality rate was 72.2%. Relative time of death was reported in 23 patients who died during the follow-up period. These patients died an average of 99.2 days (range, 22-270 days) posttransplant, or 50.9 days after the appearance of dermatologic symptoms. Frequent causes of death were sepsis and multiorgan failure. LIMITATIONS: Incomplete descriptions of skin findings and potential publication bias resulting in publication of only the most severe cases. CONCLUSIONS: GVHD is a potentially fatal condition that can occur after SOT and often presents with a skin rash. We recommend that dermatologists have a low threshold to consider and pursue this diagnosis in the setting of post-SOT skin eruption.

Clinical and histopathologic manifestations of solid organ transplantation-associated graft-versus-host disease involving the skin: A single-center retrospective study.

BACKGROUND: Graft-versus-host disease (GVHD) following solid organ transplantation (SOT) is extremely rare and infrequently described in the dermatologic literature. METHODS: We performed a retrospective clinicopathologic review of our institution's experience with patients diagnosed with SOT-associated GVHD (SOT GVHD) (May 1, 1996 to September 1, 2017). RESULTS: Of nine patients with SOT GVHD, seven had undergone liver transplantation, while two had undergone lung transplantation. All presented initially with a skin eruption, which developed an average of 63 days (range: 11-162 days) post transplant. The average time to diagnosis following the onset of the skin eruption was 12 days (range: 0-54 days). Diagnosis was often delayed because of a competing diagnosis of drug reaction. Frequent skin findings included pruritic erythematous to violaceous macules and papules with desquamation. Histopathology showed vacuolar interface dermatitis in 12 of 15 cases (80.0%). Of the 11 specimens in which a hair follicle was present for evaluation, vacuolar interface changes around the hair follicle were present in eight (72.7%) cases. Seven patients (77.8%) died from complications during the follow-up period. CONCLUSIONS: SOT GVHD presents initially with skin involvement, is associated with vacuolar interface changes on skin biopsy, and is associated with a high mortality rate. Clinicopathologic correlation is required for accurate diagnosis.

The Association of Cognitive Reserve in Chronic-Phase Functional and Neuropsychological Outcomes Following Traumatic Brain Injury.

OBJECTIVE: Examine the association of cognitive reserve (CR) factors (estimated premorbid intelligence quotient [IQ], years of education, and occupational attainment) and traumatic brain injury (TBI) severity with functional and neuropsychological outcomes 1 to 5 years following TBI. PARTICIPANTS: Patients with mild (N = 58), moderate (N = 25), or severe (N = 17) TBI. MAIN MEASURES: Cognitive reserve factors (estimated premorbid IQ, years of education, and occupational attainment); neuropsychological test battery; Glasgow Outcome Scale-Extended; Short Form-36 Health Survey. ANALYSES: Spearman-Brown correlations, linear regression models, and analyses of covariance were used to analyze the relation between CR factors and outcome measures. RESULTS: Analyses revealed significant relations between estimated premorbid IQ and neuropsychological outcomes (P < .004): California Verbal Learning Test, Wechsler Adult Intelligence Scale-Fourth Edition working memory, Booklet Category Test, Trail Making Test B, and Grooved Pegboard Test. There was also a significant correlation between estimated premorbid IQ and Wechsler Adult Intelligence Scale-Fourth Edition processing speed. Years of education had significant relations with California Verbal Learning Test and Wechsler Adult Intelligence Scale-Fourth Edition working memory and processing speed scores. There were significant differences between TBI severity groups and performance on the Trail Making Test A, Grooved Pegboard Test, and Finger Tapping Test. CONCLUSIONS: Cognitive reserve factors may be associated with outcomes following TBI. Additional alternatives to TBI severity are needed to help guide rehabilitative planning postinjury.

Ikaros is required to survive positive selection and to maintain clonal diversity during T-cell development in the thymus.

The zinc-finger protein Ikaros is a key player in T-cell development and a potent tumor suppressor in thymocytes. To understand the molecular basis of its function, we disabled Ikaros activity in vivo using a dominant negative Ikaros transgene (DN-IkTg). In DN-IkTg mice, T-cell development was severely suppressed, and positively selected thymocytes clonally expanded, resulting in a small thymus with a heavily skewed T-cell receptor (TCR) repertoire. Notably, DN-IkTg induced vigorous proliferation concomitant to downregulation of antiapoptotic factor expression such as Bcl2. Ikaros activity was required during positive selection, and specifically at the CD4(+)CD8(lo) intermediate stage of thymocyte differentiation, where it prevented persistent TCR signals from inducing aberrant proliferation and expansion. In particular, DN-IkTg induced the accumulation of CD4 single-positive (SP) thymocytes with a developmentally transitional phenotype, and it imposed a developmental arrest accompanied by massive apoptosis. Thus, we identified an in vivo requirement for Ikaros function, which is to suppress the proliferative potential of persistent TCR signals and to promote the survival and differentiation of positively selected thymocytes.

An in vivo IL-7 requirement for peripheral Foxp3+ regulatory T cell homeostasis.

All T cells are dependent on IL-7 for their development and for homeostasis. Foxp3(+) regulatory T cells (Tregs) are unique among T cells in that they are dependent on IL-2. Whether such IL-2 dependency is distinct from or in addition to an IL-7 requirement has been a confounding issue, particularly because of the absence of an adequate experimental system to address this question. In this study, we present a novel in vivo mouse model where IL-2 expression is intact but IL-7 expression was geographically limited to the thymus. Consequently, IL-7 is not available in peripheral tissues. Such mice were generated by introducing a thymocyte-specific IL-7 transgene onto an IL-7 null background. In these mice, T cell development in the thymus, including Foxp3(+) Treg numbers, was completely restored, which correlates with the thymus-specific expression of transgenic IL-7. In peripheral cells, however, IL-7 expression was terminated, which resulted in a general paucity of T cells and a dramatic reduction of Foxp3(+) Treg numbers. Loss of Tregs was further accompanied by a significant reduction in Foxp3(+) expression levels. These data suggest that peripheral IL-7 is not only necessary for Treg survival but also for upregulating Foxp3 expression. Collectively, we assessed the effect of a selective peripheral IL-7 deficiency in the presence of a fully functional thymus, and we document a critical requirement for in vivo IL-7 in T cell maintenance and specifically in Foxp3(+) cell homeostasis.

Utilizing Mobile Robotics for Pelvic Perturbations to Improve Balance and Cognitive Performance in Older Adults: A Randomized Controlled Trial.

Late-life balance disorders remain a severe problem with fatal consequences. Perturbation-based balance training (PBT), a form of rehabilitation that intentionally introduces small, unpredictable disruptions to an individual's gait cycle, can improve balance. The Tethered Pelvic Assist Device (TPAD) is a cable-driven robotic trainer that applies perturbations to the user's pelvis during treadmill walking. Earlier work showcased improved gait stability and the first evidence of increased cognition acutely. The mobile Tethered Pelvic Assist Device (mTPAD), a portable version of the TPAD, applies perturbations to a pelvic belt via a posterior walker during overground gait, as opposed to treadmill walking. Forty healthy older adults were randomly assigned to a control group (CG, n = 20) without mTPAD PBT or an experimental group (EG, n = 20) with mTPAD PBT for a two-day study. Day 1 consisted of baseline anthropometrics, vitals, and functional and cognitive measurements. Day 2 consisted of training with the mTPAD and post-interventional cognitive and functional measurements. Results revealed that the EG significantly outperformed the CG in cognitive and functional tasks while showcasing increased confidence in mobility. Gait analysis demonstrated that the mTPAD PBT significantly improved mediolateral stability during lateral perturbations. To our knowledge, our study is the first randomized, large group (n = 40) clinical study exploring new mobile perturbation-based robotic gait training technology.

Utilizing mobile robotics for pelvic perturbations to improve balance and cognitive performance in older adults: a randomized controlled trial.

Late-life balance disorders remain a severe problem with fatal consequences. Perturbation-based balance training (PBT), a form of rehabilitation that intentionally introduces small, unpredictable disruptions to an individual's gait cycle, can improve balance. The Tethered Pelvic Assist Device (TPAD) is a cable-driven robotic trainer that applies perturbations to the user's pelvis during treadmill walking. Earlier work showcased improved gait stability and the first evidence of increased cognition acutely. The mobile Tethered Pelvic Assist Device (mTPAD), a portable version of the TPAD, applies perturbations to a pelvic belt via a posterior walker during overground gait, as opposed to treadmill walking. Forty healthy older adults were randomly assigned to a control group (CG, n = 20) without mTPAD PBT or an experimental group (EG, n = 20) with mTPAD PBT for a two-day study. Day 1 consisted of baseline anthropometrics, vitals, and functional and cognitive measurements. Day 2 consisted of training with the mTPAD and post-interventional cognitive and functional measurements. Results revealed that the EG significantly outperformed the CG in several cognitive (SDMT-C and TMT-B) and functional (BBS and 4-Stage Balance: one-foot stand) measurements while showcasing increased confidence in mobility based on FES-I. To our knowledge, our study is the first randomized, large group (n = 40) clinical study exploring new mobile perturbation-based robotic gait training technology.

Applications of machine learning in routine laboratory medicine: Current state and future directions.

Machine learning is able to leverage large amounts of data to infer complex patterns that are otherwise beyond the capabilities of rule-based systems and human experts. Its application to laboratory medicine is particularly exciting, as laboratory testing provides much of the foundation for clinical decision making. In this article, we provide a brief introduction to machine learning for the medical professional in addition to a comprehensive literature review outlining the current state of machine learning as it has been applied to routine laboratory medicine. Although still in its early stages, machine learning has been used to automate laboratory tasks, optimize utilization, and provide personalized reference ranges and test interpretation. The published literature leads us to believe that machine learning will be an area of increasing importance for the laboratory practitioner. We envision the laboratory of the future will utilize these methods to make significant improvements in efficiency and diagnostic precision.

Antibiotic Prophylaxis in Alloplastic Breast Reconstruction: Regimens and Outcomes.

PURPOSE: Surgical site infections (SSI) in prosthesis-based breast reconstruction can have a significant impact on patient outcome. Despite current CDC (Centers for Disease Control and Prevention) guidelines recommending 24 hours of postoperative antibiotics, various perioperative antimicrobial regimens are reported in the literature. Consensus on the optimal duration of antibiotics remains unclear. In this study, the aim is to compare the incidence of surgical site infections following different antibiotic durations in alloplastic breast reconstruction. METHODS: In this retrospective cohort study, all consecutive patients who underwent expander/implant-based breast reconstruction between January 2009 and December 2014 at a tertiary centre were included. Data on patient demographics, risk factors, operative time, choice and timing of antibiotic used before surgery, and the duration of postoperative antibiotic use were collected. The primary outcome, SSI, is defined according to CDC criteria. RESULTS: A total of 507 consecutive expander/implant-based cases were included. Minimum follow-up time was 1 year. The overall infection incidence was 14% (95% CI: 11%-17%), and the rate of subsequent explantation was 8%. Of the infected cases, 80% (45/56) received 1 week of postoperative antibiotic, while 20% (11/56) had a prolonged course of antibiotics (2-3 weeks; P = .003, odds ratio [OR] = 2.9; 95% CI: 1.4-5.8). Most infections were superficial (65%). Prior history of radiation treatment was identified as a risk factor for developing surgical site infection (P = .02). CONCLUSION: Overall infection rate and risk factors for infections are in keeping with current literature. Prescribing one week of postoperative antibiotic was found to be associated with a higher incidence of SSI compared to a more prolonged antibiotic regimen.

OBJECTIF: Les infections au site opératoire (ISO) des reconstructions mammaires avec prothèse peuvent avoir des conséquences importantes sur le pronostic de la patiente. Malgré les directives à jour des Centers for Disease Control and Prevention (CDC) recommandant la prise d'antibiotiques pendant 24 heures après l'opération, les publications font état de diverses posologies antimicrobiennes périopératoires. La durée consensuelle optimale de la prise d'antibiotiques n'est pas bien établie. Dans la présente étude, les chercheurs comparent l'incidence d'ISO après une reconstruction mammaire alloplastique en fonction de diverses durées d'antibiothérapie. MÉTHODOLOGIE: Toutes les patientes consécutives qui ont subi une reconstruction mammaire par expanseurs ou par implants entre janvier 2009 et décembre 2014 dans un centre de soins tertiaires ont participé à la présente étude rétrospective de cohorte. Les chercheurs ont colligé les données sur la démographie, les facteurs de risque, la durée de l'opération, le choix et le moment de l'antibiothérapie préopératoire ainsi que la durée de l'antibiothérapie postopératoire. Le résultat clinique primaire, les ISO, est défini d'après les critères des CDC. RÉSULTATS: Au total, 507 cas consécutifs d'expanseurs ou d'implants ont été inclus dans l'étude. Le suivi était d'une durée minimale d'un an. L'incidence globale d'infection s'élevait à 14 % (IC à 95 %, 11 % à 17 %) et le taux d'explantations subséquent, à 8 %. De plus, 80 % des cas d'infection (45 sur 56) avaient reçu une antibiothérapie postopératoire d'une semaine, et 20 % (11 sur 56), une antibiothérapie prolongée (de 2 à 3 semaines; p=0,003, rapport de cote=2,9; IC à 95 %, 1,4 à 5,8). La plupart des infections étaient superficielles (65 %). Une radiothérapie antérieure était considérée comme un facteur de risque d'ISO (p=0,02). CONCLUSION: Le taux et les facteurs de risque globaux d'infection sont conformes aux publications à ce jour. La prescription d'antibiotiques pendant une semaine après l'opération était associée à une plus forte incidence d'ISO qu'une antibiothérapie plus longue.

Tipping the Scales With Zebrafish to Understand Adaptive Tumor Immunity.

The future of improved immunotherapy against cancer depends on an in-depth understanding of the dynamic interactions between the immune system and tumors. Over the past two decades, the zebrafish has served as a valuable model system to provide fresh insights into both the development of the immune system and the etiologies of many different cancers. This well-established foundation of knowledge combined with the imaging and genetic capacities of the zebrafish provides a new frontier in cancer immunology research. In this review, we provide an overview of the development of the zebrafish immune system along with a side-by-side comparison of its human counterpart. We then introduce components of the adaptive immune system with a focus on their roles in the tumor microenvironment (TME) of teleosts. In addition, we summarize zebrafish models developed for the study of cancer and adaptive immunity along with other available tools and technology afforded by this experimental system. Finally, we discuss some recent research conducted using the zebrafish to investigate adaptive immune cell-tumor interactions. Without a doubt, the zebrafish will arise as one of the driving forces to help expand the knowledge of tumor immunity and facilitate the development of improved anti-cancer immunotherapy in the foreseeable future.

Machine Learning Predictability of Clinical Next Generation Sequencing for Hematologic Malignancies to Guide High-Value Precision Medicine.

Advancing diagnostic testing capabilities such as clinical next generation sequencing methods offer the potential to diagnose, risk stratify, and guide specialized treatment, but must be balanced against the escalating costs of healthcare to identify patient cases most likely to benefit from them. Heme-STAMP (Stanford Actionable Mutation Panel for Hematopoietic and Lymphoid Malignancies) is one such next generation sequencing test. Our objective is to assess how well Heme-STAMP pathological variants can be predicted given electronic health records data available at the time of test ordering. The model demonstrated AUROC 0.74 (95% CI: [0.72, 0.76]) with 99% negative predictive value at 6% specificity. A benchmark for comparison is the prevalence of positive results in the dataset at 58.7%. Identifying patients with very low or very high predicted probabilities of finding actionable mutations (positive result) could guide more precise high-value selection of patient cases to test.

Risk Factors for Keratinocyte Carcinoma in Recipients of Allogeneic Hematopoietic Cell Transplants.

Importance: Allogeneic hematopoietic cell transplant (alloHCT) is known to increase the risk for keratinocyte carcinoma. The extent to which host characteristics, including pigmentary phenotype and UV radiation exposure, contribute is unknown. Objective: To identify and validate independent risk factors for keratinocyte carcinoma after alloHCT, including those associated with the transplant and the host. Design, Setting, and Participants: This retrospective cohort study analyzed a consecutive sample of alloHCT recipients from January 1, 2000, to December 31, 2014, at the Mayo Clinic, Rochester, Minnesota (n = 872) and University Hospitals Cleveland Medical Center, Cleveland, Ohio (n = 147). Participants from the Mayo Clinic were randomly allocated (2:1) into discovery (n = 581) and validation (n = 291) cohorts. Time to first keratinocyte carcinoma and information about transplant- and host-associated risk factors were extracted. A multivariate keratinocyte carcinoma risk model was created using a stepwise Cox proportional hazards regression model with P ≤ .05 for entry that incorporated all covariates that were individually statistically significant at α = 0.05 in the discovery cohort. The risk model was first internally validated using the Mayo Clinic validation cohort and then externally validated using the independent cohort of alloHCT recipients at University Hospitals Cleveland Medical Center. Data were analyzed from March 13, 2018, to June 12, 2019. Exposures: Allogeneic hematopoietic cell transplant. Main Outcomes and Measures: The primary outcome was time to development of the first cutaneous keratinocyte carcinoma after alloHCT; secondary outcome, time to development of the first individual basal and/or squamous cell carcinoma after alloHCT. Results: Of the 872 alloHCT recipients identified in the Mayo Clinic cohort (520 men [59.6%]; mean [SD] age, 48.3 [12.6] years), 95 (10.9%) developed keratinocyte carcinoma after alloHCT during 5349 person-years of follow-up. Of the 147 alloHCT recipients in the exernal validation cohort (86 men [58.5%]; mean [SD] age, 47.9 [17.5] years), 18 (12.2%) developed keratinocyte carcinoma after alloHCT in 880 person-years of follow up. Risk factors independently associated with keratinocyte carcinoma after alloHCT included age (hazard ratio [HR] per 10 years, 1.72; 95% CI, 1.21-2.42), chronic lymphocytic leukemia (HR, 2.47; 95% CI, 1.20-5.09), clinically photodamaged skin (HR, 3.47; 95% CI, 1.87-6.41), and history of cutaneous squamous cell carcinoma (HR, 2.60; 95% CI, 1.41-5.91). Harrell concordance statistics were 0.81 (95% CI, 0.72-0.90) and 0.86 (95% CI, 0.74-0.98) for internal and external validation of the keratinocyte carcinoma risk model, respectively. Conclusions and Relevance: This study found validated independent risk factors for keratinocyte carcinoma after alloHCT that are enriched with host- compared with transplant-associated risk factors. These findings highlight the importance of assessing host-associated risk factors for keratinocyte carcinoma in patients eligible for alloHCT. Future studies should examine whether keratinocyte carcinoma risk stratification before alloHCT may inform long-term surveillance strategies.

Use of an EHR-Integrated Point-of-Care Mobile Medical Photography Application in a Pediatric Emergency Department.

BACKGROUND: Mobile applications allow health care providers to capture point-of-care medical photographs and transfer them to the electronic health record (EHR). It is unclear how providers use these photographs or how they affect clinical care. OBJECTIVES: We aimed to understand the content, purpose, and outcomes of point-of-care medical photography performed in the pediatric emergency department (ED) at large academic medical center. METHODS: A retrospective chart review was conducted of patients <21 years of age who were seen in the ED and photographed between March 29, 2015 and July 1, 2017 using a secure smartphone application integrated with the EHR. Inter-rater agreement and reliability between the two reviewers was assessed for the first 50 charts, and any discrepancies in interpretation were resolved before proceeding with the remaining data abstraction. The documented rationale for photography, content of photographs, and outcomes were recorded. RESULTS: We identified 619 clinical encounters involving photographs of 605 patients who were eligible for inclusion. Skin was photographed in 499 (81%). The most common finding was rash (N = 177; 29%). Photos were of acceptable quality, with 569 (94%) achieving a score between 4 and 5 out of 5. The primary use of photography was documentation (N = 334; 54%), though teleconsultation was noted in 38 (6%). Nearly one-third (N = 187; 30%) of patients were seen in the ED or outpatient clinic for any reason within 2 weeks, and in 25 (13%), clinical notes explicitly referenced the initial photograph(s). In 53 (9%) cases, patients were photographed at a clinical visit in the subsequent 2 weeks, suggesting that photography was used to track changes over time. CONCLUSION: Documentation of findings using mobile point-of-care photography allows for high-fidelity documentation and facilitates continuity of care.

The CRISP-Q study: Communicating the risks and benefits of colorectal cancer screening

Background and objectives: Many Australians at average risk of colorectal cancer (CRC) are undergoing unnecessary colonoscopic screening, while many at increased risk are getting inadequate screening. The aim of this study was to test different ways of communicating the risks and benefits of CRC screening, as part of the development of a CRC risk prediction (CRISP) tool. Method: General practice patients were shown five different risk presentations for hypothetical 'average' and 'increased' risk cases and were asked to choose the screening method they would undergo. Associations were explored between risk presentation type and 'risk-appropriate screening' choice. Results: All risk formats were associated with improved risk-appropriate screening by participants (n = 204); however, there was a statistical trend favouring absolute risk with a government recommendation and an 'expected frequency tree'. The icon array was most weakly associated with appropriate screening. Discussion: This research will inform approaches to communicating risk in CRISP and may be of wider relevance to supporting informed decisions about cancer screening.