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Background: At a large quaternary health system, tissue specimens were frequently sent to the microbiology laboratory with an incorrect wound culture order meant for swab specimens due to poor electronic health record menu design. Wound cultures were also requested in chronic wound cases with a low index of suspicion for acute infection., Objective: To present a case report on specific changes to the design of the electronic test menu that resulted in higher numbers of appropriate ordering practices., Methods: "Wound Culture" test was renamed to "Wound Swab Culture" to distinguish from tissue specimens and "Tissue Culture" was added as a new available quick order in the microbiology menu alongside the existing wound culture quick order. In addition, a diagnostic questionnaire was added to "Wound Swab Culture" quick orders that inquired about the presence of pus/exudate and erythema and if the wound was a surgical wound to guide and assess the appropriateness of the culture order., Results: The number of tissue specimens erroneously submitted with a wound culture order decreased from 6.6% in July 2022 (pre-intervention) to 0% in July 2023 (post-intervention). The diagnostic questionnaire was utilized in 27.5% of wound culture orders. In 6 out of 98 orders (6.1%) the wound was not surgical and there was absence of pus/exudate and erythema (p = 0.038). Conversely, 92 out of 98 orders (93.9%) had at least one "Yes" response. Total numbers of tests six months before and after the test menu design interventions showed that tissue culture orders increased from 228 prior to the intervention to 349 post-intervention. Wound culture orders decreased from 575 to 460 (p < 0.0001)., Conclusions: Our case report underscores how targeted electronic health record optimization can be associated with more appropriate microbiology test ordering practices for potential wound infections., Competing Interests: JLW is a member of the Pathology Advisory Board for Sectra, Inc. The other authors declare no conflicts of interest in the research., (Thieme. All rights reserved.)

Objectives: Iron-deficiency anemia (IDA) is a common health problem worldwide, and up to 10% of adult patients with incidental IDA may have gastrointestinal cancer. A diagnosis of IDA can be established through a combination of laboratory tests, but it is often underrecognized until a patient becomes symptomatic. Based on advances in machine learning, we hypothesized that we could reduce the time to diagnosis by developing an IDA prediction model. Our goal was to develop 3 neural networks by using retrospective longitudinal outpatient laboratory data to predict the risk of IDA 3 to 6 months before traditional diagnosis., Methods: We analyzed retrospective outpatient electronic health record data between 2009 and 2020 from an academic medical center in northern Texas. We included laboratory features from 30,603 patients to develop 3 types of neural networks: artificial neural networks, long short-term memory cells, and gated recurrent units. The classifiers were trained using the Adam Optimizer across 200 random training-validation splits. We calculated accuracy, area under the receiving operating characteristic curve, sensitivity, and specificity in the testing split., Results: Although all models demonstrated comparable performance, the gated recurrent unit model outperformed the other 2, achieving an accuracy of 0.83, an area under the receiving operating characteristic curve of 0.89, a sensitivity of 0.75, and a specificity of 0.85 across 200 epochs., Conclusions: Our results showcase the feasibility of employing deep learning techniques for early prediction of IDA in the outpatient setting based on sequences of laboratory data, offering a substantial lead time for clinical intervention., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: This study assessed the effect of the COVID-19 pandemic on preventive care imaging and potential disparities because preventive care may be perceived as nonurgent. The objective was to identify the associations between the COVID-19 pandemic and changes in preventive imaging volumes for patients in general and as affected by race and ethnicities., Methods: The authors performed a retrospective observational study by extracting the weekly volumes of all imaging studies between January 7, 2019 and May 1, 2022 from a radiology data warehouse at a tertiary care medical center ( n =92,105 preventive imaging studies and 3,493,063 total radiology imaging studies) and compared preshutdown with postshutdown periods using a 2-sample t -test. Additional comparisons stratified by race and ethnicity were performed for mammograms and bone density examinations using interrupted time series models with negative binomial error distribution to assess the immediate level change and trends over time of preventive imaging volumes after shutdown., Results: The authors found a significant decrease in bilateral mammograms, bone density examinations, and aortic ultrasound examinations in the postshutdown period compared with those in the preshutdown period ( p <0.001, p =0.003, and p =0.001, respectively). There were no significant changes in low-dose computed tomography chest examinations ( p =0.46). The shutdown was associated with a significant immediate decrease in mammograms in the Hispanic and Latino group to approximately three quarters of its preshutdown level ( p =0.04). For bone density examinations, postshutdown weekly volumes tripled compared with the preshutdown volumes for Hispanic or Latino patients and doubled for non-Hispanic Black patients ( p <0.0001 for both). In comparison, a significant decrease was seen for Other patients (reduced to nearly a fifth of preshutdown volume) ( p <0.0001)., Conclusions: There was a significant decrease in overall volume of bilateral mammograms, bone density examinations, and aortic ultrasound examinations after pandemic shutdown. For mammograms, some of this decreasing trend was already seen before shutdown (such as for patients with Other race), so the shutdown was only specifically associated with an immediate decrease in mammogram levels in the Hispanic and Latino group. For bone density examinations, the shutdown was unexpectedly associated with an increase in volumes for Hispanic or Latino patients and non-Hispanic Black patients, which was countered by a significant steep decrease in volumes only for patients of Other race. Health systems should carefully explore their preventive screening examination volumes to determine which patients should be actively engaged to assure catch up on recommended care., (© 2024 The Author(s).)

Competing Interests: J.A. is a member of the Platform for AI Ethics, Netherlands Institute for Standardization (NEN), member of the NEN 7542 workgroup on standardization of medication process data and contract reviewer for the European Commission. S.A.-A. has received consulting fees from AstraZeneca, Agilent Biotechnologies, and Diazyme. A.D.B. has received grants or contracts from NIH and NSF, payment or honoraria from Adelphi University, and travel support from Microsoft. A.J.B. is a cofounder of and consultant to Personalis and NuMedii; consultant to Mango Tree Corporation, and in the recent past, Samsung, 10x Genomics, Helix, Pathway Genomics, and Verinata (Illumina); has served on paid advisory panels or boards for Geisinger Health, Regenstrief Institute, Gerson Lehman Group, AlphaSights, Covance, Novartis, Genentech, and Merck, and Roche; is a shareholder in Personalis and NuMedii; is a minor shareholder in Apple, Meta (Facebook), Alphabet (Google), Microsoft, Amazon, Snap, 10x Genomics, Illumina, Regeneron, Sanofi, Pfizer, Royalty Pharma, Moderna, Sutro, Doximity, BioNtech, Invitae, Pacific Biosciences, Editas Medicine, Nuna Health, Assay Depot, and Vet24seven, and several other non–health-related companies and mutual funds; and has received honoraria and travel reimbursement for invited talks from Johnson and Johnson, Roche, Genentech, Pfizer, Merck, Lilly, Takeda, Varian, Mars, Siemens, Optum, Abbott, Celgene, AstraZeneca, AbbVie, Westat, and many academic institutions, medical or disease specific foundations and associations, and health systems. A.J.B. receives royalty payments through Stanford University, for several patents and other disclosures licensed to NuMedii and Personalis. A.J.B.'s research has been funded by NIH, Peraton (as the prime on an NIH contract), Genentech, Johnson and Johnson, FDA, Robert Wood Johnson Foundation, Leon Lowenstein Foundation, Intervalien Foundation, Priscilla Chan and Mark Zuckerberg, the Barbara and Gerson Bakar Foundation, and in the recent past, the March of Dimes, Juvenile Diabetes Research Foundation, California Governor's Office of Planning and Research, California Institute for Regenerative Medicine, L'Oreal, and Progenity. A.B.C. has received consulting fees from Invitae Corporation. J.K.C. has received grants or contracts from the Office of Rural Health and Office of Healthcare and Equity, VHA. P.L.E. has received grants or contracts from NLM, NIAAA, and NCATS. Oluseyi Fayanju has received grants or contracts from GetSmarter. L.J.F. serves as a consultant to the American Psychiatric Association, has received travel support in relation to that role, and has also received grant support from NIMH. B.R.J. has received stock or stock options from Consent Vault, LLC. V.N.-J. occupies leadership or fiduciary roles with the Academy of Breastfeeding Medicine and West Central Illinois Breastfeeding Task Force. Ross Koppel has received consulting fees from advisors who contemplate investment in EHR companies, payment or honoraria from University at Buffalo, payment for expert testimony from the U.S. Department of Justice, stock or stock options from TrekIT, and occupies editor roles with the Journal of Applied Clinical Informatics and the International Journal of Medical Informatics. B.K. has received payment or honoraria from the Fall DeVos Medical Ethics Colloquy, and travel support to attend CSHI and AMIA conferences. C.U.L. has received royalties or licenses from Springer, has participated in a Data Safety monitoring board conducted by Lipika Samal at Harvard, and has received stock or stock options from Markel and Celanese. Z.C.L. has received consulting fees from Atrius Health, travel support from the University of Washington, Atrius Health, and Jackson Health System. R.J.M. has supported the present manuscript as a Texas Health Resources Clinical Scholar, has received grants or contracts from the Centers for Disease Control and Prevention, Sergey Brin Family Foundation, and Verily Life Sciences, payment or honoraria from Clinical Infectious Diseases, and occupies a leadership role with the Infectious Diseases Society of America. E.R.M. has received grants or contracts from the National Institute on Drug Abuse, the American Medical Association, and the Agency for Healthcare Research and Quality. A.B.N. has received grants or contracts from Royal Phillips and Eli Lilly, consulting fees from Intuity Medical, Roche, Eli Lilly, Sanofi, Greenberg Traurig, and Medtronic, payment or honoraria from The Doctors Company and TCOYD, and payment for expert testimony from AMFS. L.L.N. has received grants or contracts from GetPreCiSe, Florida State University, AHRQ, Baptist Memorial Healthcare Corporation, IBM Watson Health, and NIH/NIDDK. Deepti Pandita has received travel support from AMIA, has a patent pending with WellPulse app, and is a board member of AMIA. Raghuveer Puttagunta is a board member of Pennsylvania Medical Society. Angela Ryan is a member of AMIA and vice chair of the Australasian Institute of Digital Health. K.M.R. occupies a leadership role with the Society of Hospital Medicine Public Policy Committee. Neda Ratanawongsa occupies a leadership role with the San Francisco General Foundation. K.A.S. has received grants from Meds360 and Anonymous Foundation, honoraria from Stanford, travel support from the Society of Family Planning, and is a volunteer board member of the Society of Family Planning. Vignesh Subbian has received a grant from the National Science Foundation and occupies a leadership role with the AMIA ELSI Working Group. Ida Sim is a scientific advisor with Myovant Sciences. A.S. has received grants from NCATS Chicago Institute for Translational Medicine and PCORI Capricorn CRN, occupies leadership roles with the American Medical Informatics Association and IEEE Standards Association, and owns stock from Pfizer, Moderna, and J.B.S. holds leadership roles in AMIA and in the American College of Medical Informatics (ACMI), has received research funding from NIH and the Greenwall Foundation, and honoraria or consulting fees from the University of Kentucky, the University of Wisconsin, and the Icahn Mount Sinai School of Medicine. Peter Winkelstein has received a grant or contract from CTSA. J.X. has participated on a Data Safety Monitoring Board or Advisory Board with AfaSci, Inc. and Develo. C.Z. has received grants or contracts from CVS Foundation and Ariadne Labs, royalties, or licenses from UpToDate, consulting fees from Blue Cross Blue Shield of Massachusetts, and occupies leadership or fiduciary roles with the American Heart Association, Society for Maternal Fetal Medicine, and ACOG.

We describe a previously unreported bronchopulmonary foregut malformation wherein a segment of a bronchus of the lower lobe of the left lung in a 4-year-old girl was entirely esophageal in structure. No communication was identified between the tracheobronchial tree and the esophagus by radiologic examination or at surgery. The esophagus-like bronchus was associated with an adjacent atretic bronchus and a downstream cavity in the lower lobe of the left lung. The child sought clinical attention because of recurrent pulmonary infections localized to the lower lobe of the lung. We posit that this esophagus-like bronchus is a novel noncommunicating bronchopulmonary foregut malformation.

Background: The study of xeroderma pigmentosum has yielded unforeseen advances regarding how defects in the nucleotide excision repair pathway result in this devastating disease, but development of therapeutic strategies has trailed behind the mechanistic discoveries., Objectives: This review aims to cover clinical presentation, molecular mechanisms and current management, and highlights more recent insights into targeting the deficiencies secondary to the DNA repair defects to prevent skin cancer and/or neurological degeneration., Methods: This review article discusses novel therapeutic approaches to xeroderma pigmentosum that focus on metabolic defects downstream of nucleotide excision repair., Results: Current research demonstrates that specific sulfonylureas promote clearance of DNA damage and increase resistance to ultraviolet radiation in a cellular model of xeroderma pigmentosum. Moreover, nicotinamide attenuates the effects of ultraviolet radiation in cells, and caloric restriction decreases DNA damage burden in animal models of xeroderma pigmentosum., Conclusions: Clinical management of patients with xeroderma pigmentosum still focuses on preventative avoidance of sun exposure as opposed to therapies that would improve the patients' condition; thus, novel approaches to this disease are warranted., (© 2018 British Association of Dermatologists.)

The cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) pathway functions to incorporate inorganic Fe-S cofactors into a variety of proteins, including several DNA repair enzymes. However, the mechanisms regulating the CIA pathway are unknown. We describe here that the MAGE-F1-NSE1 E3 ubiquitin ligase regulates the CIA pathway through ubiquitination and degradation of the CIA-targeting protein MMS19. Overexpression or knockout of MAGE-F1 altered Fe-S incorporation into MMS19-dependent DNA repair enzymes, DNA repair capacity, sensitivity to DNA-damaging agents, and iron homeostasis. Intriguingly, MAGE-F1 has undergone adaptive pseudogenization in select mammalian lineages. In contrast, MAGE-F1 is highly amplified in multiple human cancer types and amplified tumors have increased mutational burden. Thus, flux through the CIA pathway can be regulated by degradation of the substrate-specifying MMS19 protein and its downregulation is a common feature in cancer and is evolutionarily controlled., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The Melanoma Antigen Gene (MAGE) protein family is a large, highly conserved group of proteins that share a common MAGE homology domain. Intriguingly, many MAGE proteins are restricted in expression to reproductive tissues, but are aberrantly expressed in a wide variety of cancer types. Originally discovered as antigens on tumor cells and developed as cancer immunotherapy targets, recent literature suggests a more prominent role for MAGEs in driving tumorigenesis. This review will highlight recent developments into the function of MAGEs as oncogenes, their mechanisms of action in regulation of ubiquitin ligases, and outstanding questions in the field., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

AMP-activated protein kinase (AMPK) is a master sensor and regulator of cellular energy status. Upon metabolic stress, AMPK suppresses anabolic and promotes catabolic processes to regain energy homeostasis. Cancer cells can occasionally suppress the growth-restrictive AMPK pathway by mutation of an upstream regulatory kinase. Here, we describe a widespread mechanism to suppress AMPK through its ubiquitination and degradation by the cancer-specific MAGE-A3/6-TRIM28 ubiquitin ligase. MAGE-A3 and MAGE-A6 are highly similar proteins normally expressed only in the male germline but frequently re-activated in human cancers. MAGE-A3/6 are necessary for cancer cell viability and are sufficient to drive tumorigenic properties of non-cancerous cells. Screening for targets of MAGE-A3/6-TRIM28 revealed that it ubiquitinates and degrades AMPKα1. This leads to inhibition of autophagy, activation of mTOR signaling, and hypersensitization to AMPK agonists, such as metformin. These findings elucidate a germline mechanism commonly hijacked in cancer to suppress AMPK., (Copyright © 2015 Elsevier Inc. All rights reserved.)