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Of 319 children with invasive candidiasis, 67 (21%) transitioned from intravenous to enteral antifungal therapy. Eight (12%) transitioned back to intravenous antifungal therapy, one due to perceived treatment failure defined by clinical progression or worsening. Global treatment response at study completion was success in 66 participants transitioned to enteral therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. 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.)

Aims: The Shock Academic Research Consortium (SHARC) recently proposed pragmatic consensus definitions to standardize classification of cardiogenic shock (CS) in registries and clinical trials. We aimed to describe contemporary CS epidemiology using the SHARC definitions in a cardiac intensive care unit (CICU) population., Methods and Results: The Critical Care Cardiology Trials Network (CCCTN) is a multinational research network of advanced CICUs coordinated by the TIMI Study Group (Boston, MA). Cardiogenic shock was defined as a cardiac disorder resulting in SBP < 90 mmHg for ≥30 min [or the need for vasopressors, inotropes, or mechanical circulatory support (MCS) to maintain SBP ≥ 90 mmHg] with evidence of hypoperfusion. Primary aetiologic categories included acute myocardial infarction-related CS (AMI-CS), heart failure-related CS (HF-CS), and non-myocardial (secondary) CS. Post-cardiotomy CS was not included. Heart failure-related CS was further subcategorized as de novo vs. acute-on-chronic HF-CS. Patients with both cardiogenic and non-cardiogenic components of shock were classified separately as mixed CS. Of 8974 patients meeting shock criteria (2017-23), 65% had isolated CS and 17% had mixed shock. Among patients with CS (n = 5869), 27% had AMI-CS (65% STEMI), 59% HF-CS (72% acute-on-chronic, 28% de novo), and 14% secondary CS. Patients with AMI-CS and de novo HF-CS were most likely to have had concomitant cardiac arrest (P < 0.001). Patients with AMI-CS and mixed CS were most likely to present in more severe shock stages (SCAI D or E; P < 0.001). Temporary MCS use was highest in AMI-CS (59%). In-hospital mortality was highest in mixed CS (48%), followed by AMI-CS (41%), similar in de novo HF-CS (31%) and secondary CS (31%), and lowest in acute-on-chronic HF-CS (25%; P < 0.001)., Conclusion: SHARC consensus definitions for CS classification can be pragmatically applied in contemporary registries and reveal discrete subpopulations of CS with distinct phenotypes and outcomes that may be relevant to clinical practice and future research., Competing Interests: Conflict of interest: D.D.B., E.A.B., S.M.P., V.M.B.-Z., J.-G.P., and D.A.M. are members of the TIMI Study Group, which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Abiomed, Amgen, Anthos Therapeutics, ARCA Biopharma, Inc., AstraZeneca, Bayer HealthCare Pharmaceuticals, Inc., Daiichi-Sankyo, Eisai, Intarcia, Ionis Pharmaceuticals, Inc., Janssen Research and Development, LLC, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Inc., Roche, Siemens Healthcare Diagnostics, Inc., Softcell Medical Limited, The Medicines Company, and Zora Biosciences. D.D.B. has received consulting fees from AstraZeneca, Pfizer, Mobility Bio, Inc., and Youngene Therapeutics; honoraria from the Metabolic Endocrine Education Foundation, and USV Private Limited; and participates on clinical endpoint committees for studies sponsored by Beckman Coulter, Kowa Pharmaceuticals, Novo Nordisk, and Tosoh Biosciences. L.S. reports speakers bureaus for Abiomed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Aims: Most paediatric inflammatory bowel disease [IBD] studies are performed after medications are approved in adults, and the majority of participants in these studies are adolescents. We hypothesised that adolescent-onset IBD is not fundamentally different from adult-onset IBD. If this is correct, the value of delaying access to novel drugs in adolescents becomes questioned., Methods: Data from 11 randomised, double-blind, placebo-controlled, adult Phases 2 and 3 trials of four biologics were analysed. Participants were categorised as having adolescent- or adult-onset disease [diagnosed 12 to <18, or ≥18 years]. Multivariable modelling explored the association between age at diagnosis and response to treatment, after adjustment for disease duration, extent, and severity at baseline. Data from dose arms were pooled to evaluate similarity of therapeutic response between adolescent- and adult-onset IBD within the same trial [not between doses or across trials]. Ratios of odds ratios [ORs] between the two groups were evaluated., Results: Data from 6283 study participants (2575 with Crohn's disease [CD], 3708 with ulcerative colitis [UC]) were evaluated. Of 2575 study participants with CD, 325 were 12-<18 years old at diagnosis; 836 participants [32.4%] received placebo. Of 3708 participants with UC, 221 were 12-<18 years old at diagnosis; 1212 [33%] were receiving placebo. The majority of the ratios of ORs were within 2-fold, suggesting that responses in adolescent- and adult-onset participants are generally similar., Conclusion: Data presented lend support for extrapolating efficacy of biologics from adults to adolescents with IBD, which would facilitate earlier labelling and patient access., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. 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.)

Background: There are limited data on the risk of new-onset anxiety disorders in patients with hidradenitis suppurativa (HS)., Objectives: To compare the risk of new-onset anxiety disorder in patients with HS and controls, and to describe risk factors for the development of anxiety in patients with HS., Methods: We carried out a retrospective cohort analysis of a US electronic health records database between 2011 and 2020. Adults newly diagnosed with HS at a dermatology or primary care visit and control participants were included. The primary outcome was a new diagnosis of generalized anxiety disorder, phobic disorders, panic disorder or unspecified anxiety. Cox proportional hazards regression was used to compare the crude risk of any anxiety disorder between groups and to assess the independent association with HS while controlling for potential demographic, clinical and healthcare-related confounders., Results: Among 9597 patients with HS and 959 493 controls, the incidence rate (IR) of anxiety was 5.74 and 3.86 per 100 person-years (PY), respectively. The crude risk among all patients was 48% higher for those with HS vs. controls [hazard ratio (HR) 1.48, 95% confidence interval (CI) 1.40-1.55]. When stratified by index encounter type, patients with HS had 2.43 (95% CI 2.13-2.77) times the risk of anxiety disorder than dermatology controls and 1.46 (95%CI 1.38-1.55) times the risk than primary care controls. The adjusted HR for patients with HS vs. controls was 1.11 (95% CI 1.05-1.17) overall, 1.26 (95% CI 1.07-1.48) in the dermatology subgroup and 1.07 (95% CI 1.01-1.13) in the primary care subgroup. Risk factors for an incident anxiety diagnosis among patients with HS included depression (HR 1.69, 95% CI 1.48-1.93), female sex (HR 1.41, 95% CI 1.23-1.60), younger age (HR 0.87 per 10-year increase, 95% CI 0.84-0.90), White race, in the Medicaid insurance programme (HR 1.22, 95% CI 1.07-1.40), tobacco smoking (HR 1.16, 95% CI 1.03-1.31) and having one or more emergency department visits in the year before a HS diagnosis. Absolute IRs of anxiety disorders were highest among patients with HS who were aged 18-29 years (7.10 per 100 PY), female (6.34 per 100 PY) and White (6.79 per 100 PY)., Conclusions: HS is independently associated with an increased risk of anxiety disorders. An increased risk remains but is attenuated when confounders are controlled for. The relative risk may be particularly high in patients managed by dermatologists., Competing Interests: Conflicts of interest A.G. is an advisor for AbbVie, Aclaris Therapeutics, Anaptys Bio, Aristea Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Cosmo Pharmaceutical, Incyte, Insmed, Janssen, Novartis, Pfizer, Sonoma Biotherapeutics, UCB, Union Therapeutics, Ventyx Biosciences and Viela Biosciences, and receives honoraria. A.G. receives research grants from AbbVie, UCB, the National Psoriasis Foundation and the CHORD COUSIN Collaboration (C3)., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. 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.)

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are multipurpose agents effective in improving glycemic control in patients with type 2 diabetes while also achieving weight loss and risk reduction of major cardiovascular (CV) events and chronic kidney disease progression. With their increased utility in diabetes, obesity, CV health and renal protection, the use of GLP-1RAs has increased. However, with this increased use, there have also been increased reports of associated kidney adverse events, including case reports of acute interstitial nephritis (AIN) associated with GLP-1RA use. We report the data from the Food and Drug Administration adverse event reporting system (FAERS) in relation to GLP-1RA use and adverse kidney events, with acute kidney injury being the most common. In addition, we report two cases of semaglutide-associated biopsy-proven AIN and one with associated podocytopathy. To our knowledge, this is the first case of biopsy-proven AIN with podocytopathy associated with semaglutide use. Both patients experienced complete remission shortly after discontinuing semaglutide and undergoing immunosuppressive therapy. Further analysis of the FAERS database revealed 17 cases of proteinuria and 1 case of glomerulonephritis associated with semaglutide in the FAERS database, however no further information was available. While further research is needed to establish causality, this case series adds to the growing body of literature that semaglutide is associated with AIN and adds a new association, semaglutide with AIN and podocytopathies. While the overall clinical and mortality benefits of GLP-1RAs may outweigh the rarer risks, prescribers need to be aware of these associations, particularly as the use of GLP-1RAs continues to expand., Competing Interests: K.D.J. reports consultancy agreements with PMV pharmaceuticals, Decipher, Otsuka, George Clinicals, Calliditas, Novartis and Citrus Oncology; reports honoraria from the American Society of Nephrology and Lexicomp; is a paid contributor to UpToDate.com and is section editor for Onconephrology for Nephrology Dialysis Transplantation; serves on the editorial boards of American Journal of Kidney Diseases, CJASN, Clinical Kidney Journal, Frontiers in Nephrology, Journal of Onco-Nephrology and Kidney International; and serves as the Editor-in-Chief of ASN Kidney News. R.W. is member of the editorial board of Clinical Kidney Journal. All other authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Patients with severe mental illness (SMI) including schizophrenia and bipolar disorder die on average 15-20 years earlier than the general population often due to sudden death that, in most cases, is caused by cardiovascular disease. This state-of-the-art review aims to address the complex association between SMI and cardiovascular risk, explore disparities in cardiovascular care pathways, describe how to adequately predict cardiovascular outcomes, and propose targeted interventions to improve cardiovascular health in patients with SMI. These patients have an adverse cardiovascular risk factor profile due to an interplay between biological factors such as chronic inflammation, patient factors such as excessive smoking, and healthcare system factors such as stigma and discrimination. Several disparities in cardiovascular care pathways have been demonstrated in patients with SMI, resulting in a 47% lower likelihood of undergoing invasive coronary procedures and substantially lower rates of prescribed standard secondary prevention medications compared with the general population. Although early cardiovascular risk prediction is important, conventional risk prediction models do not accurately predict long-term cardiovascular outcomes as cardiovascular disease and mortality are only partly driven by traditional risk factors in this patient group. As such, SMI-specific risk prediction models and clinical tools such as the electrocardiogram and echocardiogram are necessary when assessing and managing cardiovascular risk associated with SMI. In conclusion, there is a necessity for differentiated cardiovascular care in patients with SMI. By addressing factors involved in the excess cardiovascular risk, reconsidering risk stratification approaches, and implementing multidisciplinary care models, clinicians can take steps towards improving cardiovascular health and long-term outcomes in patients with SMI., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Several registries for hidradenitis suppurativa (HS) already exist in Europe and the USA. There is currently no global consensus on a core dataset (CDS) for these registries. Creating a global HS registry is challenging, owing to logistical and regulatory constraints, which could limit opportunities for global collaboration as a result of differences in the dataset collected. The solution is to encourage all HS registries to collect the same CDS of information, allowing registries to collaborate., Objectives: To establish a core set of items to be collected by all HS registries globally. The core set will cover demographic details, comorbidities, clinical examination findings, patient-reported outcome measures and treatments., Methods: Beginning in September 2022, 20 participants - including both clinicians with expertise in HS and patient advocates - from eight countries across three continents participated in a Delphi process consisting of four rounds of voting, with all participants completing each round. A list of potential items for inclusion in the core set was generated from the relevant published literature, including systematic reviews of comorbidities in HS, clinical and examination findings, and epidemiology. For disease severity and progression items, the Hidradenitis SuppuraTiva Core outcome set International Collaboration (HiSTORIC) core set and other relevant instruments were considered for inclusion. This resulted in 47 initial items. Participants were invited to suggest additional items to include during the first round. Anonymous feedback was provided to inform each subsequent round of voting to encourage consensus., Results: The eDelphi process established a CDS of 48 items recommended for inclusion in all HS registries globally., Conclusions: The routine adoption of this CDS in current and future HS registries should allow registries in different parts of the world to collaborate, enabling research requiring large numbers of participants., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Conflicts of interest A.G. is an advisor for AbbVie, Aclaris Therapeutics, Anaptys Bio, Aristea Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Incyte, Insmed, Janssen, Novartis, Pfizer, Sonoma Biotherapeutics, UCB, Union Therapeutics, Ventyx Biosciences and Viela Biosciences, and receives honoraria. A.G. receives research grants from AbbVie, UCB, National Psoriasis Foundation, and CHORD COUSIN Collaboration (C3). A.G. is a project lead for HiSTORIC. He is cocopyright holder of the Hidradenitis Suppurativa Investigator Global Assessment (HS-IGA) and Hidradenitis Suppurativa Quality of Life (HiSQOL) instruments. J.R.I. reports receiving a stipend as Editor-in-Chief of the British Journal of Dermatology and an authorship honorarium from UpToDate. He is a consultant for AbbVie, Boehringer Ingelheim, ChemoCentryx, Novartis and UCB Pharma and has served on advisory boards for Insmed, Kymera Therapeutics and Viela Bio. J.R.I. is a project lead for HiSTORIC. He is cocopyright holder of the HS-IGA, Patient Global Assessment and HiSQOL instruments. His department receives income from copyright of the Dermatology Life Quality Instrument and related instruments.

Thirty-eight states and the District of Columbia (DC) have dense breast notification laws that mandate varying levels of patient notification about breast density after a mammogram, and these cover over 90% of American women. On March 10, 2023, the Food and Drug Administration issued a final rule amending regulations under the Mammography Quality Standards Act for a national dense breast reporting standard for both patient results letters and mammogram reports. Effective September 10, 2024, letters will be required to tell a woman her breasts are "dense" or "not dense," that dense tissue makes it harder to find cancers on a mammogram, and that it increases the risk of developing cancer. Women with dense breasts will also be told that other imaging tests in addition to a mammogram may help find cancers. The specific density category can be added (eg, if mandated by a state "inform" law). Reports to providers must include the Breast Imaging Reporting and Data System density category. Implementing appropriate supplemental screening should be based on patient risk for missed breast cancer on mammography; such assessment should include consideration of breast density and other risk factors. This article discusses strategies for implementation. Currently 21 states and DC have varying insurance laws for supplemental breast imaging; in addition, Oklahoma requires coverage for diagnostic breast imaging. A federal insurance bill, the Find It Early Act, has been introduced that would ensure no-cost screening and diagnostic imaging for women with dense breasts or at increased risk and close loopholes in state laws., (© Society of Breast Imaging 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Conflicts of interest: N.S. has participated in advisory boards for Bristol Myers Squibb. A.G. is an advisor for AbbVie, Aclaris Therapeutics, Anaptys Bio, Aristea Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Incyte, Insmed, Janssen, Novartis, Pfizer, Sonoma Biotherapeutics, UCB, Union Therapeutics, Ventyx Biosciences and Viela Biosciences, and receives honoraria. A.G. receives research grants from AbbVie, UCB, National Psoriasis Foundation and CHORD COUSIN Collaboration (C3). He is co-copyright holder of the HS-IGA and HiSQOL instruments. L.A.V.O. has participated on advisory boards for Novartis and UCB, was a consultant and investigator for ChemoCentryx and has received research grants from Pfizer.

The duplication of the peripheral myelin protein 22 (PMP22) gene causes a demyelinating type of neuropathy, commonly known as Charcot-Marie-Tooth disease type 1A (CMT1A). Development of effective drugs for CMT1A still remains as an unmet medical need. In the present study, we assessed the role of the transforming growth factor beta 4 (TGFβ4)/Nodal axis in the pathogenesis of CMT1A. First, we identified PMP22 overexpression-induced Nodal expression in Schwann cells, which might be one of the downstream effectors in CMT1A. Administration of Nodal protein at the developmental stage of peripheral nerves induced the demyelinating phenotype in vivo. Second, we further isolated TGFβ4 as an antagonist that could abolish Nodal-induced demyelination. Finally, we developed a recombinant TGFβ4-fragment crystallizable (Fc) fusion protein, CX201, and demonstrated that its application had promyelinating efficacy in Schwann cells. CX201 administration improved the demyelinating phenotypes of CMT1A mouse models at both pre-symptomatic and post-symptomatic stages. These results suggest that the TGFβ4/Nodal axis plays a crucial role in the pathogenesis of CMT1A and might be a potential therapeutic target for CMT1A., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: This study explored associations between social and built environmental factors and leisure-time physical activity (LTPA) in rural cancer survivors (RCS) and whether these associations differed by exercise stage of change (SOC)., Method: RCS (n = 219) completed questionnaires assessing LTPA, SOC, and social (social status, connectedness, support) and environmental (home environment, neighborhood environment) factors. Linear regression models examined associations between social and built environmental factors and LTPA and tested for moderation by SOC., Results: Half (50.7%) of RCS were physically active, and 49.3% were not active. Social factors positively associated with LTPA included subjective social status in the community (B = 89.0, P = .014) and in the United States (B = 181.3, P < .001), social connectedness (B = 122.3, P = .024), and social support for physical activity from family (B = 41.9, P < .001) and friends (B = 44.3, P < .001). Environmental factors positively associated with LTPA included the home environment (B = 111.2, P < .001), perceived environmental support for PA (B = 355.4, P = .004), and neighborhood attributes, including bicycling infrastructure (B = 191.3, P = .003), proximity to recreation facilities (B = 140.1, P = .021), traffic safety (B = 184.5, P = .025), and aesthetics (B = 342.6, P < .001). SOC statistically significantly moderated the association between social status in the United States and LTPA (B = 160.3, P = .031)., Conclusions: Social and built environmental factors were consistently linked with LTPA and provide context for multilevel interventions promoting LTPA in RCS., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Energy balance accounts for an individual's energy intake, expenditure, and storage. Each aspect of energy balance has implications for the pharmacokinetics of cancer treatments and may impact an individual's drug exposure and subsequently its tolerance and efficacy. However, the integrated effects of diet, physical activity, and body composition on drug absorption, metabolism, distribution, and excretion are not yet fully understood. This review examines the existing literature on energy balance, specifically the role of dietary intake and nutritional status, physical activity and energy expenditure, and body composition on the pharmacokinetics of cancer therapeutics. As energy balance and pharmacokinetic factors can be influenced by age-related states of metabolism and comorbidities, this review also explores the age-related impact of body composition and physiologic changes on pharmacokinetics among pediatric and older adult populations with cancer., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Extensively drug-resistant (XDR) typhoid fever is a threat to travelers to Pakistan. We describe a multicontinental case series of travel-acquired XDR typhoid fever to demonstrate the global spread of the problem and encourage preventive interventions as well as appropriate empiric antimicrobial use., Methods: Cases were extracted from the GeoSentinel database, microbiologic laboratory records of two large hospitals in Toronto, Canada, and by invitation to TropNet sites. All isolates were confirmed XDR Salmonella enterica serovar Typhi (Salmonella typhi), with resistance to ampicillin, ceftriaxone, ciprofloxacin and trimethoprim-sulfamethoxazole., Results: Seventeen cases were identified in Canada (10), USA (2), Spain (2), Italy (1), Australia (1) and Norway (1). Patients under 18 years represented 71% (12/17) of cases, and all patients travelled to Pakistan to visit friends or relatives. Only one patient is known to have been vaccinated. Predominant symptoms were fever, abdominal pain, vomiting and diarrhoea. Antimicrobial therapy was started on Day 1 of presentation in 75% (12/16) of patients, and transition to a carbapenem or azithromycin occurred a median of 2 days after blood culture was drawn. Antimicrobial susceptibilities were consistent with the XDR S. typhi phenotype, and whole genome sequencing on three isolates confirmed their belonging to the XDR variant of the H58 clade., Conclusions: XDR typhoid fever is a particular risk for travelers to Pakistan, and empiric use of a carbapenem or azithromycin should be considered. Pre-travel typhoid vaccination and counseling are necessary and urgent interventions, especially for visiting friends and relatives travelers. Ongoing sentinel surveillance of XDR typhoid fever is needed to understand changing epidemiology., (© International Society of Travel Medicine 2022. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: To assess effectiveness of a web-based educational intervention on women's health care provider knowledge of breast cancer risk models and high-risk screening recommendations., Methods: A web-based pre- and post-test study including 177 U.S.-based women's health care providers was conducted in 2019. Knowledge gaps were defined as fewer than 75% of respondents answering correctly. Pre- and post-test knowledge differences (McNemar test) and associations of baseline characteristics with pre-test knowledge gaps (logistic regression) were evaluated., Results: Respondents included 131/177 (74.0%) physicians; 127/177 (71.8%) practiced obstetrics/gynecology. Pre-test, 118/177 (66.7%) knew the Gail model predicts lifetime invasive breast cancer risk; this knowledge gap persisted post-test [(121/177, 68.4%); P = 0.77]. Just 39.0% (69/177) knew the Gail model identifies women eligible for risk-reducing medications; this knowledge gap resolved. Only 48.6% (86/177) knew the Gail model should not be used to identify women meeting high-risk MRI screening guidelines; this deficiency decreased to 66.1% (117/177) post-test (P = 0.001). Pre-test, 47.5% (84/177) knew the Tyrer-Cuzick model is used to identify women meeting high-risk screening MRI criteria, 42.9% (76/177) to predict BRCA1/2 pathogenic mutation risk, and 26.0% (46/177) to predict lifetime invasive breast cancer risk. These knowledge gaps persisted but improved. For a high-risk 30-year-old, 67.8% (120/177) and 54.2% (96/177) pre-test knew screening MRI and mammography/tomosynthesis are recommended, respectively; 19.2% (34/177) knew both are recommended; and 53% (94/177) knew US is not recommended. These knowledge gaps resolved or reduced., Conclusion: Web-based education can reduce important provider knowledge gaps about breast cancer risk models and high-risk screening recommendations., (© Society of Breast Imaging 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Optimal reduction mammoplasty techniques to treat patients with gigantomastia have been debated and can involve extended pedicles (EP) or free nipple grafts (FNG)., Objectives: The authors compared clinical, patient-reported, and aesthetic outcomes associated with reduction mammoplasty employing EP vs FNG., Methods: A multi-institutional, retrospective study of adult patients with gigantomastia who underwent reduction mammoplasty at 2 tertiary care centers from 2017 to 2020 was performed. Gigantomastia was defined as reduction weight >1500 g per breast or sternal notch-to-nipple distance ≥40 cm. Surgeons at 1 institution employed the EP technique, whereas those at the other utilized FNG. Baseline characteristics, preoperative and postoperative BREAST-Q, and clinical outcomes were collected. Aesthetic outcomes were assessed in 1:1 propensity score-matched cases across techniques. Preoperative and postoperative photographs were provided to reviewers across the academic plastic surgery continuum (students to faculty) and non-medical individuals to evaluate aesthetic outcomes., Results: Fifty-two patients met the inclusion criteria (21 FNG, 31 EP). FNG patients had a higher incidence of postoperative cellulitis (23% vs 0%, P < 0.05) but no other differences in surgical or medical complications. Baseline BREAST-Q scores did not differ between groups. Postoperative BREAST-Q scores revealed greater satisfaction with the EP technique (P < 0.01). The aesthetic assessment of outcomes in 14 matched pairs of patients found significantly better aesthetic outcomes in all domains with the EP procedure (P < 0.05), independent of institution or surgical experience., Conclusions: This multi-institutional study suggests that, compared with FNG, the EP technique for reduction mammoplasty provides superior clinical, patient-reported, and aesthetic outcomes for patients with gigantomastia., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Currently there are no known structural parameters of the integument that can be measured noninvasively which are used in the planning of body contouring surgery., Objectives: The aim of this study was to see if mean gray value (MGV), when taken into account preoperatively, can reduce wound-related morbidity., Methods: This project was a prospective cohort study. Ultrasound imaging of the subcutaneous tissue was performed prospectively on patients undergoing body contouring surgery to quantify the superficial fascial system so that average MGV could be calculated over the proposed surgical sites. Patients with average to poor MGV (≤0.127) were identified preoperatively for tension-reducing procedures. Wound complication rates were compared with rates in a retrospective cohort which did not undergo preoperative imaging., Results: There were 115 patients in each of the 2 cohorts. There were 3 exclusions due to loss of ultrasound images, leaving 112 patients available for analysis in the prospective cohort. The cohorts were similar except for a higher incidence of patients with diabetes in the retrospective group (1 vs 9, P = 0.026). The wound complication rate was significantly reduced in the prospective group (5/112, 4.4%) when compared with the retrospective group (20/115, 17%, P = 0.0062). The revision and infection rates were also significantly reduced in the prospective group (1/112, 0.9%; 3/112, 2.6%) when compared with the retrospective group (8/115, 7%, P = 0.019; 10/115 8.6%, P = 0.051)., Conclusions: MGV is a unique, patient- and area-specific structural parameter of the integument, and its measurement may be useful in reducing wound-related morbidity in body contouring surgery., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Pain is rated by patients with hidradenitis suppurativa (HS) as the disease's most impactful symptom. HS therapies are often insufficient to control inflammatory disease activity and pain. A better understanding of patient experiences with pain may improve patient-provider relationships and help identify strategies for addressing HS pain., Objectives: This qualitative study sought to characterize lived pain experiences of those with HS., Methods: English-speaking patients ≥ 18 years old with a dermatologist-confirmed diagnosis of HS and an average numerical rating scale pain score of ≥ 1 over the preceding week were recruited from a single academic medical centre in Atlanta, Georgia, USA. Semistructured interviews were conducted from November 2019 to March 2020 to explore participants' HS pain experiences and the subsequent impact on their lives. Thematic saturation was reached after interviewing 21 participants. Interviews were audio recorded, transcribed, and analysed using thematic analysis., Results: Among 21 study participants, the median 7-day average pain score was 6 (interquartile range 3-7; scale ranges from 0 to 10, with 10 being most pain). Participants' descriptions of pain were consistent with nociceptive pain, neuropathic pain and itch. Pain impacted multiple life domains, including physical limitations (decreased mobility and impaired sleep), decreased psychological wellbeing (irritability, depression, loss of control, and difficulty communicating pain experiences) and impaired social relationships (social isolation, intimacy problems and difficulty fulfilling social responsibilities). Although participants reported chronic discomfort, acutely painful and unpredictable HS disease flares caused more distress and quality-of-life (QoL) burden. Participants frequently treated their pain without input from the medical team, sometimes with unsafe medication doses or combinations. Factors contributing to self-management of pain included difficulty accessing timely outpatient care during disease flares and fear of stigma from healthcare providers., Conclusions: When present, HS-related pain may impact not only physical wellbeing but also mental health and relationships. In addition to therapies that target the inflammatory disease burden, treating the symptom of pain may improve patients' QoL and wellbeing. Because patients with HS have difficulty explaining their pain, proactively asking them about pain may identify unmet needs, facilitate better pain control and improve QoL. Further, the influence of HS-related pain on numerous aspects of QoL suggests the need for multidisciplinary, patient-centred approaches to HS pain management., Competing Interests: Conflicts of interest: L.A.V.O. has participated on advisory boards for Novartis, was a consultant and investigator for ChemoCentryx, and received a research grant from Pfizer. A.G. is an advisor for AbbVie, Aclaris Therapeutics, Anaptys Bio, Aristea Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Incyte, InflaRx, Insmed, Janssen, Novartis, Pfizer, UCB, Union Therapeutics and Viela Biosciences, and receives honoraria. A.G. also receives research grants from AbbVie, UCB and the National Psoriasis Foundation., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: We aimed to determine whether a targeted gene expression panel could predict clinical outcomes in paediatric ulcerative colitis [UC] and investigated putative pathogenic roles of predictive genes., Methods: In total, 313 rectal RNA samples from a cohort of newly diagnosed paediatric UC patients (PROTECT) were analysed by a real-time PCR microfluidic array for expression of type 1, 2 and 17 inflammation genes. Associations between expression and clinical outcomes were assessed by logistic regression. Identified prognostic markers were further analysed using existing RNA sequencing (RNA-seq) data sets and tissue immunostaining., Results: IL13RA2 was associated with a lower likelihood of corticosteroid-free remission (CSFR) on mesalamine at week 52 (p = .002). A model including IL13RA2 and only baseline clinical parameters was as accurate as an established clinical model, which requires week 4 remission status. RORC was associated with a lower likelihood of colectomy by week 52. A model including RORC and PUCAI predicted colectomy by 52 weeks (area under the receiver operating characteristic curve 0.71). Bulk RNA-seq identified IL13RA2 and RORC as hub genes within UC outcome-associated expression networks related to extracellular matrix and innate immune response, and lipid metabolism and microvillus assembly, respectively. Adult UC single-cell RNA-seq data revealed IL13RA2 and RORC co-expressed genes were localized to inflammatory fibroblasts and undifferentiated epithelial cells, respectively, which was supported by protein immunostaining., Conclusion: Targeted assessment of rectal mucosal immune gene expression predicts 52-week CSFR in treatment-naïve paediatric UC patients. Further exploration of IL-13Rɑ2 as a therapeutic target in UC and future studies of the epithelial-specific role of RORC in UC pathogenesis are warranted., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Recent improvement in treatment and patient survival has opened the eligibility of kidney transplantation to patients who developed end-stage kidney disease (ESKD) from plasma cell dyscrasias (PCDs). Data on clinical outcomes in this population are lacking., Methods: We conducted a retrospective study of United Network for Organ Sharing/Organ Procurement and Transplantation Network dataset (2006-2018) to compare patient and graft outcomes of kidney transplant recipients with ESKD due to PCD versus other causes., Results: Among 168 369 adult first kidney transplant recipients, 0.22-0.43% per year had PCD as the cause of ESKD. The PCD group had worse survival than the non-PCD group for both living and deceased donor types {adjusted hazard ratio [aHR] 2.24 [95% confidence interval (CI) 1.67-2.99] and aHR 1.40 [95% CI 1.08-1.83], respectively}. The PCD group had worse survival than the diabetes group, but only among living donors [aHR 1.87 (95% CI 1.37-2.53) versus aHR 1.16 (95% CI 0.89-1.2)]. Graft survival in patients with PCD were worse than non-PCD in both living and deceased donors [aHR 1.72 (95% CI 1.91-2.56) and aHR 1.30 (95% CI 1.03-1.66)]. Patient and graft survival were worse in amyloidosis but not statistically different in multiple myeloma compared with the non-PCD group., Conclusion: The study data are crucial when determining kidney transplant eligibility and when discussing transplant risks in patients with PCD., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

There have been significant advances in the treatment of multiple myeloma in the last two decades. Approximately 25% of patients with newly diagnosed myeloma have some degree of kidney impairment. During the course of illness, nearly 50% of myeloma patients will develop kidney disease. Moreover, ∼10% of myeloma patients have advanced kidney disease requiring dialysis at presentation. Hemodialysis is associated with a significantly reduced overall survival (OS). In the setting of prolonged long-term OS due to the use of newer immunotherapeutic agents in the treatment of myeloma, patients with myeloma and advanced kidney disease may benefit from more aggressive management with kidney transplantation (KTx). Unfortunately, most data regarding outcomes of KTx in patients with myeloma come from single-center case series. With the advent of novel treatment choices, it remains unclear if outcomes of kidney transplant recipients with myeloma have improved in recent years. In this descriptive systematic review, we coalesced published patient data over the last 20 years to help inform clinicians and patients on expected hematologic and KTx outcomes in this complex population. We further discuss the future of KTx in patients with paraproteinemia., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Few validated instruments exist for use in hidradenitis suppurativa (HS) trials., Objectives: To develop a novel HS Investigator Global Assessment (HS-IGA) and to validate its psychometric properties., Methods: Development of HS-IGA involved discussion among stakeholders, including patients, within HISTORIC. Data from replicate phase III randomized controlled trials evaluating HS treatment were utilized. Multivariate models identified lesion type and body region as variables of importance. Classification and regression trees for ordinal responses were built. Validation included assessment of test-retest reliability, predictive validity, responsiveness and clinical meaningfulness., Results: There were 3024 unique measurements available in PIONEER I. Mean and median lesion counts by region were largely <10 and were highest in axillary and inguinal regions. The mean and median number of regions involved were ≤ 3 for individual lesions and combinations. Regardless of lesion type, axillary and inguinal regions most influenced the HS-IGA score. Accordingly, regions were combined into a six-point IGA based on the maximum lesion number in either upper or lower body regions with a score of 0 (0-1 lesions), 1 (2-5), 2 (6-10), 3 (11-15), 4 (16-20) and 5 (≥ 20 lesions). The intraclass correlation coefficient for test-retest reliability was 0·91 (95% confidence interval 0·87-0·94). Spearman's rank order correlations (SROCs) with HS-PGA and Hidradenitis Suppurativa Clinical Response (HiSCR) were 0·73 and 0·51, respectively (P < 0·001 for both comparisons). SROCs with Dermatology Life Quality Index (DLQI), pain numerical rating scale and HS-QoL were 0·42, 0·34 and -0·25, respectively (P < 0·001 for all comparisons). HS-IGA was responsive at weeks 12 and 36. Predictive convergent validity was very good with HS-PGA (area under the curve = 0·89) and with HiSCR (area under the curve = 0·82). Predictive divergent validity was low with DLQI and HS-QoL., Conclusions: HS-IGA has moderate-to-strong psychometric properties and is simple to calculate., (© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders affecting cortisol biosynthesis. Reduced activity of an enzyme required for cortisol production leads to chronic overstimulation of the adrenal cortex and accumulation of precursors proximal to the blocked enzymatic step. The most common form of CAH is caused by steroid 21-hydroxylase deficiency due to mutations in CYP21A2. Since the last publication summarizing CAH in Endocrine Reviews in 2000, there have been numerous new developments. These include more detailed understanding of steroidogenic pathways, refinements in neonatal screening, improved diagnostic measurements utilizing chromatography and mass spectrometry coupled with steroid profiling, and improved genotyping methods. Clinical trials of alternative medications and modes of delivery have been recently completed or are under way. Genetic and cell-based treatments are being explored. A large body of data concerning long-term outcomes in patients affected by CAH, including psychosexual well-being, has been enhanced by the establishment of disease registries. This review provides the reader with current insights in CAH with special attention to these new developments., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Motivation: Nucleus detection, segmentation and classification are fundamental to high-resolution mapping of the tumor microenvironment using whole-slide histopathology images. The growing interest in leveraging the power of deep learning to achieve state-of-the-art performance often comes at the cost of explainability, yet there is general consensus that explainability is critical for trustworthiness and widespread clinical adoption. Unfortunately, current explainability paradigms that rely on pixel saliency heatmaps or superpixel importance scores are not well-suited for nucleus classification. Techniques like Grad-CAM or LIME provide explanations that are indirect, qualitative and/or nonintuitive to pathologists., Results: In this article, we present techniques to enable scalable nuclear detection, segmentation and explainable classification. First, we show how modifications to the widely used Mask R-CNN architecture, including decoupling the detection and classification tasks, improves accuracy and enables learning from hybrid annotation datasets like NuCLS, which contain mixtures of bounding boxes and segmentation boundaries. Second, we introduce an explainability method called Decision Tree Approximation of Learned Embeddings (DTALE), which provides explanations for classification model behavior globally, as well as for individual nuclear predictions. DTALE explanations are simple, quantitative, and can flexibly use any measurable morphological features that make sense to practicing pathologists, without sacrificing model accuracy. Together, these techniques present a step toward realizing the promise of computational pathology in computer-aided diagnosis and discovery of morphologic biomarkers., Availability and Implementation: Relevant code can be found at github.com/CancerDataScience/NuCLS., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Race coefficients of estimated glomerular filtration rate (eGFR) formulas may be partially responsible for racial inequality in preemptive listing for kidney transplantation., Methods: We used the Scientific Registry of Transplant Recipients database to evaluate differences in racial distribution of preemptive listing before and after application of the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) race coefficients to all preemptively listed non-Black kidney transplant candidates (eGFR modulation). Odds of preemptive listing were calculated by race, with Black as the reference before and after eGFR modulation. Variables known to influence preemptive listing were included in the model., Results: Among 385 087 kidney-alone transplant candidates from 1 January 2010 to 2 December 2020, 118 329 (30.7%) candidates were identified as preemptively listed (71.7% White, 19% Black, 7.8% Asian, 0.6% multi-racial, 0.6% Native American and 0.3% Pacific Islander). After eGFR modulation, non-Black patients with an eGFR ≥20 mL/min/1.73 m 2 were removed. Compared with Black candidates, the adjusted odds of preemptive listing for White candidates decreased from 2.01 [95% confidence interval (95% CI) 1.78-2.26] before eGFR modulation to 1.18 (95% CI 1.0-1.39; P = 0.046) with the MDRD and 1.37 (95% CI 1.18-1.58) with the CKD-EPI equations after adjusting for race coefficients., Conclusions: Removing race coefficients in GFR estimation formulas may result in a more equitable distribution of Black candidates listed earlier on a preemptive basis., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

Background: While there is an increasing burden of chronic postoperative opioid use and opioid abuse in the United States, opioid use following inflatable penile prosthesis (IPP) surgery has not been well described., Aim: Describe postoperative opioid use following IPP surgery., Methods: Seventy-four consecutive patients undergoing IPP implantation by a single surgeon were enrolled. Self-reported diaries tracked the type and amount of medication taken for 2 weeks following IPP surgery. High opioid consumers were defined as those consuming more than the median amount (10 mg) of opioids during the first 2 weeks postoperatively. Multivariate analyses were performed using stepwise backward elimination., Outcomes: Quantification of opioid use postoperatively and factors related to high opioid use., Results: Fifty-six patients were included after 7 were excluded for preoperative opioid use and 11 were excluded for inability to contact. Median age was 67.5. Devices used were Boston Scientific (41, 73%) and Coloplast (15, 27%). All patients received local anesthetic. Most surgeries (44, 79%) were performed as outpatient. Preoperative analgesia with acetaminophen, celecoxib, and pregabalin was administered in 44 (78%), 44 (78%), and 28 (50%) of cases respectively; 32 (57%) of patients received 2 medications, 21 (36%) received three medications. In hospital median morphine equivalents was 7.5 (interquartile range [IQR] 0-7.5). Oxycodone prescribed at discharge was 50 mg (29, 52%), 75 mg (4; 7%), and 100 mg (23; 41%). Median milligrams of oxycodone used was 10 mg (IQR 0-23.5) at 7 days and 10 (IQR 0-37.5) at 14 days postdischarge. On univariate analysis, factors associated with an increased likelihood of high opioid use were morphine equivalents utilized in hospital (odds ratio [OR] 1.13, P < .05) and milligrams oxycodone prescribed at discharge (OR 1.05, P < .001) while patient demographics, procedure characteristics, and analgesic types were not found to be predictive of high opioid use. On multivariate analysis, milligrams oxycodone prescribed at discharge (OR 1.04, P < .005) were associated with an increased likelihood of high opioid use after discharge., Clinical Implications: Increased understanding of opioid use after IPP surgery may improve prescribing patterns after discharge., Strengths & Limitations: This study quantified post discharge opioid use over the first 14 postoperative days. It is limited by single surgeon, small sample size, and retrospective design., Conclusion: Provider opioid prescribing patterns were associated with high opioid consumption postoperatively and a substantial amount of opioids prescribed at discharge remain unused by patients, suggesting that we can reduce or replace the amount of opioids that are prescribed. Ehlers ME, Mohan CS, Akerman JP, et al. Factors Impacting Postoperative Opioid Use Among Patients Undergoing Implantation of Inflatable Penile Prosthesis. J Sex Med 2021;18:1915-1920., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: A temporal relationship between hidradenitis suppurativa (HS) and obesity has not been established., Objectives: To compare baseline body mass index (BMI) and change in BMI for patients with HS and controls before and after diagnosis., Methods: We performed a retrospective case-control analysis of 1284 patients with HS and controls matched for age, sex, race and calendar year between 1 January 1999 and 9 September 2019. BMI 7 years prior to first HS diagnosis, and rate of BMI change, were compared for patients with HS and controls using linear mixed effects models., Results: Baseline BMI was higher among patients with HS than controls [mean difference 3·03 kg m -2 , 95% confidence interval (CI) 2·44-3·62; P < 0·001)]. This difference was larger for women [mean difference 3·37 kg m -2 (95% CI 2·73-4·01)] than men [mean difference 1·27 kg m -2 (95% CI - 0·20-2·73; interaction P = 0·01)], and for patients with HS diagnosed before age 40 years [mean difference 4·10 kg m -2 (95% CI 3·15-5·06)] than those diagnosed after age 40 years [mean difference 2·38 kg m -2 (95% CI 1·63-3·12; interaction P < 0·001)]. Prior to diagnosis, average annual increase in BMI among patients with HS was slightly higher than controls. There was no statistically significant change in annual BMI among patients with HS following diagnosis., Conclusions: Baseline BMI and, to a lesser extent, rate of BMI change appear to be risk factors for developing HS. The influence of BMI may play a larger role among female patients and younger patients., (© 2020 British Association of Dermatologists.)

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory disease. The HS core outcome set calls for a patient global assessment (PtGA)., Objectives: To assess the validity, reliability and responsiveness of a candidate single-item PtGA for HS-specific health-related quality of life (HRQoL)., Methods: Cognitive debriefing interviews were conducted with patients with HS in Denmark and the USA. A cross-sectional observational study was done with adults with HS in the USA and Denmark. Candidate PtGA item, demographic items and multiple patient-reported scales - the Hidradenitis Suppurativa Quality of Life (HiSQOL), Dermatology Life Quality Index (DLQI) and numerical rating scale (NRS) for pain - were concurrently administered to evaluate convergent and known-groups validity. Scales with a single-item assessment of change were readministered 24-72 h later, to evaluate reliability and responsiveness., Results: After cognitive debriefing, the candidate PtGA for HS-specific HRQoL was finalized with five response levels. Convergent validity of the PtGA was supported by significant correlations with HiSQOL score [r = 0·79, 95% confidence interval (CI) 0·75-0·82] and DLQI (r = 0·78, 95% CI 0·74-0·82). The PtGA displayed known-groups validity with DLQI score bands based on significance of an anova (P < 0·001). Good test-retest reliability was supported by the intraclass correlation coefficient (0·82, 95% CI 0·78-0·85) for those who reported stable HS. Responsiveness was assessed by differences in PtGA score against a patient-reported assessment of change, which showed significant differences towards improvement., Conclusions: The single-item PtGA exhibits reliability, validity and responsiveness in assessing HS-specific HRQoL in HS, making it a good provisional tool for HS clinical research., (© 2020 British Association of Dermatologists.)

Childhood cancer survivors (CCS) experience significant morbidity due to treatment- related late effects and benefit from late-effects surveillance. Adherence to screening recommendations is suboptimal. Survivorship care programs often struggle with resource limitations and may benefit from understanding institution-level financial outcomes associated with patient adherence to justify programmatic development and growth. The purpose of this study is to examine how CCS adherence to screening recommendations relates to the cost of care, insurance status, and institution-level financial outcomes. A retrospective chart review of 286 patients, followed in a structured survivorship program, assessed adherence to the Children's Oncology Group follow-up guidelines by comparing recommended versus performed screening procedures for each patient. Procedure cost estimates were based on insurance status. Institutional profit margins and profit opportunity loss were calculated. Bivariate statistics tested adherent versus nonadherent subgroup differences on cost variables. A generalized linear model predicted the likelihood of adherence based on cost of recommended procedures, controlling for age, gender, race, and insurance. Adherence to recommended surveillance procedures was 50.2%. Nonadherence was associated with higher costs of recommended screening procedures compared to the adherent group estimates ($2,469.84 vs. $1,211.44). Failure to perform the recommended tests resulted in no difference in reimbursement to the health system between groups ($1,249.63 vs. $1,211.08). For the nonadherent group, this represented $1,055.13 in "lost profit opportunity" per visit for patients, which totaled $311,850 in lost profit opportunity due to nonadherence in this subgroup. In the final model, nonadherence was related to higher cost of recommended procedures (p < .0001), older age at visit (p = .04), Black race (p = .02), and government-sponsored insurance (p = .03). Understanding institutional financial outcomes related to patient adherence may help inform survivorship care programs and resource allocation. Potential financial burden to patients associated with complex care recommendations is also warranted., (© Society of Behavioral Medicine 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Acute kidney injury (AKI) is common among hospitalized patients with coronavirus disease 2019 (COVID-19), with the occurrence of AKI ranging from 0.5% to 80%. An improved knowledge of the pathology of AKI in COVID-19 is crucial to mitigate and manage AKI and to improve the survival of patients who develop AKI during COVID-19. In this review, we summarize the published cases and case series of various kidney pathologies seen with COVID-19. Both live kidney biopsies and autopsy series suggest acute tubular injury as the most commonly encountered pathology. Collapsing glomerulopathy and thrombotic microangiopathy are other encountered pathologies noted in both live and autopsy tissues. Other rare findings such as anti-neutrophil cytoplasmic antibody vasculitis, anti-glomerular basement membrane disease and podocytopathies have been reported. Although direct viral infection of the kidney is possible, it is certainly not a common or even widespread finding reported at the time of this writing (November 2020)., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Objective: We sought to identify provider knowledge gaps and their predictors, as revealed by a breast density continuing education course marketed to the radiology community., Methods: The course, continually available online during the study period of November 2, 2016 and December 31, 2018, includes demographics collection; a monograph on breast density, breast cancer risk, and screening; and a post-test. Four post-test questions were modified during the study period, resulting in different sample sizes pre- and postmodification. Multiple logistic regression was used to identify predictors of knowledge gaps (defined as > 25% of responses incorrect)., Results: Of 1649 analyzable registrants, 1363 (82.7%) were radiologic technologists, 226 (13.7%) were physicians, and 60 (3.6%) were other nonphysicians; over 90% of physicians and over 90% of technologists/nonphysicians specialized in radiology. Sixteen of 49 physicians (32.7%) and 80/233 (34.3%) technologists/nonphysicians mistakenly thought the Gail model should be used to determine "high-risk" status for recommending MRI or genetic testing. Ninety-nine of 226 (43.8%) physicians and 682/1423 (47.9%) technologists/nonphysicians misunderstood the inverse relationship between increasing age and lifetime breast cancer risk. Fifty-two of 166 (31.3%) physicians and 549/1151 (47.7%) technologists/nonphysicians were unaware that MRI should be recommended for women with a family history of BRCA1/BRCA2 mutations. Tomosynthesis effectiveness was overestimated, with 18/60 (30.0%) physicians and 95/272 (34.9%) technologists/nonphysicians believing sensitivity nearly equaled MRI. Knowledge gaps were more common in technologists/nonphysicians., Conclusions: Important knowledge gaps about breast density, breast cancer risk assessment, and screening exist among radiologic technologists and radiologists. Continued education efforts may improve appropriate breast cancer screening recommendations., (© Society of Breast Imaging 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background and Aims: Ileal strictures are the major indication for resective surgery in Crohn's disease (CD). We aimed to define ileal gene programs present at diagnosis linked with future stricturing behavior during five year follow-up, and to identify potential small molecules to reverse these gene signatures., Methods: Antimicrobial serologies and pre-treatment ileal gene expression were assessed in a representative subset of 249 CD patients within the RISK multicenter pediatric CD inception cohort study, including 113 that are unique to this report. These data were used to define genes associated with stricturing behavior and for model testing to predict stricturing behavior. A bioinformatics approach to define small molecules which may reverse the stricturing gene signature was applied., Results: 19 of the 249 patients developed isolated B2 stricturing behavior during follow-up, while 218 remained B1 inflammatory. Using deeper RNA sequencing than in our prior report, we have now defined an inflammatory gene signature including an oncostatin M co-expression signature, tightly associated with extra-cellular matrix (ECM) gene expression in those who developed stricturing complications. We further computationally prioritize small molecules targeting macrophage and fibroblast activation and angiogenesis which may reverse the stricturing gene signature. A model containing ASCA and CBir1 serologies and a refined eight ECM gene set was significantly associated with stricturing development by year five after diagnosis (AUC (95th CI) = 0.82 (0.7-0.94))., Conclusion: An ileal gene program for macrophage and fibroblast activation is linked to stricturing complications in treatment naïve pediatric CD, and may inform novel small molecule therapeutic approaches., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)