Citations

Occurrence of metabolic dysfunction–associated steatotic liver disease (MASLD) is common following liver transplantation (LT). MASLD can be classified as a recurrent disease when it occurs in patients receiving LT for metabolic dysfunction–associated steatohepatitis (MASH) or as de novo when it occurs in patients undergoing transplantation for non-metabolic dysfunction–associated steatohepatitis etiologies of liver disease. Fibrosis progression in patients with MASLD is accelerated, with progression to cirrhosis occurring more rapidly compared with the general (ie, non-LT) population. Moreover, the metabolic burden in LT recipients with MASLD is high and synergizes with liver disease to negatively affect the clinical course. Despite the oversized clinical burden of MASLD among LT recipients, there is currently a lack of regulatory approach and pathway for therapeutics development in this patient population. The present document, thus, provides guidance for therapeutics development that incorporates nuances of transplant care in patients with post-LT MASLD to facilitate drug development.

Importance Benign breast disease (BBD) comprises approximately 75% of breast biopsy diagnoses. Surgical biopsy specimens diagnosed as nonproliferative (NP), proliferative disease without atypia (PDWA), or atypical hyperplasia (AH) are associated with increasing breast cancer (BC) risk; however, knowledge is limited on risk associated with percutaneously diagnosed BBD. Objectives To estimate BC risk associated with BBD in the percutaneous biopsy era irrespective of surgical biopsy. Design, Setting, and Participants In this retrospective cohort study, BBD biopsy specimens collected from January 1, 2002, to December 31, 2013, from patients with BBD at Mayo Clinic in Rochester, Minnesota, were reviewed by 2 pathologists masked to outcomes. Women were followed up from 6 months after biopsy until censoring, BC diagnosis, or December 31, 2021. Exposure Benign breast disease classification and multiplicity by pathology panel review. Main Outcomes The main outcome was diagnosis of BC overall and stratified as ductal carcinoma in situ (DCIS) or invasive BC. Risk for presence vs absence of BBD lesions was assessed by Cox proportional hazards regression. Risk in patients with BBD compared with female breast cancer incidence rates from the Iowa Surveillance, Epidemiology, and End Results (SEER) program were estimated. Results Among 4819 female participants, median age was 51 years (IQR, 43-62 years). Median follow-up was 10.9 years (IQR, 7.7-14.2 years) for control individuals without BC vs 6.6 years (IQR, 3.7-10.1 years) for patients with BC. Risk was higher in the cohort with BBD than in SEER data: BC overall (standard incidence ratio [SIR], 1.95; 95% CI, 1.76-2.17), invasive BC (SIR, 1.56; 95% CI, 1.37-1.78), and DCIS (SIR, 3.10; 95% CI, 2.54-3.77). The SIRs increased with increasing BBD severity (1.42 [95% CI, 1.19-1.71] for NP, 2.19 [95% CI, 1.88-2.54] for PDWA, and 3.91 [95% CI, 2.97-5.14] for AH), comparable to surgical cohorts with BBD. Risk also increased with increasing lesion multiplicity (SIR: 2.40 [95% CI, 2.06-2.79] for ≥3 foci of NP, 3.72 [95% CI, 2.31-5.99] for ≥3 foci of PDWA, and 5.29 [95% CI, 3.37-8.29] for ≥3 foci of AH). Ten-year BC cumulative incidence was 4.3% for NP, 6.6% for PDWA, and 14.6% for AH vs an expected population cumulative incidence of 2.9%. Conclusions and Relevance In this contemporary cohort study of women diagnosed with BBD in the percutaneous biopsy era, overall risk of BC was increased vs the general population (DCIS and invasive cancer combined), similar to that in historical BBD cohorts. Development and validation of pathologic classifications including both BBD severity and multiplicity may enable improved BC risk stratification.

Background Data on national trends in mortality due to infective endocarditis (IE) in the United States are limited. Methods and Results Utilizing the multiple causes of death data from the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research database from 1999 to 2020, IE and substance use were identified using the International Classification of Diseases, Tenth Revision, Clinical Modification codes. Between 1999 and 2020, the IE‐related age‐adjusted mortality rates declined. IE‐related crude mortality accelerated significantly in the age groups 25–34 years (average annual percentage change, 5.4 [95% CI, 3.1–7.7]; P <0.001) and 35–44 years (average annual percentage change, 2.3 [95% CI, 1.3–3.3]; P <0.001), but remained stagnant in those aged 45–54 years (average annual percentage change, 0.5 [95% CI, −1.9 to 3]; P =0.684), and showed a significant decline in those aged ≥55 years. A concomitant substance use disorder as multiple causes of death in those with IE increased drastically in the 25–44 years age group ( P <0.001). The states of Kentucky, Tennessee, and West Virginia showed an acceleration in age‐adjusted mortality rates in contrast to other states, where there was predominantly a decline or static trend for IE. Conclusions Age‐adjusted mortality rates due to IE in the overall population have declined. The marked acceleration in mortality in the 25‐ to 44‐year age group is a cause for alarm. Regional differences with acceleration in IE mortality rates were noted in Kentucky, Tennessee, and West Virginia. We speculate that this acceleration was likely due mainly to the opioid crisis that has engulfed several states and involved principally younger adults.

Background Internal medicine (IM) resident physicians spend a considerable amount of time managing their inbox as part of their longitudinal continuity clinic experience. There are no standardized guidelines for how programs should train, monitor, or supervise residents in this type of patient care. Objective To understand how IM residency programs educate, monitor, and supervise resident electronic health record (EHR) inbox management as part of their longitudinal continuity clinic and determine whether patient safety events have occurred due to EHR inbox-related patient care decisions made by unsupervised resident physicians. Methods In August 2021, 439 program directors at accredited US IM residency programs who were members of the Association of Program Directors in Internal Medicine (APDIM) were asked 12 questions developed by the study authors and APDIM survey committee members regarding resident EHR inbox management as part of the annual APDIM survey. Results Two hundred and sixty-seven (61%) PDs responded. The majority (224 of 267, 84%) of programs provided guidelines for expected message response times; less than half (115, 43%) monitored timeliness metrics. Only half (135; 51%) of programs required faculty supervision of inbox messages for all residents; 28% (76) did not require supervision for any residents. Twenty-one percent of PDs (56) reported awareness of a patient safety event occurring due to an unsupervised resident inbox-related patient care decision. Conclusions Substantial variability exists in how IM residency programs train, monitor, supervise, and provide coverage for resident inbox work. Program directors are aware of patient safety events resulting from unsupervised resident inbox management.

ABSTRACT Hyperammonemia in adults is most often due to cirrhosis. Ammonia is metabolized through the urea cycle. With liver disease, this pathway is altered, and urea is unable to be formed, creating a buildup of ammonia with numerous side effects, including encephalopathy. A less common presentation is hyperammonemia in the absence of liver disease. We present a rare case of non-cirrhotic hyperammonemia due to a splenogonadal shunt.

INTRODUCTION: Wide-area transepithelial sampling with 3-dimensional computer-assisted analysis (WATS 3D ) has been shown to increase the detection rate of dysplasia (and intestinal metaplasia) in patients with Barrett's esophagus (BE). The purpose of this study was to evaluate the interobserver variability and accuracy of diagnosing BE-associated dysplasia in WATS 3D specimens among gastrointestinal (GI) pathologists without prior experience with this technology. METHODS: Five GI pathologists underwent a 4-hour in-person (at microscope) and virtual training session and then evaluated digital images of discrete cellular foci from 60 WATS 3D cases with BE (20 nondysplastic BE [NDBE], 20 low-grade dysplasia [LGD], and 20 high-grade dysplasia/esophageal adenocarcinoma [HGD/EAC]). Each case consisted of 1 hematoxylin and eosin–stained image (cell block), and 1 liquid cytology or papanicolaou-stained smear image (120 images in total). RESULTS: The overall kappa value among the 5 study pathologists was excellent (overall kappa = 0.93; kappa = 0.93 and 0.97 for cell block and smear specimens, respectively). There were no significant differences noted in kappa values in interpretation of the cell block vs smear specimens or in any of the individual diagnostic categories when the latter were evaluated separately. Furthermore, agreement was perfect (100%) regarding detection of neoplasia (either LGD, HGD, or EAC). Diagnoses were made with complete confidence in 91% of instances. DISCUSSION: We conclude that GI pathologists, without any prior experience in interpretation of WATS 3D specimens, can undergo a short training session and then diagnose these specimens with a very high level of accuracy and reproducibility.

Abstract Background Hori's nevus is a common and challenging dermatological condition, often complicated by post‐inflammatory hyperpigmentation following treatment. Platelet‐rich plasma (PRP) has demonstrated efficacy in the treatment of hyperpigmentation disorders such as melasma and periorbital darkening. Given the benefits and minimally invasive nature of PRP treatments, exploring its application in managing Hori's nevus through further investigation is worthwhile. Aims To evaluate the safety and effectiveness of intradermal PRP therapy for the treatment of Hori's nevus. Methods Ten female patients received bilateral intradermal PRP injections every 2 weeks for a total of four treatments. The modified dermal pigmentation and severity index (mDPASI), mean melanin index (MI), brightening score, patient self‐assessment, and clinical photographs were evaluated at 2, 4, 8, and 12 weeks post‐treatment. Adverse events were also recorded to determine treatment safety. Results At 12 weeks post‐treatment, mDPASI decreased 38.86%, from 0.929 ± 0.617 to 0.568 ± 0.415 ( p < 0.05). The mean melanin index decreased 12.75%, from 208.650 ± 26.319 to 182.052 ± 17.028 ( p < 0.05). In addition, the mean brightness score evaluated by two experts was 1.4, indicating 25–50% improvement. At the end of the study, 50% of the patients reported 50–75% improvement. Side effects included pain, mild edema, and bruising, which resolved spontaneously within 3 days. No serious side effects were found. Conclusion Our results suggest that intradermal PRP therapy may be a safe and effective alternative for the treatment of Hori's nevus and can complement conventional interventions. However, further research with a larger sample size, control groups, and longer follow‐up is needed to confirm these findings.

Abstract Background Acute hematogenous osteomyelitis (AHO) is a relatively infrequent but significant infection in pediatric patients. As Staphylococcus aureus is the most common cause of AHO, intravenous and oral first-generation cephalosporins are common therapies. Cephalexin is a commonly prescribed oral therapy for pediatric AHO, although it requires frequent dosing that may affect adherence. Cefadroxil is a comparable oral first-generation cephalosporin with a more desirable dosing schedule. Methods We reviewed pediatric patients admitted to Mayo Clinic between March 2002 and September 2020 for management of AHO who received treatment with a first-generation cephalosporin. We reviewed timing of oral therapy transition, therapy-associated adverse effects, and recurrence of disease after completion of therapy. Results There were 59 patients included in the study. There was similar occurrence of adverse effects in patients receiving cefadroxil and cephalexin, although use of cefadroxil coincided with more gastrointestinal adverse effects and leukopenia and use of cephalexin with more rash and neutropenia. One secondary treatment failure occurred in our study, in a patient receiving cephalexin for treatment of septic arthritis. Conclusions Cefadroxil may be a reasonable alternative oral therapy for methicillin-susceptible S aureus or culture-negative AHO in pediatric patients, particularly when a less frequent dosing schedule is desired. Future study with a larger sample size is warranted.