Citations

Objective: To assess the impact of extent of parotidectomy on surgical and oncologic outcomes in low grade mucoepidermoid carcinoma (LGMEC). Methods: A retrospective chart review of all patients undergoing primary surgical treatment for LGMEC from 2000 to 2022 was conducted. Clinical features collected included demographics, facial nerve function, operative techniques, postoperative complications/facial nerve function, and recurrence. Results: 58 patients were included; 10 patients underwent partial parotidectomy (PP), 38 underwent superficial parotidectomy (SP), and 10 underwent near-total/total parotidectomy. PP and SP patients had smaller tumors and more superficial tumors compared to near-total/total parotidectomy group ( P = .03). PP and SP were more likely to have negative margins and less locoregional disease compared to near-total/total parotidectomy patients ( P < .01). Near-total/total parotidectomy were more likely to undergo facial nerve resection (20% vs 0% for PP & SP respectively) ( P = .05). Immediate postoperative facial nerve function was significantly better among PP patients (73% HB I) compared to SP (44% HB I) and near-total/total parotidectomy patients (0% HB I) ( P < .01). Most patients regained their facial nerve function although only 40% of the near-total/total parotidectomy patients had a HB I at the time of last follow up ( P < .01). Patients were followed for a median of 6.2 years, during which only 1 patient (total parotidectomy) had a recurrence. Conclusions: PP offers a safe and effective approach for small LGMEC tumors, ensuring better facial nerve function postoperatively with minimal complications compared to more extensive surgery.

Abstract Obstetric training programs typically offer limited formal education on placental pathology; yet, in practice, obstetric providers are expected to incorporate placental pathology findings into the overall evaluation of obstetric complications. In this narrative review, we briefly review pathology classifications and then delve deeper into pathology findings that may change clinical decision‐making, specifically highlighting pathologic lesions with a recurrence risk and recommended management for subsequent pregnancies. Last, we present specific recommendations on how to improve clinical interpretability and utility of placental pathology reports for obstetrical practice.

Background As the population continues to age, the number of adults receiving care for hydrocephalus is expected to increase. Here, we assess trends in the utilization and physician reimbursement for ventriculoperitoneal shunts (VPS), lumboperitoneal shunting (LPS), and endoscopic third ventriculostomy (ETV) for adult hydrocephalus. Methods The Medicare Part B National Summary Data files from 2000 to 2021 were collected, and information was extracted on procedures performed per year, total charges billed, and actual payments. Linear mixed-model regression analyses were conducted to assess the significance of changes in procedural volume and physician reimbursement over time while adjusting for inflation. Results Over the period studied, there was a 26% increase in VPS placement (P = 0.11), 11.34% increase in ETV utilization (P < 0.01), and 43.1% decrease in LPS utilization (P < 0.01). This corresponded to annualized changes of + 4.29% for ETV procedures, −8.78% for LPS, and + 45.8% for VPS. There was a statistically significant difference in the change of rate of number of procedures annually between LPS and VPS (P = 0.04). In both inflation-unadjusted and inflation-adjusted analyses, all procedures experienced an annual decline in reimbursement with inflation-adjusted changes of −11.54%/year for ETV, −4.13% for LPS, and −13.12% for VPS. There was a statistically significant difference in the change of rate of reimbursement between LPS procedures and both ETV (P < 0.01) and VPS (P < 0.01). Conclusion Medicare reimbursement data shows that a commensurate decline in physician reimbursement has accompanied the ongoing rise in adult hydrocephalus procedures.

Background: Noninvasive tests (NITs) are used to risk-stratify metabolic dysfunction–associated steatotic liver disease. The aim was to survey global patterns of real-world use of NITs. Methods: A 38-item survey was designed by the Global NASH Council. Providers were asked about risks for advanced fibrosis, which NITs (cutoff values) they use to risk-stratify liver disease, monitor progression, and which professional guidelines they follow. Results: A total of 321 participants from 43 countries completed the survey (54% hepatologists, 28% gastroenterologists, and 18% other). Of the respondents, 85% would risk-stratify patients with type 2 diabetes, obesity (82%), or abnormal liver enzymes (73%). Among NITs to rule out significant or advanced fibrosis, transient elastography (TE) and fibrosis-4 (FIB-4) were most used, followed by NAFLD Fibrosis Score, Enhanced Liver Fibrosis, and magnetic resonance elastography. The cutoffs for ruling out significant fibrosis varied considerably between practices and from guidelines, with only 50% using TE <8 kPa, 65% using FIB-4 <1.30 for age <65, and 41% using FIB-4 <2.00 for age ≥65. Similar variability was found for ruling in advanced fibrosis, where thresholds of FIB-4 ≥2.67 and TE ≥10 kPa were used by 20% and 17%, respectively. To establish advanced fibrosis, 48% would use 2 NITs while 23% would consider 1 NIT, and 17% would confirm with liver biopsy. TE was used by >75% to monitor, and 66% would monitor (intermediate or high risk) annually. Finally, 65% follow professional guideline recommendations regarding NITs. Conclusions: In clinical practice, there is variability in NIT use and their thresholds. Additionally, there is suboptimal adherence to professional societies’ guidelines.

ABSTRACTUniparental Disomy (UPD) occurs when both copies of a chromosome or chromosomal segment originate from only one parent. Mosaic genome‐wide UPD (mos gwUPD) is typically identified in cases of fetal demise and placental dysplasia or in prenatal cases, where imprinting effects are associated with abnormal ultrasound findings. Children with mos gwUPD and clinical features due to UPD‐associated imprinting effects (especially Beckwith‐Wiedemann syndrome) have been reported; however, reports of adults with mos gwUPD are rare. Here we describe mos gwUPD in two apparently healthy pregnant adult women. Carrier testing noted variants with skewed allelic ratios outside of the normal heterozygous range, prompting further testing. Single nucleotide polymorphism (SNP) microarray identified mosaicism for gwUPD in both individuals, present at 85% and 90%, respectively, in blood, with varying percentages in other tissues. Neither woman displayed clinical features that would be expected with gwUPD at the time of testing, although retrospective careful personal history was consistent. Both women had uneventful pregnancies and delivered full‐term healthy infants. These two cases demonstrate that mos gwUPD can be an incidental finding identified in apparently healthy adult women. Clinical follow‐up is important for tumor monitoring, genetic counseling, and monitoring of future pregnancies due to mos gwUPD in the maternal endometrial tissue.

Abstract Clonal hematopoiesis (CH) of indeterminate potential (CHIP), driven by somatic mutations in leukemia-associated genes, confers increased risk of hematologic malignancies, cardiovascular disease, and all-cause mortality. In blood of healthy individuals, small CH clones can expand over time to reach 2% variant allele frequency (VAF), the current threshold for CHIP. Nevertheless, reliable detection of low-VAF CHIP mutations is challenging, often relying on deep targeted sequencing. Here, we present UNISOM, a streamlined workflow for enhancing CHIP detection from whole-genome and whole-exome sequencing data that are underpowered, especially for low VAFs. UNISOM utilizes a meta-caller for variant detection, in couple with machine learning models which classify variants into CHIP, germline, and artifact. In whole-exome sequencing data, UNISOM recovered nearly 80% of the CHIP mutations identified via deep targeted sequencing in the same cohort. Applied to whole-genome sequencing data from Mayo Clinic Biobank, it recapitulated the patterns previously established in much larger cohorts, including the most frequently mutated CHIP genes and predominant mutation types and signatures, as well as strong associations of CHIP with age and smoking status. Notably, 30% of the identified CHIP mutations had &lt; 5% VAFs, demonstrating its high sensitivity toward small mutant clones. This workflow is applicable to CHIP screening in population genomic studies. The UNISOM pipeline is freely available at https://github.com/shulanmayo/UNISOM and https://ngdc.cncb.ac.cn/biocode/tool/7816.

Abstract Background Instruments to assess patient-reported outcomes (PRO) should generate high-quality evidence. Reliable PRO evidence is essential to policymakers, in conjunction with outcomes such as survival and radiological response, to understand the net clinical benefit of antitumor treatments. This study aimed to establish the content validity of 215 identified PRO measures used in patients with brain tumors. Methods A survey (n = 148 items) was developed reflecting aspects of the WHO International Classification of Functioning, Disability, and Health (ICF) framework. Patients with brain tumors, their proxies, and healthcare professionals (HCPs) were asked to rate each survey item on relevance. An item was considered a relevant issue if ≥25% of the patients or proxies or ≥50% of the HCPs considered that item to be an issue. Next, all items in the identified PRO measures were linked to ICF and relevant items in the survey, and the percentage of content coverage was calculated. Results In total, 114 patients, 71 proxies, and 65 HCPs from different countries completed the survey. Fifty-six of 148 (37.8%) items in the survey were considered relevant. The most important aspects mentioned by both patients and proxies were difficulty concentrating, difficulty remembering, multitasking, and handling stress. Depending on the definition, between 35% and 49% of PRO measures were considered to have sufficient content validity (≥80% coverage). Conclusion The content validity was insufficient in more than half of the identified PRO measures, particularly multidimensional measures. Future research should investigate whether different approaches to PRO assessment better meet the needs of all stakeholders.

OBJECTIVE The optimal dose for triazoles in pediatric patients may substantially vary given the dynamic changes in pharmacokinetics and pharmacodynamics, based on disease severity. Therapeutic drug monitoring has been a valuable tool to help guide management and avoid potential toxicities associated with treatment of invasive fungal infections (IFIs). Goal azole serum concentrations are based on specific drug, indication, and minimum inhibitory concentration when known. This study aimed to determine the optimal pediatric azole doses needed to achieve targeted serum concentrations of isavuconazole, itraconazole, posaconazole, and voriconazole. METHODS This is a single center, retrospective chart review of pediatric patients who received isavuconazole, itraconazole, posaconazole, or voriconazole between January 1, 2011, and August 31, 2021. RESULTS A total of 273 pediatric patients received isavuconazole, itraconazole, posaconazole, or voriconazole in the inpatient or outpatient setting during the study period. Of the 273 patients, only 122 met criteria for inclusion in the analysis. Eighty-three percent of patients reached a goal serum concentration. Patients younger than 12 years required a higher dose (mg/kg/day) to achieve goal serum concentrations. Patients who received an azole in the form of an oral tablet or intravenously were more likely to reach a goal concentration than those not receiving these formulations. Median time to goal concentration occurred at 20 days for isavuconazole, 34 days for itraconazole, 11 days for posaconazole, and 10 days for voriconazole. CONCLUSIONS Higher starting azole doses are needed to obtain goal concentrations quickly, especially for children younger than 12 years.

Genome-wide association studies (GWAS) of multiple myeloma (MM) in individuals of genetic European ancestry (EA) have identified 35 susceptibility loci. Co-heritability analyses have revealed a strong genetic correlation between MM and its precursor condition, monoclonal gammopathy of undetermined significance (MGUS). Previous research validated the association between a polygenic risk score (PRS) based on 23 MM risk loci and the risk of MGUS. Went and colleagues recently reported 12 new MM risk loci. We constructed a MM-PRS using all 35 MM risk variants and assessed its association with MGUS. Additionally, among individuals with MGUS, we assessed associations of MM-PRS with established prognostic factors [M-protein (&lt;0.2 g/dL; 0.2-1.5 g/dL; &gt;1.5 g/dL); isotype (IgG, IgA, IgM); free light chain (FLC) ratio (Normal (0.26-1.65), Abnormal (&lt;0.26 or &gt;1.65))]. Our study population included 1,723 individuals with MGUS seen at Mayo Clinic, Rochester, MN and 14,175 controls from the Mayo Clinic Biobank who lived in the 27-county region around Rochester, MN, and screened negative for MGUS using MALDI-TOF MS. The majority of MGUS patients and controls were of EA. We used logistic or multinomial regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). All models were adjusted for age, sex, and the first three principal components. The MM-PRS was significantly associated with MGUS when assessed continuously (OR, 1.28 per standard deviation (SD); 95% CI, 1.22-1.35). When comparing to the middle quintile of the MM-PRS distribution, individuals in the highest quintile had 1.41-fold increased risk of MGUS (95% CI, 1.21-1.64), and individuals in the lowest quintile had 0.68 decreased risk of MGUS (95% CI, 0.57-0.81). Of the 35 SNPs evaluated, 27 demonstrated consistent directions of effect for risk of MGUS with published risk estimates for MM. The effect of MM-PRS differed by isotype (P = 2.2 x 105), with higher MM-PRS associated with IgA MGUS (OR, 1.40 per SD; 95% CI, 1.08-1.81) and a lower MM-PRS associated with IgM (OR, 0.66 per SD; 95% CI, 0.52-0.84) compared to IgG MGUS. The MM-PRS was higher in MGUS patients with M-protein &gt; 1.5 g/dL compared to M-protein of size 0.2-1.5 g/dL, although not statistically significant (OR, 1.41 per SD; 95% CI, 0.95-2.08); there were no differences in the MM-PRS between MGUS patients with M-protein size &lt;0.2 g/dL compared to 0.2-1.5 g/dL (OR, 1.01 per SD;95% CI, 0.81-1.26). There were also no differences in MM-PRS by FLC ratio, (OR, 0.95 per SD; 95% CI, 0.852-1.10 for abnormal vs. normal). Our findings of an association of the MM-PRS with risk of MGUS provides further evidence for shared heritability between MGUS and MM. Future studies are needed to examine whether the expanded MM-PRS adds to existing models for MGUS progression. Citation Format: Angelica Macauda, Alyssa Clay-Gilmour, Cristine Allmer, Danelle Moonen, Aaron D. Normann, Nicholas J. Boddicker, Joselle M. Cook, Linda Baughn, Elizabeth E. Brown, Vincent S. Rajkumar, Esteban Braggio, David L. Murray, Susan L. Slager, Shaji Kumar, Celine M. Vachon. Implications of multiple myeloma polygenic risk scores (PRS) for MGUS [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2274.

This case series examines long-term outcomes for 2 aquaporin-4-IgG (AQP4-IgG)–positive patients with neuromyelitis optica spectrum disorder (NMOSD) who underwent autologous hematopoietic stem cell transplantation with a nonmyeloablative conditioning regimen and rituximab.