Citations

Background: U.S. dental school graduates must complete competencies in oral health care across the life course. While they have met these requirements, little is known about graduates’ assessment of how this training prepared them for practice. Future practice setting may affect the training needs of dental school graduates. This quality improvement survey looked at alumni narratives regarding their predoctoral training in pediatric dentistry, the adequacy of this training, how practice setting influenced their training needs, and what recommendations they would make for curriculum change. Methods: As part of a larger survey, semi-structured interviews were conducted of 14 recent alumni in general dental practice; the questions covered their graduation year, current practice setting, recollection of their predoctoral pediatric dental training, the adequacy of that training, and recommendations on how to prepare future graduates to care for pediatric dental patients. Interviews were transcribed and assessed for these themes. Results: Half of the practitioners were in private practice, and half worked in rural or community clinics. Recent alumni felt comfortable and confident treating the oral health needs of a pediatric population but overwhelmingly said that they wanted more hands-on experience in dental school. They especially highlighted the need to see patients with challenging behavior and more complex operative treatment needs. Alumni working in rural areas or community clinics emphasized the need for these skills because of the lack of referral options. Conclusions: Recent alumni wish they had had more hands-on pediatric dental experiences in dental school to better prepare them for the challenges they face in practice. These experiences may be limited, and one suggestion would be to channel these opportunities to practitioners who will work in areas where there are insufficient resources and fewer options for referral. Knowledge Transfer Statement: The recommendations from this article can be used by dental educators to improve clinical and didactic teaching and to ensure dental learners’ education and competency.

ABSTRACTBackgroundAdvances in fibril typing by mass spectrometry have improved the accuracy of amyloidosis diagnosis. Dual amyloidogenic proteins have been reported in deposits in sole and multiple different organs.MethodsFive patients with dual amyloidoses were diagnosed between 1995 and 2022 by Congo red staining and fibril typing using the best available methods at the time of evaluation. Sequencing of TTR and GSN genes was performed. Literature search identified 46 additional cases.ResultsThree patients exhibited Waldenström macroglobulinemia‐associated AL (n = 3) amyloidoses in conjunction with ATTRwt or AGel amyloidosis; two patients featured AL/ATTRwt and AA/ATTRwt amyloidoses. One patient demonstrated dual amyloidoses within one anatomical site; three patients featured two amyloidosis types at different anatomical sites; and one patient had dual amyloid deposits in a single anatomical site along with different sites. The time interval between diagnoses was 0–288 months, with the heart and kidneys being the most affected organs.ConclusionsOur findings underscore the complexity of clinical presentation in amyloidosis, as multiple amyloid types can co‐exist in a single individual and affect various anatomical sites. Accurate assessment of the clinical phenotype and thorough amyloid fibril typing from the target organs are essential for precise diagnosis and tailored treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT00898235

ObjectivesThe four‐repeat (4R) tauopathies are a group of neurodegenerative diseases, including progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and globular glial tauopathy (GGT). This study aimed to characterize spatiotemporal atrophy progression using structural magnetic resonance imaging (MRI) and to examine its relationship with clinical course and neuropathology in a cohort of autopsy‐confirmed 4R tauopathies.MethodsThe study included 85 autopsied patients (54 with PSP, 28 with CBD, and 3 with GGT) who underwent multiple 3T MRI scans, as well as neuropsychological, neurological, and speech/language examinations, and standardized postmortem neuropathological evaluations. An unsupervised machine‐learning algorithm, Subtype and Stage Inference (SuStaIn), was applied to the cross‐sectional brain volumes to estimate spatiotemporal atrophy patterns and data‐driven subtypes and stages in each patient. The relationships among estimated subtypes, pathological diagnoses, and longitudinal changes in clinical testing were examined.ResultsThe SuStaIn algorithm identified 2 distinct subtypes: (1) the subcortical subtype, in which atrophy progresses from the midbrain to the cortex, and (2) the cortical subtype, in which atrophy progresses from the frontal cortex to the subcortical regions. The subcortical subtype was more associated with typical PSP, whereas the cortical subtype was more associated with atypical PSP with a cortical distribution of pathology and CBD (p < 0.001). The cortical subtype had a faster rate of change on the PSP Rating Scale than the subcortical subtype (p < 0.05).InterpretationSuStaIn analysis revealed 2 MRI‐driven subtypes with distinct spatiotemporal atrophy patterns, clinical courses, and neuropathology. Our findings contribute to a comprehensive and improved understanding of disease progression and its relationship to tau pathology in 4R tauopathies. ANN NEUROL 2025;98:492–507

ABSTRACTOverviewBlastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive hematologic neoplasm that involves multiple organs, including the skin, bone marrow and blood, lymph nodes, and central nervous system. Violaceous tumors or plaques appearing in sun‐exposed areas are characteristic and present in most patients. The disease typically affects adult men aged 60–70 years, although children and younger adults may also be affected.DiagnosisDiagnosis is based on biopsy of an involved site and is typically based on the identification of blastoid cells displaying the classical immunophenotypes CD123, CD4, and CD56 in addition to specific pDC markers.PrognosisThe median overall survival is 18–24 months. Potential risk factors for shortened survival include older age, overt bone marrow involvement, and genetic abnormalities.Therapy and ManagementEither chemotherapy‐based regimens or tagraxofusp, a CD123‐directed interleukin 3 conjugated with diphtheria toxin, may be used for upfront therapy. Eligible patients are recommended to be consolidated with hematopoietic allogeneic stem cell transplantation. Assessment and treatment of the central nervous system is mandatory, and careful monitoring of skin disease in conjunction with dermatology is essential.

Abstract Purpose Clozapine is primarily metabolized by cytochrome P450 (CYP) 1A2 and to a lesser extent by CYP2C19, CYP2D6, and CYP3A4. The global pandemic of coronavirus disease 2019 (COVID-19) and use of nirmatrelvir/ritonavir brought forth new challenges for those caring for patients prescribed clozapine. Prescribing information describes a consideration for a clozapine dose reduction while monitoring for adverse reactions when clozapine is used with nirmatrelvir/ritonavir. Other drug information resources consider the combination a contraindication. A case is reported in which therapeutic drug monitoring demonstrated a lack of interaction between clozapine and nirmatrelvir/ritonavir. The complexities of infection-associated clozapine toxicity are discussed and a review is provided of CYP3A4 drug and gene interactions with clozapine. Summary A 75-year-old woman with schizophrenia, prescribed clozapine 200 mg by mouth at bedtime, was initiated on nirmatrelvir/ritonavir after developing a mild COVID-19 infection. Two days later, the patient was brought to the emergency department after an unwitnessed fall. Clozapine toxicity was included in the differential diagnosis, although no other signs or symptoms of elevated clozapine levels were present. Nirmatrelvir/ritonavir was discontinued. Clozapine was withheld for 1 day while a clozapine level was pending, but this measurement revealed no interaction when compared to a baseline level of clozapine. Conclusion Although there are hypothetical concerns when initiating a CYP3A4 inhibitor with concomitant clozapine, the information derived from this case does not clearly support an interaction with the addition of nirmatrelvir/ritonavir during mild COVID-19 infection. It is important to understand the risks of withholding clozapine, although fortunately no psychiatric concerns developed. In reviewing the literature, CYP3A4 inhibitors or genetic polymorphisms seem to have a minimal impact on clozapine levels, although clinical monitoring is warranted.

Background: As more healthcare institutions consider providing preemptive pharmacogenomic (PGx) testing to greater numbers of their patients, it will be important to consider the potential concerns patients may have about the generation of preemptive PGx information. To date, few studies have examined the nature and incidence of patient concerns about preemptive PGx testing. Methods: We conducted a longitudinal survey study of 5000 patients receiving preemptive PGx testing in the Mayo Clinic RIGHT study. We assessed patient concerns regarding issues of data confidentiality, cost implications, comprehension of results, and potential disruption of pre-existing medication regimens. Participants were surveyed before and after they received PGx results from the RIGHT study. Results: We achieved 92.8% and 74.4% response rates on the pre- and post-results surveys, respectively. Participants had low levels of concern about PGx testing overall. However, 25.5% of participants were “quite/extremely concerned” about insurance implications, and 30.1% were “quite/extremely” concerned about increased out-of-pocket costs for prescription medications that might result from PGx testing. These same concerns were significantly reduced on the post-results survey. Patients who initially expressed concerns regarding their ability to understand PGx results were more likely to report having difficulty understanding results on the post-results survey. Conclusions: Our findings suggest that as healthcare institutions look to increase preemptive PGx screening, attention should be given to potential concerns patients may have around such testing. Educational interventions aimed at supporting patient understanding of PGx results and addressing potential concerns will be important elements of a successful PGx program.

Objectives: To analyze variations in patient characteristics, treatment patterns, clinical manifestations, clinical outcomes (i.e., response, flares and flare-free survival in HES; remission, relapses and relapse-free survival in EGPA; and overall survival), and healthcare resource utilization (HCRU) in patients with hypereosinophilic syndrome (HES) and eosinophilic granulomatosis with polyangiitis (EGPA) across five European countries. Methods: In two parallel, retrospective, non-interventional, longitudinal chart review studies (GSK ID: 214661 [EGPA] and 214657 [HES]), physicians collected data of patients they treated in France, Germany, Italy, Spain, and the UK from January 2015 to December 2019, with follow-up until August 2021. Country-level results are presented for each study; HES and EGPA data were pooled in a post hoc exploratory analysis. Results: Per-country, 22–26 HES- and 38–45 EGPA-treating physicians collected data from 52–62 (total 280) patients with HES and 80–85 (total 407) with EGPA. Patient sex and age at diagnosis differed across countries. Pooled HES/EGPA data revealed high oral corticosteroid (OCS) use in all countries (94.9% of patients; median [IQR] duration 20.7 [9.0, 33.8] months); immunosuppressive treatments and biologics use varied between countries (43.7–61.5% and 25.6–59.8%, respectively). The most frequent clinical manifestations were constitutional (51.6–78.8%) and lung (43.5–55.8%) in HES, and lung (41.3–67.9) and ENT (43.8–61.2) in EGPA. Pooled HCRU data showed country-level variation; 70.7–91.2% of patients had disease-related outpatient visits and 36.1–52.6% had ER visits or hospitalizations. Conclusions: Results demonstrate substantial disease burden, including high HCRU and extensive OCS use among patients with HES and EGPA in five European countries. The findings highlight the need for improved treatment strategies such as optimizing use of biologics to mitigate the reliance on corticosteroids.

ABSTRACT Background Over the years, prognostic indexes have been developed to help clinicians stratify patients with biliary tract cancers (BTC) into risk groups. This study aims to identify a new prognostic index for patients with BTC treated with cisplatin, gemcitabine and durvalumab (CGD) in the first‐line setting. Patients and Methods The study population consisted of patients with BTC from 11 Eastern and Western Countries. Using multivariate analysis for overall survival (OS), we identified 5 baseline statistically significant variables: stage, carcinoembryonic antigen (CEA) levels, albumin levels, gamma glutamyl transferase (GGT) levels, neutrophil‐to‐lymphocyte ratio (NLR). Metastatic disease is a prognostic factor with a superior weight considering the HR of 3.62, while all the others can be considered prognostic factors with equivalent weight as the HRs are quite similar (HRs between 1.55 and 1.92). Based on these reasons, we developed a prognostic model called the MAGIC‐D index by assigning a score of 2 for metastatic disease, and a score of 1 for CEA increased levels, albumin decreased levels, GGT increased levels, NLR ≥ 3. Patients were stratified into three risk groups as follows: low‐risk group (Score from 0 to 2), intermediate‐risk group (Score from 3 to 4) and high‐risk group (Score from 5 to 6). At the first data cutoff (April 2024), these data were available for 319 patients that composed the training cohort used for the analysis. At the second data cutoff (May 2025), 79 patients were further enrolled and composed the validation cohort. Results Median progression‐free survival was 11.7 months in low‐risk group (20.7%), 8.7 months in intermediate‐risk group (46.4%) and 5.4 months in high‐risk group (32.9%) [low‐risk hazard ratio (HR): 0.27, intermediate‐risk HR: 0.55, high‐risk HR: 1, p < 0.0001]. Median OS was 18.4 months in low‐risk group,15.9 months in intermediate‐risk group and 7.8 months in high‐risk group (low‐risk HR: 0.17, intermediate‐risk HR: 0.43, high‐risk HR: 1, p < 0.0001). There was no difference in overall response rate (low‐risk: 31.8%, intermediate‐risk: 36.5% and high‐risk: 25.7%; p = 0.0718), while disease control rate was significantly different across the three risk groups (low‐risk: 83.3%, intermediate‐risk: 70.9% and high‐risk: 60.9%; p < 0.0001) as well as the rate of patients receiving a second‐line therapy (low‐risk: 54.5%, intermediate‐risk: 48.6% and high‐risk: 25.7%; p = 0.0061). Finally, the prognostic role in terms of OS and PFS of the MAGIC‐D index was confirmed in a validation cohort of 79 patients. Conclusion The MAGIC‐D index is an easy‐to‐use tool able to stratify patients with BTC with different prognoses undergoing first‐line therapy with CGD.

Abstract Background: Classic metaphyseal lesions (CMLs) are considered specific for child abuse, but the reliability of radiologists in distinguishing CMLs from metaphyseal variations is unclear. Objective: To evaluate whether radiologists can differentiate between CMLs and metaphyseal variations in the knees. Materials and Methods: We performed a retrospective review of distal femur and proximal tibia radiographs in children under two years of age who underwent skeletal surveys for suspected child abuse. The CML group included children diagnosed with abuse and reported CMLs. The metaphyseal variation group included children not diagnosed with abuse, with reported metaphyseal variations and either no fractures or an isolated skull fracture. Radiographs were trimmed to exclude other injuries. Four pediatric and four general radiologists reviewed anonymized studies and categorized each case as CML, metaphyseal variation, normal, or indeterminate, with confidence levels (high, moderate, low). We analyzed diagnoses with moderate or high confidence. Interobserver agreement was assessed using kappa statistics. Results: There were 48 children with CMLs (40 initial, 38 follow-up) and 27 with metaphyseal variations (20 initial, 12 follow-up). Metaphyseal fragmentation was the most common variation, identified in 259 of 356 femurs (72.8%) and 69 of 83 tibias (83.1%). Fragmentations were most frequently located in the posterior or medial metaphysis, or both, in 257 of 259 femurs (99.2%) (257/259) and 68 of 69 tibias (98.6%). In the CML group, 34 of 115 initial CML diagnoses (29.4%) were read on follow-up as either metaphyseal variation (n=17) or normal (n=17). In contrast, in the metaphyseal variation group, only one follow-up case was diagnosed as a CML; the remainder were diagnosed as metaphyseal variation (n=22) or normal (n=2). Diagnostic performance for CML demonstrated high specificity (90.7%) and positive predictive value (94.9%), with moderate accuracy (76.1%), sensitivity (70.2%), and negative predictive value (55.2%). Interobserver agreement was substantial, with a mean kappa of 0.61. Conclusion: Radiologists demonstrated substantial agreement and high specificity in distinguishing CMLs from metaphyseal variations. Metaphyseal fragmentation was the most common variation and was uncommonly diagnosed as CML on follow-up.