Citations

Cleft lip with or without cleft palate (CL/P) is a common congenital facial pathology that occurs at higher incidences in Hispanic communities. The authors analyzed the availability and readability of Spanish-written patient education materials (PEMs) on CL/P from top-ranking U.S. children’s hospitals to determine the presence of health literacy barriers. Availability of PEM was evaluated by 2 methods: (1) Google search and (2) evaluation of the official hospital websites. For each institution, a Google search was conducted using the phrase, “labio leporino y/o paladar hendido (translation: CL/P) + (hospital name).” In addition, each hospital website was assessed for Spanish PEM availability. Spanish PEMs were then categorized by whether they had been generated by an automated translation function or if they were independently written Spanish text. English PEM readability was assessed using the Simple Measure of Gobbledygook (SMOG). Spanish PEM readability was assessed using spanish orthgraphic length (Spanish Orthographic Length), the SMOG converted for the Spanish language. Unpaired 2-tailed t tests were used to compare readability. Of a total of 85 pediatric hospitals, 28 (37.3%) had Spanish PEM. Five (6.7%) hospitals created their own Spanish-language document. The average spanish orthgraphic length reading level was 9.49 compared with an average SMOG of 11.38 (P < 0.001). Institutions that did not provide Spanish PEM in any format had a significantly higher SMOG for English PEM of 12.13 compared with 11.38 of those that had SMOG with English PEM (P = 0.04). Health literacy barriers not only exist for Spanish PEM but also for English PEM, indicating an opportunity to improve communication.

A subset of desmoplastic melanomas (DMs) can show extensive morphologic and immunohistochemical overlap with cutaneous diffuse-type neurofibroma. Neurofibroma-like desmoplastic melanoma (NFLDM) thus poses a significant diagnostic pitfall because the clinical implications of these 2 entities differ dramatically. A series of 17 DMs, including 5 cases of NFLDM, were compared with a cohort of 53 cutaneous diffuse-type neurofibromas to explore the utility of molecular testing in the differential diagnosis between NFLDM and neurofibroma and to determine potentially useful morphologic features in this differential diagnosis. Unlike NFLDM, cutaneous diffuse-type neurofibromas: (1) rarely feature intratumoral or peritumoral lymphoid aggregates, (2) consistently harbor an intrinsic stromal support vasculature composed of evenly spaced capillary-sized vessels, and (3) infiltrate adjacent adipose tissue in a dermatofibrosarcoma protuberans–like manner with a complete lack of chronic inflammation or fat necrosis at the leading edge of the tumor. Conversely, DMs, including NFLDM: (1) do not contain Wagner-Meissner bodies, (2) often induce fat necrosis and/or chronic inflammation at the interface with adjacent fibroadipose tissue, (3) lack the intrinsic capillary-sized stromal vasculature observed in most neurofibromas, and (4) may harbor foci of perineuriomatous differentiation, mimicking a hybrid nerve sheath tumor. Any deviation from the expected clinical or morphologic features of cutaneous diffuse-type neurofibroma should raise suspicion for NFLDM. Although not entirely sensitive or specific, molecular testing can help to support the diagnosis of NFLDM by demonstrating genetic abnormalities associated with melanoma, including a UV-light–induced mutational signature, high tumor mutational burden, and/or chromosomal copy number alterations typical of melanoma.

Objective To further evaluate a genomic classifier (GC) in a cohort of patients undergoing radical cystectomy (RC), as long non‐coding RNA (lncRNA)‐based genomic profiling has suggested utility in identifying a distinct tumour subgroup corresponding to a favourable prognosis in patients with bladder cancer. Patients and Methods Transcriptome‐wide expression profiling using Decipher Bladder was performed on transurethral resection of bladder tumour samples from a cohort of patients with high‐grade, clinically organ‐confined (cTa–T2N0M0) urothelial carcinoma (UC) who subsequently underwent RC without any neoadjuvant therapy ( n = 226). The lncRNA‐based luminal favourable status was determined using a previously developed GC. The primary endpoint was overall survival (OS) after RC. Secondary endpoints included cancer‐specific mortality and upstaging at RC. Results In the study, 134 patients were clinical non‐muscle‐invasive bladder cancer (cTa/Tis/T1) and 92 patients were cT2. We identified 60 patients with luminal favourable subtype, all of which showed robust gene expression patterns associated with less aggressive bladder cancer biology. On multivariate analysis, patients with the luminal favourable subtype (vs without) were significantly associated with lower odds of upstaging to pathological (p)T3+ disease (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.12–0.82; P = 0.02), any upstaging (OR 0.41, 95% CI 0.20–0.83; P = 0.01), and any upstaging and/or pN+ (OR 0.50, 95% CI 0.25–1.00; P = 0.05). Luminal favourable bladder cancer was significantly associated with better OS (hazard ratio 0.33, 95% CI 0.15–0.74; P = 0.007). Conclusions This study validates the performance of the GC for identifying UCs with a luminal favourable subtype, harbouring less aggressive tumour biology.

Background/Objectives: Pectus excavatum (PEx) is considered, at least partially, a familial disorder. A variety of inheritance patterns, associations with genetic syndromes, and pathogenic variants have been reported. However, the etiology of this condition is still not completely understood, and no known genes have been identified as definitive contributors. Methods: Family members with a confirmed PEx diagnosis (one proband and two first-degree relatives) and non-affected members were recruited into this study. Exome sequencing was performed on all affected familial PEx cases to systematically screen for candidate genes that are likely to be causative for PEx, and on non-affected family members for variant segregation analysis. Results: Ten families, with three affected members each, participated, providing thirty familial PEx cases. Different inheritance patterns were represented across the ten pedigrees, with possible incomplete penetrance. Genetic variants in REST (essential for neuronal development and associated with pectus deformities in prior studies), SMAD4 (variants can predispose individuals to thoracic aortic diseases), and COL5A (associated with Ehlers–Danlos syndrome and Fibromuscular dysplasia) were initially identified as potentially linked to the development of pectus deformities and segregated with the phenotype. No variants were shared across families in the studied population. Conclusions: Germline exome sequencing of families with multiple individuals affected by PEx in our study identified potential gene candidates linked to PEx. These candidates are private to individual families and no strong candidates shared across multiple families were identified. These findings suggest that the inheritance of PEx may not be strongly related to a shared single genetic variant in known genes. Given the accumulating evidence for the genetic basis of familial PEx, further studies, including polygenic analyses, as well as assessment of the non-coding genome and possible epigenetic markers are warranted.

Importance Since 2018, a movement has emerged to define Alzheimer disease (AD) as a purely biological entity based on biomarker findings. The recent revision of the Alzheimer’s Association (AA) criteria for AD furthers this direction. However, concerns about a purely biological definition of AD being applied clinically, the understanding of AD by society at large, and the translation of blood-based biomarkers into clinical practice prompt these International Working Group (IWG) updated recommendations. Objective To consider the revised AA criteria and to offer an alternative definitional view of AD as a clinical-biological construct for clinical use. The recommendations of the 2021 IWG diagnostic criteria are updated for further elaborating at-risk and presymptomatic states. Evidence Review PubMed was searched for articles published between July 1, 2020, and March 1, 2024, using the terms “biomarker” OR “amyloid” OR “tau” OR “neurodegeneration” OR “preclinical” OR “CSF” OR “PET” OR “plasma” AND “Alzheimer’s disease.” The references of relevant articles were also searched. Findings In the new AA diagnostic criteria, AD can be defined clinically as encompassing cognitively normal people having a core 1 AD biomarker. However, recent literature shows that the majority of biomarker-positive cognitively normal individuals will not become symptomatic along a proximate timeline. In the clinical setting, disclosing a diagnosis of AD to cognitively normal people with only core 1 AD biomarkers represents the most problematic implication of a purely biological definition of the disease. Conclusions and Relevance The ultimate aim of the field was to foster effective AD treatments, including preventing symptoms and dementia. The approach of diagnosing AD without a clinical and biological construct would be unwarranted and potentially concerning without a clear knowledge of when or whether symptoms will ever develop. It is recommended that those who are amyloid-positive only and, more generally, most biomarker-positive cognitively normal individuals, should not be labeled as having AD. Rather, they should be considered as being at risk for AD. The expansion of presymptomatic AD is viewed as a better diagnostic construct for those with a specific pattern of biomarkers, indicating that they are proximate to the expression of symptoms in the near future.

Study Design. Literature review. Objective. The goal of this study was to provide a comprehensive outline of spinal injuries that may transpire over the course of military service from traumatic to repetitive stress injuries and chronic sequelae. We considered studies that assessed spinal injuries in combat and non-combat settings as reported in the literature over the last 15 to 20 years. Background. Military service places servicemembers under substantial physical demands, while also exposing them to dangerous, unpredictable environments. As a result, servicemembers are at an increased risk of spinal injuries from combat-related trauma and other causes. They may have different care needs and recovery profiles when compared with civilians with spinal disorders. Materials and Methods. We performed a review of the available literature on spinal injuries and spinal care in the Military Health System from 2001 to the present. Results. The studies discussed in this review were primarily focused on the conflicts in both Iraq and Afghanistan from over 10 years ago and do not fully capture the present-day advancements in military technology that may have an impact on the potential for spinal injuries. The long-term effects of sustained military service and the relative influence of high demand versus sedentary military occupations on the development of spinal disorders remain poorly understood. Given the changing nature of military service, both with respect to the demographic in uniform and the ever-evolving nature of modern combat, we believe that only a long-term prospective observational study dedicated to the surveillance of spinal problems could effectively answer these questions. Conclusion. Further research into the present-day characterization of spinal injuries is warranted given the advancements in both military technology and spine care that have occurred over the last 10 years.