Search

Reference regions are important in laboratory medicine to interpret the test results of patients, and usually given by tolerance regions. Tolerance regions of p (≥2)$$ p\;\left(\ge 2\right) $$ dimensions are highly desirable when the test results contains p$$ p $$ outcome measures. Nonparametric hyperrectangular tolerance regions are attractive in real problems due to their robustness with respect to the underlying distribution of the measurements and ease of intepretation, and methods to construct them have been recently provided by Young and Mathew [Stat Methods Med Res. 2020;29:3569‐3585]. However, their validity is supported by a simulation study only. In this paper, nonparametric hyperrectangular tolerance regions are constructed by using Tukey's [Ann Math Stat. 1947;18:529‐539; Ann Math Stat. 1948;19:30‐39] elegant results of equivalence blocks. The validity of these new tolerance regions is proven mathematically in [Ann Math Stat. 1947;18:529‐539; Ann Math Stat. 1948;19:30‐39] under the only assumption that the underlying distribution of the measurements is continuous. The methodology is applied to analyze the kidney function problem considered in Young and Mathew [Stat Methods Med Res. 2020;29:3569‐3585]. [ABSTRACT FROM AUTHOR]

This article draws on 2 years' worth of ethnographic observation of team meetings to explore decision‐making in an NHS clinical genomics service. The focus of discussions was on ambiguous genomic results known as VUS or Variants of Uncertain Significance, which may be pathogenic but which also may turn out to be benign. In examining decision‐making around such results, we note how, in contrast to much policy and promotional material in this area, clinicians in these meetings (clinical geneticists and genetic counsellors) place great emphasis on parental phenotypes and whether the parents of a patient share the symptoms and signs of the suspected condition. This information is then combined with the result of genomic tests to decide whether the variant a patient has is responsible for their condition. This article explores the way in which clinicians attempt to flexibly enrol parents into genomic explanations through informal diagnosis of their possible phenotypes and the way in which actually meeting parents allows some clinicians to trump explanations based on documentary or photographic data. The paper sheds light on the way that earlier scholarly understandings of such decisions (around, say dysmorphology) remain relevant and explores claims that laboratory tests overrule clinical decision‐making. [ABSTRACT FROM AUTHOR]

Objective: Sarcopenia is a geriatric syndrome that occurs with age and is characterized by a gradual decline in muscle mass, power, and functionality. It serves as a prominent contributor to frailty, disability, and mortality among older individuals. Currently, no standardized global guidelines exist for the diagnosis of sarcopenia. This study aimed to establish the correlation between sarcopenia and the constitutions of traditional Chinese medicine (TCM), considering the connection between physical functioning and sarcopenia. Methods: A total of 1441 participants in this study were diagnosed with sarcopenia. The Asian Working Group for Sarcopenia (AWGS) proposed a sarcopenia definition algorithm. To determine the constitution of each participant, classification and determination standards were used in traditional Chinese medicine. This study evaluated the demographics, lifestyles, and self‐reported medical history of individuals diagnosed with sarcopenia through a self‐administered questionnaire. The constitution of the participants was determined using TCM classification and determination standards. Subsequently, we analyzed the results of univariate analysis and multivariate regression and constructed a receiver operating characteristic (ROC) curve. Results: Participants who were diagnosed with sarcopenia had substantially lower original Neutral constitution scores (P < 0.050). In comparison to those without sarcopenia, individuals with sarcopenia exhibited notably elevated original Qi‐deficiency, Yang‐deficiency, Yin‐deficiency, Blood‐stagnation, and Qi‐stagnation scores in contrast to those in the healthy group (P < 0.050). The identified risk factors associated with sarcopenia included the following: Neutral (OR = 0.903), Qi‐deficiency (in males, OR = 1.126), Yang‐deficiency (OR = 1.062), Phlegm‐dampness (in males, OR = 0.833), and Blood‐stagnation (in females, OR = 1.089). The highest area under the curve (AUC) was observed for the original neutral constitution score, followed by the Yang‐deficiency and blood‐stagnation scores (0.644, 0.613, and 0.611, respectively). Additionally, the AUC for the combined original scores of all nine constitutions among males reached 0.778. Conclusions: In this cross‐sectional study of older people with higher original Qi‐deficiency, Yin deficiency, Yang‐deficiency, Blood‐stagnation, and Qi‐stagnation were associated with sarcopenia. Notably, various TCM constitutions are significantly linked to sarcopenia. There was a significant occurrence of various body constitution types among individuals diagnosed with sarcopenia. The mixture of the nine original constitution scores exhibited good diagnostic performance for sarcopenia in males. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal eosinophilic sclerosing fibroplasia (GESF) in cats presents as mass(es) associated with the gastrointestinal tract, mesentery, and abdominal lymph nodes. Hypothesis/Objectives: To report the clinicopathological findings, treatment, and outcome of cats with GESF. Animals: Sixty client‐owned cats diagnosed with GESF. Methods: Retrospective review of medical records of cats with histopathologically confirmed GESF. Results: The median age was 5.4 years (interquartile range [IQR], 3.3‐8.9.); 30% were Domestic Shorthairs and 12% were Domestic Longhair cats, with the most prevalent pedigree breeds being Ragdolls (25%), Exotic Shorthair (10%) and Persian (8%) cats. The median duration of clinical signs was 90 days (IQR, 17.5‐247.0); the most common clinical signs were weight loss (60%), hyporexia/anorexia (55%), chronic vomiting (37%), lethargy (35%) and chronic diarrhea (27%). Masses were located in the small intestine (32%), stomach (27%), ileocolic junction (15%), colon (10%), lymph node (8%) and mesentery (8%) and 15% of cats had >1 mass. Eosinophilia was present in 50% and hypoalbuminemia in 28% of cats. The mass was removed surgically in 37% of cases. Most cats (98%) were treated with corticosteroids. Survival was not statistically different between cats treated with surgical resection and cats treated with medical therapy alone, 88% of the cats were still alive at the time of writing. Conclusions and Clinical Importance: GESF is an important differential diagnosis for abdominal masses in cats, and has a much better prognosis than previously reported. [ABSTRACT FROM AUTHOR]

An increasing number of manuscripts related to digital and computational pathology are being submitted to The Journal of Pathology: Clinical Research as part of the continuous evolution from digital imaging and algorithm‐based digital pathology to computational pathology and artificial intelligence. However, despite these technological advances, tissue analysis still relies heavily on pathologists' annotations. There are three crucial elements to the pathologist's role during annotation tasks: granularity, time constraints, and responsibility for the interpretation of computational results. Granularity involves detailed annotations, including case level, regional, and cellular features; and integration of attributions from different sources. Time constraints due to pathologist shortages have led to the development of techniques to expedite annotation tasks from cell‐level attributions up to so‐called unsupervised learning. The impact of pathologists may seem diminished, but their role is crucial in providing ground truth and connecting pathological knowledge generation with computational advancements. Measures to display results back to pathologists and reflections about correctly applied diagnostic criteria are mandatory to maintain fidelity during human–machine interactions. Collaboration and iterative processes, such as human‐in‐the‐loop machine learning are key for continuous improvement, ensuring the pathologist's involvement in evaluating computational results and closing the loop for clinical applicability. The journal is interested particularly in the clinical diagnostic application of computational pathology and invites submissions that address the issues raised in this editorial. [ABSTRACT FROM AUTHOR]

Objective: Alzheimer's disease neuropathologic change and alpha‐synucleinopathy commonly co‐exist and contribute to the clinical heterogeneity of dementia. Here, we examined tau epitopes marking various stages of tangle maturation to test the hypotheses that tau maturation is more strongly associated with beta‐amyloid compared to alpha‐synuclein, and within the context of mixed pathology, mature tau is linked to Alzheimer's disease clinical phenotype and negatively associated with Lewy body dementia. Methods: We used digital histology to measure percent area‐occupied by pathology in cortical regions among individuals with pure Alzheimer's disease neuropathologic change, pure alpha‐synucleinopathy, and a co‐pathology group with both Alzheimer's and alpha‐synuclein pathologic diagnoses. Multiple tau monoclonal antibodies were used to detect early (AT8, MC1) and mature (TauC3) epitopes of tangle progression. We used linear/logistic regression to compare groups and test the association between pathologies and clinical features. Results: There were lower levels of tau pathology (β = 1.86–2.96, p < 0.001) across all tau antibodies in the co‐pathology group compared to the pure Alzheimer's pathology group. Among individuals with alpha‐synucleinopathy, higher alpha‐synuclein was associated with greater early tau (AT8 β = 1.37, p < 0.001; MC1 β = 1.2, p < 0.001) but not mature tau (TauC3 p = 0.18), whereas mature tau was associated with beta‐amyloid (β = 0.21, p = 0.01). Finally, lower tau, particularly TauC3 pathology, was associated with lower frequency of both core clinical features and categorical clinical diagnosis of dementia with Lewy bodies. Interpretation: Mature tau may be more closely related to beta‐amyloidosis than alpha‐synucleinopathy, and pathophysiological processes of tangle maturation may influence the clinical features of dementia in mixed Lewy‐Alzheimer's pathology. [ABSTRACT FROM AUTHOR]

Background: Familial gigantiform cementoma (FGC) is a rare tumor characterized by the early onset of multi‐quadrant fibro‐osseous lesions in the jaws, causing severe maxillofacial deformities. Its clinicopathological features overlap with those of other benign fibro‐osseous lesions. FGC eventually exhibits progressively rapid growth, but no suspected causative gene has been identified. Methods: In this study, three patients with FGC were recruited, and genomic DNA from the tumor tissue and peripheral blood was extracted for whole‐exome sequencing. Results: Results showed that all three patients harbored the heterozygous mutation c.1067G > A (p.Cys356Tyr) in the ANO5 gene. Furthermore, autosomal dominant mutations in ANO5 at this locus have been identified in patients with gnathodiaphyseal dysplasia (GDD) and are considered a potential causative agent, suggesting a genetic association between FGC and GDD. In addition, multifocal fibrous bone lesions with similar clinical presentations were detected, including five cases of florid cemento‐osseous dysplasia, five cases of polyostotic fibrous dysplasia, and eight cases of juvenile ossifying fibromas; however, none of them harbored mutations in the ANO5 gene. Conclusion: Our findings indicate that FGC may be an atypical variant of GDD, providing evidence for the feasibility of ANO5 gene testing as an auxiliary diagnostic method for complex cases with multiple quadrants. [ABSTRACT FROM AUTHOR]