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Objective: To examine the clinicopathological features, immunohistochemical profiles, and differential diagnosis of sclerosing angiomatiod nodular transformation (SANT)., Methods: Three cases of SANT of the spleen, diagnosed between 2014 and 2023 at the Affiliated Hospital of Zunyi Medical University, were analysed. Pathological features were assessed using haematoxylin and eosin staining, followed by immunohistochemistry with the EnVision system. Additionally, a review of relevant literature was conducted., Results: The study included one male and two female patients aged 40-55 years, with a median age of 47.5 years. All lesions were solitary, with tumour diameters ranging from 4 to 7.4 cm (mean 5.7 cm). Gross examination demonstrated that the masses were well-demarcated from the surrounding splenic tissue, with no evident capsule. The cut surfaces of the masses exhibited irregular, porcelain-white nodules that were tough in consistency, with some areas intermingling with splenic tissue. Microscopic examination revealed round or circular nodules comprising multiple slit-like or sinusoidal capillaries, separated by concentric collagen fibres. The nodules exhibited chronic inflammatory cell infiltration, calcification, haemosiderin deposition, and fibrous connective tissue with hyaline or mucoid changes. Immunohistochemical analysis demonstrated differential expression of markers, including cluster of differentiation (CD) 34, CD31, and CD8, within the sinusoidal nodule areas. Periodic acid-Schiff staining was positive for perinodular collagen deposits, while reticulin staining highlighted nodule profiles and intranodular vessels. None of the patients experienced postoperative recurrence or metastasis, and one patient was on aspirin for thrombocytosis., Conclusion: SANT of the spleen is generally considered a rare, benign lesion with angioma-like characteristics. It exhibits exhibiting distinctive histomorphological features within the red pulp. Understanding the differential diagnosis is crucial to prevent missed or incorrect diagnoses., (© 2024. The Author(s).)

Radial sclerosing lesions (RS, also referred to as "radial scars") and complex sclerosing lesions (CSL) are uncommon breast lesions often grouped together as a single entity in practice. RS/CSL have an incidence of <0.1% to 1% at core needle biopsy (CNB). When detected on CNB, imaging and pathology features must be carefully evaluated to determine appropriate surgical management or imaging follow-up due to potential for malignant upgrade at surgery. Detection of RS/CSL has increased with the advent of tomosynthesis, in which an RS/CSL is typically detected as architectural distortion with or without associated mass with spiculated margins. On US, an RS/CSL is most often occult or manifests as subtle distortion with adjacent cysts. Imaging findings cannot distinguish benign RS/CSL from those upgraded to malignancy at surgery, although larger lesion size may be associated with higher upgrade rates. Histologically, an RS has a central fibroelastotic nidus with entrapped-appearing ducts and proliferative changes at the periphery appearing to radiate from the center; CSL are larger than RS, more disorganized, and typically include multiple patterns of epithelial proliferations, including sclerosing adenosis, sclerosing papillomas, usual ductal hyperplasia, and cysts. RS/CSL with associated atypia at CNB have a 16%to 29% rate of upgrade to malignancy on surgical excision, thus rendering surgical excision essential. Conversely, an RS/CSL without associated atypia, particularly when ≤1 cm in size, has <3% rate of upgrade to malignancy at surgery, allowing consideration of imaging follow-up in lieu of excision. Here, we review recent literature as well as radiology and pathology findings of RS/CSL., (© Society of Breast Imaging 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: The single-center retrospective cohort study investigated underlying pathogenic mechanisms and clinical significance of patients with temporal lobe epilepsy and hippocampal sclerosis (TLE-HS), in the presence/absence of gray-white matter abnormalities (usually called "blurring"; GMB) in ipsilateral temporopolar region (TPR) on MRI., Methods: The study involved 105 patients with unilateral TLE-HS (60 GMB+ and 45 GMB-) who underwent standard anterior temporal lobectomy, along with 61 healthy controls. Resected specimens were examined under light microscope. With combined T1-weighted and DTI data, we quantitatively compared large-scale morphometric features and exacted diffusion parameters of ipsilateral TPR-related superficial and deep white matter (WM) by atlas-based segmentation. Along-tract analysis was added to detect heterogeneous microstructural alterations at various points along deep WM tracts, which were categorized into inferior longitudinal fasciculus (ILF), uncinate fasciculus (UF), and temporal cingulum., Results: Comparable seizure semiology and postoperative seizure outcome were found, while the GMB+ group had significantly higher rate of HS Type 1 and history of febrile seizures, contrasting with significantly lower proportion of interictal contralateral epileptiform discharges, HS Type 2, and increased wasteosomes in hippocampal specimens. Similar morphometric features but greater WM atrophy with more diffusion abnormalities of superficial WM was observed adjacent to ipsilateral TPR in the GMB+ group. Moreover, microstructural alterations resulting from temporopolar GMB were more localized in temporal cingulum while evenly and widely distributed along ILF and UF., Interpretation: Temporopolar GMB could signify more severe and widespread microstructural damage of white matter rather than a focal cortical lesion in TLE-HS, affecting selection of surgical procedures., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Fibrosing mediastinitis (FM) is a rare yet fatal condition, caused by different triggers and frequently culminating in the obstruction of the pulmonary vasculature and airways, often leading to pulmonary hypertension and right heart failure. Percutaneous transluminal pulmonary venoplasty (PTPV) is an emerging treatment for pulmonary vein stenosis (PVS) caused by FM. Our previous study showed as high as 24% of in-stent restenosis (ISR) in FM. However, the predictors of ISR are elusive., Objectives: We sought to identify the predictors of ISR in patients with PVS caused by extraluminal compression due to FM., Methods: We retrospectively enrolled patients with PVS-FM who underwent PTPV between July 1, 2018, and December 31, 2022. According to ISR status, patients were divided into two groups: the ISR group and the non-ISR group. Baseline characteristics (demographics and lesions) and procedure-related information were abstracted from patient records and analyzed. Univariate and multivariate analyses were performed to determine the predictors of ISR., Results: A total of 142 stents were implanted in 134 PVs of 65 patients with PVS-FM. Over a median follow-up of 6.6 (3.4-15.7) months, 61 of 134 PVs suffered from ISR. Multivariate analysis demonstrated a significantly lower risk of ISR in PVs with a larger reference vessel diameter (RVD) (odds ratio (OR): 0.79; 95% confidence interval [CI]: 0.64 to 0.98; P = 0.032), and stenosis of the corresponding pulmonary artery (Cor-PA) independently increased the risk of restenosis (OR: 3.41; 95% CI: 1.31 to 8.86; P = 0.012). The cumulative ISR was 6.3%, 21.4%, and 39.2% at the 3-, 6-, and 12-month follow-up, respectively., Conclusion: ISR is very high in PVS-FM, which is independently associated with RVD and Cor-PA stenosis., Trail Registration: Chinese Clinical Trials Register; No.: ChiCTR2000033153. URL: http://www.chictr.org.cn ., (© 2024. The Author(s).)

The dentate gyrus (DG) plays a critical role in hippocampal circuitry, providing a "gate-like" function to the downstream cornu ammonis (CA) sectors. Despite this critical role, pathologies in DG are less commonly described than those in the CA sectors in the diagnosis of mesial temporal lobe epilepsy (mTLE). To elucidate the role of the DG in mTLE, we analysed hippocampal sclerosis (HS), no-HS, non-TLE epilepsy control, and non-epilepsy control cohorts using morphometry and gene expression profiling techniques. Morphometry techniques analysed DG cell spacing, nucleus size, and nucleus circularity. Our data show distinct DG morphometry and RNA expression profiles between HS and No-HS. Dentate granule cells are more dispersed in patients with HS, and the DG shows an elevated expression of the complement system, apoptosis, and extracellular matrix remodelling-related RNA. We also observe an overall decrease in neurogenesis-related RNA in HS DG. Interestingly, regardless of the pathological diagnosis, the DG morphometry correlates with post-operative outcomes. Increased cell spacing is observed in the DG of mTLE cases that achieve seizure freedom post-operatively. This study reveals the possible prognostic value of DG morphometry, as well as supporting the notion that HS and no-HS TLE may be distinct disease entities with differing contributing mechanisms., (© 2024 The Author(s). Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)

Temporal lobe epilepsy (TLE) is a prevalent form of epilepsy originating in the temporal lobes. A common pathological feature is hippocampal sclerosis (HS), characterized by the loss of neuronal cells, which is associated with the typical temporal mesial lobe epilepsy (MTLE). In this study, we aimed to analyze gray matter alterations in patients with MTLE with right and left hemisphere HS using voxel-based morphometry and compare them with control groups. A meta-analysis was performed based on the guidelines contained in the Protocol Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), using the MEDLINE database, with the keywords: "gray matter" AND "temporal lobe epilepsy " AND ("hippocampal sclerosis" OR "hippocampal abnormalities") AND ("voxel-based morphometry" OR "VBM" OR "voxel-wise"). Of the 14 articles included in the review, 8 were added by the method, in which the meta-analysis was performed. Our results indicate that in the right hemisphere, the hippocampus, caudate nucleus, parahippocampal gyrus, thalamus, dorsalis medial nucleus, insula, and right claustrum were most commonly implicated. In the left hemisphere, a significant pattern of gray matter loss was observed in the putamen, lentiform nucleus, uncus, Brodmann areas 20 and 23, cingulate gyrus, caudate nucleus, cerebellum, and cuneus compared to healthy controls.Our study highlights distinct patterns of gray matter alteration in MLTE-HS and suggests that these regions may contribute to changes in verbal memory and visuospatial impairment based on their anatomical and hemispheric locations. Our findings can be potentially helpful for future diagnostic markers, therapeutic targets, and insights into disease progression, better understanding of these findings., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Temporal lobe epilepsy is a common form of epilepsy that is often associated with hippocampal sclerosis (HS). Although HS is commonly considered a binary assessment in radiologic evaluation, it is known that histopathologic changes occur in distinct clusters. Some subtypes of HS only affect certain subfields, resulting in minimal changes to the overall volume of the hippocampus. This is likely a major reason why whole hippocampal volumetrics have underperformed versus expert readers in the diagnosis of HS. With recent advancements in MRI technology, it is now possible to characterize the substructure of the hippocampus more accurately. However, this is not consistently addressed in radiographic evaluations. The histologic subtype of HS is critical for prognosis and treatment decision-making, necessitating improved radiologic classification of HS. The International League Against Epilepsy (ILAE) has issued a consensus classification scheme for subtyping HS histopathologic changes. This review aims to explore how the ILAE subtypes of HS correlate with radiographic findings, introduce a grading system that integrates radiologic and pathologic reporting in HS, and outline an approach to detecting HS subtypes by using MRI. This framework will not only benefit current clinical evaluations, but also enhance future studies involving high-resolution MRI in temporal lobe epilepsy., (© 2024 by American Journal of Neuroradiology.)

Feline gastrointestinal eosinophilic sclerosing fibroplasia (FGESF) is a rare and poorly understood disease characterised by the infiltration of eosinophils and the development of fibrous tissue within the gastrointestinal tract of cats. A 2-year-old female neutered Ragdoll was presented for signs consistent with extrahepatic biliary tract obstruction (EHBO), including jaundice, hyporexia and lethargy. Marked progressive hyperbilirubinemia and mild anaemia were also present. Abdominal ultrasonography suggested a duodenal mass and pancreatitis as the cause of EHBO. Cytopathological results from fine needle aspirates detected mast cells and eosinophils in the duodenal mass and eosinophils in the spleen and the liver, suggestive of a possible mast cell tumour. A cholecystojejunostomy and a duodenotomy were performed to divert the biliary outflow and obtain biopsy samples, respectively. Eosinophilic sclerosing fibroplasia in the duodenal mass and fungal elements in an abdominal lymph node were reported on histopathological examination. A pan-fungal PCR targeting ITS2 performed on DNA extracted from an abdominal lymph node detected Candida albicans. This report adds to the growing body of evidence that FGESF can occur in association with fungal infections., (© 2024 The Author(s). Veterinary Medicine and Science published by John Wiley & Sons Ltd.)

Since the concept of IgG4-related disease (IgG4-RD) was proposed, that diagnosis has been considered in idiopathic fibroinflammatory diseases in various organs, particularly in cases with multi-organ involvement. We have recently encountered three cases of fibrosing disease of uncertain etiology with shared microscopic appearances. Case 1 (56-year-old man) had an irregular mass at the base of mesentery. Case 2 (29-year-old woman) presented with obstructive jaundice due to an ill-defined mass at the hepatic hilum and two lung nodules. Case 3 (53-year-old man) had multiple solid nodules in the mediastinum, peritoneum, retroperitoneum, and mesentery; he also had diffuse irregular narrowing of the intra- and extra-hepatic bile ducts in keeping with sclerosing cholangitis. Serum IgG4 concentrations were not elevated. Biopsies from the nodular lesions showed extensive hyalinizing fibrosis with an only focal lymphoplasmacytic infiltrate. Thick collagenous bundles are arranged in an irregular or partly whorl pattern. Typical storiform fibrosis or obliterative phlebitis was not observed. The number of IgG4-positive plasma cells was <10 cells/high-power field; the ratio of IgG4/IgG-positive plasma cells was <30%. After the histological diagnosis of sclerosing mesenteritis, pulmonary hyalinizing granuloma, and mediastinal fibrosis was made, they were treated with a trial of steroids, but none showed a significant response. In conclusion, a hyalinizing fibrotic condition can occur at various anatomical sites. They have shared microscopic findings, and are steroid-resistant. Although the clinical presentation may mimic IgG4-RD, the two conditions are likely distinct. We would propose a diagnostic term of 'idiopathic hyalinizing fibrosclerosis' for this under-recognized, rare, systemic condition., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: Radial sclerosing lesions (RSLs) are benign breast lesions composed of glandular and epithelial proliferations with stellate architecture and fibro-elastotic stroma, which can mimic invasive carcinoma on imaging. Surgical management following a core biopsy diagnosis of RSLs remains controversial., Methods and Results: We retrospectively identified core biopsies with RSLs without atypia who underwent subsequent surgical excision between 2015 and 2021. All core biopsy slides were reviewed to confirm the diagnosis. Imaging was reviewed to determine radiological-pathological concordance. An upgrade was defined as invasive carcinoma or ductal carcinoma in situ (DCIS) in the excision. The final cohort consisted of 130 core biopsies from 124 women (median age = 52 years, range = 27-76). The imaging modality was mammogram in 52 (40%) cases, MRI in 52 (40%) and ultrasound in 26 (20%). One hundred and seven (82%) core biopsies were vacuum-assisted and 23 (18%) were ultrasound-guided without vacuum assistance. The median lesion size on imaging was 9 mm (range = 2-41). Overall, two (1%) cases were upgraded at excision, including one microinvasive lobular carcinoma and one 2 mm focus of invasive mammary carcinoma with associated DCIS. In both cases, the upgraded foci of carcinoma were not closely associated with the biopsy site and were considered incidental upgrades., Conclusions: This study adds to the body of literature supporting observation, rather than routine excision of radial sclerosing lesions without atypia., (© 2024 John Wiley & Sons Ltd.)

Sclerosing lesions of the breast encompass a spectrum of benign and malignant entities and often pose a diagnostic challenge. Awareness of key morphologic features and pitfalls in the assessment of morphology and immunophenotype is essential to avoid over- or underdiagnosis and ensure optimal clinical management. This review summarizes nonneoplastic sclerosing lesions such as radial scar/complex sclerosing lesion, sclerosing adenosis, sclerosing intraductal papilloma, sclerosing variants of ductal adenoma and nipple adenoma, and fibroadenoma with extensive sclerosis, including their clinical presentation, characteristic morphology, differential diagnostic considerations, appropriate immunohistochemical work-up, when needed, and the clinical significance. In addition, atypical or neoplastic entities (such as atypical ductal hyperplasia, ductal carcinoma in situ, low-grade adenosquamous carcinoma, and fibromatosis-like metaplastic carcinoma) that can involve these sclerosing lesions are also briefly discussed., (© 2024 John Wiley & Sons Ltd.)

Osteosarcoma (OS) is the most common malignant primary bone tumor in humans and occurs in various subtypes. Tumor formation happens through malignant osteoblasts producing immature bone. In the present paper we studied two different subtypes of osteosarcoma, from one individual with conventional OS with massive sclerosis and one individual with parosteal OS, based on a multimodal approach including small angle x-ray scattering (SAXS), wide angle x-ray diffraction (WAXS), backscattered electron imaging (BEI) and Raman spectroscopy. It was found that both tumors showed reduced mineral particle sizes and degree of orientation of the collagen-mineral composite in the affected areas, alongside with a decreased crystallinity. Distinct differences between the tumor material from the two individuals were found in the degree of mineralization. Further differences were observed in the carbonate to phosphate ratio, which is related to the degree of carbonate substitution in bone mineral and indicative of the turnover rate. The contraction of the c-axis of the bone mineral crystals proved to be a further, very sensitive parameter, potentially indicative of malignancy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Objective: This study was undertaken to determine whether hippocampal T2 hyperintensity predicts sequelae of febrile status epilepticus, including hippocampal atrophy, sclerosis, and mesial temporal lobe epilepsy., Methods: Acute magnetic resonance imaging (MRI) was obtained within a mean of 4.4 (SD = 5.5, median = 2.0) days after febrile status on >200 infants with follow-up MRI at approximately 1, 5, and 10 years. Hippocampal size, morphology, and T2 signal intensity were scored visually by neuroradiologists blinded to clinical details. Hippocampal volumetry provided quantitative measurement. Upon the occurrence of two or more unprovoked seizures, subjects were reassessed for epilepsy. Hippocampal volumes were normalized using total brain volumes., Results: Fourteen of 22 subjects with acute hippocampal T2 hyperintensity returned for follow-up MRI, and 10 developed definite hippocampal sclerosis, which persisted through the 10-year follow-up. Hippocampi appearing normal initially remained normal on visual inspection. However, in subjects with normal-appearing hippocampi, volumetrics indicated that male, but not female, hippocampi were smaller than controls, but increasing hippocampal asymmetry was not seen following febrile status. Forty-four subjects developed epilepsy; six developed mesial temporal lobe epilepsy and, of the six, two had definite, two had equivocal, and two had no hippocampal sclerosis. Only one subject developed mesial temporal epilepsy without initial hyperintensity, and that subject had hippocampal malrotation. Ten-year cumulative incidence of all types of epilepsy, including mesial temporal epilepsy, was highest in subjects with initial T2 hyperintensity and lowest in those with normal signal and no other brain abnormalities., Significance: Hippocampal T2 hyperintensity following febrile status epilepticus predicted hippocampal sclerosis and significant likelihood of mesial temporal lobe epilepsy. Normal hippocampal appearance in the acute postictal MRI was followed by maintained normal appearance, symmetric growth, and lower risk of epilepsy. Volumetric measurement detected mildly decreased hippocampal volume in males with febrile status., (© 2024 International League Against Epilepsy.)

Purpose: This study aimed to characterize the histopathological immunohistochemical features of chronic sclerosing sialadenitis, emphasizing the IgG4-related disease., Methods: Seventeen cases of chronic sclerosing sialoadenitis were examined for histopathological aspects, (inflammation, fibrosis, glandular parenchyma, and lymphoid follicles) and immunohistochemistry (BCL2, CD3, CD20, CD34, CD163, p63, cyclin D1, mast cell, SMA, S100A4, IgG, and IgG4) which were scored. IgG4-related disease features were investigated. Demographic and clinical data were also collected., Results: Males predominated (10:7), with an average lesion size of 3.9 cm. Common histopathological findings included reduced acinar parenchyma, lymphoid follicle formation, and ductular proliferation. CD3-positive T lymphocytes and CD34- and SMA-positive stromal fibroblasts were abundant. Nine cases (53%) showed sialoliths and three cases met the criteria for IgG4-related disease., Conclusion: CSS of the submandibular gland represents a reactive pattern rather than IgG4-RD as only 3 cases seemed to be related to IgG4-RD. The immunohistochemical profile revealed an abundant population of CD3-positive T lymphocytes, as opposed to regulatory proteins such as cyclin D1, demonstrating that populations of CD34- and SMA-positive stromal fibroblasts contribute to the fibrosis characteristic of CSS. In addition, our results provide a comprehensive insight into the study of CSS and its relationship with IgG4-RD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background. Spindle cell/sclerosing rhabdomyosarcoma is a rare neoplasm and has an aggressive clinical course. Because of its rarity, we performed a multi-institutional collaboration to comprehend the overarching clinical, histopathological, and immunohistochemical characteristics of a cohort of spindle cell/sclerosing rhabdomyosarcoma. Materials and Methods. Forty-five patients with spindle cell/sclerosing rhabdomyosarcoma were identified. Demographics, clinical, histopathological, and immunohistochemistry data were reviewed and recorded. Results. The patients' age ranged from 1 to 85 years with a male to female ratio of 1.2:1. There were 15 children/adolescents and 30 adults. Eighteen (40%) tumors were located in the head and neck region. Twenty-four (53%) tumors displayed a bimorphic cellular arrangement with hypercellular areas having short, long, and sweeping fascicular and herringbone pattern, and hypocellular areas with stromal sclerosis and associated hyalinized and/or chondromyxoid matrix. Histomorphological differentials considered were leiomyosarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma, nodular fasciitis, liposarcoma, synovial sarcoma, sarcomatoid carcinoma, solitary fibrous tumor, dermatofibrosarcoma protuberans, and schwannoma. Six tumors exhibited marked stromal sclerosis. The myogenic nature was confirmed by immunohistochemistry. Positivity for at least one skeletal muscle-associated marker (MyoD1 and/or myogenin) was observed. Conclusion . Spindle cell/sclerosing rhabdomyosarcoma diagnosis can be challenging as a number of malignant spindle cell neoplasm mimic this entity. Thus a correct diagnosis requires immunohistochemical work up with a broad panel of antibodies. In view of rarity of this neoplasm, further studies on a large cohort of patients with clinical follow-up data are needed for a better understanding of this tumor., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The mechanism and medical treatment target for degenerative aortic valve disease, including aortic stenosis, is not well studied. In this study, we investigated the effect of clonal hematopoiesis of indeterminate potential (CHIP) on the development of aortic valve sclerosis (AVS), a calcified aortic valve without significant stenosis., Methods: Participants with AVS (valves ≥2 mm thick, high echogenicity, and a peak transaortic velocity of <2.5 m/sec) and an age- and sex-matched control group were enrolled. Twenty-four CHIP genes with common variants in cardiovascular disease were used to generate a next-generation sequencing panel. The primary endpoint was the CHIP detection rate between the AVS and control groups. Inverse-probability treatment weighting (IPTW) analysis was performed to adjust for differences in baseline characteristics., Results: From April 2020 to April 2022, 187 participants (125 with AVS and 62 controls) were enrolled; the mean age was 72.6±8.5 yrs, and 54.5% were male. An average of 1.3 CHIP variants was observed. CHIP detection, defined by a variant allele frequency (VAF) of ≥0.5%, was similar between the groups. However, the AVS group had larger CHIP clones: 49 (39.2%) participants had a VAF of ≥1% (vs. 13 [21.0%] in the control group; P =0.020), and 25 (20.0%) had a VAF of ≥2% (vs. 4 [6.5%]; P =0.028). AVS is independently associated with a VAF of ≥1% (adjusted odds ratio: 2.44, 95% confidence interval: 1.11-5.36; P =0.027). This trend was concordant and clearer in the IPTW cohort., Conclusions: Participants with AVS more commonly had larger CHIP clones than age- and sex-matched controls. Further studies are warranted to identify causality between AVS and CHIP.

Focal segmental glomerulosclerosis (FSGS) shares podocyte damage as an essential pathological finding. Several mechanisms underlying podocyte injury have been proposed, but many important questions remain. Rho-associated, coiled-coil-containing protein kinase 2 (ROCK2) is a serine/threonine kinase responsible for a wide array of cellular functions. We found that ROCK2 is activated in podocytes of adriamycin (ADR)-induced FSGS mice and cultured podocytes stimulated with ADR. Conditional knockout mice in which the ROCK2 gene was selectively disrupted in podocytes (PR2KO) were resistant to albuminuria, glomerular sclerosis, and podocyte damage induced by ADR injection. In addition, pharmacological intervention for ROCK2 significantly ameliorated podocyte loss and kidney sclerosis in a murine model of FSGS by abrogating profibrotic factors. RNA sequencing of podocytes treated with a ROCK2 inhibitor proved that ROCK2 is a cyclic nucleotide signaling pathway regulator. Our study highlights the potential utility of ROCK2 inhibition as a therapeutic option for FSGS., (© 2024. The Author(s).)

Osteoid osteoma is a benign osteoblastic tumour with a predilection for the lower extremity that rarely affects the forearm. It is commonly seen in adolescents and young adults, and is seldom diagnosed in the paediatric age group. We report a boy in his early childhood who presented with a swelling over the distal forearm, which was incidentally noted by the mother 3 months ago. Plain radiographs showed diffuse sclerosis of the dorsal cortex of the distal radius. CT scan showed a central lucent nidus in the intramedullary region and surrounding sclerosis in the radial metaphysis, confirming the diagnosis of osteoid osteoma. The patient was successfully treated by surgical en bloc resection of the nidus and was asymptomatic at 1-year follow-up. Non-specific symptoms at presentation make it a challenge to diagnose osteoid osteoma in children and it needs to be considered in the differential diagnosis when radiographs show lytic lesions in the bone., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Epilepsy patients are often grouped together by clinical variables. Quantitative neuroimaging metrics can provide a data-driven alternative for grouping of patients. In this work, we leverage ultra-high-field 7-T structural magnetic resonance imaging (MRI) to characterize volumetric atrophy patterns across hippocampal subfields and thalamic nuclei in drug-resistant focal epilepsy., Methods: Forty-two drug-resistant epilepsy patients and 13 controls with 7-T structural neuroimaging were included in this study. We measured hippocampal subfield and thalamic nuclei volumetry, and applied an unsupervised machine learning algorithm, Latent Dirichlet Allocation (LDA), to estimate atrophy patterns across the hippocampal subfields and thalamic nuclei of patients. We studied the association between predefined clinical groups and the estimated atrophy patterns. Additionally, we used hierarchical clustering on the LDA factors to group patients in a data-driven approach., Results: In patients with mesial temporal sclerosis (MTS), we found a significant decrease in volume across all ipsilateral hippocampal subfields (false discovery rate-corrected p [pFDR] < .01) as well as in some ipsilateral (pFDR < .05) and contralateral (pFDR < .01) thalamic nuclei. In left temporal lobe epilepsy (L-TLE) we saw ipsilateral hippocampal and some bilateral thalamic atrophy (pFDR < .05), whereas in right temporal lobe epilepsy (R-TLE) extensive bilateral hippocampal and thalamic atrophy was observed (pFDR < .05). Atrophy factors demonstrated that our MTS cohort had two atrophy phenotypes: one that affected the ipsilateral hippocampus and one that affected the ipsilateral hippocampus and bilateral anterior thalamus. Atrophy factors demonstrated posterior thalamic atrophy in R-TLE, whereas an anterior thalamic atrophy pattern was more common in L-TLE. Finally, hierarchical clustering of atrophy patterns recapitulated clusters with homogeneous clinical properties., Significance: Leveraging 7-T MRI, we demonstrate widespread hippocampal and thalamic atrophy in epilepsy. Through unsupervised machine learning, we demonstrate patterns of volumetric atrophy that vary depending on disease subtype. Incorporating these atrophy patterns into clinical practice could help better stratify patients to surgical treatments and specific device implantation strategies., (© 2024 International League Against Epilepsy.)

Importance: Morphea is a rare disease of unknown etiology without satisfactory treatment for skin sclerosis and soft tissue atrophy., Objective: To provide clinical, histologic, and transcriptome evidence of the antisclerotic and regenerative effects of sequential fat grafting with fresh fat and cryopreserved stromal vascular fraction gel (SVF gel) for morphea., Design, Setting, and Participants: This single-center, nonrandomized controlled trial was conducted between January 2022 and March 2023 in the Department of Plastic and Reconstructive Surgery of Nanfang Hospital, Southern Medical University and included adult participants with early-onset or late-onset morphea who presented with varying degrees of skin sclerosis and soft tissue defect., Interventions: Group 1 received sequential grafting of fresh fat and cryopreserved SVF gel (at 1 and 2 months postoperation). Group 2 received single autologous fat grafting. All patients were included in a 12-month follow-up., Main Outcome and Measures: The primary outcome included changes in the modified Localized Scleroderma Skin Severity Index (mLoSSI) and Localized Scleroderma Skin Damage Index (LoSDI) scores as evaluated by 2 independent blinded dermatologists. The histologic and transcriptome changes of morphea skin lesions were also evaluated., Results: Of 44 patients (median [IQR] age, 26 [23-33] years; 36 women [81.8%]) enrolled, 24 (54.5%) were assigned to group 1 and 20 (45.5%) to group 2. No serious adverse events were noted. The mean (SD) mLoSSI scores at 12 months showed a 1.6 (1.50) decrease in group 1 and 0.9 (1.46) in group 2 (P = .13), whereas the mean (SD) LoSDI scores at 12 months showed a 4.3 (1.34) decrease in group 1 and 2.1 (1.07) in group 2 (P < .001), indicating that group 1 had more significant improvement in morphea skin damage but not disease activity compared with group 2. Histologic analysis showed improved skin regeneration and reduced skin sclerosis in group 1, whereas skin biopsy specimens of group 2 patients did not show significant change. Transcriptome analysis of skin biopsy specimens from group 1 patients suggested that tumor necrosis factor α signaling via NFκB might contribute to the immunosuppressive and antifibrotic effect of sequential fat grafting. A total of 15 hub genes were captured, among which many associated with morphea pathogenesis were downregulated and validated by immunohistochemistry, such as EDN1, PAI-1, and CTGF., Conclusions and Relevance: The results of this nonrandomized trial suggest that sequential fat grafting with fresh fat and cryopreserved SVF gel was safe and its therapeutic effect was superior to that of single autologous fat grafting with improved mLoSSI and LoSDI scores. Histological and transcriptomic changes further support the effectiveness after treatment., Trial Registration: Chinese Clinical Trial Registry identifier: ChiCTR2200058003.

Anti-seizure drugs (ASDs) are the first choice for the treatment of epilepsy, but there is still one-third of patients with epilepsy (PWEs) who are resistant to two or more appropriately chosen ASDs, named drug-resistant epilepsy (DRE). Temporal lobe epilepsy (TLE), a common type of epilepsy usually associated with hippocampal sclerosis (HS), shares the highest proportion of drug resistance (approximately 70%). In view of the key role of the temporal lobe in memory, emotion, and other physiological functions, patients with drug-resistant temporal lobe epilepsy (DR-TLE) are often accompanied by serious complications, and surgical procedures also yield extra considerations. The exact mechanisms for the genesis of DR-TLE remain unillustrated, which makes it hard to manage patients with DR-TLE in clinical practice. Animal models of DR-TLE play an irreplaceable role in both understanding the mechanism and searching for new therapeutic strategies or drugs. In this review article, we systematically summarized different types of current DR-TLE models, and then recent advances in mechanism investigations obtained in these models were presented, especially with the development of advanced experimental techniques and tools. We are deeply encouraged that novel strategies show great therapeutic potential in those DR-TLE models. Based on the big steps reached from the bench, a new light has been shed on the precise management of DR-TLE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Aortic valve sclerosis (AVSc) presents similar pathogenetic mechanisms to coronary artery disease and is associated with short- and long-term mortality in patients with coronary artery disease. Evidence of AVSc-specific pathophysiological traits in acute myocardial infarction (AMI) is currently lacking. Thus, we aimed to identify a blood-based transcriptional signature that could differentiate AVSc from no-AVSc patients during AMI., Methods: Whole-blood transcriptome of AVSc (n=44) and no-AVSc (n=66) patients with AMI was assessed by RNA sequencing on hospital admission. Feature selection, differential expression, and enrichment analyses were performed to identify gene expression patterns discriminating AVSc from no-AVSc and infer functional associations. Multivariable Cox regression analysis was used to estimate the hazard ratios of cardiovascular events in AVSc versus no-AVSc patients., Results: This cross-sectional study identified a panel of 100 informative genes capable of distinguishing AVSc from no-AVSc patients with 94% accuracy. Further analysis revealed significant mean differences in 143 genes, of which 30 genes withstood correction for age and previous AMI or coronary interventions. Functional inference unveiled a significant association between AVSc and key biological processes, including acute inflammatory responses, type I IFN (interferon) response, platelet activation, and hemostasis. Notably, patients with AMI with AVSc exhibited a significantly higher incidence of adverse cardiovascular events during a 10-year follow-up period, with a full adjusted hazard ratio of 2.4 (95% CI, 1.3-4.5)., Conclusions: Our findings shed light on the molecular mechanisms underlying AVSc and provide potential prognostic insights for patients with AMI with AVSc. During AMI, patients with AVSc showed increased type I IFN (interferon) response and earlier adverse cardiovascular outcomes. Novel pharmacological therapies aiming at limiting type I IFN response during or immediately after AMI might improve poor cardiovascular outcomes of patients with AMI with AVSc., Competing Interests: Disclosures None.

Although mRNA vaccines for COVID-19 are highly beneficial and are recommended for patients with kidney disease, adverse reactions in some patients after vaccination have been problematic. Various vasculitis and renal disorders have been reported after vaccination; however, a causal relationship has not yet been identified. In this report, we describe a case of rapidly progressive glomerulonephritis that developed after SARS-CoV-2 vaccination, in which both anti-glomerular basement membrane (anti-GBM) and myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA) were present. The patient's renal biopsy showed that of the 48 glomeruli in total, four showed global sclerosis and none showed segmental sclerosis. The biopsy showed 11 cellular glomerular crescents and 5 fibrocellular glomerular crescents. Renal function improved with steroids, rituximab, and plasma exchange. Approximately 9 months later, MPO-ANCA was again elevated, and the pulmonary lesions worsened, again requiring multidisciplinary treatment. This case suggests that caution should be exercised in the development of double-positive disease after vaccination, and that long-term observation may be necessary because of the possibility of relapse., (© 2023. The Author(s) under exclusive licence to The Japan Society of Nephrology.)

The SP7 gene encodes a zinc finger transcription factor (Osterix), which is a member of the Sp subfamily of sequence-specific DNA-binding proteins, playing an important role in osteoblast differentiation and maturation. SP7 pathogenic variants have been described in association with different allelic disorders. Monoallelic or biallelic SP7 variants cause Osteogenesis imperfecta type XII (OI12), a very rare condition characterized by recurrent fractures, skeletal deformities, undertubulation of long bones, hearing loss, no dentinogenesis imperfecta, and white sclerae. Monoallelic or biallelic SP7 variants may also cause sclerotic skeletal dysplasias (SSD), partially overlapping with Juvenile Paget's disease and craniodiaphyseal dysplasia, characterized by skull hyperostosis, long bones sclerosis, large ribs and clavicles, and possible recurrent fractures. Here, we report the long-term follow-up of an 85-year-old woman presenting with a complex bone disorder including features of either OI12 (bone fragility with multiple fractures, severe deformities and short stature) or SSD (striking skull hyperostosis with optic atrophy, very large ribs and clavicles and long bones sclerosis). Exome sequencing showed previously undescribed biallelic loss of function variants in the SP7 gene: NM&#95;001173467.2(SP7): c.359&#95;362del, p.(Asp120Valfs*11); NM&#95;001173467.2(SP7): c.1163&#95;1174delinsT, p.(Pro388Leufs*33). RT-qPCR confirmed a severely reduced SP7 transcription compared to controls. Our report provides new insights into the clinical and molecular features and long-term outcome of SP7-related bone disorders (SP7-BD), suggesting a continuum phenotypic spectrum characterized by bone fragility, undertubulation of long bones, scoliosis, and very heterogeneous bone mineral density ranging from osteoporosis to osteosclerosis., Competing Interests: Declaration of competing interest All the authors declare no conflict of interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: We aimed to validate the estimation of the brain parenchymal fraction (BPF) in patients with multiple sclerosis (MS) using synthetic magnetic resonance imaging (SyMRI) by comparison with software tools of the FMRIB Software Library (FSL). In addition to a cross-sectional method comparison, longitudinal volume changes were assessed to further elucidate the suitability of SyMRI for quantification of disease-specific changes., Methods: MRI data from 216 patients with MS and 28 control participants were included for volume estimation by SyMRI and FSL-SIENAX. Moreover, longitudinal data from 35 patients with MS were used to compare registration-based percentage brain volume changes estimated using FSL-SIENA to difference-based calculations of volume changes using SyMRI., Results: We observed strong correlations of estimated brain volumes between the two methods. While SyMRI overestimated grey matter and BPF compared to FSL-SIENAX, indicating a systematic bias, there was excellent agreement according to intra-class correlation coefficients for grey matter and good agreement for BPF and white matter. Bland-Altman plots suggested that the inter-method differences in BPF were smaller in patients with brain atrophy compared to those without atrophy. Longitudinal analyses revealed a tendency for higher atrophy rates for SyMRI than for SIENA, but SyMRI had a robust correlation and a good agreement with SIENA., Conclusion: In summary, BPF based on data from SyMRI and FSL-SIENAX is not directly transferable because an overestimation and higher variability of SyMRI values were observed. However, the consistency and correlations between the two methods were satisfactory, and SyMRI was suitable to quantify disease-specific atrophy in MS., (© 2023. The Author(s).)

Aim: Hepatic fibrosis, a progressive scarring of liver tissue, is commonly caused by non-alcoholic fatty liver disease (NAFLD), which increases the risk of cardiovascular disease. The Fibrosis-4 (FIB-4) index is a non-invasive tool used to assess liver fibrosis in patients with NAFLD. Aortic valve sclerosis (AVS), a degenerative disorder characterized by thickening and calcification of valve leaflets, is prevalent in the elderly and associated with increased cardiovascular morbidity and mortality. Recent studies have suggested that AVS may also be linked to other systemic diseases such as liver fibrosis. This study aimed to investigate the relationship between the FIB-4 index and AVS in a non-alcoholic population, with the hypothesis that the FIB-4 index could serve as a potential marker for AVS., Method: A total of 92 patients were included in this study. AVS was detected using transthoracic echocardiography, and patients were divided into groups according to the presence of AVS. The FIB-4 index was calculated for all patients and compared between the groups., Results: A total of 17 (18.4%) patients were diagnosed AVS. Patients with AVS had higher rates of diabetes mellitus, older age, hypertension, angiotensin-converting enzyme inhibitor use, higher systolic blood pressure (BP) and diastolic BP in the office, coronary artery disease prevalence, left atrial volume index (LAVI), left ventricular mass index (LVMI), and late diastolic peak flow velocity (A) compared to those without AVS. Moreover, AVS patients had significantly higher creatinine levels and lower estimated glomerular filtration rate. Remarkably, the FIB-4 index was significantly higher in patients with AVS. In univariate and multivariate analyses, higher systolic BP in the office (OR, 1.044; 95% CI 1.002-1.080, p = .024) and higher FIB-4 index (1.46 ± .6 vs. .91 ± .46, p < .001) were independently associated with AVS., Conclusion: Our findings suggest that the FIB-4 index is associated with AVS in non-alcoholic individuals. Our results highlight the potential utility of the FIB-4 index as a non-invasive tool for identifying individuals at an increased risk of developing AVS., (© 2024 Wiley Periodicals LLC.)

Objective: To evaluate the relationship between nuclear sclerosis (NS) and refractive error in companion dogs., Animals Studied: One hundred and eighteen companion dogs., Procedures: Dogs were examined and found to be free of significant ocular abnormalities aside from NS. NS was graded from 0 (absent) to 3 (severe) using a scale developed by the investigators. Manual refraction was performed. The effect of NS grade on refractive error was measured using a linear mixed effects analysis adjusted for age. The proportion of eyes with >1.5 D myopia in each NS grade was evaluated using a chi-square test. Visual impairment score (VIS) was obtained for a subset of dogs and compared against age, refractive error, and NS grade., Results: Age was strongly correlated with NS grade (p < .0001). Age-adjusted analysis of NS grade relative to refraction showed a mild but not statistically significant increase in myopia with increasing NS grade, with eyes with grade 3 NS averaging 0.58-0.88 D greater myopia than eyes without NS. However, the myopia of >1.5 D was documented in 4/58 (6.9%) eyes with grade 0 NS, 12/91 (13.2%) eyes with grade 1 NS, 13/57 (22.8%) eyes with grade 2 NS, and 7/23 (30.4%) eyes with grade 3 NS. Risk of myopia >1.5 D was significantly associated with increasing NS grade (p = .02). VIS was associated weakly with refractive error, moderately with age, and significantly with NS grade., Conclusions: NS is associated with visual deficits in some dogs but is only weakly associated with myopia. More work is needed to characterize vision in aging dogs., (© 2023 American College of Veterinary Ophthalmologists.)

Objective: To compare sacroiliac joint (SIJ) lesions on MRI in women with versus without axial spondyloarthritis (ax-SpA) and establish an algorithm to determine whether such lesions are due to ax-SpA., Methods: This retrospective comparative study assessed bone marrow edema (BME), sclerosis, erosions, osteophytes, and ankylosis at the SIJ in two groups of women, one with and another without ax-SpA. Sensitivity and specificity were calculated for combinations/characteristics of lesions, using rheumatologists' assessment with assessment of spondyloarthritis international society (ASAS) criteria as the gold standard for diagnosis of ax-SpA., Results: Compared to women without ax-SpA, women with ax-SpA had more BME (61% vs 17%, p < 0.001), sclerosis (40% vs 22%, p < 0.001), erosions (35% vs 5%, p < 0.001), and ankylosis (2% vs 0%, p = 0.007), but less osteophytes (5% vs 33%, p < 0.001). The ASAS MRI criteria yielded 59% sensitivity and 88% specificity, while a new algorithm achieved 56% sensitivity and 95% specificity using the following criteria: no osteophytes at the SIJ and either (i) BME at the SIJ with at least one dimension ≥ 8 mm or (ii) at least one erosion at the SIJ., Conclusions: We recommend the following pragmatic algorithm for MRI diagnosis of ax-SpA in women: no osteophytes at the SIJ and either (i) BME at the SIJ with at least one dimension ≥ 8 mm or (ii) at least one erosion at the SIJ. The false positive rate when using the new algorithm (3.3%) is less than half than when using the ASAS MRI criteria (7.7%); thus, its application in clinical practice could reduce overdiagnosis and prevent overtreatment of ax-SpA., Clinical Relevance Statement: The developed algorithm has a false-positive rate that is less than half than when using the ASAS MRI criteria (3.3% vs 7.7%), thus its application in clinical practice could reduce overdiagnosis and prevent overtreatment of axial spondyloarthritis., Key Points: • Compared to women without axial spondyloarthritis (ax-SpA), women with ax-SpA had a significantly higher prevalence of bone marrow edema (BME), sclerosis, erosions, and ankylosis, but a significantly lower prevalence of osteophytes. • A new algorithm for positive ax-SpA based on sacroiliac joint MRI was developed: no osteophytes at the sacroiliac joint (SIJ) and either (i) BME at the SIJ with at least one dimension ≥ 8 mm or (ii) at least one erosion at the SIJ. • We recommend this new algorithm for diagnosis of ax-SpA in women, as it has a significantly better specificity than the assessment of spondyloarthritis international society (ASAS) MRI criteria and less than half the false positive rate; thus, its application in clinical practice could reduce overdiagnosis and prevent overtreatment of ax-SpA., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

Recurrent bladder neck sclerosis is one of the common complications of endoscopic treatment of benign prostate hyperplasia, which often leads to multiple re-operations, including complex open and laparoscopic reconstructive procedures. One of the most promising minimally invasive methods for preventing recurrence of bladder neck sclerosis is balloon dilatation under transrectal ultrasound guidance. To improve the results of using this technique, a urethral catheter with a biopolymer coating, capable of depositing a drug and eluting it under the influence of diagnostic ultrasound, was proposed.

Objective: To evaluate the influence of quantitative reports (QReports) on the radiological assessment of hippocampal sclerosis (HS) from MRI of patients with epilepsy in a setting mimicking clinical reality., Methods: The study included 40 patients with epilepsy, among them 20 with structural abnormalities in the mesial temporal lobe (13 with HS). Six raters blinded to the diagnosis assessed the 3T MRI in two rounds, first using MRI only and later with both MRI and the QReport. Results were evaluated using inter-rater agreement (Fleiss' kappa [Formula: see text]) and comparison with a consensus of two radiological experts derived from clinical and imaging data, including 7T MRI., Results: For the primary outcome, diagnosis of HS, the mean accuracy of the raters improved from 77.5% with MRI only to 86.3% with the additional QReport (effect size [Formula: see text]). Inter-rater agreement increased from [Formula: see text] to [Formula: see text]. Five of the six raters reached higher accuracies, and all reported higher confidence when using the QReports., Conclusion: In this pre-use clinical evaluation study, we demonstrated clinical feasibility and usefulness as well as the potential impact of a previously suggested imaging biomarker for radiological assessment of HS., (© 2023. The Author(s).)

Objective: To compare memory outcomes after surgery for unilateral hippocampal sclerosis (HS)-associated epilepsy in patients with unilateral and bilateral ictal electrographic involvement., Methods: We prospectively evaluated HS patients, aged 18-55 years and IQ ≥70. Left (L) and right (R) surgical groups underwent noninvasive video-EEG monitoring and Wada test. We classified patients as Ipsilateral if ictal EEG was restricted to the HS side, or Bilateral, if at least one seizure onset occurred contralaterally to the HS, or if ictal discharge evolved to the opposite temporal region. Patients who declined surgery served as controls. Memory was evaluated on two occasions with Rey Auditory-Verbal Learning Test and Rey Visual-Design Learning Test. Baseline neuropsychological test scores were compared between groups. Pre- and postoperative scores were compared within each group. Reliable change index Z-scores (RCI) were obtained using controls as references, and compared between surgical groups., Results: We evaluated 64 patients. Patients were classified as: L-Ipsilateral (9), L-Bilateral (15), L-Control (9), R-Ipsilateral (10), R-Bilateral (9), and R-Control (12). On preoperative evaluation, memory performance did not differ among surgical groups. Right HS patients did not present postoperative memory decline. L-Ipsilateral group presented postoperative decline on immediate (P = 0.036) and delayed verbal recall (P = 0.011), while L-Bilateral did not decline. L-Ipsilateral had lower RCI Z-scores, indicating delayed verbal memory decline compared to L-Bilateral (P = 0.012)., Significance: Dominant HS patients with bilateral ictal involvement presented less pronounced postoperative verbal memory decline compared to patients with exclusive ipsilateral ictal activity. Surgery was indicated in these patients regardless of memory impairment on neuropsychological testing, since resection of the left sclerotic hippocampus could result in cessation of contralateral epileptiform activity, and, therefore, improved memory function., (© 2023 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Objective: Bowman's capsule rupture (BCR) is a glomerular pathological change, but it is still not well recognized in immunoglobulin A vasculitis nephritis (IgAV-N). The Oxford MEST-C score is a classification for IgA nephropathy; however, its clinical correlation and prognostic value in adult patients with IgAV-N are unclear., Methods: A retrospective study of 145 adult patients with IgAV-N diagnosed by renal biopsy was conducted. Clinical manifestations, pathological changes and the prognosis of IgAV-N patients were compared depending on the presence or absence of BCR, International Study of Kidney Disease in Children (ISKDC) classification and MEST-C score. The primary endpoint events were end-stage renal disease, renal replacement therapy and all-cause death., Results: In total, 51 of 145 (35.17%) patients with IgAV-N presented with BCR. Patients with BCR had more proteinuria, lower serum albumin, and more crescents. Compared with IgAV-N patients with crescents only, 51/100 patients with crescents combined with BCR had a higher proportion of crescents in all glomeruli (15.79% vs. 9.09%; p  = 0.003). Patients with higher ISKDC grades had more severe clinical presentation, but it did not reflect the prognosis. However, the MEST-C score not only reflected clinical manifestations but also predicted prognosis ( p  < 0.05). BCR contributed to the effectiveness of the MEST-C score in predicting the prognosis of IgAV-N (C-index: 0.845 to 0.855)., Conclusions: BCR is associated with clinical manifestations and pathological changes in patients with IgAV-N. The ISKDC classification and MEST-C score are related to the patient's condition, but only the MEST-C score is correlated with the prognosis of patients with IgAV-N, while BCR can improve its predictive ability.

Objective: This cross-sectional study aimed to evaluate the presence of bone changes on magnetic resonance imaging (MRI) scans of patients with temporomandibular joint (TMJ) anterior disc displacement (ADD) with reduction (ADDWR) and without reduction (ADDWoR)., Methods: TMJ-MRI scans were screened for the presence of ADD. 285 scans presented ADD, being further divided into ADDWR (n = 188) and ADDWoR (n = 97). Bone changes on the mandibular condyle and articular eminence were also assessed and computed. The chi-square test compared the association of these bone changes with the presence of ADDWR and ADDWoR, with a significance level of 5 %. Also, the prevalence ratio (PR) was calculated., Results: In the mandibular condyle, subchondral cyst (p = 0.035, PR = 1.08) and bone edema (p = 0.044, PR = 2.40), more prevalent on ADDWR, and generalized sclerosis (p = 0.015, PR = 1.04), more prevalent on ADDWoR, presented significant association with ADD. On the articular eminence, generalized sclerosis (p = 0.015, PR = 1.04) and articular surface flattening (p = 0.003, PR = 1.19) presented significant association with ADD, both more prevalent on ADDWoR., Conclusion: Bone changes are usual findings in TMJ with ADD diagnosis. The real influence of ADD is not fully clear, although clinicians should be aware of patients with this condition, to provide an early diagnosis and improve patient´s prognosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Sclerosing encapsulating peritonitis (SEP) is a rare condition characterised by a fibrotic peritoneal membrane encasing loops of bowel often resulting in obstruction. We present a case of SEP complicated by non-resolving small bowel obstruction in the context of prior malignancies and surgical complications. A literature review on SEP was performed to outline potential aetiologies, diagnostic investigations and treatment strategies that may be considered in the management of this disease., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Chronic graft-versus-host disease (cGVHD) is a severe complication in long-term survivors of allogeneic hematopoietic stem cell transplantation. This disease is challenging to manage clinically due to a lack of validated tools to quantitatively measure skin sclerosis. The current gold standard for measuring skin sclerosis is the NIH Skin Score which has only moderate agreement among clinicians and experts. To more accurately assess skin sclerosis in cGVHD, the Myoton and durometer devices can be used to directly measure biomechanical parameters of the skin. However, the reproducibility of these devices is not known in patients with cGVHD. To determine this reproducibility, three observers independently measured 10 anatomic sites in each of seven patients with sclerotic cGVHD using the Myoton and durometer. Clinical reproducibility was measured by mean pairwise differences (U-statistic) and intraclass correlation coefficients (ICCs) with 95% confidence intervals (CIs). Mean pairwise differences, expressed in true physical units, were used to report typical errors for each anatomic site and device. Mean pairwise differences were less than 11% of the average overall values for all five Myoton parameters and durometer hardness. These were lower for Myoton creep (4.1%), relaxation time (4.7%), and frequency (5.1%) than decrement (9.0%), stiffness (10.4%), and durometer hardness (9.0%). Myoton parameters creep, relaxation time, and frequency showed promise for capturing skin biomechanics more accurately than Myoton stiffness, decrement, or durometer hardness. Mean pairwise differences trended highest in the shin and volar forearm and lowest in the dorsal forearm. The interobserver ICC for overall (averaged across all measured body sites of a patient) creep (0.94; 95% CI 0.87-1.00), relaxation time (0.96; 95% CI 0.90-1.00), and frequency (0.95; 95% CI 0.88-1.00), trended higher than that for decrement (0.43; 95% CI 0.00-0.88), stiffness (0.92; 95% CI 0.81-1.00), and durometer hardness (0.82; 95% CI 0.61-1.00). Similar trends were observed in healthy participants. These findings can help clinicians design better studies to assess therapeutic response to new cGVHD treatments and support the interpretation of future measurements., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The objective of this retrospective, observational, controlled study was to evaluate bone and soft tissue window CT images of the proximoplantar metatarsus III region in twenty horses with pain localized to the proximal suspensory ligament (PSL) and 20 horses with findings nonrelated to tarsal pain. All horses underwent CT and radiographic examination. Images were reviewed by three independent observers who graded the severity and localization of findings. Bone-related categories as well as soft tissue-related categories were evaluated. For the comparison of imaging findings in horses with and without proximal suspensory desmitis (PSD), mixed linear regression was performed. The intraclass correlation coefficient (ICC) was calculated to assess intraobserver agreement, and kappa statistics were employed to evaluate interobserver agreement. CT examination identified significantly more abnormalities in the diseased group. The scores for osseous exostosis (p = .015) and PSL enlargement (p = .004) were notably higher in PSD horses compared to controls. Intraobserver agreement was overall high (ICC .82-1.0), and interobserver agreement was substantial for the detection of mineralization (kappa = .61) and moderate for sclerosis (kappa = .43), exostosis (kappa = .43), and PSL enlargement (kappa = .48/.51). Measurements in the soft tissue window were significantly smaller than those in the bone window. Findings concurrent with PSD including osseous proliferation and sclerosis as well as soft tissue enlargement, mineralization, and avulsion can be reliably detected using CT. Findings from the current study supported the use of CT for evaluating horses with suspected PSD where high-field MRI is not available., (© 2023 The Authors. Veterinary Radiology & Ultrasound published by Wiley Periodicals LLC on behalf of American College of Veterinary Radiology.)

Mesial temporal lobe epilepsy is one of the most common causes of refractory epilepsy worldwide. A good percentage of patients do not have detectable hippocampal atrophy on magnetic resonance imaging (MRI). The objective of this study is to evaluate whether T2 relaxometry can identify hippocampal pathology and lateralize the epileptic focus in patients with intractable temporal lobe epilepsy (TLE). T2 relaxometry can also be used to correlate the clinical severity of the disease with the relaxometry readings in those who have hippocampal atrophy as well as those who do not. Thirty two patients having clinical and electrophysiological features of TLE were enrolled and a MRI brain with T2 relaxometry was done. Hippocampal T2 relaxometry values were calculated in the head, body, and tail of the hippocampus and average T2 relaxometry values were calculated, and a comparison was done with the controls. For patients with unilateral involvement, the contralateral side was taken as control and in cases of bilateral involvement, controls were identified from normal subjects. T2 relaxometry is found to be superior to MR visual analysis in the early detection of cases of hippocampal sclerosis where there is no atrophy on visual analysis. Nine out of 32 patients (28%) were normal on MR visual analysis; however, showed increased values on T2 relaxometry, correlating with clinical and electrophysiological diagnosis. The rest of the patients with hippocampal atrophy showed a correlation of T2 relaxometry values with the degree of atrophy. The hippocampal T2 measurement is thus more sensitive and specific. The study was clinically significant (p < .0001). There was a mild female predilection of the disease and there was no significant correlation with comorbidities. There was a strong positive correlation with patients having a history of febrile seizures in childhood. T2 relaxometry may accurately lateralize the majority of patients with persistent TLE and offers evidence of hippocampus injury in those patients who do not show evidence of atrophy on MRI and also the T2 relaxometry values correlated with the degree of atrophy. Early identification of hippocampal sclerosis is crucial for prompt management which offers better outcomes., (© 2023 Wiley Periodicals LLC.)

Background and Aim: The aim of this study is to evaluate the changes in the temporomandibular joint (TMJ) in patients with temporomandibular disorder (TMD) and the relationship between age, sex, and types of TMJ change using Cone Beam Computed Tomography (CBCT)., Methods and Material: CBCT records of 200 patients (123 women and 67 men) were retrieved and assessed. Right and left TMJs were evaluated separately, resulting in a total of 400 TMJs. The images were analyzed using On demand 3D Application The radiographic findings were classified as erosion, proliferative changes mainly, including flattening and osteophytes of the condyle, sclerosis, Ely cyst, hypoplasia and hyperplasia of the condyles, ankylosis, and joint cavity. Data analysis was performed using descriptive statistics, paired T-tests, and repeated measure ANOVA (Analysis of Variance) in SPSS Software., Results: The most prevalent types of condylar bony changes observed was osteophyte (63.5%) followed by flattening of the articular surface (42%), erosion (40%), ankylosis (10%) and sclerosis (10%). 7.5% of joints showed hyperplastic condyles but only 2% showed hypoplasia. The least prevalent change observed was Ely Cyst (1%). Osteophyte was the most prevalent change observed in all age groups and both sexes except for men aged 31 ~ 50, where flattening was more frequent. A statistically significant difference was found between sex and prevalence of erosion in the age group of 10 ~ 30 (P = 0.001); as well as between sex and condylar hyperplasia in the same age group., Conclusion: Based on the findings of this research, the prevalence of bony changes of TMJ from highest to lowest is as follows: osteophyte, flattening of the articular surface, erosion, ankylosis, sclerosis, hyperplastic condyles, hypoplastic condyles and Ely Cyst. CBCT is an accurate 3 dimensional imaging modality for assessment of TMJ bony structures., (© 2023. The Author(s).)

Diagnosis of axial spondyloarthritis (axSpA) is nowadays commonly made with the help of pelvic radiography or magnetic resonance imaging (MRI). However, there is an important inter-observer variability in radiography, and MRI is subject to possible false positives and is not the best modality for studying structural lesions. Conversely, pelvic computed tomography (CT) has excellent specificity and appears to be more effective than radiography for the diagnosis of ankylosing spondylitis (AS). However, its findings in patients over 50 years of age have not yet been studied. The objectives of this study were to describe the CT characteristics of sacro-iliac joints (SIJ) and the presence of intra-articular gas in patients with AS aged over 50 years and to compare them with controls of the same age and sex. This two-center, cross-sectional, observational study was performed using the medical records of the rheumatology departments of two University Hospitals. We included patients with a clinical diagnosis of axSpA, who had both definite radiographic sacroiliitis according to the modified New York criteria and met the ASAS 2009 criteria for axSpA (that is, AS), and who had undergone any CT scan including the whole SIJ. Each patient was matched for age and sex to a control randomly selected on the Picture Archiving and Communication System (PACS), symptomatic or asymptomatic, and without spondyloarthritis. For each individual, CT scans were interpreted blindly by two independent rheumatologists and scored for joint space narrowing (JSN), erosions, sclerosis, intra-articular gas, and diffuse idiopathic skeletal hyperostosis (DISH). Ninety patients and 90 controls were included in the study. The rates of positive JSN, erosion, and sclerosis scores were higher in the AS group (91% vs. 21%, p < 0.0001; 31% vs. 2%, p < 0.0001; 27% vs. 13%, p = 0.03, respectively), but the rates of intra-articular gas and DISH were higher in the control group (24% vs. 68%, p < 0.0001; 7% vs. 33%, p < 0.0001, respectively). 58% of patients had complete bilateral ankylosis. A total of 83 (92.2%) patients had a CT scan considered positive for AS, compared with only seven controls (7.8%). Sclerosis and erosions were predominantly on the anterosuperior part and iliac side of the joint in controls and were more diffuse in patients with AS. CT findings in patients with AS over 50 years of age are mostly represented by changes in the joint space; patients with AS have more erosions and sclerosis changes, but less intra-articular gas than controls., (© 2023. Springer Nature Limited.)

Aim: To clarify the clinicopathological characteristics and role of periglomerular angiogenesis in IgA nephropathy., Methods and Results: The renal biopsy specimens of 114 patients with IgA nephropathy were examined. Among them, 46 (40%) showed periglomerular angiogenesis around the glomeruli. CD34 and α-smooth muscle actin (α-SMA) staining in serial sections revealed that these vessels contained CD34+ α-SMA+ microarterioles along with CD34+ α-SMA- capillaries. We termed these "periglomerular microvessels (PGMVs)". Patients with PGMVs (PGMV group) had clinically and histologically more severe disease than those without PGMVs (non-PGMV group) at the time of biopsy. Even after adjusting for age, there were significant differences in the degree of proteinuria and estimated glomerular filtration rate reduction between the PGMV and non-PGMV groups. The PGMV group showed a higher incidence of segmental and global glomerulosclerosis and crescentic lesions than the non-PGMV group (P < 0.01). Here, PGMVs were undetectable in the acute and active inflammation phase, but were observed in the acute to chronic or chronic glomerular remodelling phase. PGMVs mainly developed around glomerular adherent lesions to the Bowman's capsule with small or minimal glomerular sclerotic lesions. Conversely, they were rarely observed in segmental sclerosis areas., Conclusion: The PGMV group is clinically and pathologically more severe than the non-PGMV group; however, they were undetectable in segmental sclerosis with mesangial matrix accumulation. PGMVs might occur after acute/active glomerular lesions, suggesting that PGMVs may inhibit segmental glomerulosclerosis progression and could be a marker for good repair response after acute/active glomerular injury in severe IgA nephropathy cases., (© 2023 John Wiley & Sons Ltd.)

Objectives: Sex-specific differences in the presentation of axial spondyloarthritis (axSpA) may contribute to a diagnostic delay in women. The aim of this study was to investigate the diagnostic performance of MRI findings comparing men and women., Methods: Patients with back pain from six different prospective cohorts (n=1194) were screened for inclusion in this post hoc analysis. Two blinded readers scored the MRI data sets independently for the presence of ankylosis, erosion, sclerosis, fat metaplasia and bone marrow oedema. Χ 2 tests were performed to compare lesion frequencies. Contingency tables were used to calculate markers for diagnostic performance, with clinical diagnosis as the standard of reference. The positive and negative likelihood ratios (LR+/LR-) were used to calculate the diagnostic OR (DOR) to assess the diagnostic performance., Results: After application of exclusion criteria, 526 patients (379 axSpA (136 women and 243 men) and 147 controls with chronic low back pain) were included. No major sex-specific differences in the diagnostic performance were shown for bone marrow oedema (DOR m: 3.0; f: 3.9). Fat metaplasia showed a better diagnostic performance in men (DOR 37.9) than in women (DOR 5.0). Lower specificity was seen in women for erosions (77% vs 87%), sclerosis (44% vs 66%), fat metaplasia (87% vs 96%)., Conclusion: The diagnostic performance of structural MRI markers is substantially lower in female patients with axSpA; active inflammatory lesions show comparable performance in both sexes, while still overall inferior to structural markers. This leads to a comparably higher risk of false positive findings in women., Competing Interests: Competing interests: STU is participant in the BIH-Charité Junior Digital Clinician Scientist Program funded by the Charité – Universitätsmedizin Berlin and the Berlin Institute of Health. FP reports grants and personal fees from Novartis, Lilly and UCB, as well as personal fees from AbbVie, AMGEN, BMS, Celgene, Hexal, Janssen, MSD, Pfizer and Roche. TD reports personal fees from Novartis, Lilly, MSD and Canon MS. JR and LCA are participants in the BIH-Charité Clinician Scientist Program funded by the Charité – Universitätsmedizin Berlin and the Berlin Institute of Health. MP reports personal fees from Novartis. K-GAH reports personal fees from AbbVie, MSD, Pfizer and Novartis, he is also the co-founder of BerlinFlame GmbH. DP reports grants and personal fees from AbbVie, Eli Lilly, MSD, Novartis, Pfizer, and personal fees from Biocad, Gilead, GlaxoSmithKline, Janssen, MSD, Moonlake, Novartis, Pfizer, Samsung Bioepis and UCB. KZ reports funding (research grant) from the Assessment of Spondyloarthritis international Society (ASAS) during the conduct of this study. All other authors have no funding to report., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Mesial Temporal Lobe Epilepsy-associated Hippocampal Sclerosis (MTLE-HS) is a syndrome associated with various aetiologies. We previously identified CD34-positive extravascular stellate cells (CD34+ cells) possibly related to BRAF V600E oncogenic variant in a subset of MTLE-HS. We aimed to identify the BRAF V600E oncogenic variants and characterise the CD34+ cells., Methods: We analysed BRAF V600E oncogenic variant by digital droplet Polymerase Chain Reaction in 53 MTLE-HS samples (25 with CD34+ cells) and nine non-expansive neocortical lesions resected during epilepsy surgery (five with CD34+ cells). Ex vivo multi-electrode array recording, immunolabelling, methylation microarray and single nuclei RNAseq were performed on BRAF wildtype MTLE-HS and BRAF V600E mutant non-expansive lesion of hippocampus and/or neocortex., Results: We identified a BRAF V600E oncogenic variant in five MTLE-HS samples with CD34+ cells (19%) and in five neocortical samples with CD34+ cells (100%). Single nuclei RNAseq of resected samples revealed two unique clusters of abnormal cells (including CD34+ cells) associated with senescence and oligodendrocyte development in both hippocampal and neocortical BRAF V600E mutant samples. The co-expression of the oncogene-induced senescence marker p16 INK4A and the outer subventricular zone radial glia progenitor marker HOPX in CD34+ cells was confirmed by multiplex immunostaining. Pseudotime analysis showed that abnormal cells share a common lineage from progenitors to myelinating oligodendrocytes. Epilepsy surgery led to seizure freedom in eight of the 10 patients with BRAF mutant lesions., Interpretation: BRAF V600E underlies a subset of MTLE-HS and epileptogenic non-expansive neocortical focal lesions. Detection of the oncogenic variant may help diagnosis and open perspectives for targeted therapies., (© 2023 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.)

Purpose: To investigate the characteristics of patients with MRI-negative temporal lobe epilepsy (TLE) (1.5 T brain MRI) in comparison with: (i) patients with hippocampal sclerosis (HS)-TLE; (ii) persons with non-HS structural TLE; and (iii) patients with dual pathology., Methods: This was a retrospective study. All patients with an electro-clinical diagnosis of TLE were studied at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2020., Results: Six hundred and forty-one patients were studied [273 (42.6%) HS, 154 (24.0%) non-HS structural TLE, 174 (27.1%) MRI-negative TLE, and 40 (6.2%) dual pathology]. The groups differed significantly. Important dissimilarities included: (i) compared with HS-TLE group, patients with MRI-negative TLE more often had a family history of epilepsy and less often had a history of febrile convulsion; (ii) compared with non-HS structural TLE group, patients with MRI-negative TLE more often had focal to bilateral tonic-clonic seizures, less often had focal seizures with impaired awareness, and more often had a family history of epilepsy; (iii) compared with the dual pathology group, patients with MRI-negative TLE less often were male and less often had a history of febrile convulsion., Conclusion: Patients with MRI-negative TLE are not a homogenous group of people and it is not necessarily a distinct entity from other forms of TLE either. With the emergence of advanced imaging technologies, the underlying pathologies of MRI-negative TLE may be revealed., (© 2022. The Author(s) under exclusive licence to Belgian Neurological Society.)