Focal Atrophy Research Articles

Macular Outer Retinal Atrophy Following Vitrectomy and Hypotony: Two Cases.

To characterize two cases of focal outer retinal atrophy and hypotony after vitrectomy. Retrospective chart review of two patients' records between 2019 and 2023. Patient 1 underwent vitrectomy, epiretinal membrane peel, and cataract extraction for visually significant macular pucker. She developed hypotony without a wound leak and was noted to have a focal parafoveal area of ellipsoid zone disruption by 1 week post-operatively, which evolved into outer retinal and chorioretinal atrophy within 6 weeks after surgery. This area of atrophy remained stable in size, but the patient later reported a paracentral scotoma. Patient 2 had multiple previous surgeries for retinal detachment with proliferative vitreoretinopathy. Seven years later, the IOL dislocated and was exchanged with scleral fixation of a new IOL. On post-operative day 1, he had hypotony with macular folds secondary to a leaking sclerotomy wound. The sclerotomies were sutured on post-operative day 3, and his intraocular pressure normalized. However, he developed a central, focal area of chorioretinal atrophy within 1 week of the initial surgery. The size of this area of atrophy remained stable over years but resulted in reduced central vision. Hypotony following vitrectomy may rarely predispose patients to the development of focal chorioretinal atrophy.

Nine Neuroimaging-AI Endophenotypes Unravel Disease Heterogeneity and Partial Overlap across Four Brain Disorders: A Dimensional Neuroanatomical Representation.

Disease heterogeneity poses a significant challenge for precision diagnostics. Recent work leveraging artificial intelligence has offered promise to dissect this heterogeneity by identifying complex intermediate brain phenotypes, herein called dimensional neuroimaging endophenotypes (DNEs). We advance the argument that these DNEs capture the degree of expression of respective neuroanatomical patterns measured, offering a dimensional neuroanatomical representation for studying disease heterogeneity and similarities of neurologic and neuropsychiatric diseases. We investigate the presence of nine such DNEs derived from independent yet harmonized studies on Alzheimer's disease (AD1-2)1, autism spectrum disorder (ASD1-3)2, late-life depression (LLD1-2)3, and schizophrenia (SCZ1-2)4, in the general population of 39,178 participants in the UK Biobank study. Phenome-wide associations revealed prominent associations between the nine DNEs and phenotypes related to the brain and other human organ systems. This phenotypic landscape aligns with the SNP-phenotype genome-wide associations, revealing 31 genomic loci associated with the nine DNEs (Bonferroni corrected P-value < 5×10-8/9). The DNEs exhibited significant genetic correlations, colocalization, and causal relationships with multiple human organ systems and chronic diseases. A causal effect (odds ratio=1.25 [1.11, 1.40], P-value=8.72×10-4) was established from AD2, characterized by focal medial temporal lobe atrophy, to AD. The nine DNEs, along with their polygenic risk scores, significantly enhanced the predictive accuracy for 14 systemic disease categories, particularly for conditions related to mental health and the central nervous system, as well as mortality outcomes. These findings underscore the potential of the nine DNEs to capture the expression of disease-related brain phenotypes in individuals of the general population and to relate such measures with genetics, lifestyle factors, and chronic diseases. All results are publicly available at https://labs-laboratory.com/medicine/.

Association of pancreatic atrophy patterns with intraductal extension of early pancreatic ductal adenocarcinoma: a multicenter retrospective study.

Focal pancreatic parenchymal atrophy (FPPA) and upstream pancreatic atrophy (UPA) may indicate the presence of early pancreatic cancer. In early pancreatic cancer, the tumor occasionally spreads laterally along the main pancreatic duct, presenting challenges in determining the extent of surgical resection. This study aimed to investigate the association of pancreatic atrophy pattern and intraductal cancer extension. Thirty-two patients with early-stage pancreatic cancer who underwent surgery at five participating centers were enrolled. Pancreatic atrophy was defined as the narrowing of parenchyma compared to the surrounding parenchyma and was classified as either FPPA (partial atrophy surrounding the pancreatic duct stenosis) or UPA (global atrophy caudal to the site of duct stenosis). Intraductal cancer extension was defined as an extension exceeding 10mm. Preoperative computed tomography revealed FPPA, UPA, and no parenchymal atrophy in 13, 13, and 6 patients. Cases with FPPA or UPA showed significantly longer cancer extensions than those without atrophy (P = 0.005 and P = 0.03, respectively). Intraductal cancer extension was present in all but one case of FPPA. 69% (9/13) of the cases with UPA showed intraductal cancer extension, whereas cases without atrophy showed no intraductal cancer extension. Importantly, two patients with FPPA or UPA showed positive resection margins during surgery and three patients with FPPA or UPA showed recurrence in the remnant pancreas. The presence of FPPA and UPA indicates lateral cancer extension in early-stage pancreatic cancer. Preoperative assessment of the pancreatic parenchyma may provide valuable insights for determining the extent of surgical resection.

Myopic Maculopathy Stabilization in a Child with Progressive Complicated Myopia and Underlying Connective Tissue Dysplasia via Optical Therapy with HAL Spectacle Lenses Inducing Retinal Peripheral Defocus: Clinical Case

Background. Myopia is a serious medical and social problem specifically due to the high risk of such complications as cataracts, myopic maculopathy, glaucoma, and retinal detachment. Children with connective tissue dysplasia (CTD) syndrome are most subjected to myopia. Prevention of myopia progression in children remains the only effective way to prevent myopic maculopathy. Significant progress in this field has been achieved via optical technologies developed on the basis of peripheral defocus theory. Clinical case description. Patient, 10 years old, with CTD, mild myopia of both eyes with rapid progression, myopic maculopathy, grade 1. Ophthalmic status: spheroequivalent refraction — right eye (–)1.5 diopters / left eye (–)1.75 diopters; vision acuity with monocular correction — 1.0. Fundoscopy: optic disc is pale pink, with clear borders, arteries and veins are well-proportioned, their courses and calibers are intact; choriocapillary layer attenuation in the macular and paramacular zones, “parquet fundus”; areas of pigment redistribution on peripheral retina; no atrophic foci detected; anterior-posterior axis of the right and left eyes — 26.2 and 26.3 mm, respectively. Optical coherence tomography (OCT) has revealed retinal thinning in the upper and nasal sectors in the right eye during the first assessment. The left eye has demonstrated losses of retinal thickness within the middle parafoveal zone and significant thinning in the upper segment. Optical therapy with HAL spectacle lenses (inducing volumetric myopic peripheral defocus) was assigned to control myopia to slow down the pathological axial growth of the child's eyes and to stabilize refraction. 4 months of wearing glasses with HAL lenses has led to the stabilization of dystrophic changes in retina, signs of improvement in several sectors by were observed on OCT. No negative changes were revealed in all parafoveal segments of the left eye. The child was recommended to continue wearing glasses with HAL lenses with dynamic follow-up every 3 months. Conclusion. CTD in children is associated with high risk of complications in case of myopia progression, moreover, retinal pathology can occur even with mild myopia. Optical therapy with HAL spectacle lenses is effective and safe first treatment of choice in the control of myopia in children with CTD, and opens new opportunities in prevention of progressive myopia disabling complications in children, whose treatment results were not previously sufficient.

Interim safety and efficacy of gene therapy for RLBP1-associated retinal dystrophy: a phase 1/2 trial

Gene therapy holds promise for treatment of inherited retinal dystrophies, a group of rare genetic disorders characterized by severe loss of vision. Here, we report up to 3-year pre-specified interim safety and efficacy results of an open-label first-in-human dose-escalation phase 1/2 gene therapy clinical trial in 12 patients with retinal dystrophy caused by biallelic mutations in the retinaldehyde-binding protein 1 (RLBP1) gene of the visual cycle. The primary endpoints were systemic and ocular safety and recovery of dark adaptation. Secondary endpoints included microperimetry, visual field sensitivity, dominant eye test and patient-reported outcomes. Subretinal delivery of an adeno-associated viral vector (AAV8-RLBP1) was well tolerated with dose-dependent intraocular inflammation which responded to corticosteroid treatment, and focal atrophy of the retinal pigment epithelium as the dose limiting toxicity. Dark adaptation kinetics, the primary efficacy endpoint, improved significantly in all dose-cohorts. Treatment with AAV8-RLBP1 resulted in the resolution of disease-related retinal deposits, suggestive of successful restoration of the visual cycle. In conclusion, to date, AAV8-RLBP1 has shown preliminary safety and efficacy in patients with RLBP1-associated retinal dystrophy. Trial number: NCT03374657.

Sub-acute dermal toxicity of Jatropha curcas Linn. leaf extract coated silver nanoparticles (SNPs) in wistar rats

The application of different nanoparticles is underway in the development of phyto-medicines. Silver nanoparticles (AgNPs) are commonly used as coating agents to treat various bacterial and viral diseases. Their safety and potential toxicity necessitate further research to explore the development of nanoparticles coated herbal drugs. The Azadirachta indica (neem) 5% leaf extract and silver nitrate was used to prepare the silver nanoparticles (SNPs) with the biological reduction (green synthesis) method [1]. The application of silver nanoparticles (SNPs) coated with J. carcus leaf extract (JcLE) on Wistar rats showed no adverse sign of toxicity on hematological parameters except an increase in the neutrophil count and increased in total erythrocyte count (TEC) on 28th day. Similarly, serum biochemical values exhibited an increase in aspartate aminotransferase (AST/SGOT) and alanine transaminase (ALT/SGPT) with JcLE-coated SNPs in treated groups. The histopathology revealed that there was no alteration in skin architecture, however, minimal alteration was observed in the liver and kidney with dilatation of the central vein and sinusoidal space, fatty change in the liver, multifocal necrobiotic changes, cystic degeneration and mild focal glomerular atrophy and hyaline cast in the lumen of tubules of kidney. It indicates the proper absorption and excretion of SNPs from the body. There was no significant effect on hematological parameters in the rats treated with J. curcas leaf extract-coated SNP. However, the serum biochemical analysis revealed a toxic effect on the kidney.

Long Term Follow Up of a Family with A3243G Mitochondrial Syndrome.

To describe the clinical and multimodal imaging (MMI) features of a family (proband, sister and mother) with A3243G mitochondrial retinopathy and long-term follow up. Medical and imaging records were retrospectively evaluated. Multimodal imaging included ultra-widefield color fundus photography, fundus autofluorescence, and spectral-domain optical coherence tomography. Long-term MMI follow up ranged from 6 to 15 years and was available for each member. The proband (Case 1) exhibited rapidly progressive bilateral macular atrophy, corneal endothelial polymegathism, and an A3243G mutation in the mitochondrial DNA. The proband also endorsed a history of early-onset myocardial infarction (MI) ten years prior at the age of 42. The proband's sister (Case 2) only exhibited unilateral focal macular atrophy but admitted to a history of severe multiorgan systemic disease, including multiple sclerosis and major depression disorder. The proband's mother (Case 3), the only one with diabetes mellitus and hearing loss, originally presented with branch retinal vein occlusion in the right eye and pattern dystrophy in the left eye which evolved to geographic atrophy, OD > OS, 15 years later. A3243G mitochondrial syndrome can exhibit heterogenous ocular and systemic features, even within members of the same family. The development of the characteristic maculopathy with early-onset MI warrants genetic testing. Early cardiac and systemic screening may be recommended in individuals with characteristic retinal findings and genetic confirmation.

Structure focused neurodegeneration convolutional neural network for modelling and classification of Alzheimer’s disease

Alzheimer’s disease (AD), the predominant form of dementia, is a growing global challenge, emphasizing the urgent need for accurate and early diagnosis. Current clinical diagnoses rely on radiologist expert interpretation, which is prone to human error. Deep learning has thus far shown promise for early AD diagnosis. However, existing methods often overlook focal structural atrophy critical for enhanced understanding of the cerebral cortex neurodegeneration. This paper proposes a deep learning framework that includes a novel structure-focused neurodegeneration CNN architecture named SNeurodCNN and an image brightness enhancement preprocessor using gamma correction. The SNeurodCNN architecture takes as input the focal structural atrophy features resulting from segmentation of brain structures captured through magnetic resonance imaging (MRI). As a result, the architecture considers only necessary CNN components, which comprises of two downsampling convolutional blocks and two fully connected layers, for achieving the desired classification task, and utilises regularisation techniques to regularise learnable parameters. Leveraging mid-sagittal and para-sagittal brain image viewpoints from the Alzheimer’s disease neuroimaging initiative (ADNI) dataset, our framework demonstrated exceptional performance. The para-sagittal viewpoint achieved 97.8% accuracy, 97.0% specificity, and 98.5% sensitivity, while the mid-sagittal viewpoint offered deeper insights with 98.1% accuracy, 97.2% specificity, and 99.0% sensitivity. Model analysis revealed the ability of SNeurodCNN to capture the structural dynamics of mild cognitive impairment (MCI) and AD in the frontal lobe, occipital lobe, cerebellum, temporal, and parietal lobe, suggesting its potential as a brain structural change digi-biomarker for early AD diagnosis. This work can be reproduced using code we made available on GitHub.

Brain and Ventricle Volume Alterations in Idiopathic Normal Pressure Hydrocephalus Determined by Artificial Intelligence-Based MRI Volumetry.

The aim of this study was to employ artificial intelligence (AI)-based magnetic resonance imaging (MRI) brain volumetry to potentially distinguish between idiopathic normal pressure hydrocephalus (iNPH), Alzheimer's disease (AD), and age- and sex-matched healthy controls (CG) by evaluating cortical, subcortical, and ventricular volumes. Additionally, correlations between the measured brain and ventricle volumes and two established semi-quantitative radiologic markers for iNPH were examined. An IRB-approved retrospective analysis was conducted on 123 age- and sex-matched subjects (41 iNPH, 41 AD, and 41 controls), with all of the iNPH patients undergoing routine clinical brain MRI prior to ventriculoperitoneal shunt implantation. Automated AI-based determination of different cortical and subcortical brain and ventricular volumes in mL, as well as calculation of population-based normalized percentiles according to an embedded database, was performed; the CE-certified software mdbrain v4.4.1 or above was used with a standardized T1-weighted 3D magnetization-prepared rapid gradient echo (MPRAGE) sequence. Measured brain volumes and percentiles were analyzed for between-group differences and correlated with semi-quantitative measurements of the Evans' index and corpus callosal angle: iNPH patients exhibited ventricular enlargement and changes in gray and white matter compared to AD patients and controls, with the most significant differences observed in total ventricular volume (+67%) and the lateral (+68%), third (+38%), and fourth (+31%) ventricles compared to controls. Global ventriculomegaly and marked white matter reduction with concomitant preservation of gray matter compared to AD and CG were characteristic of iNPH, whereas global and frontoparietally accentuated gray matter reductions were characteristic of AD. Evans' index and corpus callosal angle differed significantly between the three groups and moderately correlated with the lateral ventricular volumes in iNPH patients [Evans' index (r > 0.83, p ≤ 0.001), corpus callosal angle (r < -0.74, p ≤ 0.001)]. AI-based MRI volumetry in iNPH patients revealed global ventricular enlargement and focal brain atrophy, which, in contrast to healthy controls and AD patients, primarily involved the supratentorial white matter and was marked temporomesially and in the midbrain, while largely preserving gray matter. Integrating AI volumetry in conjunction with traditional radiologic measures could enhance iNPH identification and differentiation, potentially improving patient management and therapy response assessment.

Primary phenotypic features associated with caudal neck pathology in warmblood horses.

Detailed descriptions of clinical signs associated with radiological findings of the caudal cervical vertebral column are not available. Describe the clinical features associated with neck pain or stiffness, neck-related thoracic limb lameness, proprioceptive ataxia consistent with a cervicothoracic spinal cord or nerve lesion, and their frequency of occurrence compared with control horses. A total of 223 Warmblood horses. Case-control study. Controls and cases were recruited prospectively. All horses underwent predetermined lameness and neurologic examinations. The frequency of occurrence of each clinical feature was compared between cases and controls and relative risk (RR) were calculated. Ninety-six cases and 127 controls were included. Forty-seven (49%) of the cases were classified as neurologic, 31 (32.3%) had thoracic limb lameness, and 18 (18.7%) had neck stiffness or pain or both. Focal caudal cervical muscle atrophy (46, 47.9%), hypoesthesia (38, 39.6%), patchy sweating (16, 16.7%), hyperesthesia (11, 11.5%), and pain upon firm pressure applied over the caudal cervical articular process joints and transverse processes (58, 60.4%) were only observed in cases (P < .001). Sideways flexion of the neck was restricted in a higher proportion of cases (47/96, 49%) compared with controls (40/127, 31.8%; P = .009, RR 1.5). Hopping-type thoracic limb lameness was only observed in cases, (30, 31.6%). Deterioration in lameness after diagnostic anesthesia occurred in 13/31 (41.9%) cases. Systematic clinical evaluation using the methods described should enable clinical differentiation between horses with caudal cervical lesions and horses with other causes of gait abnormalities.

MR Imaging Features of Critical Spinal Demyelinating Lesions Associated with Progressive Motor Impairment.

Progressive MS is typically heralded by a myelopathic pattern of asymmetric progressive motor weakness. Focal individual "critical" demyelinating spinal cord lesions anatomically associated with progressive motor impairment may be a compelling explanation for this clinical presentation as described in progressive solitary sclerosis (single CNS demyelinating lesion), progressive demyelination with highly restricted MR imaging lesion burden (2-5 total CNS demyelinating lesions; progressive paucisclerotic MS), and progressive, exclusively unilateral hemi- or monoparetic MS (>5 CNS demyelinating progressive unilateral hemi- or monoparetic MS [PUHMS] lesions). Critical demyelinating lesions appear strikingly similar across these cohorts, and we describe their specific spinal cord MR imaging characteristics. We performed a retrospective, observational MR imaging study comparing spinal cord critical demyelinating lesions anatomically associated with progressive motor impairment with any additional "noncritical" (not anatomically associated with progressive motor impairment) spinal cord demyelinating lesions. All spinal cord MR images (302 cervical and 91 thoracic) were reviewed by an experienced neuroradiologist with final radiologic assessment on the most recent MR imaging. Anatomic association with clinical progressive motor impairment was confirmed independently by MS subspecialists. Ninety-one individuals (PUHMS, 37 [41%], progressive paucisclerosis 35 [38%], progressive solitary sclerosis 19 [21%]) with 91 critical and 98 noncritical spinal cord MR imaging demyelinating lesions were evaluated. MR imaging characteristics that favored critical spinal cord demyelinating lesions over noncritical lesions included moderate-to-severe, focal, lesion-associated spinal cord atrophy: 41/91 (45%) versus 0/98 (0%) (OR, 161.91; 9.43 to >999.9); lateral column axial location (OR, 10.43; 3.88-28.07); central region (OR, 3.23; 1.78-5.88); ventral column (OR, 2.98; 1.55-5.72); and larger lesion size of the axial width (OR, 2.01;1.49-2.72), transverse axial size (OR, 1.66; 1.36-2.01), or lesion area (OR, 1.14; 1.08-1.2). Multiple regression analysis revealed focal atrophy and lateral axial location as having the strongest association with critical demyelinating lesions. Focal, lesion-associated atrophy, lateral column axial location, and larger lesion size are spinal cord MR imaging characteristics of critical demyelinating lesions. The presence of critical demyelinating lesions should be sought as these features may be associated with the development of progressive motor impairment in MS.

Musculoskeletal mimics of lumbosacral radiculopathy.

Electrodiagnostic evaluations are commonly requested for patients with suspected radiculopathy. Understanding lower extremity musculoskeletal conditions is essential for electrodiagnostic medicine specialists, as musculoskeletal disorders often mimic or coexist with radiculopathy. This review delineates radicular pain from other types originating from the lumbosacral spine and describes musculoskeletal conditions frequently mimicking radiculopathy, such as those that cause radiating pain and sensorimotor dysfunction. In clinical evaluation, a history of pain radiating along a specific dermatomal territory with associated sensory disturbance suggests radiculopathy. Physical examination findings consistent with radiculopathy include myotomal weakness, depressed or absent muscle stretch reflexes, focal atrophy along a discrete nerve root territory, and potentially positive dural tension maneuvers like the straight leg raise. However, electrodiagnostic medicine specialists must be knowledgeable of musculoskeletal mimics, which may manifest as incomplete radiation within or beyond a dermatomal territory, non-radiating pain, tenderness, and give-way weakness, in the context of a normal neurological examination. A systematic approach to musculoskeletal examination is vital, and this review focuses on high-yield physical examination maneuvers and diagnostic investigations to differentiate between musculoskeletal conditions and radiculopathy. This approach ensures accurate diagnoses, promotes resource stewardship, enhances patient satisfaction, and optimizes care delivery. Musculoskeletal conditions resembling L1 to S4 radiculopathy are reviewed, emphasizing their distinctive features in history, physical examination, and diagnostic investigation. Among the more than 30 musculoskeletal disorders reviewed are hip and knee osteoarthritis, lumbar facet syndrome, myofascial pain syndrome, greater trochanteric pain syndrome, and plantar fasciitis.

Right versus left temporal lobe semiology in dementia: Lessons from two cases with focal frontotemporal dementia syndromes.

Focal atrophy of the left anterior temporal lobe has been associated with the semantic type of primary progressive aphasia evolving to semantic dementia. In contrast, focal atrophy of the right temporal lobe has more recently been described as a controverse entity reported as the right temporal variant of FTD. We describe two cases of FTD dementia syndromes: in Case 1, atrophy of the right temporal lobe led to significant behavioural impairment and difficulties in recognizing known people. In Case 2, atrophy of the left temporal lobe was associated with severe aggressive, ritualistic behaviour and aphasia.

Predictors of chronic heart failure in occupational pulmonology

The issue of occupational lung diseases, primarily dust lung diseases caused by exposure to industrial fibrogenic aerosols of varying degrees of fibrogenicity, remains relevant not only for the Russian Federation, but also for most of the world's leading economies. Purpose of the study: to investigate echocardiographic parameters and constitution features, assess the state of carbohydrate metabolism, and evaluate the concentration of leptin and resistin in patients with occupational respiratory diseases. Results of the study: fiberoptic bronchoscopy revealed both subatrophic changes in the bronchial mucosa and phenomena of focal atrophy of the bronchial mucosa and diffuse atrophy in all study groups. According to the otorhinolaryngologist’s examination, there is a high detection rate of chronic atrophic rhino-pharyngolaryngitis in the study groups, which, taking into account the data of fiberop tic bronchoscopy, indicates the systemic and descending nature of the pathological process. Furthermore, our studies demonstrated the high informative value and diagnostic significance of computer spirography for occupational respiratory diseases. Conclusion. As a result of the study, novel clinical and pathogenetic features were identified, and myocardial con tractility was assessed in chronic dust bronchitis, occupational chronic obstructive pulmo nary disease, and interstitial pneumoconiosis. This allows recommending the determination of these indicators (leptin, resistin), as well as echocardiographic assessment of the state and function of the myocardium during periodic medical examinations of workers exposed to industrial fibrogenic aerosols of varying degrees of fibrogenicity in order to assess the risk of developing and predict chronic heart failure in occupational respiratory diseases associated with exposure to highly fibrogenic, moderately fibrogenic, and low fibrogenic industrial aerosols.

Relationship between neuroimaging and cognition in frontotemporal dementia: An FDG-PET and structural MRI study.

Frontotemporal dementia (FTD) is a clinically and pathologically heterogeneous neurodegenerative condition with a prevalence comparable to Alzheimer's disease for patients under 65 years of age. Limited studies have examined the association between cognition and neuroimaging in FTD using different imaging modalities. We examined the association of cognition using Montreal Cognitive Assessment (MoCA) with both gray matter (GM) volume and glucose metabolism using magnetic resonance imaging and fluorodeoxyglucose (FDG)-PET in 21 patients diagnosed with FTD. Standardized uptake value ratio (SUVR) using the brainstem as a reference region was the primary outcome measure for FDG-PET. Partial volume correction was applied to PET data to account for disease-related atrophy. Significant positive associations were found between whole-cortex GM volume and MoCA scores (r = 0.46, p =.04). The association between whole-cortex FDG SUVR and MoCA scores was not significant (r = 0.37, p =.09). GM volumes of the frontal cortex (r = 0.54, p =.01), caudate (r = 0.62, p<.01), and insula (r = 0.57, p<.01) were also significantly correlated with MoCA, as were SUVR values of the insula (r = 0.51, p =.02), thalamus (r = 0.48, p =.03), and posterior cingulate cortex (PCC) (r = 0.47, p =.03). Whole-cortex atrophy is associated with cognitive dysfunction, and this association is larger than for whole-cortex hypometabolism as measured with FDG-PET. At the regional level, focal atrophy and/or hypometabolism in the frontal cortex, insula, PCC, thalamus, and caudate seem to be important for the decline of cognitive function in FTD. Furthermore, these results highlight how functional and structural changes may not overlap and might contribute to cognitive dysfunction in FTD in different ways.

Temporal progression of pancreatic cancer computed tomography findings until diagnosis: A large-scale multicenter study.

Focal parenchymal atrophy and main pancreatic duct (MPD) dilatation have been identified as early signs of pancreatic ductal adenocarcinoma. However, limited evidence exists regarding their temporal progression due to previous study limitations with restricted case numbers. To ascertain a more precise frequency assessment of suspicious pancreatic ductal adenocarcinoma findings as well as delineate the temporal progression of them. A multicenter retrospective study was conducted on patients diagnosed with pancreatic ductal adenocarcinoma between 2015 and 2021. We included patients who had undergone at least one computed tomography (CT) scan ≥6months before diagnosing pancreatic ductal adenocarcinoma. The temporal progression of suspicious pancreatic ductal adenocarcinoma findings on CT was investigated. Out of 1832 patients diagnosed with pancreatic ductal adenocarcinoma, 320 had a previous CT before their diagnosis. Suspicious pancreatic ductal adenocarcinoma findings were detected in 153 cases (47.8%), with focal parenchymal atrophy (26.6%) being the most common followed by MPD dilatation (11.3%). Focal parenchymal atrophy was the earliest detectable sign among all suspicious findings and became visible on average 2.7years before diagnosis, and the next most common, MPD dilatation, 1.1years before diagnosis. Other findings, such as retention cysts, were less frequent and appeared around 1year before diagnosis. Focal parenchymal atrophy followed by MPD dilatation was observed in 10 patients but not in reverse order. Focal parenchymal atrophy was more frequently detected in the pancreatic body/tail. No significant relationship was found between the pathological pancreatic ductal adenocarcinoma differentiation or tumor stage and the time course of the CT findings. All cases of focal parenchymal atrophy progressed just prior to diagnosis, and the atrophic area was occupied by tumor at diagnosis. Main pancreatic duct dilatation continued to progress until diagnosis. This large-scale study revealed that the temporal progression of focal parenchymal atrophy is the earliest detectable sign indicating pancreatic ductal adenocarcinoma. These results provide crucial insights for early pancreatic ductal adenocarcinoma detection.

Endothelial peroxiredoxin-4 is indispensable for blood–brain barrier integrity and long-term functional recovery after ischemic stroke

The endothelial lining of cerebral microvessels is damaged relatively early after cerebral ischemia/reperfusion (I/R) injury and mediates blood-brain barrier (BBB) disruption, neurovascular injury, and long-term neurological deficits. I/R induces BBB leakage within 1 h due to subtle structural alterations in endothelial cells (ECs), including reorganization of the actin cytoskeleton and subcellular redistribution of junctional proteins. Herein, we show that the protein peroxiredoxin-4 (Prx4) is an endogenous protectant against endothelial dysfunction and BBB damage in a murine I/R model. We observed a transient upregulation of Prx4 in brain ECs 6 h after I/R in wild-type (WT) mice, whereas tamoxifen-induced, selective knockout of Prx4 from endothelial cells (eKO) mice dramatically raised vulnerability to I/R. Specifically, eKO mice displayed more BBB damage than WT mice within 1 to 24 h after I/R and worse long-term neurological deficits and focal brain atrophy by 35 d. Conversely, endothelium-targeted transgenic (eTG) mice overexpressing Prx4 were resistant to I/R-induced early BBB damage and had better long-term functional outcomes. As demonstrated in cultures of human brain endothelial cells and in animal models of I/R, Prx4 suppresses actin polymerization and stress fiber formation in brain ECs, at least in part by inhibiting phosphorylation/activation of myosin light chain. The latter cascade prevents redistribution of junctional proteins and BBB leakage under conditions of Prx4 repletion. Prx4 also tempers microvascular inflammation and infiltration of destructive neutrophils and proinflammatory macrophages into the brain parenchyma after I/R. Thus, the evidence supports an indispensable role for endothelial Prx4 in safeguarding the BBB and promoting functional recovery after I/R brain injury.

Diagnostic informativeness of biopsy for chronic kidney disease in cats

The biopsy is a diagnostic method that allows in vivo sampling of kidney tissue material for histopathological examination to identify structural changes in the organ. The study aims to study the informativeness of intravital diagnosis of stage II chronic kidney disease (according to IRIS) in cats based on the results of histological and histochemical studies of biopsies. A kidney biopsy was performed on two cats aged 6 and 8 years. Research methods: histological (hematoxylin and eosin, Heidenhain test) and histochemical (PAS reaction, Gomori (PAMS)). The diagnosis of chronic kidney disease was made based on history, clinical symptoms, and blood and urine test results. Based on the biopsy, acute extracapillary serous-desquamative glomerulonephritis was established in cats with II-stage chronic kidney disease, which was characterized by vacuolar dystrophy of renal tubule epitheliocytes, desquamation of glomerular capsule epithelium. In addition, lymphoplasmacytic infiltration of the renal stroma, thickening of the Shumlyansky-Bowman capsule with significant deposition of PAS-positive substances, the collapse of the glomerular loops, and focal atrophy of the proximal tubules of the kidney pronounced extra capillary desquamation of the glomerular epithelium, segmentation of the vascular glomerulus, and dystrophy of single tubules were noted. The detected changes in kidney biopsies of cats in the II stage of chronic kidney disease are characteristic of this pathology, which makes it possible to develop and carry out effective treatment of animals promptly and improve their quality of life.

Removal of intrahepatic bile duct stone could reduce the risk of cholangiocarcinoma: A single-center retrospective study in South Korea.

Intrahepatic duct (IHD) stones are among the most important risk factors for cholangiocarcinoma (CCC). Approximately 10% of patients with IHD stones develop CCC; however, there are limited studies regarding the effect of IHD stone removal on CCC development. To investigate the association between IHD stone removal and CCC development. We retrospectively analyzed 397 patients with IHD stones at a tertiary referral center between January 2011 and December 2020. CCC occurred in 36 of the 397 enrolled patients. In univariate analysis, chronic hepatitis B infection (11.1% vs 3.0%, P = 0.03), carbohydrate antigen 19-9 (CA19-9, 176.00 vs 11.96 II/mL, P = 0.010), stone located in left or both lobes (86.1% vs 70.1%, P = 0.042), focal atrophy (52.8% vs 26.9%, P = 0.001), duct stricture (47.2% vs 24.9%, P = 0.004), and removal status of IHD stone (33.3% vs 63.2%, P < 0.001) were significantly different between IHD stone patients with and without CCC. In the multivariate analysis, CA19-9 > upper normal limit, carcinoembryonic antigen > upper normal limit, stones located in the left or both lobes, focal atrophy, and complete removal of IHD stones without recurrence were independent factors influencing CCC development. However, the type of removal method was not associated with CCC risk. Complete removal of IHD stones without recurrence could reduce CCC risk.

Kearns–Sayre Syndrome with Bilateral Ptosis and External Ophthalmoplegia: A Rare Case Report

Abstract&#x0D; Introduction : Kearns-Sayre syndrome (KSS) is a rare genetic disorder caused by a deletion of mitochondrial DNA (mtDNA) segment, typically characterized by a triad of symptoms includes external ophthalmoplegia, pigmentary retinopathy and appeared before the age of 20. The prevalence rate is about 1–3 per 100.000 individuals. It was diagnosed based on clinical features and supported by biochemical, radiological, histologic, and molecular genetic tests.&#x0D; Case Illustration : 26-year-old male with bilateral ptosis, chronic progressive external ophthalmoplegia, pigmentary retinopathy was shown from ophthalmology examination and associated with hearing loss. Physical examination showed short stature, wasting, and weakness of limb muscles. MRI examination revealed focal brain atrophy on bilateral parietal regions.&#x0D; Discussion : Mitochondrial DNA defect led to dysfunction of the central nervous system, endocrine system, extraocular muscle, myocardium, skeletal muscle, and other multiple systems. The clinical findings in this patient are appropriate for classical signs and symptoms of KSS. Central nervous involvementis shown by the neuroimaging result. There is no cardiac involvement suggested by normal cardiology examination. Although muscle pathology and molecular genetic analysis can play a great role to diagnose KSS, the classical triad of clinical signs plus one of the other symptoms could establish KSS diagnosis.&#x0D; Conclusion : KSS is a rare genetic disorder and challenging to diagnose. However, if a patient presents with the classic triad of symptoms, clinicians should have a high level of suspicion for the disorder. Additionally, It is important to perform a thorough evaluation to rule out other conditions that can cause similar symptoms.