Pathological Features Research Articles

Characteristics of Cancer in Subjects Carrying Lynch Syndrome-Associated Gene Variants in Taiwanese Population: A Hospital-Based Study in Taiwan

Lynch syndrome (LS) is an autosomal dominant disorder characterized by increased risks of colorectal and endometrial cancers. LS is defined by pathogenic variants in mismatch repair (MMR) genes, including MLH1, MSH2, and MSH6. Data on the prevalence and associated cancer risks of LS in the Han Chinese population remain limited. In this study, using a broad biobank approach through the Taiwan Precision Medicine Initiative (TPMI), we identified LS-associated MMR gene variants within a cohort of 42,828 participants from a Taiwanese medical center. A total of 89 individuals were found to carry pathogenic MMR variants: MLH1 (n = 22, 25%), MSH2 (n = 47, 53%), and MSH6 (n = 20, 22%). The overall prevalence of MMR variants was calculated, and cancer incidence rates among carriers were determined. The prevalence of MMR variants in the study population was 1 in 481. The distribution of MLH1, MSH2, and MSH6 variants were 24.7%, 52.8%, and 22.5%, respectively. Cumulative cancer incidence rates of carriers were 40.9% for MLH1 carriers, 29.8% for MSH2, and 40% for MSH6. Among the 19 individuals who underwent colonoscopy screening, the prevalence of polyps was similar to that of the control group (adenoma detection rate: 32% vs 26%, p = 0.585). A meticulous analysis of the detected polyps in seven participants, considering factors such as location, size, morphology, and pathological features, showed no significant differences from controls. A significant cancer risk is associated with LS-related MMR variants in the Taiwanese population. The apparent under diagnosis of LS highlights the urgent need for enhanced surveillance and genetic counseling in this demographic. Our findings suggest that adjustments in the current screening protocols may be warranted to better identify and manage at-risk individuals.

Skin Structure, Physiology, and Pathology in Topical and Transdermal Drug Delivery

Several industries are increasingly focused on enhancing the delivery of active ingredients through the skin to optimize therapeutic outcomes. By facilitating the penetration of active ingredients through the skin barrier, these enhancers can significantly improve the efficacy of various formulations, ranging from skincare products to therapeutic agents targeting systemic circulation. As the understanding of skin physiology and the mechanisms of drug absorption deepen, these industries are adopting permeation enhancers more widely, ultimately leading to better patient outcomes and expanded treatment options. However, the structure and physiological function of the skin can vary according to different factors, such as the area of the body and between individuals. These variations, along with external environmental exposures, aging and pathological conditions, introduce complexities that must be carefully considered when designing effective delivery systems. Considering the intricacies of skin structure and physiology, tailoring systems to account for regional differences, individual variability, and changes induced by environmental factors or disease is critical to optimizing therapeutic outcomes. This review discusses the features of skin structure, physiology, and pathologies, as well as the application of permeation enhancers in these contexts. Furthermore, it addresses the use of animal skin models in transdermal delivery and dermatological studies, along with the latest developments in this field.

Association Between Gross Features and Coexistence of BRAFV600E and TERT Promoter Mutations in Papillary Thyroid Carcinomas: A Combined Analysis Incorporating Clinicopathologic Features.

Background: The coexistence of v-Raf murine sarcoma viral oncogene homolog B1 (BRAFV600E) and telomere reverse transcriptase promoter (TERT-p) mutations is considerably associated with aggressiveness and poor prognosis in papillary thyroid carcinoma (PTC). However, the association between gross findings and genetic alterations in PTC remains unknown. We aimed to investigate the association between clinicopathologic features, including macroscopic features, and the coexistent BRAFV600E and TERT-p mutations in patients with PTC. Methods: We retrospectively analyzed 375 cases of PTC surgically resected between January 2018 and October 2023 at a single institution, based on the presence of BRAFV600E and TERT-p double mutation. Clinicopathologic features, including gross features on the cut surface of tumors, were evaluated. Subsequently, the association between clinicopathologic features and mutation status was statistically examined. Cox proportional hazard models were used to analyze the impact of molecular pathological features on disease-free survival (DFS). Results: The BRAFV600E and TERT-p double mutation was identified in 78 (20.8%) patients among the PTC cases and was significantly correlated with shorter DFS. Multivariable analysis revealed that factors such as relatively older age (≥55 years) (odds ratio [OR] = 12.083, 95% confidence interval [CI] 4.498-32.456), larger tumor size (>2.0 cm) (OR = 2.722, CI 1.104-6.712), lobulated tumor margins (OR = 16.114, CI 3.155-82.296), papillary excrescences on the cut surface (OR = 17.573, CI 3.462-89.201), solid-cut surface (OR = 4.012, CI 1.084-14.849), minimal extrathyroidal extension (ETE) (OR = 4.156, CI 1.209-14.282), gross ETE (OR = 6.517, CI 1.734-24.490), and Ki-67 labeling index (LI) (≥5%, OR = 12.145, CI 4.354-33.877) were significantly associated with the double mutation. Conclusions: The BRAFV600E and TERT-p double mutation in PTC was significantly associated with relatively old age, larger tumor size, lobulated configuration in tumor margin, papillary excrescences on the cut surface, solid-cut surface, ETE, and high Ki-67 LI. These features are suggestive of the presence of the double mutation and should be analyzed at the molecular level in patients with PTC.

SBP1 contributes to mesangial proliferation and inflammation through mitochondrial respiration in glomerulus during IgA nephropathy.

Mesangial expansion and proliferation have been implicated in the pathogenesis of IgA nephropathy (IgAN). Mesangial cells in glomerulus are important contributors to commencement of IgAN. From minimal mesangial expansion to diffuse proliferation, the mesangial alteration is linked to clinical and pathological features of IgAN. Although selenium-binding protein 1 (SBP1) is associated with tissue injury, the roles of SBP1 in mesangial proliferation and inflammation in glomerulus during IgAN remains unclear. In the present study, we found that SBP1 gene levels were elevated in kidney tissues of patients with IgAN. Also, SBP1 protein levels were elevated in proliferative mesangial cells of glomerulus in kidney tissues from patients with IgAN. Urinary SBP1 protein levels were elevated in patients with IgAN. Elevated urinary SBP1 levels were positively correlated with segmental glomerulosclerosis of the Oxford classification related to mesangial proliferation in patients with IgAN. Over-expression of SBP1 induced cellular proliferation via mitochondrial respiration in human renal mesangial cells. Consistently, SBP1 knockdown and mitochondrial respiration inhibition suppressed cellular proliferation and induced mitochondrial oxidative stress in human renal mesangial cells. Furthermore, SBP1 induced pro-inflammatory phenotype by gene expression and production of pro-inflammatory cytokines and chemokines including IL-6, CXCL10, and CCL5 via NF-κB activation in human renal mesangial cells. These results suggest that SBP1 contributes to mesangial proliferation and inflammation via mitochondrial respiration during IgAN.

Primary seminal vesicle diffuse large B-cell lymphoma: a case report and review of the literatures

Primary seminal vesicle lymphoma is a remarkably rare condition, predominantly manifesting as diffuse large B-cell lymphoma. Due to its rarity and nonspecific clinical presentations, it is often misdiagnosed or overlooked. Here, we report a case of a 68-year-old male diagnosed with primary seminal vesicle lymphoma, coinciding with prostate cancer. The diagnosis followed initial findings of elevated prostate-specific antigen levels and abnormal magnetic resonance imaging of the prostate and left seminal vesicle. Suspicion of prostate cancer led to a radical resection of both the prostate and seminal vesicle. Subsequent pathological examination and next-generation sequencing post-surgery confirmed the diagnosis of primary seminal vesicle diffuse large B-cell lymphoma, characterized by CD79B mutation type (MCD type). The patient was treated with six cycles of the R-CHOP regimen (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone), achieving complete metabolic remission as confirmed by positron emission tomography-computed tomography. Fifteen months post-treatment, the patient’s condition remains favorable. Through our literature review of additional six cases of primary seminal vesicle lymphoma, we aim to elucidate the typical clinical presentations, imaging features, pathological characteristics, genetic mutations, and therapeutic strategies, aiming to contribute to better detection and management of this rare malignancy. This case underscores the diagnostic challenges and emphasizes the necessity for heightened clinical suspicion and definitive pathological examination in the management of primary seminal vesicle lymphoma.

Can Ki-67 serve as a suitable marker to indicate the necessity of staging diagnostics in cases of low-risk breast cancer?

For many years, staging tests have not been routinely employed for low-risk early breast cancer (EBC). However, the role of Ki-67 in determining the need for staging tests in low-risk EBC remains unclear. Our study aimed to assess the number and types of staging diagnostics, additional imaging, false-positive results, and rate of distant metastases in low-risk EBC with low and high Ki-67 (< / ≥ 25%). This is a retrospective, single institution cohort study. All patients with newly diagnosed low-risk breast cancer at the University Medical Center in Freiburg in 2017 and 2021 were included. Low-risk was defined as clinical tumor stage T1/2, node negative (N0), hormone receptor positive, HER2 negative, asymptomatic EBC. Information on demographics, clinical and pathological characteristics, as well as number and type of performed staging diagnostics was obtained. Rate and type of additional imaging or follow-up diagnostics due to suspicious findings was analyzed. The patients were divided into two groups (Ki-67 < and ≥ 25%) and rates of distant metastases, performed staging diagnostics and false positive rates were compared. A total of 189 patients with low-risk EBC were identified, with 54% (n = 102) having Ki-67 < 25% and 46% (n = 87) having Ki-67 ≥ 25%. Risk for distant metastases was 0% in Ki-67 < 25% and 1.1% in patients with Ki-67 ≥ 25% (p = 0.46). Due to suspicious findings in the initial staging diagnostic, additional imaging was required for 11.8% (n = 12) of patients with Ki-67 < 25% compared to 19.5% (n = 17) of patients with Ki-67 ≥ 25% (p = 0.16). False positive rates did not differ significantly between the two groups (7.6% in Ki-67 < 25% vs. 9.8% in Ki-67 ≥ 25%; p = 0.55). Distant metastases are rare in low-risk EBC. All in all, staging diagnostics should not be routinely employed in this patient population. Only patients with high Ki-67 developed distant metastases. In these cases, staging diagnostics may be discussed with the patient.

Inflammatory arthropathies: Perspectives from a Portuguese male individual (1574–1834 CE)

AbstractArthropathies are common in past populations and can be categorized into two groups: those with predominant bone production (e.g., osteoarthritis) and those with significant bone loss (e.g., erosive arthropathies). The former is frequent in the archaeological record, whereas the latter are uncommon. We present a Post‐Medieval male individual, recovered in the Convent of the Holy Spirit (Loures, Portugal), with multiple articular and entheseal bone changes, particularly extensive periarticular, marginal, and subchondral erosive processes, often exposing trabecular bone. Proliferative lesions and extensive ankylosis are also observed in the synovial joints. These pathological changes affect both the axial and peripheral skeleton in a polyarticular, bilateral, and asymmetric pattern. Given that the appendicular skeleton, particularly the hands and feet, are the most affected areas, the most probable diagnosis is a peripheral spondyloarthropathy such as psoriatic arthritis or reactive arthritis. This case study is the first archaeological instance of psoriatic arthritis or reactive arthritis described in Portugal, highlighting the importance of a differential diagnosis and the need for reflection when pathological changes characteristics overlap, advocating for a broader diagnostic approach.

Clinical, Pathologic, and Imaging Variables Associated with Prostate Cancer Detection by PSMA PET/CT and Multiparametric MRI.

Multiparametric MRI (mpMRI) and prostate-specific membrane antigen (PSMA) PET/CT are complementary imaging modalities used in the presurgical evaluation of patients with prostate cancer (PCa). The purpose of this study was to characterize clinically significant PCa (csPCa) detected and not detected by PSMA PET/CT and mpMRI, focusing on tumors detected solely by PSMA PET/CT and overlooked by mpMRI. Methods: We conducted a single-center, retrospective analysis of patients who underwent both PSMA PET/CT and mpMRI within 3 mo of each other and before radical prostatectomy. Two nuclear medicine physicians and 2 radiologists, in a masked manner, independently contoured PCa lesions on PSMA PET/CT and mpMRI, respectively. A consensus read was done with a third reader for each modality, and a majority rule was applied (2:1). After centralized imaging, a pathologic review was done by a genitourinary pathologist. We assessed agreement between imaging modalities and correlation with pathology. Logistic regression models explored associations between clinicopathologic variables and tumor detection on imaging. Results: In total, 132 csPCa tumors from 100 patients were identified on surgical pathology. PSMA PET/CT showed higher lesion-level (87% vs. 80%) and patient-level (98% vs. 94%) sensitivity than mpMRI. Tumors detected on both imaging modalities were larger and had higher grade groups than those not detected by one or both imaging modalities. On multivariable analysis, csPCa tumors undetected by mpMRI but detected by PSMA PET/CT were smaller than those detected by both modalities. Most tumors showing aggressive pathologic features, such as the large cribriform pattern (94.7%) and the intraductal carcinoma (96%), were correctly detected by both imaging modalities. Limitations included selection bias in a surgical cohort. Conclusion: PSMA PET/CT tends to detect smaller csPCa not detected by mpMRI. Larger tumors on pathology with higher grade groups are more likely to be correctly detected by both imaging modalities. These findings provide insights for refining presurgical evaluation strategies in PCa.

Ror2 signaling regulated by differential Wnt proteins determines pathological fate of muscle mesenchymal progenitors

Skeletal muscle mesenchymal progenitors (MPs) play a critical role in supporting muscle regeneration. However, under pathological conditions, they contribute to intramuscular adipose tissue accumulation, involved in muscle diseases, including muscular dystrophy and sarcopenia, age-related muscular atrophy. How MP fate is determined in these different contexts remains unelucidated. Here, we report that Ror2, a non-canonical Wnt signaling receptor, is selectively expressed in MPs and regulates their pathological features in a differential ligand-dependent manner. We identified Wnt11 and Wnt5b as ligands of Ror2. In vitro, Wnt11 inhibited MP senescence, which is required for normal muscle regeneration, and Wnt5b promoted MP proliferation. We further found that both Wnts are abundant in degenerating muscle and synergistically stimulate Ror2, leading to unwanted MP proliferation and eventually intramuscular adipose tissue accumulation. These findings provide evidence that Ror2-mediated signaling elicited by differential Wnts plays a critical role in determining the pathological fate of MPs.

Clinicopathological Features of Membranous Nephropathy Complicated by IgA Nephropathy: A Retrospective Analysis of Seven Cases.

Aims/Background Both membranous nephropathy (MN) and immunoglobulin A nephropathy (IgAN) are immune complex-mediated glomerular diseases, but the concurrent occurrence of these two conditions in the same patient is not common, a phenomenon that is currently not supported by clinical data in terms of treatment and prognosis. This study explores the clinical and pathological characteristics, as well as the treatment outcomes, of patients affected by MN and IgAN simultaneously. Methods The clinical data, pathological features, and diagnostic and therapeutic information of seven cases of MN complicated by IgAN, treated between December 2015 and December 2022, were retrospectively analyzed. Results Among the seven cases, there were two male and five female patients, with an average age of 57.3 ± 9.2 years. All patients presented with clinical manifestations of proteinuria and edema upon admission, with an average 24-hour urine protein of 3716.6 ± 1519.4 mg/24 h. Phospholipase A2 receptor (PLA2R) expression was detected in all seven cases, and nephrotic syndrome was clinically diagnosed in five cases. Additionally, all seven cases showed microscopic hematuria, with intermittent gross hematuria in two cases. All seven patients included in this study underwent renal biopsy. After disease staging, the patients had MN stages I-III and IgAN stages II-III. Pathological findings revealed abnormal glomerular basement membrane (GBM) and diffuse immunoglobulin G (IgG) deposition in the subepithelial space, predominantly of the IgG4 subtype. Simultaneously, there was diffuse mesangial zone deposition of immunoglobulin A (IgA) to varying degrees, co-localization of complement component C3 and IgA, and mesangial cell proliferation. Treatment strategies included angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) in combination with steroids or immunosuppressive therapies such as tacrolimus, cyclophosphamide, and rituximab. After 2-6 months of treatment, all patients achieved complete remission with a favourable prognosis. Conclusion MN accompanied by IgAN tends to occur more frequently in middle-aged and elderly individuals, with a relatively low incidence. The latent feature of the comorbidities manifests as a form of IgAN superimposed on the background of MN. Utilizing ACEI or ARB in combination with steroids or various immunosuppressive therapies represents a potentially effective treatment strategy.

LncRNA MALAT1 as diagnostic and prognostic biomarker in colorectal cancers: A systematic review and meta-analysis

Objective This study investigated the relationship between the long non-coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) expression and colorectal cancer (CRC) using a thorough systematic review and meta-analysis. Methods Under the PRISMA guidelines, a systematic review was conducted on studies published from the databases’ inception to September 18, 2023. Prognostic value and diagnostic accuracy were explored. Additionally, the association between levels of MALAT1 expression and pathological features was investigated. The statistical analysis was performed using the “meta” package of R. Results Among the pathological parameters examined, based on three studies involving 51 cases of metastatic CRC and 135 cases of non-metastatic CRC, a statistically significant correlation was found between the expression level of MALAT1 and distant metastasis, with an OR of 16.0118 (95% CI: 4.5618–56.2015). Three studies involving 378 cases reported overall survival and had a pooled HR of 2.3854 (95% CI: 1.3272–4.2875). Three studies involving 436 cases reported disease-free survival and had a pooled HR of 2.4772 (95% CI: 1.3774–4.4549). All prognosis studies utilized tumor tissue samples as specimens to assess the expression level of MALAT1. Case-to-control diagnostic studies with 126 cases and 126 controls had a pooled AUC value of 0.6173 (95% CI: 0.5436–0.6909), a pooled sensitivity of 0.675 (95% CI: 0.324–0.900), and a pooled specificity of 0.771 (95% CI: 0.685–0.839). Conclusions The expression of MALAT1 in CRC is highly correlated with distant metastasis and has an impact on survival and prognosis. MALAT1 could also be employed as a diagnostic biomarker. More prospective studies should be performed to assess the MALAT1 diagnostic potential in the early stages of CRC.

Peripheral arterial pathology and osteoarthritis of the knee: US examination of arterial wall stiffness, thickness, and flow characteristics

BackgroundOsteoarthritis (OA) is a widespread chronic joint disorder characterized by the degeneration of articular cartilage, extensive bone remodeling, ligamentous fibrosis, and synovial inflammation impacting millions. Shared factors like phenotypic similarities, hypofibrinolysis, and inflammation constitute similarities in pathophysiology and clinical manifestations between OA and peripheral vascular disease (PVD). This study investigated peripheral arterial flow characteristics, vascular wall thickness, and stiffness in knee OA to clarify a potential association with early atherosclerosis. MethodsThe OA cohort consisted of 35 knees with a mean age of 69 years. The control cohort consisted of 58 knees with a mean age of 68 years. Subjects underwent arterial ultrasound scanning of the common femoral, superficial femoral, and popliteal arteries. Data measured included peak systolic volumetric flow, intima-media thickness, systolic and diastolic vessel diameter, and simultaneous EKG and flow curves. Structural and functional vascular data were quantified using the incremental Young's modulus, pulse wave velocity (PWV), and distensibility. ResultsSignificantly elevated arterial volumetric flow, measures of arterial stiffness, and intima-media wall thickness were observed in those with OA compared to those without. PWV as calculated by the Bramwell-Hill equation were found to be significantly greater in all three vessels of patients with OA. ConclusionsThis study supports the association between peripheral arterial pathology and knee OA, consistent with shared clinical and phenotypic traits. The observed characteristics of early vascular pathology suggest potential pathophysiologic linkages between OA and PVD. This foundational framework provides avenues for mechanistic studies exploring the relationship between these two disease processes.

The Association Between Lymphovascular or Perineural Invasion in Radical Prostatectomy Specimen and Biochemical Recurrence

Objective: The aim of this study was to test for the association between lymphovascular invasion or perineural invasion in radical prostatectomy (RP) specimens and biochemical recurrence (BCR). Methods: Relying on a tertiary-care database, we identified prostate cancer patients treated with RP between January 2014 and June 2023. Of these, the majority underwent robotic-assisted RP (81%). Kaplan–Meier survival analyses and Cox regression models addressed BCR according to either lymphovascular invasion or perineural invasion in RP specimens. Additionally, the linear trend test assessed the association between the Gleason Grade Group or pathologic tumor stage and lymphovascular or perineural invasion. Results: Of 822 patients, 78 (9%) exhibited lymphovascular invasion and 633 (77%) exhibited perineural invasion in RP specimens. In survival analyses, the five-year BCR-free survival rates were 62% in patients with lymphovascular invasion vs. 70% in patients without lymphovascular invasion (p = 0.04) and 64% in patients with perineural invasion vs. 82% in patients without perineural invasion (p = 0.01). In univariable Cox regression models, lymphovascular invasion (hazard ratio 1.58, 95% confidence interval 1.01–2.47; p = 0.045) and perineural invasion (hazard ratio 1.77, 95% confidence interval 1.13–2.77; p = 0.013) were both associated with a higher BCR rate. After accounting for age at surgery, PSA value, pathologic tumor stage, Gleason Grade Group, lymph node invasion, positive surgical margin, surgical approach, and adjuvant radiation therapy, lymphovascular (p = 0.740) or perineural invasion (p = 0.341) were not significantly associated with a higher BCR since the Gleason Grade Group and pathologic tumor stage highly correlated with lymphovascular as well as perineural invasion. Conclusions: In univariable models, lymphovascular or perineural invasion is associated with BCR. After adjustment for standard pathologic tumor characteristics, lymphovascular or perineural invasion is not an independent predictor for BCR.

Congenital pulmonary airway malformation in a cat.

Congenital structural anomalies of the lower airways of the respiratory tract are uncommon in cats. We describe here a case of cystic pulmonary lesions in a 6-wk-old domestic shorthair cat consistent with congenital pulmonary airway malformation (CPAM; formerly referred to as cystic adenomatoid malformation of the lung, or congenital pulmonary adenomatoid malformation; Stocker type II). CPAM is rarely reported in veterinary species and, to our knowledge, has not been reported in cats. In humans and veterinary species, individuals with CPAM (Stocker types I-IV) can be asymptomatic at birth but are predisposed to developing respiratory abnormalities that typically manifest clinically in the early years of life. We review the pathologic features of CPAM.

The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells.

Calcium homeostasis is correlated closely with the occurrence and development of various cancers. The role of calcium homeostasis in prostate cancer has remained unclear. The present study aimed to investigate the relationship between transmembrane and crimp-crimp domain 1 (TMCO1) and calreticulin (CALR) in the pathological characteristics of prostate cancer and the mechanism of action on prostate cancer metastasis. Effects of CALR recombinant protein and TMCO1 knockdown on prostate cancer cells were investigated using following methods: cell cloning, Transwell, wound scratch assay, JC-1 assay, Fluo-4 Assay, endoplasmic reticulum (ER) fluorescent probe, mitochondrial fluorescence probe, Western blot and Immunofluorescence. TMCO1 and CALR are overexpressed in prostate cancer and knockdown of TMCO1 significantly inhibited the invasion, migration and cell proliferation. Furthermore, knocking down TMCO1 modulated the intensity of ER probes and mitochondrial fluorescence probes, and affected the levels of intracellular calcium ion and mitochondrial membrane potential. In addition, CALR recombinant protein upregulated the expression of epithelial-mesenchymal transition marker, Vimentin, Conversely, knockout of TMCO1 significantly reduced the expression of CALR and Vimentin. Knockout of TMCO1 can reverse the effect of CALR recombinant protein, elucidating the pivotal roles of TMCO1 and CALR in the regulation of prostate cancer metastasis through modulation of calcium homeostasis.

Clinical characteristics of male patients with breast cancer in the Latino population.

Breast cancer is the most prevalent cancer type in Mexico, with male breast cancer accounting for only 1% of all breast cancer cases. A limited number of studies have described the clinical-pathological profiles of males with breast cancer in low- and middle-income countries. This study presents an analysis of patients with breast cancer seen at three different institutions in México. A retrospective review of the medical records was performed to analyze the clinical and pathological characteristics of 49 men diagnosed with breast cancer and their overall survival. The mean age at diagnosis was 64.65years. A significant proportion of patients presented at diagnosis with stage IV disease (n = 11, 22.45%), had triple-negative subtype (n = 6, 12.24%), and nuclear grade III (n = 20, 40.8%). Primary endocrine resistance was observed in 10 patients (31.25%). Genetic analysis was performed on 24 patients (48.9%), revealing a germline BRCA pathogenic variant in 8.33%. Our findings described the clinical and pathological profile of breast cancer in a male cohort in Mexico, with a significantly high proportion of advanced disease, triple-negative subtype, nuclear grade III, and endocrine resistance. Further comprehensive studies, including research into somatic mutations, are needed.

Intramyocardial fatty infiltration lesion in sporadic inclusion body myositis: a case report.

Sporadic inclusion body myositis (sIBM), the most common inflammatory muscle disorder in adults over 50 years, is often misdiagnosed due to its gradual onset and its common but unspecific muscle weakness in older adults. Diagnosis relies on clinical, radiological, and pathological features. Cardiac involvement is rare, prompting this case description and a comprehensive literature analysis. A 73-year-old woman diagnosed with sIBM in 2021 through muscle biopsy had been experiencing muscular symptoms since 2015. Her condition progressively worsened, affecting daily activities. Annual follow-ups revealed a moderate obstructive syndrome on respiratory testing, prompting a cardiac evaluation. Cardiac magnetic resonance (CMR) imaging identified intramyocardial lesions consistent with fatty infiltration, highlighting the interest of advanced imaging in sIBM management. Cardiac involvement in sIBM is presumed rare compared to other idiopathic inflammatory myopathies, though the exact frequency remains unclear. Early identification of heart alterations by CMR in sIBM can be prognostically valuable, guiding follow-up and interventions. However, literature on this subject is limited to small cohort studies and case reports describing complications. Given the slow progression of sIBM and the limited efficacy of current treatments, the discovery of myocardial lesions could warrant closer cardiological monitoring. Larger cohort studies are needed to explore potential new therapeutic approaches. Our case underscores the importance of CMR in detecting subtle cardiac manifestations in sIBM and illustrates the potential prognostic value of cardiac assessment in the management of sIBM.

Environmental therapy: interface design strategies for color graphics to assist navigational tasks in patients with visuospatial disorders through an analytic hierarchy process based on CIE color perception

IntroductionEnvironmental therapy theory has been applied in the research of disease prevention, and the effectiveness of using color and graphic designs to assist patients with spatial orientation has been confirmed. Visual-spatial impairments are common symptoms associated with cognitive decline. However, the interaction and driving factors between these impairments and spatial color and graphic designs remain unclear.MethodsThis paper first discusses the correlation between the characteristics of visual-spatial impairments and environmental factors and then investigates the color preferences of such patients based on the CIE 1976 color system and the Analytic Hierarchy Process (AHP). Subsequently, the paper explores spatial design strategies conducive to spatial orientation from the perspective of adaptability to pathological characteristics, utilizing case study analysis.Results(1) Pathological characteristics of visual-spatial impairments (such as difficulties in spatial orientation and spatial neglect) are related to environmental factors; (2) Emotional attachment factors play a key role in patients’ perception of satisfaction with environmental colors; (3) Color associations have the potential to strengthen spatial memory. Additionally, interface designs with high luminance, low saturation, and clear color differentiation facilitate patients’ recognition of space.DiscussionThis paper posits that spatial interface design is a feasible approach to assist with spatial orientation, and it achieves this through a mediating process that progresses from influencing visual stimuli to cognitive memory and then to behavioral orientation. The article provides insights into the operational feasibility of this method.

Metastatic Melanoma to the Small Bowel and Colon: A Systematic Review of the Global Experience and Institutional Cohort Analysis Detailing a Rare Clinical Entity.

Cutaneous melanoma is among the most common solid tumors to metastasize to the gastrointestinal (GI) tract. Literature summarizing the clinical experience and features of this unique pathology is lacking. A systematic review of the available literature reporting clinically salient features of melanoma metastases to the small and large intestines was conducted. Additionally, we surveyed our institutional experience of surgically treated melanoma metastasis to the small bowel and colon. A descriptive analysis was performed. Kaplan-Meier curves with log-rank tests were used to analyze time-to-event intervals. Univariable and multivariable Cox logistic regression models were generated to identify predictors of survival. Over 100 studies including 1153 patients were included. GI metastases predominantly affected males, were in the small bowel/jejunum, equally presented as solitary and multiple lesions, and were generally not the first site of distant metastatic disease. The median time from primary lesion diagnosis to GI metastasis was 48 months. Analysis of our institutional cohort suggested that survival in patients receiving complete GI-specific surgical resection and immune checkpoint inhibitors (ICIs) was prolonged compared to palliative resection and without ICI therapy. Positive prognostic factors for survival following GI metastasis included fewer GI metastatic lesions, complete resection, and longer duration between primary tumor diagnosis and GI metastasis. GI metastases are a sign of advanced metastatic melanoma. Clinical suspicion of metastatic involvement in patients with a history of melanoma who develop any abdominal symptoms or anemia should remain high. Receipt of complete surgical resection and ICIs may prolong survival in disseminated melanoma.

Temporal dynamics of cardiac remodelling in pressure overload: the key role of visceral adipose tissue

Abstract Background Myocardial fibrosis is a prominent pathological feature of cardiac remodelling in pressure overload. The underlying mechanisms of cardiac remodelling are complex including mechanical, inflammatory and neurohormonal factors. We have recently uncovered a pathological crosstalk between visceral adipose tissue (VAT) and heart in biological aging characterized by profibrotic proteins in both the VAT secretome and the plasma contributing to myocardial interstitial fibrosis. We hypothesize that a model of pressure overload induced by transverse aortic constriction (TAC) is responsible for VAT remodelling and a VAT profibrotic secretome, which in turn worsens cardiac fibrosis and alters cardiac function. Purpose To explore the effect of pressure overload on VAT and identify a crosstalk between heart and VAT. Methods We divided wild-type male mice (5-month-old, n=10/group) into two groups: a visceral Lipectomy group and a Sham group two weeks before a moderate TAC (26G; i.e. gradient between left ventricle and aorta of 30mmHg) or a sham surgery. We sacrificed the mice at 1- and 8-week after TAC. We performed in vivo metabolic tests, echocardiography, and invasive hemodynamics, followed by ex vivo tissue analysis. We then analysed the time-course of the cardiac transcriptomic signature in TAC vs control and the impact of visceral lipectomy in both groups. Results Our results show that TAC induced not only cardiac remodelling affecting the structure and function of the heart, but also VAT fibrosis and inflammation together with activation of adrenergic receptors (Adrb3). VAT became a major source of profibrotic (TGFb and osteopontin) and proinflammatory (TNFa, IL6 and PAI1) factors as early as 1 week after TAC. Interestingly, lipectomy prevented cardiac remodelling and dysfunction. After 1 week of TAC, cardiac transcriptomic profile showed a similar upregulation of profibrotic and prohypertrophic genes in TAC groups in presence or absence of lipectomy. After 8 weeks of TAC, lipectomy prevented the upregulation of those genes and transcriptomic profile of TAC+lipectomy was similar to sham group (Figure). PCR analysis confirmed the lower expression of profibrotic (TGFb, Osteopontin), prohypertrophic (Nppa) and contractility genes (Adr1b) in TAC+Lipectomy vs TAC group after 8 weeks of TAC. Conclusion Our results suggest that VAT is detrimental to cardiac structure and function by releasing a profibrotic and a proinflammatory secretome that aggravates the cardiac remodelling induced by TAC. Conversely, lipectomy prevents the early development of TAC-induced cardiac fibrosis.