Implications For Treatment Research Articles

Coeliac disease: complications and comorbidities.

Coeliac disease is an autoimmune disease characterized by small intestinal villus atrophy and inflammation upon exposure to gluten. It has a global prevalence of approximately 1%. Although the gluten-free diet can be an effective treatment, this diet is burdensome with practical difficulties and frequent inadvertent gluten exposure. Moreover, there are a variety of potential complications and comorbidities of coeliac disease that might be related to malabsorption and/or chronic immune activation. Overall, individuals with coeliac disease have increased mortality compared with the general population, underscoring the severity of this common disease. Comorbidities and complications that have been associated with coeliac disease include poor growth, reproductive complications, kidney and liver diseases, respiratory disease (such as pneumonia) and infections (including sepsis). Furthermore, coeliac disease has been linked to other autoimmune disease and psychiatric disease, as well as certain cancers. Data suggest that mucosal healing on a gluten-free diet might protect against some, but not all, of these complications. In this Review, we present absolute and relative risks of coeliac-associated disorders. We discuss underlying mechanisms, the role of the gluten-free diet and mucosal healing, as well as implications for follow-up and non-dietary treatment of coeliac disease.

Parental Perceptions of Access to and Utilization of Services for Autistic Children in African American Families: An Exploratory Study.

Autism spectrum disorder (ASD) occurs within all racial, ethnic, and demographic pediatric groups. However, Black children with ASD are diagnosed at later stages of their development, and as a result may not receive or may age out of early intervention services, and demonstrate poorer long-term outcomes, across a range of factors. African American parent's perceptions regarding access to and utilization of healthcare services for their autistic children vary. Research examining autism spectrum disorder and parental perceptions of service utilization among African American (AA) families is limited. This qualitative study aimed to understand the challenges African American parents face when initiating healthcare services for their autistic children. Eleven AA mothers of autistic children participated in individual semi-structured interviews. Six themes related to pediatric treatment needs, interactions with providers, and parents' roles as experts and advocates were generated. Implications for pediatric treatment needs of autistic children and areas of opportunity for providers working with AA autistic children are discussed.

Molecular and functional profiling unravels targetable vulnerabilities in colorectal cancer.

Colorectal cancer (CRC) patients with microsatellite-stable (MSS) tumors are mostly treated with chemotherapy. Clinical benefits of targeted therapies depend on mutational states and tumor location. Many tumors carry mutations in KRAS proto-oncogene, GTPase (KRAS) or B-Raf proto-oncogene, serine/threonine kinase (BRAF), rendering them more resistant to therapies. We performed whole-exome sequencing and RNA-Sequencing of 28 tumors of the Athens Comprehensive Cancer Center CRC cohort, and molecularly characterized CRC patients based on their microsatellite instability (MSI) status, single-nucleotide variations (SNVs)/copy number alterations (CNAs), and pathway/transcription factor activities at the individual patient level. Variants were classified using a computational score for integrative cancer variant annotation and prioritization. Complementing this with public multi-omics datasets, we identified activation of transforming growth factor beta (TGFβ) signaling to be more strongly activated in MSS patients, whereas Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and mitogen-activated protein kinase (MAPK) molecular cascades were activated specifically in MSI tumors. We unraveled mechanisms consistently perturbed in the transcriptional and mutational circuits and identified Runt-related transcription factors (RUNX transcription factors) as putative biomarkers in CRC, given their role in the regulation of pathways involved in tumor progression and immune evasion. Assessing the immunogenicity of CRC tumors in the context of RAS/RAF mutations and MSI/MSS status revealed a critical impact that KRAS mutations have on immunogenicity, particularly in the MSS patient subgroup, with implications for diagnosis and treatment.

Comprehensive analysis of vaginal microbiota in Chinese women with genital tuberculosis: implications for diagnosis and treatment

BackgroundTuberculosis remains an infectious disease of global concern, with potential impacts on respiratory and intestinal microbiota owing to prolonged broad-spectrum antibiotic therapy. Despite its potential to cause infertility, the vaginal microbiota of women with genital tuberculosis remains poorly understood. We comprehensively analyzed the vaginal microbiota in Chinese women with genital tuberculosis.ResultsWe recruited women with pelvic (n = 28), endometrial (n = 16), and pulmonary (n = 12) tuberculosis as the research group, and healthy women (n = 11) as the control group. Vaginal discharges were collected for metagenomic analysis of its microbiota. The alpha diversity of the vaginal microbiota in women with genital tuberculosis was slightly higher than that in healthy women, though the difference was not statistically significant (P = 0.23). Similarly, no significant differences in alpha diversity were observed between women with genital and pulmonary tuberculosis (P = 0.82) or between those with pelvic and endometrial tuberculosis (P = 0.82). Notably, the lowest alpha diversity was recorded six months to one year after initiating anti-tuberculosis treatment, with this decline being statistically significant (P = 0.023). The dominance of Lactobacillus iners in the vaginal microbiota was more common in women with genital tuberculosis than that of Lactobacillus crispatus. Furthermore, the abundance of short-chain fatty acid -producing anaerobes, such as Actinomycetes, Streptococcus, and Finegoldia, were significantly increased. Short-chain fatty acid precursor pathways, including the ko03010 ribosome pathway, ko00970 aminoacyl-tRNA synthesis, ko00230 purine metabolism, ko00240 pyrimidine metabolism, and ko00010 glycolysis gluconeogenesis pathway, were significantly upregulated in women with endometrial tuberculosis.ConclusionsExtrapulmonary tuberculosis, particularly genital tuberculosis and its associated vaginal dysbiosis impacts female fecundity. Vaginal dysbiosis is more pronounced when M. tuberculosis invades the endometrium. Given the effect of antibiotics on vaginal flora, probiotic combined interventions could be used as a future research direction.Clinical trial numberNot applicable.

Subtype-Specific Patterns of Tumor Purity and Mutation Load Suggest Treatment Implications

Subtype-Specific Patterns of Tumor Purity and Mutation Load Suggest Treatment Implications

Pathogenic pemphigus autoantibodies against desmosomal cadherins target the intracellular domain of desmocollin 3: implications for pemphigus pathogenesis, diagnosis and treatment!

Pathogenic pemphigus autoantibodies against desmosomal cadherins target the intracellular domain of desmocollin 3: implications for pemphigus pathogenesis, diagnosis and treatment!

Piezoelectric biosensor with dissipation monitoring enables the analysis of bacterial lytic agent activity

Antibiotic-resistant strains of Staphylococcus aureus pose a significant threat in healthcare, demanding urgent therapeutic solutions. Combining bacteriophages with conventional antibiotics, an innovative approach termed phage-antibiotic synergy, presents a promising treatment avenue. However, to enable new treatment strategies, there is a pressing need for methods to assess their efficacy reliably and rapidly. Here, we introduce a novel approach for real-time monitoring of pathogen lysis dynamics employing the piezoelectric quartz crystal microbalance (QCM) with dissipation (QCM-D) technique. The sensor, a QCM chip modified with the bacterium S. aureus RN4220 ΔtarM, was utilized to monitor the activity of the enzyme lysostaphin and the phage P68 as model lytic agents. Unlike conventional QCM solely measuring resonance frequency changes, our study demonstrates that dissipation monitoring enables differentiation of bacterial growth and lysis caused by cell-attached lytic agents. Compared to reference turbidimetry measurements, our results reveal distinct alterations in the growth curve of the bacteria adhered to the sensor, characterized by a delayed lag phase. Furthermore, the dissipation signal analysis facilitated the precise real-time monitoring of phage-mediated lysis. Finally, the QCM-D biosensor was employed to evaluate the synergistic effect of subinhibitory concentrations of the antibiotic amoxicillin with the bacteriophage P68, enabling monitoring of the lysis of P68-resistant wild-type strain S. aureus RN4220. Our findings suggest that this synergy also impedes the formation of bacterial aggregates, the precursors of biofilm formation. Overall, this method brings new insights into phage-antibiotic synergy, underpinning it as a promising strategy against antibiotic-resistant bacterial strains with broad implications for treatment and prevention.

Determination of Pathogens in Surgical Site Infections in Ankle Fractures and Implications for Empirical Antibiotic Treatment.

Surgical site infections (SSIs) are the most common complication after surgery for ankle fractures. This retrospective study aimed to determine the pathogens cultured in SSI and their antimicrobial susceptibility patterns to provide a recommendation for empirical therapy. Patients who underwent surgical treatment for an ankle fracture were included. Cases were screened for the occurrence of SSI and divided into superficial (short course [total of <2 weeks] of oral antibiotics) and deep SSI (surgical debridement and long course [total of >2 weeks] antibiotics). Culture results, antimicrobial susceptibility patterns, empirical antibiotic regimen, type and timing of culture collection, and treatment strategies were collected from electronic health records. In total, 81 (9%) out of 931 patients developed an SSI (39 (48%) superficial SSI and 42 (52%) deep SSI). The most common pathogens in 16 superficial SSI and 37 deep SSI with positive cultures were Staphylococcus aureus, cultured in 11 (69%) superficial SSI and 23 (62%) deep SSI, and Enterobacter cloacae species, cultured in 5 (31%) superficial SSI and 12 (32%) deep SSI. Higher frequencies of gram-negative bacteria and polymicrobial infections were found in deep SSI. It is recommended to aim for empirical treatment at gram-positive and gram-negative microorganisms in the case of both superficial and deep SSI.Level of Evidence: Prognostic, Level 2: Retrospective.

BRAF V600E and Non-V600E Mutations in RAS Wild-Type Metastatic Colorectal Cancer: Prognostic and Therapeutic Insights from a Nationwide, Multicenter, Observational Study (J-BROS)

Background/Objectives: BRAF mutations occur in 5–10% of metastatic colorectal cancer (mCRC) cases, but their implications for prognosis and optimal treatment remain unclear. Methods: This multicenter, prospective observational study analyzed 377 RAS wild-type cases from 511 patients across 32 centers, using PCR-based methods. Results: BRAF mutations were identified in 21% (79/377) of cases, predominantly V600E (89.9%) with a minority of non-V600E (10.1%). Microsatellite instability (MSI) testing revealed MSI-high in 11.3%, exclusively among V600E cases. V600E mutations were linked to right-sided tumors, poor differentiation, and elevated CA19-9 levels. Median survival was significantly lower in V600E cases compared to BRAF wild-type (12.4 vs. 37.5 months, HR 3.25, p &lt; 0.001) and marginally lower non-V600E cases (12.4 vs. 34.7 months, HR 0.61, p = 0.057). Chemotherapy regimens (doublet vs. triplet) and targeted treatments (bevacizumab vs. anti-EGFR) showed no significant survival differences in V600E patients. Similarly, RAS/BRAF wild-type patients had comparable survival with bevacizumab versus anti-EGFR, even for left-sided tumors. Conclusions: These findings highlight distinct clinical and prognostic profiles for BRAF V600E and non-V600E mutations, while treatment choice appears to have limited impact on survival in these subgroups or RAS/BRAF wild-type cases.

Potential value of novel multiparametric MRI radiomics for preoperative prediction of microsatellite instability and Ki-67 expression in endometrial cancer

Exploring the potential of advanced artificial intelligence technology in predicting microsatellite instability (MSI) and Ki-67 expression of endometrial cancer (EC) is highly significant. This study aimed to develop a novel hybrid radiomics approach integrating multiparametric magnetic resonance imaging (MRI), deep learning, and multichannel image analysis for predicting MSI and Ki-67 status. A retrospective study included 156 EC patients who were subsequently categorized into MSI and Ki-67 groups. The hybrid radiomics model (HMRadSum) was developed by extracting quantitative imaging features and deep learning features from multiparametric MRI using emerging attention mechanism. Tumor markers were subsequently predicted utilizing an XGBoost classifier. Model performance and interpretability were evaluated using standard classification metrics, Gradient-weighted Class Activation Mapping (Grad-CAM), and SHapley Additive exPlanations (SHAP) techniques. For the MSI prediction task, the HMRadSum model achieved area-under-curve (AUC) value of 0.945 (95% CI 0.862-1.000) and accuracy of 0.889. For the Ki-67 prediction task, the AUC and accuracy of HMRadSum model was 0.888 (95% CI 0.743-1.000) and 0.810. This hybrid radiomics model effectively extracted features associated with EC gene expression, providing potential clinical implications for personalized diagnosis, treatment, and treatment strategy optimization.

CDK8 as a therapeutic target for overall survival prediction in cervical squamous cell carcinoma (CESC).

Cyclin-dependent kinase 8 (CDK8) is a paracrine transcriptional regulator involved in regulating cellular stress response, growth, and neurological functions, in conjunction with mediator complex subunits 12 (MED12), MED13, and cyclin C.Cyclin-dependent kinase 8 (CDK8) is a paracrine transcriptional regulator involved in regulating cellular stress response, growth and neurological functions，in conjunction with mediator complex subunit 12 (MED12), MED13 and cyclin C. Studying the relationship between CDK8 and cervical squamous cell carcinoma (CESC) has significant clinical implications in diagnosis, treatment, and prognosis. We analyzed the relationship between CDK8 and poor prognosis of CESC. The results indicated that CDK8 was overexpressed in CESC, and the survival rate of patients in the CDK8 hypermethylation group was higher than that in the CDK8 hypomethylation group. In addition, CDK8 was associated with immune cell infiltration in tumor tissues. Overall, these findings provide more evidences for the relationship between CDK8 and patient's overall survival, which could provide insights into clinical diagnosis and prognosis prediction for CESC.

Nanomaterials-Induced Pyroptosis: Advancing Novel Therapeutic Pathways in Nanomedicine.

Pyroptosis, a form of programmed cell death characterized by cell lysis and inflammation, has significant implications for disease treatment. Nanomaterials (NMs), with their unique physicochemical properties, can precisely modulate pyroptosis, offering novel and intelligent therapeutic strategies for cancer, infectious diseases, and chronic inflammatory conditions with targeted activation and reduced systemic toxicity. This review explores the mechanisms by which NMs regulate pyroptosis, comparing molecular and NM inducers, and examines the role of intrinsic properties such as size, shape, surface charge, and chemical composition in these processes. It also discusses the balance between the beneficial and adverse effects of NM-induced pyroptosis, highlighting targeted delivery systems, surface modifications, and controlled activation as strategies to enhance therapeutic efficacy and intelligence while minimizing toxicity. Notably, mRNA-based nanomedicine can be precisely and intelligently designed to activate pyroptosis, achieving desired therapeutic outcomes tailored to the evolving microenvironment of diseases. By understanding these interactions, the therapeutic potential of NMs can be harnessed to develop innovative treatments and manage pyroptosis-associated diseases safely, effectively, and intelligently. This review also highlights their transformative potential in clinical applications.

Cardiovascular disease and bipolar disorder: A review of pathophysiology and treatment implications.

Despite the well-established increased risk of cardiovascular mortality in individuals with bipolar disorder (BD), prevention and treatment of cardiovascular risk factors and diseases have been largely overlooked in this population. This manuscript reviews the pathophysiological basis of the connection between BD and cardiovascular diseases, highlighting their shared mechanisms, reciprocal interactions, and relevant prevention and treatment strategies. For this narrative review, a search was carried out on PubMed using the keywords bipolar disorder, cardiovascular diseases, and cardiovascular risk factors. The increased frequency of cardiovascular morbidity in BD can be attributed to overlapping biological and psychosocial mechanisms. These mechanisms are complex and involve both direct effects of BD and indirect effects mediated by lifestyle and pharmacological factors. Cardiovascular diseases also significantly exacerbate the clinical course of BD and increase morbidity and healthcare costs; thus, their effective management can improve psychiatric outcomes and vice versa. However, patients with BD frequently encounter healthcare barriers. Awareness initiatives and research on integrated care are needed to determine the best strategies for improving cardiovascular and psychiatric outcomes in individuals with BD.

Global landscape of Vibrio parahaemolyticus research: a bibliometric analysis.

Vibrio parahaemolyticus poses a notable threat to marine ecosystems and can cause infections and disease outbreaks in seafood species, which can affect humans upon consumption. The global impacts of such infections and outbreaks on human and animal health led to a growing number of studies from various countries discussing the prevention, control, treatment, and overall implications of V. parahaemolyticus. Hence, this study aims to retrieve relevant studies on V. parahaemolyticus using a bibliometric analysis to understand current research status, trends, and hotspots regarding this bacteria. Relevant literature was searched across the Scopus database, and the data were subsequently analyzed using Biblioshiny software. In addition, a manual examination was conducted to identify the hosts of V. parahaemolyticus and diseases caused by the bacteria. Overall, 7,096 records were obtained from Scopus from 1963 to 2023. A bibliometric analysis identified 17,220 authors, with China emerging as the global leader. The analysis also highlighted significant keywords such as "Vibrio parahaemolyticus," "Litopenaeus vannamei," and "innate immunity," suggesting a focus on the impact of V. parahaemolyticus on L. vannamei, specifically emphasizing the shrimp's innate immune responses. Host-disease interaction network also uncovered 53 interactions between hosts and diseases involving L. vannamei or Penaeus vannamei as the primary host, with acute hepatopancreas necrosis disease (AHPND) emerging as the most prevalent among them. This study can enhance our understanding of infections caused by V. parahaemolyticus and contribute to the development of effective strategies for their prevention and management.

Coping is a moderator of relationships between cognitive fatigue and cognitive variability in multiple sclerosis.

Mean levels of cognitive functioning typically do not show an association with self-reported cognitive fatigue in persons with multiple sclerosis (PwMS), but some studies indicate that cognitive variability has an association with cognitive fatigue. Additionally, coping has been shown to be a powerful moderator of some outcomes in multiple sclerosis (MS). To date, however, coping has not been considered as a possible moderator of the relationship between cognitive fatigue and cognitive variability in MS. The current study examined this relationship. We examined 52 PwMS. All participants were administered the Fatigue Impact Scale, the Coping Orientation to Problems Experienced Questionnaire, and cognitive tests. Indices of variability for memory and attention/executive functioning tests were used as outcome variables. Avoidant coping, active coping, and composite coping indices were used as moderators. The interaction analyses for the avoidant coping and composite coping indices were significant and accounted for 8 and 11% of the attention/executive functioning variability outcome, respectively. The interactions revealed that at low levels of cognitive fatigue, attention/executive functioning variability was comparable between the low and high avoidant and composite coping groups. However, at high levels of cognitive fatigue, PwMS using lower levels of avoidant coping (less maladaptive coping) showed less variable attention/executive functioning scores compared with those using higher levels of avoidant coping. We found a similar pattern for the composite coping groups. At high levels of cognitive fatigue, PwMS using adaptive coping showed less attention/executive functioning variability. These findings should be considered in the context of treatment implications.

Zebrafish modeling of atypical PML-RARA isoform from acute promyelocytic leukemia patient and its implications for clinical treatment.

Acute promyelocytic leukemia (APL) is driven by the specific fusion gene PML-RARA produced by chromosomal translocation. Three classic isoforms, L, V, and S, are found in more than 95% of APL patients. However, atypical PML-RARA isoforms are usually associated with uncertain disease progression and treatment prognosis. Recently, we found a novel PML-RARA isoform (named PA) in a patient with atypical clinical characteristics of APL. In order to provide valuable insights for clinical treatment, we constructed the novel PML-RARA isoform zebrafish model for all-trans retinoic acid (ATRA) treatment experiments and comparison with classical isoforms. We found that the effect of PA PML-RARA on the expression of neutrophil-related genes was comparable with classical isoforms and ATRA treatment worked successfully in the zebrafish model. Sequence and structure analysis of the PA protein confirmed its similarity to classical isoforms and the fusion site of PA PML-RARA did not affect the ATRA binding site. As expected, the patient achieved complete remission within two months of treatment with ATRA in combination with arsenic trioxide (ATO) and had a favorable prognosis during the three-year follow-up. Our study highlights the accuracy and efficacy of the PML-RARA zebrafish model in combination with protein structure prediction in support of clinical treatment strategies.

Characterization of Five Natural Anthraquinone Compounds as Potent Inhibitors against CYP1B1: Implications for Cancer Treatment.

Human cytochrome P450 1B1 (CYP1B1) is an extrahepatic enzyme that is overexpressed in many tumors and is associated with tumor development and acquired resistance. Few studies have reported that anthraquinone compounds have inhibitory activity against the CYP1B1 enzyme. Cassiae semen (Leguminosae) is a well-known traditional Chinese medicine containing more than 70 compounds. The crude extracts and pure compounds of Cassiae semen have been widely used in preclinical and clinical practice for their beneficial effects, such as neuroprotective, hepatoprotective, antimicrobial, antioxidant, and hypotensive effects. Aloe-emodin, chrysophanol, obtusifolin, aurantio-obtusin, and rhein are important active natural anthraquinones in Cassiae semen. Aloe-emodin, chrysophanol, obtusifolin, aurantio-obtusin, and rhein have a wide range of pharmacological activities and have been found to have good anti-tumor and antioxidant effects. However, the underlying mechanisms of these pharmacological activities remain poorly understood. This study aimed to investigate the inhibitory effects of five natural anthraquinones on the activity of CYP1B1 and to analyze the structure- activity relationship of these compounds. In this study, 7-ethoxyresorufin O-deethylation (EROD) was used as the fluorescent substrate of CYP1B1 to investigate the inhibition effect, and molecular docking was performed to further determine the structural-activity relationship of the compound molecules. We found that aloe-emodin and chrysophanol had strong inhibitory effects on CYP1B1 with IC50 values of 0.28 and 0.34μM, respectively, while obtusifolin and aurantio-obtusin had IC50 values of 0.77μM and 9.11μM, respectively. The structural activity analysis showed that the inhibition strength was related to the position of the hydroxyl group substitution and the number of methoxy group substitutions. Rhein containing one carboxyl group showed the weakest inhibition of 23.72μM. The inhibition kinetics showed that all five compounds belonged to the non-competitive inhibition model. The inhibition kinetics revealed that all five compounds exhibited the non-competitive inhibition model. The present study provided a comprehensive analysis of the inhibitory effects of five natural anthraquinones, namely aloe-emodin, chrysophanol, obtusifolin, aurantio-obtusin and rhein, on CYP1B1 activity, and elucidated the structure-activity relationship. Molecular docking simulations further revealed the specific amino acid residues within the active site of CYP1B1, where these compounds exerted their actions. These findings offer novel insights into investigating the potential antitumor properties of natural anthraquinones.

Characterization of NAT, GST, and CYP2E1 Genetic Variation in Sub-Saharan African Populations: Implications for Treatment of Tuberculosis and Other Diseases.

Tuberculosis (TB) is a major health burden in Africa. Although TB is treatable, anti-TB drugs are associated with adverse drug reactions (ADRs), which are partly attributed to pharmacogenetic variation. The distribution of star alleles (haplotypes) influencing anti-TB drug metabolism is unknown in many African populations. This presents challenges in implementing genotype-guided therapy in Africa to decrease the occurrence of ADRs and enhance the efficacy of anti-TB drugs. In this study, we used StellarPGx to call variants and star alleles in NAT1, NAT2, GSTM1, GSTT1, GSTP1, and CYP2E1, from 1079 high-depth African whole genomes. We present the distribution of common, rare, and potential novel star alleles across various Sub-Saharan African (SSA) populations, in comparison with other global populations. NAT1*10 (53.6%), GSTT1*0 (65%), GSTM1*0 (48%), and NAT2*5 (17.5%) were among the predominant functionally relevant star alleles. Additionally, we predicted varying phenotype distributions for NAT1 and NAT2 (acetylation) and the glutathione-S-transferase (GST) enzymes (detoxification activity) between SSA and other global populations. Forty-seven potentially novel haplotypes were identified computationally across the genes. This study provides insight into the distribution of key variants and star alleles potentially relevant to anti-TB drug metabolism and other drugs prescribed across various African populations. The high number of potentially novel star alleles exemplifies the need for pharmacogenomics studies in the African context. Overall, our study provides a foundation for functional pharmacogenetic studies and potential implementation of pharmacogenetic testing in Africa to reduce the risk of ADRs related to treatment of TB and other diseases.

Oronasal mucosal melanoma is defined by two transcriptional subtypes in humans and dogs with implications for diagnosis and therapy.

Mucosal melanoma is a rare melanoma subtype associated with a poor prognosis and limited existing therapeutic interventions, in part due to a lack of actionable targets and translational animal models for preclinical trials. Comprehensive data on this tumour type are scarce, and existing data often overlooks the importance of the anatomical site of origin. We evaluated human and canine oronasal mucosal melanoma (OMM) to determine whether the common canine disease could inform the rare human equivalent. Using a human and canine primary OMM cohort of treatment-naive archival tissue, alongside clinicopathological data, we obtained transcriptomic, immunohistochemical, and microbiome data from both species. We defined the transcriptomic landscape in both species and linked our findings to immunohistochemical, microbiome, and clinical data. Human and dog OMM stratified into two distinctive transcriptional groups, which we defined using a species-independent 41-gene signature. These two subgroups are termed CTLA4-high and MET-high and indicate actionable targets for OMM patients. To guide clinical decision-making, we developed immunohistochemical diagnostic tools that distinguish between transcriptomic subgroups. We found that OMM had conserved transcriptomic subtypes and biological similarity between human and canine OMM, with significant implications for patient classification, treatment, and clinical trial design. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Implications of a new clinical classification of acute myocardial infarction.

The diagnostic criteria for type 2 myocardial infarction identify a heterogenous group of patients with variable outcomes and no clear treatment implications. We aimed to determine the implications of a new clinical classification for myocardial infarction with more objective diagnostic criteria using cardiac imaging. In a prospective cohort study, patients with type 2 myocardial infarction underwent coronary angiography and cardiac magnetic resonance imaging or echocardiography. The new classification was applied to identify (a) spontaneous myocardial infarction due to acute coronary pathology, (b) secondary myocardial infarction precipitated by acute illness in the presence of obstructive coronary artery disease, a new regional wall motion abnormality or infarct pattern scarring, and (c) no myocardial infarction in the absence of obstructive disease or new myocardial abnormality. In 100 patients (65 years, 43% women) with type 2 myocardial infarction, the new classification identified 25 and 31 patients with spontaneous and secondary myocardial infarction, respectively, and 44 without myocardial infarction. Compared to patients without myocardial infarction, those with secondary myocardial infarction were older, had more risk factors, and higher troponin concentrations (P<0.05 for all). During a median follow up of 4.4 years, death, myocardial infarction or heart failure hospitalization was more common in secondary myocardial infarction compared to those without myocardial infarction (55% [17/31] versus 16% [7/44], P<0.001). A new clinical classification of myocardial infarction informed by cardiac imaging would reduce the diagnosis of myocardial infarction in acute illness and identify those patients at highest risk who are most likely to benefit from treatment. https://clinicaltrials.gov/ct2/show/NCT03338504.