Diagnostic Strategies Research Articles

The evolving process of ferroptosis in thyroid cancer: Novel mechanisms and opportunities.

Thyroid cancer (TC) is a prevalent endocrine malignancy, with a significant increase in incidence worldwide. Ferroptosis is a novel form of programmed cell death, primarily caused by iron overload and reactive oxygen species (ROS)-dependent accumulation of lipid peroxides. The main manifestations of cellular ferroptosis are rupture of the outer membrane, crumpling of the mitochondria and shrinkage or disappearance of the mitochondrial cristae, thus leading to cell death. Ferroptosis is an important phenomenon in tumour progression, with crosstalk with tumour-associated signalling pathways profoundly affecting tumour progression, immune effects and treatment outcomes. The functions and mechanisms of ferroptosis in TC have also attracted increasing attention, mainly in terms of influencing tumour proliferation, invasion, migration, immune response, therapeutic susceptibility and genetic susceptibility. However, at present, the tumour biology of the morphological, biological and mechanism pathways of ferroptosis is much less deep in TC than in other malignancies. Hence, in this review, we highlighted the emerging role of ferroptosis in TC progression, including the novel mechanisms and potential opportunities for diagnosis and treatment, as well as discussed the limitations and prospects. Ferroptosis-based diagnostic and therapeutic strategies can potentially provide complementary management of TCs.

Pains Revisited.

The management of pain patients has not evolved as rapidly as envisioned when IASP was founded almost 50 years ago. We sought to identify factors that could contribute to this situation, with a focus on concepts of pain and the education of pain physicians. Relevant literature describing new strategies for diagnosing and managing patients with high-impact chronic pain was reviewed. It appears that the acute-chronic dichotomy has outlived its usefulness and pains should be identified as of peripheral origin or due to central processing errors. Pains of peripheral origin and those of central processing errors require different diagnostic and therapeutic strategies. Peripheral treatments and opioids are not effective for central pains. When the cause of the pain lies in the central nervous system, a more centrally focused approach is needed to minimize wasteful pursuit of peripheral causes. The education and training of pain physicians should reflect the skills needed to address these 2 very different clinical problems.

Energy-Efficient Sleep Apnea Detection Using a Hyperdimensional Computing Framework Based on Wearable Bracelet Photoplethysmography.

Sleep apnea syndrome (SAS) is a common sleep disorder, which has been shown to be an important contributor to major neurocognitive and cardiovascular sequelae. Considering current diagnostic strategies are limited with bulky medical devices and high examination expenses, a large number of cases go undiagnosed. To enable large-scale screening for SAS, wearable photoplethysmography (PPG) technologies have been used as an early detection tool. However, existing algorithms are energy-intensive and require large amounts of memory resources, which are believed to be the major drawbacks for further promotion of wearable devices for SAS detection. In this paper, an energy-efficient method of SAS detection based on hyperdimensional computing (HDC) is proposed. Inspired by the phenomenon of chunking in cognitive psychology as a memory mechanism for improving working memory efficiency, we proposed a one-dimensional block local binary pattern (1D-BlockLBP) encoding scheme combined with HDC to preserve dominant dynamical and temporal characteristics of pulse rate signals from wearable PPG devices. Our method achieved 70.17 % accuracy in sleep apnea segment detection, which is comparable with traditional machine learning methods. Additionally, our method achieves up to 67× lower memory footprint, 68× latency reduction, and 93× energy saving on the ARM Cortex-M4 processor. The simplicity of hypervector operations in HDC and the novel 1D-BlockLBP encoding effectively preserve pulse rate signal characteristics with high computational efficiency. This work provides a scalable solution for long-term home-based monitoring of sleep apnea, enhancing the feasibility of consistent patient care.

Genetic Heterogeneity in Cellular Angiofibromas.

Cellular angiofibroma, a rare benign mesenchymal neoplasm, is classified within the 13q/RB1 family of tumors due to morphological, immunohistochemical, and genetic similarities with spindle cell lipoma. Here, genetic data reveal pathogenetic heterogeneity in cellular angiofibroma. Three cellular angiofibromas were studied using G-banding/Karyotyping, array comparative genomic hybridization, RNA sequencing, and direct cycling sequencing. The first tumor carried a del(13)(q12) together with heterozygous loss and minimal expression of the RB1 gene. Tumors two and three displayed chromosome 8 abnormalities associated with chimeras of the pleomorphic adenoma gene 1 (PLAG1). In tumor 2, the cathepsin B (CTSB) fused to PLAG1 (CTSB::PLAG1) while in tumor 3, the mir-99a-let-7c cluster host gene (MIR99AHG) fused to PLAG1 (MIR99AHG::PLAG1), both leading to elevated expression of PLAG1 and insulin growth factor 2. This study uncovers two genetic pathways contributing to the pathogenetic heterogeneity within cellular angiofibromas. The first aligns with the 13q/RB1 family of tumors and the second involves PLAG1-chimeras. These findings highlight the diverse genetic landscape of cellular angiofibromas, providing insights into potential diagnostic strategies.

A seed or soil problem in early endometriosis: stromal cell origin drives cellular invasion and coupling over mesothelial cell origin

To study the role of the mesothelial cells in early endometriosis lesion formation by assessing in vitro cell to cell communication and invasion of endometrial cells across a mesothelial cell monolayer, with both cell types derived from both endometriosis and control patients. Laboratory based experimental study SETTING: University hospital and laboratory PATIENT(S): Consenting reproductive aged women who underwent laparoscopy for gynecologic reasons and were confirmed to either have endometriosis with pathology tissue diagnosis (n=8) or no endometriosis (n=8) at the time of surgery INTERVENTION: Primary stromal cells cultured from endometrial pipelle biopsies and primary mesothelial cells cultured from peritoneal explants were utilized in trans-mesothelial invasion assays and gap junction coupling assays. Comparison of potential for lesion formation, using in vitro models, of both primary endometrial and mesothelial cells from endometriosis and control patients, establishing the former as the primary disease driver. When comparing mesothelial cells from control patients to mesothelial cells from endometriosis patients, there was no significant difference in the amount of stromal cell invasion across either barrier. In contrast, when comparing stromal cell origin, the amount of invasion by endometriosis stromal cells was greater than control stromal cells regardless of whether the mesothelial cell monolayer was derived from disease or control patients. Additionally, primary mesothelial cells induced more gap junction coupling, a requirement for invasion, in stromal cells from endometriosis than control patients, again independent of mesothelial origin. The notable exception was mesothelial cells derived from endometriotic lesion affected areas that showed depressed ability to support invasion. While both endometrial and mesothelial cells need to function for establishment of endometriosis lesions, the endometrium seems to be the key player, serving as an ideal target for diagnostic strategies and therapeutic intervention. This notion is consistent with prior studies, however we are the first to directly test both primary mesothelial and endometrial cells from endometriosis and control patients to compare propensities for mesothelial invasion.

Predictive signature of murine and human host response to typical and atypical pneumonia

BackgroundPneumonia due to typical bacterial, atypical bacterial and viral pathogens can be difficult to clinically differentiate. Host response-based diagnostics are emerging as a complementary diagnostic strategy to pathogen detection.MethodsWe used...

The Australasian Registry for Severe Cutaneous Adverse Reactions (AUS-SCAR) – Providing a roadmap for closing the diagnostic, patient, and healthcare gaps for a group of rare drug eruptions

BackgroundSevere cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR. MethodsProspective multi-center registry of SCAR in Australian adult and adolescents, with planned regional expansion. The registry collects externally verified phenotypic data drug causality, therapeutics and long-term patient outcomes. In addition, biorepository specimens and DNA are collected at participating sites. Resultswe report on the first 100 patients enrolled in the AUS-SCAR database. DRESS (50%) is the most predominant phenotype followed by SJS/TEN (39%) and AGEP (10%), with median age of 52 years old (IQR 37.5, 66) with 1:1 male-to-female ratio. The median latency for all implicated drugs is highly variable but similar for DRESS (median 15 days IQR 5,25) and SJS/TEN (median 21 days, IQR 7,27), while lowest for AGEP (median 2.5 days, IQR 1,8). Antibiotics (54.5%) are more commonly listed as primary implicated drug compare with non-antibiotics agent (45.5%). Mortality rate at 90 days was highest in SJS/TEN at 23.1%, followed by DRESS (4%) and AGEP (0%). ConclusionIn the first prospective national phenotypic and biorepository of SCAR in the southern hemisphere we demonstrate notable differences to other reported registries; including DRESS-predominant phenotype, varied antibiotic causality and low overall mortality rate. This study also highlights the lack of standardised preventative pharmacogenomic measures and in vitro/in vivo diagnostic strategies to ascertain drug causality. Trial registrationANZCTR ACTRN12619000241134. Registered 19 February 2019.

Integrating myocardial metabolic imaging and stress myocardial contrast echocardiography to improve the diagnosis of coronary microvascular diseases in rabbits.

Persistent challenges associated with misdiagnosis and underdiagnosis of coronary microvascular disease (CMVD) necessitate the exploration of noninvasive imaging techniques to enhance diagnostic accuracy. Therefore, we aimed to integrate multimodal imaging approaches to achieve a higher diagnostic rate for CMVD using high-quality myocardial metabolism imaging (MMI) and myocardial contrast echocardiography (MCE). This combination diagnostic strategy may help address the urgent need for improved CMVD diagnosis. In this study, we established five distinct pretreatment groups, each consisting of nine male rabbit: a fasted group, a nonfasted group, a sugar load group, an acipimox group, and a combination group of nonfasted rabbits administered insulin. Moreover, positron emission tomography-computed tomography (PET/CT) scan windows were established at 30-, 60-, and 90-minute intervals. We developed 10 CMVD models and conducted a diagnosis of CMVD through an integrated analysis of MMI and MCE, including image acquisition and processing. For each heart segment, we calculated the standardized uptake value (SUV) based on body weight (SUVbw), as well as certain ratios of SUV including SUV of the heart (SUVheart) to that of the liver (SUVliver) and SUVheart to SUV of the lung (SUVlung). Additionally, we obtained three coronary SUVbw uptake values. To clarify the relationship between SUVbw uptake values and echocardiographic parameters of the myocardial contrast agent more thoroughly, we conducted a comprehensive analysis across different pretreatment protocols. Receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic accuracy of each parameter in the context of CMVD. In the context of MMI, the nonfasted-plus-insulin group, as observed during the 60-minute examination, exhibited a noteworthy total 18F-fluorodeoxyglucose (18F-FDG) uptake of 47.44±6.53 g/mL, which was found to be statistically different from the other groups. To ascertain the reliability of the results, two double-blind investigators independently assessed the data and achieved a good level of agreement, according to the intraclass correlation coefficient (ICC) (0.957). The SUVbw of the nonfasted-plus-insulin group exhibited a moderate correlation with the microvascular blood flow reserve (MBFR) parameters derived from the MCE examination, as evidenced by a r value of 0.686. For the diagnosis of CMVD disease, the diagnostic accuracy of the combined diagnostic method [area under the curve (AUC) =0.789; 95% confidence interval (CI): 0.705-0.873] was significantly higher than that of the MBFR (AUC =0.697; 95% CI: 0.597-0.797) and SUVbw (AUC =0.715; 95% CI: 0.622-0.807) methods (P<0.05). Our study demonstrated the feasibility of a simple premedication approach involving free feeding and intravenous insulin in producing high-quality gated heart 18F-FDG PET/CT images in adult male New Zealand white rabbits. This technique holds considerable potential for ischemic heart disease research in rabbits and can enhance CMVD diagnosis via the comprehensive assessment of myocardial metabolism and perfusion.

Peripheral lymphadenopathy of unknown origin in adults: a diagnostic approach emphasizing the malignancy hypothesis.

The term lymphadenopathy refers to an abnormality in size, consistency or morphological aspect of one or several lymph nodes. Although lymphadenopathies are commonly observed in everyday clinical practice, the difficulty of differentiating benign and malignant disease may delay therapeutic approaches. The present review aims to update diagnostic algorithms in different clinical situations based on the currently available literature. A literature review was performed to assess current knowledge of and to update the diagnostic approach. A short clinical vignette was used as an example of a typical clinical presentation. This case of metastatic lymphadenopathy with incomplete patient history demonstrates how misleading such lymphadenopathy may be, leading to a delayed diagnosis and even a fatal outcome. Any lymphadenopathy persisting for more than 2 weeks should be considered suspicious and deserves further investigation. Precise clinical examination, meticulous history-taking and a search for associated symptomatology are still cornerstones for diagnosing the origin of the condition. The next diagnostic step depends on the anatomical region and the specific patient's situation. Imaging starts with ultrasound, while computed tomography (CT) and magnetic resonance imaging (MRI) allow assessment of the surrounding structures. If the diagnosis remains uncertain, tissue sampling and histological analyses should be performed. Except for head and neck loco-regional lymphadenopathy, there are no methodical guidelines for persistent lymphadenopathy. The present review clarifies several confusing and complex situations. The accuracy of fine needle aspiration cytology could be increased by using core needle biopsy with immunocytologic and flow cytometric methods. Notably, except in the head and neck area, open biopsy remains the best option when lymphoma is suspected or when inconclusive results of previous fine needle aspiration cytology or core needle biopsy are obtained. The incidence of malignant lymphadenopathy varies with its location and the various diagnostic strategies. In metastatic lymphadenopathy of unknown primary origin, European Society for Medical Oncology (ESMO) guidelines and modern methods like next-generation sequencing (NGS) may help to manage such complex cases.

Difficult Small Bowel Bleeding in Surgical View

Small bowel bleeding (SBB) accounts for 5%-10% of all gastrointestinal bleeding (GIB) cases. Several diagnostic modalities in SBB are performed. However, the small bowel is beyond the reach of these diagnostic modalities. A large amount of bleeding in GIB is a key factor leading to a poor prognosis. Appropriate and prompt diagnostic and treatment strategies are needed. Several diagnostic and management algorithms have been proposed. However, the processing of algorithm is complex and frequent mistakes are happened. Because of surgical aspects and sudden or gradual development of hemodynamic instability in SBB, algorithms considering surgical role and treatment have been published. The intra-operative enteroscopy (IOE) is a gold-standard method for detecting lesions in SBB. The primary goal of IOE is to detect specific bleeding focus in SBB. The determining the resection range is the secondary goal. In most cases in SBB, segmental resection is treatment of choice. However, in bleeding distal duodenum from distal to the ampulla of Vater to Treitz ligament, pancreas preserving distal duodenectomy could be performed. In terminal ileum bleeding, after resection of pathologic bowel, the reconstruction option is ileo-colic anastomosis or end enterostomy. Because of frequently developed postoperative morbidity and mortality, post-operative critical care is perfectly fit for an acute care surgeon’s role. Therefore, in the entire management process, an interprofessional team or multidisciplinary approach is critical for improving the quality of care of SBB and decreasing mistakes.

Posttraumatic osteoarthritis after athletic knee injury: A narrative review of diagnostic imaging strategies.

Intraarticular knee injuries and subsequent posttraumatic arthritis (PTOA) are common in athletes. Unfortunately, PTOA may significantly affect performance and overall function, but this condition remains difficult to characterize. In this review, we provide an overview of imaging modalities used to evaluate PTOA among athletes and physically active individuals following knee injury, with the goal to discuss the strengths and limitations of their application in this population. A literature search was performed to identify clinical studies focusing of knee injuries in athletes and athletic persons, specifically using imaging for diagnosis or monitoring disease progression. A total of 81 articles were identified, and 23 were included for review. Studies on plain radiographs (n = 8) and magnetic resonance imaging (MRI) assessed arthritic burden (n = 13), with MRI able to depict the earliest cartilage changes. Few studies (n = 2) leveraged ultrasound. Challenges persist, particularly regarding standardization and reliability across different radiographic grading systems. Additionally, further research is needed to establish the clinical significance of techniques to assess cartilage composition on MRI, including ultrashort echo-time enhanced T2*, T1rho and T2 imaging. Addressing these challenges through standardized protocols and intensified research efforts will enhance the diagnostic utility of imaging modalities in musculoskeletal medicine and enable high-quality prospective studies.

Recent Advances in the Management of Non-rheumatic Atrial Fibrillation: A Comprehensive Review.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia characterized by irregular atrial electrical activity, posing significant challenges to patient management and healthcare systems worldwide. Non-rheumatic AF, distinct from AF due to rheumatic heart disease, encompasses a spectrum of etiologies, including hypertension, coronary artery disease, and structural heart abnormalities. This review examines the latest advancements in managing non-rheumatic AF, encompassing diagnostic approaches, pharmacological therapies, and innovative non-pharmacological interventions. Diagnostic strategies ranging from traditional electrocardiography to advanced imaging modalities are explored alongside emerging biomarkers and wearable technologies facilitating early detection and management. Pharmacological management options, including novel anticoagulants and rhythm control agents, are evaluated in light of current guidelines and recent clinical trials. Non-pharmacological interventions, such as catheter ablation and device-based therapies, are discussed regarding their evolving techniques and outcomes. Special considerations for diverse patient populations, including elderly individuals and athletes, are addressed, emphasizing personalized approaches to optimize therapeutic outcomes. The review concludes with insights into future directions for AF management, highlighting promising avenues in gene therapy, regenerative medicine, and precision medicine approaches. By synthesizing recent research findings and clinical innovations, this review provides a comprehensive overview of the dynamic landscape of non-rheumatic AF management, offering insights for clinicians, researchers, and healthcare stakeholders.

A three-dimensional valve-on-chip microphysiological system implicates cell cycle progression, cholesterol metabolism and protein homeostasis in early calcific aortic valve disease progression

BackgroundCalcific aortic valve disease (CAVD) is one of the most common forms of valvulopathy, with a 50 % elevated risk of a fatal cardiovascular event, and greater than 15,000 annual deaths in North America alone. The treatment standard is valve replacement as early diagnostic, mitigation, and drug strategies remain underdeveloped. The development of early diagnostic and therapeutic strategies requires the fabrication of effective in vitro valve mimetic models to elucidate early CAVD mechanisms. MethodsIn this study, we developed a multilayered physiologically relevant 3D valve-on-chip (VOC) system that incorporated aortic valve mimetic extracellular matrix (ECM), porcine aortic valve interstitial cell (VIC) and endothelial cell (VEC) co-culture and dynamic mechanical stimuli. Collagen and glycosaminoglycan (GAG) based hydrogels were assembled in a bilayer to mimic healthy or diseased compositions of the native fibrosa and spongiosa. Multiphoton imaging and proteomic analysis of healthy and diseased VOCs were performed. ResultsCollagen-based bilayered hydrogel maintained the phenotype of the VICs. Proteins related to cellular processes like cell cycle progression, cholesterol biosynthesis, and protein homeostasis were found to be significantly altered and correlated with changes in cell metabolism in diseased VOCs. This study suggested that diseased VOCs may represent an early, adaptive disease initiation stage, which was corroborated by human aortic valve proteomic assessment. ConclusionsIn this study, we developed a collagen-based bilayered hydrogel to mimic healthy or diseased compositions of the native fibrosa and spongiosa layers. When the gels were assembled in a VOC with VECs and VICs, the diseased VOCs revealed key insights about the CAVD initiation process. Statement of significanceCalcific aortic valve disease (CAVD) elevates the risk of death due to cardiovascular pathophysiology by 50 %, however, prevention and mitigation strategies are lacking, clinically. Developing tools to assess early disease would significantly aid in the prevention of disease and in the development of therapeutics. Previously, studies have utilized collagen and glycosaminoglycan-based hydrogels for valve cell co-cultures, valve cell co-cultures in dynamic environments, and inorganic polymer-based multilayered hydrogels; however, these approaches have not been combined to make a physiologically relevant model for CAVD studies. We fabricated a bi-layered hydrogel that closely mimics the aortic valve and used it for valve cell co-culture in a dynamic platform to gain mechanistic insights into the CAVD initiation process using proteomic and multiphoton imaging assessment.

Explorative study on the value of hepcidin in predicting iron non-responsiveness in paediatric inflammatory bowel disease.

In a considerable proportion of anaemic children with inflammatory bowel disease (IBD), haemoglobin (Hb) does not normalise after iron therapy. We evaluated the added value of novel iron markers (hepcidin and soluble transferrin receptor [sTfR]) as compared to traditional iron markers (ferritin and transferrin saturation [TSAT]) to determine the best strategy for the prediction of non-responsiveness to iron suppletion. In this secondary analysis of prospectively collected data, we measured iron markers in anaemic children (Hb Z-score < -2.0) with IBD at baseline and one month after the initiation of iron therapy. Non-responsiveness was defined as an increase in Hb Z-score of less than 1 within a month. Logistic regression analysis was used to construct multi-biomarker prognostic models. Of 40 anaemic paediatric IBD patients, sixteen (40%) were non-responsive to iron therapy after one month. Hb Z-score and hepcidin Z-score had the highest predictive ability (area under the ROC curve [AUROC] 0.80) providing sensitivity of 69% and specificity 92%. In a post-hoc analysis we defined hepcidin cut-off values to predict iron non-responsiveness. A diagnostic strategy that involves baseline Hb Z-score and hepcidin Z-score in anaemic children with IBD reliably identifies those who will not respond to iron therapy. Non-response to oral and intravenous iron suppletion therapy is high in paediatric IBD and should be identified early. Prediction models using baseline hepcidin demonstrated higher sensitivity and specificity to predict iron non-response compared to models using baseline traditional iron indicators (ferritin and transferrin saturation). In a post hoc analysis, we defined cut-off values for hepcidin to facilitate the correct timing of iron treatment in young anaemic patients with chronic inflammatory bowel disease.

AlphaFold2 in biomedical research: facilitating the development of diagnostic strategies for disease.

Proteins, as the primary executors of physiological activity, serve as a key factor in disease diagnosis and treatment. Research into their structures, functions, and interactions is essential to better understand disease mechanisms and potential therapies. DeepMind's AlphaFold2, a deep-learning protein structure prediction model, has proven to be remarkably accurate, and it is widely employed in various aspects of diagnostic research, such as the study of disease biomarkers, microorganism pathogenicity, antigen-antibody structures, and missense mutations. Thus, AlphaFold2 serves as an exceptional tool to bridge fundamental protein research with breakthroughs in disease diagnosis, developments in diagnostic strategies, and the design of novel therapeutic approaches and enhancements in precision medicine. This review outlines the architecture, highlights, and limitations of AlphaFold2, placing particular emphasis on its applications within diagnostic research grounded in disciplines such as immunology, biochemistry, molecular biology, and microbiology.

Identification and immune landscape of sarcopenia-related molecular clusters in inflammatory bowel disease by machine learning and integrated bioinformatics

Sarcopenia, a prevalent comorbidity of inflammatory bowel disease (IBD), is characterized by diminished skeletal muscle mass and strength. Nevertheless, the underlying interconnected mechanisms remain elusive. This study identified distinct expression patterns of sarcopenia-associated genes (SRGs) across individuals with IBD and in samples of normal tissue. By analyzing SRG expression profiles, we effectively segregated 541 IBD samples into three distinct clusters, each marked by its unique immune landscape. To unravel the transcriptional disruptions underlying these clusters, the Weighted Gene Co-expression Network Analysis (WGCNA) algorithm was employed to spotlight key genes linked to each cluster. A diagnostic model based on four key genes (TIMP1, PLAU, PHLDA1, TGFBI) was established using Random Forest and LASSO (least absolute shrinkage and selection operator) algorithms, and validated with the GSE179285 dataset. Moreover, the GSE112366 dataset facilitated the exploration of gene expression dynamics within the ileum mucosa of UC patients pre- and post-Ustekinumab treatment. Additionally, insights into the intricate relationship between immune cells and these pivotal genes were gleaned from the single-cell RNA dataset GSE162335. In conclusion, our findings collectively underscored the pivotal role of sarcopenia-related genes in the pathogenesis of IBD. Their potential as robust biomarkers for future diagnostic and therapeutic strategies is particularly promising, opening avenues for a deeper understanding and improved management of these interconnected conditions.

Antibody-mediated rejection in post-liver transplant clinical care: Are we there yet for timely diagnosis and treatment?

With improvements in medical management and surgical technique in the field of solid organ transplantation, many historically prominent causes of liver allograft injury have been ameliorated or, in the case of Hepatitis C virus, eliminated altogether. In this transformed clinical landscape, antibody-mediated rejection (AMR) has emerged as a defining barrier to maintenance of long-term liver allograft function. The liver's unique anatomy, high regenerative capacity, and tolerogenic immunological environment tend to mitigate the severest AMR manifestations. Consequently, the clinical importance of AMR in the liver has been recognized more slowly than for other solid organ allografts. Significant strides have been made in elucidating clinical and histopathologic features of acute and chronic liver AMR, with the Banff 2016 criteria among the most notable. However, current histopathologic definitions of AMR are lacking in sensitivity and specificity. C4d staining is an imperfect biological surrogate for antibody-mediated injury, and suffers from significant technical limitations. The frequent co-occurrence of T cell mediated rejection and non-immunologic allograft damage (including recurrence of primary disease) also hinders definitive identification of AMR and results in misattribution of its effects. The goal of this review is to summarize the current understanding of AMR in the context of liver transplantation, including risk factors, pathogenesis, and current diagnostic and treatment strategies. Potential directions of future research are also addressed.

Exploring the molecular landscape of osteosarcoma through PTTG family genes using a detailed multi-level methodology.

Osteosarcoma (OS) poses a significant clinical challenge, necessitating a comprehensive exploration of its molecular underpinnings. This study explored the roles of PTTG family genes (PTTG1, PTTG2, and PTTG3P) in OS, employing a multifaceted approach encompassing molecular experiments, including OS cell lines culturing, RT-qPCR, bisulfite and Whole Exome Sequencing (WES) and in silico experiments, including The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets-based validation, overall survival, gene enrichment, functional assays, and molecular docking analyses. Our findings reveal a consistent up-regulation of PTTG genes in OS cell lines, supported by RT-qPCR experiments and corroborated across various publically available expression datasets databases. Importantly, ROC curve analyses highlight their potential as diagnostic markers. Moving beyond expression profiles, we unveil the epigenetic landscape by demonstrating significant hypomethylation of CpG islands associated with PTTG genes in OS. The negative correlation between methylation status and mRNA expression emphasizes the regulatory role of promoter methylation in PTTG gene expression. Contrary to expectations, genetic mutations in PTTG genes are rare in OS, with only benign mutations observed. Moreover, functional assays also confirmed the oncogenic roles of the PTTG gene in the development of OS. Lastly, we also revealed that Calcitriol is the most appropriate drug that can be utilized to treat OS in the context of PTTG genes. The identification of PTTG genes as potential diagnostic markers and their association with epigenetic alterations opens new avenues for understanding OS pathogenesis and developing targeted therapies. As we navigate the complex landscape of OS, this study contributes essential insights that may pave the way for improved diagnostic and therapeutic strategies in its management.

COVID-19 and kidney involvement: pathophysiological approach

Introduction: Due to the great threat posed by COVID-19, the scientific community must have evidence of kidney damage in patients affected by this disease, which would make it possible to carry out actions aimed at its prevention and early detection. Objectives: deepen knowledge about COVID-19 and its impact on the kidney. Methods: a bibliographic review on COVID-19 and kidney was carried out, in research published in Spanish and English, in the PubMed, Scielo, and Dialnet databases. All documents published in the last five years (2019-2023) were selected, which included the keywords: COVID-19, kidney, kidney disease. Conclusions: within the systemic involvement caused by COVID-19, the kidney plays a predominant role in its pathophysiology and as a target organ. Kidney disease is in itself a risk factor for morbidity and mortality and acute kidney failure worsens the prognosis; Hence, it is necessary to delve deeper into these topics every day to direct novel diagnostic and therapeutic strategies

The many faces of brucellosis: diagnostic and management approach.

This review aims to highlight the multifaceted nature of brucellosis, emphasizing the latest advancements in its diagnosis and management. Given the global prevalence and potential complications of brucellosis, understanding recent advancements in diagnostic techniques and treatment strategies is crucial for clinicians. Recent literature reveals significant progress in diagnostic methods, including the application of fluorescence polarization immunoassay and time-resolved fluorescence resonance energy transfer technologies as well as the invention of artificial Brucella antigens, which offer enhanced sensitivity and specificity. Advances in molecular diagnostics and serological tests have improved early detection rates, however their interpretation remains challenging. Evolving treatment regimens such as the use of hydroxychloroquine as part of triple therapy and the use of nano-delivery systems in therapies have shown promise, in hopes of reducing relapse rates and managing chronic cases. The findings underscore the necessity for clinicians to adopt a comprehensive approach to diagnosing and managing brucellosis. Integrating advanced diagnostic tools with tailored therapeutic strategies can significantly improve patient outcomes. Future research should focus on optimizing these diagnostic techniques and exploring novel therapeutic agents.