Silent Progression Research Articles

Blinded by the Mind: Exploring the Hidden Psychiatric Burden in Glaucoma Patients.

Glaucoma is one of the leading causes of permanent vision loss worldwide and has a profound impact on patients' quality of life. Vision impairment is strongly associated with several psychiatric disorders, like depression, anxiety, and sleep problems. These psychiatric issues are often exacerbated by the gradual, irreversible, and typically silent progression of the disease, contributing to increased mental health challenges for affected individuals. A systematic review was conducted following PRISMA guidelines across six different databases (CINAHL, MEDLINE, PsycINFO, Web of Science, Scopus, and the Cochrane Library) and one gray literature source (Google Scholar), covering the period from 2013 to 2024. Twenty-nine studies involving a total of 13,326,845 subjects were included in the synthesis, highlighting a considerable prevalence of psychiatric disorders among glaucoma patients. Depression and anxiety were the most common conditions identified, with depression rates ranging from 6.6% to 57% and anxiety from 12.11% to 49%. Other less frequent but still significant conditions like sleep disorders, psychosis, dementia, and post-traumatic stress disorder were also observed. The findings also indicated that psychiatric severity was influenced by socio-demographic factors, glaucoma severity, and treatment duration. Given the high occurrence of psychiatric pathologies among individuals with glaucoma, it is essential to develop comprehensive care strategies that address both eye and mental health needs. Multidisciplinary collaboration among ophthalmologists, psychiatrists, psychologists, and primary care physicians is crucial for developing personalized treatment plans that effectively manage both the ocular and psychological aspects of the disease.

Exhaled breath metabolites reveal postmenopausal gut-bone cross-talk and non-invasive markers for osteoporosis

BackgroundMenopause driven decline in estrogen exposes women to risk of osteoporosis. Detection of early onset and silent progression are keys to prevent fractures and associated burdens.MethodsIn a discovery cohort of 120 postmenopausal women, we combined repeated quantitative pulse-echo ultrasonography of bone, assessment of grip strength and serum bone markers with mass-spectrometric analysis of exhaled metabolites to find breath volatile markers and quantitative cutoff levels for osteoporosis. Obtained markers and cutoffs were validated in an independent cohort of 49 age-matched women with six months apart seasonal follow-ups.ResultsHere, within the discovery cohort, concentrations of exhaled end-tidal dimethyl sulfide (DMS), allyl-methyl sulfide, butanethiol and butyric acid are increased (p ≤ 0.005) pronouncedly in subjects with bone mineral density (BMD) at high-risk of osteoporosis and fracture, when compared to subjects with normal BMD. Increased age and decreased grip strength are concomitant. All changes are reproduced during independent validation and seasonal follow-ups. Exhaled metabolite expressions remain age independent. Serum markers show random expressions without reproducibility. DMS exhalations differs between patients with recent, old and without fractures. Metabolite exhalations and BMDs are down-regulated during winter. ROC analysis in discovery cohort yields high classification accuracy of DMS with a cutoff for osteoporosis, which predicts subjects at high-risk within the independent validation cohort with >91% sensitivity and specificity.ConclusionsNon-invasive analysis of exhaled DMS allowed more reliable classification of osteoporosis risk than conventional serum markers. We identified associations of exhaled organosulfur and short-chain fatty acids to bone metabolism in postmenopausal osteoporosis via a gut-bone axis.

Etiology-Dependent Microbiome Differences in Hepatocellular Carcinoma Development.

Chronic liver disease is characterised by persistent inflammation, tissue damage, and regeneration, which leads to steatosis, fibrosis, and, lastly, cirrhosis and hepatocellular carcinoma (HCC). HCC, the most prevalent form of primary liver cancer, is one of the leading causes of cancer-related mortality worldwide. The gut microbiota plays a fundamental role in human physiology, and disturbances in its critical balance are widely recognised as contributors to various pathological conditions, including chronic liver diseases, both infectious and non-infectious in nature. Growing interest in microbiota research has recently shifted the focus towards the study of intratumoural microbiota, referred to as the "oncobiome", which can significantly impact the development and progression of HCC. In this review, we discuss existing research and provide an overview of the microbiota influence on viral hepatitis, particularly in shaping the progression of liver disease caused by the hepatitis B and hepatitis C viruses. We also explore microbial dysbiosis and its contribution to the silent and dangerous progression of non-alcoholic fatty liver disease. Additionally, we address the impact of alcohol on the liver and its interaction with the microbiota, tracing the pathway from inflammation to cirrhosis and cancer. The review emphasises the most common etiologies of hepatocellular carcinoma.

Massive retroperitoneal leiomyosarcoma: a case report

Soft tissue sarcoma is mesenchymal tumor of malignant in nature seen in body. Liposarcoma followed by leiomyosarcoma are most common type. Leiomyosarcoma (LMS) in retroperitoneum region develop from smooth muscle cell or from wall of large vein and detect clinically when attain huge size, causing symptom due to compression or displacement to surrounding structure. We are presenting case report of a 65 years old lady presented with progressive pain abdomen, distension, loss of weight and appetite for 1 year. Radiological investigation reveals a large bilobed intra-abdominal mass with no major vascular involvement. Patient underwent complete surgical excision with resection of surrounding structure and post operative period was uneventful. HPE and IHC of resected tumor were suggestive of Leiomyosarcoma. Leiomyosarcoma usually has slow and silent progression hence present clinically when compression or displacement of adjacent structure arises. It has malignant potential. Radiological investigation helps in deciding resection. R0 resection carries very good prognosis since chemo and radiotherapy has limited role in complete cure.

The time to include cognition in the multiple sclerosis concept of progression independent from relapse activity is now

Progression independent of relapse activity (PIRA) has been recently proposed in multiple sclerosis (MS) as a model identifying a continuous silent progression of disability without the manifestation of new clinical and magnetic resonance imaging (MRI) events that contribute to MS worsening. Despite evidence suggesting that clinical MS manifestations often affect cognitive functioning and the importance of neuropsychological monitoring over time, attention to silent cognitive progression is lacking, and the PIRA concept does not include a measure of cognitive function. In this personal viewpoint, we highlight the need to include cognition in the PIRA model to have a more comprehensive understanding of clinical progression in patients with MS.

New views on the complex interplay between degeneration and autoimmunity in multiple sclerosis.

Multiple sclerosis (MS) is a frequently disabling neurological disorder characterized by symptoms, clinical signs and imaging abnormalities that typically fluctuate over time, affecting any level of the CNS. Prominent lymphocytic inflammation, many genetic susceptibility variants involving immune pathways, as well as potent responses of the neuroinflammatory component to immunomodulating drugs, have led to the natural conclusion that this disease is driven by a primary autoimmune process. In this Hypothesis and Theory article, we discuss emerging data that cast doubt on this assumption. After three decades of therapeutic experience, what has become clear is that potent immune modulators are highly effective at suppressing inflammatory relapses, yet exhibit very limited effects on the later progressive phase of MS. Moreover, neuropathological examination of MS tissue indicates that degeneration, CNS atrophy, and myelin loss are most prominent in the progressive stage, when lymphocytic inflammation paradoxically wanes. Finally, emerging clinical observations such as "progression independent of relapse activity" and "silent progression," now thought to take hold very early in the course, together argue that an underlying "cytodegenerative" process, likely targeting the myelinating unit, may in fact represent the most proximal step in a complex pathophysiological cascade exacerbated by an autoimmune inflammatory overlay. Parallels are drawn with more traditional neurodegenerative disorders, where a progressive proteopathy with prion-like propagation of toxic misfolded species is now known to play a key role. A potentially pivotal contribution of the Epstein-Barr virus and B cells in this process is also discussed.

Rephrasing the 'David-Goliath' story in the field of diabetes.

Diabetes Mellitus has become a serious threat to public health. This non-communicable disease is spreading like wildfire to shape in the form of a global pandemic. It affects several organs during silent progression in the human body. The pathophysiological fallouts associate dysregulation of numerous cellular pathways. MicroRNAs have emerged as potent gene expression regulators by post-transcriptional mechanisms in the last two decades or so. Many microRNAs display differential expression patterns under hyperglycemia affecting coupled cellular signaling cascades. The present article attempts to unfold the involvement of microRNAs as biomarkers in diabetic conditions in current scenarios identifying their therapeutic significance.

Non-alcoholic fatty liver disease among patients undergoing ultra-sonography abdomen and its associated factors in a tertiary care hospital, Kakinada

Background: Non-alcoholic fatty liver disease (NAFLD) presents a growing global health concern, characterized by the accumulation of hepatic lipids in the absence of significant alcohol consumption. Its prevalence has surged worldwide, including in India, where it has reached alarming levels. Despite its silent progression, NAFLD can lead to severe complications, including liver cirrhosis and hepatocellular carcinoma. Objectives of the study to assess prevalence and its associated factors, which are essential for effective management and prevention strategies. Methods: An observational, analytical cross-sectional study was conducted in a tertiary care hospital in Kakinada, Andhra Pradesh, from June to July 2022. Among 100 subjects, chosen through the simple random sampling. Ethical approval was granted before conducting study. Data on demographics, lifestyle risk factors, anthropometry, and ultrasound findings were collected using a pretested and validated case record form. Statistical analysis was carried out using SPSS software, employing appropriate tests to explore associations between NAFLD and various variables. Results: Among 100 participants, the prevalence of NAFLD was found to be 41%. Significant associations were observed between NAFLD and variables such as BMI (p=0.034), waist-hip ratio (p=0.002), and history of diabetes mellitus (p=0.000). Lifestyle factors, including increased cooking oil consumption, were identified as significant risk factors. Conclusions: The study highlights the high prevalence of NAFLD among subjects undergoing ultrasound abdomen in Kakinada. Significant associations were observed with BMI, waist-hip ratio, and diabetes mellitus history. Promoting healthy behaviours is crucial for NAFLD prevention and management.

Assessment of Non-Alcoholic Hepatic Steatosis Disease and its Association with Hepatomegaly by Using Ultrasound

Background: Non-alcoholic hepatic steatosis disease (NAHSD) is increasingly recognized as a major global health concern, particularly due to its silent progression and significant impact on quality of life. The prevalence of NAHSD is particularly high in regions with widespread obesity and diabetes, conditions that are escalating in global incidence. Objective: This study aimed to evaluate the prevalence and severity of NAHSD and its association with hepatomegaly using ultrasonography in a Pakistani adult population. Methods: A cross-sectional study was conducted from November 2023 to March 2024 at the Department of Radiology, District Head Quarter’s Hospital, Swabi, Pakistan. A total of 70 adults presenting with clinical manifestations of hepatomegaly were enrolled. Ultrasonography was performed using a Toshiba Doppler machine equipped with a convex transducer (2.5—5.0 MH frequency). Liver size, shape, and echogenicity were assessed, and hepatic parenchyma was graded into three categories based on echogenicity. Data were analyzed using SPSS version 25, focusing on descriptive and inferential statistics. Results: The study comprised 41 females (58.6%) and 29 males (41.4%), with an age range from 19 to 69 years (mean age 43.79 ± 11.583 years). Hepatic steatosis was graded as mild in 20% (14), moderate in 5.7% (4), and severe in 1.4% (1) of patients with hepatomegaly. The majority, 72.9% (51), showed no signs of hepatic steatosis. Hepatomegaly was noted in 27% of patients (19). Conclusion: Ultrasonography is an effective diagnostic tool for assessing NAHSD and hepatomegaly, revealing a significant prevalence of these conditions among the studied population. Early screening and intervention are critical to managing and reducing the healthcare burden associated with NAHSD.

Immune analysis of urine and plasma samples from patients with clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the third most common type of urological malignancy worldwide, and it is associated with a silent progression and late manifestation. Patients with a metastatic form of ccRCC have a poor prognosis; however, when the disease is diagnosed early, it is largely curable. Currently, there are no biomarkers available in clinical practice for ccRCC. Thus, the aim of the present study was to measure 27 biologically relevant cytokines in preoperative and postoperative urine samples, and in preoperative plasma samples from 34 patients with ccRCC, and to evaluate their diagnostic significance. The concentrations of cytokines were assessed by multiplex immune assay. The results showed significantly higher levels of IL-1 receptor antagonist, IL-6, IL-15, chemokine (C-C motif) ligand (CCL)2, CCL3, CCL4, C-X-C motif ligand (CXCL)10, granulocyte-macrophage colony stimulating factor (GM-CSF) and platelet-derived growth factor-BB (PDGF-BB), and lower levels of granulocyte colony stimulating factor (G-CSF) in urine samples from patients prior to surgery compared with those in the controls. Notably, the urine levels of G-CSF, IL-5 and vascular endothelial growth factor differed following tumor removal compared with the preoperative urine levels. In addition, urinary G-CSF, GM-CSF, IL-6, CXCL10, CCL5 and PDGF-BB appeared to be potential markers of tumor grade. Plasma from patients with ccRCC contained significantly higher levels of IL-6 and lower levels of CCL2 than control plasma. In conclusion, the present findings indicated that urinary and circulating cytokines may represent a promising novel tool for the early diagnosis of ccRCC and/or prediction of tumor grade.

Exercise enhances hepatic mitochondrial structure and function while preventing endoplasmic reticulum stress and metabolic dysfunction-associated steatotic liver disease in mice fed a high-fat diet

Metabolic dysfunction-associated steatotic liver disease (MASLD) has attracted increasing attention from the scientific community because of its severe but silent progression and the lack of specific treatment. Glucolipotoxicity triggers endoplasmic reticulum (ER) stress with decreased beta-oxidation and enhanced lipogenesis, promoting the onset of MASLD, whereas regular physical exercise can prevent MASLD by preserving ER and mitochondrial function. Thus, the hypothesis of this study was that high-intensity interval training (HIIT) could prevent the development of MASLD in high-fat (HF)-fed C57BL/6J mice by maintaining insulin sensitivity, preventing ER stress, and promoting beta-oxidation. Forty male C57BL/6J mice (3 months old) comprised 4 experimental groups: the control (C) diet group, the C diet + HIIT (C-HIIT) group, the HF diet group, and the HF diet + HIIT (HF-HIIT) group. HIIT sessions lasted 12 minutes and were performed 3 times weekly by trained mice. The diet and exercise protocols lasted for 10 weeks. The HIIT protocol prevented weight gain and maintained insulin sensitivity in the HF-HIIT group. A chronic HF diet increased ER stress-related gene and protein expression, but HIIT helped to maintain ER homeostasis, preserve mitochondrial ultrastructure, and maximize beta-oxidation. The increased sirtuin-1/peroxisome proliferator-activated receptor-gamma coactivator 1-alpha expression implies that HIIT enhanced mitochondrial biogenesis and yielded adequate mitochondrial dynamics. High hepatic fibronectin type III domain containing 5/irisin agreed with the antilipogenic and anti-inflammatory effects observed in the HF-HIIT group, reinforcing the antisteatotic effects of HIIT. Thus, we confirmed that practicing HIIT 3 times per week maintained insulin sensitivity, prevented ER stress, and enhanced hepatic beta-oxidation, impeding MASLD development in this mouse model even when consuming high energy intake from saturated fatty acids.

Abstract LB216: Static and microfluidic platforms for novel therapeutic testing in high-grade serous ovarian cancer

Abstract Background: High-Grade Serous Ovarian Cancer (HGSOC) is the most lethal OC type because of its silent progression and lack of specific markers for early detection. In this context, the timely initiation of effective treatment is imperative to prevent disease progression extending life expectancy. However, responses to treatment can vary significantly among individuals, presenting clinical challenges in selecting effective treatments, necessitating the interpretation of molecular and genomic data of the patient on a case-by-case basis. The aim of this study is to establish a highly sensitive platform, implemented with microfluidic technology, to predict patient drug responses with the goal of assisting oncologists in shaping effective treatments. Moreover, validating this platform through a retrospective study, enabling the development of innovative drugs. Methods: In this work, patient-derived ovarian cancer organoids (PDOs) were engineered for drug screening and twenty FDA approved drugs were assessed on seven PDOs derived from both primary tumors and ascites. The fidelity of PDOs in reproducing the histopathology of the primary tumour was confirmed by immunohistochemistry. Proteomics and repeated screening on high- and low-passage PDOs confirmed the reliability of the platform over time. Furthermore, to bridge the gap between static systems and the dynamic of human tumours, a microfluidic platform was employed and using fluorescence microscopy the patients' drug sensitivity was predicted (PMID: 37143603). Results: PDOs were able to replicate patients' response to the drug in a retrospective study and surprisingly, in some cases, to predict resistance to certain drugs administered on the basis of strong, clinically validated predictive biomarkers, which proved ineffective in the clinic. The platform could predict innovative therapeutic strategies as demonstrated by inhibiting the activity of Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (Pin1), a novel druggable target for OC (PMID: 22322860, 29746956, 30697729). The Pin1 inhibitor (VS10) is effective in a subset of patients resistant to platinum-based chemotherapy and synergize with doxorubicin. Finally, a microfluidic platform fluorescence based, which improved drug penetration in PDOs was developed for efficient and faster drug screening. Conclusions: This study underscores the significance of utilizing engineered PDOs to develop predictive and easy to use platforms that can truly aid oncologists in devising patient-specific treatments while circumventing the use of drugs that, despite strong recommendations, may prove ineffective. Furthermore, these platforms have demonstrated their effectiveness in the development of innovative therapeutics, such as Pin1 inhibitors, which have been proven both effective and safe in animal models, underscoring the need for clinical studies. Acknowledgments: AIRC IG23566 Citation Format: Enrico Cavarzerani, Gloria Saorin, Matteo Mauceri, Isabella Caligiuri, Michele Bartoletti, Vincenzo Canzonieri, Flavio Rizzolio. Static and microfluidic platforms for novel therapeutic testing in high-grade serous ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB216.

Abstract 4199: Comprehensive 3D liver cancer model to study the tumor microenvironment for therapy development

Abstract Liver cancer, or hepatocellular carcinoma (HCC), is a formidable malignancy characterized by the uncontrolled growth of cells within the liver tissue. It represents a global health concern, with risk factors including chronic viral infections (such as hepatitis B and C), excessive alcohol consumption, fatty liver disease, and certain genetic conditions. The silent progression of HCC complicates early detection, emphasizing the need for a deeper understanding of the liver tumor microenvironment, which plays a crucial role in disease development. The liver model presented here incorporates a wide array of relevant liver cell types, including hepatocytes, endothelial cells, stellate cells, and resident immune cells. This is complemented by a complete vascularization system, allowing for fluid flow across a micro vascular network that faithfully models the dimensions of liver sinusoids. All these elements are seamlessly integrated into an automated and high throughput platform known as the OrganoPlate®. To model the liver tumor microenvironment, hepatocellular carcinoma cells were integrated into healthy liver tissue model. The resulting model allowed for the observation of integrated cancer colonies, providing a more realistic platform for therapy development compared to monocultures. Simultaneously, the liver's particle clearance mechanisms were investigated using fluorescent imaging. Endothelial cell phagocytosis of E. coli particles and resident macrophages' internalization of dextran molecules were studied to explore hepatic delivery of macromolecules and nanoparticles via the systemic circulation. The integration of hepatocellular carcinoma cells within healthy liver tissue revealed the formation of integrated cancer colonies, offering insights into the complex interactions within the liver tumor microenvironment. Fluorescent imaging showcased endothelial cell phagocytosis of E. coli particles and resident macrophages' internalization of fluorescent molecules. These findings elucidate the liver's particle clearance mechanisms, providing a foundation for understanding immunological processes and designing efficient drug delivery systems. Understanding the liver tumor microenvironment is critical for developing effective therapies for HCC. The integration of hepatocellular carcinoma cells within healthy liver tissue offers a more realistic platform for therapy development compared to traditional monocultures. We believe this system holds the potential for a groundbreaking progress in liver modelling which, besides including functional hepatic cells, also reflects the cellular organization and interactions found within the liver lobule. In conjunction with its high throughput capability, this has the potential to revolutionize drug discovery and develop therapies for complex liver diseases. Citation Format: Flavio Bonanini, Roelof Dinkelberg, Vincent van Duinen, Jeroen Heijmans, Desiree Gouber, Tessa Hagens, Nienke Kortekaas, Manuel Caro Torregrosa, Dorota Kurek, Paul Vulto, Kristin Bircsak. Comprehensive 3D liver cancer model to study the tumor microenvironment for therapy development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4199.

Prediction of five-year survival among esophageal cancer patients using machine learning

Background and aimConsidering the silent progression of esophageal cancer, the survival prediction of this disease is crucial in enhancing the quality of life of these patients globally. So far, no prediction solution has been introduced for the survival of EC in Iran based on the machine learning approach. So, this study aims to develop a prediction model for the five-year survival of EC based on the ML approach to promote clinical outcomes and various treatment and preventive plans. Material and methodsIn this retrospective study, we investigated the 1656 cases of survived and non-survived EC patients belonging to Imam Khomeini Hospital in Sari City from 2013 to 2020. The multivariable regression analysis was used to select the best predictors of five-year survival. We leveraged random forest, eXtreme Gradient Boosting, support vector machine, artificial neural networks, Bayesian networks, J-48 decision tree, and K-nearest neighborhood to develop the prediction models. To get the best model for predicting the five-year survival of EC, we compared them using the area under the receiver operator characteristics. ResultsThe age at diagnosis, body mass index, smoking, obstruction, dysphagia, weight loss, lymphadenopathy, chemotherapy, radiotherapy, family history of EC, tumor stage, type of appearance, histological type, grade of differentiation, tumor location, tumor size, lymphatic invasion, vascular invasion, and platelet albumin ratio were considered as the best predictors associated with the five-year survival of EC based on the regression analysis. In this respect, the random forest with the area under the receiver operator characteristics of 0.95 was identified as a superior model. ConclusionThe experimental results of the current study showed that the random forest could have a significant role in enhancing the quality of care in EC patients by increasing the effectiveness of follow-up and treatment measures introduced by care providers.

Subclinical damage to the contralateral eye in unilateral optic neuritis: A longitudinal study.

Early detection of subclinical injuries can lead to a correct diagnosis and help control the advancement of the condition. This study aims to investigate the presence of subclinical damage and silent progression to the contralateral eye's visual function and structure in patients experiencing their first episode of unilateral optic neuritis (ON). Fifty patients with first-onset unilateral ON were enrolled in this study. Based on etiology, they were classified as having neuromyelitis optica spectrum disorder-related ON (NMOSD-ON), myelin oligodendrocyte glycoprotein antibody-associated ON (MOG-ON), idiopathic ON (IDON), or multiple sclerosis-related ON (MS-ON). These cases were followed up for one year to determine whether there was any silent progression of visual function and structure in the contralateral non-ON (NON) eye. A gender- and age-matched healthy control (HC) group was included to compare the differences in visual function and structure between the patients with NON eyes and the HC group. Within two weeks of onset, best-corrected visual acuity (BCVA; P=0.008), mean deviation (MD) of the visual field (VF) (P=0.001), and peripapillary retinal nerve fiber layer (pRNFL; P=0.019) thickness were significantly worse in the NMOSD-NON patients than those in the HC group, while there were no differences in the pRNFL and the ganglion cell-inner plexiform layer (GCIPL) thicknesses and quadrant thicknesses (P > 0.05) of the groups. IDON-NON only showed subclinical damage in VF (P=0.001) and temporal pRNFL (P=0.042), while the BCVA, VF, and optic nerve structure (pRNFL, GCIPL) of the MOG-NON patients showed no subclinical damage (P > 0.05). In addition, the one-year follow-up of each NON eye type showed that there was no silent progression in NMOSD-NON, MOG-NON, or IDON-NON. A pairwise comparison of the different types of NON eyes revealed no statistical differences (P > 0.05). Among the patients with unilateral ON, NMOSD-NON and IDON-NON resulted in subclinical damage to the visual function and structure of the contralateral eye within two weeks of onset, whereas MOG-NON did not show any subclinical damage to visual function or structure. Furthermore, these subclinical damages did not show any silent progression during the one-year follow-up period.

Paramagnetic rim lesions lead to pronounced diffuse periplaque white matter damage in multiple sclerosis

Background: Paramagnetic rim lesions (PRLs) are an imaging biomarker in multiple sclerosis (MS), associated with a more severe disease. Objectives: To determine quantitative magnetic resonance imaging (MRI) metrics of PRLs, lesions with diffuse susceptibility-weighted imaging (SWI)-hypointense signal (DSHLs) and SWI-isointense lesions (SILs), their surrounding periplaque area (PPA) and the normal-appearing white matter (NAWM). Methods: In a cross-sectional study, quantitative MRI metrics were measured in people with multiple sclerosis (pwMS) using the multi-dynamic multi-echo (MDME) sequence post-processing software “SyMRI.” Results: In 30 pwMS, 59 PRLs, 74 DSHLs, and 107 SILs were identified. Beside longer T1 relaxation times of PRLs compared to DSHLs and SILs (2030.5 (1519–2540) vs 1615.8 (1403.3–1953.5) vs 1199.5 (1089.6–1334.6), both p < 0.001), longer T1 relaxation times were observed in the PRL PPA compared to the SIL PPA and the NAWM but not the DSHL PPA. Patients with secondary progressive multiple sclerosis (SPMS) had longer T1 relaxation times in PRLs compared to patients with late relapsing multiple sclerosis (lRMS) (2394.5 (2030.5–3040) vs 1869.3 (1491.4–2451.3), p = 0.015) and also in the PRL PPA compared to patients with early relapsing multiple sclerosis (eRMS) (982 (927–1093.5) vs 904.3 (793.3–958.5), p = 0.013). Conclusion: PRLs are more destructive than SILs, leading to diffuse periplaque white matter (WM) damage. The quantitative MRI-based evaluation of the PRL PPA could be a marker for silent progression in pwMS.

Holistic Understanding of the Role of Carbohydrate Antigen 19-9 in Pancreatic Cancer Screening, Early Diagnosis, and Prognosis: A Systematic Review.

Pancreatic ductal adenocarcinoma (PDAC) is a significant challenge due to its silent progression and well-advanced, unresectable, complicated presentation. Detecting this disease early on is crucial, and researchers have been investigating various potential biological markers, such as carbohydrate antigen 19-9 (CA 19-9), hoping to find indicators that can aid in its early detection. The primary focus of this reviewis on the diagnostic usefulness of CA 19-9 in detecting pancreatic cancer (PC) in the beginning stage and its usefulness in predicting progression. The database search of articles from PubMed, PMC, the Cochrane Library, and Google Scholar identified 227 articles published from 2013 to 2023. The keyword mix used in the search technique included terms like "CA 19-9," "pancreatic cancer," "diagnosis," and "early detection." This study provides evidence of CA 19-9's ability in detecting PDAC in the pre-diagnostic stage. But since the outcomes were inconsistent among the included trials, further analysis is required to develop standardized diagnostic criteria and methodologies. Furthermore, because of the variability of the study, it is not easy to make firm conclusions on CA 19-9's sensitivity as well as specificity in the first stage of pancreatic neoplasm. This in-depth overview of the available literature provides new insights into using CA 19-9 as a biological marker for detecting undiagnosed PC before progressing into the advanced stage, and was proven beneficial. However, this has to be shown in broader research with adequate sample size. Although it shows promise as a diagnostic tool, further study is required to confirm these findings.

High level of serum complement 3 is a risk factor for vascular stenosis progression in TA patients receiving tocilizumab: a prospective observational study

BackgroundThe IL-6R antibody tocilizumab has been proven effective in treating Takayasu arteritis (TA). However, some patients show silent vascular stenosis progression (VSP) despite treatment with tocilizumab. The aim of the study was to explore the related risk factors of VSP in patients treated with tocilizumab.MethodsPatients receiving tocilizumab were enrolled from the prospective living ongoing East China Takayasu Arteritis cohort. Their medical information was uniformly recorded with a homogenized evaluation method. Magnetic resonant angiography or computed tomographic angiography was employed to monitor VSP during the follow-up period, and Cox regression analysis was performed to explore the related risk factors.ResultsThirty-eight patients were enrolled, among whom 18 (47.4%) experienced VSP, and seven and three patients experienced new and worsened vascular ischemic symptoms and events (VISE) during follow-up, respectively. The median period for VSP occurrence was 6.9 months during follow-up. Patients with VSP showed higher levels of baseline complement 3 (C3) than those in the patients without VSP. Multivariate Cox regression analysis revealed baseline C3 level (hazard ratio [HR] = 7.05, 95% confidence interval: 1.50–33.07, p = 0.013) was independently associated with VSP, with a cut-off value of 1.22 g/L.Conclusions47.4% of TA patients treated with tocilizumab would suffer VSP. A high C3 level is a risk factor for VSP in TA patients receiving tocilizumab, which may facilitate the option of tocilizumab in the future.

Silent rapid progression of mycotic left main aneurysm following stenting to bailout for acute occlusion caused by infective endocarditis.

Journal Article Silent rapid progression of mycotic left main aneurysm following stenting to bailout for acute occlusion caused by infective endocarditis Get access Kojiro Toda, Kojiro Toda Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka 564-8565, JapanDepartment of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, S1W17 Chuoh-ku, Sapporo, Hokkaido 060-8556, Japan Corresponding author. Tel: +81 6 6170 1070, Email: takagi.kensuke@ncvc.go.jp Search for other works by this author on: Oxford Academic PubMed Google Scholar Kensuke Takagi, Kensuke Takagi Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka 564-8565, Japan https://orcid.org/0000-0003-3999-8536 Search for other works by this author on: Oxford Academic PubMed Google Scholar Teruo Noguchi Teruo Noguchi Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka 564-8565, JapanDepartment of Advanced Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1 Chome-1-1 Honjo, Chuo Ward, Kumamoto 860-8556, Japan https://orcid.org/0000-0001-5372-4932 Search for other works by this author on: Oxford Academic PubMed Google Scholar European Heart Journal, ehad399, https://doi.org/10.1093/eurheartj/ehad399 Published: 23 June 2023

P172 A RARE CASE OF PLATINUM CARDIOTOXICITY: CASE REPORT

Abstract Background The chemotherapy regime containing the Carboplatin–Gemcitabine combination is frequently used for improving outcomes in patients affected by metastatic breast cancer. Platinum compounds were included in the recent ESC Guidelines on cardio–oncology as potential agents which may lead to myocardial infarction, thrombosis and, rarely, heart failure. In this instance it is essential for a strict cardiological follow–up to be carried out during and after treatment. Case report: We present a clinical case report of a 38–year–old woman who was receiving standard oncology treatment for stage IV breast adenocarcinoma. The patient underwent chemotherapy cycles containing the Carboplatin–Gemcitabine combination, with a good response to treatment. It came to our attention for severe dyspnoea, which arose several days before, not compatible with her oncological situation. Transthoracic echocardiography showed severe left ventricular dysfunction (EF 25%; GLS – 9.2%; NT–proBNP 10000 pg/mL), which was not present during earlier tests, and circumferential pericardial effusions, mainly localised along the free wall of the right ventricle, non–haemodynamically significant. Lung ultrasound also showed the presence of pulmonary congestion and bilateral pleural effusions. In the circumstances, she was admitted to the Cardiac Intensive Care Unit for continuation of diagnostic treatment. She then received endo–venous diuretic treatment and haemodynamically supported with Noradrenaline and inotropic agents. A cycle of Levosimendan was performed with an excellent response. Once haemodynamic compensation was re–established, the patient underwent a cardiac CMR which excluded cardiomyopathies and myocarditis and a coronarography was performed which showed no significant lesions in the coronary arteries. After 18 days of hospitalisation in our department, the patient showed an improvement in EF (EF 38%, GLS –12.5%, NT–proBNP 2000 pg/mL), and then she was referred to the oncologist for immunological treatment. Conclusions The diagnosis of cardiotoxicity may not be straightforward due to the aspecificity of the symptoms, its silent progression or because of several comorbidities. Moreover, cardiac damage from chemotherapy is considered reversible if identified early. Treatment is based on the withdrawal of therapy and treatment of symptoms, given that these may be different and unpredictable.