Clinical Management Of Patients Research Articles

Germline findings in cancer predisposing genes from a small cohort of chordoma patients

IntroductionChordoma is a rare slow-growing tumor that occurs along the length of the spinal axis and arises from primitive notochordal remnants (Stepanek et al., Am J Med Genet 75:335–336, 1998). Most chordomas are sporadic, but a small percentage of cases are due to hereditary cancer syndromes (HCS) such as tuberous sclerosis 1 and 2 (TSC1/2), or constitutional variants in the gene encoding brachyury T (TBXT) (Pillay et al., Nat Genet 44:1185–1187, 2012; Yang et al., Nat Genet 41:1176–1178, 2009).PurposeThe genetic susceptibility of these tumors is not well understood; there are only a small number of studies that have performed germline genetic testing in this population.MethodsWe performed germline genetic in chordoma patients using genomic DNA extracted by blood or saliva.ConclusionWe report here a chordoma cohort of 24 families with newly found germline genetic mutations in cancer predisposing genes. We discuss implications for genetic counseling, clinical management, and universal germline genetic testing for cancer patients with solid tumors.

Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision.

Hereditary adenomatous polyposis syndromes, including familial adenomatous polyposis and other rare adenomatous polyposis syndromes, increase the lifetime risk of colorectal and other cancers. A team of 38 experts convened to update the 2008 European recommendations for the clinical management of patients with adenomatous polyposis syndromes. Additionally, other rare monogenic adenomatous polyposis syndromes were reviewed and added. Eighty-nine clinically relevant questions were answered after a systematic review of the existing literature with grading of the evidence according to Grading of Recommendations, Assessment, Development, and Evaluation methodology. Two levels of consensus were identified: consensus threshold (≥67% of voting guideline committee members voting either 'Strongly agree' or 'Agree' during the Delphi rounds) and high threshold (consensus ≥ 80%). One hundred and forty statements reached a high level of consensus concerning the management of hereditary adenomatous polyposis syndromes. These updated guidelines provide current, comprehensive, and evidence-based practical recommendations for the management of surveillance and treatment of familial adenomatous polyposis patients, encompassing additionally MUTYH-associated polyposis, gastric adenocarcinoma and proximal polyposis of the stomach and other recently identified polyposis syndromes based on pathogenic variants in other genes than APC or MUTYH. Due to the rarity of these diseases, patients should be managed at specialized centres.

Abstract PO2-03-08: Uncovering Novel Potential Prognostic Biomarkers in Basal-Like Breast Cancer using Transcriptomic Data of 1,899 Patients

Abstract Introduction: Patients with basal-like breast cancer (BLBC) predominantly represented by triple-negative breast cancer have shown a high recurrence rate and are characterized by poor prognosis. There is an urgent need to undercover reliable prognostic biomarkers that can help in the clinical management of such patients and identify additional therapeutic targets. The objective of this study was to create a comprehensive transcriptomic database on a large scale and leverage it to identify and prioritize cancer-related genes associated with BLBC patients’ outcomes. Methods: We identified breast cancer cohorts from public repositories that contained gene expression data at the transcriptome level, along with clinical follow-up information. BLBC were identified using the PAM50 signature. All samples were standardized using a standard array normalization coupled with scaling to have a mean expression across all genes of 1000 in each sample and incorporated into a unified database. Redundant samples were removed. For each gene, Cox univariate survival analysis was conducted, to account for multiple hypothesis testing, the false discovery rate was computed, and a significant cutoff of 1% was employed to determine the highest statistical significance. Association with RFS and OS was performed. Multivariate analysis was performed for selected genes involving clinical and pathological variables. To uncover higher-level functions related to altered RFS, gene ontology analysis was performed using the enrichGO function in the TNM plotter (http://www.tnmplot.com). Results: The complete integrated database comprises 1,899 samples from 52 breast cancer datasets. Altogether, 2,342 genes were correlated with relapse-free survival (RFS), and 1,149 genes were correlated with overall survival (OS). 619 genes were statistically significant for both RFS and OS. The most significant genes were ANGPTL4 (p=4.25E-08, HR=2.02), NHP2 (p=5.98E-10, HR=1.93), STK3 (p=4.86E-10, HR=1.93), GBE1 (p=2.77E-09, HR=1.86), and PMVK (p=3.65E-09, HR=1.85) for RFS and PINK1 (p=1.64E-05 , HR=3.31), CAMK2N1 (p=1.06E-07 , HR=2.93), CACFD1 (p=4.79E-04 , HR=2.61), SCAP (p=3.29E-04 , HR=2.6), SDC1 (p=2.81E-04 , HR=2.57), for OS. The most significant gene ontology biological processes upregulated in tumors with a worse prognosis include GO:0000184, nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (p=6.64E-18); GO:0045047 , protein targeting to ER (p=6.64E-18); GO:0006614, SRP-dependent cotranslational protein targeting to membrane (p=9.08E-18); GO:0072599, establishment of protein localization to endoplasmic reticulum (p=1.30E-17); and GO:0006613, cotranslational protein targeting to membrane (p=1.90E-17). Conclusions: Our results help to prioritize genes and to neglect those which are most likely to fail in studies aiming to establish new clinically useful biomarkers and therapeutic targets in BLBC. Citation Format: Balazs Gyorffy, Libero Santarpia. Uncovering Novel Potential Prognostic Biomarkers in Basal-Like Breast Cancer using Transcriptomic Data of 1,899 Patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-03-08.

Abstract PO2-21-01: Granular Cell Tumors of the Breast: A Case Series

Abstract Objective: Granular cell tumors (GCT) of the breast are rare, Schwann-cell derived tumors that are largely benign in nature, but may present with malignant characteristics in 1-2% of cases. There are few reports highlighting the clinical presentation, cytologic differences, operative management and clinical outcomes of patients with these benign versus malignant GCTs. Here, the authors report the clinical course of 9 patients identified with either benign or malignant GCT of the breast. Methods: The medical records for a total of 9 patients treated for histologically confirmed GCT of the breast between March 2015 and May 2023 at our institution were retrospectively reviewed. Clinical data, imaging findings, immunohistochemical markers, surgical interventions, and clinical follow-up data were collected and analyzed. Results: All patients were female, with a mean age of 46 years (Range: 29-61). 5 (56%) patients presented with left-sided lesions with an average maximum dimension of 1.1 cm (SD: 0.7 cm). All 9 (100%) tumors were positive for S100, 4 (44%) were positive for CD68, and 3 (33%) were positive for Inhibin. 4 (44%) patients underwent local mass excision, 3 (33%) underwent lumpectomy, 1 (11%) underwent lumpectomy with sentinel lymph node biopsy, and 1 (11%) underwent partial mastectomy with sentinel lymph node biopsy. There were no perioperative complications nor complications noted at postoperative follow up visits. 1 patient (11%) had 2 recorded recurrences of GCT after the initial breast mass excision, with each tumor exhibiting different positive immunohistochemical markers. 1 (11%) patient had a previous history of breast cancer at time of GCT diagnosis, and 1 (11%) patient had concurrent breast malignancy with the granular cell tumor being in the lymph node of the same breast. Conclusions: Granular cell tumors of the breast are rare Schwann cell derived tumors that often present near breast scar tissue as spiculated, ill-defined masses with microcalcifications on radiologic imaging, mimicking breast malignancy, leading to overtreatment. This study found that for GCTBs that present in lymph nodes, regardless of low malignant potential seen histologically, there was a higher risk of recurrence, and may require further workup and close follow up after wide local excision. For all other granular cell tumors presenting with normal appearing lymph nodes on imaging, a local mass excision was adequate in management, with low risk of recurrence or malignant potential. Future studies should be performed analyzing long-term follow up for these patients to determine risk of recurrence over longer periods of time, and risk for breast malignancy. Granular Cell Tumor Characteristics Tumor characteristics including laterality, tumor location, maximum dimension in centimeters, and positive immunohistochemistry markers were shown for each patient. Citation Format: Shwetha Kochi, Madeline Karsten, Monika Masanam, Teagan Thorson, Roshanak Derakhshandeh, Patricia Wehner, Lucy De La Cruz, Jennifer Son. Granular Cell Tumors of the Breast: A Case Series [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-21-01.

Clinical characteristics, management and psychological outcomes of patients with diabetes secondary to chronic pancreatitis

Abstract Aims: To determine the clinical characteristics, management, rates of complications and psychological outcomes of patients with diabetes mellitus secondary to chronic pancreatitis (DMsCP) referred to the Belfast Pancreatic Diabetes Clinic.Methods: Clinical and laboratory data were obtained from online health care records (NIECR). Psychological outcomes and a service‐based questionnaire were performed.Results: Baseline characteristics (n=63 patients [male: 41, female: 22]) at initial referral included: mean age 56.2 years (range 19–84); mean duration of chronic pancreatitis 10.7 years (range 1–40); mean duration of diabetes 7.2 years (range 1–40). Previous pancreatic surgery was performed in 19% (12/63) of patients. Initial mean HbA1c was 82mmol/mol (range 41–189); mean HbA1c at six and 12 months follow‐up was 69.9mmol/mol and 70.6mmol/mol, respectively. Rates of microvascular complications included: retinopathy (background and pre‐proliferative) 16%; microalbuminuria 17%; peripheral neuropathy 14%, with no foot ulceration/amputation occurring. Macrovascular disease occurred in 24% of patients. Sixteen (25%) had missed at least one outpatient diabetes appointment over the preceding year. Quality of life (QoL) as measured by the PANQOLI was low with a mean total score of 64.9/103; 59% (16/27) of the service cohort also breached clinical cut‐offs for the presence of both anxiety (GAD‐7) and depression (PHQ‐9).Summary: DMsCP in our cohort was characterised by significant micro‐ and macrovascular complications, sub‐optimal glycaemic control, reduced clinic attendance and impaired QoL as well as a significant component of anxiety and depression. The optimal care for these patients should consist of a collaborative approach that best meets their complex and multifaceted needs. Copyright © 2024 John Wiley & Sons.

Pediatric cardiomyopathy illustrates the importance of reinterpreting the significance of genetic variants

BackgroundClinical genetic testing is increasingly being utilized to establish a molecular diagnosis to help manage children with cardiomyopathy and to assess the risk of cardiomyopathy among family members. However, as evidence and guidelines evolve, variant classification can change with the potential to impact counseling and family screening. ObjectivesThe main purpose of this study was to investigate whether variants in cardiomyopathy genes previously interpreted by clinical genetic testing laboratories would be reclassified under current guidelines for the interpretation of sequence variants. MethodsIn 211 children enrolled in the Pediatric Cardiomyopathy Registry, we compared the results of previous clinical genetic testing with the results of research testing in 37 cardiomyopathy genes. ResultsThe mean time difference between initial testing and reinterpretation was 7 years. Using the 2015 American College of Medical Genetics and Genomics guidelines for the interpretation of sequence variants, we found that 18 % of the tested population had a change in variant classification. Ninety-two percent of the initial classifications were performed before the publication of the guidelines, with 82 % of reclassifications resulting in a variant downgrade. Most of these were changes from the pathogenic or likely pathogenic category to a variant of uncertain significance. Reclassification frequency was similar across types of cardiomyopathy. ConclusionOur results highlight that a portion of variants get downgraded, and periodic reinterpretation of genetic testing results is necessary for all types of cardiomyopathy—particularly for variant interpretations prior to 2015. Importantly, variant reclassification has potential impact on the clinical management of at-risk patients.

A Real World Observational Study Characterizing Patients With Advanced Prostate Cancer Treated With or Without Androgen Receptor-Pathway-Inhibitor Therapies in Alberta, Canada

BackgroundData are needed to improve the current understanding of clinical management and characteristics of patients with advanced prostate cancer (PC) treated with androgen receptor pathway inhibition (ARPI) therapy. MethodsThis retrospective cohort study using real-world, population-level data from Alberta, Canada included all individuals diagnosed in 2017-2020 with de novo metastatic castration-sensitive PC (mCSPC) or nonmetastatic castration-resistant PC (nmCRPC) who initiated androgen deprivation therapy (ADT). For mCSPC, patients were classified as ARPI-exposed if they received an ARPI within 180 days of initiating ADT, while patients with nmCRPC were classified as ARPI-exposed if they received an ARPI within 2 years of diagnosis. ResultsThis study included 976 patients with mCSPC and 233 with nmCRPC of which 33.5% and 25.3% received an ARPI, respectively. The proportion of patients with mCSPC treated with an ARPI increased considerably for patients diagnosed in 2020 compared to 2017 (56.2% vs. 6.0%). In contrast, the use of ARPI to treat nmCRPC only increased marginally from 2017 to 2019/2020 (19.7% vs. 28.9%). Patients with mHSPC who were ARPI-exposed had longer median survival than patients who were ARPI-naive (38.47 (95% CI = 32.84-NA) vs. 34.19 (95% CI = 33.33-38.83; P = .03)), with a higher proportion of patients surviving to 2-years. For nmCRPC, survival was similar between ARPI-exposed and ARPI-naive. In multivariable analyses, receiving ARPI for mCSPC was associated with younger patient age, more recent diagnoses, fewer comorbidities, a higher number of metastatic sites, referral to a medical oncologist as well as receiving surgery and radiation before ADT. Receiving ARPI for nmCRPC was associated with referral to a medical oncologist, younger age, and more recent diagnoses. ConclusionsOutcome analyses in this population suggest a continued unmet clinical need and complex clinical management pathways. Given that treatment pathways have evolved considerably, continued follow-up to understand the impact of these advancements on patient outcomes are warranted.

Prediction of prognosis using artificial intelligence-based histopathological image analysis in patients with soft tissue sarcomas.

Prompt histopathological diagnosis with accuracy is required for soft tissue sarcomas (STSs) which are still challenging. In addition, the advances in artificial intelligence (AI) along with the development of pathology slides digitization may empower the demand for the prediction of behavior of STSs. In this article, we explored the application of deep learning for prediction of prognosis from histopathological images in patients with STS. Our retrospective study included a total of 35 histopathological slides from patients with STS. We trained Inception v3 which is proposed method of convolutional neural network based survivability estimation. F1 score which identify the accuracy and area under the receiver operating characteristic curve (AUC) served as main outcome measures from a 4-fold validation. The cohort included 35 patients with a mean age of 64 years, and the mean follow-up period was 34 months (2-66 months). Our deep learning method achieved AUC of 0.974 and an accuracy of 91.9% in predicting overall survival. Concerning with the prediction of metastasis-free survival, the accuracy was 84.2% with the AUC of 0.852. AI might be used to help pathologists with accurate prognosis prediction. This study could substantially improve the clinical management of patients with STS.

Novel tubing connectors reduce ECMO circuit thrombosis.

Thrombosis within extracorporeal membrane oxygenation (ECMO) circuits is a common complication that dominates clinical management of patients receiving mechanical circulatory support. Prior studies have identified that over 80% of circuit thrombosis can be attributed to tubing-connector junctions. A novel connector was designed that reduces local regions of flow stagnation at the tubing-connector junction to eliminate a primary source of ECMO circuit thrombi. To compare clotting between the novel connectors and the traditional connectors, both in vitro loops and an in vivo caprine model of long-term (48 h) ECMO were used to generate tubing-connector junction clots. In vitro, the traditional connectors uniformly (9/9) formed large thrombi, while novel connectors formed a small thrombus in only one of nine (p < 0.0001). In the long-term goat ECMO circuits, the traditional connectors exhibited more thrombi (p < 0.04), and these thrombi were more likely to protrude into the lumen of the tubing (p < 0.001). Both in vitro and in vivo validation experiments successfully recreated circuit thrombosis and demonstrate that the adoption of novel connectors can reduce the burden of circuit thrombosis.

Radiographic features and molecular subtypes association of breast cancer in women younger than 40 years old

Background: Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among females, particularly in women under the age of 40 years. However, early detection of breast cancer in this population remains challenging and it tends to present at a later stage with poorer prognosis.Objective: To review mammographic and ultrasonographic findings, pathological features and molecular subtypes of breast cancer in younger than 40-year-old patients diagnosed in King Chulalongkorn Memorial Hospital and to determine which radiological characteristics are associated with molecular subtypes. Materials and Methods: The study included 278 patients aged under 40 years who were diagnosed with breast cancer and underwent mammographic and ultrasonographic studies between January 2009 and December 2019. A retrospective review of mammographic and ultrasonographic findings, histopathological reports as well as biological markers were made. The association of radiological characteristics and molecular subtypes was analyzed by SPSS. Results: In the 278 patients, the most common clinical presentation was palpable mass (268, 96.4%). The common mammographic findings were irregular shape mass (196, 77.8%) with hyperdensity (114, 45.2%) and an obscured margin (99, 39.3%). Presenting of microcalcification is not frequent (122, 48.4%). We found 27 patients with normal mammograms which were later detected in ultrasounds as 25 masses, 1 intraductal lesion and 1 focal duct change. The predominant ultrasonographic features were irregular shape mass (257, 91.5%), an angular margin (89, 31.7%), hypoechogenicity (198, 70.5%), no posterior feature (210, 74.7%) and internal vascularity (170, 60.5%). These radiological characteristics were classified as BI-RADS 5 in 194 lesions (69%). The most common histopathological type was mixed-type carcinoma (143, 50.9%), followed by invasive ductal carcinoma (114, 40.6%). Luminal B was the mostly found in this study (86, 30.6%). The patients frequently presented with stage IIA (91, 32.7%) while 15 patients were detected with an advanced stage at the first presentation. We found that triple negative, HER 2 overexpression and luminal B subtypes were associated with an obscured mass on mammography (p 0.048). Luminal B and HER 2 overexpression subtypes were also associated with the presence of fine pleomorphic microcalcification (p &lt;0.001). Conclusion: In this study, we found an association of the mass margin and suspicious calcification morphology on mammography with molecular subtypes. It would be helpful for further clinical management in young patients. The knowledge can be used for planning appropriate treatments according to molecular subtypes which are associated with these characteristics. However, the precision of cancer treatment is still based on the tissue diagnosis.

Study Of Oral Antihypertension Drug Interactions On Prescribing Geriatric Patients With Hypertension Disease In Outpatient Installations Wilujeng Hospital In The 2021 Period

Drug interactions are changes in the effectiveness or toxicity of one drug due to the presence of other drugs given simultaneously. Drugs that are often involved in potential interactions are drugs that are used daily for the clinical management of elderly patients with chronic diseases. The aim of this study is to determine the incidence of antihypertensive drug interactions in an effort to reduce the incidence of interactions between drugs in elderly patients (Geriatrics). ). Observational descriptive research with a cross-sectional research design with a quantitative approach and a retrospective sampling method in geriatric outpatients with a diagnosis of hypertension and data obtained using statistical methods by calculating the percentage of each part to be analyzed including a general description of antihypertensive drug prescribing. then whether or not there are drug interactions with patient prescriptions at Wilujeng Hospital. The results of the research show that drug interactions at Wilujeng Hospital for the 2021 period showed that the highest number of interactions occurred between hypertension drugs, namely furosemde and ramipril, where 14 incidents occurred or (14%), the interaction that occurred between furosemide and ramipril was synergistic pharmacodynamics. , and the highest use of antihypertensive drugs is amlodipine 43%; furosemide 12%; spironolactone 8%; valsartan 2%; bisoprolol 6%; candesartan 3%; ramipril 5%; captopril11%;hydrocholotiazide4%;irbesartan2%;verapamil2%andpropranolol2%.

What is new in the 5th edition of the World Health Organization classification of mature B and T/NK cell tumors and stromal neoplasms?

The classification of tumors is essential in the diagnosis and clinical management of patients with malignant neoplasms. The World Health Organization (WHO) provides a globally applicable classification scheme of neoplasms and it was updated several times. In this review, we briefly outline the cornerstones of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours on lymphoid neoplasms. As is adopted throughout the 5th edition of the WHO classification of tumors of all organ systems, entities are listed by a hierarchical system. For the first time, tumor-like lesions have been included in the classification, and modifications of nomenclature for some entities, revisions of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities are presented along with mesenchymal lesions specific to the stroma of lymph nodes and the spleen. In addition to specific outlines on constitutional and somatic genetic changes associated with given entities, a separate chapter on germline predisposition syndromes related to hematologic neoplasms has been added.

Using the CLSI rAST breakpoints of Enterobacterales in positive blood cultures

ObjectivesThe objective of this study was to provide the clinic with rapid and accurate results of antimicrobial susceptibility testing for the treatment of patients with bloodstream infections. To achieve this, we applied the Clinical and Laboratory Standards Institute (CLSI) blood culture direct rapid antimicrobial susceptibility test (rAST) to assess the susceptibility of the most common Enterobacterales found in blood cultures. MethodsIn this study, we utilized the CLSI blood culture direct rapid antimicrobial susceptibility test to assess the susceptibility (rAST) of the most common Enterobacterales present in blood cultures. We chose this method for its simplicity in analysis, and our aim was to predict minimum inhibitory concentrations (MICs) using the rAST. As a benchmark, we assumed that Broth Macrodilution method (BMD) results were 100% accurate. For data evaluation, we employed the terms categorical agreement (CA), very major errors (VME), and major errors (ME). ResultsOur findings demonstrate that the CLSI rAST method is reliable for rapidly determining the in vitro susceptibility of Enterobacterales to common antimicrobial drugs in bloodstream infections. We achieved a concordance rate of 90% in classification within a 10-hour timeframe. We identified a total of 112 carbapenem-resistant Enterobacterales (CRE) strains, and there was no significant difference in the detection rate of CRE at 6, 10, and 16 hours. This suggests that CRE can be identified as early as 6 hours. ConclusionThe CLSI rAST is a valuable tool that can be utilized in clinical practice to quickly determine the susceptibility of Enterobacterales to antimicrobial drugs within 10 hours. This capability can greatly assist in the clinical management of patients with bloodstream infections.

Improvement of coronary stent visualization using ultra-high-resolution photon-counting detector CT.

This study aimed to compare the image quality and diagnostic performance of standard-resolution (SR) and ultra-high-resolution (UHR) coronary CT angiography (CCTA) based on photon-counting detector CT (PCD-CT) of coronary stents and explore the best reconstruction kernel for stent imaging. From July 2023 to September 2023, patients were enrolled to undergo CCTA using a dual-source PCD-CT system after coronary angioplasty with stent placement. SR images with a slice thickness/increment of 0.6/0.4 mm were reconstructed using a vascular kernel (Bv48), while UHR images with a slice thickness/increment of 0.2/0.2 mm were reconstructed using vascular kernels of six sharpness levels (Bv48, Bv56, Bv60, Bv64, Bv72, and Bv76). The in-stent lumen diameters were evaluated. Subjective image quality was also evaluated by a 5-point Likert scale. Invasive coronary angiography was conducted in 12 patients (25 stents). Sixty-nine patients (68.0 [61.0, 73.0] years, 46 males) with 131 stents were included. All UHR images had significantly larger in-stent lumen diameter than SR images (p < 0.001). Specifically, UHR-Bv72 and UHR-Bv76 for in-stent lumen diameter (2.17 [1.93, 2.63] mm versus 2.20 [1.93, 2.59] mm) ranked the two best kernels. The subjective analysis demonstrated that UHR-Bv72 images had the most pronounced effect on reducing blooming artifacts, showcasing in-stent lumen and stent demonstration, and diagnostic confidence (p < 0.001). Furthermore, SR and UHR-Bv72 images showed a diagnostic accuracy of 78.3% (95% confidence interval [CI]: 56.3%-92.5%) and 88.0% (95%CI: 68.8%-97.5%), respectively. UHR CCTA by PCD-CT leads to significantly improved visualization and diagnostic performance of coronary stents, and Bv72 is the optimal reconstruction kernel showing the stent struts and in-stent lumen. The significantly improved visualization of coronary stents using ultra-high resolution CCTA could increase the diagnostic accuracy for in-stent restenosis and avoid unnecessary invasive quantitative coronary angiography, thus changing the clinical management for patients after percutaneous coronary intervention. Coronary stent imaging is challenging with energy-integrating detector CT due to "blooming artifacts." UHR images using a PCD-CT enhanced coronary stent visualization. UHR coronary stent imaging demonstrated improved diagnostic accuracy in clinical settings.

The clinical significance of mitochondrial calcium uniporter in gastric cancer patients and its preliminary exploration of the impact on mitochondrial function and metabolism.

The objective of this study is to elucidate the influence of MCU on the clinical pathological features of GC patients, to investigate the function and mechanism of the mitochondrial calcium uptake transporter MCU in the initiation and progression of GC, and to explore its impact on the metabolic pathways and biosynthesis of mitochondria. The ultimate goal is to identify novel targets and strategies for the clinical management of GC patients. Tumor and adjacent tissue specimens were obtained from 205 patients with gastric cancer, and immunohistochemical tests were performed to assess the expression of MCU and its correlation with clinical pathological characteristics and prognosis. Data from TCGA, GTEx and GEO databases were retrieved for gastric cancer patients, and bioinformatics analysis was utilized to investigate the association between MCU expression and clinical pathological features. Furthermore, we conducted an in-depth analysis of the role of MCU in GC patients. We investigated the correlation between MCU expression in GC and its impact on mitochondrial function, metabolism, biosynthesis, and immune cells. Additionally, we studied the proteins or molecules that interact with MCU. Our research revealed high expression of MCU in the GC tissues. This high expression was associated with poorer T and N staging, and indicated a worse disease-free survival period. MCU expression was positively correlated with mitochondrial function, mitochondrial metabolism, nucleotide, amino acid, and fatty acid synthesis metabolism, and negatively correlated with nicotinate and nicotinamide metabolism. Furthermore, the MCU also regulates the function of the mitochondrial oxidative respiratory chain. The MCU influences the immune cells of GC patients and regulates ROS generation, cell proliferation, apoptosis, and resistance to platinum-based drugs in gastric cancer cells. High expression of MCU in GC indicates poorer clinical outcomes. The expression of the MCU are affected through impacts the function of mitochondria, energy metabolism, and cellular biosynthesis in gastric cancer cells, thereby influencing the growth and metastasis of gastric cancer cells. Therefore, the mitochondrial changes regulated by MCU could be a new focus for research and treatment of GC.

Clinical Characteristics, Management and Outcomes in Cardiogenic Shock: insights from a high-volume Italian Cardiac Intensive Care Unit

Cardiogenic shock (CS) is a life-threatening condition. We aim to evaluate clinical characteristics, management and complication rate of patients with CS admitted in a high-volume hospital in Italy. We retrospectively reviewed the clinical, echocardiographic and laboratory data, therapeutic management and outcomes of patients with CS admitted to the Policlinico Gemelli (Rome) between January 1, 2020, and January 1, 2023. ​ We included 96 patients (median age 71 years, IQR 60-79; 65 [68%] males), of whom 49 patients (51%) presented CS secondary to acute myocardial infarction and 60 (63%) with a de-novo presentation of CS. Dobutamine was the most frequently used inotrope and noradrenaline the most frequently used vasopressor (adopted in 56% and 82% of cases respectively). Forty-five (47%) patients died during the hospitalization. Non-survivors were older, presented a higher inflammatory burden at admission, elevated lactate levels, a greater increase in lactate levels, higher left ventricular filling pressures and worse right ventricular function. C-Reactive Protein (CRP) levels [odd ratio (OR) 1.03, 95% confidence interval (CI) [1.00;1.04], p=0.027), lactate levels at admission (OR 3.49, 95% CI [1.59;7.63], p=0.02) and increase in lactate levels (OR 2.8, 95% CI [1.37;5.75], p=0.005) were independent predictors of in-hospital all cause death. Our data contribute to assess the regional variations in management and outcomes of patients with CS. We observed a high mortality and complication rate. Lactate acidosis and CRP measured at admission, may help in identifying patients at higher risk of adverse in-hospital outcomes.

A CT-based integrated model for preoperative prediction of occult lymph node metastasis in early tongue cancer.

Occult lymph node metastasis (OLNM) is an essential prognostic factor for early-stage tongue cancer (cT1-2N0M0) and a determinant of treatment decisions. Therefore, accurate prediction of OLNM can significantly impact the clinical management and outcomes of patients with tongue cancer. The aim of this study was to develop and validate a multiomics-based model to predict OLNM in patients with early-stage tongue cancer. The data of 125 patients diagnosed with early-stage tongue cancer (cT1-2N0M0) who underwent primary surgical treatment and elective neck dissection were retrospectively analyzed. A total of 100 patients were randomly assigned to the training set and 25 to the test set. The preoperative contrast-enhanced computed tomography (CT) and clinical data on these patients were collected. Radiomics features were extracted from the primary tumor as the region of interest (ROI) on CT images, and correlation analysis and the least absolute shrinkage and selection operator (LASSO) method were used to identify the most relevant features. A support vector machine (SVM) classifier was constructed and compared with other machine learning algorithms. With the same method, a clinical model was built and the peri-tumoral and intra-tumoral images were selected as the input for the deep learning model. The stacking ensemble technique was used to combine the multiple models. The predictive performance of the integrated model was evaluated for accuracy, sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC-ROC), and compared with expert assessment. Internal validation was performed using a stratified five-fold cross-validation approach. Of the 125 patients, 41 (32.8%) showed OLNM on postoperative pathological examination. The integrated model achieved higher predictive performance compared with the individual models, with an accuracy of 84%, a sensitivity of 100%, a specificity of 76.5%, and an AUC-ROC of 0.949 (95% CI [0.870-1.000]). In addition, the performance of the integrated model surpassed that of younger doctors and was comparable to the evaluation of experienced doctors. The multiomics-based model can accurately predict OLNM in patients with early-stage tongue cancer, and may serve as a valuable decision-making tool to determine the appropriate treatment and avoid unnecessary neck surgery in patients without OLNM.

Null Mismatch Repair Proteins Expression Reveals the Temporal Molecular Events in Lynch Syndrome-Related Cancers.

The immunohistochemical assessment of mismatch repair (MMR) proteins represents a pivotal screening tool for identifying Lynch syndrome (LS)-related cancers, as the loss of their expression often indicates MMR dysfunction associated with genetic or epigenetic alterations. Frequently, LS-related colorectal cancers present germline pathogenic variants in the MLH1 or MSH2 genes, which result in the simultaneous immunohistochemical loss of MLH1 and PMS2 or MSH2 and MSH6 proteins expression, respectively. Less commonly observed is the single involvement of the MSH6 or PMS2 proteins expression, indicative of the presence of germline pathogenic variants in the corresponding genes. Extremely rarely reported are the null immunohistochemistry phenotypes represented by the complete loss of expression of all MMR proteins. The molecular mechanisms contributing to the raising of this latter uncommon immunohistochemical phenotype are derived from the combination of pathogenic germline variants in MMR genes with the somatic hypermethylation of the MLH1 gene promoter. This study focuses on elucidating the molecular cascade leading to the development of the null immunohistochemical phenotype, providing valuable insights into understanding the sequential molecular events driving the LS-associated tumorigenesis, which may have pivotal implications in the clinical management of patients with LS-related cancers.

Understanding the potential role of whole genome sequencing (WGS) in managing patients with gonorrhoea: A systematic review of WGS use on human pathogens in individual patient care

The utility of whole genome sequencing (WGS) to inform sexually transmitted infection (STI) patient management is unclear. Timely WGS data might support clinical management of STIs by characterising epidemiological links and antimicrobial resistance profiles. We conducted a systematic review of clinical application of WGS to any human pathogen that may be transposable to gonorrhoea. We searched six databases for articles published between 01/01/2010-06/02/2023 that reported on real/near real-time human pathogen WGS to inform clinical intervention. All article types from all settings were included. Findings were analysed using narrative synthesis. We identified 12,179 articles, of which eight reported applications to inform tuberculosis (n=7) and gonorrhoea (n=1) clinical patient management. WGS data were successfully used as an adjunct to clinical and epidemiological data to enhance contact-tracing (n=2), inform antimicrobial therapy (n=5) and identify cross-contamination (n=1). WGS identified gonorrhoea transmission chains that were not established via partner notification. Future applications could include insights into pathogen exposure detected within sexual networks for targeted patient management. While there was some evidence of WGS use to provide individualised tuberculosis and gonorrhoea treatment, the eight identified studies contained few participants. Future research should focus on testing WGS intervention effectiveness and examining ethical considerations of STI WGS use.

Cardiac MRI for clinical dilated cardiomyopathy: Improved diagnostic power via combined T1, T2, and ECV

IntroductionEarly diagnosis of patients with dilated cardiomyopathy (DCM) remains challenging. Cardiac MR can correlate myocardial changes with their pathological basis. There have been some previous studies on the effect of T1 mapping in DCM, but there is limited data on the incremental value of T2 mapping for DCM in routine clinical practice. This study will examine whether the combination of MRI T1 and T2 mapping offers greater advantages in the diagnosis of DCM. MethodsThe study included 28 patients with DCM and 21 healthy controls. CMR evaluation included late gadolinium enhancement (LGE), T1 mapping, extracellular volume (ECV) fraction and T2 mapping. The DCM group was divided into LGE (+) and LGE (−) subgroups. The main modes of LGE are subendocardial, midwall, subepicardial, or transmural. T1 values, T2 values, and ECV in the 16 segments myocardial levels were measured by post-processing software. Student's t-tests or Mann–Whitney U test was used to compare between two groups, and one-way ANOVA or Kruskal–Wallis H test was used to compare between multiple groups, with p values corrected by Bonferroni. The difference was considered statistically significant at P < 0.05. ROC curve analysis was used to compare the area under the curve (AUC) of each index and its combined value, and the cut-off value, sensitivity and specificity were determined by Jordan's index. ResultsMean native myocardial T1, ECV and T2 were significantly higher in the DCM group compared to controls (p ≤ 0.001, respectively). The best cut-off values for T1, T2 and ECV to discriminate DCM from controls were 1184 ms, 40.9 ms and 29.2%, respectively. The AUC of T1, ECV and T2 were 0.87, 0.89, and 0.83, respectively. The combined AUC of the three values was 0.96. ConclusionNative T1 value and ECV overcome some of the limitations of LGE, and the T2 helps to understand the extent of myocardial damage. The combination of T1 and T2 mapping techniques can reveal fibrotic and oedematous changes in the early stages of DCM, providing a more comprehensive assessment of DCM and better guidance for individualised clinical management of patients. Implications for practiceWe suggest that the addition of T2 mapping to the routine CMR examination of patients with suspected DCM, and the combined assessment of T1mapping and T2 mapping can provide complementary information about the disease and improve the early diagnosis of DCM.