Clinical Management Of Patients Research Articles

A Novel Next-Generation Sequencing Assay for the Identification of BCR::ABL1 Transcript Type and Accurate and Sensitive Detection of TKI-Resistant Mutations.

The clinical management of chronic myeloid leukemia (CML) patients requires the identification of the type of BCR::ABL1 transcript at diagnosis and the monitoring of its expression and potential tyrosine kinase inhibitor (TKI) resistance mutations during treatment. Detection of resistant mutation requires transcript type-specific amplification of BCR::ABL1 from RNA. In this study, a custom RNA-based next-generation sequencing (NGS) assay (Dup-Seq BCR::ABL1) that enables (a) the identification of BCR::ABL1 transcript type and (b) the detection of resistance mutations from common and atypical BCR::ABL1 transcript types was developed and validated. The assay design covers BCR exon 1 to ABL1 exon 10 and employs duplicate PCR amplification for error correction. The custom data analysis pipeline enables breakpoint determination and overlapped mutation calling from duplicates, which minimizes the low-level mutation artifacts. This study demonstrates that this novel assay achieves high accuracy (positive percent agreement (PPA) for fusion: 98.5%; PPA and negative percent agreement (NPA) for mutation at 97.8% and 100.0%, respectively) and sensitivity (limit of detection (LOD) for mutation detection at 3% from 10 000 copies of BCR::ABL1 input). The Dup-Seq BCR::ABL1 assay not only allows for the identification of BCR::ABL1 typical and atypical transcript types and accurate and sensitive detection of TKI-resistant mutations but also simplifies molecular testing work flow for the clinical management of CML patients.

A Multicenter Cross-Sectional Study of the Swiss Cohort of LAMA2-Related Muscular Dystrophy.

LAMA2-related muscular dystrophy (LAMA2-RD) is an autosomal-recessive disorder and one of the most common congenital muscular dystrophies. Due to promising therapies in preclinical development, there is an increasing effort to better define the epidemiology and natural history of this disease. The present study aimed to describe a well-characterized baseline cohort of patients with LAMA2-RD in Switzerland. The study used data collected by the Swiss Registry for Neuromuscular Disorders (Swiss-Reg-NMD). Diagnostic findings were derived from genetics, muscle biopsy, creatine kinase-level and electrophysiological testing, as well as from brain MRIs. Further clinical information included motor assessments (CHOP INTEND, MFM20/32), joint contractures, scoliosis, ophthalmoplegia, weight gain, feeding difficulties, respiratory function, cardiac investigations, EEG findings, IQ and schooling. Eighteen patients with LAMA-RD were included in the Swiss-Reg-NMD as of May 2023 (age at inclusion into the registry: median age 8.7 years, range 1 month - 31 years F = 8, M = 10). Fourteen patients presented with the severe form of LAMA2-RD (were never able to walk; CMD), whereas four patients presented with the milder form (present or lost walking capability; LGMD). All patients classified as CMD had symptoms before 12 months of age and 11/14 before the age of six months. 15 carried homozygous or compound heterozygous pathogenic or likely pathogenic variants in LAMA2 and two were homozygous for a variant of unknown significance (one patient unknown). Brain MRI was available for 14 patients, 13 had white matter changes and 11 had additional structural abnormalities, including cobblestone malformations, pontine hypoplasia and an enlarged tegmento-vermial angle not reported before. This study describes the Swiss cohort of patients with LAMA2-RD and gives insights into measuring disease severity and disease progression, which is important for future clinical trials, as well as for a better clinical understanding and management of patients with LAMA2-RD.

Clinical implication of sarcopenia in patients with acute decompensated heart failure: Design and rationale.

Sarcopenia is widely recognized as an age-related syndrome that involves a progressive loss of skeletal muscle mass and muscle strength. Many studies have shown that sarcopenia is associated with disease severity and exercise intolerance, as well as an independent predictor of mortality in patients with chronic heart failure. However, there is little research on the impact of sarcopenia on patients hospitalized with acute decompensated heart failure (ADHF). This is a prospective, multicentre, observational cohort study. Enrolment of at least 500 participants adults aged over 18years hospitalized for ADHF is planned, with a minimum of 195 cases each for patients with and without sarcopenia. Each patient is followed up for 6months, 1year, 2years or until the occurrence of endpoint. The primary clinical outcome is all-cause mortality at 6months. Other clinical outcomes of interest include cardiovascular mortality, all-cause hospitalization, heart failure hospitalization and survival time from enrolment to event occurrence. The sympathetic nervous activity, psychosocial factors, quality of life, physical function, and physical activity will be assessed and recorded at baseline. This study will examine the correlation between sarcopenia and prognosis in different subgroups of patients, and explore the additive effect of different comorbidities and sarcopenia on prognosis in patients with ADHF. This study will provide important information and evidence on the clinical aspects of sarcopenia in patients with ADHF, potentially contributing to accurate risk stratification and optimal clinical management for patients with ADHF. (URL: https://www. gov); Unique identifier: NCT06298825.

Cardiogenic shock severity predicts bleeding events in patients with temporary mechanical circulatory support.

Data on shock severity and bleeding events in patients with temporary mechanical circulatory support (tMCS) are limited. We investigated the relationship between the Society for Cardiovascular Angiography and Interventions (SCAI) shock stage classification and bleeding events in patients with tMCS. We evaluated the data of 285 consecutive patients with tMCS who were admitted to our institution between June 2019 and May 2022. At the time of tMCS initiation, 81 patients (28.4%) were in SCAI stage A, 38 (13.3%) in stage B, 69 (24.2%) in stage C, 33 (11.6%) in stage D, and 64 (22.5%) in stage E. Multivariable logistic regression modeling was used to assess the association between the SCAI shock stage and in-hospital bleeding events. In-hospital bleeding occurred in 100 patients (35.1%). The bleeding event rate increased incrementally across the SCAI shock stages (stage A, 11.1%; stage B, 15.8%; stage C, 37.7%; stage D, 54.6%; stage E, 64.1%). In-hospital bleeding was associated with the SCAI shock stage (p < 0.001). Compared with stage A, the adjusted odds ratios for in-hospital bleeding were 1.48 (95% confidence interval [CI] 0.47-4.66), 6.47 (95% CI 2.61-10.66), 11.59 (95% CI 3.77-35.64), and 7.85 (95% CI 2.51-24.55) for stages B, C, D, and E, respectively. The SCAI shock stage predicted subsequent bleeding events in patients with tMCS. This simple scheme may be useful for tailored risk-based clinical assessment and management of patients with tMCS.

Management of Psychiatric Diagnoses in Reversible Cerebral Vasoconstriction Syndrome: The Dangers of Worsening Pathology with Serotonergic Medications: A Case Report and Literature Review.

Reversible cerebral vasoconstriction syndrome (RCVS) represents a group of conditions that show reversible multifocal narrowing or constriction of the cerebral arteries that supply blood to the brain. The initial manifestation of RCVS often includes a "thunderclap" headache that is sudden, severe, and often disabling. Stimulants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and antipsychotics with serotonergic activity can alter the cerebral arterial tone, trigger vasoconstriction, and place patients at risk of a cerebrovascular accident. Thus, psychiatric medications are commonly discontinued on admission for RCVS, and psychiatry is often consulted for input on acute medication management and longitudinal treatment options. Currently, there is a dearth of literature on managing psychiatric medications in RCVS, resulting in variable practice patterns that place patients at risk of withdrawal, decompensation, and relapse. In this article, we provide a case example and aim to consolidate the limited data surrounding the management of psychiatric illness with comorbid RCVS in our discussion. There is a clear concern about worsening and even potentially lethal consequences due to serotonin or stimulant-induced vasospasm both during an acute episode and in long-term management of RCVS. We discuss the underlying pathophysiologic mechanisms proposed for serotonergic-, noradrenergic-, and dopaminergic-induced cerebral vasospasm and how this correlates with the clinical management of patients on psychiatric medications. These data will then be organized to create a risks versus benefits outline to equip psychiatrists to make decisions about when to stop and when to restart psychiatric medications in the setting of RCVS.

Évaluation en vie réelle du parcours de soins des patients éligibles à un traitement par axicabtagene ciloleucel : cohorte multicentrique IMPA-CT

The arrival of CAR-T cell treatments in Europe in 2018 has considerably changed the clinical and logistical management of lymphoma patients. The aim of this study is to evaluate pathways of patients eligible for axicabtagene ciloleucel (axi-cel), particularly previously and afterwards of its administration, stages that are currently poorly documented in the literature. Ninety-eight patients from eleven French qualified centers eligible for axi-cel treatment between June 2020 and February 2021 were retrospectively included. Of all the stages in the care pathway evaluated, the median time observed between relapse after the previous line and prescription of axi-cel was 27days, and the median time between the multidisciplinary consultation meeting and axi-cel administration was 63days. The two main methods of discharge from hospital were a return home (65% of cases) or hospitalisation in a rehabilitation unit (20% of cases). Among all the geographical and organizational characteristics assessed, no factor was found to have a significant impact on the time length of the patient's journey, apart from the patient capacity of the qualified center, and the origin of the patient's referral (coming from a qualified or a referral center). Since the study was carried out, the number of qualified centers has continued to rise, improving territorial coverage and access to treatment.

Level of Compliance with Spanish Guideline Recommendations in the Management of Asthma.

To describe the clinical management of asthmatic patients and the level of compliance with the Guía Española para el Manejo del Asma (GEMA, Spanish Guidelines for Asthma Management) in the influential al area of Virgen de la Victoria University Hospital, Málaga (Spain). Descriptive, cross-sectional study in asthma patients from the Virgen de la Victoria University Hospital influential area, Málaga (Spain). Asthma Control Test (ACT) results, demographic and clinical characteristics, and GEMA indicators of quality asthma care were obtained from each participating patient. Two hundred and eighty-eight patients (64.2% woman, mean age 48.6 years) were included in the study. The evaluation of the level of compliance with the GEMA quality indicators showed that in 20.8% of the patients the diagnosis of asthma was confirmed by spirometry and bronchodilator test, and 52.5% of the patients with suspicion of allergic asthma performed a sensitization test. Among the smoker patients, 76.3% were recommended to stop smoking; 14.2% of the patients received a paper-based educational plan. Regarding asthma treatment, 92.3% of patients with persistent asthma received inhaled glucocorticoids (IGC). IGC and LABA were the most common treatments for asthma, used in combination (ICG + LABA) in 139 (48.3%) patients; 32.6% discontinued SABA treatment during the study period. Asthma was well controlled in 54.9% of the patients (ACT score ≥20), and 13.9% of the patients registered exacerbations during the previous year with a mean (SD) of 1.38 (0.74) events. Most of the GEMA quality indicators of asthma care are not followed in real-world clinical practice. Specialists select the best option among the available treatments but there is an unmet need for training plans in other relevant aspects, such as diagnosis and/or disease monitoring.

Enhanced machine learning models for predicting one-year mortality in individuals suffering from type A aortic dissection

ObjectiveThe study objective was to develop and validate an interpretable machine learning model to predict 1-year mortality in patients with type A aortic dissection, improving risk classification and aiding clinical decision-making. MethodsWe enrolled 289 patients with type A aortic dissection, dividing them into a training cohort (202 patients) and a validation cohort (87 patients). The Least Absolute Shrinkage and Selection Operator method with 10-fold cross-validation identified 8 key factors related to 1-year mortality. The Treebag model's performance was assessed using accuracy, F1-Score, Brier score, area under the curve, and area under the precision-recall curve with calibration and clinical utility evaluated through decision curves. Shapley Additive Explanations analysis determined the most influential predictors. ResultsThe Treebag model outperformed others, achieving a Brier score of 0.128 and an area under the curve of 0.91. Key risk factors included older age and elevated white blood cell count, whereas higher systolic blood pressure, lymphocyte, carbon dioxide combining power, eosinophil, β-receptor blocker use, and surgical intervention were protective. A web-based application, TAAD One-Year Prognostic Risk Assessment Web, was developed for clinical use (available at https://taad-1year-mortality-predictor.streamlit.app/). This platform allows for the prediction of 1-year mortality in patients with type A aortic dissection based on the identified predictive factors, facilitating clinical decision-making and patient management. ConclusionsThe Treebag machine learning model effectively predicts 1-year mortality in patients with type A aortic dissection, stratifying risk profiles. Key factors for enhancing survival include surgical intervention, β-blocker administration, and management of systolic blood pressure, lymphocyte, carbon dioxide combining power, eosinophil, and white blood cell levels, offering a valuable tool for improving patient outcomes.

Establishment of Reference Intervals for Common Renal and Liver Function Parameters in Healthy Adults in Mogadishu, Somalia: A Cross-Sectional Study.

Reference intervals (RIs) are crucial for the accurate interpretating of laboratory test results in clinical settings, serving as benchmarks for evaluating individual health status. This study investigates the influence of sex and age on common liver function tests (LFTs) and renal function tests (RFTs) in healthy adults in Mogadishu, Somalia. A community-based cross-sectional study was carried out from October 2022 to January 2023 on a randomly selected sample of 255 healthy participants from Mogadishu, Somalia. Approximately 5 mL of whole blood was collected from each participant and processed screening of hepatitis B and C, and human immunodeficiency virus, and then biochemical analyses were conducted for common liver and kidney parameters. The study found significant sex and age-related differences in the measured LFTs and RFTs parameters. For LFTs, males had higher levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared to females (ALT: 11.5 vs 7.5 U/L; AST: 25.5 vs 19.1 U/L; both p < 0.001). Age-related differences were also observed, with individuals aged 30 and above had higher levels of ALT and AST compared to those aged 18-29 (ALT: 10.9 vs 8.5 U/L; AST: 24.3 U/L vs 21.0 U/L, both p < 0.001). For RFTs, males had higher levels of creatinine (0.9 vs 0.7 mg/dL), urea (23.1 vs 16.1 mg/dL), and uric acid (5.2 vs 4.2 mg/dL) than females, all with p < 0.001. The study established population specific RIs for common liver and renal function parameters and revealed significant variations across sex and age groups. These findings underscore the importance of developing and using local RIs to ensure accurate clinical interpretation and effective patient management. Further research with larger sample sizes and in diverse regions of Somalia is highly recommended.

Clinical Management of Hospitalized Patients With High-Consequence Infectious Diseases in England.

Infectious disease physicians in England have been diagnosing and managing occasional cases of viral hemorrhagic fever since 1971, including the United Kingdom's first case of Ebola virus disease in 1976. Specialist isolation facilities to provide safe and effective care have been present since that time. Following the emergence of Middle East respiratory syndrome (MERS) in 2012, and the avian influenza A (H7N9) outbreak in 2013, and the 2014-2016 Ebola virus disease outbreak in West Africa, clinical and public health preparedness and response pathways in England have been strengthened for these types of diseases, now called high-consequence infectious diseases (HCIDs). The HCID program, led by NHS England and Public Health England between 2016 and 2018, helped to deliver these enhancements, which have since been used on multiple occasions for new UK cases and outbreaks of MERS, mpox, avian influenza, and Lassa fever. Additionally, HCID pathways were activated for COVID-19 during the first 3 months of 2020, before the pandemic had been declared and little was known about COVID-19 but HCID status had been assigned temporarily to COVID-19 as a precaution. The HCID program also led to the commissioning of a network of new airborne HCID treatment centers in England, to supplement the existing network of contact HCID treatment centers, which includes the United Kingdom's only 2 high-level isolation units. In this case study, the authors describe the airborne and contact HCID treatment center networks in England, including their formation and structures, their approach to safe and effective clinical management of patients with HCIDs in the United Kingdom, and challenges they may face going forward.

The Trend of Application of Renal Mass Biopsy for Clinical Management of Patients with Renal Mass Lesions

The Trend of Application of Renal Mass Biopsy for Clinical Management of Patients with Renal Mass Lesions

Disability independent of cerebral white matter demyelination in progressive multiple sclerosis

The pathogenic mechanisms contributing to neurological disability in progressive multiple sclerosis (PMS) are poorly understood. Cortical neuronal loss independent of cerebral white matter (WM) demyelination in myelocortical MS (MCMS) and identification of MS patients with widespread cortical atrophy and disability progression independent of relapse activity (PIRA) support pathogenic mechanisms other than cerebral WM demyelination. The three-dimensional distribution and underlying pathology of myelinated T2 lesions were investigated in postmortem MCMS brains. Postmortem brain slices from previously characterized MCMS (10 cases) and typical MS (TMS) cases (12 cases) were co-registered with in situ postmortem T2 hyperintensities and T1 hypointensities. T1 intensity thresholds were used to establish a classifier that differentiates MCMS from TMS. The classifier was validated in 36 uncharacterized postmortem brains and applied to baseline MRIs from 255 living PMS participants enrolled in SPRINT-MS. Myelinated T2 hyperintensities in postmortem MCMS brains have a contiguous periventricular distribution that expands at the occipital poles of the lateral ventricles where a surface-in gradient of myelinated axonal degeneration was observed. The MRI classifier distinguished pathologically confirmed postmortem MCMS and TMS cases with an accuracy of 94%. For SPRINT-MS patients, the MRI classifier identified 78% as TMS, 10% as MCMS, and 12% with a paucity of cerebral T1 and T2 intensities. In SPRINT-MS, expanded disability status scale and brain atrophy measures were similar in MCMS and TMS cohorts. A paucity of cerebral WM demyelination in 22% of living PMS patients raises questions regarding a primary role for cerebral WM demyelination in disability progression in all MS patients and has implications for clinical management of MS patients and clinical trial outcomes in PMS. Periventricular myelinated fiber degeneration provides additional support for surface-in gradients of neurodegeneration in MS.

Obesity and cardiovascular disease: an ESC clinical consensus statement.

The global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease. Despite the increasingly appreciated link between obesity and a broad range of cardiovascular disease manifestations including atherosclerotic disease, heart failure, thromboembolic disease, arrhythmias, and sudden cardiac death, obesity has been underrecognized and sub-optimally addressed compared with other modifiable cardiovascular risk factors. In the view of major repercussions of the obesity epidemic on public health, attention has focused on population-based and personalized approaches to prevent excess weight gain and maintain a healthy body weight from early childhood and throughout adult life, as well as on comprehensive weight loss interventions for persons with established obesity. This clinical consensus statement by the European Society of Cardiology discusses current evidence on the epidemiology and aetiology of obesity; the interplay between obesity, cardiovascular risk factors and cardiac conditions; the clinical management of patients with cardiac disease and obesity; and weight loss strategies including lifestyle changes, interventional procedures, and anti-obesity medications with particular focus on their impact on cardiometabolic risk and cardiac outcomes. The document aims to raise awareness on obesity as a major risk factor and provide guidance for implementing evidence-based practices for its prevention and optimal management within the context of primary and secondary cardiovascular disease prevention.

Obesity and cardiovascular disease: an ESC clinical consensus statement.

The global prevalence of obesity has more than doubled over the past four decades, currently affecting more than a billion individuals. Beyond its recognition as a high-risk condition that is causally linked to many chronic illnesses, obesity has been declared a disease per se that results in impaired quality of life and reduced life expectancy. Notably, two-thirds of obesity-related excess mortality is attributable to cardiovascular disease. Despite the increasingly appreciated link between obesity and a broad range of cardiovascular disease manifestations including atherosclerotic disease, heart failure, thromboembolic disease, arrhythmias, and sudden cardiac death, obesity has been underrecognized and sub-optimally addressed compared with other modifiable cardiovascular risk factors. In the view of major repercussions of the obesity epidemic on public health, attention has focused on population-based and personalized approaches to prevent excess weight gain and maintain a healthy body weight from early childhood and throughout adult life, as well as on comprehensive weight loss interventions for persons with established obesity. This clinical consensus statement by the European Society of Cardiology discusses current evidence on the epidemiology and aetiology of obesity; the interplay between obesity, cardiovascular risk factors and cardiac conditions; the clinical management of patients with cardiac disease and obesity; and weight loss strategies including lifestyle changes, interventional procedures, and anti-obesity medications with particular focus on their impact on cardiometabolic risk and cardiac outcomes. The document aims to raise awareness on obesity as a major risk factor and provide guidance for implementing evidence-based practices for its prevention and optimal management within the context of primary and secondary cardiovascular disease prevention.

Clinical characteristics, management, and survival of retinoblastoma patients: a five-year study at an Indonesian tertiary eye hospital

Background Studies on the clinical characteristics of retinoblastoma in Indonesia have been limited, even though retinoblastoma is the most common pediatric ocular malignancy worldwide and the second-most common pediatric malignancy in Indonesia. The estimated patient survival rate in lower-middle-income countries is 77%, and survival is highly dependent on early diagnosis and therapy. Objective To identify the clinical characteristics of retinoblastoma in patients at the Cicendo National Eye Hospital, as an Indonesian tertiary eye hospital. Methods This retrospective, observational study included pediatric patients &lt;18 years of age diagnosed with retinoblastoma at the Cicendo National Eye Hospital, Bandung, West Java, between January 2018 and December 2022. We collected patients’ medical record data on age, gender, laterality, chief complaints, stage of disease, grouping, histopathologic features, therapy, and survival. Results Of 247 retinoblastoma patients (328 eyes) enrolled, 53.85% presented at 1-2 years of age and 50.61% were males. Patients mostly presented with unilateral (67.21%) retinoblastoma, leukocoria (51.82%) as the chief complaint, and classified as International Retinoblastoma Staging System (IRSS) stage III (33.20%). Tumors were mostly intraocular (58.84%), particularly group E (39.02%). Most tumors showed undifferentiated (45.43%) and high-risk features (54.27%). Most eyes were treated with combination therapy (74.09%), particularly local and systemic therapy (59.45%). Survival was noted at 18.62% of patients, but 62.75% of patients were lost to follow-up. Conclusion Most patients present with advanced retinoblastoma. Most histopathological results shows undifferentiated and high-risk features of the tumor. Delays in diagnosis and therapy may occur due to a lack of awareness and knowledge regarding clinical manifestations of retinoblastoma, which leads to worse prognosis.

Clinical management of patients diagnosed with acute myeloid leukemia treated with venetoclax in combination with hypomethylating agents after achieving a response: a real-life study.

Although there is an approved indication for venetoclax and hypomethylating agents (VenHMA) and its use in different AML settings will be expanded in the following years, the management of the adverse events (AEs) lacks of harmonized algorithms during treatment of these patients. We have studied the incidence of relevant AEs of 43 patients who achieved a response to VenHMA and its management. Median overall survival of our cohort was 19months. No patients discontinued treatment due to AEs after C3D1, Regarding severe AEs, high rates of grade 4 neutropenia (97.6%) and grade 4 thrombocytopenia (65.1%) were observed. Severe infectious AEs rate was 16%. Due to severe myelotoxicity, most patients required a progressive dose reduction of both venetoclax and hypomethylating agents during follow-up, being 87.8% at C6D1. Transfusional dependence rate was 91% and G-CSF was prescribed to 86% of the patients. Finally, there was not a significant difference in hemoglobin, platelets and absolute neutrophil count after achieving complete response comparing paired samples during follow-up, although cytopenia rate was high during initial follow-up. We conclude that dose reduction of VenHMA after achieving a response in patients diagnosed with AML is required in most patients and essential to avoid prolonged cytopenia-related adverse events and a rapid and standardized method on how to perform it might decrease the AEs rate.

Associations between sleep disorders and clinical outcomes of patients with primary biliary cholangitis

PurposePrimary biliary cholangitis (PBC) is a chronic autoimmune liver disease characterized by a range of symptoms, including sleep disturbances. The present study aimed to investigate the prevalence of sleep disorders and the associations between sleep disorders and clinical outcomes in PBC. Patients and methodsWe enrolled 177 patients with PBC and 165 healthy controls (age- and sex-matched). Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). Demographic and clinical data were collected from comprehensive clinical records to investigate whether sleep disorder was correlated with disease severity, therapeutic response and liver cirrhosis. ResultsThe prevalence of sleep disorders in patients with PBC (50.8 ​%) was significantly higher than healthy controls (18.2 ​%). Patients with sleep disorders presented with higher levels of laboratory parameters including globulin (GLO), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL) and immunoglobulin M (IgM), as well as higher ratio of poor therapeutic response and liver cirrhosis (p ​< ​0.05). There was a positive correlation between global PSQI score and AST, ALP, GGT, TBIL, DBIL and IgM in patients with PBC. Patients with poor therapeutic response and liver cirrhosis in PBC had a higher proportion of sleep disorders and more chaotic sleep patterns, whereas a stronger correlation between sleep quality and laboratory parameters was found in patients with liver cirrhosis. ConclusionsSleep disorders were prevalent and manifested as adverse effects in PBC. Assessment of sleep quality and intervention were essential to the overall clinical management of patients with PBC.

Evaluation of 68Ga-FAPI PET/CT and 18F-FDG PET/CT for the diagnosis of recurrent colorectal cancers

ObjectiveThe present study aimed to compare the diagnostic value of gallium-68-labeled fibroblast activation protein inhibitor positron emission tomography/computed tomography (68Ga-FAPI PET/CT) and fluorine-18-labeled fluorodeoxyglucose PET/CT (18F-FDG PET/CT) for detecting recurrent colorectal cancers (CRCs). Materials and MethodsFifty-six patients (age: 18–80 years, 31 men and 25 women) with suspected recurrent CRC were enrolled and underwent 18F-FDG PET/CT and 68Ga-FAPI PET/CT sequentially within 1 week. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were estimated and compared between the two modalities by using Student’s t-test. The Wilcoxon signed-rank test was used to compare peritoneal carcinoma index (PCI) scores between the two imaging modalities. Results68Ga-FAPI PET/CT showed higher sensitivity for detecting recurrence (93 % vs. 79 %); lymph node metastasis (89 % vs. 78 %), particularly peritoneal lymph node metastasis (92 % vs. 63 %); and metastatic implantation on the intestinal wall (100 % vs. 25 %) compared to 18F-FDG PET/CT. However, 68Ga-FAPI PET/CT showed lower sensitivity for detecting bone metastasis (67 % vs. 100 %). The mean SUVmax values of peritoneal metastases and metastatic implantation on the intestinal wall were 4.28 ± 2.70 and 7.58 ± 1.66 for 18F-FDG PET/CT and 5.66 ± 1.97 and 6.70 ± 0.25 for 68Ga-FAPI PET/CT, respectively. Furthermore, 68Ga-FAPI PET/CT showed significantly higher TBR for peritoneal metastatic lesions (4.22 ± 1.47 vs. 1.41 ± 0.89, p < 0.0001) and metastatic implantation on the intestinal wall (5.63 ± 1.24 vs. 2.20 ± 0.5, p = 0.02) compared to 18F-FDG PET/CT. For the same patient, 68Ga-FAPI PET/CT yielded a more accurate PCI score and a greater area under the curve value for the receiver operating characteristic curve (p < 0.01) than 18F-FDG PET/CT. Conclusion68Ga-FAPI PET/CT was superior to 18F-FDG PET/CT for detecting recurrence and peritoneal metastases. Hence, we propose the combination of these two modalities for better clinical diagnosis and management of patients with CRC.

Monitoring pediatric CNS non-germinomatous germ cell tumors via cerebrospinal fluid circulating tumor DNA.

Accurate molecular and clinical stratification of patients with central nervous system (CNS) non-germinomatous germ cell tumors (NGGCTs) remains challenging, impeding the development of personalized therapeutic approaches. Herein, we investigated the translational significance of cerebrospinal fluid (CSF) circulating tumor DNA (ctDNA) in pediatric NGGCTs to identify characteristic features of CNS NGGCTs and to identify a subset of patients for whom the presence of residual disease is a risk factor and an indicator of shorter progression-free survival (PFS) and overall survival (OS). Medical records of patients with CNS NGGCTs between January 1, 2018 and December 31, 2022 were reviewed retrospectively. The cohort consisted of 11 male and six female patients. Tumor markers were elevated in four of the five people who underwent surgery. The remaining 12 patients were diagnosed with malignant NGGCTs according to elevated tumor markers. Among them, ctDNA before chemotherapy as well as ctDNA clearance were consistently associated with PFS and OS (p<.05). By setting a ctDNA positivity threshold of 6%, patients with high ctDNA (above the threshold) levels, which had limitation due to the selection based on optimal statistic from the survival analysis, had significantly inferior 5-year PFS and OS compared to those with low levels (below the threshold). ctDNA or ctDNA clearance combined with the presence of residual disease predicted significantly worse OS and PFS (p<.05). CSF ctDNA might allow the study of genomic evolution and the characterization of tumors in pediatric NGGCTs. CSF ctDNA analysis may facilitate the clinical management of pediatric NGGCT patients, and aid in designing personalized therapeutic strategies.

The association of cardiovascular disease risk with coronary artery calcification and thoracic aortic dilation: a study in idiopathic inflammatory myopathies and systemic lupus erythematosus.

We aim to explore the prevalence of coronary artery calcification (CAC) and ascending/descending thoracic aorta (AA/DA) dilation in idiopathic inflammatory myopathies (IIM) and systemic lupus erythematosus (SLE) patients, and to assess associations between cardiovascular disease (CVD) risk factors and these imaging signatures. This study recruited 151 IIM patients, 140 SLE patients, and 195 controls. The CAC and AA/DA diameters were quantified using non-gated chest CT images. The independent samples t-test or Mann-Whitney test was chosen for comparisons of continuous variables between patients and healthy controls. For categorical data, comparisons were made using the chi-square test or Fisher's exact test. Multivariate regression or Spearman's correlation analysis was employed to probe the associations between CVD risk factors and Framingham risk score (FRS) with imaging signatures. The IIM and SLE patients showed significantly higher prevalence of CAC and AA/DA dilatation (P < 0.01). Age was a risk factor for both CAC and AA/DA dilatation in all cohorts (P < 0.01). In IIM patients, the AA/DA dilatation was associated with BMI (P = 0.05). In SLE patients, CAC was associated with the elevated CRP level (P = 0.05). Without CAC, both IIM and SLE patients showed significant correlations between AA/DA diameters and FRS (P < 0.01, P < 0.01). Only in SLE patients, the interleukin-6 (IL-6) level correlated with AA/DA diameters. The IIM and SLE patients more commonly exhibit CAC and AA/DA dilation. These subclinical atherosclerosis signs are associated with traditional CVD risk factors. For AID patients without CAC, AA/DA diameters could serve as a potential biomarker for early CVD risk. Key Points • The study characterized the manifestation of subclinical atherosclerosis imaging biomarkers (CAC, AA/DA dilation) in IIM and SLE patients. • AA/DA diameters could serve as an early imaging biomarker in clinical management for IIM and SLE patients with early-onset and no CAC present.