Clinical Indications Research Articles

Identification of clinical risk factors for coronary artery lesions in children with Kawasaki disease: a retrospective cohort study.

Coronary artery lesions are the most severe complications of Kawasaki disease. Despite recent advances, evidence of the association between risk factors and coronary artery lesion is lacking. In this study, we demonstrated the potential clinical indicators that could assist to evaluate the prevalence of coronary artery lesion among paediatric patients with Kawasaki disease. We retrospectively enrolled 260 paediatric patients with Kawasaki disease. Patients with coronary dilation, coronary aneurysm, and intimal thickening of coronary arteries were included in this study. Medical records of each patient were collected. Logistic regression analysis was performed to explore risk factors and the occurrence of coronary artery lesion in patients with Kawasaki disease. Respectively, 64 (24.6%), 39 (15%), and 56 patients (21.5%) of the participants had coronary dilation, coronary aneurysm, and intimal thickening of coronary arteries. Univariate analysis revealed that age, gender, duration of fever, time of initial use of intravenous immunoglobulin, erythrocyte sedimentation rate, white blood cell counts, time of platelet increase, the maximum value of platelet, albumin, and immunoglobulin G level was associated with coronary artery lesion. In multivariable logistic analysis, those younger and mainly males were associated with all three outcomes of coronary artery lesion, lower serum albumin levels, and later initial use of intravenous immunoglobulin were linked to a higher risk of coronary dilation and coronary aneurysm. The potential risk factors that could be used to estimate the occurrence of coronary artery lesion in Kawasaki disease patients are young age, male, lower serum albumin lever, and later initial use of intravenous immunoglobulin. However, long-term follow-up and multi-centre studies are required to verify our findings in the future.

Oral health status, self-perceptions, and risk awareness among young adult users of electronic cigarettes in Pakistan.

The use of electronic cigarettes (ECs) has surged globally, particularly among young individuals. This study aimed to assess the perceptions of vaping-related oral health risks, clinical oral health status, and self-perceived dental and periodontal conditions among young adult users of ECs in Pakistan. A cross-sectional study was conducted from June 2023 to March 2024, recruiting 142 young users of ECs. Intraoral examinations assessed Decayed, Missing, and Filled Teeth (DMFT) index, Oral Hygiene Index Simplified (OHI-S), Gingival Bleeding Index (GBI), Plaque Index (PI), and dental stain. Data on sociodemographic characteristics, oral health behaviors, vaping habits, and perceptions of impact of vaping on oral health were gathered through a self-administered questionnaire. Associations between EC use and various oral health variables were analyzed using the chi-squared and Fisher's exact tests. Mean DMFT was 5.66 (SD=2.20). Poor oral hygiene (29.6%) and severe dental staining were prevalent. Most participants (76.1%) brushed once daily, while only 34.5% attended regular dental check-ups. Gingival bleeding and plaque accumulation were observed in 47.2% and 35.3% of participants. Around 66% reported daily EC use, with 80.3% initiating vaping before the age of 18 years. Most common reason for vaping was perception that ECs are safer than traditional smoking (31.7%). Participants' perceptions of vaping-related oral health risks were relatively low, with 45% associating vaping with tooth decay, 48% with gum disease, and 58.5% with tooth staining. Tooth brushing frequency, vaping frequency (per day), and time since vaping started, were significantly associated with oral clinical indicators (p<0.05). The education level was the only variable significantly associated with vaping-related risk perception (p<0.05). The study reveals that oral health awareness among young vapers is low, with many starting EC use at a young age and exhibiting poor oral health behaviors. Misconceptions about the safety of ECs compared to conventional cigarettes may contribute to increased vaping.

Bariatric Surgery in Adolescent Age Group

Obesity in children is a problematic condition which interfere with physical and mental health. It is a complicated disorder with interwoven environmental, genetic, biological components, developmental, and behavioral. A combination of medical treatment and behavioral and lifestyle modifications was typically what causes poor short-term weight loss and long-term failure. For this reason, adolescents who suffer from moderate to severe obesity and have attempted lifestyle interventions in the past but had no success should think about having bariatric surgery. Specifically, laparoscopic sleeve gastrectomy is thought to be the most often carried out bariatric procedure globally. The technique is safe and doable. It has been demonstrated that this surgical weight loss procedure is effective in young patients. However, there are obstacles that need to be removed at the levels of patients, providers, and the healthcare system. Above all, for ensuring successful long-term treatment and permit healthy growth, more should be done to stop the nutritional status decline that frequently follows bariatric surgery, as well as to prevent insufficient weight loss and weight regain. With a focus on LSG, nutritional management, and the resolution of metabolic comorbidities, we examined the clinical indications, surgical treatment options, and outcomes in adolescents with severe obesity in this narrative review.

Claims-Based Algorithm to Identify Pre-Exposure Prophylaxis Indications for Tenofovir Disoproxil Fumarate and Emtricitabine Prescriptions (2012-2014): Validation Study.

To monitor the use of tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) and related medicines for pre-exposure prophylaxis (PrEP) as HIV prevention using commercial pharmacy data, it is necessary to determine whether TDF/FTC prescriptions are used for PrEP or for some other clinical indication. This study aimed to validate an algorithm to distinguish the use of TDF/FTC for HIV prevention or infectious disease treatment. An algorithm was developed to identify whether TDF/FTC prescriptions were for PrEP or for other indications from large-scale administrative databases. The algorithm identifies TDF/FTC prescriptions and then excludes patients with International Classification of Diseases (ICD)-9 diagnostic codes, medications, or procedures that suggest indications other than for PrEP (eg, documentation of HIV infection, chronic hepatitis B, or use of TDF/FTC for postexposure prophylaxis). For evaluation, we collected data by clinician assessment of medical records for patients with TDF/FTC prescriptions and compared the assessed indication identified by the clinician review with the assessed indication identified by the algorithm. The algorithm was then applied and evaluated in a large, urban, community-based sexual health clinic. The PrEP algorithm demonstrated high sensitivity and moderate specificity (99.6% and 49.6%) in the electronic medical record database and high sensitivity and specificity (99% and 87%) in data from the urban community health clinic. The PrEP algorithm classified the indication for PrEP in most patients treated with TDF/FTC with sufficient accuracy to be useful for surveillance purposes. The methods described can serve as a basis for developing a robust and evolving case definition for antiretroviral prescriptions for HIV prevention purposes.

The Time Course of Catecholamine Dose Reduction in Septic Shock as a Predictor of Bacterial Susceptibility to Empiric Antimicrobial Therapy: A Retrospective Observational Study

Background/Objectives: The 28-day mortality rate for septic shock is high, necessitating rapid and effective empiric antimicrobial therapy. In this study, we investigate whether the rate of catecholamine dose reduction in septic shock can indicate bacterial susceptibility to initial antimicrobial therapy or not. Methods: This retrospective observational study involved 108 adult patients with bacteraemia and septic shock admitted to the intensive care unit of Nihon University Itabashi Hospital between January 2017 and December 2023. They were classified into the Susceptible or Resistant groups based on the bacteria’s susceptibility to the initial empiric antimicrobial therapy. Catecholamine dosages were converted to norepinephrine equivalent (NEE) scores, with the time course from the peak to the end of administration measured at NEE reductions. Results: Of the 108 patients, 94 were in the Susceptible group and 14 in the Resistant group. The Susceptible group showed faster reductions in catecholamine doses: the time to reduce the dose from the maximum NEE to 25% was 19 vs. 49.5 h (p = 0.0057), and to 0%, it was 29 vs. 54 h (p = 0.0475). The time to reduce the dose from the maximum NEE to 75% was 8 vs. 12.5 h (p = 0.0733), and to 50% it was 13 vs. 21.5 h (p = 0.1081). Conclusions: In septic shock with bacteraemia, a faster catecholamine dose reduction indicates bacterial susceptibility to the initial empiric antibiotics. This reduction rate can serve as an early clinical indicator of the appropriate initial empiric therapy.

Adult Code Sepsis: A Narrative Review of its Implementation and Impact.

This narrative review explores the implementation and impact of sepsis code protocols, an urgent intervention strategy designed to improve clinical outcomes in patients with sepsis. We examined the degree of implementation, activation criteria, areas of implementation, personnel involved, responses after activation, goals and targets, impact on clinical indicators, and challenges in implementation. The reviewed evidence suggests that sepsis codes can significantly reduce sepsis-related mortality and enhance early administration of treatments. However, variability in activation criteria and inconsistent application present ongoing challenges. The review considers the incorporation of newer scoring systems, such as NEWS and MEWS, and the potential integration of machine learning tools for early sepsis detection. It highlights the importance of tailoring implementation to specific healthcare contexts and the value of ongoing training to optimize sepsis response. Limitations include the ongoing controversy surrounding sepsis definitions and the need for standardized, feasible quality indicators. Future research should focus on standardizing activation criteria, improving protocol adherence, and exploring emerging technologies to enhance early sepsis detection and management. Despite challenges, sepsis codes show promise in improving patient outcomes when implemented thoughtfully and consistently across healthcare settings.

077. Ethanol Ablation as Therapeutic Options for Benign Thyroid Cyst: A Literature Review

Background: Minimally invasive management of symptomatic cystic thyroid nodules has become common practice. Ethanol ablation for benign thyroid cysts has been performed since 1990. Various consensus guidelines have been developed, but a more detailed review regarding the safety and outcomes of this procedure is still needed. This study aims to identify and summarize the indications, techniques, outcomes, and complications of ethanol ablation for benign thyroid cysts through a literature search and review using PubMed and EMBASE. Results: A database search using specific keywords identified a total of 134 titles. Screening of titles and abstracts with inclusion and exclusion criteria excluded 124 titles. After removing duplicates, checking full-text availability, and study eligibility, 7 studies met the criteria. Clinical evaluations, indications, techniques, outcomes, and complications were extracted from each study. Conclusion: Ethanol ablation (EA) is a safe, repeatable, cost-effective procedure that can be performed in an outpatient setting. It has transient side effects and complications, most of which resolve spontaneously. Thus, EA can be considered a first-line non-surgical treatment for benign thyroid cysts and predominantly cystic thyroid nodules (PCTN).

One-Step Cartilage Repair of Full-Thickness Knee Chondral Lesions Using a Hyaluronic Acid-Based Scaffold Embedded With Bone Marrow Aspirate Concentrate: Long-term Outcomes After Mean Follow-up Duration of 14 Years.

One-step cell-based techniques of cartilage repair that lead to restoration of durable chondral tissue and long-term maintenance of joint function are cost-effective and ideal for routine use. To examine the long-term clinical outcomes, after a mean follow-up duration of 14 years, of cartilage repair in the knee using a hyaluronic acid-based scaffold in association with bone marrow aspirate concentrate (HA-BMAC) and to evaluate the effect of age, lesion characteristics, and associated treatments on the outcome of this cartilage repair method. Case series; Level of evidence, 4. Patients were followed prospectively for a mean duration of 14.0 years after undergoing treatment of knee full-thickness articular cartilage injury using HA-BMAC. Clinical evaluation consisted of the patient-reported scoring tools of the visual analog scale and the Knee injury and Osteoarthritis Outcome Score, which were completed preoperatively and at the time of final follow-up. A total of 26 patients with a mean age of 48.3 years (17 male, 9 female) and median chondral lesion size of 6.6 cm2 (range, 1-27 cm2) were followed prospectively. There were 3 treatment failures, and 1 patient who underwent medial compartment unicompartmental arthroplasty 12 years after HA-BMAC treatment of patellar chondral injury. Of the 22 remaining patients, after a mean final follow-up duration of 14.0 years (range, 12-16 years), the median visual analog scale score of 0.6 was significantly decreased from the preoperative median score of 5.0 (P < .001). The median Knee injury and Osteoarthritis Outcome Score Pain (92), Symptoms (86), Activities of Daily Living (96), Sports (85), and Quality of Life (88) subscale values were all increased compared with the preoperative scores (P≤ .001). There was no correlation of clinical outcome score and body mass index. One-step cartilage repair of full-thickness chondral defects in the knee using an HA-BMAC led to successful long-term clinical outcomes and maintenance of joint junction after a mean follow-up duration of 14 years. Long-term clinical success in active, nonobese patients has been uniformly demonstrated across a wide range of patient ages and lesion types, including cases of multicompartment involvement, treatment of associated conditions, and large or bipolar chondral lesions.

Enhanced Delta-gamma Phase Amplitude Coupling during Phasic REM Sleep in isolated REM Sleep Behavior Disorder.

This study aims to analyze phase-amplitude coupling (PAC) patterns during rapid eye movement (REM) sleep in patients with isolated REM sleep behavior disorder (iRBD), compared with demography-matched healthy control (HC) participants. At baseline, electroencephalogram data from 13 iRBD patients and 10 HCs during REM sleep were analyzed. During follow-up, 4 patients (converters) later converted to alpha-synucleinopathies. Phasic and tonic REM states were determined by eye movement in 3-second epochs. PAC was compared between the groups, and correlations with clinical indicators were investigated. Additionally, the contribution of each electrode to PAC components was assessed. Patients with iRBD exhibited increased delta (1-3 Hz)-gamma (30-50 Hz) PAC only during the phasic REM state, but not during the tonic state, compared to the HCs (p < 0.05). Elevated PAC in patients negatively correlated with the REM atonia index (p = 0.011) and olfactory function (p = 0.038). Increase PACs were predominent in the fronto-temporo-occipital regions (corrected p < 0.05). Furthermore, patients showed reduced gamma-amplitude contributions of the parietal region (corrected p < 0.05). This reduction exhibited a progressively decreasing trend from HC to non-converters, and further to converters (p for trend = 0.044). Our findings suggest PAC patterns during REM sleep could provide pathophysiological insights for iRBD. The widespread increase of PAC and reduced gamma-amplitude contribution in the parietal region suggest PAC during phasic REM sleep as potential biomarkers for disease progression in iRBD.

A PROSPECTIVE STUDY ON MANAGEMENT OF CARDIOGENIC SHOCK WITH PERCUTANEOUS CORONARY INTERVENTION

Cardiogenic shock following acute myocardial infarction (AMI) is a critical condition with high mortality rates. Percutaneous coronary intervention (PCI) has emerged as a key intervention, but the outcomes and associated risk factors, including comorbidities such as hypertension, diabetes, and smoking, remain essential to understand for optimizing treatment and improving prognosis. Objective: To evaluate outcomes and identify risk factors in patients with cardiogenic shock secondary to acute myocardial infarction managed with percutaneous coronary intervention. Methods: A prospective observational study was conducted at a tertiary care hospital involving 70 patients aged 60 years and above who presented with cardiogenic shock due to AMI within 24 hours of symptom onset. Data were collected on demographics, clinical indicators of shock severity, and mechanical complications, including pump failure, papillary muscle rupture, ventricular septal rupture (VSR), and free wall rupture. The incidence of comorbidities, such as hypertension, diabetes, and smoking status, was documented. Mortality and recovery patterns were assessed during hospitalization and post-discharge. Statistical analysis was performed to examine associations between comorbidities and adverse outcomes. Results: The mean age of the cohort was 68.8 ± 4.5 years, with a male predominance of 57.1%. Key complications included pump failure in 31.4%, papillary muscle rupture in 11.4%, papillary muscle dysfunction in 34.3%, VSR in 7.1%, and free wall rupture in 4.3% of patients. Overall mortality was 12.9%. Hypertension was present in 67.1% of patients, diabetes in 61.4%, and smoking in 21.4%, all of which correlated with higher complication rates and adverse outcomes. Conclusion: Early PCI management in patients with cardiogenic shock secondary to AMI is associated with favorable survival rates. However, comorbidities such as hypertension and diabetes significantly increase complication rates. These findings underscore the importance of timely intervention and risk-targeted management to improve survival outcomes in high-risk patients.

Content validation of the nursing diagnosis “ineffective protection” in the context of adolescents with cancer

ObjectiveTo analyze the relevance of a set of clinical elements to represent the content domain of the nursing diagnosis Ineffective Protection. Design and methodsThis study employed content validation, using expert judgment to assess the appropriateness of clinical indicators, etiological factors, and conceptual and operational definitions, integrating the collective wisdom framework, the theory of predictive diversity, and the determination of rater skill level. ResultsFrom the middle range theory, 28 clinical indicators and 17 etiological factors were identified, which were rated by 34 raters. The analysis showed that the clinical indicators restlessness and insomnia and the etiological factors ambient temperature and humidity were not considered relevant for the nursing diagnosis of Ineffective Protection, because the median content validity index was lower than 0.9. ConclusionsContent validation verified that most of the components of the nursing diagnosis of Ineffective Protection were considered relevant by judges. Practical implicationsIt is believed that the data obtained can help nurses to more easily evaluate the related factors and clinical indicators of Ineffective Protection presented by adolescents with cancer, which favors the process of diagnostic inference.

The role of neutrophils-lymphocytes ratio (NLR), lymphocytes-monocytes ratio (LMR), platelets-lymphocytes ratio (PLR) in oral cancer and acute dental infections

Objectives: The present study was a cross-sectional observational study, which was carried out on patients reported to the Department of Oral Medicine and Radiology. This study aims to evaluate the hemogram parameters NLR, LMR, and PLR among 90 Patients. Methods: Patients were divided into 3 groups: Group A consists of 30 patients with histopathological confirmed oral cancer. Group B consists of 30 patients who presenting acute dental infections. Group C consists of 30 patients clinically healthy subjects. The hemogram parameters NLR, LMR and PLR were compared in the 3 groups and we studied their correlation to the clinical prognostic indicators like T stage, to the presence or absence of lymph node metastasis, and to differentiation of cancer. After obtaining personal informed consent, a thorough examination of the oral cavity and the lesion was conducted with an illuminated light and mouth mirror. Blood tests were performed on all the subjects before treatment. Under aseptic conditions, Venous blood (2 ml) was collected by venepuncture of the median cubital vein in the cubital fossa of the forearm using a disposable syringe with a 24-gauge needle. The withdrawn blood was transferred into an EDTA-containing test tube. Haematological parameters were analysed using an automated haematology analyzer. NLR, LMR, and PMR were calculated as the ratio of absolute peripheral neutrophil to lymphocyte, lymphocyte to monocyte, and platelet to lymphocyte count, respectively. Results: The present study revealed that NLR is significantly elevated in oral carcinoma compared to healthy individuals, but is lesser than in patiemts with acute dental infections. LMR is higher in oral carcinoma than in acute dental infections and healthy individuals, but no statisticaly significant difference was detected among the groups. PLR is higher in oral carcinoma than in Acute dental infections and healthy individuals, and it is statistaicaly significant. There are significant correlations in oral carcinoma between NLR, LMR, and PLR. NLR has a positive correlation with PLR and a negative correlation with LMR, which showed clinical significance as determined by the Spearman correlation coefficient. In Acute dental infections and healthy individuals, there is a significant correlation of NLR with LMR and PLR but no significant correlations between LMR and PLR and vice versa. NLR, LMR, and PLR were correlated to clinical prognostic indicators like T stage, presence or absence of lymph node metastasis, and differentiation of cancer. There is no significant difference in NLR, LMR, or PLR ratios concerning Clinical T staging since the p-value is greater than 0.05 for NLR, LMR, and PLR (p= 0.072, 0.446, 0.446, respectively). A statistically significant difference is found in LMR to the clinical presence or absence of Lymph node metastasis since the p-value is less than 0.05 only for LMR (p=0.018). The mean values of LMR in N0, N1, and N2 were 9.49, 5.65, and 4.40, respectively; this implies that the mean value of LMR decreases in advanced oral carcinoma as the nodal stage increases with lymph node metastases. A statically significant difference is found in NLR (p=0.011) and PLR (p =0.013) for differentiation of tumour (p-value is less than 0.05), which implies NLR &amp; PLR values are elevated in moderate differentiated oral carcinomas when compared to well-differentiated oral carcinoma. Conclusions: A significant elevation exists in haematological parameters like NLR, LMR, and PLR in oral carcinoma and acute dental infections.

Adaptation of the Taiwan Version of the Supportive and Palliative Care Indicators Tool (SPICT-TW) and Its Association with Six-Month Mortality: A Multi-Center Validation Study in Older People

Background: The Supportive and Palliative Care Indicators Tool (SPICT) was developed for identifying, in a timely manner, patients who may benefit from supportive and palliative care for better treatment review, care-plan discussion, and end-of-life care. Although the SPICT has been validated in different languages and for patients living in different settings, it has not been validated for patients receiving home-based medical care (HBMC), or in the context of using traditional Chinese characters. Objectives: The present study aimed to validate the Taiwanese version of the SPICT (SPICT-TW) and to measure its ability to predict six-month mortality in patients who received HBMC in Taiwan. Methods: Seven HBMC agents (five clinics and two hospitals) participated in this validation study. We recruited 129 patients aged ≥ 50 years who had been consistently receiving HBMC for &gt;two months. Results: The results revealed that the SPICT-TW demonstrated similar reliability and validity compared to other language versions of the SPICT. It may be an appropriate tool for healthcare professionals to detect, in a timely manner, the needs for palliative care in older people who receive home healthcare. Furthermore, we found that a combination of four general indicators and one clinical indicator in the SPCIT-TW has the best prediction ability at predicting six-month mortality in these HBMC recipients. This multi-center study validated the SPICT-TW among HBMC recipients in Taiwan. Conclusions: The SPICT-TW demonstrated high reliability and validity through the Kuder–Richardson 20, an intraclass correlation coefficient, Cohen’s kappa, and receiver operating characteristic analysis, supporting its potential as a practical tool for identifying older adults at risk of dying within six months who have not yet received palliative care but may benefit from it.

Time from approval to reimbursement recommendations in healthcare systems with centralized HTA processes. Focus on the Polish HTA agency

ABSTRACT Background To analyze the time from drug registration to reimbursement recommendations, we examined medicinal products, including new clinical indications, registered by the EMA between 2014 and 2019 across various therapeutic areas. Materials and Methods The Polish Agency for Health Technology Assessment and Tariffication (AOTMiT) was compared with 11 agencies in England, Wales, Ireland, Scotland, the Netherlands, Norway, France, Germany, New Zealand, Canada, Australia. A total of 1,942 recommendations published by 12 HTA agencies were analyzed. Results The time from registration to recommendation in Poland was statistically significantly longer than for the other countries. The analysis revealed noticeable differences in the time it takes from drug registration to recommendation across the countries included in this analysis. Analyzing trends from 2014 to 2019 in individual countries, it is noteworthy that in most agencies the median time from registration to recommendation is declining. Conclusions This may suggest improvements in the processes of the recommending authorities and the companies responsible for providing data for assessment. Despite Poland having one of the longest times from registration to recommendation among the countries analyzed, there has been a clear year-over-year decrease in the time to publication of reimbursement recommendations.

A study of machine learning to predict NRDS severity based on lung ultrasound score and clinical indicators

A study of machine learning to predict NRDS severity based on lung ultrasound score and clinical indicators

Transfers Among Vulnerable Long-Term Nursing Home Residents

ObjectivesTo determine whether the risk of nursing home-to-nursing home transfer is higher among long-term nursing home residents with intellectual and developmental disabilities (IDD), or serious mental illness (SMI), and/or Alzheimer's disease and related dementias (ADRD), relative to residents without these clinical diagnoses, and to assess the factors associated with transfer overall and for residents with these diagnoses. DesignCross-sectional cohort study of nursing home residents in 2019. Setting and ParticipantsMichigan long-term nursing home residents identified from the Minimum Data Set. MethodsResidents who had a nursing home-to-nursing home transfer were allocated into 5 groups: IDD, SMI and ADRD, ADRD, SMI, and all others. We examined transfer rates for each group. We assessed the odds of transfer for each group, adjusting for resident and nursing home characteristics, and behavioral issue and clinical indicators. We used stratified logistic regression to determine factors associated with transfers within each group. ResultsAmong 37,638 long-term nursing home residents, 2.3% had a nursing home-to-nursing home transfer. Transfers varied across diagnosis groups: 1.9% in IDD, 2.8% in SMI and ADRD, 1.9% in ADRD, 2.6% in SMI, and 2.5% in all others. After adjustment, residents in the SMI and ADRD group were 39% more likely to transfer than those in the all others group (adjusted odds ratio, 1.39; 95% CI, 1.14–1.68). Age ≥75 years, moderate to severe cognitive impairment, and falls were associated with a lower odds of transfer. Being married and wandering were associated with a higher odds of transfer. Factors associated with transfers varied within each group. Conclusions and ImplicationsAmong Michigan long-term nursing home residents, residents with both SMI and ADRD are at the highest risk for transfer to another nursing home when compared with residents with SMI or ADRD alone and with IDD and none of these diagnoses. Understanding the drivers of transfer of this vulnerable group warrants further investigation.

Non-invasive lipid panel of MASLD fibrosis transition underscores the role of lipoprotein sulfatides in hepatic immunomodulation.

There exists a pressing need for a non-invasive panel that differentiates mild fibrosis from non-fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). In this work, we applied quantitative lipidomics and sterolomics on sera from the PERSONS cohort with biopsy-based histological assessment of liver pathology. We trained a lasso regression model using quantitative omics data and clinical variables, deriving a combinatorial panel of lipids and clinical indices that differentiates mild fibrosis (>F1, n= 324) from non-fibrosis (F0, n= 195), with an area under receiver operating characteristic curve (AUROC) at 0.775 (95% confidence interval [CI]: 0.735-0.816). Circulating sulfatides (SLs) emerged as central lipids distinctly associated with fibrosis pathogenesis in MASLD. Lipidomics analysis of lipoprotein fractions revealed a redistribution of circulating SLs from high-density lipoproteins (HDLs) onto low-density lipoproteins (LDLs) in MASLD fibrosis. We further verified that patient LDLs with reduced SL content triggered a smaller activation of type II natural killer T lymphocytes, compared with control LDLs. Our results suggest that hepatic crosstalk with systemic immunity mediated by lipoprotein metabolism underlies fibrosis progression at early-stage MASLD.

Altered structural covariance of the cortex and hippocampal formation in patients with lung cancer after chemotherapy

ObjectiveIn this retrospective study, we aimed to investigate changes in brain morphology and structural topological networks in patients with lung cancer (LC) with or without chemotherapy. MethodsWe retrospectively recruited 191 participants for this cross-sectional study, including 113 patients with LC without chemotherapy (Ch-), 38 patients with LC with chemotherapy (Ch+), and 40 healthy controls (HC) matched for age, sex, and education. The gray matter volume (GMV) and cortical properties were compared among the three groups. We constructed the structural covariant network (SCN) based on cortical thickness, volumes of subcortical structures, and volumes of hippocampal subfields and the amygdala in all participants. The global and nodal topological properties of SCN were compared among groups. In addition, 23 patients with LC (8 Ch+ and 15 Ch-) who received two identical brain magnetic resonance scans were enrolled in the follow-up study. The paired t-test was used to compare group differences in brain morphology and topological properties in the structural network. ResultsThe GMV of the bilateral caudate and thalamus were smaller in the Ch- and Ch+ groups compared to the HC group using threshold-free cluster enhancement and permutation (P < 0.05, 5000 times permutations) for multiple comparison correction. The cortical SCN analysis suggested multiple enhanced nodal properties in several brain areas in Ch+ and Ch- compared to HC, mainly in the temporal gyrus, using permutations test and false discovery rate (FDR) (P < 0.05) corrections. Moreover, an increased sigma was found in the Ch+ compared with HC (P = 0.0238). The reduced nodal degree (P = 0.0002) and betweenness (P = 0.0008) in the right amygdala of Ch+ compared to HC were detected by subcortical SCN analysis. Furthermore, reduced gamma (P = 0.0342) and sigma (P < 0.0001) were found in Ch- compared with HC in the SCN analysis of subfields of the amygdala-hippocampal complex. In the follow-up study, reduced nodal degree (P < 0.0001) was found in the right anterior amygdala, and reduced clustering coefficient and local efficiency were found in patients with LC after the permutation test. ConclusionsOur study showed GMV defects and structural topological property abnormalities related to LC and chemotherapy. Such morphological changes associated with LC and chemotherapy could be used as imaging markers for clinical assessments and pathological indicators.

Mutations of ARID1B, PIK3C2B, KMT2B, and FAT1 genes influence clinical outcome in newly diagnosed myeloma

The study aimed to elucidate the mutational profile of patients with newly diagnosed multiple myeloma to understand correlations of alterations with clinical outcomes. A cohort of 20 patients was enrolled, and mutational analysis was conducted using the TruSight Oncology 500 DNA Kit. Identified genetic alterations were related to clinicopathologic features and treatment outcomes. A total of 724 high-quality variants were validated. All patients harbored mutations associated with the RTK-RAS pathway, with over half having alterations in PI3K, NOTCH, and WNT pathways. Several gene mutations were associated with specific clinical characteristics and prognostic indicators, revealing a complex interplay between genetic alterations and myeloma type, standard prognostic indicators, biochemical parameters, and renal function. Genetic alterations significantly influencing progression-free survival concerned PIK3C2B, ARID1B genes, and concomitant mutations in KMT2B, FAT1, and ARID1B. The findings underscore the potential of gene mutation-based prognostic tools in enhancing clinical decision-making and suggest that further exploration of identified genetic markers could pave the way for improved prognostic stratification and targeted therapeutic interventions in multiple myeloma.

Addressing data quality issues to assess clinical and epidemiological risk factors for COVID-19 among documented cases in Liberia: a single-centre, retrospective, observational study

IntroductionIdentification of risk factors for severe COVID-19 can help to inform case management in resource-constrained settings. We aimed to rigorously but retroactively address data issues to identify risk factors for...