Therapeutic Decisions Research Articles

Novel insight into neurofilament light chain and rhythm outcomes after catheter ablation of new-onset atrial fibrillation: A prospective cohort study

BackgroundAtrial fibrillation (AF) is an age-related disorder closely linked to autonomic nervous system dysfunction. Neurofilament light chain (NFL) protein is a biomarker for neurodegenerative diseases. ObjectiveThe purpose of this study was to evaluate the predictive value of NFL in forecasting AF recurrence after ablation. MethodsPatients newly diagnosed with AF who underwent catheter ablation were included. Serum NFL levels were measured using enzyme-linked immunosorbent assay. The primary outcome was AF recurrence during follow-up. ResultsA total of 215 consecutive patients were enrolled, with average follow-up period of 10.69 months. During this period, 29 patients experienced AF recurrence. Multivariate Cox regression analysis revealed that high NFL levels (≥300 pg/mL) were an independent predictor of recurrence risk (adjusted hazard ratio [HR] 3.756; 95% confidence interval [CI] 1.392–10.136). The associations between NFL levels and AF recurrence were consistent across subgroups defined by age (>65 years), gender, hypertension, and paroxysmal AF. Restricted cubic spline analysis showed a consistent linear relationship across the entire range of NFL levels. Furthermore, incorporating NFL into the CHA2DS2-VASc score model significantly improved the prediction of recurrent AF risk, as demonstrated by time-dependent area under the curve and decision curve analysis. Notable enhancements were also observed in terms of net reclassification improvement (HR 0.464; 95% CI 0.226–0.675; P <.05) and integrated discrimination improvement (HR 0.087; 95% CI 0.017–0.183; P = .08). ConclusionNFL may serve as an effective biomarker for risk stratification and therapeutic decision-making in patients with new-onset AF who have undergone catheter ablation.

Multiparametric simultaneous hybrid 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) incorporating intratumoral and peritumoral regions for grading of glioma.

Preoperative grading gliomas is essential for therapeutic clinical decision-making. Current non-invasive imaging modality for glioma grading were primarily focused on magnetic resonance imaging (MRI) or positron emission tomography (PET) of the tumor region. However, these methods overlook the peritumoral region (PTR) of tumor and cannot take full advantage of the biological information derived from hybrid-imaging. Therefore, we aimed to combine multiparameter from hybrid 18F-fluorodeoxyglucose (18F-FDG) PET/MRI of the solid component and PTR were combined for differentiating high-grade glioma (HGG) from low-grade glioma (LGG). A total of 76 patients with pathologically confirmed glioma (41 HGG and 35 LGG) who underwent simultaneous 18F-FDG PET, arterial spin labelling (ASL), and diffusion-weighted imaging (DWI) with hybrid PET/MRI were retrospectively enrolled. The relative maximum standardized uptake value (rSUVmax), relative cerebral blood flow (rCBF), and relative minimum apparent diffusion coefficient (rADCmin) for the solid component and PTR at different distances outside tumoral border were compared. Receiver operating characteristic (ROC) curves were applied to assess the grading performance. A nomogram for HGG prediction was constructed. HGGs displayed higher rSUVmax and rCBF but lower rADCmin in the solid component and 5 mm-adjacent PTR, lower rADCmin in 10 mm-adjacent PTR, and higher rCBF in 15- and 20-mm-adjacent PTR. rSUVmax in solid component performed best [area under the curve (AUC) =0.865] as a single parameter for grading. Combination of rSUVmax in the solid component and adjacent 20 mm performed better (AUC =0.881). Integration of all 3 indicators in the solid component and adjacent 20 mm performed the best (AUC =0.928). The nomogram including rSUVmax, rCBF, and rADCmin in the solid component and 5-mm-adjacent PTR predicted HGG with a concordance index (C-index) of 0.906. Multiparametric 18F-FDG PET/MRI from the solid component and PTR performed excellently in differentiating HGGs from LGGs. It can be used as a non-invasive and effective tool for preoperative grade stratification of patients with glioma, and can be considered in clinical practice.

The SEER Program's evolution: supporting clinically meaningful population-level research.

Although the Surveillance, Epidemiology, and End Results (SEER) Program has maintained high standards of quality and completeness, the traditional data captured through population-based cancer surveillance are no longer sufficient to understand the impact of cancer and its outcomes. Therefore, in recent years, the SEER Program has expanded the population it covers and enhanced the types of data that are being collected. Traditionally, surveillance systems collected data characterizing the patient and their cancer at the time of diagnosis, as well as limited information on the initial course of therapy. SEER performs active follow-up on cancer patients from diagnosis until death, ascertaining critical information on mortality and survival over time. With the growth of precision oncology and rapid development and dissemination of new diagnostics and treatments, the limited data that registries have traditionally captured around the time of diagnosis-although useful for characterizing the cancer-are insufficient for understanding why similar patients may have different outcomes. The molecular composition of the tumor and genetic factors such as BRCA status affect the patient's treatment response and outcomes. Capturing and stratifying by these critical risk factors are essential if we are to understand differences in outcomes among patients who may be demographically similar, have the same cancer, be diagnosed at the same stage, and receive the same treatment. In addition to the tumor characteristics, it is essential to understand all the therapies that a patient receives over time, not only for the initial treatment period but also if the cancer recurs or progresses. Capturing this subsequent therapy is critical not only for research but also to help patients understand their risk at the time of therapeutic decision making. This article serves as an introduction and foundation for a JNCI Monograph with specific articles focusing on innovative new methods and processes implemented or under development for the SEER Program. The following sections describe the need to evaluate the SEER Program and provide a summary or introduction of those key enhancements that have been or are in the process of being implemented for SEER.

Final Results of the ANDROCAN Study: Histopathological Characteristics and Biochemical Recurrence at 5 Years of Localized Prostate Cancer According to Preoperative Gonadal Status

Background and objectiveFailure rates after first-line treatment of localized prostate cancer (PCa) treatment remain high; therefore, it is essential to improve the selection and identification of at-risk patients to reduce mortality. The aim of the ANDROCAN study was to evaluate the biochemical recurrence (BCR) in patients with localized PCa treated by total prostatectomy at 5 yr after surgery, according to their presurgery gonadal status. MethodsA prospective cohort study was conducted including 1318 patients undergoing total prostatectomy for localized PCa with a 5-yr postoperative follow-up. Clinical and hormonal data (assays of total testosterone [TT], bioavailable testosterone [BT], dihydrotestosterone, estrone, and estradiol were performed by gas chromatography/mass spectrometry) as well as metabolic syndrome parameters were collected at baseline before surgery. Pathological data (predominant Gleason grade 4 and stage) were collected and cross-referenced centrally. Factors associated with BCR were assessed by a multivariate analysis, and BCR-free survival was assessed by a Kaplan-Meier analysis. Key findings and limitationsAmong the 1318 patients, 237 had BCR of PCa. Considering demographic characteristics, populations with and without BCR were similar. However, patients with BCR had cancers with a higher Gleason score (p = 0.0001) and higher prostate-specific antigen (PSA) values (p = 0.0005) at baseline. Gleason score, pT >3a, and PSA level at baseline were positively correlated with BCR (p < 0.0001, p < 0.0001, and p = 0.0048, respectively), while BT and TT levels were not associated with BCR. This study includes patients with varying clinical characteristics, such as cancer history and metabolic syndrome, introducing variability that makes it challenging to isolate the specific effects of gonadal status on BCR. Another limitation is the lack of evaluation of long-term BCR beyond 5 yr, potentially overlooking recurrences that occur between 5 and 15 yr after surgery. This could lead to an underestimation of the actual long-term recurrence rates. Conclusions and clinical implicationsOverall, PSA levels, high Gleason score, and pT >3a are associated with a greater likelihood of disease recurrence following initial treatment and could serve as important prognostic indicators for predicting the risk of BCR. In this prospective study, biochemical hypogonadism was not associated with a higher occurrence of BCR within 5 yr of prostatectomy. The biological gonadal status of preoperative patients could potentially be useful for therapeutic decisions but does not provide an indication for the oncological follow-up. Patient summaryFive-year follow up of patients after surgery showed that there is no association between hypogonadism (low levels of total testosterone and bioavailable testosterone) and cancer recurrence. However, cancer recurrence seems to be more associated with aggressiveness of cancer at the time of detection.

Recurrence in Eyelid Sebaceous Carcinoma: A Multicentric Study of 418 Patients.

Local recurrence predicts dismal prognosis in eyelid sebaceous carcinoma (SC). Recurrence predictors vary across studies. Accurate recurrence estimation is essential for individualized therapy in eyelid SC. This study aims to identify recurrence predictors and develop a nomogram for personalized prediction in eyelid SC. We conducted a multicenter retrospective cohort study. Chart reviews were performed in 418 consecutive patients with eyelid SC. All patients were followed up after their initial surgery. Multivariate Cox regression was used to explore the independent predictors of recurrence. A nomogram for recurrence prediction was developed and validated with bootstrap resampling. The predictive accuracy and discriminative ability were compared with the Tumor, Node, Metastasis (TNM) staging system. Over a median of 60-month follow-up, 167 patients (40%) had local recurrence. The median time from diagnosis to recurrence was 14months. The 1-year cumulative recurrence rate was 18%. Diagnostic delay (hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 1.00-1.01, P = 0.001), orbital involvement (HR = 4.47, 95% CI = 3.04-6.58, P < 0.001), Ki67 (HR = 1.01, 95% CI = 1.00-1.02, P = 0.008) and initial surgery of Mohs micrographic surgery with intraoperative frozen section control (HR = 0.53, 95% CI = 0.35-0.80, P = 0.003) were independent influencing factors of recurrence. A nomogram integrating these four factors combined with pagetoid spread displayed satisfactory discriminative ability (C-index = 0.80-0.83; area under the curve [AUC] = 0.82-0.84), which compared favorably than TNM staging (all P < 0.05). The recurrence rate is high in eyelid SC. Early detection and primary resection with Mohs micrographic surgery are recommended in controlling recurrence. Patients with orbital involvement, high Ki67 expression, and pagetoid spread may require adjuvant measures. This nomogram offers more accurate recurrence estimates, aiding in therapeutic decision making.

Multiple biomarkers are equivalent to clinical pulmonary arterial hypertension survival risk models

Risk assessment in pulmonary arterial hypertension (PAH) is fundamental to guiding treatment and improved outcomes. Clinical models are excellent at identifying high-risk patients but leave uncertainty amongst moderate risk patients. Can a multiple blood biomarker model of PAH, using previously described biomarkers, improve risk discrimination over current models? Using multiplex ELISA, we measured NT-proBNP, ST2, IL-6, Endostatin, Galectin-3, HDGF, and IGF binding proteins (IGFBP1-7) in train (n=1623), test (n=696) and validation (n=237) cohorts. Clinical variables, biomarkers were evaluated by principal component analysis. NT-proBNP was not included to develop an NT-proBNP independent model. Unsupervised k-means clustering classified subjects into clusters. Transplant-free survival by cluster was examined using Kaplan-Meier and Cox proportional hazard regressions. Hazard by cluster was compared to NT-proBNP, REVEAL, and ESC/ERS Risk models alone, and combined clinical and biomarker models. The algorithm generated 5 clusters with good risk discrimination using 6 biomarkers, weight, height, and age at PAH diagnosis. In the test and validation cohorts the biomarker model alone performed equivalent to REVEAL (AUC 0.74). Adding the biomarker model to the ESC/ERS, and REVEAL scores improved the ESC/ERS and REVEAL scores. The best overall model was the biomarker model adjusted for NT-proBNP with the best C-statistic, AIC, and calibration for the adjusted model compared to either the biomarker or NT-proBNP model alone. A multi-biomarker model alone was equivalent to current PAH clinical mortality risk prediction models and improved performance when combined, and added to NT-proBNP. Clinical risk scores offer excellent predictive models but require multiple tests; adding blood biomarkers to models can improve prediction or enable more frequent, non-invasive monitoring of risk in PAH to support therapeutic decision making.

Malignant Rhabdoid Tumor and Related Pediatric Tumors: Multimodality Imaging Review with Pathologic Correlation.

Malignant rhabdoid tumors (MRTs) are rare but lethal solid neoplasms that overwhelmingly affect infants and young children. While the central nervous system is the most common site of occurrence, tumors can develop at other sites, including the kidneys and soft tissues throughout the body. The anatomic site of involvement dictates tumor nomenclature and nosology. While the clinical and imaging manifestations of MRTs and other more common entities may overlap, there are some site-specific distinctive imaging characteristics. Irrespective of the site of occurrence, somatic and germline mutations in SMARCB1, and rarely in SMARCA4, underlie the entire spectrum of rhabdoid tumors. MRTs have a simple and remarkably stable genome but can demonstrate considerable molecular and biologic heterogeneity. Related neoplasms encompass an expanding category of phenotypically dissimilar (nonrhabdoid tumors driven by SMARC-related alterations) entities. US, CT, MRI, and fluorodeoxyglucose PET/CT or PET/MRI facilitate diagnosis, initial staging, and follow-up, thus informing therapeutic decision making. Multifocal synchronous or metachronous rhabdoid tumors occur predominantly in the context of underlying rhabdoid tumor predisposition syndromes (RTPSs). These autosomal dominant disorders are driven in most cases by pathogenic variants in SMARCB1 (RTPS type 1) and rarely by pathogenic variants in SMARCA4 (RTPS type 2). Genetic testing and counseling are imperative in RTPS. Guidelines for imaging surveillance in cases of RTPS are based on age at diagnosis. ©RSNA, 2024 Supplemental material is available for this article.

Ultrasound Characteristics Can Predict Response to Biologics Therapy in Stricturing Crohn's Disease.

Stricture is a common complication in Crohn's disease (CD). Accurate identification of strictures that poorly respond to biologic therapy is essential for making optimal therapeutic decisions. The aim of this study was to determine the association between ultrasound characteristics of strictures and their therapeutic outcomes. Consecutive CD patients with symptomatic strictures scheduled for biologic therapy were retrospectively recruited at a tertiary hospital. Baseline intestinal ultrasound was conducted to assess stricture characteristics, including bowel wall thickness, length, stratification, vascularity, and creeping fat wrapping angle. Patients were followed up for a minimum of 1 year, during which long-term outcomes including surgery, steroid-free clinical remission, and mucosal healing were recorded. Statistical analyses were performed. A total of 43 patients were enrolled. Strictures were located in the ileocecal region (39.5%), colon (37.2%), anastomosis (20.9%), and small intestine (2.3%). The median follow-up time was 17 months (interquartile range 7-25), with 27 patients (62.8%) undergoing surgery. On multivariant analysis, creeping fat wrapping angle > 180° (odds ratio: 6.2, 95% confidence interval [CI]: 1.1-41.1) and a high Limberg score (odds ratio: 2.3, 95% CI: 1.4-6.0) were independent predictors of surgery, with an area under the curve of 0.771 (95% CI: 0.602-0.940), accuracy of 83.7%, sensitivity of 96.3%, and specificity of 62.5%. On Cox survival analysis, creeping fat >180° was significantly associated with surgery (hazard ratio, 5.2; 95% CI: 1.2-21.8; P = 0.03). In addition, creeping fat was significantly associated with steroid-free clinical remission ( P = 0.015) and mucosal healing ( P = 0.06). Intestinal ultrasound characteristics can predict outcomes in patients with stricturing CD who undertook biologic therapy.

Effects of oral contrast agent on the viscoelastic properties of the terminal ileum investigated using magnetic resonance elastography.

While standard clinical magnetic resonance (MR) enterography can detect inflammatory bowel disease, it is of limited value in deciding between medical versus surgical treatment. Alternatively, intestinal MR elastography has the potential to contribute additional information to therapeutic decision-making; however, the influence of bowel distension by oral contrast agent on viscoelastic tissue properties remains elusive. Therefore, we aimed to investigate the influence of oral contrast agent-induced bowel distension on the viscoelastic properties of the terminal ileum in healthy volunteers. In this prospective pilot study, 20 healthy volunteers (33.2±8.2 years; 10 men, 10 women) underwent multifrequency MR elastography using a single-shot spin-echo echo planar imaging sequence at 1.5 Tesla and drive frequencies of 40, 50, 60 and 70 Hz. Maps of shear wave speed (c in ms-1) and loss angle (φ in rad), representing stiffness and viscous properties, respectively, were generated using tomoelastography data processing. The volunteers were scanned before and after ingestion of 1,000 mL of 2% mannitol solution as oral contrast agent. There was no significant difference in terminal ileum biomechanical properties before vs. after ingestion of an oral contrast agent (mean c: 1.47±0.24 vs. 1.40±0.25 ms-1 with P=0.37; mean φ: 0.70±0.12 rad vs. 0.68±0.12 rad with P=0.61). Moreover, there was no statistically significant correlation between MR elastography parameters before and after the ingestion of oral contrast (c: r=0.22, P=0.36; φ: r=0.24, P=0.30). The results of this study suggest that bowel distension for intestinal MR elastography has no systematic effect on the biomechanical tissue properties of the terminal ileum determined by MR elastography. Therefore, future study protocols appear feasible with or without oral contrast agents.

Functional mapping of movement and speech using task-based electrophysiological changes in stereoelectroencephalography.

Stereoelectroencephalography (SEEG) has become the predominant method for intracranial seizure localization. When imaging, semiology, and scalp EEG findings are not in full agreement or definitively localizing, implanted SEEG recordings are used to test candidate seizure onset zones (SOZs). Discovered SOZs may then be targeted for resection, laser ablation, or neurostimulation. If an SOZ is eloquent, resection and ablation are both contraindicated, so identifying functional representation is crucial for therapeutic decision-making. The authors present a novel functional brain mapping technique that utilizes task-based electrophysiological changes in SEEG during behavioral tasks and test this in pediatric and adult patients. SEEG was recorded in 20 patients with epilepsy who ranged in age from 6 to 39 years (12 female, 18 of 20 patients < 21 years of age) and underwent implanted monitoring to identify seizure onset. Each performed 1) visually cued simple repetitive movements of the hand, foot, or tongue while electromyography was recorded; and 2) simple picture-naming or verb-generation speech tasks while audio was recorded. Broadband changes in the power spectrum of the SEEG recording were compared between behavior and rest. Electrophysiological functional mapping of movement and/or speech areas was completed in all 20 patients. Eloquent representation was identified in both cortex and white matter and generally corresponded to classically described functional anatomical organization as well as other clinical mapping results. Robust maps of brain activity were identified in healthy brain, regions of developmental or acquired structural abnormality, and SOZs. Task-based electrophysiological mapping using broadband changes in the SEEG signal reliably identifies movement and speech representation in pediatric and adult epilepsy patients.

Load Dependency of Ventricular Pump Function: Impact on the Non-Invasive Evaluation of the Severity and the Prognostic Relevance of Myocardial Dysfunction.

Ventricular pump function, which is determined by myocyte contractility, preload and afterload, and, additionally, also significantly influenced by heart rhythm, synchrony of intraventricular contraction and ventricular interdependence, explains the difficulties in establishing the contribution of myocardial contractile dysfunction to the development and progression of heart failure. Estimating myocardial contractility is one of the most difficult challenges because the most commonly used clinical measurements of cardiac performance cannot differentiate contractility changes from alterations in ventricular loading conditions. Under both physiological and pathological conditions, there is also a permanent complex interaction between myocardial contractility, ventricular anatomy and hemodynamic loading conditions. All this explains why no single parameter can alone reveal the real picture of ventricular dysfunction. Over time there has been increasing recognition that a load-independent contractility parameter cannot truly exist, because loading itself changes the myofilament force-generating capacity. Because the use of a single parameter is inadequate, it is necessary to perform multiparametric evaluations and also apply integrative approaches using parameter combinations which include details about ventricular loading conditions. This is particularly important for evaluating the highly afterload-sensitive right ventricular function. In this regard, the existence of certain reluctance particularly to the implementation of non-invasively obtainable parameter combinations in the routine clinical praxis should be reconsidered in the future. Among the non-invasive approaches used to evaluate ventricular function in connection with its current loading conditions, assessment of the relationship between ventricular contraction (e.g., myocardial displacement or deformation) and pressure overload, or the relationship between ejection volume (or ejection velocity) and pressure overload, as well as the relationship between ventricular dilation and pressure overload, were found useful for therapeutic decision-making. In the future, it will be unavoidable to take the load dependency of ventricular function much more into consideration. A solid basis for achieving this goal will be obtainable by intensifying the clinical research necessary to provide more evidence for the practical importance of this largely unsolved problem.

Validation of the NULL-EASE Score for Predicting Survival in a Multiethnic Asian Cohort of Out-of-Hospital Cardiac Arrest.

NULL-PLEASE is a simple and accurate clinical scoring system developed in a Western cohort of patients with out-of-hospital cardiac arrest (OHCA). The need for blood test results limits its use in early stages of care. We adapted and validated the NULL-EASE score (without laboratory tests) in an independent, multiethnic Asian cohort of patients with out-of-hospital cardiac arrest. Using the Singapore OHCA registry, we included consecutive adult patients with out-of-hospital cardiac arrest who survived to hospital admission between April 2010 to December 2020. In-hospital mortality was the primary outcome. Logistic regression analyses were performed with STATA MP v18. Of 3274 patients (median age 64, interquartile range 54-75; 67.9% male) included in the study, 2476 (75.6%) had in-hospital mortality. NULL-EASE score was significantly lower in survivors compared with nonsurvivors (median [inter quartile range] 3 [1-4] versus 6 [4-7]; P<0.001) and strongly predictive of mortality (area under receiver operating characteristic, 0.81 [95% CI, 0.79-0.83]). Patients with a score of ≥3 had higher odds of mortality (adjusted odds ratio, 8.11 [95% CI, 6.57-10.00]) when compared with those with lower scores, after adjusting for sex, residential arrest, diabetes, respiratory disease, and stroke. A cutoff value of ≥3 predicted mortality with 92.2% sensitivity, 84.1% positive predictive value, 46.1% specificity, and 65.5% negative predictive value. NULL-EASE score performed better in younger compared with older patients (area under receiver operating characteristic, 0.82 versus 0.77, P=0.008). The NULL-EASE score has good discriminative performance (sensitivity and accuracy) in our multiethnic Asian cohort, but the cutoff of ≥3 falls short of the desired level of specificity for therapeutic decision-making.

Effective strategies for managing trimethoprim-sulfamethoxazole and levofloxacin-resistant Stenotrophomonas maltophilia infections: bridging the gap between scientific evidence and clinical practice.

To discuss the therapeutic options available for the management of difficult-to-treat strains of Stenotrophomonas maltophilia (Sma), namely those resistant to trimethoprim-sulfamethoxazole and fluoroquinolones. Recent pharmacological studies have highlighted the fact that current breakpoints for first-line antibiotics against Sma are too high. In light of these data, it is likely that the prevalence of difficult-to-treat (DTR) Sma is underestimated worldwide. Two promising alternatives for treating DTR strains are cefiderocol and the combination of aztreonam and an L2 inhibitor. However, clinical trials are currently very limited for these antibiotics and no comparative studies have been carried out to date. It is important to note that the clinical efficacy of cefiderocol appears to be inferior to that initially anticipated from in-vitro and animal studies. Consequently, minocycline and ceftazidime may remain viable options if they are used against strains with a low minimum inhibitory concentration. We advise against the use of intravenous polymyxins and tigecycline. Finally, recent literature does not support the systematic use of combination therapy or long-course treatments. In the coming years, phage therapy may become a promising approach against DTR Sma infections. Overall, clinical comparative studies focused on DTR strains are required in order to provide more accurate and actionable information for therapeutic decisions.

HIV-associated tuberculosis in infants, children, and adolescents younger than 15 years: an update on the epidemiology, diagnosis, prevention, and treatment.

HIV-associated tuberculosis (TB) remains a major driver of morbidity and mortality in children and adolescents younger than 15 years (CLWH). The purpose of this review is to highlight recent findings in the areas of prevention, diagnosis, and treatment of HIV-associated TB in CLWH and to highlight knowledge and implementation gaps. We found that despite access to antiretroviral therapy (ART), high rates of HIV-associated TB are still reported, and with an unacceptably high mortality. There are no advances in screening for TB, but shorter courses of rifapentine-based TB preventive therapy are becoming available. The use of algorithms in TB diagnosis can potentially simplify the therapeutic decision making. There are more data supporting the use of dolutegravir (DTG) with rifampicin and a need to study unadjusted DTG especially in the youngest children. Short course therapy for nonsevere pulmonary TB is currently implemented and programmatic outcome should be studied in CLWH. Low uptake of ART and poor suppression remains an important driver of HIV-associated TB. Although screening and diagnosis remains challenging, there are several advances in the prevention and treatment of HIV-associated TB. Effective implementation of these strategies is needed to advance the outcomes of CLWH.

Scalp microbiome: a guide to better understanding scalp diseases and treatments.

The scalp microbiome represents an array of microorganisms important in maintaining scalp homeostasis and mediating inflammation. Scalp microbial dysregulation has been implicated in dermatologic conditions including alopecia areata (AA), dandruff/seborrheic dermatitis (D/SD), scalp psoriasis (SP) and folliculitis decalvans (FD). Understanding the impact of scalp microbial dysbiosis gives insight on disease pathophysiology and guides therapeutic decision making. Herein we review the scalp microbiome and its functional role in scalp conditions by analysis of metagenomic medical literature in alopecia, D/SD, SP, and other dermatologic disease.Increased abundance of Malassezia, Staphylococcus, and Brevibacterium was associated with SD compared to healthy controls. A higher proportion of Corynebacterium, actinobacteria, and firmicutes are present in AA patients, and lower proportions of Staphylococcus caprae are associated with worse clinical outcomes. Decreased prevalence of actinobacteria and Propionibacterium and increased firmicutes, staphylococcus, and streptococcus are associated with scalp psoriasis. Studies of central centrifugal cicatricial alopecia (CCCA) suggest scalp microbial composition contributes to CCCA's pro-inflammatory status. The most common organisms associated with FD include methicillin-resistant S. aureus and S. lugdunensis. Antifungals have been a mainstay treatment for these diseases, while other alternatives including coconut oils and shampoos with heat-killed probiotics have shown considerable potential efficacy by replenishing the scalp microbiome.

Exploring the Continuous Glucose Monitoring in Pediatric Diabetes: Current Practices, Innovative Metrics, and Future Implications.

Continuous glucose monitoring (CGM) systems, including real-time CGM and intermittently scanned CGM, have revolutionized diabetes management, particularly in children and adolescents with type 1 diabetes (T1D). These systems provide detailed insights into glucose variability and detect asymptomatic and nocturnal hypoglycemia, addressing limitations of traditional self-monitoring blood glucose methods. CGM devices measure interstitial glucose concentrations constantly, enabling proactive therapeutic decisions and optimization of glycemic control through stored data analysis. CGM metrics such as time in range, time below range, and coefficient of variation are crucial for managing T1D, with emerging metrics like time in tight range and glycemia risk index showing potential for enhanced glycemic assessment. Recent advancements suggest the utility of CGM systems in monitoring the early stages of T1D and individuals with obesity complicated by pre-diabetes, highlighting its therapeutic versatility. This review discusses the current CGM systems for T1D during the pediatric age, established and emerging metrics, and future applications, emphasizing the critical role of CGM devices in improving glycemic control and clinical outcomes in children and adolescents with diabetes.

The effect of prognostic nutritional index on diabetic patients with myocardial infarction

BackgroundThe prognostic nutritional index (PNI), a simple and comprehensive predictor of nutritional and immunological health, is connected to cancer and cardiovascular disease. The effects of PNI on myocardial infarction (MI) in individuals with diabetes remain unclear. Thus, we aim to investigate the correlation of PNI with predictive outcomes in this specific population group to inform therapeutic decision-making.MethodsThis prospective observational study included 417 diabetic patients with MI who underwent coronary angiography intervention at Fujian Medical University Union Hospital from May 2017 to May 2020. We collected follow-up and prognostic data from these patients at 6, 12, 18, and 24 months post-procedure via outpatient visits or phone interviews. The main focus of the study was on major adverse cardiovascular events (MACE) in the two years after surgery. Based on the median PNI, patients were categorized into two groups: high PNI (H-PNI) and low PNI (L-PNI). Data were analyzed using IBM SPSS 25.0. Kalpan-Meier survival curves and Cox proportional hazards regression analysis were utilized to examine the associations between preoperative PNI and the prognosis of diabetic patients with MI.ResultsIn the study, 417 participants were observed for two years. Of these patients, 159 (38.1%) had MACE. According to the Kaplan–Meier curves, patients in the L-PNI group had more MACE than those in the H-PNI group (log-rank p < 0.001) and had a heightened susceptibility to all categories of MACE. After adjusting for confounding variables, the corrected hazard ratio for developing unstable angina in the L-PNI group was 2.55 (95% CI 1.57–4.14, p < 0.001).ConclusionLow PNI levels are associated with MACE after coronary angiography intervention in diabetic patients with myocardial infarction. This highlights the prognostic value of PNI and broadens its potential use in larger populations.Trial registration: Not applicable.

Understanding willingness and barriers to participate in clinical trials during pregnancy and lactation: findings from a US study

BackgroundDue to the exclusion of pregnant and lactating people from most clinical trials, there is an incomplete understanding of the risks and benefits of medication use in these populations and therapeutic decision-making is often conducted without adequate evidence. To change this paradigm, it is imperative to understand the perspectives of pregnant and lactating individuals concerning their participation in clinical trials.ObjectivesTo describe attitudes, perceptions, barriers, and preferences of pregnant and postpartum people in the United States (US) regarding participation in clinical trials and to identify factors influencing participation.MethodsIn November 2022, individuals aged ≥ 18 residing in the US who self-identified as pregnant or pregnant within the last 12 months were invited to complete an online survey about their perspectives regarding clinical trial participation. The survey included questions about demographic characteristics, health history, behaviors, and willingness to participate in clinical trials while pregnant and/or lactating. Multivariable logistic regression models were fit to identify predictors of clinical trial participation.ResultsAmong the 654 respondents, 34.8% and 40.9% reported being likely or extremely likely to participate in a clinical trial for a new medication while pregnant or lactating, respectively; and 24.5% and 41.7% for a new vaccine while pregnant or lactating, respectively. Higher educational attainment (≥ Bachelor’s degree) was associated with greater likelihood of clinical trial participation in pregnancy (odds ratio (OR) = 1.50, 95% Confidence Interval (CI): 1.01, 2.25 for medications; OR = 2.00, 95% CI: 1.28, 3.12 for vaccines). Chronic medical conditions were associated with a greater likelihood of participation in clinical trials for vaccines during lactation (OR = 1.59, 95% CI: 1.07, 2.36). The most cited motivator for participation in a clinical trial while pregnant or lactating was anticipated personal medical benefit (85.8% and 75.6%, respectively), while the primary deterrent was possible risk to the fetus or baby (97.9% and 97.2%, respectively).ConclusionsWillingness of a US sample to participate in clinical trials while pregnant or lactating varied by demographics and health status, with safety to the fetus being a nearly universal concern. These findings have implications for enhancing inclusion of pregnant and lactating people in clinical research and developing effective and equitable recruitment strategies.

Machine learning-driven mast cell gene signatures for prognostic and therapeutic prediction in prostate cancer

BackgroundThe role of Mast cells has not been thoroughly explored in the context of prostate cancer's (PCA) unpredictable prognosis and mixed immunotherapy outcomes. Our research aims to employs a comprehensive computational methodology to evaluate Mast cell marker gene signatures (MCMGS) derived from a global cohort of 1091 PCA patients. This approach is designed to identify a robust biomarker to assist in prognosis and predicting responses to immunotherapy. MethodsThis study initially identified mast cell-associated biomarkers from prostate adenocarcinoma (PRAD) patients across six international cohorts. We employed a variety of machine learning techniques, including Random Forest, Support Vector Machine (SVM), Lasso regression, and the Cox Proportional Hazards Model, to develop an effective MCMGS from candidate genes. Subsequently, an immunological assessment of MCMGS was conducted to provide new insights into the evaluation of immunotherapy responses and prognostic assessments. Additionally, we utilized Gene Set Enrichment Analysis (GSEA) and pathway analysis to explore the biological pathways and mechanisms associated with MCMGS. ResultsMCMGS incorporated 13 marker genes and was successful in segregating patients into distinct high- and low-risk categories. Prognostic efficacy was confirmed by survival analysis incorporating MCMGS scores, alongside clinical parameters such as age, T stage, and Gleason scores. High MCMGS scores were correlated with upregulated pathways in fatty acid metabolism and β-alanine metabolism, while low scores correlated with DNA repair mechanisms, homologous recombination, and cell cycle progression. Patients classified as low-risk displayed increased sensitivity to drugs, indicating the utility of MCMGS in forecasting responses to immune checkpoint inhibitors. ConclusionThe combination of MCMGS with a robust machine learning methodology demonstrates considerable promise in guiding personalized risk stratification and informing therapeutic decisions for patients with PCA.

Risk of new-onset diabetes and efficacy of pharmacological weight loss therapy.

To develop a clinical risk model to identify individuals at higher risk of developing new-onset diabetes and who might benefit more from weight loss pharmacotherapy. A total of 21 143 patients without type 2 diabetes at baseline from two TIMI clinical trials of stable cardiovascular patients were divided into a derivation (~2/3) and validation (~1/3) cohort. The primary outcome was new-onset diabetes. Twenty-seven candidate risk variables were considered, and variable selection was performed using multivariable Cox regression. The final model was evaluated for discrimination and calibration, and for its ability to identify patients who experienced a larger benefit from the weight loss medication lorcaserin in terms of risk of new-onset diabetes. During a median (interquartile range) follow-up of 2.3 (1.8-2.7) years, new-onset diabetes occurred in 1013 patients (7.7%). The final model included five independent predictors (glycated haemoglobin, fasting glucose, age, body mass index, and triglycerides/high-density lipoprotein). The clinical risk model showed good discrimination (Harrell's C-indices 0.802, 95% confidence interval [CI] 0.788-0.817 and 0.807, 95% CI 0.788-0.826) in the derivation and validation cohorts. The calibration plot demonstrated adequate calibration (2.5-year area under the curve was 81.2 [79.1-83.5]). While hazard ratios for new-onset diabetes with a weight-loss therapy were comparable across risk groups (annual risks of <1%, 1%-5%, and >5%), there was a sixfold gradient in absolute risk reduction from lowest to highest risk group (p = 0.027). The developed clinical risk model effectively predicts new-onset diabetes, with potential implications for personalized patient care and therapeutic decision making.