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Basal cell carcinoma (BCC), cutaneous squamous cell carcinoma (cSCC), and Merkel cell carcinoma (MCC) comprise the majority of nonmelanoma skin cancers. Advances have been made in treatment. Sentinel node biopsy should be considered for locally advanced, clinically node-negative cSCCs and MCCs. BCC patients failing traditional surgery and/or radiation are candidates for systemic hedgehog inhibitor therapy. Immune checkpoint inhibitor treatment is available for patients who failed traditional treatment with surgery and/or radiation or who are not candidates for these modalities. Specifically, cemiplimab is approved for advanced BCC; cemiplimab and pembrolizumab for advanced cSCC; and avelumab, pembrolizumab, and retifanlimab-dlwr for recurrent/metastatic MCC.

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Liver cancer is a global health challenge, causing a significant social-economic burden. Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, which is highly heterogeneous in terms of molecular and cellular signatures. Early-stage or small tumors are typically treated with surgery or ablation. Currently, chemotherapies and immunotherapies are the best treatments for unresectable tumors or advanced HCC. However, drug response and acquired resistance are not predictable with the existing systematic guidelines regarding mutation patterns and molecular biomarkers, resulting in sub-optimal treatment outcomes for many patients with atypical molecular profiles. With advanced technological platforms, valuable information such as tumor genetic alterations, epigenetic data, and tumor microenvironments can be obtained from liquid biopsy. The inter- and intra-tumoral heterogeneity of HCC are illustrated, and these collective data provide solid evidence in the decision-making process of treatment regimens. This article reviews the current understanding of HCC detection methods and aims to update the development of HCC surveillance using liquid biopsy. Recent critical findings on the molecular basis, epigenetic profiles, circulating tumor cells, circulating DNAs, and omics studies are elaborated for HCC diagnosis. Besides, biomarkers related to the choice of therapeutic options are discussed. Some notable recent clinical trials working on targeted therapies are also highlighted. Insights are provided to translate the knowledge into potential biomarkers for detection and diagnosis, prognosis, treatment response, and drug resistance indicators in clinical practice.

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Introduction: Despite the effectiveness of exercise-based interventions on symptom management and disease progression, many people with Parkinson's Disease (PwPD) do not exercise regularly. In line with the ubiquitous use of digital health technology, the MoveONParkinson digital solution was developed, comprising a Web Platform and a Mobile App with a Conversational Agent (CA). The interface features were designed based on the principles of Social Cognitive Theory with the goal of fostering behavior change in PwPD for sustained exercise participation and improved disease management. Methods: Using a mixed methods approach, this study aimed to collect feedback, assess the acceptability of the Mobile App and the Web Platform, and evaluate the usability of the latter. Quantitative data, which included questionnaire responses and the System Usability Scale (SUS) scores, were analyzed using descriptive statistics, heatmaps, and correlation matrices. Qualitative data, comprising semi-structured and thinking-aloud interview transcripts, were subjected to an inductive thematic analysis. A total of 28 participants were involved in the study, comprising 20 physiotherapists (average age: 34.50 ± 10.4), and eight PwPD (average age: 65.75 ± 8.63; mean Hoehn & Yahr: 2.0 (± 0.76)). Results: Three main themes emerged from the thematic analysis of the interviews, namely: Self-management (Theme 1), User Engagement (Theme 2), and Recommendations (Theme 3). The assessment of the Mobile App and the CA (mean score: 4.42/5.0 ± 0.79) suggests that PwPD were able to navigate this interface without notable difficulties. The mean SUS score of 79.50 (± 12.40%) with a 95% confidence interval ranging from 73.70 to 85.30, reveal good usability. Discussion: These findings indicate a high level of acceptability of the MoveONParkinson digital solution, serving as a foundation for assessing its impact on exercise engagement and, subsequently, its influence on symptom management and quality of life of PwPD.

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The NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease provide strategies for the prevention, diagnosis, and treatment of venous thromboembolism (VTE) in adult patients with cancer. VTE is a common and life-threatening condition in patients with cancer, and its management often requires multidisciplinary efforts. The NCCN panel is comprised of specialists spanning various fields, including cardiology, hematology, medical oncology, internal medicine, interventional radiology, and pharmacology. The content featured in this issue specifically addresses the evaluation and recommended treatment options outlined in the NCCN Guidelines for the diverse subtypes of cancer-associated VTE.

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Hypertensive crises in pediatric patients are rare conditions. However, determining their precise prevalence is more challenging than in adults due to the heterogeneity in the definition itself. These crises frequently occur without a prior diagnosis of hypertension and may indicate an underlying cause of secondary hypertension, including pheochromocytoma/paraganglioma (PPGL). The mechanisms of hypertensive crises in the pediatric population with PPGL are directly related to different types of catecholamine excess. Noradrenergic tumors typically present with sustained hypertension due to their predominant action on α1-adrenoceptors in the vasculature. Conversely, adrenergic tumors, through epinephrine binding to ß2-adrenoceptors in addition to stimulation of α1- and α2-adrenoceptors, more frequently cause paroxysmal hypertension. Furthermore, the biochemical phenotype also reflects the tumor localization and the presence of a genetic mutation. Recent evidence suggests that more than 80% of PPGL in pediatric cases have a hereditary background. PPGL susceptibility mutations are categorized into three clusters; mutations in cluster 1 are more frequently associated with a noradrenergic phenotype, whereas those in cluster 2 are associated with an adrenergic phenotype. Consequently, the treatment of hypertensive crises in pediatric patients with PPGL, reflecting the underlying pathophysiology, requires first-line therapy with alpha-blockers, potentially in combination with beta-blockers only in the case of tachyarrhythmia after adequate alpha-blockade. The route of administration for treatment depends on the context, such as intraoperative or pre-surgical settings, and whether it presents as a hypertensive emergency (elevated blood pressure with acute target organ damage), where intravenous administration of antihypertensive drugs is mandatory. Conversely, in cases of hypertensive urgency, if children can tolerate oral therapy, intravenous administration may initially be avoided. However, managing these cases is complex and requires careful consideration of the selection and timing of therapy administration, particularly in pediatric patients. Therefore, facing these conditions in tertiary care centers through interdisciplinary collaboration is advisable to optimize therapeutic outcomes.

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Sydenham's chorea (SC), an autoimmune disorder affecting the central nervous system, is a pivotal diagnostic criterion for acute rheumatic fever. Primarily prevalent in childhood, especially in developing countries, SC manifests with involuntary movements and neuropsychiatric symptoms. Predominantly occurring between ages 5 and 15, with a female bias, SC may recur, particularly during pregnancy or estrogen use. The autoimmune response affecting the basal ganglia, notably against dopamine, underlies the pathophysiology. Clinical management necessitates an integrated approach, potentially involving immunomodulatory therapies. To address discrepancies in SC management, a survey was conducted across Italy, targeting specialists in neurology, pediatrics, child neuropsychiatry, and rheumatology. Of the 51 responding physicians, consensus favored hospitalization for suspected SC, with broad support for laboratory tests and brain MRI. Treatment preferences showed agreement on oral prednisone and IVIG, while opinions varied on duration and plasmapheresis. Haloperidol emerged as the preferred symptomatic therapy. Post-SC penicillin prophylaxis and steroid therapy gained strong support, although opinions differed on duration. Follow-up recommendations included neuropsychological and cardiological assessments. Despite offering valuable insights, broader and more studies are needed in order to guide treatment decisions in this well-known yet challenging complication of acute rheumatic fever, which continues to warrant scientific attention and concerted clinical efforts.

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Cancer is a complex disease intrinsically associated with cellular processes and gene expression. With the development of techniques such as single-cell sequencing and sequential fluorescence in situ hybridization (seqFISH), it was possible to map the location of cells based on their gene expression with more precision. Moreover, in recent years, many tools have been developed to analyze these extensive datasets by integrating machine learning and artificial intelligence in a comprehensive manner. Since these tools analyze sequencing data, they offer the chance to analyze any tissue regardless of its origin. By applying this to cancer settings, spatial transcriptomic analysis based on artificial intelligence may help us understand cell-cell communications within the tumor microenvironment. Another advantage of this analysis is the identification of new biomarkers and therapeutic targets. The integration of such analysis with other omics data and with routine exams such as magnetic resonance imaging can help physicians with the earlier diagnosis of tumors as well as establish a more personalized treatment for pancreatic cancer patients. In this review, we give an overview description of pancreatic cancer, describe how spatial transcriptomics and artificial intelligence have been used to study pancreatic cancer and provide examples of how integrating these tools may help physicians manage pancreatic cancer in a more personalized approach.

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The therapeutic armamentarium of chronic myeloid leukemia (CML) has dramatically improved after small molecule tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 became available, with a life expectancy now close to that of the general population. Although highly effective, these drugs also have a toxicity profile that is often mild to moderate, but sometimes severe. Indeed, long-term treatment with TKIs can lead to chronic adverse events that can negatively affect patients' quality of life and can promote significant morbidity and mortality, particularly in the case of second- or third-generation TKIs. Treatment discontinuation has therefore become an emerging goal for CML patients and numerous studies have evaluated in off-TKI subjects what requirements are appropriate for an attempt at treatment-free remission (TFR). TFR eligibility is currently limited to a small population of subjects with both deep and sustained molecular responses to TKIs. For those attempting TFR, average success rates are promising, with 25%-30% of patients experiencing prolonged TFR. In case of failure to maintain sustained TFR, safety results to date are reassuring, with almost all patients responding successfully to resumption of TKIs, and advanced-phase disease progression representing a very rare event. The purpose of this review is to discuss guidelines for TKI discontinuation, clinical advances from clinical trials and real-life experiences, and describe areas of research, particularly regarding the biological factors capable of predicting the success of TFR.

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OBJECTIVE: Considerable disparities exist in access to gastrointestinal (GI) care and digestive outcomes across gender, racial, and socioeconomic groups. We evaluated (1) whether adults with chronic GI symptoms from diverse demographic groups would use a digital digestive care programme and (2) the effects of participation on GI symptom severity and other patient-reported outcomes. METHODS: Access to a digital digestive chronic care programme was provided to participants regardless of prior digestive diagnoses or symptoms for 90 days. The intervention included GI symptom tracking, personalised medical nutrition therapy, GI-specific health coaching, and targeted education on common GI symptoms. We assigned a Social Vulnerability Index (SVI) score to each participant according to their home address and compared baseline and end-intervention symptoms and other patient-reported outcomes by gender, race/ethnicity, and SVI. RESULTS: Of the 1936 participants, mean age was 43.1 years; 67% identified as white/Caucasian, 11% Asian/Pacific Islander, 6% Hispanic/Latinx, 7% black/African American, and 7% of multiple races. Participants of all demographic groups used the app symptom logging, reviewed educational materials, and interacted with their care team and reported similar statistically significant improvements in GI symptoms (by the end of the intervention, 85% improved, p<0.05). Participants reported feeling greater control of their health (83%), better able to manage their digestive symptoms (83%), increased happiness (76%), and greater productivity at work (54%), with black/African Americans and Native Americans most likely to report these changes. CONCLUSION: We conclude that a digital GI disease management programme may be of value in reducing disparities in access to GI care.

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Aortopathy encompasses a spectrum of conditions predisposing to dilation, aneurysm, dissection, or rupture of the aorta and other blood vessels. Aortopathy is diagnosed commonly in children, from infancy through adolescence, primarily affecting the thoracic aorta, with variable involvement of the peripheral vasculature. Pathogeneses include connective tissue disorders, smooth muscle contraction disorders, and congenital heart disease, including bicuspid aortic valve, among others. The American Heart Association has published guidelines for diagnosis and management of thoracic aortic disease. However, these guidelines are predominantly focused on adults and cannot be applied adeptly to growing children with emerging features, growth and developmental changes, including puberty, and different risk profiles compared with adults. Management to reduce risk of progressive aortic dilation and dissection or rupture in children is complex and involves genetic testing, cardiovascular imaging, medical therapy, lifestyle modifications, and surgical guidance that differ in many ways from adult management. Pediatric practice varies widely, likely because aortopathy is pathogenically heterogeneous, including genetic and nongenetic conditions, and there is limited published evidence to guide care in children. To optimize care and reduce variation in management, experts in pediatric aortopathy convened to generate this scientific statement regarding the cardiovascular care of children with aortopathy. Available evidence and expert consensus were combined to create this scientific statement. The most common causes of pediatric aortopathy are reviewed. This document provides a general framework for cardiovascular management of aortopathy in children, while allowing for modification based on the personal and familial characteristics of each child and family.

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Substance use disorder (SUD) affects more than 1 in 6 Americans older than 12 years and has become an increasingly relevant topic in palliative care. Lack of clear guidelines and fragmented care results in patient safety concerns and poor outcomes. This rapid review aims to present the current literature on opioid contracts/agreements, prescription drug monitoring database access, opioid risk assessment tools, and urine drug screening in the palliative care setting. Through a systematic process, we identified 19 articles published between 2018 and 2023 that pertained to substance use disorder and palliative care. Current risk mitigation strategies include prescription drug monitoring, opioid use agreements, risk assessment tools, urine drug screening, and the use of buprenorphine to manage pain. Prescription drug monitoring programs are state-based electronic databases that track controlled substances, and there are numerous risk assessment tools. Urine drug screening involves the use of both immunoassay and confirmatory chromatography to determine the presence or absence of either the prescribed controlled substance or unexpected findings including illicit drugs or prescription-controlled substances that are not prescribed to the patient. The goal of mitigating risk and reducing harm while providing expert symptom management is the challenge that palliative care transdisciplinary teams face as they continue to care for patients with substance use disorder. This review points to the need for further research on how to incorporate these harm-reducing strategies into clinical practice.

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Primary progressive multiple sclerosis (PPMS), the least frequent type of multiple sclerosis (MS), is characterized by a specific course and clinical symptoms, and it is associated with a poor prognosis. It requires extensive differential diagnosis and often a long-term follow-up before its correct recognition. Despite recent progress in research into and treatment for progressive MS, the diagnosis and management of this type of disease still poses a challenge. Considering the modern concept of progression "smoldering" throughout all the stages of disease, a thorough exploration of PPMS may provide a better insight into mechanisms of progression in MS, with potential clinical implications. The goal of this study was to review the current evidence from investigations of PPMS, including its background, clinical characteristics, potential biomarkers and therapeutic opportunities. Processes underlying CNS damage in PPMS are discussed, including chronic immune-mediated inflammation, neurodegeneration, and remyelination failure. A review of potential clinical, biochemical and radiological biomarkers is presented, which is useful in monitoring and predicting the progression of PPMS. Therapeutic options for PPMS are summarized, with approved therapies, ongoing clinical trials and future directions of investigations. The clinical implications of findings from PPMS research would be associated with reliable assessments of disease outcomes, improvements in individualized therapeutic approaches and, hopefully, novel therapeutic targets, relevant for the management of progression.

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BACKGROUND: People with diabetes, vascular disease, and asthma often struggle to maintain stability in their chronic health conditions, particularly those in rural areas, living in poverty, or racially or ethnically minoritized populations. These groups can experience inequities in healthcare, where one group of people has fewer or lower-quality resources than others. Integrating behavioral healthcare services into primary care holds promise in helping the primary care team better manage patients' conditions, but it involves changing the way care is delivered in a clinic in multiple ways. Some clinics are more successful than others in fully integrating behavioral health models as shown by previous research conducted by our team identifying four patterns of implementation: Low, Structural, Partial, and Strong. Little is known about how this variation in integration may be related to chronic disease management and if IBH could be a strategy to reduce healthcare inequities. This study explores potential relationships between IBH implementation variation and chronic disease management in the context of healthcare inequities. METHODS: Building on a previously published latent class analysis of 102 primary care clinics in Minnesota, we used multiple regression to establish relationships between IBH latent class and healthcare inequities in chronic disease management, and then structural equation modeling to examine how IBH latent class may moderate those healthcare inequities. RESULTS: Contrary to our hypotheses, and demonstrating the complexity of the research question, clinics with better chronic disease management were more likely to be Low IBH rather than any other level of integration. Strong and Structural IBH clinics demonstrated better chronic disease management as race in the clinic's location became more White. CONCLUSIONS: IBH may result in improved care, though it may not be sufficient to resolve healthcare inequities; it appears that IBH may be more effective when fewer social determinants of health are present. Clinics with Low IBH may not be motivated to engage in this practice change for chronic disease management and may need to be provided other reasons to do so. Larger systemic and policy changes are likely required that specifically target the mechanisms of healthcare inequities.

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OBJECTIVE: The family physician team has become the core carrier for delivery primary health care in China. This study aimed to measure the effect of the network structural characteristics of family physician team processes on health performance. Strategic recommendations for optimizing the family physician team processes with a view to improving performance were presented. METHODS: A cross-sectional survey was conducted from October to December 2021 in Qianjiang in Hubei Province and Changsha in Hunan Province. Task performance, contextual performance, social networks, and sociodemographic characteristics were collected. Social network analysis was conducted to calculate density and centralization, then hierarchical linear regression analysis was employed to explore the relationship between the network structural characteristics of family physician team processes and performance. RESULTS: In total, 88 family physician teams attended in this investigation. The transition processes of family physician team showed a distinctive low density (0.272 ± 0.112), high centralization (0.866 ± 0.197) network structure. For family physician team, the density of action processes significantly and positively affected task performance (B = 0.600, P < 0.05); the centralization of action processes positively affected task performance (B = 0.604, P < 0.01); the density of action processes positively affected contextual performance (B = 0.545, P < 0.01); the density of interpersonal processes significantly and positively affected contextual performance (B = 0.326, P < 0.05). CONCLUSION: The network density and centralization of family physician team processes have positive effects on chronic disease management performance. The results from this study help to enhance our conceptual understanding of social network and its implications for team-dynamics. Optimizing family physician team processes is an effective way to strengthen the construction of family physician team and promote the quality and efficiency of family physician-contracted service. It is recommended to strengthen the management of team processes, enhance the internal collaboration mechanism, and optimize the centralized network structure of family physician team.

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Diagnosing the current health status and disease burden in a population is crucial for public health interventions. The ability to compare the burden of different diseases through a single measure, such as disability-adjusted life years has become feasible and continues to be produced and updated through the Global Burden of Diseases (GBD) study. However, the disease burden values of the GBD study do not accurately reflect the unique situation in a specific country with various circumstances. In response, the Korean National Burden of Disease (KNBD) study was conducted to estimate the disease burden in Koreans by considering Korea's cultural context and utilizing the available data sources at the national level. Both studies identified non-communicable diseases, such as diabetes mellitus (DM), as the primary cause of disease burden among Koreans. However, the extent of public health interventions currently being conducted by the central and local governments does not align with the severity of the disease burden. This review suggests that despite the high burden of DM in South Korea, the current policies may not fully address its impact, underscoring the need for expanded chronic disease management programs and a shift towards prevention-focused healthcare paradigms.

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