State of the Art in Low-Grade Glioma Management: Insights From Isocitrate Dehydrogenase and Beyond.

Low-grade gliomas present a formidable challenge in neuro-oncology because of the challenges imposed by the blood-brain barrier, predilection for the young adult population, and propensity for recurrence. In the past two decades, the systematic examination of genomic alterations in adults and children with primary brain tumors has uncovered profound new insights into the pathogenesis of these tumors, resulting in more accurate tumor classification and prognostication. It also identified several common recurrent genomic alterations that now define specific brain tumor subtypes and have provided a new opportunity for molecularly targeted therapeutic intervention. Adult-type diffuse low-grade gliomas are frequently associated with mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2), resulting in production of 2-hydroxyglutarate, an oncometabolite important for tumorigenesis. Recent studies of IDH inhibitors have yielded promising results in patients at early stages of disease with prolonged progression-free survival (PFS) and delayed time to radiation and chemotherapy. Pediatric-type gliomas have high rates of alterations in BRAF, including BRAF V600E point mutations or BRAF-KIAA1549 rearrangements. BRAF inhibitors, often combined with MEK inhibitors, have resulted in radiographic response and improved PFS in these patients. This article reviews emerging approaches to the treatment of low-grade gliomas, including a discussion of targeted therapies and how they integrate with the current treatment modalities of surgical resection, chemotherapy, and radiation.

Paradigm Shifts in Hodgkin Lymphoma Treatment: From Frontline Therapies to Relapsed Disease.

Combination chemotherapy with or without radiation has served as the primary therapeutic option for classic Hodgkin lymphoma (cHL), leading to durable remission in a majority of patients with early- and advanced-stage cHL. Patients with relapsed/refractory (RR) cHL could still be cured with salvage chemotherapy and autologous stem-cell transplantation. Brentuximab vedotin (BV) and the anti-PD-1-blocking antibodies, nivolumab and pembrolizumab, are highly effective treatments for cHL and have revolutionized the management of the disease. Recent studies incorporating BV and PD-1 blockade into salvage therapy for RR cHL and into frontline treatment regimens have changed the cHL treatment paradigm. The novel agents are also useful in the treatment of older patients who have poor outcomes with traditional therapy. This manuscript will review current strategies for approaching the management of previously untreated, RR, and challenging populations with cHL, including how to incorporate the novel agents.

The ABCs of the 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease.

BACKGROUND: The 2023 Multisociety Guideline for the Management of Chronic Coronary Disease (CCD) updates recommendations for CCD, formerly known as "stable ischemic heart disease." This condition encompasses a spectrum of coronary vascular pathologies from subclinical to clinical ischemic heart disease. HYPOTHESIS: The new "ABC" mnemonic offers clinicians a streamlined framework for applying Class One Recommendations (COR1) and integrating recent updates into CCD management. METHODS: A critical analysis of the 2023 CCD guidelines was conducted, with this review highlighting key elements. RESULTS: The review outlines crucial changes, including novel recommendations supported by current clinical evidence. The focus is on these developments, clarifying their importance for day-to-day clinical practice. CONCLUSIONS: The review encourages a synergistic approach between primary healthcare providers and cardiologists to develop comprehensive strategies for lifestyle modification and medication therapy in CCD care. Furthermore, it suggests that utilizing comprehensive risk assessment tools can refine medical decision-making, ultimately enhancing patient care and clinical outcomes.

Advancements in Urothelial Cancer Care: Optimizing Treatment for Your Patient.

The standard treatment paradigm for muscle invasive bladder cancer has been neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy. However, efforts are ongoing to personalize treatment by incorporating biomarkers to better guide treatment selection. In addition, bladder preservation strategies are aimed at avoiding cystectomy in well-selected patients. Similarly, in the metastatic urothelial cancer space, the standard frontline treatment option of platinum-based chemotherapy has changed with the availability of data from EV-302 trial, making the combination of enfortumab vedotin (EV) and pembrolizumab the preferred first-line treatment option. Here, we examine the optimization of treatment intensity and sequencing, focusing on the challenges and opportunities associated with EV/pembrolizumab therapy, including managing toxicities and exploring alternative dosing approaches. Together, these articles provide a comprehensive overview of contemporary strategies in bladder cancer management, highlighting the importance of individualized treatment approaches, ongoing research, and multidisciplinary collaboration to improve patient outcomes in this complex disease landscape.

State-of-the-Art Management of Colorectal Cancer: Treatment Advances and Innovation.

Colorectal cancer (CRC) remains a significant global health challenge, ranking among the leading causes of cancer-related morbidity and mortality worldwide. Recent advancements in molecular characterization have revolutionized our understanding of the heterogeneity within colorectal tumors, particularly in the context of tumor sidedness. Tumor sidedness, referring to the location of the primary tumor in either the right or left colon, has emerged as a critical factor influencing prognosis and treatment responses in metastatic CRC. Molecular underpinnings of CRC, the impact of tumor sidedness, and how this knowledge guides therapeutic decisions in the era of precision medicine have led to improved outcomes and better quality of life in patients. The emergence of circulating tumor DNA as a prognostic and predictive tool in CRC heralds promising advancements in the diagnosis and monitoring of the disease. This innovation facilitates better patient selection for exploration of additional treatment options. As the field progresses, with investigational agents demonstrating potential as future treatments for refractory metastatic CRC, new avenues for enhancing outcomes in this challenging disease are emerging.

Germline Predisposition in Hematologic Malignancies: Testing, Management, and Implications.

Although numerous barriers for clinical germline cancer predisposition testing exist, the increasing recognition of deleterious germline DNA variants contributing to myeloid malignancy risk is yielding steady improvements in referrals for testing and testing availability. Many germline predisposition alleles are common in populations, and the increasing number of recognized disorders makes inherited myeloid malignancy risk an entity worthy of consideration for all patients regardless of age at diagnosis. Germline testing is facilitated by obtaining DNA from cultured skin fibroblasts or hair bulbs, and cascade testing is easily performed via buccal swab, saliva, or blood. Increasingly as diagnostic criteria and clinical management guidelines include germline myeloid malignancy predisposition, insurance companies recognize the value of testing and provide coverage. Once an individual is recognized to have a deleterious germline variant that confers risk for myeloid malignancies, a personalized cancer surveillance plan can be developed that incorporates screening for other cancer risk outside of the hematopoietic system and/or other organ pathology. The future may also include monitoring the development of clonal hematopoiesis, which is common for many of these cancer risk disorders and/or inclusion of strategies to delay or prevent progression to overt myeloid malignancy. As research continues to identify new myeloid predisposition disorders, we may soon recommend testing for these conditions for all patients diagnosed with a myeloid predisposition condition.

Evolving Standards of Care in the Management of Localized Colorectal Cancer.

The treatment of patients with localized rectal cancer is complex and requires input from a multidisciplinary team. Baseline local staging and mismatch repair protein testing are vital to develop individualized treatment plans. There are multiple options in terms of treatment modalities and sequencing, including transanal excision, short-course radiation, long-course chemoradiation, chemotherapy doublet or triplet, nonoperative management, and immune checkpoint blockade for patients with mismatch repair deficient tumors. While localized colon cancer is typically treated with surgical resection and consideration of adjuvant chemotherapy, emerging data suggest that neoadjuvant chemotherapy may be beneficial in patients with higher-risk disease. Quality-of-life considerations are imperative to prevent potential chronic effects on psychosocial health, neuropathy, fertility, and bowel, bladder, and sexual function. The omission of radiation or surgery can mitigate these toxicities without diminishing oncologic outcomes. The optimal treatment plan and sequence is not a one-size-fits-all approach but rather should be personalized to the patient's disease burden, tumor location, comorbidities, and preferences.

[New clinical guidelines for COPD - a paradigm shift: A review].

Chronic obstructive pulmonary disease is now one of the most common noncommunicable diseases and the main causes of morbidity, disability and mortality in the world. In recent years, new approaches to epidemiology, diagnosis, classification (categorization), evaluation of phenotypes, as well as characterization and assessment of the severity of сhronic obstructive pulmonary disease exacerbations have emerged. Modern approaches to starting and subsequent drug therapy have changed significantly. This is largely due to the results of recently conducted major clinical trials, demonstrated high efficacy of triple fixed combinations, including inhaled glucocorticosteroids, long-acting beta-agonists and long-acting anticholinergic drugs. The use of non-medication methods (smoking cessation, physical activity and respiratory rehabilitation) and modern approaches to the treatment of respiratory failure and antibiotic therapy remain important. In terms of their significance, all these updates have a significant impact on real clinical practice and can be considered as a novel paradigm of the approaches to the diagnosis and management of this disease.

MEMS Technology in Cardiology: Advancements and Applications in Heart Failure Management Focusing on the CardioMEMS Device.

Heart failure (HF) is a complex clinical syndrome associated with significant morbidity, mortality, and healthcare costs. It is characterized by various structural and/or functional abnormalities of the heart, resulting in elevated intracardiac pressure and/or inadequate cardiac output at rest and/or during exercise. These dysfunctions can originate from a variety of conditions, including coronary artery disease, hypertension, cardiomyopathies, heart valve disorders, arrhythmias, and other lifestyle or systemic factors. Identifying the underlying cause is crucial for detecting reversible or treatable forms of HF. Recent epidemiological studies indicate that there has not been an increase in the incidence of the disease. Instead, patients seem to experience a chronic trajectory marked by frequent hospitalizations and stagnant mortality rates. Managing these patients requires a multidisciplinary approach that focuses on preventing disease progression, controlling symptoms, and preventing acute decompensations. In the outpatient setting, patient self-care plays a vital role in achieving these goals. This involves implementing necessary lifestyle changes and promptly recognizing symptoms/signs such as dyspnea, lower limb edema, or unexpected weight gain over a few days, to alert the healthcare team for evaluation of medication adjustments. Traditional methods of HF monitoring, such as symptom assessment and periodic clinic visits, may not capture subtle changes in hemodynamics. Sensor-based technologies offer a promising solution for remote monitoring of HF patients, enabling early detection of fluid overload and optimization of medical therapy. In this review, we provide an overview of the CardioMEMS device, a novel sensor-based system for pulmonary artery pressure monitoring in HF patients. We discuss the technical aspects, clinical evidence, and future directions of CardioMEMS in HF management.

Hematopoietic Stem-Cell Transplantation: Exploring the Latest Advances and Gaps in Disparities, Psychosocial and Symptom Management Interventions, and Chronic Graft-Versus-Host Disease Care.

Although allogeneic hematopoietic cell transplantation (HCT) offers a potential for cure for many patients with advanced hematologic malignancies and bone marrow failure or immunodeficiency syndromes, it is an intensive treatment and accompanied by short- and long-term physical and psychological symptoms requiring specialized care. With substantial advances in therapeutic approaches for HCT and supportive care, HCT survivors experience less morbidity and mortality. However, disparities in both HCT access and outcomes persist, and HCT survivors and their caregivers often lack access to much-needed psychosocial care. Additionally, more medical and psychosocial resources are needed to holistically care for HCT survivors with chronic graft-versus-host disease (GVHD). Hence, this chapter focuses on three areas pertaining to advances and gaps in HCT care: disparities in access to and outcomes of HCT, psychosocial and physical symptom management with supportive care interventions, and GVHD prevention and management.

Are we closer to a standard of care for Richter's syndrome? Novel treatments on the horizon.

INTRODUCTION: The therapeutic landscape for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved over the past decade with dramatically improved outcomes with the introduction of targeted therapies. This unfortunately has not been the case for Richter transformation (RT), the histologic transformation to a more aggressive lymphoma, most typically diffuse large B-cell lymphoma (DLBCL). As such, RT continues to be one of the most challenging complications of CLL/SLL. Historically, RT has a poor response to treatment, with a minority reaching complete remission (CR) and overall survival (OS) being less than a year. AREAS COVERED: The focus of this review is to discuss the effectiveness of commonly used regimens, and review existing data for emerging regimens being examined in ongoing clinical trials to improve prognosis and outcomes in patients with RT. Despite extensive efforts to optimize therapies for RT, there is still no generalized consensus on either first-line treatment regimens or regimens in the relapsed/refractory setting. RT continues to carry a high mortality rate without durable response to current therapeutic agents. EXPERT OPINION: Ongoing and future research may identify novel treatment approaches that will eventually improve outcomes for patients with RT. The optimal care for RT patients is a clinical trial, when feasible.

Diagnosis, treatment, and management of rickets: a position statement from the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology.

Rickets results from impaired mineralization of growing bone due to alterations in calcium and phosphate homeostasis. Clinical signs of rickets are related to the age of the patient, the duration of the disease, and the underlying disorder. The most common signs of rickets are swelling of the wrists, knees or ankles, bowing of the legs (knock-knees, outward bowing, or both) and inability to walk. However, clinical features alone cannot differentiate between the various forms of rickets. Rickets includes a heterogeneous group of acquired and inherited diseases. Nutritional rickets is due to a deficiency of vitamin D, dietary calcium or phosphate. Mutations in genes responsible for vitamin D metabolism or function, the production or breakdown of fibroblast growth factor 23, renal phosphate regulation, or bone mineralization can lead to the hereditary form of rickets. This position paper reviews the relevant literature and presents the expertise of the Bone and Mineral Metabolism Group of the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP). The aim of this document is to provide practical guidance to specialists and healthcare professionals on the main criteria for diagnosis, treatment, and management of patients with rickets. The various forms of rickets are discussed, and detailed references for the discussion of each form are provided. Algorithms to guide the diagnostic approach and recommendations to manage patients with rare forms of hereditary rickets are proposed.

Diagnosis, treatment, and surveillance of Diamond-Blackfan anaemia syndrome: international consensus statement.

Diamond-Blackfan anaemia (DBA), first described over 80 years ago, is a congenital disorder of erythropoiesis with a predilection for birth defects and cancer. Despite scientific advances, this chronic, debilitating, and life-limiting disorder continues to cause a substantial physical, psychological, and financial toll on patients and their families. The highly complex medical needs of affected patients require specialised expertise and multidisciplinary care. However, gaps remain in effectively bridging scientific discoveries to clinical practice and disseminating the latest knowledge and best practices to providers. Following the publication of the first international consensus in 2008, advances in our understanding of the genetics, natural history, and clinical management of DBA have strongly supported the need for new consensus recommendations. In 2014 in Freiburg, Germany, a panel of 53 experts including clinicians, diagnosticians, and researchers from 27 countries convened. With support from patient advocates, the panel met repeatedly over subsequent years, engaging in ongoing discussions. These meetings led to the development of new consensus recommendations in 2024, replacing the previous guidelines. To account for the diverse phenotypes including presentation without anaemia, the panel agreed to adopt the term DBA syndrome. We propose new simplified diagnostic criteria, describe the genetics of DBA syndrome and its phenocopies, and introduce major changes in therapeutic standards. These changes include lowering the prednisone maintenance dose to maximum 0·3 mg/kg per day, raising the pre-transfusion haemoglobin to 9-10 g/dL independent of age, recommending early aggressive chelation, broadening indications for haematopoietic stem-cell transplantation, and recommending systematic clinical surveillance including early colorectal cancer screening. In summary, the current practice guidelines standardise the diagnostics, treatment, and long-term surveillance of patients with DBA syndrome of all ages worldwide.

Supporting best practice in the management of chronic diseases in primary health care settings: a scoping review of training programs for Indigenous Health Workers and Practitioners.

Background To improve diabetes management in primary health care for the Aboriginal and Torres Strait Islander peoples population, training programs that are culturally and contextually relevant to the local context are required. Using a scoping review methodology, the aim of this review was to describe the characteristics of chronic disease management training programs for Aboriginal Health Workers and Practitioners, their effectiveness on knowledge and skills, and client-related outcomes, and the enablers, barriers to delivery and participation. Methods Following protocol parameters, a systematic search was conducted in relevant databases and grey literature. Two independent reviewers screened the title and abstract of each paper to determine if the study met the inclusion criteria. Results Of the 23 included studies, most were developed with stakeholders, profession facilitated and delivered by cultural facilitators. All training programs included content knowledge, two included a professional support network, four provided on-the-job support and six had follow-up support post-training. Modes of delivery ranged from didactic, storytelling and hands-on learning. Two studies reported significant improvement in participants' knowledge and confidence; one reported improvement in knowledge (12.7% increase pre-post training), and an increase in confidence in both clinical and non-clinical skills. Enablers (relevance, modes of learning, power of networking, improved knowledge, confidence and clinical practice) and barriers (adult learning capabilities, competing work-family commitments) were reported. Few studies reported on knowledge transfer into clinical practice and client-related outcomes. Conclusions Multifaceted training programs for Aboriginal health workers are well received and may improve workforce capability.

Exploring European Consensus About the Remaining Treatment Challenges and Subsequent Opportunities to Improve the Management of Invasive Fungal Infection (IFI) in the Intensive Care Unit.

BACKGROUND: The global prevalence of invasive fungal infections (IFI) is increasing, particularly within Intensive Care Units (ICU), where Candida spp. and Aspergillus spp. represent the most important pathogens. Diagnosis and management of IFIs becomes progressively challenging, with increasing antifungal resistance and the emergence of rare fungal species. Through a consensus survey focused on assessing current views on how IFI should be managed, the aim of this project was to identify challenges around diagnosing and managing IFIs in the ICU. The current status in different countries and perceived challenges to date amongst a multidisciplinary cohort of healthcare professionals involved in the care of IFI in the ICU was assessed. METHODS: Using a modified Delphi approach, an expert panel developed 44 Likert-scale statements across 6 key domains concerning patient screening and minimal standards for diagnosis of IFIs in ICU; initiation and termination of antifungal treatments and how to minimise their side effects and insights for future research on this topic. These were used to develop an online survey which was distributed on a convenience sampling basis utilising the subscriber list held by an independent provider (M3 Global). This survey was distributed to intensivists, infectious disease specialists, microbiologists and antimicrobial/ICU pharmacists within the UK, Germany, Spain, France and Italy. The threshold for consensus was set at 75%. RESULTS: A total of 335 responses were received during the five-month collection period. From these, 29/44 (66%) statements attained very high agreement (≥ 90%), 11/44 (25%) high agreement (< 90% and ≥ 75%), and 4/44 (9%) did not meet threshold for consensus (< 75%). CONCLUSION: The results outline the need for physicians to be aware of the local incidence of IFI and the associated rate of azole resistance in their ICUs. Where high clinical suspicion exists, treatment should start immediately and prior to receiving the results from any diagnostic test. Beta-D-glucan testing should be available to all ICU centres, with results available within 48 h to inform the cessation of empirical antifungal therapy. These consensus statements and proposed measures may guide future areas for further research to optimise the management of IFIs in the ICU.

Is there any difference between Eastern and Western clinical practice guidelines in management of gastric cancer?

BACKGROUND AND RECENT FINDINGS: Gastric cancer (GC) has been known as one of the most common causes of cancer mortality both in Western and Eastern countries. However, there might be differences between how it is managed in different countries. Thus, we aimed to investigate these differences. MATERIALS AND METHODS: The most well-known clinical guidelines in field of GC management including Korean GC Association (KGCA), Japanese GC Association (JGCA), National Comprehensive Cancer Network (NCCN), European Society for Medical Oncology (ESMO), British Society of Gastroenterology (BSG), and National Institute for health and Care Excellence (NICE) have been reviewed. RESULTS: The contents of these guidelines were categorized under eight headings including (1) genetic predisposition, (2) prevention, (3) management of gastric polyp, atrophy, dysplasia and metaplasia, (4) diagnosis, (5) pathology and molecular biology, (6) treatment, (7) supportive and palliative care, and (8) follow up. Difference in each section was discussed. CONCLUSION: Considering KGCA and JGCA as Eastern and NCCN, ESMO, BSG, and NICE as Western guidelines, it is revealed that both sets of guidelines share common practices such as prioritizing comprehensive diagnostic evaluations, personalizing treatment plans, and palliative care. However, main differences can be seen in treatment regimens, the adoption of newer therapies like immunotherapy, and the utilization of emerging techniques such as HIPEC. These differences reflect the diverse clinical landscapes, research focuses, and healthcare systems within these regions.

Objective monitoring tools for improved management of childhood asthma.

Asthma is a common chronic disease amongst children. Epidemiological studies showed that the mortality rate of asthma in children is still high worldwide. Asthma control is therefore essential to minimize asthma exacerbations, which can be fatal if the condition is poorly controlled. Frequent monitoring could help to detect asthma progression and ensure treatment effectiveness. Although subjective asthma monitoring tools are available, the results vary as they rely on patients' self-perception. Emerging evidence suggests several objective tools could have the potential for monitoring purposes. However, there is no consensus to standardise the use of objective monitoring tools. In this review, we start with the prevalence and severity of childhood asthma worldwide. Then, we detail the latest available objective monitoring tools, focusing on their effectiveness in paediatric asthma management. Publications of spirometry, fractional exhaled nitric oxide (FeNO), hyperresponsiveness tests and electronic monitoring devices (EMDs) between 2016 and 2023 were included. The potential advantages and limitations of each tool were also discussed. Overall, this review provides a summary for researchers dedicated to further improving objective paediatric asthma monitoring and provides insights for clinicians to incorporate different objective monitoring tools in clinical practices.