Ryan Haumschild, PharmD, MS, MBA

Panelists discuss how disease progression monitoring requires integrating multiple data points including symptoms, six-minute walk tests, biomarkers like BNP/NT-proBNP, and imaging studies, with risk stratification tools helping guide treatment decisions while considering individual patient characteristics.

Panelists discuss how early detection barriers include nonspecific symptoms like progressive dyspnea that are often misattributed to more common conditions, leading to delayed diagnosis and the need for improved diagnostic algorithms using biomarkers and imaging.

Panelists discuss the exploration of combination therapies in treating complex or refractory NF1-associated plexiform neurofibromas, including MEK inhibitors combined with PI3K inhibitors, anti-angiogenic agents, and chemotherapies, and review early clinical findings suggesting potential synergistic effects, while highlighting concerns about toxicity and the need for careful patient monitoring.

Panelists discuss key findings supporting the use of MEK inhibitors, such as selumetinib, in treating NF1-associated plexiform neurofibromas, emphasizing its impact on clinical decision-making, particularly for pediatric patients with progressive, symptomatic tumors who are not surgical candidates, and review current guidelines recommending its use to control tumor growth and improve quality of life.

Panelists discuss how progressive pulmonary fibrosis (PPF) and idiopathic pulmonary fibrosis (IPF), though distinct in etiology, share a common trajectory of irreversible lung scarring and functional decline—highlighting the importance of recognizing progressive phenotypes across interstitial lung diseases to guide timely diagnosis, personalized treatment, and improved patient outcomes.

Panelists discuss how progressive pulmonary fibrosis (PPF) and idiopathic pulmonary fibrosis (IPF), though distinct in etiology, share a common trajectory of irreversible lung scarring and functional decline—highlighting the importance of recognizing progressive phenotypes across interstitial lung diseases to guide timely diagnosis, personalized treatment, and improved patient outcomes.

Panelists discuss how MEK inhibitors, such as trametinib and selumetinib, are emerging as first-line treatments for symptomatic NF1-associated plexiform neurofibromas, especially in progressive or inoperable cases, while emphasizing the importance of surgical resection, pain management, physical therapy, and psychosocial support for improving quality of life.

Panelists discuss the current management goals for NF1-associated plexiform neurofibromas, focusing on tumor control, symptom management, and prevention of malignant transformation, while highlighting the evolving future goals of targeted therapies, personalized treatment plans, and enhanced early detection to improve outcomes.

Panelists discuss how pulmonary arterial hypertension diagnosis requires comprehensive evaluation including right heart catheterization to confirm hemodynamic criteria, with normal mean PA pressure being ≤20 mmHg and the need to rule out other causes of pulmonary hypertension.

Panelists discuss how the pathophysiology of pulmonary arterial hypertension involves complex mechanisms across multiple genetic and treatment pathways, with over 20 identified genes and four major therapeutic targets including nitric oxide, endothelin, prostacyclin, and activin signaling inhibition.

Panelists discuss how progressive pulmonary fibrosis (PPF) and idiopathic pulmonary fibrosis (IPF), though distinct in etiology, share a common trajectory of irreversible lung scarring and functional decline—highlighting the importance of recognizing progressive phenotypes across interstitial lung diseases to guide timely diagnosis, personalized treatment, and improved patient outcomes.

Panelists discuss how idiopathic pulmonary fibrosis (IPF), a progressive and often fatal interstitial lung disease, presents significant clinical challenges due to its variable trajectory, limited treatment options, and poor prognosis—underscoring the importance of early diagnosis and specialized care and the need for therapies that can more effectively alter disease progression.

Panelists discuss the unmet needs in NF1-associated plexiform neurofibromas, highlighting gaps in effective treatment, pain management, psychosocial support, and prevention of malignant transformation, while emphasizing the importance of early intervention, multidisciplinary care, and ongoing research into targeted therapies and improved surveillance protocols.

Panelists discuss how severe symptoms in NF1-associated plexiform neurofibromas are influenced by tumor size, location, growth rate, and genetic factors, and emphasize the importance of early intervention, regular imaging, and a multidisciplinary approach for monitoring and managing risks, including malignant transformation and complications.

Panelists discuss how NF1-associated plexiform neurofibromas can cause significant morbidity, including disfigurement, pain, and neurologic impairment, with the risk of malignant transformation, and emphasize the impact of these tumors on quality of life, daily functioning, and prognosis based on tumor characteristics and access to care.

Panelists discuss how plexiform neurofibromas in NF1 often emerge in early childhood with progressive growth and symptoms such as disfigurement, pain, and neurologic deficits, noting that rapid enlargement may indicate malignant transformation, and that presentation and complications differ between pediatric and adult patients.

Panelists discuss how neurofibromatosis type 1 (NF1) is typically diagnosed in early childhood using National Institutes of Health (NIH) clinical criteria, with genetic testing supporting unclear cases, and highlight the global prevalence of NF1 and the high incidence of plexiform neurofibromas, which affect up to 50% of patients regardless of racial or geographic background.

Panelists discuss how mutations in the NF1 gene lead to loss of neurofibromin function, resulting in hyperactivation of the RAS/MAPK and PI3K/AKT/mTOR pathways, and how this molecular dysregulation drives abnormal cell proliferation and tumor development in NF1.

Panelists discuss how the management of uncomplicated urinary tract infections (UTIs) is evolving, with promising new therapies that address antibiotic resistance concerns, while emphasizing the continued importance of antimicrobial stewardship, personalized treatment approaches, preventive strategies, and comprehensive patient education to reduce recurrence rates and improve outcomes in this common but burdensome condition.

Panelists discuss how recurrent urinary tract infections (UTIs) treated with older antibiotics generate 2 to 3 times higher total costs than initial savings, warranting cost-effectiveness analyses in treatment decisions, whereas payers create barriers to newer therapies through restrictive authorizations, high co-pays, step therapy mandates, and limited formulary inclusion that providers can navigate via detailed documentation, pharmacy benefit manager engagement, patient assistance programs, and advocacy for evidence-based coverage policies.

Panelists discuss how newer urinary tract infection (UTI) therapies such as pivmecillinam, sulopenem etzadroxil/probenecid, and gepotidacin demonstrate significantly lower resistance rates (below 5%) compared with traditional first-line antibiotics (10%-30% for trimethoprim/sulfamethoxazole), with improved clinical and microbiological cure rates particularly for resistant pathogens, anticipating their integration into treatment algorithms as second-line options after nitrofurantoin and fosfomycin for patients with risk factors for resistance, prior treatment failures, recurrent infections, or confirmed resistant pathogens, although limited by higher costs and need for antimicrobial stewardship until more real-world effectiveness data become available.

Panelists discuss how sulopenem etzadroxil/probenecid, approved in October 2024, functions as an oral β-lactam/β-lactamase inhibitor effective against extended-spectrum β-lactamase producers per SURE 1 and REASSURE trial findings whereas gepotidacin works through a novel mechanism as a triazaacenaphthylene bacterial topoisomerase inhibitor targeting resistant pathogens via unique DNA gyrase and topoisomerase IV binding sites, with EAGLE trial findings demonstrating noninferiority to nitrofurantoin with approximately 90% cure rates.

Panelists discuss how American Urological Association (AUA) guidelines for recurrent uncomplicated urinary tract infections (UTIs) in women recommend culture-confirmed diagnosis, prophylactic antibiotics, nonantibiotic prevention, self-initiated treatment, and behavioral modifications while noting pivmecillinam’s recent FDA approval. Pivmecillinam features a penicillin-binding protein 2 inhibition mechanism with 85% to 95% efficacy against gram-negative uropathogens, including extended-spectrum β-lactamase producers; minimal intestinal flora disruption; low resistance rates; and primarily mild gastrointestinal adverse effects.

Panelists discuss how treatment failure in uncomplicated urinary tract infections (UTIs) creates substantial economic burden through direct costs of additional health care visits, repeated diagnostic tests, and rescue medications alongside indirect costs from productivity losses, with implications including progression to complicated infections such as pyelonephritis, increased emergency department use, antimicrobial resistance development threatening broader public health, psychological impacts on patients, and strain on health care resources that could be mitigated through more effective initial treatment strategies.

Panelists discuss how significant gaps in current uncomplicated urinary tract infection (UTI) therapies include insufficient nonantibiotic preventive strategies, limited options for multidrug-resistant pathogens, inadequate personalized treatment approaches, minimal focus on biofilm disruption, lack of rapid point-of-care diagnostics to guide targeted therapy, poor understanding of the urinary microbiome’s role in infection susceptibility, and insufficient research into immunomodulatory interventions that could address the underlying mechanisms of recurrence and resistance development.

Panelists discuss how fluoroquinolones are generally reserved for uncomplicated urinary tract infections (UTIs) only when first-line options are contraindicated or pathogen resistance is confirmed, with treatment duration ranging from single-dose fosfomycin to 3 to 5 days for most antibiotics and 7 to 10 days for nitrofurantoin, noting shorter regimens typically achieve 85% to 95% adherence rates compared with 60% to 75% for longer courses, significantly affecting treatment success, particularly when patient factors such as adverse effects, dosing complexity, and lifestyle disruptions are considered.

Panelists discuss how standard-of-care antibiotics for uncomplicated urinary tract infections (UTIs) show varying efficacy, with nitrofurantoin and fosfomycin demonstrating superior response rates (85%-95%) compared with trimethoprim/sulfamethoxazole (70%-80% due to increasing resistance) and first-generation cephalosporins (80%-90%), and how cost-effectiveness depends on local resistance patterns, patient adherence to dosing schedules, medication costs and insurance coverage, treatment duration, recurrence rates, comorbidities, and potential adverse effects requiring additional interventions.

Panelists discuss how uncomplicated urinary tract infections (UTIs) are typically managed with empiric short-course antibiotics based on local resistance patterns while identifying significant gaps in the outdated 2010 Infectious Diseases Society of America (IDSA) guidelines, including insufficient guidance on emerging resistance trends, limited recommendations for alternative therapies, inadequate consideration of patient-specific factors, absence of antimicrobial stewardship protocols, and minimal direction on prevention strategies for recurrent infections.

Panelists discuss how clinicians are addressing antimicrobial stewardship in urinary tract infection (UTI) management through implementation of evidence-based guidelines, delayed prescribing strategies, shorter treatment durations, targeted narrow-spectrum antibiotics based on local resistance patterns, increased use of culture-guided therapy, nonantibiotic preventive approaches, and enhanced patient education about appropriate antibiotic use.

Panelists discuss how patients with recurrent urinary tract infections (UTIs) describe significant burdens including constant anxiety about symptom onset, disruption to work and social life, financial strain from frequent office visits and medications, frustration with treatment-resistant infections, embarrassment discussing symptoms, sexual dysfunction, relationship difficulties, and substantial mental health impacts such as depression and diminished quality of life.