Patient Population Research Articles

From Rarity to Reality: Osimertinib's Promising Horizon in Treating Uncommon EGFR Mutations in Non-Small Cell Lung Cancer.

In the realm of advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) therapy with tyrosine kinase inhibitors (TKIs), addressing optimal treatment for uncommon EGFR mutations like G719X in exon 18, S768I in exon 20, and L861Q in exon 21 remains a pivotal yet challenging frontier. Contrary to the well-established efficacy of EGFR-TKIs in common EGFR mutations, these uncommon alterations pose unmet medical needs due to a lack of comprehensive evidence. While afatinib, a second-generation EGFR-TKI, has received FDA approval for patients with these uncommon EGFR mutations, the approval was based on a post-hoc analysis of randomized clinical trials. Recent developments include multiple clinical trials investigating the efficacy of both second and third-generation EGFR-TKIs in patients with uncommon EGFR mutations. A noteworthy example is a prospective phase II trial of osimertinib including the landmark UNICORN study, which has shown promising results in treating uncommon EGFR mutations. Despite various reports on the efficacy of afatinib and osimertinib in treating uncommon EGFR mutations, the appropriate use of these TKIs remains unclear. This review aims to consolidate the findings from the latest clinical trials focused on uncommon EGFR mutations, outlining variations in the therapeutic efficacy of these TKIs based on the specific genetic mutation. By synthesizing these findings, we aim to guide oncologists towards more informed decisions in employing TKIs for NSCLC with uncommon EGFR mutations other than exon 20 insertion. Additionally, we explore potential treatment strategies tailored to these patient populations to address the challenges posed by these mutations.

Administration of intratumoral GD2-directed interleukin-2 immunocytokine and local radiation therapy to activate immune rejection of spontaneous canine melanoma.

Canine malignant melanoma provides a clinically relevant, large animal parallel patient population to study the GD2-reactive hu14.18-IL-2 immunocytokine as it is similar to human melanoma and expresses GD2. The objectives of this study were to evaluate safety, radiation fractionation, and identify informative biomarkers of an in-situ tumor vaccine involving local radiation therapy plus intratumoral-immunocytokine in melanoma tumor-bearing dogs. Twelve dogs (six dogs/arm) with locally advanced or metastatic melanoma were randomized to receive a single 8 Gy fraction (arm A) or three 8 Gy fractions over 1 week (arm B) to the primary site and regional lymph nodes (when clinically involved) with the single or last fraction 5 days before intratumoral-immunocytokine at 12 mg/m2 on 3 consecutive days. Serial tumor biopsies were obtained. All 12 dogs completed protocol treatment, and none experienced significant or unexpected adverse events. Evidence of antitumor activity includes one dog with a complete response at day 60, one dog with a partial response at day 60, and four dogs with mixed responses. Histology of serial biopsies shows a variably timed increase in intratumoral lymphocytic inflammation in some dogs. Canine NanoString analyses of serial biopsies identified changes in gene signatures of innate and adaptive cell types versus baseline. There were no significant differences in NanoString results between arm A and arm B. We conclude that intratumoral-immunocytokine in combination with local radiation therapy in canine melanoma is well tolerated and has antitumor activity with the potential to inform clinical development in melanoma patients.

The Patient Activation Measure-13 (PAM-13) in an oncology patient population: psychometric properties and dimensionality evaluation

BackgroundAccurate assessment and enhancement of health-related skills among oncology patients are pivotal for optimizing cancer care. The Patient Activation Measure (PAM-13), a questionnaire designed to reflect an individual’s knowledge, skills, and confidence in self-healthcare management, has been validated across diverse countries and settings. Concerns have been raised regarding the cross-situational applicability, as patients with specific diseases and cultural backgrounds interpret questionnaire items differently. This study aimed to examine the structural validity and psychometric properties of the PAM-13 in an oncological patient cohort.MethodsBaseline data from a longitudinal non-randomized controlled study involving cancer out-patients (n = 1,125) from Comprehensive Cancer Centres in Southern Germany were analysed. The German version of the PAM-13 was employed. With classical test and item response theory methods data quality, reliability, convergent and structural validity, as well as psychometric properties were assessed. Exploratory (EFA) and confirmatory factor analyses (CFA) were employed to investigate the postulated unidimensionality of the underlying construct. With a partial credit model (PCM) we examined item fit, targeting, local independence and differential item functioning.ResultsParticipants were predominantly female (73.0%) with a breast cancer diagnosis (41.3%). While items were generally well-accepted, ceiling effects were observed and a high mean PAM-13 score (69.7, SD = 14.2) was noted, potentially compromising responsiveness to interventions. Reliability was adequate (Cronbach’s α = 0.81), person and item separation reliability were good to excellent (0.81 and 0.99, respectively). Explorations of the unidimensionality of the construct (EFA, CFA, PCM) yielded inconclusive results, hinting towards a two-factor solution. Item difficulty rankings deviated from the original. No differential item functioning was identified, and local independence was confirmed.ConclusionsWhile the PAM-13 serves as a valuable instrument for comprehending and promoting health-related skills in cancer patients, the identification of ceiling effects, disordered item-difficulty rankings, and inconclusive findings regarding unidimensionality contribute to the expanding body of evidence, emphasizing the dependency of PAM-13’s validity and reliability on distinctive characteristics within the population under investigation. Future research should prioritize refining or adding PAM-13 items to better capture the specific health-related challenges within diverse populations, paving the way for more effective patient engagement strategies in oncology.Trial registration numberDRKS00021779

A concept analysis of psychological trauma in labour and delivery nurses.

To facilitate an understanding of the risk for psychological trauma in labour and delivery nurses. Concept analysis. The Walker and Avant method of concept analysis was applied to 56 articles. The characteristics, antecedents, and consequences of psychological trauma in labour and delivery nurses were identified. Peer-reviewed articles in English from CINAHL, PubMed and Google Scholar were reviewed on July 2023. The characteristics of psychological trauma in labour and delivery nurses are overwhelming distress, intrusive symptoms, avoidance and numbing behaviours, hypervigilance or hyperarousal, emotional dysregulation, cognitive distortions, and interpersonal challenges. The antecedents are exposure to one or more of the following nurse-specific traumas: natural or person-made disasters, historical role limitations, second victim situations, secondary trauma, system-mediated or over-medicalized care, insufficient resources, or workplace incivility. The consequences are disruptions in mental health, diminished physical health, alterations in relationships, and variable work performance. Labour and delivery nurses experience unique causes of psychological trauma due to their practice environment and patient population. The consequences of labour and delivery nurses' psychological trauma extend beyond individual health and impact the quality of patient care and organizational capacity. Furthermore, research is needed to inform education, support and policy measures to mitigate harm effectively. WHAT PROBLEM DID THE STUDY ADDRESS?: Nurse-specific trauma theory has not been applied to the unique labour and delivery environment with a high incidence of patient trauma. WHAT WERE THE MAIN FINDINGS?: Multiple causes of trauma in the perinatal context have created a pervasive yet largely preventable issue. WHERE AND ON WHOM WILL THE RESEARCH HAVE AN IMPACT?: This research will impact labour and delivery nurses, their leadership, and their patients. No patient or public contribution.

An observational study of gastric contents in pediatric patients with long bone fracture using gastric ultrasound.

The retention of gastric contents at surgery presentation is a risk factor for perioperative aspiration. A preoperative fasting (nil per os; NPO) interval is widely used to reduce this risk, but this approach is based on assumptions about the prevalence of typical gastric emptying rates. We assessed NPO guidelines' reliability with ultrasound (US) imaging and suction in pediatric patients presenting for single long-bone fracture repair after appropriate NPO intervals, when nearly all should have had empty stomachs. This prospective cross-sectional observational study comprised 200 pediatric surgical patients. As their NPO times varied by food/drink type, we defined "weighted NPO units" as the lowest multiple of elapsed recommended NPO times between consumption and surgery for each type of food or drink. We used US to image the stomach and its contents before anesthesia induction, followed by gastric suction. We evaluated the relationships between weighted NPO units, US gastric contents grade, opioid analgesic dosage and timing, and suctioned volume. Despite meeting typical NPO standards (median 14 h fasting), many patients retained nontrivial quantities of gastric contents at surgery. Weighted NPO units did not exhibit statistically-significant relationships with either suctioned volume or US grade. However, suctioned volume did correspond well to US grade. NPO status may be a less reliable predictor of gastric contents at anesthesia induction in this patient population than has been assumed. Bedside US screening appears to provide more useful information for the planning of airway management.

Pilot study evaluating the usability of MonŒil, a ChatGPT-based education tool in ophthalmology

ImportanceThere is an increasing use of artificial intelligence (AI) in ophthalmology to respond to the needs of patients to access reliable, easy-to-understand medical information. ObjectiveTo assess patient satisfaction with the usability of MonŒil, an AI-based platform designed for patient education in ophthalmology. DesignThis was a pilot cross-sectional study of the usability of MonŒil by patients followed for advanced age-related macular degeneration (AMD). MonŒil is based on ChatGPT-4 technology with specific ophthalmology-focused customizations and accessibility enhancements, and is freely available at monoeil.help. Patients were given 20 min of unsupervised interaction with no prior training or guidance, after which their feedback was collected. SettingThe study was performed in the ophthalmology department at the Creteil University Hospital. ParticipantsParticipants included 54 patients diagnosed with advanced AMD defined presenting for follow-up. Patients had to be older than 50 years of age, capable of giving informed consent, and able to understand and interact with MonŒil. Exclusion criteria were severe visual and cognitive impairment that prevented interaction with MonŒil. Main Outcome(s) and Measure(s)The primary outcome was the usability of MonŒil as measured by the System Usability Scale (SUS) questionnaire. ResultsOf the 54 participants, 34 were female (62.96 %). The mean age of the cohort was 77.76±8.14 years (range 58 to 97 years). The mean SUS score was 90.23±12.04 with a median of 92.50 (range 42.50 to 100.00), indicating excellent usability. There was a positive relationship between visual acuity and SUS score (regression coefficient 0.30 (95 % CI 0.08 to 0.51), r2=0.19, p = 0.0077). Conclusions and RelevanceMonŒil demonstrated excellent usability and satisfaction in a sample population of elderly patients with advanced AMD. These results suggest that AI-based tools like MonŒil can enhance patient education with minimal oversight in a complex field like ophthalmology, supporting its use as an adjunct to the physician-patient discussion. Further studies may be necessary to establish the applicability of MonŒil to a broader user base, and to assess its usefulness and clinical impact on patient outcomes such as patient knowledge and vision-related quality of life.

FDA perspectives on postmarket surveillance of peripheral and aortic vascular devices.

Key points Case examples in Pyun et al., highlight value of RWD to elucidate real‐world outcomes in expanded patient population and to discern potential signals. CDRH actively engages with stakeholders through transparent communication and collaboration to resolve signals. Additional improvements in the RWD infrastructure are warranted to ensure complete and accurate data collection across the total product lifecycle.

Tooth Discoloration from 2 Silver Fluorides Used in Adults with Special Needs: A Randomized Trial.

Discoloration of carious lesions after application of silver diamine fluoride lowers patient acceptance and limits its wider use for caries arrest. To assess lesion and tooth color changes from 2 novel silver fluoride (AgF) products and its relationship to caries activity (clinical visuo-tactile scores) and bacterial load (using laser fluorescence with the DIAGNOdent). A split-mouth design was followed, with matched smooth surface carious lesions in the same arch in adults with special needs randomized for 1-min treatments with AgF/potassium iodide (KI) (Riva Star Aqua, SDI) and AgF/stannous fluoride (SnF2) (Caries Status Disclosing Solution; Whiteley). Standardized images taken at baseline, immediately postoperatively, and at 3-mo review were subjected to digital image analysis to calculate delta-E and to track changes in luminosity of carious lesions. Twelve participants were recruited in the study. A total of 56 teeth (28 pairs) were included. Significantly greater changes were seen in treated lesions than in the adjacent noncarious natural tooth structure, both immediately after treatment and at the 3-mo review (P < 0.0001). Color change and caries activity were not affected by tooth type, tooth location, plaque status, salivary status, or special needs condition. AgF/SnF2 caused transitory darkening immediately on application, while AgF/KI caused the immediate formation of yellow deposits (silver iodide). Both products caused significant darkening of treated lesions at 3 mo (P = 0.0009; P = 0.0361), with no differences between them (P = 0.506). Responding lesions showed larger and more perceptible color changes immediately after either AgF application (P = 0.002; P = 0.024). Both AgF products were highly effective for caries arrest in this patient population. Despite minor differences in the appearance of treated lesions at the time of application, both products lead to similar darkening of treated sites at 3 mo. This study shows the usefulness of silver fluoride used in conjunction with potassium iodide or stannous fluoride for achieving caries arrest in smooth surface lesions in adults with special needs. Patients need to be informed that long-term staining of the lesion occurs with both, similar to silver diamine fluoride.

The health communication orientations scale: Development and two-country validation of a questionnaire that measures health communication style preferences

ObjectiveSelf-Determination Theory posits that everyone has a basic need for autonomy that needs to be fulfilled to establish autonomous motivation for health behavior (change). Regardless, individual differences exist in health communication style preferences. This paper outlines the development and validation of the Health Communication Orientations Scale (HCOS), a new measure to assess these preferences. MethodsNationally representative online panels from the US (n = 603) and the Netherlands (n = 737) completed a survey containing the HCOS, established motivational measures, and demographic questions. ResultsFactor analyses identified five subscales valid for both populations: HCOS (1) Expert, (2) Others, (3) Self, (4) Oppositional, and (5) Internet. Scores for Expert and Internet were higher in the US sample; Others, Self, and Oppositional were higher in the Dutch sample. Internal reliability for the five factors was high across samples (range 0.84–0.91). Many significant correlations with established measures were observed in both samples indicating the construct validity of the scale. ConclusionThe HCOS subscales have strong psychometric properties. Practice implicationsThe HCOS represents a novel approach to assessing communication style preferences for general and patient populations. Further investigation in how the HCOS may be used to tailor health messaging is warranted.

Patient-Reported Experiences of Supportive Cancer Care during the COVID-19 Pandemic

Background. During the COVID-19 pandemic, people affected by cancer were in need of information about the virus and about the (self-) management of cancer symptoms and treatment. It is important to understand how patients with cancer navigated through the pandemic and to explore their experience relating to their supportive care needs. Aim. This study aimed to describe the experience of Swiss oncological patients during the COVID-19 pandemic with additional supportive cancer care. Methods. A single-center study was conducted in 2021. Patients with melanoma, breast, lung, or colon cancer who received active systemic anticancer treatment at the time of the COVID-19 pandemic and who were additionally seeing either oncology clinical nurse specialists, integrative medicine physicians, or both were included. We conducted semistructured interviews alongside the patient-reported quantitative assessment of distress and resilience. Thematic analysis was performed for the qualitative data and descriptive statistics for the quantitative data. Results. Eighteen patients with cancer were interviewed. Patients seeing an integrative medicine physician highlighted that they positively felt being addressed as a whole person during the consultations. The oncology clinical nurse specialists were perceived as the first point of contact for the patients and had more time during the pandemic compared to what the patients normally received. In general, patients did not experience delays or disruptions in their cancer treatment. As immunosuppressed and fatigued patients with cancer, they felt supported by the restrictions and hygienic measures. Access to vaccination reassured patients against the risk of infection. These results were reflected in the quantitative data, as we found moderate distress levels (M = 4.1; SD = 2.5) and high resilience scores (M = 7.5; SD = 0.9) in this patient population. Conclusion. During the COVID-19 pandemic, patients with cancer felt particularly supported by integrative medicine and cancer nurse consultations. Secured resources for nursing consultations and integrative medicine services can help to address the supportive care needs of patients with cancer.

Prevalence of urinary tract infections in pregnant women and antimicrobial resistance patterns in women in Riyadh, Saudi Arabia: a retrospective study

BackgroundUrinary tract infections (UTIs) are one of the most common health problems worldwide and mainly affect women. This study aimed to evaluate the prevalence of UTIs in pregnant women and determine the antimicrobial resistance patterns of bacterial pathogens isolated from pregnant and nonpregnant women in Riyadh, Saudi Arabia.MethodsThis retrospective cohort study was conducted at an academic medical center in Riyadh, Saudi Arabia, from January to June 2022. The study included all urine cultures performed for adult women during the study period. We excluded urine culture performed for women on antibiotics prescribed for any infection, children, and men. Using the SPSS (version 27) package, descriptive statistics and chi-square tests were used to analyze the data, and p < 0.05 was considered to indicate statistical significance.ResultsA total of 2,418 urine cultures performed during the study period were included (985 and 1,433 for pregnant and nonpregnant women, respectively). The overall prevalence of UTIs in pregnant women was 5% (95% CI 3.6–6.4); 10 (1%) women were symptomatic, and 40 (4%) women were asymptomatic. Of the entire cohort, 244 (10.1%) women were diagnosed with UTIs based on bacterial cultures. The predominant bacteria in both pregnant and nonpregnant women were Escherichia coli (134, 54.9%), followed by Klebsiella pneumoniae (48, 19.6%).The antibiotic susceptibility criteria for Escherichia coli and Klebsiella pneumoniae were as follows: nitrofurantoin (94% and 18.8%, respectively), amoxicillin-clavulanic acid (82.8% and 70.8%, respectively), ciprofloxacin (65.7% and 83.3%, respectively), trimethoprim-sulfamethoxazole (65.7% and 79.2%, respectively) and cephalothin (47% and 68.8%, respectively).ConclusionCompared to the findings of other similar studies, the prevalence of UTIs was lower in pregnant women. This may be because the patient population was composed of healthy and educated women who received prenatal education and underwent prenatal assessment as per institutional guidelines. Nitrofurantoin and amoxicillin-clavulanic acid are recommended for use as an empirical therapy for UTIs in pregnant and nonpregnant women because bacteria have the least amount of resistance to these drugs.

Serum Albumin-to-Creatinine Ratio: A Novel Predictor of Pulmonary Infection in Patients with ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

In patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), a low serum albumin-to-creatinine ratio (sACR) is associated with elevated risk of poor short- and long-term outcomes. However, the relationship between sACR and pulmonary infection during hospitalization in patients with STEMI undergoing PCI remains unclear. A total of 4,507 patients with STEMI undergoing PCI were enrolled and divided into three groups according to sACR tertile. The primary outcome was pulmonary infection during hospitalization, and the secondary outcome was in-hospital major adverse cardiovascular events (MACE) including stroke, in-hospital mortality, target vessel revascularization, recurrent myocardial infarction, and all-cause mortality during follow-up. Overall, 522 (11.6%) patients developed pulmonary infections, and 223 (4.9%) patients developed in-hospital MACE. Cubic spline models indicated a non-linear, L-shaped relationship between sACR and pulmonary infection (P=0.039). Receiver operating characteristic curve analysis indicated that sACR had good predictive value for both pulmonary infection (area under the ROC curve [AUC]=0.73, 95% CI=0.70-0.75, P＜0.001) and in-hospital MACE (AUC=0.72, 95% CI=0.69-0.76, P＜0.001). Kaplan-Meier survival analysis indicated that higher sACR tertiles were associated with a greater cumulative survival rate (P＜0.001). Cox regression analysis identified lower sACR as an independent predictor of long-term all-cause mortality (hazard ratio [HR]=0.96, 95% CI=0.95-0.98, P＜0.001). A low sACR was significantly associated with elevated risk of pulmonary infection and MACE during hospitalization, as well as all-cause mortality during follow-up among patients with STEMI undergoing PCI. These findings highlighted sACR as an important prognostic marker in this patient population.

Development of Physiologically Based Biopharmaceutical Model (PBBM) for Felodipine Prolonged-Release Tablet as useful tool for prediction of formulation.

Physiologically Based Biopharmaceutical Models (PBBMs) are advanced tools that integrate physiological parameters with drug-specific properties to simulate drug behavior in vivo. In this study, we present the development of a PBBM specifically tailored for felodipine prolonged-release (PR) tablet formulations. Felodipine, a potent calcium channel blocker, is widely used for the treatment of hypertension and angina pectoris. Prolonged-release formulations aim to provide controlled drug release, ensuring sustained therapeutic effect with reduced dosing frequency and minimized adverse effects. Our PBBM incorporates key physiological processes such as gastrointestinal transit, drug dissolution, absorption, distribution, metabolism, and elimination. Data from in vitro dissolution studies, preclinical pharmacokinetics, and clinical observations are integrated to parameterize the model accurately. Special attention is given to the physicochemical properties of felodipine and the release characteristics of the PR tablet formulation. Validation of the PBBM is conducted against clinical pharmacokinetic data obtained from bioequivalence studies and population pharmacokinetic analyses of felodipine PR tablets. The model may demonstrate excellent predictive performance, accurately capturing plasma concentration-time profiles across different dosing regimens and patient populations. The developed PBBM provides valuable insights into the biopharmaceutical behavior of felodipine PR tablets, facilitating rational formulation design, dosage regimen optimization, and therapeutic individualization. It serves as a powerful tool for drug developers, regulatory agencies, and clinicians to enhance the efficiency and effectiveness of drug development and clinical pharmacotherapy

The value of virtual molecular tumor boards for informed clinical decision-making.

Genomic profiling and other new technologies have increased the volume and complexity of information available for guiding clinical decision-making in precision oncology. Consequently, there is a need for multidisciplinary expert teams, in the form of molecular tumor boards (MTBs), who can translate this information into a therapeutic plan, including matching patients to suitable clinical trials. Virtual MTBs (vMTBs) can help to overcome many of the challenges associated with in-person MTBs, such as limited time availability, access to appropriate experts or datasets, or interactions between institutions. However, real-world experience from vMTBs is lacking. Here, we describe oncologists' vMTB experiences and the value of working with multicenter and/or multinational vMTBs. We also address knowledge gaps and barriers that could affect the implementation of vMTBs in routine clinical practice. Case studies from Argentina, Turkey, and Portugal illustrate the value of informed clinical decision-making by vMTBs, including expansion of therapeutic options for patients, faster time to treatment, and the resulting improvement in patient outcomes or impact of vMTB discussions on patients. With the uptake of comprehensive genomic profiling and the evolution of some cancers now being conceptualized as a collection of rare diseases with small patient populations based on molecular profiling, the importance of MTBs has increased in modern cancer management. However, an adjustment in clinical decision-making by healthcare professionals is required and evidence of the added value of vMTBs is lacking. Existing vMTBs and recommendations from participating oncologists could point toward a structured evaluation and analysis of this new platform.

Exacerbated Activation of the NLRP3 Inflammasome in the Placentas from Women Who Developed Chronic Venous Disease during Pregnancy

Chronic venous disease (CVD) comprises a spectrum of morphofunctional disorders affecting the venous system, affecting approximately 1 in 3 women during gestation. Emerging evidence highlights diverse maternofetal implications stemming from CVD, particularly impacting the placenta. While systemic inflammation has been associated with pregnancy-related CVD, preliminary findings suggest a potential link between this condition and exacerbated inflammation in the placental tissue. Inflammasomes are major orchestrators of immune responses and inflammation in different organs and systems. Notwithstanding the relevance of inflammasomes, specifically the NLRP3 (nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3)- which has been demonstrated in the placentas of women with different obstetric complications, the precise involvement of this component in the placentas of women with CVD remains to be explored. This study employs immunohistochemistry and real-time PCR (RT-qPCR) to examine the gene and protein expression of key components in both canonical and non-canonical pathways of the NLRP3 inflammasome (NLRP3, ASC—apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain—caspase 1, caspase 5, caspase 8, and interleukin 1β) within the placental tissue of women affected by CVD. Our findings reveal a substantial upregulation of these components in CVD-affected placentas, indicating a potential pathophysiological role of the NLRP3 inflammasome in the development of this condition. Subsequent investigations should focus on assessing translational interventions addressing this dysregulation in affected patient populations.

Delayed Enhancement in Cardiac CT: A Potential Alternative to Cardiac MRI? Technical Updates and Clinical Considerations

Despite cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) being the current gold standard for non-invasive myocardial characterization and fibrosis quantification, its accessibility is limited, particularly in acute settings and in certain patient populations with contraindications to magnetic resonance imaging. Late iodine enhancement (LIE) in computed tomography (CT) imaging has emerged as a potential alternative, capitalizing on the similarities in the contrast kinetics between gadolinium and iodinated contrast agents. Studies have investigated LIE-CT’s effectiveness in myocardial infarction (MI) detection, revealing promising outcomes alongside some disparities compared to LGE-CMR. LIE-CT also proves beneficial in diagnosing non-ischemic heart diseases such as myocarditis, hypertrophic cardiomyopathy, and sarcoidosis. While LIE-CT demonstrates good accuracy in detecting certain myocardial pathologies, including acute MI and chronic fibrotic changes, it has limitations, such as the inability to detect diffuse myocardial enhancement. Nonetheless, thanks to the availability of optimized protocols with minimal radiation doses and contrast medium administration, integrating LIE-CT into cardiac CT protocols could enhance its clinical utility, particularly in acute settings, providing valuable prognostic and management insights across a spectrum of cardiac ischemic and non-ischemic conditions.

Probiotics, prebiotics, synbiotics and other microbiome-based innovative therapeutics to mitigate obesity and enhance longevity via the gut-brain axis

The global prevalence of obesity currently exceeds 1 billion people and is accompanied by an increase in the aging population. Obesity and aging share many hallmarks and are leading risk factors for cardiometabolic disease and premature death. Current anti-obesity and pro-longevity pharmacotherapies are limited by side effects, warranting the development of novel therapies. The gut microbiota plays a major role in human health and disease, with a dysbiotic composition evident in obese and aged individuals. The bidirectional communication system between the gut and the central nervous system, known as the gut-brain axis, may link obesity to unhealthy aging. Modulating the gut with microbiome-targeted therapies, such as biotics, is a novel strategy to treat and/or manage obesity and promote longevity. Biotics represent material derived from living or once-living organisms, many of which have therapeutic effects. Pre-, pro-, syn- and post-biotics may beneficially modulate gut microbial composition and function to improve obesity and the aging process. However, the investigation of biotics as next-generation therapeutics has only just begun. Further research is needed to identify therapeutic biotics and understand their mechanisms of action. Investigating the function of the gut-brain axis in obesity and aging may lead to novel therapeutic strategies for obese, aged and comorbid (e.g., sarcopenic obese) patient populations. This review discusses the interrelationship between obesity and aging, with a particular emphasis on the gut microbiome, and presents biotics as novel therapeutic agents for obesity, aging and related disease states.

Survival Prognostication in Patients with Differentiated Thyroid Cancer and Distant Metastases: A SEER Population-Based Study.

Background: For patients with thyroid cancer, distant metastasis is a significant predictor of poor outcome. Since distant metastasis occur in less than 10% of patients with differentiated thyroid cancer, correlates of survival in this vulnerable patient population remain understudied. This study aimed to identify prognostic groups among patients with differentiated thyroid cancer and distant metastases; and to determine the role of, and interactions between, patient and tumor characteristics in determining survival. Methods: We identified adult patients diagnosed with differentiated thyroid cancer with distant metastases from the U.S. SEER-17 cancer registry (2010-2019). Analyses were performed using Cox proportional hazards regression, survival trees, and random survival forest. Relative importance of patient and tumor factors important for disease-specific and overall survival was assessed based on the random survival forest analyses. Results: Cohort consisted of 2,411 patients with differentiated thyroid cancer with distant metastases followed for a median of 62 months. Most common histopathologic subtype (86.0%) was papillary thyroid cancer, and the most common sites of distant metastasis were the lungs (33.7%) and bone (18.9%). Cox proportional hazards model illustrated significant associations between survival and: patient age (P<0.001), tumor size (P<0.01), and site of distant metastasis (P<0.05). Survival tree analyses identified three distinct prognostic groups based on disease-specific survival (DSS) (5-year survival of the prognostic groups was 92%, 64%, and 41%; P<0.001) and four distinct prognostic groups based on overall survival (OS) (5-year survival of the prognostic groups was 96%, 84%, 57%, and 31%; P<0.001). The first split in the survival trees for DSS and OS was by age at diagnosis (<57 years vs >58 years) with subsequent splits based on presence/absence of lung metastases, tumor size (<4 cm vs >4 cm), and patient age. A total of 558 patients (23.1%) died from thyroid cancer, and 757 patients (31.4%) died from all causes during the study period. Conclusions: This study identifies distinct prognostic groups for patients with differentiated thyroid cancer with distant metastases and highlights the importance of patient age, lung metastases, and tumor size to determining both disease-specific and overall survival. These findings inform risk stratification and treatment decision-making in this understudied patient population.

Mirvetuximab soravtansine: A breakthrough in targeted therapy for platinum-resistant ovarian cancer.

Ovarian cancer, ranked as the second leading cause of gynecologic malignancy-related deaths globally, poses a formidable challenge despite advances in early detection and treatment modalities. This paper explores the efficacy and safety of mirvetuximab soravtansine, the first folate receptor alpha (FRα)-targeting antibody-drug conjugate, in platinum-resistant ovarian cancer expressing FRα. A review of 4 key studies involving 453 participants consistently demonstrates mirvetuximab soravtansine's clinically meaningful antitumor activity and favorable safety profile. Clinical implications emphasize mirvetuximab soravtansine's pivotal role in targeted therapy, especially for high FRα-expressing tumors, potentially reshaping platinum-resistant ovarian cancer management. The combination therapy approach introduces a novel dimension, suggesting enhanced therapeutic outcomes. Even in heavily pretreated patients, mirvetuximab soravtansine's favorable tolerability positions it as a viable option. The reliability of archival tissue for FRα assessment simplifies patient selection, streamlining accessibility to targeted therapies. However, identified gaps, including limited diversity in patient populations, sparse quality of life data, and the need for long-term safety information, indicate areas for future research. Exploration of additional biomarkers predicting mirvetuximab soravtansine responsiveness is essential for personalized treatment.

Abstract A008: Racial differences in characteristics and outcomes of adjuvant nivolumab for muscle-invasive urothelial carcinoma (MIUC) in the real-world setting

Abstract Objectives: Historically, African-American/Black patients with bladder cancer have worse clinical outcomes compared with White/Caucasian patients. In the CheckMate 274 trial, nivolumab demonstrated a significant improvement in disease-free survival compared with placebo among patients with MIUC at high risk of recurrence following radical surgery; however, African-American/Black patients were underrepresented (&amp;lt; 1%). The objective of this analysis was to describe the characteristics and outcomes of MIUC patients treated with adjuvant nivolumab across different racial subgroups in a real-world setting. Methods: This US retrospective medical chart review included African-American/Black and White/Caucasian patients with MIUC treated with adjuvant nivolumab following radical resection between 01-Sep-2021 and 10-Sep-2022. Patient characteristics and outcomes were abstracted from the medical charts by treating oncologists. Patient characteristics and landmark survival estimates based on Kaplan-Meier analyses were summarized descriptively. Results: The analysis included 223 patients (African-American/Black: 62; White/Caucasian: 161). A numerically higher proportion of African-American/Black vs White/Caucasian patients, respectively, was male (74.2% vs 66.5%), less than 60 years old (27.4% vs 20.5%), unemployed (16.1% vs 5.6%), and had Medicaid at therapy initiation (14.5% vs 6.2%). Similar proportions in both groups had ECOG performance status 0-1 (82.3% vs 82.6%), received neoadjuvant therapy (58.1% vs 56.5%), and completed adjuvant therapy (67.7% vs 66.5%). The median follow-up time (12.5 months vs 13.1 months) and median duration of adjuvant therapy (11.0 months vs 11.3 months) were comparable. Similar estimates were observed for 12-month overall survival (96.7% vs 91.4%), 12-month disease-free survival (88.3% vs 88.4%), and 12-month distant metastasis-free survival (88.3% vs 88.4%). Conclusions: Despite higher rates of socio-economic risk factors among African-American/Black patients, this real-world study suggests similar effectiveness of adjuvant nivolumab among MIUC patients across African-American/Black and White/Caucasian patient populations. Citation Format: Regina Barragan-Carrillo, Alexander Chehrazi-Raffle, Bruce Feinberg, William S. John, Taavy A. Miller, Sarah Lucht, Prathamesh Pathak, Emily Bland, Sarah Gordon, JaLyna Laney, Andrew J. Klink, Hedyeh Ebrahimi, Nisha Singh, Carmelo Alonso, Miraj Patel, Lisa Rosenblatt, Xin Yin. Racial differences in characteristics and outcomes of adjuvant nivolumab for muscle-invasive urothelial carcinoma (MIUC) in the real-world setting [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr A008.