Clinical Patient Populations Research Articles

Results of a patient survey using an online questionnaire after implant removal for breast implant illness.

The use of silicone breast implants has a history of over 60 years. In recent years, specific health issues among implant wearers have repeatedly come into focus. The term "breast implant illness" has been circulating in scientific literature and on social media for several years. It describes a cluster of up to 60 different symptoms. The present results of an online survey conducted within a clinic's patient population of the last 8 years show, among other things, the evolution of 8 reported symptoms before and after breast implant removal. In the comparison before and after, there is a significant reduction in the intensity of symptoms after implant removal. A causal relationship with the removal of the implants is to be presumed.

Inflammation and response to nutrition interventions.

The complex interplay between nutrition and inflammation has become a major focus of research in recent years across different clinical settings and patient populations. Inflammation has been identified as a key driver for disease-related malnutrition promoting anorexia, reduced food intake, muscle loss, and on a cellular level, insulin resistance, which together stimulate catabolism. However, these effects may well be bidirectional, and there is strong evidence showing that nutrition influences inflammation. Several single nutrients and dietary patterns with either proinflammatory or anti-inflammatory properties have been studied, such as the long-chain ω-3 fatty acids eicosapentaenoic acid or docosahexaenoic acid. The Mediterranean diet combines several such nutrients and has been shown to improve medical outcomes in the outpatient setting. In addition, there is increasing evidence suggesting that inflammation affects the metabolism and modulates the response to nutrition support interventions. In fact, recent studies from the medical inpatient setting suggest that inflammation, mirrored by high levels of C-reactive protein, diminishes the positive effects of nutrition support. This may explain the lack of positive effects of some nutrition trials in severely ill patients, whereas similar approaches to nutritional support have shown positive results in less severely ill patients. The use of biomarkers, such as C-reactive protein, may help to identify patients with a lower response to nutrition, in whom other treatment options need to be used. There is need for additional research to understand how to best address the malnourished patient with inflammation by specifically lowering inflammation through anti-inflammatory medical treatments and/or nutrition interventions.

Fertility concerns and treatment decision-making among national sample of young women with breast cancer.

Diagnosis of breast cancer in young women has been shown to affect their decision-making with regard to fertility and family planning. Limited data are available from populations across the U.S. regarding this issue; thus, we sought to describe fertility concerns and efforts to preserve fertility in a national clinical trial population of young breast cancer patients. The young and strong study was a cluster-randomized controlled trial testing an intervention program for young women with breast cancer. Patients were surveyed within 3 months after diagnosis and at 3, 6, and 12 months after. Surveys asked about sociodemographics, psychosocial domains, fertility concerns, and fertility preservation strategies. Univariable and multivariable models were used to investigate sociodemographic, clinical, and psychosocial predictors of fertility concerns. Of 467 women from 54 clinical sites across the U.S. (14 academic, 40 community), 419 were evaluable regarding fertility concerns. Median age was 40 years (range 22-45), 11% were Black, 6% Hispanic, and 75% had children. Tumor stage was I (35%), II (51%), or III (14%); 82% received chemotherapy. At time of the treatment decision, 133 (32%) participants had fertility concerns, among whom 47% indicated this affected their treatment decisions. Sixty percent of participants reported having discussed fertility with their physician. Twenty percent of those with fertility concerns used fertility preservation strategies. History of difficulty becoming pregnant and younger age were associated with higher odds of fertility concerns in multivariable modeling. Many young women with newly diagnosed breast cancer are concerned about fertility in a way that impacts their treatment decisions. Concerns were discussed, but few used fertility preservation strategies. These findings have implications for counseling young patients.

Abstract A076: Trial participation in pictures: Using photo elicitation to explore minority patients’ experiences on therapeutic cancer clinical trials

Abstract Background: Much has been published about barriers to research participation for under-represented minority (URM) yet we know little about the experiences, motivations, and decision-making of the URM patients who were successfully treated on clinical trial (CT). The purpose of this study is to draw on the experiences of URM patients as insiders of practical knowledge of CT through photo elicitation to comprehensively understand the current state of recruitment and treatment of URM patients on interventional cancer CTs across the Mayo Clinic enterprise with a short-term goal of informing mechanisms to enrich CT participation and a long-term goal of building a patient-centered cancer practice and clinical trial patient population that is reflective of the diverse communities served by Mayo Clinic. Method: An Appreciative inquiry approach was adapted for this study which acknowledges that existing strengths and everyday experiences of URM patients has the potential to allow a more nuanced view as it pertains to our cancer populations. A total of 138 URM were invited to participate. Using photo elicitation technique, patients were asked to take photographs to portray factors that motivated them and/or facilitated their enrollment, barriers to enrollment and recommendations to improve the process for CT recruitment for other URM. Participant-generated photographs (59) and accompanying 13 interview narratives were analyzed using layered analysis. Results: A total of 13 patients (female =9) participated in the photo interviews. URM detailed their overall experiences around CT participation, motivations for participating in clinical trials; facilitators to clinical trial participation; and opportunities and considerations for increasing minority patients CT participation. Photo analyses provided symbolic representation of patients’ general experiences around CT including celebrating their “new identity”, finding peace in moments of nostalgia, their journey through the trial, lost times and finances and yet finding a new purpose to live through CT participation. Importantly patients described decision making in CT participation as a relational approach. Patients suggested opportunities and considerations for increasing minority patients trial participation, which included minimizing logistical barriers, decentralizing cancer clinical trials, increasing awareness via patient narratives, diversifying research staff, minimizing cost, and being clear on purpose and benefit of the trial. Conclusion: Our study highlights the potential to utilize visual data and narratives from URM in CT recruitment and education programming. It provided valuable insights from the URM community for the URM community on key issues on motivations of CT participation and decision-making in CT participation. Citation Format: Gladys B. Asiedu, Rahma Warsame, Mary O’Shea, Yong-hun Kim, Sara A. Ellingson, Katharine A. Price. Trial participation in pictures: Using photo elicitation to explore minority patients’ experiences on therapeutic cancer clinical trials [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A076.

The Role of Biomarkers in Distinguishing Infectious From Non-Infectious Diseases

Abstract Background. The use of C-reactive protein (CRP) and procalcitonin (PCT) as guiding biomarkers in treating severe infections could improve the use of antibiotics. Biomarker dynamics are more reliable than single values in predicting sepsis when making the diagnosis and evaluating the response to antibiotic therapy. Both CRP and PCT used protocols have to be consistent with the clinical context and patient populations. Objectives: reviewing the use of PCT and CRP in various clinical contexts and the patient population Sources. We analyzed the most recent studies of these biomarkers for antimicrobial stewardship, including meta-analyses and original trials. Content. According to several studies, critically ill patients who get antibiotic treatment under the guidance of CRP and PCT see a decrease in antibiotic exposure and related adverse effects. When patients are hospitalized in intensive care units (ICUs), CRP and PCT can be used to distinguish between viral and non-infectious causes of systemic inflammation. In septic patients, CRP levels are reliable to show a high negative predictive value (NPV), especially on day 1 of ICU admission. Consequently, CRP levels decrease during therapy with appropriate antibiotics in the next 3 days. Implication. In addition to other clinical and laboratory parameters, CRP and PCT provide information about the risk of the bacterial infection worsening or improving under appropriate treatment. These improve antibiotic treatment decisions, allowing individualized treatment regimens with reduced overall antibiotic exposure.

Efficacy and safety of tucidinostat in patients with advanced hormone receptor-positive human epidermal growth factor receptor 2-negative breast cancer: real-world insights.

Tucidinostat, which is a subtype-selective histone deacetylase inhibitor, has been approved in China for the treatment of hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). However, existing evidence mainly stemmed from randomized controlled trials, and might have limitations in representing the complexities of clinical practice and diverse patient populations. Therefore, there is a need to explore the efficacy and optimal therapeutic modality for tucidinostat in real-world clinical settings. The objective of this real-world study was to analyze the clinical data of 47 patients with HR+/HER2- ABC who received tucidinostat treatment at West China Hospital, Sichuan University, between August 2020 and May 2023. The primary outcomes were progression-free survival (PFS) and clinical benefit rate [CBR; defined as partial response (PR) and stable disease (SD) for ≥6 months on clinical evaluation]. A total of 47 patients were included, and the median follow-up time was 18.20 months. The median line of tucidinostat therapy was 3 (range, 1-9). In all, 52.17% patients were treated with tucidinostat plus fulvestrant, while 38.30% were treated with tucidinostat plus aromatase inhibitors. Notably, 10.64% of the patients with rapidly progressing visceral metastases received tucidinostat plus endocrine therapy as maintenance treatment after achieving disease control with chemotherapy. The median PFS was 4.43 months [95% confidence interval (CI), 2.77-10.53], and the median overall survival was 19.57 months (95% CI, 12.83-not reached). The 6-month CBR for the overall population was 41.86%. Patients undergoing maintenance therapy demonstrated a significantly longer PFS than did those who did not receive it as maintenance therapy (14.13 vs. 3.93 months; P=0.01). Univariate Cox regression analysis showed that use of tucidinostat in lines 1-2, use of tucidinostat plus fulvestrant, presence of one metastatic site, and lack of brain metastasis were favorable factors for PFS. Thrombocytopenia was the most frequently reported adverse event, with an incidence rate of 31.91% at all grades and 14.89% at grade ≥3. Four (8.51%) patients discontinued the treatment. For patients with HR+/HER2- ABC, tucidinostat combination therapy offers certain survival benefits with controllable safety. Furthermore, compared with non-maintenance therapy, maintenance therapy after chemotherapy may have promising efficacy.

Spectral graph modeling reveals global slowing of neurophysiological network transmission in Alzheimer’s disease

AbstractBackgroundAlzheimer’s disease (AD) is the most common form of dementia, progressively impairing memory and cognition. While various neuroimaging studies have revealed functional network abnormalities in patients with AD, how these relate to aberrant neuronal circuit mechanisms remains unclear. In order to answer these questions, we employed a spectral graph‐theory based model (SGM) to identify abnormal biophysical markers of neuronal activity in AD.MethodSGM is an analytic model that describes how the long‐range fiber projections in the brain mediate and couple the excitatory and inhibitory activity of local neuronal subpopulations. Unlike other coupled models, the SGM is linear, available in closed‐form, and parameterized by a small set of global parameters. This facilitates their rapid and unambiguous inference which we performed here on a well characterized clinical population of patients with AD (N = 88) and a cohort of age‐matched healthy controls (N = 88). We estimated SGM parameters that best captured the regional magnetoencephalography (MEG) frequency spectra of patients with AD and age‐matched controls.ResultSGM was able to capture the regional MEG frequency spectra of patients with AD and healthy controls, specifically, the abnormal slowing of neural oscillations in AD (Fig 1A). Patients with AD have significantly elevated long‐range excitatory neuronal time constant (tG) compared to controls (p < 0.001). Time constant tG is also the most important feature for accurate classification of patients with AD from controls (Area Under Curve = 0.85; Fig 1B). Lastly, higher tG is negatively correlated with global cognitive decline score (p = 0.02; Fig 1C).ConclusionThese results indicate that a global impairment in the long‐range excitatory neuronal activity is associated with abnormal spectral signatures and cognitive deficits in AD. Intriguingly, our work is able to recapitulate the spatial and spectral patterns of AD‐related functional activity without introducing any spatial heterogeneity whatsoever; indeed, the SGM model is entirely global and spatially‐invariant. This raises the possibility that a global increase in the long‐range excitatory time constant might be a sufficient factor underlying observed spatiotemporal alterations of neuronal activity in AD. Our findings provide new insights into potential mechanistic links between abnormal neural oscillations and their cellular correlates in AD.

Circadian Rhythms and Depression in Adolescents: A Comparative Analysis of First Episode and Recurrent-Episode Groups.

Circadian rhythm disruptions are a hallmark feature of mood disorders. Patients experiencing acute depressive episodes report noticeable changes in their sleep-wake cycles. This research explains the association between depression and various circadian rhythm metrics, explicitly focusing on adolescents diagnosed with depressive disorders. Adolescence is a critical period marked by significant physiological and psychological changes, making it imperative to understand how mood disorders manifest during this phase. However, there have been minimal specific studies in pediatric populations to determine whether circadian rhythm changes differ between adolescents with first and multiple-recurrent depressive episodes. Our study involved a group of 61 adolescents aged between 13 and 18. We performed a cross-sectional study of a clinical population of patients presenting to a child and adolescent psychiatry clinic diagnosed with depression. Participants were asked to complete self-report evaluations using several tools: the Korean version of the Biological Rhythms Interview of Assessment in Neuropsychiatry (K-BRIAN), the Korean Translation of Composite Scale to Measure Morningness-Eveningness (KtCS), and the Seasonal Pattern Assessment Questionnaire (SPAQ). Tools such as the Children's Depression Inventory (CDI), State-Trait Anxiety Inventory (STAI), and K-Mood Disorder Questionnaire (K-MDQ) were employed for the assessment of clinical characteristics of depression. Based on the frequency of their depressive episodes, participants were bifurcated into two distinct groups: those experiencing their first episode (n = 22, mean age: 15.09 ± 1.44 years) and those with recurrent episodes (n = 39, mean age: 15.95 ± 1.26 years). At first, the two groups' data revealed no significant differences regarding mood or circadian rhythm metrics (CDI: first episode 26.18 ± 10.54 and recurrent episode 25.90 ± 10.59, STAI-S: first episode 56.91 ± 12.12 and recurrent episode 57.49 ± 11.93, STAI-T: first episode 60.36 ± 11.63 and recurrent episode 59.09 ± 12.10, SPAQ-total: first episode 6.59 ± 4.86 and recurrent episode 6.77 ± 5.23, KtCS: first episode 30.32 ± 5.83 and recurrent episode 28.13 ± 7.36). However, we observed significant correlations between circadian rhythm disruptions and depression scales (CDI with SPAQ-weight (r = 0.26), KtCS (r = -0.48), K-BRIAN-sleep (r = 0.58), K-BRIAN-activity (r = 0.64), K-BRIAN-social (r = 0.71), and K-BRIAN-eating (r = 0.40)). These correlations were especially pronounced in the recurrent episode group, suggesting that with the progression and chronicity of depression, the relationship between circadian rhythms and depression becomes more intertwined and evident. In conclusion, especially in adolescents, as the severity and chronicity of depression increase, the interplay between circadian rhythms and mood disorders becomes more pronounced, warranting further research and clinical attention.

The NYCKidSeq randomized controlled trial: Impact of GUÍA digitally enhanced genetic results disclosure in diverse families

Digital solutions are needed to support rapid increases in the application of genetic/genomic tests (GTs) in diverse clinical settings and patient populations. We developed GUÍA, a bilingual digital application that facilitates disclosure of GT results. The NYCKidSeq randomized controlled trial enrolled diverse children with neurologic, cardiac, and immunologic conditions who underwent GTs. The trial evaluated GUÍA's impact on understanding the GT results by randomizing families to results disclosure genetic counseling with GUÍA (intervention) or standard of care (SOC). Parents/legal guardians (participants) completed surveys at baseline, post-results disclosure, and 6months later. Survey measures assessed the primary study outcomes of participants' perceived understanding of and confidence in explaining their child's GT results and the secondary outcome of objective understanding. The analysis included 551 diverse participants, 270 in the GUÍA arm and 281 in SOC. Participants in the GUÍA arm had significantly higher perceived understanding post-results (OR= 2.8, CI[1.004, 7.617], p= 0.049) and maintained higher objective understanding over time (OR= 1.1, CI[1.004, 1.127], p= 0.038) compared to SOC. There was no impact on perceived confidence. Hispanic/Latino(a) individuals in the GUÍA arm maintained higher perceived understanding (OR= 3.9, CI[1.603, 9.254], p= 0.003), confidence (OR= 2.7, CI[1.021, 7.277], p= 0.046), and objective understanding (OR= 1.1, CI[1.009, 1.212], p= 0.032) compared to SOC. This trial demonstrates that GUÍA positively impacts understanding of GT results in diverse parents of children with suspected genetic conditions and builds a case for utilizing GUÍA to deliver complex results. Continued development and evaluation of digital applications in diverse populations are critical for equitably scaling GT offerings in specialty clinics.

Evaluating Clinical Outcomes of Laparoscopic Subtotal and Total Cholecystectomy for Complicated Acute Cholecystitis: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to compare clinical outcomes in patients with complicated acute cholecystitis undergoing laparoscopic total vs subtotal cholecystectomy. This systematic review and meta-analysis was conducted according to PRISMA guidelines and queried PubMed, Embase, ProQuest, Google Scholar, and Cochrane databases from inception to May 2023. The primary outcome was complication rates including common bile duct injury, wound infection, reoperation, bile leak, retained stones, and subhepatic collection, whereas secondary outcomes were in-hospital mortality and hospital length of stay. A total of 7 studies with 135,233 cases were included for meta-analysis. Patients who underwent laparoscopic total cholecystectomy had a significantly lower risk of postoperative bile leaks (RR: .15; 95% CI: .03, .80) and subhepatic fluid collection (RR: 0.19; 95% CI: .06, .63) and were 2.94 times less likely to die compared to those who underwent subtotal cholecystectomy (RR .34; 95% CI: .15, .77). Patients who underwent subtotal cholecystectomy had significantly longer hospital length of stay (mean difference 1.0days; 95% CI: .5days, 1.4days). In adult patients presenting with complicated cholecystitis, management with laparoscopic subtotal cholecystectomy presents a unique complication profile with increased risk of postoperative bile leak and subhepatic fluid collection, in-hospital mortality, and longer hospital length-of-stay when used as an alternative approach to laparoscopic total cholecystectomy. Further research into the most appropriate clinical scenarios and patient populations for the use of the subtotal cholecystectomy approach may prove useful in improving its associated outcomes.

Abstract 17034: Outpatient Effort to Improve Medication Uptitration and Maintenance (OPTIMUM)

Introduction: Guideline-directed medical therapy (GDMT) reduces morbidity and mortality for patients with heart failure with reduced ejection fraction (HFrEF) starting as early as 30-days from initiation. Rapid GDMT titration programs have been shown to be effective in clinical trials. We evaluated the feasibility of a rapid GDMT clinical program in a safety-net population with HFrEF. Methods: Patients admitted to a large urban safety net hospital with newly diagnosed HFrEF (LVEF <40%) were eligible for the program. Patients with end-stage renal disease, history of cardiogenic shock, or current homelessness were excluded. The 6-week program consisted of alternating in-person heart failure clinic visits and virtual visits with a multidisciplinary team of pharmacists, nurses, and physicians to adjust medications and to provide heart failure education. Intensities of GDMT prescription at the start of the program and at 3 months were compared using an institutional GDMT score ranging from 0-11 which accounts for drug classes (beta-blocker, ACE/ARB/ARNI, MRA, SGLT2i) and percent of target doses prescribed (Figure, panel A). Results: This pilot enrolled 20 patients (mean age 58.0 +/- 15.6 years, 35% women, 25% Black, 75% Hispanic). At enrollment, patients had an average GDMT score of 5.5 on 2.9 classes of GDMT. At week 6, 15 (75%) patients were prescribed all 4 classes of GDMT with a 2.7 increase in the GDMT score for an average score of 8.2 (Figure, panel B).This was sustained at 3 months. There were no safety events requiring ED visits or hospitalization during the program duration. Conclusions: In a safety-net health system caring for the urban poor, rapid GDMT up titration was feasible and resulted in increased GDMT intensity without clinical adverse events. Our experience supports the development of rapid GDMT titration programs even in clinical settings and patient populations which differ from those enrolled in clinical trials.

Prevalence of Sleep Disordered Breathing in Adult Sickle Cell Clinic Patients and Cardiovascular Correlates

Sleep disordered breathing (SDB) is strongly correlated with hypertension and cardiovascular disease in the general population, and especially in African Americans. In Sickle Cell Disease (SCD), the adverse effect of nocturnal hypoxemia is anticipated to have additional adverse effects with the sickling of red blood cells and microvascular thrombosis unique to the disease. Prospective data regarding the prevalence and consequences of SDB in this population are lacking. In an ongoing study, 27 adult subjects (age > 18 years), with homozygous HbSS genotype, presenting to the Howard University Sickle Cell Center for routine follow up have been recruited irrespective of the presence of sleep symptoms. Exclusion criteria include previous diagnosis or treatment of a sleep disorder or requirement for supplemental oxygen. Testing occurs when subjects are in a stable phase of disease, with no hospitalizations or medication changes for 4 weeks. In addition to clinical history and questionnaires, participants are assessed with blood work, 6 minute walk testing, pain and sleep diaries during 1 week actigraphy, transthoracic echocardiography and overnight in lab polysomnography with capnography. At the time of this interim analysis, the mean age is 42 (range 29-71, +/- std dev 11) and male:female distribution is 17:10. The mean BMI is 20.4 (+/- 4.5). Mean Hgb is 9.1 g/dl (+/- 1.8) and mean LDH is 325 iu/L (+/- 163). Polysomnography scoring utilized a 3% desaturation criterion for hyponeas as per American Academy of Sleep Medicine Scoring Manual Chapter VIII, 1A. Mean sleep efficiency is 77% ( std dev +/- 4.2%). 48% of subjects demonstrate some degree of sleep disordered breathing as defined by an AHI > 5 events/hour (33% mild, 4% moderate, 11% severe). 70% of subjects demonstrate an RDI > 5 events/hour (40% mild, 19% moderate, 11% severe). Twelve participants (44%) exhibit more than 5 minutes sleep duration at saturations <89% (mean = 187 minutes). Hypercapnia is not suggested as an important component of SDB with the mean ET CO2 = 40.7 mm Hg (range 30-46 mm Hg). Echocardiographic values (LVPWd, Lad, MV E/A, PVV, and RVSP) do not correlate with any indices of sleep disordered breathing other than minutes <89% saturation correlating with RVSP. In summary, this interim analysis of sleep in a population of unselected Sickle Cell Clinic patients demonstrates a striking frequency of sleep disordered breathing. This is despite a generally low BMI for these patients which is typically considered one of the most important risk factor for sleep apnea. Ongoing recruitment is planned to confirm these findings. Correlation with clinical outcomes and potential response to therapeutic interventions will be important future research questions.

67 Extending Evidence of Validity for Symptom Severity Classification of the PostConcussion Symptom Inventory (PCSI)

Objective:External validation of symptom severity classification levels for the PostConcussion Symptom Inventory (PCSI).Participants and Methods:Two distinct samples of parents and children, ages 8-18, participated from a: (1) prospective multicenter cohort study (Predicting Persistent Post-concussive Problems in Pediatrics, 5P) (Zemek et al., 2016), including parents (n=2,852), adolescents (n=1,087; mean age=15.13; 54% male), and children (n=1,271; mean age=10.70; 65% male) and (2) published clinic sample at Children’s National Hospital (CN) including parents (n=1,197; adolescents, n=835; children, n=326) (Gioia et al., 2019). Participants completed the age-specific Post-Concussion Symptom Inventory (PCSI): Mean time postinjury = 8 hours (5P), 6 days (PCSI2), generating a post-pre-injury difference (RAPID) score. The distribution of the RAPID scores for the Total Symptom and 4 subscales (physical, emotional, cognitive, sleep/fatigue) were examined to define 4 symptom severity classification levels (minimal - within the CI for recovered, low <20th %tile, moderate 21-79th %tile, high >80th %tile) for the respective samples. These severity distributions were compared between the two distinct datasets.Results:ANOVAs were performed to examine group differences in the mean scores for each of the 4 classification levels. No significant differences were found for all the RAPID score distributions with minimal effect sizes (<.1% variance) for the parents, adolescents and children. PCSI RAPID Total Score ranges for the severity classifications were as follows: Minimal-Parent and adolescent groups 5P<=5, Clinic <=5; Children: 5P<=3, Clinic<=3; Low- Parents 5P 6-15, Clinic 6-13; Adolescents 5P 6-19, Clinic 6-16; Children: 5P 4-7, Clinic: 4-7; Moderate-Parents 5P 16-49, Clinic 14-47; Adolescents 5P 20-56, Clinic 17-51; Children 5P 8-17, Clinic: 818; High- Parents: 5P>=50, Clinic >=48; Adolescents 5P >=57, Clinic >=52; Children 5P >=18, Clinic >=19).Conclusions:Our findings reveal a parallel distribution of RAPID scores in the two distinct 5P and Clinic patient populations, yielding nearly identical severity classification level parameters across all five PCSI symptom domains (total score, physical, cognitive, emotional, and sleep/fatigue). The present investigation provides evidence of validity for the use of these severity classification levels across the ED and specialty clinic settings.

Breaking the cycle: unraveling the diagnostic, pathophysiological and treatment challenges of refractory migraine.

Refractory migraine is a poorly described complication of migraine in which migraine has chronified and become resistant to standard treatments. The true prevalence is unknown, but medication resistance is common in headache clinic patient populations. Given the lack of response to treatment, this patient population is extremely difficult to treat with limited guidance in the literature. To review the diagnostic, pathophysiological, and management challenges in the refractory migraine population. There are no accepted, or even ICHD-3 appendix, diagnostic criteria for refractory migraine though several proposed criteria exist. Current proposed criteria often have low bars for refractoriness while also not meeting the needs of pediatrics, lower socioeconomic status, and developing nations. Pathophysiology is unknown but can be hypothesized as a persistent "on" state as a progression from chronic migraine with increasing central sensitization, but there may be heterogeneity in the underlying pathophysiology. No guidelines exist for treatment of refractory migraine; once all guideline-based treatments are tried, treatment consists of n-of-1 treatment trials paired with non-pharmacologic management. Refractory migraine is poorly described diagnostically, its pathophysiology can only be guessed at by extension of chronic migraine, and treatment is more the art than science of medicine. Navigating care of this refractory population will require multidisciplinary care models and an emphasis on future research to answer these unknowns.

Screening for High-Risk Oral Human Papillomavirus (HPV31, HPV33, HPV35) in a Multi-Racial Pediatric and Adult Clinic Patient Population.

Many human papillomavirus (HPV) strains induce cancer in the cervix and the oral cavity. Although high-risk strains including HPV16 and HPV18 are commonly known, additional high-risk strains including HPV31, HPV33, and HPV35 may also induce carcinogenesis, and much less is known about their prevalence. Using an approved protocol, samples from a salivary biorepository were screened to find pediatric and adult samples from a multi-ethnic, university-based patient clinic population. A total of N = 86 samples from the saliva biorepository met the quality and concentration standards and were screened for high-risk HPV. qPCR screening of adult samples revealed n = 10/45 or 22% were HPV31- or HPV33-positive. In addition, a total of n = 9/41 or 21.9% of pediatric samples were either HPV31- or HPV33-positive (or both). No samples harbored HPV35. Most samples were derived from patients within the recommended vaccination or catch-up age range (age 9-45 years). These results demonstrated that a significant percentage of patients harbor additional high-risk HPV strains within the oral cavity, including HPV31 and HPV33. These data support oral healthcare provider recommendations for the newer nine-valent vaccine, which includes both HPV31 and HPV33.

Home-Delivered Medically Tailored Meal Engagement Among Hemodialysis Patients and Providers

Hemodialysis patients face one of the most difficult diets among clinical patient populations. Furthermore, dialysis dietary adherence is generally reported as low with providers generally lacking the time and resources to implement effective behavior change. The purpose of this study was to elucidate measures of patient and provider engagement with home-delivered medically tailored meals (MTMs). We surveyed patients and staff at dialysis centers within the Denver metropolitan area. Surveys focused on 1) patient dietary intake, 2) awareness, support, and utilization of meal programs, and 3) nutritional challenges and barriers (including food security). We surveyed 118 patients (mean age 61.0 ± 14.2 year, 58.5% male, and dialysis vintage of 4.6 ± 4.9 years) and 26 staff across the included dialysis facilities. Patients were 20.3% White/Non-Hispanic, 35.6% Hispanic/Latin and 31.4% Black/African American. Most patients reported eating two meals per day (N=53, 44.9%) and 52.2% reported difficulty with following a kidney diet. The most cited reasons for not following the diet were behavioral or knowledge (38.5%), taste (26.3%), time/convenience (26.9%) and food autonomy (16.9%). Sixty participants (52.2%) reported living in a food desert and 26.3% reported food insecurity. Seventy-one patients (61.2%) were aware of MTMs but only 40.5% had been referred. Most (76.9%) dialysis providers were aware of MTMs but only 15 (57.7%) had actually referred patients to such a service. Black individuals were less likely to be referred for MTMs than White or Hispanics/Latin (29.7% vs 48.1% White and 45.0% Hispanic/Latin) individuals. MTMs represent a potential method to alleviate or bypass some of the many barriers expressed by patients. Our findings reveal a critical need for education around MTMs for both patients and providers. MTMs could potentially demonstrate health kidney dietary patterns that might translate to altered dietary preferences or towards future behavior change.

Role of Checkpoint Inhibitors in the Management of Gastroesophageal Cancers.

This article reviews the essential clinical trials that have led to these immunotherapy approvals and explores the use of predictive biomarkers, such as PD-L1 expression and MSI status, to identify patients who are most likely to benefit from immunotherapies. This case review series describe findings from different clinical trials and contribute to the evolving understanding of the role of CPIs in managing advanced gastroesophageal cancers and may lead to improved treatment options and patient outcomes. Ongoing clinical trials also hold promise for expanding treatment options and improving patient outcomes in the future. The systematic review followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The protocol has not been registered. A systematic literature review was conducted to identify relevant clinical trials and studies that describe the role of immune checkpoint inhibitors in managing advanced gastroesophageal cancers. Electronic database (PubMed, Clinicaltrials.gov, Society of Immunotherapy of Cancer, Aliment Pharmacology & Therapeutics, BMC cancer, Molecular Cancer Research, Nature Reviews Molecular Cell Biology, American Association for Cancer Research, Science, Nature, Cancer Discovery, Journal of the National Cancer Institute, Advanced Immunology, Oncotarget, Nature Medicine, Nature Genetics, Gut, Pathology and Oncology Research, Journal of Clinical Oncology, The New England Journal of Medicine, Gastrointestinal oncology, JAMA Oncology, Journal of Gastrointestinal Oncology, Current Oncology, Annals of Oncology, The Lancet, JCO Oncology Practice, Future Oncology, Gastric Cancer, CA: A Cancer Journal for Clinicians, American Journal of Gastroenterology, Gastroenterology, Journal of the National Cancer Institute, International Journal of Epidemiology, Helicobacter, Gastroenterology Review) were searched using a combination of relevant keywords and MESH terms. The search encompassed articles published up to 5/2023. Additionally, manual searches of reference lists of selected articles and pertinent review papers were conducted to ensure comprehensive coverage of relevant studies. Studies were included if they provided insights into clinical trials evaluating the efficacy and safety of CPIs in treating advanced gastroesophageal cancers. Relevant case reviews and trials exploring combination therapies involving CPIs were also considered. Articles discussed in the utilization of predictive biomarkers were included to assess their impact on treatment outcomes. Data from selected studies were extracted to inform the narrative review. Key findings were summarized, including clinical trial designs, patient populations, treatment regimens, response rates, progression-free survival (PFS), overall survival (OS), and adverse events. The role of predictive biomarkers, particularly PD-L1 expression and MSI status, in identifying patients likely to benefit from CPIs was critically evaluated based on study results. Ongoing clinical trials investigating novel combination strategies and exploring the broader scope of CPIs in gastroesophageal cancers were also highlighted. The collected data were synthesized to provide a comprehensive overview of the crucial clinical trials that have contributed to the approval of CPIs for advanced gastroesophageal cancers. The role of CPIs in different lines of therapy, including first-line regimens, was discussed. Furthermore, the evolving landscape of predictive biomarkers was examined, emphasizing their potential significance in optimizing patient selection for CPI therapy. Ongoing clinical trials were reviewed to underscore the continuous efforts in expanding treatment options and improving patient outcomes in the future.

Pre-eruptive intracoronal resorption in orthodontic patients: A retrospective analysis of 3,143 patients

ObjectivesThe aim of this retrospective study was to analyze the occurrence and characteristics of pre-eruptive intracoronal resorptions in a clinical orthodontic patient population. Materials and methodsPatients treated in an orthodontic department (University of Pécs, Pécs, Hungary) were included. Unerupted teeth on panoramic radiographs were analyzed for intracoronal radiolucent lesions. For each patient, the demographic data, jaw localization, number of unerupted teeth with pre-eruptive intracoronal resorption lesions, number of lesions per tooth, size and localization of pre-eruptive intracoronal resorption defects, affected tooth's surface, pulp involvement and ectopic position of the tooth with defects were recorded. ResultsIn the 3,143 patients investigated, 55 teeth in 49 patients showed pre-eruptive intracoronal resorption lesions (subject incidence: 1.56%). The incidence on unerupted teeth was 0.25%. Pre-eruptive intracoronal resorption was significantly more common in mandibles (43 mandibular vs. 12 maxillary lesions) with an odds ratio of 12.84 (95% Confidence Interval: 5.19–31.74) and no gender differences were found (p = 0.746). The occurrence of pre-eruptive intracoronal resorption was highest in the youngest (7–10 years) mixed dentition status group (p < 0.001). Most of the lesions (44 of 55, or 80.0%) were localized in the dentin, occupying two-third or less of the dentin thickness. Only 12.73% (7/55) of the lesions were not localized on the occlusal surface. Of the lesions, 89.1% (49/55) showed no obvious size increase over an average follow-up of 36.4 ± 8.1 months. ConclusionsPre-eruptive intracoronal resorption may occur mainly in the mixed dentition stage in orthodontic patients. Careful and attentive radiographic evaluations may facilitate early detection and follow-up of the lesions’ possible dimensional changes, especially when resorption influences orthodontic extraction therapy.

Racial and Ethnic Distribution in Diabetic Macular Edema Clinical Trials in the United States (2002–2021)

Diabetic macular edema (DME), the leading cause of vision loss among patients with diabetes mellitus, disproportionately affects Black and Hispanic patients. Currently, non-White racial and ethnic subgroups are frequently underrepresented in clinical trials, limiting the application of results to the most pertinent patient populations. Thus, we aimed to characterize the trajectory of racial reporting as well as changes and disparities in racial and ethnic distribution among participants of DME clinical trials. This is a cross-sectional retrospective study. Patients enrolled in United States (US)-based clinical trials for DME. We examined the racial and ethnic demographic distribution of participants in clinical trials related to DME across a 20-year period from 2002 to 2021. Clinical trials were screened from ClinicalTrials.gov for DME, US trial location, study completion, and > 50 patient enrollment. Descriptive statistics, proportions, odds ratios (ORs), and chi-square tests were reported and compared with 2021 US Census demographic data and diagnosed patients with diabetes demographic data. Change in racial reporting and race/ethnicity across 2 decades and comparison of racial/ethnic distribution with 2021 US Census demographics and diagnosed patients with diabetes. There was an increase in race reporting from January 2002 to December 2011 (8 trials [40%]) versus January 2012 to December 2021 (20 trials [87%]; OR, 10.00; 95% confidence interval [CI], 2.21-45.16; P= 0.0032). Across the 2 decades, the proportion of Asian patients enrolled increased from 2.4% to 8.0% (OR, 3.47; 95% CI, 2.64-4.56; P < 0.0001). Similarly, the proportion of enrolled Hispanic patients increased from 13.4% to 19.5% (OR, 1.56; 95% CI, 1.37-1.78; P < 0.0001). Compared with diabetes prevalence, many minority groups are underrepresented in the total enrollment of DME clinical trial patients (Black [z=-18.51, P < 0.001]; Asian [z=-5.11, P< 0.0001]; Hispanic [chi-square= 274.7, df= 1, P < 0.0001]). In the past 2 decades, there has been a trend of increased racial reporting and minority patient enrollment in DME clinical trials. However, Black, Asian, and Hispanic patients remain significantly underrepresented among the DME clinical trial patient population based on diabetes prevalence. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Interrater Reliability of the Psychological Mindedness Assessment Procedure, Extended (Dutch) Version, in a Clinical Patient Population

The Psychological Mindedness Assessment Procedure, Extended Dutch Version (PMAP-plus), was developed to assess psychological mindedness in mental health care. Psychological Mindedness represents the ability to understand self and others through mental representations of internal psychodynamic states. In patients, deficits in psychological mindedness capacity can cause problems in self- and interpersonal functioning. This brief report describes interrater reliability of four PMAP-plus scenarios for evaluating psychological mindedness capacity among patients. Patients with personality disorders (N = 194) were asked to respond to four enacted videotaped PMAP-plus scenarios presenting a person talking about a personal experience. The videotaped scenarios varied in their emotional impact. All verbatim responses were scored by two clinically experienced raters on a hierarchical scale with gradually increasing complexity of psychodynamic understanding. Clinicians achieved acceptable interrater reliability on PMAP-plus in this patient population. Two scenarios with low emotional impact evoked significantly higher interrater agreement as compared to two scenarios with high emotional impact. Our results suggest that mental health professionals can reliably distinguish levels of psychological mindedness by assessing PMAP-plus in a patient population. Scenarios differ in potency to reveal psychological mindedness capacity. The variation in emotional impact in subsequent scenarios makes it a promising instrument measuring psychodynamic capacities for psychotherapeutic treatment.