Citations

Purpose: Fatigue is one of the most common and disabling symptoms experienced by people with inflammatory bowel disease; however, interventions to treat fatigue are limited. The purpose of this systematic review is to examine the relationship between sleep deficiency and fatigue in adults with inflammatory bowel disease and to describe the demographic and clinical factors associated with fatigue to inform future intervention work. Methods: We conducted a systematic review and reported the results using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search was conducted using MEDLINE, EMBASE, PsycINFO, CINAHL, and CENTRAL on 3/7/24. We included studies with adults (≥18 years of age) who had a diagnosis of inflammatory bowel disease (Crohn’s disease, ulcerative colitis, or indeterminate colitis) and measured fatigue and sleep using a validated self-report questionnaire or objective measurement. Results: Twenty-two studies met inclusion criteria for a total sample of 16 927, of whom 58.7% (n = 9937) had Crohn’s disease, and 66.3% (n = 11 226) were female. 56.1% of the participants experienced fatigue and 66.3% experienced sleep deficiency. Sleep quality and insomnia were consistently associated with fatigue. Baseline poor sleep quality was associated with persistent and worsening fatigue over 12 to 24 months. Clinical but not objective assessment of disease activity, anxiety, depression, female gender/sex, and younger age were also associated with more severe fatigue. Conclusions: Sleep quality and insomnia represent important modifiable contributors to fatigue. Future research should explore whether sleep interventions can improve fatigue in this population.

566 Background: Immune checkpoint inhibitors (ICIs) have become the preferred treatment for unresectable hepatocellular carcinoma (HCC). Conflicting data exist regarding the prognostic value of immune-related adverse events (irAEs) in these patients. We aimed to explore potential the association between irAEs and prognosis in HCC patients treated with ICIs. Methods: We searched PubMed, Scopus, Web of Science, and CENTRAL databases for articles published from inception to June 2024 using keywords including ICI, HCC, and irAEs. Two reviewers independently screened studies for eligibility and relevant data. A random effects model was used for statistical analysis, and subgroup analysis was performed by the grade of irAEs. Results: Of 3,028 studies, 25 (n=4,116 patients) met criteria for inclusion. Atezolizumab plus bevacizumab was the most common treatment regimen (n=10 studies). About half (49.5%) of patients experienced irAEs. irAEs were associated with increased objective response rate (ORR) (pooled OR: 1.72; 95% CI: 1.36 – 2.19, I 2 =39%), higher complete response rate (pooled OR: 1.45; 95% CI: 1.21-1.74, I 2 =74%), and longer progression-free survival (PFS) (pooled HR: 0.66; 95% CI: 0.52-0.84, I 2 =71%). Although irAEs were associated with longer overall survival, this difference was not statistically significant (pooled HR: 0.83; 95% CI: 0.62 – 1.11, I 2 =73%). Subgroup analysis showed a survival benefit for patients with grade 1-2 irAEs (pooled HR: 0.50; 95% CI: 0.36-0.67, I 2 =0%) but not for those with grade 3-4 irAEs (pooled HR: 0.95; 95% CI: 0.24-3.72, I 2 =84%). Conclusions: The development of irAEs is associated with a favorable prognosis in HCC, including improved PFS and higher ORR. A survival benefit was noted in patients with mild irAEs, but not in those with severe irAEs. Future studies are needed to determine if a differential survival benefit relates to the continuation vs. discontinuation of ICI therapy.

ABSTRACT Background Existing risk scores assessing geriatric vulnerability in the emergency department (ED) have shown limited predictive power, especially in diverse populations. We investigated the relationship of a quick and easy‐to‐administer geriatric vulnerability scoring system with functional decline and mortality in older patients admitted to multiple hospitals through the ED in the United States (US) and Brazil (BR). Method Federated, international, multicenter observational study of hospitalized ED patients aged ≥ 65 from US and BR. The six criteria from the PRO‐AGE score (Physical impairment, Recent hospitalization, Older age [≥ 90], Acute mental alteration, Getting thinner, and Exhaustion; 0–8; higher scores = greater vulnerability) were assessed on admission. We used proportional hazards models to investigate the relationships between PRO‐AGE score groups and 90‐day mortality and functional decline, defined as new dependence in activities of daily living (ADL) and instrumental ADL (IADL), after adjusting for age, sex, race and ethnicity, education, Charlson comorbidity score, and study site. Death was considered a competing event for the functional decline outcome. Results A total of 1390 patients were included (US = 560; Brazil = 830). The 90‐day risk of death was higher for the upper compared with the lower (reference) PRO‐AGE group in both cohorts (US: HR = 11.76; 95% confidence interval [CI] = 2.56–54.04; BR: HR = 12.29; 95% CI = 3.54–42.59), whereas the risk of new 90‐day ADL disability was higher for upper (HR = 2.08; 95% CI = 1.21–3.56) and middle groups (HR = 2.10; 95% CI = 1.35–3.27) in the US but only the upper group in BR (HR = 1.70; 95% CI = 1.02–2.85). Conclusion A higher PRO‐AGE score was associated with mortality and functional decline in older ED patients admitted to hospitals in the US and BR, demonstrating its generalizability as a geriatric vulnerability risk score.

Purpose: To update the epidemiological patterns of facial nerve palsy (FNP) in Olmsted County, Minnesota. Methods: A retrospective chart review using the Rochester Epidemiology Project database was conducted. Patients aged ≥18 years receiving a diagnosis of FNP within the Rochester Epidemiology Project database from the years 2000 to 2010 were included in the study. Data collected included age, gender, cause of FNP, degree of paralysis, medical and/or surgical management, and outcomes. Overall incidence rates were determined using gender-specific population figures for Olmsted County. Incidence trends were compared with previous Rochester Epidemiology Project studies. Results: The most common cause for FNP was Bell palsy (70.3% of cases). The overall incidence rate for Bell palsy in Olmsted County from 2000 to 2010 was 39.9 (95% CI, 36.1–43.7) per 100,000 person-years. This is an absolute increase of 14.9 per 100,000 person-years and a 60% relative increase in Bell palsy compared with a previous study performed at Mayo Clinic using the Rochester Epidemiology Project database population data from 1968 to 1982. Patients were infrequently evaluated by an ophthalmologist (8.4% of cases), and surgical intervention to address ophthalmic sequelae was rare (1.7% of cases). Conclusions: The incidence of Bell palsy has increased dramatically over previous studies, which has occurred in the setting of declining herpes simplex virus type 1 seropositivity trends and increasing herpes zoster incidence in the United States. Few patients with FNP are referred to ophthalmologists, which may represent a gap in care for both acute and long-term ophthalmic sequelae.

ABSTRACTBackgroundOlfactory neuroblastoma (ONB) is a rare sinonasal malignancy primarily treated with surgery. For tumors arising from the olfactory area, traditional treatment involves transcribriform resection of the anterior cranial fossa. Surgery can be performed with unilateral or bilateral resection depending on extent of involvement; however, there are currently no studies comparing outcomes between the two.MethodsProspective and retrospective data on primary ONB patients were collected from a multicenter registry involving eight academic sites. Propensity score matching (PSM) was used to create patient cohorts with similar baseline characteristics. Cox proportional hazards and Kaplan Meier analyses assessed overall survival (OS). Logistic regression assessed associations between extent of resection (unilateral versus bilateral) and tumor recurrence or postoperative cerebrospinal fluid (CSF) leak.ResultsA total of 187 ONB patients (47.6% female) with an average age of 53.6 ± 15.1 years were analyzed. Most tumors were unilateral (81.3%) and predominantly Kadish C (58.3%) or Hyams II (55.8%). Overall, 56.7% of patients underwent bilateral resection. Fifty‐four patients experienced tumor recurrence and nine had postoperative CSF leaks. Following PSM (n = 45/group), extent of resection was not associated with mortality (hazard ratio [HR] 1.73; p = 0.407) or OS (p = 0.400). There was no association between extent of resection and recurrence (odds ratio [OR] 0.90; p = 0.814) or postoperative CSF leak (OR 1.54; p = 0.647).ConclusionsFor ONB tumors where unilateral resection may be feasible and oncologically sound, the decision for unilateral versus bilateral resection showed no significant effect on survival, recurrence, or postoperative CSF leak. Oncologic outcomes may be comparable when resection is tailored to individual patient and tumor characteristics.

AbstractBackgroundImpaired cognition is prevalent in older adults in the emergency department (ED), but many cases go unrecognized. The Ascertain Dementia 8 (AD8) is a validated, self‐administered screening tool that can be used by patients and caregivers to assess for early cognitive changes associated with dementia. However, little is known regarding the degree of alignment between respondents in the ED setting. Our objective was to assess the agreement between the patient‐(pAD8) versus caregiver‐completed AD8 (cAD8).MethodsWe conducted a prospective observational study of community‐dwelling older adults aged 65+ years seeking emergency care and their caregivers between October 2021 and November 2023. Patients with a diagnosis of dementia indicated in the electronic health record were excluded. Collected by trained research assistants, AD8 scores ranged from 0‐8, with scores 2+ indicating cognitive impairment. Patients and caregivers were blinded to the others’ AD8 rating. The intraclass correlation coefficient (ICC) was used to assess the agreement of the presence or absence of cognitive impairment based on pAD8 and cAD8 scores.ResultsOur analytic sample included 538 dyads, of which 34.7% of patients were male with a mean age of 73.5. A total of 132 (24.5%) patients scored themselves as cognitively impaired versus 201 (37.4%) patients were scored as cognitively impaired by their caregivers. Between groups, an ICC of 0.519 (95% CI 0.454‐0.578) demonstrated moderate agreement in identifying cognitive impairment based on pAD8 and cAD8 scores.ConclusionApproximately 1 in 4 older adults without a dementia diagnosis in the emergency department identified themselves as having cognitive impairment, with caregivers even more likely to identify cognitive impairment in accompanied older adult patients. With current guidance suggesting that the pAD8 be used in the absence of the cAD8, these findings highlight important differences to account for based on the respondent when screening for cognitive impairment.

Abstract Purpose: Around 10% to 15% of prostate cancers harbor recurrent aberrations in the Forkhead Box A1 gene, FOXA1, whereby the alteration type and the effect on the forkhead (FKH) domain affect protein function. We developed a FOXA1 classification system to inform clinical management. Experimental Design: A total of 5,014 prostate cancer samples were examined using whole-exome and -transcriptome sequencing from the Caris Life Sciences database. We denoted class 1 FOXA1 alterations as missense and in-frame insertions/deletions with subclasses oriented with respect to the FKH domain. These were in the first part of the FKH domain [class 1A: amino acids (AA) 168–246], within the Wing2 region of FKH (class 1B: AA 247–269), or outside FKH (class 1C: AA 1–167, 270+). Two hotspot missense mutations at R219 were denoted class 2. Class 3 included predicted truncating mutations with subclasses partitioned based on the FKH domain (class 3A: AA 1–269 and class 3B: AA 270+). Class 4 represented FOXA1 amplifications. Real-world overall survival and therapy outcomes were determined from insurance claims. Results: FOXA1 alterations did not influence survival when considered in aggregate but had distinct prognostic effects when stratified by class. In primary prostate samples, class 1A alterations were associated with overall improved survival (HR, 0.57; P = 0.03); a similar trend was seen in metastatic biopsies with class 1B (HR, 0.84; P = 0.09). Conversely, in primary specimens, class 1C exhibited worse survival upon second-generation androgen receptor signaling inhibitor treatment (HR, 1.93; P < 0.001). Class 2 mutations (R219C/S) were enriched in neuroendocrine prostate cancers and were associated with overall poor survival (HR, 2.05; P < 0.001) and worse outcomes to first-line androgen-deprivation therapies (HR, 2.5; P < 0.001). Class 3A alterations indicated improved survival (HR, 0.70; P = 0.01), whereas class 3B alterations portended poor outcomes (HR, 1.50; P < 0.001). Amplifications (class 4) indicated poor outcomes in metastatic samples (HR, 1.48; P = 0.02). Molecularly, different FOXA1 alteration classes harbored distinct mutational and immunologic features as well as unique transcriptional programs. Finally, relative to European Americans, African Americans had increased class 1C alterations, whereas Asian/Pacific Islander patients had increased class 1B alterations. Conclusions: FOXA1 alterations should not be interpreted in aggregate, as different classes are associated with divergent molecular features and clinical outcomes. Our revised classification schema facilitates clinical decision-making for patients with prostate cancer and uncovers important racial differences.