Faculty Bibliography

OBJECTIVE:Fatigue and depression are common and disabling symptoms in people with Multiple Sclerosis (PwMS). This study aimed to examine the relationship between discordant fatigue measures and depression severity in PwMS. METHODS:A retrospective analysis was conducted on 712 PwMS evaluated over 14 years at a comprehensive MS center. All participants completed the Fatigue Severity Scale (FSS), Modified Fatigue Impact Scale (MFIS), and Beck Depression Inventory (BDI) as part of routine clinical care. Fatigue score concordance was defined as both FSS and MFIS being above or below the threshold; discordance was defined as one above and one below. Statistical analyses compared demographic, clinical, and depression-related variables between groups. RESULTS:Of the 712 patients (75.3% female; mean EDSS 2.8), 78.9% demonstrated concordant fatigue scores, while 21.1% showed discordance-most commonly with elevated MFIS and low FSS. The discordant group had significantly higher mean BDI scores (23.0 vs. 9.8; P < 0.0001) and elevated suicidality scores, despite similar clinical characteristics. CONCLUSIONS:PwMS with discordant fatigue profiles, particularly those with higher MFIS than FSS scores, exhibit significantly greater depressive symptoms. Discordance between fatigue measures may serve as a clinical marker for underlying depression, supporting the need for comprehensive psychosocial evaluation in this subgroup.

Appendiceal tumors are uncommon, and their coexistence as collision tumors is exceedingly rare, with fewer than 20 cases reported to date. The objective is to report a multi-center case series and literature review of appendiceal collision tumors, providing a comprehensive summary of clinicopathological features and outcomes. Electronic records from five tertiary centers (2016-2024) were searched. Cases with appendiceal collision tumors composed of a neuroendocrine tumor (NET) and a second component of low- or high-grade appendiceal mucinous neoplasm (LAMN/HAMN) or adenocarcinoma were included. Additional cases with the same diagnostic combinations were identified through a PubMed literature search since 2000. Clinical, pathologic, and survival data were collected and analyzed. Thirty-three cases were identified, including 17 multi-institutional and 16 literature-derived cases, with an estimated incidence of 0.11% among appendectomies. Most tumors consisted of localized NET and LAMN. Gastrointestinal (GI) symptoms were present in 62.5-65.6% of cases, and tumors were identified by imaging in 53.1-75.0%. Outcome tracks the higher-stage and grade component. Patients with localized tumors had excellent outcomes (2-year progression-free survival [PFS] and overall survival [OS]: 100%). In contrast, cases with metastatic LAMN/HAMN had 2-year PFS 66.7% and OS 100%, while those with metastatic adenocarcinoma had 2-year PFS 0% and OS 66.7%. This study represents the largest series and literature review of appendiceal collision tumors to date. These rare tumors most often consist of localized NET and LAMN, typically present with GI symptoms, are often detected by imaging. The prognosis is dictated by the component of higher stage and grade.

PURPOSE/OBJECTIVE:ZIC1 encodes a transcription factor with critical roles in vertebrate neural and skeletal development. Heterozygous deletions encompassing ZIC1 and ZIC4 cause Dandy-Walker malformation, whilst in the final exon heterozygous ZIC1 variants result in a distinct phenotype of craniosynostosis with variable intellectual disability via a gain-of-function mechanism. We describe the largest group of individuals harboring ZIC1 variants to date, significantly expanding the phenotypic spectrum and allowing genotype-phenotype correlation. METHODS:Through international collaboration we identified 18 different heterozygous ZIC1 variants from 22 families, comprising 30 individuals. RESULTS:Twelve families segregated a phenotype comprising craniosynostosis with facial dysmorphism, structural brain abnormalities and developmental delay, while 10 families had a neurodevelopmental disorder alone without craniosynostosis. Variants associated with craniosynostosis were clustered in the final exon (3) and were predominantly truncating variants predicted to escape nonsense-mediated decay. Variants associated with neurodevelopmental disorder alone included missense substitutions within exons 1 and 2 predicted to disrupt the normal function of the zinc finger domain, leading to loss of ZIC1 function which was confirmed in a functional assay. CONCLUSION/CONCLUSIONS:This study presents evidence for a ZIC1 genotype-phenotype correlation differentiating variants that cause a neurodevelopmental phenotype with and without craniosynostosis.

BACKGROUND:Antifibrotics including nintedanib and pirfenidone are effective in slowing the decline of lung function for patients with idiopathic pulmonary fibrosis (IPF). However, their adoption rates are remarkably low, and substantial proportions of patients undergo dose reduction or treatment discontinuation because of the high incidence of adverse events. RESEARCH QUESTION/OBJECTIVE:What is the impact of treatment modification on all-cause mortality and hospitalization? STUDY DESIGN AND METHODS/METHODS:Using a large administrative database, we identified patients with IPF who initiated antifibrotics. A nested case-control design was used to match cases and controls at a 1:1 ratio and conditional logistic regression was performed to estimate the effect of antifibrotic adherence and dosing. Adherence was measured using the proportion of days covered (PDC). Both adherence and dosing were determined based on the exposure period between antifibrotic initiation (cohort entry date) and outcome occurrence (index date). RESULTS:Adherence (PDC ≥ 0.75) was associated with lower risk of mortality (OR=0.563, p<0.001), regardless of which antifibrotic was used. Patients on reduced dose had a significantly greater risk of mortality compared to those on standard dose (OR=1.57, p=0.024), but this was only seen in those who started nintedanib. For hospitalization, adherence was associated with a lower risk (OR=0.692, p=0.016) overall, and reduced doses were associated with a higher risk (OR=1.667, p=0.008) only among patients who started nintedanib. Among patients who started pirfenidone, neither adherence nor dose was associated with the risk of hospitalization. INTERPRETATION/CONCLUSIONS:Results of this study suggest that antifibrotic adherence and dosing are important factors that influence mortality and hospitalization. A multidisciplinary approach involving nutritionists, drug clinical educators, and other key stakeholders to facilitate early access, affordable treatment, and adverse event mitigation may enhance adherence and ultimately improve patient outcomes.

The journey toward a fulfilling career in nephrology nursing is one of both profound challenge and immense reward. It requires skill, compassion, and an unwavering commitment to patient care. This article adapts Career Pathways into Nephrology Nursing into a guide for schools of nursing, health systems, and dialysis and transplant units. Integrating current evidence-based practices, it proposes a competency-based framework applying from pre-licensure through advanced practice and leadership, defining phased-in strategies for adoption without mandates, and suggesting an evaluation and research agenda. The goal is for the book to serve not only as a resource and reference, but also as a lever for workforce development, retention, and equitable kidney care delivery.

Apolipoprotein B (APOB) containing lipoproteins contribute to atherosclerosis by entering the arterial wall through the endothelial cell (EC) surface receptors scavenger receptor-BI (SR-BI) and activin receptor-like kinase 1 (ALK1). We used N-terminal fragments of APOB, molecular modeling, and site-directed mutagenesis to identify and block the binding of chylomicrons and LDL to these receptors in cells and mice. We discovered that different APOB regions interact with SR-BI and ALK1 expressed on ECs APOB48 lipoproteins were only internalized by SR-BI. A fragment of APOB, comprising 18% of the N-terminal sequence, APOB18, reduced the uptake and transport of both chylomicrons and LDL by ECs, whereas a shorter fragment, APOB12, only blocked ALK1 mediated uptake of APOB100 containing lipoproteins. Importantly, overexpressing APOB18 decreased atherosclerosis in hypercholesterolemic mice. These findings identify the N-terminal region of APOB as the cause of atherosclerosis and illustrate an approach to treating or preventing vascular disease.

Emergency preparedness is a critical component of patient safety in outpatient dialysis settings, where patients rely on life-sustaining treatments multiple times each week. Disruptions caused by natural disasters, infrastructure failures, or other emergencies can threaten the continuity of dialysis care and place this vulnerable population at significant risk. Tabletop exercises have emerged as an effective strategy for strengthening emergency readiness by allowing health care teams to rehearse response procedures in a structured, low-risk environment. These scenario-based simulations promote active engagement, interdisciplinary communication, and real-time problem-solving, while helping organizations identify operational gaps in existing emergency protocols. This article describes the creation and implementation of a tabletop exercise for a rapidly escalating emergency - a hurricane with a changing path and rapid intensification.

Strain imaging, performed with echocardiography and cardiovascular magnetic resonance (CMR), is a noninvasive technique for detecting subclinical myocardial dysfunction across the heart failure spectrum, in various cardiomyopathies, and within the field of cardio-oncology. By quantifying myocardial deformation, strain enhances diagnosis, risk stratification, and treatment monitoring beyond traditional measures such as ejection fraction. While echocardiography remains the most accessible modality, ongoing advances in CMR techniques-including incorporation of artificial intelligence-promise to improve standardization, reproducibility, and clinical integration of strain imaging in the management of heart failure and cardiovascular care.