Publications by Year: 2026

BACKGROUND AND OBJECTIVES: Categorizing older adults by their medication and deprescribing beliefs may support tailored communication and shared decision-making. We aimed to identify latent classes of patients using the Patient Deprescribing Typology.

RESEARCH DESIGN AND METHODS: This cross-sectional study used survey responses from 1,131 primary care patients (≥65 years, ≥5 medications) in 14 countries between May 2022 and December 2023. A latent class analysis was conducted using the 4-item Patient Deprescribing Typology, which captures older adults' views on medication importance, learning styles, decision-making preferences, and attitudes toward stopping medications. A multinomial logit model was used to compare the latent classes.

RESULTS: Among the 1,131 participants, 55.2% (n = 624) were female, and on average, participants were taking 7 regular medications (SD = 2.3). Three latent classes were identified: (1) Would consider deprescribing (n = 760, 67.2%), (2) Attached to medications (n = 249, 22.0%), and (3) Defers decision-making to others (n = 122, 10.8%). Compared with participants who Would consider deprescribing, those Attached to medications were significantly less likely to want to deprescribe one of their specific medications (odds ratio [OR] = 0.04, 95% CI: 0.02-0.09, p < .001). Participants who Defer decision-making to others reported lower trust in their GP (OR = 0.47, 95% CI: 0.32-0.67).

DISCUSSION AND IMPLICATIONS: While most participants expressed openness to deprescribing, their preferences for information sources, perceived medication importance, and decision-making roles varied. Our findings highlight the need to account for patient differences in deprescribing attitudes. Typologies offer a practical basis for personalized communication and patient-centered interventions.

BACKGROUND: Cumulative stress is a major risk factor for developing major depressive disorder (MDD), but not everyone experiencing chronic stress develops MDD. In those who do not, it is unclear at what point or by what mechanism a trajectory of stable resiliency emerges.

METHODS: Utilizing a 10-day repeated social defeat stress (RSDS) model for MDD, we observed that a critical period between 7 and 10 daily defeats marks the phenotypical divergence of resilient from susceptible male mice. Cell-type selective electrophysiology, chemogenetics, optogenetics, and RNA quantification were used to investigate the nature of stress effects on neuroadaptation in the oval nucleus of the bed nucleus of the stria terminalis (BNSTov) required to determine resilience.

RESULTS: In response to ongoing stress, corticotropin-releasing factor (CRF+, but not CRF-) neurons of the BNSTov displayed a sustained increased firing rate in resilient but not susceptible mice. This neurophysiological adaptation was self-sustaining, but only after 7 critical stress exposures, indicating that the process of developing resilience is dependent on stress history.

CONCLUSIONS: Our study reveals a novel process by which individuals may persist in the face of adversity by way of stress-provoked activation, not inhibition of a key CRF limbic region that establishes a pathway to resilience.

RATIONALE & OBJECTIVE: The Kidney Precision Medicine Project is obtaining kidney biopsies from people with chronic kidney disease (CKD) and acute kidney injury for comprehensive clinical, histopathological, and molecular characterization. Here, we describe histopathological findings from a subset of kidney biopsies from adults with CKD.

STUDY DESIGN: Descriptive case series of histopathology findings from adjudicated CKD biopsies.

SETTING & PARTICIPANTS: Kidney Precision Medicine Project enrolled adults with CKD and diabetes (DKD) and/or hypertension (HCKD) with persistent eGFR 30-59 mL/min/1.73 m2, urine albumin-creatinine ratio ≥30 mg/g, or urine protein-creatinine ratio ≥150 mg/g. Clinicopathological adjudication by study nephrologists and kidney pathologists was completed as part of a pilot program for 39 participants enrolled 2019-2022. Clinicians completed surveys to assess impacts of biopsies on diagnosis, prognosis, and management.

EXPOSURES: This is a descriptive study without defined exposures.

OUTCOMES: Characterization of glomerular, tubulointerstitial, and vascular histopathological features across CKD biopsies.

ANALYTICAL APPROACH: Continuous variables were summarized as mean (standard deviation) or median (interquartile range); categorial variables were summarized as count (percentage).

RESULTS: Participants' mean age was 59 years, 59% were female. Mean eGFR was 55 mL/min/1.73 m2; median urine albumin-creatinine ratio and urine protein-creatinine ratio were 81 mg/g and 211 mg/g, respectively. Among DKD-enrolled participants (N = 28), 15 (54%) had a primary diagnosis of diabetic nephropathy, 3 (11%) had hypertension-associated nephropathy, 2 (7%) had other glomerular diseases, and 8 (29%) had nonspecific findings. Among HCKD-enrolled participants (N = 11), 5 (46%) had hypertension-associated nephropathy and 6 (55%) had nonspecific findings. A range of glomerular, tubulointerstitial, and vascular findings was observed. 26% of clinicians stated results were different than expected; 77% stated results affected prognostic discussions.

LIMITATIONS: Small sample size and lack of longitudinal data limit generalizability.

CONCLUSIONS: Kidney biopsies in people with common causes of CKD demonstrate a broad range of histopathology and may have clinical utility. Unsuspected disease processes and unexpected and nonspecific findings precluding a definitive diagnosis are often present.

RATIONALE & OBJECTIVE: Fatigue is commonly experienced by adults with kidney failure receiving hemodialysis and those with chronic pain, but factors associated with fatigue are not fully understood. We determined the prevalence of fatigue in a clinical trial cohort of adults receiving maintenance hemodialysis who have chronic pain and identified factors associated with fatigue.

STUDY DESIGN: A cross-sectional study.

SETTING & PARTICIPANTS: The baseline data from the HOPE Consortium Trial to Reduce Pain and Opioid Use in Hemodialysis (HOPE Trial). Of the 643 participants randomized in the HOPE Trial, 636 had a baseline fatigue assessment and were included in this study.

EXPOSURES: Pain, sociodemographic, biological, dialysis-related, medical comorbid condition, psychological, and behavioral factors.

OUTCOME: Fatigue was evaluated with the patient-reported outcomes measurement information system Fatigue SF 6a and defined as a T-score of ≥ 55.

ANALYTICAL APPROACH: Logistic regression models.

RESULTS: Seventy-three percent of participants reported fatigue (n = 463), mean age was 60.4 (12.5), 289 (45.4%) were female, and 294 (46.2%) were Black/African American. In fully adjusted models, higher pain interference and opioid use in the last 14 days were each associated with higher odds of having fatigue (odds ratio ([OR) ] 1.37; 95% CI, 1.18-1.61; OR 1.80; 95% CI, 1.03-3.21, respectively), as were greater depressive symptoms and sleep disturbance (OR 1.21; 95% CI. 1.13-1.31; OR 1.08 95% CI 1.03-1.12, respectively). Higher physical function was associated with lower odds of having fatigue (OR 0.96 95% CI 0.93-0.99).

LIMITATIONS: Fatigue assessed at one point in time.

CONCLUSIONS: In adults receiving maintenance hemodialysis who have chronic pain, pain interference, opioid use, depression, and sleep disturbances are associated with increased odds of fatigue, and greater physical function is associated with lower odds of fatigue. Future work is needed to evaluate longitudinal associations, underlying mechanisms, and identify interventions.

OBJECTIVES: High-resolution anorectal manometry (HR-ARM) is a diagnostic test assessing anorectal neuromuscular function in children with constipation and/or fecal incontinence. Interrater reliability of HR-ARM in children has not been previously studied. The aim of this study was to assess the interrater reliability of pediatric HR-ARM studies.

METHODS: Ten pediatric gastroenterologists specialized in neurogastroenterology and motility analyzed ten deidentified pediatric HR-ARM studies using dedicated analysis software (Solar GI HRM v9.1, MMS, Enschede, the Netherlands). Anal canal resting pressure, squeeze pressure and duration, presence of the rectoanal inhibitory reflex (RAIR), bear down maneuver (normal/abnormal), and final interpretation of the study (normal/abnormal) were evaluated. Fleiss' Kappa (κ) and intraclass correlation coefficient (ICC) were used for categorical and continuous data, respectively.

RESULTS: Interrater reliability was excellent for resting pressure (ICC 0.97, 95% confidence interval [CI 0.93-0.99), squeeze pressure (ICC 0.97, 95% CI 0.94-0.99), and squeeze duration (ICC 0.93, 95% CI 0.85-0.98). A fair interrater agreement for the RAIR (κ = 0.35) was seen, and a moderate interrater agreement was seen for interpretation of the bear down maneuver and the final interpretation of the study either being normal or abnormal (κ = 0.50 and κ = 0.43, respectively).

CONCLUSIONS: This study demonstrated excellent interrater reliability in assessing HR-ARM anal canal resting pressure, squeeze pressure, and squeeze duration and suboptimal reliability in interpreting the detection of a RAIR and bear down maneuver. These findings highlight the need for standardization of HR-ARM protocols and interpretation criteria in children.

PURPOSE OF ARTICLE: The role of immediate precipitating activities in aneurysmal subarachnoid hemorrhage (aSAH) remains unclear, lcontributing to uncertainty regarding activity restriction. This systematic review and meta-analysis examined the relative strain of activities preceding spontaneous aSAH using metabolic equivalents of task (METs).

MATERIALS AND METHODS: A systematic search identified studies reporting activities preceding aSAH (categorised as nonstrenuous, MET 1-4, and strenuous, MET ≥5). Associations between activity category and aSAH occurrence were assessed using chi-squared testing, with Fisher's combined method evaluating overall association. Odds of aSAH were evaluated using sleep or rest (MET 1) as the reference.

RESULTS: Six studies (3,285 aSAH cases) were included. aSAH mostly preceded nonstrenuous activities (43.2%) compared with strenuous activities (23.5%). Heavy strain activities (MET 6-8) , preceded 8.9% of cases ,while Valsalva maneuversaccounted for 7.9%. Fisher's combined method showed aSAH occurred less frequently after strenuous activities (p <0.001). Compared with sleep or rest, odds of aSAH were comparable or lower across all other activity categories.

CONCLUSION: Routine nonstrenuous activities most often preceded aSAH, suggesting high physical exertion may not be a dominant immediate trigger of aneurysm rupture. Other factors, including circadian blood pressure fluctuations and impaired autoregulation, may contribute to rupture risk.

BACKGROUND AND OBJECTIVES: Despite advances in treatment for intracranial aneurysms, recurrence remains a clinical challenge. Studies have suggested associations between treatment modality, aneurysm morphology, and recanalization risk, but comprehensive evaluation of these factors and their relationships is limited. The goal of this study was to evaluate the role of aneurysm location and packing density (PD) as predictors for recurrence.

METHODS: This is a retrospective cohort study where records of patients who underwent coiling for intracranial aneurysms from 2013 to 2023 from a single institution were reviewed. Recurrence was defined as worsening of angiographic aneurysm occlusion status. Demographics, aneurysm characteristics, clinical outcomes, and follow-up data were recorded. Analysis was performed in RStudio.

RESULTS: A total of 505 were included; 195 aneurysms were ruptured (38.6%). The most frequent locations were anterior communicating artery (163), internal carotid artery (85), basilar (76), posterior communicating artery (63), and middle cerebral artery (43). Mean PD was 23.3%, with 109 recurrences (21.6%) and 76 retreatments (15.1%); 31 patients (6.1%) experienced thromboembolic complications. In multivariable analysis, incomplete occlusion (Raymond-Roy [RR] Grades II-III), presence of an incorporated branch vessel, and higher size ratio independently predicted recurrence, whereas male sex and age older than 75 years were protective. Size ratio also predicted retreatment, while stent-assisted coiling reduced the likelihood of retreatment. Although higher PD was associated with better immediate RR Grade, PD (including extremes <15% vs >30%), aneurysm volume, and anatomical location were not independently associated with recurrence or retreatment after adjustment.

CONCLUSION: In this modern series, the immediate RR Grade, not PD or anatomical site, drove long-term durability; PD improved the index occlusion but had no independent association with recurrence after adjustment. Incorporated perforators independently increased recurrence risk, and stent assistance reduced retreatment. These data reframe technical priorities toward achieving complete occlusion safely, especially in perforator-bearing lesions, rather than chasing PD thresholds alone in the contemporary era.

Hereditary renal cancer syndromes account for approximately 5% to 8% of all renal cell carcinomas (RCCs) and are caused by germline alterations, mainly in tumor suppressor genes. Advances in molecular testing have led to the identification of new hereditary syndromes and expanded our understanding of the genetic landscape of renal neoplasia. This review summarizes both well-established and recently described hereditary renal cancer syndromes, highlighting their clinical, pathologic, and molecular features. Emphases are placed on genotype-phenotype correlations and the relationship between germline and somatic alterations in tumors. Understanding these correlations is critical for diagnosis, risk assessment, surveillance, and management and underscores the importance of a high index of clinical suspicion for early detection to optimize patient outcomes.

At least 27% of women who report a history of intimate partner violence (IPV) also report experiencing IPV-related head trauma (IPV-HT) or probable brain injury (IPV-BI). Prior studies of non-IPV-related traumatic BI and IPV-BI suggest that adverse childhood experiences (ACEs) may be associated with the severity of common neurobehavioral symptoms after the injury, potentially due to their association with elevated post-traumatic stress disorder (PTSD) symptoms. This study sought to examine PTSD symptom severity as an intermediary of the relationship between ACEs and measures of symptoms commonly reported after HT among 121 women with exposure to IPV-HT. Linear regressions examined the association between ACEs and neurobehavioral symptoms assessed by the Rivermead Postconcussion Symptoms Questionnaire (RPQ), Headache Impact Test-6 (HIT-6), and Quality of Life in Neurological Disorders Cognitive Function-Version 2 (Neuro-QoL), while adjusting for other common influences on the severity of these symptoms: IPV-HT and other HT severity, time since most recent, worst IPV-HT (determined using the Brain Injury Screening Questionnaire), past year partner abuse frequency (determined using the Revised Conflict Tactics Scale), and age. Cross-sectional mediation analyses examined whether ACEs indirectly covaried with neurobehavioral symptoms via PTSD symptom severity (determined using the PTSD Checklist for DSM-5 [PCL-5]). ACE score was significantly associated with RPQ score (b = 1.65, p < 0.001) and Neuro-QoL T-score (b = -0.64, p = 0.03). The association between ACE score and RPQ score, and ACE score and Neuro-QoL T-score indirectly covaried by PCL-5 score (unstandardized indirect effect [bootstrapped 95% confidence interval]: RPQ: 0.680 [0.221,1.308]; Neuro-QoL: -0.658 [-1.255,-0.113]). The findings suggest that ACEs are associated with worse symptoms after IPV-HT, potentially by way of the association between ACEs and heightened PTSD symptom severity. Longitudinal studies are needed to determine the causality of these relationships. However, our findings suggest that ACEs and elevated PTSD symptoms may be important considerations for individuals reporting symptoms associated with IPV-HT. As such, providers of these individuals may want to consider whether childhood adversity may be impacting current symptom burden in conjunction with IPV, PTSD, and associated HT/BI.

BACKGROUND: This study aimed to compare donor-site morbidity among three common major lower extremity free flaps: fibula (FFF), anterolateral thigh (ALT), and the medial sural perforator (MSAP) using an established patient-reported outcome measure (PROM), the Lower Extremity Functional Scale (LEFS).

METHODS: Patients who underwent head and neck reconstruction with either FFF, MSAP, or ALT were included. The primary outcome was functional recovery, assessed using the modified LEFS, a PROM measuring functional status, administered at multiple post-operative timepoints.

RESULTS: Seventy-five patients were included in the analysis: 33 FFF, 22 MSAP and 20 ALT. Patients undergoing lower extremity free flap surgery overall recovered well. The LEFS scores at different time points demonstrated quicker recovery for the MSAP group, while ALT and FFF recovered later. After 360 days, the MSAP group also demonstrated improved functional outcomes compared to the ALT and FFF.

CONCLUSION: Patients undergoing lower extremity free flap surgery recover well. The MSAP had the least donor-site morbidity. Donor-site morbidity should be considered when counseling patients.