Citations

Study Design: Retrospective. Objective: To examine the long-term perioperative changes in lumbar bone quality, paraspinal muscle size and fat content, and facet degeneration after hemipelvectomy (HP) and hip disarticulation (HD). Summary of Background Data: Emerging evidence shows that transfemoral (TFA) and transtibial (TTA) amputations may accelerate lumbar modic changes and precipitate axial back pain. TFA and TTA amputation studies demonstrate that the severity of postamputation lower back pain is associated with the amputation type (TFA > TTA) and the degree of alteration in lumbopelvic kinematics. Methods: All patients who underwent HP or HD for malignancy or infection at an academic center between 2003 and 2022 were retrospectively identified. Preoperative to postoperative changes in multifidus, erector spinae, quadratus lumborum, and psoas cross-sectional area (CSA), and Hounsfield units (HU) were calculated on CT for the amputated and contralateral side at the level of the L3–4 disc space. Paired univariate analysis was utilized to compare preoperative and postoperative outcomes. Results: A total of 16 patients (8 HP, 8 HD) met the inclusion/exclusion criteria. The preoperative to postoperative changes in HUs in the L1, L3, and L5 vertebral bodies were −27.0 ( P =0.004), −51.5 ( P =0.002), and −48.1 ( P =0.001), respectively. The decrease in L1 HU was greater for prosthesis nonusers (user: −16.50, nonuser: −51.32, P =0.021). L5–S1 segment facet degeneration increased postoperatively ( P =0.030, n=7 progressed). There were significant preoperative to postoperative changes in psoas CSA (preop: 1063.4, postop: 586.5, P =0.005) and psoas HU (preop: 50.95, postop: 33.55, P <0.001) on the amputated but not the contralateral side. Conclusion: Hind-quarter amputations were associated with decreased lumbar bone quality, progression of facet degeneration, and loss of amputated side psoas muscle tone. Daily prosthesis use was moderately protective for lumbar bone quality following amputation. HP but not HD was associated with postoperative loss of amputated side quadratus lumborum tone. Level of Evidence: Level III.

Abstract Identification of gene expression changes in post-mortem brain tissue of Alzheimer’s disease donors compared to controls have implicated numerous biological pathways for Alzheimer’s disease pathophysiology. Nonetheless, there is still limited understanding of how gene expression dysregulation underpins specific proteinopathies core to Alzheimer’s disease. Here we investigate brain transcriptomic changes in a well characterized cohort of Alzheimer’s disease donors to identify genes and networks that associate with Alzheimer’s disease endophenotypes including neuropathology measures (Braak stage, Thal phase and cerebral amyloid angiopathy score) and Alzheimer’s disease-related brain protein levels (Apolipoprotein E, Amyloid-β 40, Amyloid-β 42, tau, and phospho-Tau). Bulk transcriptome measures were collected from the temporal cortex tissue of 477 Alzheimer’s disease donors. Following quality control, transcriptome-wide association studies were performed for each endophenotype. We used weighted gene co-expression network analysis to build co-expression networks and integrated transcriptome with epigenetic and genetic data from the same donors. We detected a total of 5,740 Bonferroni significant temporal cortex gene associations with Alzheimer’s disease endophenotypes, most of which were with brain tau levels. We discovered tau-associated co-expression modules enriched in known and novel Alzheimer’s disease pathways. We found that a beneficial (or neutral) brain biochemical state of higher total tau and lower phospho-Tau are associated with increased levels of synaptic, DNA damage/repair, nucleic acid metabolism and myelin processes. In contrast, in a detrimental state of lower total and higher phospho-Tau, there is upregulation of vascular and immune, and downregulation of mitochondrial and myelin pathways. There are brain gene expression perturbations that are associated with Alzheimer’s disease endophenotypes. While some of these associations are common across multiple endophenotypes, many are distinct for different Alzheimer’s disease-related proteins. Based on these findings, we propose a hypothetical model of dynamic brain gene expression changes that track with progressive Alzheimer’s disease proteostasis. These expression changes hold potential to serve as dynamic, precision biomarkers of brain Alzheimer’s disease progression. This study demonstrates the potential of integrative multiomics and deep Alzheimer’s disease endophenotype analyses in well-characterized brain tissues to uncover with precision the complex biology of Alzheimer’s disease.

Background: Telogen effluvium (TE) is one of the most common forms of nonscarring alopecia. TE typically presents as sudden diffuse shedding of hair, and generally occurs 3–4 months after a triggering event such as physiological or psychological stress, certain medications, or hormonal changes. Despite the high prevalence of TE, no standardized clinical guidelines for the management of this condition currently exist. Objective: To address the lack of standard clinical guidelines for the management of TE, a multidisciplinary panel of dermatologists, dermatology advanced practice providers, and primary care providers convened to evaluate current evidence related to the treatment of TE. Methods: The primary research team, composed of 13 individuals, completed a comprehensive literature review of TE treatment. Then an expert panel conducted 2 rounds of article review, assessing each article based on the Strength of Recommendation Taxonomy (SORT) criteria and formulating consensus statements based on this data. An expert panel of 20 clinicians then evaluated the statements utilizing a structured eDelphi consensus process. Results: A total of 18 consensus statements regarding treatment recommendations for TE were reviewed by the expert panel. Of these, 3 statements addressed acute TE, while 15 focused on chronic TE. The panel evaluated each statement through open forum discussion, followed by voting and modification using the eDelphi methodology. Ultimately, 16 statements reached consensus following 2 rounds of the eDelphi survey. Conclusion: The self-limiting nature of acute TE warrants patient education, but no specific therapies were found to improve outcomes compared with placebo. While there is a gap in quality research regarding chronic TE treatment, current evidence suggests that topical minoxidil, vitamin D supplementation, and platelet-rich plasma may provide benefit in chronic TE based on individual clinical judgement.

Abstract Objective Resective surgery achieves seizure freedom in approximately 60%–80% of patients with drug‐resistant temporal lobe epilepsy (TLE), yet the extent to which seizure cessation permits recovery of disrupted functional brain networks remains unclear. Increasing evidence suggests that recurrent seizures alter subcortical–cortical communication involved in arousal and cognition, contributing to chronic interictal deficits, such as in executive function. Prior work demonstrates that the nucleus basalis of Meynert (NBM), the primary source of cortical cholinergic input to the cortex, exhibits aberrant functional connectivity in patients with TLE. We examined NBM connectivity in patients with TLE before and after surgery using patient‐specific NBM segmentations. We sought to investigate whether seizure freedom is associated with recovery of NBM functional connectivity, consistent with previous observations of interictal network dysfunction reversal in other subcortical arousal structures. Methods Resting‐state functional magnetic resonance imaging was analyzed in 75 patients with TLE, including 34 patients postoperatively, and 106 controls. Patient‐specific NBM segmentations were used to compute functional connectivity between the NBM and frontoparietal association cortex (FPAC) and across the whole brain. Subcortical arousal network community structure was assessed using community detection. Postoperative network changes were evaluated relative to seizure outcome. Results Prior to surgery, patients exhibited reduced bilateral NBM connectivity to the FPAC and whole brain compared to controls, indicating widespread cholinergic network disruption beyond the ipsilateral hemisphere. Following surgery, NBM connectivity increased and no longer differed from controls. Seizure‐free patients demonstrated greater postoperative increases in ipsilateral NBM‐FPAC connectivity than non‐seizure‐free patients, which was not explained by time to postoperative scan or volumetric change. Subcortical arousal community structure remained altered postoperatively. Significance Successful TLE surgery is associated with partial restoration of cholinergic arousal network connectivity, supporting the idea that seizure cessation enables recovery of brain networks disrupted by recurrent seizures. These findings position the NBM as a potential biomarker of network recovery following epilepsy surgery.

Background Cerebellar tonsillar ectopia may arise from altered cerebrospinal fluid (CSF) dynamics and can mimic Chiari I malformation. Differentiating between pressure-induced tonsillar descent and congenital malformations is essential. We present an interesting case that visualizes variable tonsillar displacement levels as an indicator of CSF dynamics. Case A 3-year-old boy presented with headache and sixth nerve palsy and was diagnosed with idiopathic intracranial hypertension. Initial magnetic resonance imaging (MRI) revealed a 5 mm descent of the cerebellar tonsils. During hospitalization, the patient underwent mastoidectomy for an incidental T2 hyperintense lesion. Subsequent MRI scans demonstrated the resolution of tonsillar displacement. At age 5, the patient experienced worsening headache. Brain MRI revealed a 13 mm descent of the cerebellar tonsils below the foramen magnum and pachymeningeal enhancement. Further evaluation revealed transtemporal CSF leakage through the previous mastoidectomy site into the soft neck tissues. Conclusion This case exemplifies cerebellar tonsillar displacement associated with both intracranial hypertension (push) and hypotension (pull), illustrating opposite causal directions of CSF dynamics in the same patient. Understanding the phenomenon as a result of dynamic CSF balance rather than unidirectional force or fixed pathophysiology can enhance monitoring of patients.

Abstract Objective To evaluate the clinical value of breast MRI in radiation-associated angiosarcoma of the breast (RAASB) for assessing disease extent at diagnosis and after neoadjuvant therapy compared with clinical examination and surgical pathology. Methods This IRB-approved retrospective study included 25 patients with breast MRIs between1995 and 2020. MRI estimated disease extent was compared to clinical exam and surgical pathology. MRI findings were evaluated for additional disease and impact on clinical management. Agreement between MRI and clinical assessment of disease was evaluated using Cohen’s kappa statistic. Results Baseline MRI demonstrated moderate agreement with clinical disease extent (Cohen’s κ = 0.44; 95% CI, 0.14-0.75). Thirteen of 24 (54%) of MRIs reflected clinical exam, 4/24 (17%) MRIs underestimated disease, and 5/24 (21%) MRIs overestimated disease. Baseline MRI changed surgical management in 4/24 (17%). In 8 patients who proceeded directly to surgery, MRI reflected pathology in 6/8 (75%). In 10 patients with post-neoadjuvant MRI, 4/10 (40%) pathology and MRI extent were similar, 5/10 (50%) MRI overestimated disease, and 1/10 (10%) MRI underestimated disease. Conclusion MRI has clinical value in assessing RAASB with the potential for significantly altering surgical management. In this small cohort, post-neoadjuvant MRI demonstrated limited additional clinical value. Larger studies are needed to define the optimal role and timing of post-neoadjuvant MRI. Advances in knowledge Baseline MRI detected additional disease not identified on initial clinical exam in 5/24 (21%) and changed surgical management in 4/24 (17%). Although baseline MRI demonstrated moderate agreement with clinical examination, post-neoadjuvant MRI frequently overestimated residual disease when compared with final pathology.

ABSTRACT Introduction Sustaining interventions implemented as part of pragmatic clinical trials requires proactive planning, but how to approach this process remains understudied. The Non‐pharmacological Options in Hospital‐based and Rehabilitation pain Management stepped‐wedge cluster‐randomized pragmatic trial tested an electronic health record‐based educational bundle (known as the Healing After Surgery [HAS] initiative) that encouraged the incorporation of non‐pharmacological pain care in perioperative pain management. The HAS initiative was implemented in multiple surgical practices and hospital sites. One year prior to trial completion, a sustainment committee was established to support the transition of intervention components to clinical ownership and to support posttrial sustainment of the HAS initiative. Methods We reviewed meeting minutes from biweekly sustainment committee meetings and conducted debriefing sessions with committee members (informed by the Clinical Sustainability Assessment Tool) to identify sustainment strategies and challenges, which were then organized into meaningful themes. Results The following six themes emerged from meeting minutes and debriefings: (1) automation of low‐touch components, (2) reliance on internal champions, (3) intentional handoff communication, (4) institutional attention, (5) relaxed fidelity, and (6) continuous evaluation. Together, they highlight the importance of early, structured planning and adaptable implementation strategies. Conclusions Sustainment of the HAS initiative required extensive communication, adaptation, and stakeholder engagement across diverse institutional contexts. Proactive sustainment planning during trial design may help ensure interventions are successfully integrated into routine clinical practice posttrial.

The kinesin-5 motor protein KIF11 is crucial for mitotic spindle assembly, driving the separation of spindle poles through microtubule sliding. Src-family kinases phosphorylate KIF11 at multiple tyrosine residues within its motor domain, but the mechanistic consequences of these modifications remain unclear. Here, we dissect the role of phosphorylation at Y211 using phospho-mimetic (Y211E) and nonphosphorylatable mutants (Y211F) in biochemical, biophysical, and cellular assays. Optical trapping and Förster resonance energy transfer analyses reveal that Y211 phosphorylation slows neck-linker docking, reducing motor velocity and force generation under load. In human cells, Y211E expression impairs bipolar spindle formation and decreases spindle pole separation velocity, while Y211F shortens steady-state spindle length. Fluorescence recovery after photobleaching analyses show that Y211E accelerates motor turnover on spindle microtubules, consistent with the mutant motor’s heightened load sensitivity. Together, these findings support a model in which Src-mediated phosphorylation at Y211 acts as a rheostat to tune KIF11 mechanochemistry and spindle assembly dynamics, linking cancer-relevant kinase signaling to mitotic force generation.