Citations

Abstract BACKGROUND Some persons with late‐stage Alzheimer's disease and related dementias (ADRD) and seemingly very minimal cognitive abilities have transient episodes of unexpected, spontaneous, meaningful, and relevant communication or behavior. This phenomenon, referred to as lucidity, is not well understood, although it is frequently observed by family caregivers. METHODS An exploratory study using 24 qualitative interviews and 140 open‐ended response data documented family caregiver perspectives and experiences with lucid episodes during late‐stage ADRD. RESULTS Caregivers detailed their experiences witnessing a lucid episode and the resulting impacts. Caregivers revealed reasons they felt positive or upset about the lucid episode, discussed changes the lucid episode prompted, and shared the range of emotions they experienced. IMPLICATIONS Lucid episodes have a significant, enduring, and not always positive impact on caregivers. To better navigate and face sequelae associated with lucid episodes, caregivers should receive psychoeducation or consultation to help increase their understanding, set expectations, and cope with changes. Highlights Little is known about lucid episodes in late‐stage dementia and even less is known about how dementia family caregivers react to and are impacted by these episodes. Qualitative interviews can garner rich data on dementia family caregiving experiences with understudied phenomena such as lucidity. Lucid episodes have a varying but marked and long‐lasting impact on dementia family caregivers. The dementia care field must explore strategies for enhancing education and support to caregivers to build awareness and shape expectations of lucid episodes, a complex experience.

Introduction Due to rising incidence of Hepato-Pancreato-Biliary (HPB) malignancies and more effective therapies, there are increased survivors after curative surgery but little emphasis is placed on survivorship. This study aims to evaluate the value and yield of postoperative surveillance of surgically treated HPB cancer patients within a single surgeon’s practice. Methods A retrospective 1-year (2024) review identified 128 unique patients with prior surgical resection of a HPB malignancy undergoing active cancer surveillance by the surgical team. We excluded patients with benign indications for surgery or active cancer surveillance outside of the surgical team. Results Of these, 112 (87.5%) and 16 (12.5%) underwent pancreatic and hepatobiliary resection, respectively. Median follow up was 1.5 years from the index operation (IQR: 0.7-2.8 years). Pancreatic pathology was pancreatic adenocarcinoma (PDAC), neuroendocrine, or miscellaneous in 70, 25, and 9 patients, respectively. Hepatobiliary pathology was cholangiocarcinoma (CCA), metastatic colorectal cancer, or hepatocellular carcinoma in 16, 6, and 2 patients, respectively. We identified 12 (9.3%) patients who had findings during the study time period resulting in a repeat HPB surgery. In addition, we identified 12 (9.3%) patients who required referral to another department for additional medical, surgical, or interventional treatments. The remaining 104 (81.2%) patients had findings of either no disease recurrence or stable disease with continued surveillance as a recommendation. Conclusion This study underscores the value of cancer surveillance for HPB cancer patients, demonstrating a yield of nearly 20% of patients with findings requiring repeat surgical intervention or referral to other departments.

Abstract Vimentin intermediate filaments play essential roles in maintaining cell integrity and regulating numerous cellular functions. In particular, vimentin cooperates with the actin cytoskeleton in key cellular processes that rely on actin dynamics, such as migration, division, and mechanosensing. While there is evidence that these two cytoskeletal components interact in cells, the underlying molecular mechanisms are only partially understood. Actin and vimentin can interact through biochemical signaling pathways or via cross-linkers, but whether they engage in a direct protein-protein interaction has remained controversial, in part because such interactions are difficult to isolate and characterize in cells. Using in vitro reconstitution coupled to theoretical modeling, and total internal reflection fluorescence microscopy to monitor the elongation of single actin filaments, we show that vimentin promotes actin elongation by stabilizing actin subunits at the barbed end in a dose-dependent manner. Strikingly, this effect depends on the nucleotide state of actin, as the acceleration is only observed for the elongation from ATP-actin, and not ADP-actin monomers. We further establish that neither the vimentin tail nor head domains are required for this effect, and both filamentous and non-filamentous vimentin enhance actin elongation. Finally, we find that vimentin promotes the nucleation of actin filaments. Consistently, magnetic pull-down assays demonstrate a direct interaction between vimentin and ATP-actin monomers. Altogether, these findings identify vimentin as an unexpected new actor in the regulation of actin dynamics at the barbed end and bring new insights into the functional role of vimentin through cytoskeletal crosstalk.

PURPOSE The ECOG-ACRIN E3311 phase II trial demonstrated outstanding disease control (90.6% 54-month progression-free survival) after transoral surgery (TOS) with de-escalated, risk-based postoperative management in resectable human papillomavirus–associated oropharyngeal cancer. The goal of de-escalation was functional preservation. The objective of this work was to evaluate clinician-graded modified barium swallow (MBS) studies from E3311 over time and across arms for (1) aspiration and high-grade pharyngeal residue rates, (2) differences in swallow safety and efficiency, and (3) accuracy of site clinicians reporting against central MBS review. METHODS Eight hundred eighty-five MBS studies were performed on 314 patients from 50 of 59 sites at baseline, post-TOS, and 6 and 24 months postradiotherapy (RT). Swallow outcomes (aspiration, high-grade residue) were recorded by site clinicians. A subset of 414 MBS studies was centrally graded using penetration-aspiration scale scores and the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale. RESULTS Aspiration, residue, and dysphagia rates significantly increased from baseline to post-TOS ( P < .01) and then decreased modestly at 6 and 24 months. At 6 months, swallow outcomes favored the 50- versus 60-Gy arm, with significantly lower aspiration and high-grade dysphagia rates, but this difference was not maintained at 24 months. MBS results reported by site clinicians demonstrated substantial agreement with those assessed by the central laboratory (PABAK, 0.75-0.84; P < .01). CONCLUSION Swallowing worsened after TOS but improved by 6 and 24 months despite adjuvant therapy. De-escalated adjuvant RT at 50 Gy reduced acute aspiration. Site-reported MBS metrics strongly aligned with DIGEST, showing potential as an accessible metric in cooperative group settings.

OBJECTIVE Isthmic spondylolisthesis impacts up to 11.5% of the general population. For patients who have failed conservative therapy, decompression and fusion or decompression alone are options for surgical management. However, there remains debate as to whether reduction of mobile spondylolisthesis is integral to good patient outcomes. The present systematic review and meta-analysis aimed to address this by comparing clinical and radiological outcomes between patients treated with fusion in situ and those undergoing fusion with reduction of isthmic spondylolisthesis. METHODS The Scopus, EMBASE, Medline, and Cochrane databases were systematically queried on the basis of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify studies comparing treatment outcomes in patients with isthmic spondylolisthesis after in situ fusion or fusion with spondylolisthesis reduction. Endpoints of interest included Oswestry Disability Index (ODI) score, hospitalization duration, operative morbidity, and rates of surgical revision. Data from individual studies were aggregated using random-effects models to assess combined effects. RESULTS Of 277 identified studies, 7 studies were included with an aggregate 308 patients (143 underwent fusion in situ and 165 underwent reduction). Patients who underwent reduction for isthmic lumbar spondylolisthesis had significantly lower rates of pseudarthrosis at last follow-up (OR 0.22, p = 0.03). Estimated blood loss, operative time, hospitalization duration, change in ODI score, change in back pain (visual analog scale [VAS]), and reoperation rate did not differ significantly between groups. CONCLUSIONS For patients with isthmic spondylolisthesis, the present data suggest that fusion with reduction of spondylolisthesis may lower rates of pseudarthrosis as compared to in situ fusion. However, operative morbidity and improvement in patient-reported outcomes were similar between strategies.

OBJECTIVE Hundreds of thousands of Americans undergo decompression for lumbar spinal stenosis annually. The mild (minimally invasive lumbar decompression) procedure was developed as a potentially less invasive alternative to open decompression; however, much of the evidence has been gathered from industry-sponsored studies. The present study sought to compare real-world clinical outcomes between the mild procedure and open decompression for lumbar spinal stenosis. METHODS All patients who underwent the mild procedure at a single-institution, multisite, tertiary care center from 2005 to October 2024 were included. One-to-one propensity score matching was used to identify patients who underwent open decompression at the same institution, with age, sex, smoking, and comorbidities as covariates. Primary outcomes were change in pain on the numeric rating scale (NRS), surgical reoperation, and perioperative complications. For pain, the minimal clinically important difference (MCID) was defined as a 30% improvement in NRS score. RESULTS A total of 175 patients who underwent the mild procedure (mean age 76.3 ± 8.7 years; 44.6% female) were matched to 175 patients treated with open decompression (mean age 75.4 ± 8.7 years; 44.0% female). Among patients with at least 60 days of follow-up, those treated with open decompression were more likely to achieve the MCID for pain (43.1% vs 22.2%, p < 0.001). Patients treated with mild were more likely to require reoperation (46.2% vs 29.3%, p = 0.008). Those who underwent the mild procedure experienced lower rates of durotomies (0% vs 2.9%, p = 0.024) but had higher rates of neurological deficits (6.3% vs 0.6%, p = 0.003). CONCLUSIONS For patients with symptomatic lumbar stenosis, those who underwent open decompression were more likely to achieve pain improvement and less likely to require reoperation compared with those who underwent the mild procedure.