Citations

Abstract This review explores the pivotal role of preanalytical variables in bringing liquid biopsy approaches into the clinic for brain tumors. Preanalytical variables encompass a range of critical issues, from blood sample collection and handling to the impact of tumor heterogeneity and patient-specific factors. These variables introduce challenges such as false positives, false negatives, and variability in the analysis of tumor signals, which can hinder the diagnostic and prognostic utility of liquid biopsies. Understanding the nuances of preanalytical variables is essential for the successful implementation of liquid biopsy in clinical settings. This paper delves into strategies aimed at mitigating the influence of preanalytical variables by emphasizing the importance of standardized sample collection protocols, optimized sample processing and storage, quality control measures, and the integration of multiple liquid biopsy modalities.

BACKGROUND: Given the increasing prevalence and shifting disease demographic of vestibular schwannoma toward smaller tumors in people with less advanced symptoms, increasing emphasis has been placed on functional hearing preservation. OBJECTIVE: To provide an update to the 2018 CNS Guideline on hearing preservation outcomes in patients with sporadic vestibular schwannoma. METHODS: Systematic review and clinical practice guideline summarizing data pertaining to hearing preservation outcomes within the first 10 years after contemporary stereotactic radiation, microsurgery, or observation with serial imaging. The analysis incorporates studies included in the 2018 guideline and additional literature published up to May 20, 2022, providing a comprehensive up-to-date review of published clinical outcome data over time. RESULTS: Pooled estimated rates of serviceable hearing preservation are presented for observation, radiosurgery, and microsurgery for adults with sporadic vestibular schwannoma who have documented serviceable hearing in the ipsilateral ear at the time of diagnosis. Overall estimated rates of maintaining serviceable hearing are 78% at 2 years, 59% at 5 years, and 47% at 10 years during observation; 71% at 2 years, 59% at 5 years, and 38% at 10 years after radiosurgery; and 48% at 2 years, 40% at 5 years, and 32% at 10 years after microsurgery. In addition, features portending hearing outcome among management modalities are reported to guide accurate patient counseling. CONCLUSION: Regardless of treatment modality, fewer than half of patients with sporadic vestibular schwannoma who present with serviceable hearing will maintain useful hearing by 10 years. Across all studies, microsurgery and radiosurgery seem to accelerate this decline over the natural history, although further research is needed given limitations of available evidence. The full guideline can be seen online at https://www.cns.org/guidelines/treatment-adults-vestibular-schwannoma/4-hearing-preservation-outcomes-in-patients-with-s

Objectives Generative artificial intelligence (GAI) tools can enhance the quality and efficiency of medical research, but their improper use may result in plagiarism, academic fraud and unreliable findings. Transparent reporting of GAI use is essential, yet existing guidelines from journals and institutions are inconsistent, with no standardised principles. Design and setting International online Delphi study. Participants International experts in medicine and artificial intelligence. Main outcome measures The primary outcome measure is the consensus level of the Delphi expert panel on the items of inclusion criteria for GAMER (Rreporting guideline for the use of Generative Artificial intelligence tools in MEdical Research). Results The development process included a scoping review, two Delphi rounds and virtual meetings. 51 experts from 26 countries participated in the process (44 in the Delphi survey). The final checklist comprises nine reporting items: general declaration, GAI tool specifications, prompting techniques, tool’s role in the study, declaration of new GAI model(s) developed, artificial intelligence-assisted sections in the manuscript, content verification, data privacy and impact on conclusions. Conclusion GAMER provides universal and standardised guideline for GAI use in medical research, ensuring transparency, integrity and quality.

Abstract Introduction: Hemolytic uremic syndrome (HUS) is especially uncommon in adults and can manifest as devasting complications including severe acute kidney injury (AKI) and microangiopathic hemolytic anemia (MAHA). Transfusion-related acute lung injury (TRALI) is a rare complication of blood product transfusion that is characterized by the rapid development of noncardiogenic pulmonary edema. We present a rare case of HUS complicated by TRALI requiring mechanical ventilation. Case Description: A 41-year-old female farmer, who occasionally drank raw cow's milk, was admitted with abdominal pain and distension, bloody diarrhea, poor appetite, decreased urine output and fatigue. She was found to have MAHA and stage 3 AKI. Imaging demonstrated pancolitis and workup revealed Shiga toxin-producing E. coli, O157:H7 serotype which was consistent with a diagnosis of HUS. Tests for DIC, TTP and atypical HUS were negative. She was not a candidate for dialysis, plasma exchange or eculizumab. With supportive measures including 3 units of packed red blood cell (pRBC), her symptoms, renal function, and bicytopenia improved and she was discharged. Two days post-discharge, she presented to the ED for unilateral vision changes, left hemiparesis, and lower extremity tremor. After negative neurological evaluation, this was attributed to encephalopathy secondary to HUS. She received 1 unit of pRBCs for a hemoglobin of 6.8. Within 3 hours of transfusion, she developed acute respiratory distress requiring intubation and ICU transfer. CT chest angiogram was negative for pulmonary embolism but demonstrated diffuse bilateral lower lobe dependent consolidations concerning for TRALI (Figure 1). After diuresis, she was able to be extubated within 48 hours with return to her respiratory and neurologic baselines soon after. Discussion: The pathophysiology of TRALI involves neutrophil sequestration and priming in the pulmonary vasculature with subsequent neutrophil activation by donor blood product factors where active infection is a known risk factor. Active HUS likely contributed to neutrophil priming through endothelial damage and systemic inflammation, predisposing this patient to TRALI. There are few reports of similar cases in the literature. TRALI can be subdivided into type I and type II; type I has no risk factors for acute respiratory distress syndrome (ARDS) while type II does. TRALI must also be distinguished from ARDS and transfusion-associated circulatory overload; these distinctions are predominantly made based on timing of respiratory symptom onset. This case highlights the importance of keeping TRALI in the differential for all patients with active or recent infection, including HUS, who develop acute-onset respiratory decompensation after transfusion.

Abstract Rationale: We previously reported (PMID: 38325750) that a nebulized exosome product isolated from human platelets (PEP) attenuated murine cigarette smoke (CS)-induced emphysema. To further elucidate the mechanism by which PEP attenuates CS-induced effects in the murine lung, emphysema was induced, and mice were treated with PEP or placebo (saline). Immune and cellular mechanisms affected by PEP were then evaluated in this system. Methods: C57BL6 female black mice were exposed to CS 5 days a week for 3 months and then randomized into PEP-treated or placebo groups. CS-exposed mice were treated with 3 mL of 7.5 mg/mL PEP (∼1 x 1010 extracellular vesicles per mL) or 0.9% saline by nebulization 3 times a week for an additional 4 weeks, using a nose-sealed, pressure and humidity-controlled inhalation tower for 30 minutes. Lung compliance, cutaneous O2 saturation, mean linear intercepts, and lung inflammation were measured during and after the study. Lung tissue was further analyzed by immunostaining, and gene expression analyses to elucidate the molecular mechanisms of PEP's action. Inflammatory and immune regulatory cell markers evaluated included CD4 (CD4+ T lymphocytes), CD4/Foxp3 (T regulatory – Treg) cells, S100A9 (interstitial lung macrophages), and myeloperoxidase (MPO) for neutrophils. Results: Histologic review of lung tissue sections by mean linear intercept counts confirmed prior findings and showed a significant reduction in the free distance of chronic CS exposure-induced alveolar space enlargement in PEP-treated mice (P=0.003). In addition, lung inflammation scores showed a significant overall reduction of the lymphocytic infiltrates in PEP-nebulized lungs compared to the CS-exposed placebo control group (P<0.0001). Further analysis of the immune cell infiltrates revealed increased FOXP3+CD4+ T regulatory cells within the lymphocytic infiltrates (P<0.0001) and decreased S100A9+ interstitial lung macrophages (p=0.0002) and MPO+ neutrophils (p=0.005) in PEP nebulized lungs compared to the placebo controls. PEP-treated mice had similar oxygen saturation levels when compared to the CS control group (94.7±1.47 vs. 95.4±.1.6 respectively). Conclusions: In addition to validating prior findings on the effect of nebulized PEP in mitigating CS-induced murine lung injury and emphysema, the current data suggests an immunoregulatory role for PEP by decreasing inflammatory macrophage and neutrophil infiltration while augmenting anti-inflammatory Treg cell numbers in the lung.

Abstract Objective To (1) track the incidence of pleomorphic adenomas (PAs) and (2) compare demographic and treatment trends in PAs over the last five decades in a single county. Study Design Retrospective cohort of all patients with a pathologic diagnosis of nonrecurrent PA from January 1976 to December 2022. Setting Olmsted County, Minnesota. Methods Incidence was calculated per 100,000 persons/year and age and sex‐adjusted to the US 2020 census data. Incidence trends were identified using Poisson rate regression models. Changes in clinical features of diagnosis were evaluated using Spearman rank correlation coefficient tests, Wilcoxon rank sum tests, and Kruskal‐Wallis tests. Results In total, 251 patients with PA were identified. The median age at diagnosis was 50.0 years with a slight female predominance (1.24:1). The adjusted incidence during this period is 4.79/100,000 person‐years, increasing from 2.50 in 1976 to 1979 to 5.73/100,000 persons/year in 2020 to 2022. Less extensive surgery, including partial and superficial parotidectomies, increased significantly from 1976 to 2022, whereas total parotidectomies decreased ( P < .0001). The number of patients who presented with an incidental imaging finding increased during this time period ( P < .001), as did the age at diagnosis (45‐51 years, P = .05) Conclusion The average annual incidence of PAs in Olmsted County from 1976 to 2022 is higher than reported US estimates and has increased over the last five decades. The percentage of patients who presented with incidental imaging findings increased over this period, as did the age at diagnosis. These findings highlight modern imaging techniques and an aging population more willing to seek workup and treatment of a benign parotid mass.

AbstractObjectiveTo examine associations with changes in quality‐of‐life (QOL) outcomes following treatment of vestibular schwannoma (VS) using stereotactic radiosurgery (SRS).Study DesignProspective longitudinal study.SettingTertiary academic center.MethodsPatients who were treated for sporadic VS using SRS from 2015 to 2022 were included. QOL outcomes were measured using the disease‐specific Penn Acoustic Neuroma QOL (PANQOL) scale.ResultsSeventy‐nine patients with pre‐SRS and at least one post‐SRS PANQOL assessments were available for analysis. The mean change in total PANQOL scores was −2 (SD 13) on a 100‐point scale. The mean duration between assessments was 4.6 years (SD 2.0). Age at SRS, sex, and SRS treatment doses were not significantly associated with changes in total PANQOL scores. Total PANQOL scores improved a mean of 4 points for patients with tumors confined to the internal auditory canal but declined a mean of 5 points for patients with tumors extending into the cerebellopontine angle (P = .01); however, these changes did not exceed the minimum clinically significant threshold of 11 points. The correlation coefficient between treated tumor volume at SRS and change in total PANQOL scores was −0.30 (P = .007). Changes in PANQOL total (P = .5) and hearing domain (P = .3) scores for patients who maintained serviceable hearing or progressed to nonserviceable hearing did not significantly differ.ConclusionTumor extent and treated volume at SRS had a statistically significant but likely not clinically important impact on total PANQOL scores. Progression to nonserviceable hearing did not have a significant impact on PANQOL total or hearing domain scores.

INTRODUCTION: Evidence-based recommendations for sexual practices regarding anoreceptive intercourse (ARI) do not exist in patients with inflammatory bowel diseases undergoing restorative proctocolectomy with ileal pouch anal anastomosis (IPAA). This study surveys providers on perspectives and attitudes related to sexual practices after IPAA. METHODS: We developed a 23-item survey and distributed it to providers caring for patients with inflammatory bowel diseases. RESULTS: 95% of providers believe that it is important to discuss sexual orientation or practices before IPAA, but only 27% routinely discuss this. 50% did not feel comfortable and 74% did not feel confident discussing ARI recommendations with patients who underwent or will undergo IPAA. DISCUSSION: Future interventions should aim to standardize recommendations regarding feasibility and time line to safe ARI after IPAA.

Objective To compare the utility of intraoperative electrically evoked auditory brainstem response (eABR) and electrically evoked stapedial reflex testing (eSRT) for cochlear nerve integrity monitoring during simultaneous translabyrinthine resection of vestibular schwannoma (VS) and cochlear implantation. Study design Historical cohort study. Setting Tertiary academic referral center. Patients Eleven patients (12 cases) who underwent translabyrinthine tumor resection with simultaneous placement of a standard, unmodified cochlear implant (CI). Intervention A CI placed at the beginning of the operation before tumor resection to facilitate intraoperative cochlear nerve monitoring through a CI-delivered electrical stimulus. Main outcome measure Correlation of intraoperative monitoring outcomes with postoperative CI performance. Results Among the 12 cases (median age, 47 years), eABR waveforms were present at the conclusion of tumor resection in 10, including 6 that achieved open set speech perception. Of the 2 cases with negative eABR, 1 achieved open set speech perception. By contrast, of the 8 cases with a positive eSRT response, 7 achieved open set speech perception. Of the 4 cases with a negative eSRT response, none achieved open set speech perception. The 3 cases that did not receive auditory stimulation included 2 with positive and 1 with negative eABR; all 3 had a negative eSRT response. Conclusions Intraoperative eSRT using an unmodified CI is a promising new method for monitoring the integrity of the cochlear nerve during simultaneous VS resection. eSRT response at the conclusion of tumor resection strongly correlated with CI open set speech capacity. Although still useful, eABR was less reliable at predicting postoperative hearing outcomes in this series.