马萨诸塞州眼耳医院

PURPOSE:Neurofibromatosis type 2 (NF2) is a tumor predisposition syndrome characterized by bilateral vestibular schwannomas (VSs) resulting in deafness and brainstem compression. This study evaluated efficacy and biomarkers of bevacizumab activity for NF2-associated progressive and symptomatic VSs.PATIENTS AND METHODS:Bevacizumab 7.5 mg/kg was administered every 3 weeks for 46 weeks, followed by 24 weeks of surveillance after treatment with the drug. The primary end point was hearing response defined by word recognition score (WRS). Secondary end points included toxicity, tolerability, imaging response using volumetric magnetic resonance imaging analysis, durability of response, and imaging and blood biomarkers.RESULTS:Fourteen patients (estimated to yield > 90% power to detect an alternative response rate of 50% at alpha level of 0.05) with NF2, with a median age of 30 years (range, 14 to 79 years) and progressive hearing loss in the target ear (median baseline WRS, 60%; range 13% to 82%), were enrolled. The primary end point, confirmed hearing response (improvement maintained ≥ 3 months), occurred in five (36%) of 14 patients (95% CI, 13% to 65%; P < .001). Eight (57%) of 14 patients had transient hearing improvement above the 95% CI for WRS. No patients experienced hearing decline. Radiographic response was seen in six (43%) of 14 target VSs. Three grade 3 adverse events, hypertension (n = 2) and immune-mediated thrombocytopenic purpura (n = 1), were possibly related to bevacizumab. Bevacizumab treatment was associated with decreased free vascular endothelial growth factor (not bound to bevacizumab) and increased placental growth factor in plasma. Hearing responses were inversely associated with baseline plasma hepatocyte growth factor (P = .019). Imaging responses were associated with high baseline tumor vessel permeability and elevated blood levels of vascular endothelial growth factor D and stromal cell-derived factor 1α (P = .037 and .025, respectively).CONCLUSION:Bevacizumab treatment resulted in durable hearing response in 36% of patients with NF2 and confirmed progressive VS-associated hearing loss. Imaging and plasma biomarkers showed promising associations with response that should be validated in larger studies.

BACKGROUND AND OBJECTIVES:Complete removal of large vestibular schwannomas (VS) poses a significant risk of facial nerve [cranial nerve VII (CNVII)] paralysis. However, less-than-total removal may be associated with an increased risk of regrowth, which could require further treatment with additional risks. The objective was to assess long-term outcomes of postoperative CNVII function in relation to the extent of resection in patients who underwent removal of large VS. METHODS:A multicenter, prospective, nonrandomized cohort study of patients with large VS (≥2.5 cm) who underwent gross total resection (GTR), near-total resection (NTR), or subtotal resection (STR). GTR was defined as no visible remnant, NTR as a remnant <0.5 cm3 on postoperative MRI, and STR as any larger remnant. CNVII function was evaluated using binary variables: House-Brackmann grades I-II represented excellent-to-good function, whereas House-Brackmann grades III-VI represented fair-to-poor function. RESULTS:A total of 126 patients were included with a mean (SD) follow-up of 60 (±31) months. The mean preoperative tumor diameter was 3.3 ± 0.7 cm. Thirty-five received GTR, 39 received NTR, and 52 received STR based on postoperative MRI. Smaller preoperative tumor size (P = .03) and volume (P = .03) were associated with good immediate CNVII function. Neither immediate nor late facial nerve function was related to the extent of resection. STR was associated with a 3-fold higher surgical failure rate compared with GTR (P = .02), and patients who experienced surgical failure requiring stereotactic radiosurgery or revision surgery had increased odds of fair-to-poor long-term CNVII function (odds ratio 4.6, 95% CI, 1.7-12.5, P = .002). CONCLUSION:The degree of resection did not predict immediate or late good CNVII function. Surgical failure was associated with worse long-term function. GTR or NTR should be attempted whenever feasible to reduce the likelihood of repeat surgery and poor facial nerve outcomes.

10561 Background: Individuals without prior tobacco use account for a growing proportion of lung cancer cases, but the impact of prior lung diseases on lung cancer risk in this population remains unclear. We performed a meta-analysis of studies examining the association of prior lung diseases – tuberculosis (TB), asthma (AS), and chronic bronchitis (CB) – with lung cancer risk among individuals without prior tobacco use. Methods: PubMed and Embase were searched from inception to Jan 20 th , 2024 for studies examining the association between TB, AS, and/or CB and lung cancer risk in populations over 18 years old who never smoke. Studies were excluded if (1) “never-smoking” was not defined as having never smoked or smoked less than 100 cigarettes in their lifetime; (2) they were not written in English, Mandarin, or Korean; (2) odds ratios (OR)/hazard ratios (HR) were not reported. Summary effect estimates with 95% CI were calculated for case-control (summary OR) and cohort (summary HR) studies using random effects models with inverse variance weighting. Subgroup meta-analyses and meta-regressions were conducted among case-control studies by continent [Asia vs. non-Asia (North America and Europe)]. There was insufficient information to examine differences across the subgroups of sex and race and ethnicity. Results: 17 case-control studies and five cohort studies were examined. Among case-control studies, history of TB (13 studies), AS (10 studies), and CB (nine studies) were statistically significantly associated with an increased risk of lung cancer in patients without prior tobacco use (TB: summary OR=1.75, 95% CI 1.43-2.15, I 2 = 29; AS: summary OR=1.46, 95% CI 1.06-2.02, I 2 = 34; CB: summary OR=1.36, 95% CI 1.07-1.72, I 2 = 0). Among cohort studies, TB (four studies) was associated with a statistically significant increase in lung cancer risk (summary HR=1.81, 95% CI 1.34-2.44, I 2 = 44). There were insufficient number of cohort studies to summarize the associations of CB (no studies) or AS (one study) with lung cancer risk. The summary OR for TB and AS with lung cancer risk was larger in Asian vs. non-Asian populations (TB: Asian populations summary OR=1.79 95% CI 1.40-2.28, I 2 = 47 vs. non-Asian populations summary OR=1.47 95% CI 0.88-2.44, I 2 = 0; AS: Asian populations summary OR=2.63 95% CI 1.10-6.28, I 2 = 40 vs. non-Asian populations summary OR=1.31 95% CI 0.96-1.79, I 2 = 20). However, there was no evidence of heterogeneity in summary OR by continent using meta-regression (TB: p=0.58; AS: p=0.16). Conclusions: In this meta-analysis, history of TB, AS, and CB were associated with lung cancer risk among populations who never smoked, informing potential etiologies of the shifting global burden of lung cancer. Future studies examining these associations should analyze more diverse patient populations and disaggregate findings by sex, race and ethnicity, socioeconomic status, and geography.

The remediation of heavy metal-contaminated groundwater is often hindered by the limited mobility of conventional amendment materials,which restricts the formation of effective in situ reactive zones.Active silica-aluminum materials can not only fix heavy metals,but also migrate effectively in aquifers.To construct reaction zone in situ,an active silica-aluminum material was developed in the laboratory by physicochemical characterization,isothermal adsorption experiment,stability test,and column simulation experiment.In addition,site-scale pilot test and engineering demonstration were carried out in the historical leakage area of groundwater contaminated by Zn and Ni at downstream of the tailings pond of a non-ferrous metal mining area.The results show that the active silica-aluminum has nanoscale pore size and amorphous morphology,with the surface zero charge point of approximately 1.7;the maximum adsorption capacities for Zn and Ni are 94.41,2.40 mg/g,respectively.The fixation mechanism includes ion exchange and precipitation,and the medium of natural sand does not affect its fixation effect on heavy metals.The active silica-aluminum shows high stability,and the polymerization reaction increases with the decrease of pH and the extension of time,following the liquid-solid two phases migration mechanism.Column experiments show that Zn and Ni concentrations at the outlet rapidly decrease to below detection limits following injection,while treatment capacity increases over time.The hydraulic conductivity of the column initially decreases and then increased,with minimal net change.In-situ reaction zone was constructed by injecting active silica-aluminum to immobilize heavy metals in groundwater of the site.The concentrations of Zn and Ni in the pilot area decrease by more than 80％within 40 d.In engineering demonstration area,the migration and diffusion of active silica-aluminum is significant,and the immobilization effect was remarkable.Zn concentration decreases by more than 92.3％after 5 months,and the Zn concentration remains below the standard value of groundwater Ⅲ.Injecting active silica-aluminum can effectively construct in-situ reaction zone to remediate groundwater contaminated by heavy metals.

Ecological restoration in arid mining areas is jointly constrained by water deficit, poor soil substrate, and the legacy background of mining disturbance. Even after years of artificial revegetation, improved surface vegetation cover does not necessarily indicate synchronized recovery of belowground CN processes. Current restoration practices commonly evaluate restoration outcomes using vegetation cover, aboveground biomass, or a limited set of physicochemical indicators, while insufficient attention is paid to belowground microbial communities and their CN cycling functions. This limitation restricts the optimization of vegetation configurations and the reconstruction of soil function. This study focused on four typical vegetation configurations formed through long-term restoration in a mining area of Ordos, Inner Mongolia, including pure tree forest, pure shrub forest, tree-shrub mixed forest, and economic orchard. A total of 78 soil samples were collected. Soil physicochemical properties, enzyme activities, bacterial and fungal community structure, and C/N functional gene abundance were integrated, and structural equation modeling was used to examine the cascading regulatory relationships among vegetation configuration, soil environment, microbial communities, and functional potential. The results show that different vegetation configurations mainly altered key environmental constraints, including soil water content and nitrogen pools, and thereby shaped microbial communities as well as C-degradation and N-transformation potential. These changes further drove differences in soil CN coupling. These changes further drove differences in soil CN coupling. Pure tree forest and tree-shrub mixed forest configurations tended to promote a belowground process context characterized by stronger N retention and higher internal cycling efficiency, with enrichment of indicator taxa such as Geopora and Pseudomonas. In contrast, pure shrub forest showed suppressed microbial diversity and functional potential under stronger resource constraints. Structural equation modeling further indicated that soil water content acted as an upstream driver and had significant positive effects on bacterial and fungal α-diversity, with path coefficients of 0.68 and 0.47, respectively. N-transformation potential was closely linked to the mineral nitrogen pool, with a path coefficient of 0.49 from N-gene abundance to NH₄+-N. By contrast, C-transformation potential was mainly regulated by the soil chemical environment, with a path coefficient of 0.24 from pH to C-gene abundance. This study provides process-oriented mechanistic evidence for vegetation restoration in arid mining areas. It highlights water constraints and microbial functional potential as key components for evaluating and optimizing vegetation configurations, and clarifies the limited transferability of mechanisms observed in management-dependent configurations.