Cerebral amyloid angiopathy (CAA) is characterized by the pathologic deposition of amyloid-beta within cortical and leptomeningeal arteries, arterioles, capillaries and, in rare cases, the venules of the brain. It is often associated with the development of lobar intracerebral hemorrhages (ICHs) but may cause other neurologic symptoms or be asymptomatic. Magnetic resonance imaging characteristics, such as lobar microbleeds, support a diagnosis of CAA and assist with hemorrhage risk assessments. Immunosuppressants are used to treat rarer inflammatory forms of CAA. For the more common forms of CAA, the use of antihypertensive medications can prevent ICH recurrence while the use of antithrombotics may increase hemorrhage risk. Anti-amyloid approaches to treatment have not yet been investigated in phase 3 trials. Areas covered: A literature search was conducted using MEDLINE on the topics of imaging, biomarkers, ICH prevention and treatment trials in CAA, focusing on its current diagnosis and management and opportunities for future therapeutic approaches. Expert commentary: There is likely a significant unrecognized burden of CAA in the elderly population. Continued research efforts to discover biomarkers that allow the early diagnosis of CAA will enhance the opportunity to develop treatment interventions.
Circulating hybrid cells (CHCs) are a novel, rare cell population that harbor tumor and immune cell phenotypes and genotypes and are detectible in peripheral blood. Several recent reports implicated CHCs in the metastatic cascade and found their enumeration to provide better prognostic value than conventionally-defined circulating tumor cells (CTCs). However, methods for isolation and enrichment of CHCs are not well-studied or established. Here, we developed an ultrasensitive, antigen-independent platform leveraging the principles of magnetic levitation for the detection and isolation of disseminated neoplastic CHCs. For the first time, we demonstrate that CHCs can be magnetically focused to different levitation heights, under various paramagnetic conditions using a static levitation system, and we quantified the biophysical properties of CHCs (i.e., levitation heights). In addition, we investigated whether magnetic levitation approach can be combined with the affinity-based strategies to enrich CHCs under the magnetic field. Using clinical samples from breast and colorectal cancer patients, we demonstrated that neoplastic cells can be sorted with a magnetic levitation-based sorting device, without relying on any surface markers. Overall, we demonstrated the feasibility of the magnetic levitation method for unbiased enrichment of rare neoplastic-immune hybrid cells from peripheral blood specimens from cancer patients. This approach can be expanded to more clinical samples and cancer types to unprecedentedly explore the biology of rare neoplastic cells and develop metastasis-tailored therapies broadly impacting personalized and precision clinical treatments.
Background Pancreatic adenocarcinoma (PDAC) often impinges on the biliary tree and obstruction necessitates stent placement increasing the risk of surgical site infections (SSIs). We sought to explore the impact of neoadjuvant therapy on the biliary microbiome and SSI risk in patients undergoing resection. Methods A retrospective analysis was performed on 346 patients with PDAC who underwent resection at our institution from 2008 to 2021. Univariate and multivariate methods were utilized for analysis. Results Biliary stenting rates were similar between groups but resulted in increased bile culture positivity (97% vs. 15%, p < 0.001). Culture positivity did not differ between upfront resection or neoadjuvant chemotherapy (NAC) (77% vs. 80%, p = 0.60). NAC‐alone versus neoadjuvant chemoradiotherapy did not impact biliary positivity (80% vs. 79%, p = 0.91), nor did 5‐fluorouracil versus gemcitabine‐based regimens (73% vs. 85%, p = 0.19). While biliary stenting increased incisional SSI risk (odds ratios [OR]: 3.87, p = 0.001), NAC did not (OR: 0.83, p = 0.54). Upfront resection, NAC, and chemoradiotherapy were not associated with biliary organism‐specific changes or antibiotic resistance patterns. Conclusions Biliary stenting is the greatest predictor for positive biliary cultures and SSIs in resected PDAC patients. Neither NAC nor radiotherapy impact bile culture positivity, speciation, rates, or antibiotic resistance patterns, and perioperative antibiotic prophylaxis should not differ.
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