Citations

Cerebrospinal fluid–venous fistula is an increasingly recognized cause of spontaneous intracranial hypotension.1 The site of the leak is between the dural sleeve around a spinal nerve root and the surrounding foraminal veins. In appropriately investigated patients, transvenous embolization of the draining foraminal and paraspinal veins has been shown to be an effective way of treating the disease, with low periprocedural morbidity, improvement in symptoms and radiological appearances.2 Video 1 shows the technique employed in a typical case using Onyx (Medtronic, Minnesota, USA) to embolize a CSF–venous fistula at the right T10 neural foramen. Video 1 Video showing the technique for trans-venous embolization of a right T10 CSF-venous fistula for the treatment of spontaneous intracranial hypotension. The first section covers patient selection and work up, before then focusing on the technical aspects of navigating through the azygos system to the target foramen and completely occluding the pathway for CSF outflow.

Background Standard therapy for COVID-19 is continuously evolving. Autopsy studies showed high prevalence of platelet-fibrin-rich microthrombi in several organs. The aim of the study was therefore to evaluate the safety and efficacy of antiplatelet therapy (APT) in hospitalised patients with COVID-19 and its impact on survival. Methods 7824 consecutive patients with COVID-19 were enrolled in a multicentre international prospective registry (Health Outcome Predictive Evaluation-COVID-19 Registry). Clinical data and in-hospital complications were recorded. Data on APT, including aspirin and other antiplatelet drugs, were obtained for each patient. Results During hospitalisation, 730 (9%) patients received single APT (93%, n=680) or dual APT (7%, n=50). Patients treated with APT were older (74±12 years vs 63±17 years, p<0.01), more frequently male (68% vs 57%, p<0.01) and had higher prevalence of diabetes (39% vs 16%, p<0.01). Patients treated with APT showed no differences in terms of in-hospital mortality (18% vs 19%, p=0.64), need for invasive ventilation (8.7% vs 8.5%, p=0.88), embolic events (2.9% vs 2.5% p=0.34) and bleeding (2.1% vs 2.4%, p=0.43), but had shorter duration of mechanical ventilation (8±5 days vs 11±7 days, p=0.01); however, when comparing patients with APT versus no APT and no anticoagulation therapy, APT was associated with lower mortality rates (log-rank p<0.01, relative risk 0.79, 95% CI 0.70 to 0.94). On multivariable analysis, in-hospital APT was associated with lower mortality risk (relative risk 0.39, 95% CI 0.32 to 0.48, p<0.01). Conclusions APT during hospitalisation for COVID-19 could be associated with lower mortality risk and shorter duration of mechanical ventilation, without increased risk of bleeding. Trial registration number NCT04334291.

Changes in nuclear shape have been extensively associated with the dynamics and functionality of cancer cells. In most normal cells, nuclei have a regular ellipsoid shape and minimal variation in nuclear size; however, an irregular nuclear contour and abnormal nuclear size is often observed in cancer, including pancreatic cancer. Furthermore, alterations in nuclear morphology have become the ‘gold standard’ for tumor staging and grading. Beyond the utility of altered nuclear morphology as a diagnostic tool in cancer, the implications of altered nuclear structure for the biology and behavior of cancer cells are profound as changes in nuclear morphology could impact cellular responses to physical strain, adaptation during migration, chromatin organization, and gene expression. Here, we aim to highlight and discuss the factors that regulate nuclear dynamics and their implications for pancreatic cancer biology.

Abstract Glioblastomas (GBM) are routinely treated with ionizing radiation (IR) but inevitably recur and develop therapy resistance. During treatment, the tissue surrounding tumors is also irradiated. IR potently induces senescence, and senescent stromal cells can promote the growth of neighboring tumor cells by secreting factors that create a senescence-associated secretory phenotype (SASP). Here, we carried out transcriptomic and tumorigenicity analyses in irradiated mouse brains to elucidate how radiotherapy-induced senescence of non-neoplastic brain cells promotes tumor growth. Following cranial irradiation, widespread senescence in the brain occurred, with the astrocytic population being particularly susceptible. Irradiated brains showed an altered transcriptomic profile characterized by upregulation of CDKN1A (p21), a key enforcer of senescence, and several SASP factors, including HGF, the ligand of the receptor tyrosine kinase (RTK) Met. Preirradiation of mouse brains increased Met-driven growth and invasiveness of orthotopically implanted glioma cells. Importantly, irradiated p21−/− mouse brains did not exhibit senescence and consequently failed to promote tumor growth. Senescent astrocytes secreted HGF to activate Met in glioma cells and to promote their migration and invasion in vitro, which could be blocked by HGF-neutralizing antibodies or the Met inhibitor crizotinib. Crizotinib also slowed the growth of glioma cells implanted in preirradiated brains. Treatment with the senolytic drug ABT-263 (navitoclax) selectively killed senescent astrocytes in vivo, significantly attenuating growth of glioma cells implanted in preirradiated brains. These results indicate that SASP factors in the irradiated tumor microenvironment drive GBM growth via RTK activation, underscoring the potential utility of adjuvant senolytic therapy for preventing GBM recurrence after radiotherapy. Significance: This study uncovers mechanisms by which radiotherapy can promote GBM recurrence by inducing senescence in non-neoplastic brain cells, suggesting that senolytic therapy can blunt recurrent GBM growth and aggressiveness.

Background Elderly patients have a higher burden of comorbidities that influence clinical outcomes. We aimed to compare in‐hospital outcomes in patients ≥80 years old to younger patients, and to determine the factors associated with increased risk of major adverse events (MAE) after left atrial appendage closure. Methods and Results The National Inpatient Sample was used to identify discharges after left atrial appendage closure between October 2015 and December 2018. The primary outcome was in‐hospital MAE defined as the composite of postprocedural bleeding, vascular and cardiac complications, acute kidney injury, stroke, and death. A total of 6779 hospitalizations were identified, of which, 2371 (35%) were ≥80 years old and 4408 (65%) were <80 years old. Patients ≥80 years old experienced a higher rate of MAE compared with those aged <80 years old (6.0% versus 4.6%, P =0.01), and this difference was driven by a numerically higher rate of cardiac complications (2.4% versus 1.8%, P =0.09) and death (0.3% versus 0.1%, P =0.05) among individuals ≥80 years old. In patients ≥80 years old, higher odds of in‐hospital MAE were observed in women (1.61‐fold), and those with preprocedural congestive heart failure (≈2‐fold), diabetes (≈1.5‐fold), renal disease (≈2.6‐fold), anemia (≈2.7‐fold), and dementia (≈5‐fold). In patients <80 years old, a higher risk of in‐hospital MAE was encountered among women (≈1.4‐fold) and those with diabetes (≈1.3‐fold), renal disease (≈2.6‐fold), anemia (≈2‐fold), and dyslipidemia (≈1.2‐fold). Conclusions Patients ≥80 years old had higher rates of in‐hospital MAE compared with patients aged <80 years old. Female sex and the presence of heart failure, diabetes, renal disease, and anemia were factors associated with in‐hospital MAE among both groups.

Asystole or bradycardia is a relatively uncommon side effect seen in patients undergoing endovascular embolization using dimethylsulfoxide based liquid embolic agents. We present a case of a patient who underwent dural arteriovenous fistula embolization and experienced bradycardia during Onyx injection but was stabilized and the procedure was completed successfully.

Objective: The aim of this study was to analyze outcomes of open lobectomy (OL), VATS, and robotic-assisted lobectomy (RL). Summary Background Data: Robotic-assisted lobectomy has seen increasing adoption for treatment of early-stage lung cancer. Comparative data regarding these approaches is largely from single-institution case series or administrative datasets. Methods: Retrospective data was collected from 21 institutions from 2013 to 2019. All consecutive cases performed for clinical stage IA-IIIA lung cancer were included. Neoadjuvant cases were excluded. Propensity-score matching (1:1) was based on age, sex, race, smoking-status, FEV1%, Zubrod score, American Society of Anesthesiologists score, tumor size, and clinical T and N stage. Results: A total of 2391 RL, 2174 VATS, and 1156 OL cases were included. After propensity-score matching there were 885 pairs of RL vs OL, 1,711 pairs of RL vs VATS, and 952 pairs of VATS vs OL. Operative time for RL was shorter than VATS (P < 0.0001) and OL (P = 0.0004). Compared to OL, RL and VATS had less overall postoperative complications, shorter hospital stay (LOS), and lower transfusion rates (all P<0.02). Compared to VATS, RL had lower conversion rate (P<0.0001), shorter hospital stay (P<0.0001) and a lower postoperative transfusion rate (P =0.01). RL and VATS cohorts had comparable postoperative complication rates. In-hospital mortality was comparable between all groups. Conclusions: RL and VATS approaches were associated with favorable perioperative outcomes compared to OL. Robotic-assisted lobectomy was also associated with a reduced length of stay and decreased conversion rate when compared to VATS.