Ischemic lesion water homeostasis after thrombectomy for large vessel occlusion stroke within the anterior circulation: The impact of age

The effect of age on lesion pathophysiology in the context of thrombectomy has been poorly investigated. We aimed to investigate the impact of age on ischemic lesion water homeostasis measured with net water uptake (NWU) within a multicenter cohort of patients receiving thrombectomy for anterior circulation large vessel occlusion (LVO) stroke. Lesion-NWU was quantified in multimodal CT on admission and 24 h for calculating Δ-NWU as their difference. The impact of age and procedural parameters on Δ-NWU was analyzed. Multivariable regression analysis was performed to identify significant predictors for Δ-NWU. Two hundred and four patients with anterior circulation stroke were included in the retrospective analysis. Comparison of younger and elderly patients showed no significant differences in NWU on admission but significantly higher Δ-NWU (p = 0.005) on follow-up CT in younger patients. In multivariable regression analysis, higher age was independently associated with lowered Δ-NWU (95% confidence interval: −0.59 to −0.16, p < 0.001). Although successful recanalization (TICI ≥ 2b) significantly reduced Δ-NWU progression by 6.4% (p < 0.001), younger age was still independently associated with higher Δ-NWU (p < 0.001). Younger age is significantly associated with increased brain edema formation after thrombectomy for LVO stroke. Younger patients might be particularly receptive targets for future adjuvant neuroprotective drugs that influence ischemic edema formation.     

A role for TASK2 channels in the human immunological synapse

The immunological synapse is a transient junction that occurs when the plasma membrane of a T cell comes in close contact with an APC after recognizing a peptide from the antigen-MHC. The interaction starts when CRAC channels embedded in the T cell membrane open, flowing calcium ions into the cell. To counterbalance the ion influx and subsequent depolarization, K_v1.3 and KCa3.1 channels are recruited to the immunological synapse, increasing the extracellular K⁺ concentration. These processes are crucial as they initiate gene expression that drives T cell activation and proliferation. The T cell-specific function of the K_2P channel family member TASK2 channels and their role in autoimmune processes remains unclear. Using mass spectrometry analysis together with epifluorescence and super-resolution single-molecule localization microscopy, we identified TASK2 channels as novel players recruited to the immunological synapse upon stimulation. TASK2 localizes at the immunological synapse, upon stimulation with CD3 antibodies, likely interacting with these molecules. Our findings suggest that, together with K_v1.3 and KCa3.1 channels, TASK2 channels contribute to the proper functioning of the immunological synapse, and represent an interesting treatment target for T cell-mediated autoimmune disorders.     

A case of homozygous familial hypercholesterolemia with an atypical phenotype and delayed clinical symptoms

We describe the casuistry of a homozygous familial hypercholesterolemia female patient with a biallelic missense variant (NM_000527.4:c.1775G>A, p.Gly592Glu) in the LDLR gene, severe hypertriglyceridemia and late manifestation of coronary heart disease not earlier than at the age of 45 years. An atypical phenotype led to a delayed diagnosis.     

Balance and gait performance after maximal and submaximal endurance exercise in seniors: is there a higher fall-risk?

Impaired balance and gait performance increase fall-risk in seniors. Acute effects of different exercise bouts on gait and balance were not yet addressed. Therefore, 19 healthy seniors (10 women, 9 men, age: 64.6 ± 3.2 years) were examined on 3 days. After exhaustive treadmill testing, participants randomly completed a 2-km treadmill walking test (76 ± 8 % VO_2max) and a resting control condition. Standing balance performance (SBALP) was assessed by single limb-eyes opened (SLEO) and double limb-eyes closed (DLEC) stance. Gait parameters were collected at comfortable walking velocity. A condition × time interaction of center of pressure path length (COP_path) was observed for both balance tasks (p < 0.001). Small (Cohen’s d = 0.42, p = 0.05) and large (d = 1.04, p < 0.001) COP_path increases were found after 2-km and maximal exercise during DLEC. Regarding SLEO, slightly increased COP_path occurred after 2-km walking (d = 0.29, p = 0.65) and large increases after exhaustive exercise (d = 1.24, p < 0.001). No significant differences were found for gait parameters. Alterations of SBALP after exhaustive exercise might lead to higher fall-risk in seniors. Balance changes upon 2-km testing might be of minor relevance. Gait is not affected during single task walking at given velocities.     

Adverse effects of irreversible electroporation of malignant liver tumors under CT fluoroscopic guidance: a single-center experience

PURPOSE

We aimed to describe the frequency of adverse events after computed tomography (CT) fluoroscopy-guided irreversible electroporation (IRE) of malignant hepatic tumors and their risk factors.

METHODS

We retrospectively analyzed 85 IRE ablation procedures of 114 malignant liver tumors (52 primary and 62 secondary) not suitable for resection or thermal ablation in 56 patients (42 men and 14 women; median age, 61 years) with regard to mortality and treatment-related complications. Complications were evaluated according to the standardized grading system of the Society of Interventional Radiology. Factors influencing the occurrence of major and minor complications were investigated.

RESULTS

No IRE-related death occurred. Major complications occurred in 7.1% of IRE procedures (6/85), while minor complications occurred in 18.8% (16/85). The most frequent major complication was postablative abscess (4.7%, 4/85) which affected patients with bilioenteric anastomosis significantly more often than patients without this condition (43% vs. 1.3%, P = 0.010). Bilioenteric anastomosis was additionally identified as a risk factor for major complications in general (P = 0.002). Minor complications mainly consisted of hemorrhage and portal vein branch thrombosis.

CONCLUSION

The current study suggests that CT fluoroscopy-guided IRE ablation of malignant liver tumors may be a relatively low-risk procedure. However, patients with bilioenteric anastomosis seem to have an increased risk of postablative abscess formation.About 70% of hepatic metastases are nonresectable because of their anatomic location, the presence of comorbidities, or limited hepatic functional reserve (1). In these patients and in case of nonresectable primary liver tumors, percutaneous thermal ablation procedures, such as radiofrequency (RF) and microwave ablation, have become effective tools for treating hepatic malignancies (2–4). However, the effectiveness of RF and microwave treatment may be limited, either because of thermal damage to temperature-sensitive structures located in close proximity to the target tissue (5) or because of incomplete ablation of tumors adjacent to major hepatic vessels due to a phenomenon commonly termed “heat-sink effect” (6–10) which describes the loss of the applied thermal energy through the blood flow in those major vessels, whereby the effective energy application remains inadequate to ablate the target lesion.Irreversible electroporation (IRE) is a theoretically nonthermal ablation technique that delivers a series of high-voltage millisecond electrical pulses to the surrounding tissue, thus leading to irreversible disruption of the integrity of cell membranes and subsequent cell death by apoptosis (11–14). IRE may overcome the problems raised with thermal ablation: previous animal studies reported that bile ducts, blood vessels, nerves, and connective tissues are affected by IRE; however, regeneration is possible to some extent due to preservation of the tissue architecture (12, 13, 15–19). Moreover the feasibility of inducing cell death up to a vessel wall without any perivascular sparing was shown with IRE (12, 13, 18). The safety of IRE in the treatment of humans has been described (20). First reports have described potential complications after IRE, such as hemorrhage requiring blood transfusion (1.2%, two of 167 ablation procedures), portal vein thrombosis (3.2%, one of 31 ablation procedures), injury to bile ducts (1.8%, three of 167 ablation procedures), and infection (3.6%, six of 167 ablation procedures) (21, 22). However, few data are available for evaluating the potential risk factors associated with the occurrence of post-IRE complications.The purpose of this study was to review the frequency of mortality and morbidity after computed tomography (CT) fluoroscopy-guided liver IRE conducted at a single center and assess the factors influencing the occurrence of major complications.