Unique report of iliocaval endovascular reconstruction successfully enabling a kidney transplant.

End-stage renal disease patients with Iliocaval venous obstruction are normally nom viable recipients for kidney transplantation. We report a case of a 34-year-old male patient in hemodialysis as renal replacement therapy for six years due to IgA nephropathy. Past medical history included multiple central venous catheter infections and catheter associated thrombosis. Iliac confluence and inferior vena cava occlusion previously excluded the patient from the renal transplantation list. Exhaustion of venous access sites was already previously documented. After multidisciplinary discussion the patients was proposed to endovascular Iliocaval reconstruction aiming a future kidney transplant. Iliocaval recanalization was achieved through bilateral femoral access. Inferior vena cava and iliac angioplasty were performed. A dedicated venous stent was deployed in the inferior vena cava, followed by a double-barrel reconstruction of the iliac confluence. Successful iliocaval recanalization was accomplished. Five months after kidney transplantation was performed with a deceased-donor graft in the right iliac fossa. Post operative period was uneventful. After 12 months the patient remained free from kidney replacement therapies with a serum creatinine of 1.3mg/dL. At the best of our knowledge this is the first clinical description of successful kidney transplant in a patient with a previous iliocaval reconstruction.

Correlation Between Pedal Acceleration Time and Transcutaneous Oxygen Pressures - A Prognostic Tool for Wound Healing in the Diabetic Foot Population.

BACKGROUND: Pedal arch interrogation by ultrasound through systolic acceleration time measurement (Pedal Acceleration Time [PAT]) is a recently described technique that offers valuable insights into foot hemodynamics. Previous studies have demonstrated a correlation between PAT and the ankle-brachial index and PAT has been proposed as a prognostic tool for wound healing in patients with peripheral artery disease. This study aims to assess the correlation between PAT and Transcutaneous Pressure of Oxygen (TcPO2) in the diabetic foot population. METHODS: In this single-center cross-sectional study PAT and TcPO2 were measured in diabetic patients with ischemic foot ulcers. The assessment of wound status was performed between the 12th and 16th week after the first evaluation. The primary outcome was to assess the correlation between the values obtained for PAT and TcPO2. The secondary outcome was to establish a cut-off value for wound healing. RESULTS: Sixty limbs with ischemic foot ulcers were evaluated. The results showed a correlation between PAT and TcPO2 [F (1.52) = 16.928; R2 = 0.246; P < 0.001]. The receiver operating characteristics curve analysis showed an optimal cut-off value at PAT >186 ms for predicting a nonhealing ulcer with a 96% specificity (area under the curve = 0.774; confidence interval 0.648-0.872; P < 0.001). CONCLUSIONS: PAT showed a significant correlation with TcPO2 with high specificity to identify nonhealing foot ulcers due to insufficient foot perfusion with a potential prognostic value in the diabetic foot population.

Proximalization of Arterial Inflow for the Treatment of Limb Ischemia in a Transposed Femoral Arteriovenous Fistula-A Case Report.

INTRODUCTION: Femoral vein transposition is one of the final resorts for vascular access in patients with exhaustion of upper limb venous patrimony and central venous occlusive disease. Its major pitfalls include hemodialysis access-induced distal ischemia and infection. Surgical procedures may be warranted to preserve vascular access if ischemia develops. Several techniques are reported in the literature for femoral vein transposition. CASE REPORT: We expose an endoscopic femoral vein harvesting as an alternative to the single thigh incision in order to avoid its associated complications. In the setting of ischemia, proximalization of arterial inflow was used to manage femoral vein transposition associated limb ischemia. CONCLUSION: This case report aims to expose the aforementioned unreported surgical techniques for lower limb arteriovenous fistula, its advantages, and pitfalls, as well as considerations on its future use.

Navigating complexity: The Supera's triumph in femoropopliteal lesions.

INTRODUCTION: The femoropopliteal sector endovascular treatment is particularly challenging due to its high tortuosity and torsional forces. Better results are still needed to ensure the long-term patency of stenting in this area. The Supera stent appears to change this paradigm. METHODS: This single-center retrospective cohort study aims to evaluate the efficacy and safety of femoropopliteal stenting with Supera in a real-world population. Seventy-nine patients were treated between January 2015 and December 2020, and the results are reported with a median follow-up of 28 months. RESULTS: Indications for revascularization were chronic limb-threatening ischemia with tissue loss (73.6%) or ischemic rest pain (17.7%) and claudication (7.6%). Thirty-six patients (45.6%) were classified as GLASS stage III according to the Global Limb Anatomic Staging System, with 65.8% and 30.4% in grades 3 and 4 of femoropopliteal and infrapopliteal sectors, respectively. The 36-month primary, primary-assisted, and secondary patency rates were 68.6%, 72.0%, and 79.0%, respectively, with an amputation-free survival rate of 86.6%. There was no significant difference between primary patency rates in GLASS stages I-II compared with GLASS stage III (36-month primary patency rates of 72% vs 63% respectively, p = 0.342) nor in amputation-free survival (88% vs 84%, p = 0.877). After adjusting for potential confounders, only the stent conformation significantly affected the primary patency rates, with a higher hazard of reintervention for the elongated (HR = 3.179; p = 0.36; CI 1.081-9.347) and the compressed (HR = 3.014; p = 0.42; CI 1.039-8.746) forms. CONCLUSIONS: The 36-month patency of the Supera stents in our real-world cohort was similar to other reported series. The GLASS stage did not interfere with the stent patency, proving it is a good choice even in the most adverse anatomy patients. Only the non-nominal stent conformation affected the primary patency rates in our patients.

Nephrectomy with Autotransplantation-A Key Treasure.

Background: Nephrectomy with autotransplantation (NAT) has been performed as an alternative treatment for complex renovascular lesions, intricate ureteral strictures and nephron-sparing surgery in complex renal tumors. Methods: A retrospective observational study was conducted including patients who underwent a NAT from January 2010 to September 2023. Data collected included surgery indications, surgical technique, complications according to Clavien-Dindo classification and mean hospital stay. Descriptive and inferential statistical analysis was performed using IBM® SPSS® Statistics version 28.0.1.0. Results: A total of 34 consecutive patients underwent 38 NATs at our institution. Surgery indications were complex renovascular conditions in 35 cases (92.1%), of which 24 had renal artery aneurysms, and ureteral injuries in 3 cases (7.9%). Thirty-four kidneys (89.5%) were retrieved through a laparoscopic approach. No significant difference was observed between post- and pre-operative creatinine levels (0.81 vs. 0.72, p = 0.303). Early high-grade complications developed in 12 procedures (31.6%). Median cold ischemia time was significantly longer in patients who developed complications (163.0 vs. 115.0, p = 0.010). The median hospital stay was 10 days (8-13). The median follow-up was 51.5 months. Conclusions: NAT emerges as a successful therapeutic strategy for a highly select group of patients dealing with intricate ureteral lesions and kidney vascular abnormalities, demonstrating positive outcomes that endure in the long term.

Institutional Experience With Venous Aneurysms - Insights On The Natural History And Outcomes Of Surgical Treatment.

INTRODUCTION: Venous aneurysms are rare, so their natural history is not fully understood. Indications for treatment are often determined by the location and size of the aneurysm; however, considering the scarcity of data, there are no specific recommendations. Surgery is the mainstay for venous aneurysm treatment, but some authors reported successful endovascular treatment. We intend to describe our experience with this type of rare disorder. METHODS: A post hoc observational study of a prospectively maintained registry including consecutive patients admitted with the diagnosis of a venous aneurysm at different locations between January 2007 and September 2021. Demographic data, anatomic location, and medical history, including trauma or venous surgery, were analyzed. All vascular reconstructions and outcomes have been evaluated. RESULTS: We identified 30 venous aneurysms in 24 patients. Fifteen patients were male (63%). The most common anatomical location was the popliteal vein (n=19; 63%). Four patients had multiple venous aneurysms, and three patients had synchronous arterial aneurysms. Twelve (63%) of the popliteal vein aneurysms identified were surgically treated, most commonly by tangential aneurysmectomy and lateral venorrhaphy. The average diameter at the time of surgery was 22,8±3,6 mm. After discharge, all patients were anticoagulated for 6 to 12 months, in most cases with rivaroxaban. With a median follow-up time of 32 months (12 - 168 months), primary patency was 92%. Aneurysm recurrence was only observed in one case (1/12; 8%) with non-occlusive thrombosis of the aneurysm 14 years after surgery. One patient had a 21 mm gemelar vein aneurysm, having been proposed for surgery, with thrombosis before the intervention. Two patients had common femoral vein aneurysms treated with partial aneurysmectomy and lateral venorrhaphy without thromboembolic events during follow-up. Two patients presented with portal system aneurysms, one associated with portal hypertension. No treatment was performed, and an increase in aneurysm size was observed during follow-up. Another patient presented with acute deep vein thrombosis on chronically thrombosed bilateral iliac vein aneurysms. Three patients had aneurysms of the superficial venous system associated with previous trauma, which were treated with simple ligation and excision. CONCLUSION: Venous aneurysms are rare and most commonly located in the popliteal vein, which seems to be associated with chronic venous disease. Treating these aneurysms, even without symptoms, can be important to avoid thromboembolic complications. However, close long-term follow-up with duplex ultrasound should be considered to detect late recurrence. Aneurysms from other locations are even rarer, and treatment decisions should be individualized, weighing the risks and benefits of the intervention.

A nationwide collapse of a priority grassland bird related to livestock conversion and intensification.

Grassland birds are among the most threatened and fastest declining terrestrial vertebrate species in Europe, principally due to agricultural intensification and transformation. The little bustard is a priority grassland bird under the European Directive (2009/147/CE) that led to the classification of a network of Special Protected Areas (SPAs) in Portugal. A third national survey carried out in 2022 reveals a worsening of an ongoing population collapse at a national scale. The population declined by 77% and 56% compared to the previous surveys in 2006 and 2016, respectively. We found that the little bustard has greatly disappeared outside SPAs, while the remaining breeding population concentrated within the protected area network is showing a steep decline at a rate of 9% a year. This decline is now twice as fast when compared to the period 2006-2016. Analysis of the variation of the breeding densities between 2006 and 2022 at 49 survey sites revealed that those that initially had higher bustard densities and shifted toward a higher proportion of cattle among the total stocking rate experienced steeper declines. Areas where the density of roads increased also experienced declines over the course of the study period. Agricultural areas converted to or dominated by beef production likely relate to low breeding success and mortality of nesting females in fodder crops. Still, major habitat conversion outside SPAs to permanent crops led to overall habitat destruction, which contributed to the species decline and range contraction. Other threats are likely acting synergistically such as fragmentation, climate change and anthropogenic mortality. The extinction of the little bustard in Portugal is expected in the short term if no conservation actions are put in place.

Kidney autotransplantation as a key solution for a BEVAR type IIIb endoleak.

OBJECTIVES: Target vessel endoleaks are one of the most common causes of revision procedures after a fenestrated or branched endovascular aneurysm repair. Usually, a redo stenting is an effective therapy, however, not always feasible. We present a case of a hybrid treatment for a type IIIb endoleak using the renal autotransplantation technique. METHODS: A 60-year-old man with a thoracoabdominal aortic aneurysm has been treated with a custom-made branched endoprosthesis. Occlusion of the bridging stent to the right renal artery with total infarction of the right kidney was identified one week later and conservatively managed. After four years, a type IIIb endoleak was identified. Endovascular treatment was attempted unsuccessfully. So, the endoleak was corrected using a hybrid strategy with the kidney autotransplantation technique. RESULTS: A left kidney autotransplantation followed by an aortic stent-graft relining with a tubular graft has been done uneventfully, in a phased manner. Postoperative computed tomography angiography confirmed the patency of vascular reconstructions with no endoleaks. No adverse events occurred during one year of follow-up. CONCLUSION: Our case highlights kidney autotransplantation as a viable solution for a hybrid treatment of target vessel endoleaks and shows that this technique can assist complex endovascular aortic reconstructions.

Exploring the Ways of "The Great Imitator": A Case Report of Syphilitic Hepatitis.

Introduction: Syphilis is a chronic infection caused by Treponema pallidum. Manifestations of this disease are vast, and syphilitic hepatitis is a rarely depicted form of secondary syphilis. Case Presentation: We report the case of a 63-year-old man with worsening jaundice, maculopapular rash and perianal discomfort. Proctological examination with anoscopy revealed a perianal gray/white area with millimetric pale granules along the anal canal. Liver function tests showed a mixed pattern. Venereal Disease Research Laboratory, T. pallidum hemagglutination assay and IgM fluorescent treponemal antibody absorbance were positive. The patient was successfully treated with a single dose of penicillin G. Discussion/Conclusion: Syphilitic hepatitis is scarcely reported in the literature. Secondary syphilis with mild hepatitis rarely leads to hepatic cytolysis and jaundice. Many signs of secondary syphilis including syphilitic hepatitis may be linked to immune responses initiated during early infection. Over the past decades, evidence has emerged on the importance of innate and adaptive cellular immune responses in the immunopathogenesis of syphilis. This report raises awareness to a clinical entity that should be considered in patients at risk for sexually transmitted diseases, who present with intestinal discomfort or liver dysfunction, as it is a treatable and fully reversible condition.

Introdução: A sífilis é uma infeção crónica provocada pelo Treponema pallidum. As manifestações desta doença são vastas e a hepatite sifilítica é uma forma de sífilis secundária raramente descrita. Caso Clínico: Apresentamos o caso de um doente de 63 anos com icterícia de agravamento progressivo, rash maculopapular e desconforto perianal. O exame proctológico complementado por anuscopia revelou uma região perianal cinzenta-esbranquiçada com grânulos pálidos milimétricos ao longo do canal anal. Testes de função hepática revelaram um padrão misto e o Venereal Disease Research Laboratory, T. pallidum hemagglutination assay e IgM fluorescent treponemal antibody absorbance foram positivos. O doente foi tratado com sucesso com uma dose única de penicilina G. Discussão/Conclusão: São raros os casos de hepatite sifilítica descritos na literatura. Sífilis secundária com hepatite ligeira raramente conduz a citólise hepática e icterícia. Muitos dos sinais de sífilis secundária, incluindo a hepatite sifilítica, parecem estar associados a respostas imunitárias iniciadas durante o período de infeção precoce. Ao longo das últimas décadas, têm surgido evidências crescentes sobre a importância das respostas imunes inata e adaptativa na patogénese da sífilis. Este caso clínico descreve uma entidade nosológica que deve ser considerada em doentes em risco de contraírem doenças sexualmente transmissíveis, que se apresentem com desconforto intestinal ou disfunção hepática, visto tratar-se de uma condição tratável e totalmente reversível.

Effects of Coir-Based Growing Medium with Municipal Solid Waste Compost or Biochar on Plant Growth, Mineral Nutrition, and Accumulation of Phytochemicals in Spinach.

The use of municipal solid waste compost (MSW) and biochar, two renewable resources with a low carbon footprint as components of substrates, may be an alternative to reducing peat and coir usage. The aim of this study was to assess the suitability of selectively collected MSW and biochar as components of the coir-based substrate to spinach grown. An experiment was carried out to evaluate five substrates, coir and four coir-based blends (coir + biochar + perlite, coir + municipal waste compost + perlite, coir + biochar + pine bark, and coir + biochar + pine bark) with 12% (v/v) MSW or biochar and 10% (v/v) perlite or pine bark. Spinach seedlings were transplanted into Styrofoam planting boxes filled with the substrate. Each planting box was irrigated daily by drip with a complete nutrient solution. Plants grown with MSW had a higher content of calcium. Shoot Mn increased in the biochar-containing mixes. The shoot dry weight of the plants grown in the different blends was higher than those grown in coir. Fresh yield was higher in mixes with MSW and perlite (3 kg/m2) or pine bark (2.87 kg/m2). Total phenols and DPPH antioxidant activity were not affected by the substrates. However, shoot ascorbate (AsA) content was higher or equal to those plants grown in coir. MSW and biochar are alternatives to reduce the use of coir and peat.

Hybrid Approach of a Complex Aneurysm of the Subclavian-Axillary-Brachial Axis: A Case Report.

BACKGROUND: Upper extremity arterial aneurysms are a rare, potentially limb-threatening disorder. Due to its rarity, the best treatment modality and outcomes are not entirely established; however, there is a consensus that open surgery is the first-line treatment. We present a complex case of an arterial aneurysm of the subclavian-axillary-brachial axis adequately treated using a hybrid surgical and endovascular treatment. CASE PRESENTATION: A 59-year-old man presented to the emergency department with acute ischemia of the right upper limb. An extensive thrombosed aneurysm of the subclavian-axillary-brachial axis was identified. The treatment was carried out in two stages. In the first phase, urgent limb revascularization was performed using the great saphenous vein to perform a subclavian-brachial artery bypass. Later, the aneurysm was excluded using a vascular plug and multiple coils. Successful treatment was achieved with no morbidity for the patient. CONCLUSIONS: Although the gold standard for treating upper limb aneurysms is open surgery, endovascular techniques can be a significant adjunct, reducing treatment morbidity and even mortality.

Efficient Hardware Design and Implementation of the Voting Scheme-Based Convolution.

Due to a point cloud's sparse nature, a sparse convolution block design is necessary to deal with its particularities. Mechanisms adopted in computer vision have recently explored the advantages of data processing in more energy-efficient hardware, such as the FPGA, as a response to the need to run these algorithms on resource-constrained edge devices. However, implementing it in hardware has not been properly explored, resulting in a small number of studies aimed at analyzing the potential of sparse convolutions and their efficiency on resource-constrained hardware platforms. This article presents the design of a customizable hardware block for the voting convolution. We carried out an in-depth analysis to determine under which conditions the use of the voting scheme is justified instead of dense convolutions. The proposed hardware design achieves an energy consumption about 8.7 times lower than similar works in the literature by ignoring unnecessary arithmetic operations with null weights and leveraging data dependency. Access to data memory was also reduced to the minimum necessary, leading to improvements of around 55% in processing time. To evaluate both the performance and applicability of the proposed solution, the voting convolution was integrated into the well-known PointPillars model, where it achieves improvements between 23.05% and 80.44% without a significant effect on detection performance.

Customizable FPGA-Based Hardware Accelerator for Standard Convolution Processes Empowered with Quantization Applied to LiDAR Data.

In recent years there has been an increase in the number of research and developments in deep learning solutions for object detection applied to driverless vehicles. This application benefited from the growing trend felt in innovative perception solutions, such as LiDAR sensors. Currently, this is the preferred device to accomplish those tasks in autonomous vehicles. There is a broad variety of research works on models based on point clouds, standing out for being efficient and robust in their intended tasks, but they are also characterized by requiring point cloud processing times greater than the minimum required, given the risky nature of the application. This research work aims to provide a design and implementation of a hardware IP optimized for computing convolutions, rectified linear unit (ReLU), padding, and max pooling. This engine was designed to enable the configuration of features such as varying the size of the feature map, filter size, stride, number of inputs, number of filters, and the number of hardware resources required for a specific convolution. Performance results show that by resorting to parallelism and quantization approach, the proposed solution could reduce the amount of logical FPGA resources by 40 to 50%, enhancing the processing time by 50% while maintaining the deep learning operation accuracy.

Renal Autotransplantation for The Treatment of Renal Artery Aneurysm.

OBJECTIVE: Renal artery aneurysms are a rare condition; however, the rate of diagnosis has been increasing, because of the increasing use of complementary diagnostic methods. The best treatment strategy for RAAs remains controversial. Data on ex-vivo surgery associated with kidney autotransplantation are scarce. As a result, the goal of this study was to describe this technique and to report our results. METHODS: A retrospective monocentric study was undertaken using the clinical records and images of 35 patients diagnosed with renal artery aneurysm from 01/01/2010 to 31/12/2018. Indications for ex vivo surgery and autotransplantation were complex aneurysms with diameter >20 mm or rapid growth or symptomatic aneurysms or women wishing to become pregnant. Complex aneurysms were defined by anatomical criteria (bifurcation of the renal artery and its primary branches or hilar aneurysms) and/or physiological criteria (when time of warm ischemia in in-situ reconstruction is expected to last more than 45 minutes). The technique of ex-vivo surgery and autotransplantation consists of performing a nephrectomy, renal cooling, treatment of aneurysm in banking and implantation of the kidney in the homolateral iliac fossa. RESULTS: A total of 35 patients with 56 renal artery aneurysms (26 women, mean age 52.4 years-minimum and maximum 16 and 74 years) were included. Of these, 27 were treated by surgery and 8 were followed clinically. Among those treated surgically, 24 performed ex vivo surgery associated with autotransplantation. Regarding ex vivo surgery, nephrectomy was performed by laparoscopic surgery in 24 of the 27 surgeries, the mean surgical time was 5.3 hours, the median warm ischemia time was 4 minutes and the length of hospital stay was 12.2 days. Mortality was 0% and the kidney patency rate was 93% with a follow up of 47.2 months. Of the 17 patients with hypertension, 6 cured it, 4 improved and 7 maintained hypertension. CONCLUSION: Kidney autotransplantation appears to be efficient for most complex RAA with the possibility to minimize surgical aggression by performing laparoscopic nephrectomy.

A systematic review and meta-analysis of randomized controlled studies comparing off-pump versus on-pump coronary artery bypass grafting in the elderly.

INTRODUCTION: Comparison of short and mid-term outcomes between off-pump CABG (OPCAB) and on-pump CABG (ONCAB) in patients older than 65 throughout a meta-analysis of randomized clinical trials (RCTs). EVIDENCE ACQUISITION: A literature search was conducted using 3 databases. RCTs reporting mortality outcomes of OPCAB versus ONCAB among the elderly were included. Data on myocardial infarction, stroke, re-revascularization, renal failure and composite endpoints after CABG were also collected. Random effects models were used to compute statistical combined measures and 95% confidence intervals (CI). EVIDENCE SYNTHESIS: Five RCTs encompassing 6221 patients were included (3105 OPCAB and 3116 ONCAB). There were no significant differences on mid-term mortality (pooled HR: 1.02, 95%CI: 0.89-1.17, P=0.80) and composite endpoint incidence (pooled HR: 0.98, 95%CI: 0.88-1.09, P=0.72) between OPCAB and ONCAB. At 30-day, there were no differences in mortality, myocardial infarction, stroke and renal complications. The need for early re-revascularization was significantly higher in OPCAB (pooled OR: 3.22, 95%CI: 1.28-8.09, P=0.01), with a higher percentage of incomplete revascularization being reported for OPCAB in trials included in this pooled result (34% in OPCAB vs. 29% in ONCAB, P<0.01). CONCLUSIONS: Data from RCTs in elderly patients showed that OPCAB and ONCAB provide similar mid-term results. OPCAB was associated with a higher risk of early re-revascularization. As CABG on the elderly is still insufficiently explored, further RCTs, specifically designed targeting this population, are needed to establish a better CABG strategy for these patients.

MicroRNA-100-5p and microRNA-298-5p released from apoptotic cortical neurons are endogenous Toll-like receptor 7/8 ligands that contribute to neurodegeneration.

BACKGROUND: MicroRNA (miRNA) expression in the brain is altered in neurodegenerative diseases. Recent studies demonstrated that selected miRNAs conventionally regulating gene expression at the post-transcriptional level can act extracellularly as signaling molecules. The identity of miRNA species serving as membrane receptor ligands involved in neuronal apoptosis in the central nervous system (CNS), as well as the miRNAs' sequence and structure required for this mode of action remained largely unresolved. METHODS: Using a microarray-based screening approach we analyzed apoptotic cortical neurons of C56BL/6 mice and their supernatant with respect to alterations in miRNA expression/presence. HEK-Blue Toll-like receptor (TLR) 7/8 reporter cells, primary microglia and macrophages derived from human and mouse were employed to test the potential of the identified miRNAs released from apoptotic neurons to serve as signaling molecules for the RNA-sensing receptors. Biophysical and bioinformatical approaches, as well as immunoassays and sequential microscopy were used to analyze the interaction between candidate miRNA and TLR. Immunocytochemical and -histochemical analyses of murine CNS cultures and adult mice intrathecally injected with miRNAs, respectively, were performed to evaluate the impact of miRNA-induced TLR activation on neuronal survival and microglial activation. RESULTS: We identified a specific pattern of miRNAs released from apoptotic cortical neurons that activate TLR7 and/or TLR8, depending on sequence and species. Exposure of microglia and macrophages to certain miRNA classes released from apoptotic neurons resulted in the sequence-specific production of distinct cytokines/chemokines and increased phagocytic activity. Out of those miRNAs miR-100-5p and miR-298-5p, which have consistently been linked to neurodegenerative diseases, entered microglia, located to their endosomes, and directly bound to human TLR8. The miRNA-TLR interaction required novel sequence features, but no specific structure formation of mature miRNA. As a consequence of miR-100-5p- and miR-298-5p-induced TLR activation, cortical neurons underwent cell-autonomous apoptosis. Presence of miR-100-5p and miR-298-5p in cerebrospinal fluid led to neurodegeneration and microglial accumulation in the murine cerebral cortex through TLR7 signaling. CONCLUSION: Our data demonstrate that specific miRNAs are released from apoptotic cortical neurons, serve as endogenous TLR7/8 ligands, and thereby trigger further neuronal apoptosis in the CNS. Our findings underline the recently discovered role of miRNAs as extracellular signaling molecules, particularly in the context of neurodegeneration.