Lessons on neurodegeneration and aging from the Lagoon of Venice: the marine invertebrate Botryllus schlosseri.

In this work, the authors proposed a novel and interesting animal model for studying human neurodegenerative diseases, Botryllus schlosseri, a small invertebrate inhabiting temperate seas worldwide, which shares remarkable similarities with mammals in the expression of genes involved in pathological aging.

Feasibility and Safety of Lateral and Posterolateral Percutaneous Vertebroplasty of Osteolytic C1-C2 Lesions under Computed Tomography Guidance and Local Anesthesia.

OBJECTIVE: To evaluate the safety and effectiveness of the lateral or posterolateral percutaneous vertebroplasty (PVP) of osteolytic C1-C2 lesions performed under computed tomography (CT) guidance and local anesthesia. MATERIALS AND METHODS: Retrospective study of 16 consecutive patients (11 females and 5 males, aged from 24 to 86 years, median 65.5 years) who underwent 17 lateral or posterolateral PVP. Pain status was assessed using a visual analog scale (VAS). Patients were evaluated preoperatively as baseline and at 24 hours, 1, 6, 12 months postoperatively, or until the patient died or was lost to follow-up. The Oswestry Disability Index (ODI) was used to evaluate the patients' functional disability preoperatively. The adverse events were recorded using the SIR classification. RESULTS: The technical success was 100% (17/17) for a median SINS score about 13.5 (IQR [6.75, 20.25]). Mean clinical follow up was 10.1 months (range, 6-36 months; median 19.5 months, IQR [4, 35]). Mean VAS score decreased significantly from 7.5 ± 2.1 preoperatively to 1.6 ± 1.5 24 hours postoperatively, and 1.0 ± 1.1, 1.5 ± 1, and 0.5 ± 1.5 at 1, 6, 12 months respectively (all p<.001). No severe adverse events were observed but 3 cases of asymptomatic cement leakage (SIR grade 1) (17.6% (3/17)). CONCLUSIONS: Lateral and posterolateral PVP performed under CT guidance and local anesthesia is safe and effective to treat symptomatic osteolytic C1-C2 lesions.

Prognostic Role of Lymphocyte-to-Monocyte Ratio (LMR) in Patients with Intermediate-Stage Hepatocellular Carcinoma (HCC) Undergoing Chemoembolizations (DEM-TACE or cTACE) of the Liver: Exploring the Link between Tumor Microenvironment and Interventional Radiology.

Inflammation-based scores are biomarkers of the crosstalk between the tumor microenvironment and the immune response. Investigating the intricate relationship between the tumor stromal microenvironment, biomarkers, and the response to transcatheter arterial chemoembolization (TACE) is essential for early identification of TACE refractoriness or failure, providing insights into tumor biology and facilitating personalized therapeutic interventions. This study addresses a dearth of recent literature exploring the prognostic significance of the preoperative LMR in individuals from western countries diagnosed with stage B hepatocellular carcinoma (HCC) undergoing drug eluting microspheres TACE (DEM-TACE) or conventional TACE (cTACE). This international multi-center retrospective analysis included consecutive patients with stage B HCC who underwent TACE from January 2017 to June 2023. The study evaluated the ability of the preoperative LMR to predict complete response (CR), objective response (OR), sustained response duration (SRD) exceeding 6 months, successful downstaging at 6 months, progression-free survival (PFS) at 6 months, and overall survival (OS) at 6 months. The study population included 109 HCC patients and it was divided into low LMR (LMR < 2.24) and high LMR (LMR ≥ 2.24) groups, according to ROC curve analysis to select the optimal LMR cut-off value. High LMR was associated with lower Hepatitis C prevalence, higher absolute lymphocyte count, and a trend toward lower alpha-fetoprotein. The group with high LMRs exhibited superior CR rates (14.9% vs. 0%), overall OR (43.2% vs. 14.3%), and better PFS at 6 months (75.7% vs. 45.7%). The LMR, specifically categorized as <2.24 and ≥2.24, emerged as a robust predictor for treatment response and short-term outcomes in patients with stage B HCC undergoing DEM- or c-TACE.

A Multicenter International Retrospective Investigation Assessing the Prognostic Role of Inflammation-Based Scores (Neutrophil-to-Lymphocyte, Lymphocyte-to-Monocyte, and Platelet-to-Lymphocyte Ratios) in Patients with Intermediate-Stage Hepatocellular Carcinoma (HCC) Undergoing Chemoembolizations of the Liver.

BACKGROUND: The utilization of inflammation-based scores, such as the Neutrophil-to-Lymphocyte Ratio (NLR), Lymphocyte-to-Monocyte Ratio (LMR), and Platelet-to-Lymphocyte Ratio (PLR), has garnered attention for their potential as prognostic indicators in various cancers. However, their predictive role in patients with intermediate-stage HCC undergoing transcatheter arterial chemoembolization (TACE) remains an area that requires further investigation, as early recognition of TACE refractoriness holds the potential to guide tailored therapeutic interventions. METHODS: This multicenter international retrospective study analyzed data from patients with intermediate-stage HCC undergoing TACE between 2018 and 2024. Inflammation-based scores (NLR, LMR, PLR) were assessed preoperatively to predict treatment outcomes. RESULTS: Two hundred and fourteen patients were enrolled. Preoperative LMR showed the largest area under the curve for the prediction of 6-months PFS, based on the ROC curve analysis. Both high LMR (≥2.24) and low NLR (<4.72) were associated with improved objective response rates and 6-month progression-free survival. Lymphocyte count emerged as a strong predictor of treatment response in both simple (p < 0.001) and multiple (p < 0.001) logistic regression analyses. CONCLUSIONS: This study highlights the prognostic value of inflammation-based scores, particularly LMR and NLR, in predicting the treatment response and short-term outcomes of patients with intermediate-stage HCC undergoing TACE. Future investigations should focus on validating these scores' clinical applicability and assessing their impact on long-term patient survival and therapeutic decision-making.

Patient-Reported Outcomes and Return to Work after CT-Guided Percutaneous Lumbar Discectomy: A Prospective Study.

PURPOSE: To evaluate the effectiveness of percutaneous lumbar discectomy (PLD) under computed tomography (CT) guidance on pain and functional capacities and to estimate the speed of recovery by assessing the time to return to work. MATERIALS AND METHODS: Patients treated with PLD were prospectively included between December 2019 and April 2021. Data regarding pain, duration of symptoms, analgesia intakes, time of absence from work, and the Oswestry disability index (ODI) were collected. Patients were followed-up during 6 months. Duration of hospitalization and time to return to work were reported. The Fisher test was used to compare nominal variables, the Kruskal-Wallis test to compare ordinal variables, and the Student t test to compare quantitative continuous variables. RESULTS: A total of 87 patients were evaluated (median age, 56 years; interquartile range [IQR], 43-66 years). The median ODI decreased from 44 (IQR, 33-53) to 7 (IQR, 2-17) at 6 months (P < .001). The median visual analog scale score decreased from 8 (IQR, 8-9) to 2 (IQR, 0-3) within 6 months (P < .001). In total, 96.5% of patients were discharged on the day of the procedure, and 3.5% were discharged on the following day. No severe adverse events were reported according to the Society of Interventional Radiology (SIR) classification system. Of the 57 patients previously employed, 50 were able to return to work during the follow-up, with a median time of 8 days (IQR, 0-20 days). CONCLUSIONS: Symptomatic lumbar disc herniation can be successfully treated using PLD, resulting in significant improvement in symptoms and functional capacities and a fast return to work.

Genome-wide screening in pluripotent cells identifies Mtf1 as a suppressor of mutant huntingtin toxicity.

Huntington's disease (HD) is a neurodegenerative disorder caused by CAG-repeat expansions in the huntingtin (HTT) gene. The resulting mutant HTT (mHTT) protein induces toxicity and cell death via multiple mechanisms and no effective therapy is available. Here, we employ a genome-wide screening in pluripotent mouse embryonic stem cells (ESCs) to identify suppressors of mHTT toxicity. Among the identified suppressors, linked to HD-associated processes, we focus on Metal response element binding transcription factor 1 (Mtf1). Forced expression of Mtf1 counteracts cell death and oxidative stress caused by mHTT in mouse ESCs and in human neuronal precursor cells. In zebrafish, Mtf1 reduces malformations and apoptosis induced by mHTT. In R6/2 mice, Mtf1 ablates motor defects and reduces mHTT aggregates and oxidative stress. Our screening strategy enables a quick in vitro identification of promising suppressor genes and their validation in vivo, and it can be applied to other monogenic diseases.

Clinical and radiological outcomes following insertion of a novel removable percutaneous interspinous process spacer: an initial experience.

PURPOSE: To evaluate clinical and radiological outcomes of a series of patients treated with a removable percutaneous interspinous process spacer (IPS) (LobsterProject® Techlamed®) for symptomatic degenerative lumbar spinal stenosis (DLSS). METHODS: All patients treated in two centres with this IPS during 2019 were retrospectively reviewed. Procedures were performed under deep sedation or general anaesthesia by two interventional radiologists. Patients were clinically evaluated before intervention and at 3-month follow-up with Visual Analog Scales for pain (VAS), Oswestry Disability Index (ODI) and radiologically with MRI or CT scans. Neural foramina were independently measured for each patient on pre- and post-procedural CT scans by two radiologists. RESULTS: Fifty-nine patients were treated in the selected period of which fifty-eight had complete documentation (mean age 71.2 ± 9.2 years [55-92], 32 males, 26 females). Forty-eight interventions were performed under deep sedation and ten under general anaesthesia, without procedural complications. Clinical follow-up at 3 months showed a significant reduction of pain (VAS from 83 ± 9 to 29 ± 19, - 65%; p < 0.001) and an improvement in functional outcomes (ODI from 31 ± 12 to 13 ± 10%, - 58%; p < 0.001). There was one case of unsatisfactory positioning post procedure, two cases of posterior migration at 3-month follow-up and one case of spinous process fracture. Mean neural foramina area increased from 77 ± 23 to 95 ± 27 mm2 (+ 26%; p < 0.001) with very good inter-observer reliability (Cronbach's alpha = 0.899). CONCLUSION: Percutaneous minimally invasive insertion of a removable IPS device demonstrates a favourable safety profile, good clinical outcomes at 3 months, and apparent anatomical increase in foraminal dimensions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05203666-Release Date: 21st January 2022, retrospectively registered.

CT-Guided Percutaneous Vertebroplasty for Vertebral Non-union Following Posterior Fixation: A Preliminary Retrospective Study.

PURPOSE: Traumatic thoracolumbar vertebral fractures are frequently treated with posterior fixation (PF) and vertebral augmentation. Sometimes, it is deemed too risky to offer vertebral augmentation under fluoroscopic guidance alone. Adjuvant CT/fluoroscopy-guided percutaneous vertebroplasty (PVP) could be offered in certain scenarios. The aim was to evaluate feasibility, safety and effectiveness of PVP in patients presenting with vertebral non-union (VNU) following PF performed without concomitant vertebral augmentation. MATERIALS AND METHODS: All patients treated in our institution with PVP between July 2015 and July 2020 were retrospectively reviewed. Patients treated with CT/fluoroscopy-guided PVP under local anesthesia for symptomatic VNU following PF were selected. Three criteria were established to assess cement distribution, considering vertebral filling of: (1) fracture cleft, (2) anterior two-thirds of the vertebral body, (3) from superior to inferior endplates. Numeric pain rating scale (NPRS) assessing grade of discomfort (0 = no pain; 10 = worst pain) and complications were evaluated before and 1 month after PVP. RESULTS: Ten patients were identified (mean age 53 ± 12y). Mean time between PF and PVP was 9.6 [2-35] months. Two patients required further cement injection with a second PVP. Eight patients had satisfactory vertebral filling according to the three criteria. Mean NPRS reduction was 2.7(-42%, p < 0.05). No significant complications occurred. CONCLUSIONS: Combined CT/fluoroscopy guidance seems a useful tool to perform PVP in VNU following PF, even in presence of orthopedic metalwork. Interventional radiologists may help in these scenarios, performing an adjuvant PVP under local anesthesia. In this small series, the procedure seems safe and effective and could be taken in consideration as alternative to revision surgery.

Symptomatic Schmorl's nodes: role of percutaneous vertebroplasty. Open study on 52 patients.

PURPOSE: To assess the feasibility and clinical outcome of combined CT and fluoroscopy-guided percutaneous vertebroplasty in the management of painful Schmorl's nodes (SN). METHODS: A prospective study was carried out from January 2014 to January 2016 in 52 consecutive patients. Thirty-two men and 30 women aged between 42 and 88 years old were consecutively included. Technical success was defined as the ability to deposit cement in the subchondral endplate anteriorly, around the SN and posteriorly to the SN, in a cupule-like shape. Data regarding procedure time, amount of cement injection, and cement leakage were also noted. Assessment of pain was performed with VAS score and Oswestry disability index. All patients underwent a clinical and radiological follow-up at 1 day, 1 month, 6 months, and 1 year after procedure. RESULTS: Technical success was 100%. Mean procedural time was 15 min, and mean injected cement volume was 2.8 mL. The VAS and Oswestry disability index decreased respectively from 7.2 ± 1.5 to 2.1 ± 1.0 and from 59.2 ± 16.2 to 17.1 ± 5.0 at 1 month. Follow-up mean VAS scores were 2.4 (± 1.4) at 6 months and 2.2 (± 1.2) at 12 months. CONCLUSION: PVP appears as a feasible procedure in patients with painful SN with satisfying pain decrease in the following year after procedure.

Pathophysiology, clinical features and radiological findings of differentiation syndrome/all-trans-retinoic acid syndrome.

In acute promyelocytic leukemia, differentiation therapy based on all-trans-retinoic acid can be complicated by the development of a differentiation syndrome (DS). DS is a life-threatening complication, characterized by respiratory distress, unexplained fever, weight gain, interstitial lung infiltrates, pleural or pericardial effusions, hypotension and acute renal failure. The diagnosis of DS is made on clinical grounds and has proven to be difficult, because none of the symptoms is pathognomonic for the syndrome without any definitive diagnostic criteria. As DS can have subtle signs and symptoms at presentation but progress rapidly, end-stage DS clinical picture resembles the acute respiratory distress syndrome with extremely poor prognosis; so it is of absolute importance to be conscious of these complications and initiate therapy as soon as it was suspected. The radiologic appearance resembles the typical features of cardiogenic pulmonary edema. Diagnosis of DS remains a great skill for radiologists and haematologist but it is of an utmost importance the cooperation in suspect DS, detect the early signs of DS, examine the patients' behaviour and rapidly detect the complications.