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Background: CDKL5 Deficiency Disorder (CDD) is a rare developmental and epileptic encephalopathy characterized by dominant X-linked inheritance and early infantile onset. To date, more than 300 pathogenic variants of the CDKL5 gene have been reported with different phenotypes. As a rare genetic disease, data on CDD are still limited, making the diagnostic and therapeutic process very challenging. The objective of our study was to provide a comprehensive overview of CDD, including those aspects of the disease for which there is unfortunately still limited knowledge., Materials and Methods: The presence of a CDKL5 variant, cognitive impairment/delayed psychomotor development, and onset of epilepsy within the first year of life were screened for the diagnosis. Comprehensive clinical assessment, laboratory and radiological investigations were performed., Results: Fifteen (n=15) patients were enrolled in the study. In most cases, concordance was found between our data and those already present in the literature. In contrast, some other features, including the development of macrocephaly and the presence of congenital gastrointestinal malformations and spinal cord abnormalities, differ from previous findings., Conclusions: Our study provides an overview on CDD, including those features for which we still have limited knowledge and, albeit on a limited sample, several insights on this rare condition., (Copyright © 2024. Published by Elsevier B.V.)

Objective: This study aimed to assess the complication rate during and 24 hours after cryoablation in lung, bone, and soft tissue tumors., Methods: We reviewed complications in a total of 85 consecutive patients who underwent cryoablation using a liquid nitrogen-based system in various lesions between April 2017 and October 2022. There were no liver and renal lesions. Complications were categorized using the Society of Interventional Radiology classification., Results: Eighty-five patients were treated for 96 lesions in the bone (36.4%; 35 of 96), lung (18.8%; 18 of 96), and soft tissue (44.8%; 43 of 96). The primary technical success rate was 97.7% (83 of 85). The total grade 2 and 1 complication rates were 5.2% (5/96) and 20.8% (20/96), respectively. Two patients had asymptomatic pulmonary embolisms incidentally noted at the 24-hour follow-up computed tomography (grade 2). The most frequent complications were simple and hemorrhagic pleural effusions (18.7%; 18 of 96). Lung procedures had the highest complication rate, where 13 patients (72.2%; 13 of 18) reported complications, including 2 cases of symptomatic hydropneumothorax requiring drainage (grade 2) and an additional 2 days of hospital stay. Eight patients (24.2%; 8 of 33) with bone lesions and 4 (9.3%; 4 of 43) with soft tissue lesions experienced complications., Conclusion: Cryoablation using a liquid nitrogen-based system is safe, with only minor complications observed., Advances in Knowledge: This study provides data on the safety of liquid nitrogen-based percutaneous cryoablation in tumors located in lung, in bones and in soft tissues. Despite using larger diameter cryoprobes than those typically reported with argon-based system, our experience shows that complications are mostly low and comparable in frequency and severity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Objective: To conduct a comprehensive comparison of microwave ablation (MWA) vs radiofrequency ablation (RFA) outcomes in the treatment of small renal masses (SRMs), specifically: TRIFECTA ([i] complete ablation, [ii] absence of Clavien-Dindo Grade ≥III complications, and [iii] absence of ≥30% decrease in estimated glomerular filtration rate) achievement, operative time (OT), and local recurrence rate (LRR)., Patients and Methods: We retrospectively analysed 531 patients with SRMs (clinical T1a-b) treated with MWA or RFA at a single centre (2008-2022). First, multivariable logistic regression models were used for testing TRIFECTA achievement. Second, multivariable Poisson regression models were used to evaluate variables associated with longer OT. Finally, Kaplan-Meier plots depicted LRR over time. All analyses were repeated after 1:1 propensity score matching (PSM)., Results: Of 531 patients with SRMs, 373/531 (70.2%) underwent MWA and 158/531 (29.8%) RFA. MWA demonstrated superior TRIFECTA achievement (314/373 [84.2%]) compared to RFA (114/158 [72.2%], P = 0.001). These differences were driven by higher rates of complete ablation in MWA- vs RFA-treated patients (348/373 [93.3%] vs 137/158 [86.7%], P < 0.001). In multivariable logistic regression models, MWA was associated with higher TRIFECTA achievement, compared to RFA, before (odds ratio [OR] 1.92, P = 0.008) and after PSM (OR 1.99, P = 0.023). Finally, the median OT was shorter for MWA vs RFA (105 vs 115 min; P = 0.002). At Poisson regression analyses, MWA predicted shorter OT before (incidence rate ratio [IRR] 0.86, P < 0.001) and after PSM (IRR 0.85, P < 0.001). Local recurrence occurred in 17/373 (4.6%) MWA-treated patients and 21/158 (13.3%) RFA-treated patients (P = 0.29) after a median (interquartile range) follow-up of 24 (8-46) months. There were no differences in the LRR in Kaplan-Meier plots before (P = 0.29) and after PSM (P = 0.42)., Conclusion: Microwave ablation provides higher TRIFECTA achievement, and shorter OT than RFA. No significant differences were found regarding the LRR., (© 2024 BJU International.)

Ollier disease (OD), acute myeloid leukemia (AML), and brain glioma (BG) are three apparently completely different neoplasms in terms of histopathology, clinic, natural history, and management, but they can affect the same patient. This study aimed to identify the common molecular pathways involved in the pathogenesis of all three diseases and discuss their current and potential role as therapeutic targets. A detailed and comprehensive systematic literature review according to PRISMA guidelines on OD patients harboring BG and/or AML was made. In addition, the unique case of a patient affected by all three considered diseases has been added to our case series. Demographic, pathological, treatment, and outcome data were analyzed and discussed, mainly focusing on the molecular findings. Twenty-eight studies reported thirty-three patients affected by OD and BG, and only one study reported one patient with OD and AML, while only our patient harbored all three pathologies. The IDH R132H mutation was the only genetic alteration shared by all three pathologies and was simultaneously detected in enchondromas and brain glioma in 100% (3/3) of OD patients with BG and also in the neoplastic blood cells of the single patient hosting all three diseases. The IDH1-R132H gene mutation is the etiopathogenetic common denominator among three apparently different tumors coexisting in the same patient. The adoption of mutant-specific IDH1 inhibitor molecules could represent a potential panacea for these conditions in the era of targeted therapies. Further studies with larger clinical series are needed to confirm our results and hypothesis.

Few studies have been published on the long-term outcomes of patients with gastric neuroendocrine tumors (gNETs). We analyzed their management over a two-decade period, focusing on endoscopic and clinical outcomes. Clinical, laboratory, endoscopic, surgical, and histopathological data from Types 1 and 3 gNETs histologically diagnosed between March 2000 and December 2021 at the European Institute of Oncology (IEO, Milan) were retrospectively collected. Sixty-nine patients were included (60 Type 1, 9 Type 3): 53 (77%) were treated endoscopically, 6 (9%) surgically, and 10 (14%) did not receive any treatment. Overall, 293 lesions were removed endoscopically: 74% by forceps, 20% by endoscopic mucosal resection (EMR), and 5% by endoscopic submucosal dissection (ESD). No differences were observed between EMR and ESD in terms of complete resection rate (p value = .50) and complications rate (p value = .084). The median follow-up period was 5.8 years (range: 0.3-20.5), during which no gNET-related deaths were observed. Metachronous gNETs developed in 60% of patients with Type 1 gNET. Six patients with lymph node metastases (LNM) were younger (p value = .006) and had larger lesions (p value <.001) than patients without LNM. Most Type 1 gNETs were successfully excised using forceps, with EMR and ESD being equally effective. The presence of incomplete resection was not associated with a worse prognosis, which remains excellent in this highly recurrent disease. Younger age and a size ≥10 mm were associated with an increased risk of LNM. CLINICAL TRIAL REGISTRATION: Project code UID 2854., (© 2024 British Society for Neuroendocrinology.)

Objectives: To test for specific anthropometric parameters to predict perioperative outcomes after thermal ablation (TA) for renal cell carcinoma (RCC)., Materials and Methods: Retrospective single center (2008-2022) analysis of 538 T1a-b RCC patients treated with TA. We tested for specific anthropometric parameters, namely skin to tumor distance (STTD), perirenal fat thickness (PFT), median psoas muscle axial area (PMAA) and median paravertebral muscle axial area (PVMAA), to predict TRIFECTA achievement: (1) absence of CLAVIEN-DINDO≥ 3 complications; (2) complete ablation; (3) absence of ≥ 30% decrease in eGFR. Univariable (ULRM) and multivariable logistic regression models (MLRM) were used for testing TRIFECTA achievement., Results: Overall, 103 patients (19%) did not achieve TRIFECTA. Of all anthropometric factors, only lower PMAA was associated with no TRIFECTA achievement (10 vs. 11 cm 2 , P = .02). However, ULRMs and MLRMs did not confirmed the aforementioned association. We than tested for the 3 specific TRIFECTA items. In separate ULRM and MLRM predicting incomplete ablation, both continuously coded STTD (Odds Ratio [OR]: 1.02; CI: 1.01-1.03; P = .02) and STTD strata (STTD > 10 cm; OR: 2.1; CI: 1.1-4.1; P = .03) achieved independent predictor status. Conversely, in separate ULRM and MLRM predicting CLAVIEN-DINDO ≥3 complications, both continuously coded PFT (OR: 1.04; CI: 1.01-1.07; P = .01) and PFT strata (PFT ≥ 14 mm; OR: 3.3; CI: 1.6-10.2; P = .003) achieved independent predictor status. Last, none of the anthropometric parameters were associated with eGFR decrease ≥ 30%., Conclusion: None of the tested anthropometric parameters predicted TRIFECTA achievement. However, when the 3 specific TRIFECTA items were tested, STTD and PFT were associated with, respectively, incomplete ablation and CLAVIEN-DINDO ≥ 3 complications., Competing Interests: Disclosure None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: To date, no shared algorithms with the aim of guiding surgical strategy in complex cases of degenerative cervical myelopathy (DCM) exist. Our purpose is to present the Cervical Surgical Score (CSS) which could help in identifying complex DCM cases, suggesting a surgical strategy., Methods: We created the CSS based on multidisciplinary and literature-focused discussions, based on eight parameters including number of levels of cervical pathology and myelopathy, type and predominance of compression and grade of clinical myelopathy. We prospectively enrolled surgical DCM patients in a 15-months period, collecting clinical and radiological data. During outpatient clinic a specific surgical indication was offered to DCM patients. To validate the score, each outpatient clinic surgical indication was compared a posteriori to the one that resulted from multidisciplinary CSS scoring, focusing on patients for which both an anterior and posterior approach were considered suitable., Results: A total of 100 patients operated on for DCM at our Institution between December 2021 and February 2023 were prospectively enrolled. In 53% of patients the pathology was present at more than two levels. According to CSS calculation, 14% of patients resulted in the "grey zone", where both an anterior and posterior approach were deemed feasible. Among them, in 42.8% of cases the CSS allowed a modification of the originally planned surgery. Looking at outcome, an improvement of m-JOA score in 62% of patients was disclosed., Conclusions: This preliminary study showed the reliability and usefulness of CSS in detecting complex DCM cases, requiring further analysis by expert spine surgeons, suggesting a surgical strategy.

Introduction: Spinal cord stimulation is a widespread treatment of chronic neuropathic pain from different conditions. Several novel and improving technologies have been recently developed to increase the effect of neuromodulation in patients refractory to pharmacological therapy., Research Question: To explore spinal cord stimulation's mechanisms of action, indications, and management., Material and Methods: The paper initially explores the mechanism of action of this procedure based on the generation of an electric field between electrodes placed on the posterior dural surface of the spinal cord probably interfering with the transmission of pain stimuli to the brain. Subsequently, the most consolidated criteria for selecting patients for surgery, which constitute a major issue of debate, were defined. Thereafter, the fundamental patterns of stimulation were summarized by exploring the advantages and side effects. Lastly, the most common side effects and the related management were discussed., Results: Proper selection of the patient is of paramount importance to achieve the best results from this specific neuromodulation treatment. Regarding the different types of stimulation patterns, no definite evidence-based guidelines exist on the most appropriate approach in relation to the specific type of neuropathic pain. Both burst stimulation and high-frequency stimulation are innovative techniques that reduce the risk of paresthesias compared with conventional stimulation., Discussion and Conclusion: Novel protocols of stimulation (burst stimulation and high frequency stimulation) may improve the trade-off between therapeutic benefits and potential side effects. Likewise, decreasing the rates of hardware-related complications will be also useful to increase the application of neuromodulation in clinical settings., Competing Interests: The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript., (© 2024 The Authors.)

Background: Ziconotide is an intrathecal drug administered for the treatment of chronic pain. The current literature lacks an exhaustive benefit/risk assessment on this drug. We herein focus on Ziconotide's pharmacology and clinical applications., Methods: Literature research was conducted to identify studies on Ziconotide administration for the treatment of chronic pain, published between January 1990 and March 2023 and located via PubMed, Embase, Medline, Cinahl, and Web of Science, using the following keywords: Ziconotide, Omega conotoxin, Prialt, SNX-111, intrathecal therapy, and neuropathic pain. Only publications written in English were selected., Results: Among the 86 selected studies, we found 4 Randomized Controlled Trials (RCTs) and 3 prospective long-term studies concerning the intrathecal use of Ziconotide as a monotherapy in chronic pain. Other studies described the intrathecal infusion of Ziconotide combined with other drugs. Overall, Ziconotide has been proved to have strong efficacy for relieving chronic pain, although patients with co-morbid psychiatric disorders require a careful monitoring when treated with Ziconotide., Conclusions: Overall, the use of Ziconotide, as a monotherapy or in conjunction with other therapies for the treatment of chronic pain, was reported to be efficacious. Overall, its use in patients with chronic pain refractory to other pharmacologic agents outweighs the possible adverse consequences, thus resulting in a favorable benefit/risk assessment.

Background: Lumbar articular fusion with the facet wedge (FW) technique is gaining increasing interest among surgeons for the treatment of vertebral instability due to its limited invasiveness and ease of use. Studies on cadavers have reported biomechanical properties similar to pedicle screws. Yet, the evidence supporting their use is still limited and moreover focused only on spinal degenerative disease., Methods: 96 cases of lumbar articular fusion with the FW techniques performed at 3 different centers between 2014 and 2022 were retrospectively analyzed based on the specific surgical indications: 1) degenerative spondylolisthesis/unstable lumbar stenosis; 2) synovial cysts; 3) adjacent segment disease (ASD). Medical records were reviewed to identify rates of complications and measures of functional outcome (ODI, low back pain VAS and modified Macnab scale) were collected both at baseline and at the follow-up visits. Wilcoxon signed-rank test was adopted to test for significant functional improvements., Results: Significative clinical improvements were observed from baseline to follow-up regarding ODI and VAS scores. Overall rate of moderate and severe complications (according to Landriel-Ibañez scale) was 7.9%. Only 3.4% of patients with degenerative disease developed ASD requiring reoperations. Only one case of radicular deficit and one of device mobilization were reported. 2/4 cases of synovial cysts treated with unilateral fusions developed contralateral complications. 9 out of 16 (56.25%) patients who underwent long-term postoperative CT scans presented adequate degree of articular fusion., Conclusion: FW technique is easy, safe, and effective. Its low rate of complications justifies its use for cases of mild lumbar instability., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)