OBJECTIVE: We comprehensively characterized a large pediatric cohort with focal cortical dysplasia (FCD) type 1 to expand the phenotypic spectrum and to identify predictors of postsurgical outcomes. METHODS: We included pediatric patients with histopathological diagnosis of isolated FCD type 1 and at least 1 year of postsurgical follow-up. We systematically reanalyzed clinical, electrophysiological, and radiological features. The results of this reanalysis served as independent variables for subsequent statistical analyses of outcome predictors. RESULTS: All children (N = 31) had drug-resistant epilepsy with varying impacts on neurodevelopment and cognition (presurgical intelligence quotient [IQ]/developmental quotient scores = 32-106). Low presurgical IQ was associated with abnormal slow background electroencephalographic (EEG) activity and disrupted sleep architecture. Scalp EEG showed predominantly multiregional and often bilateral epileptiform activity. Advanced epilepsy magnetic resonance imaging (MRI) protocols identified FCD-specific features in 74.2% of patients (23/31), 17 of whom were initially evaluated as MRI-negative. In six of eight MRI-negative cases, fluorodeoxyglucose-positron emission tomography (PET) and subtraction ictal single photon emission computed tomography coregistered to MRI helped localize the dysplastic cortex. Sixteen patients (51.6%) underwent invasive EEG. By the last follow-up (median = 5 years, interquartile range = 3.3-9 years), seizure freedom was achieved in 71% of patients (22/31), including seven of eight MRI-negative patients. Antiseizure medications were reduced in 21 patients, with complete withdrawal in six. Seizure outcome was predicted by a combination of the following descriptors: age at epilepsy onset, epilepsy duration, long-term invasive EEG, and specific MRI and PET findings. SIGNIFICANCE: This study highlights the broad phenotypic spectrum of FCD type 1, which spans far beyond the narrow descriptions of previous studies. The applied multilayered presurgical approach helped localize the epileptogenic zone in many previously nonlesional cases, resulting in improved postsurgical seizure outcomes, which are more favorable than previously reported for FCD type 1 patients.

• MeSH
• Child MeSH
• Electroencephalography * methods   MeSH
• Epilepsy MeSH
• Focal Cortical Dysplasia MeSH
• Cohort Studies MeSH
• Infant MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Malformations of Cortical Development, Group I * surgery   complications   diagnostic imaging   MeSH
• Malformations of Cortical Development surgery   complications   diagnostic imaging   MeSH
• Adolescent MeSH
• Positron-Emission Tomography MeSH
• Child, Preschool MeSH
• Drug Resistant Epilepsy * surgery   diagnostic imaging   physiopathology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

INTRODUCTION AND OBJECTIVES: With increases in obesity and metabolic syndrome because of lifestyle-related factors, the prevalence of non-alcoholic fatty liver disease (NAFLD) also is increasing worldwide. In a subset of patients with NAFLD, an inflammatory process arises in the steatotic liver, known as non-alcoholic steatohepatitis, that leads to liver fibrosis and liver cirrhosis. In selected patients with obesity, bariatric surgery, and bariatric endoscopy are important therapeutic options. MATERIALS AND METHODS: This prospective interventional pilot study was conducted to investigate two types of intragastric balloons (IGB). The IGBs were the Orbera and the Spatz3. Liver fibrosis changes were monitored non-invasively using point and 2D shear wave ultrasound elastography (SWE) and transient elastography that allowed for quantification of liver steatosis using the controlled attenuation parameter (CAP). Patients were followed for 12 months. RESULTS: Of 34 patients implanted with an IGB, 30 completed follow-up at month 12; results for one patient were excluded because of initiation of obesity pharmacotherapy. Fifteen patients received the Orbera IGB, and nineteen patients received the Spatz3 type. In month 12, total and excess weight loss was 7.88 % and 30.13 %. Elastography values decreased from baseline (3.88 kPa) to 3.61 kPa at month 12 (p 0.024). 2D SWE values decreased from baseline (5.42 kPa) to a value of 4.91 kPa at month twelve (p 0.135). Transient elastography values decreased from baseline (5.62 kPa) to a value of 4.17 kPa at month twelve (p 0.009). CONCLUSIONS: Bariatric endoscopy in the form of IGB implantation leads to weight reduction and improvement of liver fibrosis and steatosis. GOV REGISTRATION: NCT04895943.

• MeSH
• Bariatric Surgery * MeSH
• Time Factors MeSH
• Equipment Design MeSH
• Adult MeSH
• Elasticity Imaging Techniques MeSH
• Weight Loss MeSH
• Liver Cirrhosis * etiology   diagnostic imaging   diagnosis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Non-alcoholic Fatty Liver Disease * diagnostic imaging   diagnosis   etiology   MeSH
• Obesity * complications   surgery   diagnosis   MeSH
• Pilot Projects MeSH
• Prospective Studies MeSH
• Treatment Outcome MeSH
• Gastric Balloon * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial MeSH

Papillary thyroid carcinoma (PTC) represents ~80% of all thyroid cancers, most frequently presenting in women in the third and fourth decade of life. The first clinical manifestation of PTC commonly includes a palpable mass in the thyroid area or cervical lymphadenopathy in cases of metastatic disease. Hematogenous distant metastases are a sign of an advanced stage of the tumour. The present study reported an extremely rare occurrence of solitary metastasis of a PTC in the left breast of a 63-year-old male patient, mimicking primary male breast cancer (MBC). The presence of a male breast lesion that did not follow the typical imaging criteria for MBC aroused suspicion of a different primary origin. The combination of imaging methods, laboratory findings and fine-needle aspiration techniques enabling cytological and histopathological examination, with the use of a wide panel of immunohistochemical markers, is crucial to establishing a definitive and correct diagnosis.

• Publication type
• Journal Article MeSH
• Case Reports MeSH

OBJECTIVE: Transgenic mice with fluorescent protein (FP) reporters take full advantage of new in vivo imaging technologies. Therefore, we generated a TRPC5- and a TRPA1-reporter mouse based on FP C-terminal fusion, providing us with better alternatives for studying the physiology, interaction and coeffectors of these two TRP channels at the cellular and tissue level. METHODS: We generated transgenic constructs of the murine TRPC5- and TRPA1-gene with a 3*GGGGS linker and C-terminal fusion to mCherry and mTagBFP, respectively. We microinjected zygotes to generate reporter mice. Reporter mice were examined for visible fluorescence in trigeminal ganglia with two-photon microscopy, immunohistochemistry and calcium imaging. RESULTS: Both TRPC5-mCherry and TRPA1-mTagBFP knock-in mouse models were successful at the DNA and RNA level. However, at the protein level, TRPC5 resulted in no mCherry fluorescence. In contrast, sensory neurons derived from the TRPA1-reporter mice exhibited visible mTag-BFP fluorescence, although TRPA1 had apparently lost its ion channel function. CONCLUSIONS: Creating transgenic mice with a TRP channel tagged at the C-terminus with a FP requires detailed investigation of the structural and functional consequences in a given cellular context and fine-tuning the design of specific constructs for a given TRP channel subtype. Different degrees of functional impairment of TRPA1 and TRPC5 constructs suggest a specific importance of the distal C-terminus for the regulation of these two channels in trigeminal neurons.

• MeSH
• Red Fluorescent Protein MeSH
• Trigeminal Ganglion metabolism   MeSH
• Gene Knock-In Techniques * MeSH
• TRPC Cation Channels * genetics   metabolism   MeSH
• TRPA1 Cation Channel * genetics   metabolism   MeSH
• Luminescent Proteins * genetics   metabolism   MeSH
• Mice, Transgenic * MeSH
• Mice MeSH
• Recombinant Fusion Proteins metabolism   genetics   MeSH
• Calcium metabolism   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

INTRODUCTION: This study aimed to assess the impact of midline lumbar fusion with cortical bone trajectory screws (MIDLF/CBT) on the multifidus muscles, focusing on the evaluation of their postoperative atrophy. CLINICAL RATIONALE FOR THE STUDY: MIDLF/CBT is a relatively new technique increasingly used to treat spinal instability. Despite its reduced invasiveness compared to traditional posterior lumbar interbody fusion with traditional pedicle screws (PLIF/TP), concerns remain about potential damage to the multifidus muscles that are crucial for spinal stability. Understanding the extent of muscular atrophy post-MIDLF/CBT is vital for improving surgical outcomes, and potentially patient rehabilitation strategies. MATERIAL AND METHODS: This study retrospectively analysed preoperative and postoperative MRI scans of patients who underwent MIDLF/CBT for degenerative segmental spondylolisthesis. The bilateral width of the multifidus muscles at the operated segment and adjacent segments was measured using axial T2-weighted MRI scans. Statistical comparisons were made using a paired t test, with significance set at p < 0.05. RESULTS: The study included 16 patients with an average age of 57 ± 10 years, 10 of whom (62.5%) were women, and featured a mean follow-up period of 37 ± 25 months. Postoperative measurements showed a significant reduction in the width of the multifidus muscles at the operated segment (mean difference -3.3mm, p = 0.02) and the inferior adjacent segment (-7.4 mm, p < 0.01). A decrease in muscle width at the superior adjacent segment was also observed, although this was not statistically significant. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study concluded that MIDLF/CBT results in significant multifidus muscle atrophy at and below the operated segment, potentially impacting postoperative rehabilitation and recovery. These findings highlight the need for further research comparing MIDLF/CBT to other spinal stabilisation techniques. Additionally, incorporating functional electromyographic assessments of paraspinal muscles could provide deeper insights into the long-term consequences of spinal surgeries and helpdevelop new approaches and strategies to mitigate paravertebral muscles atrophy, thus enhancing patient outcomes.

• MeSH
• Lumbar Vertebrae * surgery   diagnostic imaging   MeSH
• Spinal Fusion * methods   MeSH
• Paraspinal Muscles * diagnostic imaging   pathology   MeSH
• Cortical Bone surgery   diagnostic imaging   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Pedicle Screws MeSH
• Postoperative Complications diagnostic imaging   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Spondylolisthesis * surgery   diagnostic imaging   MeSH
• Muscular Atrophy * etiology   diagnostic imaging   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

OBJECTIVE: Previous retrospective studies have reported vigabatrin-associated brain abnormalities on magnetic resonance imaging (VABAM), although clinical impact is unknown. We evaluated the association between vigabatrin and predefined brain magnetic resonance imaging (MRI) changes in a large homogenous tuberous sclerosis complex (TSC) cohort and assessed to what extent VABAM-related symptoms were reported in TSC infants. METHODS: The Dutch TSC Registry and the EPISTOP cohort provided retrospective and prospective data from 80 TSC patients treated with vigabatrin (VGB) before the age of 2 years and 23 TSC patients without VGB. Twenty-nine age-matched non-TSC epilepsy patients not receiving VGB were included as controls. VABAM, specified as T2/fluid-attenuated inversion recovery hyperintensity or diffusion restriction in predefined brain areas, were examined on brain MRI before, during, and after VGB, and once in the controls (at approximately age 2 years). Additionally, the presence of VABAM accompanying symptoms was evaluated. RESULTS: Prevalence of VABAM in VGB-treated TSC patients was 35.5%. VABAM-like abnormalities were observed in 13.5% of all patients without VGB. VGB was significantly associated with VABAM (risk ratio [RR] = 3.57, 95% confidence interval [CI] = 1.43-6.39), whereas TSC and refractory epilepsy were not. In all 13 VGB-treated patients with VABAM for whom posttreatment MRIs were available, VABAM entirely resolved after VGB discontinuation. The prevalence of symptoms was 11.7% in patients with VABAM or VABAM-like MRI abnormalities and 4.3% in those without, implicating no significant association (RR = 2.76, 95% CI = .68-8.77). SIGNIFICANCE: VABAM are common in VGB-treated TSC infants; however, VABAM-like abnormalities also occurred in children without either VGB or TSC. The cause of these MRI changes is unknown. Possible contributing factors are abnormal myelination, underlying etiology, recurrent seizures, and other antiseizure medication. Furthermore, the presence of VABAM (or VABAM-like abnormalities) did not appear to be associated with clinical symptoms. This study confirms that the well-known antiseizure effects of VGB outweigh the risk of VABAM and related symptoms.

• MeSH
• Anticonvulsants * adverse effects   therapeutic use   MeSH
• Cohort Studies MeSH
• Infant MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Brain * diagnostic imaging   drug effects   MeSH
• Child, Preschool MeSH
• Prospective Studies MeSH
• Registries MeSH
• Retrospective Studies MeSH
• Tuberous Sclerosis * diagnostic imaging   complications   MeSH
• Vigabatrin * therapeutic use   adverse effects   MeSH
• Check Tag
• Infant MeSH
• Humans MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

OBJECTIVE: Epilepsy surgery in the operculoinsular cortex is challenging due to the difficult delineation of the epileptogenic zone and the high risk of postoperative deficits. METHODS: Pre- and postsurgical data from 30 pediatric patients who underwent operculoinsular cortex surgery at the Motol Epilepsy Center Prague from 2010 to 2022 were analyzed. RESULTS: Focal cortical dysplasia (FCD; n = 15, 50%) was the predominant cause of epilepsy, followed by epilepsy-associated tumors (n = 5, 17%) and tuberous sclerosis complex (n = 2, 7%). In eight patients where FCD was the most likely etiology, the histology was negative. Seven patients (23%) displayed normal magnetic resonance imaging results. Seizures exhibited diverse semiology and propagation patterns (frontal, perisylvian, and temporal). The ictal and interictal electroencephalographic (EEG) findings were mostly extensive. Multimodal imaging and advanced postprocessing were frequently used. Stereo-EEG was used for localizing the epileptogenic zone and eloquent cortex in 23 patients (77%). Oblique electrodes were used as guides for better neurosurgeon orientation. The epileptogenic zone was in the dominant hemisphere in 16 patients. At the 2-year follow-up, 22 patients (73%) were completely seizure-free, and eight (27%) experienced a seizure frequency reduction of >50% (International League Against Epilepsy class 3 and 4). Fourteen patients (47%) underwent antiseizure medication tapering; treatment was completely withdrawn in two (7%). Nineteen patients (63%) remained seizure-free following the definitive outcome assessment (median = 6 years 5 months, range = 2 years to 13 years 5 months postsurgery). Six patients (20%) experienced corona radiata or basal ganglia ischemia; four (13%) improved to mild and one (3%) to moderate hemiparesis. Two patients (7%) operated on in the anterior insula along with frontotemporal resection experienced major complications: pontine ischemia and postoperative brain edema. SIGNIFICANCE: Epilepsy surgery in the operculoinsular cortex can lead to excellent patient outcomes. A comprehensive diagnostic approach is crucial for surgical success. Rehabilitation brings a great chance for significant recovery of postoperative deficits.

• MeSH
• Child MeSH
• Electroencephalography * MeSH
• Epilepsy surgery   diagnostic imaging   MeSH
• Cohort Studies MeSH
• Infant MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Malformations of Cortical Development surgery   complications   diagnostic imaging   MeSH
• Adolescent MeSH
• Cerebral Cortex diagnostic imaging   surgery   MeSH
• Neurosurgical Procedures methods   MeSH
• Child, Preschool MeSH
• Retrospective Studies MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Limited licensed medications are available for multiple sclerosis (MS) in pediatric patients. OBJECTIVE: To evaluate the efficacy, safety, and tolerability of alemtuzumab in pediatric patients with relapsing-remitting multiple sclerosis (RRMS) and disease activity on prior disease-modifying therapies (DMTs). METHODS: LemKids was a multicenter, multinational, single-arm, open-label, switch (from ongoing DMT to alemtuzumab treatment) study in pediatric RRMS patients (aged 10-<18 years), with disease activity on DMT. The primary endpoint was a comparison of the number of new/enlarging T2 lesions on the magnetic resonance imaging of the brain between the prior-DMT period and alemtuzumab treatment. RESULTS: This study was prematurely terminated due to low enrollment and an European Medicines Agency Article-20 pharmacovigilance review of alemtuzumab in adult RRMS. Of 46 screened patients, 16 were enrolled; 12 completed prior-DMT treatment period; 11 received alemtuzumab of whom 7 completed treatment. Patients on alemtuzumab developed fewer new/enlarging T2 lesions compared with prior-DMT (7 vs 178, relative risk (95% confidence interval): 0.04 (0.01-0.14)). No significant pharmacodynamic changes or safety concerns were noted in this limited dataset. CONCLUSION: Alemtuzumab treatment was associated with a low number of new/enlarging T2 lesions in pediatric patients with RRMS and was safe and well tolerated in seven patients during infusion and the initial 4 months.

• MeSH
• Alemtuzumab * adverse effects   MeSH
• Child MeSH
• Immunologic Factors * adverse effects   administration & dosage   MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Adolescent MeSH
• Multiple Sclerosis, Relapsing-Remitting * drug therapy   diagnostic imaging   MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

PURPOSE: MRI-only adaptive brachytherapy (MRI-ABT) is the state-of-the-art for treating locally advanced cervical cancer (LACC) in combination with concurrent chemoradiotherapy. We aimed to evaluate the pattern of pelvic recurrence after the treatment. MATERIAL AND METHODS: A total of one hundred LACC patients were treated between January 2017 and December 2023 with concurrent chemoradiotherapy of 45 Gy in 25 fractions ± boost to lymphadenopathy (up to a maximum dose of 60 Gy in 25 fractions) with concurrent weekly cisplatin chemotherapy at the dose of 40 mg/m2/week, and MR-ABT. RESULTS: At a median follow-up of 30.2 months, there were 2 local recurrences (2%) and 9 regional pelvic recurrences (9%). The median time to local/regional recurrence was 11 months (range 6-21). For all stages, the 3-year local control was 97.66%, and the 3-year pelvic control was 89.45%. Twenty-four patients died during follow-up; the 3-year overall survival was 75.11%, and the 3-year disease-free survival was 70.97%. CONCLUSION: MRI-ABT combined with external beam radiotherapy and concurrent chemotherapy for LACC demonstrates excellent local and regional pelvic control. Most local/regional recurrences occur inside or at the edge of the external-beam irradiated field. Recurrences inside the field of brachytherapy are rare. Distant recurrences are the predominant cause of death in LACC patients treated with definitive CRT and MRI-ABT.

• MeSH
• Brachytherapy * methods   MeSH
• Chemoradiotherapy * MeSH
• Cisplatin therapeutic use   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local * radiotherapy   MeSH
• Magnetic Resonance Imaging * MeSH
• Uterine Cervical Neoplasms * radiotherapy   diagnostic imaging   pathology   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Glucocorticoids are potent anti-inflammatory drugs, although their use is associated with severe side effects. Loading glucocorticoids into suitable nanocarriers can significantly reduce these undesirable effects. Macrophages play a crucial role in inflammation, making them strategic targets for glucocorticoid-loaded nanocarriers. The main objective of this study is to develop a glucocorticoid-loaded PLGA nanocarrier specifically targeting liver macrophages, thereby enabling the localized release of glucocorticoids at the site of inflammation. Dexamethasone acetate (DA)-loaded PLGA nanospheres designed for passive macrophage targeting are synthesized using the nanoprecipitation method. Two types of PLGA NSs in the size range of 100-300 nm are prepared, achieving a DA-loading efficiency of 19 %. Sustained DA release from nanospheres over 3 days is demonstrated. Flow cytometry analysis using murine bone marrow-derived macrophages demonstrates the efficient internalization of fluorescent dye-labeled PLGA nanospheres, particularly into pro-inflammatory macrophages. Significant down-regulation in pro-inflammatory cytokine genes mRNA is observed without apparent cytotoxicity after treatment with DA-loaded PLGA nanospheres. Subsequent experiments in mice confirm liver macrophage-specific nanospheres accumulation following intravenous administration using in vivo imaging, flow cytometry, and fluorescence microscopy. Taken together, the data show that the DA-loaded PLGA nanospheres are a promising drug-delivery system for the treatment of inflammatory liver diseases.

• MeSH
• Anti-Inflammatory Agents pharmacology   chemistry   MeSH
• Dexamethasone * pharmacology   chemistry   analogs & derivatives   MeSH
• Liver * drug effects   metabolism   MeSH
• Polylactic Acid-Polyglycolic Acid Copolymer * chemistry   MeSH
• Macrophages * drug effects   metabolism   MeSH
• Mice MeSH
• Nanospheres * chemistry   MeSH
• Drug Carriers chemistry   pharmacology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH