Search

Purpose: Raman spectroscopy (RS) is a promising method for brain tumor detection. Near-infrared autofluorescence (AF) acquired during RS provides additional useful information for tumor identification and was investigated in comparison with RS for delineating brain tumors in situ., Methods: Raman spectra were acquired together with AF in situ within the solid tumor and at the tumor border during routine brain tumor surgeries (218 spectra; glioma WHO II-III, n = 6; GBM, n = 10; metastases, n = 10; meningioma, n = 3). Tissue classification for tumor identification in situ was trained on ex vivo data (375 spectra; glioma/GBM patients, n = 20; metastases, n = 11; meningioma, n = 13; and epileptic hippocampi, n = 4)., Results: Both in situ and ex vivo data showed that AF intensity in brain tumors was lower than that in border regions and normal brain tissue. Moreover, a positive correlation was observed between the AF intensity and the intensity of the Raman band corresponding to lipids at 1437 cm - 1 , while a negative correlation was found with the intensity of the protein band at 1260 cm - 1 . The classification of in situ AF and RS datasets matched the surgeon's evaluation of tissue type, with correct rates of 0.83 and 0.84, respectively. Similar correct rates were achieved in comparison to histopathology of tissue biopsies resected in selected measurement positions (AF: 0.80, RS: 0.83)., Conclusions: Spectroscopy was successfully integrated into existing neurosurgical workflows, and in situ spectroscopic data could be classified based on ex vivo data. RS confirmed its ability to detect brain tumors, while AF emerged as a competitive method for intraoperative tumor delineation., Competing Interests: Declarations. Ethical approval: All procedures involving humans were performed in accordance with the Helsinki Declaration. The study was approved by the Ethics Commission of the TU Dresden (study n. EK 323,122,008 and EK 24012019). Mouse brains were obtained from the Heart Center Dresden. No animals were additionally killed in the sense of the 3R in animal protection, but brains from other experiments were used (study n. DD24-5131/338/26); brain explantation took place after regular mouse killing and had no influence on the planning or execution of animal experiments. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

In patients with cerebellar ataxia (CA), symptoms related to oculomotor dysfunction significantly affect quality of life (QoL). This study aimed to analyze the literature on patient-related outcome measures (PROMs) assessing QoL impacts of vestibular and cerebellar oculomotor abnormalities in patients with CA to identify the strengths and limitations of existing scales and highlight any areas of unmet need. A systematic review was conducted (Medline, Embase) of English-language original articles reporting on QoL measures in patients with vertigo, dizziness or CA. Pre-specified parameters were retrieved, including diseases studied, scales applied and conclusions drawn. Our search yielded 3671 articles of which 467 studies (n = 111,606 participants) were deemed relevant. The most frequently studied disease entities were (a) non-specific dizziness/gait imbalance (114 studies; 54,581 participants), (b) vestibular schwannomas (66; 15,360), and (c) vestibular disorders not further specified (66; 10,259). The Dizziness Handicap Inventory (DHI) was the most frequently used PROM to assess QoL (n = 91,851), followed by the Penn Acoustic Neuroma Quality-of-Life Scale (n = 12,027) and the Activities-Specific Balance Confidence Scale (n = 2'471). QoL-scores capturing symptoms related to oculomotor abnormalities in CA were rare, focused on visual impairments (e.g., National-Eye-Institute Visual Function Questionnaire, Oscillopsia Functional Impact, oscillopsia severity score) and were unvalidated. The DHI remains the most widely used and versatile scale for evaluating dizziness. A lack of well-established PROMs for assessing the impact of oculomotor-related symptoms on QoL in CA was noted, emphasizing the need for developing and validating a new QoL-score dedicated to the oculomotor domain for individuals with CA., (© 2024. The Author(s).)

Neurological disorders, including spinal cord injury, peripheral nerve injury, traumatic brain injury, and neurodegenerative diseases, pose significant challenges in terms of diagnosis, treatment, and understanding the underlying pathophysiological processes. Label-free multiphoton microscopy techniques, such as coherent Raman scattering, two-photon excited autofluorescence, and second and third harmonic generation microscopy, have emerged as powerful tools for visualizing nervous tissue with high resolution and without the need for exogenous labels. Coherent Raman scattering processes as well as third harmonic generation enable label-free visualization of myelin sheaths, while their combination with two-photon excited autofluorescence and second harmonic generation allows for a more comprehensive tissue visualization. They have shown promise in assessing the efficacy of therapeutic interventions and may have future applications in clinical diagnostics. In addition to multiphoton microscopy, vibrational spectroscopy methods such as infrared and Raman spectroscopy offer insights into the molecular signatures of injured nervous tissues and hold potential as diagnostic markers. This review summarizes the application of these label-free optical techniques in preclinical models and illustrates their potential in the diagnosis and treatment of neurological disorders with a special focus on injury, degeneration, and regeneration. Furthermore, it addresses current advancements and challenges for bridging the gap between research findings and their practical applications in a clinical setting., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2023.)

Purpose: Patient-derived cancer cell lines can be very useful to investigate genetic as well as epigenetic mechanisms of transformation and to test new drugs. In this multi-centric study, we performed genomic and transcriptomic characterization of a large set of patient-derived glioblastoma (GBM) stem-like cells (GSCs)., Methods: 94 (80 I surgery/14 II surgery) and 53 (42 I surgery/11 II surgery) GSCs lines underwent whole exome and trascriptome analysis, respectively., Results: Exome sequencing revealed TP53 as the main mutated gene (41/94 samples, 44%), followed by PTEN (33/94, 35%), RB1 (16/94, 17%) and NF1 (15/94, 16%), among other genes associated to brain tumors. One GSC sample bearing a BRAF p.V600E mutation showed sensitivity in vitro to a BRAF inhibitor. Gene Ontology and Reactome analysis uncovered several biological processes mostly associated to gliogenesis and glial cell differentiation, S - adenosylmethionine metabolic process, mismatch repair and methylation. Comparison of I and II surgery samples disclosed a similar distribution of mutated genes, with an overrepresentation of mutations in mismatch repair, cell cycle, p53 and methylation pathways in I surgery samples, and of mutations in receptor tyrosine kinase and MAPK signaling pathways in II surgery samples. Unsupervised hierarchical clustering of RNA-seq data produced 3 clusters characterized by distinctive sets of up-regulated genes and signaling pathways., Conclusion: The availability of a large set of fully molecularly characterized GCSs represents a valuable public resource to support the advancement of precision oncology for the treatment of GBM., (© 2023. The Author(s).)

Purpose: Infrared (IR) spectroscopy has the potential for tumor delineation in neurosurgery. Previous research showed that IR spectra of brain tumors are generally characterized by reduced lipid-related and increased protein-related bands. Therefore, we propose the exploitation of these common spectral changes for brain tumor recognition., Methods: Attenuated total reflection IR spectroscopy was performed on fresh specimens of 790 patients within minutes after resection. Using principal component analysis and linear discriminant analysis, a classification model was developed on a subset of glioblastoma (n = 135) and non-neoplastic brain (n = 27) specimens, and then applied to classify the IR spectra of several types of brain tumors., Results: The model correctly classified 82% (517/628) of specimens as "tumor" or "non-tumor", respectively. While the sensitivity was limited for infiltrative glioma, this approach recognized GBM (86%), other types of primary brain tumors (92%) and brain metastases (92%) with high accuracy and all non-tumor samples were correctly identified., Conclusion: The concept of differentiation of brain tumors from non-tumor brain based on a common spectroscopic tumor signature will accelerate clinical translation of infrared spectroscopy and related technologies. The surgeon could use a single instrument to detect a variety of brain tumor types intraoperatively in future clinical settings. Our data suggests that this would be associated with some risk of missing infiltrative regions or tumors, but not with the risk of removing non-tumor brain., (© 2022. The Author(s).)

The occurrence of asymptomatic bacteriuria concomitant to urolithiasis is an issue for patients undergoing renal stone treatment. Disposing of a preoperative urine culture is essential to reduce the risk of septic events. The endpoint of the study is to report which characteristics of candidates for renal stone treatment are frequently associated with positive urine culture. 2605 patients were retrospectively enrolled from 14 centers; inclusion criteria were age > 18 and presence of a single renal stone 1-2 cm in size. The variables collected included age, gender, previous renal surgery, comorbidities, skin-to-stone distance, stone size, location, density, presence of hydronephrosis. After a descriptive analysis, the association between continuous and categorical variables and the presence of positive urine culture was assessed using a logistic regression model. Overall, 240/2605 patients (9%) had preoperative bacteriuria. Positive urine culture was more frequent in females, patients with previous renal interventions, chronic kidney disease, congenital anomalies, larger stones, increased density. Multivariate analysis demonstrated that previous renal interventions (OR 2.6; 95% CI 1.9-3.4; p < 0.001), renal-related comorbidities (OR 1.31; 95% CI 1.19-1.4; p < 0.001), higher stone size (OR 1.06; 95% CI 1.02-1.1; p = 0.01) and density (OR 1.00; 95% CI 1.0-1.00; p = 0.02) were associated with bacteriuria; male gender and lower caliceal location were inversely related to it. Beyond expected risk factors, such as female gender, other parameters are seemingly favoring the presence of positive urine culture. The awareness of variables associated with bacteriuria allows to assess which individuals are at increased risk of presenting bacteriuria and reduce the rate of septic complications., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Mutations in the isocytrate dehydrogenase 1 (IDH1) gene are early genetic events in glioma pathogenesis and cause profound metabolic changes. Because this genotype is found in virtually every tumor cell, therapies targeting mutant IDH1 protein are being developed. The intraoperative administration of those therapies would require fast technologies for the determination of IDH1 genotype. As of today, there is no such diagnostic test available. Recently, infrared spectroscopy was shown to bridge this gap. Here, we tested Raman spectroscopy for analysis of IDH1 genotype in glioma, which constitutes an alternative contact-free technique with the potential of being applicable in situ., Methods: Human glioma samples (n = 36) were obtained during surgery and cryosections were prepared. IDH1 mutations were assessed using DNA sequencing and 100 Raman spectra were obtained for each sample., Results: Analysis of Raman spectra revealed increased intensities in spectral bands related to DNA in IDH1 mutant glioma while bands assigned to molecular vibrations of lipids were significantly decreased. Moreover, intensities of Raman bands assigned to proteins differed in IDH1 mutant and IDH1 wild-type glioma, suggesting alterations in the protein profile. The selection of five bands (498, 826, 1003, 1174 and 1337 cm -1 ) allowed the classification of Raman spectra according to IDH1 genotype with a correct rate of 89%., Conclusion: Raman spectroscopy constitutes a simple, rapid and safe procedure for determination of the IDH1 mutation that shows great promise for clinically relevant in situ diagnostics.

Background: Spinal cord injury (SCI) and the consecutive devastating neurological sequelae have an enormous individual and economic impact. Implantation of functionalized hydrogels is a promising approach, because they can serve as a matrix for the regenerating tissue, carry and release bioactive molecules and various cell types. We already demonstrated that non-functionalized soft alginate hydrogel supported axonal outgrowth and protected neurons against oxidative stress in vitro. Here, we investigated the effects of such soft alginate hydrogels on locomotor recovery in small and large spinal cord lesions., Method: Hemimyelonectomy of 2 mm or 4 mm length was performed in rats and soft alginate hydrogel was implanted. Functional recovery of the hindlimbs was assessed in the open field [Batto Beattie Bresnahan (BBB) score] and using swimming test [Louisville Swim score (LSS)] for 140 days post injury (DPI). Reference histology was performed., Results: Rats that received an alginate implant into 2 mm spinal cord lesions demonstrated significantly improved locomotor recovery compared to controls detectable already at 10 DPI. At 140 DPI, they reached higher LSS and BBB scores in swimming and open field tests, respectively. However, this beneficial effect of alginate was lacking in animals with larger (4 mm) lesions. Histological examination suggested that fibrous scarring in the spinal cord was reduced after alginate implantation in comparison to controls., Conclusions: Implantation of soft alginate hydrogel in small spinal cord lesions improved functional recovery. Possible underlying mechanisms include the mechanical stabilization of the wound, reduction of secondary damage and inhibition of fibrous scarring.

Background: Surgeons of today are faced with unprecedented challenges; necessitating a novel approach to pre-operative preparation which takes into account the specific tests each case poses. In this study, we examine patient-specific mental rehearsal for pre-surgical practice and assess whether this method has an additional effect when compared to generic mental rehearsal., Methods: Sixteen medical students were trained how to perform a simulated laparoscopic cholecystectomy (SLC). After baseline assessments, they were randomised to two equal groups and asked to complete three SLCs involving different anatomical variants. Prior to each procedure, Group A practiced mental rehearsal with the use of a pre-prepared checklist and Group B mental rehearsal with the checklist combined with virtual models matching the anatomical variations of the SLCs. The performance of the two groups was compared using simulator provided metrics and competency assessment tool (CAT) scoring by two blinded assessors., Results: The participants performed equally well when presented with a "straight-forward" anatomy [Group A vs. Group B-time sec: 445.5 vs. 496 p = 0.64-NOM: 437 vs. 413 p = 0.88-PL cm: 1317 vs. 1059 p = 0.32-per: 0.5 vs. 0 p = 0.22-NCB: 0 vs. 0 p = 0.71-DVS: 0 vs. 0 p = 0.2]; however, Group B performed significantly better [Group A vs. B Total CAT score-Short Cystic Duct (SCD): 20.5 vs. 26.31 p = 0.02 η 2  = 0.32-Double cystic Artery (DA): 24.75 vs. 30.5 p = 0.03 η 2  = 0.28] and committed less errors (Damage to Vital Structures-DVS, SCD: 4 vs. 0 p = 0.03 η 2 =0.34, DA: 0 vs. 1 p = 0.02 η 2 = 0.22). in the cases with more challenging anatomies., Conclusion: These results suggest that patient-specific preparation with the combination of anatomical models and mental rehearsal may increase operative quality of complex procedures.

Purpose: Stereotactic biopsy has improved prostate cancer detection. Although the new approach is superior, standard procedure is still useful in a cohort of patients in whom MRI is not available. The standard saturation biopsy technique is still debatable. We describe our technique and analyze its outcomes., Materials and Methods: One hundred twenty-five patients underwent saturation biopsy through a single transperineal access. Mean age was 64.73 year, mean PSA was 9.49 ng/ml, mean PSA density was 0.184, and mean prostate volume was 57.95 g. All patients underwent at least one previous prostatic biopsy: 24.8% of cases had diagnosis of atypical small acinar proliferation, 39.2% of cases had multifocal high-grade prostatic intraepithelial neoplasia, and 36% of cases had inflammation or benign prostatic hyperplasia., Results: The detection rate was 38.4%. Prostate cancer occurred in 61.3% of patients with previous ASAP (p < 0.007). Cancer detection rate decreased with increasing number of previous biopsy and with increasing prostate volume (p < 0.001) and increased with increasing PSA density (p = 0.03). No major complications were reported., Conclusion: The traditional saturation biopsy may be useful when targeted biopsy cannot be used. Our technique is accurate for cancer detection. It can offer some advantages in comparison with other approaches.

Background: The role of laparoscopy in the setting of perforated appendicitis remains controversial. A retrospective study was conducted to evaluate the early postoperative outcomes of laparoscopic appendectomy (LA) compared to open appendectomy (OA) in patients with perforated appendicitis., Methods: A total of 1,032 patients required an appendectomy between January 2005 and December 2009. Among these patients, 169 presented with perforated appendicitis. Operation times, length of hospital stay, overall complication rates within 30 days, and surgical site infection (SSI) rates were analyzed., Results: Out of the 169 evaluated patients, 106 required LA and 63 OA. Although operation times were similar in both groups (92 ± 31 min for LA vs. 98 ± 45 for OA, p = 0.338), length of hospital stay was shorter in the LA group (6.9 ± 3.8 days vs. 11.5 ± 9.2, p < 0.001). Overall complication rates were significantly lower in the LA group (32.1 vs. 52.4 %, p < 0.001), as were incisional SSI (1.9 vs. 22.2 %, p < 0.001). Organ/space SSI rates were similar in both groups (23.6 % after LA vs. 20.6 % after OA, p = 0.657)., Conclusions: For perforated appendicitis, LA results in a significantly shorter hospital stay, fewer overall postoperative complications, and fewer wound infections compared to OA. Organ/space SSI rates were similar for both procedures. LA provides a safe option for treating patients with perforated appendicitis.

The mammalian target of rapamycin (mTOR) pathway is a central controller of growth and homeostasis, and, as such, is implicated in disease states where growth is deregulated, namely cancer, metabolic diseases, and hamartoma syndromes like tuberous sclerosis complex (TSC). Accordingly, mTOR is also a pivotal regulator of the homeostasis of several distinct stem cell pools in which it finely tunes the balance between stem cell self-renewal and differentiation. mTOR hyperactivation in neural stem cells (NSCs) has been etiologically linked to the development of TSC-associated neurological lesions, such as brain hamartomas and benign tumors. Animal models generated by deletion of mTOR upstream regulators in different types of NSCs reproduce faithfully some of the TSC neurological alterations. Thus, mTOR dysregulation in NSCs seems to be responsible for the derangement of their homeostasis, thus leading to TSC development. Here we review recent advances in the molecular dissection of the mTOR cascade, its involvement in the maintenance of stem cell compartments, and in particular the implications of mTOR hyperactivation in NSCs in vivo and in vitro.

The soluble mesothelin-related peptide (SMRP), a candidate marker for screening of subjects with asbestos exposure, is influenced by some individual and clinical factors. The aim of this study was to quantify the role of age, smoking, weight, presence of diseases and exposure to asbestos on serum SMRP levels in a large series of subjects exposed to asbestos, possible candidates for mesothelioma screening. One thousand seven hundred and four participants underwent clinical examination and were interviewed on medical anamnesis, occupation, smoking and weight. SMRP was measured by an ELISA assay. Overall, median SMRP was 0.4 (IQR 25-75: 0.3-0.7) nmol/l. It was higher in current smokers and in subjects with a cumulative asbestos exposure >50 ff/cc/years than in all the other subjects (p < 0.001 and p = 0.002, respectively). SMRP was positively correlated with age (ρ = 0.11, p < 0.001) and, inversely, with BMI (ρ = -0.15, p < 0.001). SMRP was lower in healthy subjects (n = 1,217: median 0.4 nmol/l) than in subjects with malignant tumors (n = 118: 0.5 nmol/l; p = 0.01), asbestos-related pleural lesions (plaques or thickenings, n = 152: 0.6 nmol/l; p < 0.001) and other benign diseases (n = 182: 0.5 nmol/l; p = 0.04). Multivariate analysis revealed significant predictors of increased SMRP: age >57 years, current smoking, a positive anamnesis for cancer and for asbestos-related pleural lesions, and BMI < 25. Some clinical and demographic variables are associated with serum SMRP levels. The degree of these associations is low, nevertheless they should be accounted for in the interpretation of SMPR as a candidate marker predictive of mesothelioma. The potential predictive value of serum SMRP in screening/surveillance programs must be validated in prospective studies.

The objective was to investigate the effects of a 3- week weight-management program including moderate energy restriction and exercise training at 2 intensities [low intensity (LI): 40% and high intensity (HI): 70% maximal oxygen uptake (V'O(2)max)] on body composition, energy expenditure, and fat oxidation rate in severely obese adolescents. Twenty obese adolescents, aged 15-17 yr (body mass index: 37.5 kg/m(2); 38.2% fat mass) participated in this study. Before starting (week 0, W0) and at the end of the weight-management period (week 3,W3), body composition was assessed by a multifrequency tetrapolar impedancemeter; basal metabolic rate (BMR), energy expenditure, and substrate oxidation rate during exercise and post-exercise recovery by indirect calorimetry. At W3, body mass and fat mass decreased significantly (p<0.005) in all groups, and the decreases were significantly greater in the LI than in the HI group (-8.1±1.6 vs -5.9±1.6 kg and -4.2±1.9 vs -2.3±1.7 kg, p<0.05, respectively). Predicted V'O(2)max, expressed in relative values, changed significantly only in the HI group by +0.010±0.006 l/(kg fat-free mass × min) (p=0.010). By contrast, no significant changes were observed at W3 in BMR, energy expenditure, and substrate oxidation rate during exercise and post-exercise recovery. In conclusion, LI (40% of V'O(2)max) physical activity favors fat oxidation and it seems advisable to encourage obese adolescents to perform LI physical activity which is more feasible and acceptable than intense exercise.

In order to assess the energy cost of cycling and aerobic capacity in juvenile obesity, responses to cycle ergometer exercise were studied in 10 pubertal obese (OB) [body mass index (BMI) SD score (SDS): 3.40+/-0.58 SD] adolescent girls (age: 16.0+/-1.2 yr) and in 10 normal-weight (NW, BMI SDS: -0.30+/-0.54) girls of the same age (15.1+/-1.9). To this aim, gas exchange, heart rate (HR), and energy expenditure (EE) were studied during graded cycle ergometer test at 40, 60, 80, 100, and 120 W. The energy cost of cycling was higher in OB, being oxygen uptake (VO2) higher (about 20%) in OB than in NW girls at all workloads (p<0.01-0.001). Estimated maximal VO2 and VO2 at anaerobic threshold were significantly (p<0.05) higher in OB girls [although lower per unit body mass (p<0.01) and similar for unit fat-free mass], and explained the higher oxygen pulse and lower HR for any EE observed during submaximal exercise in OB. While net mechanical efficiency (ME) was significantly lower in OB (p<0.01), delta ME was similar in both groups, indicating no substantial derangement of muscle intrinsic efficiency. It is concluded that, despite a higher cost of cycling, OB girls can rely on a larger aerobic capacity which makes them able to sustain this kind of exercise within a wide range of work loads, with relevant implications when planning protocols of physical activity in the context of interventions for the reduction of juvenile obesity.

The physical activity ratio (PAR) values are commonly used to convert subjects' physical activity recalls into estimates of daily energy expenditure (DEE). A PAR is defined as the ratio between energy expenditure corresponding to a sedentary or a physical activity (kJ/min) and basal metabolic rate [(BMR) kJ/min]. The objective of the present study was to determine the PAR for different sedentary and physical activities in obese adolescents. Thirty-three obese adolescents [mean body mass index: 35.1 kg/m2; 40.3 % fat mass] aged 11 to 17 yr participated in this study. BMR was assessed by indirect calorimetry after an overnight fast by means of an open-circuit, indirect computerised calorimetry with a rigid, transparent, ventilated canopy. Energy expenditures corresponding to various sedentary and physical activities in free-living conditions were determined using a portable metabolic unit, and body composition by bioelectrical impedance analysis (BIA). The PAR of each activity was obtained by dividing the assessed energy expenditure by BMR. In this study, the PAR of various sedentary and physical activities did not vary significantly with sex, age, and body mass. Thus, the data for boys and girls were combined and the PAR for 27 sedentary and physical activities were determined. The PAR values can be applied to determine the mean DEE (kJ) using the specific equation considering BMR (kJ/min), PAR, and duration (min) of each activity performed by the subject during the 24 h. This information will be useful to health-care professionals because estimation of DEE in obese adolescents is necessary in order to prescribe an adequate dietary therapy to induce a desired level of energy deficit.

Osmotic agents are still the most common treatment for controlling intracranial hypertension (ICH). Mannitol, glycerol, sorbitol, and hypertonic serum saline are the agents currently available. This work was designed to compare mannitol and glycerol in a similar population of brain injured patients, randomly divided into two groups of eight. The following mean day parameters were obtained: number of infusions, hydric balance, mean arterial pressure (MAP), and intracranial pressure (ICP). Cerebral perfusion pressure (CPP) was calculated. Brain computed tomographies (CT) were obtained on arrival, at follow-up whenever justified and at discharge. For comparison of both groups a modified therapeutic intensity level (mTIL) was used. Both agents induced a statistically equally effective decrease on ICP and increase on CPP evaluated at one and two hours post infusion but the mean day mTIL showed a statistically significant difference in favour of glycerol. The possible explanations of this difference are discussed. According to our results mannitol would be most indicated as a bolus to control sudden rises in ICP whereas glycerol would be most indicated as a basal treatment.