The rates of non-adiabatic processes in large molecular systems: Toward an effective full-dimensional quantum mechanical approach.

Two computational approaches for computing the rates of internal conversions in molecular systems where a large set of nuclear degrees of freedom plays a role are discussed and compared. One approach is based on the numerical solution of the time-dependent Schrödinger equation and allows us to include almost the whole set of vibrational coordinates, thanks to the employment of effective procedures for selecting those elements of the Hilbert space which play a significant role in dynamics. The other approach, based on the time-dependent perturbation theory and limited to the use of the harmonic approximation, allows us to include the whole Hilbert space spanned by the vibrational states of the system. The two approaches are applied to the photophysics of azulene, whose anti-Kasha behavior caused by anomalous internal conversion rates is well assessed. The calculated rates for the decays of the first two excited singlet states are in very good agreement with experimental data, indicating the reliability of both methodologies.

The "state of the art" of intraoperative neurophysiological monitoring: An Italian neurosurgical survey.

Introduction: Intraoperative Neurophysiological Monitoring (IOM) is widely used in neurosurgery but specific guidelines are lacking. Therefore, we can assume differences in IOM application between Neurosurgical centers. Research question: The section of Functional Neurosurgery of the Italian Society of Neurosurgery realized a survey aiming to obtain general data on the current practice of IOM in Italy. Materials and methods: A 22-item questionnaire was designed focusing on: volume procedures, indications, awake surgery, experience, organization and equipe. The questionnaire has been sent to Italian Neurosurgery centers. Results: A total of 54 centers completed the survey. The annual volume of surgeries range from 300 to 2000, and IOM is used in 10-20% of the procedures. In 46% of the cases is a neurologist or a neurophysiologist who performs IOM. For supra-tentorial pathology, almost all perform MEPs (94%) SSEPs (89%), direct cortical stimulation (85%). All centers perform IOM in spinal surgery and 95% in posterior fossa surgery. Among the 50% that perform peripheral nerve surgery, all use IOM. Awake surgery is performed by 70% of centers. The neurosurgeon is the only responsible for IOM in 35% of centers. In 83% of cases IOM implementation is adequate to the request. Discussion and conclusions: The Italian Neurosurgical centers perform IOM with high level of specialization, but differences exist in organization, techniques, and expertise. Our survey provides a snapshot of the state of the art in Italy and it could be a starting point to implement a consensus on the practice of IOM.

Shedding light on thermally-activated delayed fluorescence.

Thermally activated delayed fluorescence (TADF) is a hot research topic in view of its impressive applications in a wide variety of fields from organic LEDs to photodynamic therapy and metal-free photocatalysis. TADF is a rare and fragile phenomenon that requires a delicate equilibrium between tiny singlet-triplet gaps, sizable spin-orbit couplings, conformational flexibility and a balanced contribution of charge transfer and local excited states. To make the picture more complex, this precarious equilibrium is non-trivially affected by the interaction of the TADF dye with its local environment. The concurrent optimization of the dye and of the embedding medium is therefore of paramount importance to boost practical applications of TADF. Towards this aim, refined theoretical and computational approaches must be cleverly exploited, paying attention to the reliability of adopted approximations. In this perspective, we will address some of the most important issues in the field. Specifically, we will critically review theoretical and computational approaches to TADF rates, highlighting the limits of widespread approaches. Environmental effects on the TADF photophysics are discussed in detail, focusing on the major role played by dielectric and conformational disorder in liquid solutions and amorphous matrices.

Comprehensive geriatric assessment predicts listing for kidney transplant in patients with end-stage renal disease: a retrospective cohort study.

BACKGROUND: Comprehensive geriatric assessment (CGA) involves a formal broad approach to assess frailty and creating a plan for management. However, the impact of CGA and its components on listing for kidney transplant in older adults has not been investigated. METHODS: We performed a single-center retrospective study of patients with end-stage renal disease who underwent CGA during kidney transplant candidacy evaluation between 2017 and 2021. All patients ≥ 65 years old and those under 65 with any team member concern for frailty were referred for CGA, which included measurements of healthcare utilization, comorbidities, social support, short physical performance battery, Montreal Cognitive Assessment (MoCA), and Physical Frailty Phenotype (FPP), and estimate of surgical risk by the geriatrician. RESULTS: Two hundred and thirty patients underwent baseline CGA evaluation; 58.7% (135) had high CGA ("Excellent" or "Good" rating for transplant candidacy) and 41.3% (95) had low CGA ratings ("Borderline," "Fair," or "Poor"). High CGA rating (OR 8.46; p < 0.05), greater number of CGA visits (OR 4.93; p = 0.05), younger age (OR 0.88; p < 0.05), higher MoCA scores (OR 1.17; p < 0.05), and high physical activity (OR 4.41; p < 0.05) were all associated with listing on transplant waitlist. CONCLUSIONS: The CGA is a useful, comprehensive tool to help select older adults for kidney transplantation. Further study is needed to better understand the predictive value of CGA in predicting post-operative outcomes.

Deep brain stimulation of globus pallidus internus and subthalamic nucleus in Parkinson's disease: a multicenter, retrospective study of efficacy and safety.

BACKGROUND: Deep brain stimulation (DBS) is an established therapeutic option in advanced Parkinson's disease (PD). Literature data and recent guidelines remain inconclusive about the best choice as a target between the subthalamic nucleus (STN) and the globus pallidus internus (GPi). MATERIALS AND METHODS: We retrospectively reviewed the clinical efficacy outcomes of 48 DBS-implanted patients (33 STN-DBS and 15 GPi-DBS) at a short- (<1 year from the surgery) and long-term (2-5 years) follow-up. Also, clinical safety outcomes, including postoperative surgical complications and severe side effects, were collected. RESULTS: We found no difference between STN-DBS and GPi-DBS in improving motor symptoms at short-term evaluation. However, STN-DBS achieved a more prominent reduction in oral therapy (L-DOPA equivalent daily dose, P = .02). By contrast, GPi-DBS was superior in ameliorating motor fluctuations and dyskinesia (MDS-UPDRS IV, P < .001) as well as motor experiences of daily living (MDS-UPDRS II, P = .03). The greater efficacy of GPi-DBS on motor fluctuations and experiences of daily living was also present at the long-term follow-up. We observed five serious adverse events, including two suicides, all among STN-DBS patients. CONCLUSION: Both STN-DBS and GPi-DBS are effective in improving motor symptoms severity and complications, but GPi-DBS has a greater impact on motor fluctuations and motor experiences of daily living. These results suggest that the two targets should be considered equivalent in motor efficacy, with GPi-DBS as a valuable option in patients with prominent motor complications. The occurrence of suicides in STN-treated patients claims further attention in target selection.

Role of Vagus Nerve Stimulation in Refractory and Super Refractory Status Epilepticus: A Pediatric Case Series.

BACKGROUND: Status epilepticus is a life-threatening condition that is defined as refractory (RSE) when the seizure activity continues despite treatment with benzodiazepine and a second appropriate treatment. Super refractory status epilepticus (SRSE) is an RSE that persists or recurs for ≥24 h. Few papers have reported the outcomes of pediatric patients affected by RSE and SRSE and treated with neuromodulation therapies. Vagus nerve stimulation (VNS) is an approved treatment for drug-resistant epilepsy. We present our findings of pediatric patients treated with VNS for RSE/SRSE. METHODS: We present a case series of seven consecutive pediatric patients treated with VNS for SRSE since 2012 by a single surgeon in Monza and Padua. A rapid titration was started soon after implantation. We considered electroclinical data before and after VNS implantation and at the last follow-up. RESULTS: We achieved the resolution of SRSE in five out of seven patients in a mean time of two weeks. At the last follow-up, these patients had a significant reduction of seizure burden without any relapse of SE. DISCUSSION AND CONCLUSIONS: Based on our limited findings, we discuss the potential role of VNS therapy in similar but distinct clinical contexts. For patients with drug-resistant epilepsy and RSE/SRSE, prompt VNS consideration is suggested, offering rapid responses and potentially reducing pharmacological load. Meanwhile, in NORSE/FIRES, we suggest early neuromodulation during the acute phase if standard treatments prove ineffective or not tolerated. This approach may leverage VNS's potential anti-inflammatory effects and neuromodulation, enhancing patient-specific treatments. Expanding case studies and prolonged follow-ups are recommended to strengthen these clinical insights.

Thalamopeduncular Tumors in Pediatric Age: Advanced Preoperative Imaging to Define Safe Surgical Planning: A Multicentric Experience.

Background: Thalamopeduncular tumors are challenging lesions arising at the junction between the thalamus and the cerebral peduncle. They represent 1-5% of pediatric brain tumors, are mainly pilocytic astrocytoma and occur within the first two decades of life. To date, the optimal treatment remains unclear. Methods: We retrospectively reviewed pediatric patients who underwent surgery for thalamopeduncular tumors in the Academic Pediatric Neurosurgery Unit of Padova and Verona from 2005 to 2022. We collected information on age, sex, symptoms, preoperative and postoperative neuroradiological studies, histological specimens, surgical approaches, and follow-up. Results: We identified eight patients with a mean age of 9 years. All lesions were pilocytic astrocytoma. The main symptoms were spastic hemiparesis, cranial nerve palsy, headache, and ataxia. The corticospinal tract was studied in all patients using diffusion-tensor imaging brain MRI and in two patients using navigated transcranial magnetic stimulation. The transsylvian approach was the most frequently used. A gross total resection was achieved in two patients, a subtotal resection in five and a partial resection in one. In three patients, a second treatment was performed due to the regrowth of the tumor, performing an additional surgery in two cases and a second-look surgery followed by adjuvant therapy in one. After the surgery, four patients maintained stability in their postoperative neurological exam, two patients improved, and two worsened but in one of them, an improvement during recovery occurred. At the last follow-up available, three patients were disease-free, four had a stable tumor residual, and only one patient died from the progression of the disease. Conclusions: Advanced preoperative tools allow one to define a safe surgical strategy. Due to the indolent behavior of thalamopeduncular tumors, surgery should be encouraged.

Aesthetic transaxillary subpectoral placement of vagus nerve stimulator in children and young adults: A technical note.

INTRODUCTION: Vagus nerve stimulation (VNS) is a neuromodulation therapy for drug-resistant epilepsy (DRE), refractory status epilepticus, and treatment-resistant depression. The lead is tunneled into the subcutaneous space and connected to the generator, which is usually implanted in a subcutaneous pocket below the clavicle. Surgical complications in the chest region include skin breakdown or infection. An alternative approach is to perform a subclavear subpectoral implantation. In our surgical series, we report a new aesthetic implantation method for VNS generators in children and young patients: the transaxillary subpectoral placement. MATERIALS AND METHODS: From May 2021 to May 2023, 10 vagus nerve stimulation generators were placed subpectorally with a transaxillary approach by the authors. We considered operative time, surgical complications such as blood loss, infections, device migration, pain, and adverse events at follow-up. RESULTS: In this surgical series, we reviewed all cases of subpectoral implantation of VNS generators in children and young adults at our institution in the last 2 years. All patients were treated with subpectoral Sentiva 1000 (Livanova PLC) insertion with axillary access by a neurosurgeon and a pediatric surgeon. The operative time was slightly longer compared to the traditional subcutaneous implant. All generators reported impedances within the optimal range. Blood loss was not significant and no other perioperative complications were reported. Patients and families were highly satisfied with the outcomes in terms of comfort and aesthetic results after surgery and at the last follow-up. No cases of infection occurred, and no malfunctions or displacements of the generator were registered at clinical follow-up. CONCLUSION: The transaxillary subpectoral placement of theVNS generator is an aesthetic and anatomic approach, which provides several benefits to children and young adults.

Technology-assisted behavioral intervention to encourage prehabilitation in frail older adults undergoing surgery: Development and design of the BeFitMe™ Apple Watch app.

Objective: Increasing the physical activity of frail, older patients before surgery through prehabilitation (prehab) can hasten return to autonomy and reduce complications postoperatively. However, prehab participation is low in the clinical setting. In this study, we re-design an existing prehab smartphone application (BeFitMe™) using a novel standalone Apple Watch platform to increase accessibility and usability for vulnerable patients. Methods: Design Science Research Methodology was used to (1) develop an approach to clinical research using standalone Apple Watches, (2) re-design BeFitMe™ for the Apple Watch platform, and (3) incorporate user feedback into app design. In phase 3, beta and user testers gave feedback via a follow-up phone call. Exercise data was extracted from the watch after testing. Descriptive statistics were used to summarize accessibility and usability. Results: BeFitMe™ was redesigned for the Apple Watch with full functionality without requiring patients to have an iPhone or internet connectivity and the ability to passively collect exercise data without patient interaction. Three study staff participated in beta testing over 3 weeks. Six randomly chosen thoracic surgery patients participated in user testing over 12 weeks. Feedback from beta and user testers was addressed with updated software (versions 1.0-1.10), improved interface and notification schemes, and the development of educational materials used during enrollment. The majority of users (5/6, 83%) participated by responding to at least one notification and data was able to be collected for 54/82 (68%) of the days users had the watches. The amount of data collected in BeFitMe™ Watch app increased from 2/11 (16%) days with the first patient tester to 13/13 (100%) days with the final patient tester. Conclusions: The BeFitMe™ Watch app is accessible and usable. The BeFitMe™ Watch app may help older patients, particularly those from vulnerable backgrounds with fewer resources, participate in prehab prior to surgery.

Ultrasound-Guided Needle Biopsy as an Alternative to Chamberlain's Mediastinotomy and Video-Assisted Thoracoscopic Surgery (VATS) in the Diagnosis of Anterior Mediastinal Neoformations: A Retrospective Analysis.

(1) Background: The prompt diagnosis of anterior mediastinal lesions is a challenge due to their often being categorized as malignant tumours. Ultrasound-guided Transthoracic Core Needle Biopsy (US-TCNB) is an innovative technique that is arousing increasing interest in clinical practice. However, studies in this area are still scarce. This study aims to compare the diagnostic accuracy and complication rate of US-TCNB with those of traditional surgical methods-Anterior Mediastinotomy and Video Assisted Thoracoscopic Surgery (VATS)-in patients with anterior mediastinal lesions. (2) Methods: This retrospective study involved patients evaluated between January 2011 and December 2021 who had undergone US-TCNB at the Interdepartmental Unit of Internal and Interventional Ultrasound, Molinette Hospital, Città della Salute e della Scienza, Turin, Italy. Personal data, diagnostic questions, and technical information concerning the bioptic procedure, periprocedural complications and histological reports were collected. (3) Results: Eighty-three patients were included in the analysis. Histological examination was performed in 78 cases, with an overall diagnostic accuracy of 94.0% (sensitivity 94%; specificity 100%). Only in 5 patients was a diagnosis not achieved. Complications occurred in 2 patients who were quickly identified and properly treated without need of hospitalization. The accuracy of US-TCNB was comparable to the performance of the main traditional diagnostic alternatives (95.3% for anterior mediastinotomy, and 98.4% for VATS), with a much lower complication rate (2.4% vs. 3-16%). The outpatient setting offered the additional advantage of saving resources. (4) Conclusions: a US-guided needle biopsy can be considered effective and safe, and in the near future it may become the procedure of choice for diagnosing anterior mediastinal lesions in selected patients.

Navigated Transcranial Magnetic Stimulation Motor Mapping and Diffusion Tensor Imaging Tractography for Diencephalic Tumor in Pediatric Patients.

Background. In deep-seated brain tumors, adequate preoperative planning is mandatory to assess the best surgical corridor to obtain maximal safe resection. Functional diffusor tensor imaging (DTI) tractography based on navigated transcranial magnetic stimulation (nTMS) motor mapping has proven to be a valid preoperative examination method in adults. The aim of this paper is to present the application of nTMS and functional DTI tractography in a series of pediatric diencephalic tumors. Material and methods. Three patients affected by thalamic (one) and thalamopeduncular tumor (two) were successfully examined with nTMS motor mapping and DTI tractography between October 2020 and October 2021 (F:M 3:0, mean age 12 years ± 0.8). Cortical representation of leg, hand and mouth were determined in the affected hemisphere and the positive stimulation spots were set as seeds point for tractography. Results. Mapping of the motor cortex and tracts reconstruction for leg and hand were successful in all patients, while facial function was properly mapped in one patient only. In all cases, the procedure was well tolerated and no adverse events were recorded. Spatial relationships between tumor and functional tissue guided the surgical planning. Extent of the resection varied from 96.1% to 100% with a postoperative new motor deficit in one patient. Conclusions. nTMS and DTI fiber tracking is a feasible, effective and well-tolerated method to identify motor pathway in deep-seated lesion in pediatric population.

Selective Stimulus Intensity during Hotspot Search Ensures Faster and More Accurate Preoperative Motor Mapping with nTMS.

INTRODUCTION: Navigated transcranial magnetic stimulation (nTMS) has emerged as one of the most innovative techniques in neurosurgical practice. However, nTMS motor mapping involves rigorous steps, and the importance of an accurate execution method has not been emphasized enough. In particular, despite strict adherence to procedural protocols, we have observed high variability in map activation according to the choice of stimulation intensity (SI) right from the early stage of hotspot localization. We present a retrospective analysis of motor mappings performed between March 2020 and July 2022, where the SI was only chosen with rigorous care in the most recent ones, under the guide of an expert neurophysiologist. MATERIALS AND METHODS: In order to test the ability to reduce inaccurate responses and time expenditure using selective SI, data were collected from 16 patients who underwent mapping with the random method (group A) and 15 patients who underwent mapping with the proposed method (group B). The parameters considered were resting motor threshold (%), number of stimuli, number of valid motor evoked potentials (MEPs), number of valid MEPs considered true positives (TPs), number of valid MEPs considered false positives (FPs), ratio of true-positive MEPs to total stimuli, ratio of true-positive MEPs to valid MEPs, minimum amplitude, maximum amplitude and mapping time for each patient. RESULTS: The analysis showed statistically significant reductions in total stimulus demand, procedural time and number of false-positive MEPs. Significant increases were observed in the number of true-positive MEPs, the ratio of true-positive MEPs to total stimuli and the ratio of true-positive MEPs to valid MEPs. In the subgroups analyzed, there were similar trends, in particular, an increase in true positives and a decrease in false-positive responses. CONCLUSIONS: The precise selection of SI during hotspot search in nTMS motor mapping could provide reliable cortical maps in short time and with low employment of resources. This method seems to ensure that a MEP really represents a functionally eloquent cortical point, making mapping more intuitive even in less experienced centers.

Combining Transcranial Magnetic Stimulation and Deep Brain Stimulation: Current Knowledge, Relevance and Future Perspectives.

Deep brain stimulation (DBS) has emerged as an invasive neuromodulation technique for the treatment of several neurological disorders, but the mechanisms underlying its effects remain partially elusive. In this context, the application of Transcranial Magnetic Stimulation (TMS) in patients treated with DBS represents an intriguing approach to investigate the neurophysiology of cortico-basal networks. Experimental studies combining TMS and DBS that have been performed so far have mainly aimed to evaluate the effects of DBS on the cerebral cortex and thus to provide insights into DBS's mechanisms of action. The modulation of cortical excitability and plasticity by DBS is emerging as a potential contributor to its therapeutic effects. Moreover, pairing DBS and TMS stimuli could represent a method to induce cortical synaptic plasticity, the therapeutic potential of which is still unexplored. Furthermore, the advent of new DBS technologies and novel treatment targets will present new research opportunities and prospects to investigate brain networks. However, the application of the combined TMS-DBS approach is currently limited by safety concerns. In this review, we sought to present an overview of studies performed by combining TMS and DBS in neurological disorders, as well as available evidence and recommendations on the safety of their combination. Additionally, we outline perspectives for future research by highlighting knowledge gaps and possible novel applications of this approach.

Myoclonic super-refractory status epilepticus with favourable evolution in a teenager with FIRES: Is the association of vagus nerve stimulation and cannabidiol effective?

BACKGROUND: Febrile infection-related epilepsy syndrome (FIRES) is a rare and catastrophic clinical syndrome occurring in previously healthy patients. Aetiology is still unknown and outcome usually poor. We describe a case of myoclonic prolonged super refractory status epilepticus (P-SRSE) in FIRES in a patient admitted to the paediatric intensive care unit of Padova, Italy. CASE REPORT: A previously healthy 14-year-old girl with onset of myoclonic status epilepticus after a mild febrile illness was admitted to our hospital with a diagnosis of FIRES. Extensive diagnostic work-up was inconclusive. Status epilepticus and electroclinical seizures recurred every time weaning from anaesthetic agents was attempted. Eventually, a vagal nerve stimulator (VNS) was implanted and cannabidiol (CBD) administered, 43 days and 70 days after P-SRSE onset, respectively. Two days after CBD introduction, status epilepticus weaned and the girl rapidly regained complete consciousness showing a brilliant and unexpected recovery. At last follow-up, 12 months later, she is 8-months seizure free on multiple antiseizure medications, has only mild neuropsychological impairment with no neurological and intellective deficit. CONCLUSIONS: To our knowledge, this represents a unique case with an extremely favourable evolution with a possible effect of the association of VNS and CBD to traditional antiseizure medications.

Vagus Nerve Stimulation in Treatment-Resistant Depression: A Case Series of Long-Term Follow-up.

OBJECTIVES: Vagus nerve stimulation (VNS) has been shown to be effective for treatment-resistant depression (TRD). However, long-term (>5 years) studies on the efficacy and tolerability of this treatment have been lacking. Here, we report a long-term clinical follow-up of 5 patients with severe and long-standing TRD, who received a VNS implant. METHODS: Of the initial 6 patients with TRD implanted with VNS at our center, 5 of them were followed for 6 to 12 years after implantation. Primary efficacy outcomes were clinical response and improved functioning at follow-up visits. The primary safety outcome was all-cause discontinuation, and the secondary safety outcomes were the number and the severity of adverse events. RESULTS: The VNS implant was associated with a sustained response (>10 years) in terms of clinical response and social, occupational, and psychological functioning in 3 patients. Two patients dropped out after 6 and 7 years of treatment, respectively. Vagus nerve stimulation was well tolerated by all patients, who reported only mild adverse effects. One patient, who discontinued concomitant drug treatment, had a hypomanic episode in the 10th year of treatment. The parameters of the VNS device were fine-tuned when life stressors or symptom exacerbation occurred. CONCLUSIONS: Our case series showed that VNS can have long-term and durable effectiveness in patients with severe multiepisode chronic depression, and this could be associated with its neuroplastic effects in the hippocampus. In light of good general tolerability, our findings support VNS as a viable treatment option for TRD.

Deep brain stimulation for Parkinson's disease in practice: results of the survey by the Italian Neurosurgery Society.

BACKGROUND: Deep brain stimulation (DBS) is a safe and effective treatment for patients with advanced Parkinson's disease (PD) and many neurosurgical centers in Italy have a DBS program. Considering the prevalence of PD and criteria for DBS implantation, about 3200-10,350 PD patients may benefit from DBS in Italy. The global management of patients underwent DBS is complex and it can be supposed that many differences exist between centers in clinical practice. The Italian Neurosurgery Society (SINch) designed this survey to investigate the state of the art of DBS for PD in Italy. METHODS: A 26-item closed-ended question survey was designed and sanded by email at all Italian Neurosurgery centers. The main topic investigated was DBS teams, anatomical target selection, surgical procedure, neuroimaging, intraoperative target localization, DBS device and patients' follow-up. RESULTS: A total of 23 neurosurgery centers completed the survey. There are mainly low-to medium-volume centers (<20 annual DBS procedures) with dedicated DBS teams. The principal anatomical target used is subthalamic nucleus (STN) and, relative to the surgical technique, it emerges that in Italy DBS are bilaterally implanted in a single-step session with awake anesthesia and with frame-based technique. Final leads positioning is defined by microelectrode recordings (MER) and microstimulation (MS), with limited role of intraoperative neuroimaging (MRI and O-Arm). The stimulation is started at 15 or 30 days from procedure. CONCLUSIONS: Many centers of neurosurgery in Italy have a well-established DBS program for patients with advanced PD and some practical differences in technique between centers exist. Further investigation is needed to investigate specific criteria for selecting one technique over another.