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.

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.

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.

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.

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.

The rolling cyst: migrating intraventricular neurocysticercosis-a case-based update.

BACKGROUND: Neurocysticercosis is the most frequent parasitic disease of the central nervous system, and its incidence in the developed countries is increasing due to immigration and travels from endemic areas. The intraventricular location has been found to involve up to 61.3% of the patients; moreover, only 22 cases of migrating intraventricular cyst have been reported so far. Despite the rarity of the condition in western countries, its occurrence generates some concerns and the aim of this paper is to update the information concerning pathogenesis, clinical presentation, diagnosis and management of this entity. METHODS AND RESULTS: All the pertinent literature was analysed, focused on the cases of migrating intraventricular neurocysticercosis and its peculiar features. An illustrative case regarding a 14-year-old girl is also presented. CONCLUSIONS: Migrating intraventricular neurocysticercosis is a pathognomonic entity usually presenting with hydrocephalus, and its treatment is mainly surgical, preferring an endoscopic approach. When the resection of the intraventricular cyst is not performed, an accurate follow-up is mandatory to detect clinical changes due to a recurrent hydrocephalus or to the effect of the dying cyst on the surrounding area. In case of permanent shunt placement, the cysticidal and steroid treatment is recommended to reduce the risk of shunt failure.

Long-term effect of subthalamic and pallidal deep brain stimulation for status dystonicus in children with methylmalonic acidemia and GNAO1 mutation.

Status dystonicus (SD) is a rare and potentially life-threatening condition requiring intensive care management. Deep brain stimulation (DBS) has emerged as an effective treatment for SD refractory to medical management, but its application in this field is still limited. Here, we report the long-term outcome of four pediatric patients treated with DBS at the University Hospital of Padua, Italy, for SD refractory to medications. In addition, we present the results of a systematic literature review aimed at identifying published cases of SD treated with DBS, with focus on motor outcome. In our cohort, two children were affected by methylmalonic acidemia and suffered acute basal ganglia lesions, while the other two carried a pathogenic mutation in GNAO1 gene. DBS target was subthalamic nucleus (STN) in one case and globus pallidus internus (GPi) in three. All patients experienced SD resolution within 8-19 days after surgery. Mean post-operative follow-up was 5 years. We identified in the literature 53 additional SD cases treated with DBS (median age at DBS implantation: 12 years) with reported positive outcome in 51 and resolution of SD in a mean of 17 days after surgery. Our findings indicate that DBS is an effective treatment for SD refractory to medications, even in patients with acute basal ganglia lesions; STN can be an appropriate target when GPi is damaged. Moreover, data from long-term follow-up show that SD recurrences can be significantly reduced in frequency or abolished after DBS implantation.

Prone versus sitting position in pediatric low-grade posterior fossa tumors.

PURPOSE: The choice between sitting and prone position to access the infratentorial space in a suboccipital craniotomy is still a matter of debate. The comparisons in terms of complications and outcome of both positions are scarce, and the pediatric population is indeed more infrequent in these in scientific reviews. In this paper, we assess intraoperative and postoperative complications and neurological outcome in pediatric patients undergoing posterior cranial fossa surgery for pilocytic astrocytoma in sitting and prone position respectively. METHODS: We retrospectively analyzed 30 consecutive patients undergoing surgery for cerebellar pilocytic astrocytoma at the two neurosurgical units referring to the University of Padova Medical School from 1999 to 2017. Preoperative, intraoperative, and postoperative data were retrieved from our medical archives. RESULTS: The statistical analysis did not show any differences between the two groups in terms of preoperative, intraoperative, and postoperative data. The neurological status at last follow-up was similar in both groups of patients. CONCLUSIONS: Our results suggest that both sitting and prone position can be considered safe in suboccipital craniotomies. Further studies are needed to show if there are possible differences between these positions for other frequent pediatric tumors such as medulloblastomas and ependymomas.

Levels of N-terminal pro brain natriuretic peptide are enhanced in people with the uncomplicated metabolic syndrome: a case-cohort analysis of the population-based Casale Monferrato study.

BACKGROUND: Both metabolic syndrome (MetS) and N-amino terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) confer increased risk of cardiovascular diseases (CVD). We assessed if NT-proBNP levels were greater in people with uncomplicated MetS, who had neither CVD/chronic kidney disease (CKD) nor diabetes, as compared with subjects who met none of the defining criteria of the MetS. METHODS: A case-cohort study from the non-diabetic population-based Casale Monferrato study was performed, after exclusion of all subjects with established CVD, CKD [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m(2)], and CRP values ≥3 mg/L. Cases (n = 161) with MetS were compared with all subjects within the cohort (n = 124) who were completely free of any component of the MetS. Serum NT-proBNP was centrally measured by immunoenzymatic assay. RESULTS: NT-proBNP levels were significantly higher in cases than in control subjects [35.4 (15.5-98.2) vs 24.4 (11.7-49.6) pg/mL, p = 0.014]. In logistic regression analysis, compared with NT-proBNP values in the lower quartiles (≤49.64 pg/mL), higher values conferred odds ratio 4.17 (1.30-13.44) of having the MetS, independently of age, sex, microalbuminuria, CRP, eGFR, and central obesity. This association was evident even after the exclusion of hypertensive subjects. Further adjustment for log-HOMA and diastolic blood pressure did not modify the strength of the association, while central obesity was a negative confounder. CONCLUSIONS: Compared with people without any component of the MetS, those with uncomplicated MetS, who had neither CVD/CKD nor diabetes, had increased NT-proBNP values, even if they were normotensive and although absolute values were still in the low range. The insulin resistance state did not mediate this association, while central obesity was a negative confounder.

Epidural spinal cord stimulation for neuropathic pain: a neurosurgical multicentric Italian data collection and analysis.

BACKGROUND: Spinal cord stimulation (SCS) is a technique used worldwide to treat several types of chronic neuropathic pain refractory to any conservative treatment. The aim of this data collection is to enforce evidence of SCS effectiveness on neuropathic chronic pain reported in the literature and to speculate on the usefulness of the trial period in determining the long-term efficacy. Moreover, the very low percentage of undesired side effects and complications reported in our case series suggests that all implants should be performed by similarly well-trained and experienced professionals. METHOD: A multicentric data collection on a common database from 11 Italian neurosurgical departments started 3 years ago. Two different types of electrodes (paddle or percutaneous leads) were used. Of 122 patients, 73 % (N = 89) were submitted to a trial period, while the remaining patients underwent the immediate permanent implant (N = 33). Statistical comparisons of continuous variables between groups were performed. RESULTS: Most of the patients (80 %) had predominant pain to their lower limbs, while only 17 % of patients had prevalent axial pain. Significant reduction in pain, as measured by variation in visual analogue scale (VAS) score, was observed at least 1 year after implantation in 63.8 % of the cases, 59.5 % of patients who underwent a test trial and 71.4 % of patients who underwent permanent implant at once. No statistical differences were found between the lower-limb pain group and the axial pain group. CONCLUSIONS: No relevant differences in long-term outcomes were observed in previously tested patients compared with patients implanted at once. Through this analysis we hope to recruit new centres, to give more scientific value to our results.

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.

Understanding Clinician Knowledge, Attitudes, and Practices Relating to Nonpharmaceutical Fentanyl and Harm Reduction.

BACKGROUND: Nonpharmaceutical fentanyl (NPF) is driving the national epidemic of opioid overdose deaths. Clinicians can play a role in fostering awareness of this growing risk and delivering interventions to reduce mortality. However, there is limited research assessing clinician knowledge, attitudes, and practices relating to NPF and harm reduction strategies. METHODS: A 34-question survey was designed to assess knowledge, attitudes, and practices related to NPF and harm reduction strategies of adult and pediatric hospital-based and emergency clinicians at a single academic medical center. Results were summarized using descriptive statistics. Chi square and Fishers exact tests were used to compare groups. RESULTS: There were 136 survey responses. The majority (88%) of respondents correctly answered a question on NPF potency. Most respondents were aware that NPF exposure was very (84%) or somewhat likely (10%) for someone using illicit opioids and very (44%) or somewhat likely (46%) for nonopioid drugs. Respondents viewed overdose prevention as highly important for patients using illicit opioids (93%) and nonopioid drugs (86%) but few (21%) were very/extremely familiar with overdose prevention strategies and just over half (57%) were comfortable/very comfortable counseling about overdose prevention. There was wide variability in utilization of harm reduction/treatment strategies (7.3% frequently providing fentanyl test kits to 70% frequently prescribing naloxone). Higher levels of comfort and familiarity with overdose prevention were associated with more frequent counseling on harm reduction strategies. Pediatric-only clinicians had less familiarity (5% very/extremely familiar) and comfort (35% comfortable/very comfortable) with overdose prevention, and limited use of harm reduction strategies (0%-31% using each strategy frequently). CONCLUSIONS: While clinicians had knowledge and awareness of NPF and rated overdose prevention as highly important, utilization of harm reduction and treatment strategies was variable. This study highlights opportunities for education and system-based support to improve clinician-driven harm reduction practices for patients at risk of overdose.

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.

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.

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.

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.

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.