Synthesis of Azabicyclic Isosteres of Piperazine 2S-Carboxylic Acid.

Methods have been developed for the stereocontrolled synthesis of bicyclic diaza [3.3.0] octane carboxylic acids as possible isosteres of piperazine 2S-carboxylic acid. In the first approach, l-pyroglutamic acid was functionalized adopting new as well as documented reaction sequences via Michael and aza-Michael reactions, leading to two of the four intended isosteres. An alternative shorter route relying on enolate chemistry starting with N-Pf 4-keto l-proline methyl ester led to two other isosteres. Calculated pKa values and density functional theory (DFT) calculations have provided some insights into the relative basicities of the nitrogen atoms in these diaza [3.3.0] octane carboxylic acids in relation to piperazine 2S-carboxylic acid.

Burnout in neurosurgery in the post-pandemic era.

OBJECTIVE: Burnout syndrome impacts one of two neurosurgeons and negatively impacts both the individual and institution. The impact of burnout on neurosurgeons may have increased due to the SARS-COV-2 pandemic. Characteristics of burnout may differ among neurosurgeons and non-neurosurgeon physicians, and this may better target wellness initiatives designed to alleviate burnout. METHODS: Validated burnout inventories (Maslach Burnout Inventory; MBI) were provided to physicians, including neurosurgeons, at a single, large academic institution. Rates of burnout and specific characteristics of burnout were compared. Free-response answers describing specific characteristics of burnout were also collected for neurosurgeons. RESULTS: A total of 294 physicians responded to the survey, including 40 neurosurgeons. The rate of burnout between neurosurgeons and non-neurosurgeons did not differ (39% vs 34%; p=0.631), but there were notable differences in the characteristics of burnout. Neurosurgery respondents were more likely to report depersonalization (p<0.001), and an additional 42.5% of neurosurgeon respondents reported a "period of hardship," which may lead to subsequent burnout. Neurosurgeons also more frequently reported higher feelings of personal accomplishment (p<0.001). Targeted wellness interventions specific to neurosurgeons may alleviate and prevent burnout. CONCLUSIONS: We show that although the rate of burnout does not differ for neurosurgeons, the characteristics of burnout may. This may represent the key to providing specialty-specific targeted interventions to alleviate burnout. Further, there is a significant proportion of neurosurgeons at risk for subsequent burnout for which additional importance must be placed to prevent progression to burnout.

Dexmedetomidine Versus Fentanyl in Intraoperative Neuromuscular Monitoring Using A Propofol-based Total Intravenous Anaesthesia Regimen in Spine Surgeries.

Objective: This prospective, double-blind, randomized study aimed to compare the effects of dexmedetomidine and fentanyl on the latency and amplitude of transcranial motor evoked potentials (TcMEPs) under propofol-based total intravenous anaesthesia (TIVA) in spine surgery. Secondarily, intraoperative hemodynamics, total propofol consumption, recovery profile, and surgical field quality were compared. Methods: TcMEP amplitude and latency recordings of bilateral abductor pollicis brevis and abductor hallucis muscles posted for elective lumbar spine surgery under TcMEP monitoring randomly divided into two study groups. Throughout the surgery, TIVA was administered using intravenous propofol (100-150 µg kg-1 min-1) and dexmedetomidine (0.5-0.7 µg kg-1 h-1) in group D and intravenous propofol (100-150 µg kg-1 min-1) and fentanyl (1 µg kg-1 h-1) in group F. TcMEPs were recorded at various time points during the surgery. Immediately after extubation recovery from anaesthesia was noted. Additionally, hemodynamic parameters, total propofol consumption, and surgical field quality were assessed. Results: Latency and amplitude were comparable between the groups. Time to extubation was significantly longer in group D, but the mean (standard deviation) duration of stay in recovery was shorter in group D [47.55 (7.51) 95% confidence interval (CI) (44.863-50.237)] (P=0.046). Total propofol consumption was reduced in group D [220 (38) 95% CI (206.402-233.598)] (P=0.025) and surgical field condition was better in group D. Conclusions: Dexmedetomidine and fentanyl do not have any effect on TcMEP amplitude and latency. However, dexmedetomidine provides the additional advantage of reduced total propofol consumption, shorter stay in recovery, and better surgical field quality.

Motifs of human hippocampal and cortical high frequency oscillations structure processing and memory of naturalistic stimuli.

The discrete events of our narrative experience are organized by the neural substrate that underlies episodic memory. This narrative process is segmented into discrete units by event boundaries. This permits a replay process that acts to consolidate each event into a narrative memory. High frequency oscillations (HFOs) are a potential mechanism for synchronizing neural activity during these processes. Here, we use intracranial recordings from participants viewing and freely recalling a naturalistic stimulus. We show that hippocampal HFOs increase following event boundaries and that coincident hippocampal-cortical HFOs (co-HFOs) occur in cortical regions previously shown to underlie event segmentation (inferior parietal, precuneus, lateral occipital, inferior frontal cortices). We also show that event-specific patterns of co-HFOs that occur during event viewing re-occur following the subsequent three event boundaries (in decaying fashion) and also during recall. This is consistent with models that support replay as a mechanism for memory consolidation. Hence, HFOs may coordinate activity across brain regions serving widespread event segmentation, encode naturalistic memory, and bind representations to assemble memory of a coherent, continuous experience.

Assessment of fluid responsiveness after tidal volume challenge in renal transplant recipients: a nonrandomized prospective interventional study.

Background: When applying lung-protective ventilation, fluid responsiveness cannot be predicted by pulse pressure variation (PPV) or stroke volume variation (SVV). Functional hemodynamic testing may help address this limitation. This study examined whether changes in dynamic indices such as PPV and SVV, induced by tidal volume challenge (TVC), can reliably predict fluid responsiveness in patients undergoing renal transplantation who receive lung-protective ventilation. Methods: This nonrandomized interventional study included renal transplant recipients with end-stage renal disease. Patients received ventilation with a 6 mL/kg tidal volume (TV), and the FloTrac system was attached for continuous hemodynamic monitoring. Participants were classified as responders or nonresponders based on whether fluid challenge increased the stroke volume index by more than 10%. Results: The analysis included 36 patients, of whom 19 (52.8%) were responders and 17 (47.2%) were nonresponders. Among responders, the mean ΔPPV6-8 (calculated as PPV at a TV of 8 mL/kg predicted body weight [PBW] minus that at 6 mL/kg PBW) was 3.32±0.75 and ΔSVV6-8 was 2.58±0.77, compared to 0.82±0.53 and 0.70±0.92 for nonresponders, respectively. ΔPPV6-8 exhibited an area under the curve (AUC) of 0.97 (95% confidence interval [CI], 0.93-1.00; P≤0.001), with an optimal cutoff value of 1.5, sensitivity of 94.7%, and specificity of 94.1%. ΔSVV6-8 displayed an AUC of 0.93 (95% CI, 0.84-1.00; P≤0.001) at the same cutoff value of 1.5, with a sensitivity of 94.7% and a specificity of 76.5%. Conclusions: TVC-induced changes in PPV and SVV are predictive of fluid responsiveness in renal transplant recipients who receive intraoperative lung-protective ventilation.

Perioperative outcomes of 105 cases of ABO-incompatible live donor kidney transplantation: a retrospective single-center observational study.

Background: ABO-incompatible (ABOi) kidney transplantation poses significant challenges in achieving successful outcomes. This study aimed to investigate the impact of various interventions and techniques on improving the success rates of ABOi kidney transplantation. Methods: We conducted a retrospective observational analysis of patients who underwent ABOi kidney transplantation from November 2012 to March 2023. The study included a total of 105 patients. We collected and analyzed data on patient demographics, preoperative assessments, surgical details, and postoperative outcomes. Results: The mean ages of the donors and recipients were 50.52±10.32 and 36.63±11.61 years, respectively. The majority of recipients were male (81.9%), while most donors were female (89.5%). The most common blood group among recipients was O (69.5%), and among donors, it was B (46.7%). The median durations of chronic kidney disease and dialysis were 12 months (interquartile range [IQR], 7-28 months) and 6 months (IQR, 2-12 months), respectively. Baseline antibody titers (anti-A and anti-B) ranged from 64.0 to 256.0, while on the day of surgery, they were ≤8. Perioperative complications included hypotension (10.5%), acute tubular necrosis (5.7%), delayed graft function (3.8%), and reexploration (3.8%) due to hematoma. Conclusions: ABOi kidney transplantation is a viable option for recipients lacking available donors with an ABO-compatible match. Perioperative concerns, including hypoalbuminemia, heightened risk of infections, coagulopathies, aseptic precautions, and immunological surveillance, must be carefully addressed.

Harnessing Nanoparticles to Overcome Antimicrobial Resistance: Promises and Challenges.

The rise of antimicrobial resistance (AMR) has become a serious global health issue that kills millions of people each year globally. AMR developed in bacteria is difficult to treat and poses a challenge to clinicians. Bacteria develop resistance through a variety of processes, including biofilm growth, targeted area alterations, and therapeutic drug alteration, prolonging the period they remain within cells, where antibiotics are useless at therapeutic levels. This rise in resistance is linked to increased illness and death, highlighting the urgent need for effective solutions to combat this growing challenge. Nanoparticles (NPs) offer unique solutions for fighting AMR bacteria. Being smaller in size with a high surface area, enhancing interaction with bacteria makes the NPs strong antibacterial agents against various infections. In this review, we have discussed the epidemiology and mechanism of AMR development. Furthermore, the role of nanoparticles as antibacterial agents, and their role in drug delivery has been addressed. Additionally, the potential, challenges, toxicity, and future prospects of nanoparticles as antibacterial agents against AMR pathogens have been discussed. The research work discussed in this review links with Sustainable Development Goal 3 (SDG-3), which aims to ensure disease-free lives and promote well-being for all ages.

Differential Responses to Low- and High-Frequency Subthalamic Nucleus Deep Brain Stimulation on Sensor-Measured Components of Bradykinesia in Parkinson's Disease.

INTRODUCTION: The current approach to assessing bradykinesia in Parkinson's Disease relies on the Unified Parkinson's Disease Rating Scale (UPDRS), which is a numeric scale. Inertial sensors offer the ability to probe subcomponents of bradykinesia: motor speed, amplitude, and rhythm. Thus, we sought to investigate the differential effects of high-frequency compared to low-frequency subthalamic nucleus (STN) deep brain stimulation (DBS) on these quantified facets of bradykinesia. METHODS: We recruited advanced Parkinson's Disease subjects with a chronic bilateral subthalamic nucleus (STN) DBS implantation to a single-blind stimulation trial where each combination of medication state (OFF/ON), electrode contacts, and stimulation frequency (60 Hz/180 Hz) was assessed. The Kinesia One sensor system was used to measure upper limb bradykinesia. For each stimulation trial, subjects performed extremity motor tasks. Sensor data were recorded continuously. We identified STN DBS parameters that were associated with improved upper extremity bradykinesia symptoms using a mixed linear regression model. RESULTS: We recruited 22 subjects (6 females) for this study. The 180 Hz STN DBS (compared to the 60 Hz STN DBS) and dopaminergic medications improved all subcomponents of upper extremity bradykinesia (motor speed, amplitude, and rhythm). For the motor rhythm subcomponent of bradykinesia, ventral contacts yielded improved symptom improvement compared to dorsal contacts. CONCLUSION: The differential impact of high- and low-frequency STN DBS on the symptoms of bradykinesia may advise programming for these patients but warrants further investigation. Wearable sensors represent a valuable addition to the armamentarium that furthers our ability to conduct objective, quantitative clinical assessments.

Organizing a Regional In-Person Medical Student Symposium in Neuroscience and Neurosurgery Research: A How-To Guide.

BACKGROUND: Medical students are increasingly seeking out research opportunities to build their skills and network with future colleagues. Medical student-led conferences are an excellent endeavor to achieve this goal. METHODS: The American Association of Neurological Surgeons student chapter at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell designed an in-person medical student research symposium alongside the Northwell Health Department of Neurosurgery. Postconference feedback forms were sent out digitally to student attendees to evaluate event planning and execution and responses were given on a scale of 1-5 (5 being the highest score). RESULTS: In December 2023, the Northeast Medical Student Research Symposium was held with over 80 participants and 52 medical student presenters. Keynote speakers delivered lectures geared toward students interested in neurosurgery and neuroscience research, followed by an interactive poster board session and resident/attending networking dinner. After the conference, students affirmed that they learned more about neuroscience research after the event (mean: 4.3), were more inclined to attend other neuroscience research events in the future (mean: 4.7), and would attend this event if held next year (mean: 4.8). The poster sessions (mean: 4.75) and keynote lectures (mean: 5) were the highest rated events, while the resident/attending networking dinner (mean: 3.6) was a potential area for improvement. CONCLUSIONS: Regional in-person conferences are an excellent way to foster interest in neurosurgery and neuroscience research, network with like-minded peers, and prepare students for presentations at national meetings.

Unleashing the promise of emerging nanomaterials as a sustainable platform to mitigate antimicrobial resistance.

The emergence and spread of antibiotic-resistant (AR) bacterial strains and biofilm-associated diseases have heightened concerns about exploring alternative bactericidal methods. The WHO estimates that at least 700 000 deaths yearly are attributable to antimicrobial resistance, and that number could increase to 10 million annual deaths by 2050 if appropriate measures are not taken. Therefore, the increasing threat of AR bacteria and biofilm-related infections has created an urgent demand for scientific research to identify novel antimicrobial therapies. Nanomaterials (NMs) have emerged as a promising alternative due to their unique physicochemical properties, and ongoing research holds great promise for developing effective NMs-based treatments for bacterial and viral infections. This review aims to provide an in-depth analysis of NMs based mechanisms combat bacterial infections, particularly those caused by acquired antibiotic resistance. Furthermore, this review examines NMs design features and attributes that can be optimized to enhance their efficacy as antimicrobial agents. In addition, plant-based NMs have emerged as promising alternatives to traditional antibiotics for treating multidrug-resistant bacterial infections due to their reduced toxicity compared to other NMs. The potential of plant mediated NMs for preventing AR is also discussed. Overall, this review emphasizes the importance of understanding the properties and mechanisms of NMs for the development of effective strategies against antibiotic-resistant bacteria.

Functional Outcomes and Their Influencing Factors for the Surgical Management of T-type Acetabulum Fractures: A Prospective Single-Centre Study of 73 Patients.

Introduction T-type fractures of the acetabulum are uncommon injuries, typically resulting in poorer long-term outcomes compared to other patterns of acetabular fractures. Our main purpose is to analyse the epidemiology, functional outcomes, and factors affecting the functional outcomes of patients with T-type acetabular fractures. Methods This prospective, single-centre study included 73 patients with T-type and T with posterior wall acetabular fractures. They underwent treatment with open reduction internal fixation using plating through the modified Stoppa, Kocher-Langenbeck (KL), or dual approach. The post-operative reduction was assessed according to Matta's criteria, and functional outcomes were evaluated using the modified Harris hip score. Results Between September 2017 and January 2023, 53 patients underwent surgery for T-type fractures (72.6%), and 20 patients were treated for T with posterior wall acetabular fractures (27.4%). The minimum follow-up period was one year, with a mean follow-up of 3.5 years. Anatomical reduction emerged as the major contributing factor towards good functional outcomes compared to satisfactory reduction according to Matta's criteria (P value: 0.006). Overall, 65 patients (89%) achieved excellent to good modified Harris hip scores, while eight patients (11%) obtained fair to poor scores. Patients with T-type fractures demonstrated better functional outcomes compared to T with posterior wall fractures (P value: 0.031). Conclusion Anatomical reduction, as assessed by Matta's reduction criteria, serves as a predictor of favourable functional outcomes. T with posterior wall fractures exhibit poor outcomes in comparison to T-type fractures. The surgical approach employed does not influence the reduction or the final functional outcome of the patient.

Why are clinical trials of deep brain stimulation terminated? An analysis of clinicaltrials.gov.

Background: Although deep brain stimulation (DBS) has established uses for patients with movement disorders and epilepsy, it is under consideration for a wide range of neurologic and neuropsychiatric conditions. Objective: To review successful and unsuccessful DBS clinical trials and identify factors associated with early trial termination. Methods: The ClinicalTrials.gov database was screened for all studies related to DBS. Information regarding condition of interest, study aim, trial design, trial success, and, if applicable, reason for failure was collected. Trials were compared and logistic regression was utilized to identify independent factors associated with trial termination. Results: Of 325 identified trials, 79.7% were successful and 20.3% unsuccessful. Patient recruitment, sponsor decision, and device issues were the most cited reasons for termination. 242 trials (74.5%) were interventional with 78.1% successful. There was a statistically significant difference between successful and unsuccessful trials in number of funding sources (p = 0.0375). NIH funding was associated with successful trials while utilization of other funding sources (academic institutions and community organizations) was associated with unsuccessful trials. 83 trials (25.5%) were observational with 84.0% successful; there were no statistically significant differences between successful and unsuccessful observational trials. Conclusion: One in five clinical trials for DBS were found to be unsuccessful, most commonly due to patient recruitment difficulties. The source of funding was the only factor associated with trial success. As DBS research continues to grow, understanding the current state of clinical trials will help design successful future studies, thereby minimizing futile expenditures of time, cost, and patient engagement.

An Institutional Experience of Directional Deep Brain Stimulation and a Review of the Literature.

INTRODUCTION: Directional deep brain stimulation (dDBS) has been suggested to have a similar therapeutic effect when compared with the traditional omnidirectional DBS, but with an improved therapeutic window that yields optimized clinical effect owing to the ability to better direct, or "steer," electric current. We present our single-center, retrospective analysis of our experience in the use of dDBS in patients with movement disorders and provide a review of the literature. MATERIALS AND METHODS: We identified all patients with Parkinson disease (PD) and essential tremor (ET) who received a dDBS system between 2018 and 2022 and retrospectively examined characteristics of their longitudinal treatment. A total of 70 leads were identified across 42 patients (28 PD, 14 ET). RESULTS: Three types of systems were implemented (single-segment activation, 45.2% of patients; multiple independent current control, 50.0%; and local field potential sensing-enabled, 4.7%). The subthalamic nucleus or globus pallidus internus was targeted in PD, and the ventral intermediate nucleus of the thalamus in ET. Across the entire cohort (n = 70 leads), at initial programming, 54.2% of leads (n = 38) were programmed using directional stimulation. At the most recent reprogramming, 58.6% of leads (n = 41) implemented directionality. In patients with PD, the average decrease in levodopa-equivalent daily dose at six months after implantation was 35.4% ± 39.2%. Despite the ability to steer current to relieve stimulation-induced side effects, ten leads in six patients required surgical revision owing to electrode malposition. CONCLUSIONS: We show wide adaptability and implementation of directional stimulation, adding to the growing compendium of real-world uses of dDBS therapy. We used directionality to improve clinical response in both patients with PD and patients with ET and found that its programming flexibility was used at high rates long after implantation and initial programming. In patients with PD, dDBS led to a significant reduction in dopaminergic medication, suggesting sustained clinical improvement. Nonetheless, accurate surgical placement remains necessary to ensure optimal clinical outcomes.

Characterization, Antioxidant, and Antimicrobial Properties of Mulberry Lattices.

In order to find the most advantageous bioactive compounds from mulberry latex for drug development in the near future, this study was conducted to characterize and evaluate antioxidant and antimicrobial properties from four different mulberry lattices (BR-2, S-1, AR-14, and S-146). The characterization of the lattices was performed by scanning electron microscopy with energy-dispersive X-ray spectroscopy, gas chromatography coupled to mass spectroscopy, and Fourier transform infrared spectroscopy. Further, screenings of the antioxidant and antimicrobial potential of selected lattices were performed in vitro using 2,2-diphenyl-1-picrylhydrazyl assay and agar well diffusion methods, respectively. Interestingly, the outcome of the current study revealed that tested mulberry lattices contain a considerable amount of bioactive phytoconstituents, particularly antimicrobial and antioxidant compounds, as revealed by chromatographic analysis. BR-2 latex was found to have significant antioxidant activity (75%) followed by S-146 (64.6%) and AR-14 (52.9%). The maximum antimicrobial activity was found in BR-2 latex compared to other tested latex varieties. The results of this investigation showed that mulberry latex from the BR-2 type may successfully control both bacterial and fungal infections, with the added benefit of having enhanced antioxidant capabilities.

Perioperative Anxiolysis and Analgesic Effect after Premedication with Melatonin and Pregabalin in Total Hip Arthroplasty under Spinal Anaesthesia: A Prospective Comparative Trial.

Background: Preoperative anxiety plays a critical role in post-operative pain response and other outcomes. Melatonin is a naturally secreted hormone which has anxiolytic, sedative, and analgesic properties. Pregabalin, analogue of gabapentin which has property of anxiolytic and analgesic effects. Materials and Methods: Total 96 patients undergoing total hip arthroplasty, divided into 3 groups of 32 each and were given placebo (group I), melatonin 6 mg (group II), and pregabalin 150 mg (group III). Anxiety level, postoperative pain score, sedation level and duration as well as characteristics of spinal anaesthesia were assessed with other vital parameters. Results: Group I showed an increment in the anxiety score from baseline whereas in group II and group III, there was a decline in pre-operative anxiety score from baseline at all the periods of observation and more significantly in group III. Visual analogue scale (VAS) score and total dose of rescue analgesia were highest in group I, but group II and group III were comparable to each other. However, the durations of spinal anaesthesia and motor blockade showed a statistically significant difference with maximum duration in group III followed by II and then I. The level of sedation among the three groups were comparable at all the periods of observation. Conclusions: Pregabalin was found better for perioperative anxiolysis, post-operative analgesia and for prolongation of duration of spinal anaesthesia when compared to melatonin.

Exploring the Intersection of Artificial Intelligence and Neurosurgery: Let us be Cautious With ChatGPT.

BACKGROUND AND OBJECTIVES: ChatGPT is a novel natural language processing artificial intelligence (AI) module where users enter any question or command and receive a single text response within seconds. As AI becomes more accessible, patients may begin to use it as a resource for medical information and advice. This is the first study to assess the neurosurgical information that is provided by ChatGPT. METHODS: ChatGPT was accessed in January 2023, and prompts were created requesting treatment information for 40 common neurosurgical conditions. Quantitative characteristics were collected, and four independent reviewers evaluated the responses using the DISCERN tool. Prompts were compared against the American Association of Neurological Surgeons (AANS) "For Patients" webpages. RESULTS: ChatGPT returned text organized in paragraph and bullet-point lists. ChatGPT responses were shorter (mean 270.1 ± 41.9 words; AANS webpage 1634.5 ± 891.3 words) but more difficult to read (mean Flesch-Kincaid score 32.4 ± 6.7; AANS webpage 37.1 ± 7.0). ChatGPT output was found to be of "fair" quality (mean DISCERN score 44.2 ± 4.1) and significantly inferior to the "good" overall quality of the AANS patient website (57.7 ± 4.4). ChatGPT was poor in providing references/resources and describing treatment risks. ChatGPT provided 177 references, of which 68.9% were inaccurate and 33.9% were completely falsified. CONCLUSION: ChatGPT is an adaptive resource for neurosurgical information but has shortcomings that limit the quality of its responses, including poor readability, lack of references, and failure to fully describe treatment options. Hence, patients and providers should remain wary of the provided content. As ChatGPT or other AI search algorithms continue to improve, they may become a reliable alternative for medical information.

Let's make size not matter: tumor control and toxicity outcomes of hypofractionated Gamma Knife radiosurgery for large brain metastases.

PURPOSE: Management of patients with large brain metastases poses a clinical challenge, with poor local control and high risk of adverse radiation events when treated with single-fraction stereotactic radiosurgery (SF-SRS). Hypofractionated SRS (HF-SRS) may be considered, but clinical data remains limited, particularly with Gamma Knife (GK) radiosurgery. We report our experience with GK to deliver mask-based HF-SRS to brain metastases greater than 10 cc in volume and present our control and toxicity outcomes. METHODS: Patients who received hypofractionated GK radiosurgery (HF-GKRS) for the treatment of brain metastases greater than 10 cc between January 2017 and June 2022 were retrospectively identified. Local failure (LF) and adverse radiation events of CTCAE grade 2 or higher (ARE) were identified. Clinical, treatment, and radiological information was collected to identify parameters associated with clinical outcomes. RESULTS: Ninety lesions (in 78 patients) greater than 10 cc were identified. The median gross tumor volume was 16.0 cc (range 10.1-56.0 cc). Prior surgical resection was performed on 49 lesions (54.4%). Six- and 12-month LF rates were 7.3% and 17.6%; comparable ARE rates were 1.9% and 6.5%. In multivariate analysis, tumor volume larger than 33.5 cc (p = 0.029) and radioresistant histology (p = 0.047) were associated with increased risk of LF (p = 0.018). Target volume was not associated with increased risk of ARE (p = 0.511). CONCLUSIONS: We present our institutional experience treating large brain metastases using mask-based HF-GKRS, representing one of the largest studies implementing this platform and technique. Our LF and ARE compare favorably with the literature, suggesting that target volumes less than 33.5 cc demonstrate excellent control rates with low ARE. Further investigation is needed to optimize treatment technique for larger tumors.

Outcomes of children with idiopathic steroid resistant nephrotic syndrome: a single centre observational study / Desfechos de crianças com síndrome nefrótica idiopática córtico-resistente: um estudo observacional de centro único

ABSTRACT Introduction: Idiopathic steroid resistant nephrotic syndrome (SRNS) has variable outcomes in children. The primary objective of the present study was to assess the cumulative remission rate and the secondary objectives were to assess factors affecting the remission status, kidney function survival, and adverse effects of medications. Methods: One hundred fourteen patients with SRNS were included. Calcineurin inhibitor-based treatment protocol along with prednisolone and angiotensin-converting enzyme inhibitor were used, and patients were followed over 5 years. Results: Median age was 4.5 years; 53.5% of cases were between 1 to 5 years of age. Sixty-two patients (54.4%) were at initial stage and 52 (45.6%) were at a late SRNS stage. Median eGFRcr was 83.5 mL/min/1.73m2 at presentation. Of the 110 patients, 63 (57.3%) achieved remission [complete remission 30 (27.3%), partial remission 33 (30%)], and 47 (42.7%) had no remission. Kidney function survival was 87.3% and 14 cases (12.7%) had progression to CKD (G3-8, G4-3, G5-1, and G5D-2). Median duration of follow up was 36 months (IQR 24, 60). Age of onset, cyclosporine/tacrolimus, eGFRcr, and histopathology (MCD/FSGS) did not affect remission. Similarly, remission status in addition to age of onset, drug protocol, and histopathology did not significantly affect kidney function during a period of 5 years. Hypertension, cushingoid facies, short stature, cataract, and obesity were observed in 37.7, 29.8, 25.5, 17.5, and 0.7% of cases, respectively. Conclusion: About half of the cases achieved remission. Age of onset of disease, cyclosporine/tacrolimus use, and histopathological lesion neither affected remission status nor short-term kidney function survival in SRNS.

RESUMO Introdução: A síndrome nefrótica idiopática córtico-resistente (SNICR) apresenta desfechos variáveis em crianças. O objetivo principal deste estudo foi avaliar a taxa de remissão cumulativa. Os objetivos secundários foram avaliar fatores que afetam status de remissão, sobrevida da função renal e efeitos adversos de medicamentos. Métodos: Foram incluídos 114 pacientes com SNCR. Utilizou-se protocolo de tratamento baseado em inibidores de calcineurina juntamente com prednisolona e inibidor da enzima conversora de angiotensina. Os pacientes foram acompanhados durante 5 anos. Resultados: A idade mediana foi 4,5 anos; 53,5% dos casos tinham entre 1 e 5 anos. 62 pacientes (54,4%) estavam em estágio inicial; 52 (45,6%) em estágio tardio da SNCR. A TFGecr mediana foi 83,5 mL/min/1,73 m2 na apresentação. Dos 110 pacientes, 63 (57,3%) alcançaram remissão [remissão completa 30 (27,3%), remissão parcial 33 (30%)], e 47 (42,7%) não apresentaram remissão. A sobrevida da função renal foi 87,3%; 14 casos (12,7%) progrediram para DRC (G3-8, G4-3, G5-1, G5D-2). A duração mediana do acompanhamento foi 36 meses (IIQ 24, 60). Idade no início, ciclosporina/tacrolimus, TFGecr e histopatologia (DLM/GESF) não afetaram a remissão. Igualmente, status de remissão, além da idade no início, protocolo de medicamentos e histopatologia não afetaram significativamente a função renal por 5 anos. Observou-se hipertensão, fácies cushingoide, baixa estatura, catarata e obesidade em 37,7; 29,8; 25,5; 17,5; e 0,7% dos casos, respectivamente. Conclusão: Aproximadamente metade dos casos alcançou remissão. Idade no início, uso de ciclosporina/tacrolimus e lesão histopatológica não afetaram o status de remissão nem a sobrevida da função renal a curto prazo na SNICR.

Synthesis of Aza-Bridged Perhydroazulene Chimeras of Tropanes and Hederacine A.

We report the synthesis of two novel azaperhydroazulene tropane-hederacine chimeras A and B, which contain an 8-azabicyclo[3.2.1]octane ring and a 7-azabicyclo[4.1.1]octane ring, respectively. The synthesis of both chimeras was achieved by epoxide ring opening and was governed by the stereochemistry of the hydroxy-epoxide unit. Finally, a density functional theory study was conducted to explain the regioselectivity of the cyclization and the importance of the stereochemistry of the hydroxyl group.