Thalamic responsive neurostimulation for the treatment of refractory epilepsy: an individual patient data meta-analysis.

OBJECTIVE: In recent years, the treatment of drug-resistant epilepsy (DRE) has made greater use of surgery and expanded options for neurostimulation or neuromodulation. Up to this point, responsive neurostimulation (RNS) has been very promising but has mainly used only the cortex as a target. In this individual patient data meta-analysis (IPDMA), the authors sought to establish if a novel RNS target, the thalamus, can be used to treat DRE. METHODS: The literature regarding the management of DRE by targeting the thalamus with RNS was reviewed per IPDMA guidelines. Five databases were searched with keywords [((Responsive neurostimulation) OR (RNS)) AND ((thalamus) OR (thalamic) OR (Deep-seated) OR (Diencephalon) OR (limbic))] in March 2022. RESULTS: The median (interquartile range) age at implantation was 17 (13.5-27.5) years (n = 42) with an epilepsy duration of 12.1 (5.8-15.3) years. In total, 52.4% of patients had previously undergone epilepsy surgery, 28.6% had prior vagus nerve stimulation, and 2.4% had prior RNS. The median preimplant seizure frequency was 12 per week. The median seizure reduction at last follow-up was 73%. No study in this IPDMA reported complications, although 7 cases (16.3%) did require reoperation. Behavioral improvements and reduced antiepileptic drug dose or quantity were reported for 80% and 28.6% of patients, respectively. CONCLUSIONS: This review indicates that thalamic RNS may be safe and effective for treating DRE. Long-term and controlled studies on thalamic RNS for DRE would further elucidate this technique's potential benefits and complications and help guide clinical judgment in the management of DRE.

Towards the definition of progressive disease in brain metastasis treated with laser ablation: an evidence-based study.

PURPOSE: The postoperative period after laser interstitial thermal therapy (LITT) is marked by a temporary increase in volume, which can impact the accuracy of radiographic assessment. The current criteria for progressive disease (PD) suggest that a 20% increase in size of brain metastasis (BM) assessed in 6-12 weeks intervals should be considered as local progression (LP). However, there is no agreement on how LP should be defined in this context. In this study, we aimed to statistically analyze which tumor volume variations were associated with LP. METHODS: We analyzed 40 BM that underwent LITT between 2013 and 2022. For this study, LP was defined following radiographic features. A ROC curve was generated to evaluate volume change as a predictor of LP and find the optimal cutoff point. A logistic regression analysis and Kaplan Meier curves were performed to assess the impact of various clinical variables on LP. RESULTS: Out of 40 lesions, 12 (30%) had LP. An increase in volume of 25.6% from baseline within 120-180 days after LITT presented a 70% sensitivity and 88.9% specificity for predicting LP (AUC: 0.78, p = 0.041). The multivariate analysis showed a 25% increase in volume between 120 and 180 days as a negative predictive factor (p = 0.02). Volumetric changes within 60-90 days after LITT did not predict LP (AUC: 0.57; p = 0.61). CONCLUSION: Volume changes within the first 120 days after the procedure are not independent indicators of LP of metastatic brain lesions treated with LITT.

Surgical Approaches to Thalamic Gliomas: A Systematic Review.

BACKGROUND: Adult thalamic gliomas (ATGs) present a surgical challenge given their depth and proximity to eloquent brain regions. Choosing a surgical approach relies on different clinical variables such as anatomical location and size of the tumor. However, conclusive data regarding how these variables influence the balance between extent of resection and complications are lacking. We aim to systematically review the literature to describe the current surgical outcomes of ATG and to provide tools that may improve the decision-making process. METHODS: Literature regarding the surgical management of ATG patients was reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four databases were queried and a description of clinical characteristics and survival analysis were performed. An individual patient data analysis was conducted when feasible. RESULTS: A total of 462 patients were included from 13 studies. The mean age was 39.8 years with a median preoperative Karnofsky performance scale of 70. The lateral approaches were most frequently used (74.9%), followed by the interhemispheric (24.2%). Gross total and subtotal/partial resections were achieved in 81%, and 19% of all cases, respectively. New permanent neurological deficits were observed in 51/433 patients (11.8%). individual patient data was pooled from 5 studies (n = 71). In the multivariate analysis, tumors located within the posterior thalamus had worse median overall survival compared to anterior gliomas (14.5 vs. 27 months, P = 0.003). CONCLUSIONS: Surgical resection of ATGs can increase survival but at the risk of operative morbidity. Knowing which factors impact survival may allow neurosurgeons to propose a more evidence-based treatment to their patients.

Implementing competency based admissions at the Albert Einstein College of Medicine.

The Albert Einstein College of Medicine (Einstein) was founded in 1955 during an era of limited access to medical school for women, racial minorities, and many religious and ethnic groups. Located in the Bronx, NY, Einstein seeks to educate physicians in an environment of state-of-the-art scientific inquiry while simultaneously fulfilling a deep commitment to serve its community by providing the highest quality clinical care. A founding principle of Einstein, the basis upon which Professor Einstein agreed to allow the use of his name, was that admission to the student body would be based entirely on merit. To accomplish this, Einstein has long used a 'holistic' approach to the evaluation of its applicants, actively seeking a diverse student body. More recently, in order to improve its ability to identify students with the potential to be outstanding physicians, who will both advance medical knowledge and serve the pressing health needs of a diverse community, the Committee on Admissions reexamined and restructured the requirements for admission. These have now been categorized as four 'Admissions Competencies' that an applicant must demonstrate. They include: 1) cocurricular activities and relevant experiences; 2) communication skills; 3) personal and professional development; and 4) knowledge. The purpose of this article is to describe the process that resulted in the introduction and implementation of this competency based approach to the admission process.

Ambulatory high-dose methotrexate administration among pediatric osteosarcoma patients in an urban, underserved setting is feasible, safe, and cost-effective.

BACKGROUND: We describe the safety, feasibility, and provide a cost-estimate of outpatient high-dose methotrexate administration (HDMTX) among an urban, underserved population. PROCEDURE: A retrospective analysis of ambulatory HDMTX administration among osteosarcoma patients, at Montefiore Medical Center's Children's Hospital (Bronx, NY) was performed. HDMTX (12 g/m(2)) was given intravenously (IV) over 4 hr after urine alkalinization. Patients were discharged home to continue IV hydration and alkalinization delivered via a home infusion pump. Families were instructed to monitor urine pH overnight and management was adjusted according to our institution's treatment algorithm until MTX level ≤ 0.1 µmol/L. A cost estimate was performed to assess the difference in costs for outpatient versus hypothetical inpatient administrations. RESULTS: Of the 97 ambulatory HDMTX administrations, 99% were successfully completed. One patient failed outpatient administration secondary to home infusion pump malfunction. This patient successfully completed subsequent courses as an outpatient. Most patients (72%) had a MTX level of < 10 µmol/L at 24 hr post-HDMTX. No patients were found to have a MTX level of > 50 µmol/L at 24 hr. About 26% of courses were associated with grade III or IV neutropenia, 4% were associated with grade III or IV thrombocytopenia and 1% were associated with grade III/IV leukopenia. Compared to a hypothetical hospital inpatient stay, the hospital costs for ambulatory HDMTX were an average of $1400 less per cycle. CONCLUSION: Ambulatory HDMTX administration among an underserved, urban population is safe, feasible, and cost-effective.

Feasibility and response to induction chemotherapy intensified with high-dose methotrexate for young children with newly diagnosed high-risk disseminated medulloblastoma.

PURPOSE: To evaluate the feasibility of and response rate to an intensified induction chemotherapy regimen for young children with newly diagnosed high-risk or disseminated medulloblastomas. PATIENTS AND METHODS: From January 1997 to March 2003, 21 patients with high-risk or disseminated medulloblastoma were enrolled. After maximal surgical resection, patients were treated with five cycles of vincristine (0.05 mg/kg/wk x three doses per cycle for three cycles), cisplatin (3.5 mg/kg per cycle), etoposide (4 mg/kg/d x 2 days per cycle), cyclophosphamide (65 mg/kg/d x 2 days per cycle) with mesna, and methotrexate (400 mg/kg per cycle) with leucovorin rescue. Following induction chemotherapy, eligible patients underwent a single myeloablative chemotherapy cycle with autologous stem-cell rescue. RESULTS: Significant toxicities of this intensified regimen, including gastrointestinal and infectious toxicities, are described. Among the 21 patients enrolled, there were 17 complete responses (81%), two partial responses, one stable disease, and one progressive disease. The 3-year event-free survival and overall survival are 49% (95% CI, 27% to 72%) and 60% (95% CI, 36% to 84%), respectively. CONCLUSION: This intensified induction chemotherapy regimen is feasible and tolerable. With the majority of patients with disseminated medulloblastoma having M2 or M3 disease at diagnosis, the encouraging high response rate of this intensified induction regimen suggests that such an addition of methotrexate should be explored in future studies.