A Scoping Review of Focused Ultrasound Enhanced Drug Delivery for Across the Blood-Brain Barrier for Brain Tumors.

BACKGROUND AND OBJECTIVES: Previous mechanisms of opening the blood-brain barrier (BBB) created a hypertonic environment. Focused ultrasound (FUS) has recently been introduced as a means of controlled BBB opening. Here, we performed a scoping review to assess the advances in drug delivery across the BBB for treatment of brain tumors to identify advances and literature gaps. METHODS: A review of current literature was conducted through a MEDLINE search inclusive of articles on FUS, BBB, and brain tumor barrier, including human, modeling, and animal studies written in English. Using the Rayyan platform, 2 reviewers (J.P and C.Y) identified 967 publications. 224 were chosen to review after a title screen. Ultimately 98 were reviewed. The scoping review was designed to address the following questions: (1) What FUS technology improvements have been made to augment drug delivery for brain tumors? (2) What drug delivery improvements have occurred to ensure better uptake in the target tissue for brain tumors? RESULTS: Microbubbles (MB) with FUS are used for BBB opening (BBBO) through cavitation to increase its permeability. Drug delivery into the central nervous system can be combined with MB to enhance transport of therapeutic agents to target brain tissue resulting in suppression of tumor growth and prolonging survival rate, as well as reducing systemic toxicity and degradation rate. There is accumulating evidence demonstrating that drug delivery through BBBO with FUS-MB improves drug concentrations and provides a better impact on tumor growth and survival rates, compared with drug-only treatments. CONCLUSION: Here, we review the role of FUS in BBBO. Identified gaps in the literature include impact of tumor microenvironment and extracellular space, improved understanding and control of MB and drug delivery, further work on ideal pharmacologics for delivery, and clinical use.

Clinical Outcomes and Treatment Patterns in Adults With FLT3-ITDmut+ Acute Myeloid Leukemia Undergoing Allogeneic Hemopoietic Cell Transplantation in the United States and Canada.

Allogeneic hematopoietic cell transplantation (alloHCT) is used to treat patients with acute myeloid leukemia (AML) with internal tandem duplication of the FMS-like tyrosine kinase 3 gene (FLT3-ITDmut+). However, the effect of different characteristics on outcomes after transplant is not fully understood. The aim of this study was to determine the impact of patient, disease, and transplant characteristics on clinical outcomes and trends in maintenance therapy for patients with FLT3-ITDmut+ AML who underwent their first alloHCT. This was an observational cohort study of adults ≥18 years who were recipients of human leukocyte antigen identical sibling, haploidentical, 8/8 or 7/8 unrelated, or cord blood donor alloHCT in the United States and Canada between 2014 and 2019. Patient, disease, and transplant characteristics were collected from Center for International Blood & Marrow Transplant Research between 2014 and 2022. Patients enrolled in the MORPHO clinical trial (NCT02997202) were excluded. Clinical outcomes were measured from the time of alloHCT by disease status: first complete remission (CR1), second or greater complete remission (≥CR2), or relapsed/refractory (R/R). The primary endpoints of this study were overall survival (OS) and leukemia-free survival (LFS). Key secondary endpoints included relapse after alloHCT, nonrelapse mortality (NRM), time from diagnosis to complete remission, time from complete remission to alloHCT, and maintenance therapy before and after alloHCT. Univariate analyses were conducted with Gray's test and log-rank test, while multivariable analyses were conducted using Cox proportional hazards models. A total of 3147 eligible patients (CR1, n = 2389; ≥CR2, n = 340; R/R, n = 418) were included. Most patient, disease, and transplant characteristics were similar between different disease statuses. In univariate analyses, disease status of CR1 compared with ≥CR2 or R/R was significantly (P < .001) associated with improved OS and LFS, and decreased probability of relapse; NRM likely differed across cohorts after alloHCT (P = .003). In multivariable analyses, patients with a disease status of ≥CR2 and R/R compared with CR1 had significantly shorter OS (hazard ratio [HR] 95% confidence interval [CI], 1.43 [1.19 to 1.72], P = .0001, and 2.14 [1.88 to 2.44], P < .0001, respectively). Patients with a disease status of CR1 at ≤2.6 months had better LFS compared with ≥CR2 and R/R (HR [95% CI], 2.03 [1.56 to 2.63], P < .0001 and 3.98 [3.07 to 5.17], P < .0001, respectively). Patients with a ≥CR2 or R/R disease status at ≤2.6 months had an increased likelihood of relapse compared with CR1 (HR [95% CI], 2.46 [1.82 to 3.33], P < .0001 and 4.68 [3.46 to 6.34], P < .0001, respectively). Disease status was not significantly associated with NRM. We also identified several additional patient, disease, and transplant characteristics that may have been associated with inferior OS and/or LFS and greater relapse and/or NRM. Maintenance therapy usage after alloHCT increased from 2014 to 2019 primarily due to increased FLT3 inhibitor use. In this largest study to date of patients from the United States and Canada with FLT3-ITDmut+ AML, disease status of CR1 at the time of alloHCT was associated with better clinical outcomes. Additional factors were identified that may also impact clinical outcomes, and in total, have the potential to inform clinical decision-making.

Shots at goal in Australian Football: Historical trends, determinants of accuracy and common strategies.

OBJECTIVES: To understand the historical context of and relationships between, the characteristics of shots at goal and match outcome in the Australian Football League. DESIGN: Observational. METHODS: Descriptive statistics of shots at goal were calculated and compared across 20 seasons. The location, type, and outcome of all shots at goal (n = 43,254), by all teams (2017-19 & 21), were compared with match outcome. RESULTS: The total number of shots per match and the accuracy of shots haven't changed in two decades. Most teams win by having more shots at goal (Wilcoxon-r effect size 0.63) than their opponent (i.e. "majority strategy") and of these, the number of open shots (0.48) is slightly more important than set shots (0.43), followed by shot accuracy (0.29). However, some teams (14 %) win by taking fewer shots at goal from field locations with a higher likelihood of scoring a goal (i.e. "minority strategy"). Arc angle and shot type can be used to predict the outcome of a shot at goal with 60.3 % classification accuracy. The novel shot-outcome prediction model reported here provides a better opportunity to evaluate goal kicking performance of teams and players, because it accounts for the type and difficulty of the shot. CONCLUSIONS: Teams can evaluate the shot accuracy of their players more fairly, by accounting for shot location using the method reported here. Coaches can compare the two shot strategies identified and implement the one that suits the skill profile of their players and increase their likelihood of winning.

Comparison of Healthcare Costs for Women with Treated Versus Untreated Vasomotor Symptoms Due to Menopause.

INTRODUCTION: The study objective was to estimate all-cause healthcare resource utilization (HCRU) and medical and pharmacy costs for women with treated versus untreated vasomotor symptoms (VMS) due to menopause. METHODS: A retrospective study was conducted using US claims data from Optum Research Database (study period: January 1, 2012-February 29, 2020). Women aged 40-63 years with a VMS diagnosis claim and ≥ 12 and ≥ 18 months of continuous enrollment during baseline and follow-up periods, respectively, were included. Women treated for VMS were propensity score matched 1:1 to untreated controls with VMS. Standardized differences (SDIFF) ≥ 10% were considered meaningful. A generalized linear model (gamma distribution, log link, robust standard errors) estimated the total cost of care ratio. Subgroup analyses of on- and off-label treatment costs were conducted. RESULTS: Of 117,582 women diagnosed with VMS, 20.5% initiated VMS treatment and 79.5% had no treatment. Treated women (n = 24,057) were matched to untreated VMS controls. There were no differences in HCRU at follow-up (SDIFF < 10%). Pharmacy ($487 vs $320, SDIFF 28.4%) and total ($1803 vs $1536, SDIFF 12.6%) costs were higher in the treated cohort. Total costs were 7% higher in the treated cohort (total cost ratio 1.07, 95% CI 1.05-1.10, P < 0.001). The on-label treatment pharmacy costs ($546 versus $315, SDIFF 38.6%) were higher in the treated cohort. Off-label treatment had higher medical costs ($1393 versus $1201, SDIFF 10.4%). CONCLUSIONS: Most women with VMS due to menopause were not treated within 6 months following diagnosis. While both on- and off-label treatment increased the total cost of care compared with untreated controls, those increases were modest in magnitude and should not impede treatment for women who report symptom improvement as a result of treatment.

Treatment Patterns and FLT3 Mutation Testing Among Patients with Acute Myeloid Leukemia in China: A Retrospective Observational Study.

Introduction: For acute myeloid leukemia (AML), prognosis is particularly poor in patients harboring FMS-like tyrosine kinase 3 (FLT3) gene mutations, though routine screening for these mutations at diagnosis has been shown to be insufficient. The understanding of the impact of FLT3 mutations on treatment decisions is limited. Methods: In this retrospective, observational study, we investigated the key epidemiological characteristics, treatment patterns and responses among adult patients with newly diagnosed (ND) AML in China, who initiated treatment from January 1, 2015, to December 31, 2019, or progressed to relapsed/refractory (R/R) AML by December 31, 2020. Results: Of the 853 ND AML patients included, 63.4% were screened for FLT3 status, and 20.1% tested positive (FLT3MUT) at initial diagnosis. Of 289 patients who progressed to R/R AML during the study period, 24.9% were screened at the diagnosis of R/R AML, and 19.4% tested positive; 20.5% of screened patients changed FLT3 status at first diagnosis of R/R AML. Initial treatment regimens or treatment responses did not seem to differ in patients with ND AML by FLT3 mutation status. In patients with R/R AML, there was an apparent difference in second-line treatment choices by FLT3 mutation status; however, the number of FLT3-mutated patients were limited to demonstrate any meaningful distinction. FLT3-mutated R/R AML was associated with shorter relapse time. Conclusion: Study findings showed that there was a lack of routine testing for FLT3 mutations at first diagnosis of R/R AML, and initial treatment decisions did not differ by FLT3 mutation status. Given the clinical burden of FLT3MUT, likelihood of FLT3 status changes, and emerging FLT3 inhibitors, further routine FLT3 screening is needed to optimize treatment of R/R AML.

Anal fissures: An update on treatment options.

BACKGROUND: Anal fissure (AF) is the second most common anorectal complaint in healthcare settings. The presentation might be acute or chronic, characterised by severe pain with defaecation that persists for one to two hours. Non-surgical and surgical interventions are available based on the severity and persistence of the fissure. OBJECTIVE: The aim of this article is to review the pathophysiology, clinical presentation and management of AF under current guidelines. DISCUSSION: The aetiology of AF is unclear, although it is commonly associated with local trauma or associated chronic conditions. Acute AF is first treated with conservative therapy, including dietary fibre and sitz baths. Addition of topical nitrates, topical calcium channel blockers or botulinum toxin injection is indicated with failure of conservative treatment or at medical discretion. Surgical options are considered if AF persists despite treatment. Most present as hypertonic, but special consideration is needed for hypotonic or secondary presentations.

Guidelines to the Practice of Anesthesia-Revised Edition 2024.

OVERVIEW: The Guidelines to the Practice of Anesthesia-Revised Edition 2024 (the Guidelines) were prepared by the Canadian Anesthesiologists' Society (CAS), which reserves the right to determine their publication and distribution. The Guidelines are subject to revision and updated versions are published annually. The Guidelines to the Practice of Anesthesia-Revised Edition 2024 supersede all previously published versions of this document. Although the CAS encourages Canadian anesthesiologists to adhere to its practice guidelines to ensure high-quality patient care, the CAS cannot guarantee any specific patient outcome. Anesthesiologists should exercise their own professional judgement in determining the proper course of action for any patient's circumstances. The CAS assumes no responsibility or liability for any error or omission arising from the use of any information contained in its Guidelines to the Practice of Anesthesia.

RéSUMé: Le Guide d'exercice de l'anesthésie, version révisée 2024 (le Guide), a été préparé par la Société canadienne des anesthésiologistes (SCA), qui se réserve le droit de décider des termes de sa publication et de sa diffusion. Le Guide est soumis à révision et des versions mises à jour sont publiées chaque année. Le Guide d'exercice de l'anesthésie, version révisée 2024, remplace toutes les versions précédemment publiées de ce document. Bien que la SCA incite les anesthésiologistes du Canada à se conformer à son guide d'exercice pour assurer une grande qualité des soins dispensés aux patient·es, elle ne peut garantir les résultats d'une intervention spécifique. Les anesthésiologistes doivent exercer leur jugement professionnel pour déterminer la méthode d'intervention la mieux adaptée à l'état de leur patient·e. La SCA n'accepte aucune responsabilité ou imputabilité de quelque nature que ce soit découlant d'erreurs ou d'omissions ou de l'utilisation des renseignements contenus dans son Guide d'exercice de l'anesthésie.

Work absenteeism, disability, and lost wages among patients with acute myeloid leukemia and their caregivers: a cohort study using US administrative claims and productivity data.

OBJECTIVE: We describe the impact of acute myeloid leukemia (AML) diagnosis on workplace absenteeism and disability days among patients and their caregivers. METHODS: This retrospective study included adults with newly diagnosed AML (2009-2019) and adult caregivers of patients with newly diagnosed AML, identified from the US Merative™ MarketScan® Commercial Database. The Merative MarketScan Health and Productivity Management Database provided linked patient-level records of workplace absence and short-term (STD) and long-term disability (LTD) data. Endpoints included workplace absence, STD and LTD for patients and caregivers during 12 months pre-AML (baseline) and ≤3 years' follow-up, and corresponding cost of work loss. RESULTS: Patient workplace absence decreased in the months post-AML diagnosis, but the number of STD and LTD leave days claimed increased significantly by sixfold and fourfold, respectively. The proportion of patients making STD leave claims increased within 4-5 months of diagnosis, while the proportion making LTD leave claims increased significantly starting from month 5. Caregiver workplace absence peaked in the first 2 months post-diagnosis and remained elevated versus baseline throughout the study. CONCLUSION: AML diagnosis leads to workplace absenteeism and increased economic burden for patients with AML and their caregivers.

Ileal pouch-anal anastomosis provides good functional and quality of life outcomes following proctocolectomy: A 33-year single centre experience.

BACKGROUND: Restorative proctocolectomy (RP) with ileal pouch-anal anastomosis (IPAA) remains the gold standard for the surgical management of patients with medically refractive mucosal ulcerative colitis. We aimed to identify functional and quality of life (QOL) outcomes in RP and IPAA surgery patients at our institution. METHODS: A retrospective observational study was performed including all patients who had undergone RP and IPAA between August 1984 and November 2017 at Royal Prince Alfred Hospital (RPAH). RESULTS: 316 consecutive patients were identified, median age 39 (range 5 to 81) years. The median duration of disease was 60 (range 1 to 528) months. Ulcerative colitis was the main preoperative diagnosis with the main RP indication being failure of medical treatment. The median postoperative stay post-IPAA was 11 (range of 5 to 67) days. Pouchitis was the most common late complication (22.1%), bleeding pouch (3.5%) the earliest, with a 6.8% rate of symptomatic anastomotic leak. Visual analogue scale QOL measure (P-value <0.001), St Marks incontinence score (P-value = 0.001) and Cleveland clinic score (P-value = 0.002) all revealed significant improvement in functional outcomes and QOL. CONCLUSION: QOL and functional outcomes following RP with IPAA in patients at our institution are excellent and comparable to institutions with larger patient numbers.

Cost-Effectiveness of a Direct-Aspiration First-Pass Technique versus Stent Retriever in Mechanical Thrombectomy.

OBJECTIVE: A direct-aspiration first-pass technique (ADAPT) in mechanical thrombectomy has been described in recent studies as an efficacious strategy compared with using a stent retriever (SR). We sought to evaluate for cost differences of ADAPT technique versus SR as an initial approach. METHODS: We conducted a retrospective analysis of consecutive patients with mechanical thrombectomy at our institution between 2022 and 2023. Patients were grouped into ADAPT with/without SR as a rescue strategy and SR as an initial approach with allowance of concomitant aspiration. Direct cost data (consumables) were obtained. Baseline demographics, stroke metrics, procedure outcomes and cost, and last follow-up outcomes in modified Rankin Scale were compared between 2 groups. RESULTS: Fifty-six patients were included. Thirty-seven (66.1%) underwent ADAPT, with 11 (29.7%) eventually requiring an SR. Mean age was 64.8 years. The average National Institutes of Health Stroke Scale score was 13.2 in the ADAPT group and 14.0 in the SR group (P = 0.68), with a similar proportion of tissue plasminogen activator (P = 0.53), site of occlusion (P = 0.66), and tandem occlusion (P = 0.69) between the groups. Recanalization was achieved in 94.6% of all patients, with an average of 1.9 passes, 89.3% being TICI 2B or above, with no differences between the 2 groups. Significantly lower cost (P < 0.01) was observed in ADAPT ($14,243.4) compared with SR ($19,003.6). Average follow-up duration was 180.2 days, with mortality of 23.2%. At last follow-up, 55.4% remained functionally independent (modified Rankin Scale score <3) with no difference (P = 0.56) between the ADAPT (59.5%) and SR (47.4%) groups. CONCLUSIONS: Outcomes were comparable between the ADAPT and SR groups. ADAPT reduced procedural consumables cost by approximately $5000 (25%), even if stent retrievers were allowed to be used for rescue. Establishing ADPAT as initial approach may bring significant direct cost savings while obtaining similar outcomes.

Understanding passing network characteristics and their link to match outcome in elite Netball.

Player interactions in Netball are critical during attacking phases of play to ensure possession is maintained and scoring opportunities are created. This study aims to analyse the characteristics of the passing networks of elite Netball teams and their association with performance outcomes (i.e., win/loss and final margin). Five network metrics used to represent the characteristics of teamwork were calculated for all team performances (n = 112) from one season of professional Netball in Australia. A two-way ANOVA and multiple linear modelling were used to compare characteristics between teams and match outcomes and to predict score margin, respectively. Pass density (F = 65.09, df = 102, p < .001) and pass centrality (F = 7.61, df = 102, p < .01) differed (were higher) in wins/losses. They were also statistically significant contributors (p ≤ .005) to the linear model that predicted a score margin (R2 = .731). Key player centrality and mutual connectedness were different between teams but did not differ by match outcome. The results suggest that, ideally, Netball teams should maximise the number of connections between player pairings, while also relying on a subset of players to be heavily involved in passing sequences. Team cohesion (via passing) therefore appears to be an important measure of team success in elite Netball.

Incidence of Infections, Explantations, and Displacements/Mechanical Complications of Spinal Cord Stimulation During the Past Eight Years.

OBJECTIVES: The overall awareness and potential of real-world data have drastically increased in the medical field, with potential implications for postmarket medical device surveillance. The goal of this study was to evaluate real-world data on incidence of infections, explantations, and displacements/mechanical complications of spinal cord stimulation (SCS) during the past eight years and to forecast point estimates for the upcoming three years on the basis of the identified patterns. MATERIALS AND METHODS: Based on electronic health records from 80 healthcare organizations within the TriNetX data base in the USA, data of 11,934 patients who received SCS as treatment for persistent spinal pain syndrome type 2 (PSPS T2) were extracted. Events of interest were explantations and displacements/mechanical complications of both the lead and implanted pulse generator (IPG), in addition to infection rates from 2015 to 2022. Mann-Kendall tests were performed to detect monotonic trends in the time series. Forecasts were conducted for the upcoming three years for every event of interest. RESULTS: Statistically significant increasing time trends were revealed for the annual incidence of IPG and lead displacements/mechanical complications in patients with PSPS T2 over the past eight years. These time trends were visible in both male and female patients and in smokers and nonsmokers. For annual incidence of explantations and infections, no significant time effect was observed. In 2025, the incidence of displacements/mechanical complications of the lead (3.07%) is predicted to be the highest, followed by explantations of the IPG (2.67%) and lead (2.02%). CONCLUSIONS: Based on real world data, device explantation was the most frequent event of interest, with negative peaks in the time series in 2016 and 2020, presumably due to the introduction of rechargeable pulse generators and to the COVID-19 pandemic, respectively.

Acute Extra-Arachnoid Subdural Hematomas in Patients 50 Years and Older: When Subdurals Act Like Epidurals.

BACKGROUND: Some patients with subdural hematoma (SDH) with acute extra-arachnoid lesions and without concomitant subarachnoid blood or contusions may present in similarly grave neurological condition compared with the general population of patients with SDH. However, these patients often make an impressive neurological recovery. This study compared neurological outcomes in patients with extra-arachnoid SDH with all other SDH patients. METHODS: We compared a prospective series of extra-arachnoid SDH patients without subarachnoid hemorrhage or other concomitant intracranial injury with a Transforming Research and Clinical Knowledge in TBI control group with SDH only. We performed inverse probability weighting for key characteristics and ordinal regression with and without controlling for midline shift comparing neurological outcomes (Extended Glasgow Outcome Scale score) at 2 weeks. We used the Corticosteroid Randomization After Significant Head Injury prognostic model to predict mortality based on age, Glasgow Coma Scale score, pupil reactivity, and major extracranial injury. RESULTS: Mean midline shift was significantly different between extra-arachnoid SDH and control groups (7.2 mm vs. 2.7 mm, P < 0.001). After weighting for group allocation and controlling for midline shift, extra-arachnoid SDH patients had 5.68 greater odds (P < 0.001) of a better 2-week Extended Glasgow Outcome Scale score than control patients. Mortality in the extra-arachnoid SDH group was less than predicted by the Corticosteroid Randomization After Significant Head Injury prognostic model (10% vs. 21% predicted). CONCLUSIONS: Patients with extra-arachnoid SDH have significantly better 2-week neurological outcomes and lower mortality than predicted by the Corticosteroid Randomization After Significant Head Injury model. Neurosurgeons should consider surgery for this patient subset even in cases of poor neurological examination, older age, and large hematoma with high degree of midline shift.

Non-surgical Treatment of Capsular Contracture by Overfilling a Spectrum™ Saline Implant.

Capsular contracture is one of the most common complications following breast implant use in both aesthetic and reconstructive surgery procedures. Furthermore, capsular contracture remains one of the most common causes of reoperation in these patients. Therefore, it is important to identify and explore new treatment options to alleviate the risks associated with surgery as well as the financial burden of reoperation. We present a case of successful nonsurgical treatment of capsular contracture by overfilling a Spectrum™ adjustable saline implant followed by volume reduction. A 53-year-old patient was examined in our clinic post bilateral mastectomy and immediate reconstruction adjustable Spectrum™ saline implants in the subglandular plane. Two years postoperatively, the patient presented with Grade III capsular contracture in her right breast. Treatment was administered by overfilling the 275cc implant with 250cc in the right breast to rupture the capsule. The implant was kept overexpanded for a total of 14 days. The volume was subsequently reduced with optimal patient satisfaction. The patient has not had a reoccurrence of capsular contracture in one year. The treatment of capsular contracture by overfilling and temporarily overexpanding a Spectrum™ adjustable saline is a promising technique that warrants further investigation.

Racial disparities in functional outcomes following mechanical thrombectomy in a cohort of patients with ischemic stroke.

BACKGROUND: Non-Hispanic Black (NHB) patients experience increased prevalence of stroke risk factors and stroke incidence compared with non-Hispanic White (NHW) patients. However, little is known about >90-day post-stroke functional outcomes following mechanical thrombectomy. OBJECTIVE: To describe patient characteristics, evaluate stroke risk factors, and analyze the adjusted impact of race on long-term functional outcomes to better identify and limit sources of disparity in post-stroke care. METHODS: We retrospectively reviewed 326 patients with ischemic stroke who underwent thrombectomy at two centers between 2019 and 2022. Race was self-reported as NHB, NHW, or non-Hispanic Other. Stroke risk factors, insurance status, procedural parameters, and post-stroke functional outcomes were collected. Good outcomes were defined as modified Rankin Scale score ≤2 and/or discharge disposition to home/self-care. To assess the impact of race on outcomes at 3-, 6-, and 12-months' follow-up, we performed univariate and multivariate logistic regression. RESULTS: Patients self-identified as NHB (42%), NHW (53%), or Other (5%). 177 (54.3%) patients were female; the median (IQR) age was 67.5 (59-77) years. The median (IQR) National Institutes of Health Stroke Scale score was 15 (10-20). On univariate analysis, NHB patients were more likely to have poor short- and long-term functional outcomes, which persisted on multivariate analysis as significant at 3 and 6 months but not at 12 months (3 months: OR=2.115, P=0.04; 6 months: OR=2.423, P=0.048; 12 months: OR=2.187, P=0.15). NHB patients were also more likely to be discharged to rehabilitation or hospice/death than NHW patients after adjusting for confounders (OR=1.940, P=0.04). CONCLUSIONS: NHB patients undergoing thrombectomy for ischemic stroke experience worse 3- and 6-month functional outcomes than NHW patients after adjusting for confounders. Interestingly, this disparity was not detected at 12 months. Future research should focus on identifying social determinants in the short-term post-stroke recovery period to improve parity in stroke care.

Healthcare resource utilization and costs during first salvage therapy for relapsed or refractory acute myeloid leukemia in the United States.

Real-world US healthcare resource utilization (HRU) and costs during first salvage therapy for relapsed/refractory (R/R) acute myeloid leukemia (AML) are described using IBM MarketScan® data (1/1/2007-6/30/2020). Treatments included high- (HIC) and low-intensity chemotherapy (LIC) alone, and gilteritinib, other FLT3 tyrosine kinase inhibitors (TKIs), and venetoclax with or without chemotherapy. Patients were diagnosed with R/R AML at ≥18 years of age between 1/1/2017-12/31/2019. Patient monthly all-cause HRU and costs were analyzed using a fixed-effects model. Data from 399 patients were analyzed (HIC, n = 104; LIC, n = 133; gilteritinib, n = 14; other FLT3 TKIs, n = 68; venetoclax, n = 80). Inpatient HRU was generally highest with HIC, whereas outpatient HRU was generally highest with LIC and venetoclax. Total all-cause incremental monthly costs appeared to be highest with HIC ($171,982) and similar for LIC ($60,512), gilteritinib ($47,218), other FLT3 TKIs ($43,218), and venetoclax ($77,566). Results highlight HRU and cost differences for R/R AML during first salvage therapy.

Clinical outcomes of pediatric hemispherectomy following unsuccessful subhemispheric resection for refractory epilepsy: a case review study.

OBJECTIVE: Epilepsy surgery remains one of the most underutilized procedures in epilepsy despite its proven superiority to other available therapies. This underutilization is greater in patients in whom initial surgery fails. This case series examined the clinical characteristics, reasons for initial surgery failure, and outcomes in a cohort of patients who underwent hemispherectomy following unsuccessful smaller resections for intractable epilepsy (subhemispheric group [SHG]) and compared them to those of a cohort of patients who underwent hemispherectomy as the first surgery (hemispheric group [HG]). The objective of this paper was to determine the clinical characteristics of patients in whom a small, subhemispheric resection failed, who went on to become seizure free after undergoing a hemispherectomy. METHODS: Patients who underwent hemispherectomy at Seattle Children's Hospital between 1996 and 2020 were identified. Inclusion criteria for SHG were as follows: 1) patients ≤ 18 years of age at the time of hemispheric surgery; 2) initial subhemispheric epilepsy surgery that did not produce seizure freedom; 3) hemispherectomy or hemispherotomy after the subhemispheric surgery; and 4) follow-up for at least 12 months after hemispheric surgery. Data collected included the following: patient demographics; seizure etiology; comorbidities; prior neurosurgeries; neurophysiological studies; imaging studies; and surgical details-plus surgical, seizure, and functional outcomes. Seizure etiology was classified as follows: 1) developmental, 2) acquired, or 3) progressive. The authors compared SHG to HG in terms of demographics, seizure etiology, and seizure and neuropsychological outcomes. RESULTS: There were 14 patients in the SHG and 51 patients in the HG. All patients in the SHG had Engel class IV scores after their initial resective surgery. Overall, 86% (n = 12) of the patients in the SHG had good posthemispherectomy seizure outcomes (Engel class I or II). All patients in the SHG who had progressive etiology (n = 3) had favorable seizure outcomes, with eventual hemispherectomy (1 each with Engel classes I, II, and III). Engel classifications posthemispherectomy between the groups were similar. There were no statistical differences in postsurgical Vineland Adaptive Behavior Scales Adaptive Behavior Composite scores or postsurgical full-scale IQ scores between groups when accounting for presurgical scores. CONCLUSIONS: Hemispherectomy as a repeat surgery after unsuccessful subhemispheric epilepsy surgery has a favorable seizure outcome, with stable or improved intelligence and adaptive functioning. Findings in these patients are similar to those in patients who had hemispherectomy as their first surgery. This can be explained by the relatively small number of patients in the SHG and the higher likelihood of hemispheric surgeries to resect or disconnect the entire epileptogenic lesion compared to smaller resections.