Pulmonary Embolism With Syncope Treated With Inari FlowTriever®.

Pulmonary embolism (PE) is a devastating disease that can range in severity from asymptomatic to fatal. The severity and the intervention required depend on the degree of hemodynamic instability and evidence of right heart strain demonstrated on diagnostic testing. Interventions include solely anticoagulation, systemic thrombolysis, catheter-directed therapies, or surgical embolectomy depending on the severity, patient's clinical picture, and clinician choice. Currently, there is a lack of evidence regarding which treatment is most suitable for submassive PE. This report demonstrates the benefits of aspiration thrombectomy, a catheter-directed therapy, utilizing the 24Fr Triever Aspiration Catheter (FlowTriever® system;Inari Medical, Irvine, California, United States) in a 57-year-old male patient with submassive PE. The FlowTriever retrieval/aspiration system is a single-use mechanical thrombectomy device indicated for use in the peripheral vasculature and pulmonary arteries. The patient presented with syncope and concern for head trauma ultimately requiring suction embolectomy utilizing the Inari FlowTriever system. We conclude that submassive PE can be effectively treated with aspiration thrombectomy in addition to long-term anticoagulation with excellent clinical outcomes.

Diverse Proteomimetic Frameworks via Rational Design of π-Stacking Peptide Tectons.

Peptide-based frameworks aim to integrate protein architecture into solid-state materials using simpler building blocks. Despite the growing number of peptide frameworks, there are few strategies to rationally engineer essential properties like pore size and shape. Designing peptide assemblies is generally hindered by the difficulty of predicting complex networks of weak intermolecular interactions. Peptides conjugated to polyaromatic groups are a unique case where assembly appears to be strongly driven by π-π interactions, suggesting that rationally adjusting the geometry of the π-stackers could create novel structures. Here, we report peptide elongation as a simple mechanism to predictably tune the angle between the π-stacking groups to produce a remarkable diversity of pore shapes and sizes, including some that are mesoporous. Notably, rapid jumps in pore size and shape can occur with just a single amino acid insertion. The geometry of the π-stacking residues also significantly influences framework structure, representing an additional dimension for tuning. Lastly, sequence identity can also indirectly modulate the π-π interactions. By correlating each of these factors with detailed crystallographic data, we find that, despite the complexity of peptide structure, the shape and polarity of the tectons are straightforward predictors of framework structure. These guidelines are expected to accelerate the development of advanced porous materials with protein-like capabilities.

Lumbar disc herniation with radiculopathy: a comparison of NASS guidelines and ChatGPT.

Background: ChatGPT is an advanced language AI able to generate responses to clinical questions regarding lumbar disc herniation with radiculopathy. Artificial intelligence (AI) tools are increasingly being considered to assist clinicians in decision-making. This study compared ChatGPT-3.5 and ChatGPT-4.0 responses to established NASS clinical guidelines and evaluated concordance. Methods: ChatGPT-3.5 and ChatGPT-4.0 were prompted with fifteen questions from The 2012 NASS Clinical Guidelines for the diagnosis and treatment of lumbar disc herniation with radiculopathy. Clinical questions organized into categories were directly entered as unmodified queries into ChatGPT. Language output was assessed by two independent authors on September 26, 2023 based on operationally-defined parameters of accuracy, over-conclusiveness, supplementary, and incompleteness. ChatGPT-3.5 and ChatGPT-4.0 performance was compared via chi-square analyses. Results: Among the fifteen responses produced by ChatGPT-3.5, 7 (47%) were accurate, 7 (47%) were over-conclusive, fifteen (100%) were supplementary, and 6 (40%) were incomplete. For ChatGPT-4.0, ten (67%) were accurate, 5 (33%) were over-conclusive, 10 (67%) were supplementary, and 6 (40%) were incomplete. There was a statistically significant difference in supplementary information (100% vs. 67%; p=.014) between ChatGPT-3.5 and ChatGPT-4.0. Accuracy (47% vs. 67%; p=.269), over-conclusiveness (47% vs. 33%; p=.456), and incompleteness (40% vs. 40%; p=1.000) did not show significant differences between ChatGPT-3.5 and ChatGPT-4.0. ChatGPT-3.5 and ChatGPT-4.0 both yielded 100% accuracy for definition and history and physical examination categories. Diagnostic testing yielded 0% accuracy for ChatGPT-3.5 and 100% accuracy for ChatGPT-4.0. Nonsurgical interventions had 50% accuracy for ChatGPT-3.5 and 63% accuracy for ChatGPT-4.0. Surgical interventions resulted in 0% accuracy for ChatGPT-3.5 and 33% accuracy for ChatGPT-4.0. Conclusions: ChatGPT-4.0 provided less supplementary information and overall higher accuracy in question categories than ChatGPT-3.5. ChatGPT showed reasonable concordance to NASS guidelines, but clinicians should caution use of ChatGPT in its current state as it fails to safeguard against misinformation.

Atypical refractory occipital neuralgia treated with a unilateral dual-lead occipital nerve stimulator: a case report.

Aim: To describe the successful treatment of atypical occipital neuralgia (ON) using a unilateral dual-lead occipital nerve stimulator. Setting: Outpatient clinic/operating room. Patient: A 53-year-old male with atypical ON. Case description: Patient was previously diagnosed with treatment-refractory left-sided trigeminal neuralgia with atypical occipital distribution. On presentation, his symptoms were consistent with ON with distribution to the left fronto-orbital area. He received a left-sided nerve stimulator implant targeting both the greater and lesser occipital nerves. Results: Patient reported pain relief from a numerical rating scale 10/10 to 3-4/10. Conclusion: ON with referred ipsilateral trigeminal distribution should be considered when patients present with simultaneous facial and occipital pain. Further, a dual-lead unilateral stimulator approach may be a viable treatment.

Atypical, persistent inflammation to the left occipital nerve treated with a neuromodulator: a case reportAim: To describe the successful treatment of atypical headache using a one-sided nerve stimulator. Setting: Outpatient clinic/operating room. Patient: A 53-year-old male with atypical headache. Case description: Patient was previously diagnosed with left-sided chronic facial pain with pain to the back of the head. He previously failed to improve with medication and underwent Botox injections and several surgical operations targeting the nerves responsible for his pain symptoms with no improvement. He recently underwent a nerve-stimulating device trial, designed to alter the activity levels of the targeted nerve, that targeted a nerve in the back of his head. This significantly improved his pain and he ultimately presented for an official stimulator implant. Upon presentation, his symptoms were consistent with left-sided headache to the back of the head with distribution to the left eye area. Results: Patient reported significant pain relief from 10/10 to a 3-4/10, with a 10 representing the worst pain the patient has ever felt. Conclusion: Left-sided headache on the back of the head that can distribute to the left eye area should be a consistent thought for pain/headache practitioners. Further, this stimulator placement approach may be a viable treatment.

Cost-effectiveness of sutimlimab in cold agglutinin disease.

Primary cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia caused by cold-reactive antibodies that bind to red blood cells and lead to complement-mediated hemolysis. Patients with primary CAD experience the burden of increased health resource utilization and reduced quality of life. The standard-of-care (SOC) in patients with primary CAD has included cold avoidance, transfusion support, and chemoimmunotherapy. The use of sutimlimab, a humanized monoclonal antibody that selectively inhibits C1-mediated hemolysis, was shown to reduce transfusion-dependence and improve quality of life across two pivotal phase 3 studies, further supported by 2-year extension data. Using data from the transfusion-dependent patient population that led to sutimlimab's initial FDA approval, we performed the first-ever cost-effectiveness analysis in primary CAD. The projected incremental cost-effectiveness ratio (ICER) in our Markov model was $2 340 000/QALY, significantly above an upper-end conventional US willingness-to-pay threshold of $150 000/QALY. These results are consistent across scenarios of higher body weight and a pan-refractory SOC patient phenotype (i.e., treated sequentially with bendamustine-rituximab, bortezomib, ibrutinib, and eculizumab). No parameter variations in deterministic sensitivity analyses changed our conclusion. In probabilistic sensitivity analysis, SOC was favored over sutimlimab in 100% of 10 000 iterations. Exploratory threshold analyses showed that significant price reduction (>80%) or time-limited treatment (<18 months) followed by lifelong clinical remission off sutimlimab would allow sutimlimab to become cost-effective. The impact of sutimlimab on health system costs with longer term follow-up data merits future study and consideration through a distributional cost-effectiveness framework.

Recurrence of Pulmonary Arteriovenous Malformation after Embolization in Patients with Pulmonary Hypertension.

PURPOSE: To evaluate the correlation between pulmonary hypertension (PH) and recurrence of pulmonary arteriovenous malformation (PAVM) after embolization. MATERIALS AND METHODS: With institutional review board (IRB) approval, the records of 377 patients with PAVMs evaluated at a single hereditary hemorrhagic telangiectasia (HHT) center of excellence between January 1, 2013, and September 10, 2023, were retrospectively reviewed. PAVMs embolized during this time period were evaluated for recurrence. Patients and PAVMs not treated during this time period were excluded. Growth of previously untreated PAVMs was not considered recurrence. Patients without chest computed tomography (CT) follow-up were excluded. General demographics, HHT status as defined by genetic testing or Curacao criteria, presence of PH, history of smoking, anemia, and hepatic arteriovenous malformations (AVMs) were documented. Odds ratio (OR) was calculated and stratified analysis was performed to assay the correlation between PAVM recurrence, PH, and possible confounders. RESULTS: A total of 151 patients with PAVMs were treated during the study period, including 438 PAVMs, for which follow-up was available. This included 106 patients with definite, 31 with doubtful, and 14 with possible HHT. The presence of PH was significantly associated with PAVM recurrence both by patient (OR, 8.13; 95% CI, 3.50-19.67) and by lesion (OR, 4.07; 95% CI, 2.14-7.91). Multivariate analysis demonstrated that this correlation was independent of several variables including HHT status, smoking history, presence of hepatic AVMs, and anemia. CONCLUSIONS: There is a high correlation between PH and PAVM recurrence, suspected to be due to high pulmonary artery pressures causing recanalization. PH may suggest the need for shorter surveillance intervals.

Consumption of Olive Oil and Diet Quality and Risk of Dementia-Related Death.

Importance: Age-standardized dementia mortality rates are on the rise. Whether long-term consumption of olive oil and diet quality are associated with dementia-related death is unknown. Objective: To examine the association of olive oil intake with the subsequent risk of dementia-related death and assess the joint association with diet quality and substitution for other fats. Design, Setting, and Participants: This prospective cohort study examined data from the Nurses' Health Study (NHS; 1990-2018) and Health Professionals Follow-Up Study (HPFS; 1990-2018). The population included women from the NHS and men from the HPFS who were free of cardiovascular disease and cancer at baseline. Data were analyzed from May 2022 to July 2023. Exposures: Olive oil intake was assessed every 4 years using a food frequency questionnaire and categorized as (1) never or less than once per month, (2) greater than 0 to less than or equal to 4.5 g/d, (3) greater than 4.5 g/d to less than or equal to 7 g/d, and (4) greater than 7 g/d. Diet quality was based on the Alternative Healthy Eating Index and Mediterranean Diet score. Main Outcome and Measure: Dementia death was ascertained from death records. Multivariable Cox proportional hazards regressions were used to estimate hazard ratios (HRs) and 95% CIs adjusted for confounders including genetic, sociodemographic, and lifestyle factors. Results: Of 92 383 participants, 60 582 (65.6%) were women and the mean (SD) age was 56.4 (8.0) years. During 28 years of follow-up (2 183 095 person-years), 4751 dementia-related deaths occurred. Individuals who were homozygous for the apolipoprotein ε4 (APOE ε4) allele were 5 to 9 times more likely to die with dementia. Consuming at least 7 g/d of olive oil was associated with a 28% lower risk of dementia-related death (adjusted pooled HR, 0.72 [95% CI, 0.64-0.81]) compared with never or rarely consuming olive oil (P for trend < .001); results were consistent after further adjustment for APOE ε4. No interaction by diet quality scores was found. In modeled substitution analyses, replacing 5 g/d of margarine and mayonnaise with the equivalent amount of olive oil was associated with an 8% (95% CI, 4%-12%) to 14% (95% CI, 7%-20%) lower risk of dementia mortality. Substitutions for other vegetable oils or butter were not significant. Conclusions and Relevance: In US adults, higher olive oil intake was associated with a lower risk of dementia-related mortality, irrespective of diet quality. Beyond heart health, the findings extend the current dietary recommendations of choosing olive oil and other vegetable oils for cognitive-related health.

Institutional Priority-Setting for Novel Drugs and Therapeutics: A Qualitative Systematic Review.

BACKGROUND: There is a lack of guidance on approaches to formulary management and funding for high-cost drugs and therapeutics by individual healthcare institutions. The objective of this review was to assess institutional approaches to resource allocation for such therapeutics, with a particular focus on paediatric and rare disease populations. METHODS: A search of Embase and MEDLINE was conducted for studies relevant to decision-making for off-formulary, high-cost drugs and therapeutics. Abstracts were evaluated for inclusion based on the Simple Multiple-Attribute Rating Techniques (SMART) criteria. A framework of 30 topics across 4 categories was used to guide data extraction and was based on findings from the initial abstract review and previous health technology assessment (HTA) publications. Reflexive thematic analysis was conducted using QSR NVivo 12 software. RESULTS: A total of 168 studies were included for analysis. Only 4 (2%) focused on paediatrics, while 21 (12%) centred on adults and the remainder (85%) did not specify. Thirty-two (19%) studies discussed the importance of high-cost therapeutics and 34 (23%) focused on rare/orphan drugs. Five themes were identified as being relevant to institutional decision-making for high-cost therapeutics: institutional strategy, substantive criteria, procedural considerations, guiding principles and frameworks, and operational activities. Each of these themes encompassed several sub-themes and was complemented by a sixth category specific to paediatrics and rare diseases. CONCLUSION: The rising cost of novel drugs and therapeutics underscores the need for robust, evidence-based, and ethically defensible decision-making processes for health technology funding, particularly at the hospital level. Our study highlights practices and themes to aid decision-makers in thinking critically about institutional, substantive, procedural, and operational considerations in support of legitimate decisions about institutional funding of high-cost drugs and therapeutics, as well as opportunities and challenges that exist for paediatric and rare disease populations.

Cost-effectiveness of prophylaxis with recombinant vs plasma-derived VWF in severe von Willebrand disease in the United States.

ABSTRACT: We evaluated the cost-effectiveness of prophylaxis with recombinant von Willebrand factor (rVWF) vs with plasma-derived von Willebrand factor (pdVWF) for patients with severe Von Willebrand disease. We found that rVWF is a cost-saving factor replacement compared with pdVWF across all willingness-to-pay thresholds in the United States.

Transurethral Resection of Bladder Tumor Outcomes Are Predicted by a 5-Item Frailty Index.

OBJECTIVE: To evaluate the mFI-5 as a predictor of postoperative outcomes following transurethral resection of bladder tumor (TURBT). METHODS: The National Surgical Quality Improvement Program database was queried for TURBT cases from 2015-2019. mFI-5 scores were calculated by assigning a point to chronic obstructive pulmonary disease, congestive heart failure, dependent functional status, hypertension, and diabetes. Patients were stratified by mFI-5 scores. Demographics and 30-day outcomes including Clavien-Dindo (CD) complications, mortality, and increased healthcare resource utilization (HCRU) were compared. HCRU outcomes included prolonged length of stay, unplanned readmission, and discharge to continued care. Multivariate regression assessed the predictive value of mFI-5 scores on outcomes. RESULTS: 40,278 TURBT cases were identified (mFI-5 =0: 12,400, mFI-5 =1: 17,328, mFI-5 =2: 9225, mFI-5 ≥3: 1416). Patients with higher mFI-5 scores were more likely to be older, male, White, and have larger tumors, all P < .05. Increasing mFI-5 scores resulted in increased frequency of all adverse outcomes, all P < .001. On multivariate analysis, mFI-5 ≥ 3 classification was a predictor of CD I/II (OR=1.280), CD IV (OR=2.539), mortality (OR=2.202), HCRU (OR=2.094), prolonged length of stay (OR=2.136), discharge to continued care (OR=3.401), and unplanned readmission (OR=1.705), all P < .05. A mFI-5 ≥ 3 demonstrated a sensitivity ranging from 6.0%-13.5% and a specificity ranging from 96.6%-97.0% for all outcomes. CONCLUSION: The mFI-5 is an easily ascertainable preoperative risk assessment tool that is a predictor of adverse clinical and HCRU outcomes following TURBT.

Cost-effectiveness of bevacizumab therapy in the care of patients with hereditary hemorrhagic telangiectasia.

ABSTRACT: No US Food and Drug Administration- or European Medicines Agency-approved therapies exist for bleeding due to hereditary hemorrhagic telangiectasia (HHT), the second-most common inherited bleeding disorder worldwide. The current standard of care (SOC) includes iron and red cell supplementation, alongside the necessary hemostatic procedures, none of which target underlying disease pathogenesis. Recent evidence has demonstrated that bleeding pathophysiology is amenable to systemic antiangiogenic therapy with the anti-vascular endothelial growth factor bevacizumab. Despite its high cost, the addition of longitudinal bevacizumab to the current SOC may reduce overall health care resource use and improve patient quality of life. We conducted, to our knowledge, the first cost-effectiveness analysis of IV bevacizumab in patients with HHT with the moderate-to-severe phenotype, comparing bevacizumab added to SOC vs SOC alone. The primary outcome was the incremental net monetary benefit (iNMB) reported over a lifetime time horizon and across accepted willingness-to-pay thresholds, in US dollar per quality-adjusted life year (QALY). Bevacizumab therapy accrued 9.3 QALYs while generating $428 000 in costs, compared with 8.3 QALYs and $699 000 in costs accrued in the SOC strategy. The iNMB of bevacizumab therapy vs the SOC was $433 000. No parameter variation and no scenario analysis, including choice of iron supplementation product, changed the outcome of bevacizumab being a cost-saving strategy. Bevacizumab therapy also saved patients an average of 133 hours spent receiving HHT-specific care per year of life. In probabilistic sensitivity analysis, bevacizumab was favored in 100% of all 10 000 Monte Carlo iterations across base-case and all scenario analyses. Bevacizumab should be considered for more favorable formulary placement in the care of patients with moderate-to-severe HHT.

Priority-setting for hospital funding of high-cost innovative drugs and therapeutics: A qualitative institutional case study.

OBJECTIVES: Rising costs of innovative drugs and therapeutics (D&Ts) have led to resource allocation challenges for healthcare institutions. There is limited evidence to guide priority-setting for institutional funding of high-cost D&Ts. This study sought to identify and elaborate on the substantive principles and procedures that should inform institutional funding decisions for high-cost off-formulary D&Ts through a case study of a quaternary care paediatric hospital. METHODS: Semi-structured, qualitative interviews, both virtual and in-person, were conducted with institutional stakeholders (i.e. staff clinicians, senior leadership, and pharmacists) (n = 23) and two focus groups at The Hospital for Sick Children in Toronto, Canada. Participants involved in, and impacted by, high-cost off-formulary drug funding decisions were recruited through stratified, purposive sampling. Participants were approached for study involvement between July 27, 2020 and June 7, 2022. Data was analysed through reflexive thematic analysis. RESULTS: Institutional resource allocation for high-cost D&Ts was identified as ethically challenging but critical to sustainable access to novel therapies. Important substantive principles included: 1) clinical evidence of safety and efficacy, 2) economic considerations (direct costs, opportunity costs, value for money), 3) ethical principles (social justice, professional/organizational responsibility), and 4) disease-specific considerations. Multidisciplinary deliberation was identified as an essential procedural component of decision-making. Participants identified tension between innovation and the need for evidence-based decision-making; clinician and institutional responsibilities; and value for money and social justice. Participants emphasized the role of health system-level funding allocation in alleviating the financial and moral burden of decision-making by institutions. CONCLUSIONS: This study identifies values and processes to aid in the development and implementation of institutional resource allocation frameworks for high-cost innovative D&Ts.

Clinical guidelines are silent on the recommendation of physical activity and exercise therapy for low back pain: A systematic review.

OBJECTIVES: To synthesise and evaluate the quality of the recommendations for exercise therapy and physical activity from guidelines for the prevention and/or management of low back pain. DESIGN: Systematic review. METHODS: Included clinical practice guidelines for the management of low back pain published between 2014 and 2022 and searched in 9 databases until September 2022. The quality of evidence was evaluated with the Appraisal of Guidelines, Research and Evaluation tool (AGREE-II instrument). RESULTS: After screening 3448 studies, 18 clinical practice guidelines were included in this review. Only five (27 %) guidelines were judged as having a satisfactory quality of evidence (i.e., rigour of development and applicability), and 13 (72 %) of guidelines are discussed and rated as critical. Regarding physical activity, no guidelines provided recommendations for the primary prevention of low back pain or incorporated adequate physical activity aspects considering type, dosage, frequency, and intensity. For exercises, all (100 %) guidelines recommended at least one type of supervised exercise in the management of low back pain, and 16 (88 %) provided an overall recommendation for people to stay active. CONCLUSIONS: Guidelines offer minimal or, sometimes, no detail regarding physical activity or specific exercise regimens for the management and prevention of low back pain. When some guidance is provided, the recommendations typically lack specificity concerning the type, intensity, duration, and frequency of exercise and, in many cases, they represent a combination of scarce available evidence and stakeholder perspectives.

Differences in cancer presentation, treatment, and mortality between rural and urban patients diagnosed with kidney cancer in the United States.

INTRODUCTION: Rural-urban discrepancies in care and outcomes for kidney cancer (KCa) in the United States remains poorly understood. Our study aims to improve our understanding of the influence of rurality on KCa outcomes in the United States by analyzing differences in presentation, treatment, and mortality between urban areas (UAs) and rural areas (RAs) in the Surveillance, Epidemiology, and End Results (SEERs) database. METHODS: SEERs data was queried from 2000 to 2019 for KCa patients. Patient counties were classified as UAs, rural adjacent areas (RAAs), or rural nonadjacent areas (RNAs) using Rural Urban Continuum Codes. Demographic, tumor characteristics, and treatment variables were compared. Propensity score matching was performed to create matched UA-RAA and UA-RNA cohorts. Multivariate regression evaluated rural-urban status as a predictor of treatment selection. Multivariate cox regression assessed the predictive value of rural-urban status for overall survival (OS) and cancer-specific survival (CSS). Kaplan-Meier analysis was used to generate survival curves for OS and CSS. RESULTS: 179,509 KCa patients were identified (UA = 87.0%, RAA = 7.7%, RNA = 5.3%). Patients in RAs were more likely to present with tumors of higher grade and stage than UAs. Following multivariate analysis, rural residency predicted undergoing nephrectomy (RAA: OR = 1.177, RNA: OR = 1.210) but was a negative predictor of receiving partial nephrectomy (RAA: OR = 0.744, RNA: OR = 0.717), all P < 0.001. Multivariate cox regression demonstrated that RAA or RNA residency was predictive of overall and cause-specific mortality. After matching, median OS was 151, 124, and 118 months for UA, RAA, and RNA cohorts respectively; mean CSS was 152, 147, and 144 months for UA, RAA, and RNA cohorts, respectively, all P < 0.001. Stage-specific analysis of CSS demonstrated significantly poorer CSS among RNA patients for localized, regionalized, and distant KCa after matching. Only RAA patients with localized KCa experienced significantly lower CSS than UA patients. CONCLUSIONS: Patients in RAs are more likely to present with advanced KCa at diagnosis compared to those in UAs and may also experience different treatment options including a lesser likelihood of undergoing partial nephrectomy. Rural patients with KCa also demonstrated significantly worse OS and CSS compared to their urban counterparts. Further patient-level studies are required to better understand the discrepancy in CSS between urban and rural patients diagnosed with KCa.

The genomic alterations in glioblastoma influence the levels of CSF metabolites.

Cerebrospinal fluid (CSF) analysis is underutilized in patients with glioblastoma (GBM), partly due to a lack of studies demonstrating the clinical utility of CSF biomarkers. While some studies show the utility of CSF cell-free DNA analysis, studies analyzing CSF metabolites in patients with glioblastoma are limited. Diffuse gliomas have altered cellular metabolism. For example, mutations in isocitrate dehydrogenase enzymes (e.g., IDH1 and IDH2) are common in diffuse gliomas and lead to increased levels of D-2-hydroxyglutarate in CSF. However, there is a poor understanding of changes CSF metabolites in GBM patients. In this study, we performed targeted metabolomic analysis of CSF from n = 31 patients with GBM and n = 13 individuals with non-neoplastic conditions (controls), by mass spectrometry. Hierarchical clustering and sparse partial least square-discriminant analysis (sPLS-DA) revealed differences in CSF metabolites between GBM and control CSF, including metabolites associated with fatty acid oxidation and the gut microbiome (i.e., carnitine, 2-methylbutyrylcarnitine, shikimate, aminobutanal, uridine, N-acetylputrescine, and farnesyl diphosphate). In addition, we identified differences in CSF metabolites in GBM patients based on the presence/absence of TP53 or PTEN mutations, consistent with the idea that different mutations have different effects on tumor metabolism. In summary, our results increase the understanding of CSF metabolites in patients with diffuse gliomas and highlight several metabolites that could be informative biomarkers in patients with GBM.

Comparison of Single-Port Robotic Donor Nephrectomy and Laparoscopic Donor Nephrectomy.

Purpose: To compare the intra- and postoperative outcomes of single-port robotic donor nephrectomies (SP RDNs) and laparoscopic donor nephrectomies (LDNs). Materials and Methods: We retrospectively reviewed our institutional database for patients who received LDN or SP RDN between September 2020 and December 2022. Donor baseline characteristics, intraoperative outcomes, postoperative outcomes, and recipient renal function were extracted and compared between LDN and SP RDN. SP RDN learning curve analysis based on operative time and graft extraction time was performed using cumulative sum analysis. Results: One hundred forty-four patients underwent LDN and 32 patients underwent SP RDN. LDN and SP RDN had similar operative times (LDN: 190.3 ± 28.0 minutes, SP RDN: 194.5 ± 35.1 minutes, p = 0.3253). SP RDN patients had significantly greater extraction times (LDN: 83.2 ± 40.3 seconds, SP RDN: 204.1 ± 52.2 seconds, p < 0.0001) and warm ischemia times (LDN: 145.1 ± 61.7 seconds, SP RDN: 275.4 ± 65.6 seconds, p < 0.0001). There were no differences in patient subjective pain scores, inpatient opioid usage, or Clavien-Dindo II+ complications. Short- and medium-term postoperative donor and recipient renal function were also similar between the groups. SP RDN graft extraction time and total operative time learning curves were achieved at case 27 and 13, respectively. Conclusion: SP RDN is a safe and feasible alternative to LDN that minimizes postoperative abdominal incisional scars and has a short learning curve. Future randomized prospective clinical trials are needed to confirm the findings of this study and to identify other potential benefits and drawbacks of SP RDNs.

Rapid detection of mutations in CSF-cfTNA with the Genexus Integrated Sequencer.

PURPOSE: Genomic alterations are fundamental for molecular-guided therapy in patients with breast and lung cancer. However, the turn-around time of standard next-generation sequencing assays is a limiting factor in the timely delivery of genomic information for clinical decision-making. METHODS: In this study, we evaluated genomic alterations in 54 cerebrospinal fluid samples from 33 patients with metastatic lung cancer and metastatic breast cancer to the brain using the Oncomine Precision Assay on the Genexus sequencer. There were nine patients with samples collected at multiple time points. RESULTS: Cell-free total nucleic acids (cfTNA) were extracted from CSF (0.1-11.2 ng/µl). Median base coverage was 31,963× with cfDNA input ranging from 2 to 20 ng. Mutations were detected in 30/54 CSF samples. Nineteen (19/24) samples with no mutations detected had suboptimal DNA input (< 20 ng). The EGFR exon-19 deletion and PIK3CA mutations were detected in two patients with increasing mutant allele fraction over time, highlighting the potential of CSF-cfTNA analysis for monitoring patients. Moreover, the EGFR T790M mutation was detected in one patient with prior EGFR inhibitor treatment. Additionally, ESR1 D538G and ESR1::CCDC170 alterations, associated with endocrine therapy resistance, were detected in 2 mBC patients. The average TAT from cfTNA-to-results was < 24 h. CONCLUSION: In summary, our results indicate that CSF-cfTNA analysis with the Genexus-OPA can provide clinically relevant information in patients with brain metastases with short TAT.

Case Report: Early diagnosis and bevacizumab-based chemotherapy for primary pericardial mesothelioma: a case with occupational asbestos exposure history.

Background: Primary pericardial mesothelioma (PPM) is an exceedingly rare malignant cancer and has a poor prognosis, which has been partly attributed to its frequently delayed diagnosis due to its nonspecific syndromes, its similar presentation to benign pericardial diseases, and its non-definitive etiology. In many PPM cases, the time from presentation to definite diagnosis may last for several months or even over one year. Unlike pleural mesothelioma, the relationship between PPM and asbestos exposure remains unsettled. To date, there is no consensus on the treatment of PPM. Case report: The patient is a 57-year-old male who had nonspecific syndromes and inconclusive image findings. The occupational long-term asbestos exposure history of this patient raised our concerns regarding potential malignancy when confronted with unexplained pericardial effusion accompanied by cardiac tamponade. The heightened suspicion prompted us to perform pericardiocentesis and biopsy on the third day after admission to our department. An early diagnosis of PPM was established by the pathological and immunohistochemical evaluation of the biopsy specimen two weeks after admission. Positron emission tomography-computed tomography revealed that the lesion was localized at the anterior part of the mediastinum without distant metastasis. This patient refused to receive cardiac surgery. He subsequently underwent six cycles of chemotherapy (cisplatin plus pemetrexed) in combination with bevacizumab (a humanized anti-VEGF antibody) as the first-line treatment, resulting in complete relief of symptoms and satisfactory outcomes with no complications. Four months after the first course, the patient initiated a second course of chemotherapy with a similar regimen, but he opted to discontinue the medical treatment after the initiation of the second course. The patient was transferred to the hospice care unit and unfortunately expired one year after the initial presentation. Conclusion: We present a case of an early multidisciplinary clinical approach to diagnose and manage PPM with consideration of occupational asbestos exposure history and clinical symptoms. Bevacizumab-based chemotherapy remains an option for the treatment of PPM.

Pediatric Craniofacial Tumor Reconstruction.

Effective management of pediatric craniofacial tumors requires coordinated input from medical, oncologic, and surgical specialties. Reconstructive algorithms must consider limitations in pediatric donor tissue and account for future growth and development. Immediate reconstruction is often focused on filling dead space, protecting underlying structures, and ensuring skeletal symmetry. Staged reconstruction occurs after the patient has reached skeletal maturity and is focused on restoring permanent dentition. Reconstructive options vary depending on the location, size, and composition of resected tissue. Virtual surgical planning (VSP) reduces the complexity of pediatric craniofacial reconstruction and ensures more predictable outcomes.