Michael P. Catalino

PURPOSE: Brain metastases (BMETS) are commonly diagnosed in emergency care setting (ECS)—such as the emergency department (ED) or after direct admissions—yet research on their admission patterns, management, and survival is limited. This study examines the clinical course, outcomes, and potential impact of an admission algorithm for patients diagnosed with BMETS in ECS. METHODS: This is a retrospective study conducted across three academic hospitals, analyzing admissions and survival of BMETS patients in ECS. Patients were age at least 18 years with imaging-confirmed BMETS. We developed an admission algorithm that was retrospectively applied to assess the rationale for hospitalization. Primary outcomes included admission rates, length of stay (LOS) in the ED and hospital, and overall survival. RESULTS: Among 312 patients, 250 had brain imaging available at initial ECS presentation; 241 (96.4%) were admitted. Median ED LOS was 7 hours, increasing with multiple imaging studies ( P < .001) and consults ( P = .01). Median hospital LOS was 6.7 days, prolonged by inpatient interventions (9.9 v 6.2 days, P < .001) and poor functional status (8.6 v 5.4 days, P < .001). Median survival post-discharge was 4.4 months, influenced by functional status ( P < .001) and comorbidities ( P = .004). Applying the admission algorithm, 224 (89.6%) required hospitalization while 26 (10.4%) were eligible for outpatient care. CONCLUSION: BMETS patients in ECS have high admission rates and poor survival. A standardized admission algorithm may reduce ED LOS by identifying patients who require hospitalization. Further research is needed to refine triage and improve outcomes.

Objective: Pituitary neuroendocrine tumors (PitNETs) are common intracranial neoplasms that can exhibit invasive behavior, leading to increased morbidity, recurrence, and resistance to treatment. Identifying biomarkers associated with tumor invasiveness could improve early diagnosis and guide therapeutic interventions. This systematic review evaluates molecular biomarkers linked to PitNET invasiveness and explores the potential of radiolabeling for noninvasive detection. Methods: A systematic search of PubMed and Embase databases was conducted to identify studies evaluating molecular markers associated with invasive PitNETs. Biomarkers were selected based on their proposed role in tumor invasion, and evidence supporting their clinical relevance was summarized. Additionally, existing radiolabeling techniques for biomarker detection were reviewed. Results: Five key biomarker groups were identified: matrix metalloproteinases (MMPs), urokinase plasminogen activator (uPA) system, myosin 5A (MYO5A), vascular endothelial growth factor (VEGF), and survivin. MMPs were strongly linked to extracellular matrix degradation and invasion, while uPA facilitated invasion via MMP activation. MYO5A and survivin were implicated in epithelial-mesenchymal transition and tumor motility, and VEGF promoted angiogenesis. Radiolabeling techniques for MMPs, uPA/uPAR, VEGF, and survivin demonstrated feasibility for imaging tumor invasiveness, though limitations such as non-specific tracer accumulation remain. Conclusions: This review highlights the potential of molecular biomarkers in predicting PitNET invasiveness and the emerging role of radiolabeled probes in noninvasive imaging. Future research should focus on validating these biomarkers in longitudinal studies and refining radiolabeling techniques to improve diagnostic accuracy and therapeutic targeting of invasive PitNETs.

Context: In Cushing disease, the association between the rate of serum cortisol decline and recurrent disease after corticotroph adenoma removal has not been adequately characterized.Objective: To analyze postoperative serum cortisol and recurrence rates in Cushing disease.Methods: Patients with Cushing disease and pathology-confirmed corticotroph adenoma were retrospectively studied. Cortisol halving time was estimated using exponential decay modeling. Halving time, first postoperative cortisol, and nadir cortisol values were collected using immediate postoperative inpatient laboratory data. Recurrence and time-to-recurrence were estimated and compared among cortisol variables.Results: A total of 320 patients met inclusion/exclusion criteria for final analysis, and 26 of those patients developed recurrent disease. Median follow-up time was 25 months (95% CI, 19-28 months), and 62 patients had ≥ 5 years follow-up time. Higher first postoperative cortisol and higher nadir were associated with increased risk of recurrence. Patients who had a first postoperative cortisol ≥ 50 µg/dL were 4.1 times more likely to recur than those with a first postoperative cortisol < 50 µg/dL (HR 4.1, 1.8-9.2; P = .0003). Halving time was not associated with recurrence (HR 1.7, 0.8-3.8, P = .18). Patients with a nadir cortisol ≥2 µg/dL were 6.6 times more likely to recur than those with a nadir cortisol of < 2 µg/dL (HR 6.6, 2.6-16.6, P < .0001).Conclusion: Postoperative nadir serum cortisol is the most important cortisol variable associated with recurrence and time-to-recurrence. Compared to first postoperative cortisol and cortisol halving time, a nadir < 2 µg/dL showed the strongest association with long-term remission and typically occurs within the first 24 to 48 hours after surgery.

Purpose In Cushing disease, early post-operative serum cortisol fluctuations have not been adequately characterized, and their association with initial remission and recurrence is unclear. Methods A retrospective cohort study of patients with Cushing disease was conducted at two institutions. A “riser” was defined a priori as a paradoxical increase in serum cortisol with an immediate incremental increase in serum cortisol over three consecutive cortisol draws separated by roughly 6-h (definition 1). Post hoc analyses used a definition of two consecutive increases (definition 2). Risers were compared to non-risers for initial remission and time-to-recurrence. Results A total of 505 patients with Cushing disease were screened, and 469 had adequate data for group assignment. Analysis of post-operative cortisol showed a subgroup of “risers” with a frequency of 3.6% for definition 1 and 42.6% for definition 2. In these patients, cortisol levels were significantly higher until approximately 36 h post-operatively, and cortisol had a significantly longer mean serum half-life. In the post hoc analysis, definition 2 risers had a lower remission rate compared to non-risers (162/196, 82.7%, versus 243/264, 92.0%) with an odds ratio of 0.41 (0.23–0.73; p = 0.003). For both definitions, recurrence was similar between groups. Conclusions We found that almost half of Cushing disease patients experienced a temporary increase in serum cortisol level during the early post-operative period. Serum cortisol half-life was longer, and the remission rates were lower, however, recurrence rates were similar to non-risers.

"Letter to the Editor. Don’t blame the resilient corticotroph" published on 14 May 2021 by American Association of Neurological Surgeons.

BACKGROUND: Glioblastoma (GBM) is driven by various genomic alterations. Next-generation sequencing (NGS) could yield targetable alterations that might impact outcomes. The goal of this study was to describe how NGS can inform targeted therapy (TT) in this patient population. METHODS: The medical records of patients with a diagnosis of GBM from 2017 to 2019 were reviewed. Records of patients with recurrent GBM and genomic alterations were evaluated. Objective response rates and disease control rates were determined. RESULTS: A total of 87 patients with GBM underwent NGS. Forty percent (n = 35) were considered to have actionable alterations. Of these 35, 40% (n = 14) had their treatment changed due to the alteration. The objective response rate (ORR) of this population was 43%. The disease control rate (DCR) was 100%. The absolute mean decrease in contrast-enhancing disease was 50.7% (95% CI 34.8–66.6). CONCLUSION: NGS for GBM, particularly in the recurrent setting, yields a high rate of actionable alterations. We observed a high ORR and DCR, reflecting the value of NGS when deciding on therapies to match genomic alterations. In conclusion, patient selection and the availability of NGS might impact outcomes in select patients with recurrent GBM.

BACKGROUND: Glioblastoma (GBM) is driven by various genomic alterations. Next generation sequencing (NGS) could yield targetable alterations that may impact outcomes. The goal of this study was to describe how NGS can inform targeted therapy (TT) in this patient population. METHODS: The medical records of patients (pts) with a diagnosis of GBM from 2017-2019 were reviewed. Records of patients with recurrent GBM and genomic alterations were evaluated. Objective response rates and disease control rates were deter-mined. RESULTS: A total of 87 pts with GBM underwent NGS. Forty percent (n = 35) were considered to have actionable alterations. Of the 35, 40% (n=14) pts had their treatment changed due to an alteration. The objective response rate (ORR) of this population was 43%. The disease control rate (DCR) was 100%. The absolute mean decrease in contrast enhancing disease was 50.7% (95% CI 34.8 – 66.6). CONCLUSION: NGS for GBM, particularly in the recurrent setting, yields a high rate of actionable alterations. We observed a high ORR and DCR, reflecting the value of NGS in deciding on TT to match alterations that are likely to respond. In conclusion, patient selection and availability of NGS may impact outcomes in select pts with recurrent GBM.

In order to understand the energy implications of primate limb conformation, the biomechanics of swing phase and the vertical movements of limb center of gravity were examined in the arboreal rhesus macaque ( Macaca mulatta ) and the semi-terrestrial long-tailed macaque ( Macaca fascicularis ). The objective was to better understand the potential variation in locomotor adaptations in these two macaque species within different ecological environments. In particular, the objective of this study was to identify the implications that these movements have on the internal energy costs of locomotion. I show that the biomechanics of swing phase for these two species have important effects on their limb center of gravity, although they may have similar limb segment mass distributions. This study suggests that mechanical energy conservation during swing phase is important in mammalian locomotion.

OBJECTIVE: This study was done to compare corticotroph hyperplasia and histopathologically proven adenomas in patients with Cushing disease by analyzing diagnostic features, surgical management, and clinical outcomes. METHODS: Patients with suspected pituitary Cushing disease were included in a retrospective cohort study and were excluded if results of pathological analysis of the surgical specimen were nondiagnostic or normal. Cases were reviewed by two experienced neuropathologists. Total lesion removal was used as a dichotomized surgical variable; it was defined as an extracapsular resection (including a rim of normal gland) in patients with an adenoma, and for hyperplasia patients it was defined as removal of the presumed lesion plus a rim of surrounding normal gland. Bivariate and multivariate analyses were performed. Recurrence-free survival was compared between the two groups. RESULTS: The final cohort consisted of 63 patients (15 with hyperplasia and 48 with adenoma). Normal pituitary acinar architecture was highly variable. Corticotroph hyperplasia was diagnosed based on the presence of expanded acini showing retained reticulin architecture and predominant staining for adrenocorticotropic hormone. Crooke’s hyaline change was seen in 46.7% of specimens, and its frequency was equal in nonlesional tissue of both groups. The two groups differed only by MRI findings (equivocal/diffuse lesion in 46% of hyperplasia and 17% of adenoma; p = 0.03). Diagnostic uncertainty in the hyperplasia group resulted in additional confirmatory testing by 24-hour urinary free cortisol. Total lesion removal was infrequent in patients with hyperplasia compared to those with adenoma (33% vs 65%; p = 0.03). Initial biochemical remission was similar (67% in hyperplasia and 85% in adenoma; p = 0.11). There was no difference in hypothalamic-pituitary-adrenal axis recovery or disease recurrence. The median follow-up was 1.9 years (IQR 0.7–7.6 years) for the hyperplasia group and 1.2 years (IQR 0.4–2.4 years) for the adenoma group. Lack of a discrete lesion and diagnostic uncertainty were the only significant predictors of hyperplasia (sensitivity 53.3%, specificity 97.7%, positive predictive value 88.9%, negative predictive value 85.7%). An adjusted Cox proportional hazards model showed similar recurrence-free survival in the two groups. CONCLUSIONS: This study suggests an association between biochemically proven Cushing disease and histopathologically proven corticotroph hyperplasia. Imaging and operative findings can be ambiguous, and, compared to typical adenomas with a pseudocapsule, the surgical approach is more nuanced. Nevertheless, if treated appropriately, biochemical outcomes may be similar.