Impact of Frailty on Surgical Outcomes of Patients With Cushing Disease Using the Multicenter Registry of Adenomas of the Pituitary and Related Disorders Registry.

Background And Objectives: Despite growing interest in how patient frailty affects outcomes (eg, in neuro-oncology), its role after transsphenoidal surgery for Cushing disease (CD) remains unclear. We evaluated the effect of frailty on CD outcomes using the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) data set from a collaboration of US academic pituitary centers.

Methods: Data on consecutive surgically treated patients with CD (2011-2023) were compiled using the 11-factor modified frailty index.

Cushing's Disease Clinical Phenotype and Tumor Behavior Vary with Age: Diagnostic and Perioperative Implications.

Context: Little is known about presenting clinical characteristics, tumor biology, and surgical morbidity of Cushing's disease (CD) with aging.

Objective: Using a large multi-institutional dataset, we assessed diagnostic and prognostic significance of age in CD through differences in presentation, laboratory results, tumor characteristics, and postoperative outcomes.

Design: Data from the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) were reviewed for patients with CD treated with transsphenoidal tumor resection at 11 centers between 2003 and 2023.

Endothelial-specific CXCL12 regulates neovascularization during tissue repair and tumor progression.

C-X-C motif chemokine ligand 12 (CXCL12; Stromal Cell-Derived Factor 1 [SDF-1]), most notably known for its role in embryogenesis and hematopoiesis, has been implicated in tumor pathophysiology and neovascularization. However, its cell-specific role and mechanism of action have not been well characterized. Previous work by our group has demonstrated that hypoxia-inducible factor (HIF)-1 modulates downstream CXCL12 expression following ischemic tissue injury.

Botulinum Toxin Application for Treatment of Graft Vasospasm: A Reverse Translational Study.

Vascular graft vasospasm is a lethal risk when using grafts for revascularization and reconstructive surgery. Revascularization is a treatment modality for ischemic diseases including Moyamoya disease that requires bypass surgery. Cerebrovascular graft transplantation carries a 5-10% risk of vasospasm, which can lead to devastating neurological sequelae.

Development of bombesin-tubulysin conjugates using multicomponent chemistry to functionalize both the payload and the homing peptide.

Peptide-drug conjugates (PDCs) have recently gained significant attention for the targeted delivery of anticancer therapeutics, mainly due to their cost-effective and chemically defined production and lower antigenicity compared to ADCs, among other benefits. In this study, we designed and synthesized novel PDCs by conjugating new thiol-functionalized tubulysin analogs (tubugis) to bombesin, a peptide ligand with a relevant role in cancer research. Two tubulysin analogs bearing ready-for-conjugation thiol groups were prepared by an on-resin multicomponent peptide synthesis strategy and subsequently tested for their stand-alone anti-proliferative activity against human cancer cells, which resulted in IC values in the nanomolar range.

4-(Pyrazolyl)benzenesulfonamide Ureas as Carbonic Anhydrases Inhibitors and Hypoxia-Mediated Chemo-Sensitizing Agents in Colorectal Cancer Cells.

Hypoxia in tumors contributes to chemotherapy resistance, worsened by acidosis driven by carbonic anhydrases (CA IX and XII). Targeting these enzymes can mitigate acidosis, thus enhancing tumor sensitivity to cytotoxic drugs. Herein, novel 4-(pyrazolyl)benzenesulfonamide ureas () were developed and evaluated for their inhibitory activity against CA IX and XII.

The impact of 9-azaglycophymine and phenylguanidine derivatives on the proliferation of various breast cancer cell lines in vitro and in vivo.

Quinazolinones, particularly 9-azaglycophymines, and closely related derivatives and precursors were tested in vitro against various breast cancer cell lines representing the major types of breast tumors. Among the 49 compounds tested, azaglycophymine derivative 19 with an electron-withdrawing substituent demonstrated the most significant anti-proliferative effects, with IC values of around 4 µM. Extensive cell-based investigations revealed that compound 19 induced caspase-dependent apoptosis in HCC1937 (human TNBC), BT-474 (human HER2+/HR+), and 4T1 (mouse TNBC) cells.

Novel Zn(II), Co(II) and Cu(II) diflunisalato complexes with neocuproine and their exceptional antiproliferative activity against cancer cell lines.

Three novel complexes of deprotonated diflunisal () with neocuproine () were synthesized and characterized elemental, spectral (UV-vis, FTIR, fluorescence, and mass spectrometry), and single-crystal X-ray diffraction analyses. Although the compounds shared a similar composition of [MCl()()], where M represents Zn(II) (1), Co(II) (2) and Cu(II) (3), only 1 and 2 were isostructural, while 3 differed in both the molecular and supramolecular structures. In all three complex molecules, the central atom is coordinated by two nitrogen atoms of in a bidentate chelate mode, and one chlorido ligand and is bonded in either a monodentate mode one oxygen atom of the carboxylate in 1 and 2 or in a bidentate chelate mode both carboxylate oxygen atoms in 3.

Predictors of Durable Remission After Successful Surgery for Cushing Disease: Results From the Multicenter RAPID Registry.

Background And Objective: Cushing disease (CD) affects mortality and quality of life along with limited long-term remission, underscoring the need to better identify recurrence risk. The identification of surgical or imaging predictors for CD remission after transsphenoidal surgery has yielded some inconsistent results and has been limited by single-center, single-surgeon, or meta-analyses studies. We sought to evaluate the multicenter Registry of Adenomas of the Pituitary and Related Disorders (RAPID) database of academic US pituitary centers to assess whether robust nonhormonal recurrence predictors could be elucidated.

Surgical Management of Ipsilateral Internal Carotid Artery Stenosis and Unruptured Intracranial Aneurysm: Case Review and Treatment Considerations.

 The coexistence of carotid artery stenosis and a concomitant downstream ipsilateral unruptured intracranial aneurysm requires unique treatment considerations to balance the risk of thromboembolic complications from carotid artery stenosis and the risk of subarachnoid hemorrhage from intracranial aneurysm rupture. These considerations include the selection of optimal treatment modalities, the order and timing of interventions, and potential management of antiplatelet agents with endovascular approaches. We present strategies to optimize treatment in such a case.

The clinical potential of radiomics to predict hematoma expansion in spontaneous intracerebral hemorrhage: a narrative review.

Spontaneous intracerebral hemorrhage (sICH) is associated with significant morbidity and mortality, with subsequent hematoma expansion (HE) linked to worse neurologic outcomes. Accurate, real-time predictions of the risk of HE could enable tailoring management-including blood pressure control or surgery-based on individual patient risk. Although multiple radiographic markers of HE have been proposed based on standard imaging, their clinical utility remains limited by a reliance on subjective interpretation of often ambiguous findings and a poor overall predictive power.

Multicenter Registry of Adenomas of the Pituitary and Related Disorders: Initial Description of Cushing Disease Cohort, Surgical Outcomes, and Surgeon Characteristics.

Background And Objectives: To address the lack of a multicenter pituitary surgery research consortium in the United States, we established the Registry of Adenomas of the Pituitary and Related Disorders (RAPID). The goals of RAPID are to examine surgical outcomes, improve patient care, disseminate best practices, and facilitate multicenter surgery research at scale. Our initial focus is Cushing disease (CD).

Impact of Frailty on Surgical Outcomes of Patients With Cushing Disease Using the Multicenter Registry of Adenomas of the Pituitary and Related Disorders Registry.

Background And Objectives: Despite growing interest in how patient frailty affects outcomes (eg, in neuro-oncology), its role after transsphenoidal surgery for Cushing disease (CD) remains unclear. We evaluated the effect of frailty on CD outcomes using the Registry of Adenomas of the Pituitary and Related Disorders (RAPID) data set from a collaboration of US academic pituitary centers.

Methods: Data on consecutive surgically treated patients with CD (2011-2023) were compiled using the 11-factor modified frailty index.

Improved Access to Potent Anticancer Tubulysins and Linker-Functionalized Payloads Via an All-On-Resin Strategy.

Tubulysins are among the most recent antimitotic compounds to enter into antibody/peptide-drug conjugate (ADC/PDC) development. Thus far, the design of the most promising tubulysin payloads relied on simplifying their structures, e. g.

Subtemporal Approach for the Treatment of Ruptured and Unruptured Distal Basilar Artery Aneurysms: Is There a Contemporary Use?

Background And Objectives: Distal basilar artery aneurysms (DBAs) are high-risk lesions for which endovascular treatment is preferred because of their deep location, yet indications for open clipping nonetheless remain. The subtemporal approach allows for early proximal control and direct visualization of critical posterior perforating arteries, especially for posterior-projecting aneurysms. Our objective was to describe our clinical experience with the subtemporal approach for clipping DBAs in the evolving endovascular era.

Preservation of cranial nerve function in large and giant trigeminal schwannoma resection: a case series.

Background: Trigeminal schwannomas (TSs) are intracranial tumors that can cause significant brainstem compression. TS resection can be challenging because of the risk of new neurologic and cranial nerve deficits, especially with large (≥ 3 cm) or giant (≥ 4 cm) TSs. As prior surgical series include TSs of all sizes, we herein present our clinical experience treating large and giant TSs via microsurgical resection.

Treatment of pediatric intracranial aneurysms: institutional case series and systematic literature review.

Introduction: Pediatric intracranial aneurysms (IAs) are rare and have distinct clinical profiles compared to adult IAs. They differ in location, size, morphology, presentation, and treatment strategies. We present our experience with pediatric IAs over an 18-year period using surgical and endovascular treatments and review the literature to identify commonalities in epidemiology, treatment, and outcomes.

Open Surgical Treatment of Middle Cerebral Artery Aneurysms: A Single-Center Series in the Endovascular Era.

Objective: We review the outcomes of open surgical treatment of middle cerebral artery aneurysms (MCAAs) at a single center, focusing on aneurysm obliteration rates and functional outcomes at the most recent follow-up. These findings can be used for future comparisons of surgical outcomes with MCAAs.

Methods: We retrospectively reviewed cases from a prospectively maintained database of patients receiving open surgical treatment for ruptured or unruptured MCAAs between July 2014 and December 2022.