Machine Learning Analysis of Post-Operative Tumour Progression in Non-Functioning Pituitary Neuroendocrine Tumours: A Pilot Study.

Post-operative tumour progression in patients with non-functioning pituitary neuroendocrine tumours is variable. The aim of this study was to use machine learning (ML) models to improve the prediction of post-operative outcomes in patients with NF PitNET. We studied data from 383 patients who underwent surgery with or without radiotherapy, with a follow-up period between 6 months and 15 years.

Population pharmacokinetic-pharmacodynamic modeling of serum biomarkers as predictors of tumor dynamics following lenvatinib treatment in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC).

Lenvatinib is a receptor tyrosine kinase (RTK) inhibitor targeting vascular endothelial growth factor (VEGF) receptors 1-3, fibroblast growth factor (FGF) receptors 1-4, platelet-derived growth factor receptor-α (PDGFRα), KIT, and RET that have been implicated in pathogenic angiogenesis, tumor growth, and cancer. The primary objective of this work was to evaluate, by establishing quantitative relationships, whether lenvatinib exposure and longitudinal serum biomarker data (VEGF, Ang-2, Tie-2, and FGF-23) are predictors for change in longitudinal tumor size which was assessed based on data from 558 patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) receiving either lenvatinib or placebo treatment. Lenvatinib PK was best described by a 3-compartment model with simultaneous first- and zero-order absorption and linear elimination from the central compartment with significant covariates (body weight, albumin <30 g/dL, ALP>ULN, RR-DTC, RCC, HCC subjects, and concomitant CYP3A inhibitors).

Non-functioning pituitary macroadenoma following surgery: long-term outcomes and development of an optimal follow-up strategy.

Objectives: Recurrence and regrowth of non-functioning pituitary macroadenomas (NFPMs) after surgery are common but remain unpredictable. Therefore, the optimal timing and frequency of follow-up imaging remain to be determined. We sought to determine the long-term surgical outcomes of NFPMs following surgery and develop an optimal follow-up strategy.

Pituitary function at presentation and following therapy in patients with non-functional pituitary macroadenomas: a single centre retrospective cohort study.

Background: Non-functioning pituitary macroadenomas (NFPMs) may present with hypopituitarism. Pituitary surgery and radiotherapy pose an additional risk to pituitary function.

Objectives: To assess the incidence of hypopituitarism at presentation, the impact of treatment, and the likelihood of endocrine recovery during follow-up.

Post-Operative Medium- and Long-Term Endocrine Outcomes in Patients with Non-Functioning Pituitary Adenomas-Machine Learning Analysis.

Post-operative endocrine outcomes in patients with non-functioning pituitary adenoma (NFPA) are variable. The aim of this study was to use machine learning (ML) models to better predict medium- and long-term post-operative hypopituitarism in patients with NFPAs. We included data from 383 patients who underwent surgery with or without radiotherapy for NFPAs, with a follow-up period between 6 months and 15 years.

Exposure-Response Analyses of Polysomnography and Subjective Sleep Efficacy End Points From the Phase 3 Trials of Lemborexant, a Dual Orexin Receptor Antagonist for the Treatment of Insomnia.

This report describes polysomnography and sleep diary exposure-response analyses from Study E2006-G000-304 (Study 304), a 1-month trial of 5- or 10-mg lemborexant, zolpidem, or placebo; and Study E2006-G000-303 (Study 303), a 6-month trial of 5- or 10-mg lemborexant or placebo. Studies 304 and 303 included 1006 (86%) and 956 (68%) (female) participants, respectively; >40% were ≥65 years, with individual lemborexant exposures derived from a previously described pharmacokinetic model. Linear mixed-effects analyses of polysomnography: latency to persistent sleep (LPS), sleep efficiency (SE), and wake after sleep onset (WASO) quantified the change from baseline given lemborexant exposure, time, and covariates, guided by consensus recommendations regarding clinical significance.

First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E6742, a Dual Antagonist of Toll-like Receptors 7 and 8, in Healthy Volunteers.

The first-in-human phase I study for E6742, a dual toll-like receptor (TLR) 7 and TLR8 antagonist, has been conducted to assess the safety, tolerability, and pharmacokinetics of E6742 in healthy volunteers. In a single ascending dose (SAD) study, 42 subjects received 10-800 mg of E6742 in the fasted state, as well as a 100-mg cohort in the fed state for evaluating the effect of food. In a multiple ascending dose (MAD) study, 18 subjects received 100-400 mg of E6742 twice daily for 7 days.

Intravenous Perampanel as an Interchangeable Alternative to Oral Perampanel: A Randomized, Crossover, Phase I Pharmacokinetic and Safety Study.

Intravenous (IV) drug administration enables treatment of epilepsy when oral administration is temporarily not feasible. Perampanel is a once-daily antiseizure medication currently available as oral formulations. Study 050 (NCT03376997) was an open-label, randomized, single-dose, crossover study to evaluate the interchangeability of oral and IV perampanel in healthy subjects (N = 48).

Lenvatinib dose, efficacy, and safety in the treatment of multiple malignancies.

Introduction: Lenvatinib is an oral multitargeted tyrosine kinase inhibitor that has shown efficacy and manageable safety across multiple cancer types. The recommended starting doses for lenvatinib differ across cancer types and indications based on whether it is used as monotherapy or as combination therapy.

Areas Covered: This review covers clinical trials that established the dosing paradigm and efficacy of lenvatinib and defined its adverse-event profile as a monotherapy; or in combination with the mTOR inhibitor, everolimus; or the anti-PD-1 antibody, pembrolizumab; and/or chemotherapy.

The management and outcome of hyponatraemia following transsphenoidal surgery: a retrospective observational study.

Purpose: Hyponatraemia is a common complication following transsphenoidal surgery. However, there is sparse data on its optimal management and impact on clinical outcomes. The aim of this study was to evaluate the management and outcome of hyponatraemia following transsphenoidal surgery.

Assessment of morning sleep propensity with lemborexant in adults with insomnia disorder in a randomized, placebo-controlled crossover study.

Objective: To evaluate effects of lemborexant (LEM), a dual orexin receptor antagonist, on next-morning sleep propensity assessed by a modified Multiple Sleep Latency Test (M-MSLT) in adults with insomnia disorder.

Methods: Study 107 (E2006-A001-107) was a phase 1, randomized, double-blind, four-period crossover study. Subjects ( = 69) received oral single-dose placebo, LEM 5 mg (LEM5), and LEM 10 mg (LEM10) at bedtime in periods 1-3 in a randomized crossover and open-label flurazepam 30 mg in period 4.

Cabergoline reduces 3-methoxytyramine in a SDHC patient with metastatic paraganglioma and prolactinoma.

Summary: We observed a novel therapeutic response with cabergoline in a male patient with a dopamine-secreting head and neck paraganglioma (HNPGL), macroprolactinoma and germline succinate dehydrogenase C mutation (SDHC). The macroprolactinoma was treated with cabergoline which gave an excellent response. He was found to have raised plasma 3-methoxytyramine of 1014 pmol/L (NR: 0-180 pmol/L); but it was unclear if this was a drug-induced phenomenon from dopamine agonist (DA) therapy.

Dysnatremia is a Predictor for Morbidity and Mortality in Hospitalized Patients with COVID-19.

Context: Dysnatremia is an independent predictor of mortality in patients with bacterial pneumonia. There is paucity of data about the incidence and prognostic impact of abnormal sodium concentration in patients with coronavirus disease 2019 (COVID-19).

Objective: This work aimed to examine the association of serum sodium during hospitalization with key clinical outcomes, including mortality, need for advanced respiratory support and acute kidney injury (AKI), and to explore the role of serum sodium as a marker of inflammatory response in COVID-19.

Temporal trends in craniopharyngioma management and long-term endocrine outcomes: A multicentre cross-sectional study.

Background: The optimal management of craniopharyngiomas remains controversial.

Objectives: To examine temporal trends in the management of craniopharyngioma with a focus on endocrine outcomes.

Methods: This was a cross-sectional, multicentre study.

Population Pharmacokinetics and Exposure-Response Analyses for the Most Frequent Adverse Events Following Treatment With Lemborexant, an Orexin Receptor Antagonist, in Subjects With Insomnia Disorder.

Lemborexant is a novel orexin receptor antagonist approved in the United States and Japan for the treatment of insomnia. This article describes the population pharmacokinetics (PK) of lemborexant and the relationship of its daily steady-state exposure (C ) to the probability of most frequent treatment-emergent adverse events (TEAEs). The 12 230-observation, 1892-subject PK data set included data from 12 clinical studies with predominantly female subjects (66%) ranging in age from 18 to 88 years and from 37 to 168 kg in body weight.

Time above the MIC of Piperacillin-Tazobactam as a Predictor of Outcome in Pseudomonas aeruginosa Bacteremia.

bacteremia is an infection associated with a high mortality rate. Piperacillin-tazobactam is a β-lactam-β-lactamase inhibitor combination that is frequently used for the management of infections. The pharmacokinetic-pharmacodynamic index associated with maximal bacterial killing for piperacillin-tazobactam is the percentage of the time between doses at which the free fraction concentration remains above the MIC (% ).

Changes in perampanel levels during de-induction: Simulations following carbamazepine discontinuation.

Objective: To evaluate the time course of changes in perampanel levels when co-administered with carbamazepine, and following carbamazepine discontinuation, using a physiologically based pharmacokinetic (PBPK) model.

Methods: The PBPK model was developed, verified using clinical PK data, and used to simulate the effect of abrupt discontinuation and down-titration (75 mg twice daily [bid]/wk) of co-administered carbamazepine 300 mg bid on the PK of perampanel once daily (qd). Perampanel dose tapering (8-4 mg) and up-titration (2-6 mg) were simulated during abrupt carbamazepine 300 mg bid discontinuation to identify a titration schedule that minimizes changes in perampanel plasma concentrations.

Rathke's cleft cysts following transsphenoidal surgery: long-term outcomes and development of an optimal follow-up strategy.

Background: In patients with symptomatic Rathke's cleft cyst, transsphenoidal surgery is highly effective at preventing further visual loss and usually allows for some recovery of vision. However, cyst recurrence and the need for re-operation are well recognized. To this end, the aim of this study was to investigate patterns of recurrence and long-term outcomes and to use this information to develop an optimal follow-up strategy.

Craniopharyngioma in children: trends from a third consecutive single-center cohort study.

Objective: The management of children with craniopharyngioma has evolved over time, with a trend toward less invasive neurosurgical approaches as surgeons have sought to balance oncological control and treatment-related morbidity. To this end, the aim of this study was to evaluate the safety and effectiveness of the current management of children with craniopharyngioma compared to the previous management methods used at the authors' treatment center.

Methods: A prospectively maintained database was searched over a 14-year period between January 1, 2005, and December 31, 2018, to identify all children 17 years of age or younger with a new diagnosis of craniopharyngioma.

Outcomes of Patients with Nelson's Syndrome after Primary Treatment: A Multicenter Study from 13 UK Pituitary Centers.

Context: Long-term outcomes of patients with Nelson's syndrome (NS) have been poorly explored, especially in the modern era.

Objective: To elucidate tumor control rates, effectiveness of various treatments, and markers of prognostic relevance in patients with NS.

Patients, Design, And Setting: Retrospective cohort study of 68 patients from 13 UK pituitary centers with median imaging follow-up of 13 years (range 1-45) since NS diagnosis.

Two cases of spontaneous remission of primary hyperparathyroidism due to auto-infarction: different management and their outcomes.

Spontaneous remission of primary hyperparathyroidism (PHPT) due to necrosis and haemorrhage of parathyroid adenoma, the so-called 'parathyroid auto-infarction' is a very rare, but previously described phenomenon. Patients usually undergo parathyroidectomy or remain under close clinical and biochemical surveillance. We report two cases of parathyroid auto-infarction diagnosed in the same tertiary centre; one managed surgically and the other conservatively up to the present time.