Etomidate and its derivatives: time to say goodbye?

Etomidate, an intravenous hypnotic used for anaesthesia and critical care, is known for its undesirable side effects, including pain on injection, myoclonus, and adrenocortical depression. Despite its continued clinical use because of its haemodynamic stability and rapid onset and offset of effect, alternatives like propofol, ketamine, and remimazolam offer fewer drawbacks. Recent efforts to improve etomidate through chemical modifications, such as methoxyethyl etomidate hydrochloride (ET-26), have shown limited success, with persistent issues like involuntary muscle movements and adrenocortical suppression.

70-Gene signature-guided adjuvant systemic treatment adjustments in early-stage ER+ breast cancer patients: 7-year follow-up of a prospective multicenter cohort study.

Background: A previous prospective multicenter study revealed the change of the oncologists' chemotherapy advice due to the 70-Gene signature (GS) test result in half of the estrogen receptor-positive (ER+) invasive early-stage breast cancer patients with disputable chemotherapy indication. This resulted in less patients receiving chemotherapy. This study aims to complement these results by the 7-year oncological outcomes according to the 70-GS test result and the oncologists' pre-test advice.

Labeling of CC Chemokine Receptor 2 with a Versatile Intracellular Allosteric Probe.

Interest in affinity-based probes (AfBPs) as novel tools to interrogate G protein-coupled receptors (GPCRs) has gained traction in recent years. AfBPs represent an interesting and more versatile alternative to antibodies. In the present study, we report the development and validation of AfBPs that target the intracellular allosteric pocket of CCR2, a GPCR of interest for the development of therapies targeting autoimmune and inflammatory diseases and also cancer.

First-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomised, controlled, phase 3 study from the Dutch Colorectal Cancer Group.

Background: Patients with initially unresectable colorectal cancer liver metastases might qualify for local treatment with curative intent after reducing the tumour size by induction systemic treatment. We aimed to compare the currently most active induction regimens.

Methods: In this open-label, multicentre, randomised, phase 3 study (CAIRO5), patients aged 18 years or older with histologically confirmed colorectal cancer, known RAS/BRAF mutation status, WHO performance status of 0-1, and initially unresectable colorectal cancer liver metastases were enrolled at 46 Dutch and one Belgian secondary and tertiary centres.

Mask-related skin changes among healthcare workers in a community-based hospital.

Context: During the COVID-19 pandemic, dermatologists within the Beaumont Farmington Hills' Dermatology program noticed an increase in conditions associated with mask wearing, such as "maskne" (acne in a mask distribution, thought to be caused by mask wearing), as well as worsening of previously diagnosed dermatologic conditions.

Objectives: The goal of our study was to explore various factors that impacted mask-related skin changes and how these skin changes affected quality of life.

Methods: A cross-sectional study was performed.

What's New in Intravenous Anaesthesia? New Hypnotics, New Models and New Applications.

New anaesthetic drugs and new methods to administer anaesthetic drugs are continually becoming available, and the development of new PK-PD models furthers the possibilities of using arget controlled infusion (TCI) for anaesthesia. Additionally, new applications of existing anaesthetic drugs are being investigated. This review describes the current situation of anaesthetic drug development and methods of administration, and what can be expected in the near future.

Pityriasis Rosea Associated With COVID-19 Vaccination: A Common Rash Following Administration of a Novel Vaccine.

Pityriasis rosea is a common, self-limited, papulosquamous eruption, classically presenting along the Langer lines of the skin. We report a clinically typical case of pityriasis rosea that developed following COVID-19 vaccination. As the novel COVID-19 vaccine becomes more widely available during the ongoing COVID-19 pandemic, it is imperative for both patients and clinicians to be aware of its association with the onset of this benign cutaneous eruption.

Effects of a Personalized Smartphone App on Bowel Preparation Quality: Randomized Controlled Trial.

Background: Adequate bowel preparation is essential for the visualization of the colonic mucosa during colonoscopy. However, the rate of inadequate bowel preparation is still high, ranging from 18% to 35%; this may lead to a higher risk of missing clinically relevant lesions, procedural difficulties, prolonged procedural time, an increased number of interval colorectal carcinomas, and additional health care costs.

Objective: The aims of this study are to compare bowel preparation instructions provided via a personalized smartphone app (Prepit, Ferring B V) with regular written instructions for bowel preparation to improve bowel preparation quality and to evaluate patient satisfaction with the bowel preparation procedure.

Etomidate and its Analogs: A Review of Pharmacokinetics and Pharmacodynamics.

Etomidate is a hypnotic agent that is used for the induction of anesthesia. It produces its effect by acting as a positive allosteric modulator on the γ-aminobutyric acid type A receptor and thus enhancing the effect of the inhibitory neurotransmitter γ-aminobutyric acid. Etomidate stands out among other anesthetic agents by having a remarkably stable cardiorespiratory profile, producing no cardiovascular or respiratory depression.

Ray Resection for Recurrent Invasive Squamous Cell Carcinoma: A Case Report.

Squamous cell carcinoma is the most common tumor of the hand. This malignancy requires unique treatment considerations; the surgeon and patient must balance retention of maximal functional capacity of the hand and minimization of the risk of recurrence and metastasis. Digital-sparing and digital-sacrificing therapies should be considered.

Modeling the Effect of Excitation on Depth of Anesthesia Monitoring in γ-Aminobutyric Acid Type A Receptor Agonist ABP-700.

Background: γ-Aminobutyric acid type A (GABAA) receptor agonists are known to cause involuntary muscle movements. The mechanism of these movements is not known, and its relationship to depth of anesthesia monitoring is unclear. We have explored the effect of involuntary muscle movement on the pharmacokinetic-pharmacodynamic model for the GABAA receptor agonist ABP-700 and its effects on the Bispectral Index (BIS) as well as the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores.

PI3K pathway protein analyses in metastatic breast cancer patients receiving standard everolimus and exemestane.

Purpose: Everolimus plus exemestane (EVE/EXE) is a registered treatment option for ER-positive, HER2-negative (ER +/HER2-) metastatic breast cancer (MBC), but resistance mechanisms limit efficacy. We aimed to find markers that might help select patients with a higher chance on benefit from EVE/EXE.

Methods: Immunohistochemistry (IHC) of PTEN, p-AKT(Thr308), p-AKT(Ser473), p-4EBP1, p-p70S6K, p-S6RP(Ser240/244), p-ERK1/2 and p-S6RP (Ser235/236) was performed on primary tumour tissue and on biopsies immediately taken from ER +/HER2- MBC patients before the start of standard EVE/EXE (Eudract 2013-004120-11).

Toxicologic and Inhibitory Receptor Actions of the Etomidate Analog ABP-700 and Its Metabolite CPM-Acid.

Background: The etomidate analog ABP-700 produces involuntary muscle movements that could be manifestations of seizures. To define the relationship (if any) between involuntary muscle movements and seizures, electroencephalographic studies were performed in Beagle dogs receiving supra-therapeutic (~10× clinical) ABP-700 doses. γ-aminobutyric acid type A (GABAA) and glycine receptor studies were undertaken to test receptor inhibition as the potential mechanism for ABP-700 seizures.

Safety and clinical effect of i.v. infusion of cyclopropyl-methoxycarbonyl etomidate (ABP-700), a soft analogue of etomidate, in healthy subjects.

Background: Cyclopropyl-methoxycarbonyl metomidate, or ABP-700, is a second generation analogue of etomidate, developed to retain etomidate's beneficial haemodynamic and respiratory profile but diminishing its suppression of the adrenocortical axis. The objective of this study was to characterise the safety and efficacy of 30-min continuous infusions of ABP-700, and to assess its effect on haemodynamics and the adrenocortical response in healthy human volunteers.

Methods: Five cohorts involving 40 subjects received increasing infusion doses of ABP-700, propofol 60 μg kg min or placebo.

A Phase 1, Single-center, Double-blind, Placebo-controlled Study in Healthy Subjects to Assess the Safety, Tolerability, Clinical Effects, and Pharmacokinetics-Pharmacodynamics of Intravenous Cyclopropyl-methoxycarbonylmetomidate (ABP-700) after a Single Ascending Bolus Dose.

Background: Cyclopropyl-methoxycarbonylmetomidate (ABP-700) is a new "soft" etomidate analog. The primary objectives of this first-in-human study were to describe the safety and efficacy of ABP-700 and to determine its maximum tolerated dose. Secondary objectives were to characterize the pharmacokinetics of ABP-700 and its primary metabolite (cyclopropyl-methoxycarbonyl acid), to assess the clinical effects of ABP-700, and to investigate the dose-response and pharmacokinetic/pharmacodynamic relationships.

Cardiac safety, efficacy, and correlation of serial serum HER2-extracellular domain shed antigen measurement with the outcome of the combined trastuzumab plus CMF in women with HER2-positive metastatic breast cancer: results from the EORTC 10995 phase II study.

Purpose: Cardiotoxicity is a side effect of trastuzumab. We assessed efficacy and cardiac safety of CMF with trastuzumab (CMF+T) in HER2-positive metastatic breast cancer patients (MBC).

Methods: In this phase II study, centrally confirmed, previously treated HER2-positive MBC patients with measurable disease (per RECIST v 1.

One Week of Bed Rest Leads to Substantial Muscle Atrophy and Induces Whole-Body Insulin Resistance in the Absence of Skeletal Muscle Lipid Accumulation.

Short (<10 days) periods of muscle disuse, often necessary for recovery from illness or injury, lead to various negative health consequences. The current study investigated mechanisms underlying disuse-induced insulin resistance, taking into account muscle atrophy. Ten healthy, young males (age: 23 ± 1 years; BMI: 23.

Efficacy of six month neoadjuvant endocrine therapy in postmenopausal, hormone receptor-positive breast cancer patients--a phase II trial.

Background: Neoadjuvant hormonal therapy (NHT) is playing an increasing role in the clinical management of breast cancer (BC) and may improve surgical outcomes for postmenopausal, oestrogen receptor (ER)-positive BC patients. However, there is currently no consensus on the optimal duration of NHT before surgery. Here, we present the outcomes of the TEAM IIA trial, a multicentre, phase II trial investigating the efficacy of six months of neoadjuvant exemestane in postmenopausal, strong ER-positive (ER+, ⩾50%) BC patients.

First-line bevacizumab plus taxane-based chemotherapy for locally recurrent or metastatic breast cancer: safety and efficacy in an open-label study in 2,251 patients.

Background: First-line bevacizumab combined with chemotherapy significantly improves efficacy versus chemotherapy alone in human epidermal growth factor receptor 2 (HER2)-negative locally recurrent or metastatic breast cancer (LR/mBC). This large, open-label study further assesses first-line bevacizumab with taxane-based chemotherapy in routine oncology practice.

Patients And Methods: Patients with HER2-negative LR/mBC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of zero to two and no prior chemotherapy for LR/mBC received bevacizumab 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks plus taxane-based chemotherapy (or other non-anthracycline chemotherapy) until disease progression, unacceptable toxicity or patient withdrawal.

Alveolar soft-part sarcoma responding to interferon alpha-2b.

A 23-year-old woman with an alveolar soft-part sarcoma of her calf with pulmonary metastases unresponsive to chemotherapy is described. Interferon (IFN) alpha-2b induced an impressive tumour response still ongoing after IFN treatment had to be stopped because of a psychosis. An explanation of this effect is still speculative.

[A gastric signet ring cell carcinoma as the first expression of a breast carcinoma].

A 73-year-old woman presented with dull pain in the epigastric region, a rapid feeling of fullness upon eating and a weight loss of 10 kg in 6 months. Further examination showed linitis plastica due to a signet ring cell carcinoma in the stomach, multiple bone metastases, and an occult, small breast tumour. Immunohistochemical comparison of the tumours strongly suggested that all cases involved a metastasised breast carcinoma.

[Non-traumatic myositis ossificans circumscripta in the teres major muscle].

A 49-year-old male presented with a painful progressive swelling in his right axillar region, without further complaints, which had been present for 2 weeks. On radiological examination a peripheral circumferential zone of mineralisation was seen in the right teres major muscle. An incision biopsy specimen showed a lesion of fibroblastic tissue in which areas of osteoid and fragmented lamellar bone tissue, without signs of malignancy.