Case report: A rare cause of intestinal perforation in a third-trimester pregnant woman.

Background: An acute abdomen is a medical emergency that requires early diagnosis and treatment. In pregnancy, this process is significantly more challenging, and radiological findings are sometimes unclear due to the enlarged uterus displacing other structures. Moreover, endometriosis-related complications are rare, and the disease is often undiagnosed.

Inter- and intra-rater-reliability of a clinical framework for spine-related neck-arm pain.

Objective: A mechanism-based clinical framework for spine-related pain differentiates (i) somatic referred pain, ii) heightened nerve mechanosensitivity, iii) radicular pain, iv) radiculopathy and mixed-pain. This study aimed to determine the reliability of proposed framework.

Method: Fifty-one people with unilateral spine-related neck-arm pain were assessed and categorized by examiner-1.

Phase I studies of the safety, tolerability, pharmacokinetics and pharmacodynamics of the dual glucagon receptor/glucagon-like peptide-1 receptor agonist BI 456906.

Aim: To report two phase I studies of the novel subcutaneous glucagon-like peptide-1 receptor/glucagon receptor (GLP-1R/GCGR) dual agonist BI 456906 versus placebo in healthy volunteers and people with overweight/obesity.

Materials And Methods: A phase Ia study (NCT03175211) investigated single rising doses (SRDs) of BI 456906 in 24 males with a body mass index (BMI) of 20-<30 kg/m . A phase Ib study (NCT03591718) investigated multiple rising doses (MRDs) of BI 456906 (escalated over 6 [Part A] or 16 [Part B] weeks) in 125 adults with a BMI of 27-40 kg/m .

Impact of Siponimod on Enteric and Central Nervous System Pathology in Late-Stage Experimental Autoimmune Encephalomyelitis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). Although immune modulation and suppression are effective during relapsing-remitting MS, secondary progressive MS (SPMS) requires neuroregenerative therapeutic options that act on the CNS. The sphingosine-1-phosphate receptor modulator siponimod is the only approved drug for SPMS.

Neurochemical classification of serotonin-immunoreactive neurons co-innervating motor endplates in the mouse esophagus.

Serotonin immunoreactivity was previously found in myenteric neurons co-innervating motor endplates in the mouse esophagus striated muscle and an involvement in motility control was suggested. However, it is not known if other neuroactive substances are present in these neurons and to what extent they co-localize. First, vasoactive intestinal peptide (VIP) was established as a bona fide marker for putative inhibitory myenteric neurons by evaluating co-localization with neuronal nitric oxide synthase (nNOS) and neuropeptide Y (NPY).

Acute effects of linagliptin on intact and total glucagon-like peptide-1 and gastric inhibitory polypeptide levels in insulin-dependent type 2 diabetes patients with and without moderate renal impairment.

Aims: To investigate the effect of renal impairment on incretin metabolism in patients with type 2 diabetes mellitus (T2DM) before and after treatment with the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin.

Materials And Methods: Long-standing T2DM patients with normal (estimated glomerular filtration rate [eGFR] >90 mL/min/1.73m ) and impaired (eGFR <60 mL/min/1.

Effect of upper gastrointestinal disease on the pharmacokinetics of oral semaglutide in subjects with type 2 diabetes.

Aim: To investigate whether upper gastrointestinal (GI) disease has any effect on the exposure of oral semaglutide, an important consideration given that its absorption occurs primarily in the stomach.

Materials And Methods: In an open-label, parallel-group trial (NCT02877355), subjects aged 18-80 years with type 2 diabetes with mild-to-moderate upper GI disease (N = 36; chronic gastritis [n = 5], gastroesophageal reflux disease [n = 8], and both [n = 23]) or without upper GI disease (N = 19) received oral semaglutide 3 mg once daily for 5 days, followed by 7 mg for 5 days. The primary and key supportive endpoints were the area under the semaglutide plasma concentration-time curve (AUC) from 0 to 24 hours after last trial product administration on day 10 (AUC ) and the maximum semaglutide plasma concentration (C ), respectively.

Ultra-rapid lispro shows faster pharmacokinetics and reduces postprandial glucose excursions versus Humalog® in patients with type 2 diabetes mellitus in a randomized, controlled crossover meal test early phase study.

Aims: To compare the pharmacokinetics (PK), glucodynamics (GD) and tolerability following single and multiple daily subcutaneous doses of ultra rapid lispro (URLi) and Humalog® in patients with type 2 diabetes mellitus (T2D).

Materials And Methods: This was a two-part, randomized, double-blind Phase 1b study. Part A used a six-period crossover design to assess PK and GD response to a solid mixed meal tolerance test (MMTT) following a single dose of URLi or Humalog administered 15 minutes before, immediately before, or 15 minutes after the start of the meal.

Macronutrient intake, appetite, food preferences and exocrine pancreas function after treatment with short- and long-acting glucagon-like peptide-1 receptor agonists in type 2 diabetes.

Aim: To clarify the distinct effects of a long-acting (liraglutide) and a short-acting (lixisenatide) glucagon-like peptide-1 receptor agonist (GLP-1 RA) on macronutrient intake, gastrointestinal side effects and pancreas function.

Materials And Methods: Fifty participants were randomized to either lixisenatide or liraglutide for a treatment period of 10 weeks. Appetite, satiety, macronutrient intake, gastrointestinal symptoms and variables related to pancreatic function and gastric emptying were assessed at baseline and after treatment.

Murine Esophagus Expresses Glial-Derived Central Nervous System Antigens.

Multiple sclerosis (MS) has been considered to specifically affect the central nervous system (CNS) for a long time. As autonomic dysfunction including dysphagia can occur as accompanying phenomena in patients, the enteric nervous system has been attracting increasing attention over the past years. The aim of this study was to identify glial and myelin markers as potential target structures for autoimmune processes in the esophagus.

Application and utility of a clinical framework for spinally referred neck-arm pain: A cross-sectional and longitudinal study protocol.

Background: The clinical presentation of neck-arm pain is heterogeneous with varying underlying pain types (nociceptive/neuropathic/mixed) and pain mechanisms (peripheral/central sensitization). A mechanism-based clinical framework for spinally referred pain has been proposed, which classifies into (1) somatic pain, (2) neural mechanosensitivity, (3) radicular pain, (4) radiculopathy and mixed pain presentations. This study aims to (i) investigate the application of the clinical framework in patients with neck-arm pain, (ii) determine their somatosensory, clinical and psychosocial profile and (iii) observe their clinical course over time.

A single-dose euglycaemic clamp study in two cohorts to compare the exposure of SAR341402 (insulin aspart) Mix 70/30 with US- and European-approved versions of insulin aspart Mix 70/30 and SAR341402 rapid-acting solution in subjects with type 1 diabetes.

Aim: To compare the pharmacokinetic exposure of SAR341402 Mix 70/30 (SAR -Mix) with US- and European (EU)-approved versions of insulin aspart Mix 70/30 (NovoLog Mix 70/30 [NN-Mix-US]/NovoMix 30 [NN-Mix-EU]) and SAR341402 insulin aspart solution (SAR-Asp) in subjects with type 1 diabetes.

Materials And Methods: This was a randomized, double-blind, crossover trial in two cohorts. Fifty-two subjects received a single subcutaneous 0.

Effects of Lixisenatide Versus Liraglutide (Short- and Long-Acting GLP-1 Receptor Agonists) on Esophageal and Gastric Function in Patients With Type 2 Diabetes.

Objective: Short-acting glucagon-like peptide 1 receptor agonists (GLP-1 RAs) decelerate gastric emptying more than long-acting GLP-1 RAs. Delayed gastric emptying is a risk factor for gastroesophageal reflux disease. We aimed to measure esophageal reflux and function as well as gastric emptying and acid secretion during treatment with short-acting (lixisenatide) and long-acting (liraglutide) GLP-1 RAs.

Ultra rapid lispro lowers postprandial glucose and more closely matches normal physiological glucose response compared to other rapid insulin analogues: A phase 1 randomized, crossover study.

Aims: To compare the pharmacokinetic (PK) and glucodynamic (GD) characteristics of ultra rapid lispro (URLi; Eli Lilly and Company, Indianapolis, Indiana), Fiasp® (Novo Nordisk, Bagsvaerd, Denmark), Humalog® (Eli Lilly and Company) and NovoRapid® (Novo Nordisk), in patients with type 1 diabetes (T1D).

Materials And Methods: This was a randomized, double-blind, four-period, crossover study, conducted in 68 patients with T1D. Patients received the same individualized subcutaneous dose of each study drug immediately prior to a liquid test meal.

Single-Dose Euglycemic Clamp Study Demonstrating Pharmacokinetic and Pharmacodynamic Similarity Between SAR341402 Insulin Aspart and US- and EU-Approved Versions of Insulin Aspart in Subjects with Type 1 Diabetes.

The objective of this study was to demonstrate the pharmacokinetic and pharmacodynamic similarity among SAR341402 insulin aspart biosimilar/follow-on product, United States-sourced insulin aspart (NovoLog), and European Union-sourced insulin aspart (NovoRapid). This was a single-center, randomized, double-blind, 3-treatment, 3-period, single-dose, crossover euglycemic study (NCT03202875) in 30 adult male subjects with type 1 diabetes (T1D). Subjects received 0.

Effects of sequential treatment with lixisenatide, insulin glargine, or their combination on meal-related glycaemic excursions, insulin and glucagon secretion, and gastric emptying in patients with type 2 diabetes.

Aim: To examine the glucose-lowering mechanisms of the glucagon-like peptide-1 receptor agonist lixisenatide after two subsequent meals and in combination with basal insulin.

Materials And Methods: Twenty-eight metformin-treated patients with type 2 diabetes were randomly assigned to treatment sequences with either lixisenatide or insulin glargine alone for 4 weeks, and a combination of both treatments for 4 weeks. Metabolic examinations were performed before and after each treatment period following breakfast and a late lunch 8 hours later.

[The Management of Mid-Portion Achilles Tendinopathy from a Physiotherapeutic Point of View: A Systematic Review].

Tendinopathy of the mid-portion of the Achilles tendon is common in athletes and non-athletes. From a physiotherapeutic view, calf muscle training is the most recommended kind of treatment. However, there is no current systematic review evaluating the efficacy of physiotherapy in due consideration of the entire spectrum of therapeutic options.

Sequential Treatment Escalation with Dapagliflozin and Saxagliptin Improves Beta Cell Function in Type 2 Diabetic Patients on Previous Metformin Treatment: An Exploratory Mechanistic Study.

We investigated the effect of sequential treatment escalation with dapagliflozin and saxagliptin on beta cell function in patients with T2DM insufficiently controlled on metformin monotherapy during a hyperglycaemic clamp investigation. Twenty-six patients (19 males, age 63.5±7.

Impact of Injection Speed, Volume, and Site on Pain Sensation.

Background: Painful subcutaneous insulin injections may decrease treatment compliance. Improving injection comfort therefore represents a particular area of technological research in which steady progress has been made since the introduction of the insulin pen in 1985. Injection pain can be influenced by many variables, but relatively little is known about their impact.

Acceptability of Implantable Continuous Glucose Monitoring Sensor.

Background: Real-time continuous glucose monitoring is associated with significant benefits for diabetes management. Implantable sensors could overcome some challenges reportedly associated with device visibility, psychosocial functioning and sensor durability.

Methods: A psychosocial assessment was conducted to determine acceptability and impact of an implantable continuous glucose monitoring (CGM) sensor as part of the PRECISE trial.

Understanding how pharmacokinetic and pharmacodynamic differences of basal analog insulins influence clinical practice.

This article reviews pharmacokinetic (PK) and pharmacodynamic (PD) concepts relating to the pharmacology of basal insulin analogs. Understanding the pharmacology of currently available long-acting basal insulins and the techniques used to assess PK and PD parameters (e.g.

Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial.

Aims/hypothesis: Semaglutide is a glucagon-like peptide-1 analogue in development for the treatment of type 2 diabetes. Its effects on first- and second-phase insulin secretion and other measures of beta cell function and glycaemic control were assessed.

Methods: In this single-centre, double-blind, placebo-controlled, parallel-group trial, conducted at the Profil Institut für Stoffwechselforschung, Germany, 75 adult (aged 18-64 years) participants with type 2 diabetes (eligibility: HbA of 6.

Impact of insulin glargine and lixisenatide on β-cell function in patients with type 2 diabetes mellitus: A randomized open-label study.

It is known that β-cell function can be enhanced by direct stimulation of insulin secretion or by induction of β-cell rest, but whether both strategies can complement each other has not yet been examined. A total of 28 people with type 2 diabetes (glycated haemoglobin 7.8% ± 0.

Consistent findings in glycaemic control, body weight and hypoglycaemia with iGlarLixi (insulin glargine/lixisenatide titratable fixed-ratio combination) vs insulin glargine across baseline HbA1c, BMI and diabetes duration categories in the LixiLan-L trial.

Aims: To assess the impact of baseline characteristics on clinical outcomes in the LixiLan-L trial, a randomized open-label trial designed to evaluate the efficacy and safety of iGlarLixi, a novel fixed-ratio combination of insulin glargine 100 U (iGlar) plus lixisenatide, in comparison with iGlar over 30 weeks in a population of patients with type 2 diabetes mellitus (T2DM) inadequately controlled on a previous regimen of basal insulin alone or in combination with 1 or 2 oral glucose-lowering drugs.

Materials And Methods: In this exploratory analysis of LixiLan-L (N = 736), efficacy outcomes were assessed within population subgroups derived from the following baseline characteristics: glycated haemoglobin [HbA1c; <8%, ≥8% (<64, ≥64 mmol/mol)]; duration of T2DM (<10, ≥10 years); body mass index (<30, ≥30 kg/m ). Furthermore, the incidence of symptomatic hypoglycaemia with plasma glucose ≤3.