Diastereospecific Synthesis of Vicinally Substituted 2-Oxazolidinones via Oxidative Rearrangement of α,β-Unsaturated γ-Lactams.

A diastereospecific synthesis of vicinally substituted 2-oxazolidinones from α,β-unsaturated lactams using -chloroperoxybenzoic acid is reported. Several highly substituted 2-oxazolidinones were obtained in 19-46% yields in a one-pot reaction with complete control over the relative stereochemistry. The proposed reaction sequence consists of a Baeyer-Villiger oxidation, an epoxidation, and a concerted rearrangement.

Getting school-provided meals to the table: an international multiple-case study of school food service.

A school food service, which is the way children access food during the school day, is one of the many aspects in creating a health-promoting school environment. School-provided meal services differ greatly, depending on the country, region and school contexts, however, there is limited understanding of the diverse meal delivery within these settings. Therefore, the aim of this study was to understand different school-provided meal systems across different countries and contexts.

Challenges in developing response evaluation criteria for peptide receptor radionuclide therapy: A consensus report from the European Neuroendocrine Tumor Society Advisory Board Meeting 2022 and the ENETS Theranostics Task Force.

Assessing the response to systemic therapy in neuroendocrine tumors (NET) is challenging since morphological imaging response is often delayed and not necessarily reflective of clinical benefit. Peptide receptor radionuclide therapy (PRRT) has a complex mechanism of action, further complicating response assessment. In response to these challenges, the European Neuroendocrine Tumor Society (ENETS) Theranostics Task Force conducted a statement-based survey among experts to identify the current landscape and unmet needs in PRRT response assessment.

Sulfonamide-derivatized galactosides selectively target an unexplored binding site in the galectin-9N-terminal domain.

Four directional and positional variants of sulfonamide-derivatized galactopyranosides were synthesized and evaluated against human galectin-1, -3, -4C (C-terminal), -7, -8N (N-terminal), -8C (C-terminal), -9N (N-terminal), and -9C (C-terminal), which revealed that one of the sulfonamide positions and directionalities (methyl 3-{4-[2-(phenylsulfonylamino)-phenyl]-triazolyl}-3-deoxy-α-d-galactopyranosides) bound with 6-15 fold higher affinity than the corresponding phenyltriazole (lacking the phenylsulfonamide moiety) for galectin-9N. Molecular dynamic simulations suggested that inhibitor adopted a conformation that is complementary to the galectin-9N binding site and where the sulfonamide moiety protrudes into an unexplored and non-conserved binding site perpendicular to and below the A-B subsite to interact with a His61 NH proton. This resulted in the discovery of galectin-9N inhibitors with unprecedented selectivity over other galectins, thus constituting valuable tools for studies of the biological functions of galectin-9.

Design and cohort characteristics of TRACK, a prospective study of hyperkalaemia management decision-making.

Background: Guideline-recommended hyperkalaemia management includes dietary potassium (K) restriction, bicarbonate correction, diuretics and K binders with dose reduction of renin-angiotensin-aldosterone system inhibitors as a last resort. The extent to which these recommendations are implemented is uncertain, as real-world data on hyperkalaemia management are limited. The Tracking Treatment Pathways in Adult Patients with Hyperkalemia (TRACK) study is a multinational, prospective, longitudinal study that is being conducted to address this knowledge gap.

The evolutionary history of metastatic pancreatic neuroendocrine tumours reveals a therapy driven route to high-grade transformation.

Tumour evolution with acquisition of more aggressive disease characteristics is a hallmark of disseminated cancer. Metastatic pancreatic neuroendocrine tumours (PanNETs) in particular may progress from a low/intermediate to a high-grade disease. The aim of this work was to understand the molecular mechanisms underlying metastatic progression as well as PanNET transformation from a low/intermediate to a high-grade disease.

Radiation dosimetry of para-chloro-2-[F]fluoroethyl-etomidate: a PET tracer for adrenocortical imaging.

Background: [C]metomidate, a methyl ester analogue of etomidate, is used for positron emission tomography of adrenocortical cancer, and has been tested in recent clinical trials for lateralization in primary aldosteronism (PA). However, in PA, visualization as well as uptake quantification are hampered by the tracer's rather high non-specific liver uptake, and its overall clinical usefulness is also limited by the short 20-minute half-life of carbon-11. Therefore, we evaluated para-chloro-2-[F]fluoroethyl-etomidate, [F]CETO, a fluorine-18 (T=109.

Genetics-guided therapy in neuroendocrine carcinoma: response to BRAF- and MEK-inhibitors.

Background: Metastatic neuroendocrine carcinoma (NEC) is associated with short survival. Other than platinum-based chemotherapy, there is no clear standard regimen. Current guidelines suggest that combination treatment with BRAF-inhibitors should be considered for patients with V600E-mutated NEC.

Sodium Zirconium Cyclosilicate in CKD, Hyperkalemia, and Metabolic Acidosis: NEUTRALIZE Randomized Study.

Key Points: Sodium zirconium cyclosilicate effectively lowers serum potassium and maintains normokalemia in patients with CKD with concomitant hyperkalemia and metabolic acidosis. Despite high screen failure and small sample size, a nominally significant increase in sHCO was seen for sodium zirconium cyclosilicate versus placebo. Further studies on the basis of an appropriate cohort size may help validate the trend observed in sHCO levels, supporting these clinically relevant findings.

Prevalence of metastases outside the liver and abdominal lymph nodes on Ga-DOTATOC-PET/CT in patients with small intestinal and pancreatic neuroendocrine tumours.

Metastases outside the liver and abdominal/retroperitoneal lymph nodes are nowadays detected frequently in patients with neuroendocrine tumours (NETs), owing to the high sensitivity of positron emission tomography (PET) with Gallium-68-DOTA-somatostatin analogues (Ga-SSA) and concomitant diagnostic computed tomography (CT). Our aim was to determine the prevalence of extra-abdominal metastases on Ga-DOTATOC-PET/CT in a cohort of patients with small intestinal (Si-NET) and pancreatic NET (Pan-NET), as well as that of pancreatic metastasis in patients with Si-NET. Among 2090 patients examined by Ga-DOTATOC-PET/CT at two tertiary referral centres, a total of 1177 patients with a history of Si- or Pan-NET, were identified.

Hypoalbuminemia, but not derived neutrophil to lymphocyte ratio (dNLR), predicts overall survival in neuroendocrine tumours undergoing peptide receptor radionuclide therapy: A retrospective, cohort study of 557 patients.

Several inflammation scores have shown association with survival outcomes for patients with neuroendocrine tumours (NET) treated with peptide receptor radionuclide therapy (PRRT). However, whether these scores add value to established prognostic factors remains unknown. In this retrospective, cohort study of 557 NET patients undergoing PRRT in a tertiary referral centre from 2005 to 2015, we examined inflammatory markers and scores previously associated with cancer outcomes, using Cox proportional hazard models and Akaike's information criterion.

The Evolutionary History of Metastatic Pancreatic Neuroendocrine Tumours Reveals a Therapy Driven Route to High-Grade Transformation.

Tumour evolution with acquisition of more aggressive disease characteristics is a hallmark of disseminated cancer. Metastatic pancreatic neuroendocrine tumours (PanNETs) in particular, show frequent progression from a low/intermediate to a high-grade disease. To understand the molecular mechanisms underlying this phenomenon, we performed multi-omics analysis of 32 longitudinal samples from six metastatic PanNET patients.

Outcomes of pediatric pilonidal disease treatment: excision with off-midline flap reconstruction versus endoscopic pilonidal sinus treatment.

Purpose: Pilonidal disease (PD) is marked by chronic inflammation and frequent recurrence which can decrease quality of life. However, debate remains regarding the optimal treatment for PD in the pediatric population. This study compares two recommended treatment approaches-excision with off-midline flap reconstruction (OMF: Bascom cleft lift flap, modified Limberg flap) and minimally invasive endoscopic pilonidal sinus treatment (EPSiT).

Randomised, siteless study to compare systematic atrial fibrillation screening using enrichment by a risk prediction model with standard care in a Swedish population aged ≥ 65 years: CONSIDERING-AF study design.

Introduction: Atrial fibrillation (AF) is the most common arrhythmia and confers an increased risk of mortality, stroke, heart failure and cognitive decline. There is growing interest in AF screening; however, the most suitable population and device for AF detection remains to be elucidated. Here, we present the design of the CONSIDERING-AF (deteCtiON and Stroke preventIon by moDEl scRreenING for Atrial Fibrillation) study.

Changes in tumor-to-blood ratio as a prognostic marker for progression-free survival and overall survival in neuroendocrine tumor patients undergoing PRRT.

Background: Historically, patient selection for peptide receptor radionuclide therapy (PRRT) has been performed by virtue of somatostatin receptor scintigraphy (SRS). In recent years, somatostatin receptor positron emission tomography (SSTR-PET) has gradually replaced SRS because of its improved diagnostic capacity, creating an unmet need for SSTR-PET-based selection criteria for PRRT. Tumor-to-blood ratio (TBR) measurements have shown high correlation with the net influx rate Ki, reflecting the tumor somatostatin receptor expression, to a higher degree than standardized uptake value (SUV) measurements.

Non-invasive imaging of sympathetic innervation of the pancreas in individuals with type 2 diabetes.

Aims/hypothesis: Compromised pancreatic sympathetic innervation has been suggested as a factor involved in both immune-mediated beta cell destruction and endocrine dysregulation of pancreatic islets. To further explore these intriguing findings, new techniques for in vivo assessment of pancreatic innervation are required. This is a retrospective study that aimed to investigate whether the noradrenaline (norepinephrine) analogue C-hydroxy ephedrine (C-HED) could be used for quantitative positron emission tomography (PET) imaging of the sympathetic innervation of the human pancreas.

Mesenchymal STRO-1/STRO-3 precursor cells for the treatment of chronic heart failure with reduced ejection fraction.

The heart is susceptible to proinflammatory and profibrotic responses after myocardial injury, leading to further worsening of cardiac dysfunction. Important developments in the management of heart failure with reduced ejection fraction have reduced morbidity and mortality; however, these therapies focus on optimizing cardiac function through hemodynamic and neurohormonal pathways and not by repairing the underlying cardiac injury. The potential of cell-based therapy to reverse cardiac injury has received substantial attention.

Improved health-related quality of life during peptide receptor radionuclide therapy in patients with neuroendocrine tumours.

Neuroendocrine tumours (NETs) can arise in different locations in the body, and may give rise to hormonal symptoms, which amongst other factors may affect patients' health-related quality of life (HRQoL). Up to four cycles of peptide receptor radionuclide therapy (PRRT) have been shown effective for symptom alleviation and prolonging progression-free survival. The aim of this study was to assess the patient's perspective regarding changes in their HRQoL during PRRT.

Endoscopic Management of a Double Duodenal Web: A Case Report of a Rare Alimentary Anomaly.

Duodenal webs are a rare clinical entity with the presentation of a double duodenal web being exceedingly uncommon. Management of duodenal webs traditionally involves duodenal web excision with duodenoduodenostomy, which is usually performed via a laparoscopic or an open approach. We report the case of a 6-month-old child who presented with progressively worsening bilious emesis with imaging findings concerning for a duodenal web.

European Neuroendocrine Tumor Society (ENETS) 2023 guidance paper for gastroduodenal neuroendocrine tumours (NETs) G1-G3.

The aim of the present guidance paper was to update the previous ENETS guidelines on well-differentiated gastric and duodenal neuroendocrine tumours (NETs), providing practical guidance for specialists in the diagnosis and management of gastroduodenal NETs. Type II gastric NETs, neuroendocrine carcinomas (NECs), and functioning duodenal NETs are not covered, since they will be discussed in other ENETS guidance papers.

[Many adrenal incidentalomas are not adequately evaluated - updated guidelines to improve follow-up are presented].

The use of cross-sectional imaging in Sweden has increased more than twofold in the last 20 years. Inadvertently discovered adrenal lesions, adrenal incidentalomas, are reported in about one per cent of abdominal investigations. The first Swedish guidelines for the management of adrenal incidentalomas were published in 1996 and have since then been regularly revised.

Impact of administered amount of peptide on tumor dosimetry at the first cycle of peptide receptor radionuclide therapy (PRRT) in relation to total tumor somatostatin receptor expression.

Background: The accumulation of Lu-DOTATATE might be influenced by the amount of administered peptide in relation to the tumor somatostatin receptor expression. The effect of the administered peptide mass on the resulting absorbed dose in tumors and normal organs has not previously been assessed in relation to the patients' tumor load.

Method: Patients with small intestinal (n = 141) and pancreatic (n = 62) neuroendocrine tumors (NETs) who underwent PRRT were selected for retrospective evaluation.