Pan-European survey on current treatment strategies in patients with upfront resectable colorectal liver metastases.

Background: There is a lack of consensus on the definition of upfront resectability and use of perioperative systemic therapy for colorectal liver metastases (CRLM). This survey aimed to summarize the current treatment strategies for upfront resectable CRLM throughout Europe.

Methods: A survey was sent to all members of the European-African Hepato-Pancreato-Biliary Association to gain insight into the current views on resectability and the use of systemic therapy for upfront resectable CRLM.

Archaeal virus entry and egress.

Archaeal viruses display a high degree of structural and genomic diversity. Few details are known about the mechanisms by which these viruses enter and exit their host cells. Research on archaeal viruses has lately made significant progress due to advances in genetic tools and imaging techniques, such as cryo-electron tomography (cryo-ET).

Does preoperative multidisciplinary team assessment of high-risk patients improve the safety and outcomes of patients undergoing surgery?

Background: International guidelines recommend preoperative multidisciplinary team (MDT) assessment for high-risk surgical patients. Preoperative MDT meetings can help to improve surgical care, but there is little evidence on whether they improve patient outcomes.

Methods: This paper aims to share our experience of MDT meetings for high-risk surgical patients to underline their added value to the current standard of care.

Recurrent Colorectal Liver Metastases: Upfront Local Treatment versus Neoadjuvant Systemic Therapy Followed by Local Treatment (COLLISION RELAPSE): Study Protocol of a Phase III Prospective Randomized Controlled Trial.

Purpose: The objective of the COLLISION RELAPSE trial is to prove or disprove superiority of neoadjuvant systemic therapy followed by repeat local treatment (either thermal ablation and/or surgical resection), compared to repeat local treatment alone, in patients with at least one recurrent locally treatable CRLM within one year and no extrahepatic disease.

Methods: A total of 360 patients will be included in this phase III, multicentre randomized controlled trial. The primary endpoint is overall survival.

Intersurgeon Variability in Local Treatment Planning for Patients with Initially Unresectable Colorectal Cancer Liver Metastases: Analysis of the Liver Expert Panel of the Dutch Colorectal Cancer Group.

Background: Consensus on resectability criteria for colorectal cancer liver metastases (CRLM) is lacking, resulting in differences in therapeutic strategies. This study evaluated variability of resectability assessments and local treatment plans for patients with initially unresectable CRLM by the liver expert panel from the randomised phase III CAIRO5 study.

Methods: The liver panel, comprising surgeons and radiologists, evaluated resectability by predefined criteria at baseline and 2-monthly thereafter.

The Role of Tryptophan in π Interactions in Proteins: An Experimental Approach.

In proteins, the amino acids Phe, Tyr, and especially Trp are frequently involved in π interactions such as π-π, cation-π, and CH-π bonds. These interactions are often crucial for protein structure and protein-ligand binding. A powerful means to study these interactions is progressive fluorination of these aromatic residues to modulate the electrostatic component of the interaction.

International Hand Function Study Following Distal Radial Access: The RATATOUILLE Study.

Background: Distal radial access (DRA) has been proposed to improve procedure ergonomics and favor radial artery patency. Although promising data, nothing is known on evolving hand function after DRA.

Objectives: This study sought to comprehensively evaluate hand function in patients undergoing DRA.

Oligo Pools as an Affordable Source of Synthetic DNA for Cost-Effective Library Construction in Protein- and Metabolic Pathway Engineering.

The construction of custom libraries is critical for rational protein engineering and directed evolution. Array-synthesized oligo pools of thousands of user-defined sequences (up to ∼350 bases in length) have emerged as a low-cost commercially available source of DNA. These pools cost ≤10 % (depending on error rate and length) of other commercial sources of custom DNA, and this significant cost difference can determine whether an enzyme engineering project can be realized on a given research budget.

A multidisciplinary neuro-oncological triage panel reduces the time to referral and treatment for patients with a brain tumor.

Background: Regional collaboration and appropriate referral management are crucial in neuro-oncological care. Lack of electronic access to medical records across health care organizations impedes interhospital consultation and may lead to incomplete and delayed referrals. To improve referral management, we have established a multidisciplinary neuro-oncological triage panel (NOTP) with digital image exchange and determined the effects on lead times, costs, and time investment.

Liver Failure, Renal Failure, and a Rash: An Unusually Severe Case of Multi-Organ Failure Due to Murine Typhus.

Murine typhus is a vector-borne disease transmitted to humans via fleas and typically causes an infection hallmarked by nonspecific, mild symptoms of fever, rash, and headache. More severe diseases, while rare, can occur. We present a complicated case of murine typhus resulting in liver and renal failure.

Survival Benefit of Repeat Local Treatment in Patients Suffering From Early Recurrence of Colorectal Cancer Liver Metastases.

Background: A uniform treatment strategy for patients suffering from early recurrence after local treatment of CRLM is currently lacking. The aim of this observational cohort study was to assess the potential survival benefit of repeat local treatment compared to systemic therapy in patients suffering from early recurrence of CRLM.

Patients And Methods: Patients who developed recurrent CRLM within 12 months after initial local treatment with curative intent were retrospectively identified in Amsterdam University Medical Centers between 2009-2019.

Weakness Due to Anemia? Go Fish! Melena as a Red Herring in the Diagnosis of Statin-Induced Myopathy.

Statins are a ubiquitous medication class in the primary care setting where they provide effective primary and secondary prevention of coronary artery disease by lowering cholesterol. While statins are mostly safe, muscle-related adverse events are well described. Very rarely patients can actually develop elevated creatine kinase (CK) consistent with myonecrosis.

Reducing the Inappropriate Use of Proton Pump Inhibitors in an Internal Medicine Residency Clinic.

Introduction Proton pump inhibitors (PPI) are commonly prescribed in the primary care setting. While generally considered to be safe, there is growing evidence suggesting that PPI misuse is associated with a variety of significant adverse outcomes and unnecessary cost. The goal of this quality improvement project was to identify patients with non-guideline recommended PPI prescriptions in our internal medicine residency clinics and implement a process to de-prescribe or reduce the dose of PPIs across this patient population.

The Prevalence of Faculty Physician Burnout in Military Graduate Medical Education Training Programs: A Cross-Sectional Study of Academic Physicians in the United States Department of Defense.

Introduction: In military populations, physician burnout has potential to adversely affect medical readiness to deploy in support of joint operations. Burnout among Graduate Medical Education (GME) faculty may further threaten the welfare of the medical force given the central role these officers have in training and developing junior physicians. The primary aim of this investigation was to estimate the prevalence of burnout among faculty physicians in United States (US) Army, Navy, and Air Force GME programs.

Development of Covalent Ligands for G Protein-Coupled Receptors: A Case for the Human Adenosine A Receptor.

The development of covalent ligands for G protein-coupled receptors (GPCRs) is not a trivial process. Here, we report a streamlined workflow thereto from synthesis to validation, exemplified by the discovery of a covalent antagonist for the human adenosine A receptor (hAAR). Based on the 1 H,3 H-pyrido[2,1- f]purine-2,4-dione scaffold, a series of ligands bearing a fluorosulfonyl warhead and a varying linker was synthesized.

Structural and Antiviral Studies of the Human Norovirus GII.4 Protease.

Norovirus is the leading cause of acute gastroenteritis worldwide with a yearly reported 700 million cases driving a $60 billion global socioeconomic burden. With no United States Food and Drug Administration approved therapeutics and the chance for severe chronic infection and life-threatening complications, researchers have identified the protease as a potential target. However, drug development has focused on the norovirus GI.

Synthesis and antiviral evaluation of novel peptidomimetics as norovirus protease inhibitors.

A series of tripeptidyl transition state inhibitors with new P1 and warhead moieties were synthesized and evaluated in a GI-1 norovirus replicon system and against GII-4 and GI-1 norovirus proteases. Compound 19, containing a 6-membered ring at the P1 position and a reactive aldehyde warhead exhibited sub-micromolar replicon inhibition. Retaining the same peptidyl scaffold, several reactive warheads were tested for protease inhibition and norovirus replicon inhibition.

Expression, Purification and Characterization of a GII.4 Norovirus Protease from Minerva Virus.

Background: Noroviruses are the leading cause of acute gastroenteritis worldwide. Norovirus proteases, which are responsible for cleavage of the viral polyprotein, have become an attractive drug target to treat norovirus infections. Genogroup II (GII) noroviruses are responsible for a majority of outbreaks; however, limited data exists regarding GII norovirus proteases.

After the fall: improving osteoporosis treatment following hip fracture.

Unlabelled: Osteoporotic hip fractures can be life changing and can increase mortality. Treatment of osteoporosis following hip fracture is often delayed. We began offering osteoporosis medication during hospitalization for hip fracture, dramatically increasing the number of patients meeting standard of care.

Incivility in the Emergency Department: Implications for Nurse Leaders.

Uncivil behavior leads to low self-esteem, anxiety, sleep disturbance, recurrent nightmares, and depression. This article looks at the perception of incivility among emergency department nurses and the leadership required to implement evidence-based strategies to address this growing problem.

Localized Control of Curie Temperature in Perovskite Oxide Film by Capping-Layer-Induced Octahedral Distortion.

With reduced dimensionality, it is often easier to modify the properties of ultrathin films than their bulk counterparts. Strain engineering, usually achieved by choosing appropriate substrates, has been proven effective in controlling the properties of perovskite oxide films. An emerging alternative route for developing new multifunctional perovskite is by modification of the oxygen octahedral structure.

Isolated cranio-orbitofacial neurofibroma mimicking vascular malformation.

Isolated neurofibromas in the absence of systemic neurofibromatosis are known as solitary or localized neurofibromas. When present in the orbit, these lesions may appear clinically and radiographically similar to other tumors, complicating diagnosis and management. Key radiographic signs may guide clinicians to the correct diagnosis when the presentation and patient demographic data obfuscate the disease entity.