From 0 to 100: Delayed Direct to Implant Breast Reconstruction, an Alternative to Tissue Expansion.

Introduction: Implant-based reconstruction is not always feasible when mastectomy flap viability is poor. Rather than returning to the operating room for staged breast reconstruction with tissue expansion (TE), patients may instead opt for delayed direct to implant (dDTI) reconstruction. This study aimed to assess the feasibility of dDTI after patients "go flat" after their mastectomy.

Wax on, wax off: a case report discussing a potential pitfall of dissolvable bone wax substitutes such as Ostene® in neurosurgery.

Bone wax alternatives, such as Ostene®, are marketed as substitutes for traditional bone wax, offering the benefits of resorbability, improved bone osteogenesis, and reduced inflammatory reactions, granulomas, and infection risks. However, the limitations of these agents in cranial neurosurgery, particularly for sealing exposed air cells during skull base repair, are underreported. We present an early post-operative case of subcutaneous emphysema, pneumocephalus, and bone flap infection following the failure of Ostene® to provide a durable seal of air cells after temporal craniotomy and tumour resection.

Snowball Group Usability Testing for Rapid and Iterative Multisite Tool Development: Method Development Study.

Background: Usability testing is valuable for assessing a new tool or system's usefulness and ease-of-use. Several established methods of usability testing exist, including think-aloud testing. Although usability testing has been shown to be crucial for successful clinical decision support (CDS) tool development, it is often difficult to conduct across multisite development projects due to its time- and labor-intensiveness, cost, and the skills required to conduct the testing.

Efficacy and Safety of Barbed Sutures for Capsulorrhaphy in Implant-Based Breast Reconstruction.

Background: A common postoperative challenge following implant-based breast reconstruction surgery is lateral or inferior displacement of the implant, which ultimately requires surgical intervention to shape the pocket for improved symmetry. Capsulorrhaphy is traditionally performed with smooth sutures, but the use of barbed sutures has proven to be more efficient and effective in other plastic surgery procedures. This study aimed to demonstrate the safety and efficacy of barbed sutures for breast reconstruction implant capsulorrhaphy.

Verification of a simplified aneurysm dimensionless flow parameter to predict intracranial aneurysm rupture status.

Objectives: Aneurysm number (An) is a novel prediction tool utilizing parameters of pulsatility index (PI) and aneurysm geometry. An has been shown to have the potential to differentiate intracranial aneurysm (IA) rupture status. The objective of this study is to investigate the feasibility and accuracy of An for IA rupture status prediction using Australian based clinical data.

Barriers to Implementing Registered Nurse-Driven Clinical Decision Support for Antibiotic Stewardship: Retrospective Case Study.

Background: Up to 50% of antibiotic prescriptions for upper respiratory infections (URIs) are inappropriate. Clinical decision support (CDS) systems to mitigate unnecessary antibiotic prescriptions have been implemented into electronic health records, but their use by providers has been limited.

Objective: As a delegation protocol, we adapted a validated electronic health record-integrated clinical prediction rule (iCPR) CDS-based intervention for registered nurses (RNs), consisting of triage to identify patients with low-acuity URI followed by CDS-guided RN visits.

Large-scale Pan-cancer Cell Line Screening Identifies Actionable and Effective Drug Combinations.

Unlabelled: Oncology drug combinations can improve therapeutic responses and increase treatment options for patients. The number of possible combinations is vast and responses can be context-specific. Systematic screens can identify clinically relevant, actionable combinations in defined patient subtypes.

Reducing prescribing of antibiotics for acute respiratory infections using a frontline nurse-led EHR-Integrated clinical decision support tool: protocol for a stepped wedge randomized control trial.

Background: Overprescribing of antibiotics for acute respiratory infections (ARIs) remains a major issue in outpatient settings. Use of clinical prediction rules (CPRs) can reduce inappropriate antibiotic prescribing but they remain underutilized by physicians and advanced practice providers. A registered nurse (RN)-led model of an electronic health record-integrated CPR (iCPR) for low-acuity ARIs may be an effective alternative to address the barriers to a physician-driven model.

BID expression determines the apoptotic fate of cancer cells after abrogation of the spindle assembly checkpoint by AURKB or TTK inhibitors.

Background: Drugs targeting the spindle assembly checkpoint (SAC), such as inhibitors of Aurora kinase B (AURKB) and dual specific protein kinase TTK, are in different stages of clinical development. However, cell response to SAC abrogation is poorly understood and there are no markers for patient selection.

Methods: A panel of 53 tumor cell lines of different origins was used.

Pharmaceutical Reactivation of Attenuated Apoptotic Pathways Leads to Elimination of Osimertinib Drug-Tolerant Cells.

Unlabelled: Osimertinib is an EGFR tyrosine kinase inhibitor (TKI) with proven clinical efficacy; however, acquired resistance presents an obstacle to curing -driven disease. Recent studies have shown that drug-tolerant persister cells (DTP) have a distinct transcriptional profile that may confer specific vulnerabilities. By definition these cells avoid apoptosis, yet little is known about how their survival is regulated.

Impact of patient-centered prescription medication labels on adherence in community pharmacy.

Background: Prescription medication labels are often constructed in a manner which hinders safe and appropriate use of medicines. The United States Pharmacopeia released voluntary standards to revise medication labels in an effort to support patients' understanding and improve medication use.

Objective: To examine the impact of label changes on medication adherence before and after pharmacy implementation of the United States Pharmacopeia patient-centered prescription medication label standards.

The landscape of therapeutic vulnerabilities in EGFR inhibitor osimertinib drug tolerant persister cells.

Third-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs), including osimertinib, an irreversible EGFR-TKI, are important treatments for non-small cell lung cancer with EGFR-TKI sensitizing or EGFR T790M resistance mutations. While patients treated with osimertinib show clinical benefit, disease progression and drug resistance are common. Emergence of de novo acquired resistance from a drug tolerant persister (DTP) cell population is one mechanism proposed to explain progression on osimertinib and other targeted cancer therapies.

Escape from G1 arrest during acute MEK inhibition drives the acquisition of drug resistance.

Mutations and gene amplifications that confer drug resistance emerge frequently during chemotherapy, but their mechanism and timing are poorly understood. Here, we investigate amplification events that underlie resistance to the MEK inhibitor selumetinib (AZD6244/ARRY-142886) in COLO205 cells, a well-characterized model for reproducible emergence of drug resistance, and show that amplifications acquired are the primary cause of resistance. Selumetinib causes long-term G1 arrest accompanied by reduced expression of DNA replication and repair genes, but cells stochastically re-enter the cell cycle during treatment despite continued repression of pERK1/2.

A Systematic Review of Neuropsychological Outcomes After Treatment of Intracranial Aneurysms.

Background: Aneurysmal subarachnoid hemorrhage is a cause of profound morbidity and mortality. Its effects extend beyond functional neurological status to neurocognitive and psychological functioning. Endovascular treatment is becoming more prevalent after increasing evidence for its safety and efficacy; however, there is a relative paucity of evidence specific to neurocognitive status after treatment.

Combinatorial approaches for mitigating resistance to KRAS-targeted therapies.

Approximately 15% of all cancer patients harbor mutated KRAS. Direct inhibitors of KRAS have now been generated and are beginning to make progress through clinical trials. These include a suite of inhibitors targeting the KRASG12C mutation commonly found in lung cancer.

Clipping coiling: A critical re-examination of a decades old controversy.

Background: Two major studies, The International Subarachnoid Aneurysm Trial and the Barrow Ruptured Aneurysm Trial, compare the long-term outcomes of clipping and coiling. Although these demonstrated coiling's initial benefits, rebleeding and retreatment rates as well as converging patient outcomes sparked controversy regarding its durability. This article will critically examine the available evidence for and against clipping and coiling of intracranial aneurysms.

Evolution of biomarker research in autoimmunity conditions for health professionals and clinical practice.

Medical abzymology has made a great contribution to the development of general autoimmunity theory: it has put the autoantibodies (Ab) as the key brick of the theory to the level of physiological functionality by providing such Ab with the ability to catalyze and mediate direct and independent cytotoxic effect on cellular and molecular targets. Natural catalytic autoantibodies (abzymes) while being a pool of canonical Abs and possessing catalytic activity belong to the new group of physiologically active substances whose features and properties are evolutionary consolidated in one functionally active biomolecule. Therefore, further studies on Ab-mediated autoAg degradation and other targeted Ab-mediated proteolysis may provide biomarkers of newer generations and thus a supplementary tool for assessing the disease progression and predicting disability of the patients and persons at risks.

Complication Profile of Total Submuscular Versus Prepectoral Tissue Expander Placement: A Retrospective Cohort Study.

Background: We sought to compare the safety profile of prepectoral breast reconstruction with total submuscular tissue expander reconstruction, previously our standard. Primary outcomes of interest in this retrospective cohort study were incidence of infection, hematoma, seroma, mastectomy flap necrosis, and reconstruction loss.

Methods: Total submuscular and prepectoral with acellular dermal matrix reconstructions consecutively performed by a single surgeon (P.

Knowledge graph-based recommendation framework identifies drivers of resistance in EGFR mutant non-small cell lung cancer.

Resistance to EGFR inhibitors (EGFRi) presents a major obstacle in treating non-small cell lung cancer (NSCLC). One of the most exciting new ways to find potential resistance markers involves running functional genetic screens, such as CRISPR, followed by manual triage of significantly enriched genes. This triage process to identify 'high value' hits resulting from the CRISPR screen involves manual curation that requires specialized knowledge and can take even experts several months to comprehensively complete.

Feasibility of a Randomized Controlled Mixed Methods Trial to Address Health Literacy, Beliefs, Medication Adherence, and Self-Efficacy (ADHERE) in a Clinical Pharmacist-Led Clinic.

Purpose: To assess the feasibility and acceptability of a health literacy-psychosocial support intervention - ADHERE and explore changes in glycemic values and medication adherence.

Patients And Methods: Thirty-one participants with hemoglobin A1c (HbA1c) ≥ 8% were randomly allocated to control (usual care) or intervention groups (receiving usual care plus a 6-session pharmacist-led intervention focusing on the modifiable psychosocial factors that may influence medication adherence). Feasibility metrics evaluated recruitment, retention, and intervention adherence.

Anti-PD-L1 and anti-CD73 combination therapy promotes T cell response to EGFR-mutated NSCLC.

Treatment with anti-PD-1 and anti-PD-L1 therapies has shown durable clinical benefit in non-small cell lung cancer (NSCLC). However, patients with NSCLC with epidermal growth factor receptor (EGFR) mutations do not respond as well to treatment as patients without an EGFR mutation. We show that EGFR-mutated NSCLC expressed higher levels of CD73 compared with EGFR WT tumors and that CD73 expression was regulated by EGFR signaling.

Oncogenic switch and single-agent MET inhibitor sensitivity in a subset of -mutant lung cancer.

The clinical efficacy of epidermal growth factor receptor (EGFR)–targeted therapy in -mutant non–small cell lung cancer is limited by the development of drug resistance. One mechanism of EGFR inhibitor resistance occurs through amplification of the human growth factor receptor () proto-oncogene, which bypasses EGFR to reactivate downstream signaling. Tumors exhibiting concurrent mutation and amplification are historically thought to be codependent on the activation of both oncogenes.