Trastuzumab Plus Pertuzumab Versus Cetuximab Plus Irinotecan in Patients With Wild-Type, HER2-Positive, Metastatic Colorectal Cancer (S1613): A Randomized Phase II Trial.

Purpose: overexpression/amplification in wild-type (WT) metastatic colorectal cancer (mCRC; human epidermal growth factor receptor 2 [HER2]-positive mCRC) appears to be associated with limited benefit from anti-EGFR antibodies and promising responses to dual-HER2 inhibition; however, comparative efficacy has not been investigated. We conducted a randomized phase II trial to evaluate efficacy and safety of dual-HER2 inhibition against standard-of-care anti-EGFR antibody-based therapy as second/third-line treatment in HER2-positive mCRC.

Methods: Patients with -WT mCRC after central confirmation of HER2 positivity (immunohistochemistry 3+ or 2+ and in situ hybridization amplified [HER2/CEP17 ratio >2.

Enhancement of response learning in male rats with intrastriatal infusions of a BDNF - TrkB agonist, 7,8-dihydroxyflavone.

Enhancement of learning and memory by cognitive and physical exercise may be mediated by brain-derived neurotrophic factor (BDNF) acting at tropomyosin receptor kinase B (TrkB). Upregulation of BDNF and systemic administration of a TrkB agonist, 7,8-dihydroxyflavone (7,8-DHF), enhance learning of several hippocampus-sensitive tasks in rodents. Although BDNF and 7,8-DHF enhance functions of other brain areas too, these effects have mainly targeted non-cognitive functions.

Dealing With Complications as a Young Surgeon.

Rewarding and honorable, yet challenging and humbling, this is our chosen profession. No matter how robust of a residency and fellowship training we have had or how impactful our mentors have been, nothing can truly prepare us for dealing with complications as new attendings.

The Effect of Cemented Implants Placed During Initial TKA on Surgical Time and Expenses in Revision TKA.

Introduction: Revision total knee arthroplasty (rTKA) is a complex procedure that often requires the removal of previous implants. There is little information evaluating the difference between removing cemented or noncemented knee prostheses in revision surgeries. The purpose of this study was to determine whether removing cemented or noncemented implants would affect surgical time and expenses incurred during revision procedures.

How to Estimate Femoral Stem Anteversion During Direct Anterior Approach Total Hip Arthroplasty.

Background: There are various traditional landmarks used to estimate the femoral component version, yet none are widely accepted by direct anterior surgeons. The purpose of this study was to compare bony landmarks easily accessible to direct anterior surgeons and to estimate which one provides the best estimate of femoral component anteversion.

Methods: A computed tomography database was used to identify 736 left entire-femur computed tomography scans.

Intravenous immunoglobulin for patients with unexplained recurrent implantation failure: a 6-year single center retrospective review of clinical outcomes.

The effectiveness of intravenous immunoglobulin (IVIg) for patients with unexplained recurrent implantation failure (uRIF) remains debated. We retrospectively analysed outcomes of uRIF patients treated with IVIg compared to a separate control uRIF cohort within our center (01/2014-12/2021). Primary outcomes included live birth, miscarriage, or transfer failure.

Sunitinib in Patients With Breast Cancer With or Amplifications or Mutations: Results From the Targeted Agent and Profiling Utilization Registry Study.

Purpose: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. Results from cohorts of patients with metastatic breast cancer (BC) with and alterations treated with sunitinib are reported.

Methods: Eligible patients had measurable disease, Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options.

A Cautionary Tale: Malaligned Incentives in Total Hip and Knee Arthroplasty Payment Model Reforms Threaten Promising Innovation and Access to Care.

Over the past several years, there have been notable changes and controversies involving Medicare reimbursement for total hip (THA) and total knee arthroplasty (TKA). We have seen the development and implementation of experimental bundled payment model pilot programs goals of improving quality and decreasing overall costs of care during the last decade. Many orthopaedic surgeons have embraced these programs and have demonstrated the ability to succeed in these new models by implementing strategies, such as preservice optimization, to shift care away from inpatient or postdischarge settings and reduce postoperative complications.

Nivolumab Plus Ipilimumab in Patients With Solid Tumors With Mutations: Results From the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.

Purpose: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket study evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancers with genomic alterations known to be drug targets. Results of a cohort of patients with solid tumors with mutations treated with nivolumab plus ipilimumab are reported.

Methods: Eligible patients had measurable disease (RECIST v.

Allograft or Synthetic Mesh Extensor Mechanism Reconstruction After TKA Carries a High Risk of Infection, Revision, and Extensor Lag.

Background: Extensor mechanism disruption is a devastating complication after TKA. Extensor mechanism reconstruction can be performed using an allograft or synthetic mesh. Recent studies have disagreed about the durability of these reconstructions.

Intravenous immunoglobulin use in patients with unexplained recurrent pregnancy loss.

Problem: Recurrent pregnancy loss (RPL) affects up to 4% of couples attempting to conceive. RPL is unexplained in over 50% of cases and no effective treatments exist. Due to the immune system's pivotal role during implantation and pregnancy, immune-mediated RPL may be suspected and immunomodulatory treatments like intravenous immunoglobulin (IVIg) have been administered but remain controversial.

Lower Revenue Surplus in Medicare Advantage Versus Private Commercial Insurance for Total Joint Arthroplasty: An Analysis of a Single Payor Source at One Institution.

Background: Since the Affordable Care Act was passed in 2010, reductions in Medicare reimbursement have led to larger discrepancies between the relative cost of Medicare patients and privately insured patients. The purpose of this study was to compare reimbursement between Medicare Advantage and other insurance plans in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA).

Methods: Patients of a single commercial payor source who underwent primary unilateral TKA or THA at 1 institution between the dates of January 4 and June 30, 2021, were included (n = 833).

Circulating Tumor DNA as a Predictive Biomarker for Clinical Outcomes With Margetuximab and Pembrolizumab in Pretreated HER2-Positive Gastric/ Gastroesophageal Adenocarcinoma.

Purpose: To assess the ability of circulating tumor DNA (ctDNA)-based testing to identify patients with HER2 (encoded by ERBB2)-positive gastric/gastroesophageal adenocarcinoma (GEA) who progressed on or after trastuzumab-containing treatments were treated with combination therapy of anti-HER2 and anti-PD-1 agents.

Methods: ctDNA analysis was performed retrospectively using plasma samples collected at study entry from 86 patients participating in the phase 1/2 CP-MGAH22-05 study (NCT02689284).

Results: Objective response rate (ORR) was significantly higher in evaluable ERBB2 amplification-positive vs - negative patients based on ctDNA analysis at study entry (37% vs 6%, respectively; P = .

Inflammation, stress and depression: An exploration of ketamine's therapeutic profile.

Well-established animal models of depression have described a proximal relationship between stress and central nervous system (CNS) inflammation - a relationship mirrored in the peripheral inflammatory biomarkers of individuals with depression. Evidence also suggests that stress-induced proinflammatory states can contribute to the neurobiology of treatment-resistant depression. Interestingly, ketamine, a rapid-acting antidepressant, can partially exert its therapeutic effects via anti-inflammatory actions on the hypothalamic-pituitary adrenal (HPA) axis, the kynurenine pathway or by cytokine suppression.

Does Time Spent in the Post-Anesthesia Care Unit Affect Hospital Lengths of Stay following Primary Total Knee Arthroplasty?

Given the current healthcare economic environment, substantial efforts have been made to help streamline the in-hospital care for total knee arthroplasty (TKA) patients. While potential cost-reducing factors have been identified in the literature, analyses specifically considering post-anesthesia care unit (PACU) lengths of stay (LOS) are lacking. Therefore, the purpose of this study was to identify factors associated with (1) longer PACU LOS as well as (2) longer Hospital LOS.

Immunomodulation for unexplained recurrent implantation failure: where are we now?

In Brief: Immune dysfunction may contribute to or cause recurrent implantation failure. This article summarizes normal and pathologic immune responses at implantation and critically appraises currently used immunomodulatory therapies.

Abstract: Recurrent implantation failure (RIF) may be defined as the absence of pregnancy despite the transfer of ≥3 good-quality blastocysts and is unexplained in up to 50% of cases.

Revisiting and Revising Memory Consolidation: Personal Reflections on the Research Legacy of Ivan Izquierdo.

Two important themes in Ivan Izquierdo's research each offered both answers and questions about the topic of memory formation and maintenance. The first theme provided evidence supporting the view that short- and long-term memory were distinct processes and could be selectively modulated by several treatments, with some affecting only short-term, others only affecting long-term memory, and still others affecting both. Over many years, Izquierdo's laboratory documented molecular responses across time after training obtaining results that showed differences as well as similarities in the biochemical changes during the first 1-2 h and the next 4-6 h after training, i.