Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma.

Background: Talquetamab (anti-G protein-coupled receptor family C group 5 member D) and teclistamab (anti-B-cell maturation antigen) are bispecific antibodies that activate T cells by targeting CD3 and that have been approved for the treatment of triple-class-exposed relapsed or refractory multiple myeloma.

Methods: We conducted a phase 1b-2 study of talquetamab plus teclistamab in patients with relapsed or refractory multiple myeloma. In phase 1, we investigated five dose levels in a dose-escalation study.

A new class of penicillin-binding protein inhibitors to address drug-resistant .

β-Lactams are the most widely used antibiotics for the treatment of bacterial infections because of their proven track record of safety and efficacy. However, susceptibility to β-lactam antibiotics is continually eroded by resistance mechanisms. Emerging multidrug-resistant (MDR) strains possessing altered alleles (encoding PBP2) pose a global health emergency as they threaten the utility of ceftriaxone, the last remaining outpatient antibiotic.

Artificial intelligence-based real-time histopathology of gastric cancer using confocal laser endomicroscopy.

There has been a persistent demand for an innovative modality in real-time histologic imaging, distinct from the conventional frozen section technique. We developed an artificial intelligence-driven real-time evaluation model for gastric cancer tissue using confocal laser endomicroscopic system. The remarkable performance of the model suggests its potential utilization as a standalone modality for instantaneous histologic assessment and as a complementary tool for pathologists' interpretation.

Treatment and Care of Patients with ST-Segment Elevation Myocardial Infarction-What Challenges Remain after Three Decades of Primary Percutaneous Coronary Intervention?

Primary percutaneous coronary intervention (pPCI) has revolutionized the prognosis of ST-segment elevation myocardial infarction (STEMI) and is the gold standard treatment. As a result of its success, the number of pPCI centres has expanded worldwide. Despite decades of advancements, clinical outcomes in STEMI patients have plateaued.

A common polymorphism in the Intelectin-1 gene influences mucus plugging in severe asthma.

By incompletely understood mechanisms, type 2 (T2) inflammation present in the airways of severe asthmatics drives the formation of pathologic mucus which leads to airway mucus plugging. Here we investigate the molecular role and clinical significance of intelectin-1 (ITLN-1) in the development of pathologic airway mucus in asthma. Through analyses of human airway epithelial cells we find that ITLN1 gene expression is highly induced by interleukin-13 (IL-13) in a subset of metaplastic MUC5AC mucus secretory cells, and that ITLN-1 protein is a secreted component of IL-13-induced mucus.

Reducing low-value interhospital transfers for mild traumatic brain injury.

Background: The modified Brain Injury Guidelines (mBIG) were developed to stratify traumatic brain injuries (TBIs) and improve health care utilization by selectively requiring repeat imaging, intensive care unit admission, and neurosurgical (NSG) consultation. The goal of this study is to assess safety and potential resource savings associated with the application of mBIG on interhospital patient transfers for TBI.

Methods: Adult patients with TBI transferred to our Level I trauma center from January 2017 to December 2022 meeting mBIG inclusion criteria were retrospectively stratified into mBIG1, mBIG2, and mBIG3 based on initial clinicoradiological factors.

Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial.

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need.

A chimeric antigen receptor uniquely recognizing MICA/B stress proteins provides an effective approach to target solid tumors.

Background: The advent of chimeric antigen receptor (CAR) T cell therapies has transformed the treatment of hematological malignancies; however, broader therapeutic success of CAR T cells has been limited in solid tumors because of their frequently heterogeneous composition. Stress proteins in the MICA and MICB (MICA/B) family are broadly expressed by tumor cells following DNA damage but are rapidly shed to evade immune detection.

Methods: We have developed a novel CAR targeting the conserved α3 domain of MICA/B (3MICA/B CAR) and incorporated it into a multiplexed-engineered induced pluripotent stem cell (iPSC)-derived natural killer (NK) cell (3MICA/B CAR iNK) that expressed a shedding-resistant form of the CD16 Fc receptor to enable tumor recognition through two major targeting receptors.

Acute Infarcts on Brain MRI Following Aortic Arch Repair With Circulatory Arrest: Insights From the ACE CardioLink-3 Randomized Trial.

Background: to investigate the frequency and distribution of new ischemic brain lesions detected by diffusion-weighted imaging on brain magnetic resonance imaging after aortic arch surgery.

Methods: This preplanned secondary analysis of the randomized, controlled ACE (Aortic Surgery Cerebral Protection Evaluation) CardioLink-3 trial compared the safety and efficacy of innominate versus axillary artery cannulation during elective proximal aortic arch surgery. Participants underwent pre and postoperative magnetic resonance imaging.

Direct Tie2 Agonists Stabilize Vasculature for the Treatment of Diabetic Macular Edema.

Purpose: Diabetic macular edema (DME) is the leading cause of vision loss and blindness among working-age adults. Although current intravitreal anti-vascular endothelial growth factor (VEGF) therapies improve vision for many patients with DME, approximately half do not achieve the visual acuity required to drive. We therefore sought additional approaches to resolve edema and improve vision for these patients.

A molecularly engineered, broad-spectrum anti-coronavirus lectin inhibits SARS-CoV-2 and MERS-CoV infection in vivo.

"Pan-coronavirus" antivirals targeting conserved viral components can be designed. Here, we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high mannose found on viral proteins but seldom on healthy human cells, potently inhibits Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (including Omicron), and other human-pathogenic coronaviruses at nanomolar concentrations. H84T-BanLec protects against MERS-CoV and SARS-CoV-2 infection in vivo.

Novel, First-in-Human, Oral PCLX-001 Treatment in a Patient with Relapsed Diffuse Large B-Cell Lymphoma.

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) have limited treatment options, particularly if they are transplantation or chimeric antigen receptor (CAR) T-cell ineligible, and novel therapeutics are needed. An 86-year-old woman with relapsed DLBCL received a novel, first-in-class small molecule inhibitor of N-myristoyltransferase (NMT) as the initial patient on a phase I dose escalation trial. Daily oral administration of 20 mg PCLX-001 tablets produced a pharmacokinetic profile suitable for single daily dosing: rapid oral absorption, followed by an apparent elimination half-life of 16 h, without systemic accumulation of drug by day 15.

Immune response to SARS-CoV-2 after a booster of mRNA-1273: an open-label phase 2 trial.

Rising breakthrough infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in previously immunized individuals have raised concerns for the need for a booster vaccine dose to combat waning antibody levels and new variants. Here we report the results of the open-label, non-randomized part B of a phase 2 trial in which we evaluated the safety and immunogenicity of a booster injection of 50 µg of the coronavirus disease 2019 (COVID-19) vaccine mRNA-1273 in 344 adult participants immunized 6-8 months earlier with a primary series of two doses of 50 µg or 100 µg of mRNA-1273 ( NCT04405076 ). Neutralizing antibody (nAb) titers against wild-type SARS-CoV-2 at 1 month after the booster were 1.

Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift.

The recently emerged SARS-CoV-2 Omicron variant encodes 37 amino acid substitutions in the spike protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody-based therapeutics. Here we show that the Omicron RBD binds to human ACE2 with enhanced affinity, relative to the Wuhan-Hu-1 RBD, and binds to mouse ACE2. Marked reductions in neutralizing activity were observed against Omicron compared to the ancestral pseudovirus in plasma from convalescent individuals and from individuals who had been vaccinated against SARS-CoV-2, but this loss was less pronounced after a third dose of vaccine.

Randomized, Controlled Trial Comparing Mitral Valve Repair With Leaflet Resection Versus Leaflet Preservation on Functional Mitral Stenosis: The CAMRA CardioLink-2 Study.

Background: Equipoise exists between the use of leaflet resection and preservation for surgical repair of mitral regurgitation caused by prolapse. We therefore performed a randomized, controlled trial comparing these 2 techniques, particularly in regard to functional mitral stenosis.

Methods: One hundred four patients with degenerative mitral regurgitation surgically amenable to either leaflet resection or preservation were randomized at 7 specialized cardiac surgical centers.

Characteristics of COVID-19 in Homeless Shelters : A Community-Based Surveillance Study.

Background: Homeless shelters are a high-risk setting for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission because of crowding and shared hygiene facilities.

Objective: To investigate SARS-CoV-2 case counts across several adult and family homeless shelters in a major metropolitan area.

Design: Cross-sectional, community-based surveillance study.