Concurrent Panniculectomy With Abdominal Wall Reconstruction: A Propensity-scored Matched Study of Quality Improvement Outcomes.

Background: Concurrent panniculectomy with abdominal wall reconstruction (CP-AWR) as a single-stage operation has reported increased complications, but constant quality improvement can improve results. This study describes outcomes for 21 years, impacted by evidence-based-practice changes.

Methods: Prospectively maintained database was reviewed for CP-AWR and separated by surgery date: "early" (2002-2016) and "recent" (2017-2023).

Inhibitor development according to concentrate after 50 exposure days in severe hemophilia: data from the European HAemophilia Safety Surveillance (EUHASS).

Background: Patients with hemophilia have a life-long risk of developing neutralizing antibodies (inhibitors) against clotting factor concentrates. After the first 50 exposure days (EDs), ie, in previously treated patients (PTPs), data on inhibitor development are limited.

Objectives: To report inhibitor development according to factor (F)VIII or FIX concentrate use in PTPs with severe hemophilia A and B.

Inhibitor development according to concentrate in severe hemophilia: reporting on 1392 Previously Untreated Patients from Europe and Canada.

Background: Clotting factor concentrates have been the mainstay of severe hemophilia treatment over the last 50 years. Differences in risk of neutralizing antibody (inhibitor) formation according to concentrate used remain clinically relevant.

Objectives: To assess inhibitor development according to type of clotting factor concentrate in previously untreated patients (PUPs) with severe hemophilia A and B.

First-in-human, phase 1 study of PF-06753512, a vaccine-based immunotherapy regimen (VBIR), in non-metastatic hormone-sensitive biochemical recurrence and metastatic castration-resistant prostate cancer (mCRPC).

Background: This phase 1 study evaluated PF-06753512, a vaccine-based immunotherapy regimen (PrCa VBIR), in two clinical states of prostate cancer (PC), metastatic castration-resistant PC (mCRPC) and biochemical recurrence (BCR).

Methods: For dose escalation, patients with mCRPC received intramuscular PrCa VBIR (adenovirus vector and plasmid DNA expressing prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA), and prostate stem cell antigen (PSCA)) with or without immune checkpoint inhibitors (ICIs, tremelimumab 40 or 80 mg with or without sasanlimab 130 or 300 mg, both subcutaneous). For dose expansion, patients with mCRPC received recommended phase 2 dose (RP2D) of PrCa VBIR plus tremelimumab 80 mg and sasanlimab 300 mg; patients with BCR received PrCa VBIR plus tremelimumab 80 mg (Cohort 1B-BCR) or tremelimumab 80 mg plus sasanlimab 130 mg (Cohort 5B-BCR) without androgen deprivation therapy (ADT).

mRNA Signatures in Peripheral White Blood Cells Predict Reproductive Potential in Beef Heifers at Weaning.

Reproductive failure is a major contributor to inefficiency within the cow-calf industry. Particularly problematic is the inability to diagnose heifer reproductive issues prior to pregnancy diagnosis following their first breeding season. Therefore, we hypothesized that gene expression from the peripheral white blood cells at weaning could predict the future reproductive potential of beef heifers.

Preclinical development of a vaccine-based immunotherapy regimen (VBIR) that induces potent and durable T cell responses to tumor-associated self-antigens.

The development of therapeutic cancer vaccines remains an active area, although previous approaches have yielded disappointing results. We have built on lessons from previous cancer vaccine approaches and immune checkpoint inhibitor research to develop VBIR, a vaccine-based immunotherapy regimen. Assessment of various technologies led to selection of a heterologous vaccine using chimpanzee adenovirus (AdC68) for priming followed by boosts with electroporation of DNA plasmid to deliver T cell antigens to the immune system.

Oncolytic Vaccinia Virus Gene Modification and Cytokine Expression Effects on Tumor Infection, Immune Response, and Killing.

Oncolytic vaccinia viruses have promising efficacy and safety profiles in cancer therapy. Although antitumor activity can be increased by manipulating viral genes, the relative efficacy of individual modifications has been difficult to assess without side-by-side comparisons. This study sought to compare the initial antitumor activity after intravenous administration of five vaccinia virus variants of the same Western Reserve backbone and thymidine kinase gene deletion in RIP-Tag2 transgenic mice with spontaneous pancreatic neuroendocrine tumors.

Distinct Biomarker Profiles and TCR Sequence Diversity Characterize the Response to PD-L1 Blockade in a Mouse Melanoma Model.

Only a subset of patients responds to immune checkpoint blockade (ICB) in melanoma. A preclinical model recapitulating the clinical activity of ICB would provide a valuable platform for mechanistic studies. We used melanoma tumors arising from an Hgf;Cdk4 genetically engineered mouse (GEM) model to evaluate the efficacy of an anti-mouse PD-L1 antibody similar to the anti-human PD-L1 antibodies durvalumab and atezolizumab.

Effectiveness of the quadrivalent high-dose influenza vaccine for prevention of cardiovascular and respiratory events in people aged 65 years and above: Rationale and design of a real-world pragmatic randomized clinical trial.

Background: Influenza has been an acknowledged cause of respiratory disease for decades. However, considerable related, and often unappreciated, disease burden stems from cardiovascular complications, exacerbations of underlying medical conditions and secondary respiratory complications, with the highest burden in the elderly. This novel study combines the gold standard method of a randomized controlled trial with real-world data collection through national registries, to assess the relative effectiveness of high-dose (QIV-HD) vs standard-dose quadrivalent influenza vaccine (QIV-SD) in preventing cardio-respiratory hospitalizations in a large cohort of adults aged ≥65 years.

Introductory paper: High-dose influenza vaccine.

Seasonal influenza has a significant impact on global public health each year, especially in older adults 65 years of age and above. This paper presents the evolution of high-dose influenza vaccine and the quantity as well as quality of evidence on this vaccine. Its introduces other peer-reviewed manuscripts included in this supplement covering the benefits high-dose influenza vaccine over ten consecutive influenza seasons.

comparison of treatments and commercially available solutions on mortality of third-stage larvae.

On Hawai'i Island, an increase in human neuroangiostrongyliasis cases has been primarily associated with the accidental ingestion of Angiostrongylus cantonensis L3 in snails or slugs, or potentially, from larvae left behind in the slug's slime or feces. We evaluated more than 40 different treatments in vitro for their ability to kill A. cantonensis larvae with the goal of identifying a safe and effective fruit and vegetable wash in order to reduce the risk of exposure.

Assessment of the benefits of seasonal influenza vaccination: Elements of a framework to interpret estimates of vaccine effectiveness and support robust decision-making and communication.

Systematic reviews and meta-analyses confirm that influenza vaccination reduces the risk of influenza illness by between about 40% and 60% in seasons when circulating influenza stains are well matched to vaccine strains. Influenza vaccine effectiveness (IVE) estimates, however, are often discordant and a source of confusion for decision makers. IVE assessments are increasingly publicized and are often used by policy makers to make decisions about the value of seasonal influenza vaccination.

Quantifying the Impact of Influenza Among Persons With Type 2 Diabetes Mellitus: A New Approach to Determine Medical and Physical Activity Impact.

Background: We describe the impact of influenza on medical outcomes and daily activities among people with and without type 2 diabetes mellitus (T2DM).

Methods: Retrospective cohort analysis of a US health plan offering a digital wellness platform connecting wearable devices capable of tracking steps, sleep, and heart rate. For the 2016 to 2017 influenza season, we compared adults with T2DM to age and gender matched controls.

Hybrid clinical trials to generate real-world evidence: design considerations from a sponsor's perspective.

Randomized controlled trials have traditionally been the gold standard for evaluating efficacy and safety of medical products and for regulatory decision-making. With the advancement of information technologies, vast amounts of data pertinent to patient health status and health care delivery are becoming available from a variety of real-world sources, including electronic health records, medical claims, patient registries, and patient-generated data. In 2016, the United States Congress passed the 21st Century Cures Act, mandating the U.

Postharvest Population Reservoirs of Coffee Berry Borer (Coleoptera: Curculionidae) on Hawai'i Island.

Coffee berry borer, Hypothenemus hampei Ferrari (Coleoptera: Curculionidae: Scolytinae), is the most damaging insect pest of coffee worldwide. Old coffee berries (raisins) are widely acknowledged as coffee berry borer reservoirs, yet few studies have attempted to quantify coffee berry borer populations in raisins remaining on farms postharvest. We collected ground and tree raisins at six coffee farms on Hawai'i Island to assess raisin density, infestation, coffee berry borer abundance, and adult mortality in three areas of each farm: trees, driplines (ground below the tree foliage), and center aisles (ground between tree rows).

Coffee berry borer (Hypothenemus hampei) (Coleoptera: Curculionidae) development across an elevational gradient on Hawai'i Island: Applying laboratory degree-day predictions to natural field populations.

Coffee berry borer (CBB, Hypothenemus hampei) (Coleoptera: Curculionidae: Scolytinae) is the most destructive pest of coffee worldwide. Information on CBB development times can be used to predict the initiation of new infestation cycles early in the coffee-growing season and thus inform the timing of insecticide applications. While laboratory estimates of CBB development under constant conditions exist, they have not been applied under the heterogeneous environmental conditions that characterize many coffee-growing regions.

Turning the corner on therapeutic cancer vaccines.

Recent advances in several areas are rekindling interest and enabling progress in the development of therapeutic cancer vaccines. These advances have been made in target selection, vaccine technology, and methods for reversing the immunosuppressive mechanisms exploited by cancers. Studies testing different tumor antigens have revealed target properties that yield high tumor versus normal cell specificity and adequate immunogenicity to affect clinical efficacy.

Immunogenicity of high-dose trivalent inactivated influenza vaccine: a systematic review and meta-analysis.

Introduction: High-dose trivalent, inactivated, split-virus influenza vaccine (IIV3-HD) has been available in the US since 2009 for adults aged ≥ 65 years. To better understand how IIV3-HD provides improved protection against influenza, we systematically reviewed clinical studies comparing immune responses to IIV3-HD and standard-dose trivalent vaccine (IIV3-SD).

Areas Covered: The primary objective was to determine the relative hemagglutination inhibition (HAI) antibody response of IIV3-HD vs.

Immunoglobulin use in immune deficiency in the UK: a report of the UKPID and National Immunoglobulin Databases.

Supply of immunoglobulin in the UK faces pressures due to increasing demand, cost and variable supply. This paper describes immunoglobulin replacement therapy (IGRT) in primary immunodeficiency (PID) and secondary immunodeficiency (SID) to assist in the ongoing planning of UK immunoglobulin provision. A retrospective analysis of the National Immunoglobulin Database and the UKPID registry was carried out.

Reactions of dicobalt octacarbonyl with dinucleating and mononucleating bis(imino)pyridine ligands.

This work focuses on the application of dicobalt octacarbonyl (Co(CO)) as a metal precursor in the chemistry of formally low-valent cobalt with redox-active bis(imino)pyridine [NNN] ligands. The reactions of both mononucleating mesityl-substituted bis(aldimino)pyridine (L) and dinucleating macrocyclic xanthene-bridged di(bis(aldimino)pyridine) (L) with Co(CO) were investigated. Independent of the metal-to-ligand ratio (1 : 1 or 1 : 2 ligand to Co(CO)), the reaction of the dinucleating ligand L with Co(CO) produces a tetranuclear complex [Co(L)(CO)] featuring two discrete [Co[NNN](CO)] units.

Use of intravenous immunoglobulin for the treatment of autoimmune encephalitis: audit of the NHS experience.

Objectives: The treatments of limbic and other autoimmune encephalitis include immunosuppression, symptomatic treatment, and in the case of paraneoplastic syndromes, appropriate therapy for underlying neoplasms. When immunotherapy is considered, intravenous immunoglobulin is one option for treatment, either alone or in combination with corticosteroids. To date, however, evidence for the use of intravenous immunoglobulin in this context comes from case series/expert reviews as no controlled trials have been performed.

Cooperative bimetallic reactivity of a heterodinuclear molybdenum-copper model of Mo-Cu CODH.

The synthesis of a heterodinucleating ligand LH2 (LH2 = (E)-3-(((2,7-di-tert-butyl-9,9-dimethyl-5-((pyridin-2-ylmethylene)amino)-9H-xanthen-4-yl)amino)methyl)benzene-1,2-diol) was undertaken toward a functional model of the bimetallic active site found in Mo-Cu carbon monoxide dehydrogenase (Mo-Cu CODH), and to understand the origins of heterobimetallic cooperativity exhibited by the enzyme. LH2 features a hard potentially dianionic catechol chelate for binding Mo(vi) and a soft iminopyridine chelate for binding Cu(i). Treatment of LH2 with either Cu(i) or M(vi) (M = Mo, W) sources leads to the anticipated site-selective incorporation of the respective metals.

The Hawaii Protocol for Scientific Monitoring of Coffee Berry Borer: a Model for Coffee Agroecosystems Worldwide.

Coffee berry borer (CBB) is the most devastating insect pest for coffee crops worldwide. We developed a scientific monitoring protocol that is aimed at capturing and quantifying the dynamics and impact of this invasive insect pest as well as the development of its host plant across a heterogeneous landscape. The cornerstone of this comprehensive monitoring system is timely georeferenced data collection on CBB movement, coffee berry infestation, mortality by the fungus Beauveria bassiana, and coffee plant phenology via a mobile electronic data recording application.