Type I interferon blockade with anifrolumab in patients with systemic lupus erythematosus modulates key immunopathological pathways in a gene expression and proteomic analysis of two phase 3 trials.

Introduction: Anifrolumab is a type I interferon (IFN) receptor 1 (IFNAR1) blocking antibody approved for treating patients with systemic lupus erythematosus (SLE). Here, we investigated the immunomodulatory mechanisms of anifrolumab using longitudinal transcriptomic and proteomic analyses of the 52-week, randomised, phase 3 TULIP-1 and TULIP-2 trials.

Methods: Patients with moderate to severe SLE were enrolled in TULIP-1 and TULIP-2 and received intravenous anifrolumab or placebo alongside standard therapy.

Machine Learning Predicts Oxaliplatin Benefit in Early Colon Cancer.

Purpose: A combination of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is the standard for adjuvant therapy of resected early-stage colon cancer (CC). Oxaliplatin leads to lasting and disabling neurotoxicity. Reserving the regimen for patients who benefit from oxaliplatin would maximize efficacy and minimize unnecessary adverse side effects.

Innate immune dysregulation in multisystem inflammatory syndrome in children (MIS-C).

MIS-C is a systemic inflammation disorder with poorly characterised immunopathological mechanisms. We compared changes in the systemic immune response in children with MIS-C (n = 12, 5-13 years) to healthy controls (n = 14, 5-15 years). Analysis was done in whole blood treated with LPS.

Multi-omic interactions in the gut of children at the onset of islet autoimmunity.

Background: The gastrointestinal ecosystem is a highly complex environment with a profound influence on human health. Inflammation in the gut, linked to an altered gut microbiome, has been associated with the development of multiple human conditions including type 1 diabetes (T1D). Viruses infecting the gastrointestinal tract, especially enteroviruses, are also thought to play an important role in T1D pathogenesis possibly via overlapping mechanisms.

Multisystem inflammatory syndrome in the context of paediatric COVID-19 infection in the Republic of Ireland April 2020 to April 2021.

Aim: Our aim was to describe the epidemiology of multisystem inflammatory syndrome in children (MIS-C) in the Republic of Ireland, in the context of all cases of COVID-19 in children, during the first year of the SARS-CoV-2 pandemic.

Methods: Cases of MIS-C were identified by prospective surveillance in Irish hospitals from April 2020 to April 2021. Paediatric COVID-19 cases and outbreaks in schools or childcare facilities were notified to and routinely investigated by Public Health.

Emergence of Congenital Chagas Disease in Ireland.

Chagas disease (CD) is an under-diagnosed tropical disease that is increasingly being observed outside of Latin America. We describe the first 2 infants with congenital Chagas Disease (cCD) in Ireland. Clinicians in nonendemic countries need to be aware of the potential for cCD due to the migration of women from countries of high prevalence.

Metaproteomic sample preparation methods bias the recovery of host and microbial proteins according to taxa and cellular compartment.

Faecal proteomics studies have focussed on identification of microbial proteins, however; stool represents a valuable resource to interrogate the host interactions with the microbiota without the need for invasive intestinal biopsies. As the widely used enrichment method (differential centrifugation, DC) enriches for microbial proteins, we compared two other methods for enrichment of host proteins, termed 'host enriched' (HE) and ALL (all proteins). The HE and ALL protocols identified 1.

An acetate-yielding diet imprints an immune and anti-microbial programme against enteric infection.

Objectives: During gastrointestinal infection, dysbiosis can result in decreased production of microbially derived short-chain fatty acids (SCFAs). In response to the presence of intestinal pathogens, we examined whether an engineered acetate- or butyrate-releasing diet can rectify the deficiency of SCFAs and lead to the resolution of enteric infection.

Methods: We tested whether a high acetate- or butyrate-producing diet (HAMSA or HAMSB, respectively) condition infection in mice and assess its impact on host-microbiota interactions.

Validation of the NSABP/NRG Oncology 8-Gene Trastuzumab-benefit Signature in Alliance/NCCTG N9831.

Our objective was to validate the NSABP 8-gene trastuzumab-benefit signature, developed and initially validated in NRG Oncology/NSABP B-31 in Alliance/NCCTG N9831. The B-31 and N9831 trials demonstrated the benefit of adding trastuzumab to chemotherapy in the adjuvant setting for HER2+ breast cancer patients. NSABP investigators utilized gene expression profiles of N9831 patients (N = 892) to blindly assign patients to large-, moderate-, or no-trastuzumab benefit groups and then NCCTG investigators assessed the degree of trastuzumab benefit using Cox models adjusted for age, nodes, estrogen receptor/progesterone receptor status, tumor size, and grade.

Neratinib-Plus-Cetuximab in Quadruple-WT () Metastatic Colorectal Cancer Resistant to Cetuximab or Panitumumab: NSABP FC-7, A Phase Ib Study.

Purpose: In metastatic colorectal cancer (mCRC), () gene amplification is implicated in anti-EGFR therapy resistance. We sought to determine the recommended phase II dose (RP2D) and efficacy of neratinib, a pan-ERBB kinase inhibitor, combined with cetuximab, in patients with progressive disease (PD) on anti-EGFR treatment.

Patients And Methods: Twenty-one patients with quadruple-wild-type, refractory mCRC enrolled in this 3+3 phase Ib study.

The clinical presentation, treatment and outcome of serologically confirmed paediatric Lyme disease in the Republic of Ireland over a 5-year period: a retrospective cohort study.

Lyme disease (LD) is the most common tick-borne illness in Europe. Population-based studies in European children are few. This study aimed to assess the incidence, clinical presentation, treatment and outcome of serologically confirmed paediatric LD in the Republic of Ireland over a 5-year period.

Correction to: NSABP FB-7: a phase II randomized neoadjuvant trial with paclitaxel + trastuzumab and/or neratinib followed by chemotherapy and postoperative trastuzumab in HER2+ breast cancer.

After the publication of this work [1] the authors have reported that in Table 3 The letter "T" in columns 5 and 7 should not be there.

NSABP FB-7: a phase II randomized neoadjuvant trial with paclitaxel + trastuzumab and/or neratinib followed by chemotherapy and postoperative trastuzumab in HER2 breast cancer.

Purpose: The primary aim of NSABP FB-7 was to determine the pathologic complete response (pCR) rate in locally advanced HER2-positive (HER2) breast cancer patients treated with neoadjuvant trastuzumab or neratinib or the combination and weekly paclitaxel followed by standard doxorubicin plus cyclophosphamide. The secondary aims include biomarker analyses.

Experimental Design: pCR was tested for association with treatment, gene expression, and a single nucleotide polymorphism (SNP) in the Fc fragment of the IgG receptor IIIa-158V/F (FCGR3A).

A case report of multiple cerebral abscess formation complicating serogroup B Neisseria meningitidis meningitis.

Background: Invasive meningococcal disease (IMD) presenting with meningitis causes significant mortality and morbidity. Suppurative complications of serogroup B meningococcal sepsis are rare and necessitate urgent multidisciplinary management to mitigate long-term morbidity or mortality.

Case Presentation: We present a rare case of invasive meningococcal disease in a 28-month old boy complicated by multiple abscess formation within a pre-existing antenatal left middle cerebral artery territory infarct.

Incidence of Late Relapses in Patients With HER2-Positive Breast Cancer Receiving Adjuvant Trastuzumab: Combined Analysis of NCCTG N9831 (Alliance) and NRG Oncology/NSABP B-31.

Purpose: Recent trials have shown potential benefit of extended adjuvant endocrine therapy and relatively high risk of recurrence (RoR) after 5 years in hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Although risk of late relapse in HR+ HER2- breast cancer is fairly well defined, the risk in HER2-positive (HER2+) breast cancer treated with adjuvant trastuzumab-based chemotherapy remains largely unknown.

Methods: We included 3,177 patients with HER2+ breast cancer treated with adjuvant chemotherapy alone or with trastuzumab from the North Central Cancer Treatment Group N9831 (ClinicalTrials.

Patients' information needs and attitudes about post-treatment surveillance for colorectal cancer in the United States: a multi-perspective, mixed methods study.

Objective: We sought to determine patients' informational needs for post-treatment surveillance and elicit clinicians' and patient advocates' (ie, stakeholders) opinions regarding what patients should know about post-treatment surveillance in the USA.

Design: A mixed-methods study, using semi-structured interviews followed by a survey study.

Setting: Participants for the interviews were from two large academic medical centres and a safety-net hospital.

The gut microbiota in type 1 diabetes: friend or foe?

Purpose Of Review: Evidence is mounting that disturbances in the gut microbiota play a role in the rising incidence of type 1 diabetes (T1D) and new technologies are expanding our ability to understand microbial function and host interactions. Longitudinal data from large cohorts of children at risk of T1D are nor solidifying our understanding of the function of the microbiota in this disease.

Recent Findings: Although taxonomic changes in the gut microbiota associated with T1D are relatively modest, a functional defect in production of short-chain fatty acids (SCFAs) remains as a unifying feature across multiple studies and populations.

Stromal Tumor-infiltrating Lymphocytes in NRG Oncology/NSABP B-31 Adjuvant Trial for Early-Stage HER2-Positive Breast Cancer.

We retrospectively assessed association of stromal tumor-infiltrating lymphocytes (sTILs) with clinical outcomes and molecular variables reportedly predictive of trastuzumab-benefit in National Surgical Adjuvant Breast and Bowel Project B-31 (N = 2130). sTILs were assessed in 1581 eligible B-31 cases utilizing all available hematoxylin and eosin slides. Mean concordance between main reviewer and six other pathologists was 90.

The role of real-time PCR testing in the investigation of paediatric patients with community-onset osteomyelitis and septic arthritis.

Background: Culture yield in osteomyelitis and septic arthritis is low, emphasising the role for molecular techniques.

Aims: The purpose of this study was to review the laboratory investigation of childhood osteomyelitis and septic arthritis.

Methods: A retrospective review was undertaken in an acute tertiary referral paediatric hospital from January 2010 to December 2016.

Molecular subtypes of colorectal cancer in pre-clinical models show differential response to targeted therapies: Treatment implications beyond KRAS mutations.

Molecular subtypes of colorectal tumors are associated with prognosis and prediction for treatment benefit from chemotherapy. The purpose of this study was two-fold: 1) to determine the association of colorectal (CRC) molecular subtypes with response to targeted therapies in pre-clinical models and 2) to identify treatments for CRC stem-like subtype because these tumors are associated with a very poor patient prognosis. Eleven CRC cell lines were classified into molecular subtypes and tested for their response to pan-ERBB, MEK, and ERK inhibitors as single agents and in combination.

Intestinal Metaproteomics Reveals Host-Microbiota Interactions in Subjects at Risk for Type 1 Diabetes.

Objective: Dysbiosis of the gut microbiota has been linked to disease pathogenesis in type 1 diabetes, yet the functional consequences to the host of this dysbiosis are unknown. We investigated the functional interactions between the microbiota and the host associated with type 1 diabetes disease risk.

Research Design And Methods: We performed a cross-sectional analysis of stool samples from subjects with recent-onset type 1 diabetes ( = 33), islet autoantibody-positive subjects ( = 17), low-risk autoantibody-negative subjects ( = 29), and healthy subjects ( = 22).

Epidemiology of an upsurge of invasive group A streptococcal infections in Ireland, 2012-2015.

Objectives: Group A streptococcus (GAS) is responsible for mild to very severe disease. The epidemiology of an upsurge in invasive GAS (iGAS) infections in Ireland, 2012-2015 was investigated.

Methods: Epidemiological typing of iGAS (n = 473) isolates was performed and compared to non-invasive (n = 517) isolates.

Effects of low-intensity pulsed ultrasound on radiographic healing of tibial plateau leveling osteotomies in dogs: a prospective, randomized, double-blinded study.

Objective: To determine the influence of low-intensity pulsed ultrasound (LIPUS) on radiographic healing and limb function after uncomplicated, stable osteotomies in dogs.

Study Design: In vivo, prospective, randomized, double-blinded, placebo-control study.

Sample Population: Fifty client-owned dogs.

Future career intentions of higher specialist trainees in general Paediatrics.

Background: A survey of paediatric higher specialist trainees was carried out in 2002 assessing career intentions and perception of training. Fourteen years later, with increased numbers of trainees and a national model of care and a tertiary paediatric hospital on the horizon, we re-evaluated the career intentions of the current trainee workforce.

Aims: To assess the career intentions of the current paediatric higher specialist trainees.