Role of breastfeeding in disease prevention.

Human milk provides the infant with many bioactive factors, including immunomodulating components, antimicrobials and prebiotics, which modulate the infant microbiome and immune system maturation. As a result, breastfeeding can impact infant health from infancy, through adolescence, and into adulthood. From protecting the infant from infections, to reducing the risk of obesity, type 1 diabetes and childhood leukaemia, many positive health outcomes are observed in infants receiving breastmilk. For the mother, breastfeeding protects against postpartum bleeding and depression, increases weight loss, and long-term lowers the risk of type 2 diabetes, breast and ovarian cancer, and cardiovascular diseases. Beyond infants and mothers, the wider society is also impacted because of avoidable costs relating to morbidity and mortality derived from a lack of human milk exposure. In this review, Medline was used to search for relevant articles to discuss the health benefits of breastfeeding and its societal impact before exploring future recommendations to enhance our understanding of the mechanisms behind breastfeeding's positive effects and promote breastfeeding on a global scale.

Factors Associated With Healthcare and Financial Decision Making Among Older Black Adults Without Dementia.

OBJECTIVES: The study aims to identify factors associated with health care and financial decision-making among older Black adults without dementia. METHODS: Participants (N = 326) underwent assessments of decision-making and completed measurements of factors from four categories: cognitive, contextual, psychosocial, and personality. We performed separate linear regression models to examine the association between each factor and decision-making and created a fully adjusted model. RESULTS: Higher global cognition (estimate = 1.92, SE = 0.21, p < .0001) was associated with better decision-making. Contextual factors including higher current annual income (estimate = 0.23, SE = 0.05, p < .0001), higher childhood socioeconomic status (estimate = 0.48, SE = 0.18, p = .006), higher health and financial literacy (estimate = 0.08, SE = 0.01, p < .0001), and lower financial stress (estimate = -0.19, SE = 0.07, p = .01) were associated with better decision-making. More psychological well-being (estimate = 0.07, SE = 0.22, p = .001), a psychosocial factor, and less neuroticism (estimate = -0.06, SE = 0.02, p = .002), a personality factor, were associated with better decision-making. In the fully adjusted model, two factors, higher global cognition and higher literacy (health and financial), remained associated with better decision-making. CONCLUSIONS: Cognitive and contextual factors serve as drivers of decision-making among older Black adults. CLINICAL IMPLICATIONS: Clinicians may implement strategies to bolster cognition and improve health and financial literacy to facilitate optimal decision-making among older Black adults.

Characterising glycosaminoglycans in human breastmilk and their potential role in infant health.

Human breastmilk is composed of many well researched bioactive components crucial for infant nutrition and priming of the neonatal microbiome and immune system. Understanding these components gives us crucial insight to the health and wellbeing of infants. Research surrounding glycosaminoglycans (GAGs) previously focused on those produced endogenously; however, recent efforts have shifted to understanding GAGs in human breastmilk. The structural complexity of GAGs makes detection and analysis complicated therefore, research is time consuming and limited to highly specialised teams experienced in carbohydrate analysis. In breastmilk, GAGs are present in varying quantities in four forms; chondroitin sulphate, heparin/heparan sulphate, dermatan sulphate and hyaluronic acid, and are hypothesised to behave similar to other bioactive components with suspected roles in pathogen defense and proliferation of beneficial gut bacteria. Chondroitin sulphate and heparin, being the most abundant, are expected to have the most impact on infant health. Their decreasing concentration over lactation further indicates their role and potential importance during early life.

Monitoring immunE DysregulAtion foLLowing Immune checkpOint-inhibitioN (MEDALLION): protocol for an observational cancer immunotherapy cohort study.

BACKGROUND: Checkpoint inhibitors (CPIs) are widely used in cancer treatment, with transformative impacts on survival. They nonetheless carry a significant risk of toxicity in the form of immune-related adverse events (IrAEs), which may be sustained and life-altering. IrAEs may require high-dose and/or prolonged steroid use and represent a significant healthcare burden. They mimic immune-mediated inflammatory diseases (IMIDs) but understanding of their pathogenesis is limited. The MEDALLION project aims to determine targetable mechanisms of immune dysregulation in IrAE development, employing an immune monitoring approach to determine changes in circulating and tissue resident cells of CPI recipients who do/do not develop them and assessing the contribution of the microbiome in parallel. METHODS: MEDALLION is a non-randomised longitudinal cohort study aiming to recruit 66 cancer patient recipients of anti-PD1/PD-L1, anti-CTLA-4 or combination therapy. Eligible participants include those with malignant melanoma in the adjuvant or metastatic setting, mesothelioma and non-small cell lung carcinoma (NSCLC) treated in the metastatic setting. Comprehensive clinical evaluation is carried out alongside blood, skin swab and stool sampling at the time of CPI initiation (baseline) and during subsequent routine hospital visits on 6 occasions over a 10-month follow-up period. It is conservatively anticipated that one third of enrolled patients will experience a "significant IrAE" (SirAE), defined according to pre-determined criteria specific to the affected tissue/organ system. Those developing such toxicity may optionally undergo a biopsy of affected tissue where appropriate, otherwise being managed according to standard of care. Peripheral blood mononuclear cells will be analysed using multi-parameter flow cytometry to investigate immune subsets, their activation status and cytokine profiles. Stool samples and skin swabs will undergo DNA extraction for 16 S ribosomal RNA (rRNA) sequencing and internal transcribed spacer (ITS) gene sequencing to determine bacterial and fungal microbiome diversity, respectively, including species associated with toxicity. Stored tissue biopsies will be available for in situ and single-cell transcriptomic evaluation. Analysis will focus on the identification of biological predictors and precursors of SirAEs. DISCUSSION: The pathogenesis of IrAEs will be assessed through the MEDALLION cohort, with the potential to develop tools for their prediction and/or strategies for targeted prevention or treatment. TRIAL REGISTRATION: The study was registered on 18/09/2023 in the ISRCTN registry (43,419,676).

Health and Financial Literacy and the Acquisition of COVID-19 Knowledge in Older Adults.

Knowledge about COVID-19 enters into many aspects of decision making, especially for older people who are at increased risk of severe disease or death. Yet little is known about the resources that supported older people's uptake of COVID-19 knowledge. Here, we hypothesized that higher pre-pandemic health and financial literacy was associated with higher COVID-19 knowledge. Participants were 434 community-based older people without dementia. COVID-19 knowledge was assessed via a 5-item measure, and health and financial literacy was assessed via a 32-item measure. In an ordinal regression model adjusted for age, gender, and education, higher literacy was associated with higher COVID-19 knowledge (p < .0001), and this association persisted after further adjusting for robust measures of global cognition or one of five specific cognitive domains (all p's ≤ .0001). These findings suggest that literacy plays a key role in supporting older people's acquisition of impactful knowledge in the real world.

Squaric esters as peptide stapling reagents.

We report that squaric esters can serve as bifunctional reagents for selective peptide stapling reactions. Formation of the squaric amide staple occurs under mild conditions with amine-containing side chains. We show that short resin-bound peptides are readily stapled on solid phase and that stapling can occur at various relative positions along the peptide and with various amine tether lengths (e.g. Lysine, ornithine, etc). The squaric amide staples are stable to strong acid conditions used to cleave the stapled peptide from the resin and the stapled peptides show an increase in helicity as analyzed through circular dichroism.

Metabolism of L-arabinose converges with virulence regulation to promote enteric pathogen fitness.

Virulence and metabolism are often interlinked to control the expression of essential colonisation factors in response to host-associated signals. Here, we identified an uncharacterised transporter of the dietary monosaccharide ʟ-arabinose that is widely encoded by the zoonotic pathogen enterohaemorrhagic Escherichia coli (EHEC), required for full competitive fitness in the mouse gut and highly expressed during human infection. Discovery of this transporter suggested that EHEC strains have an enhanced ability to scavenge ʟ-arabinose and therefore prompted us to investigate the impact of this nutrient on pathogenesis. Accordingly, we discovered that ʟ-arabinose enhances expression of the EHEC type 3 secretion system, increasing its ability to colonise host cells, and that the underlying mechanism is dependent on products of its catabolism rather than the sensing of ʟ-arabinose as a signal. Furthermore, using the murine pathogen Citrobacter rodentium, we show that ʟ-arabinose metabolism provides a fitness benefit during infection via virulence factor regulation, as opposed to supporting pathogen growth. Finally, we show that this mechanism is not restricted to ʟ-arabinose and extends to other pentose sugars with a similar metabolic fate. This work highlights the importance integrating central metabolism with virulence regulation in order to maximise competitive fitness of enteric pathogens within the host-niche.

Defining predictors of responsiveness to advanced therapies in Crohn's disease and ulcerative colitis: protocol for the IBD-RESPONSE and nested CD-metaRESPONSE prospective, multicentre, observational cohort study in precision medicine.

INTRODUCTION: Characterised by chronic inflammation of the gastrointestinal tract, inflammatory bowel disease (IBD) symptoms including diarrhoea, abdominal pain and fatigue can significantly impact patient's quality of life. Therapeutic developments in the last 20 years have revolutionised treatment. However, clinical trials and real-world data show primary non-response rates up to 40%. A significant challenge is an inability to predict which treatment will benefit individual patients.Current understanding of IBD pathogenesis implicates complex interactions between host genetics and the gut microbiome. Most cohorts studying the gut microbiota to date have been underpowered, examined single treatments and produced heterogeneous results. Lack of cross-treatment comparisons and well-powered independent replication cohorts hampers the ability to infer real-world utility of predictive signatures.IBD-RESPONSE will use multi-omic data to create a predictive tool for treatment response. Future patient benefit may include development of biomarker-based treatment stratification or manipulation of intestinal microbial targets. IBD-RESPONSE and downstream studies have the potential to improve quality of life, reduce patient risk and reduce expenditure on ineffective treatments. METHODS AND ANALYSIS: This prospective, multicentre, observational study will identify and validate a predictive model for response to advanced IBD therapies, incorporating gut microbiome, metabolome, single-cell transcriptome, human genome, dietary and clinical data. 1325 participants commencing advanced therapies will be recruited from ~40 UK sites. Data will be collected at baseline, week 14 and week 54. The primary outcome is week 14 clinical response. Secondary outcomes include clinical remission, loss of response in week 14 responders, corticosteroid-free response/remission, time to treatment escalation and change in patient-reported outcome measures. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Wales Research Ethics Committee 5 (ref: 21/WA/0228). Recruitment is ongoing. Following study completion, results will be submitted for publication in peer-reviewed journals and presented at scientific meetings. Publications will be summarised at www.ibd-response.co.uk. TRIAL REGISTRATION NUMBER: ISRCTN96296121.

Safety and feasibility of colonoscopy in nonagenarians: A systematic review, meta-analysis and meta-regression analysis.

AIM: The aim of this work was to evaluate the safety and feasibility of performing colonoscopy in patients aged 90 years or over. METHOD: In compliance with PRISMA statement standards, a systematic review of studies reporting the outcomes of colonoscopy in patients aged ≥90 years was conducted. A proportional meta-analysis model was constructed to quantify the risk of outcomes and a direct comparison meta-analysis model was constructed to compare outcomes between nonagenarians and patients aged between 50 and 89 years via random-effects models. RESULTS: Seven studies enrolling 1304 patients (1342 colonoscopies) were included. Analyses showed that complications related to bowel preparation occurred in 0.7% (95% CI 0.1%-1.6%), procedural complications in 0.6% (0.00%-1.7%), 30-day complications in 1.5% (0.6%-2.7%), procedural mortality in 0.3% (0.0%-1.1%) and 30-day mortality in 1.1% (0.3%-2.2%). Adequate bowel preparation and colonoscopy completion were achieved in 81.3% (73.8%-87.9%) and 92.1% (86.7%-96.3%), respectively. No difference was found in bowel preparation-related complications [risk difference (RD) 0.00, p = 0.78], procedural complications (RD 0.00, p = 0.60), 30-day complications (RD 0.01, p = 0.20), procedural mortality (RD 0.00, p = 1.00) or 30-day mortality (RD 0.01, p = 0.34) between nonagenarians and patients aged between 50 and 89 years. The colorectal cancer detection rate was 14.3% (9.8%-19.5%), resulting in therapeutic intervention in 65.9% (54.5%-76.6%). CONCLUSIONS: Although the evidence is limited to a selected group of nonagenarians, it may be fair to conclude that if a colonoscopy is indicated in a nonagenarian with good performance status (based on initial less-invasive investigations), the level 2 evidence supports its safety and feasibility. Age on its own should not be a reason for failing to offer colonoscopy to a nonagenarian.

Gut microbiome derived short chain fatty acids: Promising strategies in necrotising enterocolitis.

Necrotising enterocolitis (NEC) is a devastating condition that poses a significant risk of morbidity and mortality, particularly among preterm babies. Extensive research efforts have been directed at identifying optimal treatment and diagnostic strategies but results from such studies remain unclear and controversial. Among the most promising candidates are prebiotics, probiotics and their metabolites, including short chain fatty acids (SCFAs). Such metabolites have been widely explored as possible biomarkers of gut health for different clinical conditions, with overall positive effects on the host observed. This review aims to describe the role of gut microbiome derived SCFAs in necrotising enterocolitis. Until now, information has been conflicting, with the primary focus on the main three SCFAs (acetic acid, propionic acid, and butyric acid). While numerous studies have indicated the relationship between SCFAs and NEC, the current evidence is insufficient to draw definitive conclusions about the use of these metabolites as NEC biomarkers or their potential in treatment strategies. Ongoing research in this area will help enhance both our understanding of SCFAs as valuable indicators of NEC and their practical application in clinical settings.

Patterns of Craniomaxillofacial Trauma at an Urban Level I Trauma Center.

Background: There is a paucity in the literature concerning craniomaxillofacial trauma (CMF) in the USA. Better recognition of these fracture patterns and their management clarifies how to best evaluate and treat them. Methods: A retrospective chart review was conducted of CMF trauma patients who required surgical intervention at a level I trauma center between 2015 and 2018. Descriptive statistics and univariate and bivariate analyses were conducted (α = 0.05). Results: A total of 1001 patients were included. Most patients were Black (n = 665; 66%) and/or male individuals (n = 813; 57%) with an average age of 37 years (range 15 -110). The most common etiologies were assault (n = 471; 44%), motor vehicle collision (n = 238; 22%), and fall (n = 117; 11%). The mechanism of injury was a determinant of fracture type (P = 0.045). The most common CMF injuries were mandibular fracture (n = 953; 95%), maxillary fracture (n = 815; 81%), and orbital fracture (n = 206; 21%). Male sex predicted panfacial fractures (P = 0.045). Black patients experienced more severe CMF trauma compared with other races (P < 0.001). ORIF was the most common treatment for mandibular (n = 481; 73%) and maxillary (n = 62; 66%) fractures. Conclusions: Etiology and patterns of CMF trauma differ globally, with assault and motor vehicle collisions being the leading causative factors in our patient population. Patient demographics are relatively consistent worldwide, with most injuries occurring in 30- to 40-year-old men. This study offers insight into at-risk populations and guidance on their management.

Low versus standard central venous pressure during laparoscopic liver resection: A systematic review, meta-analysis and trial sequential analysis.

To compare the outcomes of low central venous pressure (CVP) to standard CVP during laparoscopic liver resection. The study design was a systematic review following the PRISMA statement standards. The available literature was searched to identify all studies comparing low CVP with standard CVP in patients undergoing laparoscopic liver resection. The outcomes included intraoperative blood loss (primary outcome), need for blood transfusion, mean arterial pressure, operative time, Pringle time, and total complications. Random- effects modelling was applied for analyses. Type I and type II errors were assessed by trial sequential analysis (TSA). A total of 8 studies including 682 patients were included (low CVP group, 342; standard CVP group, 340). Low CVP reduced intraoperative blood loss during laparoscopic liver resection (mean difference [MD], -193.49 mL; 95% confidence interval [CI], -339.86 to -47.12; p = 0.01). However, low CVP did not have any effect on blood transfusion requirement (odds ratio [OR], 0.54; 95% CI, 0.28-1.03; p = 0.06), mean arterial pressure (MD, -1.55 mm Hg; 95% CI, -3.85-0.75; p = 0.19), Pringle time (MD, -0.99 minutes; 95% CI, -5.82-3.84; p = 0.69), operative time (MD, -16.38 minutes; 95% CI, -36.68-3.39; p = 0.11), or total complications (OR, 1.92; 95% CI, 0.97-3.80; p = 0.06). TSA suggested that the meta-analysis for the primary outcome was not subject to type I or II errors. Low CVP may reduce intraoperative blood loss during laparoscopic liver resection (moderate certainty); however, this may not translate into shorter operative time, shorter Pringle time, or less need for blood transfusion. Randomized controlled trials with larger sample sizes will provide more robust evidence.

Evidence of Hematoma Prevention After Facelift.

Hematoma is a common complication after facelift procedures. Multiple factors have been shown to increase the risk of hematoma formation, such as male gender, anticoagulant medication use, perioperative hypertension, increased intrathoracic pressure, and operative technique. The purpose of this manuscript is to provide an overview of existing literature to provide surgeons with evidence-based recommendations on how to minimize hematoma risk during facelift surgery. A literature search for hematoma and facelift surgery was performed that identified 478 unique manuscripts. Abstracts were reviewed, excluding articles not describing facelift surgery, those written before 1970, studies with a sample size of fewer than 5 patients, non-English studies, and those that did not provide postoperative hematoma rates. Forty-five articles were included in this text, with their recommendations. Measures such as the prophylactic management of pain, nausea, and hypertension, the use of fibrin glue tissue sealants, the use of local anesthesia rather than general anesthesia, and strict blood pressure control of at least <140 mmHg were found to significantly reduce hematoma formation. Quilting sutures has shown benefit in some high-risk patients. Measures such as drains, compression dressings, perioperative use of selective serotonin reuptake inhibitors, and perioperative steroids had no significant effect on hematoma formation. In addition to appropriate patient selection and careful intraoperative hemostasis, many adjunct measures have been shown to reduce postoperative hematoma formation in facelift procedures.

SCAN for Abuse: Electronic Health Record-Based Universal Child Abuse Screening.

BACKGROUND: Identification of physical abuse at the point of care without a systematic approach remains inherently subjective and prone to judgement error. This study examines the implementation of an electronic health record (EHR)-based universal child injury screen (CIS) to improve detection rates of child abuse. METHODS: CIS was implemented in the EHR admission documentation for all patients age 5 or younger at a single medical center, with the following questions. 1) "Is this patient an injured/trauma patient?" 2) "If this is a trauma/injured patient, where did the injury occur?" A "Yes" response to Question 1 would alert a team of child abuse pediatricians and social workers to determine if a patient required formal child abuse clinical evaluation. Patients who received positive CIS responses, formal child abuse work-up, and/or reports to Child Protective Services (CPS) were reviewed for analysis. CPS rates from historical controls (2017-2018) were compared to post-implementation rates (2019-2021). RESULTS: Between 2019 and 2021, 14,150 patients were screened with CIS. 286 (2.0 %) patients screened received positive CIS responses. 166 (58.0 %) of these patients with positive CIS responses would not have otherwise been identified for child abuse evaluation by their treating teams. 18 (10.8 %) of the patients identified by the CIS and not by the treating team were later reported to CPS. Facility CPS reporting rates for physical abuse were 1.2 per 1000 admitted children age 5 or younger (pre-intervention) versus 4.2 per 1000 (post-intervention). CONCLUSIONS: Introduction of CIS led to increased detection suspected child abuse among children age 5 or younger. LEVEL OF EVIDENCE: Level II. TYPE OF STUDY: Study of Diagnostic Test.

The association between lateral hip muscle size/intramuscular fat infiltration and hip strength in active young adults with long standing hip/groin pain.

OBJECTIVES: To investigate associations between lateral hip muscle size/intramuscular fat infiltration (MFI) and hip strength in active young adults with longstanding hip/groin pain. DESIGN: Cross-sectional study. SETTING: University/Clinical. PARTICIPANTS: Sub-elite soccer and Australian Football players (n = 180; 37 female) with long standing hip/groin pain. MAIN OUTCOME MEASURES: Muscle size (volume) and MFI of gluteus maximus, medius, and minimis, and tensor fascia latae (TFL) were assessed using magnetic resonance imaging. Isometric hip strength was measured with handheld dynamometry. Associations between muscle size/MFI were assessed using linear regression models, adjusted for body mass index and age, with sex-specific interactions. RESULTS: Positive associations were identified between lateral hip muscle volume and hip muscle strength, particularly for gluteus maximus and gluteus minimus volume. For all muscles, hip abduction was associated with an increase in strength by up to 0.69 N (R2 ranging from 0.29 to 0.39). These relationships were consistent across sexes with no sex interactions observed. No associations were found between MFI and strength measures. CONCLUSION: Greater lateral hip muscle volumes are associated with greater hip strength in active young adults with long standing hip/groin pain, irrespective of sex. Gluteus maximus and minimus volume showed the most consistent relationships with hip strength across multiple directions.

A Consultation for Pediatric Neck Mass Resulting in a Rare Diagnosis of Klippel-Feil Syndrome: A Case Report.

Klippel-Feil syndrome (KFS) is a rare congenital cervical vertebrae fusion syndrome characterized by the clinical triad of low posterior hairline, limited head and neck range of motion, and short neck. The gene defects described with this syndrome are involved in the maturation and differentiation of bone during embryological development. As such, related defects seen in patients with KFS include genitourinary anomalies, cardiac defects, neurological abnormalities, and other musculoskeletal anomalies. Patients with this syndrome should be worked up for these related malformations, evaluated for risk of comorbidities, and educated on avoiding contact sports or activities that may put the cervical spine at risk for trauma. The case report here describes a pediatric patient who presents to the outpatient otolaryngologist complaining of a pediatric neck mass. Workup of the mass, including imaging, revealed a diagnosis of Klippel-Feil syndrome. The presentation of this case highlights the importance of maintaining KFS on the list of possible diagnoses along with scoliosis, synostosis syndrome, and Wildervanck syndrome for the otolaryngologist working up a neck mass and the role making an early diagnosis can have in preventing patient morbidity and mortality.

Natural language processing with machine learning methods to analyze unstructured patient-reported outcomes derived from electronic health records: A systematic review.

OBJECTIVE: Natural language processing (NLP) combined with machine learning (ML) techniques are increasingly used to process unstructured/free-text patient-reported outcome (PRO) data available in electronic health records (EHRs). This systematic review summarizes the literature reporting NLP/ML systems/toolkits for analyzing PROs in clinical narratives of EHRs and discusses the future directions for the application of this modality in clinical care. METHODS: We searched PubMed, Scopus, and Web of Science for studies written in English between 1/1/2000 and 12/31/2020. Seventy-nine studies meeting the eligibility criteria were included. We abstracted and summarized information related to the study purpose, patient population, type/source/amount of unstructured PRO data, linguistic features, and NLP systems/toolkits for processing unstructured PROs in EHRs. RESULTS: Most of the studies used NLP/ML techniques to extract PROs from clinical narratives (n = 74) and mapped the extracted PROs into specific PRO domains for phenotyping or clustering purposes (n = 26). Some studies used NLP/ML to process PROs for predicting disease progression or onset of adverse events (n = 22) or developing/validating NLP/ML pipelines for analyzing unstructured PROs (n = 19). Studies used different linguistic features, including lexical, syntactic, semantic, and contextual features, to process unstructured PROs. Among the 25 NLP systems/toolkits we identified, 15 used rule-based NLP, 6 used hybrid NLP, and 4 used non-neural ML algorithms embedded in NLP. CONCLUSIONS: This study supports the potential utility of different NLP/ML techniques in processing unstructured PROs available in EHRs for clinical care. Though using annotation rules for NLP/ML to analyze unstructured PROs is dominant, deploying novel neural ML-based methods is warranted.