Predicting programmed death-ligand 1 (PD-L1) expression with fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) metabolic parameters in resectable non-small cell lung cancer.

BACKGROUND: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). PD-L1 and glucose transporter 1 expression are closely associated, and studies demonstrate correlation of PD-L1 with glucose metabolism. AIM: The aim of this study was to investigate the association of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) metabolic parameters with PD-L1 expression in primary lung tumour and lymph node metastases in resected NSCLC. METHODS: We conducted a retrospective analysis of 210 patients with node-positive resectable stage IIB-IIIB NSCLC. PD-L1 tumour proportion score (TPS) was determined using the DAKO 22C3 immunohistochemical assay. Semi-automated techniques were used to analyse pre-operative [18F]FDG-PET/CT images to determine primary and nodal metabolic parameter scores (including max, mean, peak and peak adjusted for lean body mass standardised uptake values (SUV), metabolic tumour volume (MTV), total lesional glycolysis (TLG) and SUV heterogeneity index (HISUV)). RESULTS: Patients were predominantly male (57%), median age 70 years with non-squamous NSCLC (68%). A majority had negative primary tumour PD-L1 (TPS < 1%; 53%). Mean SUVmax, SUVmean, SUVpeak and SULpeak values were significantly higher (p < 0.05) in those with TPS ≥ 1% in primary tumour (n = 210) or lymph nodes (n = 91). However, ROC analysis demonstrated only moderate separability at the 1% PD-L1 TPS threshold (AUCs 0.58-0.73). There was no association of MTV, TLG and HISUV with PD-L1 TPS. CONCLUSION: This study demonstrated the association of SUV-based [18F]FDG-PET/CT metabolic parameters with PD-L1 expression in primary tumour or lymph node metastasis in resectable NSCLC, but with poor sensitivity and specificity for predicting PD-L1 positivity ≥ 1%. CLINICAL RELEVANCE STATEMENT: Whilst SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography metabolic parameters may not predict programmed death-ligand 1 positivity ≥ 1% in the primary tumour and lymph nodes of resectable non-small cell lung cancer independently, there is a clear association which warrants further investigation in prospective studies. TRIAL REGISTRATION: Non-applicable KEY POINTS: • Programmed death-ligand 1 immunohistochemistry has a predictive role in non-small cell lung cancer immunotherapy; however, it is both heterogenous and dynamic. • SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG-PET/CT) metabolic parameters were significantly higher in primary tumour or lymph node metastases with positive programmed death-ligand 1 expression. • These SUV-based parameters could potentially play an additive role along with other multi-modal biomarkers in selecting patients within a predictive nomogram.

The Australian New Zealand Consortium in Children, Adolescents, and Young Adults Oncofertility action plan.

International and national oncofertility networks, including the US-led Oncofertility Consortium, FertiProtekt, and the Danish Network, have played pivotal roles in advancing the discipline of oncofertility over the last decade. Many other countries lack a shared approach to pediatric oncofertility health service delivery. This study aims to describe baseline oncofertility practices at Australian New Zealand Children's Haematology/Oncology Group centers in 2019-2021, describe binational priorities for care, and propose a 5-year action plan for best practice to be implemented by the newly formed Australian New Zealand Consortium in Children, Adolescents, and Young Adults (CAYA) Oncofertility (ANZCO).

Exploring the influence of context on social norms around Australian parents' food provision using story completion.

OBJECTIVE: To explore the differences in social norms around parents' food provision in different provision contexts and by demographics. DESIGN: Qualitative study using story completion methodology via an online survey in September 2021. Adults 18+ with or without children were randomised to one of three story stems focusing on food provision in different contexts; food provision at home (non-visitor), with visitors present and with the involvement of sport. Stories were coded and themed using thematic analysis. A content analysis was performed to determine count and frequency of codes in stories by participant demographics and story assumptions. SETTING: Australia. PARTICIPANTS: Adults (n 196). RESULTS: Nine themes were identified from the data resulting in four social norms around providing healthy foods and justifying non-adherence to healthy eating guidelines, evolution of family life and mealtime values, the presence of others influencing how we engage with food provision and unhealthy foods used as incentives/rewards in sport. Following content analysis, no differences of themes or norms by participant demographics or story assumptions were found. CONCLUSIONS: We identified pervasive social norms around family food provision and further identified how contextual factors resulted in variations or distinct norms. This highlights the impact context may have on the social norms parents face when providing food to their children and the opportunities and risks of leveraging these social norms to influence food choice in these contexts. Public health interventions and practitioners should understand the influence of context and social environments when promoting behaviour change and providing individualised advice. Future research could explore parents' experiences of these norms and to what extent they impact food choice.

REDUCE missed oral healthcare: The outcomes of and learnings from an implementation project in an acute geriatric unit.

Oral healthcare is one of the most missed aspects of fundamental care. Failure to provide reliable and effective daily oral healthcare for older patients can lead to hospital-acquired pneumonias, longer hospital stays, increased health costs, and poor patient experience. The objective of this study was to codesign, implement, and evaluate an oral healthcare intervention for older adults in a geriatric unit. This mixed methods implementation project combined the hospital's quality improvement processes with the i-PARIHS knowledge translation framework. Multilevel facilitation guided the development of multidisciplinary implementation strategies, which were co-designed, tailored, and implemented at the ward and organizational level, targeting: awareness/engagement; clinical guideline development; building workforce capacity; access to appropriate products; patient awareness and support; utilization of multidisciplinary/dental referral pathways; and systematizing oral healthcare documentation. Gaps between evidence-based and current oral healthcare practice were identified through audits of practice and interviews with patients. Interviews and surveys with staff evaluated the feasibility and acceptability of the oral healthcare intervention and the success of implementation strategies. At the conclusion of the project, awareness, attitudes, and capacity of staff had increased, however, we could not demonstrate change in multidisciplinary oral healthcare practices or improvements for individual patients. Despite mixed success, the project informed discussions about including oral healthcare as a national healthcare standard for the acute care sector in Australia. Attempts to address oral healthcare may have started locally, but its impact was through policy change, which will empower health practitioners and managers to support practice change more widely.

More than a mouth to clean: Case studies of oral health care in an Australian hospital.

OBJECTIVE: This study aimed to explore older patients' oral health status, their opinions about oral health care and their experiences with oral health care while in hospital. BACKGROUND: Improving older adults' oral health is considered an urgent priority at both the national and international levels, especially for hospitalised older patients who have been found to have poor oral health. However, a one-size-fits-all standardised approach to oral care delivery may not be the answer. MATERIALS AND METHODS: This study was an embedded, multiple-case study, integrating qualitative and quantitative data. Seven patients were recruited from a geriatric ward of an acute hospital in Australia and participated in semi-structured interviews and oral health assessments using the Oral Health Assessment Tool (OHAT) in June-July 2022. Data were analysed descriptively and presented in case summaries. RESULTS: OHAT assessments identified oral health problems in all patients, but not all patients self-reported problems with their mouths. Each patient valued oral health care, but the reasons given varied. Patients had established, individualised oral health care routines, which they brought to hospital. CONCLUSION: Clinical observations of patient's oral health status might not match the patient's own judgement of their oral health and, if not explicitly addressed, may mask the need for oral health and hygiene intervention. Assessment and care planning needs to incorporate patients' own perceptions of their oral health and existing oral health care routines. Oral health histories may provide a means of facilitating this person-centred oral health care for older patients in hospital.

Supportive Housing for Sexual and Gender Minority Individuals with Criminal Justice Histories: Challenges and Opportunities Identified by Providers and Clients.

Sexual and gender minority (SGM) individuals experience high rates of homelessness and criminal justice system involvement, underscoring the need for supportive housing services. To explore the service needs of this population, we interviewed providers (n = 11) and clients (n = 10) from eight supportive housing organizations working with SGM populations in Los Angeles County, USA. We used the Consolidated Framework for Implementation Research to synthesize interview responses into themes (by domain and cross-cutting). Take-aways included the need for investment in systems of care for vulnerable SGM populations; the particular marginalization of Trans individuals and providers that serve them; the roles of supportive housing staff, residents, and leadership in cultivating an affirming environment; prevalence of discrimination and stigma within supportive housing programs and broader society; and the complex interrelationships among SGM identity, homelessness, and criminal justice system involvement. These findings have important implications for supportive housing services and related policy.

Born in the mitochondrion and raised in the nucleus: evolution of a novel tandem repeat family in Medicago polymorpha (Fabaceae).

Plant nuclear genomes harbor sequence elements derived from the organelles (mitochondrion and plastid) through intracellular gene transfer (IGT). Nuclear genomes also show a dramatic range of repeat content, suggesting that any sequence can be readily amplified. These two aspects of plant nuclear genomes are well recognized but have rarely been linked. Through investigation of 31 Medicago taxa we detected exceptionally high post-IGT amplification of mitochondrial (mt) DNA sequences containing rps10 in the nuclear genome of Medicago polymorpha and closely related species. The amplified sequences were characterized as tandem arrays of five distinct repeat motifs (2157, 1064, 987, 971, and 587 bp) that have diverged from the mt genome (mitogenome) in the M. polymorpha nuclear genome. The mt rps10-like arrays were identified in seven loci (six intergenic and one telomeric) of the nuclear chromosome assemblies and were the most abundant tandem repeat family, representing 1.6-3.0% of total genomic DNA, a value approximately three-fold greater than the entire mitogenome in M. polymorpha. Compared to a typical mt gene, the mt rps10-like sequence coverage level was 691.5-7198-fold higher in M. polymorpha and closely related species. In addition to the post-IGT amplification, our analysis identified the canonical telomeric repeat and the species-specific satellite arrays that are likely attributable to an ancestral chromosomal fusion in M. polymorpha. A possible relationship between chromosomal instability and the mt rps10-like tandem repeat family in the M. polymorpha clade is discussed.

Podocyte protease activated receptor 1 stimulation in mice produces focal segmental glomerulosclerosis mirroring human disease signaling events.

About 30% of patients who have a kidney transplant with underlying nephrotic syndrome (NS) experience rapid relapse of disease in their new graft. This is speculated to be due to a host-derived circulating factor acting on podocytes, the target cells in the kidney, leading to focal segmental glomerulosclerosis (FSGS). Our previous work suggests that podocyte membrane protease receptor 1 (PAR-1) is activated by a circulating factor in relapsing FSGS. Here, the role of PAR-1 was studied in human podocytes in vitro, and using a mouse model with developmental or inducible expression of podocyte-specific constitutively active PAR-1, and using biopsies from patients with nephrotic syndrome. In vitro podocyte PAR-1 activation caused a pro-migratory phenotype with phosphorylation of the kinase JNK, VASP protein and docking protein Paxillin. This signaling was mirrored in podocytes exposed to patient relapse-derived NS plasma and in patient disease biopsies. Both developmental and inducible activation of transgenic PAR-1 (NPHS2 Cre PAR-1Active+/-) caused early severe nephrotic syndrome, FSGS, kidney failure and, in the developmental model, premature death. We found that the non-selective cation channel protein TRPC6 could be a key modulator of PAR-1 signaling and TRPC6 knockout in our mouse model significantly improved proteinuria and extended lifespan. Thus, our work implicates podocyte PAR-1 activation as a key initiator of human NS circulating factor and that the PAR-1 signaling effects were partly modulated through TRPC6.

Breech specialist midwives and clinics in the OptiBreech Trial feasibility study: An implementation process evaluation.

BACKGROUND: Attendance of skilled and experienced professionals at breech births has been associated with a reduction in adverse perinatal outcomes. We aimed to determine whether United Kingdom National Health Service (NHS) sites could reliably provide attendants with OptiBreech training and/or advanced proficiency (intervention feasibility) and consistent care (fidelity) that meets women's needs (acceptability), with low neonatal admission rates (safety) and recruitment adequate to support a clinical trial (trial feasibility). METHODS: Mixed methods implementation evaluation was used. Settings were 13 services in England and Wales. Participants were 82 women requesting support for a vaginal breech birth (VBB) at term. Outcomes were descriptively analyzed. Twenty-one women were interviewed, and transcripts were analyzed using the Theoretical Framework of Acceptability. Iterative analysis informed subsequent interviews and the ongoing process of implementation across sites. RESULTS: Although we initially suggested multidisciplinary teams, actively recruiting Trusts yielded services where VBB care was provided through a dedicated clinic, organized and delivered primarily by a lead midwife who functioned as a specialist. This model achieved 87.5% fidelity with the intervention's goal of ensuring the attendance of OptiBreech-trained professionals. Neonatal outcomes remained stable, with an admission rate of 5.5%. Women reported care from specialist midwives as highly acceptable, but the model is vulnerable without a strategic effort to develop additional proficient team members. CONCLUSIONS: Dedicated clinics coordinated by specialist midwives appear to be an acceptable and feasible implementation strategy to test the safety and effectiveness of proficient team care for VBB in a clinical trial. Back-up arrangements should be maintained while additional members of the team develop proficiency.

'I wasn't made to feel like a nut case after all': A qualitative story completion study exploring healthcare recipient and carer perceptions of good professional caregiving relationships.

BACKGROUND: Professional caregiving relationships are central to quality healthcare but are not always developed to a consistently high standard in clinical practice. Existing literature on what constitutes high-quality relationships and how they should be developed is plagued by dyadic conceptualisations; discipline, context and condition-specific research; and the absence of healthcare recipient and informal carer voices. This study aimed to address these issues by exploring how healthcare recipients and carers conceptualise good professional caregiving relationships regardless of discipline, care setting and clinical condition. DESIGN: A qualitative story completion approach was used. Participants completed a story in response to a hypothetical stem that described a healthcare recipient (and, in some instances, carer) developing a good relationship with a new healthcare provider. Stories were analysed using reflexive thematic analysis. PARTICIPANTS: Participants were 35 healthcare recipients and 37 carers (n = 72 total). RESULTS: Participants' stories were shaped by an overarching discourse that seeking help from new providers can elicit a range of unwanted emotions for both recipients and carers (e.g., anxiety, fear, dread). These unwanted emotions were experienced in relation to recipients' presenting health problems as well as their anticipated interactions with providers. Specifically, recipient and carer characters were fearful that providers would dismiss their concerns and judge them for deciding to seek help. Good relationships were seen to develop when healthcare providers worked to relieve or minimise these unwanted emotions, ensuring healthcare recipients and carers felt comfortable and at ease with the provider and the encounter. Participants positioned healthcare providers as primarily responsible for relieving recipients' and carers' unwanted emotions, which was achieved via four approaches: (1) easing into the encounter, (2) demonstrating interest in and understanding of recipients' presenting problems, (3) validating recipients' presenting problems and (4) enabling and respecting recipient choice. Participants' stories also routinely oriented to temporality, positioning relationships within recipients' and carers' wider care networks and biographical and temporal contexts. CONCLUSION: The findings expand our understanding of professional caregiving relationships beyond dyadic, static conceptualisations. Specifically, the findings suggest that high-quality relationships might be achieved via a set of core healthcare provider behaviours that can be employed across disciplinary, context and condition-specific boundaries. In turn, this provides a basis to support interprofessional education and multidisciplinary healthcare delivery, enabling different healthcare disciplines, specialties, and teams to work from the same understanding of what is required to develop high-quality relationships. PATIENT OR PUBLIC CONTRIBUTION: The findings are based on stories from 72 healthcare recipient and carer participants, providing rich insight into their conceptualisations of high-quality professional caregiving relationships.

Barriers and enablers to managing challenging behaviours after traumatic brain injury in the acute hospital setting: a qualitative study.

BACKGROUND: Challenging behaviours after traumatic brain injury (TBI) in the acute setting are associated with risk of harm to the patient and staff, delays in commencing rehabilitation and increased length of hospital stay. Few guidelines exist to inform practice in acute settings, and specialist services providing multi-disciplinary expertise for TBI behaviour management are predominantly based in subacute inpatient services. This study aims to investigate acute and subacute staff perspectives of barriers and enablers to effectively managing challenging behaviours after TBI in acute hospital settings. METHODS: Qualitative focus groups were conducted with 28 staff (17 from acute setting, 11 from subacute setting) across two sites who had experience working with patients with TBI. Data were analysed using inductive-deductive reflexive thematic analysis. Data were applied to the constructs of the integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework to generate themes representing barriers and enablers to managing challenging behaviours after TBI in the acute hospital setting. RESULTS: Four barriers and three enablers were identified. Barriers include (1) Difficulties with clinical decision making; (2) Concerns for risks to staff and patients; (3) Hospital environment; (4) Intensive resources are required. Enablers were (1) Experienced staff with practical skills; (2) Incorporating person-centred care; and (3) Supportive teams. CONCLUSION: These findings can inform pre-implementation planning for future improvements to TBI behaviour management in acute hospital settings. Difficulties with clinical decision making, concerns for risks of injury, the hospital environment and lack of resources are major challenges. Implementation strategies developed to address barriers will need to be trialled, with multi-disciplinary team approaches, and tailored to the acute setting.

Early CRP Trends in Childhood Osteomyelitis Predict Complicated Disease.

BACKGROUND: Acute hematogenous osteomyelitis (AHO) remains a cause of severe illness among children. Contemporary research aims to identify predictors of acute and chronic complications. Trends in C-reactive protein (CRP) after treatment initiation may predict disease course. We have sought to identify factors associated with acute and chronic complications in the New Zealand population. METHODS: A retrospective review of all patients younger than16 years with presumed AHO presenting to a tertiary referral centre between 2008 and 2018 was performed. Multivariate was analysis used to identify factors associated with an acute or chronic complication. An "acute" complication was defined as the need for 2 or more surgical procedures, a hospital stays longer than 14 days, or recurrence despite intravenous antibiotics. A "chronic" complication was defined as growth or limb length discrepancy, avascular necrosis, chronic osteomyelitis, pathologic fracture, frozen joint, or dislocation. RESULTS: One hundred fifty-one cases met the inclusion criteria. The median age was 8 years (69.5% male). Within this cohort, 53 (34%) experienced an acute complication and 18 (12%) a chronic complication. Regression analysis showed that contiguous disease, delayed presentation, and failure to reduce CRP by 50% at day 4/5 predicted an acutely complicated disease course. Chronic complication was predicted by the need for surgical management and failed CRP reduction by 50% at day 4/5. CONCLUSIONS: CRP trends over 96 hours after the commencement of treatment differentiate patients with AHO likely to experience severe disease. LEVEL OF EVIDENCE: Level II, retrospective study.

Ten-year Review of Acute Pediatric Hematogenous Osteomyelitis at a New Zealand Tertiary Referral Center.

BACKGROUND: Acute hematogenous osteomyelitis (AHO) remains a cause of severe illness among children with the possibility of long-term consequences for growth and development. Recent research has highlighted an unusually high burden of disease in the New Zealand population compared with other Western regions. We have sought to identify trends in presentation, diagnosis, and management of AHO, with added focus on ethnicity and access to health care. METHODS: A 10-year retrospective review of all patients <16 years with presumed AHO presenting to a tertiary referral center between 2008 and 2018 was performed. RESULTS: One hundred fifty-one cases met inclusion criteria. The median age was 8 years with a male predominance (69.5%). Staphylococcus aureus was the most common pathogen using traditional laboratory culture method (84%). The number of cases per year decreased from 2008 to 2018. Assessment using New Zealand deprivation scores showed Maori children were most likely to experience socioeconomic hardship ( P ≤0.01). Median distance traveled by families to first hospital consult was 26 km (range 1 to 178 km). Delayed presentation was associated with need for prolonged antibiotic therapy. Incidence of disease varied by ethnicity with 1:9000 cases per year for New Zealand European, 1:6500 for Pacific, and 1:4000 for Maori. Overall recurrence rate was 11%. CONCLUSIONS: The incidence of AHO in New Zealand is concerningly high within Maori and Pacific populations. Future health interventions should consider environmental, socioeconomic, and microbiological trends in the burden of disease. LEVEL OF EVIDENCE: Retrospective study, Level III.

Exploring the role of a facilitator in supporting family carers when embedding the iSupport for Dementia programme in care services: A qualitative study.

AIMS: To explore stakeholders' perceptions of a facilitator's role in supporting carers when embedding iSupport for Dementia psychoeducation program, in care services. METHODS: A qualitative descriptive study design was applied. Data were collected from workshops and interviews with carers of people living with dementia (PLWD)and with health and social care professionals from two tertiary hospitals and two community aged care organisations across three Australian states between October 2021 and March 2022. A thematic analysis was used to analyse data. The COREQ guideline was followed to report our findings. RESULTS: A total of 30 family carers and 45 health and social care professionals participated in the study. Three main themes and seven subthemes were identified from the data. We described the main themes as (1) the facilitator's role at the time of dementia diagnosis, (2) the facilitator's role throughout the everyday dementia care journey and (3) the facilitator's role during transition moments. CONCLUSIONS: Caring for family members with dementia is demanding and stressful for carers. Embedding a facilitator-enabled iSupport for Dementia program in hospital and community aged care settings has the potential to mitigate sources of stress associated with care recipient factors, carer factors and care service factors, and improve the health and well-being of carers and those for whom they care. RELEVANCE TO CLINICAL PRACTICE: Our findings will inform the establishment of iSupport facilitators appointed by dementia care providers in hospital and community care settings and help determine their roles and responsibilities in delivering the iSupport program. Our findings relate to nurse-led and coordinated dementia care in hospital and community aged care settings. PATIENT OR PUBLIC CONTRIBUTION: This study was co-designed with stakeholders from two aged care organisations and two tertiary hospitals. The study participants were staff employed by these organisations and carers of PLWD who were service users.

Qualitative Story Completion: Opportunities and Considerations for Health Research.

Qualitative story completion (QSC) is an innovative research method that offers researchers a range of unique opportunities for generating and analysing data. Participants are asked to write a 'story' in response to a hypothetical 'story stem', often in the third-person and involving fictional characters, rather than reporting on their direct experiences. QSC is being developed and increasingly taken up by researchers working across a range of fields; but it has been little used in health research, especially in the fields of nursing, health services research, medicine, and allied health. This means that health researchers have few examples to draw on when considering what QSC can offer them and how to rigorously design, conduct, and report a QSC study within health-related fields. We aim to address this gap and contribute to existing QSC literature by promoting increased use of QSC by health researchers and supporting them to produce rigorous QSC research. We outline three case examples illustrating how we have used QSC to conduct multidisciplinary health research relevant to nursing, medicine and nutrition. Drawing on these case examples, we reflect on challenges that we encountered, describe decision-making processes, and offer recommendations for conducting rigorous health research using QSC.

Perspectives Regarding Medications for Opioid Use Disorder Among Individuals with Mental Illness.

Most people with co-occurring opioid use disorder (OUD) and mental illness do not receive effective medications for treating OUD. To investigate perspectives of adults in a publicly-funded mental health system regarding medications for OUD (MOUD), we conducted semi-structured telephone interviews with 13 adults with OUD (current or previous diagnosis) receiving mental health treatment. Themes that emerged included: perceiving or using MOUDs as a substitute for opioids or a temporary solution to prevent withdrawal symptoms; negative perceptions about methadone/methadone clinics; and viewing MOUD use as "cheating". Readiness to quit was important for patients to consider MOUDs. All participants were receptive to discussing MOUDs with their mental health providers and welcomed the convenience of receiving care for their mental health and OUD at the same location. In conclusion, clients at publicly-funded mental health clinics support MOUD treatment, signaling a need to expand access and build awareness of MOUDs in these settings.

Utility of bile acids in large airway bronchial wash versus bronchoalveolar lavage as biomarkers of microaspiration in lung transplant recipients: a retrospective cohort study.

BACKGROUND: Bronchoalveolar lavage (BAL) is a key tool in respiratory medicine for sampling the distal airways. BAL bile acids are putative biomarkers of pulmonary microaspiration, which is associated with poor outcomes after lung transplantation. Compared to BAL, large airway bronchial wash (LABW) samples the tracheobronchial space where bile acids may be measurable at more clinically relevant levels. We assessed whether LABW bile acids, compared to BAL bile acids, are more strongly associated with poor clinical outcomes in lung transplant recipients. METHODS: Concurrently obtained BAL and LABW at 3 months post-transplant from a retrospective cohort of 61 lung transplant recipients were analyzed for taurocholic acid (TCA), glycocholic acid (GCA), and cholic acid by mass spectrometry and 10 inflammatory proteins by multiplex immunoassay. Associations between bile acids with inflammatory proteins and acute lung allograft dysfunction were assessed using Spearman correlation and logistic regression, respectively. Time to chronic lung allograft dysfunction and death were evaluated using multivariable Cox proportional hazards and Kaplan-Meier methods. RESULTS: Most bile acids and inflammatory proteins were higher in LABW than in BAL. LABW bile acids correlated with inflammatory proteins within and between sample type. LABW TCA and GCA were associated with acute lung allograft dysfunction (OR = 1.368; 95%CI = 1.036-1.806; P = 0.027, OR = 1.064; 95%CI = 1.009-1.122; P = 0.022, respectively). No bile acids were associated with chronic lung allograft dysfunction. Adjusted for risk factors, LABW TCA and GCA predicted death (HR = 1.513; 95%CI = 1.014-2.256; P = 0.042, HR = 1.597; 95%CI = 1.078-2.366; P = 0.020, respectively). Patients with LABW TCA in the highest tertile had worse survival compared to all others. CONCLUSIONS: LABW bile acids are more strongly associated than BAL bile acids with inflammation, acute lung allograft dysfunction, and death in lung transplant recipients. Collection of LABW may be useful in the evaluation of microaspiration in lung transplantation and other respiratory diseases.

Influence of Substituents in the Benzene Ring on the Halogen Bond of Iodobenzene with Ammonia.

The effects on the C-I⋅⋅N halogen bond between iodobenzene and NH3 of placing various substituents on the phenyl ring are monitored by quantum calculations. Substituents R=N(CH3 )2 , NH2 , CH3 , OCH3 , COCH3 , Cl, F, COH, CN, and NO2 were each placed ortho, meta, and para to the I. The depth of the σ-hole on I is deepened as R becomes more electron-withdrawing which is reflected in a strengthening of the halogen bond, which varied between 3.3 and 5.5 kcal mol-1 . In most cases, the ortho placement yields the largest perturbation, followed by meta and then para, but this trend is not universal. Parallel to these substituent effects is a progressive lengthening of the covalent C-I bond. Formation of the halogen bond reduces the NMR chemical shielding of all three nuclei directly involved in the C-I⋅⋅N interaction. The deshielding of the electron donor N is most closely correlated with the strength of the bond, as is the coupling constant between I and N, so both have potential use as spectroscopic measures of halogen bond strength.

Global epidemiology of childhood bone and joint infection: a systematic review.

PURPOSE: Childhood bone and joint infection (BJI) is a potentially severe disease that may have permanent sequelae, including growth impairment and limb deformity. It has been characterised in the literature with a focus on Western epidemiology; there are currently no reports detailing global epidemiology and bacteriology. This omits key data from determining temporal trends, appropriate antibiotic therapy, and resource allocation. This review aims to identify studies that characterise the incidence of childhood bone and joint infection or provide detailed bacteriology within their region. METHODS: A systematic review of the literature was performed from 01/01/1980 to 31/12/2020. Data has been analysed to give incidence of disease per 100,000 children, primary pathogen by country where available, and risk ratio (RR) for disease by ethnicity. This is applicable for areas that experience race-related inequitable burden of disease. RESULTS: Forty-four articles met the inclusion area; of these, seven were population-wide studies, primarily from Europe or the United States, and the remainder were cohort studies. Incidence could be derived from 26 studies compromising over 34, 000 children. Information on bacteriology was available from 39 publications (10, 957 cases). Methicillin-sensitive Staphylococcus aureus is the most common pathogen in the West. Recently, disease secondary to Kingella kingae and methicillin-resistant S. aureus has increased. Salmonella remains a dominant pathogen in African regions. Increased risk of disease is observed in Aboriginal, New Zealand Maori, Pacific, Indigenous Fijian, and Bedouin children. CONCLUSION: The current state of the literature detailing incidence of childhood BJI focuses on disease patterns from the West. There is a paucity of high-quality publications in the developing world. Despite these limitations, global trends in burden of disease show race-related inequitable risk of BJI. Temporal and regional variation in bacteriology can be demonstrated. LEVEL OF EVIDENCE: III.

COVID-19 vaccination in children and adolescents aged 5 years and older undergoing treatment for cancer and non-malignant haematological conditions: Australian and New Zealand Children's Haematology/Oncology Group consensus statement.

INTRODUCTION: The Australian Technical Advisory Group on Immunisation and New Zealand Ministry of Health recommend all children aged ≥ 5 years receive either of the two mRNA COVID-19 vaccines: Comirnaty (Pfizer), available in both Australia and New Zealand, or Spikevax (Moderna), available in Australia only. Both vaccines are efficacious and safe in the general population, including children. Children and adolescents undergoing treatment for cancer and immunosuppressive therapy for non-malignant haematological conditions are particularly vulnerable, with an increased risk of severe or fatal COVID-19. There remains a paucity of data regarding the immune response to COVID-19 vaccines in immunosuppressed paediatric populations, with data suggestive of reduced immunogenicity of the vaccine in immunocompromised adults. RECOMMENDATIONS: Considering the safety profile of mRNA COVID-19 vaccines and the increased risk of severe COVID-19 in immunocompromised children and adolescents, COVID-19 vaccination is strongly recommended for this at-risk population. We provide a number of recommendations regarding COVID-19 vaccination in this population where immunosuppressive, chemotherapeutic and/or targeted biological agents are used. These include the timing of vaccination in patients undergoing active treatment, management of specific situations where vaccination is contraindicated or recommended under special precautions, and additional vaccination recommendations for severely immunocompromised patients. Finally, we stress the importance of upcoming clinical trials to identify the safest and most efficacious vaccination regimen for this population. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: This consensus statement provides recommendations for COVID-19 vaccination in children and adolescents aged ≥ 5 years with cancer and immunocompromising non-malignant haematological conditions, based on evidence, national and international guidelines and expert opinion. ENDORSED BY: The Australian and New Zealand Children's Haematology/Oncology Group.