Risk of Social Isolation as a Contributing Factor to Diet Quality in Community-Dwelling Older Persons Living in the Australian Capital Territory-A Pilot Study.

OBJECTIVES: Social isolation is recognised as a risk factor in the inflammatory process. This study explored the association between social isolation and the Dietary Inflammatory Index (DII) in community-dwelling older persons. METHODS: This cross-sectional pilot study recruited 107 community-dwelling people aged over 55 years living in the Australian Capital Territory. Participants completed an extensive food frequency questionnaire and provided anthropometric and sociodemographic data. Social isolation was evaluated using the Lubben Social Network Scale (LSNS). Diet quality was assessed using DII. RESULTS: Average age was 70.1 (±8.61) years and 62.8% were female. The average DII score was -1.10 (±1.21), indicating an anti-inflammatory diet. Higher LSNS was associated with lower DII (b (95% CI) = -0.041 (-0.066, -0.17); p < 0.01) and was positively influenced by the number of people in household (b (95% CI) = 5.731 (2.336, 9.127); p = 0.001). CONCLUSION: Increased risk of social isolation was associated with an increased tendency towards a more inflammatory diet. Reducing social isolation may decrease the inflammatory component of dietary intake for older persons living independently in the community.

Testosterone is lower in men with non-alcoholic fatty liver disease and alcohol-related cirrhosis and is associated with adverse clinical outcomes.

BACKGROUND/AIMS: Low serum testosterone is common in cirrhotic men, but the impact of disease aetiology remains uncertain. This study compares serum total testosterone (TT) levels by disease aetiology and assesses its prognostic value. METHODS: Single-centre retrospective study of cirrhotic men who had TT levels measured between 2002 and 2020. A cut-off of 12 nmol/L was used to define low TT and 230 pmol/L for calculated free testosterone (cFT). Linear and logistic regression used to adjust for variables known to affect testosterone levels and assess for an association between levels and outcomes. RESULTS: Of 766 cirrhotic men, 33.3% had alcohol-related liver disease (ALD) and 11.9% had non-alcoholic fatty liver disease (NAFLD). The median age was 56 years (interquartile range (IQR) 50-61), and the model for end-stage liver disease (MELD) score 14 (IQR 9-20). TT levels were low in 53.3% of patients, (median 11.0 nmol/L; IQR 3.7-19.8) and cFT low in 79.6% (median 122 pmol/L; IQR 48.6-212). Median TT was lower in men with ALD (7.6 nmol/L; IQR 2.1-16.2) and NAFLD (9.8 nmol/L; IQR 2.75-15.6) compared to other aetiologies (11.0 nmol/L; IQR 3.73-19.8) (p < 0.001 for all), which remained true after adjustment for age and MELD score. TT was inversely associated with 12-month mortality or transplant (381 events, p = 0.02) and liver decompensation (345 events, p = 0.004). CONCLUSIONS: Low serum testosterone is common in cirrhotic men and is associated with adverse clinical outcomes. TT levels are significantly lower in ALD and NAFLD compared to other disease aetiologies. Further large-scale studies are required to assess the potential benefits of testosterone therapy.

Radiation exposure from radiological procedures in liver transplant candidates with hepatocellular carcinoma.

PURPOSE: Candidates for liver transplantation (LT) with hepatocellular carcinoma (HCC) undergo a large number of diagnostic and interventional radiology procedures. A significant proportion of such procedures involve ionizing radiation with increased lifetime risk of cancer. The objective of our study was to review LT candidates with HCC to quantify ionizing radiation doses from different radiology procedures performed at a single transplant center. METHOD: We retrospectively reviewed 179 adult patients with HCC (median age 58.6 years [IQR, 55-62]; 155 [86.6%] males) who were accepted for LT between April 2010 and Dec 2018. Radiology procedures and radiation doses were retrieved and the total and median radiation effective dose in millisieverts (mSv) were calculated for different procedures. Exposure to ionizing radiation was categorized based on previously reported thresholds. RESULTS: We assessed 9,986 radiology procedures for our cohort. Patients had a median effective dose prior to transplantation of 254 mSv (IQR, 130-421) with an annualized rate of 152 mSv (IQR, 92-266). Patient median dose increased to 316 mSv (IQR, 159-478) when including exposures post-LT within the study period. 85% of overall exposure was in the extremely high exposure category (>100 mSv). Interventional procedures represented 13% of procedures with substantial radiation and contributed to 45% of radiation exposure while abdominal CTs represented 39% of total procedures and contributed to 45% of radiation exposure. CONCLUSIONS: Patients with HCC considered for LT undergo radiology procedures with significant cumulative radiation exposure. Attempts to reduce radiation exposure are suggested by minimizing unnecessary procedures and utilizing ones without ionizing radiation. Improving interventional techniques to reduce radiation doses is needed without compromising treatment delivery.

Low participation in preventative health measures in a cohort of liver transplant recipients: A cross-sectional analysis.

BACKGROUND: Despite high rates of infection and malignancy post-solid organ transplant, there are little data on patient participation in preventative health care. METHODS: We conducted a cross-sectional survey of post-liver transplant patients to evaluate insight into transplant-associated infective and neoplastic risks, and receipt of vaccination and cancer surveillance in accordance with Australian and local institution-specific guidelines. Descriptive analyses were used to assess characteristics potentially influencing adherence. RESULTS: Of 219 patients surveyed, adherence to bowel cancer surveillance was significantly reduced in those distant from transplantation compared with those recently transplanted (95.8% if transplanted ≤ 5 years ago vs. 68.3% if transplanted > 5 years ago, P < .001). Skin cancer surveillance participation with annual physician-directed examination was low (42.9%), particularly in younger patients (29.5% in < 50yo vs. 48.1% in ≥ 50yo, P = .01), who were also less adherent to vaccination recommendations (72.1% in < 50yo vs. 87.3% in ≥ 50yo, P = .008). CONCLUSIONS: This is the first analysis of preventative healthcare participation in a cohort of Australian liver transplant recipients, revealing concerning adherence to bowel and skin cancer surveillance recommendations. Major interventions to avoid preventable disease in this high-risk cohort are warranted.

Hepatocellular carcinoma surveillance and quantile regression for determinants of underutilisation in at-risk Australian patients.

BACKGROUND: While clinical guidelines recommend hepatocellular carcinoma (HCC) surveillance for at-risk individuals, reported surveillance rates in the United States and Europe remain disappointingly low. AIM: To quantify HCC surveillance in an Australian cohort, and assess for factors associated with surveillance underutilisation. METHODS: All patients undergoing HCC surveillance liver ultrasounds between January 1, 2018 to June 30, 2018 at a tertiary hospital in Melbourne, Australia, were followed until July 31, 2020, or when surveillance was no longer required. The primary outcome was the percentage of time up-to-date with HCC surveillance (PTUDS). Quantile regression was performed to determine the impact of factors associated with HCC surveillance underutilisation. RESULTS: Among 775 at-risk patients followed up for a median of 27.5 months, the median PTUDS was 84.2% (IQR: 66.3%-96.3%). 85.0% of patients were followed up by specialist gastroenterologists. Amongst those receiving specialist care, quantile regression demonstrated differential associations at various quantile levels of PTUDS for several factors. Older age at the 25th quantile (estimate 0.002 per percent, P = 0.03), and cirrhotic status at the 75th quantile (estimate 0.021, P = 0.017), were significantly associated with greater percentage of time up-to-date. African ethnicity (estimate -0.089, P = 0.048) and a culturally and linguistically diverse (CALD) background (estimate -0.063, P = 0.01) were significantly associated with lower PTUDS at the 50th quantile, and again for CALD at the 75th quantile (estimate -0.026, P = 0.045). CONCLUSION: While median PTUDS in this Australian cohort study was 84.2%, awareness of the impact of specific factors across PTUDS quantiles can aid targeted interventions towards improved HCC surveillance.

Food Habits of Older Australians Living Alone in the Australian Capital Territory.

The link between adequate nutrition and quality of life for older persons is well established. With the proportion of older adults increasing, policy regarding support and care for the ageing has shifted emphasis to keeping older adults in their homes for as long as possible. Risk of malnutrition is an issue of importance for this population and, while this risk is well researched within the hospital setting, it is still relatively under-researched within the community-dwelling elderly, particularly with respect to the lived experience. This qualitative study (underpinned by interpretative phenomenology philosophy) explores how the lived experiences of community-dwelling older people living in one-person households in the Australian Capital Territory (ACT) influences dietary patterns, food choices and perceptions about food availability. Using purposeful and snowballing sampling, older people (65 years and over) living alone in the community participated in focus group discussions triangulated with their family/carers. Data were thematically analysed using a previously established approach. Participants (n = 22) were interviewed in three focus groups. Three themes were identified: active and meaningful community connectedness; eating well and behaviours to promote dietary resilience. Of these, community connectedness was pivotal in driving food patterns and choices and was a central component influencing behaviours to eating well and maintaining dietary resilience.

The impact of delayed rapid response call activation on patient outcomes.

PURPOSE: To investigate the impact of delay in rapid response call (RRC) activation on Hospital mortality. MATERIALS AND METHODS: This study was conducted in a university affiliated hospital providing medical, surgical, mental health, maternity, and pediatric services. RRCs were considered delayed if RRC activation was delayed by ≥15min. The primary outcome measure was in-hospital mortality. Secondary outcomes included hospital length of stay (LOS), requirement of ICU admission, as well as requirement of mechanical ventilation and ICU LOS for patients requiring ICU admission. RESULTS: A total of 826 RRCs occurred in 629 patient admissions. A quarter of all RRCs were delayed by ≥15min, with a median delay of 1h and 20min. Patients with a delayed RRC had significantly higher in-hospital mortality (34.7% vs. 21.2%; p=0.001,) and significantly longer hospitalizations (11.6 vs. 8.4days; p=0.036). After adjusting for confounders, RRC activation was independently associated with increased in-hospital mortality (OR=1.79; 95% CI=1.17-2.72: p=0.007). CONCLUSIONS: A delay of ≥15min was associated with significantly increased in-hospital mortality and longer hospitalization. The factors contributing to the observed increase in mortality with delayed RRCs require further exploration.

Rescaling the Post-Traumatic Stress Disorder Checklist for Use in Primary Care.

The Posttraumatic Stress Disorder (PTSD) Checklist (PCL) is a 17-item self-report measure of PTSD symptom severity that has demonstrated excellent psychometric properties across a variety of settings, purposes, and populations. The PCL is widely used in busy Department of Defense primary care settings as part of routine PTSD screening, requiring that it is easy for patients to complete and providers to score. The clinical utility of the PCL may be improved through use of a zero-anchored Likert-type response scale by providing intuitive anchors for respondents and fewer calculations for clinic staff; however, changes to the response scale may invalidate the known psychometric properties of the measure. The purpose of this study is to evaluate the equivalence of a zero-anchored PCL to the traditional one-anchored PCL. Differences in total scores were examined using inferential confidence intervals. Substantial overlap of the inferential confidence intervals and small Rg (maximum probable difference) value of 0.68 indicated that the zero-anchored PCL is equivalent to the one-anchored PCL on the basis of our specified delta (amount of difference considered inconsequential). These findings support the use of a zero-anchored PCL in clinical practice, and more broadly, the use of zero-anchored measures in the larger field of psychological assessment.

Genome-wide RNA-seq analysis of human and mouse platelet transcriptomes.

Inbred mice are a useful tool for studying the in vivo functions of platelets. Nonetheless, the mRNA signature of mouse platelets is not known. Here, we use paired-end next-generation RNA sequencing (RNA-seq) to characterize the polyadenylated transcriptomes of human and mouse platelets. We report that RNA-seq provides unprecedented resolution of mRNAs that are expressed across the entire human and mouse genomes. Transcript expression and abundance are often conserved between the 2 species. Several mRNAs, however, are differentially expressed in human and mouse platelets. Moreover, previously described functional disparities between mouse and human platelets are reflected in differences at the transcript level, including protease activated receptor-1, protease activated receptor-3, platelet activating factor receptor, and factor V. This suggests that RNA-seq is a useful tool for predicting differences in platelet function between mice and humans. Our next-generation sequencing analysis provides new insights into the human and murine platelet transcriptomes. The sequencing dataset will be useful in the design of mouse models of hemostasis and a catalyst for discovery of new functions of platelets. Access to the dataset is found in the "Introduction."

Hematopoietic and nonhematopoietic cell tissue factor activates the coagulation cascade in endotoxemic mice.

Tissue factor (TF) is the primary activator of the coagulation cascade. During endotoxemia, TF expression leads to disseminated intravascular coagulation. However, the relative contribution of TF expression by different cell types to the activation of coagulation has not been defined. In this study, we investigated the effect of either a selective inhibition of TF expression or cell type-specific deletion of the TF gene (F3) on activation of coagulation in a mouse model of endotoxemia. We found that inhibition of TF on either hematopoietic or nonhematopoietic cells reduced plasma thrombin-antithrombin (TAT) levels 8 hours after administration of bacterial lipopolysaccharide (LPS). In addition, plasma TAT levels were significantly reduced in endotoxemic mice lacking the TF gene in either myeloid cells (TF(flox/flox),LysM(Cre) mice) or in both endothelial cells (ECs) and hematopoietic cells (TF(flox/flox),Tie-2(Cre) mice). However, deletion of the TF gene in ECs alone had no effect on LPS-induced plasma TAT levels. Similar results were observed in mice lacking TF in vascular smooth muscle cells. Finally, we found that mouse platelets do not express TF pre-mRNA or mRNA. Our data demonstrate that in a mouse model of endotoxemia activation of the coagulation cascade is initiated by TF expressed by myeloid cells and an unidentified nonhematopoietic cell type(s).

IgA ASC accumulation to the lactating mammary gland is dependent on VCAM-1 and alpha4 integrins.

The homing and migration of IgA antibody secreting cells (ASC) to the lactating mammary gland is essential to the passive transfer of immunity from mother to nursing neonate. Antibody secreting cells, located within the lactating mammary gland, produce high levels of antigen-specific IgA antibodies. These antibodies, which are subsequently transferred to the nursing neonate via breast milk, provide passive immune protection against antigens previously encountered by the mother to the nursing infant. The efficient homing and accumulation of lymphocytes is highly dependent on cellular adhesion molecules expressed on the vascular endothelium and their integrin ligands. Vasculature within the lactating mammary gland is known to express several adhesion molecules, including VCAM-1 and MAdCAM-1. However, the role of these molecules in vivo has not been previously described. Here we show that alpha4 integrins and VCAM-1 play essential roles in mediating the accumulation of IgA ASCs to the lactating mammary gland. Conversely, neither MAdCAM-1 nor its major ligand alpha4beta7 are required for efficient IgA ASC accumulation to this tissue.