Prevalence of hyperthyroidism and hypothyroidism in liver transplant recipients and associated risk factors.

The prevalence of hyperthyroidism and hypothyroidism and associated risk factors are unknown in liver transplant recipients. We aimed to determine the prevalence of hyperthyroidism and hypothyroidism and associated risk factors in liver transplant recipients and to compare it with controls from the general population. As part of the Danish Comorbidity in Liver Transplant Recipients (DACOLT) Study, all Danish liver transplant recipients over the age of 20 were invited for measurements of concentrations of thyrotropin and thyroid hormones. The prevalence of hyperthyroidism and hypothyroidism was compared to age- and sex-matched controls from the Copenhagen General Population Study. Using logistic regression adjusted for age, sex, smoking, and body-mass index, we investigated potential risk factors. We recruited 489 liver transplant recipients and 1808 controls. Among liver transplant recipients, 14 (2.9%) had hyperthyroidism compared with 21 (1.2%) of controls (adjusted odds ratio [aOR] 2.24, 95% confidence interval [CI] 1.05-4.75, P = 0.04), while 42 (5.7%) had hypothyroidism compared with 139 (7.7%) of controls (aOR 0.68, 95% CI 0.43-1.08, P = 0.10). Female sex, and autoimmune hepatitis and primary sclerosing cholangitis as causes of transplantation were associated with hyperthyroidism after adjustments. Age, female sex, and autoimmune liver diseases as cause of transplantation were associated with hypothyroidism after adjustments. DACOLT is registered in ClinicalTrials.gov (NCT04777032).

Improving family grief outcomes: A scoping review of family-based interventions before and after the death of a child.

BACKGROUND: Experiencing the illness and death of a child is a traumatic experience for the parents and the child's siblings. However, knowledge regarding effective grief interventions targeting the whole family is limited, including how to integrate age-appropriate support for siblings. AIM: We aimed to synthesize the empirical literature regarding grief interventions that target the whole family before and/or after the death of a child. DESIGN: A scoping review following the Joanna Briggs Institute and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. DATA SOURCES: We searched PubMed, PsycINFO, Embase, CINAHL, and Scopus covering January 1998-May 2022. We included studies describing any type of structured intervention targeting the whole family (i.e. parents and siblings) before or/and after the death of a child (below 18 years), with pre-post assessments of grief-related symptoms in the family as an outcome. RESULTS: After removal of duplicates, we screened the titles and abstracts of 4078 publications and identified 30 publications for full-text screening. None of the studies met the inclusion criteria. Most of the studies were excluded because they either did not target the whole family or did not target families who had lost a child below 18 years. Bereavement camps were a popular form of family intervention, but none were evaluated in a pre-post design. No grief interventions offering support pre-death were found. CONCLUSIONS: There is great need for research to improve bereavement outcomes for the entire family and to potentially integrate this in pediatric palliative care.

Fraction of exhaled nitric oxide is higher in liver transplant recipients than in controls from the general population: a cohort study.

Background: Fraction of exhaled nitric oxide with an expiratory flow of 50 mL/s (FENO50) is a biomarker of eosinophilic airway inflammation. Liver transplant recipients have an increased risk of pulmonary infections, but little is known about the burden of chronic pulmonary diseases in this group. We aimed to assess the prevalence of elevated FENO50 in liver transplant recipients and compare it to controls from the general population. Methods: FENO50 was measured in 271 liver transplant recipients from The Danish Comorbidity in Liver Transplant Recipients (DACOLT) study and 1,018 age- and sex-matched controls from The Copenhagen General Population Study (CGPS). Elevated FENO50 was defined as ≥25 or ≥50 parts per billion (ppb). The analyses were adjusted for known and suspected confounders. Results: The median age of the liver transplant recipients was 55 years (interquartile range (IQR) 46-64), and 58% were men. The liver transplant recipients had a higher median FENO50 than the controls [16 ppb (IQR 10-26) vs. 13 ppb (IQR 8-18.), p < 0.001]. Furthermore, the liver transplant recipients had a higher prevalence of elevated FENO50 (for FENO50 ≥25 ppb 27% vs. 11%, p < 0.001 and ≥50 ppb 4% vs. 2%, p = 0.02). The results were similar after adjusting for age, sex, smoking status, use of airway medication, and blood eosinophil counts [the adjusted odds ratio (OR) for FENO50 ≥25 ppb was 3.58 (95% CI: 2.50-5.15, p < 0.0001) and the adjusted OR for FENO50 ≥50 ppb was 3.14 (95% CI: 1.37-7.20, p = 0.007)]. Conclusion: The liver transplant recipients had elevated FENO50, implying increased eosinophilic airway inflammation. The clinical impact of this finding needs further investigation.

Characteristics of de novo cancer in liver transplant recipients.

Liver transplant recipients receive immunosuppressive treatment to avoid organ rejection, increasing the risk of developing de novo cancer after transplantation. We investigated the cumulative incidence of de novo cancer in a cohort of Danish liver transplant recipients. The study was a retrospective cohort study of adult liver transplant recipients transplanted at Rigshospitalet, Copenhagen, Denmark, between January 1, 2010, and December 31, 2019. De novo cancer was defined as cancer arising at least 30 days after liver transplantation, excluding relapses from prior cancers and donor-derived cancers. We determined the incidence of de novo cancer in the cohort using the Aalen-Johansen estimator, with death and retransplantation as competing risks. We included 389 liver transplant recipients and identified 47 recipients (12%) with de novo cancer after liver transplantation, including 25 recipients with non-melanoma skin cancers. The cumulative incidences at 5 years after liver transplantation for all cancers and non-skin cancers were 10.7% and 4.9%, respectively. De novo cancer after liver transplantation is relatively common, with the majority being non-melanoma skin cancer. Future studies of sufficient size are needed to identify risk factors for de novo cancer after liver transplantation.

Insulin resistance in people living with HIV is associated with exposure to thymidine analogues and/or didanosine and prior immunodeficiency.

BACKGROUND: As people living with HIV (PLWH) are growing older, there is increased incidence of metabolic diseases, including type 2 diabetes mellitus, for which insulin resistance is a key determinant. In this study, we aimed to investigate risk factors associated with insulin resistance in PLWH. METHODS: We included well-treated PLWH without hepatitis co-infection, and with available fasting serum insulin and plasma glucose (n = 643) from the Copenhagen Comorbidity in HIV Infection Study. Insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). We investigated the association between risk factors and high HOMA-IR in a logistic regression model adjusted for age, sex, abdominal obesity, smoking status, and origin. When including use of thymidine analogues and/or didanosine in the model, we also adjusted for time with HIV. RESULTS: Median (IQR) age of PLWH was 52 years (46-61), and 87% (n = 557) were male. Median (IQR) HOMA-IR was 1.86 (1.23-3.14) mmol/L × mU/L. Risk factors significantly associated with high HOMA-IR included older age, BMI ≥ 25, abdominal obesity, waist circumference, use of thymidine analogues and/or didanosine, time with HIV, and CD4+ nadir < 200 cells/µL. CONCLUSIONS: Insulin resistance in PLWH is associated with both use of thymidine analogues and/or didanosine and prior immunodeficiency suggesting that increased attention on blood glucose in these patients could be beneficial.

Monocyte count and soluble markers of monocyte activation in people living with HIV and uninfected controls.

BACKGROUND: Monocytes play an important role in inflammation, and monocytosis and monocyte activation are features of chronic inflammation. We aimed to investigate if HIV status was associated with monocyte count and monocyte activation and to assess the relationship between monocyte count and monocyte activation markers and HIV-related factors. METHODS: Persons living with HIV (PLWH) with measured monocyte count and sCD14 and sCD163 were included from the Copenhagen Comorbidity in HIV infection (COCOMO) study and matched 1:5 on sex and age with uninfected controls. In addition, 74 uninfected individuals from COCOMO with measured sCD14 and sCD163 were included. Identical protocols and equipment were used to determine monocyte counts and monocyte activation in PLWH and uninfected controls. Linear regression adjusted for age, sex, smoking and waist-to-hip-ratio was used to analyze the association between possible risk factors and monocyte outcomes. RESULTS: We included 871 PLWH and 4355 uninfected controls. PLWH had - 0.021 [- 0.031 - 0.011] × 109/L) lower monocyte count than uninfected controls, and in adjusted analyses HIV status was independently associated with - 0.035 [- 0.045, - 0.025] × 109/L lower monocyte count. In contrast, PLWH had higher sCD163 and sCD14 concentrations than uninfected controls. After adjustment, HIV-status was associated with higher sCD14 and sCD163 concentrations (588 [325, 851] ng/ml, and 194 [57, 330] ng/ml, respectively). CONCLUSION: PLWH had lower monocyte counts than controls, but the absolute difference was small, and any clinical impact is likely limited. In contrast, concentrations of monocyte activation markers, previously implicated as drivers of non-AIDS comorbidity, were higher in PLWH than in controls.

High incidence of subclinical peripheral artery disease in people with HIV.

OBJECTIVE: Atherosclerosis is common in people with HIV (PWH). Peripheral artery disease (PAD) is the peripheral manifestation of atherosclerosis, but little is known about the incidence of PAD in PWH. Our objective was to determine the PAD incidence in PWH and to investigate potential risk factors. DESIGN: Prospective longitudinal study on PWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) study cohort. METHODS: We performed ankle-brachial index (ABI) measurements at study entry and at 2-year follow-up and included participants with normal ABI at study entry. We defined de novo PAD as ABI ≤0.9 at follow-up. Using Poisson regression adjusted for age, sex, and smoking, we investigated the role of traditional and HIV-related risk factors, including inflammatory markers. RESULTS: Of 844 PWH followed for a median duration of 2.3 years, 30 (3.6%) developed de novo PAD. All cases were subclinical. Diabetes (relative risk [RR] = 4.90 [95% confidence interval [CI]: 1.99-12.1]), current CD4 + cell count <350 cells/µl (2.66 [1.06-6.71]), longer duration of antiretroviral therapy (antiretroviral therapy [ART], 1.88 [1.06-3.33] per decade), and concentrations of high-sensitivity C-reactive protein (1.33 [1.08-1.63] per doubling) and interleukin-6 (1.38 [1.06-1.80] per doubling), were associated with de novo PAD. CONCLUSIONS: PWH had a high incidence of de novo subclinical PAD. Diabetes, low current CD4 + cell count, duration of ART, and inflammatory markers were associated with de novo PAD, indicating a possible role in PAD pathogenesis in PWH.

De novo electrocardiographic abnormalities in persons living with HIV.

Persons living with HIV (PLWH) may have increased incidence of cardiovascular events and longer QTc intervals than uninfected persons. We aimed to investigate the incidence and risk factors of de novo major electrocardiogram (ECG) abnormalities and QTc prolongation in well-treated PLWH. We included virologically suppressed PLWH without major ECG abnormalities, who attended the 2-year follow-up in the Copenhagen comorbidity in HIV infection (COCOMO) study. ECGs were categorized according to Minnesota Code Manual. We defined de novo major ECG abnormalities as new major Minnesota Code Manual abnormalities. Prolonged QTc was defined as QTc > 460 ms in females and QTc > 450 ms in males. Of 667 PLWH without major ECG abnormalities at baseline, 34 (5%) developed de novo major ECG abnormalities after a median of 2.3 years. After adjustment, age (RR: 1.57 [1.08-2.28] per decade older), being underweight (RR: 5.79 [1.70-19.71]), current smoking (RR: 2.34 [1.06-5.16]), diabetes (RR: 3.89 [1.72-8.80]) and protease inhibitor use (RR: 2.45 [1.27-4.74) were associated with higher risk of getting de novo major ECG abnormalities. Of PLWH without prolonged QTc at baseline, only 11 (1.6%) participants developed de novo prolonged QTc. Five percent of well-treated PLWH acquired de novo major ECG abnormalities and protease inhibitor use was associated with more than twice the risk of de novo major ECG abnormalities. De novo prolonged QTc was rare and did not seem to constitute a problem in well-treated PLWH.

The central role of the glutamate metabolism in long-term antiretroviral treated HIV-infected individuals with metabolic syndrome.

Metabolic syndrome (MetS) is a significant factor for cardiometabolic comorbidities in people living with HIV (PLWH) and a barrier to healthy aging. The long-term consequences of HIV-infection and combination antiretroviral therapy (cART) in metabolic reprogramming are unknown. In this study, we investigated metabolic alterations in well-treated PLWH with MetS to identify potential mechanisms behind the MetS phenotype using advanced statistical and machine learning algorithms. We included 200 PLWH from the Copenhagen Comorbidity in HIV-infection (COCOMO) study. PLWH were grouped into PLWH with MetS (n = 100) defined according to the International Diabetes Federation (IDF) consensus worldwide definition of the MetS or without MetS (n = 100). The untargeted plasma metabolomics was performed using ultra-high-performance liquid chromatography/mass spectrometry (UHPLC/MS/MS) and immune-phenotyping of Glut1 (glucose transporter), xCT (glutamate/cysteine transporter) and MCT1 (pyruvate/lactate transporter) by flow cytometry. We applied several conventional approaches, machine learning algorithms, and linear classification models to identify the biologically relevant metabolites associated with MetS in PLWH. Of the 877 identified biochemicals, 9% (76/877) differed significantly between PLWH with and without MetS (false discovery rate < 0.05). The majority belonged to amino acid metabolism (43%). A consensus identification by combining supervised and unsupervised methods indicated 11 biomarkers of MetS phenotype in PLWH. A weighted co-expression network identified seven communities of positively intercorrelated metabolites. A single community contained six of the potential biomarkers mainly related to glutamate metabolism. Transporter expression identified altered xCT and MCT in both lymphocytic and monocytic cells. Combining metabolomics and immune-phenotyping indicated altered glutamate metabolism associated with MetS in PLWH, which has clinical significance.

The impact of ultraviolet therapy on stratum corneum ceramides and barrier function.

The ceramide profile as well as the barrier function is known to be deteriorated in atopic eczema and psoriasis, and ultraviolet (UV) light is known to improve the barrier function. The impact of UV light on ceramides, however, is not clarified. The aim of this study was to examine the effect of UV therapy in dermatological patients on ceramides and skin barrier function. We found that UV light treatment does not change the ratio of important stratum corneum lipids, but we confirm earlier findings of decreased susceptibility to irritants after UV- therapy.