Long-term outcome of liver transplantation for autoimmune hepatitis: A French nationwide study over 30 years

Background & Aims

Autoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). The aims of this study were to evaluate long-term survival after LT for AIH and prognostic factors, especially the impact of recurrent AIH (rAIH).

Methods

A multicentre retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Early deaths and retransplantations (≤6 months) were excluded.

Results

The study population consisted of 301 patients transplanted from 1987 to 2018. Median age at LT was 43 years (IQR, 29.4–53.8). Median follow-up was 87.0 months (IQR, 43.5–168.0). Seventy-four patients (24.6%) developed rAIH. Graft survival was 91%, 79%, 65% at 1, 10 and 20 years respectively. Patient survival was 94%, 84% and 74% at 1, 10 and 20 years respectively. From multivariate Cox regression, factors significantly associated with poorer patient survival were patient age ≥58 years (HR = 2.9; 95% CI, 1.4–6.2; p = 0.005) and occurrence of an infectious episode within the first year after LT (HR = 2.5; 95% CI, 1.2–5.1; p = 0.018). Risk factors for impaired graft survival were: occurrence of rAIH (HR = 2.7; 95% CI, 1.5–5.0; p = 0.001), chronic rejection (HR = 2.9; 95% CI, 1.4–6.1; p = 0.005), biliary (HR = 2.0; 95% CI, 1.2–3.4; p = 0.009), vascular (HR = 1.8; 95% CI, 1.0–3.1; p = 0.044) and early septic (HR = 2.1; 95% CI, 1.2–3.5; p = 0.006) complications.

Conclusion

Our results confirm that survival after LT for AIH is excellent. Disease recurrence and chronic rejection reduce graft survival. The occurrence of an infectious complication during the first year post-LT identifies at-risk patients for graft loss and death.     

Clotting factor activity levels and bleeding risk in people with haemophilia playing sports

Background

Improved treatment options for people with haemophilia (PWH) have increased the possibilities for sports participation, but the risk of sports-induced bleeding (SIB) is still considered considerable by many.

Aim

To assess sports associated injury- and bleeding risk in PWH and to assess clotting levels associated with safe sports participation.

Methods

Sports injuries and SIBs were prospectively collected for 12 months in PWH aged 6–49 without inhibitors playing sports at least once weekly. Injuries were compared according to factor levels, severity, joint health, sports risk category and sports intensity. Factor activity at the time of injury was estimated using a pharmacokinetic model.

Results

125 participants aged 6–49 (41 children, 90% haemophilia A; 48% severe, 95% severe on prophylaxis) were included. Sports injuries were reported by 51 participants (41%). Most participants (62%) reported no bleeds at all and only 16% reported SIBs. SIBs were associated with factor levels at time of injury (OR: 0.93/%factor level (CI 0.88–0.99); p = .02), but not with haemophilia severity (OR: 0.62 (CI 0.20–1.89); p = .40), joint health, sports risk category or sports intensity. PWH with factor levels <10% during sports injury had a bleeding risk of 41% versus 20% in those with higher (>10%) factor levels.

Conclusion

The results of this study emphasize the importance of clotting factor levels in prevention of bleeds. This information is vital for patient counselling and tailoring prophylactic treatment with clotting factors and non-replacement therapy.     

COVID-19 is associated with increased care needs and a decreased likelihood of returning home following a hip fracture: The IMPACT frailty study

Purpose

The primary aim was to evaluate the impact of COVID-19 on frailty in patients surviving a hip fracture. Secondary aims were to assess impact of COVID-19 on (i) length of stay (LoS) and post-discharge care needs, (ii) readmissions, and (iii) likelihood of returning to own home.

Methods

This propensity score-matched case-control study was conducted in a single centre between 01/03/20–30/11/21. A ‘COVID-positive’ group of 68 patients was matched to 141 ‘COVID-negative’ patients. ‘Index’ and ‘current’ Clinical Frailty Scale (CFS) scores were assigned for frailty at admission and at follow-up. Data were extracted from validated records and included: demographics, injury factors, COVID-19 status, delirium status, discharge destination, and readmissions. For subgroup analysis controlling for vaccination availability, the periods 1 March 2020–30 November 2020 and 1 February 2021–30 November 2021 were considered pre-/post-vaccine periods.

Results

Median age was 83.0 years, 155/209 (74.2%) were female and median follow-up was 479 days (interquartile range [IQR] 311). There was an equivalent median increase in CFS in both groups (+1.00 [IQR 1.00–2.00, p = 0.472]). However, adjusted analysis demonstrated COVID-19 was independently associated with a greater magnitude change (Beta coefficient [β] 0.27, 95% confidence interval [95% CI] 0.00–0.54, p = 0.05). COVID-19 in the post-vaccine availability period was associated with a smaller increase versus pre-vaccine (β −0.64, 95% CI −1.20 to −0.09, p = 0.023). COVID-19 was independently associated with increased acute LoS (β 4.40, 95% CI 0.22–8.58, p = 0.039), total LoS (β 32.87, 95% CI 21.42–44.33, p < 0.001), readmissions (β 0.71, 95% CI 0.04–1.38, p = 0.039), and a four-fold increased likelihood of pre-fracture home-dwelling patients failing to return home (odds ratio 4.52, 95% CI 2.08–10.34, p < 0.001).

Conclusions

Hip fracture patients that survived a COVID-19 infection had increased frailty, longer LoS, more readmissions, and higher care needs. The health and social care burden is likely to be higher than prior to the COVID-19 pandemic. These findings should inform prognostication, discharge-planning, and service design to meet the needs of these patients.     

The obesity paradox in ST-segment elevation myocardial infarction patients: A meta-analysis

Objective

The aim of this study was to investigate whether there was a difference in survival after initial percutaneous coronary intervention (PCI) among ST-segment elevation myocardial infarction (STEMI) patients with different body mass index (BMI).

Methods

Literature retrieval was conducted on PubMed, Web of Science, Embase, CNKI, and Wanfang databases to obtain the published studies on the survival of STEMI patients with different BMI after initial PCI from the establishment of the database to 2022. All statistical analyses were performed using STATA16.0.

Results

Two hundred thirty-nine studies were retrieved, and 12 studies were eventually included. Meta-analysis showed that overweight patients [OR = 0.66, 95% CI (0.58, 0.76), p < .001] and obese patients [OR = 0.60, 95% CI (0.51, 0.72), p < .001] had lower in-hospital mortality than healthy-weight patients. Overweight patients [OR = 0.66, 95% CI (0.58, 0.74), p < .001] and obese patients [OR = 0.62, 95% CI (0.53, 0.72), p < .001] had lower short-term mortality than healthy-weight patients. In addition, overweight patients [OR = 0.63, 95% CI (0.58, 0.69), p < .001] and obese patients [OR = 0.59, 95% CI (0.52, 0.66), p < .001] also had lower long-term mortality than healthy-weight patients. There was no significant difference in in-hospital mortality [OR = 1.06, 95% CI (0.89, 1.27), p > .05], short-term mortality [OR = 1.04, 95% CI (0.89, 1.22), p > .05], and long-term mortality [OR = 1.07, 95% CI (0.95, 1.20), p > .05] between overweight and obese patients.

Conclusion

This meta-analysis confirmed an obesity paradox in STEMI patients following PCI. The obesity paradox exists in in-hospital, short-term, and long-term conditions.     

Factors associated with fragility fractures in type 2 diabetes: An analysis of the randomised controlled Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study

Aims

Fracture risk is elevated in some type 2 diabetes patients. Bone fragility may be associated with more clinically severe type 2 diabetes, although prospective studies are lacking. It is unknown which diabetes-related characteristics are independently associated with fracture risk. In this post-hoc analysis of fracture data from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial (ISRCTN#64783481), we hypothesised that diabetic microvascular complications are associated with bone fragility.

Materials and Methods

The FIELD trial randomly assigned 9795 type 2 diabetes participants (aged 50–75 years) to receive oral co-micronised fenofibrate 200 mg (n = 4895) or placebo (n = 4900) daily for a median of 5 years. We used Cox proportional hazards models to identify baseline sex-specific diabetes-related parameters independently associated with incident fractures.

Results

Over 49,470 person-years, 137/6138 men experienced 141 fractures and 143/3657 women experienced 145 fractures; incidence rates for the first fracture of 4∙4 (95% CI 3∙8–5∙2) and 7∙7 per 1000 person-years (95% CI 6∙5–9∙1), respectively. Fenofibrate had no effect on fracture outcomes. In men, baseline macrovascular disease (HR 1∙52, 95% CI 1∙05–2∙21, p = 0∙03), insulin use (HR 1∙62, HR 1∙03–2∙55, p = 0∙03), and HDL-cholesterol (HR 2∙20, 95% CI 1∙11–4∙36, p = 0∙02) were independently associated with fracture. In women, independent risk factors included baseline peripheral neuropathy (HR 2∙04, 95% CI 1∙16–3∙59, p = 0∙01) and insulin use (HR 1∙55, 95% CI 1∙02–2∙33, p = 0∙04).

Conclusions

Insulin use and sex-specific complications (in men, macrovascular disease; in women, neuropathy) are independently associated with fragility fractures in adults with type 2 diabetes.     

Long-term outcomes of patients with conjunctival extranodal marginal zone lymphoma

Comprehensive information on clinical features and long-term outcomes of primary conjunctival extranodal marginal zone lymphoma (PCEMZL) is scarce. We present a large single-institution retrospective study of 72 patients. The median age was 64 years, and 63.9% were female. Stage I was present in 87.5%. Radiation therapy (RT) alone was the most common treatment (70.8%). Complete response (CR) was 87.5%, and 100% in RT-treated patients. With a median follow-up of 6.7 years, relapse/progression and death occurred in 19.4% each, with one relapse within the RT field. The 10-year progression-free survival (PFS) and overall survival (OS) were 68.4% (95% CI 52.8%–79.8%) and 89.4% (95% CI 77.4%–95.2%), respectively. The 10-year rate for time to progression from diagnosis was 22.5% (95% CI 11.6%–35.7%). The 10-year PFS and OS of MALT-IPI 0 versus 1–2 were 83.3% versus 51.3%, (p = .022) and 97.6% versus 76.6%, (p = .0052), respectively. The following characteristics were associated with shorter survival: age > 60 years (PFS: HR = 2.93, 95% CI 1.08–7.95; p = .035, OS: HR = 9.07, 95% CI 1.17–70.26; p = .035) and MALT-IPI 1–2 (PFS: HR = 2.67, 95% CI 1.12–6.31; p = .027, OS: HR = 6.64, 95% CI 1.45–30.37; p = .015). CR following frontline therapy was associated with longer PFS (HR = 0.13, 95% CI 0.04–0.45; p = .001), but not OS. Using the Fine and Gray regression model with death without relapse/progression as a competing risk, RT and CR after frontline therapy were associated with lower risk of relapse (SHR = 0.34, 95% CI 0.12–0.96 p = .041 and SHR = 0.11, 95% CI 0.03–0.36; p < .001, respectively). Patients with PCEMZL treated with frontline RT exhibit excellent long-term survival, and the MALT-IPI score appropriately identifies patients at risk for treatment failure.     

Early repolarization pattern in adult females with eating disorders

Introduction

The risk of cardiovascular death is increased in patients with eating disorders (ED), but the background for this is unknown. Early repolarization pattern (ERP) on the electrocardiogram (ECG) has been associated with increased risk of sudden cardiac death.

Methods

We investigated the prevalence of ERP in 233 female patients with anorexia nervosa (AN) and bulimia nervosa (BN) (age 18–35 years) compared with 123 healthy female controls.

Results

Early repolarization pattern was present in 52 (22%) of ED patients (16 (15%) AN patients and 36 (29%) BN patients) and 17 (14%) of healthy controls. When adjusting for age, BMI, heart rate, use of selective serotonin reuptake inhibitors (SSRI), and potassium level, the odds ratio (OR) for ERP was 2.1 (95% CI 1.1–4.2, p = .03). There was an increased prevalence of inferolateral ERP in patients with ED compared with healthy controls (OR = 4.3, 95% CI 1.7–11.3, p = .003) as well as ERP with a downward/horizontal sloping ST segment (OR = 3.1, 95% CI 1.3–7.6, p = .01). Additionally, J-point elevation >0.2 mV was more prevalent in patients with ED (OR = 3.3, 95% CI 1.1–9.7, p = .03).

Conclusion

The prevalence of ERP was increased in patients with ED compared with healthy controls. This finding may provide a possible explanation for the increased cardiovascular mortality in ED patients.

     

Intravenous iron in patients with heart failure and iron deficiency: an updated meta-analysis

Aims

For patients with heart failure (HF) and iron deficiency (ID), randomized trials suggest that intravenous (IV) iron reduces hospitalizations for heart failure (HHF), but uncertainty exists about the effects in subgroups and the impact on mortality. We conducted a meta-analysis of randomized trials investigating the effect of IV iron on clinical outcomes in patients with HF.

Methods and results

We identified randomized trials published between 1 January 2000 and 5 November 2022 investigating the effect of IV iron versus standard care/placebo in patients with HF and ID in any clinical setting, regardless of HF phenotype. Trials of oral iron or not in English were not included. The main outcomes of interest were a composite of HHF and cardiovascular death (CVD), on HHF alone and on cardiovascular and all-cause mortality. Ten trials were identified with 3373 participants, of whom 1759 were assigned to IV iron. IV iron reduced the composite of recurrent HHF and CVD (rate ratio 0.75, 95% confidence interval [CI] 0.61–0.93; p < 0.01) and first HHF or CVD (odds ratio [OR] 0.72, 95% CI 0.53–0.99; p = 0.04). Effects on cardiovascular (OR 0.86, 95% CI 0.70–1.05; p = 0.14) and all-cause mortality (OR 0.93, 95% CI 0.78–1.12; p = 0.47) were inconclusive. Results were similar in analyses confined to the first year of follow-up, which was less disrupted by the COVID-19 pandemic. Subgroup analyses found little evidence of heterogeneity for the effect on the primary endpoint, although patients with transferrin saturation <20% (OR 0.67, 95% CI 0.49–0.92) may have benefited more than those with values ≥20% (OR 0.99, 95% CI 0.74–1.30) (heterogeneity p = 0.07).

Conclusion

In patients with HF and ID, this meta-analysis suggests that IV iron reduces the risk of HHF but whether this is associated with a reduction in cardiovascular or all-cause mortality remains inconclusive.     

High prevalence of lower limb atherosclerosis is linked with the gut–liver axis in patients with primary biliary cholangitis

Background and Aims

Hypercholesterolemia is frequent in people with primary biliary cholangitis (PBC); however, it does not seem to confer an increased risk of cardiovascular disease. We aimed to evaluate the prevalence of peripheral arterial disease in PBC women and its association with the gut–liver axis and systemic inflammation.

Methods

Thirty patients affected by PBC and hypercholesterolemia were enrolled, with equal-sized groups of women with non-alcoholic fatty liver disease (NAFLD) and healthy controls (CTRL). All patients underwent Doppler ultrasound examination of peripheral arteries, assessment of flow-mediated dilation, quantification of circulating cytokines and vasoactive mediators and characterization of the gut microbiota.

Results

PBC patients had a higher prevalence of lower extremity arterial disease (LEAD) defined as atherosclerotic plaques in any of femoral, popliteal and/or tibial arteries compared with both NAFLD and CTRL women (83.3% vs. 53.3% and 50%, respectively; p = .01). Factors associated with LEAD at univariate analysis were VCAM-1 (p = .002), ICAM-1 (p = .003), and TNF-alpha (p = .04) serum levels, but only VCAM-1 (OR 1.1, 95% CI 1.0–1.1; p = .04) and TNF-alpha (OR 1.12, 95% CI 0.99–1.26; p = .04) were confirmed as independent predictors in the multivariate model. Gut microbiota analysis revealed that Acidaminococcus (FDR = 0.0008), Bifidobacterium (FDR = 0.001) and Oscillospira (FDR = 0.03) were differentially expressed among groups. Acidaminococcus, which was increased in PBC, was positively correlated with TNF-alpha serum levels. Down-regulation of metabolic pathways linked to fatty acid and butyrate metabolism, glyoxylate metabolism and branched-chain amino acids degradation was found in the functional gut metagenome of PBC women.

Conclusions

LEAD is common in patients affected by PBC and is associated with inflammatory markers and alterations in the gut–liver axis.     

Sublingual microcirculation and internal environment changes as early indications of sepsis: A prospective observational study

Objective

This study aims to investigate the changes in microcirculation and internal environment before sepsis in patients with infectious diseases.

Methods

In this single-center prospective observational study, all patients did not meet the diagnostic criteria of sepsis 3.0 at admission. Blood samples and sublingual microcirculation were collected at admission, 24 and 48 h after admission.

Results

A total of 101 patients completed this study. In total, 46 patients met the diagnostic criteria of sepsis 3.0 within 5 days after admission, while the remaining 55 patients did not. The platelet (PLT) was significantly lower in the sepsis patients (195.17 ± 63.89 vs. 242.02 ± 68.59, p = .01), Microvascular Flow Index (MFI) (2.45 ± 0.33 vs. 2.70 ± 0.18, p = .00) and Proportion of Perfused Vessels (PPV) (92.44 ± 4.45 vs. 95.88 ± 3.20, p = .00) were significantly lower, while Flow Heterogeneity Index (FHI) (0.32 ± 0.13 vs. 0.22 ± 0.10, p = .00) was significantly higher in the in the sepsis patients at admission. Decreased levels of MFI (p = .00, OR 0.02, 95% CI: 0.00, 0.15) and PLT (p = .00, OR 0.99, 95% CI: 0.98, 1.00) were independent risk factors for sepsis. Additionally, the 24 h PLT change rate (AUC 0.85, Cutoff −0.17, sensitivity 0.70, specificity 0.93, and Youden index 0.63) suggested a potential early warning effect for sepsis.

Conclusion

Changes in microcirculation disturbance and the internal environment occurred before sepsis. The MFI and PLT are independent risk factors for sepsis. Sublingual microcirculation and PLT deterioration can be used as early warning indicators before sepsis.     

Predictors of stroke or systemic embolism in patients with non-valvular atrial fibrillation with CHA2DS2-VASc score of 0

Background

Anticoagulant therapy has been important for stroke prevention in patients with atrial fibrillation (AF). However, it was not recommended due to its relatively higher risk of bleeding than its lower risk of stroke in patients with a CHA₂DS₂-VASc score of 0.

Hypothesis

This study aimed to evaluate the predictors of stroke in AF patients with very low risk of stroke.

Methods

Between 1990 and 2020, 542 patients with non-valvular AF (NVAF) with a CHA₂DS₂-VASc score of 0 followed up for at least 6 months were enrolled. Patients with only being woman as a risk factor were included as a CHA₂DS₂-VASc score of 0 in this study. The primary outcome was stroke or systemic embolism.

Results

The primary outcome rate was 0.78%/year. In Cox hazard model, age of ≥50 years at diagnosis (hazard ratio [HR] 6.710, 95% confidence interval [CI] 1.811–24.860, p = .004), LVEDD of ≥46 mm (HR 4.513, 95% CI 1.038–19.626, p = .045), and non-paroxysmal AF (HR 5.575, 95% CI 1.621–19.175, p = .006) were identified as independent predictors of stroke or systemic embolism. Patients with all three independent predictors had a higher risk of stroke or systemic embolism (4.21%/year), whereas those without did not have a stroke or systemic embolism.

Conclusion

The annual stroke or systemic embolism rate in NVAF patients with CHA₂DS₂-VASc score of 0 was 0.78%/year, and age at AF diagnosis, LVEDD, and non-paroxysmal AF were independent predictors of stroke or systemic embolism in patients considered to have a very low risk of stroke.     

Subclinical liver traits are associated with structural and hemodynamic brain imaging markers

Background & Aims

Impaired liver function affects brain health and therefore understanding potential mechanisms for subclinical liver disease is essential. We assessed the liver–brain associations using liver measures with brain imaging markers, and cognitive measures in the general population.

Methods

Within the population-based Rotterdam Study, liver serum and imaging measures (ultrasound and transient elastography), metabolic dysfunction-associated fatty liver disease (MAFLD), non-alcoholic fatty liver disease (NAFLD) and fibrosis phenotypes, and brain structure were determined in 3493 non-demented and stroke-free participants in 2009–2014. This resulted in subgroups of n = 3493 for MAFLD (mean age 69 ± 9 years, 56% ♀), n = 2938 for NAFLD (mean age 70 ± 9 years, 56% ♀) and n = 2252 for fibrosis (mean age 65 ± 7 years, 54% ♀). Imaging markers of small vessel disease and neurodegeneration, cerebral blood flow (CBF) and brain perfusion (BP) were acquired from brain MRI (1.5-tesla). General cognitive function was assessed by Mini-Mental State Examination and the g-factor. Multiple linear and logistic regression models were used for liver-brain associations and adjusted for age, sex, intracranial volume, cardiovascular risk factors and alcohol use.

Results

Higher gamma-glutamyltransferase (GGT) levels were significantly associated with smaller total brain volume (TBV, standardized mean difference (SMD), −0.02, 95% confidence interval (CI) (−0.03 to −0.01); p = 8.4·10⁻⁴), grey matter volumes, and lower CBF and BP. Liver serum measures were not related to small vessel disease markers, nor to white matter microstructural integrity or general cognition. Participants with ultrasound-based liver steatosis had a higher fractional anisotropy (FA, SMD 0.11, 95% CI (0.04 to 0.17), p = 1.5·10⁻³) and lower CBF and BP. MAFLD and NAFLD phenotypes were associated with alterations in white matter microstructural integrity (NAFLD ~ FA, SMD 0.14, 95% CI (0.07 to 0.22), p = 1.6·10⁻⁴; NAFLD ~ mean diffusivity, SMD −0.12, 95% CI (−0.18 to −0.05), p = 4.7·10⁻⁴) and also with lower CBF and BP (MAFLD ~ CBF, SMD −0.13, 95% CI (−0.20 to −0.06), p = 3.1·10⁻⁴; MAFLD ~ BP, SMD −0.12, 95% CI (−0.20 to −0.05), p = 1.6·10⁻³). Furthermore, fibrosis phenotypes were related to TBV, grey and white matter volumes.

Conclusions

Presence of liver steatosis, fibrosis and elevated serum GGT are associated with structural and hemodynamic brain markers in a population-based cross-sectional setting. Understanding the hepatic role in brain changes can target modifiable factors and prevent brain dysfunction.     

Impact of P-wave indices in prediction of atrial fibrillation—Insight from loop recorder analysis

Background

Several P-wave indices are associated with the development of atrial fibrillation (AF). However, previous studies have been limited in their ability to reliably diagnose episodes of AF. Implantable loop recorders allow long-term, continuous, and therefore more reliable detection of AF.

Hypothesis

The aim of this study is to identify and evaluate ECG parameters for predicting AF by analyzing patients with loop recorders.

Methods

This study included 366 patients (mean age 62 ± 16 years, mean LVEF 61 ± 6%, 175 women) without AF who underwent loop recorder implantation between 2010–2020. Patients were followed up on a 3 monthly outpatient interval.

Results

During a follow-up of 627 ± 409 days, 75 patients (20%) reached the primary study end point (first detection of AF). Independent predictors of AF were as follows: age ≥68 years (hazard risk [HR], 2.66; 95% confidence interval [CI], 1.668–4.235; p < .001), P-wave amplitude in II <0.1 mV (HR, 2.11; 95% CI, 1.298–3.441; p = .003), P-wave terminal force in V₁ ≤ −4000 µV × ms (HR, 5.3; 95% CI, 3.249–8.636; p < .001, and advanced interatrial block (HR, 5.01; 95% CI, 2.638–9.528; p < .001). Our risk stratification model based on these independent predictors separated patients into 4 groups with high (70%), intermediate high (41%), intermediate low (18%), and low (4%) rates of AF.

Conclusions

Our study indicated that P-wave indices are suitable for predicting AF episodes. Furthermore, it is possible to stratify patients into risk groups for AF using simple ECG parameters, which is particularly important for patients with cryptogenic stroke.

     

Higher FT4 level within the normal range predicts the outcome of cryoballoon ablation in paroxysmal atrial fibrillation patients without structural heart disease

Background

Accumulated evidence has indicated that a high-normal FT4 level is an independent risk factor for the clinical progression of AF. However, the association between elevated FT4 concentration within the normal range and AF recurrence after cryoballoon ablation in China is unknown.

Methods

This retrospective and observational study included 453 AF patients who underwent cryoballoon ablation from January 2016 to August 2018. Patients were classified into quartiles based on preprocedural serum FT4 concentration. The clinical characteristics of the patients and the long-term rate of AF recurrence after ablation were assessed.

Results

After a mean follow-up period of 17.4 ± 9.0 months, 91 (20.1%) patients suffered from AF recurrence. The AF recurrence rate by FT4 quartile was 17.7%, 19.0%, 21.4%, and 22.3% for participants with FT4 in quartile 1, 2, 3, and 4, respectively (p < .001). On multivariate Cox regression, FT4 concentration (HR: 1.187, 95% CI: 1.093–1.290, p < .001) and left atrial diameter (HR: 1.052, 95% CI: 1.014–1.092, p = .007) were significant predictors of AF recurrence. When stratifying for AF type, the rate of postoperative recurrence was independently increased as FT4 concentration increased in paroxysmal AF, but not in persistent AF (p < .001 in paroxysmal AF and p = .977 in persistent AF).

Conclusion

Higher FT4 level within the normal range predicted the outcome of cryoballoon ablation in Chinese paroxysmal AF patients without structural heart disease.

     

Characteristics and outcomes of patients with a history of cancer recruited to heart failure trials

Aims

Heart failure (HF) therapy trials usually exclude cancer patients. We examined the association between cancer history and outcomes in trial participants with HF and reduced (HFrEF) or preserved ejection fraction (HFpEF).

Methods and results

We combined PARADIGM-HF and ATMOSPHERE, which enrolled HFrEF patients (n = 15 415) and we pooled HFpEF patients (ejection fraction ≥45%) enrolled in PARAGON-HF and CHARM-Preserved (n = 7363). The associations between cancer history, cardiovascular (CV) death, HF hospitalization, non-CV and all-cause death in these trials were examined. Incident cancer diagnoses during these trials were also measured. There were 658 (4.3%) and 624 (8.5%) patients with a cancer history in the HFrEF and HFpEF trials, respectively. HFrEF patients with a cancer history had a higher risk of HF hospitalization (adjusted hazard ratio [HR] 1.28; 95% confidence interval [CI] 1.07–1.52, p = 0.007) and non-CV death (adjusted HR 1.57; 95% CI 1.16–2.12, p = 0.003) than those without. The risks of other outcomes were similar. There were no differences in the risk of any outcome in HFpEF patients with and without a cancer history. Adjusting for age and sex, the incidence of new cancer in the HFrEF and HFpEF trials was 1.09 (95% CI 0.83–1.36) and 1.07 (95% CI 0.81–1.32) per 100 person-years, respectively.

Conclusions

Although participants in HFrEF trials with a cancer history had higher risks of HF hospitalization and non-CV death than those without, the risks of CV and all-cause death were similar. Outcomes in HFpEF patients with and without a cancer history were similar. Incident cancer diagnoses were similar in HFrEF and HFpEF trials.     

A cross-sectional follow-up study of physical activity in adults with moderate and severe haemophilia

Aim

To conduct a cross-sectional follow-up assessment of physical activity (PA) in people with moderate and severe haemophilia (PwMSH) from the Irish Personalised Approach to the Treatment of Haemophilia (iPATH) study.

Methods

Between June–December 2021, participants’ PA was measured over one week using accelerometery, and was compared with their previously measured data from the original iPATH assessment. Self-awareness of PA and the impact of the Covid-19 pandemic on PA, pain, mobility and function were retrospectively examined using a survey.

Results

Of 30 participants who returned surveys [n = 19, severe (FVIII, <.01 IU/mL); n = 4, moderate (FVIII, .01–.05 IU/mL); n = 7, severe (FIX, <.01 IU/mL); age: 47 (36, 55) years], 28 completed accelerometery (follow-up time: 3 years). There were no significant differences in accelerometer PA (all p > .05), but achievement of World Health Organisation guidelines increased (67.9%–75.0%; p = .646). Increased self-awareness of PA was reported by 76.7%, and 66.7% reported desires to become more physically active. Compared to normal, most reported either no differences or lower levels of PA during lockdown restrictions. Self-reported PA increased for most when restrictions eased from April 2021 onwards. Beyond the pandemic, concerns included pain and access to exercise resources.

Conclusion

Self-reported PA throughout the pandemic was variable, whilst there were no significant differences in objectively measured PA between assessment periods, despite reports of increased self-awareness and desires to be physically active at follow-up. Further qualitative research is needed to design personalised PA and health interventions, capturing perspectives of patients, their families, and multi-disciplinary haemophilia healthcare providers.     

SARS-CoV-2-reactive antibody detection after SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Prospective survey from the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group

This is a multicenter prospective observational study that included a large cohort (n = 397) of allogeneic (allo-HSCT; (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3–6 weeks after complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from February 1, 2021, to July 20, 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of the recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia < 1 × 10⁹/ml (odds ratio [OR] 0.33, 95% confidence interval [95% CI] 0.16–0.69, p = .003), active graft versus host disease (GvHD; OR 0.51, 95% CI 0.27–0.98, p = .04) and vaccination within the first year of transplant (OR 0.3, 95% CI 0.15–0.9, p = .04) associated with lower antibody detection whereas. In ASCT, non-Hodgkin's lymphoma (NHL; OR 0.09, 95% CI 0.02–0.44, p = .003) and active corticosteroid therapy (OR 0.2, 95% CI 0.02–0.87, p = .03) were associated with lower detection rate. We report an encouraging rate of SARS-CoV-2-reactive antibodies detection in these severe immunocompromised patients. Lymphopenia, GvHD, the timing of vaccine, and NHL and corticosteroids therapy should be considered in allo-HSCT and ASCT, respectively, to identify candidates for SARS-CoV-2 antibodies monitoring.     

Burden of illness and costs among paediatric haemophilia patients with and without central venous access devices treated in US hospitals

Introduction

Central venous access devices (CVADs) facilitate repeated or urgent treatments for paediatric haemophilia patients, but are associated with complications. This study examined the burden of illness, healthcare utilization and costs for CVADs in a real‐world hospital setting.

Materials and Methods

This study included haemophilia patients ages ≤18 years with discharges during 2006‐2014 in the US Premier Healthcare Database. Haemophilia was identified using ICD‐9 diagnosis codes and CVAD exposure using billing information. After matching haemophilia patients with and without CVADs on demographic and clinical characteristics, we compared infection, thrombosis, length of stay (LOS), inflation‐adjusted hospital cost (2014 $USD) and readmission outcomes using generalized estimating equation models adjusted for hospital teaching status.

Results

Among 4793 paediatric haemophilia patients treated at one of 548 hospitals, a total of 197 patients were identified with CVAD exposure. The matched sample included 310 haemophilia patients (155 CVAD and 155 non‐CVAD). CVAD cases had greater frequencies of all‐cause infections (29% vs 17%, P = .01) and thrombosis (6% vs 1%, P = .06), longer adjusted mean LOS (9.5 vs 4.7 days, P = .002), higher adjusted mean inpatient total hospitalization costs ($47200 vs $25389, P = .02) as well as more inpatient and outpatient visits at 30‐, 60‐ and 90‐days (P < .05 for all differences) compared with non‐CVAD patients.

Conclusion

Paediatric haemophilia patients with CVADs experienced greater infection rates, healthcare utilization and higher hospitalization costs compared with non‐CVAD patients. The results of this study may inform further research efforts to understand the costs and benefits of novel treatment alternatives for young haemophilia patients requiring CVADs.     

Sex-differences in the association of interleukin-10 and interleukin-12 variants with the progression of hepatitis B virus infection in Caucasians

Aim

Interleukin (IL)-10 and IL-12 contribute to immune responses against hepatitis B virus (HBV) infection. Polymorphisms in the IL-10 and IL-12A genes might affect the clinical outcome of HBV infection. We evaluated the association of IL-10 rs1800896 and rs3024490, and IL-12A rs568408 and rs2243115 with the progression of HBV infection and development of severe liver disease stages in a white European population.

Method

A total of 636 white European patients with chronic HBV infection, 239 individuals with spontaneous HBV surface antigen seroclearance, and 254 healthy controls were enrolled. The chronic HBV infection group included patients with hepatitis B envelope antigen (HBeAg) negative chronic hepatitis B (n = 255), with HBeAg positive chronic hepatitis B (n = 99) and with HBeAg negative HBV infection (n = 228). A total of 104 chronically infected patients were diagnosed with liver cirrhosis. Serum levels of cytokines were measured in patients with HBV infection (n = 195) and in healthy controls (n = 160).

Results

In adjusted multivariate analysis, the IL-10 rs1800896 AG/GG genotypes were significantly associated with an increased probability of HBV surface antigen seroclearance (OR = 1.75, 95% CI 1.04–2.94, p = 0.034), with an increased likelihood of HBeAg negative chronic infection (OR = 1.93, 95% CI 1.05–3.54, p = 0.034) and with increased serum cytokines levels in female patients. In contrast, the IL-12A rs568408 AG/AA genotypes were independently associated with an increased risk to develop liver cirrhosis, with an OR of 1.90 (95% CI 1.07–3.39, p = 0.029) in male patients.

Conclusion

The current study shows a sex-related association of the IL-10 single-nucleotide polymorphism rs1800896 and IL-12A single-nucleotide polymorphism rs568408 with different stages of HBV infection and with HBV-related liver cirrhosis in white European patients.     

Conditional recurrence analysis of intrahepatic cholangiocarcinoma: Changes in recurrence rate and survival after recurrence resection by disease-free interval

Aim

The prognosis of patients with resected intrahepatic cholangiocarcinoma (ICC) is still unsatisfactory, with a high recurrence rate. We aimed to evaluate risks of recurrence changing over time and the survival benefit of resection for recurrent ICC.

Methods

This study included patients who underwent hepatectomy for ICC during 1995–2020. Risk factors for recurrence-free survival (RFS) in patients undergoing initial resection and overall survival (OS) in patients who developed recurrence after initial resection were analyzed. Conditional cumulative incidence of recurrence was assessed.

Results

A total of 169 patients were included in the study and 114 patients (67.5%) developed recurrence. Cumulative analyses showed that the 5-year recurrence rate was 69.3% at the time of initial resection but decreased to 24.8% in patients free from recurrence at 2 years after initial resection and 2.6% in patients free from recurrence at 4 years. Re-resection was carried out in 26 (22.8%) of 114 patients who developed recurrence. Multivariable Cox proportional hazards model analysis indicated re-resection (hazard ratio [HR] 0.19; 95% confidence interval [CI] 0.11–0.40, p < 0.001), microvascular invasion (MVI) (HR 2.39; 95% CI 1.05–5.40, p = 0.037), and disease-free interval (months) (HR 0.97; 95% CI 0.95–1.00, p = 0.067) were significantly associated with longer OS after recurrence.

Conclusions

Although the rate of recurrence remains high, conditional cumulative recurrence rate analysis showed that the rate of recurrence decreased by disease-free interval. Resection of recurrent ICC was associated with improved OS, particularly among patients with longer disease-free interval and absence of MVI after initial hepatectomy.