Complications of congenital portosystemic shunts: liver tumors are affected by shunt severity, but pulmonary and neurocognitive associations are not.

BACKGROUND AND PURPOSE: Congenital portosystemic shunts (CPSS) are associated with multisystem complications, with the most common being liver tumors. The purpose of this study is to investigate the incidence of complications of CPSS, and to determine the natural history of liver tumors and their relationship with shunt closure. METHODS: Single-center retrospective cohort study of patients with CPSS referred from 1990 to 2020. Data on demographics, laboratory, radiological and histological investigations, clinical evolution, and surgery were reviewed. Mann-Whitney for continuous data and Fisher's exact test for categorical data were used. A p value of 0.05 was considered significant. RESULTS: 54 patients were investigated for CPSS with a median age of 1.1 years (IQR 0.2-11.8 years) at presentation-7 intrahepatic shunts resolved spontaneously and were excluded. Type 1 (without intrahepatic portal flow) had a higher rate of all hepatic tumors than Type 2 (partial intrahepatic portal flow) [18/22(82%) vs. 9/25(36%); p = 0.003); and malignant tumors (6/22(27%) vs 1/25(4%); (p = 0.04). Following shunt closure, 4/11(36%) of patients experienced partial and 3/11(27%) complete tumor regression. Pulmonary hypertension and hepatopulmonary syndrome affected 4(9%), and 3(6%) patients, respectively. Pulmonary complications affected 1 patient with Type 1 and 6 with Type 2 shunts (p = 0.1). Neurocognitive anomalies were identified in 16/47(34%) patients, 8/22(35%) with Type 1 shunts and 8/25(32%) with Type 2 shunts (p = 0.76). 9/47 (19%) required special needs schooling. CONCLUSIONS: Severity of portal venous deprivation (Type 1 CPSS) increases the risk of hepatic tumors and surgical closure is associated with a reduction in size or complete resolution of benign tumors.

Nonmalignant portal vein thrombi in patients with cirrhosis consist of intimal fibrosis with or without a fibrin-rich thrombus.

BACKGROUND AND AIM: Portal vein thrombosis (PVT) is a common complication of cirrhosis. The exact pathophysiology remains largely unknown, and treatment with anticoagulants does not lead to recanalization of the portal vein in all patients. A better insight into the structure and composition of portal vein thrombi may assist in developing strategies for the prevention and treatment of PVT. APPROACH AND RESULTS: Sixteen prospectively and 63 retrospectively collected nonmalignant portal vein thrombi from patients with cirrhosis who underwent liver transplantation were included. Histology, immunohistochemistry, and scanning electron microscopy were used to assess structure and composition of the thrombi. Most recent CT scans were reanalyzed for thrombus characteristics. Clinical characteristics were related to histological and radiological findings. All samples showed a thickened, fibrotic tunica intima. Fibrin-rich thrombi were present on top of the fibrotic intima in 9/16 prospective cases and in 21/63 retrospective cases. A minority of the fibrotic areas stained focally positive for fibrin/fibrinogen (16% of cases), von Willebrand factor (VWF; 10%), and CD61 (platelets, 21%), while most of the fibrin-rich areas stained positive for those markers (fibrin/fibrinogen, 100%; VWF, 77%; CD61, 100%). No associations were found between clinical characteristics including estimated thrombus age and use of anticoagulants and presence of fibrin-rich thrombi. CONCLUSION: We demonstrate that PVT in patients with cirrhosis consists of intimal fibrosis with an additional fibrin-rich thrombus in only one-third of cases. We hypothesize that our observations may explain why not all portal vein thrombi in patients with cirrhosis recanalize by anticoagulant therapy.

Alginate microencapsulated human hepatocytes for the treatment of acute liver failure in children.

BACKGROUND & AIMS: Liver transplantation (LT) is the most effective treatment for patients with acute liver failure (ALF), but is limited by surgical risks and the need for life-long immunosuppression. Transplantation of microencapsulated human hepatocytes in alginate is an attractive option over whole liver replacement. The safety and efficacy of hepatocyte microbead transplantation have been shown in animal models. We report our experience of this therapy in children with ALF treated on a named-patient basis. METHODS: Clinical grade human hepatocyte microbeads (HMBs) and empty microbeads were tested in immunocompetent healthy rats. Subsequently, 8 children with ALF, who were awaiting a suitable allograft for LT, received intraperitoneal transplantation of HMBs. We monitored complications of the procedure, assessing the host immune response and residual function of the retrieved HMBs, either after spontaneous native liver regeneration or at the time of LT. RESULTS: Intraperitoneal transplantation of HMBs in healthy rats was safe and preserved synthetic and detoxification functions, without the need for immunosuppression. Subsequently, 8 children with ALF received HMBs (4 neonatal haemochromatosis, 2 viral infections and 2 children with unknown cause at time of infusion) at a median age of 14.5 days, range 1 day to 6 years. The procedure was well tolerated without complications. Of the 8 children, 4 avoided LT while 3 were successfully bridged to LT following the intervention. HMBs retrieved after infusions (at the time of LT) were structurally intact, free of host cell adherence and contained viable hepatocytes with preserved functions. CONCLUSION: The results demonstrate the feasibility and safety of an HMB infusion in children with ALF. LAY SUMMARY: Acute liver failure in children is a rare but devastating condition. Liver transplantation is the most effective treatment, but it has several important limitations. Liver cell (hepatocyte) transplantation is an attractive option, as many patients only require short-term liver support while their own liver recovers. Human hepatocytes encapsulated in alginate beads can perform the functions of the liver while alginate coating protects the cells from immune attack. Herein, we demonstrated that transplantation of these beads was safe and feasible in children with acute liver failure.

What are the main symptoms and concerns reported by patients with advanced chronic heart failure?-a secondary analysis of the Palliative care Outcome Scale (POS) and Integrated Palliative care Outcome Scale (IPOS).

There is a lack of valid disease-specific patient-reported outcome measures (PROMs) for detecting symptoms and concerns in patients with advanced chronic heart failure (CHF). The Palliative care Outcome Scale (POS) and Integrated Palliative care Outcome Scale (IPOS) are specifically developed to capture the main symptoms and concerns of people severely affected by advanced disease. The aim of this study was to determine whether POS and IPOS captures the main symptoms and concerns self-reported by patients with advanced CHF. A secondary analysis of existing POS/IPOS data collected in three longitudinal studies was conducted. POS and IPOS start with an open-ended question for patients to report their main problems and concerns, followed by subsequent closed questions on a range of symptoms and other concerns. Descriptive statistics were used to report the results. The 102 participants from the three datasets had median age 81 years (SD ±9.84 years); 62% male; 87% white. A total of 107 concerns were reported in the first, open POS/IPOS question seeking the patient's main concerns. Of these, 83 (77%) were reflected in the subsequent IPOS/POS closed questions. The high correspondence between the free-text responses and the closed questions indicates that most issues are captured by the POS/IPOS items. In conclusion, the generic versions of POS and IPOS do capture the main problems and concerns of patients with advanced CHF. Minor adaptations and further psychometric validation of POS and IPOS are needed in this population.

Modern Outcomes Following Treatment of Hepatocellular Carcinoma in Hereditary Hemochromatosis: A Matched Cohort Study.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a complication of the common genetic condition hereditary hemochromatosis (HH). It is unknown whether HH as an etiology of liver disease impacts the outcome. We compared the results of liver transplantation (LT), surgical resection and locoregional therapies in a matched cohort study and investigated whether HH as an etiology has an impact on survival. MATERIALS AND METHODS: Consecutive patients with HH and HCC (2000 to 2015) were compared with age, sex and Barcelona Clinic Liver Cancer (BCLC) stage-matched non-HH HCC cases. Patients were offered curative or noncurative treatment according to BCLC stage and Milan criteria. The primary endpoint was all-cause mortality. RESULTS: A total of 102 patients (52 HH; total cohort median age: 67 [44 to 78] y, 97% male, Model for End-stage Liver Disease: 9 [5 to 31]) were studied with a median follow-up of 22 (3 to 126) months. Of the HH cases, the median serum ferritin at diagnosis of HCC was 326 (27 to 5718) µg/L and α-fetoprotein 33 (2 to 197,926) kIU/L. Five-year survival for HH patients receiving curative therapy was 77% (80% for LT, 67% for resection/radiofrequency ablation), and 15% (23% for transarterial chemoembolization) for those undergoing noncurative therapy. Survival for HH patients compared with controls was similar (hazard ratio=0.949; P=0.839). On multivariate Cox regression survival analysis, BCLC stage, and diagnosis of ischemic heart disease (but not HH diagnosis) were independently associated with reduced survival. CONCLUSIONS: Patients with HCC and HH can achieve comparable survival rates following curative or LRT modalities to other liver diseases. The BCLC staging system accurately stratifies survival and excellent 5-year survival is possible following LT in selected patients.

Synchronous Unicentric Castleman Disease and Inflammatory Hepatocellular Adenoma: a Case Report.

Systemic symptoms such as fever and fatigue are non-specific manifestations spanning from inflammation to neoplasia. Here we report the case of a 34 year-old man who presented with systemic symptoms for four months. CT-scan and MRI revealed a 3.4 cm arterialized hepatic lesion and a 7 cm paraduodenal mass. Surgical resection of both lesions and histological examination revealed an inflammatory hepatocellular adenoma and a unicentric plasma cell type of Castleman disease. Moreover, a diffuse AA amyloid deposition in the liver was observed. Resection of both lesions was associated with an improvement of the symptoms. To our knowledge, this is the first report of a synchronous presentation of a unicentric plasma cell type of Castleman disease, inflammatory hepatocellular adenoma and AA amyloidosis.

Complications from percutaneous microwave ablation of liver tumours: a pictorial review.

Percutaneous microwave ablation of liver tumours is a well-established technique that has been proven to be effective in the curative and palliative treatment of small volume primary and secondary liver tumours. Microwave ablation is designed to achieve larger areas of necrosis compared to radiofrequency ablation and has a good safety profile among liver tumour treatments. Mortality is unreported and major complications are rare. Knowledge of potential complications is essential for interventional radiologists performing liver ablation in order to reduce patient morbidity. The aim of this review is to illustrate major complications post microwave ablation in a pictorial format as well as a discussion on how best to avoid these complications.

Clinical and prognostic associations of liver volume determined by computed tomography in acute liver failure.

BACKGROUND: Liver volume (LV) can be non-invasively determined from the analysis of computed tomography (CT) images, and in patients with acute liver injury (ALI) or failure (ALF), it can reflect the balance of structural collapse with hepatic regeneration. We examined its relation to cause of liver injury, measures of liver function and histopathological findings, and utility in prediction of complications and mortality. METHODS: Two hundred and seventy-three patients with ALF/ALI admitted to a specialist intensive care unit were studied. One hundred and ninety-nine patients (73%) had non-acetaminophen (NA) aetiologies and 74 (27%) had acetaminophen-induced disease. LV and proportion of predicted LV (PLV%) were determined from admission CT imaging. RESULTS: LV and PLV% showed marked variation when aetiologic groups were compared (P < .0001), including loss in cases with indeterminate cause (LV 939 cm3 [IQR 680-1259], PLV% 56% [42-84]) and increase in Budd-Chiari syndrome (1891 cm3 [1601-2094], 121% [111-131]). Progression to high-grade encephalopathy was more common with smaller LV and PLV. A < 1000 cm3 threshold identified NA patients who later developed it with 93% (95%CI 83-98) specificity and odds ratio 10.6 (3.3-34.5) at median 5 days prior to onset, and risk of death in those with NA-drug-induced (DILI) or indeterminate disease with 91% (71-99) specificity and 63% (50-75) sensitivity. CONCLUSION: In patients with ALF/ALI, LV shows marked variation by the cause of disease, and in prognostic importance. In indeterminate and DILI cases, loss of volume to <1000 cm3 may indicate irreversible liver injury and regenerative failure and serve as an early clinical predictor for the development of high-grade encephalopathy and death.

Strategies to address the shortcomings of commonly used advanced chronic heart failure descriptors to improve recruitment in palliative care research: A parallel mixed-methods feasibility study.

BACKGROUND: Recruitment challenges contribute to the paucity of palliative care research with advanced chronic heart failure patients. AIM: To describe the challenges and outline strategies of recruiting advanced chronic heart failure patients. DESIGN: A feasibility study using a pre-post uncontrolled design. SETTING: Advanced chronic heart failure patients were recruited at two nurse-led chronic heart failure disease management clinics in Ireland Results: Of 372 patients screened, 81 were approached, 38 were recruited (46.9% conversion to consent) and 25 completed the intervention. To identify the desired population, a modified version of the European Society of Cardiology definition was used together with modified New York Heart Association inclusion criteria to address inter-study site New York Heart Association classification subjectivity. These modifications substantially increased median monthly numbers of eligible patients approached (from 8 to 20) and median monthly numbers recruited (from 4 to 9). Analysis using a mortality risk calculator demonstrated that recruited patients had a median 1-year mortality risk of 22.7 and confirmed that the modified eligibility criteria successfully identified the population of interest. A statistically significant difference in New York Heart Association classification was found in recruited patients between study sites, but no statistically significant difference was found in selected clinical parameters between these patients. CONCLUSION: Clinically relevant modifications to the European Society of Cardiology definition and strategies to address New York Heart Association subjectivity may help to improve advanced chronic heart failure patient recruitment in clinical settings, thereby helping to address the paucity of palliative care research this population.

Understanding how a palliative-specific patient-reported outcome intervention works to facilitate patient-centred care in advanced heart failure: A qualitative study.

BACKGROUND: Palliative care needs of patients with chronic heart failure are poorly recognised. Policy makers advise a patient-centred approach to holistically assess patients' needs and care goals. Patient-reported outcome measures are proposed to facilitate patient-centred care. AIM: To explore whether and how a palliative care-specific patient-reported outcome intervention involving the Integrated Palliative care Outcome Scale influences patients' experience of patient-centred care in nurse-led chronic heart failure disease management clinics. DESIGN: A feasibility study using a parallel mixed-methods embedded design was undertaken. The qualitative component which examined patients and nurses experience of the intervention is reported here. Semi-structured interviews were conducted and analysed using framework analysis. SETTING/PARTICIPANTS: Eligible patients attended nurse-led chronic heart failure disease management clinics in two tertiary referral centres in Ireland with New York Heart Association functional class II-IV. Nurses who led these clinics were eligible for inclusion. RESULTS: In all, 18 patients and all 4 nurses involved in the nurse-led clinics were interviewed. Three key themes were identified: identification of unmet needs, holistic assessment and patient empowerment. The intervention impacted on processes of care by enabling a shared understanding of patients' symptoms and concerns, facilitating patient-nurse communication by focusing on these unmet needs and empowering patients to become more involved in clinical discussions. CONCLUSION: This Integrated Palliative care Outcome Scale-based intervention empowered patients to become more engaged in the clinical consultation and to highlight their unmet needs. This study adds to the evidence for the mechanism of action of patient-reported outcome measures to improve patient-centred care and will help inform outcome selection for future patient-reported outcome measure research.

Feasibility and acceptability of a patient-reported outcome intervention in chronic heart failure.

Patients with chronic heart failure (CHF) have symptoms and concerns which are inadequately addressed. Patient-reported outcome measures (PROMs) can potentially improve the identification and management of advanced symptoms and palliative concerns. However, these have not been used in CHF. OBJECTIVES: To examine the feasibility and acceptability of using a PROM-the Integrated Palliative care Outcome Scale (IPOS)-together with heart failure nurse education and training to improve the identification and management of symptoms and concerns among patients with CHF. METHODS: A parallel, mixed methods design with an embedded qualitative component was used to examine the feasibility of recruitment, retention, intervention adherence/compliance and follow-up assessment completion (symptom burden, quality of life, psychological well-being). Patient and nurse qualitative semistructured interviews explored intervention and study design feasibility and its acceptability. RESULTS: Conversion to consent was 46.9% (372 screened, 81 approached, 38 recruited). 66% of patient participants completed the IPOS; 6% of IPOS questionnaire items were missing (non-response). Over two-thirds (65.6%) of these missing items related to three patients. No item was consistently missing; appetite was the most frequent missing item (1.4%). 92% of participants who completed the IPOS completed all follow-up assessments (1-2 days, 1-2 weeks and 4-6 weeks post-IPOS completion) with no missing data. The a priori feasibility objectives were met. Patients and nurses reported the intervention and study design feasible and acceptable. CONCLUSIONS: A palliative-specific PROM-based intervention is feasible and acceptable to both patients with CHF and nurses in nurse-led disease management clinics for the purposes of both clinical care and research.

Primary Budd-Chiari Syndrome in Children: King's College Hospital Experience.

Primary Budd-Chiari syndrome is a rare cause of liver disease in children in the western world. Here we present a retrospective review of children with Primary Budd-Chiari syndrome presenting from January 2001 to November 2015 to our hospital. Seven children were identified. Their presentation was mostly chronic. All had predisposing factors for thrombosis and were started on anticoagulation. Radiological interventions (2 transjugular intrahepatic portosystemic shunts and 1 hepatic vein stenting), liver transplant and mesocaval shunt were done in 3, 2, and 1 patients, respectively; 1 child underwent bone marrow transplantation following transjugular intrahepatic portosystemic shunts and 1 child was managed only medically. After liver transplantation, one child died 3 years later as a result of subarachnoid haemorrhage, whereas others remain well at a median follow-up of 6 years. Despite high morbidity, the disease can have a good long-term outcome with a multidisciplinary approach.

Prevalence of symptoms in patients with multiple myeloma: a systematic review and meta-analysis.

OBJECTIVES: Multiple myeloma (MM) is an incurable haematological disease. Due to novel agents, overall survival has improved in this group, yet there are no systematic reviews to understand the symptom profiles resulting from disease and treatment-related toxicities. We aimed to synthesise data on the prevalence of symptoms in patients with MM. METHODS: A systematic database and grey literature search were conducted in six databases. Random-effects meta-analysis with inverse variance weighting to pool prevalence data was performed. RESULTS: Thirty-six studies were included of which 34 studies (N = 3023) provided data for meta-analysis. Twenty-seven distinct symptoms were reported, with the majority of studies focusing on pain (n = 27), fatigue (n = 19) and problems with functioning (n = 15). The most prevalent symptoms were fatigue (98.8%, 95% CI 98.1-99.2%), pain (73%, 39.9-91.7), constipation (65.2%, 22.9-92.2) and tingling in the hands/feet with 53.4% (0.4-99.7). The most common problems were decreased physical functioning (98.9%, 98.2-99.3), decreased cognitive functioning (80.2%, 40-96.1) and financial difficulties (78.4%, 39.1-95.4). These problems were present in newly diagnosed to advanced disease stage. CONCLUSIONS: Optimal quality of life and good symptom management in this incurable disease can only be achieved by routinely assessing symptoms throughout the disease trajectory.

Measures to assess commonly experienced symptoms for people with dementia in long-term care settings: a systematic review.

BACKGROUND: High symptom burden is common in long-term care residents with dementia and results in distress and behavioral challenges if undetected. Physicians may have limited time to regularly examine all residents, particularly those unable to self-report, and may rely on reports from caregivers who are frequently in a good position to detect symptoms quickly. We aimed to identify proxy-completed assessment measures of symptoms experienced by people with dementia, and critically appraise the psychometric properties and applicability for use in long-term care settings by caregivers. METHODS: We searched Medline, EMBASE, PsycINFO, CINAHL and ASSIA from inception to 23 June 2015, supplemented by citation and reference searches. The search strategy used a combination of terms: dementia OR long-term care AND assessment AND symptoms (e.g. pain). Studies were included if they evaluated psychometric properties of proxy-completed symptom assessment measures for people with dementia in any setting or those of mixed cognitive abilities residing in long-term care settings. Measures were included if they did not require clinical training, and used proxy-observed behaviors to support assessment in verbally compromised people with dementia. Data were extracted on study setting and sample, measurement properties and psychometric properties. Measures were independently evaluated by two investigators using quality criteria for measurement properties, and evaluated for clinical applicability in long-term settings. RESULTS: Of the 19,942 studies identified, 40 studies evaluating 32 measures assessing pain (n = 12), oral health (n = 2), multiple neuropsychiatric symptoms (n = 2), depression (n = 8), anxiety (n = 2), psychological wellbeing (n = 4), and discomfort (n = 2) were included. The majority of studies (31/40) were conducted in long-term care settings although none of the neuropsychiatric or anxiety measures were validated in this setting. The pain assessments, PAINAD and PACSLAC had the strongest psychometric evidence. The oral health, discomfort, and three psychological wellbeing measures were validated in this setting but require further psychometric evaluation. Depression measures were poor at detecting depression in this population. All measures require further investigation into agreement, responsiveness and interpretability. CONCLUSIONS: Measures for pain are best developed for this population and setting. All other measures require further validation. A multi-symptom measure to support comprehensive assessment and monitoring in this population is required.