Clinical impact of CEUS on non-characterizable observations and observations with intermediate probability of malignancy on CT/MRI in patients at risk for HCC.

BACKGROUND: Hepatocellular carcinoma (HCC) is a unique cancer allowing tumor diagnosis with identification of definitive patterns of enhancement on contrast-enhanced imaging, avoiding invasive biopsy. However, it is still unclear to what extent Contrast-Enhanced Ultrasound (CEUS) is a clinically useful additional step when Computed tomography (CT) or Magnetic resonance imaging (MRI) are inconclusive. METHODS: A prospective international multicenter validation study for CEUS Liver Imaging Reporting and Data System (LI-RADS) was conducted between January 2018 and August 2021. 646 patients at risk for HCC with focal liver lesions were enrolled. CEUS was performed using an intravenous ultrasound contrast agent within 4 weeks of CT/MRI. Liver nodules were categorized based on LI-RADS (LR) criteria. Histology or one-year follow-up CT/MRI imaging results were used as the reference standard. The diagnostic performance of CEUS was evaluated for inconclusive CT/MRI scan in two scenarios for which the AASLD recommends repeat imaging or imaging follow-up: observations deemed non-characterizable (LR-NC) or with indeterminate probability of malignancy (LR-3). RESULTS: 75 observations on CT or MRI were categorized as LR-3 (n = 54) or LR-NC (n = 21) CEUS recategorization of such observations into a different LR category (namely, into one among LR-1, LR-2, LR-5, LR-M, or LR-TIV) resulted in management recommendation changes in 33.3% (25/75) and in all but one (96.0%, 24/25) observation, the new management recommendations were correct. CONCLUSION: CEUS LI-RADS resulted in management recommendations change in substantial number of liver observations with initial indeterminate CT/MRI characterization, identifying both non-malignant lesions and HCC, potentially accelerating the diagnostic process and alleviating the need for biopsy or follow-up imaging. CLINICALTRIALS: gov number, NCT03318380.

Enhanced Recovery After Surgery (ERAS) Reduces Hospital Costs and Improve Clinical Outcomes in Liver Surgery: a Systematic Review and Meta-Analysis.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols are evidence-based, multimodal and patient-centred approach to optimize patient care and experience during their perioperative pathway. It has been shown to be effective in reducing length of hospital stay and improving clinical outcomes. However, evidence on its effective in liver surgery remains weak. The aim of this review is to investigate clinical benefits, cost-effectiveness and compliance to ERAS protocols in liver surgery. METHODS: A systematic literature search was conducted using CINAHL Plus, EMBASE, MEDLINE, PubMed and Cochrane for randomized control trials (RCTs) and cohort studies published between 2008 and 2019, comparing effect of ERAS protocols and standard care on hospital cost, LOS, complications, readmission, mortality and compliance. RESULTS: The search resulted in 6 RCTs and 21 cohort studies of 3739 patients (1777 in ERAS and 1962 in standard care group). LOS was reduced by 2.22 days in ERAS group (MD = -2.22; CI, -2.77 to -1.68; p < 0.00001) compared to the standard care group. Fewer patients in ERAS group experienced complications (RR, 0.71; 95% CI, 0.65-0.77; p = < 0.00001). Hospital cost was significantly lower in the ERAS group (SMD = -0.98; CI, -1.37 to - 0.58; p < 0.0001). CONCLUSION: Our review concluded that the introduction of ERAS protocols is safe and feasible in hepatectomies, without increasing mortality and readmission rates, whilst reducing LOS and risk of complications, and with a significant hospital cost savings. Laparoscopic approach may be necessary to reduce complication rates in liver surgery. However, further studies are needed to investigate overall compliance to ERAS protocols and its impact on clinical outcomes.

Guidelines for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in critically ill patients (Part I): Society of Critical Care Medicine (SCCM) and European Society of Intensive Care Medicine (ESICM) 2017

OBJECTIVE: To update the 2008 consensus statements for the diagnosis and management of critical illness-related corticosteroid insufficiency (CIRCI) in adult and pediatric patients. PARTICIPANTS: A multispecialty task force of 16 international experts in Critical Care Medicine, endocrinology, and guideline methods, all of them members of the Society of Critical Care Medicine and/or the European Society of Intensive Care Medicine. DESIGN/METHODS: The recommendations were based on the summarized evidence from the 2008 document in addition to more recent findings from an updated systematic review of relevant studies from 2008 to 2017 and were formulated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The strength of each recommendation was classified as strong or conditional, and the quality of evidence was rated from high to very low based on factors including the individual study design, the risk of bias, the consistency of the results, and the directness and precision of the evidence. Recommendation approval required the agreement of at least 80% of the task force members. RESULTS: The task force was unable to reach agreement on a single test that can reliably diagnose CIRCI, although delta cortisol (change in baseline cortisol at 60 min of <9 µg/dl) after cosyntropin (250 µg) administration and a random plasma cortisol of <10 µg/dl may be used by clinicians. We suggest against using plasma free cortisol or salivary cortisol level over plasma total cortisol (conditional, very low quality of evidence). For treatment of specific conditions, we suggest using intravenous (IV) hydrocortisone <400 mg/day for ≥3 days at full dose in patients with septic shock that is not responsive to fluid and moderate- to high-dose vasopressor therapy (conditional, low quality of evidence). We suggest not using corticosteroids in adult patients with sepsis without shock (conditional recommendation, moderate quality of evidence). We suggest the use of IV methylprednisolone 1 mg/kg/day in patients with early moderate to severe acute respiratory distress syndrome (PaO2/FiO2 < 200 and within 14 days of onset) (conditional, moderate quality of evidence). Corticosteroids are not suggested for patients with major trauma (conditional, low quality of evidence). CONCLUSIONS: Evidence-based recommendations for the use of corticosteroids in critically ill patients with sepsis and septic shock, acute respiratory distress syndrome, and major trauma have been developed by a multispecialty task force.

Low emotion-oriented coping and informal help-seeking behaviour as major predictive factors for improvement in major depression at 5-year follow-up in the adult community.

PURPOSE: Given the broad range of biopsychosocial difficulties resulting from major depressive disorder (MDD), reliable evidence for predictors of improved mental health is essential, particularly from unbiased prospective community samples. Consequently, a broad spectrum of potential clinical and non-clinical predictors of improved mental health, defined as an absence of current major depressive episode (MDE) at follow-up, were examined over a 5-year period in an adult community sample. METHODS: The longitudinal population-based PsyCoLaus study from the city of Lausanne, Switzerland, was used. Subjects having a lifetime MDD with a current MDE at baseline assessment were selected, resulting in a subsample of 210 subjects. Logistic regressions were applied to the data. RESULTS: Coping styles were the most important predictive factors in the present study. More specifically, low emotion-oriented coping and informal help-seeking behaviour at baseline were associated with the absence of an MDD diagnosis at follow-up. Surprisingly, neither formal help-seeking behaviour, nor psychopharmacological treatment, nor childhood adversities, nor depression subtypes turned out to be relevant predictors in the current study. CONCLUSIONS: The paramount role of coping styles as predictors of improvement in depression found in the present study might be a valuable target for resource-oriented therapeutic models. On the one hand, the positive impact of low emotion-oriented coping highlights the utility of clinical interventions interrupting excessive mental ruminations during MDE. On the other hand, the importance of informal social networks raises questions regarding how to enlarge the personal network of affected subjects and on how to best support informal caregivers.

Stigma-related stress, shame and avoidant coping reactions among members of the general population with elevated symptom levels.

BACKGROUND: It is unclear whether mental illness stigma affects individuals with subthreshold syndromes outside clinical settings. We therefore investigated the role of different stigma variables, including stigma-related stress and shame reactions, for avoidant stigma coping among members of the general population with elevated symptom levels. METHODS: Based on a representative population survey, general stress resilience, stigma variables, shame about having a mental illness as well as avoidant stigma coping (secrecy and social withdrawal) were assessed by self-report among 676 participants with elevated symptom levels. Stigma variables and resilience were examined as predictors of avoidant stigma coping in a path model. RESULTS: Increased stigma stress was predicted by lower general stress resilience as well as by higher levels of perceived stigma, group identification and perceived legitimacy of discrimination. More shame was associated with higher perceived legitimacy. Lower resilience as well as more perceived stigma, group identification and perceived legitimacy predicted avoidant coping. Stigma stress partly mediated effects of resilience, perceived stigma and group identification on avoidant coping; shame partly mediated effects of perceived legitimacy on coping. Stigma stress and shame were also directly and positively related to avoidant stigma coping. Analyses were adjusted for symptoms, neuroticism and sociodemographic variables. CONCLUSIONS: Stigma may affect a larger proportion of the population than previously thought because stigma variables predicted secrecy and withdrawal among members of the general population with elevated, but overall mild symptom levels. Avoidant stigma coping likely has harmful effects, potentially exacerbating pre-existing psychological distress and undermining social networks. This highlights the need to reduce public stigma as well as to support individuals with subthreshold syndromes in their coping with stigma stress and shame reactions.

Mental illness stigma, secrecy and suicidal ideation.

AIMS: Whether the public stigma associated with mental illness negatively affects an individual, largely depends on whether the person has been labelled 'mentally ill'. For labelled individuals concealing mental illness is a common strategy to cope with mental illness stigma, despite secrecy's potential negative consequences. In addition, initial evidence points to a link between stigma and suicidality, but quantitative data from community samples are lacking. METHODS: Based on previous literature about mental illness stigma and suicidality, as well as about the potential influence of labelling processes and secrecy, a theory-driven model linking perceived mental illness stigma and suicidal ideation by a mediation of secrecy and hopelessness was established. This model was tested separately among labelled and unlabelled persons using data derived from a Swiss cross-sectional population-based study. A large community sample of people with elevated psychiatric symptoms was examined by interviews and self-report, collecting information on perceived stigma, secrecy, hopelessness and suicidal ideation. Participants who had ever used mental health services were considered as labelled 'mentally ill'. A descriptive analysis, stratified logistic regression models and a path analysis testing a three-path mediation effect were conducted. RESULTS: While no significant differences between labelled and unlabelled participants were observed regarding perceived stigma and secrecy, labelled individuals reported significantly higher frequencies of suicidal ideation and feelings of hopelessness. More perceived stigma was associated with suicidal ideation among labelled, but not among unlabelled individuals. In the path analysis, this link was mediated by increased secrecy and hopelessness. CONCLUSIONS: Results from this study indicate that among persons labelled 'mentally ill', mental illness stigma is a contributor to suicidal ideation. One explanation for this association is the relation perceived stigma has with secrecy, which introduces negative emotional consequences. If our findings are replicated, they would suggest that programmes empowering people in treatment for mental illness to cope with anticipated and experienced discrimination as well as interventions to reduce public stigma within society could improve suicide prevention.

Effects of an air pollution personal alert system on health service usage in a high-risk general population: a quasi-experimental study using linked data.

BACKGROUND: There is no evidence to date on whether an intervention alerting people to high levels of pollution is effective in reducing health service utilisation. We evaluated alert accuracy and the effect of a targeted personal air pollution alert system, airAware, on emergency hospital admissions, emergency department attendances, general practitioner contacts and prescribed medications. METHODS: Quasi-experimental study describing accuracy of alerts compared with pollution triggers; and comparing relative changes in healthcare utilisation in the intervention group to those who did not sign-up. Participants were people diagnosed with asthma, chronic obstructive pulmonary disease (COPD) or coronary heart disease, resident in an industrial area of south Wales and registered patients at 1 of 4 general practices. Longitudinal anonymised record linked data were modelled for participants and non-participants, adjusting for differences between groups. RESULTS: During the 2-year intervention period alerts were correctly issued on 208 of 248 occasions; sensitivity was 83.9% (95% CI 78.8% to 87.9%) and specificity 99.5% (95% CI 99.3% to 99.6%). The intervention was associated with a 4-fold increase in admissions for respiratory conditions (incidence rate ratio (IRR) 3.97; 95% CI 1.59 to 9.93) and a near doubling of emergency department attendance (IRR=1.89; 95% CI 1.34 to 2.68). CONCLUSIONS: The intervention was associated with increased emergency admissions for respiratory conditions. While findings may be context specific, evidence from this evaluation questions the benefits of implementing near real-time personal pollution alert systems for high-risk individuals.

Comparison of von Willebrand factor (VWF) activity levels determined by HemosIL AcuStar assay and HemosIL LIA assay with ristocetin cofactor assay by aggregometry.

INTRODUCTION: Diagnosis of von Willebrand disease (VWD) requires quantitative as well as qualitative determination of von Willebrand factor (VWF) levels. For functional assessment of VWF, ristocetin cofactor assay by aggregometry is considered to be the gold standard. However, need for technical expertise, labour intensiveness, difficult standardization and high intra- and inter- assay variabilities are some of the limitations of this methodology. Various assays for determination of VWF adhesive function using different methodologies have been developed in recent years. AIM: To evaluate the HemosIL AcuStar chemiluminescence assay (VWF:RCo[Acu]) and the HemosIL latex immunoassay (VWF:act) as diagnostic tests for VWD and identification of type 2 VWD in comparison with the ristocetin cofactor assay performed by aggregometry (VWF:RCo[Agg]). METHODS: Results from 96 samples analysed by VWF:RCo[Acu] and 128 samples by VWF:act were compared with VWF:RCo[Agg]. Sixty of these samples (25 normal, 17 type 1 and 18 type 2) were analysed by all three assays. RESULTS: VWF:RCo[Acu] showed excellent agreement with VWF:RCo[Agg], and readily identified all type 2 VWD samples tested. VWF:act showed reasonable agreement with VWF:RCo[Agg] for most patients, but had a slightly lower sensitivity for detection of type 2 VWD. CONCLUSION: VWF:RCo[Acu] assay has the potential to replace VWF:RCo[Agg] for the diagnosis of VWD.

Subclinical psychosis syndromes in the general population: results from a large-scale epidemiological survey among residents of the canton of Zurich, Switzerland.

Aims. Prevalence and covariates of subclinical psychosis have gained increased interest in the context of early identification and treatment of persons at risk for psychosis. Methods. We analysed 9829 adults representative of the general population within the canton of Zurich, Switzerland. Two psychosis syndromes, derived from the SCL-90-R, were applied: 'schizotypal signs' and 'schizophrenia nuclear symptoms'. Results. Only a few subjects (13.2%) reported no schizotypal signs. While 33.2% of subjects indicated mild signs, only a small proportion (3.7%) reported severe signs. A very common outcome was no 'schizophrenia nuclear symptoms' (70.6%). Although 13.5% of the participants reported mild symptoms, severe nuclear symptoms were very rare (0.5%). Because these two syndromes were only moderately correlated (r = 0.43), we were able to establish sufficiently distinct symptom clusters. Schizotypal signs were more closely connected to distress than was schizophrenia nuclear symptoms, even though their distribution types were similar. Both syndromes were associated with several covariates, such as alcohol and tobacco use, being unmarried, low education level, psychopathological distress and low subjective well-being. Conclusions. Subclinical psychosis symptoms are quite frequent in the general population but, for the most part, are not very pronounced. In particular, our data support the notion of a continuous Wald distribution of psychotic symptoms in the general population. Our findings have enabled us to confirm the usefulness of these syndromes as previously assessed in other independent community samples. Both can appropriately be associated with well-known risk factors of schizophrenia.

Challenges in implementing the new BASHH guidelines for the management of gonorrhoea.

Neisseria gonorrhoeae has progressively developed reduced sensitivity to different classes of antibiotics. The British Association for Sexual Health and HIV (BASHH) updated guidelines for the diagnosis and management of gonorrhoea in 2011. New recommendations include an increased dose of ceftriaxone with adjuvant use of azithromycin, as well as test of cure (TOC) in all cases. We present an audit of adherence to new antibiotic prescribing guidelines as well as TOC uptake in an inner city genitourinary medicine clinic. Among the 271 (242 male, 29 female) patients included, 96% (n = 260) received the new first-line treatment. Test of cure uptake was found to be suboptimal at 55% (n = 149) with the majority (67%) of these taking place within 20 days of treatment. The new first-line treatment for gonorrhoea is feasible and generally accepted by patients. However the TOC uptake is low, emphasising the need for robust follow-up and recall policies. Further study is required into the optimal timing for TOC.

Shame, perceived knowledge and satisfaction associated with mental health as predictors of attitude patterns towards help-seeking.

Aims. To examine stigma- and knowledge-related barriers to help-seeking among members of the general population. Methods. In a representative survey of young to middle-aged Swiss adults (n = 8875), shame about a potential own mental illness, perceived knowledge about and satisfaction with one's mental health, psychiatric symptoms and attitudes towards help-seeking were assessed. Results. A latent profile analysis of all participants yielded two groups with different attitudes towards help-seeking. Relative to the majority, a one-in-four subgroup endorsed more negative attitudes towards seeking professional help, including psychiatric medication, and was characterized by more shame, less perceived knowledge, higher satisfaction with their mental health, younger age, male gender and lower education. Among participants with high symptom levels (n = 855), a third subgroup was reluctant to seek help in their private environment and characterized by high symptoms as well as low satisfaction with their mental health. Conclusions. Shame as an emotional proxy of self-stigma as well as poor subjective mental health literacy may be independent barriers to help-seeking. Interventions to increase mental health service use could focus on both variables and on those individuals with more negative views about professional help, in the general public as well as among people with a current mental illness.

Sex-related and non-sex-related comorbidity subtypes of tic disorders: a latent class approach.

BACKGROUND AND PURPOSE: Recent evidence suggests that there may be more than one Gilles de la Tourette syndrome (GTS)/tic disorder phenotype. However, little is known about the common patterns of these GTS/tic disorder-related comorbidities. In addition, sex-specific phenomenological data of GTS/tic disorder-affected adults are rare. Therefore, this community-based study used latent class analyses (LCA) to investigate sex-related and non-sex-related subtypes of GTS/tic disorders and their most common comorbidities. METHODS: The data were drawn from the PsyCoLaus study (n = 3691), a population-based survey conducted in Lausanne, Switzerland. LCA were performed on the data of 80 subjects manifesting motor/vocal tics during their childhood/adolescence. Comorbid attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder, depressive, phobia and panic symptoms/syndromes comprised the selected indicators. The resultant classes were characterized by psychosocial correlates. RESULTS: In LCA, four latent classes provided the best fit to the data. We identified two male-related classes. The first class exhibited both ADHD and depression. The second class comprised males with only depression. Class three was a female-related class depicting obsessive thoughts/compulsive acts, phobias and panic attacks. This class manifested high psychosocial impairment. Class four had a balanced sex proportion and comorbid symptoms/syndromes such as phobias and panic attacks. The complementary occurrence of comorbid obsessive thoughts/compulsive acts and ADHD impulsivity was remarkable. CONCLUSIONS: To the best of our knowledge, this is the first study applying LCA to community data of GTS symptoms/tic disorder-affected persons. Our findings support the utility of differentiating GTS/tic disorder subphenotypes on the basis of comorbid syndromes.

Childhood adversity in association with personality disorder dimensions: new findings in an old debate.

BACKGROUND: Various studies have reported a positive relationship between child maltreatment and personality disorders (PDs). However, few studies included all DSM-IV PDs and even fewer adjusted for other forms of childhood adversity, e.g. bullying or family problems. METHOD: We analyzed questionnaires completed by 512 participants of the ZInEP epidemiology survey, a comprehensive psychiatric survey of the general population in Zurich, Switzerland. Associations between childhood adversity and PDs were analyzed bivariately via simple regression analyses and multivariately via multiple path analysis. RESULTS: The bivariate analyses revealed that all PD dimensions were significantly related to various forms of family and school problems as well as child abuse. In contrast, according to the multivariate analysis only school problems and emotional abuse were associated with various PDs. Poverty was uniquely associated with schizotypal PD, conflicts with parents with obsessive-compulsive PD, physical abuse with antisocial PD, and physical neglect with narcissistic PD. Sexual abuse was statistically significantly associated with schizotypal and borderline PD, but corresponding effect sizes were small. CONCLUSION: Childhood adversity has a serious impact on PDs. Bullying and violence in schools and emotional abuse appear to be more salient markers of general personality pathology than other forms of childhood adversity. Associations with sexual abuse were negligible when adjusted for other forms of adversity.

Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase.

BACKGROUND: Arginine-depleting therapy with pegylated arginine deiminase (ADI-PEG20) was reported to have activity in advanced melanoma in early phase I-II trial, and clinical trials are currently underway in other cancers. However, the optimal patient population who benefit from this treatment is unknown. METHODS: Advanced melanoma patients with accessible tumours had biopsy performed before the start of treatment with ADI-PEG20 and at the time of progression or relapse when amenable to determine whether argininosuccinate synthetase (ASS) expression in tumour was predictive of response to ADI-PEG20. RESULTS: Twenty-seven of thirty-eight patients treated had melanoma tumours assessable for ASS staining before treatment. Clinical benefit rate (CBR) and longer time to progression were associated with negative expression of tumour ASS. Only 1 of 10 patients with ASS-positive tumours (ASS+) had stable disease, whereas 4 of 17 (24%) had partial response and 5 had stable disease, when ASS expression was negative (ASS-), giving CBR rates of 52.9 vs 10%, P=0.041. Two responding patients with negative ASS expression before therapy had rebiopsy after tumour progression and the ASS expression became positive. The survival of ASS- patients receiving at least four doses at 320 IU m(-2) was significantly better than the ASS+ group at 26.5 vs 8.5 months, P=0.024. CONCLUSION: ADI-PEG20 is safe and the drug is only efficacious in melanoma patients whose tumour has negative ASS expression. Argininosuccinate synthetase tumour positivity is associated with drug resistance and tumour progression.

The hepatitis B e antigen suppresses IL-1ß-mediated NF-κB activation in hepatocytes.

Previous clinical studies have demonstrated an association between the hepatitis B e antigen and Toll-like receptor (TLR) expression and signalling. Therefore, the aim of this study was to develop an in vitro assay to measure the effect of hepatitis B virus proteins, including the precore protein, on signalling mediated by members of the Toll-like/interleukin 1 (TIR) superfamily, by measuring NF-κB promoter activity. The basal level of NF-κB reporter activity was measured in three hepatocyte cell lines (Huh7, HepG2 and PH5CH8) and one kidney cell line (HEK293) using a luciferase assay. All cell lines were virtually refractory to stimulation with lipopolysaccharide; however, PH5CH8 cells had a robust activation of NF-κB in response to IL-1ß stimulation, with ∼ 40-fold higher activation than the unstimulated control, a higher degree of activation than that observed in either Huh7 and HepG2, or HEK293 and HEK293-TLR2 cells. In PH5CH8 cells transfected with pCI expression constructs and stimulated with IL-1ß, we showed that the precursor form of the precore protein, p25, inhibits NF-κB activation by up to 30% and the cytosolic form, p22, inhibits NF-κB activation by 70%. The core protein, p21, which shares significant homology with the precore protein except for a 10-amino acid extension at the N-terminus, had no effect on NF-κB activation. We hypothesize that the inhibition of IL-1ß-mediated NF-κB activation by the precore protein may be a mechanism that allows the virus to persist, suggesting a role for the pool of precore protein that remains intracellular.

Pediatric health-related quality of life: Feasibility, reliability and validity of the PedsQL transplant module.

The measurement properties of the newly developed Pediatric Quality of Life Inventory (PedsQL) 3.0 Transplant Module in pediatric solid organ transplant recipients were evaluated. Participants included pediatric recipients of liver, kidney, heart and small bowel transplantation who were cared for at seven medical centers across the United States and their parents. Three hundred and thirty-eight parents of children ages 2-18 and 274 children ages 5-18 completed both the PedsQL 4.0 Generic Core Scales and the Transplant Module. Findings suggest that child self-report and parent proxy-report scales on the Transplant Module demonstrated excellent reliability (total scale score for child self-report alpha= 0.93; total scale score for parent proxy-report alpha= 0.94). Transplant-specific symptoms or problems were significantly correlated with lower generic HRQOL, supporting construct validity. Children with solid organ transplants and their parents reported statistically significant lower generic HRQOL than healthy children. Parent and child reports showed moderate to good agreement across the scales. In conclusion, the PedsQL Transplant Module demonstrated excellent initial feasibility, reliability and construct validity in pediatric patients with solid organ transplants.