Rhinovirus/enterovirus identification by electron microscopy in lower respiratory tract infection in a patient with relapsed myelodysplastic syndrome after allogeneic hematopoietic cell transplantation and donor lymphocyte infusion

Donor lymphocyte infusion (DLI) is a curable treatment option, inducing a graft-versus-tumor effect in patients with relapsed hematological malignancies after allogeneic hematopoietic cell transplantation (allo-HCT). However, not only graft-versus-host disease but also pulmonary complications are problematic adverse events after DLI. Although viral infections can be associated with pulmonary complications after DLI, the mechanism underlying these complications remains unclear. Detecting the causative virus infections after pulmonary complications following DLI is challenging, as invasive examinations, such as bronchoalveolar lavage and lung biopsies, are necessary. Family Picornaviridae, including Human-Rhinovirus (HRV) and Enterovirus (EnV), can induce fatal lower respiratory tract infection (LRTI) in recipients who undergo allo-HCT, which can be underdiagnosed. We encountered a 62-year-old man with relapsed myelodysplastic syndrome 20 days after a second HLA-haplo-identical allo-HCT and 4 DLI procedures who was later found to have HRV and EnV LRTI by postmortem electron microscopy. Despite high-dose immunosuppression, severe hypoxemia did not improve, and he succumbed to respiratory failure. Immunosuppressive therapy for idiopathic pneumonia syndrome after allo-HCT may be effective, but its efficacy for acute respiratory failure after DLI is controversial. Our case indicated that the control of viral replication should be prioritized over that of inflammation in HRV and EnV LRTI after DLI.     

Classification of PRSS1 variants responsible for chronic pancreatitis: An expert perspective from the Franco-Chinese GREPAN Study Group

BackgroundPRSS1 was the first reported chronic pancreatitis (CP) gene. The existence of both gain-of-function (GoF) and gain-of-proteotoxicity (GoP) pathological PRSS1 variants, together with the fact that PRSS1 variants have been identified in CP subtypes spanning the range from monogenic to multifactorial, has made the classification of PRSS1 variants very challenging.MethodsAll currently reported PRSS1 variants (derived primarily from two databases) were manually reviewed with respect to their clinical genetics, functional analysis and population allele frequency. They were classified by variant type and pathological mechanism within the framework of our recently proposed ACMG/AMP guidelines-based seven-category system.ResultsThe total number of distinct germline PRSS1 variants included for analysis was 100, comprising 3 copy number variants (CNVs), 12 5′ and 3′ variants, 19 intronic variants, 5 nonsense variants, 1 frameshift deletion variant, 6 synonymous variants, 1 in-frame duplication, 3 gene conversions and 50 missense variants. Based upon a combination of clinical genetic and functional analysis, population data and in silico analysis, we classified 26 variants (all 3 CNVs, the in-frame duplication, all 3 gene conversions and 19 missense) as “pathogenic”, 3 variants (missense) as “likely pathogenic”, 5 variants (four missense and one promoter) as “predisposing”, 13 variants (all missense) as “unknown significance”, 2 variants (missense) as “likely benign”, and all remaining 51 variants as “benign”.ConclusionsWe describe an expert classification of the 100 PRSS1 variants reported to date. The results have immediate implications for reclassifying many ClinVar-registered PRSS1 variants as well as providing optimal guidelines/standards for reporting PRSS1 variants.     

Association of Tooth Loss and Diet Quality with Acceleration of Aging: Evidence from NHANES

BackgroundAlthough tooth loss is widely recognized as a typical sign of aging, whether it is associated with accelerated aging, and to what extent diet quality mediates this association are unknown.MethodsData were collected from the National Health and Nutrition Examination Survey. The missing tooth counts were recorded as the number of edentulous sites. Phenotypic accelerated aging was calculated using 9 routine clinical chemistry biomarkers and chronological age. Healthy Eating Index 2015 (HEI-2015) score was used to evaluate diet quality. Multivariate logistic regression and linear regression were used to analyze the association between tooth loss and accelerated aging. Mediation analyses were used to examine the mediation role of diet quality in the association.ResultsThe association between tooth loss and accelerated aging was confirmed. The highest quartile of tooth loss showed a positive association with accelerated aging (β=1.090; 95% confidence interval, 0.555 to 1.625; P < .001). Diet quality decreased with increase number of missing teeth and showed a negative association with accelerated aging. Mediation analysis suggested that the HEI-2015 score partially mediated the association between tooth loss and accelerated aging (proportion of mediation: 5.302%; 95% confidence interval, 3.422% to 7.182%; P < .001). Plant foods such as fruits and vegetables were considered the key mediating food.ConclusionsThe association between tooth loss and accelerated aging, as well as the partially mediating role of dietary quality in this association was confirmed. These findings suggested that more attention should be paid to the population with severe tooth loss and the changes of their dietary quality.     

Resveratrol Prevents Vibrio vulnificus-Induced Sepsis by Attenuating Necroptosis

Objective This study investigated how the natural phytophenol and potent SIRT1 activator resveratrol(RSV) regulate necroptosis during Vibrio vulnificus(V. vulnificus)-induced sepsis and the potential mechanism.Methods The effect of RSV on V. vulnificus cytolysin(VVC)-induced necroptosis was analyzed in vitro using CCK-8 and Western blot assays. Enzyme-linked immunosorbent assays and quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry and survival analyses wer...     

Mortality and costs related to severe acute pancreatitis in the intensive care units of Australia and New Zealand (ANZ), 2003–2020

Background and objectiveComprehensive data on the burden of severe acute pancreatitis (SAP) in global intensive care units (ICUs) and trends over time are lacking. Our objective was to compare trends in hospital and ICU mortality, in-hospital and ICU length of stay, and costs related to ICU admission in Australia and New Zealand (ANZ) for SAP.MethodsWe performed a retrospective, observational, cohort study of ICU admissions reported to the ANZ Intensive Care Society Adult Patient Database over three consecutive six-year time periods from 2003 to 2020.Results12,635 patients with SAP from 189 ICUs in ANZ were analysed. No difference in adjusted hospital mortality (11.4% vs 11.5% vs 11.0%, p = 0.85) and ICU mortality rates (7.5% vs 8.0% vs 8.1%, p = 0.73) were noted over the study period. Median length of hospital admission reduced over time (13.9 days in 2003-08, 13.1 days in 2009-14 and 12.5 days in 2015-20; p < 0.01). No difference in length of ICU stay was noted over the study period (p = 0.13). The cost of managing SAP in ANZ ICUs remained constant over the three time periods.ConclusionsIn critically-ill SAP patients in ANZ, no change in mortality has been noted over nearly two decades. There was a slight reduction in hospital stay (1 day), while the length of ICU stay remained unchanged. Given the significant costs related to care of patients with SAP in ICU, these findings highlight the need to prioritise resource allocation for healthcare delivery and targeted clinical research to identify treatments aimed at reducing mortality.     

Emergency department and intensive care unit health professionals' knowledge and application of the law that applies to end-of-life decision-making for adults: A scoping review of the literature

BackgroundLaws that regulate healthcare practice at the end of life reflect the values of the society where they apply. Traditionally, healthcare professionals rely on their clinical knowledge to inform treatment decisions, but the extent to which the law also informs health professionals’ decision-making at the end of life is uncertain.ObjectiveThe objective of this study was to describe what healthcare professionals working in emergency departments and intensive care units know about the law that relates to end-of-life decision-making for hospitalised adults and what affects its application.Review methodThis review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews.Data sourcesData were sourced by searching the following databases: Cumulative Index to Nursing and Allied Health Literature (CINAHL [via EBSCOhost]), Nursing and Allied Health and Health and Medical Collection (via ProQuest Central), Excerpta Medica dataBASE (Embase), PubMed, PsycINFO, and HeinOnline.ResultsSystematic screening of the search results and application of inclusion criteria resulted in the identification of 18 quantitative and three qualitative articles that were reviewed, summarised, and reported. Ten of the quantitative studies assessed knowledge and attitudes to law or end-of-life decision-making using hypothetical scenarios or vignettes. Qualitative studies focussed on how the law was applied when end-of-life decisions were made. End-of-life decision-making is mostly based on the clinical needs of the patient, with the law having a secondary role.ConclusionAround the world, there are significant gaps in healthcare professionals’ legal knowledge. Clinical factors are considered more important to end-of-life decision-making than legal factors. End-of-life decision-making is perceived to carry legal risk, and this results in the provision of nonbeneficial end-of-life care. Further qualitative research is needed to ascertain the clinician-related factors that affect the integration of law with end-of-life decision-making.     

Emotional reactions to infertility diagnosis: thematic and natural language processing analyses of the 1000 Dreams survey

Research questionWhat are the emotional effects of infertility on patients, partners, or both, and how can qualitative thematic analyses and natural language processing (NLP) help evaluate textual data?DesignA cross-sectional, multi-country survey conducted between March 2019 and May 2019. A total of 1944 patients, partners, or both, from nine countries responded to the open-ended question asking about their initial feelings related to an infertility diagnosis. A mixed-method approach that integrated NLP topic modelling and thematic analyses was used to analyse responses. Sentiment polarity was quantified for each response. Linear regression evaluated the association between patient characteristics and sentiment negativity.ResultsCommon emotional reactions to infertility diagnoses were sadness, depression, stress, disappointment, anxiety, frustration, confusion and loss of self-confidence. NLP topic modelling found additional reactions, i.e. shared feelings with partners, recollections about causes of infertility and treatment experience. Responses to the open-ended question were brief (median: three words) with 71.8% conveying negative sentiments. Some respondent characteristics showed small but significant associations with sentiment negativity, i.e. country (Spain, China and France were more negative than the USA, P < 0.001, P < 0.003 and P < 0.009 respectively), treatment engagement (no treatment was more negative than one or more treatment, P = 0.027) and marital status (missing/other was more negative than divorced, P = 0.003).ConclusionInfertility diagnoses create an emotional burden for patients and partners. The mixed-method approach provides a compelling synergy in support of the validity of these findings and shows potential for these techniques in future research.     

Hepatocytic ballooning in non-alcoholic steatohepatitis: Dilemmas and future directions

Hepatocytic ballooning is a key histological feature in the diagnosis of non-alcoholic steatohepatitis (NASH) and is an essential component of the two most widely used histological scoring systems for diagnosing and staging non-alcoholic fatty liver disease (NAFLD) [namely, the NAFLD activity score (NAS), and the steatosis, activity and fibrosis (SAF) scoring system]. As a result of the increasing incidence of NASH globally, the diagnostic challenges of hepatocytic ballooning are unprecedented. Despite the clear pathological concept of hepatocytic ballooning, there are still challenges in assessing hepatocytic ballooning in ‘real life’ situations. Hepatocytic ballooning can be confused with cellular oedema and microvesicular steatosis. Significant inter-observer variability does exist in assessing the presence and severity of hepatocytic ballooning. In this review article, we describe the underlying mechanisms associated with hepatocytic ballooning. Specifically, we discuss the increased endoplasmic reticulum stress and the unfolded protein response, as well as the rearrangement of the intermediate filament cytoskeleton, the appearance of Mallory-Denk bodies and activation of the sonic Hedgehog pathway. We also discuss the use of artificial intelligence in the detection and interpretation of hepatocytic ballooning, which may provide new possibilities for future diagnosis and treatment.     

Health literacy of critical care patients in a remote area health service: A cross-sectional survey

BackgroundLower life expectancy, higher rates of chronic disease, and poorer uptake of health services are common in remote patient populations. Patients with poor health literacy (HL) are less likely to attend appointments, adhere to medications, and have higher rates of chronic illness. Evidence underpinning the relationship between HL and inequity in remote critical care populations is sparse.ObjectivesThe primary study aim was to explore a multidimensional HL profile of patients requiring critical care in a remote area health service. Secondary aims were to explore HL in subgroups of the sample and to explore associations between HL and emergency department representation and discharge against medical advice.MethodsThis was a cross-sectional study of consecutive eligible patients admitted to the Mount Isa hospital intensive care unit. The Health Literacy Questionnaire was administered in a semistructured interview.ResultsIn a 5-month period, there were 141 patient admissions to the five-bed intensive care unit, 67 patients (47.5%) met inclusion criteria and were not discharged prior to recruitment, and 37 (26.2%) agreed to participate. Participants felt understood and supported by healthcare providers, had sufficient information to manage their health, proactively engaged with healthcare providers, and had strong social supports. More challenging was their capacity to advocate on their own behalf, to explore and appraise information and to navigate healthcare systems. Patients who represented to the emergency department (n = 8, 21.6%) felt more empowered to seek healthcare advice. Of the 11 patients that discharged against medical advice, only one participated in the study.ConclusionTrends in the data showed that Aboriginal and Torres Strait Islander participants were marginally less likely to be information explorers and to understand all written information. Findings provide guidance for the development of interventions to progress a reduction in health disparities experienced by this population.