Appraising diagnostic performance of ELF test by pathological staging and digital quantification of liver fibrosis.

INTRODUCTION AND OBJECTIVES: A crucial issue when appraising the performance of non-invasive markers is the limitations of the reference standard they are compared to. Digital image analysis (DIA) was suggested as a reproducible approach expressing fibrosis numerically as a proportionate area (PA) (%). We aimed to evaluate ELF test with direct reference to PA (%), thereby explore the improvement in accuracy to discriminate significant fibrosis which may actually have been underestimated by categorical pathological staging. MATERIALS AND METHODS: PA (%) data were obtained by DIA of trichrome-stained liver biopsies of 52 chronic hepatitis patients. Paired serum samples of patients and additional 36 controls were performed to measure ELF test. Diagnostic performance characteristics of ELF test was derived in predicting significant fibrosis in the patient cohort, and also, in distinguishing healthy controls from patients with significant fibrosis. RESULTS: We found an AUROC value of 0.73 for ELF to predict significant fibrosis as assessed by DIA and a lower AUROC value of 0.66 when assessed by conventional pathology. Importantly, ELF test provided considerably high diagnostic accuracy to discriminate healthy controls from patients with significant fibrosis defined by Ishak F≥2 and TPA≥5% (AUROCs 0.93 and 0.94, respectively) with optimal ELF cut-off point of 8.4 for both. CONCLUSIONS: Digital quantification could represent a better reference standard than conventional pathology allowing a better discriminatory capability for ELF test. ELF test provided high diagnostic accuracy to discriminate healthy controls from patients with significant fibrosis suggesting a role as a screening strategy in the community setting.

Vox Sanguinis International Forum on the use of prehospital blood products and pharmaceuticals in the treatment of patients with traumatic haemorrhage.

While specific practices and transported blood products vary around the world, most of the respondents in this International Forum transported at least one blood product for the transfusion to bleeding patients en route to the hospital. The most commonly carried product was RBCs, while the use of whole blood will likely increase given the recent reports of its successful use in the civilian setting, and because of the change in the AABB's Standards regulating its use. It will be interesting to see if plasma use in the prehospital setting becomes more widely used given today's enhanced appreciated of the coagulopathy of trauma and plasma's beneficial effect in reversing it, and if blood products are transported to the scene of injury by more vehicles, that is, not just predominantly in helicopters. It was not surprising that TXA is being widely administered as close to the time of injury as possible given its potential benefit in these patients. This International Forum highlights the importance of focusing attention on prehospital transfusion management with a need to further high­quality research in this area to guide optimal resuscitation strategies.

Towards a systematic approach for (de)implementation of patient blood management strategies.

Despite the increasing availability of evidence in transfusion medicine literature, this evidence does not automatically find its way into practice. This is also applicable to patient blood management (PBM). It may concern the lack of implementation of effective new techniques or treatments, or it may apply to the (over)use of techniques and treatments (e.g. inappropriate transfusions) that have proven to be of limited benefit for patients (low-value care) and could be abandoned (de-implementation). In PBM literature, the implementation of restrictive transfusion thresholds and the de-implementation of inappropriate transfusions are described. However, most implementation strategies were not preceded by the identification of relevant barriers, and the used strategies were not often supported by literature on behavioural changes. In this article, we describe implementation vs de-implementation, highlight the current situation of (de)implementation in PBM and describe a systematic approach for (de)implementation illustrated by an example of a PBM de-implementation study regarding '(cost-) effective patient blood management in total hip and knee arthroplasty'. The systematic approach used for (de)implementation is based on the implementation model of Grol, which consists of the following five steps: the detection of improvement goals, a problem analysis, the selection of (de)implementation strategies, the execution of the (de)implementation strategy and an evaluation. Based on the description of the current situation and the experiences in our de-implementation study, we can conclude that de-implementation may be more difficult than expected as other factors may play a role in effective de-implementation compared to implementation.

An international consensus statement on the management of postoperative anaemia after major surgical procedures.

Despite numerous guidelines on the management of anaemia in surgical patients, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in the postoperative period. A number of experienced researchers and clinicians took part in a two-day expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the postoperative period. These statements include: a diagnostic approach to iron deficiency and anaemia in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up that is easy to implement. Available data allow the fulfilment of the requirements of Pillar 1 of Patient Blood Management. We urge national and international research funding bodies to take note of these recommendations, particularly in terms of funding large-scale prospective, randomised clinical trials that can most effectively address the important clinical questions and this clearly unmet medical need.

International consensus statement on the peri-operative management of anaemia and iron deficiency.

Despite current recommendations on the management of pre-operative anaemia, there is no pragmatic guidance for the diagnosis and management of anaemia and iron deficiency in surgical patients. A number of experienced researchers and clinicians took part in an expert workshop and developed the following consensus statement. After presentation of our own research data and local policies and procedures, appropriate relevant literature was reviewed and discussed. We developed a series of best-practice and evidence-based statements to advise on patient care with respect to anaemia and iron deficiency in the peri-operative period. These statements include: a diagnostic approach for anaemia and iron deficiency in surgical patients; identification of patients appropriate for treatment; and advice on practical management and follow-up. We urge anaesthetists and peri-operative physicians to embrace these recommendations, and hospital administrators to enable implementation of these concepts by allocating adequate resources.

Erythropoietin to reduce allogeneic red blood cell transfusion in patients undergoing total hip or knee arthroplasty.

BACKGROUND AND OBJECTIVES: To determine the value of erythropoietin in reducing allogeneic transfusions, it is important to assess the effects, safety and costs for individual indications. Previous studies neither compared the effects of erythropoietin between total hip and total knee arthroplasty, nor evaluated the safety or costs. We performed a meta-analysis to assess the effects of erythropoietin in total hip and knee arthroplasty separately. Safety and costs were evaluated as secondary outcomes. MATERIALS AND METHODS: A systematic literature search was performed to identify randomized controlled trials evaluating the effect of erythropoietin in total hip and knee arthroplasty until April 2014. Study data were extracted using standardized forms and pooled using a random-effects model. Strength of the evidence was evaluated using Cochrane's Collaboration's tool for risk of bias assessment. RESULTS: Seven studies were included (2439 patients). Erythropoietin significantly reduced exposure to allogeneic transfusion in both hip (RR 0·45; 95%CI 0·33-0·61) and knee (RR 0·38; 95%CI 0·27-0·53) arthroplasty, without differences between indications (P = 0·44). Mean number of transfused red blood cell units was significantly decreased in erythropoietin-treated patients (mean difference -0·57; 95%CI -0·86 to -0·29)(unable to split). No differences in thromboembolic or adverse events were found. Only one study evaluated costs, so that no pooled cost-effectiveness estimates could be given. CONCLUSION: Erythropoietin is effective in both hip and knee arthroplasty and can be considered as safe. However, the decision to use erythropoietin on a routine base should be balanced against its costs, which may be relatively high.

Treatment-specific risk of subsequent malignant neoplasms in five-year survivors of diffuse large B-cell lymphoma.

BACKGROUND: The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors. METHODS: Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression. RESULTS: After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin versus ≤2250 mg/m2/≤150 mg/m2, respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab. CONCLUSION: Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up for rituximab-treated patients.

The impact of Coronavirus disease 2019 (COVID-19) on urinalysis parameters.

BACKGROUND: Creatinine elevation and changes in urinalyse parameters may be seen due to acute kidney injury during COVID-19. In the present study, we aimed to investigate the changes in urinalysis of COVID-19 patients with normal kidney function. METHODS: The data of COVID-19 patients with normal renal functions were retrospectively analyzed. Urinalysis parameters of these patients were recorded. The patients were divided into three groups as mild, moderate and severe with respect to the clinical course of the disease. It was examined whether the urine analysis values in the groups were different from normal reference values and whether these values were different between the groups. In addition, possible relationship between the urinalysis parameters and the clinical severity of the disease was investigated. RESULTS: There are three groups; mild (N.=40), moderate (N.=38) and severe (N.=42). Mean age were significantly higher in the severe group, while gender distribution of the groups was similar (P=0.033, P=0.091) Creatinine values of all patients were normal. There were 6.7% glucose positivity, 13.4% protein positivity, 5.8% urobilinogen positivity and 7.5% ketone positivity in urine dipstick analysis and these changes were all significantly higher than the reference values (P=0.008, P<0.0001, P=0.016, P=0.016). Pyuria and hematuria were detected in 8.3% and 9.2%, respectively. The urinalysis parameters and urine microscopy findings were not affected by the severity of the disease. CONCLUSIONS: Glycosuria, proteinuria, pyuria and hematuria may occur during COVID-19 disease, regardless of comorbidity and renal dysfunction. However, these urine parameters were not correlated with the severity of the disease.

Determining the morphology of polystyrene-block-poly(2-vinylpyridine) micellar reactors for ZnO nanoparticle synthesis.

We report the use of reverse PS-b-P2VP diblock copolymer micelles as true nanoscale-sized reactor vessels to synthesize ZnO nanoparticles. The reverse micelles were formed in toluene and then sequentially loaded with zinc acetate dihydrate and tetramethylammonium hydroxide reactants. Moreover, high spatial resolution Z-contrast imaging and EDX spectroscopy techniques were used to confirm the segregation of the Zn cation to the core of the loaded micelles. Determining the chemical distribution with high nanoscale spatial resolution is shown to complement the less direct characterization by AFM, DLS and FTIR, thus demonstrating broader implications for the characterization of hybrid nanocomposite systems.

A randomized comparison of transfusion triggers in elective orthopaedic surgery using leucocyte-depleted red blood cells.

OBJECTIVE: In elective orthopaedic hip- and knee replacement surgery patients, we studied the effect of implementation of a uniform transfusion policy on RBC usage. STUDY DESIGN AND METHODS: A randomized, controlled study. A new uniform, restrictive transfusion policy was compared with standard care, which varied among the three participating hospitals. Only prestorage leucocyte-depleted RBC(s) were used. Primary end-point was RBC usage, related to length of hospital stay. Secondary end-points were Hb levels, mobilization delay and postoperative complications. RESULTS: Six hundred and three patients were evaluated. Adherence to the protocol was over 95%. Overall mean RBC usage was 0.78 U/patient in the new policy group and 0.86 U/patient in the standard care policy group (mean difference 0.08;95% CI [-0.3; 0.2]; P = 0.53). In two hospitals, the new transfusion policy resulted in a RBC reduction of 30% (0.58U RBC/patient) (P = 0.17) and 41% (0.29 U RBC/patient) (P = 0.05) respectively. In the third hospital, however, RBC usage increased by 39% (0.31 U RBC/patient) (P = 0.02) with the new policy, due to a more restrictive standard care policy in that hospital. Length of hospital stay was not influenced by either policy. CONCLUSIONS: Implementation of a uniform transfusion protocol for elective lower joint arthroplasty patients is feasible, but does not always lead to a RBC reduction. Length of hospital stay was not affected.

Triggers and appropriateness of red blood cell transfusions in the postpartum patient--a retrospective audit.

BACKGROUND AND OBJECTIVE: Despite published guidelines, a proportion of red blood cell (RBC) transfusions seem unnecessary. To evaluate the indications for and the appropriateness of RBC transfusions in the postpartum patient, we performed a retrospective audit over a 1-year period in two Dutch hospitals. STUDY DESIGN AND METHODS: Observational study of transfused obstetric patients, admitted in 2006 to the Departments of Obstetrics of a university and a general hospital, was carried out. Relevant clinical and laboratory data were recorded. The appropriateness of RBC transfusions was assessed using the national and age-based transfusion guidelines for the general population; for the studied group the transfusion threshold haemoglobin (Hb) value was 6.4 g/dl for non-massive and 8.1 g/dl for massive blood loss. From these we derived target Hb levels. RESULTS: Ninety patients received one or more RBC units within 48 h of delivery. Mean pretransfusion Hb level was 6.9 [SD 1.2] g/dl. Median number of transfusions was 2. Mean Hb level at discharge was 9.7 [SD 1.1] g/dl. Taking threshold Hb and the derived target Hb level into account, 68% (n = 61) of the patients may have received one or more RBC units inappropriately. Of 311 RBC units transfused, 143 units (46%) were possibly inappropriate, partly due to over-transfusion. CONCLUSION: A significant proportion of postpartum RBC transfusions are possibly inappropriate, partly due to over-transfusion. If current guidelines would be more specific, in particular, with respect to the target Hb levels, the total amount of RBC transfusions may be considerably decreased.

Serum fatty acid chain length associates with prevalent symptomatic end-stage osteoarthritis, independent of BMI.

Higher body mass index (BMI) is associated with osteoarthritis (OA) in both weight-bearing and non-weight-bearing joints, suggesting a link between OA and poor metabolic health beyond mechanical loading. This risk may be influenced by systemic factors accompanying BMI. Fluctuations in concentrations of metabolites may mark or even contribute to development of OA. This study explores the association of metabolites with radiographic knee/hip OA prevalence and progression. A 1H-NMR-metabolomics assay was performed on plasma samples of 1564 cases for prevalent OA and 2,125 controls collected from the Rotterdam Study, CHECK, GARP/NORREF and LUMC-arthroplasty cohorts. OA prevalence and 5 to 10 year progression was assessed by means of Kellgren-Lawrence (KL) score and the OARSI-atlas. End-stage knee/hip OA (TJA) was defined as indication for arthroplasty surgery. Controls did not have OA at baseline or follow-up. Principal component analysis of 227 metabolites demonstrated 23 factors, of which 19 remained interpretable after quality-control. Associations of factor scores with OA definitions were investigated with logistic regression. Fatty acids chain length (FALen), which was included in two factors which associated with TJA, was individually associated with both overall OA as well as TJA. Increased Fatty Acid chain Length is associated with OA.

Psychological distress, quality of life and coping in cancer patients: a prospective study.

We present the results and conclusions of an observational prospective cohort design study using self-administered questionnaires to determine correlation between psychosocial factors and cancer outcome among 80 consecutive newly diagnosed treatment naïve cancer subjects who were being referred to the Oncology Clinic, Hospital Universiti Kebangsaan Malaysia. Subjects were recruited over a period of 43 weeks from October 2000 till July 2001. Follow-up assessments were carried out at 6-months and 12 to 26 months later. The prediction of survival time was performed by the Cox Regression Analysis method with adjustments for biological and psychosocial risk factors. It was noted that depression (p = 0.001), stage 4 cancer disease (p = 0.016), neurological (p = 0.032), gastrointestinal tract (p = 0.04), head and neck (p = 0.011), gynaecological (p = 0.005) and bone and soft tissue (p = 0.030) malignancies were independent and statistically significant prognostic factor of survival during the study period. It was further shown than depressed patients were found to have almost four fold greater risk of dying than non-depressed patients and patients with stage 4 cancer illness have a five fold greater risk of dying than patients with stage 1 disease. Furthermore, based on tumour types subjects with neurological, gynaecological, head and neck, bone and soft tissue and gastro intestinal tract malignancies were found to have approximately thirty-six, twenty-five, twenty-two, sixteen and seven fold greater risk of dying respectively when compared to subjects with genitourinary cancers. This study further affirms the need for health care providers to be aware of the psychological aspects of the cancer patient and provide appropriate therapy so as to ensure that this group of individuals would have enhanced survival rates.

Turkey 2017 Clinical Practice Guidelines on recommendations for screening diagnosing and managing hepatitis C virus.

The present guideline updates the Turkish recommendations for the screening, diagnosis and management of Hepatitis C virus (HCV) infection prepared by the Turkish Association for the Study of the Liver (TASL) and Viral Hepatitis Society (VHS). The aim of this guidance was to provide updates recommendations to physicians, who are interested in HCV care on the optimal screening, diagnosis and pre-treatment management for patients with HCV infection in Turkey. These recommendations, produced by panel experts, were aimed to addresses the management issues ranging from diagnosis and linkage to care, to the optimal treatment regimen in patients with HCV infection. Recommendations are based on evidence and opinions of more than 70% of the panelists. This guidance is supported by the memberships of two societies and not by pharmaceutical companies. This guidance will be updated frequently as new data become available.

Cost consciousness among physicians in the neonatal intensive care unit.

OBJECTIVE: The objectives of this study were (1) to describe the prevalence and correlates of cost consciousness among physician providers in neonatology and (2) to describe knowledge of cost of common medications, laboratory/imaging evaluations, hospitalization costs and reimbursements. STUDY DESIGN: A 54-item survey was administered to members of the Section on Neonatal-Perinatal Medicine of the American Academy of Pediatrics. RESULTS: Of the 602 participants, 37% reported cost consciousness in decision making. Adjusting for years in practice, gender, training level, type of practice setting and region of practice, formalized education about costs was associated with increased cost consciousness in practice (adjusted odds ratio (AOR): 3.4; 95% confidence interval (CI): 1.2 to 9.8). Working in a private practice setting was also associated with increased cost consciousness when ordering laboratory (AOR: 3.0; (95% CI: 1.2 to 7.6)) or imaging tests (AOR: 2.0; 95% CI: 1.0 to 4.8). CONCLUSIONS: We found variation in knowledge of cost. Formal education about costs and working in a private practice setting were associated with increased cost consciousness.

Does being a chief resident predict leadership in pediatric careers?

OBJECTIVE: Many organizations make efforts to identify future pediatric leaders, often focusing on chief residents (CRs). Identifying future leaders is an issue of great importance not only to the ultimate success of the organization but also to the profession. Because little is known regarding whether completing a CR predicts future leadership in medicine, we sought to determine if former pediatric CRs when compared with pediatric residents who were not CRs reported more often that they were leaders in their profession. DESIGN/METHODS: Twenty-four pediatric training programs stratified by resident size (<18, 18-36, and >36) and geography (East, South, Midwest, and West) were selected randomly from the Graduate Medical Education Directory (American Medical Association, Chicago, IL). Program directors were contacted by mail and telephone and asked to provide their housestaff rosters from 1965-1985. The resulting resident sample was surveyed by questionnaire in 1995. RESULTS: Fifteen of 17 program directors (88%) who possessed the requested data provided 1965-1985 rosters yielding a sample of 963 residents. Fifty-five percent of the resident sample (533) responded. Fifty-eight of the respondents had not completed a pediatric residency, leaving a survey sample of 475. Thirty-four percent (163) were CRs. The sample had a mean age of 47, 67% were male and 87% married. Fellowships were completed by 51%. More former CRs compared with non-CRs (75% vs 64%), more former fellows than non-fellows (75% vs 60%) and more males than females (74% vs 55%) reported they were professional leaders. These associations persisted in a logistic regression that controlled for CR status, gender, marital status, and fellowship status as leadership predictors. Former CRs, former fellows, and men were, respectively, 1.8, 2.3, and 2.3 times more likely to report professional leadership. CONCLUSIONS: Pediatric residents who were former CRs and/or fellows, and males were more likely to report professional leadership. Although men were more likely to report professional leadership, with more women entering pediatrics the reported gender differences will likely disappear over time.

Naloxone and vitamin E block stress-induced reduction of locomotor activity and elevation of plasma corticosterone.

Normal rats, on being repetitively stressed by being restrained in a tight container for two hours, had higher levels of plasma corticosterone compared to pre stress values. These rats also reacted to the stress by a behavioral response in which there was marked decrease in locomotor activity assessed by the open field test (pre stress: 71.3 +/- 2.6 squares crossed versus post stress: 14.3 +/- 2.5 squares crossed) by counting the number of squares entered by the rat over 5 minutes. By the 6th to 7th exposures to the repetitive stress, the rats adapted to the stress and had normal plasma corticosterone levels and locomotor activity scores comparable to the pre stress values. These responses to stress were completely blocked by the administration of 0.32 microg/100 g BW of naloxone i.p at 10 minutes prior to the stress. In rats fed with rat chow supplemented with 90 mg/kg rat chow or 150 mg/kg rat chow of vitamin E, there was significant reduction of the plasma corticosterone levels and improvement in the locomotor activity. Stress thus caused opioid mediated increase in plasma corticosterone and reduction in locomotor activity which could be blocked by naloxone. These stress responses probably also involved generation of oxygen free radicals which were scavenged by the vitamin E, thus reducing the effects of repetitive stress on locomotor activity and serum corticosterone levels.

Lymphocytotoxic antibodies in SLE: a review of the literature.

In a great majority of patients with systemic lupus erythematosus (SLE) lymphocytotoxic antibodies (LCA) are detected. The reported prevalence depends on the methods of detection and definition of test-positivity. The pathogenetic role of LCA remains unclear. Different reports show that LCA can have an influence on mononuclear cell function, e.g., on production of interferon, or specifically on T-cell function. In several studies T-cell specificity of LCA cannot be shown. Sometimes an overlap between LCA and anti-B2M antibodies is found, suggesting that LCA have anti-B2M activity. Anti-B2M activity might have an impact on T-cell as well as on B cell function. Next to the anti-B2M activity, binding to nuclear material is claimed. Investigating the role of LCA in respect to lymphopenia, a direct relationship cannot be found; however, LCA might induce interferon production, resulting in lymphopenia. Several studies show or claim a relationship between the presence of LCA and neurological manifestations in SLE patients; the results, however, remain questionable due to the difference in detection methods as well as in definition of central nervous system (CNS) involvement. In other studies, an increased incidence of LCA is reported in relatives of SLE patients as well. In addition, LCA are reported in quite a lot of other diseases such as rheumatoid arthritis, ankylosing spondylitis, malignancies and viral illnesses. This latter association has led to the assumption that LCA might have a virus-related origin.

Patient acceptable symptom states after totalhip or knee replacement at mid-term follow-up: Thresholds of the Oxford hip and knee scores.

OBJECTIVES: To define Patient Acceptable Symptom State (PASS) thresholds for the Oxford hip score (OHS) and Oxford knee score (OKS) at mid-term follow-up. METHODS: In a prospective multicentre cohort study, OHS and OKS were collected at a mean follow-up of three years (1.5 to 6.0), combined with a numeric rating scale (NRS) for satisfaction and an external validation question assessing the patient's willingness to undergo surgery again. A total of 550 patients underwent total hip replacement (THR) and 367 underwent total knee replacement (TKR). RESULTS: Receiver operating characteristic (ROC) curves identified a PASS threshold of 42 for the OHS after THR and 37 for the OKS after TKR. THR patients with an OHS ≥ 42 and TKR patients with an OKS ≥ 37 had a higher NRS for satisfaction and a greater likelihood of being willing to undergo surgery again. CONCLUSIONS: PASS thresholds appear larger at mid-term follow-up than at six months after surgery. With- out external validation, we would advise against using these PASS thresholds as absolute thresholds in defining whether or not a patient has attained an acceptable symptom state after THR or TKR. Cite this article: Bone Joint Res 2014;3:7-13.