Summary
Donation after circulatory death (DCD) has become an accepted practice in many countries and remains a focus of intense interest in the transplant community. The present study is aimed at ...providing a description of the current situation of DCD in European countries. Specific questionnaires were developed to compile information on DCD practices, activities and post‐transplant outcomes. Thirty‐five countries completed the survey. DCD is practiced in 18 countries: eight have both controlled DCD (cDCD) and uncontrolled DCD (uDCD) programs, 4 only cDCD and 6 only uDCD. All these countries have legally binding and/or nonbinding texts to regulate the practice of DCD. The no‐touch period ranges from 5 to 30 min. There are variations in ante and post mortem interventions used for the practice of cDCD. During 2008–2016, the highest DCD activity was described in the United Kingdom, Spain, Russia, the Netherlands, Belgium and France. Data on post‐transplant outcomes of patients who receive DCD donor kidneys show better results with grafts obtained from cDCD versus uDCD donors. In conclusion, DCD is becoming increasingly accepted and performed in Europe, importantly contributing to the number of organs available and providing acceptable post‐transplantation outcomes.
Summary
The access of non‐resident patients to the deceased donor waiting list (DDWL) poses different challenges. The European Committee on Organ Transplantation of the Council of Europe (CD‐P‐TO) ...has studied this phenomenon in the European setting. A questionnaire was circulated among the Council of Europe member states to inquire about the criteria applied for non‐residents to access their DDWL. Information was compiled from 28 countries. Less than 1% of recipients of deceased donor organs were non‐residents. Two countries never allow non‐residents to access the DDWL, four allow access without restrictions and 22 only under specific conditions. Of those, most give access to non‐resident patients already in their jurisdictions who are in a situation of vulnerability (urgent life‐threatening conditions). In addition, patients may be given access: (i) after assessment by a specific committee (four countries); (ii) within the framework of official cooperation agreements (15 countries); and (iii) after patients have officially lived in the country for a minimum length of time (eight countries). The ethical and legal implications of these policies are discussed. Countries should collect accurate information about residency status of waitlisted patients. Transparent criteria for the access of non‐residents to DDWL should be clearly defined at national level.
The access of non‐resident patients to the deceased donor waiting list (DDWL) poses different challenges. This study shows the different policies in place in the European setting and discuss its ethical and legal implications.
SARS-CoV-2 is the virus that causes coronavirus disease (COVID-19) which has reached pandemic levels resulting in significant morbidity and mortality affecting every inhabited continent. The large ...number of patients requiring intensive care threatens to overwhelm healthcare systems globally. Likewise, there is a compelling need for a COVID-19 disease severity test to prioritize care and resources for patients at elevated risk of mortality. Here, an integrated point-of-care COVID-19 Severity Score and clinical decision support system is presented using biomarker measurements of C-reactive protein (CRP), N-terminus pro B type natriuretic peptide (NT-proBNP), myoglobin (MYO), D-dimer, procalcitonin (PCT), creatine kinase-myocardial band (CK-MB), and cardiac troponin I (cTnI). The COVID-19 Severity Score combines multiplex biomarker measurements and risk factors in a statistical learning algorithm to predict mortality. The COVID-19 Severity Score was trained and evaluated using data from 160 hospitalized COVID-19 patients from Wuhan, China. Our analysis finds that COVID-19 Severity Scores were significantly higher for the group that died versus the group that was discharged with median (interquartile range) scores of 59 (40-83) and 9 (6-17), respectively, and area under the curve of 0.94 (95% CI 0.89-0.99). Although this analysis represents patients with cardiac comorbidities (hypertension), the inclusion of biomarkers from other pathophysiologies implicated in COVID-19 (e.g., D-dimer for thrombotic events, CRP for infection or inflammation, and PCT for bacterial co-infection and sepsis) may improve future predictions for a more general population. These promising initial models pave the way for a point-of-care COVID-19 Severity Score system to impact patient care after further validation with externally collected clinical data. Clinical decision support tools for COVID-19 have strong potential to empower healthcare providers to save lives by prioritizing critical care in patients at high risk for adverse outcomes.
Variability in large-scale wind power generation Kiviluoma, Juha; Holttinen, Hannele; Weir, David ...
Wind energy (Chichester, England),
September 2016, Letnik:
19, Številka:
9
Journal Article
The coronavirus disease (COVID-19) pandemic has resulted in significant morbidity and mortality; large numbers of patients require intensive care, which is placing strain on health care systems ...worldwide. There is an urgent need for a COVID-19 disease severity assessment that can assist in patient triage and resource allocation for patients at risk for severe disease.
The goal of this study was to develop, validate, and scale a clinical decision support system and mobile app to assist in COVID-19 severity assessment, management, and care.
Model training data from 701 patients with COVID-19 were collected across practices within the Family Health Centers network at New York University Langone Health. A two-tiered model was developed. Tier 1 uses easily available, nonlaboratory data to help determine whether biomarker-based testing and/or hospitalization is necessary. Tier 2 predicts the probability of mortality using biomarker measurements (C-reactive protein, procalcitonin, D-dimer) and age. Both the Tier 1 and Tier 2 models were validated using two external datasets from hospitals in Wuhan, China, comprising 160 and 375 patients, respectively.
All biomarkers were measured at significantly higher levels in patients who died vs those who were not hospitalized or discharged (P<.001). The Tier 1 and Tier 2 internal validations had areas under the curve (AUCs) of 0.79 (95% CI 0.74-0.84) and 0.95 (95% CI 0.92-0.98), respectively. The Tier 1 and Tier 2 external validations had AUCs of 0.79 (95% CI 0.74-0.84) and 0.97 (95% CI 0.95-0.99), respectively.
Our results demonstrate the validity of the clinical decision support system and mobile app, which are now ready to assist health care providers in making evidence-based decisions when managing COVID-19 patient care. The deployment of these new capabilities has potential for immediate impact in community clinics and sites, where application of these tools could lead to improvements in patient outcomes and cost containment.
Adefovir dipivoxil, a nucleotide analogue, demonstrated clinically significant antiviral activity in patients with chronic hepatitis B in phase 1 and 2 clinical trials.
We randomly assigned 185 ...patients with chronic hepatitis B who were negative for hepatitis B e antigen (HBeAg) to receive either 10 mg of adefovir dipivoxil or placebo once daily for 48 weeks in a 2:1 ratio and a double-blind manner. The primary end point was histologic improvement.
At week 48, 64 percent of patients who had base-line liver-biopsy specimens available in the adefovir dipivoxil group had improvement in histologic liver abnormalities (77 of 121), as compared with 33 percent of patients in the placebo group (19 of 57, P<0.001). Serum hepatitis B virus (HBV) DNA levels were reduced to fewer than 400 copies per milliliter in 51 percent of patients in the adefovir dipivoxil group (63 of 123) and in 0 percent of those in the placebo group (0 of 61, P<0.001). The median decrease in log-transformed HBV DNA levels was greater with adefovir dipivoxil treatment than with placebo (3.91 vs. 1.35 log copies per milliliter, P<0.001). Alanine aminotransferase levels had normalized at week 48 in 72 percent of patients receiving adefovir dipivoxil (84 of 116), as compared with 29 percent of those receiving placebo (17 of 59, P<0.001). No HBV polymerase mutations associated with resistance to adefovir were identified. The safety profile of adefovir dipivoxil was similar to that of placebo.
In patients with HBeAg-negative chronic hepatitis B, 48 weeks of adefovir dipivoxil treatment resulted in significant histologic, virologic, and biochemical improvement, with an adverse-event profile similar to that of placebo. There was no evidence of the emergence of adefovir-resistant HBV polymerase mutations.
A small fraction of oral lichenoid conditions (OLC) have potential for malignant transformation. Distinguishing OLCs from other oral potentially malignant disorders (OPMDs) can help prevent ...unnecessary concern or testing, but accurate identification by nonexpert clinicians is challenging due to overlapping clinical features. In this study, the authors developed a 'cytomics-on-a-chip' tool and integrated predictive model for aiding the identification of OLCs.
All study subjects underwent both scalpel biopsy for histopathology and brush cytology. A predictive model and OLC Index comprising clinical, demographic, and cytologic features was generated to discriminate between subjects with lichenoid (OLC+) (N = 94) and nonlichenoid (OLC−) (N = 237) histologic features in a population with OPMDs.
The OLC Index discriminated OLC+ and OLC− subjects with area under the curve (AUC) of 0.76. Diagnostic accuracy of the OLC Index was not significantly different from expert clinician impressions, with AUC of 0.81 (P = .0704). Percent agreement was comparable across all raters, with 83.4% between expert clinicians and histopathology, 78.3% between OLC Index and expert clinician, and 77.3% between OLC Index and histopathology.
The cytomics-on-a-chip tool and integrated diagnostic model have the potential to facilitate both the triage and diagnosis of patients presenting with OPMDs and OLCs.
As of 8 August 2022, SARS-CoV-2, the causative agent of COVID-19, has infected over 585 million people and resulted in more than 6.42 million deaths worldwide. While approved SARS-CoV-2 spike (S) ...protein-based vaccines induce robust seroconversion in most individuals, dramatically reducing disease severity and the risk of hospitalization, poorer responses are observed in aged, immunocompromised individuals and patients with certain pre-existing health conditions. Further, it is difficult to predict the protection conferred through vaccination or previous infection against new viral variants of concern (VoC) as they emerge. In this context, a rapid quantitative point-of-care (POC) serological assay able to quantify circulating anti-SARS-CoV-2 antibodies would allow clinicians to make informed decisions on the timing of booster shots, permit researchers to measure the level of cross-reactive antibody against new VoC in a previously immunized and/or infected individual, and help assess appropriate convalescent plasma donors, among other applications. Utilizing a lab-on-a-chip ecosystem, we present proof of concept, optimization, and validation of a POC strategy to quantitate COVID-19 humoral protection. This platform covers the entire diagnostic timeline of the disease, seroconversion, and vaccination response spanning multiple doses of immunization in a single POC test. Our results demonstrate that this platform is rapid (~15 min) and quantitative for SARS-CoV-2-specific IgG detection.
As COVID-19 pandemic public health measures are easing globally, the emergence of new SARS-CoV-2 strains continue to present high risk for vulnerable populations. The antibody-mediated protection ...acquired from vaccination and/or infection is seen to wane over time and the immunocompromised populations can no longer expect benefit from monoclonal antibody prophylaxis. Hence, there is a need to monitor new variants and its effect on vaccine performance. In this context, surveillance of new SARS-CoV-2 infections and serology testing are gaining consensus for use as screening methods, especially for at-risk groups. Here, we described an improved COVID-19 screening strategy, comprising predictive algorithms and concurrent, rapid, accurate, and quantitative SARS-CoV-2 antigen and host antibody testing strategy, at point of care (POC). We conducted a retrospective analysis of 2553 pre- and asymptomatic patients who were tested for SARS-CoV-2 by RT-PCR. The pre-screening model had an AUC (CI) of 0.76 (0.73-0.78). Despite being the default method for screening, body temperature had lower AUC (0.52 0.49-0.55) compared to case incidence rate (0.65 0.62-0.68). POC assays for SARS-CoV-2 nucleocapsid protein (NP) and spike (S) receptor binding domain (RBD) IgG antibody showed promising preliminary results, demonstrating a convenient, rapid (<20 min), quantitative, and sensitive (ng/mL) antigen/antibody assay. This integrated pre-screening model and simultaneous antigen/antibody approach may significantly improve accuracy of COVID-19 infection and host immunity screening, helping address unmet needs for monitoring vaccine effectiveness and severe disease surveillance.
Copy number alteration (CNA) profiling of human tumors has revealed recurrent patterns of DNA amplifications and deletions across diverse cancer types. These patterns are suggestive of conserved ...selection pressures during tumor evolution but cannot be fully explained by known oncogenes and tumor suppressor genes. Using a pan‐cancer analysis of CNA data from patient tumors and experimental systems, here we show that principal component analysis‐defined CNA signatures are predictive of glycolytic phenotypes, including 18F‐fluorodeoxy‐glucose (FDG) avidity of patient tumors, and increased proliferation. The primary CNA signature is enriched for p53 mutations and is associated with glycolysis through coordinate amplification of glycolytic genes and other cancer‐linked metabolic enzymes. A pan‐cancer and cross‐species comparison of CNAs highlighted 26 consistently altered DNA regions, containing 11 enzymes in the glycolysis pathway in addition to known cancer‐driving genes. Furthermore, exogenous expression of hexokinase and enolase enzymes in an experimental immortalization system altered the subsequent copy number status of the corresponding endogenous loci, supporting the hypothesis that these metabolic genes act as drivers within the conserved CNA amplification regions. Taken together, these results demonstrate that metabolic stress acts as a selective pressure underlying the recurrent CNAs observed in human tumors, and further cast genomic instability as an enabling event in tumorigenesis and metabolic evolution.
Synopsis
A pan‐cancer and cross‐species analysis of recurrent copy number alteration (CNA) patterns reveals that coordinated CNA of energy metabolism genes provides a selective advantage during tumorigenesis by promoting glycolytic metabolism.
Amplifications of glycolysis‐associated genes are conserved and enriched in tumors with high genomic instability, with glycolysis thus functioning as an “oncopathway” in regard to shaping the cancer CNA genome.
Copy number signatures predict the glycolytic activity of primary breast cancers and breast cancer cell lines.
Genetic manipulation of glycolysis genes prior to the initiation of genomic instability alters the resulting genomic copy number landscape at the endogenous loci.
Complex but coordinated DNA copy number changes can contribute to cancer phenotypes in genomically unstable tumors.
A pan‐cancer and cross‐species analysis of recurrent copy number alteration (CNA) patterns reveals that coordinated CNA of energy metabolism genes provides a selective advantage during tumorigenesis by promoting glycolytic metabolism.
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