Identification of the rat NKG2D ligands,RAE1L and RRLT,and their role in allograft rejection

NKG2D is a receptor expressed by NK cells and subsets of T lymphocytes. On NK cells, NKG2D functions as a stimulatory receptor that induces effector functions. We cloned and expressed two rat NKG2D ligands, both members of the RAE1 family, RAE1L and RRLT, and demonstrate that these ligands can induce IFN‐γ secretion and cytotoxicity by rat NK cells. To examine changes in expression of NKG2D and the NKG2D ligands RAE1L and RRLT after transplantation, we used a Dark Agouti (DA)→Lewis rat model of liver transplantation. NKG2D expression was significantly increased in allogeneic liver grafts by day 7 post‐transplant. Ligands of NKG2D, absent in normal liver, were readily detected in both syngeneic and allogeneic liver grafts by day 1 post‐transplant. By day 7 post‐transplant, hepatocyte RAE1L and RRLT expression was significantly and specifically increased in liver allografts. In contrast to acute rejection that develops in the DA→Lewis model, transplantation of Lewis livers into DA recipients (Lewis→DA) results in spontaneous tolerance. Interestingly, expression of RAE1L and RRLT is low in Lewis→DA liver allografts, but significantly increased in DA→Lewis liver allografts undergoing rejection. In conclusion, our results suggest that expression of NKG2D ligands may be important in allograft rejection.     

An evaluation of venous thromboembolic risk in acutely ill medical patients immobilized at home: the AT-HOME Study.

Many risk factors for venous thromboembolism (VTE) in hospitalized medical patients are also present in medical outpatients. VTE prevention represents an important challenge for physicians treating patients at home. The AT-HOME study was a prospective cross-sectional observational study designed to assess awareness of the risk of VTE in immobilized acutely ill medical outpatients among German physicians, many of whom were participating in a national Continuing Medical Education (CME) program designed to raise awareness of VTE. The study involved 1210 medical patients who were acutely confined to bed at home. Physicians performed a subjective assessment of VTE risk, which was rated on a 10-point scale (1 = very low risk; 10 = very high risk). The risk of VTE was also assessed retrospectively by using a scorecard developed for use in hospitalized medical patients. Of the 1210 patients, 198 (16%) had risk scores of 0-4, 319 (26%) had scores of 5 or 6, and 693 (57%) had scores > or =7. Overall, 966 patients (80%) received thromboprophylaxis. The proportion of patients receiving thromboprophylaxis was 0% to 47% in risk score groups 0-4, 76% to 85% in groups 5 and 6, and 90% to 100% in risk score groups 7-10. In the retrospective assessment of VTE risk, 74% of patients were at high risk, 15% were at intermediate risk, and 11% were at low risk. The proportions of patients receiving thromboprophylaxis in these groups were 87%, 61%, and 55%, respectively. The involvement of physicians in educational activities focusing on VTE awareness appeared to create awareness of the risks of VTE in acutely ill medical outpatients.     

No difference in the skeletal muscle angiogenic response to aerobic exercise training between young and aged men

Ischaemia-induced skeletal muscle angiogenesis is impaired in aged compared with young mice. In humans, vascular endothelial growth factor (VEGF) mRNA and protein following an acute exercise bout are lower in aged compared with young untrained men. We hypothesized that exercise-induced skeletal muscle angiogenesis would be attenuated in aged compared with young men. In eight aged (mean age: 64 years) and six young (mean age: 25 years) sedentary men, muscle biopsies were obtained from the vastus lateralis prior to (Pre), after 1 week and after 8 weeks of an aerobic exercise training program for the measurement of capillarization and VEGF mRNA. Dialysate VEGF protein collected from the muscle interstitial space was measured at rest and during submaximal exercise at Pre, 1 week and 8 weeks. Exercise training increased capillary contacts (CC) and capillary-to-fibre perimeter exchange index (CFPE) of type I and IIA fibres similarly in young and aged. The CC of type IIA and IIB fibres was lower in aged compared with young independent of training status. Exercise-induced interstitial VEGF protein was lower in aged compared with young independent of training status. In untrained, greater exercise-induced interstitial VEGF protein during exercise was associated with greater type I, IIA and IIB CC. Exercise training increased VEGF mRNA similarly in young and aged. These results demonstrate that the angiogenic response to aerobic exercise training is not altered during the ageing process in humans. In addition, muscular activity-associated increases in interstitial VEGF protein may play an important role in the maintenance of skeletal muscle capillarization across the life span.     

NAT screening of blood donors for severe acute respiratory syndrome coronavirus can potentially prevent transfusion associated transmissions

BACKGROUND: The severe acute respiratory syndrome (SARS) was first described in February 2003. Close contact with symptomatic patients appears to be the main route of transmission, whereas blood transfusion transmission could not be ruled out. STUDY DESIGN AND METHODS: A SARS coronavirus (SARS-CoV) detection kit developed by C. Drosten (Bernhard Nocht Institute, BNI) was used to amplify SARS-CoV sequences from blood donor samples. We tested 31,151 blood donor samples in minipools of up to 96 samples. To validate the sensitivity of the assay, routine donor minipools (88 +/- 8 samples per pool) were spiked with plasma of an imported case of SARS or of a subsequently infected contact person, respectively. Gamma-irradiated cell culture supernatants of Vero E6 cells, infected with SARS-CoV, were used as positive controls. RESULTS: None of 31,151 blood donors were positive for the presence of SARS. Two 96-member plasma pools that were each spiked with 100 microL of plasma of the German index patient or his wife, respectively, were positive. Overall, 0.85 percent of test results had to be considered invalid owing to negative internal controls. CONCLUSION: A real-time CoV PCR test is able to detect SARS-CoV in viremic blood donor samples even in the beginning of the disease when patients present minor clinical symptoms. Thus the assay could potentially help to prevent transfusion-associated SARS-CoV transmissions.     

Impact of renal function in high bleeding risk patients undergoing percutaneous coronary intervention: a patient-level stratified analysis from four post-approval studies

Background

Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established.

Objective

We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF.

Methods

An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users.

Results

The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52–0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74–0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52–0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50–0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47–0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78–1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78–1.06; p 0.24).

Conclusions

In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

     

E-business in health care: does it contribute to strengthen consumer interest?

One of the goals of the reforms in the European health-care systems over the last two decades has been to make the health-care system more demand-oriented. There is not much known about the possible impact of E-business like approaches on this goal. This paper describes the concept of E-business. Two cases are introduced to illustrate the use of a simple E-business approach in a health-care setting. On the basis of these case studies, we aspect a reduction of the information disadvantages of patients. In our analysis, we also apply new institutional economy concepts, namely agency theory and transaction costs economics to focus on the position of the patient. Concluded is that it is more probable that preferences of demanders are answered by the suppliers of health care.     

Consistency and Completeness of Reported Outcomes in Randomized Trials of Primary Immunosuppression in Kidney Transplantation

Inconsistent and incomplete outcome reporting may make estimates of treatment effects from published randomized trials unreliable. We aimed to determine outcome reporting practices and source of differences in reporting quality among randomized trials of primary immunosuppression in kidney transplantation. We searched the Cochrane Renal Group's Specialized Register, 2000–2012, specified four core outcomes we expected trials to report, and recorded if and how completely each was reported. We identified 179 trials. One hundred sixty‐eight (94%) reported death, 145 (81%) as number dead and 119 (66%) as time to death. One hundred sixty‐five (92%) reported graft loss, 158 (88%) as number with graft loss and 127 (71%) as time to graft loss. One hundred twenty‐one (68%) reported creatinine and 114 (64%) estimated GFR (eGFR). One hundred forty‐one (79%) provided complete reports of number dead, 95 (53%) censored and 99 (55%) uncensored number with graft loss. Seventy‐three (41%) provided complete reports of time to death, 67 (37%) censored and 31 (17%) uncensored time to graft loss. Complete reporting of graft function was infrequent: 62 (35%) eGFR and 50 (28%) creatinine. All four outcomes were reported in any form in 61 (34%) and completely in 28 (16%) trials. No single trial or journal characteristic was consistently associated with complete outcome reporting. Outcome reporting in kidney transplant trials is inconsistent and frequently incomplete, and published estimates of treatment effects may be unreliable.     

Renal Angiotensin receptor type 1 and 2 upregulation in intrauterine growth restriction of newborn piglets

Epidemiological and experimental studies suggest that intrauterine growth restriction (IUGR) is associated with abnormalities in kidney development which is thought to be linked with alterations causing adult cardiovascular diseases. The renin-angiotensin system (RAS) plays an important role in the development of renal vascular and tubular structures, and is known to be altered by experimentally induced IUGR. These experimental models of IGUR have been criticized because they may have a more severe impact on intrauterine development than that which is normally encountered in humans. Therefore, we asked whether naturally occurring small-for-gestational-age newborn piglets exhibit features of altered RAS activity. We investigated the regional renal expression of angiotensin II type 1 (AT1) and AT2 receptors in normal-weight and IUGR piglets. The AT1 receptor mRNA expression was markedly enhanced in IUGR piglets, in the renal cortex by 64% and in the renal medulla by 52% (p < 0.05, compared with normal littermates). In contrast, mRNA expression for the AT2 receptor was similar in both the normal-weight and IUGR piglets. A significantly higher AT1 receptor protein expression was found in the IUGR piglets (p < 0.05) in the glomeruli, in the proximal and distal tubules, as well as in the collecting ducts by immunohistochemistry. Furthermore, AT2 receptor protein expression was significantly higher in the IUGR piglets (p < 0.05) in the subcapsular nephrogenic zone and in the distal tubules and collecting ducts. Thus, IUGR is accompanied by an upregulation of angiotensin II receptor expression in the kidneys of newborn piglets. This may indicate an alteration of the RAS in newborns suffering from naturally occurring IUGR.