Analysis of platelet adhesion to a collagen-coated surface under flow conditions: the involvement of glycoprotein VI in the platelet adhesion

Platelet adhesion to the exposed surface of the extracellular matrix in flowing blood is the first and critical reaction for in vivo thrombus formation. However, the mechanism of this in vivo platelet adhesion has yet to be studied extensively. One of the reasons for this is the lack of a practical assay method for assessing platelet adhesion under flow conditions. We have devised an assay method (the fluorescent adhesion assay) that is based on the technique originally reported by Hubbell and McIntire (Biomaterials 7:354, 1986) with some modifications to make it more amenable for assaying small samples and have developed an analysis method to quantify the extent of platelet adhesion and aggregation from fluorescence images by using a computer-assisted image analysis system. In our assay, platelet adhesion, expressed as the percentage of the area covered by adhered platelets, was found to increase biphasically as a function of time. In the first phase, platelets interacted with the coated collagen, transiently stopping on the surface; we called this reaction the temporary arrest. In the second phase, platelets adhered much more rapidly and permanently on the surface, and this adhesion was dependent on the shear rate; platelets formed aggregates in this phase. We used our assay to analyze the effects of platelet aggregation inhibitors on platelet adhesion. All three examined inhibitors, EDTA (10 mmol/L), antiglycoprotein (GP) IIb/IIIa, and GRGDS peptide (1 mmol/L), inhibited the second phase adhesion in flowing blood. Furthermore, GPVI-deficient platelets also showed defective second-phase adhesion under the same conditions. These results suggested that GPIIb/IIIa activation and GPVI contribute to the reaction inducing the second phase. The second-phase adhesion has been extensively investigated, and the consensus is that this reaction is mainly attributable to the platelet-platelet interaction. In this report, we were able to detect an earlier reaction, the temporary arrest. This temporary arrest would reflect the fast and weak interaction between platelet GPIb/IX and collagen-von Willebrand factor complexes on the collagen-coated surface.     

Hematopoietic growth factors for graft failure after bone marrow transplantation: a randomized trial of granulocyte-macrophage colony- stimulating factor (GM-CSF) versus sequential GM-CSF plus granulocyte- CSF

Delay in hematologic recovery after bone marrow transplantation (BMT) can extend and amplify the risks of infection and hemorrhage, compromise patients' survival, and increase the duration and cost of hospitalization. Because current studies suggest that granulocyte- macrophage (GM) colony-stimulating factor (CSF) may potentiate the sensitivity of hematopoietic progenitor cells to G-CSF, we performed a prospective, randomized trial comparing GM-CSF (250 micrograms/m2/d x 14 days) versus sequential GM-CSF x 7 days followed by G-CSF (5 micrograms/kg/d x 7 days) as treatment for primary or secondary graft failure after BMT. Eligibility criteria included failure to achieve a white blood cell (WBC) count > or = 100/microL by day +21 or > or = 300/microL by day +28, no absolute neutrophil count (ANC) > or = 200/microL by day +28, or secondary sustained neutropenia after initial engraftment. Forty-seven patients were enrolled: 23 received GM-CSF (10 unrelated, 8 related allogeneic, and 5 autologous), and 24 received GM- CSF followed by G-CSF (12 unrelated, 7 related allogeneic, and 5 autologous). For patients receiving GM-CSF alone, neutrophil recovery (ANC > or = 500/microL) occurred between 2 and 61 days (median, 8 days) after therapy, while those receiving GM-CSF+G-CSF recovered at a similar rate of 1 to 36 days (median, 6 days; P = .39). Recovery to red blood cell (RBC) transfusion independence was slow, occurring 6 to 250 days (median, 35 days) after enrollment with no significant difference between the two treatment groups (GM-CSF: median, 30 days; GM-CSF+G- CSF; median, 42 days; P = .24). Similarly, platelet transfusion independence was delayed until 4 to 249 days (median, 32 days) after enrollment, with no difference between the two treatment groups (GM- CSF: median, 28 days; GM-CSF+G-CSF: median, 42 days; P = .38). Recovery times were not different between patients with unrelated donors and those with related donors or autologous transplant recipients. Survival at 100 days after enrollment was superior after treatment with GM-CSF alone. Only 1 of 23 patients treated with GM-CSF died versus 7 of 24 treated with GM-CSF+G-CSF who died 16 to 84 days (median, 38 days) after enrollment, yielding Kaplan-Meier 100-day survival estimates of 96% +/- 8% for GM-CSF versus 71% +/- 18% for GM-CSF+G-CSF (P = .026). These data suggest that sequential growth factor therapy with GM-CSF followed by G-CSF offers no advantage over GM-CSF alone in accelerating trilineage hematopoiesis or preventing lethal complications in patients with poor graft function after BMT.(ABSTRACT TRUNCATED AT 400 WORDS)     

National Patterns of Risk-Standardized Mortality and Readmission After Hospitalization for Acute Myocardial Infarction,Heart Failure,and Pneumonia: Update on Publicly Reported Outcomes Measures Based on the 2013 Release

BACKGROUND

The Centers for Medicare & Medicaid Services publicly reports risk-standardized mortality rates (RSMRs) within 30-days of admission and, in 2013, risk-standardized unplanned readmission rates (RSRRs) within 30-days of discharge for patients hospitalized with acute myocardial infarction (AMI), heart failure (HF), and pneumonia. Current publicly reported data do not focus on variation in national results or annual changes.

OBJECTIVE

Describe U.S. hospital performance on AMI, HF, and pneumonia mortality and updated readmission measures to provide perspective on national performance variation.

DESIGN

To identify recent changes and variation in national hospital-level mortality and readmission for AMI, HF, and pneumonia, we performed cross-sectional panel analyses of national hospital performance on publicly reported measures.

PARTICIPANTS

Fee-for-service Medicare and Veterans Health Administration beneficiaries, 65 years or older, hospitalized with principal discharge diagnoses of AMI, HF, or pneumonia between July 2009 and June 2012. RSMRs/RSRRs were calculated using hierarchical logistic models risk-adjusted for age, sex, comorbidities, and patients’ clustering among hospitals.

Results

Median (range) RSMRs for AMI, HF, and pneumonia were 15.1% (9.4–21.0%), 11.3% (6.4–17.9%), and 11.4% (6.5–24.5%), respectively. Median (range) RSRRs for AMI, HF, and pneumonia were 18.2% (14.4–24.3%), 22.9% (17.1–30.7%), and 17.5% (13.6–24.0%), respectively. Median RSMRs declined for AMI (15.5% in 2009–2010, 15.4% in 2010–2011, 14.7% in 2011–2012) and remained similar for HF (11.5% in 2009–2010, 11.9% in 2010–2011, 11.7% in 2011–2012) and pneumonia (11.8% in 2009–2010, 11.9% in 2010–2011, 11.6% in 2011–2012). Median hospital-level RSRRs declined: AMI (18.5% in 2009–2010, 18.5% in 2010–2011, 17.7% in 2011–2012), HF (23.3% in 2009–2010, 23.1% in 2010–2011, 22.5% in 2011–2012), and pneumonia (17.7% in 2009–2010, 17.6% in 2010–2011, 17.3% in 2011–2012).

Conclusions

We report the first national unplanned readmission results demonstrating declining rates for all three conditions between 2009–2012. Simultaneously, AMI mortality continued to decline, pneumonia mortality was stable, and HF mortality experienced a small increase.     

Hypertension Awareness and Control Among Young Adults in the National Longitudinal Study of Adolescent Health

BACKGROUND

Young adults are less likely than older adults to be aware they have hypertension or to be treated for hypertension.

OBJECTIVE

To describe rates of hypertension awareness and control in a cohort of young adults and understand the impact of health insurance, utilization of preventive care, and self-perception of health on rates of hypertension awareness and control in this age group.

DESIGN AND PARTICIPANTS

Cross-sectional study of 13,512 young adults participating in Wave IV of the National Longitudinal Study of Adolescent Health in 2007–2008.

MAIN MEASURES

We defined hypertension as an average of two measured systolic blood pressures (SBP) ≥ 140 mmHg, diastolic blood pressures (DBP) ≥ 90 mmHg, or self-report of hypertension. We defined hypertension awareness as reporting having been told by a health care provider that one had high blood pressure, and assessed awareness among those with uncontrolled hypertension. We considered those aware of having hypertension controlled if their average measured SBP was < 140 mmHg and DBP was < 90 mmHg.

KEY RESULTS

Of the 3,303 young adults with hypertension, 2,531 (76 %) were uncontrolled, and 1,893 (75 %) of those with uncontrolled hypertension were unaware they had hypertension. After adjustment for age, sex, race/ethnicity, weight status, income, education, alcohol and tobacco use, young adults with uncontrolled hypertension who had (vs. didn’t have) routine preventive care in the past 2 years were 2.4 times more likely (95 % confidence interval [CI] 1.68–3.55) to be aware, but young adults who believed they were in excellent (vs. less than excellent) health were 64 % less likely to be aware they had hypertension (OR 0.36, 95 % CI 0.23–0.57). Neither preventive care utilization nor self-rated health was associated with blood pressure control.

CONCLUSIONS

In this nationally representative group of young adults, rates of hypertension awareness and control were low. Efforts to increase detection of hypertension must address young adults’ access to preventive care and perception of their need for care.     

Missing canines: a novel aetiology

Infant oral mutilation is the practice of removing developing tooth germs, commonly the mandibular canine, in infants up to the age of 1 year. Subsequent complications include missing, impacted or hypoplastic permanent anterior and canine teeth. We report on a case of bilaterally missing lower canines thought to be due to infant oral mutilation. It is important that general dental practitioners are aware of this practice and resulting complications when treating families from sub‐Saharan East Africa.     

A prospective study on TT virus infection in transfusion-dependent patients with beta-thalassemia

A novel DNA virus designated TT virus (TTV) has been reported to be involved in the development of posttransfusion non-A-C hepatitis. We evaluated the frequency and natural course of TTV infection in a cohort of transfusion-dependent thalassemic patients in a 3-year follow-up study. Ninety-three serum hepatitis C virus (HCV) antibody-negative patients (median age of 8 years; range, 0 to 25) from eight centers were studied. Of them, 34 (37%) had an abnormal alanine-aminotransferase (ALT) baseline pattern, and the other 12 (13%) showed ALT flare-ups during the follow-up. TTV DNA in patient sera collected at the time of enrollment and at the end of follow-up was determined by polymerase chain reaction (PCR). In parallel, serum samples from 100 healthy blood donors were also tested. At baseline, 87 patient sera (93.5%) tested positive for the TTV DNA. Of these TTV DNA-positive patients, 84 (96.5%) remained viremic at the end of the study period. Of the 6 TTV DNA-negative patients, 3 acquired TTV infection during follow-up. However, no definite relation was observed between the results of TTV DNA determination and ALT patterns. TTV viremia was also detectable in 22% of blood donors. In conclusion, TTV infection is frequent and persistent among Italian transfusion-dependent patients. The high rate of viremia observed in healthy donors indicates that the parenteral route is not the only mode of TTV spread.     

Singapore Paediatric Resuscitation Guidelines 2021

We present the 2021 Singapore Paediatric Resuscitation Guidelines. The International Liaison Committee on Resuscitation’s Pediatric Taskforce Consensus Statements on Science and Treatment Recommendations, which was published in October 2020, and the updated resuscitation guidelines from the American Heart Association and European Resuscitation Council, were reviewed and discussed by the committee. These recommendations were derived after deliberation of peer-reviewed evidence updates on paediatric resuscitation and took into consideration the local setting and clinical practice.     

肺癌CT普查--疾病分期与肿瘤大小的关系

目的：肺癌分期与肿瘤直径的关系已被证实是一个预后指标,因此被纳入1986年肺癌分类的国际系统。近年来由于CT飞速发展,人们可以诊断出更小的肺癌,于是有人提倡对肺癌Ⅰ期进一步分期,即根据肿瘤直径小于还是大于30mm,将无确切远处淋巴结转移的病例（Ⅰ期病例）细分为Ⅰa和Ⅰb期。在诊断无症状（即潜伏）的肺癌时,CT普查的开展使人们考虑肿瘤大小的预后价值。在此我们对CT普查诊断的无症状潜伏型肺癌作了分期与大小关系的报道。