Role of subcutaneous tissue endotoxin in the production of prostanoid-induced lung injury: comparison with intravenous endotoxin response

Local injection of endotoxin into soft tissues of the flank results in hypoxia and pulmonary hypertension. Our purpose was to determine whether this was caused by tissue prostanoid production or production by the lung as is seen with endotoxemia. Twenty-six sheep were prepared with lung and flank tissue lymph fistulae. Thirteen sheep were given 2 micrograms/kg Escherichia coli endotoxin into the flank soft tissue, six of which were pretreated with ibuprofen, 12.5 mg/kg. Thirteen sheep were given intravenous endotoxin, 2 micrograms/kg, with six pretreated with ibuprofen. An early hypertensive phase was noted with both insults characterized by pulmonary hypertension, hypoxia, and increased lung lymph flow (QL). With subcutaneous tissue endotoxin, there was a significant increase in tissue lymph TxB2 and 6-keto-PGF1 alpha when compared to lung lymph and increased values in venous plasma compared to arterial plasma, indicating tissue to be the source. With intravenous endotoxin, lung lymph and aortic plasma levels were significantly higher than tissue lymph and venous plasma, respectively. The hypoxia, hypertension and increased prostanoids were prevented using ibuprofen. An increased lung permeability phase was noted with intravenous endotoxin but not with tissue endotoxin. As expected, this phase was not inhibited with ibuprofen and, therefore, not prostanoid-induced.     

Epidemiology of human T cell leukemia virus type I infection in East Sepik Province, Papua New Guinea

A serological survey of 317 healthy residents of rural Papua New Guinea (PNG) showed a 26% prevalence of antibodies to human T cell leukemia virus type I (HTLV-I). Antibody to HTLV-I was detected in 16% of children less than or equal to 10 years old (including an 18-month-old child) and increased to greater than or equal to 24% in subjects greater than 20 years old. Prospective examination for antibody in 104 residents of one village revealed a seroconversion rate of 13% over a one-year period. The mean titer of antibody in these subjects (1:183) was lower (P less than .0005) than that in persons who were persistently seropositive (1:718). Analysis for clustering of infected subjects suggested that personal contact within the home played a role in the horizontal spread of HTLV-I. These data indicate that HTLV-I infection has a higher prevalence in PNG than in other endemic parts of the world, exposure occurs at an early age, and infection and/or seroconversion is common in adults as well as in children.     

Immune responses to major histocompatibility complex homozygous lymphoid cells in murine F1 hybrid recipients: implications for transfusion-associated graft-versus-host disease

Graft-versus-host disease (GVHD) is currently encountered after bone marrow transplantation and transfusion. GVHD associated with transfusion (TA-GVHD) in apparently immunocompetent recipients has been recently reported with increasing frequency. A consistent finding in many of these cases is that the recipient received blood from a donor homozygous for one of the recipient's HLA haplotypes. However, the observed frequency of TA-GVHD is much lower than the estimated probability of this donor/recipient combination. The potential role of recipient immune responses in controlling TA-GVHD was investigated using an analogous murine model in which GVHD is induced by the injection of parental lymphoid cells into unirradiated F1 hybrid recipients. The effect of various immune manipulations of the recipient of GVHD induction was assessed by determining the number of donor lymphoid cells required to induce GVHD responses. Whereas depletion of recipient CD4+ cells increased the number of donor cells needed to induce GVHD, depletion of recipient CD8+ and natural killer cells resulted in fewer donor cells being needed to induce a GVHD response. These studies suggest a central role for functioning recipient CD8 and natural killer cells in the down-regulation of TA-GVHD development in recipients.     

Shared decision-making for older adults with cardiovascular disease

Shared decision-making is appropriate for clinical decisions involving multiple reasonable options, which occur frequently in the cardiovascular care of older adults. The process includes the communication of relevant factual information between the patient and the clinician, elicitation of patient preferences, and a mutual agreement on the best course of action to meet the patient's personal goals. For older adults, there are common challenges and considerations with regard to shared decision-making, some of which (eg, cognitive impairment) may be biologically linked to cardiovascular disease. There are tools designed to facilitate the shared decision-making process, known as decision aids, which are broadly effective although have shortcomings when applied to older adults. Novel approaches in clinical research and health systems changes will go some way toward improving shared decision-making for older adults, but the greatest scope for improvement may be within the grass roots areas of communication skills, interdisciplinary teamwork, and simply asking our patients what matters most.     

The Impact of COVID-19 on Routine Medical Care and Cancer Screening

BackgroundCOVID-19 restrictions and fear dramatically changed the use of medical care. Understanding the magnitude of cancelled and postponed appointments and associated factors can help identify approaches to mitigate unmet need.ObjectiveTo determine the proportion of medical visits cancelled or postponed and for whom. We hypothesized that adults with serious medical conditions and those with higher anxiety, depressive symptoms, and avoidance-oriented coping would have more cancellations/postponements.DesignFour nationally representative cross-sectional surveys conducted online in May, July, October, and December 2020.Participants59,747 US adults who completed 15-min online surveys. 69% cooperation rate.MeasuresPhysical and mental health visits and cancer screening cancelled or postponed over prior 2 months. Plan to cancel or postpone visits over the next 2 months. Relationship with demographics, medical conditions, local COVID-19 death rate, anxiety, depressive symptoms, coping, intolerance of uncertainty, and perceived COVID-19 risk.Key ResultsOf the 58% (N = 34,868) with a medical appointment during the 2 months before the survey, 64% had an appointment cancelled or postponed in May, decreasing to 37% in December. Of the 41% of respondents with scheduled cancer screening, 20% cancelled/postponed, which was stable May to December. People with more medical conditions were more likely to cancel or postpone medical visits (OR 1.19 per condition, 95% CI 1.16, 1.22) and cancer screening (OR 1.20, 95% CI 1.15, 1.24). Race, ethnicity, and income had weak associations with cancelled/postponed visits, local death rate was unrelated, but anxiety and depressive symptoms were strongly related to cancellations, and this grew between May and December.ConclusionsCancelled medical care and cancer screening were more common among persons with medical conditions, anxiety and depression, even after accounting for COVID-19 deaths. Outreach and support to ensure that patients are not avoiding needed care due to anxiety, depression and inaccurate perceptions of risk will be important.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-07254-x.KEY WORDS: COVID-19, missed medical appointments, cancer screening     

Changes in left ventricular systolic wall stress during biventricular circulatory assistance

Extracorporeal membrane oxygenation (ECMO) reduces the systolic stress integral (SSI) in the normal left ventricle. We tested the hypothesis that the SSI does not decrease in poorly contracting, dilated, ejecting hearts during ECMO. In 14 sheep, four pairs of ultrasonic crystals measured changes in left ventricular (LV) wall thickness and three LV diameters. Volume calculations were validated by balloon distention of the ventricles after death (slope = 0.85; r = 0.85). SSI was measured during ECMO flows of 20 to 100 ml/kg/min in both normal and dilated, poorly contracting hearts produced by 30 minutes of warm ischemia. After warm ischemia, end-systolic elastance, an index of contractility, decreased from 8.3 +/- 0.6 mm Hg/ml to 2.9 +/- 0.4 mm Hg/ml (p = 0.001) and peak systolic pressure decreased from 47.4 +/- 0.7 mm Hg to 37.5 +/- 0.08 mm Hg (p = 0.01). In normal hearts, as ECMO flow increased, SSI decreased from 10.5 +/- 2.2 mm Hg.sec to 7.7 +/- 0.8 mm Hg.sec at 60 ml/kg/min (p = 0.001). However, in postischemic hearts, SSI progressively increased from 6.6 +/- 0.3 mm Hg.sec before ECMO to 12.4 +/- 1.8 mm Hg.sec at ECMO = 100 ml/kg/min. These studies indicate that the initial effect of ECMO on the poorly contracting, dilated heart increases LV wall stress and that the increase in stress is proportional to ECMO flow. The increase in stress is primarily due to an increase in afterload, which more than offsets decreases in systolic and diastolic volumes.