Care processes and clinical outcomes of continuous outpatient support with inotropes (COSI) in patients with refractory endstage heart failure

BACKGROUND: This study describes the process and outcomes of continuous outpatient support with inotropes (COSI) in patients with Stage D heart failure (HF). Although Stage D HF has recently been defined as end-stage disease requiring special interventions for survival such as COSI or ventricular assist devices, concern has been raised regarding the safety, efficacy, mortality outcomes, and ethics of COSI. METHODS AND RESULTS: Inotrope dependence was defined as worsening of the patient's clinical status with attempted inotrope withdrawal such that the patient was deemed unlikely to survive to permit hospital discharge. A care process for COSI was designed; baseline and outcome variables were evaluated. COSI was administered to 36 inotrope-dependent patients (age 55.4 +/- 9.5 years, 24 males). Baseline characteristics (mean +/- SD) were consistent with Stage D HF: left ventricular ejection fraction 19.9 +/- 8.5, left ventricular end-diastolic dimension (LVEDD) 70 +/- 10 mm, systolic blood pressure 97.4 +/- 13.4 mm Hg, serum creatinine 1.5 +/- 0.6, serum sodium 131.7 +/- 5.3; 69 HF hospitalizations (mean 1.9 +/- 1.8) 6 months before COSI initiation. Symptomatic hypotension, increasing dyspnea, renal dysfunction, and hypoperfusion most commonly prevented inotrope withdrawal. Despite Stage D HF, patients were discharged with COSI ambulatory, oriented, and pain free. Rehospitalizations were 46; 6 subjects accounted for 24 hospitalizations; 23 had 0 or 1 rehospitalization. Median survival was 3.4 months (range 0.2-26.3 months); and 3-, 6-, and 12-month Kaplan Meier survival was 51%, 26%, and 6%, respectively. The majority of patients died at home and chose to not undergo resuscitation attempts. CONCLUSION: COSI may be an acceptable treatment option for Stage D HF.     

Hepatosplenic T-cell lymphoma: sinusal/sinusoidal localization of malignant cells expressing the T-cell receptor gamma delta

Peripheral T-cell lymphomas consist of a clinically heterogeneous group of malignant disorders whose immunophenotype usually corresponds to that of normal mature T cells. We describe and correlate the clinical, histopathologic, phenotypic, and genotypic findings in two patients with malignant lymphoma presenting with hepatosplenic disease. The morphologic pattern of lymphoma was that of a sinusal/sinusoidal infiltration in spleen, marrow, and liver. This morphologic characteristic was associated with the presence of a productive clonal rearrangement of the T-cell receptor (TCR) delta gene. Lymphoma cells expressed a CD3-TCR-gamma delta- phenotype. They were also double negative (ie, CD4-CD8-) and lacked the CD5 and CD7 antigens. In one patient, tumor progression was associated with phenotypic changes that resulted in a CD3-TCR-gamma delta- phenotype with the same delta-gene rearrangement as initially. These observations suggest the existence of a new type of peripheral T-cell lymphoma characterized by its hepatosplenic presentation, and by the sinusal/sinusoidal tropism and the TCR-gamma delta phenotype of the malignant cells.     

Further specificity characterization of von Willebrand factor inhibitors developed in two patients with severe von Willebrand disease

Circulating inhibitors against von Willebrand factor (vWF) that show the properties of heterologous IgG antibodies have been described in a few patients with severe von Willebrand disease (vWD). The present study provides further characterization of inhibitors from two patients with severe vWD. Inhibitors in both, like polyclonal rabbit antibody, detected all sizes of multimers and the complex structure of each multimer from platelets and plasma of normal individuals as well as from plasma of patients with IIA, IIB, and IIC vWD. Both inhibitors and the rabbit antibody reacted mainly with the intact 225-Kd vWF subunit and the 189-H and 140-Kd fragments in contrast to monoclonal antibodies specific for vWF fragments that detected a higher relative proportion of 176-Kd fragment. Furthermore, all these antibodies recognized fragment III, although one inhibitor and rabbit polyclonal antibody reacted poorly and the other inhibitor did not react at all with reduced fragment II of vWF digested with Staphylococcus aureus V-8 protease. These data suggest that although human inhibitors from severe vWD patients may behave, to some extent, as polyclonal heterologous antibodies against native vWF, the former show striking differences in their target specificity as well as a much broader specificity than that described for human factor VIII inhibitors.     

Aerobic Reduction of Cytochrome b566 in Pigeon-Heart Mitochondria

In anaerobic, uncoupled pigeon-heart mitochondria treated with oxidizable substrate, the cytochrome b(566) remains largely oxidized. In the presence of antimycin A, addition of oxygen induces a reduction of this cytochrome. The rate of cytochrome b(566) reduction is comparable to and dependent on the rate of cytochrome c(1) oxidation. Kinetic data suggest that either ubiquinone or another donor of similar potential provides electrons for the reduction of cytochrome b(566). It is postulated that the aerobic reduction of cytochrome b(566) is directly related to the energy conservation at site II.     

Chemoreceptor influence on pulmonary blood flow during unilateral hypoxia in dogs

Dogs anesthetized with 30 mg/kg pentobarbital were artificially respired after differential cannulation of the main stem bronchi. Following median sternotomy, blood flow was monitored by electromagnetic flow probes on the left pulmonary artery (QL) and on the pulmonary trunk or aorta, QT. Following 10 min of bilateral 100% O2, QL was 42.5 +/- 7% of QT. When 6% O2, was substituted as the gas mixture inspired by the left lung while the right lung remained on 100% O2, PaO2 was above 70 mm Hg and QL fell to 24.5 +/- 5% of QT. Room air was then used to ventilate the right lung while the left lung remained on 6% O2. This caused PaO2 to fall to 42.3 +/- 3 MM Hg and QL to rise to 38.3 +/- 6% QT. This increase in blood flow to the unilaterally hypoxic lung during systemic hypoxemia did not occur in dogs after peripheral chemoreceptor denervation. Therefore, interference with the local response to alveolar hypoxia during systemic hypoxemia appears to be mediated by the arterial chemoreceptors.     

Changes in cell surface antigen expression during hemopoietic differentiation

Human bone marrow cells were separated on a fluorescence activated cell sorter (FACS) according to their binding of a series of monoclonal antibodies; the positive and negative fractions were cloned for erythroid burst and colony-forming units (BFU-E and CFU-E) and myeloid colony-forming units (CFU-GM), and cytocentrifuge slides were prepared for microscopy of maturing precursors. The pattern of antigen expression on hemopoietic progenitor and precursor populations has been established using antibodies defining blood group (A, I/i), HLA- associated (*A, B, C, DR, DC1), lineage specific, and transferrin receptor antigens. Like monomorphic HLA-DR, the antigen defined by monoclonal antibody OKT10 is expressed on the earliest progenitors and lost during differentiation, suggesting a role in interactions regulating the differentiation of these cells. The HLA-linked DC1 determinant, in contrast to HLA-DR, is not expressed at a detectable level on progenitor cells. Although a lineage-specific early antigen has not been identified, the transferrin receptor is expressed on the majority of erythroid progenitors, but only weakly on myeloid progenitors, and may provide an approach to isolating erythroid progenitors. These and earlier studies with monoclonal antibodies against HLA-DR and glycophorin now provide a detailed "map" of antigen expression during hemopoietic differentiation.     

Differential effects of hormones on precocious yolk sac retraction in chick embryos following administration by a new technique.

A simple new technique allowing continuous application of hormones to the chorioallantoic membrane of the embryonated chicken egg is described. By use of this technique, by grafting the pars distalis, and by monitoring the hormonal response, with inhibitors and with induction of glucocorticoid-dependent liver enzymes, yolk sac retraction has been shown to be linked with thyroidal and not with adrenocortical or several other hormones. Evidence is also presented that the pars distalis, from chickens up to at least 18 months old, is capable of autonomous performance of certain adrenocorticotrophic or thyrotrophic functions when grafted on the chorioallantoic membrane of embryonated eggs.     

Combating an invisible enemy:The American military response to global pandemics

The present moment is not the first time that America has found itself at war with a pathogen during a time of international conflict.Between crowded barracks at home and trenches abroad,wartime conditions helped enable the spread of influenza in the fall of 1918 during World War Ⅰ such that an estimated 20％-40％ of U.S.military members were infected.While the coronavirus disease 2019 (COVID-19) pandemic is unparalleled for most of today's population,it is essential to not view it as unprecedented lest the lessons of past pandemics and their effect on the American military be forgotten.This article provides a historical perspective on the effect of the most notable antecedent pandemic,the Spanish Influenza epidemic,on American forces with the goal of understanding the interrelationship of global pandemics and the military,highlighting the unique challenges of the current pandemic,and examining how the American military has fought back against pandemics both at home and abroad,both 100 years ago and today.