Metagenomic analysis of bloodstream infections in patients with acute leukemia and therapy-induced neutropenia.

Leukemic patients are often immunocompromised due to underlying conditions, comorbidities and the effects of chemotherapy, and thus at risk for developing systemic infections. Bloodstream infection (BSI) is a severe complication in neutropenic patients, and is associated with increased mortality. BSI is routinely diagnosed with blood culture, which only detects culturable pathogens. We analyzed 27 blood samples from 9 patients with acute leukemia and suspected BSI at different time points of their antimicrobial treatment using shotgun metagenomics sequencing in order to detect unculturable and non-bacterial pathogens. Our findings confirm the presence of bacterial, fungal and viral pathogens alongside antimicrobial resistance genes. Decreased white blood cell (WBC) counts were associated with the presence of microbial DNA, and was inversely proportional to the number of sequencing reads. This study could indicate the use of high-throughput sequencing for personalized antimicrobial treatments in BSIs.

Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin.

Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N=39) with defined cognitive deficit (>or=1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40,000 IU rhEPO (N=20) or placebo (N=19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) - perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.

Status of the myocardium and infarct-related coronary artery in 19 necropsy patients with acute recanalization using pharmacologic (streptokinase, r-tissue plasminogen activator), mechanical (percutaneous transluminal coronary angioplasty) or combined types of reperfusion therapy.

In acute myocardial infarction, myocardial salvage is dependent on rapid restoration of blood flow. Pharmacologic (streptokinase, recombinant tissue-type plasminogen activator), mechanical (percutaneous transluminal coronary angioplasty, guide wire perforation) or combined forms of reperfusion therapy can accomplish this goal, but their effects on infarcted myocardium and vessel occlusion site have not been compared at necropsy. The heart of 19 necropsy patients who had received various forms of acute reperfusion therapy was studied: 14 had pharmacologic or combined forms of reperfusion therapy (13 streptokinase and 1 tissue-type plasminogen activator, including 4 with combined balloon angioplasty) and 5 had had purely mechanical (balloon angioplasty) reperfusion therapy. Reperfusion was initially clinically successful in all 19 patients with the average time from onset of symptoms to reperfusion being 3.7 hours. Necropsy observations separated the 19 patients into distinct subgroups based on changes in the myocardium and infarct-related coronary arteries. Of the 19 patients, 14 (74%) had hemorrhagic myocardial infarction and they all received pharmacologic or combined forms of reperfusion therapy. The remaining five patients (26%) had nonhemorrhagic (anemic) infarction and were treated with balloon angioplasty therapy alone. Increased luminal cross-sectional area was present in 8 of 9 patients with acute balloon angioplasty but severe coronary atherosclerotic plaque remained in 9 of 10 patients without acute balloon angioplasty. Severe hemorrhage surrounded angioplasty sites in all four patients who also received streptokinase or tissue-type plasminogen activator. Severe bleeding at the angioplasty site compromised the dilated coronary lumen in one patient. No patient with angioplasty alone had intraplaque bleeding. Thus, acute coronary balloon angioplasty reperfusion therapy alone appears to avoid the potentially adverse effects of myocardial and intraplaque hemorrhage while simultaneously increasing luminal cross-sectional area at the site of acute occlusion.

Histologic evidence of distal coronary thromboembolism. A complication of acute proximal coronary artery thrombolysis therapy.

Distal migration of occluding coronary thrombus during thrombolysis therapy for acute myocardial infarction rarely has been observed angiographically. Necropsy documentation of the final location of embolic fragments in this circumstance has not been reported previously. This report documents multiple occluded intramyocardial vessels with thrombus observed to have showered distally during thrombolysis therapy. Depending on size and number, fragments of dislodging proximal coronary embolus may produce additional myocardial necrosis.

[Quantitative determination of human bone marrow proliferation kinetics during three culture days]. / Quntitative Bestimmung der Proliferationskinetik des menschlichen Knochenmarks während drie Kulturtagen

In order to obtaon of human bone marrow cells, fresh bioptic material was homogenized and the cell suspensions were incubated for 72 hs in a fluid medium. After 24, 48 and 72 hs of incubation the total cell number of the culture was determined. At the same time differential counts of stained smears were performed. Both, erythrocytopoiesis and granulocytopoiesis showed regeneration, maturation, and an absolute increase of the number of precursors and of mature cells. The quantitative data obtained in vitro during 24 hs correspond with our data of kinetics obtained by observed mitotic duration and cell differential countings in vivo. However, after a longer cultivation time we found a diminution of divisible precursors, and an increase of mature erythroblasts as well as an excessibe survival of the PMNs.