[Weaning from Mechanical Ventilation in Patients with SARS-CoV-2 Infection after Prolonged Mechanical Ventilation - First Experience]. / Entwöhnung von der Beatmung (Weaning) nach Langzeitbeatmung infolge SARS-CoV-2-Infektion.

AIM: With the emergence of a new virus and the associated pandemic, the ICU started to see a brand new kind of patient with severe ARD. As with any disease, sometimes the discontinuation of mechanical ventilation for any reason can be difficult. As a center specializing in weaning patients after prolonged mechanical ventilation, we wanted to compare our results with weaning patients who had prolonged mechanical ventilation for other reasons than those of patients who had prolonged mechanical ventilation due to SARS-CoV-2 infection. METHODS: We obtained our data from WeanNet register, the weaning register of the German Institute for Lung Research (ILF). In our analysis, we included only patient data from January until July 2020, which was recorded in our in-house study files. RESULTS: Our analysis included data on 28 patients; 11 were treated with prolonged mechanical ventilation due to SARS-CoV-2 pneumonia, 17 had no SARS-CoV-2 infection. 81.2 % of SARS-CoV-2 patients were successfully weaned from invasive ventilator therapy compared to 76.4 % of patients without SARS-CoV-2. Mortality in the SARS-CoV-2 group was 18.2 % compared to 11.8 % in the other group. Patients with SARS-CoV-2 infections were predominantly males with preexisting cardiovascular disease or a history of nicotine abuse. ARDS was the most common cause of respiratory failure which led to primary intubation. CONCLUSION: Even though we were only able to analyze a small number of patient histories due to the novelty of the disease, we were able to show that patients with prolonged mechanical ventilation after SARS-CoV-2 infection can be equally successfully weaned compared to patients with prolonged mechanical ventilation due to other diseases. Risk factors for prolonged mechanical ventilation after a severe case of SARS-CoV-2 infection seemed to be male gender, nicotine abuse and cardiovascular disease.

A novel flex-rigid and soft-release ECoG array.

This article addresses a novel fabrication process for an electrocorticogram (ECoG) electrode array. It consists of three regions: a flexible recording area, a flexible cable, and a rigid field for soldering the connectors. The flexible components can adapt to the curved shape of the cerebral cortex. Furthermore, the entire structure is a free-standing membrane, attached by removable polyimide straps to its carrier substrate. This configuration allows for a high level of control during soldering, electrode characterization and sterilization, as well as a soft release of the array off its carrier just before implantation. The array contains 128 gold electrodes, each 300 nm thick, sandwiched between two 5 µm thick polyimide films. The measuring area of the device is a regular hexagon with a side length of 7.2 mm, designed for implantation on the primary visual cortex of a Rhesus monkey. The flexible cable is 4 cm long. The rigid soldering area was designed for 4 × 32 OMNETICS connectors. The line resistance from an electrode site to the corresponding electrical connector pin is 540 Ω.

Mutations in the C-terminal region of the HIV-1 reverse transcriptase and their correlation with drug resistance associated mutations and antiviral treatment.

OBJECTIVE: replication of HIV-1 after cell entry is essentially dependent on the reverse transcriptase (RT). Antiretroviral drugs impairing the function of the RT currently aim at the polymerase subunit. One reason for failure of antiretroviral treatment is the evolvement of resistance-associated mutations in the viral genome. For RT inhibitors, almost all identified mutations are located within the polymerase; therefore, general genotyping confines to investigate this subunit. Recently several studies have shown that substitutions within the RNase H and the connection domain increase antiviral drug-resistance in vitro, and some of them are present in patient isolates. AIM: the aim of the present study was to investigate the prevalence of these substitutions and their association with mutations in the polymerase domain arising during antiretroviral treatment. MATERIAL AND METHODS: we performed genotypic analyzes on seventy-four virus isolates derived from treated and untreated patients, followed at the HIV Centre of the Johann Wolfgang Goethe University Hospital (Frankfurt/Main, Germany). We subsequently ana?lysed the different substitutions in the c-terminal region to evaluate whether there were associations with each other, n-terminal substitutions or with antiretroviral treatment. RESULTS: We identified several primer grip substitutions, but almost all of them were located in the connection domain. This is consistent with other in-vivo studies, in which especially the primer grip residues located in the RNase H were unvaried. Furthermore, we identified other substitutions in the connection domain and in the RNase H. Especially E399D seemed to be associated with an antiretroviral treatment and N-terminal resistance-delivering mutations. CONCLUSION: some of the identified substitutions were associated with antiviral treatment and drug resistance-associated mutations. Due to the low prevalence of C-terminal mutations and as only a few of them could be associated with antiviral treatment and N-terminal resistance-delivering mutations, we would not recommend routinely testing of the C-terminal RT region.

[Practice, problems and perspectives of opioid substitution treatment (OST) in Germany]. / Praxis, Probleme und Perspektiven der Substitutionsbehandlung Opioidabhängiger in Deutschland.

Opioid dependency is a complex and chronically relapsing disease with high risks of morbidity and mortality. Frequent relapses and in most of the cases a long process of maturing out characterize this disease. Opioid substitution programs with methadone, buprenorphine and other opioids are a suitable intervention and form the first choice in the treatment of this disease. In Germany, compared to its neighboring countries, this treatment was introduced relatively late. However, in the last five years, the number of patients in substitution treatment has increased significantly to more than 70,000 patients, which marks an increase of 50%, meaning that one third to one half of the estimated opiate users are being reached. Despite the widely acknowledged success with respect to the improvement of the quality of life, survival rates, and accessibility of the target groups for ongoing treatments of drug-related diseases (such as HIV/HCV infections), opioid substitution treatment is still discussed controversially. In this contribution, problems in the areas of service provision, juristic, social, health and research policies are discussed and possibilities of increasing the access and quality of this treatment are introduced.

International variations in youth drug use: the effect of individual behaviours, peer and family influences, and geographical location.

This international study investigates factors underlying international variations in rates of youth drug use among representative samples of 15-year-olds in five cities (Bremen, n = 871; Dublin, n = 983; Groningen, n = 487; Newcastle upon Tyne, n = 880; Rome, n = 666). It reveals a higher level of drug use in English-speaking compared to continental populations. Drug use was associated with peer, family and individual factors. Logistic regression showed that family structure and sport were associated with lower rates and delinquent behaviour with higher rates of drug use in all cities and among males and females. Among males, city of residence also independently predicted drug use. The effect of traditional families and studiousness in reducing drug use was most evident for male drug use in low-use cities: higher rates of use in English-speaking cities appear partially due to the drug use of low-risk males.

Heparin-associated thrombocytopenia: immune complexes are attached to the platelet membrane by the negative charge of highly sulphated oligosaccharides.

The interaction of sulphated oligosaccharides (SO) with platelets and the antibody of heparin-associated thrombocytopenia (HAT type II) was investigated. 3H-heparin binding to platelets was inhibited by different SO, depending on their grade of sulphation. Dextran sulphate, pentosan polysulphate, and heparin were more effective than were LMW heparins. De-N-sulphated heparin and a LMW heparinoid (Org 10172) had no effect. Platelets preincubated with high-grade SO and washed, released serotonin in the presence of HAT sera without additional heparin. Platelets preincubated with HAT sera and then washed were not activated when heparin was added. Only high-grade SO which inhibited heparin binding to platelets caused platelet activation with HAT sera. However, low- and high-grade SO in high concentrations (0.11 g/l) inhibited serotonin release induced by HAT sera and heparin. 32P-phosphorylation of platelet proteins was enhanced by HAT-IgG and heparin and by heat-aggregated IgG, and was inhibited by the moab IV.3. High SO concentrations inhibited only the effect of HAT-IgG and not that of aggregated IgG. We assume that the antigen in HAT involves a releasable platelet protein with a binding site for SO. This was corroborated by studies with an anti-platelet factor 4 antibody causing Fc-receptor dependent platelet activation inhibitable by high SO concentrations.

Heparin-associated thrombocytopenia in a patient treated with polysulphated chondroitin sulphate: evidence for immunological crossreactivity between heparin and polysulphated glycosaminoglycan.

Heparin-associated thrombocytopenia (HAT) type II, a severe side effect of heparin therapy, is thought to be induced by an immunological mechanism. By crossreactivity studies we have demonstrated that sera of patients with HAT type II activate platelets in vitro not only after the addition of heparin but also after addition of a chemically polysulphated chondroitin-like substance, Arteparon, used for treatment of degenerative joint disease. In addition here, we describe a patient who developed deep venous thrombosis and pulmonary embolism following administration of Arteparon and typical HAT type II with thrombocytopenia, 36 h after the first administration of heparin. This patient had never received heparin, but had repeatedly been treated with Arteparon for degenerative joint disease. We conclude that this patient had been presensitized by Arteparon, as indicated by his clinical course. In vitro studies again confirm crossreactivity between heparin and Arteparon.

Heparin-associated thrombocytopenia: the antibody is not heparin specific.

In this study the hypothesis was assessed whether heparin-associated thrombocytopenia (HAT) may be caused by an antibody dependent on polysulfated oligosaccharide epitopes, present not only on heparin but also on different polysulfated substances such as dextran sulfate and pentosan polysulfate. We found that the major factor for eliciting platelet activation with sera of HAT type II patients is neither the structure nor the AT III binding capacity of an oligosaccharide, but rather its grade of sulfation. This was shown by in vitro crossreactivity studies with 40 sera of HAT type II patients using unfractionated heparins, LMW heparins (Fragmin, Fraxiparin), enoxaparin, LMW heparinoid (Org 10172 and its subfractions), de-N-sulfated heparin, dermatan sulfate, dextran sulfate, pentosan polysulfate and dextran. Platelet activation was measured by the heparin induced platelet activation (HIPA) assay and the serotonin release assay (SRA). The platelet activating factor was isolated with the IgG fraction, but did not bind to heparin and dextran sulfate fixed to a solid phase. By isoimmune fixation electrophoresis a monoclonal gammopathy was ruled out in the three sera assessed. The in vivo effect of different LMW heparins and the heparinoid Org 10172 was observed in 10 patients with HAT type II. In a prospective study, a compatible heparin-like anticoagulant was selected for 10 HAT patients for whom further parenteral anticoagulation was required. The only substance that showed no crossreactivity in vitro was the LMW heparinoid Org 10172, which differs from heparin and LMW heparins by its low-grade sulfation. Upon treatment with the heparinoid, all 10 patients had a good clinical outcome, even if they had previously developed thromboembolic complications under LMW heparin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

[Heparin-associated thrombocytopenia: successful therapy of patients after prospective selection of a compatible heparinoid with the heparin-induced platelet activation test]. / Heparin-assoziierte Thrombozytopenie (HAT): Erfolgreiche Therapie von Patienten nach prospektiver Auswahl eines kompatiblen Heparinoids mit dem Heparin-induzierten Plättchenaktivierungs-(HIPA)-Test.

Diagnosis of HAT type II and treatment of thromboembolic complications in these patients are difficult. Recently we have developed the heparin-induced platelet activation (HIPA) assay which allows a rapid confirmation of the tentative diagnosis of HAT type II. In vitro studies with sera of 25 patients revealed cross-reactivity to the LMW heparins Fragmin, Fraxiparin and Clexane whereas a LMW heparinoid, Org 10172 (Orgaran), did not. In a prospective study this heparinoid was selected for 10 HAT patients, for whom further parenteral anticoagulation was required. In 7 of these patients who received LMW heparins prior to laboratory investigations low platelet counts persisted under treatment with LMW heparins and 2 patients developed additional thromboembolic complications. Upon treatment with Org 10172 platelet counts normalized in 9 patients, in 1 patient thrombocytopenia was unrelated to parenteral anticoagulation, in 1 patient platelet count normalized after discontinuation of Org 10172. We conclude that the HIPA assay allows the laboratory diagnosis of HAT type II and the selection of a compatible heparin or heparinoid for further parenteral anticoagulation.

Heparin-associated thrombocytopenia: successful therapy with the heparinoid Org 10172 in a patient showing cross-reaction to LMW heparins.

A patient suffering from heparin-associated thrombocytopenia (HAT), recurrent arteriothromboses, and acute renal failure after treatment with standard heparin is described. He failed to improve when therapy was continued with low-molecular-weight (LMW) heparin (Fragmin, Kabi Pfrimmer, Erlangen, FRG). By means of the in vitro heparin-induced platelet activation (HIPA) assay it was shown that standard heparin and the LMW heparins Fragmin and Fraxiparin (Sanofi Labaz, Munich, FRG), as well as the enoxaparine Clexane (Nattermann, Cologne, FRG), all induced platelet activation with the patient's serum. In contrast, the LMW heparinoid Org 10172 (Organon, Oss, The Netherlands) did not cause platelet activation. When the patient was subsequently treated by parenteral administration of Org 10172 as anticoagulant over a period of several weeks the number of platelets rapidly increased and the patient almost completely recovered. This case shows that strong in vivo and in vitro cross-reactivity between standard heparin and LMW heparins may occur, but can be avoided by the use of a novel heparinoid, Org 10172. The HIPA assay provides a simple and sensitive laboratory method for the choice of an innocuous heparin or heparinoid for continued parenteral anticoagulation.

A rapid and sensitive test for diagnosing heparin-associated thrombocytopenia.

Heparin-associated thrombocytopenia (HAT) is a severe complication of heparin therapy. Its diagnosis is difficult. Conventional assays employ platelet aggregometry (PAA) and/or 14C-serotonin release (SRA) which are either insensitive (PAA) or require radioactive tracers (SRA). We here describe a newly developed sensitive and rapid assay based on visual evaluation of heparin-induced platelet activation (HIPA) in microtiter wells. Using sera of 34 patients with clinically suspected HAT we found the HIPA assay to be as sensitive as the SRA and superior to PAA. The HIPA assay allows investigation of crossreactivity with different types of heparins, low molecular weight (LMW) heparins and heparinoids. Three patients who required further parenteral anticoagulation and in whom the HIPA assay was negative before treatment with the LMW heparinoid Org 10172, were treated with this new heparinoid without adverse reactions. We conclude that the HIPA assay may be a useful tool for differential diagnosis and therapy in patients with HAT.