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1.
Article in English | MEDLINE | ID: mdl-39245620

ABSTRACT

Evaluation of treatment outcomes in patients supported by temporary mechanical circulatory support (tMCS) currently relies mainly on mortality, which may not sufficiently address other patient benefits or harms. Bleeding and thrombosis are major contributors to mortality. Still, current bleeding scores are not designed for critically ill patients undergoing tMCS, only consider selected populations, and do not account for the high heterogeneity among bleeding and thrombotic adverse events. To improve clinical management, a group of European experts has proposed a revised scoring system based on the MOMENTUM 3 Hemocompatibility Score and the Society of Cardiac Angiography and Interventions (SCAI)classification of cardiogenic shock. The new system termed the Scoring Haemostasis Events and Assessment for Risk (SHEAR) score, is divided into a baseline characterization stage and four escalating scoring stages encompassing all aspects of clinical relevance. This report summarizes the literature on hemocompatibility-related adverse events associated with tMCS, including bleeding, stroke, vascular access complications, hemolysis, thrombosis, and device failure. The SHEAR score provides a simple and rapid bedside scoring system aiming to provide a univocal tool to increase physician awareness of hemocompatibility complications at baseline and beyond, improve clinical research, and enable the capture of device-related complications that will inform relevant outcomes beyond mortality.

3.
Front Neurol ; 14: 1232401, 2023.
Article in English | MEDLINE | ID: mdl-37941577

ABSTRACT

Background and aim: Loss of time is a major obstacle to efficient stroke treatment. Our telestroke path intends to optimize prehospital triage using a video link connecting ambulance personnel and a stroke physician. The objectives were as follows: (1) To identify patients suffering a stroke and (2) in particular large vessel occlusion (LVO) strokes as candidates for endovascular treatment. We have chosen the Rapid Arterial Occlusion Evaluation (RACE) scale for this purpose. Methods: This analysis aimed to verify the feasibility of prehospital stroke identification by video assessment. In this prospective telestroke cohort study, we included 97 subjects, in which the RACE score (items: facial palsy, arm and leg motor function, head and gaze deviation, and aphasia or agnosia) was applied, and the assessment videotaped by a trained member of the Emergency Medical Services (EMS) in the field using a mobile device. Each recorded patient video was independently assessed by three experienced stroke physicians from a certified stroke center and compared to the neuroimaging gold standard. Within this feasibility study, the stroke code was not altered by the outcome of the RACE assessment, and all patients underwent the standard procedures within the emergency unit. Results: We analyzed 97 patients (median age 78 years, 53% women), of whom 51 (52.6%) suffered an acute stroke, 12 (23.5%) of which were due to an LVO and 46 patients had symptoms mimicking a stroke. The sensitivity of stroke identification was 77.8%, and specificity was 53.6%. In regard to the identification of an LVO, sensitivity was 69.4% and specificity was 84.3%. The inter-rater agreement in the RACE-score assessment was ICC = 0.82 (intraclass-correlation coefficient). Conclusion: These results confirm our hypothesis that the local telestroke concept is feasible. It allows correct (i) stroke and (ii) LVO identification in the majority of the cases and thus has the potential to assist in efficient prehospital triage.

4.
EClinicalMedicine ; 53: 101649, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36128334

ABSTRACT

Background: Patients with type 2 diabetes and obesity have chronic activation of the innate immune system possibly contributing to the higher risk of hyperinflammatory response to SARS-CoV2 and severe COVID-19 observed in this population. We tested whether interleukin-1ß (IL-1ß) blockade using canakinumab improves clinical outcome. Methods: CanCovDia was a multicenter, randomised, double-blind, placebo-controlled trial to assess the efficacy of canakinumab plus standard-of-care compared with placebo plus standard-of-care in patients with type 2 diabetes and a BMI > 25 kg/m2 hospitalised with SARS-CoV2 infection in seven tertiary-hospitals in Switzerland. Patients were randomly assigned 1:1 to a single intravenous dose of canakinumab (body weight adapted dose of 450-750 mg) or placebo. Canakinumab and placebo were compared based on an unmatched win-ratio approach based on length of survival, ventilation, ICU stay and hospitalization at day 29. This study is registered with ClinicalTrials.gov, NCT04510493. Findings: Between October 17, 2020, and May 12, 2021, 116 patients were randomly assigned with 58 in each group. One participant dropped out in each group for the primary analysis. At the time of randomization, 85 patients (74·6 %) were treated with dexamethasone. The win-ratio of canakinumab vs placebo was 1·08 (95 % CI 0·69-1·69; p = 0·72). During four weeks, in the canakinumab vs placebo group 4 (7·0%) vs 7 (12·3%) participants died, 11 (20·0 %) vs 16 (28·1%) patients were on ICU, 12 (23·5 %) vs 11 (21·6%) were hospitalised for more than 3 weeks, respectively. Median ventilation time at four weeks in the canakinumab vs placebo group was 10 [IQR 6.0, 16.5] and 16 days [IQR 14.0, 23.0], respectively. There was no statistically significant difference in HbA1c after four weeks despite a lower number of anti-diabetes drug administered in patients treated with canakinumab. Finally, high-sensitive CRP and IL-6 was lowered by canakinumab. Serious adverse events were reported in 13 patients (11·4%) in each group. Interpretation: In patients with type 2 diabetes who were hospitalised with COVID-19, treatment with canakinumab in addition to standard-of-care did not result in a statistically significant improvement of the primary composite outcome. Patients treated with canakinumab required significantly less anti-diabetes drugs to achieve similar glycaemic control. Canakinumab was associated with a prolonged reduction of systemic inflammation. Funding: Swiss National Science Foundation grant #198415 and University of Basel. Novartis supplied study medication.

5.
PLoS Negl Trop Dis ; 15(12): e0009486, 2021 12.
Article in English | MEDLINE | ID: mdl-34855748

ABSTRACT

BACKGROUND: Schistosomiasis, caused by Schistosoma mansoni, is of great significance to public health in sub-Saharan Africa. In the Democratic Republic of Congo (DRC), information on the burden of S. mansoni infection is scarce, which hinders the implementation of adequate control measures. We assessed the geographical distribution of S. mansoni infection across Ituri province in north-eastern DRC and determined the prevailing risk factors. METHODS/PRINCIPAL FINDINGS: Two province-wide, community-based studies were conducted. In 2016, a geographical distribution study was carried out in 46 randomly selected villages across Ituri. In 2017, an in-depth study was conducted in 12 purposively-selected villages, across the province. Households were randomly selected, and members were enrolled. In 2016, one stool sample was collected per participant, while in 2017, several samples were collected per participant. S. mansoni eggs were detected using the Kato-Katz technique. In 2017, a point-of-care circulating cathodic S. mansoni antigen (POC-CCA) urine test was the second used diagnostic approach. Household and individual questionnaires were used to collect data on demographic, socioeconomic, environmental, behavioural and knowledge risk factors. Of the 2,131 participants in 2016, 40.0% were positive of S. mansoni infection. Infection prevalence in the villages ranged from 0 to 90.2%. Of the 707 participants in 2017, 73.1% were tested positive for S. mansoni. Prevalence ranged from 52.8 to 95.0% across the health districts visited. Infection prevalence increased from north to south and from west to east. Exposure to the waters of Lake Albert and the villages' altitude above sea level were associated with the distribution. Infection prevalence and intensity peaked in the age groups between 10 and 29 years. Preschool children were highly infected (62.3%). Key risk factors were poor housing structure (odds ratio [OR] 2.1, 95% 95% confidence interval [CI] 1.02-4.35), close proximity to water bodies (OR 1.72, 95% CI 1.1-2.49), long-term residence in a community (OR 1.41, 95% CI 1.11-1.79), lack of latrine in the household (OR 2.00, 95% CI 1.11-3.60), and swimming (OR 2.53, 95% CI 1.20-5.32) and washing (OR 1.75, 95% CI 1.10-2.78) in local water bodies. CONCLUSIONS/SIGNIFICANCE: Our results show that S. mansoni is highly endemic and a major health concern in Ituri province, DRC. Infection prevalence and intensity, and the prevailing socioeconomic, environmental, and behavioural risk factors in Ituri reflect intense exposure and alarming transmission rates. A robust plan of action is urgently needed in the province.


Subject(s)
Schistosoma mansoni/pathogenicity , Schistosomiasis mansoni/epidemiology , Adolescent , Adult , Animals , Anthelmintics/therapeutic use , Child , Child, Preschool , Cross-Sectional Studies , Democratic Republic of the Congo/epidemiology , Family Characteristics , Feces/parasitology , Female , Humans , Infant , Male , Middle Aged , Prevalence , Risk Factors , Schistosoma mansoni/immunology , Schistosomiasis mansoni/drug therapy , Young Adult
6.
PLoS Negl Trop Dis ; 15(12): e0009375, 2021 12.
Article in English | MEDLINE | ID: mdl-34855763

ABSTRACT

BACKGROUND: Reducing morbidity is the main target of schistosomiasis control efforts, yet only rarely do control programmes assess morbidity linked to Schistosoma sp. infection. In the Democratic Republic of Congo (DRC), and particularly in north-eastern Ituri Province, little is known about morbidity associated with Schistosoma mansoni infection. For this reason, we aimed to assess intestinal and hepatosplenic morbidity associated with S. mansoni infection in Ituri Province. METHODS/PRINCIPAL FINDINGS: In 2017, we conducted a cross-sectional study in 13 villages in Ituri Province, DRC. S. mansoni infection was assessed with a Kato-Katz stool test (2 smears) and a point-of-care circulating cathodic antigen (POC-CCA) urine test. A questionnaire was used to obtain demographic data and information about experienced intestinal morbidity. Each participant underwent an abdominal ultrasonography examination to diagnose hepatosplenic morbidity. Of the 586 study participants, 76.6% tested positive for S. mansoni. Intestinal morbidity reported in the two preceding weeks was very frequent, and included abdominal pain (52.7%), diarrhoea (23.4%) and blood in the stool (21.5%). Hepatosplenic morbidity consisted of abnormal liver parenchyma patterns (42.8%), hepatomegaly (26.5%) and splenomegaly (25.3%). Liver pathology (adjusted odds ratio [aOR] 1.20, 95% confidence interval [CI] 1.06-1.37, p = 0.005) was positively and significantly associated with S. mansoni infection. Hepatomegaly (aOR 1.52, 95% CI 0.99-2.32, p = 0.053) and splenomegaly (aOR 1.12, 95% CI 0.73-1.72, p = 0.619) were positively but not significantly associated with S. mansoni infection at the individual level. At the village level, S. mansoni prevalence was positively associated with the prevalence of hepatomegaly and splenomegaly. High-intensity S. mansoni infections were associated with diarrhoea, blood in the stool, hepatomegaly, splenomegaly, and liver parenchyma (C, D, E and F pathology patterns). Four study participants were diagnosed with ascites and five reported hematemesis. CONCLUSIONS/SIGNIFICANCE: Our study documents a high burden of intestinal and hepatosplenic morbidity associated with S. mansoni infection status in Ituri Province. The findings call for targeted interventions to address both S. mansoni infection and related morbidity.


Subject(s)
Schistosoma mansoni/pathogenicity , Schistosomiasis mansoni/complications , Schistosomiasis mansoni/epidemiology , Adolescent , Adult , Animals , Anthelmintics/therapeutic use , Antibodies, Helminth/blood , Child , Cross-Sectional Studies , Democratic Republic of the Congo/epidemiology , Female , Humans , Male , Middle Aged , Morbidity , Prevalence , Rural Population/statistics & numerical data , Schistosoma mansoni/immunology , Schistosomiasis mansoni/drug therapy , Schistosomiasis mansoni/immunology , Splenomegaly/epidemiology , Young Adult
7.
BMJ Open ; 11(10): e047772, 2021 10 12.
Article in English | MEDLINE | ID: mdl-34642190

ABSTRACT

OBJECTIVES: In COVID-19, transfer of respiratory materials transmits disease and drives the pandemic but the interplay of droplet and aerosol physics, physiology and environment is not fully understood. To advance understanding of disease transmission mechanisms and to find novel exposure minimisation strategies, we studied cough-driven material transport modes and the efficacy of control strategies. DESIGN: Computer simulations and real-world experiments were used for integrating an intensive care setting, multiphysics and physiology. Patient-focused airflow management and air purification strategies were examined computationally and validated by submicron particle exhalation imaging in volunteers. SETTING: Hospital setting during a respiratory virus pandemic with transmission by respiratory droplets and aerosols. PARTICIPANTS: Healthy volunteers. OUTCOME MEASURES: Distribution of, and exposure to, potentially infectious respiratory secretions. RESULTS: Respiratory materials ejected by cough exhibited four transport modes: long-distance ballistic, short-distance ballistic, 'jet rider' and aerosol modes. Interaction with air conditioning driven flow contaminated a hospital room rapidly. Different than large droplets or aerosols, jet rider droplets travelled with the turbulent air jet initially, but fell out at a distance, were not well eliminated by air conditioning and exposed bystanders at larger distance and longer time; their size predisposes them to preferential capture in the nasal mucosa, the primordial COVID-19 infection site. 'Cough shields' captured large droplets but induced lateral dispersion of aerosols and jet riders. An air purification device alone had limited efficacy. A 'Shield and Sink' approach combining cough shields with 'virus sinks' minimised exposure to all secretions in modelling and real-life experiments. CONCLUSIONS: Jet riders have characteristics of highly efficient respiratory infection vectors and may play a role in COVID-19 transmission. Exposure to all droplet types can be minimised through an easily implemented Shield and Sink strategy.


Subject(s)
Air Conditioning , COVID-19 , Aerosols , Hospitals , Humans , SARS-CoV-2
8.
Eur Heart J Suppl ; 23(Suppl A): A3-A9, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33815008

ABSTRACT

Cardiogenic shock is a highly lethal syndrome, leading to rapid death or secondary multiorgan damage, but current shock therapies, including mechanical support devices, also have a significant side effect profile. The overarching goal of shock therapy is ensuring long-term survival with good quality of life. This implies averting death, modifying the disease course by promoting heart recovery and avoiding additional cardiac damage, protecting other organs, and circumventing complications. Monitoring and supportive therapies are subordinate to these goals. Rather than merely following preconceived notions, the rapid evolution in mechanical support technology requires iterative and critical review of the benefits of current procedures, protocols and drugs in view of their overall contribution to the therapeutic goals. This article discusses various monitoring and supportive pharmaceutical modalities typically used in patients with cardiogenic shock requiring mechanical support.

9.
Eur Heart J Suppl ; 23(Suppl A): A10-A14, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33815009

ABSTRACT

Even with current generation mechanical circulatory support (MCS) devices, vascular complications are still considerable risks in MCS that influence patients' recovery and survival. Hence, efforts are made to reduce vascular trauma and obtaining safe and adequate arterial access using state-of-the-art techniques is one of the most critical aspects for optimizing the outcomes and efficiency of percutaneous MCS. Femoral arterial access remains necessary for numerous large-bore access procedures and is most commonly used for MCS, whereas percutaneous axillary artery access is typically considered an alternative for the delivery of MCS, especially in patients with severe peripheral artery disease. This article will address the access, maintenance, closure and complication management of large-bore femoral access and concisely describe alternative access routes.

10.
Eur Heart J Suppl ; 23(Suppl A): A27-A34, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33815012

ABSTRACT

The main reason for the emergency implantation of venoarterial extracorporeal membrane oxygenation (VA-ECMO) is the restoration of adequate systemic perfusion, while protecting the failing heart and promoting myocardial recovery are equally important goals. Following initial haemodynamic stabilization and often the urgent revascularization of the culprit lesion, the clinical focus is then directed towards the most efficient strategy for cardioprotection. Frequent echocardiography measurements may help to estimate the degree of unwanted left ventricular (LV) overloading during VA-ECMO. Additionally, the estimation of high LV filling pressures by Doppler echocardiography or their (in-)direct measurement using a dedicated surgical left atrial pressure line and conventional pulmonary artery catheter in a wedge position or a pigtail catheter in the left ventricle can be performed. Mechanical overload of the left ventricle is the major adverse effect and an obvious mechanistic and prognostic challenge of contemporary ECMO care. Many efforts are under way to overcome this phenomenon by LV unloading, which was effectively achieved by the current combined approach using an axial decompression device, while novel technical developments and approaches are tested and urgently anticipated. The aim of this report is to introduce in depth pathophysiological background, current concepts, and future perspectives in LV unloading strategies.

11.
Eur Heart J Suppl ; 23(Suppl A): A35-A40, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33815013

ABSTRACT

Cardiogenic shock (CS) is a clinical entity that includes a wide spectrum of different scenarios. Mechanical circulatory support (MCS) plays a fundamental role in the contemporary treatment of CS, and device selection is a key element in determining optimal treatment in this complex population. Cardiac support with mechanical devices should allow reduction and complete weaning from inotropes. Persistence of elevated left ventricular (LV) filling pressures, pulmonary congestion, metabolic decompensation, and end-organ damage during current MCS are criteria for MCS escalation. Precise diagnosis of the underlying cause of right ventricular (RV) failure is fundamental for undertaking the correct escalation strategy. In the setting of both MCS escalation and de-escalation, it is important to select a strategy in relation to long-term perspectives (bridge-to-recovery, bridge-to-LV assist device, or bridge-to-heart transplantation). Small retrospective studies have demonstrated that the BiPella approach is feasible, reduces cardiac filling pressures and improves cardiac output across a range of causes of CS. Simultaneous LV and RV device implantation and lower RV afterload may be associated with better outcomes in biventricular CS, but prospective studies are still required.

12.
Infect Dis Poverty ; 10(1): 39, 2021 Mar 25.
Article in English | MEDLINE | ID: mdl-33762007

ABSTRACT

BACKGROUND: Severe hepatosplenic complications arise in patients with chronic Schistosoma mansoni infection after heavy exposure to disease agents in endemic areas. These complications are rarely reported and, hence, underestimated. CASE PRESENTATION: We report on eight patients with severe morbidity associated with S. mansoni infection in Ituri Province, northeastern Democratic Republic of Congo (DRC). The patients were identified during a community-based survey in 2017; one patient was seen at the district hospital. After taking the patients' history, a clinical examination and an abdominal ultrasonographical examination were performed. S. mansoni infection was diagnosed in fecal (Kato-Katz technique) and urine (point-of-case circulating cathodic antigen test) samples. These eight patients with severe intestinal and hepatosplenic complications were identified from four villages with high S. mansoni infection prevalence and related morbidity. The patients' ages ranged from 19 to 57 years; four patients were women. Three patients reported hematemesis. Two patients were severely anemic. All patients reported non-specific abdominal symptoms, such as diarrhea (six patients), abdominal pain (seven patients), and blood in the stool (five patients), as well as weight loss (two patients). Abdominal ultrasonography revealed ascites in four patients. All patients had portal hypertension with hepatomegaly (seven patients) or splenomegaly (five patients). Of the six patients with a discernable liver parenchyma pattern, five displayed pattern F and three patient displayed pattern E. Liver parenchyma was not visible for two patients with severe ascites. An S. mansoni infection was confirmed in six patients, with infection intensity ranging from light to heavy. All S. mansoni positive patients were treated with praziquantel (40 mg/kg body weight) and referred to the district hospital for follow-up. One patient with severe ascites died two weeks after we saw her. Due to security and accessibility reasons, the villages could not be visited again and the patients were lost to follow-up. CONCLUSIONS: Our observations of patients with severe schistosomiasis document the severe degree of endemicity of S. mansoni in the province and suggest an urgent need for adequate schistosomiasis control measures that target vulnerable population groups and address severe complications.


Subject(s)
Schistosomiasis mansoni , Schistosomiasis , Adult , Animals , Democratic Republic of the Congo/epidemiology , Feces , Female , Humans , Middle Aged , Praziquantel , Prevalence , Schistosoma mansoni , Schistosomiasis mansoni/complications , Schistosomiasis mansoni/drug therapy , Schistosomiasis mansoni/epidemiology , Ultrasonography , Young Adult
13.
ASAIO J ; 67(1): 12-17, 2021 01 01.
Article in English | MEDLINE | ID: mdl-32804773

ABSTRACT

Coronavirus disease (COVID-19) is overwhelming hospitals with patients requiring respiratory support, including ventilators and Extracorporeal Membrane Oxygenation (ECMO). Bottlenecks in device availability may contribute to mortality, and limited device availability even in ECMO centers has led to rationing recommendations. Therefore, we explored options for ad hoc construction of venovenous ECMO using readily available components, essentially, large cannulas, membrane oxygenators, and blood pumps. As thousands of certified cardiac Impella pumps are distributed worldwide, we assembled lean ECMO by embedding Impella pumps coaxially in tubes, combined with standard gas exchangers. Ad hoc integration of Impella blood pumps with gas exchange modules, large-bore venous cannulas, regular ECMO tubing, Y-pieces, and connectors led to lean ECMO systems with stable performance over several days. Oxygenation of 2.5-5 L of blood per minute is realistic. Benefit/risk analysis appears favorable if a patient needs respiratory support but required support systems in a center are exhausted. Ad hoc assembly of venovenous ECMO is feasible using Impella blood pumps, results in stable blood flow across gas exchange modules, and thus may offer another opportunity to oxygenate, "recover the lungs" and hopefully save lives in selected patients with severe COVID-19 disease even when conventional life support equipment is exhausted. The lean design also yields inspirations for future ECMO systems.


Subject(s)
COVID-19/therapy , Extracorporeal Membrane Oxygenation/instrumentation , Extracorporeal Membrane Oxygenation/methods , Oxygenators, Membrane , Equipment Design , Hemodynamics , Humans , Oxygen , Risk
14.
ESC Heart Fail ; 7(4): 1982-1986, 2020 08.
Article in English | MEDLINE | ID: mdl-32351016

ABSTRACT

Post-operative right coronary artery occlusion is a serious complication that demands acute coronary revascularization to prevent myocardial infarction. We present two cases with acute right coronary artery obstruction caused by (1) transfemoral aortic valve implantation and (2) acute type A aortic dissection. Although coronary artery bypass grafting was performed intraoperatively, right heart failure was observed in both cases. The Impella RP® device offers temporary right ventricular mechanical support; wherefore, we decided to deploy it in both patients. The devices were uneventfully and successfully implanted to bridge for recovery of the right heart. We report the perioperative course of the patients as well as their condition at 1 year follow-up.


Subject(s)
Heart Failure , Heart-Assist Devices , Myocardial Infarction , Heart Failure/etiology , Heart Ventricles , Humans , Treatment Outcome
15.
J Cardiovasc Transl Res ; 13(5): 744-757, 2020 10.
Article in English | MEDLINE | ID: mdl-32072564

ABSTRACT

The pathobiology of atherosclerosis and its current and potential future treatments are summarized, with a spotlight on three central cell types involved: (i) endothelial cells (ECs), (ii) macrophages, and (iii) vascular smooth muscle cells (VSMCs). (i) EC behaviour is regulated by the central transcription factors YAP/TAZ in reaction to biomechanical forces, such as hemodynamic shear stress. (ii) VSMC transdifferentiation (phenotype switching) to a macrophage-like phenotype contributes to the majority of cells positive for common cell surface macrophage markers in atherosclerotic plaques. (iii) Intra-plaque macrophages originate in a significant number from vascular resident macrophages. They can be activated via pattern recognition receptors on cell membrane (e.g. toll-like receptors) and inside cells (e.g. inflammasomes), requiring priming by neutrophil extracellular traps (NETs). ECs and macrophages can also be characterized by single-cell RNA sequencing. Adaptive immunity plays an important role in the inflammatory process. Future therapeutic options include vaccination, TRAF-STOPs, senolysis, or CD47 blockade. Graphical Abstract.


Subject(s)
Atherosclerosis/pathology , Endothelial Cells/pathology , Macrophages/pathology , Myocytes, Smooth Muscle/pathology , Adaptive Immunity , Animals , Atherosclerosis/immunology , Atherosclerosis/metabolism , Atherosclerosis/therapy , Cell Proliferation , Cell Transdifferentiation , Endothelial Cells/immunology , Endothelial Cells/metabolism , Humans , Macrophage Activation , Macrophages/immunology , Macrophages/metabolism , Mechanotransduction, Cellular , Myocytes, Smooth Muscle/immunology , Myocytes, Smooth Muscle/metabolism , Stress, Mechanical
16.
ACS Appl Bio Mater ; 3(10): 6919-6931, 2020 Oct 19.
Article in English | MEDLINE | ID: mdl-35019353

ABSTRACT

Nanomaterials allow designing targeted therapies, facilitate molecular diagnostics, and are therefore enabling platforms for personalized medicine. A systematic science and a predictive understanding of molecular/supramolecular structure relationships and nanoparticle structure/biological property relationships are needed for rational design and clinical progress but are hampered by the anecdotal nature, nonsystematic and nonrepresentative nanomaterial assortment, and oligo-disciplinary approach of many publications. Here, we find that a systematic and comprehensive multidisciplinary approach to production and exploration of molecular-structure/nanostructure relationship and nano-bio structure/function relationship of medical nanomaterials can be achieved by combining systematic chemical synthesis, thorough physicochemical analysis, computer modeling, and biological experiments, as shown in a nanomaterial family of amphiphilic, micelle-forming oxazoline/siloxane block copolymers suited for the clinical application. This comprehensive interdisciplinary approach leads to improved understanding of nanomaterial structures, allows good insights into binding modes for the nanomaterial protein corona, induces the design of minimal cell-binding materials, and yields rational strategies to avoid toxicity. Thus, this work contributes to a systematic and scientific basis for rational design of medical nanomaterials.

17.
Biomacromolecules ; 20(11): 4065-4074, 2019 11 11.
Article in English | MEDLINE | ID: mdl-31603657

ABSTRACT

We introduce a method to monitor the integrity of micellar nanocarriers using a novel fluorescent dye, IR-780-PDMS and Förster resonance energy transfer (FRET) as a readout. In addition, these dye-loaded nanocarriers can be used as a phototoxic agent in vitro. Mainly, a nanocarrier was designed, based on a previously described amphiphilic ABA-copolymer (Pip-PMOXA-PDMS-PMOXA-Pip) scaffold that incorporates the fluorescent FRET dye partners IR-780-PDMS (donor) and IR-780 (acceptor). The confirmation of FRET (that only occurs when donor and acceptor are in the required close proximity of less than ∼10 nm) in the nanocarriers is used to prove that the acceptor dye (IR-780) is still contained in its hydrophobic core. We measured such FRET signals of the nanocarriers also upon cellular uptake into HeLa cells using fluorescence-lifetime imaging microscopy (FLIM). Confocal laser scanning microscopy after incubation with nanocarriers demonstrated the intracellular uptake of the particles and their localization in an intracellular granular pattern. To demonstrate the intactness of the nanocarriers by detection of FRET we measured the fluorescence lifetime (FLIM) of the donor dye. FLIM showed that both types of lifetimes, that of the quenched donor, and that of the unquenched donor were present, in a granular pattern and homogeneously in the cytosol, respectively, indicating the presence of intracellular intact and disintegrated micellar nanocarriers. These data show that the herewith-described FRET method allows monitoring the intactness of nanocarriers while en route to the target, and also that the cargo is delivered and released within a potential target cell. In addition, near-infrared (NIR) irradiation of IR-780-loaded micellar nanocarriers leads to photocytotoxicity, which we demonstrated in in vitro experiments. Our findings open potential avenues in photodynamic therapy (PDT) of cancer.


Subject(s)
Drug Carriers , Fluorescent Dyes/chemistry , Indoles/chemistry , Nanoparticles/therapeutic use , Dimethylpolysiloxanes/chemistry , Dimethylpolysiloxanes/therapeutic use , Drug Carriers/chemistry , Drug Carriers/therapeutic use , Fluorescence Resonance Energy Transfer , Fluorescent Dyes/therapeutic use , Green Fluorescent Proteins/chemistry , HeLa Cells , Humans , Indoles/therapeutic use , Luminescent Proteins/chemistry , Nanoparticles/chemistry , Neoplasms/therapy , Nylons/chemistry , Photochemotherapy/trends
18.
Int J Cardiol ; 291: 96-104, 2019 09 15.
Article in English | MEDLINE | ID: mdl-31155332

ABSTRACT

For patients with myocardial infarct-related cardiogenic shock (CS), urgent percutaneous coronary intervention is the recommended treatment strategy to limit cardiac and systemic ischemia. However, a specific therapeutic intervention is often missing in non-ischemic CS cases. Though drug treatment with inotropes and/or vasopressors may be required to stabilize the patient initially, their ongoing use is associated with excess mortality. Coronary intervention in unstable patients often leads to further hemodynamic compromise either during or shortly after revascularization. Support devices like the intra-aortic balloon pump failed to improve clinical outcomes in infarct-related CS. Currently, more powerful and active hemodynamic support devices unloading the left ventricle such as transvalvular microaxial pumps are available and are being increasingly used. However, as for other devices large randomized trials are not yet available, and device use is based on registry data and expert consensus. In this article, a multidisciplinary group of experienced users of transvalvular microaxial pumps outlines the pathophysiological background on hemodynamic changes in CS, the available mechanical support devices, and current guideline recommendations. Furthermore, different hemodynamic situations in several case-based scenarios are used to illustrate candidate settings and to provide the theoretic and scientific rationale for left-ventricular unloading in these scenarios. Finally, organization of shock networks, monitoring, weaning, and typical complications and their prevention are discussed.


Subject(s)
Heart Failure/epidemiology , Heart Failure/therapy , Heart-Assist Devices/trends , Shock, Cardiogenic/epidemiology , Shock, Cardiogenic/therapy , Europe/epidemiology , Extracorporeal Membrane Oxygenation/methods , Extracorporeal Membrane Oxygenation/trends , Heart Failure/diagnosis , Hemodynamics/physiology , Humans , Intra-Aortic Balloon Pumping/methods , Intra-Aortic Balloon Pumping/trends , Shock, Cardiogenic/diagnosis
19.
BMJ Simul Technol Enhanc Learn ; 5(2): 102-107, 2019.
Article in English | MEDLINE | ID: mdl-35519829

ABSTRACT

Background: Performance of interdisciplinary teams and their leaders is crucial in acute medical care and can be monitored by observing specific events. Standardised operational procedures (SOP) are easily observable, whereas the unpredictability of medical emergencies makes performance monitoring in these situations difficult. The aim of this study was therefore to assess whether performance in emergency situations can be predicted by performance observed during an SOP. Methods: 30 intensive care unit teams composed of one staff physician (leader), one resident and three nurses performed a simulated scenario of an elective electrical cardioversion (SOP) followed by a cardiac arrest (emergency). Video recordings obtained during simulations were used for data analysis. The primary outcome was the correlation between performance scores of electrical cardioversion and performance during cardiopulmonary resuscitation (hands-on time, time to first defibrillation). Results: None of the cardioversion performance scores significantly correlated with resuscitation performance. Leadership scores during electrical cardioversion correlated positively with leadership scores during cardiopulmonary resuscitation (r=0.365, p=0.047). Moreover, there was a positive correlation of leaders being hands-off during both electrical cardioversion and cardiopulmonary resuscitation (r=0.645, p<0.0001). Conclusions: Team performance in SOP carried no predictive value for emergency situations. Observing teams in easily observable SOP is therefore no suitable substitute for monitoring the performance in medical emergencies. There was a between-situation consistency for specific elements of leadership.

20.
Swiss Med Wkly ; 148: w14639, 2018.
Article in English | MEDLINE | ID: mdl-30044474

ABSTRACT

Morbid obesity plays an increasingly important role in healthcare. Patients who are severely obese often suffer from a range of medical problems. One problem is obesity-related hypoventilation syndrome with its resulting hypercapnia. We report a case of a 33-year-old female patient who was in an extraordinarily bad medical state, with severe hypercapnia (pCO2 15.1 kPa), sepsis, acute anuric kidney failure and resulting acidosis (pH 6.96). Her body mass index was 84 kg/m2. Her chances of survival were considered very low after failed attempts at noninvasive ventilation. Based on prior research, we refrained from intubation and chose venovenous extracorporeal membrane oxygenation to treat the hypercapnia. In the entire medical literature, we are not aware of a similarly extraordinary case of obesity-related hypoventilation syndrome that could finally be treated successfully. The idea behind this case report is to consider venovenous extracorporeal membrane oxygenation as an alternative to intubation in this patient collective.


Subject(s)
Extracorporeal Membrane Oxygenation/methods , Hypercapnia/therapy , Obesity, Morbid/complications , Acute Kidney Injury/therapy , Adult , Female , Humans , Intensive Care Units , Obesity Hypoventilation Syndrome/therapy , Sepsis , Switzerland , Treatment Outcome
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