Continuation of chronic antiplatelet therapy is not associated with increased need for transfusions: a cohort study in critically ill septic patients.

BACKGROUND: The decision to maintain or halt antiplatelet medication in septic patients admitted to intensive care units presents a clinical dilemma. This is due to the necessity to balance the benefits of preventing thromboembolic incidents and leveraging anti-inflammatory properties against the increased risk of bleeding. METHODS: This study involves a secondary analysis of data from a prospective cohort study focusing on patients diagnosed with severe sepsis or septic shock. We evaluated the outcomes of 203 patients, examining mortality rates and the requirement for transfusion. The cohort was divided into two groups: those whose antiplatelet therapy was sustained (n = 114) and those in whom it was discontinued (n = 89). To account for potential biases such as indication for antiplatelet therapy, propensity score matching was employed. RESULTS: Therapy continuation did not significantly alter transfusion requirements (discontinued vs. continued in matched samples: red blood cell concentrates 51.7% vs. 68.3%, p = 0.09; platelet concentrates 21.7% vs. 18.3%, p = 0.82; fresh frozen plasma concentrates 38.3% vs. 33.3%, p = 0.7). 90-day survival was higher within the continued group (30.0% vs. 70.0%; p < 0.001) and the Log-rank test (7-day survivors; p = 0.001) as well as Cox regression (both matched samples) suggested an association between continuation of antiplatelet therapy < 7 days and survival (HR: 0.24, 95%-CI 0.10 to 0.63, p = 0.004). Sepsis severity expressed by the SOFA score did not differ significantly in matched and unmatched patients (both p > 0.05). CONCLUSIONS: The findings suggest that continuing antiplatelet therapy in septic patients admitted to intensive care units could be associated with a significant survival benefit without substantially increasing the need for transfusion. These results highlight the importance of a nuanced approach to managing antiplatelet medication in the context of severe sepsis and septic shock.

The Cell and Gene Therapy Consortium's Perspective on Harmonizing Data Collection for Patient Enrollment, Therapy Ordering and Scheduling, and Cell Collection.

Established in October 2021, the Cell and Gene Therapy (CGT) Consortium convened with the goal to bring together key CGT stakeholders - manufacturers, treatment centers, regulators, services providers, and ecosystem partners - to gain alignment on process definitions, terminology, challenges, and opportunities for process and data standardization from CGT program start-up and patient enrollment to therapy administration. With the recognition that the number of investigational and commercial cell and gene therapies will scale over the next several years, so will the number of manufacturer-specific processes and solutions (e.g., portals). As a result, this will increase the burden on academic medical centers, community hospitals, standalone clinics, collection facilities, and labs. Healthcare professionals (HCPs) and other industry stakeholders agree that a multiplicity of manufacturer portals with varying data requirements and nomenclature is unsustainable and adds unnecessary complexity - risk, cost, and time - in coordinating patient treatment. Following extensive discussions and multiple stakeholder meetings and interviews, we have developed a manuscript reporting on our activities and conclusions. Through the course of the manuscript, we delineate a framework for defining common principles, terminology, and user experiences for enrolling patients, ordering therapies, and collecting starting material in a standardized way. We also provide substantial background information on opportunities to streamline communications between manufacturing and healthcare organizations from the HCP end-user's perspective.

Downlink communication experiments with OSIRISv1 laser terminal onboard Flying Laptop satellite.

Downlink measurement campaigns from the optical downlink terminal OSIRISv1 onboard the LEO satellite Flying Laptop were carried out with the French Observatoire de la Côte d'Azur and with two Optical Ground Stations of the German Aerospace Center. On/off keyed data at 39 Mb/s were modulated on the laser signal, and according telecom reception was performed by the ground stations. The pointing of the laser terminal was achieved by open-loop body pointing of the satellite orientation, with its star sensor as attitude control signal. We report here on the measurements and investigations of the downlink signal and the data transmission.

Effects of Gender-Affirming Hormone Therapy on Progression Along the HIV Care Continuum in Transgender Women.

BACKGROUND: Progression along the HIV care continuum has been a key focus for improving outcomes for people with HIV (PWH). Transgender women with HIV (TGWWH) have not made the same progress as their cisgender counterparts. METHODS: All PWH identifying as transgender women receiving care at our clinic from 1/1/2015 to 12/31/2019 were identified from the electronic health records (EHRs) using International Classification of Diseases (ICD) codes. Demographics, laboratory data, prescription of gender-affirming hormone therapy (GAHT), and visit history were abstracted from the EHR. Retention in care and viral suppression were defined using Centers for Disease Control and Prevention definitions. The proportions of TGWWH who were consistently retained in care or virally suppressed over time were calculated using a binary response generalized mixed model including random effects and correlated errors. RESULTS: Of the 76 PWH identified by ICD codes, 2 were excluded for identifying as cisgender and 15 for insufficient records, leaving 59 TGWWH included for analysis. Patients were on average 35 years old and Black (86%), with a median CD4 count of 464 cells/µL. There were 13 patients on GAHT at study entry and 31 receiving GAHT at any point during the study period. Fifty-five percent were virally suppressed at study entry and 86% at GAHT initiation. The proportion of TGWWH who were consistently virally suppressed over time was greater among those receiving GAHT compared with those who were not (P = .04). CONCLUSIONS: Rates of viral suppression were significantly greater among TGWWH receiving GAHT when compared with those who were not. More research to evaluate the reasons behind this effect is needed.

[Intra-abdominal pressure measurement]. / Intraabdominelle Druckmessung ­ Schritt für Schritt.

An elevated intra-abdominal pressure (IAP) above 12 mmHg is a pathological finding in critically ill patients. IAP are classified into different degrees of intra-abdominal hypertension and, in the presence of associated organ failure, as abdominal compartment syndrome. Both disease entities represent an underestimated factor in intensive care patients and are associated with increased mortality and prolonged intensive care and hospital stay. The measurement of intra-abdominal pressure in critically ill patients in intensive care units is not widely established and there is often considerable uncertainty regarding measurement conditions and methods. If risk factors are present, intra-abdominal pressure should be monitored every 4 hours. Bladder pressure measurement is the gold standard for determining intra-abdominal pressure. The measurement is a non-invasive, cost-effective, easy to perform bedside and safe method for the patient.

On-site blood culture incubation shortens the time to knowledge of positivity and microbiological results in septic patients.

INTRODUCTION: To determine whether on-site incubation of blood cultures at the intensive care unit (ICU) improves not only the time to incubation but also time to positivity, time to knowledge of positivity and time to results (identification and antibiotic susceptibility testing). METHODS: This observational single-centre study in ICU patients with severe sepsis and septic shock investigated the impact of blood culture incubation immediately on-site at the ICU (ICU group) by comparison with traditional processing in a remote laboratory (LAB group) on different time intervals of blood culture diagnostics from obtaining blood to clinician notification of final result. The effect of on-site incubation was evaluated in Kaplan-Meier estimates for the time to positivity, time to knowledge of positivity and time to microbiological results and a linear mixed model was built. RESULTS: A total of 3,549 blood culture sets from 657 ICU patients were analysed: 2,381 in the LAB group and 1,168 in the ICU group. Overall, 660 (18.6%) blood culture sets were positive and 2,889 (81.4%) sets remained negative. On-site incubation was associated with reduced time to knowledge of positivity (46.9 h [CI 43.4-50.8 h] vs. 28.0 h [CI 23.6-32.2 h], p < 0.001) and reduced time to result (61.4 h [CI 58.4-64.8 h] vs. 42.1 h [CI 39.1-47.5 h], p < 0.001). In blood cultures processed instantaneously at the ICU compared to incubation in the remote laboratory within 4 h, the time to microbiological result was significantly reduced by 8.5 h (p < 0.001). Pre-existing anti-infective therapy had no significant impact on diagnostic time intervals. CONCLUSIONS: Instantaneous incubation of blood cultures in the ICU compared to incubation in a remote laboratory significantly improves time to knowledge to positivity and time to result. These effects are even more pronounced during off-hours of the microbiological laboratory. The results underline the importance of 24/7 diagnostics to provide round-the-clock processing of blood culture samples in patients with sepsis and septic shock and an immediate to communication of the results to the clinicians.

Correlation of optical properties and interface morphology in type-II semiconductor heterostructures.

(Ga,In)As/GaAs/Ga(As,Sb) and (Ga,In)As/GaAs/Ga(N,As) type-II double quantum well heterostructures have been grown by metal-organic vapor phase epitaxy. A growth interruption procedure was used to intentionally modify the morphology of the internal interfaces. The heterostructures were investigated using continuous wave and time-resolved photoluminescence as well as optical pump-optical probe spectroscopy. We find a correlation between the interface morphology and optical and kinetic properties. A growth interruption of about 120 s yielded substantially smoother interfaces both on vertical as well as lateral length scales. On the other hand a considerably enhanced type-II recombination time as well as a longer electron tunneling time are observed. We attribute this to a reduced interface localization in case of smoother interfaces.

Do Sepsis-3 Criteria Facilitate Earlier Recognition of Sepsis and Septic Shock? A Retrospective Cohort Study.

BACKGROUND: New Sepsis-3 criteria are supposed to "facilitate earlier recognition … of patients with sepsis." To test this, we performed novel and direct comparisons of Sepsis-1 vs. Sepsis-3 criteria with respect to time differences of sepsis onset. METHODS: In a cohort of intensive care unit (ICU) patients prospectively diagnosed with severe sepsis or septic shock according to Sepsis-1 criteria between 01/2010 and 12/2015, the time differences between meeting Sepsis-1 vs. Sepsis-3 criteria as time of sepsis onset and the corresponding differences in illness severity were tested. Similar comparisons were performed for septic shock subset meeting different Sepsis-1 vs. Sepsis-3 criteria. Patients with non-ICU-acquired sepsis and patients with sepsis onset more than 48 h postadmission (ICU-acquired sepsis) were analyzed separately to account for differences in availability of routinely collected organ dysfunction data. RESULTS: A total of 10,905 ICU patients were screened; 862 patients met Sepsis-1 criteria, of whom 834 (97%) also met Sepsis-3 criteria. In patients, admitted to the ICU with sepsis, Sepsis-3 criteria compared with Sepsis-1 criteria were more frequently fulfilled within the first 3 h (84% vs. 75%, P < 0.001).In patients with ICU-acquired sepsis, sepsis onset was in 50% at least 1 day earlier after application of Sepsis-3 (P = 0.011). These patients were systemic inflammatory response syndrome negative at the earlier sepsis onset, but suffered already from organ dysfunction. Sepsis-3 criteria were timely in 86% and 1 day delayed in 7%. Only 7% (8 patients) did not meet Sepsis-3 criteria in this group. These patients had already an increased SOFA score and did develop neither a further increase nor the new septic shock criteria. Classification according to Sepsis-3 reduced the proportion of septic shock (51% vs. 75%, P < 0.001).Twenty-eight-day mortality was 38% for new septic shock compared with 33% of Sepsis-1 septic shock (P > 0.05). Patients not detected by Sepsis-3 had a 28-day mortality of 11%. CONCLUSIONS: Sepsis-3 criteria facilitate an earlier and more predictive recognition of sepsis and septic shock in patients with non-ICU and ICU-acquired sepsis primarily diagnosed by Sepsis-1 criteria. These results require further validation with prospectively collected data.

Crystallization of Poly(ethylene oxide) on the Surface of Aqueous Salt Solutions Studied by Grazing Incidence Wide-Angle X-ray Scattering.

We report the thin layer crystallization of high-molar mass poly(ethylene oxide) (PEO) on a liquid support using a 4 M K2CO3 aqueous solution as a subphase. Because of the Hofmeister effect, PEO does not dissolve and remains at the surface during compression on a Langmuir trough. The transition from the flat pancake conformation upon compression of the spread polymer film to an entangled monolayer results in a plateau region of the Langmuir isotherm. Using grazing incidence wide-angle X-ray scattering, the final crystallization of PEO was observed, and the crystal orientation was determined. The fold surface was (209̅), that is, the helix axis has a tilt angle of 2.9° to the normal vector of the water surface.

Quality Improvement Initiative for Severe Sepsis and Septic Shock Reduces 90-Day Mortality: A 7.5-Year Observational Study.

OBJECTIVE: To investigate the impact of a quality improvement initiative for severe sepsis and septic shock focused on the resuscitation bundle on 90-day mortality. Furthermore, effects on compliance rates for antiinfective therapy within the recommended 1-hour interval are evaluated. DESIGN: Prospective observational before-after cohort study. SETTING: Tertiary university hospital in Germany. PATIENTS: All adult medical and surgical ICU patients with severe sepsis and septic shock. INTERVENTION: Implementation of a quality improvement program over 7.5 years. MEASUREMENTS: The primary endpoint was 90-day mortality. Secondary endpoints included ICU and hospital mortality rates and length of stay, time to broad-spectrum antiinfective therapy, and compliance with resuscitation bundle elements. MAIN RESULTS: A total of 14,115 patients were screened. The incidence of severe sepsis and septic shock was 9.7%. Ninety-day mortality decreased from 64.2% to 45.0% (p < 0.001). Hospital length of stay decreased from 44 to 36 days (p < 0.05). Compliance with resuscitation bundle elements was significantly improved. Antibiotic therapy within the first hour after sepsis onset increased from 48.5% to 74.3% (p < 0.001). Multivariate analysis revealed blood cultures before antibiotic therapy (hazard ratio, 0.60-0.84; p < 0.001), adequate calculated antibiotic therapy (hazard ratio, 0.53-0.75; p < 0.001), 1-2 L crystalloids within the first 6 hours (hazard ratio 0.67-0.97; p = 0.025), and greater than or equal to 6 L during the first 24 hours (hazard ratio, 0.64-0.95; p = 0.012) as predictors for improved survival. CONCLUSIONS: The continuous quality improvement initiative focused on the resuscitation bundle was associated with increased compliance and a persistent reduction in 90-day mortality over a 7.5-year period. Based on the observational study design, a causal relationship cannot be proven, and respective limitations need to be considered.

Effects of vasodilators on haemodynamic coherence.

Vasodilators are a potential therapeutic option for patients with persisting microcirculatory disorders despite adequate cardiac output and mean arterial pressure due to conventional haemodynamic stabilization. Venous vasodilation may decrease post-capillary venular pressure and thus increase capillary flow resulting in reduced extravasation and oedema formation. Arteriolar vasodilation may increase microvascular flow by 'opening' the microcirculation. In particular, inodilators that combine vasodilation with positive inotropy may be promising. The present article summarizes the impact of different vasodilators (nitroglycerin, calcium antagonists and prostaglandins) and inodilators (dobutamine, phosphodiesterase-inhibitors and levosimendan) on haemodynamic coherence in the treatment of shock and microvascular dysfunction. In summary, there is presently no hard evidence to recommend any vasodilator for routine practice. If used in selected patients, microvascular monitoring before and during this therapy is a pre-requisite to indicate and guide vasodilator therapy. Further clinical trials are necessary to generate more evidence in the above-mentioned patient population.

Platelet-bound cyclophilin A in patients with stable coronary artery disease and acute myocardial infarction.

OBJECTIVE: Recently, we reported that extracellular cyclophilin A (CyPA) is an important agonist for platelets. Whereas soluble CyPA-levels have been associated with cardiovascular risk factors, cell-bound CyPA has not been investigated yet. In this study, we analyzed for the first time platelet-bound CyPA in patients with symptomatic coronary artery disease (CAD). METHODS AND RESULTS: blood was obtained from 388 consecutive patients: 204 with stable CAD and 184 with acute coronary syndrome (76 with unstable angina, 78 with non ST-elevation myocardial infarction (NSTEMI), and 30 with STEMI). In vitro stimulation of platelets with classical agonists revealed an enhanced expression of CyPA on the platelet surface. In patients with stable CAD, platelet-bound CyPA correlated excellently with platelet activity measured by P-selectin exposure in flow cytometry. The analysis of classical risk factors for atherosclerosis revealed that patients with hypertension and hypercholesterolemia had significantly enhanced platelet-bound CyPA, whereas diabetes and smoking were not associated with enhanced CyPA-binding to the platelet surface. In multivariate analysis, hypercholesterolemia was the only significant predictor of enhanced platelet-bound CyPA. Interestingly, in patients with acute myocardial infarction (AMI) platelet-bound CyPA was significantly decreased compared with patients with stable CAD. CONCLUSIONS: Enhanced platelet-bound CyPA is associated with hypertension and hypercholesterolemia in stable CAD patients. In patients with AMI platelet-bound CyPA is significantly decreased.

Self-organization of poly(ethylene oxide) on the surface of aqueous salt solutions.

It is demonstrated that stable Langmuir films of poly(ethylene oxide) (PEO) can be formed up to surface pressures of 30 mN m(-1) when potassium carbonate K2CO3 is added to the aqueous subphase. Generally, PEO homopolymer cannot stay on the water surface at a surface pressure ≥10 mN m(-1) due to its high water solubility. To prepare stable monolayer films, PEO can be modified with hydrophobic moieties. However, by exploiting the salting out effect by adding certain salts (K2CO3 or MgSO4) into the aqueous subphase, not only very stable films but also unusual self-organization can be achieved by the PEO homopolymer on the surface of the aqueous solution. Thus, a series of OH-terminated PEOs is found to form a stable monolayer at K2CO3 concentrations of 2 M and above in the aqueous subphase, and the stability of the film increases with an increase in K2CO3 concentration. Hysteresis experiments are also carried out. During the phase transition induced by progressive compression, self-organization into well-defined domains with sizes in the micrometer range are observed, and with further compression and holding of the film for 30 min and above the microdomains transform into a crystalline morphology as visualized by Brewster angle microscopy.

Molecular arrangement of symmetric and non-symmetric triblock copolymers of poly(ethylene oxide) and poly(isobutylene) at the air/water interface.

The behavior of a series of amphiphilic triblock copolymers of poly(ethylene oxide) (PEO) and poly(isobutylene) (PIB); including both symmetric (same degree of polymerization (DP) of the terminal PEO blocks) PEOm-b-PIBn-b-PEOm and non-symmetric (different DP of the terminal PEO blocks) PEOm-b-PIBn-b-PEOz, is investigated at the air/water interface by measuring surface pressure vs mean molecular area isotherms (π vs mmA), Langmuir-Blodgett (LB) technique, and infrared reflection-absorption spectroscopy (IRRAS). The block copolymer (PEO32-b-PIB160-b-PEO32) with longer PEO segments forms a stable monolayer and the isotherm reveals a pseudo-plateau starting at π∼5.7 mN/m, also observed in the IRRAS, which is assigned to the pancake-to-brush transition related to the PEO dissolution into the subphase and subsequent PEO brush dehydration. Another plateau is observed at π∼40 mN/m, which is attributed to the film collapse due to multilayer formation. The pancake-to-brush transition could not be observed for samples with smaller PEO chains. The isotherms for block copolymers, with short PEO chains, both symmetric (PEO3-b-PIBn-b-PEO3) and non-symmetric (PEO12-b-PIBn-b-PEO3), reveal another transition at π∼20-25 mN/m. This is interpreted to be due to the conformational transition from a folded state where the middle PIB block is anchored to the water surface at both ends by the terminal hydrophilic segments to an unfolded state with PIB anchored to the water surface at one end. It is assumed that this transition involves the removal of PEO3 chains from the water surface in case of non-symmetric PEO12-b-PIB85-b-PEO3 and in case of symmetric, probably one PEO3 of each PEO3-b-PIB85-b-PEO3 chain. Because of the weaker interaction of the short PEO3 chains with the water surface as compared with the relatively longer PEO12 chains, the film of PEO3-b-PIB85-b-PEO3 collapses at much lower surface pressure after the transition as compared with the PEO12-b-PIB85-b-PEO3. The AFM images reveal the formation of microdomains of almost uniform height (6-7 nm) in LB films of PEO3-b-PIB85-b-PEO3 and PEO12-b-PIB85-b-PEO3 after transferring onto silicon surfaces. These domains are assumed to be the mesomorphic domains of ordered and folded PIB chains.

Argatroban administration reduces leukocyte adhesion and improves capillary perfusion within the intestinal microcirculation in experimental sepsis.

Co-activation of pro-coagulatory pathways in sepsis may result in disseminated intravascular coagulation and contributes to microvascular dysfunction. We investigated the effects of the direct thrombin inhibitor, argatroban (ARG), on the sepsis-induced impairment of the intestinal microcirculation (capillary perfusion, leukocyte adhesion) and the vascular contractility in rats. Forty male Lewis rats were randomly assigned to one of four groups: sham surgery (SHAM), experimental sepsis (colon ascendens stent peritonitis--CASP), CASP+ARG, and SHAM+ARG. At 16 hours after colon stent insertion (or sham surgery), 2 mg/kg argatroban or buffer were given intravenously, and 1 hour thereafter, intravital microscopy was performed. In addition, experiments to study the impact of ARG on vascular contractility were conducted in vitro . ARG administration in CASP rats significantly increased functional capillary density in mucosal (+128%) and muscular layers (longitudinal: +42%; circular: +64%) and decreased the number of firmly adhering leukocytes in the intestinal submucosa compared to untreated animals. In vitro findings indicated a vasodilating effect of ARG. ARG administration during experimental sepsis improved intestinal microcirculation by preserving functional capillary density, an indicator of microvascular perfusion, and by reducing leukocyte adherence to the endothelium in submucosal venules.

Cyberethics and co-operation in the information society.

The task of this paper is to ground the notion of cyberethics of co-operation. The evolution of modern society has resulted in a shift from industrial society towards informational capitalism. This transformation is a multidimensional shift that affects all aspects of society. Hence also the ethical system of society is penetrated by the emergence of the knowledge society and ethical guidelines for the information age are needed. Ethical issues and conflicts in the knowledge society are connected to topics of ecological and social sustainability. For information ethics and cyberethics, the sustainable design of society, social, and socio-technological systems is important. In this context the notions of sustainability and co-operation are discussed. Based on these categories, the approach of cyberethics of co-operation can be theoretically grounded.

Characterization of dendritic cells from human oral mucosa: a new Langerhans' cell type with high constitutive FcepsilonRI expression.

BACKGROUND: The oral mucosa represents a unique immunologic unit with a high frequency of native allergen contact within the gastrointestinal tract in which immune tolerance is the natural outcome of allergen contact. Although Langerhans' cells (LC), known to play a crucial role in initiating allergen-dependent immune responses in the skin, have also been detected in the oral mucosa, little is known about their phenotype and exact physiologic role. OBJECTIVE: To elucidate whether LC from oral mucosa (oLC) differ from skin LC (sLC), these cells were subjected to detailed comparative analysis. METHODS: Crude epidermal and oral mucosa cell suspensions were prepared by trypsinization. oLC and sLC were compared phenotypically by flow cytometry techniques and functionally in T-cell proliferation assays. RESULTS: In contrast to sLC, freshly isolated oLC expressed significantly higher amounts of MHC class I and II, as well as costimulatory molecules CD40, CD80/B7.1, and CD86/B7.2. oLC displayed FcgammaRIII/CD16 and FcgammaRI/CD64. Most surprisingly, oLC constitutively expressed the high affinity receptor for IgE (FcepsilonRI) even in nonatopic donors. FcepsilonRI expression on oLC was further increased and correlated with the serum IgE levels in atopic individuals. oLC showed a higher allogeneic stimulatory activity than sLC, whereas the activation of autologous T cells correlated to the FcepsilonRI expression. CONCLUSION: Taken together, our results strongly indicate that oLC profoundly differ from their skin counterparts. The constitutive high expression of FcepsilonRI on oLC could point to particular skills of these cells within the regional immune system of the oral mucosa.