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Introduction: Although major amputations can often be avoided due to evolving methods of endovascular and surgical revascularizations techniques, in patients with chronic limb-threatening ischemia, it is still necessary in some cases. Aim of this study was the detection of wound healing disorders through intraoperative microcirculation measurements in major limb amputations. Materials and methods: In this single-center clinical study, patients with an indication for major amputation were enrolled prospectively. Cause of amputation, patients' comorbidities including cardiovascular risk profile were assessed. Macrocirculation, as well as microcirculation were assessed. Microcirculation measurements were performed by fluorescence angiography with the administration of indocyanine green. A preoperative measurement was obtained at the amputation level, followed by three additional measurements of the amputation stump postoperatively. Wound healing was monitored and correlated with the microcirculatory findings, based on the perfusion parameters ingress and ingress rate, calculated in the indocyanine green fluorescence video sequences of the amputation stumps. Results: Forty-five patients were enrolled, including 19 (42%) below-the-knee amputations and 26 (58%) above-the-knee amputations. When considering the need for revision, a change in the microperfusion parameters was observed postoperatively. The mean value for ingress was significantly lower directly postoperatively in stumps requiring revisions (5 ± 0 A.U. versus 40.5 ± 42.5 A.U., p < 0.001). The mean value of ingress rate behaved similarly (0.15 ± 0.07 A.U./s versus 2.8 ± 5.0 A.U./s, p = 0.005). The evaluation of indocyanine green measurements when wound healing disorders occurred also showed nonsignificant differences in the mean values. Conclusion: Fluorescence angiography after major lower limb amputations appears to be an option of depicting microperfusion. Especially, the early postoperative detection of reduced perfusion can indicate a subsequent need for revision. Therefore, this method could possibly serve as a tool for intraoperative quality control after major limb amputation.
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BACKGROUND: Carotid endarterectomy (CEA) is a well-established standard therapy for patients with symptomatic or asymptomatic high-grade carotid stenosis. The aim of carotid endarterectomy is to decrease the risk of stroke and avoid relevant functional loss. However, carotid endarterectomy is known to be associated with hemodynamic dysregulation. In this study we compared eversion CEA (E-CEA) and conventional CEA (C-CEA) regarding postoperative blood pressure values as well as preoperative and postoperative baroreceptor sensitivity in the first 7 days after surgery. The aim was to find possible factors influencing changes in baroreceptor sensitivity. METHODS: Patients (111 patients were enrolled, of which 50 patients received C-CEA and 61 patients E-CEA) were prospectively enrolled in this study. For the measurement of baroreceptor sensitivity, a noninvasive Finometer measuring device from Finapres Medical System B.V. (Amsterdam, The Netherlands) was used. Measurements were performed 1 day before surgery (PRE), directly after surgery (F1), on day 1 (F2), day 2 (F3), and on day 7 (F4) postoperatively. RESULTS: Postoperative blood pressure values were significantly higher in the E-CEA group on the day of surgery (F1) (P < 0.001) and on day 1 (F2) (P < 0.001). From day 2 (F3, F4) postoperatively, no significant difference was found between the 2 groups. The invasive blood pressure measurement in the postoperative recovery room showed significantly higher systolic blood pressure values in the E-CEA group (P = 0.001). The need of acute antihypertensive therapy was significantly higher in the recovery room in the E-CEA group (P = 0.020). With regard to changes in baroreceptor sensitivity, significantly lower baroreceptor sensitivity (BRS) values were recorded in the E-CEA group at 1 day (F2) postoperatively (P = 0.005). The regression analysis showed that the applied surgical technique and the patient's age were significant factors influencing changes in baroreceptor sensitivity. CONCLUSIONS: In this study we could confirm higher blood pressure levels after E-CEA in the first 2 days after surgery. Additionally, we identified 22 factors possibly influencing baroreceptor sensitivity: surgical technique and age. Based on the data obtained in this study, hemodynamic dysregulation after CEA (E-CEA, C-CEA) is temporary and short-term. Already after the second postoperative day, there was no significant difference between the E-CEA and E-CEA groups, this effect remained stable after 7 days.
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Background: Arterio-venous fistulas (AVF) are used as first-line access for hemodialysis (HD) in the pediatric population. The aim of this investigation was to describe a single-center experience in the creation of AVF, together with its patency in children. Methods: This single-center retrospective study included all patients aged ≤18 years with AVFs created between 1993 and 2023. The collected data included patients' demographics, hemodialysis history, intraoperative data, and required reinterventions in order to determine the impact of these variables on primary, primary-assisted, and secondary patency. Results: Fifty-seven patients were analyzed with a median age of 15 years (range, 7-18 years). Fifty-four forearm and four upper arm fistulas were performed. The median follow-up was 6.9 years (range, 0-23 years). The primary failure rate was 10.5%. The primary patency rate was 67.6%, 53.6%, 51.4%, and 38.1% after 1, 3, 5, and 10 years; primary-assisted patency was 72.9%, 62.8%, 60.6%, and 41.5%; and secondary patency was 87.3%, 81.3%, 76.8%, and 66.6% after 1, 3, 5, and 10 years in the studied population. Conclusions: AVFs showed an acceptable rate of primary failure and excellent long-term patency. In this context, AVFs are an appropriate option for HD access, especially in pediatric patients.
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OBJECTIVES: This study aimed to develop a patient-centred approach to the burden of acute type A aortic dissection (ATAAD) through modelling. The main objective was to identify potential improvements in managing this life-threatening cardiovascular condition and to provide evidence-based recommendations to optimise outcomes. DESIGN: We developed a predictive model along patient pathways to estimate the burden of ATAAD through the years of life lost (YLLs) metric. The model was created based on a systematic review of the literature and was parameterised using demographic data from the German healthcare environment. The model was designed to allow interactive simulation of different scenarios resulting from changes in key impact factors. SETTING: The study was conducted using data from the German healthcare environment and results from the literature review. PARTICIPANTS: The study included a comprehensive modelling of ATAAD cases in Germany but did not directly involve participants. INTERVENTIONS: There were no specific interventions applied in this study based on the modelling design. PRIMARY AND SECONDARY OUTCOME MEASURES: The single outcome measure was the estimation of YLL due to ATAAD in Germany. RESULTS: Our model estimated 102 791 YLL per year for ATAAD in Germany, with 62 432 and 40 359 YLL for men and women, respectively. Modelling an improved care setting yielded 93 191 YLL or 9.3% less YLL compared with the current standard while a worst-case scenario resulted in 113 023 or 10.0% more YLL. The model is accessible at https://acuteaorticdissection.com/ to estimate custom scenarios. CONCLUSIONS: Our study provides an evidence-based approach to estimating the burden of ATAAD and identifying potential improvements in the management of pathways. This approach can be used by healthcare decision-makers to inform policy changes aimed at optimising patient outcomes. By considering patient-centred approaches in any healthcare environment, the model has the potential to improve efficient care for patients suffering from ATAAD.
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Dissecção Aórtica , Humanos , Alemanha , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Aneurisma Aórtico , Expectativa de Vida , Adulto , Doença Aguda , Idoso de 80 Anos ou mais , Efeitos Psicossociais da DoençaRESUMO
In this review, we aim to highlight the advantages, challenges, and limitations of electronic tongues (e-tongues) in pharmaceutical drug development. The authors, therefore, critically evaluated the performance of e-tongues regarding their qualification to assess peroral formulations containing bitter active pharmaceutical ingredients. A literature search using the keywords 'electronic', 'tongue', 'bitter', and 'drug' in a Web of Science search was therefore initially conducted. Reviewing the publications of the past decade, and further literature where necessary, allowed the authors to discuss whether and how e-tongues perform as expected and whether they have the potential to become a standard tool in drug development. Specifically highlighted are the expectations an e-tongue should meet. Further, a brief insight into the technologies of the utilized e-tongues is given. Reliable protocols were found that enable (i) the qualified performance of e-tongue instruments from an analytical perspective, (ii) proper taste-masking assessments, and (iii) under certain circumstances, the evaluation of bitterness.
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High quality laboratory results are critical for patient management. However, poor sample quality can impact these results and patient safety. To ensure reliable and accurate results laboratories must be aware of each analyte's stability under various storage conditions and matrices to guarantee correct and dependable outcomes. This knowledge allows laboratories to define the allowable delay between sample collection and centrifugation/analysis for all analytes to guarantee appropriate results quality and interpretation. The EFLM WG-PRE therefore established a 4-step plan to tackle this issue, aiming to standardize and harmonize stability studies for improved comparison and meta-analysis. The plan included the development of checklists and how-to guides for performing and reporting stability studies as well as a central resource of stability data. This manuscript deals with the issue of evaluating publications and incorporating them into a central resource. To evaluate stability studies, the CRESS checklist was used to structure 20 sections used to judge the quality of studies. Each section has 4 levels of quality, with scores converted to numerical values and weighted based on expert opinion. Based on this, a final score ranging from A to D was determined. The procedure was then tested on six manuscripts and checked for agreement between expert judgements. The results demonstrated that the proposed evaluation process is a useful tool to distinguish between best in class manuscripts and those of lower quality. The EFLM WG-PRE strongly believes that the provided recommendations and checklists will help improving stability studies both in quality and standardisation.
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BACKGROUND: Understanding the clinical features of myocarditis in various age groups is required to identify age-specific disease patterns. OBJECTIVES: The objective of this study was to examine differences in sex distribution and clinical outcomes in patients with myocarditis of various ages. METHODS: Patients with acute or chronic myocarditis in 3 centers in Berlin, Germany from 2005 to 2021 and in the United States (National Inpatient Sample) from 2010 to 2019 were included. Age groups examined included "prepubescent" (below 11 years for females and below 13 years for males), adolescents (11 [female] or 13 [male] to 18 years), young adults (18-35 years), "middle-aged adults" (35-54 years), and older adults (age >54 years). In patients admitted to the hospital, hospital mortality, length of stay, and medical complication rates were examined. RESULTS: Overall, 6,023 cases in Berlin and 9,079 cases in the U.S. cohort were included. In both cohorts, there were differences in sex distribution among the 5 age categories, and differences in the distribution were most notable in adolescents (69.3% males vs 30.7% females) and in young adults (73.8% males vs 26.3% females). Prepubescent and older adults had the highest rates of in-hospital mortality, hospital length of stay, and medical complications. In the Berlin cohort, prepubescent patients had higher levels of leukocytes (P < 0.001), antistreptolysin antibody (P < 0.001), and NT-proBNP (P < 0.001) when compared to young adults. CONCLUSIONS: In this study, we found that sex differences in myocarditis and clinical features of myocarditis were age-dependent.
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AIM: Blood Sampling Guidelines have been developed to target European emergency medicine-related professionals involved in the blood sampling process (e.g. physicians, nurses, phlebotomists working in the ED), as well as laboratory physicians and other related professionals. The guidelines population focus on adult patients. The development of these blood sampling guidelines for the ED setting is based on the collaboration of three European scientific societies that have a role to play in the preanalytical phase process: EuSEN, EFLM, and EUSEM. The elaboration of the questions was done using the PICO procedure, literature search and appraisal was based on the GRADE methodology. The final recommendations were reviewed by an international multidisciplinary external review group. RESULTS: The document includes the elaborated recommendations for the selected sixteen questions. Three in pre-sampling, eight regarding sampling, three post-sampling, and two focus on quality assurance. In general, the quality of the evidence is very low, and the strength of the recommendation in all the questions has been rated as weak. The working group in four questions elaborate the recommendations, based mainly on group experience, rating as good practice. CONCLUSIONS: The multidisciplinary working group was considered one of the major contributors to this guideline. The lack of quality information highlights the need for research in this area of the patient care process. The peculiarities of the emergency medical areas need specific considerations to minimise the possibility of errors in the preanalytical phase.
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Coleta de Amostras Sanguíneas , Serviço Hospitalar de Emergência , Humanos , Coleta de Amostras Sanguíneas/normas , Coleta de Amostras Sanguíneas/métodos , Medicina de Emergência/normas , Fase Pré-Analítica/normas , Europa (Continente) , Sociedades Médicas , Química Clínica/normas , Química Clínica/métodosRESUMO
The durability of an antibody (Ab) response is highly important for antiviral vaccines. However, due to the complex compositions of natural virions, the molecular determinants of Ab durability from viral infection or inactivated viral vaccines have been incompletely understood. Here we used a reductionist system of liposome-based virus-like structures to examine the durability of Abs from primary immune responses in mice. This system allowed us to independently vary fundamental viral attributes and to do so without additional adjuvants to model natural viruses. We show that a single injection of protein antigens (Ags) orderly displayed on a virion-sized liposome is sufficient to induce a long-lived neutralizing Ab (nAb) response. The introduction of internal nucleic acids dramatically modulates the magnitude of Ab responses without an alteration of the long-term kinetic trends. These Abs are characterized by very slow off-rates of ~0.0005 s-1, which emerged as early as day 5 after injection and these off-rates are comparable to that of affinity-matured monoclonal Abs. A single injection of these structures at doses as low as 100 ng led to lifelong nAb production in mice. Thus, a minimal virus-like immunogen can give rise to potent and long-lasting antiviral Abs in a primary response in mice without live infection. This has important implications for understanding both live viral infection and for optimizing vaccine design.
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Class-switched neutralizing antibody (nAb) production is rapidly induced upon many viral infections. However, due to the presence of multiple components in typical virions, the precise biochemical and biophysical signals from viral infections that initiate nAb responses remain inadequately defined. Using a reductionist system of synthetic virus-like structures (SVLS) containing minimal, highly purified biochemical components commonly found in enveloped viruses, here we show that a foreign protein on a virion-sized liposome can serve as a stand-alone danger signal to initiate class-switched nAb responses in the absence of cognate T cell help or Toll-like receptor signaling but requires CD19, the antigen (Ag) coreceptor on B cells. Introduction of internal nucleic acids (iNAs) obviates the need for CD19, lowers the epitope density (ED) required to elicit the Ab response and transforms these structures into highly potent immunogens that rival conventional virus-like particles in their ability to elicit strong Ag-specific IgG. As early as day 5 after immunization, structures harbouring iNAs and decorated with just a few molecules of surface Ag at doses as low as 100 ng induced all IgG subclasses of Ab known in mice and reproduced the IgG2a/2c restriction that has been long observed in live viral infections. These findings reveal a shared mechanism for nAb response upon viral infection. High ED is capable but not necessary for driving Ab secretion in vivo . Instead, even a few molecules of surface Ag, when combined with nucleic acids within these structures, can trigger strong antiviral IgG production. As a result, the signaling threshold for the induction of neutralizing IgG is set by dual signals originating from both ED on the surface and the presence of iNAs within viral particulate immunogens. One-sentence summary: Reconstitution of minimal viral signals necessary to initiate antiviral IgG.
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Peripheral arterial disease (PAD) leads to chronic vascular occlusion and results in end organ damage in critically perfused limbs. There are currently no clinical methods available to determine the muscular damage induced by chronic mal-perfusion. This monocentric prospective cross-sectional study investigated n = 193 adults, healthy to severe PAD, in order to quantify the degree of calf muscle degeneration caused by PAD using a non-invasive hybrid ultrasound and single wavelength optoacoustic imaging (US/SWL-OAI) approach. While US provides morphologic information, SWL-OAI visualizes the absorption of pulsed laser light and the resulting sound waves from molecules undergoing thermoelastic expansion. US/SWL-OAI was compared to multispectral data, clinical disease severity, angiographic findings, phantom experiments, and histological examinations from calf muscle biopsies. We were able to show that synergistic use of US/SWL-OAI is most likely to map clinical degeneration of the muscle and progressive PAD.
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Dispersive early life stages are common in nature. Although many dispersing organisms ("propagules") are passively moved by outside forces, some improve their chances of successful dispersal through weak movements that exploit the structure of the environment to great effect. The larvae of many coastal marine invertebrates, for instance, swim vertically through the water column to exploit depth-varying currents, food abundance, and predation risk. Several swimming behaviors and their effects on dispersal between habitats are characterized in the literature, yet it remains unclear when and why these behaviors are advantageous. We addressed this gap using a mathematical model of larval dispersal that scored how well behaviors allowed larvae to simultaneously locate habitats, avoid predators, and gather energy. We computed optimal larval behaviors through dynamic programming, and compared those optima against passive floating and three well documented behaviors from the literature. Optimal behaviors often (but not always) resembled the documented ones. However, our model predicted that the behaviors from the literature performed robustly well, if not optimally, across many conditions. Our results shed light on why some larval behaviors are widespread geographically and across species, and underscore the importance of carefully considering the weak movements of otherwise passive propagules when studying dispersal.
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Modelos Biológicos , Natação , Animais , Larva , Conceitos Matemáticos , EcossistemaRESUMO
However, due to the complex compositions of natural virions, the molecular determinants of Ab durability from viral infection or inactivated viral vaccines have been incompletely understood. Here we used a reductionist system of liposome-based virus-like structures to examine the durability of Abs in primary immune responses in mice. This system allowed us to independently vary fundamental viral attributes and to do so without additional adjuvants to model natural viruses. We show that a single injection of antigens (Ags) orderly displayed on a virion-sized liposome is sufficient to induce a long-lived neutralizing Ab (nAb) response. Introduction of internal nucleic acids dramatically modulates the magnitude of long-term Ab responses without alteration of the long-term kinetic trends. These Abs are characterized by exceptionally slow off-rates of ~0.0005 s-1, which emerged as early as day 5 after injection and these off-rates are comparable to that of affinity-matured monoclonal Abs. A single injection of these structures at doses as low as 100 ng led to lifelong nAb production in BALB/c mice. Thus, a minimal virus-like immunogen can give rise to potent and long-lasting antiviral Abs in a primary response in mice without live infection. This has important implications for understanding both live viral infection and for optimized vaccine design.
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BACKGROUND: Arteriovenous (AV) loops help to overcome absent or poor-quality recipient vessels in highly complex microvascular free flap reconstruction cases. There are no studies on blood flow and perfusion patterns. The purpose of this study was to evaluate and compare intraoperative hemodynamic characteristics of AV loops followed by free tissue transfer for thoracic wall and lower extremity reconstruction. METHODS: this prospective clinical study combined Transit-Time Flowmetry and microvascular Indocyanine Green Angiography for the assessment of blood flow volume, arterial vascular resistance and intrinsic transit time at the time of AV loop construction and on the day of free flap transfer. RESULTS: A total of 11 patients underwent AV loop creation, of whom five required chest wall reconstruction and six required reconstruction of the lower extremities. In seven of these cases, the latissimus dorsi flap and in four cases the vertical rectus abdominis myocutaneous (VRAM) flap was used as a free flap. At the time of loop construction, the blood flow volume of AV loops was 466 ± 180 mL/min, which increased to 698 ± 464 mL/min on the day of free tissue transfer (p > 0.1). After free flap anastomosis, the blood flow volume significantly decreased to 18.5 ± 8.3 mL/min (p < 0.001). There was no significant difference in blood flow volume or arterial vascular resistance between latissimus dorsi and VRAM flaps, nor between thoracic wall and lower extremity reconstruction. However, a significant correlation between the flap weight and the blood flow volume, as well as to the arterial vascular resistance, was found (p < 0.05). CONCLUSION: This is the first study to perform intraoperative blood flow and hemodynamic measurements of AV loops followed by free tissue transfer. Our results show hemodynamic differences and contribute to deeper understanding of the properties of AV loops for free flap reconstruction.
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Treatment of complex ischemic lower leg defects with exposure of deep anatomic structures represents a considerable challenge to involved specialties. In selected patients, limb salvage can be achieved as an alternative to major amputation by means of a combined approach including arterial reconstruction and subsequent free flap transfer. Arterial reconstruction can be performed either by endovascular or open surgical treatment (bypass reconstruction or implantation of an arteriovenous loop) preliminary to defect reconstruction using microsurgical free flap transplantation. Whereas the aim of the arterial reconstruction comprises the establishment of sufficient perfusion and creation of adequate target vessels for the free flap transfer, the selection of the appropriate flap entity depends on the extent of the wound as wells as on the presence of osteomyelitis. Arterial reconstruction and defect reconstruction can be performed as one-stage or two-stage procedure and has become an established and feasible treatment approach in centers. Evaluation of microperfusion by means of indocyanine green can further increase safety and feasibility of this method. Against this background, combined arterial reconstruction and subsequent free flap transfer provides excellent results in terms of amputation free survival and postoperative mobility. Essential is however an individualized decision making in consideration of patient selection and possible contraindications. This approach may be evaluated in mobile patients with complex wounds prior to major amputation.
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Assessing the factors responsible for differences in outbreak severity for the same pathogen is a challenging task, since outbreak data are often incomplete and may vary in type across outbreaks (e.g., daily case counts, serology, cases per household). We propose that outbreaks described with varied data types can be directly compared by using those data to estimate a common set of epidemiological parameters. To demonstrate this for chikungunya virus (CHIKV), we developed a realistic model of CHIKV transmission, along with a Bayesian inference method that accommodates any type of outbreak data that can be simulated. The inference method makes use of the fact that all data types arise from the same transmission process, which is simulated by the model. We applied these tools to data from three real-world outbreaks of CHIKV in Italy, Cambodia, and Bangladesh to estimate nine model parameters. We found that these populations differed in several parameters, including pre-existing immunity and house-to-house differences in mosquito activity. These differences resulted in posterior predictions of local CHIKV transmission risk that varied nearly fourfold: 16% in Italy, 28% in Cambodia, and 62% in Bangladesh. Our inference method and model can be applied to improve understanding of the epidemiology of CHIKV and other pathogens for which outbreaks are described with varied data types.
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Aedes , Febre de Chikungunya , Vírus Chikungunya , Animais , Humanos , Febre de Chikungunya/epidemiologia , Teorema de Bayes , Surtos de DoençasRESUMO
Background: Aim of this study was to assess the influence of intermitted negative pressure (INP) therapy on the foot microcirculation in patients with no-option CLTI. Patients and methods: CLTI patients defined as no option for revascularization on the basis of an interdisciplinary vascular board decision (interventional radiology, vascular surgery) were included in this study. INP therapy was performed at home. Therapy regime was: 1 hour twice daily. Follow-up was after 6 weeks and 3 months. Microcirculation measurement was performed by laser Doppler flowmetry and white light spectrometry (oxygen to see, O2CTM). Following parameters were evaluated: oxygen saturation (sO2 in%), relative hemoglobin (rHb) and flow (in arbitrary units A.U.). Additionally the clinical outcome of the patients was assessed. Results: From September 2020 to June 2022, 228 patients were screened. In total 19 patients (13 men, 6 women, mean age was 73.95 years) were included. 6 weeks after INP therapy the microcirculation showed a significant improvement for the parameter sO2 (%) (p=0.004). After 3 months a non-significant decrease compared to 6 weeks follow-up was seen for the parameter sO2; however, the perfusion was still improved compared to baseline measurement. With regard to the microperfusion values flow (AU) and hemoglobin (AU), the changes were not significant. Clinically, the patients reported a significant reduction of rest pain after therapy (p=0.005). Conclusions: INP therapy in no-option CLTI patients showed a significant improvement of the skin perfusion after 6 weeks. Therefore, INP therapy might have therapeutic potential in these critical ill patients.
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Isquemia Crônica Crítica de Membro , Extremidade Inferior , Masculino , Humanos , Feminino , Idoso , Extremidade Inferior/irrigação sanguínea , Pé/irrigação sanguínea , Pele/irrigação sanguínea , Hemoglobinas , Isquemia/diagnóstico por imagem , Isquemia/terapia , MicrocirculaçãoRESUMO
BACKGROUND: The Society for Cardiovascular Angiography and Interventions (SCAI) shock classification has been shown to provide robust mortality risk stratification in a variety of cardiovascular patients. OBJECTIVES: This study sought to evaluate the SCAI shock classification in postoperative cardiac surgery intensive care unit (CSICU) patients. METHODS: This study retrospectively analyzed 26,792 postoperative CSICU admissions at a heart center between 2012 and 2022. Patients were classified into SCAI shock stages A to E using electronic health record data. Moreover, the impact of late deterioration (LD) as an additional risk modifier was investigated. RESULTS: The proportions of patients in SCAI shock stages A to E were 24.4%, 18.8%, 8.4%, 35.5%, and 12.9%, and crude hospital mortality rates were 0.4%, 0.6%, 3.3%, 4.9%, and 30.2%, respectively. Similarly, the prevalence of postoperative complications and organ dysfunction increased across SCAI shock stages. After multivariable adjustment, each higher SCAI shock stage was associated with increased hospital mortality (adjusted OR: 1.26-16.59) compared with SCAI shock stage A, as was LD (adjusted OR: 8.2). The SCAI shock classification demonstrated a strong diagnostic performance for hospital mortality (area under the receiver operating characteristic: 0.84), which noticeably increased when LD was incorporated into the model (area under the receiver operating characteristic: 0.90). CONCLUSIONS: The SCAI shock classification effectively risk-stratifies postoperative CSICU patients for mortality, postoperative complications, and organ dysfunction. Its application could, therefore, be extended to the field of cardiac surgery as a triage tool in postoperative care and as a selection criterion in research.
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Procedimentos Cirúrgicos Cardíacos , Choque , Humanos , Estudos Retrospectivos , Insuficiência de Múltiplos Órgãos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Unidades de Terapia Intensiva , Choque Cardiogênico/epidemiologia , Choque Cardiogênico/etiologia , Complicações Pós-Operatórias/epidemiologia , Mortalidade HospitalarRESUMO
Multivalent viral epitopes induce rapid, robust and T cell-independent humoral immune responses, but the biochemical basis for such potency remains incompletely understood. We take advantage of a set of liposomes of viral size engineered to display affinity mutants of the model antigen (Ag) hen egg lysozyme. Particulate Ag induces potent 'all-or-none' B cell responses that are density dependent but affinity independent. Unlike soluble Ag, particulate Ag induces signal amplification downstream of the B cell receptor by selectively evading LYN-dependent inhibitory pathways and maximally activates NF-κB in a manner that mimics T cell help. Such signaling induces MYC expression and enables even low doses of particulate Ag to trigger robust B cell proliferation in vivo in the absence of adjuvant. We uncover a molecular basis for highly sensitive B cell responses to viral Ag display that is independent of encapsulated nucleic acids and is not merely accounted for by avidity and B cell receptor cross-linking.