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1.
Microvasc Res ; 136: 104164, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33831406

RESUMEN

INTRODUCTION: Microcirculatory alterations are key mechanisms in sepsis pathophysiology leading to tissue hypoxia, edema formation, and organ dysfunction. Hyperspectral imaging (HSI) is an emerging imaging technology that uses tissue-light interactions to evaluate biochemical tissue characteristics including tissue oxygenation, hemoglobin content and water content. Currently, clinical data for HSI technologies in critical ill patients are still limited. METHODS AND ANALYSIS: TIVITA® Tissue System was used to measure Tissue oxygenation (StO2), Tissue Hemoglobin Index (THI), Near Infrared Perfusion Index (NPI) and Tissue Water Index (TWI) in 25 healthy volunteers and 25 septic patients. HSI measurement sites were the palm, the fingertip, and a suprapatellar knee area. Septic patients were evaluated on admission to the ICU (E), 6 h afterwards (E+6) and three times a day (t3-t9) within a total observation period of 72 h. Primary outcome was the correlation of HSI results with daily SOFA-scores. RESULTS: Serial HSI at the three measurement sites in healthy volunteers showed a low mean variance expressing high retest reliability. HSI at E demonstrated significantly lower StO2 and NPI as well as higher TWI at the palm and fingertip in septic patients compared to healthy volunteers. StO2 and TWI showed corresponding results at the suprapatellar knee area. In septic patients, palm and fingertip THI identified survivors (E-t4) and revealed predictivity for 28-day mortality (E). Fingertip StO2 and THI correlated to SOFA-score on day 2. TWI was consistently increased in relation to the TWI range of healthy controls during the observation time. Palm TWI correlated positively with SOFA scores on day 3. DISCUSSION: HSI results in septic patients point to a distinctive microcirculatory pattern indicative of reduced skin oxygenation and perfusion quality combined with increased blood pooling and tissue water content. THI might possess risk-stratification properties and TWI could allow tissue edema evaluation in critically ill patients. CONCLUSION: HSI technologies could open new perspectives in microcirculatory monitoring by visualizing oxygenation and perfusion quality combined with tissue water content in critically ill patients - a prerequisite for future tissue perfusion guided therapy concepts in intensive care medicine.


Asunto(s)
Imágenes Hiperespectrales , Microcirculación , Imagen de Perfusión , Pruebas en el Punto de Atención , Sepsis/diagnóstico por imagen , Piel/irrigación sanguínea , Espectroscopía Infrarroja Corta , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Agua Corporal/metabolismo , Estudios de Casos y Controles , Enfermedad Crítica , Femenino , Hemoglobinas/metabolismo , Humanos , Imágenes Hiperespectrales/instrumentación , Masculino , Persona de Mediana Edad , Puntuaciones en la Disfunción de Órganos , Oxígeno/metabolismo , Imagen de Perfusión/instrumentación , Proyectos Piloto , Sistemas de Atención de Punto , Valor Predictivo de las Pruebas , Estudios Prospectivos , Flujo Sanguíneo Regional , Sepsis/metabolismo , Sepsis/fisiopatología , Piel/metabolismo , Espectroscopía Infrarroja Corta/instrumentación , Factores de Tiempo
2.
Eur Cell Mater ; 41: 245-268, 2021 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-33660785

RESUMEN

Reconstruction of bone defects and compensation of deficient repair mechanisms represent important goals within the field of regenerative medicine and require novel safe strategies for translation into the clinic. A non-viral osteogenic gene therapeutic vector system ('hybrid vectors') was generated, combining an improved bone morphogenetic protein 2 (BMP2) gene cassette and single pro-osteogenic microRNAs (miR-148b-3p, miR-20-5p, miR-590b-5p), driven by the U6 promoter. The vectors were tested in vitro for their osteogenic differentiation potential in C2C12 and C3H/10T1/2 cell lines, using BMP2 alone as control. After confirming BMP2 expression and miRNA transcription, increased osteogenic differentiation was observed by all hybrid vectors, but most consistently by BMP2/miR-590-5p, using alkaline phosphatase enzyme activity assays and osteogenic marker mRNA quantitation, including runt-related transcription factor 2 (Runx2), collagen type 1 (Col1a1) and osteocalcin. To visualise target mRNAs of the respective miRNAs, next generation sequencing was performed, confirming down-regulation of mRNA targets of the hybrid vectors. Since the hybrid vector consisting of BMP2 and miR-590-5p showed the largest increase in osteogenic differentiation in vitro, this was tested in a mouse ectopic-bone model. Mineralisation was more than with BMP2 alone. The present study showed hybrid vectors as a novel non-viral gene therapeutic plasmid system for combining therapeutic effects of recombinant protein expression and miRNA transcription that did not add to the burden of the translation machinery, while improving the therapeutic efficacies. In vivo proof-of-principle in the context of bone regeneration suggested that such hybrid vectors will be applicable in a wide array of gene therapeutic strategies.


Asunto(s)
Proteína Morfogenética Ósea 2/genética , Regeneración Ósea/genética , Huesos/fisiología , MicroARNs/genética , Animales , Células CHO , Diferenciación Celular/genética , Línea Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Cricetulus , Regulación hacia Abajo/genética , Femenino , Ratones , Osteoblastos/fisiología , Osteocalcina/genética , Osteogénesis/genética , ARN Mensajero/genética
3.
Anaesthesist ; 68(6): 403-418, 2019 06.
Artículo en Alemán | MEDLINE | ID: mdl-31049602

RESUMEN

Liver transplantation (LTPL) is the only curative option for patients with end stage liver disease (ESLD) or with hepatocellular carcinoma (HCC). Eurotransplant in Leiden, the Netherlands, is responsible for organ allocation. The model of end stage liver disease (MELD) score, which describes the severity of the liver disease, is decisive for organ allocation. The heterogeneous patient collective and hepatic-related comorbidities and their dynamics represent challenges. The anesthesiologist is responsible for evaluating the overall prognosis, whereby cardiac, pulmonary, renal and neurological comorbidities must be taken into consideration. During LTPL surgery is divided into several stages. Besides volume management, heat preservation and coagulation management, major challenges for the anesthesiologist are hemodynamic stabilization and regulation of the acid-base balance.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Trasplante de Hígado/métodos , Hígado/cirugía , Enfermedad Hepática en Estado Terminal , Selección de Paciente , Pronóstico , Factores de Riesgo , Obtención de Tejidos y Órganos
4.
Anaesthesist ; 68(11): 785-800, 2019 11.
Artículo en Alemán | MEDLINE | ID: mdl-31555832

RESUMEN

Multidrug-resistant pathogens often lead to treatment failure of antimicrobial regimens. After a period of imbalance between the occurrence/spread of resistance mechanisms and the development of new substances, some new substances have meanwhile been approved and many more are currently undergoing clinical testing. They are particularly effective against specific resistance mechanisms/pathogens and should be preserved for definitive treatment of an isolated pathogen. In the absence of alternatives reserve antibiotics, such as aztreonam and colistin have experienced a renaissance. They are again used in special infection scenarios and clinically tested in combination with new substances. Despite the introduction and development of new substances the building of resistance will at some time also render these (at least partially) ineffective. Therefore, their implementation must be carried out according to the antibiotic or infectious diseases stewardship.


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/tratamiento farmacológico , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Aztreonam/uso terapéutico , Colistina/uso terapéutico , Humanos , Pruebas de Sensibilidad Microbiana
5.
Anaesthesist ; 68(10): 711-730, 2019 10.
Artículo en Alemán | MEDLINE | ID: mdl-31555833

RESUMEN

The increase in resistant pathogens has long been a global problem. Complicated life-threatening infections due to multidrug-resistant pathogens (MRD) meanwhile occur regularly in intensive care medicine. An important and also potentially modifiable factor of the rapid spread of resistance is the irrational use of broad spectrum antibiotics in human medicine. In addition to many other resistance mechanisms, beta-lactamases play an important role in Gram-negative pathogens. They are not uncommonly the leading reason of difficult to treat infections and the failure of known routinely used broad spectrum antibiotics, such as cephalosporins, (acylamino)penicillins and carbapenems. Strategies for containment of MRDs primaríly target the rational use of antibiotics. In this respect interdisciplinary treatment teams, e.g. antibiotic stewardship (ABS) and infectious diseases stewardship (IDS) play a major role.


Asunto(s)
Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana/efectos de los fármacos , Carbapenémicos/uso terapéutico , Cefalosporinas/uso terapéutico , Humanos , Penicilinas/uso terapéutico
6.
Anaesthesist ; 68(Suppl 1): 40-62, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-29383395

RESUMEN

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective calculated antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed infection and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account during the selection of anti-infective treatment. Many pathophysiologic alterations influence the pharmacokinetics (PK) of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of ß­lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM, but for continuous infusion, TDM is generally necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug-resistant (MDR) pathogens in the intensive care unit. For effective treatment, antibiotic stewardship teams (ABS teams) are becoming more established. Interdisciplinary cooperation of the ABS team with infectious disease (ID) specialists, microbiologists, and clinical pharmacists leads not only to rational administration of antibiotics, but also has a positive influence on treatment outcome. The gold standards for pathogen identification are still culture-based detection and microbiologic resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction(PCR)-based procedures for pathogen identification and resistance determination are currently only an adjunct to routine sepsis diagnostics, due to the limited number of studies, high costs, and limited availability. In complicated septic courses with multiple anti-infective therapies or recurrent sepsis, PCR-based procedures can be used in addition to treatment monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically (still) absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation). (Contribution available free of charge by "Free Access" [ https://link.springer.com/article/10.1007/s00101-017-0396-z ].).


Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológico , Programas de Optimización del Uso de los Antimicrobianos , Biomarcadores , Monitoreo de Drogas , Humanos , Unidades de Cuidados Intensivos , Choque Séptico/tratamiento farmacológico , beta-Lactamas/farmacocinética , beta-Lactamas/uso terapéutico
7.
Anaesthesist ; 67(12): 936-949, 2018 12.
Artículo en Alemán | MEDLINE | ID: mdl-30511110

RESUMEN

In January 2018 the recent revision of the S2k guidelines on calculated parenteral initial treatment of bacterial diseases in adults-update 2018 (Editor: Paul Ehrlich Society for Chemotherapy, PEG) was realized. It is a helpful tool for the complex infectious disease setting in an intensive care unit. The present summary of the guidelines focuses on the topics of anti-infective agents, including new substances, pharmacokinetics and pharmacodynamics as well as on microbiology, resistance development and recommendations for calculated drug therapy in septic patients. As in past revisions the recent resistance situation and results of new clinical studies are considered and anti-infective agents are summarized in a table.


Asunto(s)
Antibacterianos/administración & dosificación , Infecciones Bacterianas/tratamiento farmacológico , Choque Séptico/tratamiento farmacológico , Guías como Asunto , Humanos , Infusiones Parenterales
8.
Anaesthesist ; 66(8): 614-621, 2017 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-28497242

RESUMEN

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) have been available since the beginning of 2016. SEPSIS-3 completely replaces the old SIRS criteria in the definition of sepsis and defines sepsis from now on as "life-threatening organ dysfunction caused by a dysregulated host response to infection". However, it seems questionable whether in clinical practice the new definition is really superior to the old one. The most important question is the following: Is it helpful to have a definition that first recognizes a patient once organ dysfunction has occurred and the patient already needs intensive care?


Asunto(s)
Sepsis/diagnóstico , Sepsis/terapia , Consenso , Cuidados Críticos , Humanos , Puntuaciones en la Disfunción de Órganos , Pronóstico , Sepsis/fisiopatología , Choque Séptico/diagnóstico , Choque Séptico/terapia , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Terminología como Asunto
9.
Anaesthesist ; 66(9): 672-678, 2017 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-28474244

RESUMEN

Accidents in which a person is run over are often associated with multiple serious injuries. Immediate bleeding control is crucial. Pressure and shear stress at the borders of subcutaneous tissue to the muscle fascia can cause hypoperfusion and the emergence of blood-filled cavities that are associated with a high risk of infection and necrosis, a so-called Morel-Lavallée lesion. Insufficient therapy can lead to local complications and furthermore to live-threatening sepsis.


Asunto(s)
Traumatismo Múltiple/terapia , Heridas y Lesiones/terapia , Accidentes de Tránsito , Adolescente , Desbridamiento , Hemorragia/etiología , Hemorragia/terapia , Humanos , Masculino , Traumatismo Múltiple/etiología , Traumatismo Múltiple/cirugía , Necrosis , Manejo del Dolor , Sepsis/etiología , Sepsis/terapia , Síndrome , Heridas y Lesiones/complicaciones
10.
Anaesthesist ; 66(10): 737-761, 2017 Oct.
Artículo en Alemán | MEDLINE | ID: mdl-28980026

RESUMEN

The mortality of patients with sepsis and septic shock is still unacceptably high. An effective antibiotic treatment within 1 h of recognition of sepsis is an important target of sepsis treatment. Delays lead to an increase in mortality; therefore, structured treatment concepts form a rational foundation, taking relevant diagnostic and treatment steps into consideration. In addition to the assumed focus and individual risks of each patient, local resistance patterns and specific problem pathogens must be taken into account for selection of anti-infection treatment. Many pathophysiological alterations influence the pharmacokinetics of antibiotics during sepsis. The principle of standard dosing should be abandoned and replaced by an individual treatment approach with stronger weighting of the pharmacokinetics/pharmacodynamics (PK/PD) index of the substance groups. Although this is not yet the clinical standard, prolonged (or continuous) infusion of beta-lactam antibiotics and therapeutic drug monitoring (TDM) can help to achieve defined PK targets. Prolonged infusion is sufficient without TDM but for continuous infusion TDM is basically necessary. A further argument for individual PK/PD-oriented antibiotic approaches is the increasing number of infections due to multidrug resistant pathogens (MDR) in the intensive care unit. For effective treatment antibiotic stewardship teams (ABS team) are becoming more established. Interdisciplinary cooperation of the ABS team with infectiologists, microbiologists and clinical pharmacists leads not only to a rational administration of antibiotics but also has a positive influence on the outcome. The gold standards for pathogen detection are still culture-based detection and microbiological resistance testing for the various antibiotic groups. Despite the rapid investigation time, novel polymerase chain reaction (PCR)-based procedures for pathogen identification and resistance determination, are currently only an adjunct to routine sepsis diagnostics due to the limited number of studies, high costs and limited availability. In complicated septic courses with multiple anti-infective treatment or recurrent sepsis, PCR-based procedures can be used in addition to therapy monitoring and diagnostics. Novel antibiotics represent potent alternatives in the treatment of MDR infections. Due to the often defined spectrum of pathogens and the practically absent resistance, they are suitable for targeted treatment of severe MDR infections (therapy escalation).


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/diagnóstico , Infecciones Bacterianas/tratamiento farmacológico , Sepsis/diagnóstico , Sepsis/tratamiento farmacológico , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/mortalidad , Farmacorresistencia Bacteriana , Humanos , Unidades de Cuidados Intensivos , Sepsis/microbiología , Sepsis/mortalidad , Choque Séptico/diagnóstico , Choque Séptico/tratamiento farmacológico
12.
Anaesthesist ; 65(9): 696-702, 2016 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-27596367

RESUMEN

Here, we present a case of a tracheal fistula due to an anastomotic insufficiency following abdominothoracic esophageal resection. Despite immediate discontinuity resection, the tracheal fistula could not be surgically closed, resulting in incomplete control of the source of infection and an alternative treatment concept in the form of interventional fistula closure using a Y-tracheal stent. However, owing to existing severe acute respiratory distress syndrome (ARDS), which is associated with a considerable risk of peri-interventional hypoxia, a temporary bridging concept using venovenous extracorporeal membrane oxygenation (ECMO) was implemented successfully.


Asunto(s)
Oxigenación por Membrana Extracorpórea/métodos , Fístula/cirugía , Control de Infecciones/métodos , Síndrome de Dificultad Respiratoria/terapia , Sepsis/prevención & control , Enfermedades de la Tráquea/cirugía , Anastomosis Quirúrgica/métodos , Broncoscopía , Humanos , Masculino , Persona de Mediana Edad , Síndrome de Dificultad Respiratoria/diagnóstico por imagen , Síndrome de Dificultad Respiratoria/etiología , Sepsis/diagnóstico por imagen , Stents , Tomografía Computarizada por Rayos X
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