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(1) Background: Sepsis is a leading cause of death and a global public health problem. Accordingly, deciphering the underlying molecular mechanisms of this disease and the determinants of its morbidity and mortality is pivotal. This study examined the effect of the rs951818 SNP of the negative costimulatory lymphocyte-activation gene 3 (LAG-3) on sepsis mortality and disease severity. (2) Methods: 707 consecutive patients with sepsis were prospectively enrolled into the present study from three surgical ICUs at University Medical Center Goettingen. Both 28- and 90-day mortality were analyzed as the primary outcome, while parameters of disease severity served as secondary endpoints. (3) Results: In the Kaplan-Meier analysis LAG-3 rs951818 AA-homozygote patients showed a significantly lower 28-day mortality (17.3%) compared to carriers of the C-allele (23.7%, p = 0.0476). In addition, these patients more often received invasive mechanical ventilation (96%) during the course of disease than C-allele carriers (92%, p = 0.0466). (4) Conclusions: Genetic profiling of LAG-3 genetic variants alone or in combination with other genetic biomarkers may represent a promising approach for risk stratification of patients with sepsis. Patient-individual therapeutic targeting of immune checkpoints, such as LAG-3, may be a future component of sepsis therapy. Further detailed investigations in clinically relevant sepsis models are necessary.
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OBJECTIVES: Early diagnosis of infections is pivotal in critically ill patients. Innovative gene expression-based approaches promise to deliver precise, fast, and clinically practicable diagnostic tools to bedside. This study aimed to validate the SepsisMetaScore, an 11-gene signature previously reported by our study group, in a representative longitudinal cohort of trauma patients. DESIGN: Prospective observational cohort study. SETTING: Surgical ICUs of the University Medical Center Goettingen, Germany. PATIENTS: Critically ill patients with severe traumatic injuries. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Paired box gene (PAXgene) RNA blood tubes were drawn at predefined time points over the course of disease. The performance of the SepsisMetaScore was tested using targeted polymerase chain reaction and compared with Procalcitonin using area under the receiver operating characteristics analyses. The SepsisMetaScore showed significant differences between infected and noninfected patients (n = 52). It was able to accurately discriminate infectious from noninfectious acute inflammation with an area under the receiver operating characteristics of 0.92 (95% CI, 0.85-0.99) and significantly outperformed Procalcitonin (area under the receiver operating characteristics curve = 0.53; 95% CI, 0.42-0.64) early in the course of infection (p = 0.014). CONCLUSIONS: We demonstrated the clinical utility for diagnosis of infections with higher accuracy using the SepsisMetaScore compared with Procalcitonin in a prospective cohort of severe trauma patients. Future studies should assess whether the SepsisMetaScore may substantially improve clinical practice by accurate differentiation of infections from sterile inflammation and identification of patients at risk for sepsis. Our results support further investigation of the SepsisMetaScore for the development of tailored precision treatment of critically ill patients.
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Expresión Génica , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/metabolismo , Adulto , Biomarcadores/sangre , Estudios de Cohortes , Enfermedad Crítica/terapia , Alemania , Humanos , Unidades de Cuidados Intensivos/organización & administración , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Síndrome de Respuesta Inflamatoria Sistémica/genéticaRESUMEN
Background: Previous studies have reported the fundamental role of immunoregulatory proteins in the clinical phenotype and outcome of sepsis. This study investigated two functional single nucleotide polymorphisms (SNPs) of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), which has a negative stimulatory function in the T cell immune response. Methods: Patients with sepsis (n = 712) were prospectively enrolled from three intensive care units (ICUs) at the University Medical Center Goettingen since 2012. All patients were genotyped for the TIM-3 SNPs rs1036199 and rs10515746. The primary outcome was 28-day mortality. Disease severity and microbiological findings were secondary endpoints. Results: Kaplan-Meier survival analysis demonstrated a significantly lower 28-day mortality for TIM-3 rs1036199 AA homozygous patients compared to C-allele carriers (18% vs. 27%, p = 0.0099) and TIM-3 rs10515746 CC homozygous patients compared to A-allele carriers (18% vs. 26%, p = 0.0202). The TIM-3 rs1036199 AA genotype and rs10515746 CC genotype remained significant predictors for 28-day mortality in the multivariate Cox regression analysis after adjustment for relevant confounders (adjusted hazard ratios: 0.67 and 0.70). Additionally, patients carrying the rs1036199 AA genotype presented more Gram-positive and Staphylococcus epidermidis infections, and rs10515746 CC homozygotes presented more Staphylococcus epidermidis infections. Conclusion: The studied TIM-3 genetic variants are associated with altered 28-day mortality and susceptibility to Gram-positive infections in sepsis.
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Receptor 2 Celular del Virus de la Hepatitis A/genética , Sepsis/genética , Sepsis/mortalidad , Adulto , Anciano , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad/genética , Genotipo , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Heterocigoto , Homocigoto , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Índice de Severidad de la EnfermedadRESUMEN
Septic shock is a frequent life-threatening condition and a leading cause of mortality in intensive care units (ICUs). Previous investigations have reported a potentially protective effect of obesity in septic shock patients. However, prior results have been inconsistent, focused on short-term in-hospital mortality and inadequately adjusted for confounders, and they have rarely applied the currently valid Sepsis-3 definition criteria for septic shock. This investigation examined the effect of obesity on 90-day mortality in patients with septic shock selected from a prospectively enrolled cohort of septic patients. A total of 352 patients who met the Sepsis-3 criteria for septic shock were enrolled in this study. Body-mass index (BMI) was used to divide the cohort into 24% obese (BMI ≥ 30 kg/m2) and 76% non-obese (BMI < 30 kg/m2) patients. Kaplan-Meier survival analysis revealed a significantly lower 90-day mortality (31% vs. 43%; p = 0.0436) in obese patients compared to non-obese patients. Additional analyses of baseline characteristics, disease severity, and microbiological findings outlined further statistically significant differences among the groups. Multivariate Cox regression analysis estimated a significant protective effect of obesity on 90-day mortality after adjustment for confounders. An understanding of the underlying physiologic mechanisms may improve therapeutic strategies and patient prognosis.
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Intraneural injection of a local anesthetic can damage the nerve, yet it occurs frequently during distal sciatic block with no neurological sequelae. This has led to a controversy about the optimal needle tip placement that results from the particular anatomy of the sciatic nerve with its paraneural sheath. The study population included patients undergoing lower extremity surgery under popliteal sciatic nerve block. Ultrasound-guidance was used to position the needle tip subparaneurally and to monitor the injection of the local anesthetic. Sonography and magnetic resonance imaging were used to assess the extent of the subparaneural injection. Twenty-two patients participated. The median sciatic cross-sectional area increased from 57.8 mm2 pre-block to 110.8 mm2 immediately post-block. An intraneural injection according to the current definition was seen in 21 patients. Two patients had sonographic evidence of an intrafascicular injection, which was confirmed by MRI in one patient (the other patient refused further examinations). No patient reported any neurological symptoms. A subparaneural injection in the popliteal segment of the distal sciatic nerve is actually rarely intraneural, i.e. intrafascicular. This may explain the discrepancy between the conventional sonographic evidence of an intraneural injection and the lack of neurological sequelae.
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Sepsis is a life-threatening condition and a significant challenge for those working in intensive care, where it remains one of the leading causes of mortality. According to the sepsis-3 definition, sepsis is characterized by dysregulation of the host response to infection. The TREM-1 gene codes for the triggering receptor expressed on myeloid cells 1, which is part of the pro-inflammatory response of the immune system. This study aimed to determine whether the functional TREM-1 rs2234237 single nucleotide polymorphism was associated with mortality in a cohort of 649 Caucasian patients with sepsis. The 90-day mortality rate was the primary outcome, and disease severity and microbiological findings were analyzed as secondary endpoints. TREM-1 rs2234237 TT homozygous patients were compared to A-allele carriers for this purpose. Kaplanâ»Meier survival analysis revealed no association between the clinically relevant TREM-1 rs2234237 single nucleotide polymorphism and the 90-day or 28-day survival rate in this group of septic patients. In addition, the performed analyses of disease severity and the microbiological findings did not show significant differences between the TREM-1 rs2234237 genotypes. The TREM-1 rs2234237 genotype was not significantly associated with sepsis mortality and sepsis disease severity. Therefore, it was not a valuable prognostic marker for the survival of septic patients in the studied cohort.
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Cytotoxic T lymphocyte-associated protein 4 (CTLA-4) is a coinhibitory checkpoint protein expressed on the surface of T cells. A recent study by our working group revealed that the rs231775 single nucleotide polymorphism (SNP) in the CTLA-4 gene was associated with the survival of patients with sepsis and served as an independent prognostic variable. To further investigate the impact of CTLA-4 genetic variants on sepsis survival, we examined the effect of two functional SNPs, CTLA-4 rs733618 and CTLA-4 rs3087243, and inferred haplotypes, on the survival of 644 prospectively enrolled septic patients. Kaplanâ»Meier survival analysis revealed significantly lower 90-day mortality for rs3087243 G allele carriers (n = 502) than for AA-homozygous (n = 142) patients (27.3% vs. 40.8%, p = 0.0024). Likewise, lower 90-day mortality was observed for TAA haplotype-negative patients (n = 197; compound rs733618 T/rs231775 A/rs3087243 A) than for patients carrying the TAA haplotype (n = 447; 24.4% vs. 32.9%, p = 0.0265). Carrying the rs3087243 G allele hazard ratio (HR): 0.667; 95% confidence interval (CI): 0.489â»0.909; p = 0.0103) or not carrying the TAA haplotype (HR: 0.685; 95% CI: 0.491â»0.956; p = 0.0262) remained significant covariates for 90-day survival in the multivariate Cox regression analysis and thus served as independent prognostic variables. In conclusion, our findings underscore the significance of CTLA-4 genetic variants as predictors of survival of patients with sepsis.
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OBJECTIVE: The mortality associated with sepsis remains unacceptably high, despite modern high-quality intensive care. Based on the results from previous studies, anaemia and its management in patients with sepsis appear to impact outcomes; however, the transfusion policy is still being debated, and the ideal approach may be extremely specific to the individual. This study aimed to investigate the long-term impact of anaemia requiring red blood cell (RBC) transfusion on mortality and disease severity in patients with sepsis. We studied a general surgical intensive care unit (ICU) population, excluding cardiac surgery patients. 435 patients were enrolled in this observational study between 2012 and 2016. RESULTS: Patients who received RBC transfusion between 28 days before and 28 days after the development of sepsis (n = 302) exhibited a significantly higher 90-day mortality rate (34.1% vs 19.6%; P = 0.004, Kaplan-Meier analysis). This association remained significant after adjusting for confounders in the multivariate Cox regression analysis (hazard ratio 1.68; 95% confidence interval 1.03-2.73; P = 0.035). Patients who received transfusions also showed significantly higher morbidity scores, such as SOFA scores, and ICU lengths of stay compared to patients without transfusions (n = 133). Our results indicate that anaemia and RBC transfusion are associated with unfavourable outcomes in patients with sepsis.
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Anemia/terapia , Transfusión Sanguínea , Estimación de Kaplan-Meier , Sepsis/complicaciones , Procedimientos Quirúrgicos Operativos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Sepsis/mortalidad , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Continuous blockade of the femoral nerve is widely used for postoperative analgesia after hip surgery. It can be achieved by ultrasound-guided placement of a femoral nerve catheter via either the in plane (IP) or out of plane (OOP) technique. On the basis of postoperative radiographs, we evaluated the paths of femoral nerve catheters with respect to both techniques and its effect on postoperative analgesia. METHODS: Thirty-four patients were randomized to receive a radiopaque femoral nerve catheter via either the IP or OOP technique. The paths and tip position of the catheters were evaluated in postoperative frontal radiographs of the operated hip joint concerning a predefined target region and four neighboring regions. Pain scores were assessed using a numeric rating scale (0-10). RESULTS: Sixteen IP patients and 18 OOP patients were included in the study. The catheter path was radiographically evaluated in 13 IP patients and in 10 OOP patients. The catheter tips were located within the target region in 39% of the IP group and in 50% of the OOP group. The catheter tip was 0.00âcm [-3.80 to 3.84] and -1.19âcm [-12.27 to 0.00] (median [range]) from the target region in the OOP group and IP group, respectively (Pâ=â.045). Catheters flipped distally more often in the IP group (IP: 61.5%, OOP: 10.0%; Pâ=â.01). There were no marked differences in the pain scores of either group. CONCLUSION: Femoral nerve catheters inserted by the ultrasound-guided IP technique flip distally more frequently than catheters inserted by the OOP technique. Moreover, the distance between the catheter tip and the trunk of the femoral nerve is greater for IP catheters than for OOP catheters. Despite these findings, postoperative analgesia did not seem to differ between the 2 techniques.
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Cateterismo/métodos , Nervio Femoral , Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Anciano , Anciano de 80 o más Años , Analgésicos/administración & dosificación , Femenino , Articulación de la Cadera/diagnóstico por imagen , Articulación de la Cadera/cirugía , Humanos , Bombas de Infusión , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Estudios Prospectivos , Ultrasonografía IntervencionalRESUMEN
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a surface protein on T cells, that has an inhibitory effect on the host immune reaction and prevents overreaction of the immune system. Because the functional single-nucleotide polymorphism (SNP) rs231775 of the CTLA-4 gene is associated with autoimmune diseases and because of the critical role of the immune reaction in sepsis, we intended to examine the effect of this polymorphism on survival in patients with sepsis. 644 septic adult Caucasian patients were prospectively enrolled in this study. Patients were followed up for 90 days. Mortality risk within this period was defined as primary outcome parameter. Kaplan-Meier survival analysis revealed a significantly lower 90-day mortality risk among GG homozygous patients (n = 101) than among A allele carriers (n = 543; 22% and 32%, respectively; p = 0.03565). Furthermore, the CTLA-4 rs231775 GG genotype remained a significant covariate for 90-day mortality risk after controlling for confounders in the multivariate Cox regression analysis (hazard ratio: 0.624; 95% CI: 0.399-0.975; p = 0.03858). In conclusion, our study provides the first evidence for CTLA-4 rs231775 as a prognostic variable for the survival of patients with sepsis and emphasizes the need for further research to reveal potential functional associations between CTLA-4 and the immune pathophysiology of sepsis.
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Alelos , Antígeno CTLA-4/genética , Genotipo , Sepsis/genética , Sepsis/mortalidad , Población Blanca/genética , Biomarcadores , Comorbilidad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , Sepsis/diagnóstico , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Factores de TiempoRESUMEN
BACKGROUND: Out-of-hospital analgosedation in trauma patients is challenging for emergency physicians due to associated complications. We compared peripheral nerve block (PNB) with analgosedation (AS) as an analgetic approach for patients with isolated extremity injury, assuming that prehospital required medical interventions (e.g. reduction, splinting of dislocation injury) using PNB are less painful and more feasible compared to AS. METHODS: Thirty patients (aged 18 or older) were randomized to receive either ultrasound-guided PNB (10 mL prilocaine 1%, 10 mL ropivacaine 0.2%) or analgosedation (midazolam combined with s-ketamine or with fentanyl). Reduction-feasibility was classified (easy, intermediate, impossible) and pain scores were assessed using numeric rating scales (NRS 0-10). RESULTS: Eighteen patients were included in the PNB-group and twelve in the AS-group; 15 and 9 patients, respectively, suffered dislocation injury. In the PNB-group, reduction was more feasible (easy: 80.0%, impossible: 20.0%) compared to the AS-group (easy: 22.2%, intermediate: 22.2%, impossible: 55.6%; p = 0.01). During medical interventions, 5.6% [1/18] of the PNB-patients and 58.3% [7/12] of the AS-patients experienced pain (p<0.01). Recorded pain scores were significantly lower in the PNB-group during prehospital medical intervention (median[IQR] NRS PNB: 0[0-0]) compared to the AS-group (6[0-8]; p<0.001) as well as on first day post presentation (NRS PNB: 1[0-5], AS: 5[5-7]; p = 0.050). All patients of the PNB-group would recommend their analgesic technique (AS: 50.0%, p<0.01). CONCLUSIONS: Prehospital ultrasound-guided PNB is rapidly performed in extremity injuries with high success. Compared to the commonly used AS in trauma patients, PNB significantly reduces pain intensity and severity.
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Analgesia/métodos , Anestésicos Locales/administración & dosificación , Extremidades/lesiones , Luxaciones Articulares/complicaciones , Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Ultrasonografía/métodos , Extremidades/diagnóstico por imagen , Estudios de Factibilidad , Femenino , Humanos , Luxaciones Articulares/diagnóstico por imagen , Luxaciones Articulares/fisiopatología , Masculino , Persona de Mediana Edad , Manejo del Dolor , Dolor Postoperatorio/etiología , Estudios ProspectivosRESUMEN
BACKGROUND: Previous studies on the Miscellaneous Crenarchaeota Group, recently assigned to the novel archaeal phylum Bathyarchaeota, reported on the dominance of these Archaea within the anaerobic carbohydrate cycle performed by the deep marine biosphere. For the first time, members of this phylum were identified also in mesophilic and thermophilic biogas-forming biofilms and characterized in detail. RESULTS: Metagenome shotgun libraries of biofilm microbiomes were sequenced using the Illumina MiSeq system. Taxonomic classification revealed that between 0.1 and 2% of all classified sequences were assigned to Bathyarchaeota. Individual metagenome assemblies followed by genome binning resulted in the reconstruction of five metagenome-assembled genomes (MAGs) of Bathyarchaeota. MAGs were estimated to be 65-92% complete, ranging in their genome sizes from 1.1 to 2.0 Mb. Phylogenetic classification based on core gene sets confirmed their placement within the phylum Bathyarchaeota clustering as a separate group diverging from most of the recently known Bathyarchaeota clusters. The genetic repertoire of these MAGs indicated an energy metabolism based on carbohydrate and amino acid fermentation featuring the potential for extracellular hydrolysis of cellulose, cellobiose as well as proteins. In addition, corresponding transporter systems were identified. Furthermore, genes encoding enzymes for the utilization of carbon monoxide and/or carbon dioxide via the Wood-Ljungdahl pathway were detected. CONCLUSIONS: For the members of Bathyarchaeota detected in the biofilm microbiomes, a hydrolytic lifestyle is proposed. This is the first study indicating that Bathyarchaeota members contribute presumably to hydrolysis and subsequent fermentation of organic substrates within biotechnological biogas production processes.
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BACKGROUND: Non-ST elevation myocardial infarction (NSTEMI) is a common manifestation of acute coronary syndrome (ACS), but delayed diagnosis can increase mortality. In this proof of principle study, the emergency physician performed transthoracic echocardiography (TTE) on scene to determine whether NSTEMI could be correctly diagnosed pre-hospitalization. This could expedite admission to the appropriate facility and reduce the delay until initiation of correct therapy. METHODS: Pre-hospital TTE was performed on scene by the emergency physician in patients presenting with ACS but without ST-elevation in the initial 12-lead electrocardiography (ECG) (NSTE-ACS). A presumptive NSTEMI diagnosis was made if regional wall motion abnormalities (RWMA) were detected. These patients were admitted directly to a specialist cardiac facility. Patient characteristics and pre-admission and post-admission clinical, pre-hospital TTE data, and therapeutic measures were recorded. RESULTS: Patients with NSTE-ACS (n = 53; 72.5 ± 13.4 years of age; 23 female) were studied. The 20 patients with pre-hospital RWMA and presumptive NSTEMI, and two without RWMA were conclusively diagnosed with NSTEMI in hospital. Percutaneous coronary intervention was performed in 50% of the patients presumed to have NSTEMI immediately after admission. The RWMA seen before hospital TTE corresponded with the in-hospital ECG findings and/or the supply regions of the occluded coronary vessels seen during PCI in 85% of the cases. The diagnostic sensitivity of pre-hospital TTE for NSTEMI was 90.9% with 100% specificity. CONCLUSIONS: Pre-hospital transthoracic echocardiography by the emergency physician can correctly diagnose NSTEMI in more than 90% of cases. This can expedite the initiation of appropriate therapy and could thereby conceivably reduce morbidity and mortality. TRIAL REGISTRATION: Deutsche Register klinischer Studien, DRKS00004919 . Registered on 29 April 2013.
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Ecocardiografía/métodos , Servicios Médicos de Urgencia/métodos , Infarto del Miocardio sin Elevación del ST/diagnóstico , Medición de Riesgo/métodos , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/mortalidad , Anciano , Anciano de 80 o más Años , Diagnóstico Tardío/mortalidad , Ecocardiografía/normas , Electrocardiografía/métodos , Servicios Médicos de Urgencia/normas , Femenino , Alemania , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio sin Elevación del ST/mortalidad , Estadísticas no ParamétricasRESUMEN
A recent genome-wide association study showed that a genetic variant within the FER gene is associated with survival in patients with sepsis due to pneumonia. Because severe pneumonia is the main cause of acute respiratory distress syndrome (ARDS), we aimed to investigate the effect of the FER polymorphism rs4957796 on the 90-day survival in patients with ARDS due to pneumonia. An assessment of a prospectively collected cohort of 441 patients with ARDS admitted to three intensive care units at the University Medical Centre identified 274 patients with ARDS due to pneumonia. The 90-day mortality risk was recorded as the primary outcome parameter. Sepsis-related organ failure assessment (SOFA) scores and organ support-free days were used as the secondary variables. FER rs4957796 TT-homozygous patients were compared with C-allele carriers. The survival analysis revealed a higher 90-day mortality risk among T homozygotes than among C-allele carriers (p = 0.0144) exclusively in patients with severe ARDS due to pneumonia. The FER rs4957796 TT genotype remained a significant covariate for the 90-day mortality risk in the multivariate analysis (hazard ratio, 4.62; 95% CI, 1.58-13.50; p = 0.0050). In conclusion, FER rs4957796 might act as a prognostic variable for survival in patients with severe ARDS due to pneumonia.
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Alelos , Genotipo , Neumonía/complicaciones , Proteínas Tirosina Quinasas/genética , Síndrome de Dificultad Respiratoria/etiología , Síndrome de Dificultad Respiratoria/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía/epidemiología , Pronóstico , Modelos de Riesgos Proporcionales , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/epidemiología , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
BACKGROUND: Effective methods for postoperative pain relief are an important concern in outpatient surgery. For arthroscopies we combine a single-shot peripheral nerve block using low-volume, low-concentration ropivacaine with general anesthesia. We hypothesized that the patients would have less postoperative pain and be more rapidly home ready than after general anesthesia alone. METHODS: Patients (American Society of Anesthesiologists I-III, 18-80 years old) scheduled for outpatient arthroscopy on the upper or lower extremity were randomized to have either a combination of peripheral nerve block and general anesthesia (NB + GA, study group) or general anesthesia alone (GA, control group). The relevant nerve was localized by ultrasound and 10âmL ropivacaine 0.2% was injected. General anesthesia was with propofol and remifentanil. Numeric rating scales were used to assess pain and patient satisfaction in the recovery room, on the evening of surgery, and on the following 2 days. RESULTS: A total of 120 patients participated in the study (NBâ+âGA: 61; GA: 59). The percentage of patients reporting relevant pain in the recovery room were 0% versus 44% (Pâ<â0.001), on the evening after surgery 3% versus 80% (Pâ<â0.001), and on days 1 and 2 postsurgery 12% versus 73% and 12% versus 64% (NBâ+âGA vs GA, respectively). Median time to home discharge was NBâ+âGA 34.5âmin (range 15-90) versus GA 55âmin (20-115) (Pâ<â0.001). CONCLUSIONS: The combination of a peripheral nerve block with low-dose ropivacaine and general anesthesia reduced postoperative pain compared with general anesthesia alone for several days after outpatient arthroscopy. It also shortened the time to home discharge.
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Amidas/uso terapéutico , Anestesia General/métodos , Anestésicos Locales/uso terapéutico , Artroscopía/métodos , Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Procedimientos Quirúrgicos Ambulatorios/métodos , Amidas/administración & dosificación , Anestésicos Locales/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Periodo Perioperatorio , Ropivacaína , Factores de Tiempo , Adulto JovenRESUMEN
The aim of this study was to analyze the effect of the addition of rice straw and clay residuals on the prokaryote methane-producing community structure in a semi-continuously stirred tank reactor fed with swine manure. Molecular techniques, including terminal restriction fragment length polymorphism and a comparative nucleotide sequence analyses of the prokaryotic 16S rRNA genes, were performed. The results showed a positive effect of clay addition on methane yield during the co-digestion of swine manure and rice straw. At the digestion of swine manure, the bacterial phylum Firmicutes and the archaeal family Methanosarcinaceae, particularly Methanosarcina species, were predominant. During the co-digestion of swine manure and rice straw the microbial community changed, and with the addition of clay residual, the phylum Bacteroidetes predominated. The new nutritional conditions resulted in a shift in the archaeal family Methanosarcinaceae community as acetoclastic Methanosaeta species became dominant.
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Silicatos de Aluminio/química , Reactores Biológicos/microbiología , Estiércol/microbiología , Oryza/química , Porcinos/microbiología , Anaerobiosis , Animales , Archaea/clasificación , Archaea/aislamiento & purificación , Bacterias/clasificación , Bacterias/aislamiento & purificación , Arcilla , Metano , ARN de Archaea/genética , ARN Bacteriano/genética , ARN Ribosómico 16S/genéticaRESUMEN
Hyperglycemia is common during and after Coronary Artery Bypass Graft Surgery (CABGS) and has been shown to be associated with poor clinical outcomes. In this study, we hypothesized that a moderate perioperative mean blood glucose level ofâ<150âmg/dL improves long-term survival in cardiac surgery patients. We conducted a prospective, observational cohort study in the heart center of the University Medical Center of Goettingen, Germany. Patients undergoing on-pump cardiac surgery were enrolled in this investigation. After evaluating perioperative blood glucose levels, patients were classified into 2 groups based on mean glucose levels: Glucose ≥150âmg/dL and Glucoseâ<150âmg/dL. Patients were followed up for 5 years, and mortality within this period was recorded as the primary outcome parameter. Secondary outcome parameters included the length of ICU stay, the use of inotropic agents, the length of hospital stay, and the in-hospital mortality. A total of 455 consecutive patients who underwent cardiac surgery with cardiopulmonary bypass were enrolled in this investigation. A Kaplan-Meier survival analysis of the 5-year mortality risk revealed a higher mortality risk among patients with glucose levels ≥150âmg/dL (Pâ=â0.0043, log-rank test). After adjustment for confounders in a multivariate Cox regression model, the association between glucose ≥150âmg/dL and 5-year mortality remained significant (hazard ratio, 2.10; 95% CI, 1.30-3.39; Pâ=â0.0023). This association was corroborated by propensity score matching, in which Kaplan-Meier survival analysis demonstrated significant improvement in the 5-year survival of patients with glucose levelsâ<150âmg/dL (Pâ=â0.0339). Similarly, in-hospital mortality was significantly higher in patients with glucose ≥150âmg/dL compared with patients with glucoseâ<150âmg/dL. Moreover, patients in the Glucose ≥150âmg/dL group required significantly higher doses of the inotropic agent Dobutamine (mg/d) compared with patients in the Glucoseâ<150âmg/dL group (20.6â±â62.3 and 10.5â±â40.7, respectively; Pâ=â0.0104). Moreover, patients in the Glucose ≥150âmg/dL group showed a significantly longer hospital stay compared with patients in the Glucoseâ<150âmg/dL group (28â±â23 and 24â±â19, respectively; Pâ=â0.0297). We conclude that perioperative blood glucose levelsâ<150âmg/dL are associated with improved 5-year survival in patients undergoing cardiac surgery. More studies are warranted to explain this effect.
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Glucemia , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/mortalidad , Hiperglucemia/complicaciones , Periodo Perioperatorio , APACHE , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Alemania , Mortalidad Hospitalaria , Humanos , Estimación de Kaplan-Meier , Tiempo de Internación , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Prospectivos , Factores de Riesgo , Factores SexualesRESUMEN
According to previous studies, the clinical course of sepsis could be affected by preexisting medical conditions, which are very common among patients with sepsis. This observational study aimed at investigating whether common chronic medical conditions affect the 90-day mortality risk in adult Caucasian patients with sepsis. A total of 482 patients with sepsis were enrolled in this study. The ninety-day mortality was the primary outcome; organ failure was the secondary outcome. Sepsis-related organ failure assessment (SOFA) scores and the requirements for organ support were evaluated to assess organ failure. A multivariate Cox regression model for the association between the 90-day mortality risk and chronic preexisting medical conditions adjusted for all relevant confounders and mortality predictors revealed the highest hazard ratio for patients with chronic kidney disease (CKD) (hazard ratio, 2.25; 95% CI, 1.46-3.46; p = 0.0002). Patients with CKD had higher SOFA scores than patients without CKD (8.9 ± 4.0 and 6.5 ± 3.4, respectively; p < 0.0001). Additionally, an analysis of organ-specific SOFA scores revealed higher scores in three organ systems (kidney, cardiovascular and coagulation). Patients with CKD have the highest 90-day mortality risk compared with patients without CKD or with other chronic medical conditions.
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Insuficiencia Renal Crónica/patología , Sepsis/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , Demografía , Femenino , Humanos , Unidades de Cuidados Intensivos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Insuficiencia Multiorgánica/etiología , Modelos de Riesgos Proporcionales , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/mortalidad , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
According to previous investigations, CD14 is suggested to play a pivotal role in initiating and perpetuating the pro-inflammatory response during sepsis. A functional polymorphism within the CD14 gene, rs2569190, has been shown to impact the pro-inflammatory response upon stimulation with lipopolysaccharide, a central mediator of inflammation in sepsis. In this study, we hypothesized that the strong pro-inflammatory response induced by the TT genotype of CD14 rs2569190 may have a beneficial effect on survival (30-day) in patients with sepsis. A total of 417 adult patients with sepsis (and of western European descent) were enrolled into this observational study. Blood samples were collected for rs2569190 genotyping. Patients were followed over the course of their stay in the ICU, and the 30-day mortality risk was recorded as the primary outcome parameter. Sepsis-related organ failure assessment (SOFA) scores were quantified at sepsis onset and throughout the observational period to monitor organ failure as a secondary variable. Moreover, organ support-free days were evaluated as a secondary outcome parameter. TT-homozygous patients were compared to C-allele carriers. Kaplan-Meier survival analysis revealed a higher 30-day mortality risk among C-allele carriers compared with T homozygotes (p = 0.0261). To exclude the effect of potential confounders (age, gender, BMI and type of infection) and covariates that varied at baseline with a p-value < 0.2 (e.g., comorbidities), we performed multivariate Cox regression analysis to examine the survival time. The CD14 rs2569190 C allele remained a significant covariate for the 30-day mortality risk in the multivariate analysis (hazard ratio, 2.11; 95% CI, 1.08-4.12; p = 0.0282). The 30-day mortality rate among C allele carriers was 23%, whereas the T homozygotes had a mortality rate of 13%. Additionally, an analysis of organ-specific SOFA scores revealed a significantly higher SOFA-Central nervous system score among patients carrying the C allele compared with T-homozygous patients (1.9±1.1 and 1.6±1.0, respectively; p = 0.0311). In conclusion, CD14 rs2569190 may act as a prognostic variable for the short-term outcome (30-day survival) in patients with sepsis.
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Alelos , Homocigoto , Receptores de Lipopolisacáridos/genética , Polimorfismo Genético , Sepsis/genética , Sepsis/mortalidad , Adulto , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Estudios Prospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND: Even extremely high-doses of the potent opioid, sufentanil, cannot reliably suppress stress responses to intense surgical stimuli such as sternotomy. The chemically related opioid remifentanil with its different pharmacokinetics and binding affinities for delta- and kappa-opioid receptors might be more effective in attenuating these responses. METHODS: ASA I-III patients scheduled for a surgical procedure with sternotomy under balanced anesthesia (sevoflurane and sufentanil 3 µg.kg(-1) bolus, 0.017 µg.kg(-1).min(-1) infusion) were randomized into two groups. Patients in the study group were supplemented with remifentanil (2 µg.kg(-1) bolus, 2-7 µg.kg(-1).min(-1) infusion) starting ten minutes before sternotomy. Heart rate, arterial blood pressures, cardiac index, ejection fraction, systemic vascular resistance index (SVRI), total body oxygen uptake (VO2) and electric dermal response were measured and compared between the groups. RESULTS: 62 patients were studied (study group 32, control group 30). Systolic and mean arterial blood pressures, SVRI, VO2 and skin conductance increased during sternotomy and sternal spread in the control group but not in the study group. Systolic blood pressure increase: 7.5 ± 19 mmHg vs. -3.4 ± 8.9 (p = 0.005); VO2 increase: 31 ± 46% vs. -0.4 ± 32%; incidence of systolic blood pressure increase greater than 15 percent: 20% vs. 3% (p = 0.035) (control vs. study group). CONCLUSION: High-dose remifentanil added to sevoflurane-sufentanil anesthesia suppresses the sympathoadrenergic response to sternotomy and sternal spread better than high-dose sufentanil alone. CLINICAL TRIAL NUMBER: DRKS00004327, August 31, 2012.