Relationship between Intraoperative Bile Culture Outcomes and Subsequent Postoperative Infectious Complications: A Retrospective Cohort Study.

The presence of positive bile culture during intraoperative procedures has been associated with elevated morbidity and mortality rates in hepatobiliopancreatic surgeries, contributing to increased healthcare expenditures. However, the precise impact of bactobilia on the development of postoperative complications remains uncertain due to existing disparities in the published literature. In this retrospective cohort study, we assessed 137 patients who underwent major hepatobiliopancreatic surgery to examine the relationship between intraoperative bile culture outcomes and subsequent postoperative infectious complications. Among patients with bactobilia, a significant 35.1% exhibited systemic or local infectious complications, whereas only 11.1% of those with negative culture results experienced any infectious complications (p = 0.002). Similarly, a notable difference was observed in the incidence of surgical site infections, with 24.3% in the bactobilia group compared to 7.9% in the negative culture group (p = 0.01). A total of 74 monomicrobial cultures with microbiological growth were isolated, predominantly featuring Gram-negative microorganisms, primarily Enterobacteriaceae in 49 cultures. Escherichia coli was identified in 37.8% of positive cultures, while Klebsiella pneumoniae was evident in 21.6%. Gram-positive microorganisms were present in 10 cultures, with Enterococcus emerging as the prevailing species. The logistic regression model identified a positive bile culture as an independent factor significantly associated with infection development (OR: 2.26; 95% confidence interval: 1.23-11; p = 0.02). Considering the limitations of the study, these findings underscore the critical importance of conducting bile cultures during the intraoperative phase to enable vigilant monitoring and prompt management of infectious complications.

Wernicke's Encephalopathy in a Patient With Type III Intestinal Failure: A Case Report.

This case is about a 38-year-old male patient with a history of type III intestinal failure due to chronic intestinal pseudo-obstruction caused by gastrointestinal dysmotility, cardiac and intestinal arrhythmia syndrome, dependence on parenteral nutrition, sinus dysfunction, and carrying a pacemaker. The patient presented with symptoms suggestive of a new episode of intestinal obstruction. A contrast-enhanced abdominal computed tomography scan was performed, revealing intestinal obstruction with a transition zone in the jejunum. Non-operative medical management of the obstructive condition was initiated. However, after 10 days of medical management, the patient began experiencing nausea and dizziness. Initially, symptomatic management was provided, but the patient reported persistent vertigo-like sensations. Following evaluation by multiple specialties, magnetic resonance imaging (MRI) was requested, which showed bilateral and symmetrical hyperintensity on T2-weighted images of the dorsomedial aspect of the thalami around the third ventricle, in the periaqueductal gray matter, the mesencephalic tectum, and, to a lesser extent, the bulbar tectum, findings suggestive of Wernicke's encephalopathy. Urgent intravenous thiamine replacement was initiated. After 10 days of effective treatment, the patient exhibited a nearly complete improvement in symptoms. A follow-up MRI was ordered, indicating considerable improvement when compared to the previous study.

Sub-lineage B.1.6 of hMPXV in a global context: Phylogeny and epidemiology.

During the 2022 COVID-19 pandemic, monkeypox emerged as a significant threat to global health. The virus responsible for the disease, the human monkeypox virus (hMPXV), underwent various genetic changes, resulting in the emergence of over a dozen distinct lineages, which could be identified by only a small number of unique mutations. As of January 25, 2023, genomic information of hMPXV generated had reached 4632 accessions in the GISAID database. In this study, we aimed to investigate the epidemiological and phylogenetic characteristics of the B.1.6 sub-lineage of hMPXV in Peru, compared with other circulating sub-lineages during the global outbreak. The B.1.6 sub-lineage, characterized by the 111029G>A mutation, was estimated to have emerged in June 2022 and was found mainly in Peru. Most cases (95.8%) were men with an average age of 33 years, and nearly half of the patients had HIV, of whom only 77.35% received antiretroviral therapy. Our findings revealed that the B.1.6, B.1.4, and B.1.2 sub-lineages were well represented and had a higher number of mutations despite having the lowest media substitution rates per site per year. Moreover, it was estimated that B.1.2 and B.1.4 appeared in February 2022 and were the first two sub-lineages to emerge. A mutation profile was also obtained for each sub-lineage, reflecting that several mutations had a pattern similar to the characteristic mutation. This study provides the first estimation of the substitution rate and ancestry of each monkeypox sub-lineage belonging to the 2022 outbreak. Based on our findings, continued genomic surveillance of monkeypox is necessary to understand better and track the evolution of the virus.

Emergence and Molecular Epidemiology of Campylobacter jejuni ST-2993 Associated with a Large Outbreak of Guillain-Barré Syndrome in Peru.

Campylobacter jejuni infection is considered the most frequent factor associated with Guillain-Barré syndrome (GBS). In 2019, a large outbreak of GBS was detected in Peru, being associated with C. jejuni detected in stool samples from these patients. The aim of this study was to determine the molecular epidemiology of C. jejuni strains (ST-2993) associated with a large GBS outbreak in Peru. In this study, 26 C. jejuni strains belonging to the ST-2293, obtained from 2019 to 2020, were sequenced using Illumina technology. Five low-quality sequences were removed using bioinformatics, and 21 genomes (17 clinical strains and 4 chicken strains) were considered in the phylogenetic analysis and comparative genomics. Phylogenetic reconstruction, including genomes from international databases, showed a connection between Peruvian and Chinese GBS strains, both of them having lipooligosaccharides (LOS) locus genes related to molecular mimicry with gangliosides in peripheral nerves. Also, ST-2993 was detected in Amazon strains recovered many years before the 2019 outbreak, but with no epidemiological connection with GBS. Besides, a close relationship between human and chicken C. jejuni strains indicated chicken as one of the probable reservoirs. Finally, comparative genomics revealed differences between Chinese and Peruvian strains, including the presence of a prophage inserted into the genome. In conclusion, C. jejuni ST-2993 strains recovered from the GBS outbreak are closely related to Peruvian Amazon strains. Moreover, ST-2993 has been circulated in Peru since 2003 in the Peruvian Amazonia, showing the necessity to reinforce the epidemiological surveillance of C. jejuni to improve the prevention and control of future GBS outbreaks. IMPORTANCE This article describes the molecular epidemiology of C. jejuni strains (ST-2993) associated with a large Guillain-Barré Syndrome (GBS) outbreak in Peru, sequencing several strains recovered from GBS patients and chickens from 2019 to 2020. Phylogenetic analysis showed a connection between Peruvian and Chinese GBS strains, both of them having lipooligosaccharides (LOS) locus genes related to molecular mimicry with gangliosides in peripheral nerves. Also, ST-2993 strains were detected in isolates recovered many years before the 2019 outbreak, but with no epidemiological connection with GBS. Besides, a close relationship between human and chicken strains indicated those animals as a probable reservoir. This information will help to understand the real situation of GBS in Peru and its causal agent, C. jejuni ST-2993, showing the necessity to increase epidemiological tracking of these kinds of pathogens to detect them and avoid GBS outbreaks in the future.

Genomic surveillance of the Lambda SARS-CoV-2 variant in a global phylogenetic context.

The massive sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and global genomic surveillance strategies allowed the detection of many variants of concern and interest. The variant of interest Lambda (C.37), which originated in South America, has been the most prevalent in Peru and Chile, but its dispersion in other continents still remains unknown. The current study aims to determine the phylogenetic relationship among C.37 isolates worldwide, focusing on spike mutations to understand the spread of Lambda in pandemics. A total of 7441 sequences identified as C.37 were downloaded from the GISAID database; local analysis was carried out to identify spike mutations and phylogenetic analysis was carried out to determine the rate of spread of the virus. Our results showed some spike mutations of Lambda that allowed us to detect small local outbreaks in different countries that occurred in the past and identify several clades that have not yet been designated. Although the lineage C.37 is not epidemiologically relevant in Europe or North America, the endemic behavior of this variant in Peru had a major impact on the second SARS-CoV-2 wave.

Neoplasia de células dendríticas plasmocitoides blásticas, un reporte de caso / Blast plasmacytoid dendritic cell neoplasia, a case report

Introducción: La neoplasia de células dendríticas plasmocitoides blásticas (NCDPB) es una patología agresiva y representa menos del 1% de neoplasias hematológicas, se caracteriza por lesiones cutáneas nodulares violáceas sin evidencia de adenopatías en la mayoría de casos. Estudios observacionales demuestran que el Protocolo de quimioterapia Hyper-CVAD y la consolidación con tras-plante de células progenitoras hematopoyéticas se han asociado con una mayor supervivencia general. Caso Clínico: mujer de 82 años con antecedentes de Diabetes Mellitus tipo con cinco meses de lesiones hiperpigmentadas, elevadas, induradas, violáceas no dolorosas en mejilla, brazos, tórax anterior y posterior y piernas. Evolución: En citometría de flujo se determinó un fenotipo compatible con células patológicas (5.86%) con CD123++, HLADR+++, NG2++, CD56+++, CD4++, que sugiere una NCDPB. La biopsia de médula ósea presentó infiltración. PET CT posterior a terapia corticoide: no evidencia enfermedad tumoral macroscópica metabólicamente activa. Se inicia tratamiento con Dexametasona, con lo que las lesiones cutáneas disminuyeron en un 80%. Se inició Quimioterapia Protocolo CHOP like, ha recibido 6 ciclos hasta octubre del 2021, actualmente en remisión completa. Conclusión: En el presente caso el curso clínico de la NCDPB no fue agresivo hasta el momento del cierre del caso presentando disminución del 80% de las lesiones.

Introduction: blast plasmacytoid dendritic cell neoplasia (BPDCN) is an aggressive pathology and represents less than 1% of hematological neoplasms, it is characterized by violaceous nodular skin lesions without evidence of adenopathy in most cases. Observational studies show that the Hyper-CVAD chemotherapy protocol and consolidation with transplantation of hematopoietic progenitor cells have been associated with greater overall survival. Clinical case: a 82-year-old woman with a history of type Diabetes Mellitus with five months of hyperpigmented, raised, indurated, non-painful violaceous lesions on the cheek, arms, anterior and posterior thorax and legs. Evolution: Flow cytometry determined a phenotype compatible with pathological cells (5.86%) with CD123 ++, HLADR +++, NG2 ++, CD56 +++, CD4 ++, which suggests a BPDCN. The bone marrow biopsy showed infiltration. PET CT after corticosteroid therapy: there is no evidence of metabolically active macroscopic tumor disease. Dexamethasone treatment was started, with which skin lesions decreased by 80%. The CHOP-like Chemotherapy Protocol was started, she has received 6 cycles until October 2021, currently in complete remission. Conclusion: In the present case, the clinical course of NCDPB was not aggressive until the moment of closure of the case, presenting a decrease of 80% of the lesions.

Genomic analysis reveals a rapid spread and predominance of lambda (C.37) SARS-COV-2 lineage in Peru despite circulation of variants of concern.

The pandemic generated by SARS-Cov-2 has caused a large number of cases and deaths in the world, but South America has been one of the continents that were most hard hit. The appearance of new variants causes concern because of the possibility that they may evade the protection generated by vaccination campaigns, their greater capacity to be transmitted, or their higher virulence. We analyzed the circulating variants in Peru after improving our Genomic Surveillance program. The results indicate a steep increase of the lambda lineage (C.37) until becoming predominant between January and April 2021, despite the cocirculation of other variants of concern or interest. Lambda lineage deserves close monitoring and could probably become a variant of concern in the near future.

Genomic Analysis and Antimicrobial Resistance of Campylobacter jejuni and Campylobacter coli in Peru.

Campylobacter is the leading cause of human bacterial gastroenteritis worldwide and has a major impact on global public health. Whole Genome Sequencing (WGS) is a powerful tool applied in the study of foodborne pathogens. The objective of the present study was to apply WGS to determine the genetic diversity, virulence factors and determinants of antimicrobial resistance of the populations of C. jejuni and C. coli in Peru. A total of 129 Campylobacter strains (108 C. jejuni and 21 C. coli) were sequenced using Illumina Miseq platform. In silico MLST analysis identified a high genetic diversity among those strains with 30 sequence types (STs), several of them within 11 clonal complexes (CC) for C. jejuni, while the strains of C. coli belonged to a single CC with 8 different STs. Phylogeny analysis showed that Peruvian C. jejuni strains were divided into 2 clades with 5 populations, while C. coli formed a single clade with 4 populations. Furthermore, in silico analyses showed the presence of several genes associated with adherence, colonization and invasion among both species: cadF (83.7%), jlpA (81.4%), racR (100%), dnaJ (83.7%), pebA (83.7%), pldA (82.1%), porA (84.5%), ceuE (82.9%), ciaB (78.3%), iamB (86.8%), and flaC (100%). The majority (82.9%) of the Campylobacter strains carried the cdtABC operon which code for cytolethal distending toxin (CDT). Half of them (50.4%) carried genes associated with the presence of T6SS, while the frequency of genes associated with T4SS were relatively low (11.6%). Genetic markers associated with resistance to quinolones, tetracycline (tetO, tetW/N/W), beta-lactamases (blaoxa-61 ), macrolides (A2075G in 23S rRNA) were found in 94.5, 21.7, 66.7, 6.2, 69.8, and 18.6% of strains, respectively. The cmeABC multidrug efflux operon was present in 78.3% of strains. This study highlights the importance of using WGS in the surveillance of emerging pathogens associated with foodborne diseases, providing genomic information on genetic diversity, virulence mechanisms and determinants of antimicrobial resistance. The description of several Campylobacter genotypes having many virulence factors and resistance to quinolones and tetracyclines circulating in Peru provides important information which helps in the monitoring, control and prevention strategies of this emerging pathogen in our country.

Tratamiento Neoadyuvante en cáncer de mama HER2 positivo. La era de la terapia dirigida / Neoadjuvant treatment in HER2 positive breast cancer. The Age of Targeted Therapy

Introducción: El tratamiento neodyuvante del cáncer de mama HER2 positivo ha ido evolucionando a través del tiempo, con la implementación de nuevas estrategias de manejo terapéutico. Es de esta manera como el trastuzumab, un anticuerpo monoclonal anti-HER2sigue siendo el tratamiento estándar en este subtipo de cáncer, los primeros estudios en los que se evidencia su eficacia son el realizado por el Dr. Buzdar y el estudio NOAH en los cuales las pacientes alcanzaron mayores tasas de respuesta patológica completa en comparación con quimioterapia sola, así como también un mayor número de cirugías conservadoras de mama en lugar de mastectomía.Con el paso de los años se han ido desarrollando nuevas estrategias de manejo terapéutico, así tenemos el doble bloqueo anti-HER2 con los anticuerpos monoclonales trastuzumab y pertuzumab que han mejorado las tasas de respuesta patológica completa. Además se ha incluido al lapatinib un inhibidor de tirosina quinasa como parte de las terapias dirigidas. Se ha dilucidado si las antraciclinas confieren un beneficio adicional al tratamiento neoadyuvante y los estudios demuestran que el beneficio es el mismo queotros esquemas de quimioterapia. Es en realidad la quimioterapia indispensable en la neoadyuvancia, el estudio PHERGain demuestra que existen pacientes que pueden alcanzar respuesta patológica completa solo con el doble bloqueo anti-her2 (trastuzumab y pertuzumab) lo que evitaría la toxicidad innecesaria por quimioterapia, y se podrían desarrollar estrategias para el manejo de aquellas pacientes que no alcanzaron una respuestapatológica completa posterior al doble bloqueo. Aún queda un campo amplio por explorar y con estudios en curso al momento. Palabras claves:DsCS:Receptor ErbB-2, Trastuzumab, Neoplasias de la Mama, Quimioterapia Adyuvante, Ado-Trastuzumab Emtansina

Introduction:The neodyuvanttreatment of HER2 positive breast cancer has evolved over time, with the implementation of new therapeutic management strategies. It is in this way that trastuzumab, an anti-HER2 monoclonal antibody continues to be the standard treatment in this subtype of cancer, the first studies in which its efficacy is evidenced are the one carried out by Dr. Buzdar and the NOAH study in which patients achieved higher rates of complete pathological response compared to chemotherapy alone, as well as a higher number of breast-conserving surgeries rather than mastectomy.Over the years, new therapeutic management strategies have been developed, thus we have the double anti-HER2 blockade with the monoclonal antibodies trastuzumab and pertuzumab that have improved the ratesof complete pathological response. In addition, lapatinib, a tyrosine kinase inhibitor, has been included as part of targeted therapies. It has been elucidated whether anthracyclines confer an additional benefit to neoadjuvant treatment and studies show that the benefit is the same as other chemotherapy regimens.It is actually the essential chemotherapy in neoadjuvant therapy, the PHERGain study shows that there are patients who can achieve a complete pathological response only with the double anti-her2 blockade (trastuzumab and pertuzumab), which would avoid unnecessary toxicity due to chemotherapy, and strategies could be developed for the management of those patients who did not achieve a complete pathological response after double blockade. There is still a wide field to explore and with studies underway at the moment. Keywords:MESH:Receptor, ErbB-2;Trastuzumab; Breast Neoplasms; Chemotherapy, Adjuvant; Ado-Trastuzumab Emtansine

Vasculitis reumatoidea. Estudio de un caso / Rheumatoid vasculitis. Study of a case

Se presenta un caso, portadora de artritis reumatoide de varios años de evolución, que tras abandonar el tratamiento presentó una exacerbación de la actividad de la enfermedad, acompañada de un síndrome general y lesiones dérmicas y neurológicas producidas por una vasculitis leucocitoclastica, fue necesario actualizar el tratamiento con metotrexate y bolos de metilprednisolona obteniendo una respuesta favorable demostrada al desaparecer la actividad de la enfermedad y cicatrización de las lesiones ulcerosas.

present a case, with rheumatoid arthritis of several years of evolution, that after leaving the treatment presented an exacerbation of the activity of the disease, accompanied by a general syndrome and dermal and neurological lesions caused by a leukocytoclastic vasculitis, it was necessary to update the treatment with methotrexate and boluses of methylprednisolone obtaining a favorable response demonstrated when the activity of the disease disappeared and cicatrization of the ulcerous lesions.

Hyperhomocysteinaemia induced by dietary folate restriction causes kidney oxidative stress in rats.

Diet is the most common cause of mild hyperhomocysteinaemia (HHcy), which occurs in approximately 5-7 % of the general population. Since HHcy causes endothelial damage by oxidative stress in different organs, the present study was designed to examine whether HHcy might be involved in renal oxidative stress. Twenty-five male Wistar rats were randomly divided into two groups: one (n 13) was fed ad libitum a folate-free diet (FF) and the other (n 12) was fed the same diet supplemented with folic acid (control, CO). After 8 weeks the animals were killed and kidneys removed. Malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured in plasma and kidney homogenates. Renal tissue sections were analysed by indirect immunostaining with the primary antibody against oxidatively modified LDL receptor (LOX-1). A marked HHcy was confirmed in the FF group. As compared with CO animals, MDA levels in plasma and kidney homogenate were significantly higher in FF rats (P < 0.05). Similarly, renal GPx and SOD activities were significantly higher in the FF group (P < 0.001). No differences were found in LOX-1 immunohistochemical expression, which in the two groups was displayed in tubular cells. The present study provides evidence that HHcy does produce renal oxidative stress mediated by lipid peroxidation, and that the increased kidney MDA displayed by FF animals may enhance kidney antioxidant activity and thereby attenuate both kidney damage and expression of LOX-1.

Autoantibodies against EPCR are found in antiphospholipid syndrome and are a risk factor for fetal death.

The antiphospholipid syndrome (APS) is associated with thrombosis and fetal death but the pathologic mechanisms are poorly understood. Since endothelial protein C receptor (EPCR) plays a role in the anticoagulant system and in placental development, we hypothesized that anti-EPCR autoantibodies may be involved in clinical manifestations of APS and in fetal loss. The levels of immunoglobulin M (IgM) and IgG anti-EPCR autoantibodies were analyzed by enzyme-linked immunosorbent assay (ELISA) in 43 patients with APS and 43 controls. Anti-EPCR levels were higher in APS patients than in controls. Interestingly, one of the IgM anti-EPCR autoantibodies inhibited the generation of activated protein C on endothelium. Since markedly high anti-EPCR levels were found in women with fetal death, 87 patients with a first episode of unexplained fetal death were subsequently analyzed and their anti-EPCR levels were compared with 87 matched controls. We found that anti-EPCR autoantibodies constitute an independent risk factor for a first fetal death episode: the adjusted odds ratios (ORs) for anti-EPCR autoantibodies above the 95th percentile were 23.0 (95% confidence interval [CI], 2.0-266.3) for IgM and 6.8 (95% CI, 1.2-38.4) for IgG. Anti-EPCR autoantibodies can be detected in APS patients and are independent risk factors for fetal death.

Tumor necrosis factor-alpha inhibition reduces CXCL-8 levels but fails to prevent fibrin generation and does not improve outcome in a rabbit model of endotoxic shock.

The effects of a monoclonal antibody (mAb) to tumor necrosis factor-alpha (TNF-alpha) were examined in a rabbit model of endotoxic shock. Intravenous administration of lipopolysaccharide (100 microg/kg/hr) for 6 hours (n = 11) increased TNF-alpha levels. Fibrinogen was partially consumed, and fibrin deposits were seen in kidney and lungs at 24 hours. Mortality at 24 hours was 64%. Levels of interleukin-8 (aka CXCL-8) were notably increased. Mean arterial pressure (MAP) and leukocyte counts decreased, whereas creatinine levels were enhanced. The anti-TNF-alpha mAb (20 mg/kg i.v. bolus + 5 mg/kg/h i.v. for the first 90 minutes) (n = 10) efficiently inhibited the TNF-activity. Rabbits exhibited lower CXCL-8 levels; MAP improved, the decrease in leukocyte counts was partially prevented and creatinine levels were lower, but fibrinogen, fibrin deposits in kidneys and lungs and mortality, 55%, were similar to the LPS group. Rabbits that did not survive exhibited lower fibrinogen levels, more fibrin in kidneys and lungs and higher CXCL-8 and creatinine levels than survivors, while there were no differences in TNF-alpha, MAP and leukocytes. Thus, the inhibition of TNF-alpha, although beneficial through lowering CXCL-8 levels, is not enough to improve the outcome, which could be partly due to the inability to prevent the fibrin deposits formation in kidneys and lungs.

The endotoxin-induced plasminogen activator inhibitor-1 increase in rabbits is not tumor necrosis factor-alpha dependent and can occur in the absence of interleukin-1beta.

The plasminogen activator inhibitor-1 (PAI-1)-dependent fibrinolytic inhibition occurring in endotoxemia contributes to disseminated intravascular coagulation (DIC). Previous findings suggest that tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) are responsible for the increase in the level of PAI-1. These observations usually arose from mild endotoxemia models. We analyzed the effect of FR167653, an inhibitor of the TNF-alpha/IL-1beta production, on the PAI-1 levels in rabbits given endotoxin at a dose sufficient to induce DIC: the steep plasma PAI-1 increase was not attenuated by FR167653, in spite of achieving efficient inhibition of the TNF-alpha production. No IL-1beta was detected during endotoxemia. These results suggest that PAI-1 increase might be independent of TNF-alpha and IL-1beta. If these findings applied to humans, therapeutic intervention directing these cytokines would not be useful for the treatment of fibrinolysis in patients with severe sepsis.

Interleukin (IL)-8 and growth related oncogene-alpha in severe endotoxemia and the effects of a tumor necrosis factor-alpha/IL-1beta inhibitor on these chemokines.

FR167653 inhibits the production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, powerful inducers of CXC chemokines IL-8 and growth related oncogene (GRO)-alpha. The production of IL-8 and GRO-alpha was investigated and the effects of FR167653 were examined in a rabbit model of endotoxin shock. Male New Zealand rabbits were given endotoxin at a dose sufficient to induce DIC. Three groups of rabbits received FR167653 at different doses. TNF-alpha, IL-1beta, IL-8, and GRO-alpha levels were measured, several pathologic features were evaluated, and the results were compared with those obtained in control rabbits, which received only endotoxin. Endotoxin increased serum levels of IL-8 and GRO-alpha, which were associated with hypotension, renal dysfunction, and mortality, peaking at 4 h. FR167653 improved mortality, an event that was associated with decreased levels of not only TNF-alpha and IL-1beta but also IL-8 and GRO-alpha. TNF-alpha peaked at 2 h, at a time point before IL-8 and GRO-alpha reached their peak, and the TNF-alpha level was tightly correlated with that of IL-8 and GRO-alpha. Altogether, these data suggest the possible involvement of IL-8 and GRO-alpha in endotoxin shock, and FR167653 may foster a beneficial outcome in part by modulating the chemokines level by inhibiting TNF-alpha and IL-1beta.