An algorithm based on immunotherapy discontinuation and liver biopsy spares corticosteroids in two thirds of cases of severe checkpoint inhibitor-induced liver injury.

BACKGROUND: There are few data on corticosteroids (CS)-sparing strategies for checkpoint inhibitor (ICI)-induced liver injury (ChILI). AIM: We aimed to assess the performance of a 2-step algorithm for severe ChILI, based on ICI temporary discontinuation (step-1) and, if lack of biochemical improvement, CS based on the degree of necroinflammation at biopsy (step-2). METHODS: Prospective study that included all subjects with grade 3/4 ChILI. Peripheral extended immunophenotyping was performed. Indication for CS: severe necroinflammation; mild or moderate necroinflammation with later biochemical worsening. RESULTS: From 111 subjects with increased transaminases (January 2020 to August 2023), 44 were diagnosed with grade 3 (N = 35) or grade 4 (N = 9) ChILI. Main reason for exclusion was alternative diagnosis. Lung cancer (13) and melanoma (12) were the most common malignancies. ICI: 23(52.3%) anti-PD1, 8(18.2%) anti-PD-L1, 3(6.8%) anti-CTLA-4, 10(22.7%) combined ICI. Liver injury pattern: hepatocellular (23,52.3%) mixed (12,27.3%) and cholestatic (9,20.5%). 14(32%) presented bilirubin >1.2 mg/dL. Overall, 30(68.2%) patients did not require CS: 22(50.0%) due to ICI discontinuation (step-1) and 8/22 (36.4%) based on the degree of necroinflammation (step-2). Biopsy mainly impacted on grade 3 ChILI, sparing CS in 8 out of 15 (53.3%) non-improvement patients after ICI discontinuation. CD8+ HLA-DR expression (p = 0.028), central memory (p = 0.046) were lower in CS-free managed subjects, but effector-memory cells (p = 0.002) were higher. Time to transaminases normalisation was shorter in those CS-free managed (overall: p < 0.001, grade 3: p < 0.001). Considering our results, a strategy based on ICI discontinuation and biopsy for grade 3 ChILI is proposed. CONCLUSIONS: An algorithm based on temporary immunotherapy discontinuation and biopsy allows CS avoidance in two thirds of cases of severe ChILI.

Changes in Immune Response during Pig Gestation with a Focus on Cytokines.

Pigs have the highest percentage of embryonic death not associated with specific diseases of all livestock species, at 20-45%. During gestation processes, a series of complex alterations can arise, including embryonic migration and elongation, maternal immunological recognition of pregnancy, and embryonic competition for implantation sites and subsequent nutrition requirements and development. Immune cells and cytokines act as mediators between other molecules in highly complex interactions between various cell types. However, other non-immune cells, such as trophoblast cells, are important in immune pregnancy regulation. Numerous studies have shed light on the crucial roles of several cytokines that regulate the inflammatory processes that characterize the interface between the fetus and the mother throughout normal porcine gestation, but most of these reports are limited to the implantational and peri-implantational periods. Increase in some proinflammatory cytokines have been found in other gestational periods, such as placental remodeling. Porcine immune changes during delivery have not been studied as deeply as in other species. This review details some of the immune system cells actively involved in the fetomaternal interface during porcine gestation, as well as the principal cells, cytokines, and molecules, such as antibodies, that play crucial roles in sow pregnancy, both in early and mid-to-late gestation.

IFN-γ and IL-10: seric and placental profile during pig gestation Seric and placental cytokines in pig gestation.

Concentration of interferon-gamma and interleukin-10 in maternal serum and in maternal and fetal porcine placental extracts from different gestation periods was determined. Crossbred pigs' placental samples of 17, 30, 60, 70, and 114 days gestation and non-pregnant uteri were used. Interferon-gamma concentration was increased at the placental interface at 17 days, in maternal and fetal placenta, and decreased significantly in the remaining gestation periods. Interferon-gamma showed a peak in serum at 60 days. Regarding interleukin-10, placental tissue concentrations were unaltered, there were no significant differences with non-gestating uteri samples. In serum interleukin-10 increased at 17, 60, and 114 days gestation. At 17 days there are uterus structural and molecular changes that allow the embryos implantation and placenta development. The presence of interferon-gamma found at this moment in the interface would favor that placental growth. Moreover, its significant increase in serum at 60 days, would generate a proinflammatory cytokine pattern that facility the placental remodeling characteristic of this moment of porcine gestation. On the other hand, a significant interleukin-10 increase in serum at 17, 60 and 114 days could indicate its immunoregulatory role at a systemic level during pig gestation.

Integrins and ligands, are correlated at pig placental interface during pregnancy?

In the present work, we emphasize the studies about integrins and their receptors in pig placental interface at different times of gestation. Uterine placental interface (n=24) of 17-, 30-, 60- and 70-days gestation (dg) and non-pregnant uterus (n=4) of crossbred sows were used. The presence of αvß3 and α5ß1 integrins, and their ligands fibronectin (FN), and osteopontin (OPN) were detected by immunohistochemistry, and the immunolabelled area percentage (IAP) and the optical density (OD) were determined. The integrins and its ligands analyzed have presented peaks of expression in early and mid-gestation, both in IAP and the OD area decreasing at 70 dg. These temporal changes showed us that the molecules studied in this work participate in embryo/feto-maternal attachment, variably. Besides, we found a significant correlation both in the intensity and in the extension of immunostaining for trophoblastic FN and endometrial αvß3, and trophoblastic OPN and endometrial α5ß1, throughout the entire pig pregnancy. At late gestation, take place a notable placental remodelation with subsequent removal or renewal of folds at the uterine-placental interface that results in the loss of focal adhesions. The decrease of the expression of some integrins and their ligands in late gestation, particularly at 70 dg, would demonstrate that there would be other adhesion molecules and other ligands that could be participating in the establishment of the maternal-fetal interface.

The Low Incidence of Viral Hepatitis Reactivation Among Subjects on Immunotherapy Reduces the Impact of Suboptimal Screening Rate.

Background and Aims: Immunotherapy with immune checkpoint inhibitors (ICIs) is a pillar of many advanced tumors. However, there is scarce data concerning the rate of viral hepatitis screening in this population or the risk of viral reactivation. Methods: Retrospective-prospective study that includes all patients who began ICIs between January/2019 and December/2020 in a University Hospital. Data on viral hepatitis screening prior to the beginning of ICIs were collected. In subjects lacking information, serological tests were requested prospectively. Among HBsAg, anti-HBc, or anti-HCV positive subjects, reactivation was prospectively assessed. Results: During the 2-year period of study, 595 subjects received ICIs (61.2% male, mean age 63 years). The most prevalent cancers found were 35.5% lung cancer, 12.1% melanoma, and 8.2% head and neck; ICIs schemes were mainly anti-PD1 (65.7%), followed by anti-PD-L1 (19.2%), and combined therapy (13.6%). Prior to immunotherapy, anti-HCV screening was performed in 462 (77.6%) subjects, HBsAg in 462 (77.6%), anti-HBc in 335 (56.3%), and the complete screening in 328 (55.1%). The anti-HBc screening was more frequently ordered among patients treated with concomitant systemic therapy (p = 0.003), especially in the case of chemotherapy (p = 0.015), though HCV screening was more commonly performed in concomitant therapies different from chemotherapy (p = 0.001). Serological tests were completed prospectively in those alive, leading to an overall prevalence for anti-HCV of 3.5%, HBsAg at 1.3%, and anti-HBc of 15.2%. HCV-RNA was detected in 2/19 (both patients with hepatocellular carcinoma), HBV-DNA in 4/7 HBsAg positive, and in 1/75 anti-HBc positive subject. Five out of the 7 HBsAg carriers and 1/75 anti-HBc+ subjects (due to concomitant antiretroviral therapy) received antiviral prophylaxis. Neither cases of HBV reactivation nor changes in HCV viral load were observed. Discussion: HBV and HCV screening prior to immunotherapy is suboptimal. Though the rate of viral hepatitis reactivation seems extremely low, efforts should be made to optimize viral hepatitis screening prior to immunotherapy for the selection of candidates for either antiviral prophylaxis or periodical follow-up.

SARS-CoV-2 Outbreak on a Spanish Mink Farm: Epidemiological, Molecular, and Pathological Studies.

Farmed minks have been reported to be highly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and may represent a risk to humans. In this study, we describe the first outbreak of SARS-CoV-2 occurred on a mink farm in Spain, between June and July 2020, involving 92,700 animals. The outbreak started shortly after some farm workers became seropositive for SARS-CoV-2. Minks showed no clinical signs compatible with SARS-CoV-2 infection throughout the outbreak. Samples from 98 minks were collected for histopathological, serological, and molecular studies. Twenty out of 98 (20.4%) minks were positive by RT-qPCR and 82 out 92 (89%) seroconverted. This finding may reflect a rapid spread of the virus at the farm with most of the animals overcoming the infection. Additionally, SARS-CoV-2 was detected by RT-qPCR in 30% of brain samples from positive minks. Sequencing analysis showed that the mink sequences were not closely related with the other mink SARS-CoV-2 sequences available, and that this mink outbreak has its probable origin in one of the genetic variants that were prevalent in Spain during the first COVID-19 epidemic wave. Histological studies revealed bronchointerstitial pneumonia in some animals. Immunostaining of viral nucleocapsid was also observed in nasal turbinate tissue. Farmed minks could therefore constitute an important SARS-CoV-2 reservoir, contributing to virus spread among minks and humans. Consequently, continuous surveillance of mink farms is needed.

Salivary markers of oxidative stress and periodontal pathogens in patients with periodontitis from Santander, Colombia. / Marcadores salivales de estrés oxidativo y agentes patógenos periodontales en pacientes con periodontitis en Santander, Colombia

INTRODUCTION: Periodontitis affects more than 20% of the Latin American population. Oxidative markers are associated with greater progression of periodontitis; therefore, its role in pathogenesis should be studied. OBJECTIVE: To determine the prevalence of the main oral bacteria and viruses associated with periodontitis and estimate the total antioxidant capacity and lipid peroxidation in saliva from patients with periodontitis. MATERIALS AND METHODS: We conducted systemically a cross-sectional study in 101 healthy subjects, 87 of whom had been diagnosed with periodontitis (P), according to the criteria of the Centers of Disease Control and Prevention and the American Academy of Periodontology, and 14 without periodontal pockets as controls (C). In subgingival samples, major viruses and dental pathogenic bacteria were identified using PCR techniques. The levels of total antioxidant capacity and malon-di-aldehyde (MDA) were determined by spectrophotometry in samples of unstimulated saliva. RESULTS: The mean of periodontal depth pocket and clinical attachment loss in patients with periodontitis was 5.6 ± 1.7 and 6.1 ± 3.1 mm, respectively. The most prevalent microorganisms were Aggregatibacter actinomycetemcomitans (32.5%) and Porphyromonas gingivalis (18.6%). The patients from rural areas showed a higher percentage of A. actinomycetemcomitans (urban: 17.9% vs. rural: 48.9%, p=0.0018). In patients with periodontitis, the frequency of EBV, HSV1 and 2, and HCMV genes was 2.3%. Periodontitis patients had higher levels of MDA (P: 2.1 ± 1.5; C: 0.46 ± 0.3 µmol/g protein; p=0.0001) and total antioxidant capacity (P: 0.32 ± 0.2; C: 0.15 ± 0.1 mM; p< 0.0036). Oxidative markers showed no modifications due to the presence of periodontopathic bacteria. CONCLUSIONS: Aggregatibacter actinomycetemcomitans was the most prevalent bacteria; its presence did not modify the levels of oxidative markers in the saliva of patients with periodontitis.

Introducción. La periodontitis afecta a más del 20 % de la población latinoamericana. La presencia de marcadores de estrés oxidativo se asocia con una mayor progresión de periodontitis, por lo que su rol en la patogenia debe estudiarse. Objetivo. Determinar la prevalencia de las principales bacterias y virus asociados con la periodontitis y estimar la capacidad antioxidante total y la peroxidación de lípidos en la saliva de los pacientes con periodontitis. Materiales y métodos. Se hizo un estudio transversal en 87 sujetos sanos diagnosticados con periodontitis (P) según los criterios de los Centers of Disease Control and Prevention y la American Academy of Periodontology y 14 sujetos sin enfermedad periodontal como grupo control (C). En las muestras subgingivales se identificaron los principales virus y bacterias mediante técnicas de PCR. Los niveles de capacidad antioxidante total y malon-di-aldehído (MDA) se establecieron mediante espectrofotometría en muestras de saliva no estimulada. Resultados. Las medias de profundidad del sondaje y del nivel de inserción clínico periodontal en pacientes con periodontitis fueron 5,6 ± 1,7 y 6,1 ± 3,1 mm, respectivamente. Los microorganismos más prevalentes fueron Aggregatibacter actinomycetemcomitans (32,5 %) y Porphyromonas gingivalis (18,6 %). Los pacientes de áreas rurales registraron un mayor porcentaje de A. actinomycetemcomitans (urbano: 17,9 % Vs. rural: 48,9 %; p=0,0018). La frecuencia de los genes EBV, HSV1 y 2, y HCMV fue de 2,3 %. En pacientes con periodontitis se evidenciaron mayores niveles de MDA (P: 2,1 ± 1,5; C: 0,46 ± 0,3 µmol/g proteína; p=0,0001) y capacidad antioxidante total (P: 0,32 ± 0,2; C: 0,15 ± 0,1 mM; p<0,0036). La presencia de bacterias periodontales patógenas no modificó los marcadores oxidativos. Conclusiones. Aggregatibacter actinomycetemcomitans fue el agente patógeno mas prevalente. Su presencia no modificó los niveles de marcadores oxidativos en la saliva de los pacientes con periodontitis.

Salivary markers of oxidative stress and periodontal pathogens in patients with periodontitis from Santander, Colombia / Marcadores salivales de estrés oxidativo y agentes patógenos periodontales en pacientes con periodontitis en Santander, Colombia

Introduction: Periodontitis affects more than 20% of the Latin American population. Oxidative markers are associated with greater progression of periodontitis; therefore, its role in pathogenesis should be studied. Objective: To determine the prevalence of the main oral bacteria and viruses associated with periodontitis and estimate the total antioxidant capacity and lipid peroxidation in saliva from patients with periodontitis. Materials and methods: We conducted systemically a cross-sectional study in 101 healthy subjects, 87 of whom had been diagnosed with periodontitis (P), according to the criteria of the Centers of Disease Control and Prevention and the American Academy of Periodontology, and 14 without periodontal pockets as controls (C). In subgingival samples, major viruses and dental pathogenic bacteria were identified using PCR techniques. The levels of total antioxidant capacity and malon-di-aldehyde (MDA) were determined by spectrophotometry in samples of unstimulated saliva. Results: The mean of periodontal depth pocket and clinical attachment loss in patients with periodontitis was 5.6 ± 1.7 and 6.1 ± 3.1 mm, respectively. The most prevalent microorganisms were Aggregatibacter actinomycetemcomitans (32.5%) and Porphyromonas gingivalis (18.6%). The patients from rural areas showed a higher percentage of A . actinomycetemcomitans (urban: 17.9% vs. rural: 48.9%, p=0.0018). In patients with periodontitis, the frequency of EBV, HSV1 & 2, and HCMV genes was 2.3%. Periodontitis patients had higher levels of MDA (P: 2.1 ± 1.5; C: 0.46 ± 0.3 µmol/g protein; p=0.0001) and total antioxidant capacity (P: 0.32 ± 0.2; C: 0.15 ± 0.1 mM; p< 0.0036). Oxidative markers showed no modifications due to the presence of periodontopathic bacteria. Conclusions: Aggregatibacter actinomycetemcomitans was the most prevalent bacteria; its presence did not modify the levels of oxidative markers in the saliva of patients with periodontitis.

Introducción. La periodontitis afecta a más del 20 % de la población latinoamericana. La presencia de marcadores de estrés oxidativo se asocia con una mayor progresión de periodontitis, por lo que su rol en la patogenia debe estudiarse. Objetivo. Determinar la prevalencia de las principales bacterias y virus asociados con la periodontitis y estimar la capacidad antioxidante total y la peroxidación de lípidos en la saliva de los pacientes con periodontitis. Materiales y métodos. Se hizo un estudio transversal en 87 sujetos sanos diagnosticados con periodontitis (P) según los criterios de los Centers of Disease Control and Prevention y la American Academy of Periodontology y 14 sujetos sin enfermedad periodontal como grupo control (C). En las muestras subgingivales se identificaron los principales virus y bacterias mediante técnicas de PCR. Los niveles de capacidad antioxidante total y malon-di-aldehído (MDA) se establecieron mediante espectrofotometría en muestras de saliva no estimulada. Resultados. Las medias de profundidad del sondaje y del nivel de inserción clínico periodontal en pacientes con periodontitis fueron 5,6 ± 1,7 y 6,1 ± 3,1 mm, respectivamente. Los microorganismos más prevalentes fueron Aggregatibacter actinomycetemcomitans (32,5 %) y Porphyromonas gingivalis (18,6 %). Los pacientes de áreas rurales registraron un mayor porcentaje de A. actinomycetemcomitans (urbano: 17,9 % Vs. rural: 48,9 %; p=0,0018). La frecuencia de los genes EBV, HSV1 y 2, y HCMV fue de 2,3 %. En pacientes con periodontitis se evidenciaron mayores niveles de MDA (P: 2,1 ± 1,5; C: 0,46 ± 0,3 µmol/g proteína; p=0,0001) y capacidad antioxidante total (P: 0,32 ± 0,2; C: 0,15 ± 0,1 mM; p<0,0036). La presencia de bacterias periodontales patógenas no modificó los marcadores oxidativos. Conclusiones.Aggregatibacter actinomycetemcomitans fue el agente patógeno mas prevalente. Su presencia no modificó los niveles de marcadores oxidativos en la saliva de los pacientes con periodontitis.

Immune-related hepatitis related to checkpoint inhibitors: Clinical and prognostic factors.

BACKGROUND & AIMS: Check point inhibitors (CPI) have improved survival of oncology patients but adverse effects that mimic autoimmune disorders have been reported. Our aim was describe the characteristics of immune-related hepatitis (irH) and prognosis, and compared them to those of patients with autoimmune hepatitis (AIH). METHODS: This is a retrospective study including all grade ≥ 3 (severe) irH diagnosed among 414 patients treated with CPI from 2016 to 2018. RESULTS: Twenty-eight cases of severe irH were recorded: 10 on anti-CTLA-4 ± anti-PD1/PD-L1 and 18 on anti-PD1/PD-L1. Half were female, age 63 years, median time on CPI three cycles. Four (14.3%) presented acute liver injury or failure and one (3.6%) died as consequence. 94% presented normal immunoglobulin G (IgG). Six (21.4%) patients were retreated with CPI and none presented relapse or new immune-related adverse events after a median cycles of 11 (range 6-36). Subjects with irH were older and had lower IgG values than a cohort of AIH (N = 38). Presentation tended to be more severe in AIH. Twenty-five percent of irH and 84% AIH presented ANAs ≥ 1:80 (P = .001). In irH Initial dose of corticosteroids was higher (60 vs 30 mg, P < .001) but duration shorter (2.3 vs 7 months, P < .001) and frequently in monotherapy (41.7% vs 91.3%, P < .001). CONCLUSIONS: Immune-related hepatitis can lead to acute liver failure, with absence of increased values of IgG and ANAs. In contrast to autoimmune hepatitis, initial corticosteroids dose were higher, duration shorter with few requiring additional immunosuppression. Retreatment with CPI was not associated with recurrence.

Effective Gold Biosorption by Electrospun and Electrosprayed Bio-composites with Immobilized Lysinibacillus sphaericus CBAM5.

Electro-hydrodynamic processing, comprising electrospinning and electrospraying techniques, is a novel technology used in the production of nano- and sub-micro-scale materials with specific properties suitable for environmental remediation processes. Polycaprolactone (PCL) micro-fibrous mats and alginate microcapsules were produced using electrospinning and electrospraying techniques respectively, and Lysinibacillus sphaericus CBAM5, a bacterium capable of metal removal by adsorption and accumulation inside the cell, was immobilized in these matrices. The polymeric structure was able to protect and maintain cell viability and the bio-composite materials were used to capture gold from synthetic water samples. The micro-fibrous membranes with immobilized bacteria were able to remove 93% of the gold after 120 h of inclusion in the aqueous medium. Using a filtration system, an efficiency of 64% was obtained for the removal of the precious metal after 10 cycles of filtration (2 h of exposure to the gold solution). In contrast, the microencapsulated L. sphaericus CBAM5 captured 64% of the gold after 4 h of the assay. Thus, both micro-structured matrices were suitable for the immobilization and protection of L. sphaericus CBAM5 and they showed high efficiencies of gold biosorption. Hence, these bio-composite materials could be used to concentrate gold from industrial wastewaters.

The role of ipilimumab after anti-PD-1 treatment: two case reports and a literature review.

Metastatic melanoma has been historically associated with a poor prognosis; however, the therapeutic landscape has experimented and impressive change in the last years due to rapid advances in the immunotherapy field. The first immunotherapy treatment for metastatic melanoma was ipilimumab (anti-CTLA-4), which showed a significant improvement of overall survival compared to chemotherapy. However, in 2015 anti-PD-1 pembrolizumab shown an improved overall survival, progression-free survival and response rate compared to ipilimumab with either a better toxicity profile. Moreover, other immunotherapy combinations and target therapies, such as BRAF and MEK inhibitors combinations, have shown better outcomes than ipilimumab. Thus, ipilimumab seems to have no role in frontline metastatic melanoma treatment and even their role in second line is being less frequent due to clinical efficacy of those other treatments. Actually, the role of ipilimumab in second line after anti-PD-1 progression is not clear although there is clinical evidence for its use. Here, we report two cases of treatment response with ipilimumab in second line setting after receiving anti-PD-1 combination. So that, ipilimumab may have a role after progression to an anti-PD-1 treatment.

IL-1ß, IL-2 and IL-4 concentration during porcine gestation.

In pigs, given the type of epitheliochorial and non-invasive placenta, the trophoblast is in intimate contact with maternal tissues. The dialogue established between the conceptus and the endometrium involves, among others, the immune system, which minimizes the chances of rejection of the embryo and promotes the establishment of pregnancy. The aim of this work was to determine the concentration of IL-1ß, IL-2 and IL-4 in sera and in extracts of maternal and fetal placenta from sows of different gestational periods. Reproductive tracts from 23 crossbreed sows, between 30 and 114 days of gestation (dg), and from 8 non-pregnant sows were used. The concentration of the cytokines was determined by ELISA. IL-1ß, IL-2 and IL-4 demonstrated a similar pattern of concentration at the placental interface and serum; they were found elevated in tissues at 30 and 60-70 dg, and significantly decreased at term, period in which the cytokines were significantly increased in serum. These results show that IL-1ß, IL-2, and IL-4 are differentially modulated during pregnancy and at term, and suggest an important role of these cytokines in defining the proinflammatory stage of these periods.

Uso adecuado de antibióticos en pacientes con exacerbaciones de EPOC atendidos en un hospital de Medellín, Colombia / Appropriate use of antibiotics in patients with exacerbations of chronic obstructive pulmonary disease (COPD) treated in a hospital at Medellín, Colombia / Uso adequado de antibióticos em pacientes com exacerbações de EPOC atendidos num hospital de Medellín, Colômbia

Objetivo: evaluar la adherencia a las guías de uso de antibióticos en pacientes con EPOC exacerbada y explorar la asociación entre dicha prescripción y los desenlaces clínicos. Métodos: estudio de cohorte retrospectivo con pacientes admitidos entre el 1 de enero del 2010 y el 31 de diciembre del 2012 con diagnóstico de EPOC. Se registraron variables sociodemográficas, clasificación espirométrica, uso de oxígeno domiciliario, exacerbaciones en el último año, uso reciente de antibióticos, necesidad de ventilación mecánica, vacunación previa, comorbilidades, presentación clínica, indicación para el uso de antibióticos, tratamiento y estado al alta. Resultados: de 419 pacientes 59 % (n = 247) eran mujeres, la mediana de la edad fue de 76 años, 61,8 % tenían diagnóstico clínico, 74,7 % tenían instaurado algún tratamiento ambulatorio y 11 % habían sido tratados anteriormente para exacerbación de EPOC. De 170 pacientes con indicación para el uso de antibióticos hubo prescripción en 140 (82 %), mientras que se les formularon a 118 (47,4 %) de los 249 que no cumplían ningún criterio para el uso de los mismos. Se encontró una mayor tasa de mortalidad en el grupo que requería antibióticos. Conclusiones: se observó un aceptable nivel de adherencia a las guías en el uso de antibióticos en los casos indicados. Sin embargo, el porcentaje de pacientes a los que se les prescribieron antibióticos innecesariamente parece ser mayor de lo esperado y amerita investigación adicional.

Objective: to evaluate the adherence to clinical guidelines for appropriate use of antibiotics in patients with COPD exacerbations, and to explore the association between this prescription and clinical outcomes. Methods: a retrospective cohort study of patients admitted with COPD diagnosis between January 1, 2010 and December 31, 2012. The following variables were recorded: socio-demographic characteristics, spirometric classification, oxygen use at home, number of exacerbations in the previous year, recent antibiotic use, previous need for mechanical ventilation, previous vaccination, comorbidities, clinical presentation, antibiotic use indications and vital status. Results: 419 patients were included, 59 % (n = 247) were women, median age was 76 years, 62 % had clinical diagnosis, 75 % had an established outpatient management and 11 % had been previously treated for exacerbation of COPD. Out of 170 patients with any indication for using antibiotics the latter were prescribed in 140 (82 %), while 118 (47 %) of 249 patients with no criterion for their use received them. Mortality rate was higher in the group with indications for antibiotics. Conclusions: an acceptable level of adherence to guidelines was observed in the use of antibiotics when indicated. However, the percentage of patients in whom antibiotics were unnecessarily prescribed seems to be larger than expected and demands further investigation.

Objetivo: avaliar a aderência às guias de uso de antibióticos em pacientes com EPOC exacerbada e explorar a associação entre dita prescrição e os desenlaces clínicos. Métodos: estudo de coorte retrospectivo com pacientes admitidos entre o dia 1º de janeiro de 2010 e 31 de dezembro de 2012 com diagnóstico de EPOC. Se registraram variáveis sócio-demográficas, classificação espirométrica, uso de oxigeno domiciliário, exacerbações no último ano, uso recente de antibióticos, necessidade de ventilação mecânica, vacinação prévia, comorbilidades, apresentação clínica, indicação para o uso de antibióticos, tratamento e estado à alta. Resultados: de 419 pacientes 59 % (n = 247) eram mulheres, a média da idade foi de 76 anos, 62 % tinham diagnóstico clínico, 75 % tinham instaurado algum tratamento ambulatório e 11 % haviam sido tratados anteriormente para exacerbação de EPOC. De 170 pacientes com indicação para o uso de antibióticos houve prescrição em 140 (82 %), enquanto que se lhes formularam a 118 (47 %) dos 249 que não cumpriam nenhum critério para o uso dos mesmos. Se encontrou uma maior taxa de mortalidade no grupo que requeria antibióticos. Conclusões: se observou um aceitável nível de aderência às guias no uso de antibióticos nos casos indicados. Embora, a porcentagem de pacientes aos que se prescreveram antibióticos desnecessariamente parece ser maior do esperado e merece investigação adicional.

Molecular detection of Rickettsia felis in different flea species from Caldas, Colombia.

Rickettsioses caused by Rickettsia felis are an emergent global threat. Historically, the northern region of the province of Caldas in Colombia has reported murine typhus cases, and recently, serological studies confirmed high seroprevalence for both R. felis and R. typhi. In the present study, fleas from seven municipalities were collected from dogs, cats, and mice. DNA was extracted and amplified by polymerase chain reaction (PCR) to identify gltA, ompB, and 17kD genes. Positive samples were sequenced to identify the species of Rickettsia. Of 1,341 fleas, Ctenocephalides felis was the most prevalent (76.7%). Positive PCR results in the three genes were evidenced in C. felis (minimum infection rates; 5.3%), C. canis (9.2%), and Pulex irritans (10.0%). Basic Local Alignment Search Tool (BLAST) analyses of sequences showed high identity values (> 98%) with R. felis, and all were highly related by phylogenetic analyses. This work shows the first detection of R. felis in fleas collected from animals in Colombia.

Flea-borne rickettsioses in the north of Caldas province, Colombia.

Rickettsia typhi and R. felis are the etiological agents of murine typhus and flea-borne spotted fever, respectively. Both are emerging acute febrile zoonotic diseases for which fleas are vectors; they also have similar clinical characteristics and global distribution. In 2005, we identified the circulation of murine typhus in 6 towns within the mountainous coffee-growing area north of Caldas, Colombia. We now report the specific seroprevalence against R. typhi and R. felis, and associated risk factors in 7 towns of this province. The combined seroprevalence against the 2 flea-borne rickettsioses is the highest yet reported in the literature: 71.7% (17.8% for R. felis, 25.2% for R. typhi, and 28.7% for both). We also report a prospective analysis of 26 patients with a febrile illness compatible with rickettsioses, including murine typhus; 9 of these patients had a rickettsiosis. This supports our sero-epidemiological results and highlights the diagnostic complexity of febrile syndromes in this region.

Fresh frozen plasma for progressive and refractory angiotensin-converting enzyme inhibitor-induced angioedema.

BACKGROUND: Angioedema secondary to angiotensin-converting enzyme inhibitors (ACEI) is a commonly encountered problem in the Emergency Department (ED). The treatment of ACEI-induced edema with conventional methods such as epinephrine, steroids, and antihistamines is usually not effective. There is limited experience using bradykinin receptor blockers and fresh frozen plasma (FFP) as a treatment modality for ACEI-induced angioedema. OBJECTIVE: To emphasize alternative treatment option for ACEI-induced angioedema in the ED. CASE REPORTS: We report a case series of progressive and refractory presumed ACEI-induced angioedema that all improved in temporal association with administration of FFP, with a brief review of the literature. CONCLUSION: There was a temporal association between the administration of FFP and improvement in angioedema in seven cases of presumed ACEI-induced angioedema that were refractory to antihistamines, corticosteroids, and epinephrine.

Supervivencia de pacientes con cáncer de pulmón de célula no pequeña: en cuatro instituciones de Colombia / Superlife in patients with lung cancer no smal cells: in four Colombian institutes

Describir los resultados del tratamiento en pacientes con carcinoma de células no pequeñas avanzado. El 70 % de los pacientes debutan con enfermedad avanzada con supervivencia global de 5 años menor del 13 %. MÉTODOS: Se analizaron variables clínicas de 176 pacientes tratados en Bogotá. RESULTADOS: Promedio de edad 64 años, 64 % hombres 51 % tenía ECOG ≤1. El 90 % tenía compromiso metastásico principalmente a nivel pulmonar y en sistema nervioso central. El 76 % recibió terapia combinada como primera línea; 126 sujetos fueron tratados con (cisplatino 38/21,6 % y carboplatino 88 / 50% más algún agente de tercera generación o etopósido. Treinta y cuatro pacientes recibieron monoterapia, ocho, erlotinib. Se suministraron 3,7 ± 1,7 ciclos por paciente, la tasa de respuesta global fue 29 %, beneficio clínico 39 %, la mediana del tiempo de progresión 3,4 meses. La tercera parte de la población recibió segunda línea; en este grupo tasa de respuesta completa 15,8 %, beneficio clínico 33,8 % la mediana de tiempo libre de progresión 3,1 meses. El 69,3 % había muerto, la mediana de sobrevida global para la población total fue 9,2 meses, la proporción de sujetos vivos a 1 año 26 %. Variables como sexo, estado funcional, historia de tabaquismo, administración de segunda línea, adenocarcinoma, influyeron sobre la supervivencia. CONCLUSIONES: El comportamiento clínico y los objetivos del tratamiento de los pacientes incluidos en este estudio son similares a los reportados en la literatura médica.

Describing results of treatment in patients suffering advanced no small cell according to routine clinical practice. The 70 % of patients suffering debut with advanced disease are determining less than 13 % overall survival in 5 years. METHODS: 176 patients treated in Bogotá. RESULTS: The mean age was 64 years; 64 % were male 51 % had ≤1 ECOG. The 90 % had metastasis, mainly in the lung and in central nervous system. 76 % received combined therapy as the first line of intervention; 126 subjects were treated with a platinum compounds (cisplatin 38/21.6 % carboplatin 88/50 %) plus some third generation agent or etoposide. Thirty-four received monotherapy and eight erlotinib; 3.7 ± 1.7 cycles per patient were supplied on average, overall response rate was 29 %, clinical benefit 39 % and the median time to progression was 3.4 months. Only the third part of the population received a second line intervention; in this group overall response was 15.8 %, clinical benefit 33.8 % and free time progression was 3.1 months. When follow-up finished, 69.3 % had died, median the overall survival was 9.2 months 26 % of the subjects lived for up to one year. Some variables such gender, functional state, history of smoking, administering second line agent and a diagnosis of adenocarcinoma influenced in superlife. CONCLUSIONS: Clinical behaviour and outcomes treatment of patients included in this study were similar to those previously reported in the medical literature.