Root Regeneration with Photobiomodulation of an Upper Lateral Incisor Associated with Root Resorption Due to an Impacted Maxillary Canine: A Case Report.

Objective: To present a case report of maxillary lateral incisor root regeneration after severe root resorption, treated with photobiomodulation (PBM). Background: Impacted maxillary canines often come with the risk of maxillary lateral incisor root resorption, which is widely recognized as the predominant adverse effect in these situations. This progressive process of root resorption is currently irreversible, with no known way to reverse it. Materials and methods: A male patient was 14 years old. Radiographically it was observed that canine 23 is impacting against the root of 22 producing signs of root resorption and having a less than 1:1 crown-to-root ratio with mobility grade 1. From the beginning of the treatment, PBM-assisted orthodontics was proposed. To address the patient's dental concerns, the treatment plan outlined the extraction of the deciduous upper left canine tooth leaving the lateral as long as possible in the mouth. During each appointment, PBM was applied with a diode laser. The wavelength was 810 nm, Ap = 0.2 W, 4.4 J, 22 sec every 21 days, 13 applications in total (57.2J), with a 400 µm inactive surgical tip, in a scanning movement, 1 mm from the mucosa while moving following the vestibular surface of the upper left lateral and canine roots. Results: After 12 months, the 22 had root neoformation and complete closure of the apex with vitality. Conclusions: PBM with an 810 nm diode laser in this clinical case promoted root regeneration of an upper lateral incisor, with severe root resorption, owing to an impacted maxillary canine while still vital.

Imaging and Quantification of mRNA Molecules at Single-Cell Resolution in the Human Fungal Pathogen Candida albicans.

The study of gene expression in fungi has typically relied on measuring transcripts in populations of cells. A major disadvantage of this approach is that the transcripts' spatial distribution and stochastic variation among individual cells within a clonal population is lost. Traditional fluorescence in situ hybridization techniques have been of limited use in fungi due to poor specificity and high background signal. Here, we report that in situ hybridization chain reaction (HCR), a method that employs split-initiator probes to trigger signal amplification upon mRNA-probe hybridization, is ideally suited for the imaging and quantification of low-abundance transcripts at single-cell resolution in the fungus Candida albicans. We show that HCR allows the absolute quantification of transcripts within a cell by microscopy as well as their relative quantification by flow cytometry. mRNA imaging also revealed the subcellular localization of specific transcripts. Furthermore, we establish that HCR is amenable to multiplexing by visualizing different transcripts in the same cell. Finally, we combine HCR with immunostaining to image specific mRNAs and proteins simultaneously within a single C. albicans cell. The fungus is a major pathogen in humans where it can colonize and invade mucosal surfaces and most internal organs. The technical development that we introduce, therefore, paves the way to study the patterns of expression of pathogenesis-associated C. albicans genes in infected organs at single-cell resolution. IMPORTANCE Tools to visualize and quantify transcripts at single-cell resolution have enabled the dissection of spatiotemporal patterns of gene expression in animal cells and tissues. Yet the accurate quantification of transcripts at single-cell resolution remains challenging for the much smaller microbial cells. Widespread phenomena such as stochastic variation in transcript levels among cells-even within a clonal population-seem to play important roles in the biology of many microorganisms. Investigating this process requires microbial cell-optimized procedures to image and measure mRNAs at single-molecule resolution. In this report, we adapt and expand in situ hybridization chain reaction (HCR) combined with split-initiator probes to visualize transcripts in the human-pathogenic fungus Candida albicans at high resolution.

Characterisation of Aspergillus fumigatus Endocytic Trafficking within Airway Epithelial Cells Using High-Resolution Automated Quantitative Confocal Microscopy.

The precise characterization of the mechanisms modulating Aspergillus fumigatus survival within airway epithelial cells has been impaired by the lack of live-cell imaging technologies and user-friendly quantification approaches. Here we described the use of an automated image analysis pipeline to estimate the proportion of A. fumigatus spores taken up by airway epithelial cells, those contained within phagolysosomes or acidified phagosomes, along with the fungal factors contributing to these processes. Coupling the use of fluorescent A. fumigatus strains and fluorescent epithelial probes targeting lysosomes, acidified compartments and cell membrane, we found that both the efficacy of lysosome recruitment to phagosomes and phagosome acidification determines the capacity of airway epithelial cells to contain A. fumigatus growth. Overall, the capability of the airway epithelium to prevent A. fumigatus survival was higher in bronchial epithelial than alveolar epithelial cells. Certain A. fumigatus cell wall mutants influenced phagosome maturation in airway epithelial cells. Taken together, this live-cell 4D imaging approach allows observation and measurement of the very early processes of A. fumigatus interaction within live airway epithelial monolayers.

Gut Bacteria Shape Intestinal Microhabitats Occupied by the Fungus Candida albicans.

The human gut microbiota is composed of diverse microbes that not only compete but also rely on one another for resources and access to microhabitats in the intestine [1, 2]. Indeed, recent efforts to map the microbial biogeography of the gastrointestinal tract have revealed positive and negative co-associations between bacterial taxa [3, 4]. Here, we examine the spatial organization that the most prominent fungus of the human flora, Candida albicans, adopts in the gut of gnotobiotic mice either as the sole colonizer or in the presence of single bacterial species. We observe that, as a lone colonizer, C. albicans cells are distributed either adjacent to the inner mucus layer in the colon or throughout the intestinal lumen. In contrast to this pattern, in the presence of the saccharolytic Bacteroides thetaiotaomicron, the fungal cells localize to the interior of a Bacteroides-promoted outer mucus layer in which fungal and bacterial cells are in close association. We show that, in vitro, although mucin provides minimal support to the proliferation of the fungus, barely altering its transcriptional landscape, Bacteroides- and glucanase-processed mucin can better fuel the growth of C. albicans. Our observations illustrate how a commensal fungus can settle in an intestinal microhabitat generated by the presence of a single gut bacterial taxon.

Phagolysosomal Survival Enables Non-lytic Hyphal Escape and Ramification Through Lung Epithelium During Aspergillus fumigatus Infection.

Aspergillus fumigatus is the most important mould pathogen in immunosuppressed patients. Suboptimal clearance of inhaled spores results in the colonisation of the lung airways by invasive hyphae. The first point of contact between A. fumigatus and the host is the lung epithelium. In vitro and ex vivo studies have characterised critical aspects of the interaction of invasive hyphae on the surface of epithelial cells. However, the cellular interplay between internalised A. fumigatus and the lung epithelium remains largely unexplored. Here, we use high-resolution live-cell confocal microscopy, 3D rendered imaging and transmission electron microscopy to define the development of A. fumigatus after lung epithelium internalisation in vitro. Germination, morphology and growth of A. fumigatus were significantly impaired upon internalisation by alveolar (A549) and bronchial (16HBE) lung epithelial cells compared to those growing on the host surface. Internalised spores and germlings were surrounded by the host phagolysosome membrane. Sixty per cent of the phagosomes containing germlings were not acidified at 24 h post infection allowing hyphal development. During escape, the phagolysosomal membrane was not ruptured but likely fused to host plasma membrane allowing hyphal exit from the intact host cell in an non-lytic Manner. Subsequently, escaping hyphae elongated between or through adjacent epithelial lung cells without penetration of the host cytoplasm. Hyphal tips penetrating new epithelial cells were surrounded by the recipient cell plasma membrane. Altogether, our results suggest cells of lung epithelium survive fungal penetration because the phagolysosomal and plasma membranes are never breached and that conversely, fungal spores survive due to phagosome maturation failure. Consequently, fungal hyphae can grow through the epithelial cell layer without directly damaging the host. These processes likely prevent the activation of downstream immune responses alongside limiting the access of professional phagocytes to the invading fungal hypha. Further research is needed to investigate if these events also occur during penetration of fungi in endothelial cells, fibroblasts and other cell types.

The Regulatory Proteins Rtg1/3 Govern Sphingolipid Homeostasis in the Human-Associated Yeast Candida albicans.

Integrating nutrient sensing with the synthesis of complex molecules is a central feature of metabolism. Yet the regulatory mechanisms underlying such integration are often unknown. Here, we establish that the transcription regulators Rtg1/3 are key determinants of sphingolipid homeostasis in the human fungal pathogen Candida albicans. Quantitative analysis of the C. albicans lipidome reveals Rtg1/3-dependent alterations in all complex sphingolipids and their precursors, ceramides. Mutations in the regulators render the fungus susceptible to myriocin, a sphingolipid synthesis inhibitor. Rtg1/3 exert control on the expression of several enzymes involved in the synthesis of sphingolipids' building blocks, and the regulators are activated upon engulfment of C. albicans cells by human neutrophils. We demonstrate that Rtg1p and Rtg3p are regulated at two levels, one in response to sphingolipids and the other by the nutrient sensor TOR. Our findings, therefore, indicate that the Rtg1/3 system integrates nutrient sensing into the synthesis of complex lipids.

Photobiomodulation as oedema adjuvant in post-orthognathic surgery patients: A randomized clinical trial.

OBJECTIVE: Photobiomodulation therapy (PBMT) has been used in multiple applications in general medicine as powerful anti-inflammatory, analgesic and reducing oedema in different parts of the body. The aim of this study is to compare the effect on post-surgical oedema after mandibular orthognathic surgery, between two different laser power densities and oral medication with non-steroidal anti-inflammatory. MATERIALS AND METHODS: In a randomized clinical trial, on 60 patients who were subject to mandibular orthognathic surgery were divided into three groups. All groups received sodium naproxen 250mg every 8hours for 6days. Two groups were irradiated with two different laser application protocols and the other was a control group. In G1 group the irradiation parameters three times per week for two weeks were: 940nm, in continuous mode, 2.5W, 120s, 85.71J/cm2, 0.89W/cm2, over the right and left side with a distance from the skin surface of 1mm with the whitening handpiece (spot size of 2.8cm2). In G2, the irradiation parameters three times a week for two weeks were: 940nm, in continuous mode, 4.1W, 120s, 68.33J/cm2, 0.58W/cm2 over the right and left side with a distance from the skin surface of 15mm, with the deep tissue handpiece (spot size of 7.1cm2). In all the groups, millimetric facial measurements were taken from tragus to lateral commissure, and from lateral commissure to gonion in both sides. RESULTS: All differences between T1 and T6 were significant for the three groups, (paired T, P<0.05). The differences between the groups were generally not significant (P>0.05) except for commissure - right and left gonion when compared G1 vs CG (P<0.05) and G2 vs CG (P<0.05). Initial changes (T1-T2) between groups were significantly different except for the measurement from commissure to right tragus G1 vs CG (P=0.411) and from commissure to left tragus G2 vs CG (P=0.94). The faster resolution of the oedema occurred in G2 group. PTBM with an energy density of 68.33J/cm2 was the most effective adjuvant to oral medication with non-steroidal anti-inflammatory, to decrease post-surgical oedema after mandibular orthognathic surgery.

Caspofungin-Mediated Growth Inhibition and Paradoxical Growth in Aspergillus fumigatus Involve Fungicidal Hyphal Tip Lysis Coupled with Regenerative Intrahyphal Growth and Dynamic Changes in ß-1,3-Glucan Synthase Localization.

Caspofungin targets cell wall ß-1,3-glucan synthesis and is the international consensus guideline-recommended salvage therapy for invasive aspergillosis. Although caspofungin is inhibitory at low concentrations, it exhibits a paradoxical effect (reversal of growth inhibition) at high concentrations by an undetermined mechanism. Treatment with caspofungin at either the growth-inhibitory concentration (0.5 µg/ml) or paradoxical growth-inducing concentration (4 µg/ml) for 24 h caused similar abnormalities, including wider, hyperbranched hyphae, increased septation, and repeated hyphal tip lysis, followed by regenerative intrahyphal growth. By 48 h, only hyphae at the colony periphery treated with the high caspofungin concentration displayed paradoxical growth. A similar high concentration of caspofungin also induced the paradoxical growth of Aspergillus fumigatus during human A549 alveolar cell invasion. Localization of the ß-1,3-glucan synthase complex (Fks1 and Rho1) revealed significant differences between cells exposed to the growth-inhibitory and paradoxical growth-inducing concentrations of caspofungin. At both concentrations, Fks1 initially mislocalized from the hyphal tips to vacuoles. However, only continuous exposure to 4 µg/ml of caspofungin for 48 h led to recovery of the normal hyphal morphology with renewed localization of Fks1 to hyphal tips. Rho1 remained at the hyphal tip after treatment with both caspofungin concentrations but was required for paradoxical growth. Farnesol blocked paradoxical growth and relocalized Fks1 and Rho1 to vacuoles. Our results highlight the importance of regenerative intrahyphal growth as a rapid adaptation to the fungicidal lytic effects of caspofungin on hyphal tips and the dynamic localization of Fks1 as part of the mechanism for the caspofungin-mediated paradoxical response in A. fumigatus.

Pool sanguíneo intramural aórtico. Presentación de un caso y revisión de la literatura / Aortic Blood Pool. Case Report and Review of the Literature

El hematoma intramural aórtico (HIM) forma parte del espectro del síndrome aórtico agudo. En el HIM se pueden presentar colecciones de medio de contraste conocidas en la literatura como "pool sanguíneo intramural" (PSIM) y "proyección similar a una úlcera" (PSU). El PSIM puede estar comunicado con ramas de la aorta o con la luz de la misma por un orificio intimal pequeño (1-2 mm). La PSU presenta una solución de continuidad intimal mayor de 3 mm de diámetro y, a diferencia de la úlcera aterosclerótica penetrante, no se acompaña de una placa ateroesclerótica. En general, la presencia de PSIM en pacientes con HIM aórtico no se asocia a mal pronóstico. Se presenta el caso de una paciente con dolor torácico y sospecha de disección aórtica, estudiada en nuestra institución con angiografía por tomografía computada, que demostró HIM y una colección de medio de contraste en el espesor del hematoma, interpretada como pool sanguíneo intramural. Se revisan las imágenes iniciales y el control con endoprótesis aórtica.

Aortic intramural hematoma (IMH) is part of the spectrum of acute aortic syndromes. Collections of contrast medium known in the literature as "intramural blood pool" (IMBP) and "ulcer-like projections" (ULP), may be present in the IMH. An IMBP could be connected with branches of the aorta or with the aortic lumen through a small tear in the intima (1-2 mm). The ULP represents a disruption of the intima greater than 3mm of diameter and unlike the penetrating atherosclerotic ulcer, this is not associated with an atherosclerotic plaque. In general, the presence of IMBP in patients with aortic IMH is not associated with poor prognosis. We present a case of a patient with chest pain and suspected aortic dissection, studied at our institution with CT angiography, which showed an IMH and a collection of contrast medium within the thickness of the hematoma, interpreted as an intramural blood pool. The initial images and control with aortic endograft are reviewed.

Engrosamiento nodular difuso de la pleura / Diffuse nodular thickening of the pleura

Paciente masculino de 52 años con dolor torácico de características pleuríticas y disnea de cuatro meses de evolución. La radiografía (imagen IA) y la tomografía computarizada (TC) de tórax (Figura IB), mostraron engrosamiento nodular difuso de la pleura y efusión pleural. El engrosamiento pleural se define por un espesor de la pleura > de 3 mm que puede ser focal o difuso. En la radiografía frontal se considera un engrosamiento pleural difuso a la alteración mayor de 25% de la superficie pleural (bilateral) o mayor de 50% (unilateral). En TC se puede considerar difuso al engrosamiento pleural con una longitud > 8 cm y un diámetro mayor de 5 cm . El engrosamiento del paciente: difuso, concéntrico y nodular sugiere enfermedad neoplásica (primaria o secundaria), principalmente: enfermedad metastásica, mesotelioma, linfoma y timoma invasivo. Ocasionalmente entidades infecciosas pueden presentar este hallazgo. La patología pleural del paciente confirmó mesotelioma maligno epitelioide. Este mesotelioma es más frecuente en personas entre la sexta y séptima década de la vida, predomina en hombres y se asocian a la exposición a asbestos.

Frecuencia de grupos sanguíneos ABO y Rh en donantes del banco de sangre del Hospital Pablo Tobón Uribe, entre 2000 y 2009, 50 años después del primer trabajo realizado en Medellín / Frequency of ABO and Rh blood group in blood bank donors of Hospital Pablo Tobon Uribe between 2000 and 2009, 50 years after the first report in Medellin

En 1964 se publicó en la revista Antioquia Médica el primer trabajo original sobre la frecuencia de grupos sanguíneos en Medellín, dirigido por el Dr. Alberto Restrepo Mesa, uno de los pioneros de la Hematología en Colombia; posteriormente se realizaron dos importantes trabajos en los años 1999 y 2006, sin embargo, no se cuenta con reportes actuales. Objetivo: Establecer la frecuencia de los grupos sanguíneos en Medellín y el Valle de Aburrá, después de 50 años de publicada la primera investigación. Metodología: Se realizó un estudio observacional descriptivo con una muestra de 87.000 personas adultas, de ambos sexos, sin discriminación racial, que donaron hemoderivados en el banco de sangre del Hospital Pablo Tobón Uribe de la ciudad de Medellín (Colombia), entre 2000 y 2009, y se calculó la frecuencia de los grupos sanguíneos ABO y Rh...

At 1964, Antioquia Medica journal published the first original work of blood type frequencies in Medellin led by Dr. Alberto Restrepo Mesa, one of Hematology pioneers in Colombia; later there have been two important investigations in 1999 and 2006, however, there are not current reports. Objective: Establish the blood type frequencies in Medellin and the Valle de Aburrá after 50 years of the first published investigation. Methods: An observational descriptive study was made, with a sample of 87.000 adult people of both sexes, without racial discrimination, who donated blood at the Hospital Pablo Tobón Uribe blood bank of Medellin (Colombia) between 2000 and 2009; and frequency of ABO and Rh blood groups was calculated...

Characterization of nCD64 expression in neutrophils and levels of s-TREM-1 and HMGB-1 in patients with suspected infection admitted in an emergency department / Caracterización de la expresión de nCD64 en neutrófilos y de los niveles de s-TREM-1 y HMGB-1 en pacientes con sospecha de infección admitidos en el departamento de emergencias

Introduction: The nCD64 receptor, the soluble triggering receptor expressed in myeloid cells (s-TREM-1), and the high mobility group-box 1 protein (HMGB-1) have been proposed as significant mediators in sepsis. Objective: To evaluate the prognostic value of these markers in patients with suspected infection recently admitted in an emergency department (ED). Materials and methods: All patients who presented to the ED with suspected infection were eligible for enrollment in this study. Baseline clinical data, Sequential Organ Failure Assessment score (SOFA) score, APACHE II score, HMGB-1 levels, s-TREM-1 levels, and nCD64 levels were analyzed. The HMGB-1 and sTREM-1 serum concentrations were determined using commercially available ELISA kits, and CD64 on the surface of neutrophils was measured by flow cytometry. Results:. A total of 579 patients with suspected infection as their admission diagnosis were enrolled in this study. The median patient age was 50 years (IQR = 35-68). Morbidity during the 28-day followup period was 11.1% (n=64). The most frequent diagnosis at the time of admission was communityacquired pneumonia (CAP) in 23% (n=133) patients, followed by soft tissue infection in 16.6% (n=96), and urinary tract infection in 15% (n=87). After multivariable analysis, no significant association was identified between any biomarker and 28-day mortality. Conclusion: In the context of a tertiary care hospital emergency department in a Latin-American city, the nCD64 receptor, s-TREM-1, and HMGB-1 biomarkers do not demonstrate prognostic utility in the management of patients with infection. The search continues for more reliable prognostic markers in the early stages of infection.

Introducción. El receptor CD64, receptor soluble ´desencadenador´ expresado en células mieloides (sTREM-1) y la proteína del grupo Box-1 de alta movilidad (HMGB-1), se han propuesto como mediadores en la sepsis. Objetivo. Evaluar el valor pronóstico de estos marcadores en pacientes con sospecha de infección, recientemente admitidos en un departamento de emergencias. Materiales y métodos. Se incluyeron en el estudio pacientes que consultaron al hospital con sospecha de infección. Se analizó la base de datos clínica, el puntaje SOFA, el puntaje APACHE II, los niveles de HMGB-1, los niveles de sTREM-1 y los niveles de nCD64. Se determinaron las concentraciones en suero de HMGB-1 y sTREM-1, usando kits de ELISA disponibles comercialmente, y la de CD64 se midió por citometría de flujo. Resultados. Se analizaron 579 pacientes con sospecha de infección al ingreso. La edad media fue de 50 años (rango intercuartílico=35-68), y 11,1 % (n=64) murieron durante el seguimiento de 28 días. El diagnóstico más frecuente en el momento del ingreso fue neumonía adquirida en la comunidad, en 23 % (n=133) de los pacientes, seguida de infección de tejidos blandos, en 16,6 % (n=96), e infección urinaria, en 15 % (n=87). Después de un análisis multivariado, no hubo asociación significativa entre ningún biomarcador y la mortalidad a los 28 días. Conclusión. Los resultados sugieren que en el contexto de un departamento de emergencias de tercer nivel de una ciudad latinoamericana típica, los tres marcadores evaluados no ofrecieron ninguna ventaja en el pronóstico de infección. La búsqueda de marcadores pronósticos más confiables en estadios tempranos de la infección aún continúa abierta.

Neurospora crassa NKIN2, a kinesin-3 motor, transports early endosomes and is required for polarized growth.

Biological motors are molecular nanomachines, which convert chemical energy into mechanical forces. The combination of mechanoenzymes with structural components, such as the cytoskeleton, enables eukaryotic cells to overcome entropy, generate molecular gradients, and establish polarity. Hyphae of filamentous fungi are among the most polarized cells, and polarity defects are most obvious. Here, we studied the role of the kinesin-3 motor, NKIN2, in Neurospora crassa. We found that NKIN2 localizes as fast-moving spots in the cytoplasm of mature hyphae. To test whether the spots represented early endosomes, the Rab5 GTPase YPT52 was used as an endosomal marker. NKIN2 colocalized with YPT52. Deletion of nkin2 caused strongly reduced endosomal movement. Combined, these results confirm the involvement of NKIN2 in early endosome transport. Introduction of a rigor mutation into NKIN2 labeled with green fluorescent protein (GFP) resulted in decoration of microtubules. Interestingly, NKIN2(rigor) was associated with a subpopulation of microtubules, as had been shown earlier for the Aspergillus nidulans orthologue UncA. Other kinesins did not show this specificity.

Effect of low-level laser therapy on pain following activation of orthodontic final archwires: a randomized controlled clinical trial.

OBJECTIVE: The purpose of this study was to evaluate the efficacy of GaAlAs laser light to reduce pain induced by post-adjustment orthodontic final archwire, compared with a placebo control group, and also to evaluate if there are differences in pain gradient when conventional brackets or self-ligating brackets are used for orthodontic treatment. BACKGROUND DATA: Previous reports indicate that laser therapy is a safe and efficient alternative to alleviate pain caused in the initial stages of treatment, but there are no studies about its efficacy during the last stages of orthodontic treatment. METHODS: The initial sample was 60 orthodontic patients from a private practice, treated by straight wire technique, 30 of them with mini brackets Equilibrium(®) (Dentaurum, Ispringen, Germany) and 30 with self-ligation In-Ovation C(®) (GAC/Dentsply, Tokyo, Japan) slot 0.022 inch brackets. The archwires used in the final stage of orthodontic treatment were stainless steel 0.019×0.025 inch, slot 0.022 inch in both groups. In a design of divided mouth, the dental arches were randomly assigned to receive one dental arch irradiation with 830 nm 100mW therapeutic laser (Photon Lase II), for 22 sec (2.2 J, 80 J/cm(2)) along the vestibular surface and 22 sec (2.2 J, 80 J/cm(2)) along the palatal surface of the root in the randomly selected arch. The opposite dental arch received placebo treatment, with the laser light off. Pain was evaluated using a visual analog scale (VAS) after 2, 6, and 24 h, and 2, 3, and 7 days of application. RESULTS: The time course of pain showed the same tendency in both groups, reaching a peak 24 h after the archwire activation. The application of laser therapy reduced pain for any period of time up to 7 days (p<0.00001) and for any kind of bracket. CONCLUSIONS: Low intensity laser application reduces pain induced by archwires used during the final stage of orthodontic treatment, without any interference regarding the kind of bracket, as reported by patients.

Characterization of nCD64 expression in neutrophils and levels of s-TREM-1 and HMGB-1 in patients with suspected infection admitted in an emergency department.

INTRODUCTION: The nCD64 receptor, the soluble triggering receptor expressed in myeloid cells (s-TREM-1), and the high mobility group-box 1 protein (HMGB-1) have been proposed as significant mediators in sepsis. OBJECTIVE: To evaluate the prognostic value of these markers in patients with suspected infection recently admitted in an emergency department (ED). MATERIALS AND METHODS: All patients who presented to the ED with suspected infection were eligible for enrollment in this study. Baseline clinical data, Sequential Organ Failure Assessment score (SOFA) score, APACHE II score, HMGB-1 levels, s-TREM-1 levels, and nCD64 levels were analyzed. The HMGB-1 and sTREM-1 serum concentrations were determined using commercially available ELISA kits, and CD64 on the surface of neutrophils was measured by flow cytometry. RESULTS: . A total of 579 patients with suspected infection as their admission diagnosis were enrolled in this study. The median patient age was 50 years (IQR = 35-68). Morbidity during the 28-day followup period was 11.1% (n=64). The most frequent diagnosis at the time of admission was communityacquired pneumonia (CAP) in 23% (n=133) patients, followed by soft tissue infection in 16.6% (n=96), and urinary tract infection in 15% (n=87). After multivariable analysis, no significant association was identified between any biomarker and 28-day mortality. CONCLUSION: In the context of a tertiary care hospital emergency department in a Latin-American city, the nCD64 receptor, s-TREM-1, and HMGB-1 biomarkers do not demonstrate prognostic utility in the management of patients with infection. The search continues for more reliable prognostic markers in the early stages of infection.

Tratamiento de la enfermedad arterial periférica de las extremidades inferiores con células mononucleares de médula ósea autólogas: reporte de seguimiento a un año / Experience of autologous bone marrow mononuclear cells implantation as a treatment in patients with peripheral arterial disease: one year follow-up

Introducción: las células mononucleares de la médula ósea son efectivas para el tratamiento de pacientes con enfermedad arterial periférica (EAP). Los factores de crecimiento que ellas sintetizan se usan para inducir angiogénesis. Objetivo: establecer en Colombia la seguridad, factibilidad y resultado del tratamiento de la EAP utilizando células autólogas, para evitar su progreso a estadios más avanzados. Métodos: previo consentimiento, se hizo aspirado de médula ósea bajo anestesia local. Las células obtenidas se concentraron y se inyectaron intramuscularmente en los gastrocnemios de las extremidades isquémicas. El grupo control retrospectivo no recibió células. La evaluación clínica incluyó varios parámetros. Las células se analizaron por citometría de flujo. Resultados: edad media de los pacientes: 69 ± 11 años; viabilidad celular: 99,15% ± 0,76%; número de células inyectadas: 9,2 x 108 ± 6,2 x 108. Los análisis angiográficos postratamiento mostraron formación de vasos colaterales nuevos en las extremidades afectadas, con mínimo engrosamiento. Se observaron aumento en la distancia caminada libre de dolor y mejoría del dolor en reposo. La obtención y aplicación de las células no se asoció con ninguna complicación. Conclusiones: este estudio preliminar demostró que la terapia celular autóloga es segura, factible y cambia positivamente la historia natural de la EAP. Se sugiere el estudio de un número mayor de pacientes antes de establecer este tratamiento en Colombia.

Introduction: Autologous bone marrow mononuclear cells have been shown to be safe and effective for treatment of patients with peripheral arterial disease (PAD). Angiogenesis can also be induced by growth factors synthesized by them. Objective: To determine in Colombia the feasibility, safety and outcome of the afore-mentioned treatment. Methods: After informed consent, bone marrow was obtained by aspiration under local anesthesia; mononuclear cells were concentrated and their number and viability were established. They were suspended in saline solution and implanted by intramuscular injection into the gastrocnemius muscles of ischemic legs. Control patients were left untreated. Clinical evaluation included several parameters. Flow cytometry was used for cell analysis. Results: Mean age of patients: 69 ± 11 years; cell viability: 99.15 ± 0.76%; total number of injected cells: 9.2 x 108 ± 6.2 x 108. After treatment, angiographic studies showed the formation of new collateral vessels in all patients, with minimal thickness increase. There were no complications from bone marrow aspiration and intramuscular administration of cells. All treated patients experienced increase in the walking distance and improvement of rest pain. Conclusions: These preliminary results demonstrate that autologous cell therapy is safe, feasible and positively changes the natural history of patients with advanced peripheral arterial disease. In order to establish this treatment as a current practice in Colombia, we suggest the study of a larger number of patients.