Generating signals at converging liquid fronts to create line-format readouts of soluble assay products in three-dimensional paper-based devices.

The correct interpretation of the result from a point-of-care device is crucial for an accurate and rapid diagnosis to guide subsequent treatment. Lateral flow tests (LFTs) use a well-established format that was designed to simplify the user experience. However, the LFT device architecture is inherently limited to detecting analytes that can be captured by molecular recognition. Microfluidic paper-based analytical devices (µPADs), like LFTs, have the potential to be used in diagnostic applications at the point of care. However, µPADs have not gained significant traction outside of academic laboratories, in part, because they have often demonstrated a lack of homogeneous shape or color in signal outputs, which consequently can lead to inaccurate interpretation of results by users. Here, we demonstrate a new class of µPADs that form colorimetric signals at the interfaces of converging liquid fronts (i.e., lines) to control where colorimetric signals are formed without relying on capture techniques. We demonstrate our approach by developing assays for three classes of analytes-an ion, an enzyme, and a small molecule-to measure using iron(III), acetylcholinesterase, and lactate, respectively. Additionally, we show these devices have the potential to support multiplexed assays by generating multiple lines in a common readout zone. These results highlight the ability of this new paper-based device architecture to aid the interpretation of assays that create soluble products by using flow to constrain those colorimetric products in a familiar, line-format output.

Adolescents in the Community: Extracurricular Activities and Sexual Harassment.

Sexual harassment and participation in extracurricular activities are two common experiences for adolescents, yet little research examines the interplay between these two phenomena, particularly among low-income, racial/ethnic minority adolescents. This study examined whether participation in four types of extracurricular activities-school-based, structured community-based, unstructured community-based, and home-based-was associated with adolescents' PTSD and depressive symptoms over time, and whether those relations were mediated by neighborhood-based sexual harassment. Participants were 537 adolescents who were on average 15.6 years old, 54% girls, and majority Latino/a (n = 416; 77.5%). Path analyses revealed a significant indirect effect between unstructured community-based activities, but not structured community-based, school- nor home-based extracurricular activities and PTSD symptoms via sexual harassment. The findings point to the importance of examining how unstructured community-based extracurricular activities may increase neighborhood risks for adolescents, and the need for creating opportunities for adolescents to engage in structured and well supervised after-school extracurricular activities.

Emergence of KPC-31, a KPC-3 Variant Associated with Ceftazidime-Avibactam Resistance, in an Extensively Drug-Resistant ST235 Pseudomonas aeruginosa Clinical Isolate.

A ceftazidime-avibactam-resistant KPC-producing Pseudomonas aeruginosa strain was isolated in Argentina from a tracheal aspirate. The patient was treated with ceftazidime-avibactam in combination with other agents for 130 days. Whole-genome sequencing of P. aeruginosa identified a D179Y substitution in the Ω loop of KPC-3, corresponding to KPC-31, integrated at the chromosome. The strain belonged to the sequence type 235/O11 (ST235/O11) high-risk clone. Evaluation of carbapenemase detection assays most used by clinical laboratories failed to identify the isolate as a KPC producer.

Drug-Induced Hyperthermia Review.

Humans maintain core body temperature via a complicated system of physiologic mechanisms that counteract heat/cold fluctuations from metabolism, exertion, and the environment. Overextension of these mechanisms or disruption of body temperature homeostasis leads to bodily dysfunction, culminating in a syndrome analogous to exertional heat stroke (EHS). The inability of this thermoregulatory process to maintain the body temperature is caused by either thermal stress or certain drugs. EHS is a syndrome characterized by hyperthermia and the activation of systemic inflammation. Several drug-induced hyperthermic syndromes may resemble EHS and share common mechanisms. The purpose of this article is to review the current literature and compare exertional heat stroke (EHS) to three of the most widely studied drug-induced hyperthermic syndromes: malignant hyperthermia (MH), neuroleptic malignant syndrome (NMS), and serotonin syndrome (SS). Drugs and drug classes that have been implicated in these conditions include amphetamines, diuretics, cocaine, antipsychotics, metoclopramide, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and many more. Observations suggest that severe or fulminant cases of drug-induced hyperthermia may evolve into an inflammatory syndrome best described as heat stroke. Their underlying mechanisms, symptoms, and treatment approaches will be reviewed to assist in accurate diagnosis, which will impact the management of potentially life-threatening complications.

Latino/a adolescents facing neighborhood dangers: An examination of community violence and gender-based harassment.

While ample research examines community violence as a serious public health problem that disproportionately affects minority adolescents, less attention focuses on adolescents' experiences of gender-based harassment in poor, urban neighborhoods. Using data from 416 urban, low-income Latino/a adolescents (53% female; Mage = 15.5), this study examined (a) the relations between community violence exposure (CVE), gender-based harassment, and posttraumatic stress disorder (PTSD) symptoms and (b) the role of parent-child cohesion as a moderator of the relations between CVE/harassment and PTSD symptoms. Whereas both CVE and gender-based harassment were associated with greater PTSD symptoms, the effect of gender-based harassment on PTSD symptoms was far greater than the effect of community violence. Additionally, the association between gender-based harassment and PTSD symptoms was exacerbated when parent-child cohesion was high, compared to when cohesion was low or average. Finally, Latino/a adolescents exposed to high levels of both CVE and gender-based harassment had worse PTSD symptoms compared to those exposed primarily to gender-based harassment, who in turn had worse PTSD symptoms than those exposed primarily to community violence. Findings highlight the importance of including adolescents' experiences with gender-based harassment when studying community violence.

Estrogen Receptors as Molecular Targets of Endocrine Therapy for Glioblastoma.

Hormonal factors may participate in the development and progression of glioblastoma, the most aggressive primary tumor of the central nervous system. Many studies have been conducted on the possible involvement of estrogen receptors (ERs) in gliomas. Since there is a tendency for a reduced expression of ERs as the degree of malignancy of such tumors increases, it is important to understand the role of these receptors in the progression and treatment of this disease. ERs belong to the family of nuclear receptors, although they can also be in the plasmatic membrane, cytoplasm and mitochondria. They are classified as estrogen receptors alpha and beta (ER⍺ and ERß), each with different isoforms that have a distinct function in the organism. ERs regulate multiple physiological and pathological processes through the activation of genomic and nongenomic pathways in the cell. Nevertheless, the role of each isoform in the development and progression of glioblastoma is not completely clear. Diverse in vitro and in vivo studies have shown encouraging results for endocrine therapy as a treatment for gliomas. At the same time, many questions have arisen concerning the nature of ERs as well as the mechanism of action of the proposed drugs. Hence, the aim of the current review is to describe the drugs that could possibly be utilized in endocrine therapy for the treatment of high-grade gliomas, analyze their interaction with ERs, and explore the involvement of these drugs and receptors in resistance to standard chemotherapy.

Antibody affinity as a driver of signal generation in a paper-based immunoassay for Ebola virus surveillance.

During epidemics, such as the frequent and devastating Ebola virus outbreaks that have historically plagued regions of Africa, serological surveillance efforts are critical for viral containment and the development of effective antiviral therapeutics. Antibody serology can also be used retrospectively for population-level surveillance to provide a more complete estimate of total infections. Ebola surveillance efforts rely on enzyme-linked immunosorbent assays (ELISAs), which restrict testing to laboratories and are not adaptable for use in resource-limited settings. In this manuscript, we describe a paper-based immunoassay capable of detecting anti-Ebola IgG using Ebola virus envelope glycoprotein ectodomain (GP) as the affinity reagent. We evaluated seven monoclonal antibodies (mAbs) against GP-KZ52, 13C6, 4G7, 2G4, c6D8, 13F6, and 4F3-to elucidate the impact of binding affinity and binding epitope on assay performance and, ultimately, result interpretation. We used biolayer interferometry to characterize the binding of each antibody to GP before assessing their performance in our paper-based device. Binding affinity (KD) and on rate (kon) were major factors influencing the sensitivity of the paper-based immunoassay. mAbs with the best KD (3-25 nM) exhibited the lowest limits of detection (ca. µg mL-1), while mAbs with KD > 25 nM were undetectable in our device. Additionally, and most surprisingly, we determined that observed signals in paper devices were directly proportional to kon. These results highlight the importance of ensuring that the quality of recognition reagents is sufficient to support desired assay performance and suggest that the strength of an individual's immune response can impact the interpretation of assay results.

Review of Medical Therapies for the Management of Pulmonary Embolism.

Traditionally, the management of patients with pulmonary embolism has been accomplished with anticoagulant treatment with parenteral heparins and oral vitamin K antagonists. Although the administration of heparins and oral vitamin K antagonists still plays a role in pulmonary embolism management, the use of these therapies are limited due to other options now available. This is due to their toxicity profile, clearance limitations, and many interactions with other medications and nutrients. The emergence of direct oral anticoagulation therapies has led to more options now being available to manage pulmonary embolism in inpatient and outpatient settings conveniently. These oral therapeutic options have opened up opportunities for safe and effective pulmonary embolism management, as more evidence and research is now available about reversal agents and monitoring parameters. The evolution of the pharmacological management of pulmonary embolism has provided us with better understanding regarding the selection of anticoagulants. There is also a better understanding and employment of anticoagulants in pulmonary embolism in special populations, such as patients with liver failure, renal failure, malignancy, and COVID-19.

A propósito de un caso: Resolución quirúrgica en dos tiempos de Pentalogía de Cantrell / Case Report: Two-stage surgical resolution of Cantrell's Pentalogy

INTRODUCCIÓN: La pentalogía de Cantrell abarca la presencia de cinco defectos congénitos que representan un gran desafío para los cirujanos. Las anomalías del corazón, pericardio, diafragma, esternón y pared abdominal anterior son los hallazgos principales. Su incidencia es baja, sin embargo, es fundamental identificarla oportunamente para adoptar una terapia adecuada para todos los defectos descritos, puesto que se reporta una mortalidad elevada. CASO CLÍNICO: Se trató de un recién nacido a término, de sexo masculino, con antecedentes de defecto de la pared abdominal compatible con onfalocele detectado mediante ecografía prenatal. Tras cesárea programada, se evidenció defecto en la pared abdominal a través del cual emergían el lóbulo hepático izquierdo, intestinos y corazón; el esternón además presentaba una fisura baja. En ecocardiograma se evidenció foramen oval permeable, insuficiencia tricuspídea leve e hipertensión pulmonar severa. EVOLUCIÓN: Se decidió su manejo quirúrgico inmediato. Se colocó silo, con cierre progresivo de la línea media en 7 días. En segundo tiempo quirúrgico, se corrigió el defecto diafragmático y pericárdico con prótesis de pericardio bovino. Pese a la evolución adecuada de la cirugía, a los 28 días, el paciente presentó cianosis súbita, sin responder a maniobras de reanimación y falleció. CONCLUSIÓN: La Pentalogía de Cantrell es una enfermedad rara, con características clínicas, anatómicas y embriológicas peculiares, representa un desafío único para los cirujanos. Su diagnóstico temprano, así como el seguimiento durante el embarazo, la planificación de una cesárea en un centro de alto nivel y la aproximación quirúrgica inmediata con un equipo multidisciplinario, son componentes clave en el manejo integral de pacientes con Pentalogía de Cantrell.

BACKGROUND: Cantrell's pentalogy includes the presence of five birth defects that represent a great challenge for surgeons. Abnormalities of the heart, pericardium, diaphragm, sternumand anterior abdominal wall are the main findings. Its incidence is low, however, it is essential to identify Cantrell´s pentalogy timely to adopt an adequate therapy for all specific defects, since it has high mortality. CASE REPORT: The patient was a full- term male newborn, with a history of abdominal wall defect compatible with an omphalocele detected by prenatal ultrasound. After the caesarean section, the abdominal wall defect was notable, the left liver lobe, intestines and heart emerged through it, the sternum also had a low fissure. The echocardiogram revealed a permeable oval foramen, mild tricuspid regurgitation, and severe pulmonary hypertension. EVOLUTION: Immediate surgical management was decided. Silo was placed, with progressive closure of the midline in 7 days. During the second surgical procedure, the diaphragmatic and pericardial defect was corrected with a bovine pericardial prosthesis. Despite the adequate evolution after surgery, at day 28 he presented with sudden cyanosis and didn't respond to cardiopulmonary resuscitation and died. CONCLUSIONS: Cantrell's Pentalogy is a rare disease, with peculiar clinical, anatomical and embryological characteristics, it represents a unique challenge for surgeons. Early diagnosis, as well as follow-up during pregnancy, planning a cesarean section in a high-level center and immediate surgical approach with a multidisciplinary team, are the key components in the management of patients with Cantrell's Pentalogy.

Clinical Correlations of Positive Herpes Simplex PCR in Cerebrospinal Fluid.

OBJECTIVES: Herpes simplex viruses (HSV) can produce encephalitis (HSE), which requires early detection, typically using polymerase chain reaction (PCR) in cerebrospinal fluid (CSF). However, other neurological conditions not directly caused by HSV may also present with a positive HSV PCR in the CSF (NCNHPCR+). We aimed to analyze the clinical features of both groups of patients (HSE vs. NCNHPCR+) and to consider the potential relevance of this finding in the latter. METHODS: A retrospective analysis of clinical presentation, workup (CSF, EEG, and MRI) and outcome of patients with an HSV+ result in CSF was conducted from Jan-2007 to Sep-2015 in our institution. Patients under 18 years and those with nonencephalitic HSV associated disorders were excluded. Group comparison between HSE and NCNHPCR+ patients was conducted using parametric and nonparametric tests accordingly. RESULTS: Sixteen HSE and 23 NCNHPCR+ patients were included. Patients with HSE presented a higher incidence of headache (87.5% vs. 43.5%; P=0.008), meningeal symptoms (50% vs. 17.4%; P=0.04), pleocytosis (75% vs. 18%; P=0.001), EEG abnormalities (46.67% vs. 22%; P=0.02) and typical MRI findings (50% vs. 0%; P<0.001), whereas 35% of patients with NCNHPCR+ had an underlying immunologic disorder (35% vs. 0%; P=0.012). CONCLUSIONS: The pathogenic role of HSV in NCNHPCR+ is uncertain. This finding must be interpreted in the appropriate clinical, EEG, and neuroimaging context. Immunocompromise and neuroinflammation states could be related to a higher presence of HSV in CSF.

Infecciones en pacientes con tumores sólidos de sistema nervioso central y de cabeza y cuello / Infections in patients with solid tumors of the central nervous system and head and neck

Los tumores sólidos representan el 90% de las patologías oncohematológicas que se diagnostican en Argentina. Las infecciones son una de las complicaciones más frecuentes, causando una importante morbimortalidad, y en muchos casos retrasan la prosecución de los tratamientos específicos. La incidencia y tipo de infección depende del sitio específico del tumor, los fenómenos post obstructivos, el tipo e intensidad del tratamiento que se administre, las comorbilidades del paciente y la epidemiología local, entre otros factores. En forma constante se van incorporando nuevos tratamientos al arsenal terapéutico, tales como nuevos esquemas de quimioterapia, terapias blanco e inmunoterapia, y el manejo de las complicaciones asociadas a los mismos representa un desafío para el equipo tratante.En esta revisión abordamos la epidemiología, prevención y manejo de las complicaciones infecciosas más frecuentes en los pacientes con tumores de sistema nervioso central y de cabeza y cuello

Solid tumours represent 90 percent of the oncohematologic pathologies diagnosed in Argentina. Infections are one of the most frequent complications causing important morbidity and mortality and delay in prosecution of their specific treatment. The type of infection depends on the specific site of the tumour, the presence of post obstructive phenomena, the treatment administered, comorbidity and local epidemiology, among others. New therapies are being continuously incorporated to the armamentarium of cancer treatment such as new chemotherapies regimes, target therapy and immunotherapy. The management of adverse events and infectious complications associated with them are a challenge for the physician in charge of these patients.The epidemiology, prevention and management of the most frequent infectious complications in patients with tumours of the central nervous system and head and neck are reviewed in this paper

Clinical Impact of Rapid Intravenous Rehydration With Dextrose Serum in Children With Acute Gastroenteritis.

OBJECTIVES: We designed a study to compare rapid intravenous rehydration based on 0.9% normal saline (NS) or on NS + glucose 2.5% serum (SGS 2.5%) in patients with dehydration secondary to acute gastroenteritis. Our hypothesis is that the addition of glucose 2.5% serum (SGS 2.5%) to 0.9% saline solution could reduce the proportion of hospital admissions and return emergency visits in these patients. The secondary objective was to identify differences in the evolution of blood glucose and ketonemia between the groups. METHODS: We designed a prospective randomized open-label clinical trial that was conducted in 2 tertiary hospitals over 9 months. Patients were randomized to receive SGS 2.5% or NS. Baseline clinical, analytical, and disease-related data were collected. Data were analyzed using SPSS. RESULTS: The frequency of hospitalization in the SGS 2.5% group was 30.3% (n = 23) compared with 34.8% (n = 24) in the NS group, although the difference was not statistically significant (P = 0.59). The frequency of return visits to the emergency department was 17.8% (n = 8) in the NS group and 5.6% (n = 3) in the SGS 2.5% group (P = 0.091). Changes in glucose and ketone levels were more favorable in the SGS 2.5% group. CONCLUSIONS: Our results enabled us to conclude that there were no significant differences in hospital admission or return visits to the emergency department between children with dehydration secondary to acute gastroenteritis.

Utilidad y aplicación del ecodoppler en el embarazo de alto riesgo / Utility and application of ecodoppler in high risk pregnancy

Introducción: La detección de alteraciones en la circulación fetal y materna advierte sobre las alteraciones hemodinámicas que comienza a sufrir el feto. Si la edad gestacional garantiza la viabilidad fetal no se requiere prolongar la gestación, evitando complicaciones por hipoxia crónica. Sin embargo, en fetos con inmadurez pulmonar se esperan trastornos más severos por alteraciones en el sistema venoso fetal. En embarazos de alto riesgo, la ecografía fetal con Doppler es el método de elección debido a su alta sensibilidad que, además de ser no invasivo y accesible, permite la identificación de alteraciones que ponen en riesgo la vida del feto, ayudando al diagnóstico y monitoreo de las mismas. Su buen uso reduce el riesgo de muerte fetal en casos de alto riesgo. La evaluación de las arterias uterinas en el tamizaje de patologías del embarazo es de utilidad en preeclampsia, restricción de crecimiento intrauterino, desprendimiento de placenta y muerte fetal. El estudio de la morfología de onda de la arteria umbilical se utiliza ante sospecha de hipoxia, siendo el mejor indicador para interrupción de la gestación ante la presencia de anomalías, mientras que los cambios en la velocimetría de la arteria cerebral media son de utilidad en la evaluación de fetos con insuficiencia placentaria y anemia. El índice cerebro-placentario es el marcador más sensible para diagnosticar la redistribución cerebral como primer fenómeno adaptativo del feto ante la injuria. El estudio del sistema venoso fetal detecta estados más avanzados de hipoxia fetal, acompañados de acidemia e insuficiencia cardíaca. Objetivo: Describir aspectos a evaluar con EcoDoppler fetal para identificar alteraciones sugerentes de patología materno-fetal. Destacar su utilidad en embarazos de alto riesgo. Revisión de bibliografía actualizada. Materiales y Método: Para la localización de la bibliografía se utilizaron varias fuentes documentales, abarcando una búsqueda crítica en internet desde Google Académico, incluyendo artículos publicados a partir del año 2002, utilizando los descriptores: ecografía, ecoDoppler, embarazo, control prenatal, preeclampsia, restricción del crecimiento intrauterino. Se seleccionaron aquellos documentos que informasen sobre los aspectos físicos del ecoDoppler, aplicación del ecoDoppler en embarazos de alto riesgo y metodología del estudio

Introduction: The detection of alterations in the fetal and maternal circulation warns about the hemodynamic alterations that the fetus begins to suffer. If gestational age guarantees fetal viability, it is not necessary to prolong gestation, avoiding complications due to chronic hypoxia. However, in fetuses with pulmonary immaturity more severe disorders are expected due to alterations in the fetal venous system. In high-risk pregnancies, fetal ultrasound with Doppler is the method of choice due to its high sensitivity that, in addition to being non-invasive and accessible, allows the identification of alterations that put the life of the fetus at risk, aiding diagnosis and monitoring from the same. Its good use reduces the risk of fetal death in high-risk cases. The evaluation of the uterine arteries in the screening of pathologies of pregnancy is useful in preeclampsia, intrauterine growth restriction, placental abruption and fetal death. The study of the wave morphology of the umbilical artery is used when hypoxia is suspected, being the best indicator for interruption of gestation in the presence of anomalies, while changes in the velocimetry of the middle cerebral artery are useful in the evaluation of fetuses with placental insufficiency and anemia. The brain-placental index is the most sensitive marker to diagnose cerebral redistribution as the first adaptive phenomenon of the fetus before injury. The study of the fetal venous system detects more advanced stages of fetal hypoxia, accompanied by acidemia and heart failure. Objective: Describe aspects to be evaluated with Fetal EcoDoppler to identify alterations suggestive of maternal-fetal pathology. Highlight its usefulness in high risk pregnancies. Review of updated bibliography. Materials and Method:Several documentary sources were used to locate the bibliography, covering a critical search on the Internet from Google Scholar, including articles published since 2002, using the descriptors: ultrasound, ecoDoppler, pregnancy, prenatal control, preeclampsia, intrauterine growth restriction . We selected those documents that reported on the physical aspects of ecoDoppler, application of ecoDoppler in high-risk pregnancies and study methodology.

Quantitative Measurement of Akinesia in Parkinson's Disease.

BACKGROUND: There is great interest in developing simple, user-friendly, and inexpensive tools for the quantification and elucidation of motor deficits in patients with Parkinson's disease (PD). These systems could help to monitor the clinical status of patients with PD, to develop better treatments, and to identify individuals who have subtle motor signs that might pass unnoticed in the conventional neurological examination. METHODS: Mememtum, a smartphone application that allows for the quantification of several parameters of movement, such as regularity, rhythm, and changes in the number of taps while taping with a single finger and with alternating fingers, was developed and then tested in a pilot study in Madrid and in an extensive study in Quito, Ecuador. RESULTS: Almost all patients could successfully perform single-finger tapping, but approximately 10% of patients with severe parkinsonism had problems taping with alternating fingers. The results revealed changes in the regularity of the pressure applied while tapping and a reduction in the number of taps on the device screen when alternating tapping among patients who had idiopathic PD and vascular parkinsonism compared with controls and individuals who had prediagnostic motor abnormalities of PD. CONCLUSION: Applications available in smartphones could be used for investigation and treatment of patients with PD, but much research is needed to optimize the ideal parameters to be investigated and the potential usefulness of this technique for patients with PD in different stages of the disease.

[Cervical aspergillosis with dissemination to the central nervous system: Case reports and review of the literature]. / Aspergilosis cervical con diseminación al sistema nervioso central. Presentación de un caso y revisión de bibliografía.

BACKGROUND: Invasive aspergillosis (IA) of the central nervous system (CNS) is an uncommon condition that usually occurs in immunocompromised patients. This illness can manifest as meningitis, or as a micotic aneurism, stroke or abscess. The infection affects the CNS either primarily or, more often, secondarily via blood dissemination from a distant focus, and has a poor prognosis. We present a patient with IA primarily affecting the cervical bones, with later spread into the brain. CASE DESCRIPTION: A 25-year old male was receiving chemotherapy for acute lymphocytic leukemia when he developed pneumonitis secondary to methotrexate and was started on corticosteroids. He subsequently developed cervicalgia, prompting a needle biopsy of the fourth vertebrae, after which a diagnosis of osteomyelitis was made. Even though the biopsy culture was negative, empirical antibiotics were initiated. A parietal lobe lesion was treated surgically months later after the patient presented with three episodes of transient aphasia. After A. fumigatus grew in culture, the patient's antibiotic regimen was changed to treat the specific agent with a good response. CONCLUSION: IA must be considered a possibility whenever an immunocompromised patient presents with a new brain lesion. These lesions require surgical evacuation, a procedure that allows for diagnostic confirmation and enhances prognosis. Appropriate anti-fungal therapy must be started as soon as the diagnosis is confirmed. In addition, the patient's neurological exam must be repeated and images obtained periodically to monitor treatment and detect possible recurrences.

Aspergilosis cervical con diseminación al sistema nervioso central. Presentación de caso y revisión de bibliografía / Cervical aspergillosis with dissemination to the central nervous system. Case presentation and bibliography review

INTRODUCCIÓN: la Aspergilosis Invasiva (AI) del Sistema Nervioso Central (SNC) es infrecuente y ocurre generalmente en pacientes inmunocomprometidos. Puede presentarse con cuadros de meningitis, aneurismas micóticos, infartos o abscesos. Es una infección con pronóstico reservado y puede afectar el SNC de forma primaria o secundaria a partir de un foco que se disemina por vía hematógena. Presentamos el caso de un paciente con AI con invasión primaria a nivel óseo y diseminación posterior al cerebro. CASO CLÍNICO: paciente masculino de 25 años con diagnóstico de leucemia linfática aguda en tratamiento quimioterápico que presentó neumonitis por metotrexate por lo que inicia tratamiento con corticoides. Posteriormente agregó cervicalgia y con el diagnóstico de osteomielitis cervical se realiza punción bajo tomografía computada (TC) sin aislarse gérmenes. Se colocó Halo Vest e inició tratamiento antibiótico empírico. Posteriormente presentó afasia de expresión secundaria a lesión frontal izquierda. Se realizó evacuación de absceso cerebral aislando A. fumigatus. El tratamiento antibiótico específico posterior permitió una buena respuesta clínica y radiológica. CONCLUSIÓN: la presencia de lesiones en el SNC de pacientes inmunocomprometidos debe incluir a las micosis como diagnóstico diferencial. La evacuación quirúrgica permite llegar rápidamente al diagnóstico mejorando la respuesta posterior al tratamiento antibiótico. Para evaluar la respuesta terapéutica y posibles recaídas se debe realizar un seguimiento periódico clínico radiológico

INTRODUCTION: invasive aspergillosis (IA) of the central nervous system (CNS) is an uncommon condition that usually occurs in immunocompromised patients. This illness can manifest as meningitis, or as a micotic aneurism, stroke or abscess. The infection affects the CNS either primarily or, more often, secondarily via blood dissemination from a distant focus, and has a poor prognosis. We present a patient with IA primarily affecting the cervical bones, with later spread into the brain. CASE REPORT: a 25-year old male was receiving chemotherapy for acute lymphocytic leukemia when he developed pneumonitis secondary to methotrexate and was started on corticosteroids. He subsequently developed cervicalgia, prompting a needle biopsy of the fourth vertebrae, after which a diagnosis of osteomyelitis was made. Even though the biopsy culture was negative, empirical antibiotics were initiated. A parietal lobe lesion was treated surgically months later after the patient presented with three episodes of transient aphasia. After A. fumigatus grew in culture, the patient's antibiotic regimen was changed to treat the specific agent with a good response. CONCLUSION: IA must be considered a possibility whenever an immunocompromised patient presents with a new brain lesion. These lesions require surgical evacuation, a procedure that allows for diagnostic confirmation and enhances prognosis. Appropriate anti-fungal therapy must be started as soon as the diagnosis is confirmed. In addition, the patient's neurological exam must be repeated and images obtained periodically to monitor treatment and detect possible recurrences

Cerebrospinal fluid lactate in post-neurosurgical bacterial meningitis diagnosis.

BACKGROUND: Differential diagnosis between post-neurosurgical bacterial meningitis (PNBM) and aseptic meningitis is difficult. Inflammatory and biochemical cerebrospinal fluid (CSF) changes mimic those classically observed after CNS surgery. CSF lactate assay has therefore been proposed as a useful PNBM marker. OBJECTIVE: To evaluate the diagnostic accuracy of CSF lactate as a PNBM marker in patients hospitalized after a neurosurgical procedure. METHODS: Between July 2005 and June 2009, a prospective clinical study, in which all patients with clinical suspicion of PNBM were enrolled, was conducted at our neurosurgical Intensive Care Unit. PNBM diagnosis was categorized as proven, probable or negative before the analysis. RESULTS: Seventy-nine patients, 51 males with a mean age of 50 years (range 32-68 years) were included. Surgery was elective in 76% patients, mostly for brain tumors (57%); thirty PNBM episodes were identified. CSF parameters were significantly different in glucose concentration (27 mg% vs. 73 mg%, p<0.001), lactate (8 mmol/L vs. 2.8 mmol/L, p<0.001), CSF neutrophil pleocytosis (850 mm(-3) vs. 10mm(-3), p<0.001), and protein levels (449 mg% vs. 98 mg%) between the PNBM and non-PNBM groups. The ROC curve that best fits PNBM diagnosis is lactate. CONCLUSION: Increased CSF lactate is a useful PNBM marker, with better predictive value than CSF hypoglycorrhachia or pleocytosis. Lactate levels ≥ 4 mmol/L showed 97% sensitivity and 78% specificity, with a 97% negative predictive value.

[Candida: epidemiology and risk factors for non-albicans species]. / Candida: epidemiología y factores de riesgo para especies no albicans.

INTRODUCTION: Nosocomial fungal infections have increased significantly in the last decade. Candida detection in clinical specimens can mean either colonization or an infection which can be local (muguet) or invasive. Knowledge of the species helps in choosing the best treatment. The aims of this study were to determine the frequency and distribution of Candida species detected in clinical samples, to analyze the clinical characteristics of the involved population and to determine the risk factors for Candida non-albicans species. METHODS: Retrospective, observational. PERIOD: 2006-2010. INCLUSION CRITERIA: all isolates of Candida in clinical specimens from patients hospitalized at least 48 hours in a neurological center. We analyzed epidemiological characteristics, co morbidities, risk factors, factors associated with Candida non-albicans detection, antifungal treatment, development of adverse events and mortality. RESULTS: Candida spp. was isolated from 321 clinical specimens: 139 (43.3%) were C. albicans and 182 (56.7%) Candida non-albicans. The distribution of the sample was: urine 122 (Candida non-albicans 67.2%), airway 81, oropharynx 45 (C. albicans) and candidemia 40 (Candida non-albicans 75%). The most frequent co-morbidity was solid tumor (35.5%). The main risk factors were antibiotic therapy (85.5%), steroid therapy (61.7%) and in ICU at diagnosis (61.6%). The analysis of risk factors and the isolation of Candida non-albicans shows that chemotherapy, previous surgery, treatment with aminopenicillins, carbapenems and glycopeptides were statistically significant (P<.05). There is a trend in neutropenic patients (P=.055) and in ICU at diagnosis (P=.076). Overall survival was 71%. CONCLUSIONS: Candida species distribution varies with the type of sample analyzed. Non-albicans species make up the majority of the isolates. The identification of the species involved per sample helps to optimize treatment. The high frequency of isolation of Candida in patients on steroids and antibiotics and admitted to ICU, is worth pointing out. Patients with previous surgery, treated with the aforementioned antibiotics or chemotherapy, could receive non-azole antifungals in the initial empirical treatment strategy.

Characteristics and predictive value of blood transcriptome signature in males with autism spectrum disorders.

Autism Spectrum Disorders (ASD) is a spectrum of highly heritable neurodevelopmental disorders in which known mutations contribute to disease risk in 20% of cases. Here, we report the results of the largest blood transcriptome study to date that aims to identify differences in 170 ASD cases and 115 age/sex-matched controls and to evaluate the utility of gene expression profiling as a tool to aid in the diagnosis of ASD. The differentially expressed genes were enriched for the neurotrophin signaling, long-term potentiation/depression, and notch signaling pathways. We developed a 55-gene prediction model, using a cross-validation strategy, on a sample cohort of 66 male ASD cases and 33 age-matched male controls (P1). Subsequently, 104 ASD cases and 82 controls were recruited and used as a validation set (P2). This 55-gene expression signature achieved 68% classification accuracy with the validation cohort (area under the receiver operating characteristic curve (AUC): 0.70 [95% confidence interval [CI]: 0.62-0.77]). Not surprisingly, our prediction model that was built and trained with male samples performed well for males (AUC 0.73, 95% CI 0.65-0.82), but not for female samples (AUC 0.51, 95% CI 0.36-0.67). The 55-gene signature also performed robustly when the prediction model was trained with P2 male samples to classify P1 samples (AUC 0.69, 95% CI 0.58-0.80). Our result suggests that the use of blood expression profiling for ASD detection may be feasible. Further study is required to determine the age at which such a test should be deployed, and what genetic characteristics of ASD can be identified.

Moderate to high use of opioid analgesics are associated with an increased risk of Clostridium difficile infection.

INTRODUCTION: Risk factors for Clostridium difficile infection (CDI) include use of broad-spectrum antibiotics, advanced age and lack of an appropriate immune response. Whether antiperistaltics such as opioid analgesics also increase the risk of CDI is uncertain. The purpose of this preliminary study was to determine whether opioid analgesics increase the risk of developing CDI in hospitalized patients receiving broad-spectrum antibiotics. METHODS: Hospitalized patients were assessed for incidence of CDI in relation to usage of opioid analgesics controlling for other known risk factors for CDI. RESULTS: During the study period, a total of 32,775 patients were identified of whom 192 had CDI. In univariate analysis, incidence of CDI increased significantly with moderate or high usage of opioids (P < 0.0001). One hundred of 21,396 (0.47%) patients who did not receive opioids developed CDI. Twenty-two of 6955 patients (0.32%) with mild usage of opioids developed CDI [odds ratio (OR): 0.68; 95% confidence interval (CI): 0.43-1.1; P = 0.10]. Thirty of 33,203 (0.93%) with moderate usage developed CDI (OR: 2.0; 95% CI: 1.3-3.0; P = 0.0009). Forty of 1029 (3.7%) patients with high usage of opioids developed CDI (OR: 8.3; 95% CI: 5.7-12.1; P < 0.0001). Similar results were observed using a multivariate Cox proportional hazard model. CONCLUSIONS: Moderate to high use of opioid analgesics were associated with an increased risk of CDI.