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Importance There is a major need for effective, well-tolerated treatments for idiopathic pulmonary fibrosis (IPF). Objective To assess the efficacy and safety of the autotaxin inhibitor ziritaxestat in patients with IPF. Design, Setting, and Participants The 2 identically designed, phase 3, randomized clinical trials, ISABELA 1 and ISABELA 2, were conducted in Africa, Asia-Pacific region, Europe, Latin America, the Middle East, and North America (26 countries). A total of 1306 patients with IPF were randomized (525 patients at 106 sites in ISABELA 1 and 781 patients at 121 sites in ISABELA 2). Enrollment began in November 2018 in both trials and follow-up was completed early due to study termination on April 12, 2021, for ISABELA 1 and on March 30, 2021, for ISABELA 2. Interventions Patients were randomized 1:1:1 to receive 600 mg of oral ziritaxestat, 200 mg of ziritaxestat, or placebo once daily in addition to local standard of care (pirfenidone, nintedanib, or neither) for at least 52 weeks. Main Outcomes and Measures The primary outcome was the annual rate of decline for forced vital capacity (FVC) at week 52. The key secondary outcomes were disease progression, time to first respiratory-related hospitalization, and change from baseline in St George’s Respiratory Questionnaire total score (range, 0 to 100; higher scores indicate poorer health-related quality of life). Results At the time of study termination, 525 patients were randomized in ISABELA 1 and 781 patients in ISABELA 2 (mean age: 70.0 [SD, 7.2] years in ISABELA 1 and 69.8 [SD, 7.1] years in ISABELA 2; male: 82.4% and 81.2%, respectively). The trials were terminated early after an independent data and safety monitoring committee concluded that the benefit to risk profile of ziritaxestat no longer supported their continuation. Ziritaxestat did not improve the annual rate of FVC decline vs placebo in either study. In ISABELA 1, the least-squares mean annual rate of FVC decline was –124.6 mL (95% CI, −178.0 to −71.2 mL) with 600 mg of ziritaxestat vs –147.3 mL (95% CI, −199.8 to −94.7 mL) with placebo (between-group difference, 22.7 mL [95% CI, −52.3 to 97.6 mL]), and –173.9 mL (95% CI, −225.7 to −122.2 mL) with 200 mg of ziritaxestat (between-group difference vs placebo, −26.7 mL [95% CI, −100.5 to 47.1 mL]). In ISABELA 2, the least-squares mean annual rate of FVC decline was –173.8 mL (95% CI, −209.2 to −138.4 mL) with 600 mg of ziritaxestat vs –176.6 mL (95% CI, −211.4 to −141.8 mL) with placebo (between-group difference, 2.8 mL [95% CI, −46.9 to 52.4 mL]) and –174.9 mL (95% CI, −209.5 to −140.2 mL) with 200 mg of ziritaxestat (between-group difference vs placebo, 1.7 mL [95% CI, −47.4 to 50.8 mL]). There was no benefit with ziritaxestat vs placebo for the key secondary outcomes. In ISABELA 1, all-cause mortality was 8.0% with 600 mg of ziritaxestat, 4.6% with 200 mg of ziritaxestat, and 6.3% with placebo; in ISABELA 2, it was 9.3% with 600 mg of ziritaxestat, 8.5% with 200 mg of ziritaxestat, and 4.7% with placebo. Conclusions and Relevance Ziritaxestat did not improve clinical outcomes compared with placebo in patients with IPF receiving standard of care treatment with pirfenidone or nintedanib or in those not receiving standard of care treatment. Trial Registration ClinicalTrials.gov Identifiers: NCT03711162 and NCT03733444

Resumen Las neoplasias en glándulas salivales son infrecuentes, representando menos del 3% de los tumores de cabeza y cuello. El carcinoma mucoepidermoide es el tumor maligno más común en glándulas salivales, siendo su principal ubicación la parótida. Clínicamente se asemeja a otras lesiones de mucosa oral, por lo cual, es importante realizar un correcto diagnóstico diferencial. Su comportamiento biológico se relaciona con el grado histológico tumoral, factor relevante en el pronóstico y tratamiento de esta neoplasia. Presentamos el caso de un paciente hombre de 75 años afectado con un tumor en paladar con diagnóstico de carcinoma mucoepidermoide de bajo grado. Como tratamiento se realizó una maxilectomía parcial y una placa obturadora en base a una prótesis removible y posterior reconstrucción con un colgajo libre microvascularizado. Actualmente el paciente se encuentra en controles periódicos, libre de enfermedad. Los tumores de glándulas salivales son un desafío diagnóstico, requieren de exámenes imagenológicos y del estudio histopatológico. Cuando existen dudas en el diagnóstico, se debe considerar repetir la toma de la muestra o la obtención de biopsias de más de una zona representativa que permita el diagnóstico de la lesión.

Gerstmann-Sträussler-Scheinker (GSS) syndrome is a fatal autosomal dominant neurodegenerative prionopathy clinically characterized by ataxia, spastic paraparesis, extrapyramidal signs and dementia. In some GSS familiar cases carrying point mutations in the PRNP gene, patients also showed comorbid tauopathy leading to mixed pathologies. In this study we developed an induced pluripotent stem (iPS) cell model derived from fibroblasts of a GSS patient harboring the Y218N PRNP mutation, as well as an age-matched healthy control. This particular PRNP mutation is unique with very few described cases. One of the cases presented neurofibrillary degeneration with relevant Tau hyperphosphorylation. Y218N iPS-derived cultures showed relevant astrogliosis, increased phospho-Tau, altered microtubule-associated transport and cell death. However, they failed to generate proteinase K-resistant prion. In this study we set out to test, for the first time, whether iPS cell-derived neurons could be used to investigate the appearance of disease-related phenotypes (i.e, tauopathy) identified in the GSS patient.

Poultry is a main reservoir and source of human infection in campylobacteriosis. Three hundred and forty one stool samples (291 human, 50 avian) were analyzed. In the human group, 220 samples were collected from children with acute diarrheal disease (183 inpatients, 37 outpatients) and 71 from healthy children. Erythromycin and ciprofloxacin agar dilution MIC tests, Penner serotyping and RAPD-PCR genotyping were performed on 23 strains isolated. C. jejuni was reported only in patients with acute diarrhea (5.4% inpatients, 2.2% outpatients). Campylobacter prevalence in poultry was 34%. Cross-resistance to nalidixic acid and ciprofloxacin was found in 33.3% of human samples and 11.8% of animal samples. Human samples could not be typed using the Penner method. F serotype was the most expressed in poultry. We obtained a total of 14 genotypes (4 / 5 human and 10/15 avian). In conclusion, the predominant species in poultry and humans was C. jejuni, a significant amount of quinolone-resistant human and avian samples were obtained, and avian genotypes and serotypes were not found in human samples. The latter would mean that another source of infection could exist; therefore other reservoirs must be studied.

Las aves de consumo constituyen uno de los principales reservorios y fuente de infección humana de la campilo-bacteriosis. Se analizaron 341 muestras de deposiciones, 291 humanas y 50 aviares. De las muestras, 220 de niños con síndrome diarreico agudo-SDA (183 hospitalizados y 37 consultantes ambulatorios) y 71 niños sanos. A las 23 cepas obtenidas se les realizó CIM por dilución en agar a eritromicina y ciprofloxacina, serotipificación de Penner y genotipiicación por RAPD-PCR. Se encontró Campylobacterjejuni sólo en pacientes con SDA, de ellos 5,4% ambulatorios y 2,2% hospitalizados. En aves, la prevalencia de Campylobacter spp., fue de 34%. Hubo resistencia cruzada a ácido nalidixico y ciprofloxacina en 33,3% cepas de origen humano y 11,8% animal. Las cepas humanas fueron no tipiicables por el método de Penner. Predominó entre las aves el serotipo F. Se obtuvo un total de 14 genotipos (4/5 humanos y 10/15 aviares). En conclusión, la especie predominante en aves de corral y en humanos fue C. jejuni, existiendo una alta prevalencia de cepas de origen humano y aviar resistentes a quinolonas. Los genotipos y serotipos aviares no fueron encontrados en cepas de origen humano, lo que indica que podría existir otra fuente de infección, por lo que se requiere estudiar otros reservorios. Poultry is a main reservoir and source of human infection in campylobacteriosis. Three hundred and forty one stool samples (291 human, 50 avian) were analyzed. In the human group, 220 samples were collected from children with acute diarrheal disease (183 inpatients, 37 outpatients) and 71 from healthy children. Erythromycin and ciprofloxacin agar dilution MIC tests, Penner serotyping and RAPD-PCR genotyping were performed on 23 strains isolated. C. jejuni was reported only in patients with acute diarrhea (5.4% inpatients, 2.2% outpatients). Campylobacter prevalence in poultry was 34%. Cross-resistance to nalidixic acid and ciprofloxacin was found in 33.3% of human samples and 11.8% of animal samples. Human samples could not be typed using the Penner method. F serotype was the most expressed in poultry. We obtained a total of 14 genotypes (4 / 5 human and 10/15 avian). In conclusion, the predominant species in poultry and humans was C. jejuni, a significant amount of quinolone-resistant human and avian samples were obtained, and avian genotypes and serotypes were not found in human samples. The latter would mean that another source of infection could exist; therefore other reservoirs must be studied.

Dopamine modulation of excitatory neurotransmission is critical in the control of movement, emotion and reward. In the striatum, medium size spiny neurons (MSNs) are responsible for the integration of cortical and thalamic information that flows through parallel, partly overlapping, loops and determines adequate experience-dependent responses. Dopamine acts on MSNs through two sets of G protein-coupled receptors (GPCRs), the D1-like and D2-like receptors, which can have opposing or synergistic downstream effects. Notably, these two types of striatal dopamine receptors are segregated into the striatonigral (direct) and striatopallidal (indirect) projecting neurons. Thus, dopamine receptor expression determines the morphological and functional neuronal phenotype of MSNs. Moreover, dopamine regulates glutamatergic corticostriatal transmission, critically controlling the induction of long-term potentiation and long-term depression at these synapses, regulating striatal synaptic plasticity. In addition to dopamine receptors, the induction and expression of plasticity mechanisms is regulated by other GPCRs, most importantly adenosine A 2A receptors, metabotropic glutamate mGluR5 receptors and endocannabinoid CB1 receptors. This review focuses on synaptic modulation and plasticity on excitatory corticostriatal synapses by GPCRs.

El Síndrome de Melkersson Rosenthal se describe como la asociación de edema labial (queilitis granulomatosa de Miescher) y/o facial recurrente, parálisis facial recidivante y lengua fisurada. El edema labial recurrente se presenta en uno o ambos labios, el cual puede llegar a ser persistente. Cuando se presenta en forma aislada se considera como una forma monosintomatica de este síndrome. El objetivo de esta revisión es mostrar el seguimiento de un caso clínico atendido en nuestro servicio con el diagnóstico síndrome de Melkersson Rosenthal que presenta una gran queilitis granulomatosa asociada a lengua fisurada, cuyo tratamiento consistió en la infiltración de corticoides intralesionales y una posterior queiloplastía. Melkersson-Rosenthal syndrome is described as the association of recurrent lip edema (Miescher’s cheilitis granulomatosa) and/or facial edema, recurrent facial paralysis, and plicated tongue. Recurrent edema occurs in one or both lips, and can be persistent. When lip edema alone occurs, the case is considered a monosymptomatic form of this syndrome. The aim of this review was to discuss the follow-up of a patient seen in our department with the diagnosis of Melkersson-Rosenthal syndrome who presented intense cheilitis granulomatosa associated with plicated tongue. The patient was treated with infiltration of intralesional corticoids and later cheiloplasty.

Se evaluó el Índice de Gravedad de Fine (IG) en neumonías de la comunidad (NAC) hospitalizadas en el Hospital Regional de Concepción en trabajo retrospectivo con 57 casos entre Junio y Agosto del año 2000. Se estudiaron 23 pacientes catalogados de bajo riesgo y 34 de alto riesgo. Características de alto riesgo fueron, mayor edad (p < 0,00001), mayor comorbilidad (p < 0,0004), estadía prolongada (p < 0,00007) y mayor mortalidad (p < 0,018). La mortalidad de bajo riesgo fue similar a la de Fine, 4,3% versus 3,5%, siendo menor en el grupo de alto riesgo, 26% versus 38%. Factores de mayor complicación en NAC fueron, ventilación mecánica (43,8%), PaO2/FiO2 < 250 mmHg (43,8%) y coma hepático (35,8%). Conclusión: es aconsejable el uso del IG en NAC a nivel de Servicios de Urgencia, para evaluar los riesgos de mortalidad, optimizando así los criterios de ingreso al hospital Fine's severity prediction index (SPI), was retrospectively analyzed in community acquired pneumonia (CAP), in patients at Concepción Regional Hospital, from June to August 2000. We studied 57 CAP patients: 23 as low risk and 34 as high risk patients. In comparison to low risk patients the main features of high risk patients were: older age (p < 0.00001), higher comorbility (p < 0.004), longer hospitalization (p < 0.0007) and higher mortality (p < 0.018). Mortality in low risk patients was similar to Fine's study: 4.3 versus 3.5%. In high risk patients mortality was 26% versus 38%. Main complications in our series were mechanical ventilation (43.8%), PaO2/FiO2 < 250 mmHg (43.8%), and hepatic coma (38.5%). As a conclusion, we recommend the use of SPI in CAP at Emergency Services in order to better evaluate mortality, optimizing criteria of hospital admission