Durvalumab plus tremelimumab for the treatment of advanced neuroendocrine neoplasms of gastroenteropancreatic and lung origin.

Single immune checkpoint blockade in advanced neuroendocrine neoplasms (NENs) shows limited efficacy; dual checkpoint blockade may improve treatment activity. Dune (NCT03095274) is a non-randomized controlled multicohort phase II clinical trial evaluating durvalumab plus tremelimumab activity and safety in advanced NENs. This study included 123 patients presenting between 2017 and 2019 with typical/atypical lung carcinoids (Cohort 1), G1/2 gastrointestinal (Cohort 2), G1/2 pancreatic (Cohort 3) and G3 gastroenteropancreatic (GEP) (Cohort 4) NENs; who progressed to standard therapies. Patients received 1500 mg durvalumab and 75 mg tremelimumab for up to 13 and 4 cycles (every 4 weeks), respectively. The primary objective was the 9-month clinical benefit rate (CBR) for cohorts 1-3 and 9-month overall survival (OS) rate for Cohort 4. Secondary endpoints included objective response rate, duration of response, progression-free survival according to irRECIST, overall survival, and safety. Correlation of PD-L1 expression with efficacy was exploratory. The 9-month CBR was 25.9%/35.5%/25% for Cohorts 1, 2, and 3 respectively. The 9-month OS rate for Cohort 4 was 36.1%, surpassing the futility threshold. Benefit in Cohort 4 was observed regardless of differentiation and Ki67 levels. PD-L1 combined scores did not correlate with treatment activity. Safety profile was consistent with that of prior studies. In conclusion, durvalumab plus tremelimumab is safe in NENs and shows modest survival benefit in G3 GEP-NENs; with one-third of these patients experiencing a prolonged OS.

Epigenetic regulation of folate receptor-α (FOLR1) in human placenta of preterm newborns.

INTRODUCTION: Folates are essential nutrients for fetal development and pregnancy outcomes; they are transported to the fetus during gestation through specific folate transporters located in the placenta. In preterm newborns, we previously showed a lower placental mRNA expression of FOLR1 along with higher folate and lower vitamin B12 cord blood levels. Thereby we aimed to explore FOLR1 methylation in placentas of preterm newborns and hypothesized an increased FOLR1 methylation associated with cord blood folates and vitamin B12 concentrations. METHODS: FOLR1 methylation and mRNA were determined by methylation sensitive - high resolution melting (MS-HRM) and by real-time PCR respectively, in two placental sides of placental tissues: maternal (basal, BP) and fetal plates (chorionic, CP) of moderate preterm infants (32-36 gestational age) and term birth (37-41 gestational weeks). Folates and vitamin B12 were determined by electrochemiluminescence in umbilical cord blood samples from term and preterm newborns. RESULTS: We found that in preterm newborns, FOLR1 mRNA was lower in both plates of placenta compared with term newborns (p < 0,05) and was negatively associated with methylation of FOLR1 in CP. Preterm newborns presented higher folate and lower vitB12 concentrations in cord blood which correlated with increased placental FOLR1 methylation. DISCUSSION: In preterm newborns, placental FOLR1 expression is regulated by epigenetic mechanisms and presumably by maternal concentrations of folate and vitamin B12.

Impact of specific modes of circumferential resection margin involvement in rectal cancer local recurrence: A retrospective study.

PURPOSE: To compare the local recurrence rate and overall survival between patients with circumferential resection margin (CRM) involvement by direct tumor spread and by a tumor within a lymph node. METHODS: A total of 776 patients diagnosed with rectal cancer underwent rectal resection. Patients with CRM involvement by direct tumor spread were named group A. CRM involvement by tumor within a lymph node formed group B. Patient data, including sex, age, pT, pN, stage I-III versus IV, neoadjuvant radiotherapy, adjuvant chemotherapy, carcinoembryonic antigen, primary tumor location, lymph node retrieval, and need for abdominoperineal resection, were compared between both groups. RESULTS: In total, 10.5% of the patients had CRM involvement. Of these, in 57 cases (7.3%), it was by direct tumor spread and in 19 cases (2.4%) by tumor within a lymph node. Other types of CRM involvement were found in six patients. With a mean follow-up of 32.9 months, 18 patients from group A (31.5%) and one patient from group B (5.2%) suffered a local recurrence. Local recurrence-free survival was significantly higher in patients from group B (P = 0.049). Patients in stage I-III (P = 0.037) and from group B ( P = 0.049) had better overall survival. CONCLUSION: Patients with CRM involvement by tumor within a lymph node have a low risk of local recurrence and better overall survival than patients with CRM involvement by direct tumor spread.

[Retrorectal cystic hamartoma (tailgut cyst): an uncommon cause of recurrent abdominal pain.] / Hamartoma quístico retrorrectal (tailgut cyst): una causa infrecuente de dolor abdominal recurrente.

Retrorectal cystic hamartomas are rare congenital lesions that arise from aberrant remnants of the postanal gut. Most of them appear as asymptomatic lesions in middle-aged women but they can manifest with nonspecific symptoms such as abdominal or pelvic pain, constipation or diarrhoea, genitourinary symptoms, etc. Due to their anatomical position and variable presentation these lesions are often misdiagnosed. Complications include infection and malignant transformation, which is the reason why surgical treatment is always indicated. We report a case of a woman with recurrent episodes of abdominal pain that lasted for many years and increased progressively, conditioning her daily life activities. Image studies showed a non-complicated retrorectal cystic hamartoma. Complete surgical excision was achieved and the patient remains asymptomatic nowadays. Key words. Retrorectal cystic hamartoma. Abdominal pain.

Symptoms, signs and radiologic findings in patients having reoperative surgery for malignant peritoneal mesothelioma.

BACKGROUND: A reasonable estimate is that 50% of patients treated with cytoreductive surgery (CRS) and perioperative chemotherapy for malignant peritoneal mesothelioma will recur. Recognition of this recurrence and knowledgeable selection for additional surgical intervention is important in improving survival of patients who progress. MATERIAL AND METHODS: Patients treated for malignant peritoneal mesothelioma with CRS and perioperative chemotherapy were placed in follow-up for assessment of symptoms and signs and radiologic abnormalities by CT. The data were prospectively maintained and retrospectively reviewed. RESULTS: From a database of 130 patients with malignant peritoneal mesothelioma, 38 patients who had 50 reoperations with disease recurrence that was histologically confirmed were studied. The median time to first recurrence was 14 months with a range of 3-102. Considering 50 reoperative events the most common symptoms or signs were abdominal pain (40%) and abdominal distention (34%). The most common radiologic finding was a tumor mass (56%). Patients with an abdominal or pelvic mass had a reduced prognosis (p = 0.006) and patients with an absence of radiologic abnormalities had an improved survival (p = 0.047). CONCLUSIONS: In patients having reoperative surgery, symptoms, signs and radiologic abnormalities associated with recurrent (progressive) malignant peritoneal mesothelioma are abdominal pain, abdominal distention, and a tumor mass. An abdominal or pelvic mass was associated with a reduced prognosis and an absence of radiologic abnormalities with an improved prognosis.

Reporte de dos casos de miocardiopatía periparto en la Unidad de Terapia Intensiva Obstétrica / Report of two cases of peripartum cardiomyopathy in the Intensive Care Unit Obstetric

La miocardiopatía periparto es una enfermedad poco frecuente de causa desconocida, que se caracteriza por la aparición de insuficiencia cardíaca aguda en embarazadas que cursan el último mes de gestación y en el puerperio. En las poblaciones estudiadas, la frecuencia más alta se observa en Haití, donde se estima 1 caso cada 299 nacidos vivos; Sudáfrica 1 caso cada 1000 nacidos vivos. Las frecuencias más bajas corresponden a los Estados Unidos (1 caso cada 4000 nacidos vivos) y Europa. La tasa de mortalidad hospitalaria estimada es del 1,36% y la tasa global de mortalidad, del 2,05%. Se desconoce su verdadera prevalencia e incidencia en la Argentina, probablemente como consecuencia de subregistros. En nuestra Unidad de Terapia Intensiva Obsté- trica, ingresaron dos casos de miocardiopatía periparto, en un período de dos años, que fueron abordados por el equipo multidisciplinario compuesto por intensivistas, cardiólogos, nefrólogos y obstetras.(AU)

Peripartum cardiomyopathy is an unusual condition of unknown origin that is characterized by an acute heart failure during the last months of pregnancy and the puerperium. Most case studies show that Haiti has the highest rate of peripartum cardiomyopathy, 1 in 299 live births, followed by South Africa with 1 in 1,000 and the lowest rate is observed in United States (1 in 4,000 live births) and Europe. Hospital case mortality rate is 1.36% with a global mortality rate of 2.05%. Its prevalence and incidence in Argentina are unknown, perhaps as a result of underreporting cases. Two cases of peripartum cardiomyopathy were treated in our Obstetric Intensive Care Unit within a period of two years by a multidisciplinary team of intensivists, cardiologists, nephrologists and obstetricians.(AU)

Evacuación del meconio intestinal para mejorar tolerancia alimentaria en prematuro de muy bajo peso (protocolo Emita) / Meconium evacuation to improve feeding tolerance in very low birth weight preterm infants (Emita Protocol)

Introducción: Se ha descrito que la tolerancia alimentaria en el extremo prematuro se asocia a una precoz eliminación de meconio. Estudios prospectivos, randomizados o con controles históricos de estimulación de evacuación de meconio reportan diferentes resultados. El objetivo de este estudio fue evaluar el uso sistemático de enemas que aceleren la evacuación de meconio, y por ende la tolerancia alimentaria. Pacientes y Método: Estudio controlado, aleatorizado y multicéntrico que evaluó el uso de enemas de solución fisiológica con glicerina (0,8 ml de glicerina + 3 ml de solución fisiológica o 1 ml de glicerina + 5 ml de solución fisiológica según peso al nacer menor o mayor de 800 g, respectivamente) versus simulación, iniciado en las primeras 96 h de vida, en prematuros con peso al nacimiento entre 500 y 1.250 g. Se registraron antecedentes maternos (parto prematuro, infección ovular, síndrome hipertensivo del embarazo, administración de sulfato de magnesio, y corticoides prenatales, doppler fetal alterado, tipo de parto, sexo, peso y edad gestacional, evaluación de apgar y necesidad de ventilación asistida y oxígenoterapia) y nutricionales (edad al alcanzar volúmenes de alimentación de 100 ml//kg/día y alimentación enteral completa, edad para eliminar meconio, número de días en nutrición parenteral, peso a los 28 días, volúmenes semanales de leche materna y fórmula de prematuros). Resultados: En 101 sujetos incluidos en el estudio, no se obtienen diferencias significativas en la variable principal de edad para alcanzar el aporte enteral total o los 100 ml por kg por día. Tampoco se observan diferencias en las variables secundarias: número de episodios de sepsis tardías con o sin hemocultivo positivo, hiperbilirrubinemia, enterocolitis necrotizante o hemorragia intracraneana. Conclusiones: El uso sistemático de enemas de solución fisiológica y glicerina, en la forma utilizada en este estudio, no modifica la tolerancia alimentaria enteral de prematuros de muy bajo peso al nacer.

Introduction: it has been reported that feeding tolerance in preterm infants is associated with an early passage of meconium. prospective, randomized or historical control studies that stimulate meconium evacuation have reported varied results. this study was intented to evaluate the use of enemas to speed up meconium evacuation, facilitating feeding tolerance. Patients and Method: a controlled multicenter randomized trial that evaluated the use of physiological saline enemas with glycerol (0.8 ml glycerol + 3 ml saline or 1 ml glycerol + 5 ml saline depending on babies weighing less or more than 800 g at birth, respectively) versus simulation. This procedure was performed in the first 96 hours of life in infants with birth weight between 500 and 1,250 g. Maternal (preterm delivery, clinical chorioamnionitis, gestational hypertension, administration of magnesium sulfate and prenatal corticosteroids, fetal doppler altered, type of delivery, gender, weight and gestational age, assessment of apgar and need for assisted ventilation and oxygenotherapy) and nutritional history (age when feeding volumes of 100 ml/kg/day and full enteral feeding were reached, age to remove meconium, number of days on parenteral nutrition, weight at 28 days, weekly volumes of breast milk and preterm formula) were described. Results: No significant differences were obtained regarding the age to reach full enteral intake or 100 ml/kg/day were found among the 101 patients in the study. also, no differences in the following secondary variables are observed: number of episodes of late sepsis with or without positive blood culture, hyperbilirubine mia, necrotizing enterocolitis and intraventricular hemorrhage. Conclusions: the routine use of saline enemas and glycerin in this study does not alter the enteral feeding tolerance in very low birth weight preterm infants.

Health-related quality of life in well-differentiated metastatic gastroenteropancreatic neuroendocrine tumors.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms capable of producing hormones. The development of new treatments has improved progression-free survival, albeit with increased toxicity. Health-related quality of life (HRQoL) has become an important endpoint in clinical research to evaluate patients' well-being in such a contradictory scenario. In this review, we examine key reported outcomes across clinical studies exploring HRQoL in patients with GEP-NETs. We have conducted a review of the literature using PubMed, The Cochrane Library, EMBASE, and Google Scholar. Selection criteria for articles were (1) publication in English between 1995 and 2014, (2) patients with GEP-NET, and (3) analysis of HRQoL, including mental health and psychological symptoms. Forty-nine studies met the inclusion criteria (31 clinical trials, 14 observational studies, and 4 developments of NET-specific HRQoL instruments). The scope and nature of the literature was diverse with 27 instruments used to measure aspects of HRQoL. EORTC QLQ-C30 was the most frequently used, in 38 of the 49 studies. Standardized measures revealed that in spite of generally good HRQoL, GEP-NET patients have specific psychological and physical complaints. The clinical benefit of somatostatin analogs and sunitinib has been clearly supported by HRQoL assessment. Improvement in HRQoL scores or symptom relief over time was also reported in 14 trials of peptide receptor radionuclide therapy, however the absence of randomized studies obviate definitive conclusions. We have also identified several unanswered questions that should be addressed in further research concerning chemotherapy, everolimus, surgery, local ablative therapies, and chemoembolization. Future research should incorporate GEP-NET-specific HRQoL instruments into phase III trials. This review may help both clinicians and researchers to select the most appropriate tools to assess changes in HRQoL in this population.

The endocannabinoid anandamide during lactation increases body fat content and CB1 receptor levels in mice adipose tissue.

Type 1 cannabinoid receptors (CB1R) modulate energy balance; thus, their premature activation may result in altered physiology of tissues involved in such a function. Activation of CB1R mainly occurs after binding to the endocannabinoid Anandamide (AEA). The objective of this study was to evaluate the effects of AEA treatment during lactation on epididymal and body fat content, in addition to CB1R protein level at weaning. With this purpose, male mice pups were orally treated with AEA (20 µg g(-1) body weight) or vehicle during lactation. Mice (21 days old) were killed and epididymal fat was extracted to evaluate its amount, adipocyte size and CB1R protein levels by western blot analysis. Total body fat percentage was also evaluated. Anandamide-treated mice showed an increased body fat content at 21 and 150 days of age. Moreover, epididymal adipose tissue amount, adipocyte size and CB1R protein levels were higher in the AEA-treated group. This in vivo study shows for the first time that a progressive increase in body fat accumulation can be programmed in early stages of life by oral treatment with the endocannabinoid AEA, a fact associated with an increased amount of epididymal fat pads and a higher expression of CB1R in this tissue.

Proapoptotic effect of endocannabinoids in prostate cancer cells.

In the early stages, prostate cancer is androgen­ dependent; therefore, medical castration has shown significant results during the initial stages of this pathology. Despite this early effect, advanced prostate cancer is resilient to such treatment. Recent evidence shows that derivatives of Cannabis sativa and its analogs may exert a protective effect against different types of oncologic pathologies. The purpose of the present study was to detect the presence of cannabinoid receptors (CB1 and CB2) on cancer cells with a prostatic origin and to evaluate the effect of the in vitro use of synthetic analogs. In order to do this, we used a commercial cell line and primary cultures derived from prostate cancer and benign prostatic hyperplasia. The presence of the CB1 and CB2 receptors was determined by immunohistochemistry where we showed a higher expression of these receptors in later stages of the disease (samples with a high Gleason score). Later, treatments were conducted using anandamide, 2-arachidonoyl glycerol and a synthetic analog of anandamide, methanandamide. Using the MTT assay, we proved that the treatments produced a cell growth inhibitory effect on all the different prostate cancer cultures. This effect was demonstrated to be dose-dependent. The use of a specific CB1 receptor blocker (SR141716) confirmed that this effect was produced primarily from the activation of the CB1 receptor. In order to understand the MTT assay results, we determined cell cycle distribution by flow cytometry, which showed no variation at the different cell cycle stages in all the cultures after treatment. Treatment with endocannabinoids resulted in an increase in the percentage of apoptotic cells as determined by Annexin V assays and caused an increase in the levels of activated caspase-3 and a reduction in the levels of Bcl-2 confirming that the reduction in cell viability noted in the MTT assay was caused by the activation of the apoptotic pathway. Finally, we observed that endocannabinoid treatment activated the Erk pathway and at the same time, produced a decrease in the activation levels of the Akt pathway. Based on these results, we suggest that endocannabinoids may be a beneficial option for the treatment of prostate cancer that has become nonresponsive to common therapies.

Evacuación del meconiointestinal para mejorar tolerancia alimentaria en prematuro de muy bajo peso (protocolo Emita) / Meconium evacuation to improve feeding tolerance in very low birth weight preterm infants (Emita protocol)

Se ha descrito que la tolerancia alimentaria en el extremo prematuro se asocia a una precoz eliminación de meconio. Estudios prospectivos, randomizados o con controles históricos de estimulación de evacuación de meconio reportan diferentes resultados. El objetivo de este estudio fue evaluar el uso sistemático de enemas que aceleren la evacuación de meconio, y por ende la tolerancia alimentaria. Pacientes y Método: Estudio controlado, aleatorizado y multicéntrico que evaluó el uso de enemas de solución fisiológica con glicerina (0,8 ml de glicerina + 3 ml de solución fisiológica o 1 ml de glicerina + 5 ml de solución fisiológica según peso al nacer menor o mayor de 800 g, respectivamente) versus simulación, iniciado en los primeras 96 h de vida, en prematuros con peso al nacimiento entre 500 y 1.250 g. Se registraron antecedentes maternos (parto prematuro, infección ovular, síndrome hipertensivo del embarazo, administración de sulfato de magnesio, y corticoides prenatales, doppler fetal alterado, tipo de parto, sexo, peso y edad gestacional, evaluación de apgar y necesidad de ventilación asistida y oxígenoterapia) y nutricionales (edad al alcanzar volúmenes de alimentación de 100 ml//kg/día y alimentación enteral completa, edad para eliminar meconio, número de días en nutrición parenteral, peso a los 28 días, volúmenes semanales de leche materna y fórmula de prematuros). Resultados: En 101 sujetos incluidos en el estudio, no se obtienen diferencias significativas en la variable principal de edad para alcanzar el aporte enteral total o los 100 ml por kg por día. Tampoco se observan diferencias en las variables secundarias: número de episodios de sepsis tardías con o sin hemocultivo positivo, hiperbilirrubinemia, enterocolitis necrotizante o hemorragia intracraneana...

Introduction: It has been reported that feeding tolerance in preterm infants is associated with an early passage of meconium. Prospective, randomized or historical control studies that stimulate meconium evacuation have reported varied results. This study was intented to evaluate the use of enemas to speed up meconium evacuation, facilitating feeding tolerance. Patients and Method: A controlled multicenter randomized trial that evaluated the use of physiological saline enemas with glycerol (0.8 ml glycerol + 3 ml saline or 1 ml glycerol + 5 ml saline depending on babies weighing less or more than 800 g at birth, respectively) versus simulation. This procedure was performed in the first 96 hours of life in infants with birth weight between 500 and 1,250 g. Maternal (preterm delivery, clinical chorioamnionitis, gestational hypertension, administration of magnesium sulfate and prenatal corticosteroids, fetal Doppler altered, type of delivery, gender, weight and gestational age, assessment of Apgar and need for assisted ventilation and oxygenotherapy) and nutritional history (age when feeding volumes of 100 ml/kg/day and full enteral feeding were reached, age to remove meconium, number of days on parenteral nutrition, weight at 28 days, weekly volumes of breast milk and preterm formula) were described. Results: No significant differences were obtained regarding the age to reach full enteral intake or 100 ml/kg/day were found among the 101 patients in the study. Also, no differences in the following secondary variables are observed: number of episodes of late sepsis with or without positive blood culture, hyperbilirubinemia, necrotizing enterocolitis and intraventricular hemorrhage...

[Meconium evacuation to improve feeding tolerance in very low birth weight preterm infants (Emita Protocol)]. / Evacuación del meconiointestinal para mejorar tolerancia alimentaria en prematuro de muy bajo peso (protocolo Emita).

INTRODUCTION: It has been reported that feeding tolerance in preterm infants is associated with an early passage of meconium. Prospective, randomized or historical control studies that stimulate meconium evacuation have reported varied results. This study was intented to evaluate the use of enemas to speed up meconium evacuation, facilitating feeding tolerance. PATIENTS AND METHOD: A controlled multicenter randomized trial that evaluated the use of physiological saline enemas with glycerol (0.8 ml glycerol + 3 ml saline or 1 ml glycerol + 5 ml saline depending on babies weighing less or more than 800 g at birth, respectively) versus simulation. This procedure was performed in the first 96 hours of life in infants with birth weight between 500 and 1,250 g. Maternal (preterm delivery, clinical chorioamnionitis, gestational hypertension, administration of magnesium sulfate and prenatal corticosteroids, fetal Doppler altered, type of delivery, gender, weight and gestational age, assessment of Apgar and need for assisted ventilation and oxygenotherapy) and nutritional history (age when feeding volumes of 100 ml/kg/day and full enteral feeding were reached, age to remove meconium, number of days on parenteral nutrition, weight at 28 days, weekly volumes of breast milk and preterm formula) were described. RESULTS: No significant differences were obtained regarding the age to reach full enteral intake or 100 ml/kg/day were found among the 101 patients in the study. Also, no differences in the following secondary variables are observed: number of episodes of late sepsis with or without positive blood culture, hyperbilirubinemia, necrotizing enterocolitis and intraventricular hemorrhage. CONCLUSIONS: The routine use of saline enemas and glycerin in this study does not alter the enteral feeding tolerance in very low birth weight preterm infants.

Incidencia y evolución de membrana hialina en menores de 35 semanas según crecimiento intrauterino / Incidence and evolution of hyaline membrane in newborns under 35 weeks of gestational age according intrauterine growth

Introduction: It is thought that intrauterine growth restriction induces respiratory maturation. The information varies if the studies consider analysis based on birth weight or gestational age. Objective: The goal of this study is to compare the incidence and evolution of hyaline membrane disease (HMD) between small and adequate premature babies under 35 weeks of gestational age (< 35 wGA) based on data in the literature. Patients and Methods: Two databases were created and analyzed: a) 2 022 newborns < 35 wGA admitted to the Service, whose incidence of HMD was calculated, and b) 733 newborns < 35 wGA with HMD and treated with surfactant, to describe the evolution. Results: Analysis of GA group shows a higher incidence of HMD (35.2 percent) among small for GA, and less (29.1 percent) among those who are not small for GA (p: 0.026). If a subset is formed for the newborns < 1 500 g in birth weight, those small for gestational age have a lower incidence (47.5 percent) than those adequate for GA (60.7 percent). Logistic regression analysis for discharge with oxygen of newborns with HMD shows association with lower z score for birth weight, corticosteroid use and oxygen dependence at 36 weeks. Conclusions: Preterm newborns small for GA show a higher incidence of HMD and oxygen dependence when comparing for GA.

Introducción: Tradicionalmente se ha considerado que la restricción de crecimiento intrauterina produce maduración respiratoria, pero la información es diferente según si los estudios consideran el análisis por grupos de peso de nacimiento o edad gestacional. Objetivo: El objetivo de este análisis fue comparar la incidencia y evolución de membrana hialina, de los prematuros menores de 35 semanas de edad gestacional según fueran pequeños o no para edad gestacional. Pacientes y Método: Se analizaron dos bases de datos: 2 022 menores de 35 semanas hospitalizados en el Servicio para determinar incidencia de membrana hialina y 733 menores de 35 semanas tratados con surfactante con diagnóstico de membrana hialina para comparar evolución de ésta. Resultados: El análisis por grupos de edad gestacional muestra una incidencia de membrana hialina mayor, de 35,2 por ciento, en los pequeños para la edad gestacional, y de 29,1 por ciento en los no pequeños (p: 0,026). Si se analiza sólo menores de 1 500 gramos de peso de nacimiento, el grupo pequeño tiene una incidencia menor, de 47,5 por ciento, y los no pequeños de 60,7 por ciento. El análisis de regresión logística para alta con oxígeno de los que tuvieron membrana hialina, muestra asociación con menor puntaje z de peso de nacimiento, uso de corticoides y dependencia de oxígeno a las 36 semanas. Conclusiones: El recién nacido pretérmino pequeño para edad gestacional tiene mayor incidencia de membrana hialina y evoluciona con mayor dependencia de oxígeno al comparar por edad gestacional.

Compromiso pulmonar en síndrome de Sjõgren: caso clínico: [revisión] / Pulmonary involvement in primary Sjõgren's syndrome: a case report: [review]

Se presenta el caso de una mujer de 53 años con historia de aumento de volumen y dolor articular, pérdida de peso y síntomas sicca. El estudio de laboratorio mostró VHS elevada, anemia, linfopenia, hipocomplementemia y autoanticuerpos contra SSA/Ro y SSB/La, compatibles con un síndrome de Sjõgren (SS). Además, la radiografía de tórax mostró múltiples nódulos pulmonares, lo que fue confirmado por una TAC de tórax. El estudio histológico de los nódulos, plasmocitosis y proliferación linfocitaria atípica no demostró linfoma. Es ampliamente conocido que el SS confiere un mayor riesgo de desarrollar sindromes linfoproliferativos, lo que aumenta cuando hay presencia de vasculitis, hipo-complementemia y linfopenia. En este caso clínico el diagnóstico diferencial de la etiología de los nódulos pulmonares fue particularmente difícil. Dado lo anterior, se discute y revisa la literatura disponible acerca de compromiso pulmonar en SS.

We report the case of a 53-year old woman with a history of joint swelling and pain, weight loss and sicca symptoms. The laboratory showed a high ESR, anemia, lymphopenia, low complements and circulating auto-antibodies against SSA/Ro and SSB/La consistent with Sjõgren´s Syndrome (SS). Interestingly, the chest x-ray revealed multiple nodules in both lungs, which were corroborated by CT scan. The histological study of the pulmonary nodules showed plasmocytosis and atypical lymphocytes, but failed to demonstrate lymphoma. It is widely acknowledged that SS confers a high risk of developing lymphoproliferative syndromes, which is increased when vasculitis, low complements and lymphopenia are present. In this case, it was particularly difficult to elucidate the differential diagnosis of lung nodules. Accordingly, we discuss and review the available literature regarding pulmonary involvement in SS.

Cadmium exposure during pregnancy reduces birth weight and increases maternal and foetal glucocorticoids.

Cadmium exposure induces low birth weight through unknown mechanisms. Since low birth weight is associated to foetal exposure to high glucocorticoids (GC) concentrations, we hypothesized that low birth weight induced by prenatal exposure to Cd(2+) is, at least in part, mediated by higher foetal exposure to GC, specifically corticosterone, the main active GC in rodents. Pregnant rats were exposed to different dose of CdCl(2) administered in drinking water during the whole pregnancy period. At term, corticosterone was measured by enzyme immunoassay in maternal and foetal blood and in placental tissues. Cadmium was determined in placentas, maternal tissues (liver and kidney) and foetuses by inductively coupled plasma-mass spectrometry (ICP-MS). Placental 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity and expression were determined by a radiometric conversion assay and quantitative RT-PCR respectively. Results demonstrated that 50 ppm of Cd(2+), which was accumulated in different maternal tissues but not in the foetus, reduced pup birth weights and increased plasma corticosterone concentrations, both in mother and foetus. Placental 11beta-HSD2 activity and expression did not change by the treatment. We conclude that 50 ppm of Cd(2+) administered during pregnancy, increase foetal corticosterone concentrations due, probably, to alterations of the regulatory mechanisms of placental barrier to GC causing a mild but significant reduced birth weight.

Treatment with type I interferons induces a regulatory T cell subset in peripheral blood mononuclear cells from multiple sclerosis patients.

Type I Interferon (IFN-alpha/beta) therapy has altered the natural course of multiple sclerosis. In this paper we evaluate the possible molecular mechanisms involved in the in vitro effects of IFN-alpha/beta on peripheral blood mononuclear cells from patients with clinically definite Relapsing-Remitting Multiple Sclerosis. The total RNA from IFN-alpha, IFN-beta treated cells and untreated cells was extracted and amplified for CD86, CD28, CTLA-4, TNF-alpha, IFN-gamma, CCL2, CCR5, IL-13, MMP-9, TIMP-1, CD25, TGF-beta, IL-10 and the transcriptional factor Foxp3 by Reverse Transcription-Polymerase Chain Reaction and the CD4+CD25high subset was evaluated using flow cytometry. In general, there were no significant differences concerning the modulation of the genes studied in the response to IFN-alpha and IFN-beta treatments, which suggest a similar mechanism of action for both interferons. However, we found a significant increment in IFN-gamma expression after IFN-alpha but not after IFN-beta treatments. The in vitro treatment of mononuclear cells from multiple sclerosis patients with both interferons significantly increased the CD25 mRNA. Furthermore, we observed a CD25/Foxp3 correlation and an increment of the CD4+CD25high subset, indicating that the induction of regulatory T cells could be a crucial mechanism involved in the type I interferon effects.

Sobrecrecimiento bacteriano intestinal un factor de riesgo de peritonitis bacteriana espontánea y mortalidad en pacientes con cirrosis hepática / Intestinal bacterial overgrowth is a risk factor for spontaneous bacterial peritonitis and mortality in patients with liver cirrhosis

Spontaneous bacterial peritonitis (SBP) is a major and serious complication of liver cirrhosis. Small intestinal bacterial overgrowth (SIBO) has been shown to occur with increased frequency in patients with cirrhosis. Studies have suggested that SIBO may contribute to the development of SBP. Aims: to assess the prevalence of SIBO and its relationship with the mortality in patients with cirrhosis. Patients and Methods: One hundred three cirrhotic patients, 62 male, mean age 56.6 (range 35-89) entered in the study in a four year period with a mean follow-up of 22.2 months (range 3-76). SIBO was evaluated by breath hydrogen test (BHT) with lactulose. A positive BHT was defined as an increase of 20 ppm during the first 60 min after lactulose ingestion. SBP was diagnosed by a polymorphonuclear leukocyte count greater than or equal to of 250 cells/mm3 in ascitic fluid. Results: A 50 percent of cirrhotic patients had SIBO at the beginning of follow-up period. The prevalence of SIBO was similar in patients with Child-Pugh class A, B, or C (48 percent 51 percent and 48 percent patients respectively). The presence of SBP was significantly higher in patients with SIBO (17/54 patients) than patients without SIBO (1/53 patients), p < 0.05. The mortality of cirrhotic patients was higher in the SIBO group than in the non-SIBO group (25/50 versus 16/35 patients. p < 0.05). Conclusions: The results of this study confirm that the presence of SIBO is a risk factor for SBP and mortality in patients with liver cirrhosis. SIBO should be investigated and treated during the follow-up in these patients.

La peritonitis bacteriana espontánea (PBE) es una complicación frecuente y grave en pacientes con cirrosis hepática. El sobrecrecimiento bacteriano intestinal (SBI) ha sido descrito con frecuencia en pacientes con cirrosis. Estudios han sugerido que el SBI puede ser un factor importante en el desarrollo de la PBE. Objetivos: Evaluar la prevalencia de SBI y su relación con la mortalidad en pacientes con cirrosis hepática. Pacientes y métodos: Ciento tres pacientes cirróticos, 67 hombres, edad promedio 58,6 (rango 35-89) entraron al estudio en un período de cuatro años con un seguimiento promedio de 22,2 meses (rango 3-76). El SBI fue evaluado por test de hidrógeno en aire espirado (THE) con lactulosa. Un examen era considerado positivo con un nivel mayor de 20 ppm después de la ingesta de lactulosa en los primeros 60 min. El diagnóstico de PBE se fundamentó en un recuento de polimorfonucleares mayor o igual que 250 células/mm3 en muestra de líquido ascítico. Resultados: El 50 por ciento de los pacientes cirróticos presentó SBI al comienzo de su seguimiento. La prevalencia de SBI fue similar en pacientes cirróticos Child-Pugh A, B, o C (48 por ciento, 50 por ciento y 50 por ciento respectivamente). La presencia de PBE fue significativamente mayor en pacientes con SBI (17/50 pacientes) que en pacientes sin SBI (1/53 pacientes). p < 0,05. La mortalidad de los pacientes cirróticos fue mayor en el grupo con SBI que en el grupo sin SBI (25/50 versus 16/53 pacientes, p < 0,05). Conclusiones: Los resultados de este estudio confirman que la presencia de SBI es un factor de riesgo de PBE y mortalidad en pacientes con cirrosis hepática. El SBI debería ser investigado y tratado durante el seguimiento de estos pacientes.