Prediction of response to immune checkpoint blockade in patients with metastatic colorectal cancer with microsatellite instability.

BACKGROUND: Mismatch repair-deficient (dMMR) tumors displaying microsatellite instability (MSI) represent a paradigm for the success of immune checkpoint inhibitor (ICI)-based immunotherapy, particularly in patients with metastatic colorectal cancer (mCRC). However, a proportion of patients with dMMR/MSI mCRC exhibit resistance to ICI. Identification of tools predicting MSI mCRC patient response to ICI is required for the design of future strategies further improving this therapy. PATIENTS AND METHODS: We combined high-throughput DNA and RNA sequencing of tumors from 116 patients with MSI mCRC treated with anti-programmed cell death protein 1 ± anti-cytotoxic T-lymphocyte-associated protein 4 of the NIPICOL phase II trial (C1, NCT03350126, discovery set) and the ImmunoMSI prospective cohort (C2, validation set). The DNA/RNA predictors whose status was significantly associated with ICI status of response in C1 were subsequently validated in C2. Primary endpoint was progression-free survival by immune RECIST (iRECIST) (iPFS). RESULTS: Analyses showed no impact of previously suggested DNA/RNA indicators of resistance to ICI, e.g. MSIsensor score, tumor mutational burden, or specific cellular and molecular tumoral contingents. By contrast, iPFS under ICI was shown in C1 and C2 to depend both on a multiplex MSI signature involving the mutations of 19 microsatellites hazard ratio cohort C2 (HRC2) = 3.63; 95% confidence interval (CI) 1.65-7.99; P = 1.4 × 10-3] and the expression of a set of 182 RNA markers with a non-epithelial transforming growth factor beta (TGFB)-related desmoplastic orientation (HRC2 = 1.75; 95% CI 1.03-2.98; P = 0.035). Both DNA and RNA signatures were independently predictive of iPFS. CONCLUSIONS: iPFS in patients with MSI mCRC can be predicted by simply analyzing the mutational status of DNA microsatellite-containing genes in epithelial tumor cells together with non-epithelial TGFB-related desmoplastic RNA markers.

Discordance between immunochemistry of mismatch repair proteins and molecular testing of microsatellite instability in colorectal cancer.

BACKGROUND: DNA mismatch repair system deficiency (dMMR) is found in 15% of colorectal cancers (CRCs). Two methods are used to determine dMMR, immunohistochemistry (IHC) of MMR proteins and molecular testing of microsatellite instability (MSI). Only studies with a low number of patients have reported rates of discordance between these two methods, ranging from 1% to 10%. MATERIALS AND METHODS: Overall, 3228 consecutive patients with CRCs from two centers were included. Molecular testing was carried out using the Pentaplex panel and IHC evaluated four (MLH1, MSH2, MSH6, and PMS2; cohort 1; n = 1085) or two MMR proteins (MLH1 and MSH2; cohort 2; n = 2143). The primary endpoint was the rate of discordance between MSI and MMR IHC tests. RESULTS: Fifty-one discordant cases (1.6%) were initially observed. Twenty-nine out of 51 discordant cases were related to IHC misclassifications. In cohort 1, after re-reading IHC and/or carrying out new IHC, 16 discordant cases were reclassified as nondiscordant. In cohort 2, after the addition of MSH6/PMS2 IHC and re-examination, 13 were reclassified as nondiscordant. In addition, 10 misclassifications of molecular tests were identified. Finally, only 12 discordant cases (0.4%) remained: 5 were proficient MMR/MSI and 7 were dMMR/microsatellite stable. CONCLUSIONS: Our study confirmed the high degree of concordance between MSI and MMR IHC tests. Discordant cases must be reviewed, and if needed, tests must be repeated and analyzed by an expert team.

Clinical and molecular characterisation of hereditary and sporadic metastatic colorectal cancers harbouring microsatellite instability/DNA mismatch repair deficiency.

BACKGROUND: Patients treated with chemotherapy for microsatellite unstable (MSI) and/or mismatch repair deficient (dMMR) cancer metastatic colorectal cancer (mCRC) exhibit poor prognosis. We aimed to evaluate the relevance of distinguishing sporadic from Lynch syndrome (LS)-like mCRCs. PATIENTS AND METHODS: MSI/dMMR mCRC patients were retrospectively identified in six French hospitals. Tumour samples were screened for MSI, dMMR, RAS/RAF mutations and MLH1 methylation. Sporadic cases were molecularly defined as those displaying MLH1/PMS2 loss of expression with BRAFV600E and/or MLH1 hypermethylation and no MMR germline mutation. RESULTS: Among 129 MSI/dMMR mCRC patients, 81 (63%) were LS-like and 48 (37%) had sporadic tumours; 22% of MLH1/PMS2-negative mCRCs would have been misclassified using an algorithm based on local medical records (age, Amsterdam II criteria, BRAF and MMR statuses when locally tested), compared to a systematical assessment of MMR, BRAF and MLH1 methylation statuses. In univariate analysis, parameters associated with better overall survival were age (P < 0.0001), metastatic resection (P = 0.001) and LS-like mCRC (P = 0.01), but not BRAFV600E. In multivariate analysis, age (hazard ratio (HR) = 3.19, P = 0.01) and metastatic resection (HR = 4.2, P = 0.001) were associated with overall survival, but not LS. LS-like patients were associated with more frequent liver involvement, metastatic resection and better disease-free survival after metastasectomy (HR = 0.28, P = 0.01). Median progression-free survival of first-line chemotherapy was similar between the two groups (4.2 and 4.2 months; P = 0.44). CONCLUSIONS: LS-like and sporadic MSI/dMMR mCRCs display distinct natural histories. MMR, BRAF mutation and MLH1 methylation testing should be mandatory to differentiate LS-like and sporadic MSI/dMMR mCRC, to determine in particular whether immune checkpoint inhibitors efficacy differs in these two populations.

¿Es la música un complemento a la analgesia en la litotricia extracorpórea? / No disponible

No disponible

Epstein-Barr virus-driven B Cell Proliferation with CD4+ T Cell Expansion: A Lymphomatoid Granulomatosis-like Disease Related to Hyperinterleukin-10 Secretion of Remarkably Favourable Outcome with Rituximab.

Granulomatous lymphomatosis is an Epstein-Barr virus (EBV)-driven B cell proliferation associated with an exuberant CD4(+) T cell reaction with usually histopathological pictures of angiocentrism. So far, the characteristics of CD4(+) T cells in granulomatous lymphomatosis and the mechanism leading to their expansion remain poorly explored. We report a 56-year-old female with a past history of cold agglutinin disease, which was successfully treated with 4 weekly infusions of rituximab. She presented one year later with features of granulomatous lymphomatosis that resulted in severe lung and bone marrow infiltration. We provide evidence that CD4(+) T cell expansion was oligoclonal, involved anergic cells and did not result from an EBV-driven stimulation. Rather, it resulted possibly from a high production of interleukin-10 by immunoblastic EBV-positive B cells. The outcome was remarkably favourable with rituximab and steroids. Our results suggest that an EBV-driven B cell proliferation should be investigated in patients presenting with a CD4(+) T cells alveolitis or other systemic manifestations resulting from a CD4(+) T cell expansion. These features should prompt to introduce an immunosuppressive therapy including steroids and rituximab. Our results deserve further investigations to confirm our pathophysiological hypotheses in CD4(+) T cell expansions associated with EBV-driven B cell proliferations and to assess whether granulomatous lymphomatosis could result from comparable mechanisms.

JAK3 deregulation by activating mutations confers invasive growth advantage in extranodal nasal-type natural killer cell lymphoma.

Extranodal, nasal-type natural killer (NK)/T-cell lymphoma (NKCL) is an aggressive malignancy with poor prognosis in which, usually, signal transducer and activator of transcription 3 (STAT3) is constitutively activated and oncogenic. Here, we demonstrate that STAT3 activation mostly results from constitutive Janus kinase (JAK)3 phosphorylation on tyrosine 980, as observed in three of the four tested NKCL cell lines and in 20 of the 23 NKCL tumor samples under study. In one of the cell lines and in 4 of 19 (21%) NKCL primary tumor samples, constitutive JAK3 activation was related to an acquired mutation (A573V or V722I) in the JAK3 pseudokinase domain. We then show that constitutive activation of the JAK3/STAT3 pathway has a major role in NKCL cell growth and survival and in the invasive phenotype. Indeed, NKCL cell growth was slowed down in vitro by targeting JAK3 with chemical inhibitors or small-interfering RNAs. In a human NKCL xenograft mouse model, tumor growth was significantly delayed by the JAK3 inhibitor CP-690550. Altogether, the constitutive activation of JAK3, which can result from JAK3-activating mutations, is a frequent feature of NKCL that deserves to be tested as a therapeutic target.

Combined HER2 analysis of biopsies and surgical specimens to optimize detection of trastuzumab-eligible patients in eso-gastric adenocarcinoma: a GERCOR study.

BACKGROUND: HER2 is overexpressed in 10 to 20% of gastro-esophageal adenocarcinoma (GE-ADK), and is a target for trastuzumab in metastatic patients. We conducted a study to compare HER2 expression between diagnostic biopsies (DBs) and surgical specimens (SSs) of GE-ADK, and to determine the influence of non-trastuzumab containing neoadjuvant chemotherapy (NAC) on this expression. PATIENTS AND METHODS: Pathological specimens from biopsies of 228 patients operated on between 2004 and 2011 were collected. Two cohorts treated (n = 141) or not (n = 87) with a NAC were constituted. Two blind independent pathological HER2 analyses on DB and on SS were carried out using immunohistochemistry (IHC) and colorimetric in situ hybridization (CISH). HER-2 overexpression (HER2+) was defined by a score 3+ in IHC, or 2+ with a positive CISH test, according to the specific HER2 scoring guidelines for GE-ADK. RESULTS: Paired HER2 status could be determined for 218 out of the 228 patients (95.6%). HER2+ rates were 13.3% on DB (29/218) and 14.7% on SS (32/218). HER2+ tumors were mainly cardial or esophageal adenocarcinomas, with a well-differentiated, intestinal histological type. HER2 status differed between DB and SS in 6% of cases. When DB analyses were added to SS analyses, the relative increase in HER2+ cases was 13.5% (17.1% for patients with NAC and 23.5% for patients with histological response to NAC, versus 7.1% for patients without NAC, P = 0.4, NS). Differences between DB and SS HER2 expression could be explained by intratumoral heterogeneity and by a HER2 expression decrease in SS after NAC in responding patients possibly due to a higher chemosensitivity of HER2-positive clones. CONCLUSION: The determination of HER2 status on DB provides results that complete those obtained with SS. Combining the analysis of DB and of SS enables to optimize the selection of trastuzumab-eligible patients in case of metastatic relapse, and particularly in previously NAC-responding patients.

Frequencies of KIT and PDGFRA mutations in the MolecGIST prospective population-based study differ from those of advanced GISTs.

Gastrointestinal stromal tumors (GISTs) are the most common human sarcoma. Most of the data available on GISTs derive from retrospective studies of patients referred to oncology centers. The MolecGIST study sought to determine and correlate clinicopathological and molecular characteristics of GISTs. Tumor samples and clinical records were prospectively obtained and reviewed for patients diagnosed in France during a 24-month period. Five hundred and ninety-six patients were included, of whom 10% had synchronous metastases. GISTs originated from the stomach, small bowel or other site in 56.4, 30.2 and 13.4% of cases, respectively. The main prognostic markers, tumor localization, size and mitotic index were not independent variables (P < 0.0001). Mutational status was determined in 492 (83%) patients, and 138 different mutations were identified. KIT and PDGFRA mutations were detected in 348 (71%) and 74 (15%) patients, respectively, contrasting with 82.8 and 2.1% in patients with advanced GIST (MetaGIST) (P < 0.0001). Further comparison of localized GISTs in the MolecGIST cohort with advanced GISTs from previous clinical trials showed that the mutations of PDGFRA exon18 (D842V and others) as well as KIT exon11 substitutions (W557R and V559D) were more likely to be seen in patients with localized GISTs (odds ratio 7.9, 3.1, 2.7 and 2.5, respectively), while KIT exon 9 502_503dup and KIT exon 11 557_559del were more frequent in metastatic GISTs (odds ratio of 0.3 and 0.5, respectively). These data suggest that KIT and PDGFRA mutations and standardized mitotic count deserve to be investigated to evaluate the relapse risk of GISTs.

[Pathology: on the way to molecular analysis]. / Anatomie pathologique: en marche vers l'analyse moléculaire.

For a long time, pathology has been playing an important role in digestive diseases, especially in digestive cancers. This contribution was based and is still based on classical morphological techniques: staining of cells and tissues and recognition of diagnostic morphological patterns characteristic for a disease. Pathology is changing, and accompanies major improvements in endoscopy and imaging of gastrointestinal diseases, and new high throughput biological techniques. Recent examples show that molecular pathology (including immunohistochemistry), often included in wider "biopathology" processes, participates to pathophysiological research (for example recognition of the serrated pathway in colorectal carcinogenesis and its relation with microsatellite instability and methylation of promoters), and to diagnostic and therapeutic procedures (for example targeted therapies of gastrointestinal stromal tumours). However, the current example of the recognition of predictive factors of response to anti-EGFR treatments in colorectal cancer shows that morphological and non morphological techniques have to find their respective role in this kind of process.

[Cholesterol crystal emboli presenting as a mononeuropathy]. / Maladie des embolies de cristaux de cholestérol révélée par un tableau de mononeuropathie.

Cholesterol crystal embolism is observed in polyvascular patients usually following a medical procedure. We report a 93-year-old patient with lower limb mononeuropathy in whom cholesterol crystal embolism was confirmed by neuromuscular biopsy. Previously, an ophthalmoscopy and a livedo biopsy had been performed and the results were normal. Mononeuropathy simplex or multiplex is a clinical expression for cholesterol crystal embolism that may thus be confounded with polyarteritis nodosa. Neuromuscular biopsy can provide accurate diagnosis if other investigations are inconclusive.

Corrección quirúrgica del puente epifi sario longitudinal en metatarsianos y falanges del pie / No disponble

El puente epifi sario longitudinal es un trastorno congénito infrecuentede la osifi cación encondral que afecta a pacientes esqueléticamenteinmaduros. Se presenta la revisión retrospectiva de los resultados deltratamiento quirúrgico en 4 pacientes (6 pies) entre los años 1999-2004. El puente epifi sario longitudinal, se localizó de forma bilateralen las falanges proximales del primer dedo del pie en 2 pacientes (4pies) y unilateralmente en los primeros metatarsianos de 2 pacientes(2 pies). El objetivo fue analizar los resultados obtenidos en nuestrocentro tras el tratamiento quirúrgico de esta patología. La técnicaquirúrgica, consistió en resección de la región central del puente deforma aislada en 1 caso y resección central de la lesión asociada aosteotomía en cuña de adición correctora de la deformidad angular ydel acortamiento óseo en los 5 casos restantes. El seguimiento mediofue de 6 años (4-8 años). Los resultados se valoraron en función dela mejoría postoperatoria de la desviación angular en varo del primerdedo y el aumento postoperatorio del crecimiento longitudinal delhueso. Todos los pacientes presentaron una evolución satisfactoria yno se registraron compliciones secundarias a la cirugía realizada. Eltratamiento del puente epifi sario longitudinal es siempre quirúrgico yla técnica ha de individualizarse para cada paciente(AU)

The longitudinal epiphyseal bracket is a rare ossifi cation defect in immaturepatients. We report our results in the surgical treatment of 4 patients(6 feet) from 1999 to 2004. The longitudinal epiphyseal bracket wasbilateral in the proximal phalanx of the toe in 2 patients (4 feet) andunilateral in the fi rst metatarsal in 2 patients (2 feet).The aim was toconsider the results of surgical treatment for this deformity. The surgicaltechnique consisted of excision of the central area of the longitudinalepiphyseal bracket in one case and central physiolysis associated withcorrective addition osteotomy of angular and shortening deformity in theother 5 cases. The average follow-up was 6 years (range 4-8 years).The results were assessed considering correction of angular deviationof the toe and increase in longitudinal bone growth. All patients presentsatisfactory evolution with no complications of surgical treatmentreported. Surgical treatment is always indicated in such cases, and theapproach should be individualized(AU)

Peripheral insertion of double-lumen central venous catheter using the Seldinger technique in newborns.

OBJECTIVE: To report the experience of peripheral insertion of double-lumen central catheters (PIDLCC) in preterm and term newborn infants and to analyze the technical characteristics of the procedure and any observed complications. STUDY DESIGN: Retrospective review of 61 newborns that had a PIDLCC between 2003 and 2006. The study comprised clinical data analysis, anthropometrics, indications, duration, complications and reasons for withdrawal of the catheters. RESULT: Weight of the patients was <1 kg in 10%, and >2 kg in 75%. Catheters tip placement was as aimed, mostly superior cava vein (SCV), in 65.5%, and subclavian vein in remaining 34.5% and average duration of catheterization was 13.5+/-9.6 and 8.9+/-5.8 days, respectively. Blood sampling through both lumens was possible especially when the tip was at SCV. Reasons for catheter withdrawal were end of indication (45.9%), phlebitis/edema (21.3%), suspected infection (3.2%), accidental withdrawal (3.2%) and rupture of proximal end (3.2%). In three (4.9%) patients, withdrawal was due to serious complications (two cases of pleural leakage of infusion fluid and one breakage of the metallic guide). About 16.3% of the patients died with the catheter still in situ. Infection findings were positive tip culture (14.7%) and catheter-related sepsis (3.2%). CONCLUSION: Insertion of PIDLCC is possible in neonates. The incidence of complications, mostly mechanical, requires careful evaluation of indications, and strict adherence to the procedure of insertion and manipulation.

[Schwannoma of the duodenojejunal angle]. / Schwannome kystique de l'angle duodénojéjunal.

Neurogenic tumors of the small intestine are extremely rare. Although schwannoma is often clinically indolent for many years, complications such as gut compression or bleeding might occur. In these cases, surgical management is required. We reported a case of asymptomatic schwannoma of the duodenojejunal angle. Surgical treatment was performed to provide definitive immunohistochemistry diagnosis and to prevent complications.

Catéteres centrales en pediatría / Central catheters in pediatrics

Se estudian las indicaciones de la colocación de catéteres centrales en pediatría. Se describen las téncicas de colocación y retirada de los catéteres umbilicales en el neonato por vía venosa y arterial. Se detalla la canalización percutánea venosa central y la técnica de Seldinger para accesos vasculares centrales

The indications for placement of central catheters in pediatrics are studied. Venous and arterial placement and removal techniques of the umbilical catheters in the newborn are described. Central venous percutaneous canalization and the Seldinger technique for central vascular accesses are detailed

[Effect of hygiene interventions on the thermal stability of extremely low-birth-weight newborns in the first two weeks of life]. / Repercusión del aseo en la estabilidad térmica del recién nacido de extremado bajo peso durante las primeras dos semanas de vida.

INTRODUCTION: A prospective study was performed of a cohort of extremely low-birth-weight (ELBW) premature neonates (birth weight 500 to 1,000 g) consecutively admitted to the neonatal intensive care unit. The aim of this study was to examine the thermal changes that occur during all the hygiene-related interventions in ELBW infants in the first 2 weeks of life. PATIENTS AND METHODS: The study was carried out for 10 consecutive months in the Neonatology Service of La Paz University Hospital. We studied all consecutively admitted ELBW infants who satisfied the following criteria: a) adequate weight for gestational age; b) survival for at least 1 week, and c) no major congenital malformations or dysmorphic features. The infants included in the study were managed according to a standard care protocol for maintaining thermal stability and preventing cold-induced stress. Central temperature (Tc) was measured in the axilla and peripheral temperature (Tp) was measured on the sole of the foot. Both temperatures were continuously monitored for a) a period of scheduled non-handling--baseline period--and b) during and after a series of "hygiene interventions". In each of these periods, Tc and Tp were continuously monitored and recorded at 10 min intervals for the first 30 minutes and then at 30 min intervals until completing a 180 min period. RESULTS: Although incubator temperature was raised by a mean of 3 degrees C during hygiene interventions, hygiene was accompanied by a change in body temperature that remained fairly constant throughout the study period; Tc and Tp decreased by a mean of 1 degrees C with respect to baseline temperature. A fall in axillary temperature to less than 36.5 degrees C was observed in 87.4 % of recordings and a fall to less than 36 degrees C was observed in 45.5 %; axillary temperature remained below 36.5 degrees C for a mean duration of almost 1 hour. The differential temperature (Td 5 Tc - Tp), an indicator of thermal stress, was more than 1 degrees C for a mean duration of more than 80 min and > 2 degrees C for more than 20 minutes in both the first and second weeks of life. CONCLUSIONS: During hygiene interventions, ELBW infants experienced a sharp fall in central and peripheral body temperature. After hygiene interventions, these neonates had a Td suggestive of prolonged thermal stress, despite the use of standardized care protocols designed to avoid or minimize the potential effects of hygiene interventions on neonatal temperature.

Repercusión del aseo en la estabilidad térmica del recién nacido de extremado bajo peso durante las primeras dos semanas de vida / Effect of hygiene interventions on the thermal stability of extremely low-birth-weight newborns in the first two weeks of life

El objetivo del estudio fue examinar los cambios térmicos que tienen lugar durante un conjunto de acciones agrupadas en relación con el aseo corporal en los RNEBP durante las primeras 2 semanas de vida. Pacientes y métodos. El estudio se realizó durante 10 meses consecutivos en el Servicio de Neonatología del Hospital Universitario La Paz. Se estudiaron todos los RNEBP ingresados consecutivamente que cumplieron los siguientes criterios: a) peso adecuado a la edad gestacional; b) sobrevivir al menos una semana, y c) no presentar malformaciones congénitas mayores o rasgos dismórficos. Los niños incluidos en el estudio fueron manejados según los protocolos de cuidado estándar dirigidos a mantener la estabilidad térmica y evitar el estrés por frío. La temperatura central (Tc) se midió en el hueco axilar y la periférica (Tp) en la planta de un pie. Ambas temperaturas se monitorizaron de forma continua durante: a) un período de no manipulación programada (período basal), y b) durante y después de un conjunto de intervenciones agrupadas que denominamos "aseo". Durante ambos períodos se monitorizaron de forma continua la Tc y la Tp, registrándose a intervalos de 10 min durante los primeros 30 min y posteriormente cada 30 min hasta completar un período de registro de 180 min. Resultados. A pesar que durante el aseo la temperatura de la incubadora se incrementó casi 3 °C por término medio, el aseo conllevó un patrón de cambio en la temperatura corporal similar durante todo el período de estudio; la Tc y la Tp descendieron aproximadamente 1 °C por término medio respecto a la temperatura basal. Se observó una caída de la temperatura axilar por debajo de 36,5 °C en el 87,4 % de los registros y por debajo de 36 °C en el 45,5 % y la temperatura axilar permaneció inferior a 36,5 °C durante prácticamente una hora por término medio. Además, la temperatura diferencial (Td 5 Tc ­ Tp), un indicador de estrés térmico, fue superior a 1 °C durante más de 80 min y a 2 °C durante más de 20 min por término medio, tanto en la primera como en la segunda semana de vida. Conclusiones. Durante el aseo de los RNEBP tiene lugar un marcado descenso de la temperatura corporal, tanto central como periférica. Tras el aseo, estos recién nacidos presentan una Td indicativa de estrés térmico, durante períodos prolongados. Estos cambios térmicos tienen lugar aun siguiendo protocolos de aseo estandarizados dirigidos a evitar o aminorar la potencial repercusión de este en la temperatura del recién nacido

Introduction. A prospective study was performed of a cohort of extremely low-birth-weight (ELBW) premature neonates (birth weight 500 to 1,000 g) consecutively admitted to the neonatal intensive care unit. The aim of this study was to examine the thermal changes that occur during all the hygiene-related interventions in ELBW infants in the first 2 weeks of life. Patients and methods. The study was carried out for 10 consecutive months in the Neonatology Service of La Paz University Hospital. We studied all consecutively admitted ELBW infants who satisfied the following criteria: a) adequate weight for gestational age; b) survival for at least 1 week, and c) no major congenital malformations or dysmorphic features. The infants included in the study were managed according to a standard care protocol for maintaining thermal stability and preventing cold-induced stress. Central temperature (Tc) was measured in the axilla and peripheral temperature (Tp) was measured on the sole of the foot. Both temperatures were continuously monitored for a) a period of scheduled non-handling ­baseline period­ and b) during and after a series of "hygiene interventions". In each of these periods, Tc and Tp were continuously monitored and recorded at 10 min intervals for the first 30 minutes and then at 30 min intervals until completing a 180 min period. Results. Although incubator temperature was raised by a mean of 3 °C during hygiene interventions, hygiene was accompanied by a change in body temperature that remained fairly constant throughout the study period; Tc and Tp decreased by a mean of 1 °C with respect to baseline temperature. A fall in axillary temperature to less than 36.5 °C was observed in 87.4 % of recordings and a fall to less than 36 °C was observed in 45.5 %; axillary temperature remained below 36.5 °C for a mean duration of almost 1 hour. The differential temperature (Td 5 Tc ­ Tp), an indicator of thermal stress, was more than 1 °C for a mean duration of more than 80 min and > 2 °C for more than 20 minutes in both the first and second weeks of life. Conclusions. During hygiene interventions, ELBW infants experienced a sharp fall in central and peripheral body temperature. After hygiene interventions, these neonates had a Td suggestive of prolonged thermal stress, despite the use of standardized care protocols designed to avoid or minimize the potential effects of hygiene interventions on neonatal temperature

Perfil de las competencias profesionales del diplomado en nutrición humana y dietética / Profile of profesional skills and abilities of the graduate in nutrition and dietetics

No disponible

Comparison of somatostatin receptor expression in human gliomas and medulloblastomas.

The expression of the five somatostatin receptor subtypes, sst1-5 was compared on tissue containing glial tumours (glioblastomas or oligodendrogliomas), medulloblastomas, and on normal human cortex. By semiquantitative reverse transcription coupled to polymerase chain reaction, the receptor expression profiles were high in cortex and in tissue containing oligodendrogliomas. It was moderate in medulloblastomas. Tissue containing glioblastomas displayed lower expression of somatostatin receptor subtypes, sst1 and sst3 being mostly expressed. By 125I-Tyr0DTrp8 somatostatin-14 or 125I-Leu8DTrp22 Tyr25 somatostatin-28 autoradiography combined with synaptophysin immunohistochemistry, it was possible to differentiate between isolated tumoral cell component infiltrating the cerebral parenchyma (cortex or white matter) and tumoral tissue (without residual parenchyma) in glioblastomas or oligodendrogliomas. Glial tumoral tissue per se presented few somatostatin receptors. By contrast, medulloblastoma tumoral cells exhibited numerous octreotide sensitive somatostatin receptors. sst2 immunocytochemistry demonstrated immunostaining of neuronal cells and neuropile; sst2 and sst3 immunostaining was identified on glioblastoma proliferating vessels endothelial cells and on medulloblastomas tumoral cells. Faint sst2 immunostaining among glial tumoral cells was due to microglia, while glioma cells did not significantly stain. In summary, medulloblastoma tumoral cells express sst2/sst3 receptors at a high level while glioma cells do not. In gliomas, sst expression is restricted to endothelial cells on proliferating vessels (displaying both sst2 and sst3 receptors), including parenchyma and reactive microglia (only sst2). The differential expression of sst2/sst3 receptors on gliomas and medulloblastomas has implications for the therapy of these tumours.