Evolution of children diagnosed with attention deficit/hyperactivity disorder. Follow-up study in a Spanish simple.

BACKGROUND: Attention deficit/hyperactivity disorder (ADHD) is a chronic condition with long-term associated risks. OBJECTIVE: To analyze the clinical status, occupation, and daily life difficulties of two cohorts of children diagnosed with ADHD (2004 and 2009) after five and 10 years. MATERIAL AND METHOD: Descriptive, longitudinal study using the WOMI database corresponding to Oviedo, Asturias, Spain. Children with ADHD detected by their primary care pediatrician were included. A voluntary follow-up telephone interview was requested. Outcome variables were current clinical and occupational status, ADHD symptoms according to SNAP-IV, and Strengths and Difficulties Questionnaire (SDQ). RESULTS: The interviewed sample consisted of 95 subjects, out of whom 71 answered the SNAP-IV and SDQ questionnaires; 60.70% of the sample did not receive treatment at the time of follow-up, 4.7% had no occupation, 25.40% still had ADHD global symptoms above the clinical cutoff point, and 66.2% had difficulties with moderate interference. CONCLUSIONS: ADHD symptoms decline as people grow up. Mental health comorbidities and academic dropout were not confirmed in the sample.

ANTECEDENTES: El trastorno de déficit de atención e hiperactividad (TDAH) constituye una condición crónica con riesgos asociados a largo plazo. OBJETIVO: Analizar el estado clínico, la ocupación y las dificultades de la vida diaria de dos cohortes de niños con diagnóstico de TDAH (2004 y 2009) después cinco y 10 años. MATERIAL Y MÉTODO: Estudio descriptivo y longitudinal de la base de datos WOMI correspondiente a Oviedo, Asturias, España. Se incluyeron niños detectados con TDAH por su pediatra de atención primaria. Se solicitó una entrevista telefónica voluntaria de seguimiento. Las variables de resultado fueron estado clínico y ocupacional al momento de la entrevista, síntomas de TDAH según SNAP-IV y Cuestionario de Fortalezas y Dificultades (SDQ). RESULTADOS: La muestra entrevistada estuvo formada por 95 sujetos, de los cuales 71 respondieron a los cuestionarios SNAP-IV y SDQ; 60.7 % de la muestra no recibía tratamiento en el momento del seguimiento, 4.7 % no tenía ninguna ocupación, 25.4 % mantenía síntomas globales de TDAH en nivel superior al punto de corte clínico y 66.2 % presentaba dificultades con interferencia moderada. CONCLUSIONES: Los síntomas del TDAH disminuyen conforme las personas crecen. Las comorbilidades de salud mental y el abandono académico no se confirmaron en la muestra.

Evolución de menores diagnosticados con trastorno de déficit de atención e hiperactividad. Estudio de seguimiento en una muestra española / Evolution of children diagnosed with attention deficit/hyperactivity disorder. Follow-up study in a Spanish sample

Resumen Antecedentes: El trastorno de déficit de atención e hiperactividad (TDAH) constituye una condición crónica con riesgos asociados a largo plazo. Objetivo: Analizar el estado clínico, la ocupación y las dificultades de la vida diaria de dos cohortes de niños con diagnóstico de TDAH (2004 y 2009) después cinco y 10 años. Material y método: Estudio descriptivo y longitudinal de la base de datos WOMI correspondiente a Oviedo, Asturias, España. Se incluyeron niños detectados con TDAH por su pediatra de atención primaria. Se solicitó una entrevista telefónica voluntaria de seguimiento. Las variables de resultado fueron estado clínico y ocupacional al momento de la entrevista, síntomas de TDAH según SNAP-IV y Cuestionario de Fortalezas y Dificultades (SDQ). Resultados: La muestra entrevistada estuvo formada por 95 sujetos, de los cuales 71 respondieron a los cuestionarios SNAP-IV y SDQ; 60.7 % de la muestra no recibía tratamiento en el momento del seguimiento, 4.7 % no tenía ninguna ocupación, 25.4 % mantenía síntomas globales de TDAH en nivel superior al punto de corte clínico y 66.2 % presentaba dificultades con interferencia moderada. Conclusiones: Los síntomas del TDAH disminuyen conforme las personas crecen. Las comorbilidades de salud mental y el abandono académico no se confirmaron en la muestra.

Abstract Background: Attention deficit/hyperactivity disorder (ADHD) is a chronic condition with long-term associated risks. Objective: To analyze the clinical status, occupation, and daily life difficulties of two cohorts of children diagnosed with ADHD (2004 and 2009) after five and 10 years. Material and method: Descriptive, longitudinal study using the WOMI database corresponding to Oviedo, Asturias, Spain. Children with ADHD detected by their primary care pediatrician were included. A voluntary follow-up telephone interview was requested. Outcome variables were current clinical and occupational status, ADHD symptoms according to SNAP-IV, and Strengths and Difficulties Questionnaire (SDQ). Results: The interviewed sample consisted of 95 subjects, out of whom 71 answered the SNAP-IV and SDQ questionnaires; 60.70% of the sample did not receive treatment at the time of follow-up, 4.7% had no occupation, 25.40% still had ADHD global symptoms above the clinical cutoff point, and 66.2% had difficulties with moderate interference. Conclusions: ADHD symptoms decline as people grow up. Mental health comorbidities and academic dropout were not confirmed in the sample.

International on-line questionnaire about severe lower gastrointestinal bleeding management: Do we have it clear? / Encuesta internacional on-line sobre el manejo de la hemorragia digestiva baja grave. ¿Lo tenemos claro?

BACKGROUND AND AIMS: The diagnostic and therapeutic strategy in severe lower gastrointestinal bleeding (LGIB) varies depending on the patient's clinical situation. Actual clinical practice guidelines propose different management strategies. We aim to know the attitude of the gastroenterologists from different hospitalary centers in the management of this entity. METHODS: Descriptive and observational study using an on-line questionnaire, addressed to gastroenterologists in Spain and Latin America, in December 2021. RESULTS: We included 281 anonymous questionnaires of gastroenterologists from Spain and Latin America. Diagnostic and therapeutic management of severe LGIB was heterogeneous among the participants. Regarding to the first diagnostic modalities they showed variability between performing computed tomography angiography (CTA) (44.5%), gastroscopy (33.1%), colonoscopy (20.6%) and arteriography (1.1%). The therapeutic attitude after a positive CTA mostly varied between performing arteriography (38.1%) and colonoscopy (44.1%). If negative CTA, in the majority of cases a gastroscopy was performed. If the patient needed intensive critical unit (ICU) care and to undergo colonoscopy, most participants performed an urgent colonoscopy (<24h) (31% always, 43.4% in most cases); while if the patient did not require ICU admission this percentage was lower (10% always, 33.8% in most cases). The 40.9% of the participants admitted having doubts about the management of this patients and the 98.2% considered the need for a creation of an action protocol. CONCLUSIONS: There is a high interhospitalary variability on the management of severe lower gastrointestinal bleeding among gastroenterologists. It is necessary to unify the diagnostic and therapeutic management of this pathology.

Assessing ADHD symptoms in clinical public practice: Is a reliable final diagnosis possible?

INTRODUCTION: Attention deficit and hyperactivity disorder (ADHD) rates vary between 1% and 20% depending on the type of diagnosis guide used, the test used in the assessment, psychosocial factors, and professional in charge of the assessment. GOAL: to describe and compare current clinical ADHD assessment processes in public health system in two cohorts and analyze variables related to final diagnosis. DESIGN: Descriptive, multicenter, longitudinal (retrospective-prospective). LOCATION: primary care (PC) centers in Oviedo, Asturias (Spain). PARTICIPANTS: a Spanish clinical ADHD symptomatic sample (n=134) from two cohorts (2004 and 2009). VARIABLES: clinical professional in charge of ADHD assessment (PC, mental health professional [MH], neuropediatrician [NP]), type of test used in the assessment, confirmation/disconfirmation of ADHD diagnosis, and final diagnosis. RESULTS: the use of symptoms checklists and the assessments in charge of primary care (PC) and neuropediatrician (NP) professionals show an upward trend from 2004 to 2009. ADHD final diagnosis shows low inter-professional (NP-MH) reliability (kappa=0.39). Final diagnoses for the same symptoms are different depending on the professional (NP or MH). DISCUSSIONS: the professional in charge of the assessment appears to be a relevant variable for the final diagnosis. ADHD diagnosis criteria seem not to be clear. This data suggests that ADHD diagnosis must be used with caution to ensure good quality clinical standards when assessing and treating ADHD symptoms. Assessments supported by symptoms checklists and performed by NP or PC could be contributing factors to an ADHD over-diagnosis tendency.

[Updated report on STOPP-START criteria in Primary Care]. / Evaluación de la actualización de los criterios STOPP-START en atención primaria.

INTRODUCTION: The aim of this study is to determine the rate of potentially inappropriate prescriptions (PIP) in people older than 64 years of age in Avilés, Asturias, Spain. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted in six Health Care Centres. A sample of 400 people was selected, obtained by a random sampling proportional to the population registered in each Health Centre. A review was made of the computerised clinical records, and the STOPP-START (version 2014 with 114 items) criteria were applied to evaluate the PIP. RESULTS: The study contained 378 (95.5%) patients with a mean age of 75.4 (SD: 7.4) and of which 57.7% were women. Almost all (94.2%: 95% CI; 91.7-96.7) met some PIP criteria. Taking only the STOPP criteria into consideration, 52.4% (95%CI: 47.2-57.6) met at least one breach, and in the START criteria a 90.5% (95%CI; 87.4-93.6), which was reduced to 40.5% (95%CI; 36.4-45.6) if criteria on vaccination were removed. In the STOPP criteria, the most frequent PIP was taking benzodiazepines followed by the use of medication without indications based on the evidence; in the START, the criteria was the anti-pneumococcus vaccination, and the lack of taking vitamin D supplements and calcium in osteoporosis. CONCLUSIONS: There were high levels of PIP, very superior to the previous version, especially for the START criteria. There is a high level of PIP related to the use of benzodiazepines and the use of medication without any clinic evidence. The STOPP-START criteria are useful in Primary Care to assess the PIP.

Expression and Prognostic Value of Oestrogen Receptor Beta in Colorectal Cancer.

Differences between men and women in the incidence and biological mechanisms of colorectal cancer (CRC) suggest that estrogens may play a role in the pathogenesis of this disease. The identification of the human estrogen receptor beta (ERß) and its expression in the intestinal mucosa led to further studies that revealed that estrogens have a protective function against CRC mediated by the activation of ERß. However, ERß expression and its role in CRC is controversial. The purpose of this study was to determine the distribution and prognostic value of ERß expression in the intestinal mucosa of patients diagnosed and surgically treated for CRC, and its association with other known prognostic factors. A total of 109 paraffin-embedded samples of the wild-type ERß isoform were analyzed by immunohistochemical nuclear staining in patients with colorectal adenocarcinoma. Clinical/pathological and survival data were collected. Immunohistochemical quantification was performed using the category scoring system, which has been validated for assessing estrogen receptor alfa. The wild-type ERß isoform -also called ERß1- was positive in 101 patients (92.7%) and negative in nine patients (7.3%). Univariate analysis revealed that the absence of expression of the ERß1 gene was correlated with mucinous adenocarcinoma (p < 0.05). Also, a non-significant tendency was observed for ERß expression to be down-regulated in advanced tumors. With a median follow-up of 47 months, the overall survival and progression-free survival were not found to be associated with ERß1 expression (p = 0.2). Although the wild-type ERß isoform was expressed in most study patients with colorectal cancer, it does not seem to have any prognostic value for the course of the disease. Further studies should be conducted to investigate whether the down-regulation of ERß expression has any biological function in mucinous colorectal cancer.

[Rates of surgical wound infection in hip arthroplasty (2007-2015)]. / Tasas de infección de herida quirúrgica en artroplastia de cadera (2007-2015).

OBJECTIVE: To estimate the incidence of surgical site infection in the hip replacement procedure during nine years of follow-up in a local public hospital. MATERIAL AND METHODS: A prospective study conducted between 2007 and 2015, using the Clinical Indicators of Continuous Quality Improvement (INCLIMECC) tool. All primary hip prostheses and revisions were studied. The definitions, criteria and categories for surgical site infection were those estimated for the risk index of the National Nosocomial Infections Surveillance of Centres for Disease Control and Prevention. Crude and adjusted rates were calculated by risk index. RESULTS: A total of 999 interventions were included. The overall infection rate was 1.5% (95%CI: 0.75-2.25). Surgical prophylaxis was prescribed in 98.3% of the cases, and was adequate in 70.7%, with the main cause of inadequacy being its prolonged duration in 71.3%. The infection rate was 53%, being better than the rates published for Spanish hospitals INCLIMECC in the period 1997-2012. But they were 19% higher than those published for the USA according to the National Healthcare Safety Network, and 50% higher than expected according to data published for Europe by the European Centre for Disease Prevention and Control. DISCUSSION: The infection rate in the present study is better than those described in the Spanish literature, but it is higher than those published for Europe and North America. Strategies for surveillance and control of infections associated with health care allow the evaluation of trends and the impact of prevention measures.

Treatment patterns of adjuvant interferon-α2b for high-risk melanoma: a retrospective study of the Grupo Español Multidisciplinar de Melanoma - Prima study.

Adjuvant interferon-α2b (IFN-α2b) has been studied extensively in clinical trials, but there have been few studies of real-world use. The aim of this study is to describe the IFN-α2b real-world patterns in patients with high-risk melanoma in Spain. This was a retrospective and multicentre chart review study of an unselected cohort of patients with melanoma at high risk for relapse (stage IIB/IIC/III) treated with IFN-α2b. Patterns were assessed in terms of dose and compliance to planned treatment. A survival analysis was carried out for the full population and according to Kirkwood scheme compliance and the presence of ulceration. Of 327 patients treated with IFN-α2b, 318 received a high-dose regimen following the standard Kirkwood scheme; thus, patterns are described for this regimen. A total of 121 (38%) and 88 (28%) patients had at least one dose reduction during the induction and maintenance phases, respectively. Dose delay was required in fewer than 10% of patients. A total of 78, 40 and 38% of the patients completed the induction phase, maintenance phase and completed treatment, respectively. The median progression-free and overall survival for the full population were 3.2 and 10.5 years, respectively. There were no differences in progression-free survival and overall survival according to Kirkwood scheme compliance and the presence of ulceration. The most frequent adverse events were neutropenia (31%) and fatigue (30%). High-dose IFN-α2b is the most frequently used regimen in Spain as an adjuvant systemic treatment for high-risk melanoma. Despite poor compliance, in this retrospective study, IFN-α2b treatment provided a benefit consistent with that described previously.

[Effect of the economic crisis on consumption of psychotropic drugs in Asturias (Spain)]. / Efecto de la crisis económica sobre el consumo de psicofármacos en Asturias.

OBJECTIVE: To assess whether the economic crisis of 2008 has changed the consumption of anxiolytics, hypnotics-sedatives and antidepressants in Asturias (Spain). METHOD: We conducted a descriptive study of drug use from 2003 -2013. The defined daily doses of 1000 inhabitants per day (DHD) were calculated for anxiolytics, hypnotics-sedatives and antidepressants. Linear regression coefficients (b) of the DHD were obtained for the pre-crisis period (2003-2008) and the crisis period (2009-2013). RESULTS: The consumption of anxiolytics increased by 40.25%, that of hypnotics by 88.11% and that of antidepressants by 80.93%. For anxiolytics: b-(2003-2008)=4.38 DDI/year and b-(2009-2013)=1.08 DDI/year. For hypnotics-sedatives: b-(2003-2008)=2.30 DDI/year and b-(2009-2013)=0.40 DDI/year. For antidepressants: b-(2003-2008)=5.79 DDI/year and b-(2009-2013)=2.83 DDI/year. CONCLUSIONS: The rise in consumption of the three subgroups during the crisis period was lower than that of the pre-crisis period. This study does not confirm the influence of the economic crisis on the rise in consumption of these drugs.

[Potentially inappropriate prescription according to the "STOPP" Criteria in heavily polymedicated elderly patients]. / Prescripción potencialmente inadecuada en pacientes mayores grandes polimedicados según criterios "STOPP".

INTRODUCTION: Appropriate prescribing is especially relevant in elderly people. The objective of this study is to analyse the potentially inappropriate prescription (PIP) in heavily polymedicated elderly patients according to the criteria Screening Tool of Older Person's Prescriptions. PATIENTS AND METHODS: A descriptive cross-sectional study was conducted in Primary Care on patients assigned to the Siero-Sariego (Asturias) Health Centre, who were over 64 years old and heavily polymedicated (consumption >10 drugs for six months). The 65 Screening Tool of Older Person's Prescriptions criteria were reviewed in the electronic Primary Care patient records, collecting sociodemographic variables, prescribed medications, and chronic diseases. Frequency distributions were made for each criterion, and causes related to PIP were explored using contingency tables, the Spearman correlation coefficient, and logistic regression. RESULTS: A total of 349 polymedicated elderly patients were analysed with a prevalence of 6.4 (95% CI:5.76-7.08), a mean age of 79.2 years (SD:3.7), 62.2% were female, 14% institutionalised, a Charlson index of 2.9. The mean of number of drugs was 11.5 (SD:1.7), and the most frequent pathologies were high blood pressure (64%), diabetes (46%), and osteoarticular diseases (41%). There was at least one PIP in 72.9% of heavily polymedicated elderly patients [(Mean: 1.32 (SD:1.2)]. The Screening Tool of Older Person's Prescriptions criteria least complied with were: therapeutic duplication (25.2%), use of long-acting benzodiazepines (15.8%), and inappropriate use of aspirin (10.9%). An association was found between having any inappropriate prescription and the number of medications prescribed (OR=1.22 [95% CI:1.04-1.43]) and inversely to the Charlson index (OR=0.76 [95% CI:0.65-0.89]). CONCLUSIONS: PIP is common in heavily polymedicated elderly patients. Special attention must be paid to the use of psychotropic drugs, which are implicated in a high volume of PIP.

[Results of provisional use of a system for voluntary anonymous reporting of incidents that threaten patient safety in the emergency medical services of Asturias]. / Resultados de la instauración provisional de un sistema voluntario y anónimo de notificación de incidentes en seguridad del paciente en el SAMU de Asturias.

OBJECTIVES: To describe the reported incidents and adverse events in the emergency medical services of Asturias, Spain, and assess their consequences, delays caused, and preventability. MATERIAL AND METHODS: Prospective, observational study of incidents reported by the staff of the emergency medical services of Asturias after implementation of a system devised by the researchers. RESULTS: Incident reports were received for 0.48% (95% CI, 0.41%-0.54%) of the emergencies attended. Patient safety was compromised in 74.7% of the reported incidents. Problems arising in the emergency response coordination center (ERCC) accounted for 37.6% of the incidents, transport problems for 13.4%, vehicular problems for 10.8%, and communication problems for 8.8%. Seventy percent of the reported incidents caused delays in care; 55% of the reported incidents that put patients at risk (according to severity assessment code ratings) corresponded to problems related to human or material resources. A total of 88.1% of the incidents reported were considered avoidable. Some type of intervention was required to attenuate the effects of 46.2% of the adverse events reported. The measures that staff members most often proposed to prevent adverse events were to increase human and material resources (28.3%), establish protocols (14.5%), and comply with quality of care recommendations (9.7%). CONCLUSION: It is important to promote a culture of safety and incident reporting among health care staff in Asturias given the number of serious adverse events. Reporting is necessary for understanding the errors made and taking steps to prevent them. The ERCC is the point in the system where incidents are particularly likely to appear and be noticed and reported.

OBJETIVO: Conocer los incidentes y eventos adversos (EA) que se notificaron en el Servicio de Atención Médica Urgente (SAMU) de Asturias y caracterizarlos, evaluando sus consecuencias, el retraso asistencial provocado y su evitabilidad. METODO: Estudio observacional y prospectivo en el que se analizaron las notificaciones realizadas por los profesionales sanitarios del SAMU Asturias, en un sistema de notificación diseñado por los investigadores. RESULTADOS: Se obtuvo una tasa de notificación de 0,5% (IC 95%: 0,41-0,54). Un 74,7% supusieron daño al paciente. El 37,6% de los problemas estuvo relacionado con el centro coordinador de urgencias (CCU), 13,4% con el transporte, 10,8% con el vehículo y 8,8% con problemas de comunicación. Un 70% de los sucesos adversos (SA) notificados conllevó un retraso en la asistencia sanitaria. Un 55% de las notificaciones del CCU en las que hubo riesgo SAC (Severity Assessment Code) correspondió a problemas de recursos humanos y materiales. Los notificantes consideraron que un 88,1% eran evitables. Un 46,2% de los EA precisaron algún tipo de intervención para paliar sus efectos. Las medidas más propuestas por los profesionales para evitar los EA fueron aumento de recursos humanos y materiales (28,3%), elaboración de protocolos (14,5%) y cumplimiento de criterios de calidad (9,7%). CONCLUSIONES: Fomentar la cultura de seguridad y la notificación de los profesionales sanitarios es de especial importancia en nuestro medio, por el número de EA graves, para así conocer los errores y establecer medidas para evitarlos. Los CCU son lugares sensibles para la aparición, detección y notificación de Incidentes.

Characterization of the autoimmune response against the nerve tissue S100ß in patients with type 1 diabetes.

Type 1 diabetes results from destruction of insulin-producing beta cells in pancreatic islets and is characterized by islet cell autoimmunity. Autoreactivity against non-beta cell-specific antigens has also been reported, including targeting of the calcium-binding protein S100ß. In preclinical models, reactivity of this type is a key component of the early development of insulitis. To examine the nature of this response in type 1 diabetes, we identified naturally processed and presented peptide epitopes derived from S100ß, determined their affinity for the human leucocyte antigen (HLA)-DRB1*04:01 molecule and studied T cell responses in patients, together with healthy donors. We found that S100ß reactivity, characterized by interferon (IFN)-γ secretion, is a characteristic of type 1 diabetes of varying duration. Our results confirm S100ß as a target of the cellular autoimmune response in type 1 diabetes with the identification of new peptide epitopes targeted during the development of the disease, and support the preclinical findings that autoreactivity against non-beta cell-specific autoantigens may have a role in type 1 diabetes pathogenesis.

Ipilimumab for advanced melanoma: experience from the Spanish Expanded Access Program.

Ipilimumab, a fully human, recombinant, monoclonal antibody to cytotoxic T-lymphocyte antigen 4 improves overall survival (OS) in previously treated and untreated metastatic melanoma. This retrospective analysis reports data gathered by a questionnaire on the demographics, outcomes, and toxicity of ipilimumab administered through an Expanded Access Program (EAP). Ipilimumab 3 mg/kg was administered intravenously every 3 weeks for four cycles to adults with metastatic melanoma. Efficacy outcomes included complete response, partial response (PR), progressive disease, stabilized disease, and OS. EAP data were collected from EAP physicians. A subgroup analysis examined efficacy in elderly patients (≥70 years) and factors predictive of survival were identified. Of 355 requests for ipilimumab, resulting in 288 treatments, completed questionnaires were received for 153 ipilimumab recipients (median age 58 years, 57.2% men). Efficacy was evaluated in 144 patients: complete response in 1.3%, PR in 9.6%, PR with previous progression 8.4%, stabilized disease in 14.5%, and progressive disease in 66.2%. The median OS was 6.5 months (199 days); 1-year survival was 32.9%. Predictive survival factors included lymphocytes over 1000/ml (P=0.0008) and lactate dehydrogenase more than 1.5×upper limit of normal (P=0.003). Cutaneous, hepatic, and gastrointestinal toxicities were mild. In 30 patients aged more than 70 years, ipilimumab efficacy and tolerability was similar to that of the overall population. In the clinical practice setting, ipilimumab is effective and well tolerated in patients with advanced melanoma, including elderly patients, when administered at the recommended dosage. Ipilimumab improves treatment options for patients who, until recently, have had little hope of an improved prognosis.

Gonadotropin and steroid receptors as prognostic factors in advanced ovarian cancer: a retrospective study.

INTRODUCTION: Ovarian cancer is a chemosensitive tumour, but two thirds of women have a recurrence during the follow- up, even after an optimal surgical debulking followed by chemotherapy with a platinum and a taxane compound. Cytotoxic drugs are used in a second- or third-line setting but tumour progression is the rule. Also patients with the same histology achieve different outcomes in terms of survival. We decided to study gonadotropin and steroid receptors and to consider if these histological markers could select patients with different prognosis. MATERIALS AND METHODS: In our study we have measured by immunohistochemistry oestrogen, progestin and gonadotropin- releasing hormone receptors (Gn-RHRs) in paraffinembedded ovarian cancer tissue in a sample of 62 consecutive patients with advanced ovarian cancer treated with surgery and adjuvant chemotherapy. Descriptive methods, a survival analysis (Kaplan-Meier) and a Cox regression analysis were done. RESULTS: Oestrogen receptors (ERs) were positive in 65% of patients and the same positivity was obtained for progestin receptors (PRs), with 74% showing some positivity for Gn-RHR receptors. Maximal cytoreduction and ERs, but not gonadotropin receptors, were independently associated with overall survival, with better survival for oestrogennegative tumours. No association was established for progression- free survival. CONCLUSIONS: We can conclude that ER status in our series is an independent prognostic factor for ovarian cancer with better survival for oestrogen-negative receptor tumours. PRs could also have a prognostic role in association with ERs.

Glutamine homeostasis and mitochondrial dynamics.

Glutamine is a multifaceted amino acid that plays key roles in many metabolic pathways and also fulfils essential signaling functions. Although classified as non-essential, recent evidence suggests that glutamine is a conditionally essential amino acid in several physiological situations. Glutamine homeostasis must therefore be exquisitely regulated and mitochondria represent a major site of glutamine metabolism in numerous cell types. Glutaminolysis is mostly a mitochondrial process with repercussions in organelle structure and dynamics suggesting a tight and mutual control between mitochondrial form and cell bioenergetics. In this review we describe an updated account focused on the critical involvement of glutamine in oxidative stress, mitochondrial dysfunction and tumour cell proliferation, with special emphasis in the initial steps of mitochondrial glutamine pathways: transport into the organelle and hydrolytic deamidation through glutaminase enzymes. Some controversial issues about glutamine catabolism within mitochondria are also reviewed.

Negative prognostic impact of the coexpression of epidermal growth factor receptor and c-erbB-2 in locally advanced cervical cancer.

OBJECTIVE: The objective was to determine the impact of the coexpression of epidermal growth factor receptor (EGFR) and tumor marker c-erbB-2 on disease-free survival (DFS) and pelvic relapse-free survival (PRFS) in patients with locally advanced cervical cancer (LACC) receiving concurrent chemoradiotherapy. METHODS: The expression of EGFR and c-erbB-2 was assessed by immunohistochemistry, which was centralized and blinded to outcome. Univariate and multivariate analyses were used to evaluate the impact of EGFR and c-erbB-2 on DFS and PRFS. RESULTS: 170 patients with LACC were included and received concurrent chemoradiotherapy. 25 (15%) biopsies were considered EGFR and c-erbB-2 positive; 100 (59%) were either EGFR or c-erbB-2 positive, and 45 (26%) were EGFR and c-erbB-2 negative. The 3- and 5-year DFS was 39% each for EGFR- and c-erbB-2-positive patients, 54 and 49%, respectively, for EGFR- or c-erbB-2-positive patients, and 76 and 72%, respectively, for EGFR- and c-erbB-2-negative patients (p = 0.006). EGFR- and c-erbB-2-positive tumors were significantly associated with a decrease in PRFS (hazard ratio, HR, 3.99; 95% confidence interval, CI, 1.44-11.05, p = 0.007), and DFS (HR 2.9; 95% CI, 1.26-6.66, p = 0.01). CONCLUSION: Patients with LACC coexpressing EGFR and c-erbB-2, and treated with concurrent chemoradiotherapy, had a worse clinical prognosis with shorter DFS and PRFS.