Near-optimal feedback control for postprandial glucose regulation in type 1 diabetes.

This paper is focused on feedback control of postprandial glucose levels for patients with type 1 Diabetes Mellitus. There are two important limitations that make this a challenging problem. First, the slow subcutaneous insulin pharmacokinetics that introduces a significant lag into the control loop. Second, the positivity constraint on the control action, meaning that it is not possible to remove insulin from the body. In this paper, both issues are explicitly considered in the design process using the internal model control framework, to derive a near-optimal feedback controller. Optimality is understood here as minimizing the blood glucose peak after a meal intake and, at the same time, preventing glucose values below a prescribed threshold. It is shown how the proposed controller approaches the optimal closed-loop performance as a limit case. The theoretical results are supported by a numerical example and the feasibility of the overall strategy under uncertainties is illustrated using an extended version UVa/Padova metabolic simulator.

Super-twisting-based meal detector for type 1 diabetes management: Improvement and assessment in a real-life scenario.

BACKGROUND AND OBJECTIVE: Hybrid automated insulin delivery systems rely on carbohydrate counting to improve postprandial control in type 1 diabetes. However, this is an extra burden on subjects, and it introduces a source of potential errors that could impact control performances. In fact, carbohydrates estimation is challenging, prone to errors, and it is known that subjects sometimes struggle to adhere to this requirement, forgetting to perform this task. A possible solution is the use of automated meal detection algorithms. In this work, we extended a super-twisting-based meal detector suggested in the literature and assessed it on real-life data. METHODS: To reduce the false detections in the original meal detector, we implemented an implicit discretization of the super-twisting and replaced the Euler approximation of the glucose derivative with a Kalman filter. The modified meal detector is retrospectively evaluated in a challenging real-life dataset corresponding to a 2-week trial with 30 subjects using sensor-augmented pump control. The assessment includes an analysis of the nature and riskiness of false detections. RESULTS: The proposed algorithm achieved a recall of 70 [13] % (median [interquartile range]), a precision of 73 [26] %, and had 1.4 [1.4] false positives-per-day. False positives were related to rising glucose conditions, whereas false negatives occurred after calibrations, missing samples, or hypoglycemia treatments. CONCLUSIONS: The proposed algorithm achieves encouraging performance. Although false positives and false negatives were not avoided, they are related to situations with a low risk of hypoglycemia and hyperglycemia, respectively.

Atención a la patología infecciosa en Urgencias de Pediatría: pandemia y pospandemia / Attention to infectious pathology in Pediatric Emergencies: pandemic and post-pandemic

La llegada de un nuevo virus y la declaración de pandemia han supuesto un cambio muy importante en la aproximación a la patología infecciosa en el ámbito sanitario y especialmente en las Urgencias de Pediatría. Estamos permanentemente amenazados por el aumento de la demanda desencadenada por los virus hasta ahora conocidos como estacionales, sin saber cuál será cada año la fuerza con la que impacte la infección en la población infantil en forma de incidencia; hasta que ha llegado el SARS-CoV-2 que ha cambiado completamente el paradigma infeccioso, y que en la actualidad seguimos sufriendo sus coletazos (AU)

Inadequate response to imatinib treatment in chronic myeloid leukemia due to a drug interaction with phenytoin.

Imatinib mesylate and the newer BCR-ABL tyrosine kinase inhibitors are the standard therapy for chronic myeloid leukemia. Although these are remarkably effective drugs, some mechanisms of resistance have been identified including drug-to-drug interactions. Here we present the case of a chronic myeloid leukemia patient with an inadequate response to imatinib due to concurrent phenytoin administration. Conspicuously low imatinib plasma trough levels were documented. Imatinib dose was increased from 400 to 800 mg with good response. In conclusion, drug-to-drug interactions should be ruled out in cases of resistance to tyrosine kinase inhibitor treatment. Potent inducers of cytochrome P450 isoenzyme CYP3A4, as phenytoin, could induce inadequate responses due to increased imatinib clearance and low imatinib trough plasma levels. Thus, this interaction should be avoided. When this is not possible, dose escalation of imatinib and measurement of plasma levels, if available, is recommended.

Síndrome de burnout en una unidad de gestión clínica de obstetricia y ginecología / Burnout syndrome in an obstetrics and gynaecology management unit

Objetivo. Conocer la prevalencia del síndrome de burnout entre los integrantes de una UGC de Obstetricia y Ginecología. Material y método. Estudio transversal anónimo utilizando un cuestionario sociodemográfico y la versión española del Maslach Burnout Inventory. Resultados. La encuesta fue contestada por 21 médicos, 11 matronas, 14 DUE, 22 auxiliares de clínica, 2 administrativas y 1 celador, lo que supone una tasa de respuesta del 43,2% Los valores medios fueron de 20,1 puntos para el agotamiento emocional, 7,6 puntos para la despersonalización y 42,1 puntos para la realización personal. Se encontraron valores más elevados de agotamiento emocional y despersonalización en el colectivo de médicos en relación con las demás categorías profesionales. Conclusiones. Consideramos preocupante que el 33,8% de los integrantes del estudio presente cifras elevadas de agotamiento emocional y que este sea alto en el 52,3% de los médicos especialistas. Valores elevados de satisfacción profesional hacen que solo en el 2,8% coincidan puntuaciones altas de las 3 subescalas(AU)

Objective. To determine the prevalence of the Burnout Syndrome among the members of an Obstetrics and Gynaecology Unit. Material and methods. Cross-sectional study using an anonymous questionnaire and socio-Spanish version of the Maslach Burnout Inventory. Results. The survey was answered by 21 doctors, 11 matrons, 14 DUE, 22 nurses, 2 administrative officers and 1 watchman, with a response rate of 43.2%. Average values were 20.1 points for the emotional exhaustion, depersonalization 7.6 points to 42.1 points and for personal fulfilment. We found higher values of emotional exhaustion and depersonalization in the group of doctors in relation to other professional groups. Conclusion. We believe that 33.8% is an alarmingly high level of emotional exhaustion in the members of the present study, and this level is even higher in medical specialists (52.3%). Only the 2.8% of the professionals had high values in the three sub-scales(AU)

[Burnout syndrome in an obstetrics and gynaecology management unit]. / Síndrome de burnout en una unidad de gestión clínica de obstetricia y ginecología.

OBJECTIVE: To determine the prevalence of the Burnout Syndrome among the members of an Obstetrics and Gynaecology Unit. MATERIAL AND METHODS: Cross-sectional study using an anonymous questionnaire and socio-Spanish version of the Maslach Burnout Inventory. RESULTS: The survey was answered by 21 doctors, 11 matrons, 14 DUE, 22 nurses, 2 administrative officers and 1 watchman, with a response rate of 43.2%. Average values were 20.1 points for the emotional exhaustion, depersonalization 7.6 points to 42.1 points and for personal fulfilment. We found higher values of emotional exhaustion and depersonalization in the group of doctors in relation to other professional groups. CONCLUSION: We believe that 33.8% is an alarmingly high level of emotional exhaustion in the members of the present study, and this level is even higher in medical specialists (52.3%). Only the 2.8% of the professionals had high values in the three sub-scales.

Hipertrofia bilateral de apófisis coronoides / Bilateral Hypertrophy of the coronoid process

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Transcription and activation under environmental stress of the complex telomeric repeats of Chironomus thummi.

In contrast to their traditional role, telomeres seem to behave as transcriptionally active regions. RNAs complementary to the short DNA repeats characteristic of telomerase-maintained telomeres have recently been identified in various mammalian cell lines, representing a new and unexpected element in telomere architecture. Here, we report the existence of transcripts complementary to telomeric sequences characteristic of Chironomus thummi telomeres. As in other Diptera, the non-canonical telomeres of chironomids lack the simple telomerase repeats and have instead more complex repetitive sequences. Northern blots of total RNA hybridized with telomere probes and RT-PCR with telomere-specific tailed primers confirm the existence of small non-coding RNAs of around 200 bp, the size of the DNA repeated telomeric unit. Telomere transcripts are heterogeneous in length, and they appear as a ladder pattern that probably corresponds to multimers of the repeat. Moreover, telomeres are activated under conditions of environmental stress, such as heat shock, appearing highly decondensed and densely labelled with acetylated H4 histone, as well as with RNA polymerase II antibodies, both marks of transcriptional activity. Changes in the expression levels of telomeric RNA were detected after heat shock. These findings provide evidence that transcriptional activity of the repetitive telomere sequences is an evolutionarily conserved feature, not limited to telomerase telomeres. The functional significance of this non-coding RNA as a new additional element in the context of telomere biology remains to be explained.

Lacrimal sac metastases from renal cell carcinoma.

PURPOSE: To report the first case of metastasis from renal cell carcinoma to the lacrimal sac and review the therapeutic options. METHODS: We have reviewed the case of a woman who was operated on for a renal cell carcinoma that developed epiphora and a lacrimal sac tumor, which corresponded to a metastasis from her previous tumor. Although renal cell carcinoma shows a great tendency for distant metastasis, this is the first reported case of metastasis to the lacrimal sac. RESULTS: We comment on the rarity of the case and on the therapeutic alternatives for these cases according to the reviewed literature. CONCLUSION: Metastasis to the lacrimal sac are rather infrequent and should be borne in mind on the appearance of a tumor in this location in people with a history of malignancy.

[Results of treatment of retinal angiomatous proliferation with photodynamic therapy]. / Resultados del tratamiento de la proliferación angiomatosa retiniana mediante terapia fotodinámica.

PURPOSE: To determine the effects of phothodynamic therapy using verteporfin in the treatment of patients with retinal angiomatous proliferation (RAP) and the incidence of this retinal disease in our area. METHODS: We performed a retrospective study of 11 cases of RAP who were treated with photodynamic therapy using verteporfin (PDT). RESULTS: The incidence of RAP in the group of eyes with minimally classic or occult subfoveal choroidal neovascularization was 8%. The mean follow-up time after treatment was 15 months. The visual acuity improved in 3, remained the same in 4, and decreased in 4. In 4 patients, angiomatous lesions were observed in both eyes. CONCLUSIONS: There is no method proven to be effective for the treatment of retinal angiomatous proliferation. Our results suggest that PDT may be useful therapy in patients with RAP as it appeared to reduce the risk of visual loss.

[Submacular hemorrhage following photodynamic therapy in the treatment of choroidal neovascularization]. / Hemorragia submacular tras terapia fotodinámica en el tratamiento de la neovascularización coroidea.

PURPOSE: To describe the incidence, clinical features and evolution of submacular hemorrhage (SMH) occurring after photodynamic therapy (PDT) with verteporfin in the treatment of choroidal neovascularization (CNV). METHODS: A retrospective analysis of the patients treated with PDT in our hospital between July 2002 and May 2005 was undertaken. RESULTS: 8 out of 504 eyes treated with PDT (1.58%) developed SMH; 4 of them (0.79%) required surgical attack. The incidence of SMH for every application of PDT was 0.65% (8/1221). The underlying disorder defined was age-related macular degeneration (AMD) in 7 cases (87.5%), and high myopia in one case (12.5%). Regarding the type of lesion, 5 were occult (62.5%; p=0.01), 1 predominantly classic, 1 minimally classic, and the last one was not classified. The average final visual acuity (VA) was 0.057, with 25% of patients having a VA >or= 0.1. Patients lost 4 Snellen lines on average. CONCLUSIONS: SMH after PDT was an event of unknown etiology and low frequency. The incidence in our series (1.58%) was comparable with that described in the world literature (0.24-9.0%). The greatest incidence of AMD was in the occult group with no classic type of CNV, suggesting a possible higher risk for SMH in this type of lesion. It is mandatory to inform patients of the possibility of this complication, which can compromise the visual result of the PDT, and sometimes require surgery. The low risk of SMH related to the PDT justifies its application when it is indicated.

Long-term outcome of allogeneic PBSC transplantation in pediatric patients with hematological malignancies: a report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON) and the Spanish Group for Allogeneic Peripheral Blood Transplantation (GETH).

We analyzed the clinical outcome in 90 children undergoing allogeneic PBSC transplantation from HLA-identical relative for leukemia. GvHD prophylaxis was CsA+ methotrexate in 50 and CsA+/-steroids in 40. Median CD34+ cells infused were 6 x 10(6)/kg (range, 1.4-32). Median follow-up was 60 months (range, 6-115). CI of transplant-related mortality (TRM) was 18.4+/-4%. On multivariate analysis, high Lansky score (>80) at transplantation was associated with lower TRM (HR, 0.9; P<0.0002). Relapse incidence (RI) was 33.6+/-6%. On multivariate analysis, high Lansky score at transplantation and cGvHD were associated with lower RI (HR, 0.04; P<0.0005 and HR, 0.23; P<0.03, respectively). Disease-free survival (DFS) was 57.8+/-5%. Disease status at transplantation (HR, 0.33; P<0.02), steroid treatment at day +90 (HR, 5.61; P<0.005) and cGvHD (HR, 0.23; P<0.005) had a significant impact on DFS in multivariate analysis. CI of cGvHD was 63.7+/-7%. Patients with cGvHD had better DFS (65+/-5%) because of lower RI (15.7+/-6%) and similar TRM (27.4+/-4%). These data suggest acceptable long-term outcomes after allogeneic PBSC transplantation in children despite the high incidence of cGvHD. These patients had a lower risk of relapse and a better DFS.

Relapse of chronic myeloid leukemia after allogeneic stem cell transplantation: outcome and prognostic factors: the Chronic Myeloid Leukemia Subcommittee of the GETH (Grupo Español de Trasplante Hemopoyético).

In order to analyze the outcome of patients with chronic myeloid leukemia (CML) who relapse after allogeneic stem cell transplantation (SCT), we investigated data from 107 patients reported to the Spanish Registry, GETH. In all, 93 (87%) patients were treated after relapse; 36 out of 49 that failed to achieve a response received a second relapse-treatment, and seven a third one. At the last follow-up, the number of patients in molecular or cytogenetic remission was 29 and 13, respectively. Overall survival and progression-free survival after relapse were 53.6% (95% CI: 42.9--64.2) and 52% (95% CI: 41-63) at 5 years, respectively. In multivariate analysis, survival was significantly related to CML phase at relapse (cytogenetic or chronic phase vs advanced phases) and time from transplant to relapse (<1 vs >or=1 year). Patients with no adverse factors had a better survival compared with patients with one or two adverse features (65 vs 35 vs 0%, respectively). We conclude that a significant proportion of CML patients that relapse after transplantation can regain complete and long-lasting remissions with one or more salvage therapies. Disease stage at relapse and time from transplant to relapse should be taken into account when comparing results of different salvage treatments.

Diagnóstico prenatal del síndrome de Down en España: análisis comparativo de diversas estrategias de detección / Prenatal diagnosis of Down’s syndrome in Spain: comparative analysis of different detection strategies

Objetivo. Analizar el resultado que se obtendría tras aplicar distintas estrategias de diagnóstico prenatal del síndrome de Down, en función de la distribución real de la edad materna, en el conjunto de España y en cada una de las comunidades autónomas. Método. Se realizan estimaciones a partir de los datos estadísticos publicados por el Instituto Nacional de Estadística para el año 2001. Resultados. La elevada proporción de gestantes añosas hace que sea inaceptable continuar basando la estrategia de detección exclusivamente en la edad materna. La estrategia emergente de ofrecer libremente una técnica invasiva a todas las gestantes según su deseo produciría tal incremento de demanda que podría no ser asumible por el sistema sanitario público. El test combinado es la estrategia que presentaría una mejor relación coste-eficacia. Conclusiones. Es necesario promover institucionalmente la difusión de estrategias de detección prenatal del síndrome de Down, basadas en cribado poblacional, que puedan ser ofrecidas a las gestantes como alternativa a la libre elección de técnicas invasivas

Objective. To analyse the results obtained by the application of different strategies of prenatal diagnosis of Down's syndrome, on the basis of the real distribution of maternal age, both in Spain as a whole and within each of the country's autonomous regions. Method. Estimates were made from the statistical data published by the Spanish National Statistical Institute (INE) for 2001. Results. The high proportion of older pregnant women means it is no longer acceptable for detection strategy to continue to be based exclusively on maternal age. The currently favoured approach of freely offering all pregnant women an invasive study, if they wish, would lead to a demand increase that could well be beyond the possibilities of the public health system. The combined test is the strategy that presents the best cost-efficacy ratio. Conclusions. Institutions should promote strategies for the prenatal detection of Down's syndrome, based on population screening programmes, offered to pregnant women as an alternative to the free choice of invasive techniques

Risk assessment and outcome of chronic graft-versus-host disease after allogeneic peripheral blood progenitor cell transplantation in pediatric patients.

We retrospectively evaluated the incidence, risk factors for chronic graft-versus-host disease (cGvHD) and outcome in 80 pediatric patients (36 male) (median age 13 years) who underwent allogeneic peripheral blood progenitor cell transplantation. Patients were grafted from an HLA-identical sibling after myeloablative conditioning (total body irradiation (TBI) based 52; non-TBI 28). GvHD prophylaxis used were: cyclosporin A (CsA)+ short methotrexate (MTX) in 52 and CsA+/-prednisone in 28. The median number of CD34+ cells infused were 5.8 x 10(6)/kg (range: 1.4-32.8). The median follow-up was 24 months (range: 3-94). In all, 28 patients had cGvHD (confidence interval (CI): 54.2+/-10%). Factors that were significant on univariate analysis were diagnosis (P=0.03) and GvHD prophylaxis administered (P=0.04). On multivariate analysis, only GvHD prophylaxis used was associated with a significant risk of cGvHD (hazard ratio (HR): 3.94; 95% CI: 1.41-10.91, P=0.009). The CI of cGvHD for patients receiving CsA+MTX was 40.9+/-12 vs 76.5+/-18% for patients who did not (P=0.03). The probability of relapse was 36+/-6% for all patients (12.5+/-8% for patients with cGvHD vs 47.9+/-8% without cGvHD). The probability of disease-free survival was better for patients with cGvHD (69.9+/-10 vs 37.9+/-7%; HR: 3.59, 95% CI: 1.47-5.56; P=0.001). Our data suggest that the GvHD prophylaxis used is the most relevant predictor of cGvHD. Patients with cGvHD had a lower risk of relapse and a better survival.