Unusual long survival in a case of heterotaxy and polysplenia.

Heterotaxy syndrome with polysplenia is an extremely rare congenital disorder caused by a disruption in the embryonic development that results in an abnormal arrangement of the abdominal and thoracic organs. We present the case of a 59-year-old female patient with invasive ductal carcinoma of the right breast (luminal A type) and CT findings of heterotaxy syndrome with polysplenia. The most remarkable anomalies identified were a left inferior vena cava draining into the hemiazygos vein, absent inferior vena cava at the thoracic level, and hepatic veins directly draining into the right atrium. Moreover, an atrial septal defect was identified, explaining the pulmonary hypertension of unknown cause previously detected in the patient. The relevance of this case lies in the unusual anatomical abnormalities found and the large patient survival, having in to account the great rate of heterotaxy syndrome mortality in the first years of life.

A phase 2 study of panitumumab with irinotecan as salvage therapy in chemorefractory KRAS exon 2 wild-type metastatic colorectal cancer patients.

BACKGROUND: Targeted agents are standard treatment for RAS wild-type metastatic colorectal cancer in the first- and second-line settings. This phase 2 study determined the benefit of targeting the epidermal growth factor receptor (EGFR) with panitumumab plus irinotecan in irinotecan-refractory patients. METHODS: KRAS exon-2 wild-type patients failing prior irinotecan received panitumumab (6 mg/kg) and irinotecan (180 mg/m²) every 2 weeks. The primary endpoint was the overall response rate (ORR). Secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). KRAS exon-2 status was evaluated centrally, along with NRAS, BRAF mutations, epiregulin, amphiregulin, PTEN and EGFR copy number status, and correlated with efficacy. RESULTS: Sixty-one patients were treated. Among the 46 wild-type RAS patients, the ORR was 15.2% (seven partial responses), with median PFS of 3.8 months (95% CI 2.7-4.3) and median OS of 12.5 months (95% CI 6.7-15.9). Wild-type BRAF patients showed a 13.0% response rate. No significant correlations between response and baseline biomarker expression were identified. Common grade 3-4 adverse events were diarrhoea and rash (18.0% each), hypomagnesaemia and asthenia (8.2% each). CONCLUSIONS: The addition of panitumumab to irinotecan as salvage therapy is feasible but has limited activity in irinotecan-refractory metastatic colorectal cancer. No biomarkers predictive of response were identified.

The impact of PKR activation: from neurodegeneration to cancer.

An inverse association between cancer and neurodegeneration is plausible because these biological processes share several genes and signaling pathways. Whereas uncontrolled cell proliferation and decreased apoptotic cell death governs cancer, excessive apoptosis contributes to neurodegeneration. Protein kinase R (PKR), an interferon-inducible double-stranded RNA protein kinase, is involved in both diseases. PKR activation blocks global protein synthesis through eIF2α phosphorylation, leading to cell death in response to a variety of cellular stresses. However, PKR also has the dual role of activating the nuclear factor κ-B pathway, promoting cell proliferation. Whereas PKR is recognized for its negative effects on neurodegenerative diseases, in part, inducing high level of apoptosis, the role of PKR activation in cancer remains controversial. In general, PKR is considered to have a tumor suppressor function, and some clinical data show a correlation between suppressed or inactivated PKR and a poor prognosis for several cancers. However, other studies show high PKR expression and activation levels in various cancers, suggesting that PKR might contribute to neoplastic progression. Understanding the cellular factors and signals involved in the regulation of PKR in these age-related diseases is relevant and may have important clinical implications. The present review highlights the current knowledge on the role of PKR in neurodegeneration and cancer, with special emphasis on its regulation and clinical implications.

Uncovering Tumour Heterogeneity through PKR and nc886 Analysis in Metastatic Colon Cancer Patients Treated with 5-FU-Based Chemotherapy.

Colorectal cancer treatment has advanced over the past decade. The drug 5-fluorouracil is still used with a wide percentage of patients who do not respond. Therefore, a challenge is the identification of predictive biomarkers. The protein kinase R (PKR also called EIF2AK2) and its regulator, the non-coding pre-mir-nc886, have multiple effects on cells in response to numerous types of stress, including chemotherapy. In this work, we performed an ambispective study with 197 metastatic colon cancer patients with unresectable metastases to determine the relative expression levels of both nc886 and PKR by qPCR, as well as the location of PKR by immunohistochemistry in tumour samples and healthy tissues (plasma and colon epithelium). As primary end point, the expression levels were related to the objective response to first-line chemotherapy following the response evaluation criteria in solid tumours (RECIST) and, as the second end point, with survival at 18 and 36 months. Hierarchical agglomerative clustering was performed to accommodate the heterogeneity and complexity of oncological patients' data. High expression levels of nc886 were related to the response to treatment and allowed to identify clusters of patients. Although the PKR mRNA expression was not associated with chemotherapy response, the absence of PKR location in the nucleolus was correlated with first-line chemotherapy response. Moreover, a relationship between survival and the expression of both PKR and nc886 in healthy tissues was found. Therefore, this work evaluated the best way to analyse the potential biomarkers PKR and nc886 in order to establish clusters of patients depending on the cancer outcomes using algorithms for complex and heterogeneous data.

Impact of Self-Efficacy on The Quality of Life of Children With Asthma and Their Caregivers. / Impacto de la autoeficacia en la calidad de vida de niños con asma y sus cuidadores.

INTRODUCTION: Health-related quality of life is an important outcome measurement in the monitoring of asthma control. Self-efficacy is a determinant of self-management behaviors that can contribute to the improvement of asthma control and quality of life. Our objective was to analyze the relationship between self-efficacy and quality of life in children with asthma and their caregivers. METHODS: We included 176 patients aged 6-14 years with asthma, and determined their level of self-efficacy according to three groups (low, medium and high levels). Each child and their main caregiver completed the PAQLQ and PACQLQ questionnaires, respectively. RESULTS: PAQLQ range=1-7: 5.61±1.11; PACQLQ range=1-7: 5.42±1.35; self-efficacy range=0-60: low level 28.44±4.58; average level 37.41±1.7, and high level 47.50±5.5. Significant differences were observed in quality of life according to low-medium vs. high levels of self-efficacy. Specific related domains: PAQLQ emotions and PAQLQ symptoms with self-efficacy in problem-solving skills related to asthma and treatment self-efficacy; PACQLQ emotions with self-efficacy in problem-solving skills related to asthma. CONCLUSIONS: A high level of self-efficacy is associated with a better quality of life for children and their caregivers. Based on these results, the measurement of self-efficacy could be incorporated in the assessment of educational interventions in self-management targeted at the quality of life of the patient and his or her family.

Displasia de desarrollo de la cadera en niños menores de 5 años de edad en el período de 2004-2006 en el Instituto Nacional de Salud del Niño-Lima-Perú / Developmental dysplasia of the hip in children under 5 years of age in the period 2004-2006 at the National Institute of Child Health, Lima, Peru

Antecedentes: la dispasia de desarrollo de la cadera constituye un problema incapacitante en la ortopedia infantil. se investigó los hallazgos clínicos, radiológicos y medidas terapéuticas en niños menores de 5 años de edad con el fin de encontrar mayor información sobre la realidad de dichapatología en el Perú. Métodos: se realizó un estudio descriptivo y retrospectivo mediante la revisión de 165 historias clínicas de niños con diagnóstico de Displasia de desarrollo de la cadera correspondientes periodo 1 de Enero del 2004 al 31 de Diciembre del 2006, proporcionadas por la Oficina de Estadística e Informática del Instituto Nacional de Salud del Niño - Lima Perú. Resultados: Un total de 165 pacientes (73,9 por ciento de sexo femenino)fueron incluidos. No referían antecedentes familiares 95 pacientes (57,6 por ciento) sesenta y nueve pacientes (47,9 por ciento) tuvieron parto eutócico. Ochenta y tres pacientes (50,3 por ciento) fueron normopeso. La articulación coxofemoral izquierda estuvo comprometida en 78 pacientes (47,3 por ciento), evidenciandose en 111 pacientes (78,2 por ciento) limitación de abducción. El diagnóstico inagenológico fue por radiografía en 114 pacientes (69,1 por ciento), siendo la edad más frecuente lactante menor en 140 pacientes (84,8 por ciento). El tratamiento médico más utilizado fue Arnés de Pavlik en 36 pacientes (21,8 por ciento), no recibiendo tratamiento quirúrgico 117 pacientes (70,95 por ciento). La evolución clínica favorable en 114 pacientes (69,1 por ciento). Conclusiones: La mayoria de pacientes con displasia de desarrollo de la cadera fueron lactantes menores de sexo femenino, presentando la articulación coxofemoral izquierda comprometida y limitación a la abducción como hallazgo primario. El diagnósticofue preferentemente por radiografía, recibiendo tratamiento médico con una evolución favorable

Background. Developmental dysplasia of the hip is a disabling problem in children's orthopedics. We investigated the clinical, radiological and therapeutic findings in children under 5 years old in order tofind out further about the reality in Perú. Methods: We preformed a retrospective descriptive study through reviewing of 165 medical records for the period January 1, 2004 to December 31, 2006, provided by Ofinina de Estadídtica e Informática of Instituto Nacional de Salud del Niño-Lima, Perú. Results: a total of 165 patients (73.9 por ciento female)were included. Family history was not referred by 95 patients (57.6 per cent). Seventy-nine patients (47.9 per cent) had vaginal delivery in cephalic presentation. Eighty-three patients (50.3 per cent)had normal birth weight. The left hip joint was affected in 78 patients (47.3 per cent) and 111 patients (78.2 per cent) had limitation of abduction. the diagnosis was by radiographic imaging in 114 patients(69.1 per cent), being the most frequnet age in 140 patients (84.8) `young infantd. The most widely used medical treatment was Pavlik harness in patients (21.8 per cent), and 117 patients (70.95 per cent) did not receive surgical treatment. Clinical evolution was favorable in 114 patients (69.1 per cent). Conclusion: Most patients with developmental dysplasia of the hip were young female infants, having the left hip joint affected and limitation of abduction. The diagnosis was mainly by radiographic,receiving treatment with favorable results