Is eribulin treatment prognostic factor in patients with metastatic breast cancer treated with this drug? Retrospective analysis of a multicentre study.

PURPOSE: This study aimed to analyze prognostic factors for survival and the reliability and the effectiveness of eribulin therapy in metastatic breast cancer (MBC) patients. METHODS: A total of 80 patients treated with eribulin in 12 medical oncology centers in Turkey between 2013-2017 were retrospectively evaluated. Sixteen potential prognostic variables were assessed for analysis. RESULTS: The patients had received a median of 5 prior chemotherapy regimens and a median of 3 eribulin cycles for MBC. Median progression-free survival (PFS) was 5.5 months (95% Cl: 4.1-7.8) and median overall survival (OS) was 11 months (95 % Cl: 6-15). Multivariate analysis showed that eribulin treatment line was shown to have independent prognostic significance for PFS. PFS difference was demostrated in patients who received 3 chemotherapy lines for advanced disease compared to those who had more than 3 chemotherapy lines [median PFS; 3 lines: 8.6 months (6.2-11) and ˃3 lines: 4.6 months (3.7-4.6) p=0.00]. The clinical benefit rate (CBR) was 52.5 and 35% in patients treated with three lines and with ˃3 previous chemotherapeutic regimens. Most common toxicities were neutropenia (62.5%), fatigue (52.5%), alopecia (50%) and nausea (37.5%). CONCLUSIONS: Eribulin treatment line was identified as indepedent prognostic factor for PFS in MBC patients.

Is eribulin treatment prognostic factor in patients with metastatic breast cancer treated with this drug? Retrospective analysis of a multicentre study.

PURPOSE: This study aimed to analyze prognostic factors for survival and the reliability and the effectiveness of eribulin therapy in metastatic breast cancer (MBC) patients. METHODS: A total of 80 patients treated with eribulin in 12 medical oncology centers in Turkey between 2013-2017 were retrospectively evaluated. Sixteen potential prognostic variables were assessed for analysis. RESULTS: The patients had received a median of 5 prior chemotherapy regimens and a median of 3 eribulin cycles for MBC. Median progression-free survival (PFS) was 5.5 months (95% Cl: 4.1-7.8) and median overall survival (OS) was 11 months (95 % Cl: 6-15). Multivariate analysis showed that eribulin treatment line was shown to have independent prognostic significance for PFS. PFS difference was demostrated in patients who received 3 chemotherapy lines for advanced disease compared to those who had more than 3 chemotherapy lines [median PFS; 3 lines: 8.6 months (6.2-11) and ˃3 lines: 4.6 months (3.7-4.6) p=0.00]. The clinical benefit rate (CBR) was 52.5 and 35% in patients treated with three lines and with ˃3 previous chemotherapeutic regimens. Most common toxicities were neutropenia (62.5%), fatigue (52.5%), alopecia (50%) and nausea (37.5%). CONCLUSIONS: Eribulin treatment line was identified as indepedent prognostic factor for PFS in MBC patients.

Efectos de la edad al momento del diagnóstico y cumplimiento de la dieta sobre los parámetros de crecimiento de los pacientes con celiaquía / Effects of age of diagnosis and dietary compliance on growth parameters of patients with celiac disease

Introducción. El objetivo fue evaluar la relación entre edad al diagnóstico y cumplimiento de dieta sin gluten (DSG) y su efecto sobre el crecimiento de niños celiácos y factores que influenciaron el cumplimiento de la DSG. Población y métodos. Se incluyeron pacientes celíacos con seguimiento en nuestro hospital entre enero 2015 a enero 2017. Se los clasificaron según edad al diagnóstico y cumplimiento de la DSG. Se compararon características antropométricas al diagnóstico y durante el seguimiento. Resultados. Participaron 73 pacientes con edad promedio de 10,4 ± 4,5 años; 35 (47,9%), los pacientes de talla baja al diagnóstico; eran mayores (7,8 ± 4,2 años) que los demás (5,1 ± 4,3 años de edad) (p= 0,005). Al diagnóstico, 33 (45,2%) pacientes tenían ≤6 años y 40 (54,8%) tenían >6 años. Los puntajes Z de estatura y peso a la edad >6 años eran significativamente menores que los diagnosticados a ≤6 años, en el diagnóstico (p= 0,01 y 0,04, respectivamente) como en el último control (p= 0,001 y 0,001, respectivamente). Tuvieron cumplimiento riguroso con DSG en 45 (61,6%) pacientes. Al comparar datos antropométricos , el aumento del índice de masa corporal (IMC) y del puntaje Z de peso en el grupo que cumplió la dieta fue significativamente mayor que en el otro grupo.Conclusiones. Demorar el diagnóstico de celiaquía afectó la estatura y peso. El cumplimiento de la DSG mejoró los parámetros de crecimiento, principalmente, el puntaje Z de peso y el IMC.

Introduction. The objective of this study was to evaluate the relation between age at diagnosis and compliance to gluten free diet (GFD) on growth in children with celiac disease and the factors that influenced compliance to GFD. Population and Methods. Celiac disease (CD) patients with villous atrophy followed in our hospital between January 2015 and January 2017, were included. They were classified according to diagnosis age and GFD compliance. Patients' anthropometric characteristics at diagnosis and follow-up were compared. Results. There were 73 patients with 10.4 ± 4.5 years of average age, 35 (47.9%) patients had a short stature at diagnosis, the ages of patients who had short stature (7.8 ± 4.2 years) were higher than those who did not (5.1 ± 4.3 years) (p= 0.005). At diagnosis, 33 (45.2%) patients were aged ≤6 years, 40 (54.8%) were aged >6 years. The height and weight z-scores of patients who were diagnosed at >6 years of age were significantly lower than those who were diagnosed ≤6 years of age both at diagnosis (p= 0.01 and 0.04) and at last control (p= 0.001 and 0.001), respectively. Forty-five (61.6%) patients were fully compliant with GFD. In comparison of anthropometric data in terms of GFD compliance, the increase in BMI and weightz-score in the fully compliant group was found to be significantly higher when compared with the other group. Conclusions. Delay in CD diagnosis negatively affected both the height and weight and other growth parameters. GFD compliance positively affected the patients' all growth parameters, especially weight and BMI z-score.

Effects of age of diagnosis and dietary compliance on growth parameters of patients with celiac disease. / Efectos de la edad al momento del diagnóstico y cumplimiento de la dieta sobre los parámetros de crecimiento de los pacientes con celiaquía.

INTRODUCTION: The objective of this study was to evaluate the relation between age at diagnosis and compliance to gluten free diet (GFD) on growth in children with celiac disease and the factors that influenced compliance to GFD. POPULATION AND METHODS: Celiac disease (CD) patients with villous atrophy followed in our hospital between January 2015 and January 2017, were included. They were classified according to diagnosis age and GFD compliance. Patients' anthropometric characteristics at diagnosis and follow-up were compared. RESULTS: There were 73 patients with 10.4 ± 4.5 years of average age, 35 (47.9%) patients had a short stature at diagnosis, the ages of patients who had short stature (7.8 ± 4.2 years) were higher than those who did not (5.1 ± 4.3 years) (p= 0.005). At diagnosis, 33 (45.2%) patients were aged ≤6 years, 40 (54.8%) were aged >6 years. The height and weight z-scores of patients who were diagnosed at >6 years of age were significantly lower than those who were diagnosed ≤6 years of age both at diagnosis (p= 0.01 and 0.04) and at last control (p= 0.001 and 0.001), respectively. Forty-five (61.6%) patients were fully compliant with GFD. In comparison of anthropometric data in terms of GFD compliance, the increase in BMI and weight z-score in the fully compliant group was found to be significantly higher when compared with the other group. CONCLUSIONS: Delay in CD diagnosis negatively affected both the height and weight and other growth parameters. GFD compliance positively affected the patients' all growth parameters, especially weight and BMI z-score.

Introducción. El objetivo fue evaluar la relación entre edad al diagnóstico y cumplimiento de dieta sin gluten (DSG) y su efecto sobre el crecimiento de niños celiácos y factores que influenciaron el cumplimiento de la DSG. Población y métodos. Se incluyeron pacientes celíacos con seguimiento en nuestro hospital entre enero 2015 a enero 2017. Se los clasificaron según edad al diagnóstico y cumplimiento de la DSG. Se compararon características antropométricas al diagnóstico y durante el seguimiento. Resultados. Participaron 73 pacientes con edad promedio de 10,4 ± 4,5 años; 35 (47,9%), los pacientes de talla baja al diagnóstico; eran mayores (7,8 ± 4,2 años ) que los demás (5,1 ± 4,3 años de edad) (p= 0,005). Al diagnóstico, 33 (45,2%) pacientes tenían ≤6 años y 40 (54,8%) tenían >6 años. Los puntajes Z de estatura y peso a la edad >6 años eran significativamente menores que los diagnosticados a ≤6 años, en el diagnóstico (p= 0,01 y 0,04, respectivamente) como en el último control (p= 0,001 y 0,001, respectivamente). Tuvieron cumplimiento riguroso con DSG en 45 (61,6%) pacientes. Al comparar datos antropométricos , el aumento del índice de masa corporal (IMC) y del puntaje Z de peso en el grupo que cumplió la dieta fue significativamente mayor que en el otro grupo. Conclusiones. Demorar el diagnóstico de celiaquía afectó la estatura y peso. El cumplimiento de la DSG mejoró los parámetros de crecimiento , principalmente, el puntaje Z de peso y el IMC.

Lactose and Fructose Intolerance in Turkish Children with Chronic Abdominal Pain.

OBJECTIVE: To investigate the prevalence of lactose and fructose intolerance in children with chronic abdominal pain. METHODS: Hydrogen breath tests were done to detect lactose and fructose malabsorption in 86 children with chronic abdominal pain (44 irritable bowel syndrome, 24 functional abdominal pain and 17 functional abdominal pain syndrome as per Rome III criteria) presenting to a Pediatric Gastroentreology department. RESULTS: 14 (16.3%) of patients were diagnosed with lactose intolerance and 11 (12.8%) with fructose intolerance. CONCLUSION: Lactose and fructose intolerance in children can lead to chronic abdominal pain and symptoms improve with dietary modifications.

Assessment of Endothelial Dysfunction With Adhesion Molecules in Patients With Celiac Disease.

OBJECTIVES: Celiac disease (CD) is a systemic immune disorder. We assessed serum levels of adhesion molecules as a marker of endothelial dysfunction in patients with CD at first diagnosis and in those on a gluten-free diet. METHODS: Sixty-five patients with CD (mean age 6.74 ±â€Š4.6 years) and 51 age- and sex-matched control patients participated in the present case-controlled, prospective clinical study. Serum levels of vascular adhesion molecule-1, intercellular adhesion molecule-1, endothelial selectin, vascular endothelial cadherin, high-sensitivity C-reactive protein, and homocysteine levels were measured. RESULTS: Average soluble vascular adhesion molecule-1 (CD vs control group: 1320 ±â€Š308 vs 1120 ±â€Š406 ng/mL, P = 0.006), soluble intercellular adhesion molecule-1 (336 ±â€Š99 vs 263 ±â€Š67 ng/mL, P = 0.025), and soluble endothelial selectin (113.9 ±â€Š70 vs 76.9 ±â€Š32 ng/mL, P = 0.007) levels were significantly higher in cases of newly diagnosed CD than in the control group. Soluble vascular adhesion molecule-1 (1050 ±â€Š190 ng/mL) and soluble endothelial selectin (68.7 ±â€Š45 ng/mL) levels in patients with CD, who were fully compliant with a gluten-free diet, were significantly lower than that in those newly diagnosed as having CD (P = 0.003 and P = 0.0012, respectively). CONCLUSIONS: These results show that serum adhesion molecule levels are higher in patients with CD. Some of the risks associated with endothelial dysfunction may be related to CD and these risks can be reduced with an appropriate and fully controlled diet.

Detection of gastroesophageal reflux in children with cerebral palsy using combined multichannel intraluminal impedance-ph procedure.

Gastroesophageal reflux (GER) is a very common condition in children with neurological impairment and this can influence nutritional and respiratory outcomes. The aim of this study was to investigate the presence of GER in children with cerebral palsy (CP) using multiple intraluminal impedance (MII)-pH monitoring. The use of combined MII-pH allows for the detection of both acid and non-acid reflux episodes. A total of 29 CP patients with symptoms suggesting GER, aged 2 to 10 years old, underwent 24-hour combined MII-pH monitoring. There were a total of 3899 reflux episodes, of which 29% were acid, 60% were weakly acid and 11% were alkaline. The number of non-acid reflux episodes was statistically significantly greater (p < 0.01). These findings confirm that GER disease is seen frequently in children with cerebral palsy and most of the reflux episodes are not acidic. Non-acid reflux can also influence the morbidity in patients with cerebral palsy. It can be concluded that 70% of the reflux episodes would not have been recognized by pH measurement alone.

Ascites and abdominal pseudocyst: two uncommon ventriculoperitoneal shunt complications in two cases.

Ascites and abdominal pseudocysts (APC) are two rare complications that can occur following placement of a ventriculoperitoneal (VP) shunt. Both complications are characterized by abnormal intraperitoneal cerebrospinal fluid (CSF) collections. Although various factors have been implicated, the exact pathogenesis of the two conditions remains elusive. This paper presents two cases of VP shunt placement resulting from hydrocephaly. The first patient presented with generalized ascites and the other with APC, both of whom were six years old. APC and ascites after VP shunt placement are rare and distinct conditions; therefore, they may require different management strategies.

Senataxin, defective in the neurodegenerative disorder ataxia with oculomotor apraxia 2, lies at the interface of transcription and the DNA damage response.

The neurodegenerative disorder ataxia with oculomotor apraxia 2 (AOA-2) is caused by defects in senataxin, a putative RNA/DNA helicase thought to be involved in the termination of transcription at RNA polymerase pause sites. RNA/DNA hybrids (R loops) that arise during transcription pausing lead to genome instability unless they are resolved efficiently. We found that senataxin forms distinct nuclear foci in S/G(2)-phase human cells and that the number of these foci increases in response to impaired DNA replication or DNA damage. Senataxin colocalizes with 53BP1, a key DNA damage response protein, and with other factors involved in DNA repair. Inhibition of transcription using α-amanitin, or the dissolution of R loops by transient expression of RNase H1, leads to the loss of senataxin foci. These results indicate that senataxin localizes to sites of collision between components of the replisome and the transcription apparatus and that it is targeted to R loops, where it plays an important role at the interface of transcription and the DNA damage response.

An ECT2-centralspindlin complex regulates the localization and function of RhoA.

In anaphase, the spindle dictates the site of contractile ring assembly. Assembly and ingression of the contractile ring involves activation of myosin-II and actin polymerization, which are triggered by the GTPase RhoA. In many cells, the central spindle affects division plane positioning via unknown molecular mechanisms. Here, we dissect furrow formation in human cells and show that the RhoGEF ECT2 is required for cortical localization of RhoA and contractile ring assembly. ECT2 concentrates on the central spindle by binding to centralspindlin. Depletion of the centralspindlin component MKLP1 prevents central spindle localization of ECT2; however, RhoA, F-actin, and myosin still accumulate on the equatorial cell cortex. Depletion of the other centralspindlin component, CYK-4/MgcRacGAP, prevents cortical accumulation of RhoA, F-actin, and myosin. CYK-4 and ECT2 interact, and this interaction is cell cycle regulated via ECT2 phosphorylation. Thus, central spindle localization of ECT2 assists division plane positioning and the CYK-4 subunit of centralspindlin acts upstream of RhoA to promote furrow assembly.

MAP kinases regulate unfertilized egg apoptosis and fertilization suppresses death via Ca2+ signaling.

The default fate for eggs from many species is death by apoptosis and thus, successful fertilization depends upon suppression of the maternal death program. Little is known about the molecular triggers which activate this process or how the fertilization signal suppresses the default maternal apoptotic pathway. The MAP kinase (MAPK) family member, ERK, plays a universal and critical role in several stages of oocyte meiotic maturation, and fertilization results in ERK inactivation. In somatic cells, ERK and other MAPK family members, p38 and JNK, provide opposing signals to regulate apoptosis, however, it is not known whether MAPKs play a regulatory role in egg apoptosis, nor whether suppression of apoptosis by fertilization is mediated by MAPK activity. Here we demonstrate that MAPKs are involved in starfish egg apoptosis and we investigate the relationship between the fertilization induced signaling pathway and MAPK activation. ERK is active in post-meiotic eggs just until apoptosis onset and then p38, JNK and a third kinase are activated, and remain active through execution. Sequential activation of ERK and p38 is necessary for apoptosis, and newly synthesized proteins are required both upstream of ERK and downstream of p38 for activation of the full apoptotic program. Fertilization causes a dramatic rise in intracellular Ca2+, and we report that Ca2+ provides a necessary and sufficient pro-survival signal. The Ca2+ pathway following fertilization of both young and aged eggs causes ERK to be rapidly inactivated, but fertilization cannot rescue aged eggs from death, indicating that ERK inactivation is not sufficient to suppress apoptosis.