Incidence of Seizure and Associated Risk Factors in Patients in the Medical Intensive Care Unit (ICU) at Memorial Sloan Kettering Cancer Center (MSK) from 2016-2017.

Background: Seizures and status epilepticus are common neurologic complications in the intensive care unit (ICU) but the incidence in a cancer ICU is unknown. It is important to understand seizure risk factors in cancer patients to properly diagnose the seizure type to ensure appropriate therapy. Methods: We identified patients admitted to the medical ICU at Memorial Sloan Kettering Cancer Center (MSK) from January 2016 to December 2017 who had continuous or routine electroencephalography (EEG) and identified clinical and electrographic seizures by chart review. Results: Of the 1059 patients admitted to the ICU between 2016 and 2017, 50 patients had clinical and/or electrographic seizures (incidence of 4.7%, 95% CI: 3.4-6.0). The incidences of clinical and electrographic seizure were 4.1% and 1.1%, respectively. In a multivariable stepwise regression model, history of seizure (OR: 2.9, 95% CI: 1.1-7.8, P: .03), brain metastasis (OR: 2.5, 95% CI: 1.1-5.8, P: .03), vasopressor requirement (OR: 2.2, 95% CI: 1.0-4.9, P: .05), and age < 65 (2.4, 95% CI: 1.2-5.0, P: .02) were associated with increased risk of seizure (either clinical or electrographic). Obtaining continuous EEG instead of routine EEG increased the yield of seizure detection significantly (OR: 3.9, 95% CI: 1.3-11.1, P: .01). No chemotherapy in the past 30 days, no antibiotic use, vasopressor requirement, and having a brain tumor increased risk of electrographic seizure. Length of continuous EEG > 24 h significantly increased the chances of both clinical and electrographic seizure detection, (OR: 2.6 [95% CI: 1.2-5.7] and 15.0 [95% CI: 2.7-82.5], respectively). Conclusions: We identified known and cancer-related risk factors which can aid clinicians in diagnosing seizures in cancer ICUs. Long-term video EEG monitoring should be considered, particularly given the treatable and reversible nature of seizures.

Contribution of dietary intake to relapse rate in early paediatric multiple sclerosis.

OBJECTIVE: The role of diet in multiple sclerosis (MS) course remains largely unknown. Children with MS have a higher relapse rate compared with MS in adults. Thus, studying the effect of diet on relapse rate in this age group is likely to provide more robust answers. METHODS: This is a multicentre study done at 11 paediatric MS centres in the USA. Patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome (CIS) with disease onset before 18 years of age and duration of less than 4 years were included in this study. Dietary intake during the week before enrolment was assessed with the validated Block Kids Food Screener. The outcome of the study was time from enrolment to the next relapse. 219 patients with paediatric RRMS or CIS were enrolled. Each 10% increase in energy intake from fat increased the hazard of relapse by 56% (adjusted HR 1.56, 95% CI 1.05 to 2.31, p=0.027), and in particular each 10% increase in saturated fat tripled this hazard (adjusted HR: 3.37, 95% CI 1.34 to 8.43, p=0.009). In contrast, each additional one cup equivalent of vegetable decreased the hazard of relapse by 50% (adjusted HR: 0.50, 95% CI 0.27 to 0.91, p=0.024). These associations remained with mutual adjustment and persisted when adjusting for baseline 25(OH) vitamin D serum level. Other studied nutrients were not associated with relapse. CONCLUSIONS: This study suggests that in children with MS, high energy intake from fat, especially saturated fat, may increase the hazard to relapse, while vegetable intake may be independently protective.

α8ß1 integrin regulates nutrient absorption through an Mfge8-PTEN dependent mechanism.

Coordinated gastrointestinal smooth muscle contraction is critical for proper nutrient absorption and is altered in a number of medical disorders. In this work, we demonstrate a critical role for the RGD-binding integrin α8ß1 in promoting nutrient absorption through regulation of gastrointestinal motility. Smooth muscle-specific deletion and antibody blockade of α8 in mice result in enhanced gastric antral smooth muscle contraction, more rapid gastric emptying, and more rapid transit of food through the small intestine leading to malabsorption of dietary fats and carbohydrates as well as protection from weight gain in a diet-induced model of obesity. Mechanistically, ligation of α8ß1 by the milk protein Mfge8 reduces antral smooth muscle contractile force by preventing RhoA activation through a PTEN-dependent mechanism. Collectively, our results identify a role for α8ß1 in regulating gastrointestinal motility and identify α8 as a potential target for disorders characterized by hypo- or hyper-motility.

Sporadic Retinoblastoma and Parental Smoking and Alcohol Consumption before and after Conception: A Report from the Children's Oncology Group.

BACKGROUND: Retinoblastoma is the most frequent tumor of the eye in children and very little is known about the etiology of non-familial (sporadic) retinoblastoma. In this study we examined whether parental tobacco smoking or alcohol consumption (pre- or post-conception) contribute to the two phenotypes (bilateral or unilateral) of sporadic retinoblastoma. METHODS: Two large multicenter case-control studies identified 488 cases through eye referral centers in the United States and Canada or through the Children's Oncology Group. Controls (n = 424) were selected from among friends and relatives of cases and matched by age. Risk factor information was obtained via telephone interview. We employed multivariable logistic regression to estimate the effects of parental tobacco smoking and alcohol consumption on retinoblastoma. FINDINGS: Maternal smoking before and during pregnancy contributed to unilateral retinoblastoma risk in the child: year before pregnancy conditional Odds Ratio (OR), 8.9; 95% confidence interval (CI) 1.5-51, and unconditional OR, 2.4; 95% CI, 1.3-4.7; month before or during pregnancy, conditional OR, 3.3; 95% CI, 0.5-20.8, and unconditional OR, 2.8; 95% CI, 1.1-7.0. No association was found for maternal or paternal alcohol consumption. CONCLUSION: The results of this study indicate that maternal active smoking during pregnancy may be a risk factor for sporadic retinoblastoma. Our study supports a role for tobacco exposures in embryonal tumors.

A case-control study of sporadic retinoblastoma in relation to maternal health conditions and reproductive factors: a report from the Children's Oncology group.

BACKGROUND: The early age at retinoblastoma occurrence, the most common eye malignancy in childhood, suggests that perinatal factors may contribute to its etiology. METHODS: In a large multicenter study of non-familial retinoblastoma, we conducted structured interviews with the parents of 280 cases and 146 controls to elicit information on health during the perinatal period. We used unconditional logistic regression to assess associations between retinoblastoma and parental fertility treatment, birth control use in the year prior to pregnancy, maternal health conditions and the use of prescription medications during pregnancy, and whether mothers breastfed the index child. RESULTS: Bilateral retinoblastoma was related to maternal underweight (body mass index <18.5) prior to pregnancy [Odds Ratio (OR) = 4.5, 95 % confidence interval (CI) 1.0, 20]. With regards to unilateral retinoblastoma, we observed a negative association with the use of condoms in the year prior to pregnancy (OR = 0.4, CI 0.2, 0.9), and a trend towards a positive association with maternal diabetes (OR = 2.2, CI 0.8, 6.6). CONCLUSIONS: Results from our study suggest a role for several maternal health and reproductive factors. Given that there are few epidemiologic studies of retinoblastoma, our results require replication in studies which utilize medical record review.

Maternal diet during pregnancy and unilateral retinoblastoma.

PURPOSE: Previous studies have suggested a role for parental diet in childhood cancer prevention, but there are few studies of retinoblastoma. The aim of this study was to examine the relation between maternal diet and unilateral retinoblastoma. METHODS: A case-control study of 163 unilateral RB cases and 136 controls ascertained information on maternal diet during pregnancy using a standardized food frequency questionnaire. Logistic regression was used to assess the relation between retinoblastoma and food groups and dietary patterns. RESULTS: We observed a negative association between retinoblastoma and intake of fruit [odds ratio (OR) 0.38, 95 % confidence interval (CI) 0.14-1.02]. Positive associations were seen with intake of cured meats (OR 5.07, 95 % CI 1.63-15.70) and fried foods (OR 4.89, 95 % CI 1.72-13.89). A food pattern of high fruits and vegetables and low fried food and sweets was negatively associated with disease (OR 0.75, 95 % CI 0.61-0.92). CONCLUSION: Our study provides preliminary evidence that mothers who consume diets higher in fruit and lower in fried foods and cured meats during pregnancy may reduce the risk of unilateral retinoblastoma in their offspring.

Antinociceptive and antidiarrheal effects of pioglitazone in a rat model of diarrhoea-predominant irritable bowel syndrome: role of nitric oxide.

Irritable bowel syndrome (IBS) is a prevalent disease characterized by abdominal pain and abnormal bowel habits. Pioglitazone is a peroxisome proliferator-activated receptor (PPAR) γ agonist and, although it is mostly used as an antidiabetic agent, it has been reported to have analgesic effects. Nitric oxide (NO), a gaseous molecule that mediates many of the effects of pioglitazone, has been implicated in the pathophysiology of IBS. The aim of the present study was to investigate the effects of pioglitazone on symptoms in a rat model of diarrhoea-predominant IBS (D-IBS).and to determine the role of NO in these effects. Diarrhoea-predominant IBS was induced by intracolonic instillation of acetic acid. Pioglitazone (2 mg/kg, i.p.) was administered on Days 7, 9 and 11 after acetic acid instillation. To investigate the mechanism involved in pioglitazone action, rats were also administered either the PPARγ antagonist GW9662 (3 mg/kg, i.p.), the NO synthase (NOS) inhibitor N(G) -nitro-l-arginine methyl ester (l-NAME; 10 mg/kg, i.p.) or the NO precursor l-arginine (250 mg/kg, i.p.) along with pioglitazone. Visceral hypersensitivity, nociceptive thresholds, defecation frequency, stool form, serum and colon NO production and inducible (i) NOS activity were assessed 1 h after the final injection of pioglitazone or dimethylsulphoxide (used as the vehicle). Pioglitazone reduced visceral hypersensitivity and defecation frequency, increased nociceptive thresholds, NO production and iNOS activity and shifted stool form towards hard stools in D-IBS rats. These effects of pioglitazone were significantly reversed by l-NAME, but not GW9662. l-Arginine augmented the effects of pioglitazone. In conclusion, pioglitazone alleviates symptoms in a rat model of D-IBS through an NO-dependent mechanism.

Intrasphincteric botulinum toxin injection in treatment of chronic idiopathic constipation in children.

OBJECTIVE: Injection of botulinum toxin into the anal sphincter is a novel and safe new treatment of chronic idiopathic constipation and anal fissure in children. The purpose of this study was to determine the utility of intra sphincteric injection of botox in the treatment of children with refractory constipation. METHODS: All children who suffered from chronic constipation for more than three months, and who had not responded to medical treatment, were referred to pediatrics surgical clinic for surgical intervention by pediatric gastroenterologist. The patients were randomly divided into cases and control group. The control group received no injection and was only treated with stool softeners. The case group received this therapy in addition to injection. After the botox injection, patients were asked about the presence of the signs of constipation including painful defecation, vomiting, stool consistence, soiling and defecation interval. FINDINGS: Defecation of painful stool existed in 88% of patients before botox injection and it was reduced to 15% after botox injection. In the control group, 90% of patients had painful defecation, which reduced to 86% after medical treatment (P=0.0001). Stool was hard in 80% of patients before was reduced to 28% after botox injection. In the control group, it existed in 81% of children and reduced to 78% after medical treatment (P=0.0001). Soiling existed in 62% of patients before and was reduced to 8% after botox injection, but in the control group it reduced from 62% to 42.5% after medical treatment (P=0.0001). In the control group, 98% of the patients had defecation intervals more than 3 days and it was the same after medical treatment. In case group, this index before botox injection was 9.1 days, and after botox injection was reduced to 2.6 days (P=0.0001). CONCLUSION: Our study results showed that injection of botulinum toxin into anal sphincter is an effective and safe new treatment of chronic idiopathic constipation in children.

Literacy and breast cancer prevention: a population-based study from Iran.

Breast cancer is the most common cancer in women worldwide and the leading cause of death from cancer among women. Evidence suggests that early diagnosis and screening interventions might help to improve outcomes. This population-based study was conducted to determine breast cancer awareness and screening behavior among Iranian women and to examine its association with women's literacy. The study was carried out in two provinces, with 1,477,045 population, located in central and eastern part of Iran. Overall, 770 women were studied. Of these, 482 (62.7%) were literate and 287 (37.3%) were not. The results obtained from the data analysis indicated that there was a significant difference between literate and illiterate women. Further analysis of the data using logistic regression showed that literacy was an important contributing factor for breast cancer prevention behavior. The findings suggest that in order to improve women's health and breast cancer outcomes providing equal educational opportunities for women seems necessary.