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Concept: Second grade

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Objective: To evaluate the complications, survival and oncological outcome of patients ≥75 years of age after radical cystectomy for muscle-invasive bladder cancer. Patients and Methods: Between April 1993 and August 2010, 765 patients with muscle-invasive bladder cancer underwent radical cystectomy at one high-volume center. Of these, 70 patients were ≥75 years of age. All 70 patients had at least one severe systemic comorbidity with an American Society of Anesthesiologists score of 3. Primary endpoints of this retrospective study were overall and recurrence-free survival with a mean follow-up of 22 months (1-159). Perioperative parameters such as need for blood transfusions, hospital stay, mortality, short- and long-term complications were also assessed. Complications were graded according to the Clavien-Dindo classification. Results: Perioperative complications occurred in 23/70 patients (33%) with a 30-day mortality rate of 1.4%. 16/70 patients (23%) developed late complications requiring hospitalization. Within 30 days of surgery, according to the Clavien-Dindo grading, 27% had no complications, 3% grade 1, 49% grade 2, 14% grade 3, 6% grade 4 and 1.4% grade 5 complications. Within 31-90 days after surgery, 76% had grade 1 complications, 3% grade 2, 6% grade 3, 9% grade 4 and 6% grade 4 complications. The calculated 5- and 8-year overall survival rates were 30 and 25%, respectively, with a recurrence-free survival rate of 52% at 5 and 42% at 8 years. Conclusions: Radical cystectomy is an appropriate and effective treatment for comorbid elderly patients. The oncological long-term outcome is the same as in younger patients while overall survival is comparatively lower. Mortality and complication-related morbidity are comparable to those in younger patients with modern perioperative management.

Concepts: Grade, Third grade, Fourth grade, Bladder cancer, Second grade, Surgery, Cancer, Educational years

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OBJECTIVE: Endometrial cancer patients may benefit from systemic adjuvant chemotherapy, alone or in combination with targeted therapies. Prognostic and predictive markers are needed, however, to identify patients amenable for these therapies. METHODS: Primary endometrial tumors were genotyped for >100 hot spot mutations in genes potentially acting as prognostic or predictive markers. Mutations were correlated with tumor characteristics in a discovery cohort, replicated in independent cohorts and finally, confirmed in the overall population (n=1,063). RESULTS: PIK3CA, PTEN and KRAS mutations were most frequently detected, respectively in 172 (16.2%), 164 (15.4%) and 161 (15.1%) tumors. Binary logistic regression revealed that PIK3CA mutations were more common in high-grade tumors (OR=2.03; P=0.001 for grade 2 and OR=1.89; P=0.012 for grade 3 compared to grade 1), whereas a positive TP53 status correlated with type II tumors (OR=11.92; P<0.001) and PTEN mutations with type I tumors (OR=19.58; P=0.003). Conversely, FBXW7 mutations correlated with positive lymph nodes (OR=3.38; P=0.045). When assessing the effects of individual hot spot mutations, the H1047R mutation in PIK3CA correlated with high tumor grade and reduced relapse-free survival (HR=2.18; P=0.028). CONCLUSIONS: Mutations in PIK3CA, TP53, PTEN and FBXW7 correlate with high tumor grade, endometrial cancer type and lymph node status, whereas PIK3CA H1047R mutations serve as prognostic markers for relapse-free survival in endometrial cancer patients.

Concepts: Lymph, Second grade, Endometrial cancer, Lymph node, Mutation, Regression analysis, Oncology, Cancer

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Objective: The purpose of this study was to describe computed tomography (CT) features of the ununited anconeal process and relate them with the following elbow dysplasia signs: medial coronoid disease, medial humeral condyle changes, osteoarthritis (OA), and radioulnar incongruence. Methods: Computed tomographic images of dogs older than six months with an ununited anconeal process were evaluated (n = 13). Ununited anconeal process features were described as being complete or incomplete, and the degree of displacement, volume, and presence of cysts and sclerosis were also evaluated. Medial coronoid disease was defined as an irregular medial coronoid process shape, presence of sclerosis and fragmentation. Medial humeral condyle changes were defined as subchondral bone flattening, lucencies, and sclerosis. Osteoarthritis was graded depending on the osteophytes size. Radioulnar incongruence was measured on a sagittal view at the base of the medial coronoid process. Results: Eleven elbows had a complete and two had an incomplete ununited anconeal process. All ununited anconeal processes had cystic and sclerotic lesions. Seven ununited anconeal processes were displaced and six were non-displaced. Mean ununited anconeal process volume was 1.35 cm3 (0.61 cm³ - 2.08 cm³). Twelve elbows had signs of medial coronoid disease (4 of them with a fragmented medial coronoid process), and one elbow did not show any evidence of medial coronoid disease. Ten elbows had medial humeral condyle changes. One elbow had grade 1 OA, seven elbows had grade 2, and five elbows grade 3. All elbows had radioulnar incongruence: three elbows had a negative and 10 elbows had a positive radioulnar incongruence. Mean radioulnar incongruence was 1.49 mm (0.63 mm - 2.61 mm). Computed tomographic findings were similar in the majority of the elbows studied: complete ununited anconeal processes with signs of medial coronoid disease, positive radioulnar incongruence, high grade of OA, sclerotic medial humeral condyle changes, and large ununited anconeal process volumes. Clinical significance: Incomplete small ununited anconeal process volumes could be associated with a lower incidence of medial coronoid disease or medial humeral condyle changes. We recommend performing preoperative CT of elbows with an ununited anconeal process to evaluate concurrent lesions.

Concepts: Brachioradialis, Tomographic reconstruction, Brachialis muscle, Second grade, Humerus, Tomography, Coronoid process of the ulna, Elbow

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BACKGROUND: School children usually use a backpack to carry their school materials. Carrying heavy schoolbags exceeding the recommended limit may have negative health implications.OBJECTIVE: To investigate the weight of schoolbags carried by primary school pupils (aged 7-9 years) in Grades 1-3 and determine how many pupils carry backpacks in excess of the recommended limit of 10 per cent of body weight (%BW). A comparison of the schoolbag weight carried by male and female pupils will also be performed. PARTICIPANTS: One hundred and eight healthy pupils chosen at random from two participating schools from south-west Poland; 54 male and 54 female.METHODS: The personal body weight scale was used for measuring the weight. The height and weight of each participating pupil was measured, and the schoolbag weight of every participant checked over five consecutive days, from Monday to Friday. RESULTS: The mean schoolbag weight of Grade 1 pupils was 3.23 kg, (i.e.13.1%BW); of Grade 2 pupils, 3.61 kg (i.e.12.9%BW) and of Grade 3 pupils 3.37 kg (i.e. 11.1%BW).CONCLUSIONS: 78.3% of Grade 1 pupils, 43.3% of Grade 2 pupils and 40.0% of Grade 3 pupils carried backpacks exceeding 10%BW. There were no statistically significant differences between the mean schoolbag weight of males and females in particular school grades.

Concepts: High school, School, Sex, Female, Male, Primary school, Second grade, Primary education

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This study examined whether the negative association between children’s attention difficulties and their academic functioning is largely confined to children whose attention problems persist across early grades and whether it depends on when attention problems emerge in children’s schooling. Children from the normative sample of the Fast Track study were classified into four attention problem groups based on the presence versus absence of attention problems in first and second grade. Those with attention problems in both grades showed a decline in reading and math achievement during the K-5 interval relative to children with attention problems in first grade only. Both groups of inattentive first graders also performed worse than comparison children. In contrast, children whose attention problems emerged in second grade did not differ from comparison children on any achievement outcome performed significantly better than inattentive first graders. The implications of these findings are discussed. (J. of Att. Dis. XXXX; XX(X) XX-XX).

Concepts: Educational years, Problem solving, Problem, Second grade, First grade, Grade

5

Although much research has been concerned with the development of kinematic aspects of handwriting, little is known about the development along with age of two principles that govern its rhythmic organization: Homothety and Isochrony. Homothety states that the ratio between the durations of the single motor events composing a motor act remains invariant and independent from the total duration of the movement. Isochrony refers to the proportional relationship between the speed of movement execution and the length of its trajectory. The current study shows that children comply with both principles since their first grade of primary school. The precocious adherence to these principles suggests that an internal representation of the rhythm of handwriting is available before the age in which handwriting is performed automatically. Overall, these findings suggest that despite being a cultural acquisition, handwriting appears to be shaped by more general constraints on the timing planning of the movements.

Concepts: Organization, Kindergarten, Primary education, Second grade, Primary school, Ratio, Rhythm

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Background In this phase 3 trial we evaluated the efficacy and safety of the interferon-free combination of ABT-450 with ritonavir (ABT-450/r), ombitasvir (also known as ABT-267), dasabuvir (also known as ABT-333), and ribavirin for the retreatment of HCV in patients who were previously treated with peginterferon-ribavirin. Methods We enrolled patients with HCV genotype 1 infection and no cirrhosis who had previously been treated with peginterferon-ribavirin and had a relapse, a partial response, or a null response. Patients were randomly assigned in a 3:1 ratio to receive coformulated ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir) and dasabuvir (250 mg twice daily) with ribavirin (1000 or 1200 mg daily) or matching placebos during the 12-week double-blind period. The primary end point was the rate of sustained virologic response 12 weeks after the end of study treatment. The primary efficacy analysis compared this rate among patients assigned to the active regimen with a historical response rate (65%) among previously treated patients with HCV genotype 1 infection and no cirrhosis who had received retreatment with telaprevir and peginterferon-ribavirin. Results A total of 394 patients received at least one study-drug dose. In the active-regimen group, 286 of 297 patients had a sustained virologic response at post-treatment week 12, for an overall rate of 96.3% (95% confidence interval, 94.2 to 98.4). This rate was noninferior and superior to the historical control rate. Rates were 95.3% among patients with a prior relapse (82 of 86 patients), 100% among patients with a prior partial response (65 of 65 patients), and 95.2% among patients with a prior null response (139 of 146 patients). Pruritus occurred more frequently with the active regimen (in 13.8% of patients) than with placebo (5.2%, P=0.03). Three patients in the active-regimen group (1.0%) discontinued the study drugs owing to adverse events. Hemoglobin values of grade 2 (8.0 to <10.0 g per deciliter) and grade 3 (6.5 to <8.0 g per deciliter) occurred in 4.7% and 0.3% of patients in the active-regimen group, respectively. Conclusions Rates of response to a 12-week interferon-free combination regimen were more than 95% among previously treated patients with HCV genotype 1 infection, including patients with a prior null response. (Funded by AbbVie; SAPPHIRE-II ClinicalTrials.gov number, NCT01715415 .).

Concepts: Medical terms, Placebo, Second grade, Statistical inference, Clinical trial, Hepatitis C

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OBJECTIVE This is the first clinical outcomes report of NRG Oncology RTOG 0539, detailing the primary endpoint, 3-year progression-free survival (PFS), compared with a predefined historical control for intermediate-risk meningioma, and secondarily evaluating overall survival (OS), local failure, and prospectively scored adverse events (AEs). METHODS NRG Oncology RTOG 0539 was a Phase II clinical trial allocating meningioma patients to 1 of 3 prognostic groups and management strategies according to WHO grade, recurrence status, and resection extent. For the intermediate-risk group (Group 2), eligible patients had either newly diagnosed WHO Grade II meningioma that had been treated with gross-total resection (GTR; Simpson Grades I-III) or recurrent WHO Grade I meningioma with any resection extent. Pathology and imaging were centrally reviewed. Patients were treated with radiation therapy (RT), either intensity modulated (IMRT) or 3D conformal (3DCRT), 54 Gy in 30 fractions. The RT target volume was defined as the tumor bed and any nodular enhancement (e.g., in patients with recurrent WHO Grade I tumors) with a minimum 8-mm and maximum 15-mm margin, depending on tumor location and setup reproducibility of the RT method. The primary endpoint was 3-year PFS. Results were compared with historical controls (3-year PFS: 70% following GTR alone and 90% with GTR + RT). AEs were scored using NCI Common Toxicity Criteria. RESULTS Fifty-six patients enrolled in the intermediate-risk group, of whom 3 were ineligible and 1 did not receive RT. Of the 52 patients who received protocol therapy, 4 withdrew without a recurrence before 3 years leaving 48 patients evaluable for the primary endpoint, 3-year PFS, which was actuarially 93.8% (p = 0.0003). Within 3 years, 3 patients experienced events affecting PFS: 1 patient with a WHO Grade II tumor died of the disease, 1 patient with a WHO Grade II tumor had disease progression but remained alive, and 1 patient with recurrent WHO Grade I meningioma died of undetermined cause without tumor progression. The 3-year actuarial local failure rate was 4.1%, and the 3-year OS rate was 96%. After 3 years, progression occurred in 2 additional patients: 1 patient with recurrent WHO Grade I meningioma and 1 patient with WHO Grade II disease; both remain alive. Among 52 evaluable patients who received protocol treatment, 36 (69.2%) had WHO Grade II tumors and underwent GTR, and 16 (30.8%) had recurrent WHO Grade I tumors. There was no significant difference in PFS between these subgroups (p = 0.52, HR 0.56, 95% CI 0.09-3.35), validating their consolidation. Of the 52 evaluable patients, 44 (84.6%) received IMRT, and 50 (96.2%) were treated per protocol or with acceptable variation. AEs (definitely, probably, or possibly related to protocol treatment) were limited to Grade 1 or 2, with no reported Grade 3 events. CONCLUSIONS This is the first clinical outcomes report from NRG Oncology RTOG 0539. Patients with intermediate-risk meningioma treated with RT had excellent 3-year PFS, with a low rate of local failure and a low risk of AEs. These results support the use of postoperative RT for newly diagnosed gross-totally resected WHO Grade II or recurrent WHO Grade I meningioma irrespective of resection extent. They also document minimal toxicity and high rates of tumor control with IMRT. Clinical trial registration no.: NCT00895622 (clinicaltrials.gov).

Concepts: Second grade, Adverse event, Medicine, Radiation therapy, Tumor, Oncology, Clinical trial, Cancer

3

Using a longitudinal cluster-randomized controlled design, we examined whether students' reading outcomes differed when they received 1, 2, or 3 years of individualized reading instruction from first through third grade, compared with a treated control group. More than 45% of students came from families living in poverty. Following students, we randomly assigned their teachers each year to deliver individualized reading instruction or a treated control condition intervention focused on mathematics. Students who received individualized reading instruction in all three grades showed the strongest reading skills by the end of third grade compared with those who received fewer years of such instruction. There was inconsistent evidence supporting a sustained first-grade treatment effect: Individualized instruction in first grade was necessary but not sufficient for stronger third-grade reading outcomes. These effects were achieved by regular classroom teachers who received professional development, which indicates that policies that support the use of evidence-based reading instruction and teacher training can yield increased student achievement.

Concepts: School, Educational years, Profession, Reading, Education, Student, Second grade, Teacher

1

Since the last two decades, the feasibility of fertility-sparing surgery (FSS) in early-stage epithelial ovarian cancer has been explored by several teams and is reconsidered in this systematic review undertaken using the PRISMA guidelines. Borderline ovarian tumours and non-epithelial ovarian cancers were excluded. This review comprises 1150 patients and 139 relapsing patients reported by 21 teams. This conservative treatment can be safely performed for stage IA and IC grade 1 and 2 disease and stage IC1 according to the new FIGO staging system. Nevertheless the number of patients reported with grade 2 disease is too small to definitively confirm whether FSS is safe in this subgroup. For patients with “less favourable” prognostic factors (grade 3 or stage IC3 disease), the safety of FSS could not be confirmed but patients should be informed that radical treatment probably may not necessarily improve their oncological outcome, because the poorest survival observed could be related to the natural history of the disease itself and not specifically to the use of conservative therapy. FSS could probably be considered in stage I clear-cell tumours but should remain contraindicated for stage II/III disease (whatever the histologic subtype). As the disease stage and the histologic data (tumour type and grade) are crucial to patient selection for this treatment, this implies careful and mandatory complete surgical staging surgery in this context and a pathologic analysis (or review) of the tumour by an expert pathologist.

Concepts: Second grade, Metastasis, Cancer staging, Tumor, Oncology, Medicine, Ovarian cancer, Cancer