Cellular Density in Adult Glioma, Estimated with MR Imaging Data and a Machine Learning Algorithm, Has Prognostic Power Approaching World Health Organization Histologic Grading in a Cohort of 1181 Patients.

BACKGROUND AND PURPOSE: Recent advances in machine learning have enabled image-based prediction of local tissue pathology in gliomas, but the clinical usefulness of these predictions is unknown. We aimed to evaluate the prognostic ability of imaging-based estimates of cellular density for patients with gliomas, with comparison to the gold standard reference of World Health Organization grading. MATERIALS AND METHODS: Data from 1181 (207 grade II, 246 grade III, 728 grade IV) previously untreated patients with gliomas from a single institution were analyzed. A pretrained random forest model estimated voxelwise tumor cellularity using MR imaging data. Maximum cellular density was correlated with the World Health Organization grade and actual survival, correcting for covariates of age and performance status. RESULTS: A maximum estimated cellular density of >7681 nuclei/mm2 was associated with a worse prognosis and a univariate hazard ratio of 4.21 (P < .001); the multivariate hazard ratio after adjusting for covariates of age and performance status was 2.91 (P < .001). The concordance index between maximum cellular density (adjusted for covariates) and survival was 0.734. The hazard ratio for a high World Health Organization grade (IV) was 7.57 univariate (P < .001) and 5.25 multivariate (P < .001). The concordance index for World Health Organization grading (adjusted for covariates) was 0.761. The maximum cellular density was an independent predictor of overall survival, and a Cox model using World Health Organization grade, maximum cellular density, age, and Karnofsky performance status had a higher concordance (C = 0.764; range 0.748-0.781) than the component predictors. CONCLUSIONS: Image-based estimation of glioma cellularity is a promising biomarker for predicting survival, approaching the prognostic power of World Health Organization grading, with added values of early availability, low risk, and low cost.

Comparing febrile children presenting on and off antibiotics to the emergency department: a retrospective cohort study.

BACKGROUND: It is not yet known how antibiotics may affect Serious Bacterial Infections (SBI). Our aim is to describe the presentation, management, and serious bacterial infections (SBI) of febrile children on or off antibiotics. METHODS: Retrospective, cohort study of febrile Emergency Department patients, 0-36 months of age, at a single institution, between 2009and 2012. RESULTS: Seven hundred fifty-three patients were included: 584 in the No-Antibiotics group and 169 (22%) in the Antibiotics group. Age and abnormal lung sounds were predictors for being on antibiotics (OR 2.00 [95% CI 1.23-3.25] and OR 1.04 [95% CI 1.02-1.06] respectively) while female gender, and lower temperatures were negative predictors (OR 0.68 [95%0.47-0.98] and OR 0.47 [95% CI 0.32-0.67] respectively). Antibiotics were prescribed by a physician 89% of the time; the most common one being Amoxicillin/Clavulanic Acid (39%). The antibiotic group got more blood tests (57% vs 45%) and Chest X-Rays (37% vs 25%). Overall, the percent of SBIs (and pneumonias) was statistically the same in both groups (6.5% in the No-antibiotic group VS 3.6%). CONCLUSIONS: Children presenting on antibiotics and off antibiotics were significantly different in their presentation and management, although the overall percentages of SBI were similar in each group. Further investigations into this subgroup of febrile children are needed.

Acute neurological visual loss in young adults: causes, diagnosis and management.

Visual loss in the young adult can be caused by demyelinating diseases, inflammatory and autoimmune processes, infections, ischaemic events, and compressive lesions of the optic nerve. Diagnosis of the aetiologies of visual loss is reached by combining data from radiological studies, electrophysiological tests, and blood and cerebrospinal fluid analysis. Treatment is primarily aimed at decreasing the insult on the optic nerve and eventually controlling the primary disorder. The literature discusses separately the different aetiologies of visual loss. We present a review of the clinical characteristics of visual loss in the young adult, the different diagnostic measures, and the latest therapeutic strategies. The aim of this work is to summarise this entity in a practical way to guide clinicians in the diagnosis and management of this disorder.

Review article: the biology, diagnosis and management of gastrointestinal stromal tumours.

BACKGROUND: Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the gastrointestinal tract with an increasing incidence. AIMS: To review the biology, diagnosis and treatment of gastrointestinal stromal tumours. METHODS: A PubMed search using the phrases 'Gastrointestinal stromal tumor', 'imatinib', 'c-kit'. RESULTS: The diagnosis of GIST is established by histology supplemented by the immunohistochemical marker CD117, which is positive in 95% of cases. The most common site of the tumour is the stomach. Most GIST are benign with 20-30% malignant. Five-year survival for malignant GIST ranges between 35% and 65% and depends primarily on tumour size, mitotic index and location. The malignant behaviour of GIST is best assessed by invasion of adjacent structures and distant metastases. The gold standard for treatment is surgical resection. Imatinib, a tyrosine kinase inhibitor, is the primary therapy for unresectable, recurrent or metastatic disease. CONCLUSIONS: Gastrointestinal stromal tumours are rare tumours of the gastrointestinal tract and they vary in presentation. When surgical resection is not achievable, imatinib is the treatment of choice.

Irritable bowel syndrome-type symptoms in female patients with mild systemic lupus erythematosus: frequency, related factors and quality of life.

BACKGROUND: Irritable bowel syndrome (IBS) impairs quality of life (HRQOL), as does systemic lupus erythematosus (SLE). Both are more common in women and are associated with fibromyalgia (FM). However, the relationship between IBS and SLE and its impact on HRQOL has not been explored. Therefore, we aimed to study the frequency and features likely to influence the presence of IBS-type symptoms in SLE and their impact on HRQOL. METHODS: Female patients with SLE were studied. The presence of IBS-type symptoms and bowel habit subtype were established by Rome III criteria and HRQOL was assessed using the SF-36. Fibromyalgia and depression were assessed using the American College of Rheumatology criteria and CES-D scale, respectively. KEY RESULTS: A total of 105 consecutive patients (43.62 ± 11.34 years old) were included; 48.6% had IBS-type symptoms (SLE+IBS) and were classified as IBS-C: 23.5%, IBS-D: 37.3%, and IBS-M: 39.2%. In addition, 23.8% had FM. SLE+IBS vs Non-IBS SLE patients had higher SLE activity scores (2.55 ± 1.65 vs 1.74 ± 2.19; p = 0.03), were more likely to have FM (33.0% vs 14.8%; p = 0.02) and depression (41.1% vs 25.9%, p = 0.04). Logistic multivariate analysis showed that IBS-type symptoms were associated with FM (OR = 2.85, 95% CI: 1.11-7.43) and depression (OR = 1.07, 95% CI: 1.02-1.13). Finally, SLE+IBS vs Non-IBS SLE patients had lower SF-36 scores (49.65 ± 18.57 vs 62.67 ± 18.14; p = 0.02). CONCLUSIONS & INFERENCES: IBS-type symptoms are highly prevalent among women with SLE and are associated with FM and depression. SLE+IBS patients had worse HRQOL vs Non-IBS SLE, independently of FM status. We suggest that treating IBS symptoms may improve HRQOL in women with SLE.

Use of the Montreal global definition as an assessment of quality of life in reflux disease.

According to the Montreal Consensus Group's classification, gastroesophageal reflux disease develops when the reflux of stomach contents causes troublesome symptoms and/or complications such as esophagitis. The characteristic gastroesophageal reflux disease symptoms included in this statement are retrosternal burning and regurgitation. Troublesome is meant to imply that these symptoms impact on the well-being of affected individuals; in essence, quality of life (QOL). Whether heartburn and regurgitation symptoms would be characterized as more troublesome in those with confirmed pathologic acid reflux was determined. A second purpose was to assess how well troublesome scores correlated with the results of a validated, disease-specific QOL instrument. Subjects who underwent esophagogastroduodenoscopy (EGD) with 48-hour wireless esophageal pH testing off proton pump inhibitor therapy were interviewed. Esophagitis on EGD or pH < 4.0 for ≥4.5% of time over the 2-day period was considered positive for acid reflux. Assessment of how troublesome their symptoms of heartburn and regurgitation were made using separate 0-100 visual analog scales (VAS). Subjects were then asked to complete the Quality of Life in Reflux and Dyspepsia (QOLRAD) 25-item questionnaire. Sixty-seven patients (21 males, 46 females) with mean age 47.8 ± 15.6 years were identified. Forty (59.7%) had an EGD or pH study positive for acid reflux. Overall 35/40 (87.5%) complained of either heartburn or regurgitation. There was no difference (P= 0.80) in heartburn VAS troublesome ratings for those with (54.0 ± 43.9) and without (56.7 ± 37.6) confirmed acid reflux. The same was true for regurgitation VAS troublesome ratings (P= 0.62). Likewise, mean QOLRAD scores did not differ between those with and without confirmed acid reflux by pH or EGD (4.5 ± 1.7 vs. 4.3 ± 1.7; P= 0.61). There was a moderately strong inverse correlation between patient self-rated VAS troublesome scores for both heartburn and regurgitation with each dimension (emotional distress, sleep disturbance, eating problems, physical/social functioning, and vitality) of the QOLRAD (P < 0.05 for all comparisons). In regression analysis, both heartburn and regurgitation troublesome ratings were associated with the overall QOLRAD score independent of pH data, frequency of reflux episodes, age, and gender. Use of the term troublesome in the Montreal Consensus Group classification is supported by our findings. It correlates well with the results of a validated disease-specific QOL instrument. Use of heartburn and regurgitation VAS may serve as accurate measures of the burden of reflux disease on patients. It is likely that these scales will not have sufficient discriminate value to identify individuals with pathologic acid reflux from those with negative studies.

Acute quadriplegia in a young man secondary to prothrombin G20210A mutation.

STUDY DESIGN: We present the case of an 18-year-old man, previously healthy, who presented with acute quadriplegia and respiratory failure. Physical examination was compatible with a high cervical anterior spinal cord lesion. OBJECTIVE: We plan to evaluate the cause of such a neurological presentation in a healthy young man. SETTING: American University Medical Center, Beirut, Lebanon. METHODS: The patient underwent routine blood hematological and chemistry work-up, hypercoagulable profile studies, genetic profile for thrombophelias, radiographic studies of the brain and cervical cord, cerebrospinal analysis and extensive electrophyisological studies. RESULTS: Magnetic resonance imaging and magnetic resonance angiogram of the brain, carotid and intracranial vessels were normal. Cerebral angiography was normal. Magnetic resonance imaging of the cervical cord revealed lesion of the anterior segment of the cervical cord between C2 and C5 levels. Hypercoagulable profile studies were normal. Electrophysiological studies confirmed an isolated lesion of the descending cortico-spinal tracts. DNA analysis revealed the presence of a G20210A mutation-causing hyperprothrombinemia. CONCLUSION: We conclude that a G20210A mutation causing-hyperprothrombinemia can cause anterior spinal artery thrombosis and anterior spinal cord infarction with the resultant neurological deficits in otherwise healthy patients.

PRODIGE: a randomized placebo-controlled trial of dalteparin low-molecular-weight heparin thromboprophylaxis in patients with newly diagnosed malignant glioma.

BACKGROUND AND OBJECTIVES: Venous thromboembolism (VTE) occurs in 20-30% of patients with malignant glioma per year of survival. We tested the efficacy of long-term dalteparin low-molecular-weight heparin (LMWH) for prevention of VTE in these patients. PATIENTS/METHODS: Adults with newly diagnosed malignant glioma were randomized to receive dalteparin 5000 anti-Xa units or placebo, both subcutaneously once daily for 6 months starting within 4 weeks of surgery. Treatment continued for up to 12 months. The primary outcome was the cumulative risk of VTE over 6 months. The target sample size was 512 patients. Events were adjudicated by a committee unaware of treatment. RESULTS: The trial began in 2002 and closed in May 2006 because of expiration of study medication. Ninety-nine patients were randomized to LMWH and 87 to placebo. Twenty-two patients developed VTE in the first 6 months: nine in the LMWH group and 13 in the placebo group [hazard ratio (HR) = 0.51, 95% confidence interval (CI): 0.19-1.4, P = 0.29]. At 6 months, there were three major bleeds on LMWH and none on placebo; at 12 months, 5 (5.1%) major bleeds on LMWH and 1 (1.2%) on placebo occurred (HR = 4.2, 95% CI: 0.48-36, P = 0.22). All major bleeds were intracranial and occurred while on study medication. The 12-month mortality rates were 47.8% for LMWH and 45.4% for placebo (HR = 1.2, 95% CI: 0.73-2.0, P = 0.48). CONCLUSIONS: Trends suggesting reduced VTE and increased intracranial bleeding were seen in the LMWH thromboprophylaxis group. The role of long-term anticoagulant thromboprophylaxis in patients with brain tumors remains uncertain.

Inhibition of gliomagenesis and attenuation of mitotic transition by MIIP.

The migration and invasion inhibitor protein (MIIP, also known as IIp45) was discovered as a negative regulator of cell migration and invasion in glioma. Our previous studies have shown that the MIIP protein was reduced or undetectable in some tissue samples obtained from patients with glioblastoma. The significance of MIIP in gliomagenesis is unknown. In this study, we report that MIIP has an important role in the inhibition of gliomagenesis and attenuation of mitotic transition. Increased MIIP expression levels inhibited colony formation and cell growth of glioma cell lines in vitro, whereas decreased expression by specific small interfering RNA for MIIP resulted in increased cell growth. Expression of MIIP in a glial-specific mouse model blocked glioma development and progression, thus showing that MIIP is an inhibitor of gliomagenesis. Furthermore, we show that MIIP attenuates mitotic transition and results in increased mitotic catastrophe. The biochemical mechanism of MIIP in this process is associated with its regulation of anaphase-promoting complex (APC/C) activity. MIIP interacts directly with Cdc20, and the interaction of MIIP with Cdc20 inhibits APC/C-mediated degradation of cyclin B1. Thus, MIIP attenuates mitotic transition and increases mitotic catastrophe, thereby inhibiting glioma development and progression.

Early neurologic complications following coronary bypass surgery.

BACKGROUND: Coronary artery bypass surgery is associated with central and peripheral nervous system complications in the period following surgery. Recognising these complications may help in their prevention or early treatment. METHODS: We reviewed medical records of all the patients who underwent coronary artery bypass surgery at our institution over a period of two years. We studied their risk factors, reasons for surgery, operative variables, and post operative neurologic complications. RESULTS: Of the 587 coronary artery bypass surgeries performed at our centre over a two year period. We found that 2.04% of these patients developed neurologic complication in the two weeks following the surgery. Fifty percent of these patients suffered from cerebrovascular insults and 50% suffered from cognitive decline. No patients in this group developed seizures or peripheral nerve lesions. Patients with renal failure, carotid stenosis, history of cerebral strokes, and redo coronary bypass surgery were more predisposed to develop neurologic complications after bypass surgery. Furthermore, a longer stay in the coronary care unit and the development of arrhythmias predisposed patients to neurologic complications. Mortality for patients who developed neurologic complications post bypass surgery ranged between 16.7% and 33.4%. CONCLUSIONS: Around 2% of patients who undergo coronary artery bypass surgery develop neurologic complications in the period directly after the surgery. Patients with previous history of cerebral, coronary, or carotid disease are more predisposed for such complications, as well as patients who spend more time in the intensive units after the surgery.