Image-Guided Intensity-Modulated Radiation Therapy for IgG4-Related Ophthalmic Disease.

BACKGROUND: IgG4-related ophthalmic disease is a rare, newly recognized entity with high failure rates on first-line therapy of systemic corticosteroids and no other proven management options. Case Presentation. Here, we present the clinical course of a patient with IgG4 ophthalmic disease who achieved a favorable response from radiotherapy. Our patient initially presented with a history of recurrent painful flares of orbital inflammation, a pathologic diagnosis follicular lymphoid hyperplasia from a right lacrimal gland biopsy, and MRI imaging noting expansion of the lateral rectus muscle of the right eye. Initial treatment with dacryoadenectomy and multiple courses of corticosteroids failed to keep his symptoms at bay. Further evaluation revealed florid IgG4 staining. In this context, he was evaluated for image-guided intensity-modulated radiotherapy (IG-IMRT) to the orbit to 20 Gy in 10 fractions. His ophthalmic symptoms resolved. CONCLUSIONS: This treatment experience suggests radiotherapy may be a favorable option for symptom relief in patients with IgG4-related ophthalmic disease not controlled by corticosteroids.

Vision, Aphasia, Neglect Assessment for Large Vessel Occlusion Stroke.

BACKGROUND AND PURPOSE: Vision, Aphasia, Neglect (VAN) is a large vessel occlusion (LVO) screening tool that was initially tested in a small study where emergency department (ED) nurses were trained to perform VAN assessment on stroke code patients. We aimed to validate the VAN assessment in a larger inpatient dataset. METHODS: We utilized a large dataset and used National Institute of Health Stroke Scale (NIHSS) performed by physicians to extrapolate VAN. VAN was compared to NIHSS greater than or equal to 6 and established prehospital LVO screening tools including Rapid Arterial Occlusion Evaluation scale (RACE), Field Assessment Stroke Triage for Emergency Destination (FAST-ED), and Cincinnati Pre-hospital Stroke Scale (CPSS). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under receiver operating characteristics curve was calculated to estimate the predictive value of LVO. RESULTS: VAN was comparable in sensitivity (79% versus 80%) and NPV (88% versus 87%) to NIHSS greater than or equal to 6. It was superior in specificity (69% versus 57%), PPV (53% versus 46%) and accuracy to NIHSS greater than or equal to 6 (72% versus 64%) with significant receiver operating curve (.74 versus .69, P = .02). VAN also had comparable area under the curve when compared to RACE, FAST-ED, and CPSS however slightly lower accuracy (69%-73%) compared to RACE (76%), FAST-ED (77%), and CPSS (75%). VAN had the highest NPV among all screening assessments (88%). CONCLUSIONS: VAN is a simple screening tool that can identify LVOs with adequate accuracy in hospital setting. Future studies need to be conducted in prehospital setting to validate its utility to detect LVOs in the field.

Vision, Aphasia, Neglect Assessment to Predict Neurosurgical Intervention in Patients with Nontraumatic Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: The Vision, Aphasia, and Neglect (VAN) screening tool is a simple bedside test developed to identify patients with large vessel occlusion stroke. In the setting of intracerebral hemorrhage (ICH), there are very few bedside predictors of need for neurosurgical interventions other than age and Glasgow Coma Scale (GCS). We aimed to assess the utility of the VAN screening tool in predicting the need for neurosurgical intervention in patients with ICH. METHODS: We accessed sensitivity, specificity, positive predictive value, negative predictive value (NPV), and area under receiver operating characteristics curve of VAN for identifying ICH patients who require neurosurgical intervention. RESULTS: Among 228 ICH patients, 176 were VAN positive and 52 were VAN negative. On unadjusted analyses, VAN positive patients had a significantly higher ICH volume, GCS score, and National Institutes of Health Stroke Scale score (P < .001 for all). As compared to VAN negative patients, significantly higher proportion of VAN positive ICH patients (15.4% versus 32.4%) underwent a neurosurgical procedure such as external ventricular drain (EVD) and/or hematoma evacuation with craniotomy or craniectomy. The VAN screening tool had high sensitivity and NPV (100%) in predicting the need for craniectomy or hematoma evacuation, but had lower sensitivity (87.7%) for any neurosurgical procedure, as 15.4% of VAN negative patients received EVD. CONCLUSIONS: Our study suggests that VAN screening tool can identify high-risk ICH patients who are more likely to undergo craniotomy or craniectomy but is less sensitive to rule out need for EVD.

Differential association of cytochrome P450 3A4 genotypes with onsets of breast tumors in African American versus Caucasian patients.

INTRODUCTION: Malignant breast tumors are often hormone-dependent, and to this end, both estrogen and progesterone receptors are good prognostic markers for evaluation of the outcomes after therapy. In addition, HER-2/neu, whose expression is increasingly being associated with poor prognosis of breast cancer, has predictive potential after immunotherapy. Cytochrome P450 3A4 is highly involved in the metabolism of steroids. Thus, we investigated the impact of CYP 3A4 gene variants in association with clinical outcomes in African American (AFAM) versus Caucasian (CAU) patients with breast cancer diagnosis. METHODS: Patients who had undergone biopsy procedures for diagnosis or for partial or radical mastectomy were recruited. The CYP 3A4 genotypes (A or G) were detected using polymerase chain reaction amplification and primers designed for a single nucleotide polymorphism. The messenger RNA (mRNA) transcripts were screened by reverse transcription-polymerase chain reaction. Clinical data including tumor staging, pathology grades, and family history were evaluated. RESULTS: Frequency of the CYP 3A4-G (mutated variant) was significantly increased in AFAM patients as compared with controls (P < 0.001). No statistically significant difference was observed between the genotypes comparing the benign versus ductal carcinomas in situ (DCIS) or infiltrating ductal carcinomas (IDCAs). In AFAM patients, GG alleles were increased in IDCA with stage III tumors, and in CAU patients, the AA alleles were increased with stage III tumors. The mRNA expression was reduced in patients with IDCA versus DCIS or benign tumors (benign vs IDCA, P < 0.0009; DCIS vs IDCA, P < 0.005), as well in HER-2/neu-positive tumors versus samples negative for receptors (P < 0.0024). CONCLUSIONS: Genotype association was affected by race. Expression levels of total CYP 3A4 mRNA were inversely correlated with clinical diagnosis. This may suggest mRNA testing as an additional tool that accelerates improvement in the diagnosis of the onsets of breast cancer.

Epidemic of illicit drug use, mechanisms of action/addiction and stroke as a health hazard.

Drug abuse robs individuals of their jobs, their families, and their free will as they succumb to addiction; but may cost even more: a life of disability or even life lost due to stroke. Many illicit drugs have been linked to major cardiovascular events and other comorbidities, including cocaine, amphetamines, ecstasy, heroin, phencyclidine, lysergic acid diethylamide, and marijuana. This review focuses on available epidemiological data, mechanisms of action, particularly those leading to cerebrovascular events, and it is based on papers published in English in PubMed during 1950 through February 2011. Each drug's unique interactions with the brain and vasculature predispose even young, healthy people to ischemic or hemorrhagic stroke. Cocaine and amphetamines have the strongest association with stroke. However, the level of evidence firmly linking other drugs to stroke pathogenesis is weak. Large epidemiological studies and systematic evaluation of each drug's action on the brain and cardiovascular system are needed to reveal the full impact of drug use on the population.

Effect of hepatic artery flow on bile secretory function after cold ischemia.

These studies evaluated the influence of hepatic arterial flow on biliary secretion after cold ischemia. Preparation of livers for transplantation or hepatic support impairs biliary secretion. The earliest indication of cold preservation injury during reperfusion is circulatory function. Arterial flow at this time may be critical for bile secretion. Porcine livers were isolated, maintained at 4 degrees for 2 h and connected in an extracorporeal circuit to an anesthetized normal pig. The extracorporeal livers were perfused either by both the hepatic artery and portal vein (dual) or by the portal vein alone (single). Incremental doses of sodium taurocholate were infused into the portal vein of both the dual and single perfused livers, and the bile secretion was compared. Most endogenous bile acids are lost during hepatic isolation. After supplementation, the biliary secretion of phosphatidyl choline and cholesterol was significantly better in the dual than single vessel-perfused livers; however, no difference was seen in bilirubin output. Single perfused livers were completely unable to increase biliary cholesterol in response to bile acid. The dependence of bile cholesterol secretion on arterial flow indicates the importance of this flow to the detoxification of compounds dependent on phosphatidyl choline transport during early transplantation.