Paradoxical worsening of ocular symptoms after transvenous embolization of cavernous sinus dural arteriovenous fistula due to coil-induced perifocal inflammation: A case report.

Ocular symptoms usually completely resolve after successful transvenous embolization of cavernous sinus dural arteriovenous fistulas (CS-dAVFs). Herein, we report a case of CS-dAVF in which sinus packing of the superior ophthalmic vein (SOV) caused coil-induced inflammation in orbital tissue, leading to deteriorating ocular symptoms. A 73-year-old woman presented with right-eye exophthalmos and chemosis. Cerebral angiography demonstrated right CS-dAVF, which retrogradely drained into the right SOV. We conducted sinus packing with coils via the right inferior petrosal sinus, resulting in obliteration of the shunts. One day after sinus packing, right exophthalmos and chemosis progressed, suggesting dAVF recurrence. However, no residual angiographic shunts were observed. Orbital magnetic resonance imaging (MRI) revealed edema in intraorbital tissue and gadolinium contrast enhancement of SOV wall. We presumed that the coils in SOV induced perifocal inflammation at the venous wall and surrounding orbital tissue, leading to aggravation of ocular symptoms. Following steroid therapy for 2 months, ocular symptoms and contrast enhancement on orbital MRI significantly improved without anticoagulant treatment. Posttreatment paradoxical worsening of ocular symptoms could be caused by coil-induced inflammation of the SOV wall near the orbital tissue. Steroid therapy could be effective in reducing orbital inflammatory reactions.

Population Pharmacokinetics and Adverse Events of Erlotinib in Japanese Patients with Non-small-cell Lung Cancer: Impact of Genetic Polymorphisms in Metabolizing Enzymes and Transporters.

Determinants of interindividual variability in erlotinib pharmacokinetics (PK) and adverse events remain to be elucidated. This study with 50 Japanese non-small-cell lung cancer patients treated with oral erlotinib at a standard dose of 150 mg aimed to investigate whether genetic polymorphisms affect erlotinib PK and adverse events. Single nucleotide polymorphisms (SNPs) in genes encoding metabolizing enzymes (CYP1A1, CYP1A2, CYP2D6, CYP3A4, CYP3A5, UGT1A1, UGT2B7, GSTM1, and GSTT1) or efflux transporters (ABCB1, and ABCG2) were analyzed as covariates in a population PK model. The ABCB1 1236C>T (rs1128503) polymorphism, not ABCB1*2 haplotype (1236TT-2677TT-3455TT, rs1128503 TT-rs2032582 TT-rs1045642 TT), was a significant covariate for the apparent clearance (CL/F), with the TT genotype showing a 29.4% decrease in CL/F as compared with the CC and the CT genotypes. A marginally higher incidence of adverse events (mainly skin rash) was observed in the TT genotype group; however, patients with high plasma erlotinib exposure did not always experience skin rash. None of the other SNPs affected PK or adverse events. The ABCB1 genotype is a potential predictor for erlotinib adverse events. Erlotinib might be used with careful monitoring of adverse events in patients with ABCB1 polymorphic variants.

Association of ABCB1 polymorphisms with erlotinib pharmacokinetics and toxicity in Japanese patients with non-small-cell lung cancer.

AIMS: We analyzed the association of ABCB1 polymorphisms with erlotinib-induced toxicity and the pharmacokinetics in patients with non-small-cell lung cancer. MATERIALS & METHODS: After erlotinib 150 mg was administered to 50 patients, ABCB1 polymorphisms were analyzed via either TaqMan(®) assays or direct nucleotide sequencing. Plasma concentrations were measured by HPLC. RESULTS: The trough concentration at steady state in patients with the ABCB1 1236TT-2677TT-3435TT genotype was higher compared with others groups (p = 0.021) and patients carrying this genotype had a higher risk of developing higher grade 2 toxicity (p = 0.012). CONCLUSION: The present study suggested that the ABCB1 1236TT-2677TT-3435TT genotype was associated with higher plasma concentration and the risk of developing higher toxicity in patients treated with erlotinib.

Fibroproliferative changes on high-resolution CT in the acute respiratory distress syndrome predict mortality and ventilator dependency: a prospective observational cohort study.

OBJECTIVES: To examine whether the extent of fibroproliferative changes on high-resolution CT (HRCT) scan influences prognosis, ventilator dependency and the associated outcomes in patients with early acute respiratory distress syndrome (ARDS). DESIGN: A prospective observational cohort study. SETTING: Intensive care unit in a teaching hospital. PARTICIPANTS: 85 patients with ARDS who met American-European Consensus Conference Criteria and eligible criteria. INTERVENTIONS: HRCT scans were performed and prospectively evaluated by two independent observers on the day of diagnosis and graded into six findings according to the extent of fibroproliferation. An overall HRCT score was obtained by previously published method. PRIMARY AND SECONDARY OUTCOMES: The primary outcome was 60-day mortality. Secondary outcomes included the number of ventilator-free days, organ failure-free days, the incidence of barotraumas and the occurrence of ventilator-associated pneumonia. RESULTS: Higher HRCT scores were associated with statistically significant decreases in organ failure-free days as well as ventilator-free days. Multivariate Cox proportional hazards model showed that the HRCT score remained an independent risk factor for mortality (HR 1.20; 95% CI 1.06 to 1.36; p=0.005). Multivariate analysis also revealed that the CT score had predictive value for ventilator weaning within 28 days (OR 0.63; 95% CI 0.48 to 0.82; p=0.0006) as well as for an incidence of barotraumas (OR 1.61; 95% CI 1.08 to 2.38; p=0.018) and for an occurrence of ventilator-associated pneumonia (OR 1.46; 95% CI 1.13 to 1.89; p=0.004). A HRCT score <210 enabled prediction of 60-day survival with 71% sensitivity and 72% specificity and of ventilator-weaning within 28 days with 75% sensitivity and 76% specificity. CONCLUSIONS: Pulmonary fibroproliferation assessed by HRCT in patients with early ARDS predicts increased mortality with an increased susceptibility to multiple organ failure, including ventilator dependency and its associated outcomes.

[Solid malignancy in patients who received cyclosporine for fibrosing interstitial pneumonia].

OBJECTIVE: Since more solid malignancies are observed in transplant recipients treated with cyclosporine (CsA) than in healthy persons. We sought to describe the incidence of malignancy in patients treated with CsA for fibrosing interstitial pneumonia. METHODS: We prospectively reviewed 43 patients who received CsA and prednisolone for fibrosing interstitial pneumonia over 180 days at our hospital between April 2004 and October 2008. The duration of CsA treatment was 632 +/- 364 days. RESULTS: Malignancy developed in 6 (14.0%) patients. Time to diagnosis after medical intervention ranged from 394 days to 1325 days (mean, 783 days). Non-small cell lung cancer was diagnosed in 4 cases. These were discovered by routine computed tomography in all cases. Hepatocellular carcinoma and gastric cancer were each diagnosed in 1 case, respectively. Incidence of malignancy tended to be higher in patients who had been treated with CsA for 567 days or more than in those who had been treated for less than 567 days, but this was not statistically significant. CONCLUSION: Our results highlight the need for close follow-up for patients who receive CsA for over 2 years. This could lead to cancer detection at an early stage.