Metastatic Lung Cancer Masquerading as Endophthalmitis.

A 41-year-old man presented to the emergency department with a painful and red left eye associated with chronic vision loss. He had a history of homelessness and polysubstance abuse including intravenous drug use. Fundus examination revealed several cream-colored lesions encroaching on the macula of the right eye, and a total retinal detachment with secondary neovascular glaucoma in the left eye. Further work-up with imaging and endobronchial ultrasound-guided fine needle aspiration revealed stage IV epidermal growth factor receptor (EGFR) mu- tant (L858R) lung adenocarcinoma with brain, bone, adrenal, lymph node and bilateral choroid- al metastases. Herein we present a case of metastatic lung cancer masquerading as endophthalmitis.

Aircrew and Handheld Laser Exposure.

BACKGROUND: Laser devices are ubiquitous in everyday operations. These devices pose a hazard to the eye and numerous injuries have been documented. However, there lies a misunderstanding in the propensity to damage aircrews' eyes during an exposure. Patient encounters and article review is presented in hopes to raise awareness that aircrew laser exposure at altitude, outside of critical phases of flight, is a distraction and not a threat. Also, to propose a change to Air Force policy regarding such exposures and further educating flight surgeons. METHODS: An electronic medical record (EMR) search at a deployed clinic was performed from July 2016 through Jan 2017. The "reason for visit" column was perused for any reference to the eye and laser exposure. Subsequently, the patient encounters were scrutinized specifically for eye injury, optometry visit, color of laser, and suspension of flight duties. All members were military aircrew spanning loadmasters, boom operators, and pilots. No protective lenses or other forms of optics were employed at time of exposure. RESULTS: There were 21 encounters reviewed; 1 patient was seen twice due to 2 separate instances. Of the encounters, 14 were green lasers, 6 did not comment, and 1 indicated white. Zero acute injuries were discovered. DISCUSSION: Patients were needlessly sent for further examination and prohibited from performing their duties. Following military patient encounters and civilian literature regarding laser injury, the evidence highly supports the hypothesis that hand-held laser exposure in flight from a ground base does not engender eye injury. More emphasis should be placed on recognizing the laser threat as a distraction or disruption to critical phases of flight, and a policy change may be in order for the USAF laser exposure guide.Dietrich KC. Aircrew and handheld laser exposure. Aerosp Med Hum Perform. 2017; 88(11):1040-1042.

Fighter Pilot with Recurrent Central Serous Chorioretinopathy.

BACKGROUND: Central serous chorioretinopathy (CSC) is usually a self-limiting condition; however, there is potential for recurrence and permanent visual defects. Aviation demands perfect vision to minimize risk to pilots and aircraft. Consequently, this ailment disqualifies pilots and pilots to be. CASE REPORT: A fully trained fighter pilot with 1260 h in fighter airframes has been contending with central serous chorioretinopathy in the right eye over the course of 3 yr. The condition was diagnosed after the member presented with visual disturbances. His course was followed with multiple treatment modalities: watchful waiting, micropulse laser, and rifampin. His disease responded well with rifampin, but was ultimately stopped secondary to elevated liver enzymes. Micropulse laser failed to resolve subretinal fluid. Ultimately the pilot is left with a chronic area of CSC without visual defects and faces career termination. DISCUSSION: Uncompromised vision is inherently crucial in aerospace careers, especially that of a fighter pilot. With persistent CSC resistant to treatment, there is a risk for progression to permanent visual disturbances and/or defects. Safety concerns of authority figures overseeing pilots and aircraft are warranted. However, the concern could be mitigated in air frames that require two pilots. Another factor partially responsible for ending his career is the fear of G force affecting his prognosis. The author is not aware of any other studies illuminating the effects or consideration of excess G force on subretinal fluid in CSC. This is an area that requires further study. Dietrich KC. Fighter pilot with recurrent central serous chorioretinopathy. Aerosp Med Hum Perform. 2016; 87(10):901-905.

Increased plasminogen activator inhibitor results in a hypofibrinolytic state in adolescents with obesity: in vivo and ex vivo evidence.

Obesity in adolescents increases their risk for deep vein thrombosis. The objectives of this study were to determine potential mechanisms for thrombotic risk by investigating the fibrinolytic pathway in a sample of adolescents with and without obesity. Thirty-seven adolescents with obesity and 16 normal weight age-matched controls were recruited. Plasma levels of components of the fibrinolytic system were measured in addition to a Global Haemostasis Potential assay (GHP), which assesses plasma capacity to generate and lyse a fibrin clot. Levels of plasminogen activator inhibitor (PAI) and tissue plasminogen activator (tPA)/PAI complexes were increased in adolescents with obesity when compared to normal weight controls. There was a significant inverse association of increasing PAI with a decrease in plasmin-antiplasmin complexes. The GHP in obese adolescents displayed a hypofibrinolytic response with a markedly increased t½ clot lysis time, as well as an increase in fibrin clot density as indicated by increased absorbance at maximum peak height. In the obese group, immunodepletion of PAI decreased both t½ lysis time and absorbance at maximum peak height. We have shown in vivo and ex vivo there is a hypofibrinolytic state in obese adolescents and have established the hypofibrinolytic state is due to increased PAI levels.

Age at cancer diagnosis, non-O blood group and asparaginase therapy are independently associated with deep venous thrombosis in pediatric oncology patients: A risk model.

INTRODUCTION: Pediatric oncology patients are at increased risk for deep venous thrombosis (DVT). Determining the sub-population of children at increased DVT risk is critical for optimum clinical management. Therefore, the aim of the current study was to identify clinical risk factors for DVT which are easily identifiable at cancer diagnosis. MATERIALS AND METHODS: A Canadian multicenter case control study in survivors of childhood cancer. Survivors who had DVT (Cases) while being treated for pediatric cancer where matched by center with a minimum of two survivors who did not experience DVT (Controls). Clinical information including age at diagnosis, type of cancer and chemotherapy were collected. Genotyping of blood group was done by single nucleotide polymorphisms analysis. RESULTS: 218 subjects were recruited at 4 Canadian pediatric centers. Multivariable analysis demonstrated 3 significant variables (reported as Odds Ratio (OR), (95% CI), p value): age at diagnosis p<0.001, non-O blood group OR 2.6 (1.3-5.2) p=0.005 and asparaginase treatment OR 2.4 (1.2-4.8) p=0.011. In order to optimise clinical utility, we reanalysed the study data with age at diagnosis categorised into four subgroups 0-≤2years, >2-≤7years, >7≤10years, >10years. A significant association with DVT were seen in children 0-≤2years (OR 3.1 (1.1-8.3) p=0.026) and >10years (OR 3.8, 1.7-8.5 p=0.001). Significant associations with DVT remained for non-O blood group, OR 2.2 (1.2-4.4) p=0.016 and asparaginase treatment, OR 2.1 (1.1-4.0) p=0.027. The value for the clinical risk model receiver operating characteristics curve was 0.67. CONCLUSIONS: We have shown 3 independent risk factors for DVT in childhood cancer.

Assessing the anticoagulant effect of dabigatran in children: an in vitro study.

OBJECTIVES: Age-related changes in the hemostatic system result in variation in response to anticoagulants and coagulation assays over childhood. This study used in vitro methods to determine i) optimum coagulation assays for dabigatran in children and ii) anticoagulant effect of dabigatran across pediatric age groups. MATERIALS AND METHODS: Pooled plasma samples from healthy children aged 0 to <1, 1 to <5, 5 to <10, 10 to <17 years and adults were spiked with increasing concentrations of dabigatran and the effect was assessed in five coagulation assays. The samples were also assessed for overall hemostasis potential using a fibrin clot formation and lysis assay. RESULTS: In all five coagulation assays, there were no differences in responses to dabigatran over all pediatric age groups. The international normalized ratio was the least sensitive measure. Activated partial thromboplastin time showed moderate sensitivity and a nonlinear response curve. Thrombin time (TT), dilute TT (dTT) and ecarin clotting time were linearly correlated with dabigatran concentrations; however, the ecarin time and TT were overly sensitive. In the overall hemostasis potential assay, increasing dabigatran concentrations delayed the initiation of clot formation and reduced the time to 50% clot lysis. The responses to initiation of clot formation and clot lysis were consistent across all pediatric groups and comparable to responses in adults. CONCLUSION: The dTT is the most suitable assay for measuring dabigatran concentrations in children. Fibrin clot generation and lysis assay responses to dabigatran in children over all ages were consistent and comparable to those of adults.

In pediatric patients, age has more impact on dosing of vitamin K antagonists than VKORC1 or CYP2C9 genotypes.

Anticoagulation with vitamin K antagonists (VKAs) is problematic because of difficulties in safely managing dosing. Polymorphisms in cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase genes (VKORC1) have been shown to affect VKA dosing in adults. The association of these polymorphisms on VKA dosing in children has not been investigated. The objective of the study was to assess associations of CYP2C9 and VKORC1 polymorphisms and clinical variables on VKA dosing in children. A nonselected cohort of pediatric patients receiving VKA were tested for CYP2C9 and VKORC1 polymorphisms, and clinical data were collected. Multiple linear regression modeling was used to assess relationships of VKA dose with genetic and clinical variables. Fifty-nine patients were recruited; 55.9% were receiving warfarin, and 44.1% were on phenprocoumon. There was a negative association of age with VKA dose (P < .001). Comparing VKORC1 genotypes, the AA group required significantly lower daily doses than GG group (P = .011). In the full model including age, VKORC1 and CYP2C9 genotypes accounted for 38% of dose variation. Age explained 28.3% of VKA dose variations; VKORC1 and CYP2C9 explained only 3.7% and 0.4%, respectively. In children, the most critical factor in determining VKA dose is age. VKORC1/CYP2C9 genotypes only marginally explain dose variations.

Identification of a minimal region of loss on the short arm of chromosome 1 in Wilms tumor.

We have analyzed the short arm of chromosome 1 using loss of heterozygosity (LOH) analysis in Wilms tumors (WT) to identify a minimal region of loss. 1909 WT, 22 malignant rhabdoid tumors of the kidney and 90 clear cell carcinomas of the kidney (CCSK) were subjected to LOH analysis using five markers flanked by D1S243 and D1S244. 225 WT and 4 CCSK displayed LOH for this region. A group of 16 cases which had lost heterozygosity for at least one locus but also retained heterozygosity for at least one locus within this region were more finely analyzed using a panel of 24 microsatellite markers. A minimum region of loss located between D1S2694 and D1S244 spanning an area of 3.23 Mb was found in 15/16 of these tumors. No evidence for a second locus within this region was identified. This region of loss overlaps that found in neuroblastoma and harbors candidate genes highly expressed in fetal kidney i.e., LZIC, ICAT, and DNB5. Denaturing HPLC and quantitative RT-PCR analysis of these three genes, however, revealed no aberrations in WT samples retaining heterozygosity (8 cases) or displaying LOH 1p (8 cases). Further studies are required to identify the presumed tumor suppressor gene located within this region of 1p.

Paired box genes, PAX-2 and PAX-8, are not frequently mutated in Wilms tumor.

To determine whether PAX-2 and PAX-8 are involved in Wilms tumor (WT) pathogenesis, we sought mutations in these two genes in 99 Wilms tumors of favorable histology. We screened the entire protein coding sequences as well as the intronic regions adjacent to exons, using denaturing HPLC followed by sequencing of samples displaying abnormal chromatograms. In PAX-2, a silent polymorphism was found within exon 2 and exon 8 in 1% and 21% of cases, respectively. Three apparently silent polymorphisms were also found in PAX-8, two in exon 5 (2 of 99 cases or 2%) and one in exon 6 (22 of 99 cases or 22%), all of which were located 3' to the exons. In conclusion, no evidence for disease causing mutation was found using this technique, and so the direct involvement of either of these two genes in WT is unlikely.