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Background Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis characterized by painful and ulcerating lesions on the skin. It rarely involves the face and is often difficult to diagnose. There are few cases reported in the literature of PG involving the face. Aim To share our experience with 5 patients in whom the final diagnosis was PG involving the face, and to review the literature. Methods We report a series of 5 patients with a final diagnosis of PG involving the face and reviewed relevant literature. We searched through PubMed and EMBASE using keywords such as “face” and “pyoderma gangrenosum,” “blastomycosis-like pyoderma gangrenosum, vegetative pyoderma gangrenosum and granulomatous pyoderma gangrenosum.” Results We report 5 patients (4 females) with pyoderma gangrenosum involving the face. All 5 had a final diagnosis of superficial granulomatous PG. All cases presented with nonhealing facial ulcer most commonly on cheeks and a common histopathology of mixed inflammatory infiltrates, multinucleated giant cells, and plasma cells with some granulomatous inflammation. Conclusions PG can involve the face, and all 5 of our patients had the superficial granulomatous as the most common form.

Background: Mycosis fungoides (MF) and Sezary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). There is currently no cure for CTCL, and treatment is aimed at limiting disease progression. This study evaluated the efficacy and tolerability of alitretinoin in CTCL management. Methods: A retrospective, multicenter study was conducted on CTCL patients treated with alitretinoin as a primary agent or in combination with standard therapies. Results: Forty-eight patients with MF ( n = 40) and SS ( n = 8) with a median age of 59.7 years (±14.3) were eligible for study inclusion. Treatment response data were evaluated in 40 patients and safety in 42 patients. 40.0% of the patients had early-stage, 43.8% had advanced-stage CTCL, and in 16.7% of patients there was insufficient information for staging. 40.0% (16/40) of the patients achieved a complete or partial response, whereas 47.5% (19/40) achieved stable disease, 12.5% (5/40) had progressive disease, and there were no cases of disease relapses in responders. Both early and advanced stages of CTCL were responsive to alitretinoin as a primary or combined modality. Alitretinoin was well tolerated, and 64.3% (27/42) of patients did not report any side effects. The most commonly observed side effect was hypertriglyceridemia. Conclusions: This retrospective analysis supports the efficacy and safety of alitretinoin in clearing skin disease and preventing disease progression in CTCL as a monotherapy or in combination with standard therapies.

A man aged 51 years was referred to dermatology for hand dermatitis. The dorsal hands and fingers had superficial erosions with pale pink shallow scars and milia suggestive of porphyria cutanea tarda (PCT). Urine and fecal studies were typical of PCT. The patient had daily alcohol use and was found to have elevated serum ferritin, aspartate aminotransferase, and alanine transaminase. Genetic testing for common hemochromatosis genetic variants (HFE C282Y and H63D) was normal. He underwent next-generation sequencing analysis using the 16-gene hyperferritinemia gene panel for genes known to be associated with hereditary hyperferritinemia, iron overload, or both and was discovered to have a genetic variant in bone morphogenetic 6 (BMP6, c.287T> C, p.Leu96Pro). The skin lesions improved with phlebotomy therapy.

The majority of structural damage and loss of life during a hurricane is due to storm surge, thus it is important for communities in hurricane-prone regions to understand their risk due to surge. Storm surge in particular is largely influenced by coastal features such as topography/bathymetry and bottom roughness. Bottom roughness determines how much resistance there is to the flow. Manning’s formula can be used to model the bottom stress with the Manning’s n coefficient, a spatially dependent field. Given a storm surge model and a set of model outputs, an inverse problem may be solved to determine probable Manning’s n fields to use for predictive simulations.The inverse problem is formulated and solved in a measure-theoretic framework using the state-of-the-art Advanced Circulation (ADCIRC) storm surge model. The use of measure theory requires minimal assumptions and involves the direct inversion of the physics-based map from model inputs to output data determined by the ADCIRC model. Thus, key geometric relationships in this map are preserved and exploited. By using a recently available subdomain implementation of ADCIRC that significantly reduces the computational cost of forward model solves, the authors demonstrate the method on a case study using data obtained from an ADCIRC hindcast study of Hurricane Gustav (2008) to quantify uncertainties in Manning’s n within Bay St. Louis. However, the methodology is general and could be applied to any inverse problem that involves a map from model input to output quantities of interest.

Objectives: To investigate the rate of prostate cancer-specific mortality (PCSM) and disease characteristics in patients diagnosed with localised prostate cancer at age 80–89 years in comparison with men diagnosed at age 70–79 years. Patients and Methods: This is a retrospective study of data from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC). Included were men diagnosed between 2005 and 2014, aged ≥70 years with no evidence of metastatic disease at presentation. Propensity score matching and competing risk Fine and Grey regression were used to assess the chance of treatment (curative vs non-curative) and treatment effect on PCSM. Results: Of the 1 951 eligible patients, 1 428 (76%) were aged 70–79 years and 460 (24%) were aged 80–89 years at diagnosis, with a median (interquartile range) age of 74 (72–76) and 83 (81–85) years, respectively. The 80–89 years group had higher Gleason scores and Prostate Specific Antigen (PSA) values (all P < 0.001) in comparison with the younger group. The 80–89 years group were less likely to be treated with curative treatment (odds ratio 0.12, 95% confidence interval 0.09–0.16; P < 0.001). The proportion of deaths attributable to prostate cancer was similar in both groups: 73 of 263 deaths (28%) in the 80–89 years group vs 97 of 310 deaths (31%) in the 70–79 years group. The risk of PCSM in individuals treated with curative intent was reduced in both groups. Conclusions: The proportion of prostate cancer deaths was similar in both groups. These findings support carefully selected individualised management of elderly patients diagnosed with localised prostate cancer. Refereed/Peer-reviewed

We consider the utilization of a computational model to guide the optimal acquisition of experimental data to inform the stochastic description of model input parameters. Our formulation is based on the recently developed consistent Bayesian approach for solving stochastic inverse problems, which seeks a posterior probability density that is consistent with the model and the data in the sense that the push-forward of the posterior (through the computational model) matches the observed density on the observations almost everywhere. Given a set of potential observations, our optimal experimental design (OED) seeks the observation, or set of observations, that maximizes the expected information gain from the prior probability density on the model parameters. We discuss the characterization of the space of observed densities and a computationally efficient approach for rescaling observed densities to satisfy the fundamental assumptions of the consistent Bayesian approach. Numerical results are presented to compare our approach with existing OED methodologies using the classical/statistical Bayesian approach and to demonstrate our OED on a set of representative partial differential equations (PDE)-based models.

Background: Erosive oral lichen planus and desquamative gingivitis are uncommon but severe debilitating variants of oral lichen planus. Treatment of these presentations is difficult and challenging. Main observation: A 44-year-old woman was referred to the dermatology clinic with chronic painful lichen planus-related gingivitis and buccal erosions. She has failed multiple treatments including topical clobetasol and tacrolimus, intralesional corticosteroids and several systemic and immunosuppressive agents. Following completion of three months of treatment with oral apremilast at a dose of 30 mg twice daily, significant improvement was noted in her disease activity. Conclusion: Oral apremilast may be a safe and effective treatment for erosive oral lichen planus. ( J Dermatol Case Rep . 2016; 10(3): 56-57)

Staphylococcus aureus promotes the onset and severity of atopic dermatitis (AD), which is exacerbated by superantigen toxins SEB and SEC. The genetic identity of these isolates, and their relationship to common hospital- or community-associated methicillin resistant S. aureus (HA-MRSA and CA-MRSA) has not been defined. We conducted spa typing, partial multi-locus sequence typing (MLST), and toxin profiling (seb, sec, lukS-PV) of S. aureus from 119 pediatric and 40 adult AD patients. MLST clonal complexes CC45, CC5, CC15, CC1, CC8 and CC30 accounted for 79% of isolates, representing the same major groups reported for nosocomial S. aureus in hospital intensive care units. The highest disease severity was associated with CC1, which was significantly greater relative to CC15 (p = 0.017) or CC30 (p = 0.040), but with no significant difference relative to CC45, CC5 or CC8. Although there were two few lukS-PV, seb or sec isolates to infer a role in disease severity, CC45 was identified as a source of SEC producing strains, and lukS-PVL was associated with a small number of CC5 pediatric isolates. CC1 harbored the only CA-MRSA that was identified, and was a source of isolates that expressed both seb and sec, and closely resembled the USA400 strain of CA-MRSA.

Objective Lack of dose adjustment for renally cleared drugs in the presence of poor renal function is a common problem in the hospital setting. The absence of a clinical decision support system (CDSS) from direct clinician workflows such as computerized provider order entry (CPOE) hinders the uptake of CDSS. This study implemented CDSS in an environment independent of CPOE, introduced to prescribers via academic detailing, to address the dosing of renally cleared drugs. Design GFR+ was designed to automatically calculate and update renal function, doses of key drugs adjusted for renal function, and highlight clinically significant decreases in renal function. Prescribers were made aware of GFR+, its navigation, and surrounding clinical issues, using academic detailing. Measurement The rate of dosing conformity and management for key renally cleared drugs in hospitalized patients, before and after GFR+ implementation. Results Improvements were seen in dosing conformity for enoxaparin (from 68% to 86%, p¼0.03), gentamicin (63e87%, p¼0.01), and vancomycin (47e77%, p¼0.07), as well as the appropriate use of gentamicin therapeutic drug monitoring (70e90%, p¼0.02). During episodes of acute renal impairment, renally cleared drugs were held on 38% of instances in the pre-intervention period compared with 62% post-intervention (p¼0.01). Conclusion Clinical decision support implemented with academic detailing improved dosing conformity and management of key renally cleared drugs in a hospitalized population. Academic detailing should be strongly considered to facilitate the introduction of CDSS systems that cannot be placed directly into the clinician workflow.

Purpose: Sorafenib and erlotinib are potent, orally administered receptor tyrosine kinase inhibitors with antiproliferative and antiangiogenic activities. Given their inhibitory target profile and efficacy as single agents, the combination of these drugs is of considerable interest in solid malignancies. This study aimed to determine the recommended phase II dose of this targeted combination, their toxicity profile, pharmacokinetic interaction, and preliminary clinical activities. Experimental Design: Sorafenib was administered alone for a 1-week run-in period, and then both drugs were given together continuously, with every 28 days considered as a cycle. Three dose levels were assessed. Results: Seventeen patients with advanced solid tumors received 75 cycles of treatment. The most frequent adverse events of all grades were constitutional and gastrointestinal in nature followed by electrolytes and dermatologic toxicities. Fatigue was the most common adverse event (17 patients; 100%) followed by diarrhea (15 patients; 88%), hypophosphatemia (13 patients; 76%), and acneiform rash (12 patients; 71%). These adverse events were predominantly mild to moderate. The recommended phase II dose of this combination was determined as 400 mg twice daily sorafenib and 150 mg daily erlotinib. Pharmacokinetic analysis revealed no significant effect of erlotinib on the pharmacokinetic profile of sorafenib. Among 15 evaluable patients, 3 (20%) achieved a confirmed partial response and 9 (60%) had stable disease as best response. Conclusions: Sorafenib and erlotinib are well tolerated and seem to have no pharmacokinetic interactions when administered in combination at their full single-agent recommended doses. This well tolerated combination resulted in promising activity that needs further validation in phase II studies.

Background Pemphigus herpetiformis (PH) is a rare subtype of pemphigus that presents challenges in diagnosis. Objective To review the presentation, diagnosis, and management of PH. Methods We reviewed the charts of all patients diagnosed and treated for PH in an immunobullous referral center between September 2007 and June 2013. Results Eight patients were identified with a diagnosis of PH. All presented initially with pruritus. Clinical disease was manifest as either urticated erythematous plaques or a vesiculobullous eruption. Histological evaluation demonstrated eosinophilic spongiosis in all patients with acantholysis in half of cases (n = 4/8). Peripheral eosinophilia was noted in three of eight (37.5%) patients. In all cases, direct immunofluorescence showed intercellular deposition of immunoglobulin G in the epidermis. All patients required high-dose corticosteroid initially. All patients treated with dapsone or sulfasalazine (n = 4) achieved at least partial control. Other effective treatments included intravenous immunoglobulin (n = 2), azathioprine (n = 2), and leflunomide (n = 1). Rituximab was ineffective in two patients. Conclusion The clinical and histological features of PH develop over time and with treatment, making distinction between pemphigus subtypes challenging and delay in diagnosis common. Diagnosis of PH requires a high index of suspicion and is made on clinical grounds (urticated erythema) in the context of compatible histology and immunofluorescence findings. Treatment may be challenging, although efficacy of sulfonamide derivatives appears to offer a therapeutic effect.

Efficient local expression from recombinant adeno-associated virus (rAAV)-cystic fibrosis (CF) transmembrane conductance regulator (CFTR) vectors has been observed in the airways of rabbits and monkeys for up to 6 months following a single bronchoscopic delivery. However, it is likely that repeated administrations of rAAV vectors will be necessary for sustained correction of the CF defect in the airways. The current study was designed to test the feasibility of repeated airway delivery of rAAV vectors in the rabbit lung. After two doses of rAAV-CFTR to the airways, rabbits generated high titers of serum anti-AAV neutralizing antibodies. Rabbits then received a third dose of a rAAV vector containing the green fluorescent protein (GFP) reporter gene packaged in either AAV serotype 2 (AAV2) or serotype 3 (AAV3) capsids. Each dose consisted of 1 ml containing 5 × 10 9 DNase-resistant particles of rAAV vector, having no detectable replication-competent AAV or adenovirus. Three weeks later, GFP expression was observed in airway epithelial cells despite high anti-AAV neutralizing titers at the time of delivery. There was no significant difference in the efficiency of DNA transfer or expression between the rAAV3 and rAAV2 groups. No significant inflammatory responses to either repeated airway exposure to rAAV2-CFTR vectors or to GFP expression were observed. These experiments demonstrate that serum anti-AAV neutralizing antibody titers do not predict airway neutralization in vivo and that repeated airway delivery rAAV allows for safe and effective gene transfer.

Two previous reports indicated that recombinant adeno-associated virus (rAAV) vectors were dependent on helper adenovirus (Ad) for efficient conversion of single-stranded (ss) rAAV DNA to the double-stranded (ds) form. This finding is somewhat paradoxical, however, since during a latent infection wild-type (wt)-AAV is rapidly converted to a ds form in the absence of Ad. Our hypothesis was that the effect observed in the previous studies was due to kinetic factors, i.e. to a relative delay in conversion to ds-DNA rather than to an absolute requirement for Ad. To test this, Hela cells were infected with a rAAV-CMV-green fluorescent protein (GFP) vector either in the presence or absence of Ad. Within the first 2 days, Ad infection resulted in a 4-fold increase in AAV vector expression and an augmentation of conversion to a ds-AAV DNA. By 6 days, however, the total number of GFP-expressing cells in the Ad-free culture had exceeded the original number in the Ad co-infected cells, and the conversion to ds-DNA episomes was substantial and ongoing.

Nanotechnology has the potential to deliver considerable benefits to society. Some of the properties of nanomaterials, however, call into question the adequacy of current methods for determining hazard and exposure and for controlling risks. Given the limitations of existing regulatory tools and policies, three distinct initiatives are urgently needed: first, a major increase in nanomaterial risk research; second, rapid development and implementation of voluntary standards of care; and third, development of adequate regulatory policies on nanomaterial risk management.

PSORIASIS IS AN IMMUNE-MEDIATED SKIN DISEASE in which chronic T-cell stimulation by antigen-presenting cells (APC) occurs in the skin. This interplay between the T-cell and APC has been likened to a “T-AP dance” where specific steps must occur in sequence to result in T-cell activation and the disease phenotype; otherwise T-cell anergy would occur. Several novel engineered proteins designed to block specific steps in immune activation (biologic agents) have demonstrated efficacy in the treatment of psoriasis. These agents include fusion proteins, monoclonal antibodies and recombinant cytokines. These medications act at specific steps during the T-AP dance either to inhibit T-cell activation, costimulation and subsequent proliferation of T-cells, lead to immune deviation or induce specific cytokine blockades. The potential increased selectivity for specific pathways in immune activation, clinical efficacy and relative safety of these new agents offers an alternative for the treatment of moderate to severe psoriasis.

Aim: PCa is among the most common cancers. It is the cause of death in half of cases diagnosed. Data on elderly men, especially ≥80, is limited. We describe the patient and disease characteristics and the primary cause of death (PCa versus non-PCa) in patients (pts) diagnosed when aged ≥ 80 and compare them with pts diagnosed at the age of 70-79 using data from a large clinical registry. Methods: Data for elderly men (≥ 70 yrs) with PCa were obtained from SA-PCCOC (a longitudinal, observational registry of biopsy-proven PCa cases, throughout the Australian state of South Australia since 1998) including cause of death. Proportions were compared using a Chi squared test. A multivariable model used logistic regression to assess the variables: age at diagnosis, clinical stage and Gleason score at biopsy. Results: There were 601 pts in the ≥ 80 group (median age at diagnosis 84, range 80-101) and 1232 pts aged 70-79 (median age at diagnosis 74, range 70-79). At data cut-off, 431(72%) had died in the ≥ 80 group; 187 (43%; 95% CI 39-48%) caused by PCa. In the 70-79 group, 290 (24%), had died with PCa as the primary cause in 142 (49%; 95% CI 43-55%). Pts were more likely to die if diagnosed with PCa when over 80 compared to those aged 70-79 at diagnosis [OR 8.24; 95% CI 6.56-10.33]. We did not observe a statistically significant difference in the distribution of cause of death between the two groups (PCa versus non-PCa) [OR 0.80; 95% CI 0.59-1.09]. In pts aged ≥80, a Gleason score >7 at diagnosis was associated with death caused by PCa (p = 0.01); however this was not significant in multivariable analysis [OR 1.2; 95% CI 0.62-2.33]. In pts aged 70-79, death due to PCa was associated with clinical stage 3 [OR 3.56; 95% CI 1.19-11.44, p = 0.03], and Gleason score >7 [OR 3.01; 95% CI 1.22-7.66, p = 0.02] in multivariable analysis. Conclusions: A large proportion of elderly men with PCa are likely to die from the disease. The proportion of elderly men (≥80 years) dying from PCa is similar to those aged 70-79. To our knowledge this is the first study focusing on the population of pts older than 80 with PCa. Disclosure: All authors have declared no conflicts of interest.

Importance Rituximab induces B-lymphocyte apoptosis by targeting CD20 antigen and has shown efficacy in antibody-mediated autoimmune disease. Rituximab is increasingly being acknowledged as an effective and safe treatment option for pemphigus. Objective To assess the clinical response of patients with pemphigus to rituximab using a modified fixed-dose rheumatoid arthritis protocol (1 g intravenously on days 1 and 15, followed by 500 mg intravenously if clinically warranted at 6-month intervals or repeated full dosing). Design, Setting, and Participants A retrospective cohort study was conducted using records from a tertiary referral center for autoimmune bullous disorders. Participants included 92 patients (pemphigus vulgaris, 84 [91%], and pemphigus foliaceus, 8 [9%]) who received rituximab treatment between May 1, 2006, and August 30, 2012. Main Outcomes and Measures The primary outcomes were time to relapse and achievement of a complete response with or without treatment at the end of the study. Results Median time to relapse after the first treatment cycle was 15 months (95% CI, 10.3-19.7). All patients experienced improvement. Complete remission rates with or without adjuvant treatment at final follow-up were 89% (56 patients [61%] were in complete remission without treatment and 26 patients [28%] were in complete remission during adjuvant treatment). No serious infectious adverse events occurred. Conclusions and Relevance The fixed-dose, modified rheumatoid arthritis protocol for rituximab was efficacious and well tolerated in patients with pemphigus. Patients who do not achieve remission after 1 cycle or patients who experience relapse benefit from further cycles of rituximab. Our results need to be confirmed in larger and controlled trials.

Use of rituximab in patients with chronic viral hepatitis can worsen pre-existing hepatitis or reactivate occult infection. There are no reports of use of rituximab in pemphigus patients with co-existing viral hepatitis. Herein, we report three pemphigus patients with co-existing chronic viral hepatitis (hepatitis C (n = 2), hepatitis B (n = 1)), who were treated successfully with rituximab under close supervision and concurrent antiviral drug administration. There was no derangement of the liver function tests or increase in viral load in any of the patients. By incorporating good collaboration with a hepatologist and close follow-up, such patients can be managed successfully with biologic therapies when the conventional treatment modalities have failed.

Germline mutations in genes encoding several components of the retinoblastoma pathway have been linked with inherited predisposition to melanoma. Most commonly, such mutations involve CDKN2A, a cyclin-dependent kinase inhibitor of two kinases, CDK4 and CDK6, which phosphorylate the retinoblastoma protein (pRB) and thereby promote passage through the G1/S cell-cycle restriction point. Less frequently, germline mutations in the CDK4 gene have also been linked with an increased risk of melanoma. Despite the sequence and functional homology between CDK4 and CDK6, the role of germline mutations in CDK6 in melanoma predisposition is unknown. We detected no CDK6 mutations within the p16 (CDKN2A) binding domain in index cases from 60 melanoma-prone kindreds that lacked germline mutations in the coding regions of either CDKN2A or within the entire CDK4 coding region. We conclude that germline mutations in CDK6 do not make a significant contribution to melanoma predisposition.

Fungal epizootics occurred in abundant Orgyia vetusta (western tussock moth; Lepidoptera: Lymantriidae) populations on Lupinus arboreus bushes growing on the Pacific coast north of San Francisco, California. The causative pathogen was isolated and identified as Entomophaga aulicae, Group II, based on RFLPs using rDNA and PCR-amplified rDNA products. Inability of this fungus to infect the lymantriid Lymantria dispar (gypsy moth) confirmed its distinction from Entomophaga maimaiga, the only other member of this species complex which predominantly infects lymantriids. Later instar wandering by O. vetusta in outbreak populations and close proximity of larvae in dense populations are characteristics most probably promoting development of E. aulicae epizootics; these life history patterns are also typical of Lymantria dispar populations experiencing epizootics of E. maimaiga.

Introduction: Sezary syndrome is a rare, aggressive and advanced stage of cutaneous T cell lymphoma where patients exhibit total body erythroderma and peripheral blood involvement. Patients can progress from preexisting mycoses fungoides or present de-novo. Historically median survival has been less than two years however with current combinations of skin directed and immunomodulatory therapy median survival has been documented up to 3–4 years, however randomized trials are lacking given the rarity of this disorder. We describe the outcomes 23 patients followed in our centre diagnosed with sezary syndrome based on peripheral blood involvement and erythroderma who have been treated primarily with combination skin and immunomodulatory therapy. Methods: A review of all patients diagnosed with sezary syndrome in our centre was conducted. Base line characteristics, survival, number and type of therapies as well as responses to treatments were recorded Results: 23 patients were identified. 11 male, 12 female, average age at diagnosis 64.7 yrs (range 47–85). Therapies included total skin electron beam (TSEB), PUVA, Interferon, oral retinoids, and extracorporeal photophoresis (ECP). 5 patients had received prior traditional chemotherapy including CHOP, chlorambucil and purine analogues with either no or transient responses. 19 patients received a combination of all 5 therapies. 19 patients received IFN, 13 TSEB, 21 PUVA, 18 ECP and 16 oral retinoids. 7 patients received 3 or fewer therapies (3 in process of escalating therapy, 1 CR to TSEB, 3 pts refused multiagent therapy as elderly and stable on PUVA +/− retinoids). 6 patients achieved a durable complete remission while on therapy (4 received IFN/TSEB/PUVA/ECP, 1 IFN/PUVA/ECP, 1 TSEB alone), 3 patients had progressive disease, and the remainder either had partial responses or stable disease. Median follow-up was 44 months (range 9–127). Median survival of the entire cohort was 37 months (mean 52 months, range 6–108 months, 5 patients have been diagnosed in the last 12 months). There have been 5 deaths to date, median 43 months (range 33–101) from the time of diagnosis. Cause of death included 2 cardiac, 1 renal, 1 infection, and 1 progressive disease. There was no correlation between survival and LDH at presentation, sezary cell count or number of therapies. There was a modest correlation between survival and age at diagnosis (R2=0.1263). Patients who received TSEB had an average of 57 months survival vs. 33.5 months than those who did not, however this was not statistically significant. Reasons not to receive TSEB included 5 patient refusal, 3 still escalating therapy, 2 had adequate response to other therapies. Patients who achieved a CR to therapy had a median survival of 63 months (average 65 months) vs. those who did not achieve a CR had a median survival of 22 months (average 65 months). Conclusions: Patients receiving combination immunotherapy and skin based treatments for sezary syndrome appear to be living longer than historical series. Given the small number of this cohort it was not possible to statistically determine variables predictive of prolonged survival, however patients who received TSEB and or achieved a CR to treatment had median survival of approximately 5 years. The majority of patients received maintenance immunotherapy to sustain disease control.

In 1989, populations of North American gypsy moth, Lymantria dispar, in seven contiguous northeastern states were severely reduced by a fungal pathogen. Based on morphology, development, and pathology, this organism appeared to be Entomophaga maimaiga. We have now used allozyme and restriction fragment length polymorphism analyses to confirm this identification. Previously, this mycopathogen had been reported only from gypsy moth populations in Japan. During 1989, E. maimaiga occurred only in areas that had been initially defoliated by gypsy moth >10 years ago. E. maimaiga caused 60-88% mortality in late instar larvae on research sites in central Massachusetts.

Mepolizumab is a humanized anti-IL-5 monoclonal antibody that blocks the actions of IL-5, the hematopoietin most responsible for eosinophil production, differentiation, and survival. Clinical experience in small numbers of patients with hypereosinophilic syndrome (HES), asthma, and atopic dermatitis indicated that intravenous (IV) mepolizumab therapy was associated with a reduction in blood eosinophils and was well-tolerated. A multicenter (26 sites worldwide), randomized, double-blind, placebo-controlled, and parallel-group trial has been conducted to evaluate the steroid-sparing effects of mepolizumab in patients with HES, and its efficacy and safety in controlling the signs and symptoms of this disease. The trial recruited patients 18–85 years of age with HES (blood eosinophil count >1500/μl for ≥6 months with evidence of eosinophilia-related organ involvement or dysfunction, without any known cause of eosinophilia), who tested negative for the FIP1L1-PDGFRα gene rearrangement and required 20–60 mg/day prednisone (monotherapy) to maintain blood eosinophils at Patient demographics Placebo (n=42) Mepolizumab (n=43) Total (n=85) Age, y (mean±SD) 49.1±14.4 47.0±16.2 48.1±15.3 Men, % 17 (40%) 26 (60%) 43 (51%) Caucasian, % 34 (81%) 38 (88%) 72 (85%) Weight, kg (mean±SD) 79.7±18.3 80.9±22.2 80.3±20.3 BMI, kg/m2 (mean±SD) 27.8±5.8 27.0±6.4 27.4±6.1 Baseline prednisone≤30 mg, n (%) 30 (71%) 30 (70%) 60 (71%) Baseline prednisone >30 mg, n (%) 12 (29%) 13 (30%) 25 (29%) Previously treated for HES, n (%) 40 (95%) 41 (95%) 81 (95%) HES duration, y (mean±SD) 6.5±9.5 4.3±5.6 5.4±7.8 Age at HES onset, y (mean±SD) 42.7±16.2 42.7±17.7 42.7±16.9