Treatment patterns and outcomes of high-grade immune checkpoint inhibitor-related pneumonitis in an oncology hospitalist service.

PURPOSE: Immune checkpoint inhibitors (ICI) have become standard of care for some types of lung cancer. Along with expanding usage comes the emergence of immune-related adverse events (irAEs), including ICI-related pneumonitis (ICI-P). Treatment guidelines for managing irAEs have been developed; however, how clinicians manage irAEs in the real-world setting is less well known. We aimed to describe the outcomes and care patterns of grade ≥ 3 ICI-P in an onco-hospitalist service. PATIENTS AND METHODS: We included patients with lung cancer treated with ICI who were admitted to an oncology hospitalist service with a suspicion of ICI-P. We described the hospitalization characteristics, treatment patterns, discharge practices, and clinical outcomes of patients with confirmed ICI-P. The primary outcome was time to start treatment for ICI-P. RESULTS: Among 49 patients admitted with a suspicion of ICI-P, 31 patients were confirmed to have ICI-P and subsequently received ICI-P directed treatment. Pulmonology was consulted in 97% of patients. Median time to start treatment for ICI-P was 1 day (IQR 0-3.5 days). All 31 patients received corticosteroids. Inpatient mortality was 32%. Majority of patients discharged with steroids were prescribed prophylaxis for gastritis and opportunistic infections. Thirty-eight percent of patients were seen by pulmonology and 86% were seen by the oncology team post-discharge. CONCLUSION: Our study confirms prior findings of high mortality among patients with high-grade ICI-P. Early diagnosis and treatment are key to improving clinical outcomes. Understanding the care patterns and adherence to treatment guidelines of clinicians caring for this patient population may help identify ways to further standardize management practices and improve patient outcomes.

Activity of decitabine as maintenance therapy in core binding factor acute myeloid leukemia.

BACKGROUND: Posttherapy measurable residual disease (MRD) positivity in core binding factor acute myeloid leukemia (CBF-AML) is associated with shorter relapse-free survival (RFS). Elimination of MRD measured via quantitative reverse transcription polymerase chain reaction (qRTPCR) for disease specific transcripts can potentially lead to better outcomes in CBF-AML. METHODS: We prospectively monitored the MRD using qRTPCR and flow cytometry on bone marrow samples in patients with newly diagnosed CBF-AML who received decitabine (DAC) maintenance therapy after fludarabine/cytarabine/G-CSF (FLAG)-based induction/consolidation regimen. Negative qRTPCR (CMR) was defined as fusion transcript <0.01%. RESULTS: Thirty-one patients with CBF-AML including 14 with t(8;21) and 17 with inv(16) received parenteral DAC as maintenance therapy. Fifteen patients (48.3%) had completed FLAG-based induction/consolidation but with positive MRD (0.35%, range = 0.01%-0.91%) (Group 1). Sixteen patients (51.7%) could not complete recommended consolidations with FLAG-based regimen (due to older age or complications) and were switched to DAC maintenance (Group 2). In Group 2, eight patients (50%) had undetectable MRD (Group 2A) (all had qRTPCR ≤ 0.01%) and the other eight patients (50%) had residual fusion product by qRTPCR (0.1%, range = 0.02%-0.36%) (Group 2B) prior to starting DAC. Amongst the 23 patients who had a PCR ≥ 0.01% before maintenance therapy (Groups 1 and 2B), 12 patients (52%) attained a CMR as their best response (responders). The median pre-DAC qRTPCR amongst responders were 0.03% compared to 0.14% in nonresponders (p = .002). The median estimated molecular RFS amongst responders were 93.9 months. At a median follow-up of 59.3 months (13.2-106 months) from DAC initiation, 16 patients (51.6%) had to be initiated on a second line of therapy (40%, 25%, and 100% patients, respectively, in Groups1, 2A, and 2B). The median estimated time to new treatment between responders was 112.4 versus 5.8 months in nonresponders (hazard ratio = 0.16, 95% confidence interval = 0.04-0.54); however, there were no difference in overall survival between these groups (p = .37). CONCLUSION: DAC is an effective maintenance therapy for CBF-AML patients with persistent fusion transcript at a low level after FLAG-based regimen. Attainment of CMR with DAC maintenance can lead to long-term remission in patients who have persistent MRD positive after FLAG-based regimen or are unable to receive the full course of consolidation therapy.

Retrospective Analysis of Taxane-Based Therapy in Small Bowel Adenocarcinoma.

Currently, treatment of small bowel adenocarcinoma (SBA) mirrors that of colorectal cancer (CRC). Recent genomic data have demonstrated SBA to be a genetically unique entity, suggesting that therapies not traditionally utilized in CRC should be explored. In order to further characterize the activity of taxanes in this rare cancer, we completed a single-center retrospective study. Twenty patients were found to have been treated with taxane-based regimens (monotherapy in 3, combination therapy in 17). Median time to progression was 3.8 months (95% confidence interval [CI] 2.9-4.6), and median overall survival was 10.7 months (95% CI: 3.1-18.3). The results of this study demonstrate clinical activity from taxane-based therapy in advanced SBA and support further clinical trial investigation.

Attraction of the Green Lacewing Chrysoperla comanche (Neuroptera: Chrysopidae) to Yeast.

Many adult Chrysoperla comanche (Stephens) green lacewings were caught in traps baited with live yeast cultures during tests designed to catch olive fruit flies. All 13 yeast species tested were more attractive than the industry-standard dried torula yeast (Cyberlindnera jadinii; syn. Candida utilis). Live C. jadinii culture attracted significantly more lacewings than the inactive dried-pellet form of the same yeast species, demonstrating that volatiles from live yeast cultures attract adults of this lacewing. Odor profiles for two of the highly active yeasts tested herein (Lachancea thermotolerans and Solicoccozyma terrea) were similar to that for Metschnikowia pulcherrima, a yeast species isolated earlier from the gut diverticulum of Chrysoperla rufilabris. A new Metschnikowia species (M. chrysoperlae), along with two new Candida spp. that were recently realigned to one of the Metschnikowia clades (M. picachoensis and M. pimensis), were also identified from the diverticulum of C. comanche. Thus, one clade of Metschnikowia yeasts that commonly occur in floral nectar appears to exhibit mutualistic symbioses with Chrysoperla green lacewings. Both male and female C. comanche adults were attracted in the present study, and we speculate that males have exploited this symbiosis by offering Metschnikowia-laden regurgitant, including attractive volatiles, to females ('mating trophallaxis') as a nuptial gift.

Chemical Ecology of Neuroptera.

With 6,000 species, Neuroptera (lacewings, antlions, dustywings, and allies) is a relatively small order; however, most larval neuropterans are predacious, often in agricultural systems, lending added importance to this group. Advances in neuropteran phylogeny, most recently through genomic studies, stabilized the nomenclature of this ancestral order of Holometabola, facilitating basic and applied research on these important and interesting insects. The first pheromones for green lacewings (Chrysopidae) have been identified; this, and other research on antlions (Myrmeleontidae), suggests that male-produced long-range pheromones are the norm for the order. Characterizations of the myriad neuropteran exocrine gland systems, including prothoracic, metathoracic, abdominal, dermal, and anal glands, are revealing unforeseen trophic relationships with biological control implications. For examples, males of Chrysopa and other lacewing genera evidently must sequester specific chemical precursors from prey or plants to produce their attractant pheromones, and larval antlion venoms are potentially important genetic leads for insecticidal peptides.

Volatiles Mediating Parasitism of Euschistus conspersus and Halyomorpha halys Eggs by Telenomus podisi and Trissolcus erugatus.

This study identified chemicals found on the eggs of two stink bug species, one native to western North America, Euschistus conspersus, and an invasive species from Asia, Halyomorpha halys. The responses of two scelionid egg parasitoids, Trissolcus erugatus and Telenomus podisi, toward natural stink bug egg volatiles, and synthetic reconstructions of egg volatiles, were tested in bioassays. A compound, methyl (2E,4Z)-2,4-decadienoate, previously identified as the major component of the male-produced aggregation pheromone of E. conspersus, was the major volatile identified from extracts of E. conspersus eggs. In contrast, for H. halys, the sesquiterpenoids that compose the male-produced aggregation pheromone of this species were not detected on eggs, whereas the presence of hexadecanal, octadecanal, and eicosanal was detected. In laboratory olfactometer tests, both Tr. erugatus and Te. podisi females were attracted to extracts of E. conspersus eggs, and to synthetic methyl (2E,4Z)-2,4-decadienoate. However, female Tr. erugatus and Te. podisi wasps were repelled, both by extracts of H. halys eggs and by a blend of the aldehydes identified from H. halys eggs. A follow-up field study, using hexane-washed and intact E. conspersus as sentinel eggs, showed that the parasitoids Trissolcus erugatus and Gryon obesum emerged from these eggs. Sentinel hexane-washed eggs treated with 3 ng of methyl (2E,4Z)-2,4-decadienoate were parasitized more by these two species than were hexane-washed or unwashed eggs, whereas hexane-washed eggs treated with a comparable dose of the C16,18,20 aldehyde mixture were avoided by these parasitoids. In a further field experiment, Trissolcus basalis was the primary parasitoid found in sticky traps baited with methyl (2E,4Z)-2,4-decadienoate, indicating that this species was attracted to, but either did not oviposit or develop in the E. conspersus sentinel eggs in the previous experiment.

North American Invasion of the Tawny Crazy Ant (Nylanderia fulva) Is Enabled by Pheromonal Synergism from Two Separate Glands.

A new invader, the "tawny crazy ant", Nylanderia fulva (Hymenoptera: Formicidae; Formicinae), is displacing the red imported fire ant, Solenopsis invicta (Formicidae: Myrmicinae), in the southern U.S., likely through its superior chemical arsenal and communication. Alone, formic acid is unattractive, but this venom (= poison) acid powerfully synergizes attraction of tawny crazy ants to volatiles from the Dufour's gland secretion of N. fulva workers, including the two major components, undecane and 2-tridecanone. The unexpected pheromonal synergism between the Dufour's gland and the venom gland appears to be another key factor, in addition to previously known defensive and detoxification semiochemical features, for the successful invasion and domination of N. fulva in the southern U.S. This synergism is an efficient mechanism enabling N. fulva workers to outcompete Solenopsis and other ant species for food and territory. From a practical standpoint, judicious point-source release formulation of tawny crazy ant volatiles may be pivotal for enhanced attract-and-kill management of this pest.

Behavioral responses of the invasive Halyomorpha halys (Stål) to traps baited with stereoisomeric mixtures of 10,11-epoxy-1-bisabolen-3-OL.

The brown marmorated stink bug, Halyomorpha halys, is an invasive insect in the United States that is capable of inflicting significant yield losses for fruit, vegetable, and soybean growers. Recently, a male-produced aggregation pheromone of H. halys was identified as a 3.5:1 mixture of (3S,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol and (3R,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol, two stereoisomers of a natural sesquiterpene with a bisabolane skeleton, potentially existing in 16 stereoisomeric forms. In this study, we assessed attraction to pheromonal and non-pheromonal stereoisomeric mixtures of 10,11-epoxy-1-bisabolen-3-ol, which are easier to synthesize than single isomers, and evaluated dose-dependent responses to attractive mixtures in field trials. Some treatments not containing the natural pheromone components were moderately active in field-trapping studies, signifying that some stereoisomers of 10,11-epoxy-1-bisabolen-3-ol are sufficiently similar to the true pheromone in structure to trigger behavioral responses. Importantly, we found that mixtures of stereoisomers containing pheromone components were also highly attractive to H. halys, even in the presence of multiple "unnatural" stereoisomers. Further, adult and nymphal captures were dose-dependent, regardless of whether the lure contained pheromonal or non-pheromonal components. Our findings of attraction to pheromonal and non-pheromonal stereoisomers and lack of inhibition from non-pheromonal stereoisomers of 10,11-epoxy-1-bisabolen-3-ol increase the flexibility of developing pheromone-based products for H. halys.

Determination of the stereochemistry of the aggregation pheromone of harlequin bug, Murgantia histrionica.

Preparation of a complete stereoisomeric library of 1,10-bisaboladien-3-ols and selected 10,11-epoxy-1-bisabolen-3-ols was pivotal for the identification of the aggregation pheromone of the brown marmorated stink bug, Halyomorpha halys. Herein, we describe syntheses of the remaining 10,11-epoxy-1-bisabolen-3-ols, and provide additional evidence on the assignment of relative and absolute configurations of these compounds by single-crystal X-ray crystallography of an intermediate, (3S,6R,7R,10S)-1-bisabolen-3,10,11-triol. To demonstrate the utility of this stereoisomeric library, we revisited the aggregation pheromone of the harlequin bug, Murgantia histrionica, and showed that the male-produced pheromone consists of two stereoisomers of 10,11-epoxy-1-bisabolen-3-ol. Employment of eight cis-10,11-epoxy-1-bisabolen-3-ol stereoisomeric standards, two enantioselective GC columns, and NMR spectroscopy enabled the identification of these compounds as (3S,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol and (3S,6S,7R,10R)-10,11-epoxy-1-bisabolen-3-ol, which are produced by M. histrionica males in 1.4:1 ratio.

Discovery of the aggregation pheromone of the brown marmorated stink bug (Halyomorpha halys) through the creation of stereoisomeric libraries of 1-bisabolen-3-ols.

We describe a novel and straightforward route to all stereoisomers of 1,10-bisaboladien-3-ol and 10,11-epoxy-1-bisabolen-3-ol via the rhodium-catalyzed asymmetric addition of trimethylaluminum to diastereomeric mixtures of cyclohex-2-enones 1 and 2. The detailed stereoisomeric structures of many natural sesquiterpenes with the bisabolane skeleton were previously unknown because of the absence of stereoselective syntheses of individual stereoisomers. Several of the bisabolenols are pheromones of economically important pentatomid bug species. Single-crystal X-ray crystallography of underivatized triol 13 provided unequivocal proof of the relative and absolute configurations. Two of the epoxides, (3S,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol (3) and (3R,6S,7R,10S)-10,11-epoxy-1-bisabolen-3-ol (4), were identified as the main components of a male-produced aggregation pheromone of the brown marmorated stink bug, Halyomorpha halys, using GC analyses on enantioselective columns. Both compounds attracted female, male, and nymphal H. halys in field trials. Moreover, mixtures of stereoisomers containing epoxides 3 and 4 were also attractive to H. halys, signifying that the presence of additional stereoisomers did not hinder attraction of H. halys and relatively inexpensive mixtures can be used in monitoring, as well as control strategies. H. halys is a polyphagous invasive species in the U.S. and Europe that causes severe injury to fruit, vegetables, and field crops and is also a serious nuisance pest.

A systematic review and meta-analysis of observational studies and uncontrolled trials reporting on the use of checkpoint blockers in patients with cancer and pre-existing autoimmune disease.

BACKGROUND: Cancer patients with autoimmune disease have been excluded from randomized trials of immune checkpoint blockers (ICBs). We conducted a systematic review of observational studies and uncontrolled trials including cancer patients with pre-existing autoimmune disease who received ICBs. METHODS: We searched 5 electronic databases through November 2023. Study selection, data collection, and quality assessment were performed independently by 2 investigators. We performed a meta-analysis to pool incidence of immune-related adverse events (irAEs), including de novo events and flares of existing autoimmune disease, hospitalizations due to irAEs, as well as deaths. RESULTS: A total of 95 studies were included (23,897 patients with cancer and preexisting autoimmune disease). The most common cancer evaluated was lung cancer (30.7 %) followed by skin cancer (15.7 %). Patients with autoimmune disease were more likely to report irAEs compared to patients without autoimmune disease (relative risk 1.3, 95 % CI 1.0 to 1.6). The pooled occurrence rate of any irAEs (flares or de novo) was 61 % (95 % CI 54 % to 68 %); that of flares was 36 % (95 % CI 30 % to 43 %), and that of de novo irAEs was 23 % (95 % CI 16 % to 30 %). Flares were mild (grade <3) in half of cases and more commonly reported in patients with psoriasis/psoriatic arthritis (39 %), inflammatory bowel disease (37 %), and rheumatoid arthritis (36 %). 32 % of the patients with irAEs required hospitalization and treatment of irAEs included corticosteroids in 72 % of the cases. The irAEs mortality rate was 0.07 %. There were no statistically significant differences in cancer response to ICBs between patients with and without autoimmune disease. CONCLUSIONS: Although more patients with pre-existing autoimmune disease had irAEs, these were mild and managed with corticosteroids in most cases, with no impact on cancer response. These results suggest that ICBs can be used in these patients, but careful monitoring is required, as over a third of the patients will experience a flare of their autoimmune disease and/or require hospitalization. These findings provide a crucial foundation for oncologists to refine their monitoring and management strategies, ensuring that the benefits of ICB therapy are maximized while minimizing its risks.

Exocrine secretions of wheel bugs (Heteroptera: Reduviidae: Arilus spp.): clarification and chemistry.

Wheel bugs (Heteroptera: Reduviidae: Harpactorinae: Arilus) are general predators, the females of which have reddish-orange subrectal glands (SGs) that are eversible like the osmeteria in some caterpillars. The rancid odor of Arilus and other reduviids actually comes from Brindley's glands, which in the North (A. cristatus) and South (A. carinatus) American wheel bugs studied emit similar blends of 2-methylpropanoic, butanoic, 3-methylbutanoic, and 2-methylbutanoic acids. The Arilus SG secretions studied here are absolutely species-specific. The volatile SG components of A. carinatus include (E)-2-octenal, (E)-2-nonenal, (E)-2-decenal, (E,E)-2,4-nonadienal, (E)-2-undecenal, hexanoic acid, 4-oxo-nonanal, (E,E)-2,4-decadienal, (E,Z)-2,4- or (Z,E)-2,4-decadienal, and 4-oxo-(E)-2-nonenal; whereas in A. cristatus the SG secretion contains beta-pinene, limonene, terpinolene, terpinen-4-ol, thymol methyl ether, alpha-terpineol, bornyl acetate, methyl eugenol, beta-caryophyllene, caryophyllene oxide, and farnesol. Arilus spp. SG secretions may be sex pheromones, but verification of this hypothesis requires further testing.

Monitoring of Triple Negative Breast Cancer After Neoadjuvant Chemotherapy.

Triple negative breast cancer (TNBC) is an aggressive disease with a poor prognosis that disproportionately affects young women and African Americans, and represents a major unmet need in the field. TNBCs display a more aggressive growth pattern with an increased risk of advanced disease and high recurrence risk in patients with early stage TNBC. The addition of immunotherapy to chemotherapy for the treatment of patients with early stage TNBC in the (neo) adjuvant setting per the pivotal KEYNOTE 522 significantly improved pCR rates. Despite this advancement, however, approximately 35% of patients had residual disease at the time of surgery and reduced event free survival. Further techniques to assess for molecular residual disease after completion of neoadjuvant chemotherapy (NAC) may allow us to identify patients at high risk of relapse who may benefit from salvage adjuvant systemic therapy, while also potentially de-escalating treatment in those achieving a molecular complete response.

Racial Disparities in Clinical Outcomes on Investigator-Initiated Breast Cancer Clinical Trials at an Urban Medical Center.

BACKGROUND: Black women are 40% more likely to die of breast cancer compared to White women. Inadequate representation of Black patients in clinical trials may contribute to health care inequity. We aimed to assess breast cancer clinical outcomes in Non-Hispanic Black (Black) versus Non-Hispanic White (White) women with metastatic breast cancer (MBC) enrolled on investigator-initiated clinical trials at Winship Cancer Institute at Emory University, given the significant number of patients from underrepresented minority groups seen at Winship. MATERIALS AND METHODS: Black and White women with MBC on investigator-initiated trials at Emory between 2009 and 2019 were retrospectively evaluated. Univariate analyses and multiple logistic regression models were used to assess clinical response and treatment toxicities. Differences in overall survival between groups was assessed using quantile analysis. RESULTS: Sixty-two women with MBC were included (66% White vs. 34% Black). Black patients had less clinical benefit from the trial therapy as only 57% had partial response or stable disease as best response compared to 78% of White women (P = .09). Quantile analysis showed significant difference in mean survival between Whites and Blacks by the end of follow up (64 vs. 38 months). There were no significant differences in toxicities between groups. CONCLUSION: Participation rates of Black women with MBC on investigator-initiated clinical trials at an urban cancer center were higher compared to key national trials. Black women had worse treatment response and survival. These results reinforce the need for assessment of tumor differences by ancestry and continued improvement in minority representation on clinical trials.

The male-produced sex pheromone of the true bug, Phthia picta, is an unusual hydrocarbon.

Phthia picta is part of a complex of true bugs (Heteroptera) in Brazil that attack tomatoes, being particularly damaging because nymphs and adults feed on both leaves and fruit. Gas chromatography (GC) of aeration extracts of adult males vs. females revealed the presence of a male-specific compound. GC-electroantennographic detector experiments indicated that the antennae of females are highly sensitive to this male-specific compound. GC-mass spectrometry and GC-FTIR analyses suggested a methyl branched hydrocarbon structure for this compound. After synthesis of three different proposed structures, the natural product was indentified as 5,9,17-trimethylhenicosane, which was strongly attractive to females in Y-tube olfactometer bioassays. Analysis of dissected body parts of adults revealed that the pheromone is produced in the lateral accessory glands of the metathoracic scent gland of males only.

Dynamics in Pest Status of Phytophagous Stink Bugs in the Neotropics.

In this review article, we present and discuss the main factors influencing the change in pest status of phytophagous stink bugs (Hemiptera: Heteroptera: Pentatomidae) in the Neotropics. We have surveyed the published records over the past 50 years and divided this timeframe into decades. This was done to rank in time the relative abundance (percentage) of the following species, known pests of commodities, in the Neotropical Region: the Neotropical brown stink bug, Euschistus heros (F.); the green-bellied stink bugs, Diceraeus melacanthus Dallas and D. furcatus (F.); the redbanded stink bug, Piezodorus guildinii (Westwood); the southern green stink bug, Nezara viridula (L.); and the brown-winged stink bug, Edessa meditabunda (F.). The analysis showed that E. heros, D. melacanthus, and D. furcatus, formerly minor pests, in the last decade (2010s) became major pests. The once most important pest species, N. viridula and P. guildinii, decreased their pest status in the last decade. Edessa meditabunda, which never achieved high populations, showed a tendency to increase in abundance in the last two decades (2000s and 2010s). Major factors believed to influence the dynamics of pest populations of stink bugs in the Neotropics include cropping systems (no-tillage replacing conventional soil plowing, and crop rotation); genetically modified (GM) plants (mostly plants expressing insecticidal crystalline proteins derived from Bacillus thuringiensis Berliner - Bt); change in availability of host and associated plants in the new landscape scenario; increased usage of chemicals (insecticides, fungicides, and herbicides); and change in the role of natural enemies in modern day agriculture.

Spatially variant immune infiltration scoring in human cancer tissues.

The Immunoscore is a method to quantify the immune cell infiltration within cancers to predict the disease prognosis. Previous immune profiling approaches relied on limited immune markers to establish patients' tumor immunity. However, immune cells exhibit a higher-level complexity that is typically not obtained by the conventional immunohistochemistry methods. Herein, we present a spatially variant immune infiltration score, termed as SpatialVizScore, to quantify immune cells infiltration within lung tumor samples using multiplex protein imaging data. Imaging mass cytometry (IMC) was used to target 26 markers in tumors to identify stromal, immune, and cancer cell states within 26 human tissues from lung cancer patients. Unsupervised clustering methods dissected the spatial infiltration of cells in tissue using the high-dimensional analysis of 16 immune markers and other cancer and stroma enriched labels to profile alterations in the tumors' immune infiltration patterns. Spatially resolved maps of distinct tumors determined the spatial proximity and neighborhoods of immune-cancer cell pairs. These SpatialVizScore maps provided a ranking of patients' tumors consisting of immune inflamed, immune suppressed, and immune cold states, demonstrating the tumor's immune continuum assigned to three distinct infiltration score ranges. Several inflammatory and suppressive immune markers were used to establish the cell-based scoring schemes at the single-cell and pixel-level, depicting the cellular spectra in diverse lung tissues. Thus, SpatialVizScore is an emerging quantitative method to deeply study tumor immunology in cancer tissues.

Inflammatory Myositis in Cancer Patients Receiving Immune Checkpoint Inhibitors.

OBJECTIVE: To estimate the incidence of immune checkpoint inhibitor-related myositis (ICI-myositis) in cancer patients receiving ICIs, and to report associated clinical manifestations, patterns of care, and outcomes. METHODS: We identified a retrospective cohort of patients receiving ICIs between 2016 and 2019 seen at the University of Texas MD Anderson Cancer Center. Cases of ICI-myositis were identified using International Classification of Disease codes and confirmed by reviewing medical records and pathology, as available. RESULTS: A total of 9,088 patients received an ICI. Thirty-six patients (0.40%) were identified as having ICI-myositis: 17 patients (47%) with ICI-myositis alone and 19 (53%) with overlap manifestations (5 patients with myocarditis, 5 with myasthenia gravis, and 9 with both). The incidence of ICI-myositis was 0.31% in those receiving ICI monotherapy and 0.94% in those receiving combination ICI therapy (relative risk 3.1 [95% confidence interval 1.5-6.1]). Twenty-five patients (69%) received ≥1 treatment in addition to glucocorticoids: plasmapheresis in 17 patients (47%), intravenous immunoglobulin in 12 (33%), and biologics in 11 (31%). Patients with overlap conditions had worse outcomes than those with myositis alone, and 79% of them developed respiratory failure. Eight patients died as a result of ICI-myositis, and all had overlap syndrome with myasthenia gravis or myocarditis (P < 0.05); 75% of these patients had a concomitant infection. CONCLUSION: ICI-myositis is a rare but severe adverse event. More than half of the patients presented with overlap manifestations and had deleterious outcomes, including respiratory failure and death. None of the patients with ICI-myositis alone died as a result of adverse events. Optimal treatment strategies have yet to be determined.

4-oxo-aldehydes from the dorsal abdominal glands of the bed bug (Hemiptera: Cimicidae).

Analyses of the dorsal abdominal glands of fourth- and fifth-instar nymphs of the bed bud, Cimex lectularius L. (Hemiptera: Cimicidae), indicated the predominant constituents were (E)-2-hexenal and (E)-2-octenal, with lesser amounts of 4-oxo-(E)-2-hexenal and 4-oxo-(E)-2-octenal. The latter two compounds have not been reported previously as occurring in bed bugs. There were no differences in the chemical composition of the dorsal abdominal glands excised from exuviae left behind by either male or female adults, nor from glands excised from fourth-instar exuviae. Because the two oxo-aldehydes made up at least 16% of the gland contents, further study of the functional role of these chemicals seem advisable.

Olive Fruit Fly, Bactrocera oleae (Diptera: Tephritidae), Attraction to Volatile Compounds Produced by Host and Insect-Associated Yeast Strains.

The olive fruit fly, Bactrocera oleae (Rossi), is one of the most damaging insect pests of olives worldwide, requiring the use of insecticides for fruit protection in many orchards. Olive fruit flies are attracted to volatile composunds, including a female-produced pheromone, and host-plant and bacterial volatiles. Preliminary laboratory bioassays were conducted for olive fruit fly attraction to over 130 yeast strains from among 400 that were isolated from B. oleae adults and larvae or other insects, infested olives, and potential feeding sites. Kuraishia capsulata, Scheffersomyces ergatensis, Peterozyma xylosa, Wickerhamomyces subpelliculosus, and Lachancea thermotolerans appeared to attract B. oleae as well or better than did torula yeast pellets (Cyberlindnera jadinii; syn. Candida utilis). Volatile compounds emitted by these yeast strains were chemically identified, and included isobutanol, isoamyl alcohol, 2-phenethyl alcohol, isobutyl acetate, and 2-phenethyl acetate. The behavioral response of B. oleae adults to these volatile compounds at three concentrations was tested in a laboratory Y-tube olfactometer. The same volatile compounds were also tested in the field. Isoamyl alcohol was more attractive than the other compounds tested in both laboratory and field bioassays. Isobutanol was not attractive to B. oleae in either laboratory bioassay or field bioassay. Identifying yeast volatiles attractive to the olive fruit fly may lead to development of a more effective lure for detection, monitoring, and possibly control of B. oleae.