Pulmonary palytoxin poisoning on CT imaging

Background: Palytoxin poisoning is an uncommon exposure in the US, and is most frequently encountered amongst hobbiests and professionals in the aquarium industry. The toxin is produced by the microalgae Ostreopsis as well as the coral Palythoa toxica. Discovered in Hawaii, the name limu-make-o-Hana translates to "seaweed of death from Hana." Palytoxin interrupts Na+/ K+ ATPase pump, resulting in widespread cellular dysfunction. Persons are at highest risk when cleaning a fish tank housing the coral that produces palytoxin, resulting in cutaneous or inhalational exposure. We present a case of palytoxin inhalational exposure with computed tomography (CT) imaging. Case report: A 41-year-old male presented to the emergency department (ED) with dyspnea, cough, and wheezing after cleaning his saltwater fish tank. He reported that he maintains Zoanthid corals in his home saltwater fish tank and typically wears personal protective equipment when cleaning the tank. He had taken off his mask directly after using hot water to clean the tank, and quickly developed shortness of breath. He contacted Poison Control and was instructed to take loratadine with initial improvement in his symptoms. He then developed decreased appetite, nausea, and chills. The following day, in addition to these symptoms, he developed a fever of 102.5 degreeF and an oxygen saturation of 88% measured with an at-home pulse oximeter. He then proceeded to the ED where he was found to be hypoxic to 91% on room air, tachycardic to 120 bpm, hypotensive to 93/ 70mmHg, febrile to 100.9 degreeF and tachypneic at a respiratory rate of 30. Physical exam revealed clear lung sounds. Application of supplemental oxygen at 2 L resulted in improvement in his oxygen saturation and his hypotension and tachycardia responded to intravenous fluids. Significant laboratory results included WBC count of 20.4 with bands of 14%, elevated lactate of 2.4mmol/L, elevated D-dimer of 0.48 mug/mL and a negative COVID PCR test. CTA thorax revealed patchy ground-glass opacities in the bilateral upper and lower lobes with mosaicism. The patient received doxycycline in addition to broad spectrum antibiotics due to concern for inhalational marine toxicity. He was also started on 60mg prednisone, inhaled steroids, and bronchodilators for symptomatic treatment, with improvement in his symptoms. During his hospitalization, a respiratory viral panel was negative for common viruses associated with atypical pneumonia including influenza, coronavirus, metapneumovirus, rhinovirus, enterovirus, adenovirus, parainfluenza, bocavirus, Chlamydophila pneumoniae, and Mycoplasma pneumonia. His dyspnea gradually improved and he was weaned off supplemental oxygen prior to discharge home on hospital day 2. Discussion(s): It is unclear what changes are expected on thoracic imaging in patients with inhalational palytoxin exposure. Chest radiographs in two previous cases displayed scattered infiltrates, and a chest CT in another case showed pleural based consolidations. The ground-glass mosaicism suggests that a more diffuse reactive airway process after an inhalational palytoxin insult. Conclusion(s): Patients with inhalational palytoxin exposure may be found to have reactive airway symptoms along with ground glass opacities with mosaicism on CT imaging.

Hyperinflammatory ARDS Is Characterized by Interferon-High, Neutrophil-Predominant Inflammation in the Lower Respiratory Tract

Background: Latent class analyses in patients with acute respiratory distress syndrome (ARDS) have identified “hyper-inflammatory” and “hypo-inflammatory” phenotypes with divergent clinical outcomes and treatment responses. ARDS phenotypes are defined using plasma biomarkers and clinical variables. It is currently unknown if these phenotypes have distinct pulmonary biology and if pre-clinical models of disease replicate the biology of either phenotype. Methods: 45 subjects with ARDS (Berlin Definition) and 5 mechanically ventilated controls were selected from cohorts of mechanically ventilated patients at UCSF and ZSFG. Patients with COVID-19 were excluded from this analysis. A 3-variable classifier model (plasma IL-8, protein C, and bicarbonate;Sinha 2020) was used to assign ARDS phenotypes. Tracheal aspirate (TA) RNA was analyzed using established bulk and single-cell sequencing pipelines (Langelier 2018, Sarma 2021). Differentially expressed (DE) genes were analyzed using Ingenuity Pathway Analysis (IPA). Microbial community composition was analyzed with vegan. Fgsea was used to test for enrichment of gene sets from experimental ARDS models in genes that were differentially expressed between each phenotype and mechanically ventilated controls. Results: Bulk RNA sequencing (RNAseq) was available from 29 subjects with hypoinflammatory ARDS and 10 subjects with hyperinflammatory ARDS. 2,777 genes were differentially expressed between ARDS phenotypes. IPA identified several candidate upstream regulators of gene expression in hyperinflammatory ARDS including IL6, TNF, IL17C, and interferons (Figure 1A). 2,953 genes were differentially expressed between hyperinflammatory ARDS and 5 ventilated controls;in contrast, only 243 genes were differentially expressed between hypoinflammatory ARDS and controls, suggesting gene expression in the hypoinflammatory phenotype was more heterogeneous. Gene sets from experimental models of acute lung injury were enriched in hyperinflammatory ARDS but not in hypoinflammatory ARDS (Figure 1B). Single cell RNA sequencing (scRNAseq) was available from 6 additional subjects with ARDS, of whom 3 had hyperinflammatory ARDS. 14,843 cells passed quality control filters. Hyperinflammatory ARDS subjects had a markedly higher burden of neutrophils (Figure 1C), including a cluster of stressed neutrophils expressing heat shock protein RNA that was not present in hypoinflammatory ARDS. Expression of a Th1 signature was higher in T cells from hyperinflammatory ARDS. Differential expression analysis in macrophages identified increased expression of genes associated with mortality in a previous study of ARDS patients (Morell 2019). Conclusions: The respiratory tract biology of ARDS phenotypes is distinct. Hyperinflammatory ARDS is characterized by neutrophilic inflammation with distinct immune cell polarization. Transcriptomic profiling identifies candidate preclinical disease models that replicate gene expression observed in hyperinflammatory ARDS.

Impact of the COVID-19 pandemic on social and health behaviors among rural and urban cancer patients at Huntsman Cancer Institute (HCI)

Purpose: The COVID-19 pandemic has disrupted many facets of life for rural and urban patients with cancer. Here, we characterize the impact of the pandemic on social and health behaviors of rural and urban cancer patients. Methods: N=1,326 adult cancer patients, who visited HCI in the last 4 years and enrolled in either Total Cancer Care or Precision Exercise Prescription studies, completed a COVID-19 survey. The survey was administered between Aug and Sept 2020 and included questions on demographic and clinical information as well as employment status, health behaviors, and COVID-19 prevention measures. Results: The mean age was 61 (19-92) years, with 54% female, 97% non-Hispanic White, 80% stage I-III, 42% employed full or part-time, 25% living in rural counties, and 85% reporting good to excellent overall health. Cancer patients in rural compared to urban counties were more likely to be older (rural=63 vs. urban=60 years;p=0.01), retired or not employed (rural=63% vs. urban=56%;p=0.04), not have health insurance coverage (rural=4% vs. urban=2%;p=0.01), and have ever smoked (rural=35% vs. urban=24%;p=0.001). However, urban patients reported “somewhat” to “a lot” of change in their daily lives more frequently than rural patients (urban=86% vs. rural=77%;p<0.001), but there were no differences in change in social interaction or feeling lonely between populations. Changes in health behaviors namely exercise habits due to the pandemic were more common in patients residing in urban vs. rural counties (urban=51% vs. rural=39%;p<0.001), with more urban patients either exercising less (urban=23% vs. rural=17%) or more frequently (urban=12% vs. rural=8%);however, there were no significant differences with respect to changes in alcohol consumption between these groups. In terms of prevention measures, urban patients compared to rural patients were more likely to use face masks “fairly” or “very often” (urban=94% vs. rural=83%;p<0.001) and also felt they were more likely to contract a COVID-19 infection (22% vs. 14%;p=0.003), but there were no differences for other risk mitigation behaviors, such as hand sanitizer use. Conclusion: These findings suggest that the first 6 months of the COVID-19 pandemic had disparate effects on cancer patients living in rural and urban counties. Rural patients were more likely to have risk factors associated with poor health outcomes, such as not having health insurance coverage and having a history of smoking. However, urban patients were more likely to experience larger changes in their daily lives and exercise habits. Urban patients were more likely to follow preventive measures (e.g., wearing face masks) and felt they were at a greater risk of contracting the virus. Further research is needed to better characterize the pandemic's short- and long-term effects on cancer patients in rural and urban settings and appropriate interventions.

Effects of demographic and behavioral factors on social isolation in a cancer center population during COVID-19 pandemic

The COVID-19 pandemic has led to extensive social changes, which may increase the risk of experiencing social isolation, particularly in cancer patients who are at high risk of having poor outcomes if infected with COVID-19. It is unclear if pandemic-related risk mitigation behaviors (e.g., limiting attendance at social gatherings, mask wearing) influence social isolation. We leveraged data from 9,514 patients with cancer, or at high risk for cancer, from Moffitt Cancer Center to examine whether social isolation is associated with sociodemographic factors and risk mitigation behaviors. Eligible patients who had an appointment at the cancer center in the past five years, reported an email address, and had consented to the institutional biobanking protocol were invited to complete a survey regarding demographic, behavioral, and lifestyle factors as well as social isolation measured using the 4-item PROMIS Social Isolation scale. The raw PROMIS score was converted to a T-score and was split at 50, the average for the general U.S. population, and univariable and multivariable logistic regression was performed. Behavioral factors were measured on a Likert scale, ranging from “never” or “not at all”, to “very often” or “a lot”, and were evaluated continuously. Most participants were female (60.5%), Non-Hispanic White (90.3%), and had been diagnosed with cancer (89.6%);mean age was 64 years old. Only 3.5% reported ever testing positive for COVID-19, and 4.6% reported currently smoking. In univariable models, younger age, women, current smokers, and Hispanic ethnicity or Non-White race were associated with higher odds of social isolation. Among risk mitigation behaviors, leaving the house less often, attending social gatherings less often, a greater change in day-to-day life due to the pandemic, less physical contact with others outside their home, and wearing a mask more often were also associated with increased odds of social isolation. In the multivariable model including significant univariate factors, older patients (OR, per one year: 0.97;95%CI: 0.97-0.98) and males (OR, vs. females: 0.64;95%CI: 0.58-0.71) had lower odds of social isolation. Further, perceived changes in day-to-day life (OR, per one unit increase: 1.64 95%CI: 1.56-1.73), leaving the house less often (OR, per one unit increase: 0.75;95%CI: 0.71-0.80), and attending social gatherings less often (OR, per one unit increase: 0.92 95%CI: 0.84-0.95) remained associated with social isolation. Overall, behavior change to mitigate risk of COVID-19 infection was associated with more social isolation for cancer patients and survivors. Women, younger patients, and current smokers may be particularly at risk, suggesting targeted interventions to reduce feelings of social isolation in these populations may be warranted.

From vaping and smoking: Risk assessment of new tobacco and nicotine releasing systems

90% of all e-cigarette users use tobacco cigarettes instead of quitting smoking and, due to sweet-flavored liquids and advertising as a lifestyle product, young never-smokers are increasingly using these new products. Even though e-cigarettes may also contain lower levels of harmful substances, no e-cigarette was free from potentially toxic and carcinogenic substances, and there is also evidence that e-cigarettes contain new toxic substances;in 2019, they led to EVALI in the USA with 68 deaths. In the steam from tobacco heaters, 295% increased amounts of carcinogenic acenaphthene compared to tobacco cigarettes were found. The use of nicotine-containing e-cigarettes and tobacco heaters did not reduce tobacco-related diseases. Shisha lead to a similar nicotine addiction potential, a considerably higher pollution, and carbon monoxide exposure. Shiazzo steam stones have a significantly lower health risk than shishas with the same risk of carbon monoxide poisoning. The consumption of e-cigarettes by adolescents and young adults led to a 5-fold increased risk of contracting COVID-19, in combination with tobacco cigarettes even to a 7-fold increased risk. The new tobacco or nicotine-releasing substances are neither harmless to health nor suitable for smoking cessation.

Vom Dampfen und Rauchen: Risikobewertung neuer tabak- und nikotinfreisetzender Systeme

90% aller Nutzer von E-Zigaretten verwenden statt Rauchstopp gleichzeitig Tabakzigaretten, und bedingt durch süßlich aromatisierte Liquids und Werbung als Lifestyle Produkt nutzen jugendliche Nie-Raucher zunehmend diese neuen Produkte. Auch wenn E-Zigaretten z. T. möglicherweise geringere Schadstoffe enthalten, so war doch keine E-Zigarette frei von potenziell toxischen und karzinogenen Substanzen. Zudem bestehen Hinweise, dass E-Zigaretten neue ­toxische Substanzen enthalten, 2019 führten sie zu EVALI (E-cigarette or vaping associated lung injury) in den USA mit 68 Todesfällen. Im Dampf von Tabakerhitzern fanden sich um 295% erhöhte Mengen kanzerogenes ­Acenaphten versus Tabakzigaretten. Der Gebrauch von nikotinhaltigen E-Zigaretten und Tabakerhitzern konnte tabakbedingte Krankheiten nicht vermindern. Shisha-Gebrauch führt zu ähnlichem Nikotin-Suchtpoten­zial, einer erheblich höheren Schadstoff- und Kohlenmonoxydbelastung, Shiazzo-Dampfsteine haben bei gleicher Kohlenmonoxyd-Vergiftungsgefahr ein deutliches geringeres Gesundheitsrisiko als Shishas. Der Konsum von E-Zigaretten bei Jugendlichen und jungen Erwachsenen führte zu einem 5-fach erhöhten Risiko, an COVID-19 zu erkranken, in Kombination mit Tabakzigaretten sogar zu einem 7-fach erhöhten Risiko. Die neuen tabak- oder nikotinfreisetzenden Substanzen sind weder gesundheitlich unbedenklich, noch geeignet zur Raucherentwöhnung.

Tracheal aspirate sequencing identifies unique features of dysregulated host response in SARS-CoV 2 associated acute respiratory distress syndrome

Background: The coronavirus disease 2019 (COVID-19) pandemic has led to a rapid increase in the incidence of acute respiratory distress syndrome (ARDS). The distinct features of pulmonary biology in COVID-19 ARDS compared to other causes of ARDS, including other lower respiratory tract infections (LRTIs), are not well understood. Methods: Tracheal aspirates (TA) and plasma were collected within five days of intubation from mechanically ventilated adults admitted to one of two academic medical centers. ARDS and LRTI diagnoses and were verified by study physicians. Subjects were excluded if they received immunosuppression. TA from subjects with COVID-ARDS was compared to gene expression in TA from subjects with other causes of ARDS (OtherARDS) or mechanically ventilated control subjects without evidence of pulmonary pathology (NoARDS). Plasma concentrations of IL-6, IL-8, and protein C also were compared between these groups. Upstream regulator and pathway analysis was performed on significantly differentially expressed genes with Ingenuity Pathway Analysis (IPA). Subgroup analyses were performed to compare gene expression in COVID to ARDS associated with other viral LRTIs and bacterial LRTIs. The association of interferon-stimulated gene expression with SARS-CoV2 viral load was compared to the same association in nasopharyngeal swabs in a cohort of subjects with mild SARS-CoV2. Results: TA sequencing was available from 15 subjects with COVID, 32 subjects with other causes of ARDS (OtherARDS), and 5 mechanically ventilated subjects without evidence of pulmonary pathology (NoARDS). 696 genes were differentially expressed between COVID and OtherARDS (Figure 1A). IL-6, IL-8, B-cell receptor, and hypoxia inducible factor-1a signaling were attenuated in COVID compared to OtherARDS. Peroxisome proliferator-activated receptor (PPAR) and PTEN signaling were higher in COVID compared to OtherARDS (Figure 1B). Plasma levels of IL-6, IL-8, and protein C were not significantly different between COVID and OtherARDS. In subgroup analyses, IL-8 signaling was higher in COVID compared to viral LRTI, but lower than bacterial LRTI. Type I/III interferon was higher in COVID compared to bacterial ARDS, but lower compared to viral ARDS (Figure 1C). Compared to nasopharyngeal swabs from subjects with mild COVID-19, expression of several interferon stimulated genes was less strongly correlated with SARS-CoV2 viral load in TA (Figure 1D). IPA identified several candidate medications to treat COVID-19, including dexamethasone, G-CSF, and etanercept. Conclusions: TA sequencing identifies unique features of the host response in COVID-19. These differentially expressed pathways may represent potential therapeutic targets. An impaired interferon response in the lung may increase susceptibility to severe SARS-COV2.

Improving survey response rates among patients at a cancer center during a global pandemic

This study evaluated approaches for recruiting patients at a cancer center to an electronic survey about their experience with the COVID-19 pandemic. Eight groups (n = 2,750 patients total) were contacted via email to complete a 15-minute survey. Groups consisted of: 1) a detailed email only, 2) a brief email only, 3) a mailed letter and brief email, 4) a mailed letter, small prize in the envelope, and brief email, 5) a mailed postcard and brief email, 6) a brief email and $10 gift card, 7) a mailed letter, brief email and $10 gift card, and 8) a mailed postcard, brief email, and $10 gift card. Patients were considered eligible if they had a valid email address, were seen at the cancer center since January 1, 2015, had English as a preferred language, a last known vital status of alive, an address inside the cancer center's catchment area, and were between 40 and 89 years old. Patients were over sampled for Hispanic ethnicity and African American race, then randomly sampled. Response rates were evaluated overall, by race/ethnicity, gender, time since visit to the cancer center and age. Multiple logistic regression was used to assess the odds of completing the survey. 259 patients (9.4%) completed the survey across all pilot groups. Response rates varied by pilot group, ranging from 2.6% response for a detailed email only, to 18.4% response for a brief email, postcard and gift card. The latter group was also among the highest for response rates among Hispanics (25.6%) and Non-Hispanic/Non-White patients (15.9%). In a multivariate model adjusting for race, ethnicity, age, and gender, we found those who received a gift card had 1.86 times (95% CI: 1.40-2.48) higher odds of completing the survey than those who did not. Additionally, those who received a postcard or letter compared to those who only received an email had 1.46 times (95% CI: 1.05-2.04) higher odds of completing the survey. In our study of cancer patients seen at a major cancer center, prompting potential study participants with a letter or postcard before an email improved response rates. Further including a gift card increased response rates, particularly for underrepresented minorities. Future analyses include evaluating response rates by insurance status and cancer type.

Impact of COVID-19 pandemic on healthcare delivery, behavioral outcomes, and financial stress in 1,253 individuals with cancer at huntsman cancer institute (HCI)

Purpose: The COVID-19 pandemic has substantially changed social practices, economic stability, and access to medical care that may significantly affect cancer patients, especially those undergoing active treatment. We characterized the pandemic's influence on healthcare delivery, behavioral health, and financial stress in cancer patients. Methods: We included data from N = 1,253 adult cancer patients, who visitedHCI in the last 4 years, consented to the Total Cancer Care study, and completed a COVID-19 survey as part of the COPES consortium. The survey was administered between Aug and Sept 2020 and included questions on change/cancellation of medical visits, change in exercise and alcohol consumption, daily life, social interactions, and financial stress sinceMarch 2020. Results:The cohort'smean agewas 60.4 (19-92) years, with 54% female, 68% non-Hispanic White, 41% retired, 43% employed full or part-time, and 24% living in rural counties.Among the 27% of patients who reported receiving current treatment at HCI, 30% had to change or cancel a medical visit due to the pandemic, with 2% reported a change/cancellation in a biopsy, surgery, radiotherapy, and chemotherapy;5% reported a change/cancellation in imaging;and 3% and 23%reported a change/cancellation in cancer screening and doctor's visit, respectively. 18% rescheduled an appointment to a telehealth visit. Changes in exercise habits due to the pandemic were common (47%), with 10% no longer exercising regularly, 21% exercising less, and 11% exercising more than before. 5% reported increased alcohol consumption, while 6% reported a decrease. Most patients (84%) experienced a change in their daily lives (ranging from somewhat to a lot of change). 69% had fewer social interactions, and 49% reported financial stress due to the pandemic, with 11% reporting being quite a bit/very much financially stressed. Conclusions: These findings suggest that within approximately the first 6 months, the COVID-19 pandemic had a substantial impact on cancer patients' lives, with adverse effects on health behaviors and financial stress. Healthcare delivery continued for essential cancer care but was disrupted for other services, such as cancer screening. Further analyses are underway.